proba float64 0.5 1 | text stringlengths 16 174k |
|---|---|
0.999662 | While many healthcare providers have been quick to adopt an EHR, some physicians have been more reluctant. Here are 10 important ways that an EHR will benefit physicians.
1) Accurate data capture: Handwritten notes cannot accurately capture patient information because of illegible writing. EHR solutions allow doctors to enter data as accurately as possible, ensuring no mistakes.
2) Safer prescriptions: Another consequence of handwritten notes is the potential for errors in prescriptions. When a note is entered electronically, there is little chance of a pharmacist misreading it.
3) Ease of reporting: Writing a patient report using handwritten notes can be time-consuming. EHR solutions allow physicians to generate reports automatically. Information is collected seamlessly, allowing for quick and comprehensive reports.
4) Transferability of files: When a patient moves, their medical records should travel with them. Instead of causing delays, electronic records can be sent immediately and at virtually no cost, leading to faster care and better patient outcomes.
5) More time spent with patients: Handwritten notes must be cataloged and retrieved using an old-fashioned filing system. This can take time and lead to errors. Physicians who use EHR never have this problem, leading to more time spent treating patients.
6) Automated workflow: EHR solutions also save physicians time in other ways. An EHR can provide a seamless file for tracking all patient procedures. In addition, an EHR can give alerts when a patient has an upcoming test, ensuring that physicians are up to date on all aspects of their patients' care.
7) Increased revenue: Payroll is a major expenditure for most practices. An EHR allows physicians to spend less on human resources, leading to increased revenues. With an EHR that maximizes efficiency, staff are not needed for overtime filing. Staff can be reallocated to where they are most needed.
8) Integrated office technologies: An EHR allows physicians to use a single system for patient records and all other digital equipment. The result is a smooth workflow that is easy to use.
9) Work from home: Because an EHR allows doctors to access files from anywhere, physicians can maximize their efficiency by reviewing patient records at home or on vacation. All you need is an internet connection.
10) Increased patient satisfaction: Patients who have more face time with doctors, who receive quality care and accurate assessments are happy patients. An EHR allows doctors to answer patients' questions immediately and accurately.
EHR solutions benefit physicians in a variety of ways. Contact HIS for more information on adopting electronic records. |
0.999823 | Meet the team, we are all work colleagues that have become a family, here to support each other when someone has a bad day, come on we all know it happens! Trust, respect, humility and collaboration is the key in our team.
- Passion: Passion is at the heart of our company, we are committed in heart and mind.
- Quality: What we do we do well.
- Customer Satisfaction: Our customers are our priority and their satisfaction is our goal.
- Integrity: Honesty is the best policy, we are honest, real and genuine.
- Humility: We are humble and learn every day from everyone around us.
- Courage: We are entrepreneurial, reaching beyond our boundaries, taking risks and are not afraid to try.
- Harmony: We are a team, a family and it is together we are able to excel in what we do. |
0.999552 | Santeri "Naama" Lahtinen is a retired Terran player from Finland. He was formerly playing for Fnatic.
Naama started his RTS-career from Warcraft III, which he played a lot with his brother Sein. He didn't achieve a lot in Warcraft III, but things changed when he got the beta key for StarCraft II.
After receiving the beta key, he quickly became a force to be reckoned with in the Finnish scene. He also gained some recognition in the international scene when he won the 4th Viking Cup. Since the release of the game, Naama has won the 33rd Go4SC2 cup. He also came 4th in the monthly finals with HuK. He also showed off his skills in a showmatch between Finland and Sweden, where he all killed the Swedish team, which consisted of SjoW, ThorZaIN, Jimpo and merz. Naama's play earned him an invitation to the DreamHack Winter 2010, where he notched impressive wins over top players such as TOP and MaNa to take 1st Place.
On February 28, 2011, Naama left Mousesports and joined a less-known team, Virus Gaming, where he partnered-up with his brother Sein and his friend Satiini. During the following few months, he slowly faded away from the European scene, appearing less and less in major events. He eventually left Virus Gaming on August 18, 2011, in order to become a member of the Fightline project, alongside other former members of Virus. One month later, Naama released a statement explaining that Virus Gaming didn't pay him his due wages while he was under contract with them, and that the team made him false promises concerning the payment of hotel fees. He also explained that the lack of communication of Virus's staff and his own lack of motivation had influenced his skill in a bad way. On October 31st, Naama left Fightline and joined eSahara alongside his teammate and friend Satiini.
In January 2012, Naama practiced in Korea with MVP's B-team (Project Supreme), alongside his teammates DeathAngel, Check and cArn, and tried to qualify for GSL Code A On July 15th, Naama announced that he had left Absolute Legends (which had previously acquired eSahara's roster, including Naama).
July 17th, it was announced that Naama joined Fnatic.
On July 28th, 2012, Naama participated in the World Championship Series 2012 Finland and ended up in 1st place after overcoming kiljardi, Winsti, Protosser, Welmu, and then elfi in the finals with a score of 0-2, 2-1.
He is the younger brother of Sein.
Known as The Beast in the Nordic countries, named by TheBeard - the caster and admin of the ESL Viking Cup.
Once said in an interview that the biggest mistake of his life was "leaving mousesports to join Virus".
โ Sweden vs Finland Showmatch VoDs Twitch.tv, 4 September 2010.
โ "Naama leaves mouz to join Virus." mousesports.com, 28 February 2011. |
0.976368 | The original use of biofeedback to train single muscle activity in static positions or movement unrelated to function did not correlate well to motor function improvements in patients with central nervous system injuries. The concept of task-oriented repetitive training suggests that biofeedback therapy should be delivered during functionally related dynamic movement to optimize motor function improvement. Current, advanced technologies facilitate the design of novel biofeedback systems that possess diverse parameters, advanced cue display, and sophisticated control systems for use in task-oriented biofeedback. In light of these advancements, this article: (1) reviews early biofeedback studies and their conclusions; (2) presents recent developments in biofeedback technologies and their applications to task-oriented biofeedback interventions; and (3) discusses considerations regarding the therapeutic system design and the clinical application of task-oriented biofeedback therapy. This review should provide a framework to further broaden the application of task-oriented biofeedback therapy in neuromotor rehabilitation.
Biofeedback can be defined as the use of instrumentation to make covert physiological processes more overt; it also includes electronic options for shaping appropriate responses [1โ3]. The use of biofeedback provides patients with sensorimotor impairments with opportunities to regain the ability to better assess different physiological responses and possibly to learn self-control of those responses . This approach satisfies the requirement for a therapeutic environment to "heighten sensory cues that inform the actor about the consequences of actions (forward modeling) and allows adaptive strategies to be sought (inverse modeling)" . The clinical application of biofeedback to improve a patient's motor control begins by re-educating that control by providing visual or audio feedback of electromyogram (EMG), positional or force parameters in real time [6, 7]. Studies on EMG biofeedback indicated that patients who suffer from sensorimotor deficits can volitionally control single muscle activation and become more cognizant of their own EMG signal [8, 9]. The neurological mechanisms underlying the effectiveness of biofeedback training are unclear, however. Basmajian has suggested two possibilities: either new pathways are developed, or an auxiliary feedback loop recruits existing cerebral and spinal pathways. Wolf , favoring the latter explanation, posited that visual and auditory feedback activate unused or underused synapses in executing motor commands. As such, continued training could establish new sensory engrams and help patients perform tasks without feedback . Overall, biofeedback may enhance neural plasticity by engaging auxiliary sensory inputs, thus making it a plausible tool for neurorehabilitation.
From the 1960s to the 1990s, many studies investigated the effects of biofeedback therapy on the treatment of motor deficits in the upper extremity (UE) [11โ18] and lower extremity (LE) [19โ30] by comparing the effects of biofeedback training with no therapy or with conventional therapy (CT). Patients included those with strokes [12โ14, 18โ24, 26โ31], traumatic brain injury [15, 32], cerebral palsy [25, 33, 34], and incomplete spinal cord injury [16, 17]. Because this review focuses on new technologies and to avoid repeating past study findings, we only summarize briefly the main characteristics of clinical applications of biofeedback for neuromotor therapy.
The applied physiological sources to be fed back included EMG [11โ14, 17, 22โ24, 26, 29, 30, 35], joint angle [20, 29, 31, 36], position [37, 38], and pressure or ground reaction force [39โ41]. EMG was employed as a primary biofeedback source to down-train activity of a hyperactive muscle or up-train recruitment of a weak muscle, thus improving muscular control over a joint . Angular or positional biofeedback was used to improve patients' ability to self-regulate the movement of a specific joint. Parameters such as center of gravity or center of pressure, derived from ground reaction forces measured by a force plate, were often used as feedback sources during balance retraining programs.
Although EMG was used most frequently, it may not always be the best biofeedback source for illustrating motor control during dynamic movement. For example, Mandel et al. demonstrated that with hemiparetic patients, rhythmic ankle angular biofeedback therapy generated a faster walking speed than EMG biofeedback without increasing the patients' energy cost.
Regardless of the type of biofeedback employed cues in past designs were usually displayed in a relatively simplistic format with analog, digital or binary values. The feedback is indicated through visual display, auditory pitch or volume, or mechanical tactile stimulation, with the last arising from a simple mechanical vibrating stimulator attached to the skin .
In addition, patients in older biofeedback studies learned to regulate a specific parameter through a quantified cue while in a static position, or they performed a simple movement unrelated to the activities of daily living (ADL) [13, 23, 24, 30]. We define this as "static biofeedback"; EMG is a classic form. Traditional EMG biofeedback studies showed that patients can improve voluntary control of the activity of the trained muscle and/or increase the range of motion of a joint that the trained muscle controls [12, 22, 23]. The overall effect of this type of biofeedback training on motor recovery is inconsistent, however. Meta-analyses of studies on stroke patients exemplify this [3, 42โ44]. Schleenbaker and Mainous showed a statistically significant effect from EMG biofeedback, whereas the other studies concluded that little, if any, improvement could be definitively determined [3, 43, 44]. As is true for many meta-analyses, contradictory conclusions might result from different assessment criteria or from incongruities in the specification of performance measurements. Schleenbaker and Mainous included non-randomized control studies in their analysis; other analyses considered data only from randomized controlled trials (RCT) [3, 43, 44].
Diversity among outcome measurements also promotes alternative conclusions among biofeedback studies. Glanz et al. used range of motion as an assessment criterion, while the other analyses used functional scores. EMG biofeedback yielded positive effects if the outcome measurement was related to control of a specific muscle or joint [12, 22, 23, 45]. Most results and reviews of static biofeedback therapy, however, do not demonstrate that it leads to significant motor function recovery [16, 18, 30, 43, 46]. For example, Wolf et al . down-trained the antagonist and up-trained the agonist of an elbow extensor by static EMG biofeedback. This did not help stroke patients to extend their elbows during a goal-directed reaching task, and muscle co-contraction still occurred during coordinated movement . Furthermore, the application of static EMG biofeedback training to LE of hemiplegic patients did not affect functional walking [30, 43]. Static EMG biofeedback therapy may thus produce only specific and limited effects on motor function recovery .
Variables such as the site or size of the brain lesion, the patient's motivation during therapy, and his/her cognitive ability may influence the effectiveness of biofeedback or any therapy. Moreland and colleagues [3, 43] included in their meta-analyses studies with control groups that received conventional physical therapy, whereas the other two reports analyzed studies with no therapy in the control group. The latter are potentially biased in favor of biofeedback therapy. These inconsistent experimental protocols surely contributed to the contradictory conclusions . A better design for experimental protocols to evaluate the efficacy of biofeedback therapy needs to be adopted [7, 43, 44]. Randomized controlled trials (RCT) are the gold standard for obtaining a statistically acceptable conclusion; double blind experimental designs best eliminate bias . Given contemporary ethical considerations, however, double blind feedback studies in which neither the patient nor the evaluator knows if the feedback was bogus or real are probably impractical.
Biofeedback provided during function-related task training is defined as task-oriented or "dynamic biofeedback" (in comparison to static biofeedback). While several past studies employed a form of dynamic biofeedback for rehabilitation of postural control or walking [26, 29, 37] or with reaching and grasping tasks , the applied technology and training protocol were relatively simplistic by today's standards.
One major goal of rehabilitation is for patients with motor deficits to reacquire the ability to perform functional tasks. This is intended to facilitate independent living. Contemporary opinion on motor control principles suggests that improvement in functional activities would benefit from task-oriented biofeedback therapy [5, 30, 43, 46]. Because any functional ADL task explicitly requires an interaction between the neuromuscular system and the environment, effective motor training should incorporate movement components and an environment that resemble the targeted task in the relevant functional context [49, 50]. Thus, task learning must be linked to a clearly defined functional goal. In neuromotor rehabilitation, task-oriented training encourages a patient to explore the environment and to solve specific movement problems . Therefore, effective biofeedback therapy for patients with motor deficits should re-educate the motor control system during dynamic movements that are functionally-goal oriented rather than relying primarily upon static control of a single muscle or joint activity.
Several studies have focused on repetitive task-oriented training in which real-time biofeedback is provided during task performance [20, 29, 35, 37, 38, 43, 51, 52]. However, a task-oriented feedback therapy approach requires overcoming several difficulties.
During the training of functional tasks, it is important to choose the best information or variable to feed back. Muscle activity is not always superior . The choice of a biofeedback vehicle should depend upon the motor control mechanism, training task, and therapeutic goal . Assume that the training task for a hemiparetic patient is to reach for and grasp a cup of coffee using only the affected arm. Recent motor control models suggest that the brain may control limb kinematics in a reaching task by shifting the equilibrium points or creating a "virtual trajectory" of the end-point , instead of scaling individual muscle activity patterns . Therefore, hand trajectory may be a more viable feedback variable than muscle activity for reaching related tasks . In addition to hand transportation, successful reaching and grasping actions also require a hand orientation permitting the alignment of the finger-thumb opposition axis with that of the object [57โ59], and control of the finger grip aperture . These variables should be considered when designing dynamic feedback options to facilitate limb control .
Using multiple indices brings out another difficulty, however: how does the system feed back multiple sources of information to patients whose cognition and perception may also be impaired without overloading them with information? If the variables were displayed with traditional abstract and quantitative cues, either visual or auditory, patients may not pay attention to all of them. Inevitably, the ability to process multiple sources will become overburdened . The patient may become confused and distracted, resulting in rapid deterioration of task performance. Designing a biofeedback system that overcomes the "information overloading" obstacle for task retraining is both a technical and conceptual challenge.
Therefore, an effective task-oriented biofeedback system requires orchestrated feedback of multiple variables that characterize the task performance without overwhelming a patient's perception and cognitive ability. A usable system of biofeedback for repetitive task training in neuromotor rehabilitation requires sophisticated technology for sensory fusion and presentation to be available for adoption. Fortunately, technology in this area has advanced considerably since early studies on biofeedback.
An information/sensory fusion approach is one way to reduce information overload to patients during biofeedback therapy. Information fusion involves integrating a dynamic and volatile flow of information from multimodal sources and multiple locations to determine the state of the monitored system. [62โ64]. Information fusion can occur at different conceptual levels, including data acquisition (numerical/symbolic information), processing (such as features and decisions), and modeling . This approach is beneficial because it mimics human intelligence. As a result, it improves the robustness of machine perception or decision making to monitor or control dynamic systems or those with uncertain states .
Information fusion is analogous to augmented feedback information given by therapists while training patients to perform a task. It can be designed to identify the patient's performance based on sensing data and to decide the usefulness of providing feedback through cues. The composite variables that information fusion constructs from multiple information flows provide intuitive and easily presented information relevant for knowledge of performance (KP) and therapeutic result.
Figure 1 summarizes the general architecture of a task-oriented biofeedback system with multimodal sensor inputs [65, 66]. Table 1 lists the function of each module shown in Figure 1. The central controller is the system kernel and contains the fusion algorithms. It receives processed data observed or derived from sensors, a priori knowledge from a database or data storage, and biofeedback rules from the rule base. The embedded fusion algorithm recognizes the current state of the performance based on these inputs and makes decisions for the feedback display.
General architecture of a multisensing task-oriented biofeedback system. The detailed functions of each module in the flowchart are described in Table 1.
Function of Basic Modules in Multisensing Biofeedback Systems for Task Training.
Multiple sensors transform various physiological or movement related information into recordable electronic signals.
Analog signals from multiple sensors are sampled, quantified and streamed into a control system.
The digital filter smoothes the data. The embedded algorithm or mathematical model can derive the secondary parameters as biofeedback indices.
The central controller is the kernel of the system. This module receives data from multiple sensors. Based on the biofeedback rules and user's pervious performance, the fusion algorithm in the controller identifies the participant's current state of task performance and decides the cue display.
This module stores a set of rules or criteria that can be defined by therapist via user interface or by prior knowledge of performance contained in the database. The rules or criteria are elements of the fusion algorithm. Decision making regarding the feedback display must obey these rules.
This component configures the display hardware such as the screen, speaker, and haptic device. The program controls the display of augmented multimodal feedbacks based on commands from the controller.
The database functions the same as traditional memory but with a more efficient structure for data management. It stores the parameters that are important to quantitatively evaluate the motor performance of patient. The controller and rule base access the database, query the patient's prior performance, and then adjust the feedback parameters and display. The database also allows direct access from authorized users.
This module configures the operation setting, rule choosing, etc. Through the human-machine interface, clients can customize the biofeedback training program based on their preferences. Authorized therapists or clients can access the record of a specific patient from the database to evaluate progress toward recovery.
The appropriate sensors to use in a biofeedback system depend on the training task and therapeutic goal. Ever-increasing processing power allows both data streams from multiple sensory sources and instant displays of the parameters derived by a complex algorithm or mathematical model. For instance, biomechanical models have been applied in several task-oriented biofeedback studies to calculate and feed back several variables in real time. These include joint angles and their derivatives from a motion capture camera [67, 68], the configuration of fingers from an RMII Glove sensitive to fingertip positions , and the patient's self-generated joint torque from force and angle sensors .
A database is classically defined as a collection of information organized efficiently for data storage and query . The biofeedback rule database contains rules that define how sensory information will be processed, how decisions will be made, and in what format information will be presented to the patient or therapist. They often take the form of direct mapping from sensory information to various types of augmented feedback, such as visual, auditory or tactile. Other rules are complex models that process the sensory information before feedback. These rules can be stored with raw data and should be updated and expanded as technology or knowledge advance. A simple device may only require data storage, while a complicated fusion algorithm may require the execution of data mining algorithms to obtain a patient's previous performance as prior knowledge, and then adjust the rule and decision criteria to form a user specific training protocol and interface .
Previous studies typically used a limited number of sensors so that the data fusion method and the structure of the applied biofeedback system were relatively simple [29, 35, 73]. For example, one study retrained spinal injured patients to correct a Trendelenburg gait . The microcontroller-based portable biofeedback device integrated the data from EMG and insole pressure sensors, classified the patient's gait into "proper," "improper due to slow walking speed," or "improper due to low muscle activities during the swing phase," and then fed back the classification to patients through different auditory tones. In this case, the data fusion algorithm was equivalent to a classifier with manually set threshold. The biofeedback rules simply mapped a movement condition to a type of auditory tone. For a complicated task-oriented biofeedback system with more sensor inputs and intelligent monitoring and control, effective data fusion may require more sophisticated algorithms, such as artificial neural networks or a fuzzy logic based approach .
Two examples that apply complex multisensing systems and fusion algorithms are real-time movement tracking [75, 76] and movement pattern recognition . One reported multisensing system included magnetic, angular rate, and gravity sensors to track the 3-D angular motion of body segments. The sensory fusion employed a quaternion-based Kalman filter [75, 77]. The movement status was fed back by animating a virtual human on the screen. In another study, a Kalman filter-based fusion algorithm fused data from a tri-axis accelerometer, gyro and magnetometer to more accurately track the position and orientation of human body segments . The authors proposed that the system could be applied to virtual reality for medicine without discussing details.
In addition, a research team from the Arts, Media, and Engineering program at Arizona State University applied information fusion to an interactive art performance. They developed a fusion algorithm to recognize gesture patterns presented by dancers in real-time. The information was then fed back through digital graphics and sounds that reacted to, accompanied, and commented on the choreography . A motion capture system with multiple cameras was used to monitor the position in 3D space of markers attached to a dancer. Postural features such as joint angles were extracted and then fused for recognition of movement patterns . Due to variations in dancers' morphology and execution of the same gestures, a database was developed to store fusion algorithms in addition to customized parameters that allowed the algorithm to adapt to different users. However, none of these studies reported technical details on the implemented fusion algorithms [67, 75, 76].
Although information fusion is a potentially powerful tool for advanced biofeedback systems integrating multimodal and multisensor information, the challenge of determining the most appropriate and effective means to provide feedback remains.
A challenge in neuromotor rehabilitation is to identify the best methods to provide repetitive therapy for task training; these should involve multimodal processes to facilitate motor function recovery . Task-oriented biofeedback therapy might be more widely effective if the biofeedback cues were: (1) multimodal, so perceptive and cognitive functions are involved in the physical therapy; (2) attractive and motivating, to keep the subject attentive; and (3) easy-to-understand, to avoid the information overloading problem. Multimedia based technology can be used to design biofeedback cues possessing these features. Multimedia uses computerized graphics/animation, sound, and/or haptic stimulation to immerse the user in a constructed virtual environment. This technology is thus called virtual reality (VR) in many studies.
Multimedia environments can offer real-life experiences by providing visual, auditory and physical interactions in an engaging manner. This may make them more effective than classic biofeedback presentation methods for task-oriented therapy. For example, a "room" scenario is designed to simulate ADL [72, 73, 79]. In the virtual room patients can practice functional tasks such as making coffee, pouring water into a glass , and reaching and grasping an object on a table or shelf (Figure 2) [79, 80]. However, the real therapeutic benefits of these systems remain to be proven by well designed clinical trials.
Virtual environment design. The design of a virtual living room is illustrated. The virtual arm animates the patient's arm movement in real time. The patient can explore the virtual environment and perform the goal-directed reaching task. The green line indicates the ideal trajectory. The cone shape constrains the spatial error of endpoint position and provides direct knowledge of performance .
An immersive multimedia environment is ideal for multimodal sensory feedback. Visual feedback is easily accomplished via computer graphics. A 3D stereo visual environment can be created with head-mounted displays (HMD) or 3D monitors [82, 83]. These methods may not be suitable for neuromotor therapy among patients with brain injury, however, because motion sickness, dizziness and visual problems may occur . A large screen with depth reference frames to aid 3D perception is an alternative choice.
Surround sound can provide an immersive environment in which to provide auditory biofeedback. Sound is a very effective feedback source for temporal information; visual information works better for spatial feedback . Auditory feedback can take the form of pleasant and captive music pieces rather than the simplistic and often annoying tones or beeps in older biofeedback studies. Studies have shown that music can synchronize motor outputs [85, 86], improve the motor coordination of Parkinson patients , and enhance motor learning in a patient with large-fiber sensory neuropathy .
A research team at ASU is developing an immersive multimedia environment for biofeedback therapy (Fig. 2). The visual feedback presents the arm configuration and ideal trajectory of the hand from initial location to target. A cone shaped object indicates the spatial error of the endpoint. If the spatial error is large and the hand moves outside the boundary (spatial limits) of the guiding cone, the transparency of the cone becomes reduced, i.e., the cone is more visible. This produces the KP that tells the patient to correct the error. In addition to the visual feedback, auditory feedback in the form of musical notes indicates the smoothness and temporal-spatial parameters of the endpoint trajectory to improve multi-joint coordination (Figure 3) and to map the movement quality of the participant in real-time. Music notes within a phrase are distributed spatially along the specified path. These notes indicate the distance the hand has moved toward the target, with each note corresponding to a short distance along the path. When the hand reaches a point along the path where a musical note is located, the corresponding note starts to play. The duration of each note depends on movement speed. Therefore, patients could "compose" different melodies based on movement pattern and quality. If the movement is spastic, for example, the musical phrase could be distorted by multiple repetitions of a note. This music will play the same role as beeps in pacing the patient, but it will also provide information on speed and smoothness. In addition, another music phrase monitors trunk motion to signal the patient to reduce the compensatory motion in reaching . In this case the volume indicates the amount of compensation.
Musical feedback design. Musical notes are distributed along the hand's path from initial location to the target. Reaching a particular distance triggers the corresponding note to play. The curve indicates the hand-to-target distance during the arm reaching and withdrawal .
Finally, haptic feedback has also been developed for task-oriented biofeedback studies [33, 61, 69, 79, 88โ91]. Haptic interfaces allow the patient to interact with and to manipulate a virtual object. Results [69, 89] have shown that haptic information provides knowledge of results (KR) and feeds back kinaesthetic sensations that are important for task performance. Haptics also encourage patients to immerse themselves in the virtual environment . Haptic devices include the six degree of freedom (DOF) Cybergrasp from Immersion Corporation , the PHANTOM Haptic Interface , the 3DOF Haptic Master from Fokker Control Systems , and the Rutgers Master II-ND (RMII) force feedback [69, 92].
Motivation and attention are two key factors in the success of therapies to induce neuroplasticity . In earlier biofeedback approaches, the information presented often took the form of lines or bars on a computer screen or simple beeps. These were neither intuitive nor attention grabbing. Such feedback often makes participants, especially children, tire or become distracted quickly . Novel VR based biofeedback systems can promote sustained attention, self-confidence, and motivation of participants during the repetitive task therapy through multimodal immersive displays and interactive training programs [79, 90, 94]. In some studies, the scenarios were also designed as games, such as goal keeping or tennis playing , in an effort to engage the patient's active participation.
Finally, VR used as an integrated information technology can increase the patient's ability to process perceptual information in multisensing task-oriented biofeedback applications . In virtual environments, the multimodal sensory cues that feed back multiple flows of information are presented to resemble scenes in the "real world" or in nature. Such an intuitive form of feedback is more easily perceived by brain injured patients than multiple abstract and quantified presentations that use formulas or numerics. Because the multisensing biofeedback system for functional retraining must also solve the information overloading problem, multimodal VR based feedback display offers a promising alternative approach.
There are other advantages of VR technology in task-oriented biofeedback as well. The virtual environment and training tasks are easily customized by the computer program . Also, VR technology can assess the motor function recovery of patients [96, 97]. Piron and co-workers showed that objective measurements of task performance in VR produced high sensitivity and repeatability. Moreover, the augmented feedback, i.e., KR and KP, displayed in virtual environment can improve motor learning [50, 98]. KR indicates the degree to which the performer achieved the desired movement outcome or therapeutic goal. KP is the augmented feedback of the quality of produced performance . Virtual training environments can easily display both forms of feedback to inform patients about instant errors in task performance, motivate patients in task learning, and reinforce previous gains .
The major application of VR-based biofeedback to treat sensorimotor deficits has focused on UE exercise. Preliminary studies on VR based biofeedback for motor functional recovery in neurally injured patients are promising. Holden et al. utilized VR to train reaching and hand orientation in stroke patients. Patients saw a virtual mailbox with different slot heights and orientations. To put the "mail" into the slot, the patient must reach the slot with correct hand orientation. A virtual "teacher mail" demonstrated the motion for patients to imitate. In preliminary findings, one of two stroke patients improved their upper extremity Fugl-Meyer Test (FM) score and their performance in a real mailing task. That patient was also able to complete some functional activities that previously were impossible. No improvement was observed in the other patient, however. Later, nine more participants were recruited for further testing . All participants showed significant improvement in their FM score, the Wolf Motor Function score (WMF), and selected strength tests as compared to before the training. The study contained no comparison control or alternative treatment group, however. Also, the study provided no data or discussion on what parameters may affect the outcome. The inconsistent results in one patient suggest that a single VR system design may not be effective for all stroke survivors. Wann and Turnbull developed game-like VR based biofeedback programs to improve the amplitude and direction control of arm movement kinematics in eight adolescents with cerebral palsy. Each participant received two training sessions: VR based biofeedback and conventional occupational therapy, but in different orders. The researchers reported results from only three of the eight patients. In two patients with spastic diplegia, the VR-based biofeedback made the UE movement smoother than conventional therapy, as measured by the number of velocity peaks of elbow trajectory. No obvious benefit from VR-based training was observed in the third patient, who had severe athetosis. In studies investigating VR-based biofeedback for hand function rehabilitation in stroke survivors, investigators used multisensing data from the Cyberglove, which sensed finger joint angles, or the RMII glove, which measured both the applied force under each finger and the position of the fingertips [69, 90]. Different scenarios were designed for exercises to improve joint range of motion, finger fractionation, and grasp strength on the impaired hand. Patients improved grasping force, finger joint range of motion, and movement speed after two weeks of VR-based biofeedback therapy . Moreover, three participants showed an improvement on the Jebsen hand functional test . This study focused on training of grasping movement and force, however, while the major impairment to hand function in stroke survivors is motor incapability for hand opening (extension of metacarpophalangeal joints) and wrist extension. In addition, pathological grasping, as seen in the tonic grasp reflex, for example, is common in brain injured patients. They may grasp the object tightly with finger flexion and adduction of thumb but then cannot release the object . To improve the effectiveness of hand functional recovery in patients with brain injury, future designs of VR based biofeedback should emphasize motor tasks that encourage hand opening and wrist extension rather than retraining hand closure.
The number of reported VR-based biofeedback studies on LE motor function is relatively small at present, possibly due to the technical challenge of how to process a multitude of information and then present it to the patient. LE functional retraining depends not only on lower-limb mobility and bilateral coordination, but also requires other motor skills, such as balance control. A recent study used a video camera to track stroke patients' 2D motion and then fed back the motion by directly projecting and integrating the patient's image into a 2D game-like VR (IREX System, Toronto, ON, Canada) . The experimental group included five stroke survivors. Each played three VR games with the goal of training LE range of motion, balance, mobility, stepping, and ambulation skills. KR and KP, such as error rate or movement quality, were quantified and indicated on the screen at the end of each game. The control group, also five stroke patients, did not receive any intervention. The experimental group significantly improved motor function in the LE and significantly increased activity in the primary sensorimotor cortex as determined by functional MRI data . The investigators concluded that VR may have contributed to positive changes in neural reorganization and associated functional ambulation.
One inherent limitation of biofeedback therapy is that patients with more severe motor deficits cannot participate due to an inability to initiate any functional movement, thus preventing utilization of biofeedback for improving performance. Rehabilitation robots or other devices could solve the problem by providing mechanical assistance for movement.
Active research and development designs for robotic-focused UE or LE motor rehabilitation exist [101โ105]. Several research groups have built robots with biofeedback features. One study used a robotic end-effector to help patients with stroke move their arms while receiving real-time feedback of endpoint position . The robot could produce the force needed to correct the participant's hand position when it was out of the appropriate range. In gait training with Lokomatยฎ, which can predefine the pattern of LE kinematics, estimation of self-generated joint torques is fed back. This provides information about the walking effort and motivates the patient to produce better gait patterns . The combination of rehabilitation robot assisted therapy with advanced biofeedback is such an attractive approach for sensorimotor rehabilitation that we anticipate many new studies will forthcoming.
Advanced technical developments in communication, including wireless vehicles and Internet use, have the potential to permit implementation of task-oriented biofeedback anytime and anywhere, thus enabling telerehabilitation. Jovanov et al. designed a wireless body area network that connects data from multiple sensors on the body to a personal server such as a cell phone or personal digital assistant (PDA) . This data could be sent to other computers through a wireless network. The researchers suggested that this equipment could be used to provide biofeedback during ambulatory settings and to monitor trends during recovery. Another study presented an in-home biofeedback system in which many patients could access the same server via a telemedicine network. The VR based biofeedback training program could be customized to each participant, and retraining could then be performed using a personal computer at home . Each provider would need many clients to establish a database and to keep records for each client efficiently while concurrently generating customizable training protocols to fit individual requirements . The database would also be accessible to clinicians for evaluation of patient compliance and improvement. All these technological developments allow us to foresee the prevalence of task-oriented biofeedback applications in neurorehabilitation.
In the future, researchers should carefully choose the applied sensors and assign necessary biofeedback indexes in task-oriented biofeedback training. On one hand, the system should incorporate sufficient numbers and types of sensors to accurately detect the state of dynamic variables during movement. On the other hand, many catastrophically injured patients requiring physical therapy also have impaired perceptual and cognitive abilities. Therefore, it is important to develop an information fusion algorithm and to carefully design intuitive forms of feeding back integrated sensor information to avoid overloading patients' perceptions. In general, investigators should determine the factors contributing to motor deficits in each patient diagnostic group, establish training goals, explore the parameters that characterize functional movement, and then limit the number of feedback sources within the dynamic biofeedback paradigm.
The key ingredients for motor functional recovery are the intensity of task training and the patient's active involvement during the therapy . Task-oriented biofeedback therapy and robot or other assistive device aided repetitive task practice should be more effective because this integrated sensorimotor therapy would provide patients with motor deficits an opportunity to actively and repetitively practice a task [79, 107]. VR based displays could also increase the motivation and attention of patients in the task training, improve sensorimotor integration through multimodal augmented feedback, and, consequently, improve training efficiency. Therefore, comparing the effects of robot-aided therapy with task-oriented biofeedback intervention to conventional therapy for enhancement of motor function could be enlightening.
The application of virtual reality among patients with neuropathology is limited, however. VR-based biofeedback therapy requires that the patient demonstrate preservation of some auditory and/or cognitive ability or possess reasonable visual field perception. A certain level of movement control is also necessary to carry out tasks in the virtual environment. Immersive visual interfaces have been reported to increase the risk of seizure occurrence in patients with a history of epilepsy . Pre-screening of participants should be performed based on clearly defined inclusion/exclusion criteria.
The most challenging question for all VR studies is whether the effect of VR training is transferable to task performance in the real world. If this transition cannot be acquired, VR may not be applicable in motor rehabilitation. Further evidence is needed to effectively address this question. Additionally, therapeutic goals from VR based studies need to be clinically and functionally relevant to be credible. For example, flexor spasticity develops in the hemiplegic hands and wrists of most patients with brain injuries . Therefore, difficulties in opening the metacarpophalangeal and interphalangeal joints and extending the wrist are the relevant clinical problems, not the ability to close the hand for grasping, as one previous study attempted to correct [67, 86]. Another problem with grasping task performance is that patients with brain injuries may have difficulty releasing objects due to uninhibited grasp reflexes . Failure to release the grasped object during repetitive task training usually frustrates patients and may adversely impact motivation. Virtual reality offers an opportunity for patients to practice hand opening to release objects without haptic sensation, which avoids the tonic grasp reflex. Therefore, aVR based biofeedback system that trains patients to grasp and release virtual objects without haptic feedback may be effective to enhance the mobility of the hand, increase the active range of motion in metacarpophalangeal, interphalangeal and wrist joints, and motivate patients to practice hand opening activities in the early stages of the intervention. When patients regain active control of hand movement, haptic feedback could be added to the VR to enhance learning and interaction with the environment.
Preliminary results of clinical tests have demonstrated the benefits of task-oriented biofeedback on motor functional recovery [26, 29, 69, 82, 100]. However, these studies lack strong evidence. The number of patients in each study is small. Some reported benefits from task-oriented biofeedback were not consistently observed among all subjects . Moreover, some of the applied technologies are immature. Clearly, future work should focus on techniques to enhance and ultimately foster RCTs directed toward task-oriented biofeedback applications. These RCTs should then use comprehensive statistical analyses to further prove and quantify the efficacy of task-oriented biofeedback for functional motor recovery.
This article reviewed recent developments in biofeedback concepts, technologies, and applications. New technology propels the application of diverse biofeedback therapy options within the context of functional training to improve motor control among neurorehabilitation patients. Promising techniques for task-oriented biofeedback study, both developed and proposed, were summarized. Some preliminary clinical tests offer encouraging results. However, these techniques are relatively new, so there is a dearth of clinical RCTs available to definitively prove the efficacy of using contemporary technologies for task-oriented biofeedback within the field of neurorehabilitation. Further studies are needed.
The authors wish to express their appreciation for the input provided through many fruitful discussions with Thanassis Rikakis, Todd Ingalls, Loren Olson and Gang Qian and their practical implementation of an immersive multimedia based rehabilitation environment, and valuable comments from Dr. Doug Stuart to improve the manuscript. We would also like to thank anonymous reviewers for their helpful comments.
The work is supported in part by a grant from NICHD/NIBIB N01-HD 3-3353, a grant from NSFC 60340420431, both to JH, and in part by the Arts, Media and Engineering program at Arizona State University. |
0.999755 | Can Quickbase support a 1 to 1 relationship?
I have an application that consists of 2 tables, Orders and Equipment. Orders are created by hand while Equipment is a predefined list of records i.e. Dell Computer Serial Number 1234, Dell Computer Serial Number 1235 etc.
An Equipment record can only be associated with a single Order but an Order can have many Equipment. (The current relationship is that an Order can have many Equipment.) But.. the Equipment table should be static data, the user should not have to create an Equipment record each time they are creating an Order record. Rather than Add an Equipment record from the Order page i'd like to link or relate an Equipment record with an Order, is this possible?
What you would usually do here is have an orders table, and equipment table, and a line items table, where an order can have many line items, an equipment item can have many line items.
From there you can add a quantity field to the line item record, and a total field that takes the base equipment price multiplied by the quantity.
Delete your existing orders to equipment relationship and give the above a shot. it is the standard way of handling what you are describing.
But each equipment only has a quantity of 1. All equipment is unique, there's not a pool of a single "Equipment".
Ok - that being said, I think you would still have the same tables. I laid out above. However, once an equipment has a child 'line item' record, it would not show up in the list for the next time you add a line item to an order. You still need a place to store these unique equipment assets. And, in order to link many of these unique equipment assets to one order, you need a join table.
So to implement this, create a summary field on the equipment table that counts the number of line items related. Then, create a formula field (text or checkbox) that has a formula something like: if([# of Line Items]=0,"Available","Issued") where if there line items is equal to 0, it is available, if it is not equal to 0, it has been issued.
Then create a report labeled 'Available Equipment' I would recommend only putting 1 to 3 fields on that report. Add a filter to that report: where [# of Line Items]=0. This report will be your active equipment list for use on orders.
Now go to your line item table form, and on the form element for the equipment reference field, have it display choices from your 'Available Equipment' report instead of the standard record picker fields.
That did it, you nailed it. Thank you Eric! |
0.993218 | What is it I love about summer? Long summer days and warm nights with a cool breeze blowing. The lightning bugs lighting up the night like fairy lights leading the way. Going to festivals and fairs where the food is bad but perfect. The sounds of people laughing, having a good time. The feel of warm grass on my bare feet. Open windows and the sound of frogs and crickets singing. Fresh vegetables and grilled anything. Yes, I love summer.
Summer brings the fair and late nights and early days. The fair at dusk as the sun is setting and the lights are starting to glow. |
0.99706 | For the English cricketer, see Francis Wyatt (cricketer).
Sir Francis Wyatt (1588โ1644) was an English nobleman, knight, politician, and government official. He was the first English royal governor of Virginia. He sailed for America on August 1, 1621 on board the George. He became governor shortly after his arrival in October, taking with him the first written constitution for an English colony. Also sailing with him on this voyage was his second cousin Henry Fleete Sr., who helped found colonies in both Virginia and Maryland. In 1622 he rallied the defense of Jamestown which was attacked by Native Americans, during which the lives of some 400 settlers were lost and he then oversaw the contraction of the colony from scattered outposts into a defensive core.
Francis was the son of Sir George Wyatt and his wife Jane Finch. He was born at Boxley Manor in Kent, and attended St Mary Hall, Oxford, (from July 1, 1603) and Grey's Inn (1604). He was knighted July 7, 1618 at Windsor.
Wyatt was governor of Virginia from November 1621. Virginia became a royal colony in 1624, but Sir Francis, at the request of the crown, remained on as governor until September 18, 1625, when Sir George Yeardley, whom he had succeeded, resumed the office. In 1624, Wyatt resided in Jamestown with his wife, his brother Haute, and seventeen servants. In 1625, he received a black servant girl after a court settlement from her previous employer. After leaving office, he left Virginia for Ireland and England to settle his father's estate. He was appointed governor again in 1639, sailing from England to take up his post. He served from November 1639 until February 1641 and was then succeeded by Sir William Berkeley. He arranged the purchase of the home of the previous governor to use as the first designated "state house" of the colony, the government previously having met in the church.
Wyatt returned to England after his second term as governor and died in Boxley. He was buried there on August 24, 1644.
Sir Francis Wyatt organized the General Assembly which had been called in 1619. This was the first legislative body in America. Sir Francis caused its privileges to be embodied in a written constitution, the first of its kind in the New World.
Francis Wyatt's grandfather was Sir Thomas Wyatt the younger, who had led the Kent faction of Wyatt's rebellion to the Spanish marriage of Queen Mary in support of Lady Elizabeth, and was executed for treason as a result. His great-grandfather Thomas Wyatt the elder, the poet, was briefly imprisoned in the Tower of London for an alleged relationship with Anne Boleyn.
Sir Francis's wife Margaret was the daughter of Sir Samuel Sandys and the niece of George Sandys, the treasurer of Jamestown. Francis and Margaret's children included Henry, whose daughter Frances briefly held Boxley; Francis, who was at King's College, Cambridge, in 1639; Edwin, an MP who successfully sued his niece to regain Boxley, but whose son died without issue; and Elizabeth, whose grandson Robert Marsham, 1st Baron Romney (1685โ1724), eventually inherited Boxley. Boxley remained with the barons and earls of Romney for more than two hundred years. Sir Francis left no direct descendants in what would later become the United States of America.
Sir Francis had a daughter Elizabeth Wyatt who married Christopher Garlington who immigrated to America (Virginia) between 1637 and 1638. He was born between 1614-1620, in England (his father, Nicholas was born in 1582, in Thurland Castle, Lancashire, England). He returned to England briefly to marry Elizabeth Wyatt abt. 1644, sister of Sir Dudley Wyatt, Cavalier who came to Virginia. He had served in the army of Charles I, King of England, and was one of the grantees of the northern Neck, all the tract of land between the Potomac and Rappahannock Rivers, from Charles I, dated at the St. Germains in France, September 18, 1650. Virginia was the only place that these faithful soldiers of King Charles I had to go to seek new fortunes. "Cavaliers and Pioneers, Volume I, Abstracts of Virginia Land Patents and Grants, 1623-1800", by Nell Marion Nugent and published in 1934, on Page 186.
We see that Christopher Garlington, from a prominent and titled family in England, paid his way to Virginia and purchased land, in Virginia, on or before 1638. Christopher found Virginia to be a safe haven for worshiping freely and in an attempt to recreate the Garlington fortune. The first record found for Christopher is recorded in :York County, Deeds, Orders, Wills, Etc. Book 2, p. 58: "โฆChristopher Carlington(a misspelling of the name) his heirs executors administrators or asignes to their owne use forever one hundred acres of land sett lying & being at the heed of the New Pocosin River being bounded by the sd river on the North & running South unto the Maine woods & by the Gleabe land on the East side & on the West by the s'd Thomas Curtice โฆ"Christopher Garlington is mentioned in Nell Marion Nugent's Book, "Cavaliers & Pioneers, Volume I, abstracts of Virginia Land Patents and Grants, 1623-1800, Page 371, page 383, Page 467, and Page 556, and many more. From these land records it would seem that Christopher Garlington moved from York County to Northumberland County by the year 1658. Christopher Garlington became a substantial tobacco plantation owner.
Christopher Garlington III, grandson of Christopher Garlington I, married Elizabeth Conway in Lancaster County, Virginia on May 5, 1724. Miss Conway was born in 1705/1705 to Col. Edwin Conway III and his wife Ann Ball. Ann Ball, daughter of Col. Joseph Ball and Elizabeth Romney Ball, and half sister to Mary Ball, the mother of George Washington. Rita Carpenter Jenrette is a direct descendant of Christopher Garlington.
His younger brother, the Reverend Hawte Wyatt (1594โ1638), who was the rector of Maidstone, Kent, traveled to Virginia with Francis in 1621 and returned with him to England in 1624, after their father died. Rev. Wyatt's many descendants in America include the late Duchess of Windsor, wife of Edward VIII, later the Duke of Windsor.
^ Allington & Boxley: a compilation of original sources on Allington Castle and Boxley Abbey. Accessed 2012 April 03.
This page was last edited on 8 December 2018, at 21:16 (UTC). |
0.896067 | How would you line up an 11-player all-star team based on the players' performances at the World Cup? Here's what we came up with.
France was often frustrating to watch, but it's a team chock full of world-class players who dominated in the knockout stage.
Here's our World Cup 2018 all-star team of players whose stock rose significantly by performances in Russia.
A strong run at the 2018 World Cup that ended with a 2-1 semifinal loss to Croatia is cause for both concern and optimism.
Croatia will attempt to emulate what France did in 1998: win the World Cup in its first appearance in the final.
With the tournament's best defense and most exciting player, Les Bleus will be favored in the final.
There are parallels between the 2018 World Cup team and the '98ers, but Didier Deschamps doesn't like to talk about them.
The Real Madrid star has taken Croatia to the brink of replicating or bettering its third-place finish of 1998.
Belgium's golden generation is underachieving no longer, thanks to its leader, who returned for the toughest games of the World Cup.
Following Croatia's shootout win over Russia, Alexi Lalas suggested that Russia 2018 was the greatest World Cup ever.
England aims to push deeper into the World Cup than it has gone since losing to West Germany in the 1990 semifinals.
Diego Godin briefly quit soccer at age 17. Now 32, he ranks among the world's best defenders.
In March, Pavard was not on the list of 23 players France would likely take to Russia. After Saturday, he was a national hero.
After missing the last two World Cups, Sweden heads into the round of 16 with hopes of recalling its glory years. |
0.992488 | Which yoga practice would i use to address resistance to change?
I think the best video would be the yoga for grounding video, it is available in my shop or on the membership site.
I also recommended the Keepinโ it Real Yogi Style series which is a great series on mindfulness. |
0.960838 | My sister bought a home that had been flooded two years before she bought it. Since she bought the home as-is without a home inspection, she had no idea that the damage from the flood was never repaired. She began suffering from allergy symptoms and began to wonder if the guy she bought the house from had lied when he said everything was repaired after the flood. It wasn't until she brought in a flood repair contractor that she learned that there was a lot of work that was neglected after the flood. To find out what can be neglected without being noticed, visit through my blog.
Asbestos is a construction material that was used in the 80's and 90's, primarily because it is fire resistant. It was not until after it was used in the construction of many homes that the material started to become scrutinized because of the threat the material presented to people's health. It led to the material being banned in many countries, and should be removed from homes whenever possible to protect the health of those living in it.
A house fire changes your life in a moment, but if your property isn't destroyed, then you're in a position to use restorative techniques to save your assets. While there are professional fire restorers who can help restore some of your items, there are a few tips you can use to get started sooner. Smelly Clothing? Baking Soda Has Benefits If your clothing is smokey from the fire, the key to saving your garments is getting that smell to be eliminated. |
0.999533 | I need to calculate the different of total from numbers given and convert it into percentage. We can use Google Calculator to help us.
A total of 1700 and a given number of 1450, what is the percentage different between the total and the number given. |
0.999953 | I have always thought quite well of O'Neills. Their website offers a thousand welcomes, which is rather a lot, and they tend to offer a consistent drinking experience no matter which one you go to.
My dining experience was less pleasant however. We arrived at lunch time and the place felt dark and gloomy. The tables were sticky and did not look like they had been cleaned recently.
The food arrived in 22 minutes and I felt a little cheated by how thin my gammon was, while the sausage was cooked to what I would consider burned. We were also missing some chips from our order. I would have mentioned it if someone had come to ask us how our food was, but nobody did.
We could not agree on the rating for this one - Elina really enjoyed her food. |
0.999989 | There are four important techniques to keep in mind when using a zoom lens.
1. With a two touch lens focus carefully at the longest focal length before zooming back to the image size you want.
2. With a one touch lens zoom first and then focus in order to minimize focus shift.
3. As with almost any lens, close down two or three stops from the maximum opening, if possible, for the best optical performance.
4. Treat longer zooms like unifocal telephotos; use a tripod or, when hand-holding, use the fastest shutter speeds. |
0.999981 | im 19years old and am really worried about when i get better because i was watching a program which stated that people that suffered with depression were prone to it for the rest of their lives. is this true and if so is it worth me even making the effort to get better. i don't want to be sick the rest of my life but im trying so hard to get better and don't want to slip down that path again. i want to live my life not just exist for the many years that god has put me on this earth, which is all im doing right now. im just a shell of who i used to be. please help.
I'm just about to turn 40. Depression onset at puberty.
Yes, we're prone to it for the rest of our lives, but it doesn't mean that our lives will be filled with nothing but sadness and that it's not worth moving forward.
The transition from puberty into your early 20's is in itself rough and bumpy terrain. It will get easier. :) And now that I'm leaving me and my friends are leaving our 30's, it's getting better still (shocking, huh?).
What you might want to take from that program and studies is that, knowing that you are susceptible to depression, you want to make sure you concerted build a "coping toolbox" for the stresses of life. For instance, I've learned that I cannot let myself get too run down or tired, or I am vulnverable. So, I make decisions for how to live my daily life that ensure I don't burn the midnight oil too many nights in a row. I saw a therapist. I'm taking Effexor. I've started doing guided meditation. I've learned how to better speak up against trespasses against me, in a way that honors myself without having to get hysterical at the other person. I've figured out ways to be more true to who I am and what *I* want, instead of what I think I'm SUPPOSED to want, or what others expect. (And it's only NOW -- at nearly 40 -- that I'm really discovering who "me" is).
And my life has become gratifying and fulfilling. I wish that for you. And you can have it. Feel free to message me anytime (I have to run out now). I hope I didn't sound patronizing!
I won't speak to whether or not I will be depressed the rest of my life since it's not over yet but since being diagnosed (and I felt like this long before that) I have suffered fits of deep self loathing, and days, weeks, and sometimes months of happiness and contentment. It's a roller coaster for sure, and the only thing that keeps me going is the hope that I'll hit a hill tomorrow and feel good again, even if it's a brief one. I'll take what I can get, live my life one day at a time and always try to remember that as bad as it may seem, I make it seem ten times worse than it actually is by the attitude I take when I approach it.
I know how you feel. I feel it myself right now. I know that i will get better, I know that i will get happy again but you do wonder when you are here what the point is. Your not alone in wondering if its worth getting better and neither am i so it seems. Good luck hun i send you a hug.
there are some people who will have to take med`s the rest of thier lives like me.relapse`s are very common with depression,even though i have some side effect`s with my med`s,i think it`s a small price to pay,becuase i am doing much better.
Depression is a different experience for everybody - and fear of it is part of it!!
Some people have exruciating, debilitating depression virtually all the time, while others have one hard slam of it and never have it again.
But most are in-between somewhere, dealing with it in some form or another. There is no way to tell what yours is actually going to be like until you walk through your life and see.
But there are lots of things you can do, including joining a site like this one, to help ease the burden and make your experience less frightening, and less overwhelming.
Are there some things you have found so far that ease your depression symptoms when you feel depressed?? |
0.999765 | Call a specialist to talk about Maasai Mara now.
The most visited of Kenyaโs National Reserves, the Maasai Mara lies adjacent to Tanzaniaโs Serengeti National Park in the south west corner of Kenya. It covers over 1500 sq km and is 1500 to 2000 metres above sea level. It has a high rainfall due to the altitude and its proximity to Lake Victoria. The Mara River runs from north to south through the park. The landscape is mainly gently rolling grassland and is home to the highest concentration of wildlife of any Kenyan reserve.
In particular, the Mara is home to the spectacular annual migration of thousands of wildebeest, zebra and gazelle which arrive in the Maasai Mara, from the Serengeti in neighbouring Tanzania, in July and August and return south to the Serengeti around October when the grass is becoming sparse in the Maasai Mara.
It is also home to the long-running BBC TV series 'Big Cat Diary', although you should not necessarily expect to encounter the sort of scenes that you have seen on screen. |
0.913118 | What are the tax savings of a qualified retirement/cafeteria plan?
Implementation of a Qualified Plan and/or Section 125 Cafeteria Plan can result in significant tax savings and benefits to both the employer and employee. Use the following calculator to estimate the potential savings generated by implementing one or both of these plans.
Please email me special offers and promotions. Information collected is for internal purposes only and will never be sold to third parties.
This information may help you analyze your financial needs. It is based on information and assumptions provided by you regarding your goals, expectations and financial situation. This service shall not infer that the company or its affiliates and email service provider, DocuMatix, Inc, assumes any fiduciary duties. In addition, such service should not be relied upon as the only source of information. This information is supplied from sources we believe to be reliable but we cannot guarantee its accuracy. Hypothetical illustrations may provide historical or current performance information. Past performance does not guarantee nor indicate future results. Use of service is provided without warranty of any kind, either express, implied or statutory, including FITNESS FOR A PARTICULAR PURPOSE, MERCHANTABILITY, AND ACCURACY. Use of service is entirely at users own risk and user should seek professional financial and legal advice without reliance on service. Provider and email service provider shall not be liable for any lost profits, lost business, direct or indirect, punitive or consequential damages or damages of any kind arising out of service use. This agreement shall be governed and enforced by Utah law, with courts located in Salt Lake County, Utah the sole and exclusive venue. User agrees to indemnify and hold harmless company, email service provider, and affiliates from any and all liabilities and costs (including attorney fees) for any improper use or violation of these terms. |
0.919412 | Molecular clouds are nebulous patches of gas located primarily in the spiral arms of galaxies. Dense regions within these clouds collapse and form 'protostars.' Therefore, the birthplace of stars are molecular clouds where stars begin their lives as large and comparatively cool masses of gas. The contraction of this gas and the subsequent rise of temperature continues until the interior temperature of the star reaches a value of about 1,000,000ยฐC (about 1,800,000ยฐF).
At this point, a nuclear reaction takes place in which the nuclei of hydrogen atoms combine with heavy hydrogen deuterons (nuclei of so-called heavy hydrogen atoms) to form the nucleus of the inert gas helium. The latter reaction liberates large amounts of nuclear energy, and the further contraction of the star is halted. Once the star has started nuclear fusion, it becomes a 'main sequence' star.
Main sequence stars are stars, like our Sun, that burn hydrogen to helium in their cores. For a given chemical composition and stellar age, a star's luminosity (the total energy radiated by the star per unit time) depends only on its mass. Stars that are ten times more massive than the Sun are over a thousand times more luminous than the Sun. However, we should not be too embarrassed by the Sun's low luminosity: It is ten times brighter than a star half its mass. The more massive a main sequence star, the brighter and bluer it is.
For example, Sirius - the dog star, located to the lower left of the constellation Orion, is more massive than the Sun and is noticeably bluer. On the other hand, Alpha Centauri, our nearest neighbour, is less massive than the Sun and is thus redder and less luminous.
Since stars have a limited supply of hydrogen in their cores, they have a limited lifetime as main sequence stars. This lifetime is proportional to f M / L, where f is the fraction of the total mass of the star, M, available for nuclear fusion in the core and L is the average luminosity of the star during its main sequence lifetime. Because of the strong dependence of luminosity on mass, stellar lifetimes depend sensitively on mass. Thus, it is fortunate that our Sun is not more massive than it is, since high mass stars rapidly exhaust their core hydrogen supply.
Once a star exhausts its core hydrogen supply, the star becomes redder, larger, and more luminous: It becomes a red giant star. This relationship between mass and lifetime enables astronomers to put a lower limit on the age of the universe.
After a low mass star like the Sun exhausts the supply of hydrogen in its core, there is no longer any source of heat to support the core against gravity. The core of the star collapses under gravity's pull until it reaches a high enough density to start converting helium to carbon. Meanwhile, the star's outer envelope expands and the star evolves into a red giant. When the Sun becomes a red giant, its atmosphere will envelop the Earth and our planet will be consumed in a fiery death. The Sun will eventually evolve into a red supergiant as it exhausts the helium in its core. At this stage, it will have an outer envelope extending out towards Jupiter. During this brief phase of its existence, which last only a few tens of thousands of years, the Sun will lose mass in a powerful wind.
Eventually, the Sun will lose all of the mass in its envelope and leave behind a hot core of carbon embedded in a nebula of expelled gas. Radiation from this hot core will ionise the nebula, producing a striking 'planetary nebula', much like the nebulas seen around the remnants of other stars. The carbon core will eventually cool and become a white dwarf, the dense dim remnant of a once-bright star. The final fate of low-mass dwarfs is unknown, except that they cease to radiate appreciably. Most likely they become burned-out cinders, or black dwarfs.
Massive stars burn brighter and perish more dramatically than most. When a star ten times more massive than the Sun exhausts the helium in its core, the nuclear fusion cycle continues. The carbon core contracts further and reaches high enough temperature to burn carbon to oxygen, neon, silicon, sulphur and finally to iron.
Iron is the most stable form of nuclear matter, and there is no energy to be gained by converting it to any heavier element. Without any source of heat to balance the gravity, the iron core collapses until it reaches nuclear densities. This high-density core resists further collapse, causing the in-falling matter to 'bounce' off the core.
This sudden core bounce (which includes the release of energetic neutrinos from the core) produces a supernova explosion. For one brilliant month, a single star burns brighter than a whole galaxy of a billion stars. Supernova explosions inject carbon, oxygen, silicon and other heavy elements up to iron into interstellar space. They are also the site where most of the elements heavier than iron are produced.
Future generations of stars formed from this heavy element-enriched gas will therefore start life with a richer supply of heavier elements than the earlier generations of stars. Without supernovas, the fiery death of massive stars, there would be no carbon, oxygen or other elements that make life possible.
The fate of the hot neutron core depends upon the mass of the progenitor star. If the progenitor mass is around ten times the mass of the Sun, the neutron star core will cool to form a neutron star. Neutron stars are potentially detectable as 'pulsars', powerful beacons of radio emission. A limit exists for the size of neutron stars, however, beyond which such stars are gravitationally bound to keep contracting until they become a black hole, from which light radiation cannot escape.
If the progenitor mass is larger, then the resultant core is so heavy that not even nuclear forces can resist the pull of gravity and the core collapses to form a black hole. |
0.999961 | Give a gift with sentiment with a word that celebrates the beautiful things in life! This "JOY" 18K rose gold vermeil floating charm/pendant has a modern & sleek hidden hinge clasp that allows you to take it on and off any bangle or necklace. Attach and layer it onto your own jewelry or purchase a bangle or necklace to go with it. Charm pendant measures 16mm round & weighs 4 grams. |
0.998224 | Have you ever thought of flying a commercial airplane to distant locations? How about teaching others how to fly a plane? Both of these goals can be met by increasing the amount of flight time a person has by becoming a flight instructor.
A certification is needed to be able to teach other pilots how to fly. Some of the basic requirements are a valid medical certificate, ability to read and speak in English and pass the knowledge based and practical flight test. The requirements needed to become a flight instructor is a challenging route to a career, but also very rewarding.
The road to become a flight instructor starts with gaining a series of pilot certificates. In order to obtain the flight instructor certification, there will be others that need to be completed in sequence to get to that level. While there is not a formal degree requirement for any of the certifications, the appropriate courses will need to be completed.
The first certificate is that of a Private Pilot. A candidate must pass the FAA written and practical test. They must also be at least 17 years old, be able to communicate in English and hold a current third class medical certificate. Typical requirements for the flight school portion will be 40 hours of flight time with the time divided between solo and dual flights. Most programs can be finished in about 60 hours maximum.
A commercial pilot certificate is the next step to become a flight instructor. One condition for this certificate is that you must hold a Private Pilot Certificate, and attaining a passing score of the FAA knowledge and practical test pertaining to commercial flight is also required. The amount of flight time needed is about 190 to 250 hours of total pilot in command time, but the amount of time needed to go through the program, excluding flight time, is around 90 hours.
The final certification is the Certified Flight Instructor or CFI certificate. A candidate needs to have a Commercial Pilot Certificate prior to taking the exam, and you can expect to take a knowledge and practical test, pass the Fundamentals of Instructing. The type of certification you get will depend on the type of airplanes you expect to teach. A general CFI, CFI Instrument Rating Course and CFI Multi-Engine Course are all available. Most students can complete their training in as little as 20 hours.
A flight instructor is there to help other future pilot gain their "wings." Only certified flight instructors may teach other pilots how to fly. Some of the duties they have include conducting dual flight instruction, ground instruction and perform flight briefings for students. They are typically responsible for the maintenance of the aircraft to ensure a safe flight, and flight instructors need to be able to make corrections in a way that is constructive and safe while in the air. The specific duties may vary depending on what type of place they are teaching, but the main focus of the job is to ensure that everyone that learns to fly does it safely.
Some pilots may choose to become a flight instructor to gain more flight time to be able to move on to a career in flying commercially. Large airlines will usually require their pilots to have more flight time than just the minimum required for the credentials. Other instructors will continue to find a rewarding career in teaching. Exceptional instructors can gain the FAA gold seal, indicating their high standards for pilot education.
The average salary of a flight instructor will depend on location and how much you fly. Basically, the more you fly, the more money you can potentially make. Lots of instructors are on a commission system which pays for when they pick up another contract. You can expect to make anywhere from $20 to $50 an hour depending on your certifications and location. Some instructors can make upwards of $35,000 or more per year from just teaching. Some instructors may decide to pick up some charter flights for extra money and add to their yearly earnings. In this field, if there is someone willing to learn how to fly a plane, there is work to go around. Many flight instructors do not make as much as a commercial pilot would, but still enough to do something as enjoyable as flying every day. |
0.999997 | The present invention relates to a connector to be mounted on a device, particularly to a circuit board connector.
A conventional circuit board connector is known from Japanese Unexamined Patent Publication No. 2005-166492. This circuit board connector includes a housing which is fixed to one surface of a circuit board and into which a mating connector is fittable from front. Fixing brackets separate from the housing and made of a metal plate are mounted in this housing, and the circuit board connector is fixed to the circuit board by placing the circuit board connector on the circuit board and soldering the bottom ends of the fixing brackets to the circuit board.
The fixing brackets are inserted from above into mount grooves formed in the opposite side surfaces of the housing and mounted such that the plate surfaces thereof extend along the side surfaces of the housing. The width of upper end portions of the fixing brackets in forward and backward directions is set larger than the width of lower parts of the fixing brackets, and restricting surfaces that can come into contact with the bottom edges of parts (engaging portions) of the upper end portions of the fixing brackets bulging out forward and backward are formed in the mount grooves. By the contact of the engaging portions with the restricting surfaces, the fixing brackets are mounted in themount grooves with downward displacements thereof relative to the housing restricted.
The circuit board connector is used with the mating connector connected therewith. Thus, if a wiring harness drawn out from the mating connector is, for example, shaken upward and downward during the use of the circuit board connector, forces resulting from such upward and downward shaking movements are transmitted to the housing of the circuit board connector via the mating connector. In other words, a force (upward acting force) to separate the housing from the circuit board repeatedly acts on the housing. Accordingly, in order to improve the durability of the circuit board connector, it is essential to improve durability against the separating forces.
In the construction described above, if the separating force acts on the housing, the restricting surfaces of the housing and the engaging portions of the fixing brackets come into contact with each other, whereby large forces repeatedly act on the contact surfaces. Here, since the parts of the engaging portions in contact with the restricting surfaces are bottom edges of plate members, contact areas between the engaging portions and the restricting surfaces are not very large. Thus, large stresses are generated on the contact surfaces by the contact of the engaging portions and the restricting surfaces. Accordingly, in order to realize a circuit board connector capable of enduring the use under a severe environment such as vibration over a long time, it is necessary to prevent the engaging portions and restricting surfaces from being damaged or broken even if the separating forces repeatedly act on the housing.The present invention was developed in view of the above situation, and an object thereof is to provide a connector to be mounted to or on a device having an improved durability against forces acting on a housing to separate the housing from the device.
This object is solved according to the invention by the features of the independent claim. Preferred embodiments of the invention are subject of the dependent claims.
wherein the engaging portion is so bent or folded or shaped as to increase the area at least of the bottom end thereof in the thickness direction thereof.
The engaging portion is so bent or folded or shaped as to increase the area of the bottom end thereof in the thickness direction thereof. Since thecontact area of the engaging portion and the restricting surface is increased by this, a force acting on the contact surface is substantially distributed to become smaller. Accordingly, even if large separating forces repeatedly act on the housing, the damage and the like of the engaging portion and the restricting surface can be presented, with the result that durability against separating forces can be improved.
Here, if the area of the bottom end is increased in the direction of the plate surface of the engaging portion (direction along the side surface of the housing) by increasing the projecting distance of the engaging portion instead of bending the engaging portion, the side surface of the housing needs to be enlarged, i.e. the housing needs to be enlarged in forward and backward directions. However, according to the above construction, the area of the bottom end is increased in the thickness direction of the engaging portion by bending or folding the engaging portion, wherefore the housing needs not be enlarged in forward and backward directions. Accordingly, the contact area of the engaging portion and restricting surface can be increased and the durability of the circuit board connector can be improved without enlarging the housing.
According to a preferred embodiment of the invention, the at least one respective mount groove is formed in a side surface of the housing such that the plate surface thereof extends substantially along the side surface of the housing.
Preferably, at least one engaging portion formed on the fixing member and having a plate surface projecting along the side surface of the housing at least from one of the front and rear edges of the fixing member.Further preferably, at least one solder portion projecting in a direction at an angle different from 0ยฐ or 180ยฐ, preferably substantially normal to the side surface of the housing is provided at the bottom end of the fixing member.
Most preferably, the fixing member is fixed to the device preferably by soldering or welding the solder portion to the outer surface of the device.
According to a further preferred embodiment of the invention, the engaging portion is bent at a projecting end position thereof toward a projecting side of the fixing member, preferably of the solder portion, with at least one bent part thereof located more inward than the position of the projecting end of the fixing member, preferably of the solder portion.
Preferably, the engaging portion is folded back such that two parts substantially are in surface contact with each other.
Further preferably, the engaging portion is bent so as to be substantially L-, V or U-shaped.
Still further preferably, at least one part arranged deeper in the inserting direction as the restricting surface serve as at least one narrowing portion for narrowing the width of the respective mount grooves preferably in forward and backward directions.
Most preferably, when the fixing bracket is at least partly inserted into the mount grooves, one or more retaining portions of the fixing bracket gradually bite in the narrowing portions and the fixing bracket is held retained in the housing.
wherein the engaging portion is so bent as to increase the area of the bottom end thereof in the thickness direction thereof.
The engaging portion is so bent as to increase the area of the bottom end thereof in the thickness direction thereof. Since the contact area of the engaging portion and the restricting surface is increased by this, a force acting on the contact surface is distributed to become smaller. Accordingly, even if large separating forces repeatedly act on the housing, the damage and the like of the engaging portion and the restricting surface can be presented, with the result that durability against separating forces can be improved.
Here, if the area of the bottom end is increased in the direction of the plate surface of the engaging portion (direction along the side surface of the housing) by increasing the projecting distance of the engaging portion instead of bending the engaging portion, the side surface of the housing needs to beenlarged, i.e. the housing needs to be enlarged in forward and backward directions. However, according to the above construction, the area of the bottom end is increased in the thickness direction of the engaging portion by bending the engaging portion, wherefore the housing needs not be enlarged in forward and backward directions. Accordingly, the contact area of the engaging portion and restricting surface can be increased and the durability of the circuit board connector can be improved without enlarging the housing.
the engaging portion is bent at a projecting end position thereof toward a projecting side of the solder portion with a bent part thereof located more inward than the position of the projecting end of the solder portion.
Since the engaging portion is bent at the projecting end position thereof toward the projecting side of the solder portion and the bent part is located more inward than the projecting end position of the solder portion, the thickness (dimension in a direction normal to the side surface of the housing) of the entire fixing member can be suppressed to that of a fixing member in which an engaging portion is not bent. This can maximally suppress the lateral enlargement of the circuit board connector.
Most preferably, the engaging portion is folded back such that two parts adhere to each other.Since the engaging portion is folded back such that the two parts adhere to each other, the area of the restricting surface can be made smaller as compared to the case where there is a clearance between the two parts while ensuring the same contact area of the engaging portion and restricting surface. Therefore, the space efficiency of the housing is better.
These and other objects, features and advantages of the present invention will become more apparent upon reading of the following detailed description of preferred embodiments and accompanying drawings. It should be understood that even though embodiments are separately described, single features thereof may be combined to additional embodiments.
FIG. 7 is a partial enlarged plan view of a fixing bracket showing the shape of an engaging portion according to a third embodiment, andFIG. 8 is a partial enlarged plan view of a fixing bracket showing the shape of an engaging portion according to a fourth embodiment.
Hereinafter, a first preferred embodiment of the present invention is described with reference to FIGS. 1 to 5.
A circuit board connector 1 of this embodiment is fixed or fixable or mountable to the upper surface (front surface) of an electric or electronic device such as a circuit board K, and an unillustrated mating connector is at least partly fittable thereinto from front (right side in FIG. 1).
The circuit board connector 1 includes a housing 10 e.g. made of a synthetic resin (preferably a highly heat resistant synthetic resin) and preferably substantially having a laterally long block shape as a whole. A front part of the housing 10 serves as a receptacle 10A (preferably substantially in the form of a rectangular tube) into which the mating connector is at least partly fittable or insertable. When the mating connector is at least partly fitted or inserted into this receptacle 10A, the mating connector and the housing 10 are held properly connected by unillustrated locking means.
normal or down after extending backward from the housing 10 and the bottom end thereof serves as a connecting portion 11A to be connected (preferably soldered or welded or press-fitted) to a conductor path (not shown) on the upper surface of the device, preferably the circuit board K (see FIG. 3).
As shown in FIG. 1, one or more mount grooves 12 into which one or more fixing brackets 20 (corresponding to a preferred fixing bracket) to be described later are mountable are formed in the (preferably substantially opposite) lateral (left and/or right) surface(s) of the housing 10. The lateral (left and/or right) mount groove(s) 12 is/are formed by recessing the lateral (left and/or right) surface(s) of the housing 10 inward in areas from positions near the front end(s) to position(s) near the back end(s), and make openings preferably in both upper and lower surfaces of the housing 10. The fixing brackets 20 are at least partly insertable into the mount grooves 12 in an insertion direction ID, preferably substantially from above. It should be noted that the mount grooves 12 are described in detail after the shape of the fitting brackets 20 is described.
The fixing brackets 20 are for fixing the housing 10 onto the device such as the circuit board K, and preferably are formed by punching or cutting a metal plate material out into a specified (predetermined or predeterminable) shape and bending, folding and/or embossing the punched-out or cut-out material.
(in a direction at an angle different from 0ยฐ or 180ยฐ, preferably substantially normal to the side surface of the housing 10) from the lateral (bottom) end of the main body 12, and preferably the cross-sectional shape thereof in forward and backward directions FBD is substantially L-shaped or bent.
As shown in FIGS. 2 and 3, the main body 21 is in the form of a flat plate preferably having substantially the same width as the width of the back surface 12A of the mount groove 12 in forward and backward directions FBD and having a substantially rectangular shape slightly longer in forward and backward directions FBD. This main body 21 is to be closely mounted in the mount groove 12 such that almost no clearance is defined between the inner side surface thereof (surface at a side opposite to the side where the solder portion 22 projects) and the back surface 12A of the mount groove 12.
The fixing or solder portion 22 is so bent at the distal or bottom end position of the main body 21 as to extend in a direction at an angle different from 0ยฐ or 180ยฐ, preferably substantially normal to the plate surface of the main body 21. When the circuit board connector 1 is placed on the respective (upper) surface of the device particularly of the circuit board K, the plate surface (lower surface) of the solder portions 22 are substantially opposed to the respective (upper) surface of the device (circuit board K). By fixing the fixin portion, preferably by soldering the solder portions 22, the circuit board connector 1 is placed and fixed on the outer surface of the device (circuit board K). The solder portions 22 preferably have a substantially rectangular shape having a width necessary to solder and fix, and extend from the front ends to the rear ends of the bottom ends of the main bodies 21 (see FIG. 4).
As shown in FIG. 3, one or more (preferably a pair of front and/or rear) retaining portions 23 substantially projecting forward and backward are formed at one or more vertically intermediate positions (preferably at substantially vertically middle positions) of the front and/or rear edges of the main body 21. The retaining portion(s) 23 bite(s) in one or more narrowing portions 15 of the mount groove(s) 12 as the one or more fixing brackets 20 are mounted into the respective mount grooves 12, thereby retaining the fixing bracket(s) 20 in the mount groove(s) 12.
One or more (preferably a pair of front and/or rear) engaging portions 24 are provided at or near the upper end of the main body 21. The respective engaging portions 24 preferably have substantially rectangular shapes and substantially project forward and backward from the front and/or rear edges of the main body 21, and are bent or substantially folded back at their projecting end portions as shown in FIG. 4. Each engaging portion 24 is comprised of a part up to the projecting position (hereinafter, "projecting portion") and a part folded back or bent at or near the projecting end position (hereinafter, "folded portion 24B).
more preferably over more than about 90%, most preferably over more than about 95% of their respective surface. The leading ends of the folded portions 24B (ends at sides opposite to the bent sides) reach positions more inward than the front and rear edges of the main body 21. Thus, the engaging portions 24 preferably have a thickness that is about twice the thickness of the metal plate material over the substantially entire width in the projecting direction. Therefore, the engaging portions 24 are thickened outward (projecting sides of the solder portions 22) as compared to the other part of the main body 21.
The bottom ends of the engaging portions 24 serve as engaging surfaces 25 that can come substantially into contact with restricting surfaces 14 of the mount grooves 12 to be described. Each engaging surface 25 is a sum or a combination of the bottom end surface (hereinafter, "inner engaging surface 25A") of the projecting portion 24A and the bottom end surface (hereinafter, "outer engaging surface 25B") of the folded portion 24B. The engaging surfaces 25 preferably are surfaces substantially parallel to the outer surface of the device (circuit board K) with the housing 10 placed on the outer surface of the device (circuit board K). When viewed from below, the engaging surfaces 25 preferably are widened outward by as much as the outer engaging surfaces 25B as compared to the other parts of the main bodies 21.
The entire thickness (dimension normal to the side surfaces of the housing 10) of each fixing bracket 20 is a sum or a combination of the thickness of the main body 21 and a dimension of the fixing or solder portion 22 from the plate surface of the main body 21 to the projecting end position.
The mount grooves 12 are recessed parts with a depth substantially equal to the entire thickness of the fixing brackets 20. As shown in FIG. 1, the front and rear end surfaces of each groove 12 are formed with a pair of facing walls 13 projecting backward and forward from these front and rear end surfaces while facing the back surface 12A of each mount groove 12. These facing walls 13 preferably are arranged substantially along the front and rear end edges of each mount groove 12. Clearances substantially equal to or slightly larger than the thickness of the main body 21 of the fixing bracket 20 are defined between the back surface 12A of the mount groove 12 and the inner surface (surface facing the back surface 12A) of the facing walls 13.
At the front and rear ends of each mount groove 12, one or more insertion grooves 12B having the front and rear end surfaces as bottom surfaces, and the back surface 12A and facing walls 13 as side surfaces are formed. The insertion grooves 12B substantially vertically extend along the front and/or rear end edges of the mount groove 12, and the front and rear end edges of the main body 21 are at least partly inserted into the insertion grooves 12B, whereby the fixing brackets 20 are so held as not to come out sideways from the mount grooves 12.
As shown in FIGS. 2 and 3, the restricting surfaces 14 extending in a direction (intersecting with an inserting direction ID of the fixing brackets 20) at an angle different from 0ยฐ or 180ยฐ, preferably substantially normal to the bottom surfaces of the insertion grooves 12B formed at the front and/or rear sides are formed at positions of the bottom surfaces of the insertion grooves 12B near the upper ends.
The restricting surfaces 14 preferably are substantially parallel to the upper surface of the device (circuit board K) with the housing 10 placed on the upper surface of the device (circuit board K). As shown in FIG. 5, the restricting surfaces 14 are shaped to extend from parts formed in the insertion grooves 12B to the inner parts of the facing walls 13. Hereinafter, the parts formed in the insertion grooves 12B are referred to as inner restricting surfaces 14A, and parts formed on the facing walls 13 as outer restricting surfaces 14B. Thus, the inner surfaces of the facing walls 13 have upper parts thereof recessed more outward than the outer restricting surfaces 14B (as can be seen in particular in FIG. 5).
The width of the inner restricting surfaces 14A in inward and outward directions preferably is substantially equal to the width of the insertion grooves 12B, and the width of the outer restricting surfaces 14B in inward and outward directions preferably is substantially equal to the width of the inner restricting surfaces 14A. The width in inward and outward directions of each restricting surfaces 14 as a sum of the inner and outer restricting surfaces 14A, 14B preferably is slightly larger than twice the thickness of the fixing brackets 20. When the restricting surfaces 14 are viewed from above, the outer restricting surfaces 14B project more forward or backward than the inner restricting surfaces 14A. Since the outer restricting surfaces 14B are formed on upper end portions of the facing walls 13 (or on distal sides of the facing walls 13), the restricting surfaces 14 can laterally expand without laterally enlarging the housing 10.
When the fixing brackets 20 are at least partly inserted into the respective mount grooves 12, the engaging surfaces 25 of the engaging portions 24 come substantially into contact with the restricting surfaces 14 of the respective mount grooves 12 to position the fixing brackets 20 along the inserting direction ID (or substantially in vertical direction). More specifically, the inner engaging surfaces 25B of the engaging surfaces 25 come substantially into contact with the inner restricting surfaces 14A and the outer engaging surfaces 25B come substantially into contact with the outer restricting surface 14B. Since a dimension of the outer restricting surfaces 14B in forward and backward directions FBD is larger than that of the outer engaging surfaces 25B in forward and backward directions FBD as shown in FIG. 5, the entire outer engaging surfaces 25B come substantially into contact with the outer restricting surfaces 14B.
partly accommodated in the mount grooves 12 substantially without laterally projecting from the side surfaces of the housing 10.
Next, functions and effects of the first embodiment constructed as above are described.
First, the circuit board connector 1 is fixed to the mounting surface (upper surface) of the device (preferably the circuit board K). Cream solder preferably is applied to lands (not shown) on the mounting (upper) surface of the device (circuit board K) beforehand, and the housing 10 is placed on the device (circuit board K) with the connecting portions 11A of the terminals 11 and the fixing or solder portions 22 of the fixing brackets 20 substantially positioned on the corresponding lands. When the device (circuit board K) bearing the housing 10 is transported in a reflow furnace (not shown), the cream solder melts to adhere to the connecting portions 11A of the terminals 11 and the solder portions 22 of the fixing brackets 20. When the solder is solidified, the connecting portions 11A of the terminals 11 are electrically connected with the conductor paths of the device (circuit board K) and the solder portions 22 of the fixing brackets 20 are fixed to the device (circuit board K), whereby the circuit board connector 1 is fixed to the device (circuit board K).
circuit board connector 1 via the mating connector. Thus, upward (direction to separate the circuit board connector 1) forces may repeatedly act on the housing 10 as the wiring harness moves upward and downward.
Every time the upward force acts on the housing 10, the restricting surfaces 14 of the mount grooves 12 are pressed against the engaging surfaces 25 of the engaging portions 24. Here, according to the construction of this embodiment, since the engaging portions 24 are bent or substantially folded back, the contact areas of the restricting surfaces 14 and engaging surfaces 25 are increased by as much as the outer engaging surfaces 25B as compared to conventional engaging portions having no folded portions 24B. The contact areas preferably are substantially twice as much as in the case where there are no folded portions 24B. If the same forces act on the contact surfaces, a pressing force per unit area of the contact surface is reduced to about half. As a result, stresses generated on the contact surfaces become smaller. Therefore, even under a severe environment e.g. where the wiring harness vibrates very much, the damage or the like of the engaging portions 24 and the restricting surfaces 14 can be prevented, with the result that durability against the separating forces can be improved.
forward and backward directions FBD since the projecting distance of the engaging portions 24 are increased at both front and rear sides. This makes it necessary to expand the restricting surfaces 14 in forward and backward directions FBD by as much as the dimension of the folded portions 24B in forward and backward directions FBD, leading to the enlargement of the housing 10 in forward and backward directions FBD. However, since the engaging portions 24 are bent or substantially folded in this embodiment, the housing 10 needs not be enlarged in forward and backward directions FBD. In the case of strictly restricting a space to arrange the circuit board connector 1 for the high-density mounting of the device (circuit board K), the smaller width of the housing 10 in forward and backward directions FBD is particularly advantageous.
The folded portions 24B of the engaging portions 24 preferably are substantially folded back toward the side of the solder portions 22 and the thickness (dimension normal to the side surfaces of the housing 10) of the fixing brackets 20 preferably are the substantially same as in the case where there are no folded portions 24B. This can prevent the circuit board connector 1 from being laterally enlarged.
restricting surfaces 14B) of the restricting surfaces 14 can be so dimensioned as to be formed on the upper parts of the facing walls 13, with the result that the width of the housing 10 in lateral direction (or in a direction at an angle different from 0ยฐ or 180ยฐ, preferably substantially normal to the forward and backward directions FBD) is the substantially same as the conventional one (in which the areas of the engaging surfaces are not expanded). Therefore, in this embodiment, the durability of the circuit board connector 1 is improved while the size of the circuit board connector 1 is suppressed to that of the conventional circuit board connector.
As described above, according to the first embodiment, the engaging portions 24 are bent or substantially folded so that the areas of the engaging surfaces 25 increase in the thickness direction TD of the engaging portions 24. Since the contact areas of the engaging portions 24 and restricting surfaces 14 are increased by this, forces acting on the contact surfaces are substantially distributed to become smaller. Accordingly, even if large separating forces repeatedly act on the housing 10, the damage and the like of the engaging portions 24 and restricting surfaces 14 can be presented, with the result that durability against the separating forces can be improved. Further, according to this embodiment, an improvement in the durability of this circuit board connector 1 is realized without enlarging the housing 10.
thereof. Since contact areas of the engaging portions 24 and restricting surfaces 14 increase in this way, forces acting on the contact surfaces are distributed to become smaller. Accordingly, even if large separating forces repeatedly act on a housing 10, the damage and the like of the engaging portions 24 and restricting surfaces 14 can be presented, with the result that durability against the separating forces can be improved. Further, according to the present invention, an improvement in the durability of this circuit board connector 1 is realized without enlarging the housing 10. Next, a second preferred embodiment of the present invention is described with reference to FIG. 6.
This embodiment differs from the first embodiment in the shape of each engaging portion 30 in which a projecting portion 30A and a folded portion 30B do not adhere to or contact each other. This engaging portion 30 is substantially L-shaped by the projecting portion 30A and the folded portion 30B. The folded portion 306 projects up to a position more inward than the position of a projecting end 31A of a solder portion 31, and the entire thickness of a fixing bracket 32 is suppressed to that of a fixing bracket in which an engaging portion is not bent. Next, a third preferred embodiment of the present invention is described with reference to FIG. 7.
do not adhere to or contact each other. This engaging portion 40 is substantially U-shaped or bent by the projecting portion 40A and the folded portion 40B. The folded portion 40B projects up to a position more inward than the position of a projecting end 41A of a solder portion 41, and the entire thickness of a fixing bracket 42 is suppressed to that of a fixing bracket in which an engaging portion is not bent.
Next, a fourth preferred embodiment of the present invention is described with reference to FIG. 8.
This embodiment differs from the first embodiment in the shape of each engaging portion 50 in which a projecting portion 50A and a folded portion 50B do not adhere to or contact each other. This engaging portion 50 is substantially V-shaped by the projecting portion 50A and the folded portion 50B. The folded portion 506 projects up to a position more inward than the position of a projecting end 51A of a solder portion 51, and the entire thickness of a fixing bracket 52 is suppressed to that of a fixing bracket in which an engaging portion is not bent.
The present invention is not limited to the above described and illustrated embodiments. For example, the following embodiments are also embraced by the technical scope of the present invention as defined by the claims.
and the engaging portions may be provided at only one of the front and rear sides.
the thickness of the entire fixing brackets.
wherein the engaging portion (24; 30; 40; 50) is so bent or folded as to increase the area at least of the bottom end (25) thereof in the thickness direction (TD) thereof.
surface (12A) of the housing (10).
surface (12A) of the housing (10) at least from one of the front and rear edges of the fixing member (20; 32; 42; 52).
welding the solder portion (22) to the outer surface of the device (K).
fixing member (20; 32; 42; 52), preferably of the solder portion (22).
substantially are in surface contact with each other.
restricting surface (14) serve as at least one narrowing portion (15) for narrowing the width of the respective mount grooves (12) preferably in forward and backward directions (FBD).
10. A circuit connector (1) according to claim 9, wherein when the fixing bracket (20) is at least partly inserted into the mount grooves (12), one or more retaining portions (23) of the fixing bracket (20) gradually bite in the narrowing portions (15) and the fixing bracket (20) is held retained in the housing (10).
1-14, NISHISUEHIRO-CHO, YOKKAICHI-CITY, MIE 510-8503, JAPAN.
1 HIROSHI NAKANO C/O SUMITOMO WIRING SYSTEMS,LTD 1-14, NISHISUEHIRO-CHO, YOKKAICHI-CITY, MIE 510-8503, JAPAN. |
0.999997 | You want to reinstall your Sonos speaker. That is why you reset the speaker to factory settings. This clears all settings of the speaker, so you can reset it again. In this article I explain step by step how to reset a Sonos Play: 1, Play: 3, Play: 5, Sub, Playbar or Playbase.
Play: One: the pause button on the top of the speaker.
Play: 1: the pause button on the top of the speaker.
Play: 3: the pause button on the top of the speaker.
Play: 5 (gen 1): the pause button on the top of the speaker.
Play: 5 (gen 2): the Join button on the back of the speaker.
Sub: the Join button on the right side of the speaker.
Playbar: the pause button on the right side of the soundbar.
Playbase: the Join button on the left side of the speaker.
Beam: the join button on the back of the speaker.
Unplug your speaker from the socket. Wait 10 seconds before continuing.
Hold down the pause or Join button while plugging the speaker back into the socket. Continue holding down the button. After 10 seconds, the LED will start to flash white. After about 30 seconds, the LED starts to flash orange. Now let go of the button.
Within 30 seconds, the LED will flash green. Wait for that before continuing.
The speaker is has been restored to factory settings. Set up your speaker again to use it. Read how by clicking on the button below.
How do I add a streaming service to my Sonos? |
0.999974 | You can import Python modules and access Python builtin types and functions via the Python global variable.
// Use builtin types and functions.
print(Python.type(list) == Python.list) // Prints true. |
0.998791 | Recently the media has been saturated with overly-hyped reports that NASA's Alpha Magnetic Spectrometer (AMS) may have detected dark matter. These claims may have some justification if the word "may" is shouted, but they rest on a number of really major assumptions and guesses, some of which are on weak and shifting soil. So just what was seen in the experiment, and what are the possible explanations?
antimatter was first predicted by Paul Dirac in 1931, followed quickly by Carl Anderson's discovery in 1932 of the antielectron, or positron, in cosmic rays.
How is antimatter detected? Normally, this is done by looking for gamma rays produced when antimatter is annihilated on contact with normal matter, or by measuring its properties as it moves through matter.
For example, in a cloud chamber or a bubble chamber, a particle moving through the detector leaves a track of its motion by ionizing the matter in the chamber. If you apply an electric or a magnetic field properly, an electron moving to the right will curve up, while a positron moving to the right will curve down. The difference reflects their opposite charges. More sophisticated detectors can measure the mass, charge, energy, and direction of a particle or an antiparticle.
Both matter and antimatter were created during the early moments of the Big Bang, but it's believed that the antimatter currently in the Universe is not left over from this event. This is because matter and antimatter appear to have mutually annihilated in the high-density environment about a minute after the Big Bang, leaving one part of normal matter from a billion parts of the original matter-antimatter mix.
No one currently knows why the early Universe showed a preference for matter at the cost of antimatter (this is one of the hints mentioned earlier), but here we are.
These days, antimatter is created everywhere in the Universe that is sufficiently hot or where high-energy particle collisions take place. Supernovae, pulsars, neutron stars, black hole accretion discs, and quasars โ even planetary thunderstorms are known to be sources of antimatter.
The main source of cosmic positrons is the interaction of high energy cosmic rays colliding with interstellar gas and dust. These are called secondary positrons, because they are generated as a product of the primary cosmic ray collisions. Those we see are typically produced within a few thousand light years of our Solar System, as positrons from more distant sources lose energy and eventually are trapped before they can reach Earth.
This source of electron-positron pairs peters out for positrons with energy over a few GeV. The balance works out so the the ratio known as the positron fraction (the number of positrons detected divided by the total number of electrons and positrons detected at that same energy) decreases steadily for positron energy more than about one GeV.
Experimental studies of the positron fraction in either the upper atmosphere or in space have been carried out since the 1960s. These have suggested that the decrease of the positron fraction with increasing energy slows beginning at a few GeV, and then the positron fraction roughly doubles as the energy approaches 100 GeV. At this point the positron fraction is over ten percent, which is quite a lot of antimatter, suggesting that another source of high energy positrons must be active in our galactic neighborhood.
The Alpha Magnetic Spectrometer (AMS) got its original impetus from American politics. In 1993, the U.S. Congress cancelled construction of the Superconducting Supercollider (SSC), which was to have a design energy of 20 TeV (producing 40 TeV proton-proton collisions). This cancellation left a very large tunnel in Texas (now being used to house a data center), and dramatically reduced the opportunities for discovering new particles and new physics until the 2010 advent of the substantially less powerful LHC.
Partially in response to the SSC cancellation, Nobel Laureate Prof. Samuel Ting of the MIT Department of Physics proposed in 1995 that NASA construct and launch the space based Alpha Magnetic Spectrometer. The AMS is in essence a very capable particle detector whose purpose is to investigate extreme matter in the universe by carefully measuring the properties of very high energy cosmic rays. To do so, it is designed to discriminate particles from electrons to nuclei at energies up to 2,000 GeV.
In the end, NASA agreed to give the AMS space on the ISS and to transport it via the Space Shuttle, but Prof. Ting had to construct it under the auspices of the US Department of Energy. He funded this effort by convincing the DOE to take on the project, which also attracted a good deal of support from other countries. A simple version of the detector was sent to orbit for a few days on the Space Shuttle in 1998, and the full AMS was launched and installed on the ISS in May of 2011.
As an aside, in a pattern not unusual for space projects, the initial AMS estimated cost of US$33 million with a launch date in 2003 ballooned to an instrument cost estimated at US$1.5 billion and a launch in 2011 that required the US Congress to approve an additional flight at the end of the Space Shuttle program. It appears that even minds capable of elucidating the fundamental nature of the universe cannot accurately predict program costs.
The AMS has recorded a total of 25 billion cosmic ray interactions in the past 18 months, of which nearly seven million involved electrons and positrons having energies between 0.5 and 350 GeV. Analysis indicates that the positrons appear to arrive equally from all directions. Despite the large number of measurements, at energies larger than 250 GeV there are not yet sufficient particles detected on which to produce trustworthy data.
In essence, although the new data is more precise, at this point the impact is mainly limited to confirming the increase in positron fraction seen in previous studies. The one hint of new behavior is that the increase in positron fraction may be slowing as energies over 200 GeV are examined.
There are numerous possible explanations for the large number of positrons at high energies, but they narrow to three main classes. The first is that they are due to local astrophysical sources, such as pulsars in our general neighborhood.
There are fairly realistic sounding mechanisms by which pulsars could generate high energy electrons and positrons, and such particles could be smeared out by the influence of interstellar electric and magnetic fields to appear to come from all directions equally. However, it seems a rather large coincidence that the locations of the pulsars and the configuration of interstellar electromagnetic fields combine to make it appear that the high energy positrons come from all directions. Such sources of high energy positrons are taken seriously, but many astronomers remain skeptical.
The second explanation is that they are due to dark matter annihilations and/or decays. The third is that they are generated by something else, from a normal astrophysical source that just hasn't yet been considered to something entirely new and unexpected. Of these three, the most compelling is arguably the second, so let's take a look at how realistic it is.
Our latest cosmological models indicate that a full 27 percent of the mass-energy of the Universe is in the form of cold dark matter. Dark matter is thought to be composed of particles that have considerable mass, but only interact with "normal matter" through gravitation, and perhaps the weak nuclear force. As a result, while these particles contribute to the mass and pressure of the Universe, we can't directly see them.
So what might dark matter actually consist of? That such dark matter particles could exist isn't a big stretch. The extraordinarily elusive neutrinos would qualify as dark matter, as they only have weak and gravitational interactions with the rest of the Universe, but they don't have enough mass.
The current hot idea is that dark matter consists (at least in part) of hypothetical particles called WIMPS (Weakly Interacting Massive ParticleS), and that mutual annihilation of WIMPS is the source of the high energy positrons.
However, the Standard Model of Particle Physics, which rather nicely explains every known particle, contains no possible WIMP candidates. If the positron excess is due to WIMP annihilation, then new physics is required at a fundamental level.
The reason this explanation is dicey, but very attractive at the same time, is that it depends rather strongly on at least two paradigm-altering assumptions โ supersymmetry and the existence of Majorana fermions.
Supersymmetry, in which a new symmetry is postulated between fermions and bosons, so that if you turn all fermions into bosons (and vice versa), the physics of the system doesn't change. However, this doesn't hold with current observations of the Universe, so theorists further postulate that the symmetry is broken, meaning that it is only exact at very large energies.
Supersymmetry produces new aspects of particle physics that are so alluring that it is sometimes taken for granted, even though there is as yet no experimental data suggesting that supersymmetry actually holds in the universe. However, supersymmetric versions of the Standard Model do contain excellent candidates for dark matter WIMP particles.
The lead candidate for a supersymmetric WIMP is a neutralino, which is not only undiscovered, but is predicted to be a Majorana fermion, a particle which is its own antiparticle. Although collective excitations in superconductors that behave as Majorana particles have been seen, there is no evidence as yet for fundamental Majorana particles.
If supersymmetry is how the Universe works, and neutralinos indeed have the predicted properties, then although an individual neutralino may be stable, a pair can mutually annihilate when they interact. Such interactions would be rare, owing to the large distances between neutralinos and their very small interaction cross-sections. However, if neutralino masses are, as suspected, in the general range of one TeV, there is plenty of energy in an annihilation to make gamma rays and normal matter particle-antiparticle pairs.
It has also been suggested that the dark matter side of the Universe may be as complex and diverse as is the part to which we are accustomed. If true, this would open the possibility of dark matter annihilations, reactions, and decays which might still produce electrons and positrons without requiring any Majorana particles.
Can AMS data really add up to dark matter?
According to the initial CERN report, the results of the AMS data and analysis, "are consistent with the positrons originating from the annihilation of dark matter particles in space, but not yet sufficiently conclusive to rule out other explanations." However, early media coverage was strongly oriented toward explaining the observed positron excess as associated with dark matter annihilation, and appeared dismissive of other explanations.
Following a discussion of dark matter annihilation as the source of the positron excess, the report also states that their model fits the data "surprisingly well" โ without mentioning that the model is not connected with dark matter in any sense. As a result, the subsequent media reports often read as if dark matter had indeed been discovered, and all that remained was to dot the i's and cross the t's. The result was to spread an incorrect impression of the science involved far and wide.
So, what factors argue against the dark matter hypothesis? Probably the clearest signature (although not proof) that the positron excess is the result of dark matter annihilations would be if the positron excess declines abruptly above a given energy. This would suggest that the source of the positrons has a maximum energy, likely associated with the mass of the dark energy particles. If such a maximum energy is seen at a realistic WIMP mass, that will be evidence for, but not proof of, dark matter annihilation. In the present absence of this signature, there is very little in the data pointing toward the dark matter explanation.
Another difficulty is that, all things being equal, one would expect nearly as many proton-antiproton pairs to be generated in WIMP annihilation as electron-positron pairs, as there is plenty of energy to go around. In fact, though, the AMS data shows that essentially no antiprotons are detected in the energy range where the positron excess is observed. This anomaly would likely require yet another bit of postulated new physics to explain. One hates to add unrelated new physics to fix an explanation already based on new physics.
A final point is that most dark matter appears to be located in the galactic halos, or in filaments connecting galaxies and galactic clusters, rather than amongst the stars in the spiral arms. If the dark matter annihilation mechanism for the positron excess is correct, then there are also a large density of extremely high energy electrons and positrons in intergalactic space. As a result, the extragalactic gamma ray spectrum would show the effects of scattering from these energetic charged particles. Specifically, the average gamma ray energy would be increased in a specific manner by the inverse Compton effect. Such an effect is not observed, which strongly constrains the electron-positron density, and along with it the density of dark matter, in the galactic halo.
It would seem to require a perfect storm of just the right new physics, plus some complex explaining away of known physics, for the dark matter annihilation hypothesis for the positron excess to be true. Stranger things have happened in scientific history, of course. The proof of the pudding, however, comes when such ideas are tested in many more-or-less unrelated ways โ the final result is usually a simple, nearly inevitable explanation. The current and future AMS data alone cannot bring astrophysics to that level concerning the source of excess high-energy cosmic positrons and, given the difficulties inherent in other experimental directions, the issue of dark matter is not likely to be resolved soon.
Prof. Jonathan Feng of UC Irvine sums the situation up nicely: "If anything mentioned here is correct, life will be very interesting in the coming years!" |
0.966608 | As an investor, it's fascinating to see similar business models emerge simultaneously in different markets. Observing the parallel environments is intellectually satisfying and there is much that can be learned. One category in particular where this has played out is food delivery, both in Europe and the US.
The first era of online food ordering was really marketplace aggregators. These two-sided marketplaces acted as middlemen between restaurants and consumers and took a fee per transaction. Seamless was one of the first to pop up in the US, founded back in 1999, and GrubHub soon followed in 2004. Meanwhile, in Europe, Just-Eat found its legs in 2001 and Hungryhouse soon followed in 2003. Over the years, a wide variety of food ordering aggregators popped up in various locales, but the key focus of this post is GrubHub vs Just-Eat.
Despite operating on two entirely different continents without competing with each other at all, the businesses are strikingly similar. Both companies' market values were close to $3B, valuation multiples were almost identical, as were scale, margins and growth. However, the two companies diverged shortly after IPO. As you can see in the stock chart below, GrubHub's shares tanked while Just-Eat's swelled.
Today, GrubHub has a market cap of just $1.8B and trades at just 3.4x 2016 revenue. Just-Eat on the other hand commands almost double the market cap ($3.5B) even after a recent pullback, and trades at 7x 2016 revenue. How did these two identical businesses diverge so much? The answer lay in market dynamics.
The US and UK food delivery markets are both massive, multi-hundred billion dollar categories. The US is significantly bigger, but the UK takeaway market has higher online penetration than the US (30-35% penetration in UK vs 10% in US). In the UK, Just-Eat was able to dominate the market by capturing London and the surrounding areas and essentially forming a monopoly. Today, Just-Eat has 85-90% market share in the UK and #1 or #2 positions in a dozen other markets. The majority of Just-Eat's revenue is still UK-based, and few competitors have been able to threaten their position.
In the US, the industry played out very differently. The US market is even more massive than the UK, and since online penetration is relatively low, many food startups saw the growth opportunity to move food ordering online and leveraged a healthy VC funding environment to do so. Aggregators with models similar to GrubHub started popping up, but perhaps even more importantly, on-demand delivery companies joined the fray. Combined with the relatively low customer acquisition costs in the US, many small startups were able to quickly gain traction in different segments of the market. GrubHub (including Seamless) was certainly a major force in top US cities (which tend to look more like the UK in terms of penetration), but there was plenty of opportunity in the rest of the country. Companies such as Postmates, Caviar, DoorDash, UberEats and Amazon all started putting their own spin on local food delivery.
As a result, GrubHub saw a significant decline in market value due to negative outlook on Wall Street and earnings revisions. This was largely driven by the new competition and the subsequent alteration of Grub's business model (now essentially forced to offer delivery service in certain markets). Just-Eat has seen a little bit of pressure from logistics competition as well, namely Deliveroo, but the UK is still far less noisy than the US and the downward pressure on Just-Eat has been limited.
The food aggregator case study is just one good example of parallel market dynamics. There are of course many others. Sticking to food, another terrific case study would be the meal kit space. We tend to think that the US is where most great tech startup ideas form, but the meal kit space is a great counter-example. Pioneered by a Swedish company called Linas Matkasse about a decade ago, the meal kit model was then cloned by Blue Apron, HelloFresh and a variety of other startups and subsequently brought to other markets. I'm curious to see how the meal kit space evolves in the US versus Europe. |
0.999925 | For other uses, see The Big Bounce (disambiguation).
TheUniverse is all of space and time and their contents, including planets, stars, galaxies, and all other forms of matter and energy. While the spatial size of the entire Universe is unknown, it is possible to measure the size of the observable universe: it is currently estimated to be 93 billion light years in diameter. In various multiverse hypotheses, auniverse is one of many causally disconnected constituent parts of a larger multiverse, which itself comprises all of space and time and its contents.
A cyclic model is any of several cosmological models in which the universe follows infinite, or indefinite, self-sustaining cycles. For example, the oscillating universe theory briefly considered by Albert Einstein in 1930 theorized a universe following an eternal series of oscillations, each beginning with a big bang and ending with a big crunch; in the interim, the universe would expand for a period of time before the gravitational attraction of matter causes it to collapse back in and undergo a bounce.
The concept of the Big Bounce envisions the Big Bang as the beginning of a period of expansion that followed a period of contraction. In this view, one could talk of a Big Crunch followed by a Big Bang, or more simply, a Big Bounce. This suggests that we could be living at any point in an infinite sequence of universes, or conversely the current universe could be the very first iteration. However, if the condition of the interval phase "between bounces", considered the 'hypothesis of the primeval atom', is taken into full contingency such enumeration may be meaningless because that condition could represent a singularity in time at each instance, if such perpetual return was absolute and undifferentiated.
A gravitational singularity, spacetime singularity or simply singularity is a location in spacetime where the gravitational field of a celestial body becomes infinite in a way that does not depend on the coordinate system. The quantities used to measure gravitational field strength are the scalar invariant curvatures of spacetime, which includes a measure of the density of matter. Since such quantities become infinite within the singularity, the laws of normal spacetime cannot exist.
The main idea behind the quantum theory of a Big Bounce is that, as density approaches infinity, the behavior of the quantum foam changes. All the so-called fundamental physical constants, including the speed of light in a vacuum, need not remain constant during a Big Crunch, especially in the time interval smaller than that in which measurement may never be possible (one unit of Planck time, roughly 10โ43 seconds) spanning or bracketing the point of inflection.
Quantum foam or spacetime foam is the fluctuation of spacetime on very small scales due to quantum mechanics. The idea was devised by John Wheeler in 1955.
In quantum mechanics, the Planck time is the unit of time in the system of natural units known as Planck units. A Planck time unit is the time required for light to travel a distance of 1 Planck length in a vacuum, which is a time interval of approximately 5.39 ร 10 โ44 s. The unit is named after Max Planck, who was the first to propose it.
If the fundamental physical constants were determined in a quantum-mechanical manner during the Big Crunch, then their apparently inexplicable values in this universe would not be so surprising, it being understood here that a universe is that which exists between a Big Bang and its Big Crunch.
The Big Bounce Models, however do not explain much about that how the currently expanding universe will manage to contract. This constant and steady expansion is explained by NASA through the expansion of the universe.
Willem de Sitter was a Dutch mathematician, physicist, and astronomer.
Carl Friedrich Freiherr von Weizsรคcker was a German physicist and philosopher. He was the longest-living member of the team which performed nuclear research in Germany during the Second World War, under Werner Heisenberg's leadership. There is ongoing debate as to whether or not he and the other members of the team actively and willingly pursued the development of a nuclear bomb for Germany during this time.
By the early 1980s, the advancing precision and scope of observational cosmology had revealed that the large-scale structure of the universe is flat, homogenous and isotropic, a finding later accepted as the Cosmological Principle to apply at scales beyond roughly 300 million light-years. It was recognized that it was necessary to find an explanation for how distant regions of the universe could have essentially identical properties without ever having been in light-like communication. A solution was proposed to be a period of exponential expansion of space in the early universe, as a basis for what became known as Inflation theory. Following the brief inflationary period, the universe continues to expand, but at a less rapid rate.
One of the main problems with the Big Bang theory is that at the moment of the Big Bang, there is a singularity of zero volume and infinite energy. This is normally interpreted as the end of the physics as we know it; in this case, of the theory of general relativity. This is why one expects quantum effects to become important and avoid the singularity.
However, research in loop quantum cosmology purported to show that a previously existing universe collapsed, not to the point of singularity, but to a point before that where the quantum effects of gravity become so strongly repulsive that the universe rebounds back out, forming a new branch. Throughout this collapse and bounce, the evolution is unitary.
Bojowald also claims that some properties of the universe that collapsed to form ours can also be determined. Some properties of the prior universe are not determinable however due to some kind of uncertainty principle.
In 2011, Nikodem Popลawski showed that a nonsingular Big Bounce appears naturally in the Einstein-Cartan-Sciama-Kibble theory of gravity. This theory extends general relativity by removing a constraint of the symmetry of the affine connection and regarding its antisymmetric part, the torsion tensor, as a dynamical variable. The minimal coupling between torsion and Dirac spinors generates a spin-spin interaction which is significant in fermionic matter at extremely high densities. Such an interaction averts the unphysical Big Bang singularity, replacing it with a cusp-like bounce at a finite minimum scale factor, before which the universe was contracting. This scenario also explains why the present Universe at largest scales appears spatially flat, homogeneous and isotropic, providing a physical alternative to cosmic inflation.
In 2012, a new theory of nonsingular big bounce was successfully constructed within the frame of standard Einstein gravity. This theory combines the benefits of matter bounce and Ekpyrotic cosmology. Particularly, the famous BKL instability, that the homogeneous and isotropic background cosmological solution is unstable to the growth of anisotropic stress, is resolved in this theory. Moreover, curvature perturbations seeded in matter contraction are able to form a nearly scale-invariant primordial power spectrum and thus provides a consistent mechanism to explain the cosmic microwave background (CMB) observations.
The ekpyrotic universe is a cosmological model of the early universe that explains the origin of the large-scale structure of the cosmos. The model has also been incorporated in the cyclic universe theory, which proposes a complete cosmological history, both the past and future.
In theoretical physics, the EinsteinโCartan theory, also known as the EinsteinโCartanโSciamaโKibble theory, is a classical theory of gravitation similar to general relativity. The theory was first proposed by รlie Cartan in 1922 and expounded in the following few years.
Quantum cosmology is the attempt in theoretical physics to develop a quantum theory of the Universe. This approach attempts to answer open questions of classical physical cosmology, particularly those related to the first phases of the universe.
Paul Joseph Steinhardt is an American theoretical physicist and cosmologist who is currently the Albert Einstein Professor in Science at Princeton University.
The Weyl curvature hypothesis, which arises in the application of Albert Einstein's general theory of relativity to physical cosmology, was introduced by the British mathematician and theoretical physicist Sir Roger Penrose in an article in 1979 in an attempt to provide explanations for two of the most fundamental issues in physics. On the one hand one would like to account for a universe which on its largest observational scales appears remarkably spatially homogeneous and isotropic in its physical properties, on the other hand there is the deep question on the origin of the second law of thermodynamics.
Eternal inflation is a hypothetical inflationary universe model, which is itself an outgrowth or extension of the Big Bang theory.
Loop quantum cosmology (LQC) is a finite, symmetry-reduced model of loop quantum gravity (LQG) that predicts a "quantum bridge" between contracting and expanding cosmological branches.
Nikodem Janusz Popลawski is a Polish theoretical physicist, most widely noted for the hypothesis that every black hole could be a doorway to another universe and that the universe was formed within a black hole which itself exists in a larger universe. This hypothesis was listed by National Geographic and Science magazines among their top ten discoveries of 2010. Popลawski appeared in a bonus episode of the TV show Through the Wormhole titled "Are There Parallel Universes?" and an episode of the Discovery Channel show Curiosity titled "Parallel Universes โ Are They Real?", which were hosted by Morgan Freeman and aired in 2011. He was named by Forbes magazine in 2015 as one of five scientists in the world most likely to become the next Albert Einstein.
The EinsteinโMaxwellโDirac equations (EMD) are a classical field theory defined in the setting of general relativity. They are interesting both as a classical PDE system in mathematical relativity, and as a starting point for some work in quantum field theory.
1 2 Brandenberger, Robert; Peter, Patrick (2017). "Bouncing Cosmologies: Progress and Problems". Foundations of Physics. 47 (6): 797โ850. arXiv: 1603.05834 . Bibcode:2017FoPh...47..797B. doi:10.1007/s10701-016-0057-0. ISSN 0015-9018.
โ Kragh, Helge (1996). Cosmology. Princeton, NJ, USA: Princeton University Press. ISBN 978-0-691-00546-1.
โ McKee, Maggie (25 September 2014). "Ingenious: Paul J. Steinhardt โ The Princeton physicist on what's wrong with inflation theory and his view of the Big Bang". Nautilus (017). NautilusThink Inc. Retrieved 31 March 2017.
โ Steinhardt, Paul J.; Turok, Neil (2005). "The cyclic model simplified". New Astronomy Reviews. 49 (2โ6): 43โ57. arXiv: astro-ph/0404480 . Bibcode:2005NewAR..49...43S. doi:10.1016/j.newar.2005.01.003. ISSN 1387-6473.
โ Lehners, Jean-Luc; Steinhardt, Paul J. (2013). "Planck 2013 results support the cyclic universe". Physical Review D. 87 (12): 123533. arXiv: 1304.3122 . Bibcode:2013PhRvD..87l3533L. doi:10.1103/PhysRevD.87.123533. ISSN 1550-7998.
โ Overduin, James; Hans-Joachim Blome; Josef Hoell (June 2007). "Wolfgang Priester: from the big bounce to the ฮ-dominated universe". Naturwissenschaften. 94 (6): 417โ429. arXiv: astro-ph/0608644 . Bibcode:2007NW.....94..417O. doi:10.1007/s00114-006-0187-x. PMID 17146687.
โ Bojowald, Martin (2007). "What happened before the Big Bang?". Nature Physics. 3 (8): 523โ525. Bibcode:2007NatPh...3..523B. doi:10.1038/nphys654.
โ Ashtekar, Abhay; Corichi, Alejandro; Singh, Parampreet (2008). "Robustness of key features of loop quantum cosmology". Physical Review D. 77 (2): 024046. arXiv: 0710.3565 . Bibcode:2008PhRvD..77b4046A. doi:10.1103/PhysRevD.77.024046.
โ David Adam (14 August 2003). "The Strange story of Peter Lynds". The Guardian .
โ "Penn State Researchers Look Beyond The Birth Of The Universe". Science Daily . May 17, 2006. Referring to Ashtekar, Abhay; Pawlowski, Tomasz; Singh, Parmpreet (2006). "Quantum Nature of the Big Bang". Physical Review Letters . 96 (14): 141301. arXiv: gr-qc/0602086 . Bibcode:2006PhRvL..96n1301A. doi:10.1103/PhysRevLett.96.141301. PMID 16712061.
โ Poplawski, N. J. (2012). "Nonsingular, big-bounce cosmology from spinor-torsion coupling". Physical Review D . 85 (10): 107502. arXiv: 1111.4595 . Bibcode:2012PhRvD..85j7502P. doi:10.1103/PhysRevD.85.107502.
โ Cai, Yi-Fu; Damien Easson; Robert Brandenberger (2012). "Towards a Nonsingular Bouncing Cosmology". Journal of Cosmology and Astroparticle Physics . 08 (8): 020. arXiv: 1206.2382 . Bibcode:2012JCAP...08..020C. doi:10.1088/1475-7516/2012/08/020.
โ Landau, Elizabeth; Baรฑados, Eduardo (6 December 2017). "Found: Most Distant Black Hole". NASA . Retrieved 6 December 2017. "This black hole grew far larger than we expected in only 690 million years after the Big Bang, which challenges our theories about how black holes form," said study co-author Daniel Stern of NASA's Jet Propulsion Laboratory in Pasadena, California.
โ Jamie Seidel (7 December 2017). "Black hole at the dawn of time challenges our understanding of how the universe was formed". News Corp Australia. Retrieved 9 December 2017. It had reached its size just 690 million years after the point beyond which there is nothing. The most dominant scientific theory of recent years describes that point as the Big Bang โ a spontaneous eruption of reality as we know it out of a quantum singularity. But another idea has recently been gaining weight: that the universe goes through periodic expansions and contractions โ resulting in a โBig Bounceโ. And the existence of early black holes has been predicted to be a key telltale as to whether or not the idea may be valid. This one is very big. To get to its size โ 800 million times more mass than our Sun โ it must have swallowed a lot of stuff. ... As far as we understand it, the universe simply wasnโt old enough at that time to generate such a monster.
โ Youmagazine staff (8 December 2017). "A Black Hole that is more ancient than the Universe" (in Greek). You Magazine (Greece). Retrieved 9 December 2017. This new theory that accepts that the Universe is going through periodic expansions and contractions is called "Big Bounce"
Angha, Nader (2001). Expansion & Contraction Within Being (Dahm). Riverside, CA: M.T.O Shahmaghsoudi Publications. ISBN 0-910735-61-1.
Bojowald, Martin (2008). "Follow the Bouncing Universe". Scientific American. 299 (October 2008): 44โ51. Bibcode:2008SciAm.299d..44B. doi:10.1038/scientificamerican1008-44. PMID 18847084.
Magueijo, Joรฃo (2003). Faster than the Speed of Light: the Story of a Scientific Speculation. Cambridge, MA: Perseus Publishing. ISBN 978-0-7382-0525-0.
Taiebyzadeh, Payam (2017). String Theory; A unified theory and inner dimension of elementary particles (BazDahm). Riverside, Iran: Shamloo Publications Center. ISBN 978-600-116-684-6. |
0.999477 | Good News: A busload of lawyers ran off a cliff. The bus was destroyed and there were no survivors.
Bad News: There were three empty seats. |
0.998645 | but youโre missing the designer dining chairs. But before you buy them, you should know that chairs should be both comfortable and modern. The chairs you place in your living area must certanly be comfortable because the dining room is where you gather your household and friends around a meal. They must also be modern and match your tastes along with reflect your personality. Chairs may be produced from different materials, probably the most used of which are wood and metal. Additionally, there are many different styles and colors available that you should think about before choosing. |
0.928264 | What is the normative justification for individual employment law? For a number of legal scholars, the answer is economic efficiency. Other scholars argue, to the contrary, that employment law protects against (vaguely defined) imbalances of bargaining power and exploitation. Against both of these positions, this Article argues that individual employment law is best understood as advancing a particular conception of equality. That conception, which many legal and political theorists have called social equality, focuses on eliminating hierarchies of social status. This Article argues that individual employment law, like employment discrimination law, is justified as preventing employers from contributing to or entrenching social status hierarchies--and that it is justifiable even if it imposes meaningful costs on employers.
This Article argues that the social equality theory can help us critique, defend, elaborate, and extend the rules of individual employment law. It illustrates this point by showing how concerns about social equality, at an inchoate level, underlie some classic arguments against employment at will. It also shows how engaging with the question of social equality can enrich analysis of a number of currently salient doctrinal issues in employment law, including questions regarding how the law should protect workers' privacy and political speech, the proper scope of maximum-hours laws and prohibitions on retaliation, and the framework that should govern employment arbitration.
The problem with Murray Energy's reported activities, I submit, is that they threaten social equality. Social equality, as described by a number of scholars, seeks "a society in which people regard and treat one another as equals, in other words a society that is not marked by status divisions such that one can place different people in hierarchically ranked categories." (7) Murray Energy's reported activities threaten social equality because they enable the company to transform its economic power over its employees into an additional voice in the political realm. And that additional voice enhances the company's political power while at the same time squelching the political power of its employees. To the extent that employment law limits activities like the ones in which Murray Energy reportedly engaged--and employment laws in many states do limit these activities--the law serves social equality. To the extent that the law does not limit those activities, a social equality perspective suggests that it should.
But social equality is threatened even when employers do not seek to leverage their economic power over their employees into additional political power. Social equality is threatened as well when employer practices needlessly lead to hierarchies within or outside the workplace. Although some hierarchies within the workplace may be inevitable in productive enterprises, it is not inevitable that workers should bow and scrape before their bosses. Nor is it inevitable that employees who are subordinate within the workplace should, as a result, be limited in their opportunities to participate in community life outside the workplace. When one takes these aspects of social equality seriously, they have implications for a wide array of employment law doctrines.
This Article offers a social equality theory of individual employment law. It draws on my earlier work that offered a similar theory of employment discrimination law. (8) In that earlier work, I argued that employment discrimination law serves the goal of advancing social equality. Although employment discrimination law imposes undeniable costs on employers, I argued that those costs are justified because employers can properly be required to forgo some profit to avoid contributing to a system of social inequality. A very similar argument, I contend, provides a justification for individual employment law: Individual employment law can profitably be understood as pervasively promoting social equality. And specific employment law doctrines can profitably be elaborated, assessed, and critiqued by reference to that conception of equality.
But outside the antidiscrimination precinct, individual employment law does not protect particular axes of identity. Its protections are, in an important sense, universal. (11) The social equality that individual employment law can protect is also universal. It targets not merely those practices that entrench caste-based deprivations but also those practices that would tend to undermine any worker's status as an equal to her employer, boss, or supervisor. The application and effects of employment law may be especially important for people in lower socioeconomic classes--the social equality project seeks to ensure that hierarchies of work do not harden into class-type hierarchies of person. But the project extends more broadly than simply redistributing from a disadvantaged class. When we explore the application of employment law outside the discrimination context, we will find that concerns about social equality--although not named as such--lie at the heart of the questions the doctrine asks and answers.
This is not to say that employment law's rules, as currently structured, always do promote social equality. Indeed, one of the benefits of a social equality focus is that it offers a critical lens through which we can examine current doctrine. When viewed through that lens, many of today's employment law rules come up short. But a focus on social equality helps to show that the seemingly disparate critiques of a wide array of doctrines can be profitably understood as stemming from the same underlying goal. Although the general principle of social equality can hardly dictate answers to specific doctrinal questions, it can orient critiques of the current doctrine and ground a case for reform. Or so I hope to show.
The social equality theory differs in significant ways from the two leading normative approaches to employment law in the literature. One approach, exemplified by the work of Stewart Schwab and Alan Hyde, argues that individual employment law is justified if, and to the extent that, it serves the goal of economic efficiency. (12) Employment law rules should thus be explained, assessed, and if necessary reformed, based on whether they make labor markets more efficient.
In line with that argument, employment law scholarship fairly drips with economic-efficiency analysis. The number of employment law articles relying on economic arguments is far too numerous to cite--or even to count. But there are a couple of telling data points: A leading casebook on employment law uses economic efficiency as its first "strong unifying theme[ ]," and it "uses economics to relate seemingly disparate issues and to explore issues in a rigorous way." (13) Leading defenses and critiques of employment law's baseline principle--the at-will rule--rely heavily on economic analysis. (14) Indeed, one can find leading scholars offering economic analyses of virtually any employment law problem. (15) Although much scholarship relating to particular employment law issues continues to take the form of traditional doctrinal analysis, it is fair to say that economic efficiency provides the only overarching normative theory of employment law. |
0.999995 | it's your passage to India!
The country is reforming which has led to the transformation of India becoming the worldโs most open economy. A human capital of 1.5 billion with more than 65% under the age of 35, India is moving towards becoming a global power house of the future. |
0.96195 | Allosteric ribozymes (aptazymes) that have extraordinary activation parameters have been generated in vitro by design and selection. For example, hammerhead and ligase ribozymes that are activated by small organic effectors and protein effectors have been selected from random sequence pools appended to extant ribozymes. Many ribozymes, especially self-splicing introns, are known control gene regulation or viral replication in vivo. We attempted to generate Group I self-splicing introns that were activated by a small organic effector, theophylline, and to show that such Group I aptazymes could mediate theophylline-dependent splicing in vivo.
By appending aptamers to the Group I self-splicing intron, we have generated a Group I aptazyme whose in vivo splicing is controlled by exogenously added small molecules. Substantial differences in gene regulation could be observed with compounds that differed by as little as a single methyl group. The effector-specificity of the Group I aptazyme could be rationally engineered for new effector molecules.
Group I aptazymes may find applications as genetic regulatory switches for generating conditional knockouts at the level of mRNA or for developing economically viable gene therapies.
Ribozymes whose activities are modulated by effector molecules have previously been engineered. For example, Herschlag and co-workers have previously shown that a nucleobase could complement an abasic site within the hammerhead ribozyme, restoring cleavage activity . Similarly, Porta and Lizardi engineered a hammerhead ribozyme that assumed an inactive secondary structure; upon the addition of an oligonucleotide that disrupted the engineered secondary structure, the ribozyme was activated . More recently, it has previously been shown that many selected nucleic acid binding species (aptamers) undergo conformational changes upon ligand binding [3โ6] In addition, when aptamers are conjoined to ribozymes, the ligand-induced conformational changes in the aptamers frequently modulate the structures and hence the activities of the ribozymes [7โ9] For example, binding of theophylline to the anti-theophylline aptamer modulates the conformation of residue [11, 12] and the overall stability of the aptamer [10, 13]. Appending the anti-theophylline aptamer to the hammerhead ribozyme allowed cleavage activity to be modulated by 110-fold by theophylline . Similarly, appending the anti-theophylline aptamer to a small ribozyme ligase (L1) generated an aptazyme that was activated 1,600-fold by saturating theophylline concentrations .
The methods for engineering and selecting Group I aptazymes appear to be generalizable to several different types of ribozymes. Adjoining aptamers to the Group I self-splicing intron would potentially allow the control of splicing not only in vitro, but in vivo. To this end, we have attempted to generate and assay Group I aptazymes.
In order to convert the Group I self-splicing intron to a regulatable aptazyme, it was necessary to first identify sequences or structures in the ribozyme whose conformation might modulate splicing activity. The structural and kinetic properties of the Group I self-splicing intron from the thymidylate synthase (td) gene in bacteriophage T4 have been extensively studied. In particular, a series of nested deletions of the P6 stem-loop have been shown to partially or completely compromise ribozyme activity . More importantly, either magnesium or the tyrosyl tRNA synthetase from Neurospora mitochondria (CYT18) can suppress many of these defects [16, 17]. Previous studies with other introns have also revealed that deletion of the P5 stem-loop can modulate ribozyme activity [18, 19]. We hypothesized that sites where deletions modulated ribozyme activity might also prove to be sites where aptamer conformational changes would modulate ribozyme activity. Based on these studies, we designed a series of Group I aptazymes in which the anti-theophylline aptamer was substituted for either a portion of P6 or P5 (Figure 1). The anti-theophylline aptamer was attached at the same point as had previously proven successful in the design of theophylline-dependent cleavases and ligases [13, 14].
Theophylline-dependent td group I intron constructs. a) The figure shows the predicted secondary structure and tertiary interactions of the 265 nt deletion construct[15, 41] of the td intron drawn in the format of Cech et al. (1994) The intron is in uppercase and the exons are in lower case letters. The 5' and 3' splice sites are indicated by arrows. The P4-P6 domain is boxed. b) The B11 construct was based on the ฮ 85โ863 deletion mutant of the td intron which showed no activity in vivo or at low Mg2+ (3 mM) in vitro. An anti-theophylline aptamer, highlighted in gray, was substituted for the P6a stem of the intron in constructs Th1P6, Th2P6, Th3P6, Th4P6, Th5P6 and Th6P6, and for the P5 stem in constructs Th1P5 and Th2P5. Mutations in the anti-theophylline aptamer are boxed in black for constructs MeX2P6 and Th2P6.D. The C-to-A mutation in MeX2P6 changes specificity from theophylline to 3-methylxanthine . The A-to-U and C-to-U mutations in Th2P6.D abolish theophylline-binding [11, 43].
The self-splicing activities of the Group I aptazymes were examined in vitro using a standard splicing assay (Table 1). Magnesium had previously been shown to suppress structural defects in the td intron, and ligand-induced suppressions of splicing defects were examined by carrying out splicing reactions at either low (3 mM, stringent) or high (8 mM, permissive) magnesium concentrations . Several of the constructs were either relatively inactive (e.g., Th3P6, Th5P6, and Th6P6) or did not consistently show differential splicing activity (e.g., Th4P6 and Th2P5). However, four of the constructs, Th1P6, Th2P6, Th3P6, and Th1P5, showed good activity (>10% of wild-type) and increased self-splicing in the presence of theophylline. For example, Th2P6 showed the greatest activation (8-fold at 8 mM MgCl2), while Th1P5 showed low activation (1.2-fold) at both magnesium concentrations.
Relative in vitro splicing activity of constructs containing anti-theophylline aptamers. Extent of reaction is relative to the parental construct in 3 mM MgCl2 with no theophylline at 2 hrs.
For all of the aptazymes except Th3P6, the ligand-induced splicing activity was greater in a standard assay at the more stringent (3 mM) magnesium concentration (Table 1). The construct Th3P6 was inactive at lower magnesium concentrations, but underwent ligand-induced splicing at the more permissive concentration (8 mM). Interestingly, those aptazyme constructs that showed ligand-dependent activity closely resembled the original deletion variants that showed magnesium-dependent recovery of splicing activity. For example, the junction between the aptamer and the Group I ribozyme in the aptazyme Th2P6 resembled the deletion variant td ฮP6-6; the aptazyme was activated by theophylline, while the splicing defect of the deletion variant at 3 mM magnesium was suppressed by 8 mM magnesium or by stabilization of a tetraloop sequence that capped the P6 helix . Defects that poise a ribozyme between active and inactive conformers have previously been used to engineer effector-dependence .
The kinetics of splicing of two of the most activated variants, Th1P5 and Th2P6, were examined in the presence and absence of theophylline (Figure 2). As in the single point assays, the theophylline-dependence of the engineered introns was readily apparent (Figure 2a). The time courses reveal that the extents of splicing of the aptazymes were significantly affected by the addition of theophylline (Figures 2b,2c). The aptazyme modified at P5 (Th1P5) showed less theophylline-dependent enhancement of the extent of reaction than the aptazyme modified at P6 (Th2P6), consistent with the single point assays described above. Th1P5 was activated 1.4-fold at 15 minutes (Figure 2b), while Th2P6 showed a 4.0-fold rate enhancement at 15 minutes (Figure 2c). These levels of ligand-dependent activation were similar to those observed with the original hammerhead aptazyme constructs, and it may prove possible to use in vitro selection to further optimize activation [13, 14]. However, when the time course data were fit with a single exponential equation, the rates of the initial reactions turned out to be very similar in both the presence and absence of theophylline (Table 2).
In vitro activation of td group I aptazymes by theophylline. a) Autoradiogram showing the splicing activity of the parental, B11, Th1P6, Th2P6 and Th1P5 intron constructs in the presence and absence of 1.5 mM theophylline. LI, linear intron; CI, circular intron; E1โE2, exon 1โexon 2 ligation product; Crp, cryptic ligation product; pre-mRNA, unspliced mRNA. b) Kinetics of splicing for Th1P5. c) Kinetics of splicing for Th2P6. For both figures, solid circles represent the reaction in the presence of 1.5 mM theophylline and open circles represent the reaction in the absence of theophylline. Data points are the average of four determinations.
Kinetic rate constants for constructs containing anti-theophylline aptamers. Rate constants were calculated based on the data shown in Figures 2b and 2c, and the equations presented in Methods.
Based on these results, the primary mechanism of activation is likely the same as has been observed for other aptazymes: ligand-induced conformational changes that stabilize functional ribozyme sequences and structures. However, the Group I self-splicing intron is a much more complicated ribozyme than either the hammerhead or the L1 ligase; for example, the tertiary structure of the Group I intron is established by a complicated folding pathway. [22โ26] Therefore, it was possible that theophylline-binding influenced the overall folding pathway of the engineered Group I aptazyme. In order to assess this possibility we examined the theophylline-dependence of Th2P6 splicing reactions in vitro following prolonged incubation (30 minutes) to allow for re-folding. No significant change in the extent of ligand-dependent activation was observed following pre-incubation (data not shown). These results argue that both GTP and theophylline may need to be present to influence the folding pathway of the engineered Group I aptazymes. These results are also consistent with previous physical and kinetic [28โ30] data that shows that the folding of the Group I intron is dependent in part upon GTP.
Each of the successful aptazyme constructs was subsequently cloned into an interrupted thymidylate synthase gene in place of the parental td self-splicing intron. The vectors were introduced into an E. coli strain (C600ThyA::KanR) that lacked a functional thymidylate synthase gene and that was a thymidine auxotroph. When bacteria grown in rich media were subsequently plated on minimal media lacking thymidine, no colony growth was observed with the exception of Th1P5. However, when theophylline (7.5 mM) was included in the minimal media, bacteria containing the intron Th2P6 formed colonies, and bacteria containing the intron Th1P5 showed increased growth (Figure 3). All introns that originally showed no or low splicing in vitro (including Th3P6) could not rescue bacteria either in the presence or absence of theophylline. Finally, no growth was observed in a negative control that contained a non-functional Group I intron (B11), and no theophylline-dependent changes in growth were observed in a negative control in which mutations were introduced into the aptazyme to abolish theophylline binding (Th2P6.D). Interestingly, no growth was observed for bacteria harboring the intron Th1P6, despite the fact that this aptazyme showed the greatest activation by theophylline in vitro. The plating results were consistent and reproducible over a variety of experiments.
In vivo splicing activity. The parental, B11 and theophylline constructs were spotted in the presence and absence of 7.5 mM theophylline on minimal media (MM).
To better characterize the influence of the effector on intron-splicing, we also carried out a series of growth experiments in liquid culture (Figure 4a). An overnight bacterial culture that contained the td gene divided by the aptazyme Th2P6 was inoculated into fresh, minimal media, effector was added, and growth was continuously monitored. As expected based on growth assays on solid media, little growth was observed in the absence of theophylline. However, when theophylline (0.5 mM) was added to liquid medium, bacteria grew almost as well as a control in which the parental intron was inserted into the td gene. Most importantly, bacterial growth was not activated by the structurally-related effector caffeine (i.e., 7-methyltheophylline); the anti-theophylline aptamer is known to discriminate between caffeine and theophylline by a factor of 10,000-fold . No effector-dependent growth differences were observed with cultures containing td genes divided by the non-functional Group I intron B11. Similar results were obtained with cultures that contained the td gene divided by the aptazyme Th1P5 (Figure 4b). However, in this instance there was some background growth of uninduced bacteria, consistent with the higher level of background splicing activity in vitro. If theophylline is regulating intron splicing in vivo, then the extent of bacterial growth should be dependent upon the concentration of theophylline introduced into the media (Figure 4c). However, theophylline was toxic to bacteria, and caused a decrease in the growth of bacteria containing the parental td intron at concentrations greater than 0.5 mM. Consistent with this observation, low concentrations of theophylline progressively increased bacterial growth (by activating the td intron) while concentrations of theophylline above 2 mM progressively decreased bacterial growth (although levels of growth were still well above background).
Theophylline-dependent growth. Relative growth curves are shown for C600:ThyA cells containing either Th2P6 (a) and Th1P5 (b) in the presence (black filled circles) and absence (black open circles) of 0.5 mM theophylline or 0.5 mM caffeine (black diamonds). Parental (grey filled squares) and B11 (grey open squares) controls were grown in the 0.5 mM theophylline for comparison. Plots are standardized to the extent of growth of cells containing the parental intron. Each point represents the average of three replicate growth curves. c) Extent of growth at 12 hours for parental, Th2P6 and Th1P5 introns over a range of theophylline concentrations. Background growth (B11) has been subtracted, and results are standardized to parental growth with no theophylline.
These results were all consistent with the hypothesis that theophylline regulates intron splicing in vivo. To further probe whether this was in fact the case mRNA was isolated from E. coli treated with theophylline or not, and RT-PCR was used to confirm the presence of spliced introns (Figure 5). For each of the introns known to be responsive to theophylline in vivo (Th2P6 and Th1P5) an increase in spliced mRNA was observed, while most other introns that were not responsive to theophylline in vivo did not show an increase in the levels of spliced mRNA. An exception to this was Th1P6, which originally showed theophylline-dependent splicing in vitro and also showed theophylline-dependent splicing in vivo. However, Th1P6 did not mediate theophylline-dependent growth. The bacterial mRNAs were extracted, cloned, and sequenced, and half of them appeared to use a cryptic splice site.
RT-PCR analysis of whole cell RNA. Bands corresponding to spliced and unspliced mRNAs are indicated. The upper set of RT-PCR reactions was seeded with RNA from cells grown in the absence of theophylline. The lower set was seeded with RNA from cells grown in the presence of 0.5 mM theophylline.
Several discrepancies were noted between intron activation in vitro and effector-dependent growth. This is not surprising; other studies have revealed that there is often little correlation between ribozyme activity in vitro and in vivo . However, since it is known that relatively small changes in gene expression can greatly affect the metabolism of an organism, another possible explanation for the apparent discrepancies is that relatively small modulations in intron splicing are amplified via cellular metabolism to yield growth phenotypes. This would seem especially true in the current set of experiments, since the modulation of Thymidylate Synthase expression is known to greatly affect thymidine levels and cell growth . For example, E. coli that are starved for thymine quickly die, a phenomenon known as 'thymineless death' . In this respect, Group I aptazymes that may have yielded lower amounts of functional Thymidylate Synthase (e.g., Th3P6, which was less active than Th2P6; or Th1P6, which mis-spliced) did not allow bacterial growth. In contrast, aptazymes that may have yielded even modestly greater amounts of functional Thymidylate Synthase (e.g., Th1P5, which was both highly active and modestly activated in vitro) allowed bacterial growth.
In order to examine effector-specificity in vivo, a new series of Group I aptazymes was constructed in which the anti-theophylline aptamer was mutated to bind 3-methylxanthine (3MeX2P6) . These variants proved to be responsive to 3-methylxanthine both in vitro and in vivo (Figure 6a). However, the variants were no longer responsive to theophylline, nor were they responsive to a variety of other analogues, including caffeine, 1-methylxanthine, 7-methylxanthine, 1,3-dimethyl urilic acid, hypoxanthine, xanthine, and theobromine (Figure 6b). In contrast, the original aptamer was known to also bind 3-methylxanthine, and the original Group I aptazyme (Th2P6) also proved to be responsive to 3-methylxanthine in vivo (Figure 6c). Thus, the responsivity of the aptazymes in vivo appears to mirror their effector specificity in vitro.
3-Methylxanthine dependent growth. a) Relative growth curves are shown for C600:ThyA cells containing 3MeX2P6 in the presence (black filled circles) and absence (black open circles) of 1 mM 3-methlyxanthine or 1 mM theophylline (black diamonds). Parental (grey filled squares) and B11 (grey open squares) controls were also grown in 1 mM 3-methylxanthine. Plots are standardized to the extent of growth of cells containing the parental intron. Each point represents the average of three replicate growth curves. b) Specificity of growth of 3MeX2P6 on theophylline analogs. Background growth (B11) has been subtracted, and results are standardized to parental growth on minimal media at 12 hrs. Negative values were not greater than -0.05, and were set to zero. Each analog was present in the media at 0.5 mM. c) Specificity of growth of Th2P6 on theophylline analogs. Presentation of the data is the same as in Figure 6b. Each analog was present in the media at 0.5 mM.
Group I aptazymes that were dependent upon theophylline both in vitro and in vivo were engineered by conjoining the thymidylate synthase (td) intron with an anti-theophylline aptamer. Although the in vitro activation of splicing was modest (up to an 18-fold change in initial rate), this change was more than enough to mediate the survival of a thymidine-dependent E. coli strain. The ligand specificity of the anti-theophylline aptamer carried over to the theophylline-dependent aptazyme, and no activation was seen with caffeine, which differed by a single methyl group from theophylline. The effector specificity could be rationally changed by changing the specificity of the conjoined aptamer: when a mutation was introduced into the anti-theophylline aptamer that led to discrimination against theophylline and in favor of 3-methylxanthine (that also differed from theophylline by a single methyl group), the aptamer became solely responsive to 3-methylxanthine in vivo. Group I aptazymes may have a number of important biotechnology applications, including use as in vivo, real-time reporters and as regulatable gene therapeutics.
E. coli strain C600ThyA::KanR was used for the plate assays and in vivo growth curves. INVaF' (Invitrogen, Carlsbad, CA) was used for cloning and plasmid amplification. Bacterial starter cultures were grown in LB supplemented with thymine (50 mg/l). Screening for thymidine auxotrophy was done in minimal media supplemented with 0.1% Norit A-treated casamino acids (MM) and MM supplemented with thymine (50 mg/l) (MMT). Plates contained Bacto agar (1.5%). Ampicillin (50 mg/l) and kanamycin (100 mg/l) were added to all growth media.
The wild type plasmid pTZtd1304 contains a fully functional 265 nt derivative of the 1016 nt wild type intron . This derivative also contains the substitutions U34A, which introduces a SpeI site, and U976G, which introduces an EcoRI site. The constructs were made using standard solid phase DNA synthesis, then were PCR-amplified and cloned into pTZtd1304. The parental P6 aptazyme construct was generated by two overlapping oligos, Gp1Wt2 Gp1Wt2.122 (GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCT AAA TTG TAG GAC TGC CCG GGT TCT ACA TAA ATG CCT AAC GAC TAT CCC TT) and Gp1Wt3.129 (TAA TCT TAC CCC GGA ATT ATA TCC AGC TGC ATG TCA CCA TGC AGA GCA GAC TAT ATC TCC AAC TTG TTA AAG CAA GTT GTC TAT CGT TTC GAG TCA CTT GAC CCT ACT CCC CAA AGG GAT AGT CGT TAG). These oligonucleotides (100 pmole) were annealed and extended with AMV reverse transcriptase (Amersham Pharmacia Biotech, Piscataway, NJ; 45 units) in AMV RT buffer (50 mM Tris-HCl, pH 8.3, 8 mM MgCl2, 50 mM NaCl, 1 mM DTT) and dNTPS (200 ฮผM) for 30 minutes at 37ยฐC. The resulting double-stranded DNA was diluted 1:50 and amplified using primers SpeI.24 (TTA TAC TAG TAA TCT ATC TAA ACG; 0.4 ฮผM) and EcoRI.24 (CCC GGA ATT CTA TCC AGC TGC ATG; 0.4 ฮผM) in PCR buffer (10 mM Tris-HCl, pH 8.3, 50 mM KCl, 1.5 mM MgCl2, 0.1% Triton X-100, 0.005% gelatin), dNTPS (200 ฮผM) and Taq DNA polymerase (Promega, Madison, WI; 1.5 units). The reactions were thermocycled 15 times at 94ยฐC for 30 seconds, 45ยฐC for 30 seconds, 72ยฐC for 1 minute and then purified with a QIAquick PCR purification kit (Qiagen, Valencia, CA). The PCR product was digested with SpeI (New England Biolabs, Beverly, MA; 20 units) and EcoRI (50 units) in buffer (50 mM NaCl, 100 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 0.025% Triton X-100, 100 ฮผg/ml BSA) at 37ยฐC for 60 minutes, purified, and cloned into SpeI/EcoRI digested pTZtd1304. The negative control and aptazyme constructs were made as described except that Gp1Wt3.129 was replaced with oligonucleotides of the appropriate sequence: B11 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCT AAA TGC CTA ACG ACT ATC CCT T, Th1P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCT AAA TTA TAC CAG CAT CGT CTT GAT GCC CTT GGC AGA TAA ATG CCT AAC GAC TAT CCC TT, Th2P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCT AAA TTG ATA CCA GCA TCG TCT TGA TGC CCT TGG CAG CAT AAA TGC CTA ACG ACT ATC CCT T, Th3P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCA TAC CAG CAT CGT CTT GAT GCC CTT GGC AGG CCT AAC GAC TAT CCC TT, Th4P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GCT AAA TAT ACC AGC ATC GTC TTG ATG CCC TTG GCA GTA AAT GCC TAA CGA CTA TCC CTT, Th5P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT ATA CCA GCA TCG TCT TGA TGC CCT TGG CAG CTA ACG ACT ATC CCT T, Th6P6 GCC TGA GTA TAA GGT GAC TTA TAC TTG TAA TCT ATC TAA ACG GGG AAC CTC TCT AGT AGA CAA TCC CGT GAT ACC AGC ATC GTC TTG ATG CCC TTG GCA GCC TAA CGA CTA TCC CTT, Th1P5 TGA GTA TAA GGT GAC TTA TAC TAG TAA TCT ATC TAA ACG GGG AAC CTC TAT ACC AGC ATC GTC TTG ATG CCC TTG GCA GAG ACA ATC CCG TGC TAA ATT GTA GGA CTG CCC GGG TTC TAC ATA AAT GCC TAA CGA CTA TCC CTT, Th2P5 TGA GTA TAA GGT GAC TTA TAC TAG TAA TCT ATC TAA ACG GGG AAC CTA TAC CAG CAT CGT CTT GAT GCC CTT GGC AGA CAA TCC CGT GCT AAA TTG TAG GAC TGC CCG GGT TCT ACA TAA ATG CCT AAC GAC TAT CCC TT, 3Mex2P6 GTA ATC TAT CTA AAC GGG GAA CCT CTC TAG TAG ACA ATC CCG TGC TAA ATT GAT ACC AGC ATC GTC TTG ATG CCA TTG GCA GCA TAA ATG CCT AAC GAC TAT CCC TT, and Th2P6.D GTA ATC TAT CTA AAC GGG GAA CCT CTC TAG TAG ACA ATC CCG TGC TAA ATT GAT ACC AGC ATC GTC TTG ATG CCC TTG GTT GCA TAA ATG CCT AAC GAC TAT CCC TT.
The introns were PCR-amplified with KM37 (GAT AAT ACG ACT CAC TAT AAT GGC ATT ACC GCC TTG T) and GM24 (GCT CTA GAC TTA GCT ACA ATA TGA AC) in 25 ฮผl reactions under the conditions stated above and cycled 20 times. A portion of the reaction (5 ฮผl) was run on a 3% agarose gel and the PCR product band was stabbed with a pipette tip. The agarose plug was added to a fresh PCR reaction (100 ฮผl) and cycled 15 times; DNA was purified using a QIAquick kit and quantitated. The PCR product (2 ฮผg in 50 ฮผl) was added to an in vitro transcription reaction containing Ampliscribe T7 RNA polymerase (Epicentre), RNase inhibitor (GIBCO BRL, Rockville, MD; 5 units), low Mg2+ buffer (30 mM Tris-HCl, pH 8, 7.5 mM DTT, 4.5 mM MgCl2, 1.5 mM spermidine), UTP (1.25 mM), ATP (2.5 mM), GTP (2.5 mM), CTP (7.5 mM) and ฮฑ-32P UTP (NEN, Boston, MA; 20 ฮผCi; 3000 mCi/mmol), and incubated at 37ยฐC for 2 hours. DNase (GIBCO BRL, 295 units) was added and the reaction was incubated at 37ยฐC for an additional 30 minutes. The RNA was purified using Centri-Sep columns (Princeton Separations, Adelphia, NJ) and quantitated.
The assays were performed by heating the RNA (500 nM) in H2O to 70ยฐC for 3 minutes then transferring to ice for 1 minute. Splicing buffer (20 mM Tris-HCl, pH 7.5, 100 mM KCl, 3 mM MgCl2), effector (theophylline, 1.5 mM) was added and the reactions were incubated on ice for an additional 15 minutes. At this time a 4.5 ฮผl aliquot was removed for a zero time point and quenched with 5 ฮผl stop dye (95% formamide, 20 mM EDTA, 0.5% xylene cyanol, and 0.5% bromophenol blue). GTP (50 ฮผM) was added to the remaining reaction (5 ฮผl total volume) to start the splicing reaction. The reaction was incubated at 37ยฐC for 30 minutes and then terminated with stop dye (5 ฮผl). The reactions were heated to 70ยฐC for 3 minutes and 5 ฮผl was analyzed on a 8% denaturing polyacrylamide gel. The gel was dried, exposed to a phosphor screen and analyzed using a Molecular Dynamics Phosphorimager (Sunnyvale, CA).
The plotted data and rate constants for Th1P5 and Th2P6 constructs are shown in Figures 2b and 2c and Table 2. The changes in the extent of reaction observed between individual experiments, and thus the attendant error bars, were consistent with those observed during the kinetic analyses of other ribozymes. For example, studies of the hairpin ribozyme have shown that data points can vary between individual experiments by as much as 50% . Our data points typically varied from one another by less than 30%.
The plasmids containing the various group I constructs were transformed into competent C600ThyA::KanR cells and grown in LB with kanamycin overnight. A small aliquot (3 ฮผl) of overnight cell culture was mixed with effector (theophylline, 7.5 mM) or H2O, spotted on plates, and grown overnight at 37ยฐC. As a positive control, all constructs were also plated on minimal media plates with thymine (MMT) and assayed for viability.
Cells grown overnight in LB were diluted 1:100 in MM containing either theophylline, caffeine, 3-methylxanthine or no effector, and analyzed on a Microbiology Workstation Bioscreen C (Labsystems, Inc., Franklin, MA).
RNA was isolated from an overnight culture using a MasterPure RNA purification kit (Epicentre, Madison, WI) and amplified by RT-PCR using primers KM37 and GM24 following the protocol provided for Tth polymerase. The products were separated and analyzed on a 3% agarose gel.
This work was funded by the Office of Naval Research (Grant #: N00014-99-1-0861), the Defense Advanced Research Projects Agency (Grant #: DAAD19-99-1-0207), and the National Institutes of Health (Grant #: 1R01 GM61789-01). We would like to thank Ken Johnson for assistance with kinetic analyses.
Kristin M. Thompson conceived of, designed, and carried out most of the experiments described in this paper and analyzed the resultant data. Heather A. Syrett repeated a number of these experiments and showed that the in vivo activation of the intron was reproducible. Scott M. Knudsen assisted in data analysis. Andrew D. Ellington conceived of these experiments and assisted in the design of experiments and data analysis. |
0.999653 | List Rules Good old classic country - as opposed to the more pop/rock "contemporary country" sound that dominates the airwaves today.
Country music is one of the most popular genres of music in the United States, and old country songs are appreciated by fans of all ages. No list of the top country songs of all time would be complete without the classic country music of legendary artists like Johnny Cash and Patsy Cline.
Sometimes called country western, or country and western music, classic country songs are steeped in Americana and tell the story of ordinary, loving, hard working, often hard drinking, and sometimes long-suffering people, just like many of us. Sometimes the best country songs are deceptively simple sounding in their portraits of American life, but that's what makes classic country so endearing - and so relatable.
Out of all the classic country western singers, Johnny Cash had some of the biggest crossover success. The singer/songwriter eventually tapped into rock, gospel, folk, and other genres, but is best remembered for classic country songs like "Ring of Fire," "Folsom Prison Blues," and "I Walk the Line." He and wife June Carter Cash - classic country music royalty in her own right - were together best known for their duet of "Jackson," a No. 2 hit on the Country Music charts in 1967.
Patsy Cline may now be remembered as one of the women in classic country, but she fought her for it, particularly in era that didn't accord female country western singers the same advantages of their male counterparts. Though she didn't live to fully appreciate her legacy (Cline was killed in a plane crash at age 30), her old country songs like "Crazy" and "I Fall to Pieces" are counted along with the best country songs of all time.
Hank Williams, considered by some to be the godfather of 20th century country music, performed popular country songs of his era that still influence musicians to this day. "Your Cheatin' Heart" and "Hey, Good Lookin'" are but two examples. Those old radio hits are as ingrained into American culture as apple pie.
What are your favorite country music songs that are considered classics? Vote up good country songs from the best of old country music, or add one that makes you cherish the best classic country songs. If you like both older and newer country music, vote on the best country artists of all time.
No one does starker love songs than Johnny Cash and perhaps this is the ultimate of his to June Carter.
This heart-breaking and flagellating song by Patsy Cline has always been a country classic.
George Straight sings about the understated woes of a rodeo cowboy.
This wailing tune from Tammy Wynette is an ode to being faithful that is quintessentially country.
The name is pretty self-explanatory on this one.
As Merle Haggard says, "mamma tried" to raise her boy right, but it just didn't work out that way.
This sad Hank Williams song is one to which your can drown your sorrows in a tall glass of wine or beer.
This WIllie Nelson song about eternal love is so classic its practically been covered to death.
An ode to a lost love that Conway Twitty done wrong.
Another ode to the occupations of the south and the lives lived by the hard-driving coal workers and their family. This Loretta Lynn song is a classic.
This sad sack Hank Williams song was made even more famous when Elvis re-recorded it.
Johnny Cash's signature song with the famous line, "I shot a ran in Reno, just to watch him die."
John Denver's ode to the Blue Ridge Mountains and Shenandoah River.
A veteran gambler teaches a young man when to hold 'em and when to fold 'em.
Another Dolly Parton hit to make the list, this song is about the pleas on one woman to Jolene to stop cheating with her husband.
Nobody quite does self pity like Cline, another classic and cry-worthy tune from her makes the list. |
0.929958 | First Professional Woman Astronomer in the U.S.
Taught by her astronomer father, Maria Mitchell (August 1, 1818 - June 28, 1889) was the first professional woman astronomer in the United States. She became a professor of astronomy at Vassar College (1865 - 1888). She was the first woman member of the American Academy of Arts and Sciences (1848), and was president of the American Association for the Advancement of Science.
On October 1, 1847, she spotted a comet, for which she was given credit as the discoverer.
She was also involved in the anti-slavery movement. She refused to wear cotton because of its connection with slavery in the South, a commitment she continued after the Civil War ended. She also supported women's rights efforts and traveled in Europe.
Maria Mitchell's father, William Mitchell, was a banker and an astronomer. Her mother, Lydia Coleman Mitchell, was a librarian. She was born and raised on Nantucket Island.
Maria Mitchell attended a small private school, denied, at that time, higher education because there were few opportunities for women. She studied mathematics and astronomy, the latter with her father. She learned to make precise astronomical calculations.
She began her own school, which was unusual in that it accepted as students people of color. When the Atheneum opened on the island, she became a librarian, as her mother had been before her. She took advantage of her position to teach herself more mathematics and astronomy. She continued to assist her father in documenting the positions of stars.
On October 1, 1847, she saw through a telescope a comet that had not been recorded before. She and her father recorded their observations and then contacted the Harvard College Observatory. For this discovery, she also won recognition for her work. She began to visit the Harvard College Observatory, and met many scientists there. She won a paying position for some months in Maine, the first woman in America to be employed in a scientific position.
She continued her work at the Atheneum, which served not only as a library but also as a place welcoming visiting lecturers, until in 1857 she was offered a position to travel as the chaperon for a wealthy banker's daughter. The trip included a visit to the South where she observed the conditions of those who were enslaved. She was able to visit England, as well, including several observatories there. When the family that employed her returned home, she was able to remain for a few more months.
Elizabeth Peabody and others arranged, on Mitchell's return to America, to present her with her own five-inch telescope. She moved with her father to Lynn, Massachusetts, when her mother died, and used the telescope there.
When Vassar College was founded, she was already more than 50 years old. Her fame for her work led to being asked to take up a position teaching astronomy. She was able to use a 12-inch telescope at the Vassar observatory. She was popular with the students there, and used her position to bring in many guest speakers, including advocates for women's rights.
She also published and lectured outside of the college, and promoted the work of other women in astronomy. She helped to form a precursor of the General Federation of Women's Club, and promoted higher education for women.
In 1888, after twenty years at the college, she retired from Vassar. She returned to Lynn and continued to view the universe through a telescope there.
Maria Mitchell: A Life in Journals and Letters. Henry Albers, editor. 2001.
Gormley, Beatrice. Maria Mitchell - The Soul of an Astronomer. 1995. Ages 9-12.
Hopkinson, Deborah. Maria's Comet. 1999. Ages 4-8.
McPherson, Stephanie. Rooftop Astronomer. 1990. Ages 4-8.
Melin, G. H. Maria Mitchell: Girl Astronomer. Ages: ?.
Morgan, Helen L. Maria Mitchell, First Lady of American Astronomy.
Oles, Carole. Night Watches: Inventions on the Life of Maria Mitchell. 1985.
Wilkie, K. E. Maria Mitchell, Stargazer.
Women of Science- Righting the Record. G. Kass-Simon, Patricia Farnes and Deborah Nash, editors. 1993. |
0.999999 | Despite the Civil Rights Act and the Department of Justice's myriad lawsuits against Alabama state officials for voter discrimination, racial discrimination among Alabama's voters persisted. Tensions in Selma thus also persisted throughout the late 1950s and 1960s. Ultimately, an injunction issued in this case would enable the Selma-to-Montgomery marches to take place in March 1965. For additional context on the year leading up to the marches, go to this case.
In February 1965, a state trooper shot black man in Marion, AL during a riot following demonstrations in front of a courthouse, which sparked renewed tension in Selma and led to the planning of the marches from Selma to the state capital, Montgomery, as a peaceful protest against discrimination. On March 6, 1965, Governor George Wallace issued a statement banning any march. Nevertheless, the first attempted march took place on March 7, 1965, a day known as Bloody Sunday because of the violence that erupted between the protesters and state troopers. Although demonstrators were walking peacefully to Montgomery, state troopers gave them two minutes to disperse, though only a minute into their command and after the demonstrators had not dispersed, the state troopers began their attack. The troopers deployed tear gas, nausea gas, and canisters of smoke. They used clubs and horses to chase and beat the demonstrators.
Seeking protection for their future marches, civil rights leaders Hosea Williams, John Lewis, and Amelia Boynton filed this class action suit on March 8, 1965 pursuant to the Civil Rights Act against Alabama Governor George Wallace, Dallas County Sheriff James Clark, and other state officials. Governor Wallace was a famous segregationist with repeated bids for president, while Sheriff Clark was known for his support of segregation and resort to violence in opposing the civil rights movement.
In addition to their complaint, the plaintiffs filed motions seeking a temporary restraining order and a preliminary injunction. The plaintiffs claimed violations of the Civil Rights Act, as well as equal protection violations under the Fourteenth Amendment, and deprivation of rights under the First and Fifteenth Amendments. Accordingly, they sought to enjoin the State from interfering with their right to peacefully assemble and demonstrate their grievances concerning the right to register to vote in Alabama. The plaintiffs specifically asked for an injunction allowing them to march peacefully from Selma to Montgomery free of the State's interference, coercion, and harassment. Two days later, the Department of Justice (DOJ) intervened. This action was brought in the U.S. District Court for the Middle District of Alabama.
On March 9, 1965, the court (Judge Frank Johnson) denied the application for temporary restraining order and instead issued an order temporarily restraining the plaintiffs from "any further attempts...to enforce the rights they ask this Court to judicially determine" until the court could conduct a hearing on the matter. That same day, Dr. King led protesters to the border of Selma but no further, strategically choosing to respect the restraining order and not alienate a judge sympathetic to voter discrimination issues in Alabama. That day came to be known as "Turnaround Tuesday."
On March 17, 1965, Judge Johnson enjoined the state from interfering with the protesters, enabling the Selma-to-Montgomery marches to proceed (240 F. Supp. 100).
The court found that in Dallas County where Selma is located, as well as several other Alabama counties, less than 10% of the black voting age population was registered to vote. The court noted that in response, black communities organized voter registration drives as well peaceful demonstrations, while the numerous cases were filed in federal court to fight voter discrimination. Despite these efforts, the court found that while the black voting age population was greater than the white voting age population as of November 1964, only small or nonexistent percentages of black eligible voters were registered to vote across the various counties. These findings suggested "an almost continuous pattern of conduct...on the part of...Sheriff Clark [and his agents] of harassment, intimidation, coercion, threatening conduct, and, sometimes, brutal mistreatment" of demonstrators. The court found that this conduct ranged from unjustified mass arrests to forced marches into the countryside while using electrical shocking devices on the demonstrators. Indeed, the court found that state troopers sometimes assisted the Sheriff, including during the violence of Bloody Sunday. Moreover, the court found that Governor Wallace was aware of the tactics to be employed by the state troopers on that day.
The court held that these acts of violence on the part of the State were for the sole purpose of preventing and discouraging black citizens from the right to register to vote, the right to peacefully protest discrimination, and the right to petition one's government for redress of grievances. The acts were not meant to enforce any valid law. While governments have a right and duty to maintain safety and keep roads open for regular use, the court held that there is room for both this duty and the right to peacefully protest grievances. So long as the protest is peaceful and does not unreasonably interfere with other citizens' right to use the roads, the protest does not undermine the government's aforementioned duty. Thus, the court further held that Governor Wallace's March 6 proclamation banning all marches, as well as its subsequent enforcement, was an unreasonable and unconstitutional interference with the right to protest.
Judge Johnson poignantly noted that "it seems basic to our constitutional principles that the extent of the right to assemble, demonstrate and march peaceably along the highways and streets in an orderly manner should be commensurate with the enormity of the wrongs that are being protested and petitioned against. In this case, the wrongs are enormous. The extent of the right to demonstrate against these wrongs should be determined accordingly." Indeed, Judge Johnson stated that this principle was especially true when the protester has been deprived of the usual and basic constitutional means of protest - voting.
The court ultimately found the plaintiffs' proposed march plan to be reasonable and a constitutional exercise of the right to peacefully assemble and petition the government for redress. While the plan "reaches...to the outer limits of what is constitutionally allowed," Judge Johnson held that "the wrongs and injustices inflicted upon these plaintiffs and the members of their class...have clearly exceeded - and continue to exceed - the outer limits of what is constitutionally permissible." Moreover, the court found that the State did not offer any evidence apart from its hostility to the plan to indicate that the plan was in fact unreasonable.
Crucially, Judge Johnson issued an injunction compelling the State to provide the marchers protection from the State's law enforcement, which was to be supplemented with federal forces if requested by the State. The court further enjoined the State and its officers from intimidating, threatening, coercing, or otherwise interfering with the proposed march.
The next day, the State moved to stay the injunction, arguing that the march posed a threat of violence to white citizens opposing it. But Judge Johnson denied the motion, finding that argument unpersuasive and that there was nothing new to suggest a stay would be justified.
On March 21, 1965, thousands of protesters assembled in Selma to begin the march to Montgomery, which concluded on March 25. Along the way, they were protected by the United States Army and Alabama National Guard. |
0.999997 | What are Articles of Incorporation for a Corporation?
Many businesses decide to incorporate - that is, to form the business as a corporation. In order to begin the process of incorporating, the business must file a form with the state in which does business. This form is called the Articles of Incorporation. In some states, these articles may be called something else. The document may be called a Certificate of Incorporation (as in Delaware) or a Corporate Charter (another general term).
A corporation is a specific type of business that is formed in the state where the company is doing business. To form a corporation, there are specific steps that must be taken and some decisions that must be made. One of the most import steps in incorporating a business in a state is to create Articles of incorporation. The form of these articles depends on the laws of the state. To find out the requirements for articles of incorporation in your state, go to the website of your state's secretary of state and the business division.
The Articles of Incorporation provide the basic information needed to form the business and register the business in the state. The state needs to know the name of the business, its purpose, and the people who will be in charge. For a corporation, the state also needs to know about any stock the business will be selling.
The name of the corporation: Each state has different requirements for the corporation's name, but in most cases, it must include the term "Inc." or "Incorporated" to specifically designate this business as a corporation.
The name and address of the registered agent: People need to have someone who can receive important documents and legal papers on behalf of the corporation, so the registered agent needs to be someone who is available all the time during regular business hours. Many businesses hire a registered agent service., but you can be your own registered agent.
The specific type of corporation: (stock corporation, non-stock corporation, non-profit corporation, etc.) For a stock corporation, the authority of the corporation for an initial issue of a specific number of shares of stock and the price of those shares. You may also want to designate a certain class of shares (Class A, for example).
The purpose(s) for which the corporation was formed: What is the corporation selling? What type of business is it in? Each state has different requirements and levels of detail for this section.
The names and addresses of the initial directors: You will need to form a board of directors, and you may have to list the board members or the corporate officers (president, vice president, secretary, treasurer) on the Articles of Incorporation.
The name and address of the incorporator: (the person preparing the incorporation documents). An incorporator is a person in charge of setting up a corporation. The incorporator files the Articles of Incorporation with the state in which the corporation is registering and filing any other corporate documents needed until the corporation is formally registered and recognized by the state. Other duties of the incorporator might include selecting members of the board of directors or organizing an initial meeting of the board. An incorporator can be but does not necessarily have to be, an attorney. The person designated as the incorporator is listed on the Articles of Incorporation so he or she may be contacted by the state, if necessary. The incorporator has no formal duties once the corporation has been registered with the state.
The duration of the corporation: either perpetual or for a fixed period of time. Most corporations are set up as perpetual organizations.
The Articles of Incorporation are filed with the office of the Secretary of State for your state. Then get the help of an attorney to construct the document. Forming a corporation is complicated. While many states allow you to file the articles of incorporation online, it is a good idea to get an attorney to help you with the process of forming a corporation, so you don't miss anything critical.
Is There a General Template for Articles of Incorporation?
Pre-emptive Rights: Initial or current shareholders may have the right to purchase shares in any offering before non-shareholders can purchase. In other words, they can pre-empt others and buy these shares.
Amending or Repealing Bylaws: The bylaws are the operating procedures for a corporation. They are created as part of the process of incorporation. Procedures for amending or repealing bylaws may be included in the articles of incorporation.
Fiscal year-end: A company's fiscal year is its financial year. The year-end determines when annual reports are due and when taxes must be paid.
Indemnification of Officers, Directors, Employees, and Agents: To indemnify means to hold harmless. An indemnity agreement attempts to state that those individuals who make decisions and act on behalf of the corporation should be held harmless from liability.
Limitation of Liability: This clause is similar to the indemnity clause above. It's sometimes called an "errors and omissions" clause because it states that responsible parties should not be liable for general errors or omissions in their ordinary work. |
0.999912 | More detail on this person: Mr Stephen V Hailey, 63 of Mesa, Washington In Memory Of...B3 1-2-09 Tri-City Herald (Kennewick, WA) - Thursday, January 1, 2009 State Representative Stephen V. Hailey, of Mesa, WA., died Sunday, December 28, 2008, at his home with his family by his side. Steve was born on January 29, 1945, to Lester and Virginia (Valentine) Hailey in Seattle where his parents were stationed during WWII. Nine months later he moved with his family to the ranch in Mesa that was begun in 1909 by his grandfather and uncle. He was raised in Mesa and attended school in Connell, WA, graduating from Connell High School in 1963. During that time he worked with his father on the family ranch raising fat cattle and dry and irrigated wheat. After high school he attended college until 1967 when he was drafted into the U.S. Army. Steve attended the Army helicopter training school at Ft. Wolters, in Mineral Wells, Texas, where he met Patricia McAmis. Steve served in Vietnam from 1968-69 in the Assault Helicopter Company, Flying Special Operations Group Missions. During his enlistment Steve received many decorations including: The Distinguished Flying Cross, The Air Medal and the Bronze Star. After returning to the States, Steve married Patricia in Fort Worth, Texas, on November 29, 1969. After his discharge he returned to the family ranch where he enjoyed being involved in the day to day operations of farm life. In 2006, Steve was elected to the Washington State House of Representatives, District 9. He was re-elected in 2008. He was the President of Hailey Company, Inc., a member and past president of Washington Cattlemen's Association (1998-99), and National Chairman of the Cattlemen's Beef Promotion and Research Board in 1999. His other memberships included the Washington State Farm Bureau, Washington Wheat Growers Association, Veterans of Foreign Wars, Special Operations Association, and the NRA. Steve served his local community by being on the Franklin County Planning Commission for 10 years and as a Commissioner for the Franklin County Fire District #1. He then served the people of the 9th Legislative District as a member of the State House of Representatives from 2006 through 2008. He was re-elected in November of 2008 to another two year term. In his private life he loved flying and belonged to the "Mesa Air Corps," a neighborhood group flying single engine tail-draggers. He was proud of refurbishing and flying his 1947 Aeronca Champ airplane. Steve loved life, had a marvelous ability of talking to anyone about anything at anytime, fishing in his own "special" pond and starting his day with a "little male bonding at the coffee shop" in Mesa. He is survived by his wife, Patricia of Mesa; his children, B.J. Hailey (Lindsay) of Mesa and Suzie Hartley (Mark) of Connell; his only grandchild, Colby Hartley of Connell; his mother, Virginia V. Hailey of Madera, CA; his father, Lester C. Hailey of Lake Stevens, WA; his sisters, Leslie Hailey Hurst (Joe) of Jamestown, CA, and Melissa Hailey Layne (Loren) of Madera, CA; and sister-in-law, Carol Miller (Gary) of Othello; and numerous nieces, nephews, uncles and cousins. A celebration of Steve's life will be held at the Connell Community Center on Saturday, January 3, 2009, at 2:00 p.m. Memorials are suggested to the Tri-City Cancer Center, the American Cancer Society or the Washington Cattlemen's Association Endowment Trust Fund. Hailey remembered as man of virtue Tri-City Herald (Kennewick, WA) - Sunday, January 4, 2009 Five hundred friends joined the family of Stephen Vey Hailey, a longtime Mesa farmer and a state legislator, to say goodbye Saturday. The Connell Community Center was standing room-only for the memorial service, which was attended by a half-dozen state legislators and Reps. Doc Hastings and Cathy McMorris Rodgers, both R-Wash. Hailey, who died of cancer Dec. 28, was 63. Hailey, who grew up on the family ranch in Mesa, spent his life working the land and raising cattle save for his service in the Army in Vietnam and his time in Olympia representing the 9th legislative district. "We are here to celebrate his accomplishments, his commitment to family, community and issues important to this state and country. And to his character," said Don Cox, former state representative who officiated at the service. Known as a problem solver and good listener, Hailey was eulogized as a gentleman who valued relationships, especially with his buddies at the Mesa Coffee Shop. "Steve Hailey epitomized public virtue. He grew wiser by accepting one challenge after another," said Dennis Calfee of Gainesville, Fla., a childhood friend who spoke at the service. Calfee described his friend as "always evolving, expanding his intellect, happy with the accomplishments of others." Hailey, a firm conservative politically, was "thoughtful of opinions of others" and "was not afraid to change his opinion," Calfee said. State Senator Mark Schoesler, R-Ritzville, said, "Steve was a great American to his community and his country." Joe Schmick, R-Colfax, said Hailey was so well respected in Olympia that "people stood and cheered when he entered the caucus room." State representatives Maureen Walsh, R-Walla Walla and Larry Haler, R-Richland also attended the service, among others. Cowboy singer Wylie Gustafson of Eastern Washington sang for the service, and the Washington Army National Guard with the Veterans of Foreign Wars Post 7952 provided military honors. A 1963 graduate of Connell High School, Hailey attended Washington State University, was drafted into the Army in 1967 and married Pat in late 1969. They have two children, B.J. and Suzie. He ran the family ranch at Mesa, and was elected 9th district representative to the state Legislature in 2006 and was re-elected in November. Hailey also found time for community service. He was president of the Washington Cattlemen's Association and belonged to the Franklin County Cattlemen's Association, the Washington Farm Bureau and the Washington Wheat Growers Association. He also was on the Franklin County Planning Commission and the Franklin County Fire District No. 1 Board of Commissioners. |
0.975104 | Solution: You are given the following three half-reactions:(1) Fe3+(aq) + eโ โ Fe2+(aq)(2) Fe2+(aq) + 2eโ โ Fe(s)(3) Fe3+(aq) + 3eโ โ Fe(s)(a) Calculate ฮGยฐ for (1) and (2) from their Eยฐhalf-cell values.(b) Calculate ฮGยฐ for (3) from (1) and (2).(c) Calculate Eยฐhalf-cell for (3) from its ฮGยฐ.
(a) Calculate ฮGยฐ for (1) and (2) from their Eยฐhalf-cell values.
(b) Calculate ฮGยฐ for (3) from (1) and (2).
(c) Calculate Eยฐhalf-cell for (3) from its ฮGยฐ. |
0.946951 | Meiosis is a special type of cell division for gametogenesis, errors in which cause several genetic disorders such as infertility and Down syndrome. In meiotic prophase I, chromosomes are tethered to the nuclear envelope (NE) through telomeres, and move rapidly along the NE to get homologs aligned and juxtaposed. Following homologous recombination and synapsis, the bivalent chromosome structure is established, which promotes genetic varieties, and also ensures accurate chromosome segregation in following anaphase I. Although there have been extensive studies addressing meiotic chromosome dynamics in yeast and worms, the same in mammalian meiosis remains largely elusive. Here, we utilized an in vivo electroporation (EP) technique to visualize chromosome movement in live mouse spermatocytes. We, for the first time, define the meiotic sub-stages in live cells based on telomeres and chromosome axis morphologies, and reveal chromosome movements regulated in a stage-specific manner. Putting the live-observations together with our cytological observations in fixed cells, we propose that meiotic chromosome movements in mammals are mediated by the rail-tracking movement of telomeres along the MT cables surrounding the meiotic nucleus.
Meiosis is a specialized cell division for gametogenesis that involves unique chromosomal regulations, such as pairing/synapsis and recombination of homologous chromosomes. These processes are ensured by the dynamic chromosomal rearrangements that occur during meiotic prophase I, as have been extensively characterized in model systems involving Saccharomyces cerevisiae, Schizosaccharomyces pombe and Caenorhabditis elegans , . In these organisms, chromosomes move within the nucleus during meiotic prophase I, which facilitates the juxtaposition of homologous chromosomes and also may dissolve unfavorable entanglements between non homologous chromosomes. To this end, telomeres (or pairing centers in worm) are tethered to the nuclear envelope (NE) and assemble a conserved transmembrane-protein complex, the LINC-complex (Linker of Nucleoskeleton and Cytoskeletone). The LINC-complex is connected to the cytoskeleton via actin cables in S. cerevisiae and microtubules (MTs) in S. pombe and C. elegans, which then facilitates telomere (or pairing center) mediated chromosome movements along the NE , , , , , , , , , , . In mammals, early studies reported the characteristic rotational movements of spermatocyte nuclei in rodent species , , . The rotary movements observed in mammalian meiosis had been thought to be the consequence of telomere movements along the NE, as is the case in lower eukaryotes. Indeed, later studies clarified the requirement of the mammalian LINC-complex protein, SUN1, for normal meiotic progressions in mice .
In a previous study, we established an efficient DNA electroporation (EP) technique for live mouse testis, which enables rapid genetic manipulations for spermatocytes without the need for genetically engineered mice . 3D time-lapse imaging of pachytene mouse spermatocytes, with visualizations of axial elements and telomeres by EPs of GFP-Scp3 and GFP-Trf1 transgenes respectively, not only confirmed the rotary nuclear movements, but also, for the first time, characterized the concomitant rapid telomere movements on the NE . These superimposed-types of chromosome movements depend totally on MT polymerization activities and also the accumulation of the mammalian LINC-complex, SUN1-KASH5, to the telomeres under the regulation of a meiosis-specific telomere binding protein, TERB1 , . These results highlight the existence of dynamic chromosome movements driven by telomeres in mammalian meiosis as well, while their mechanical and molecular properties, or stage-specific properties, remain largely unclear.
In this study, we optimized the EP conditions and used them to dissect chromosome and microtubule organizing centers (MTOCs) movements in each meiotic sub-stage, leptotene/zygotene, bouquet, pachytene and diplotene. Further, we reveal that two cytoskeletal elements, MTs and actin, play different roles in meiotic nuclear dynamics. A combination of live-imaging and fixed cell observations provides insights into MT and MTOC dynamics for the regulation of rapid chromosome movements, supplying the mechanical scheme for chromosome movements during meiotic prophase I in mammals.
We have recently established an efficient DNA EP method for live mouse testes (Fig. 1A; detailed procedures in S1, S2 Figures) , . To optimize the EP efficiency, testes from mice of various ages, 17, 30 and 60 dpp (day post-partum), were subjected to EP of a Green Fluorescent Protein (GFP) expression vector harboring the full-length cDNA of SYCE3 (synaptonemal complex central element) (Fig. 1BโD) . The majority of germ cells underwent the first wave of spermatogenesis at 17 dpp, and completed meiosis at 30 dpp and spermatogenesis at 60 dpp (Fig. 1C). We obtained reproducibly high EP efficiencies at 17 dpp (31%) and 30 dpp (22%), but not at 60 dpp (3.5%), although the profiles of the sub-stage distribution of meiotic prophase cells were similar at each point (Fig. 1D). We could detect GFP-SYCE3 expression not only in spermatocytes, but also in mitotic and haploid cells (spermatogonia, round and elongated spermatids) as seen in histological sections of testes after EPs (S3 Figure). Transgene expression was increased when the lag time between DNA injection and EP was lengthened to at least 60 min (Fig. 1E). Further, transgene expression was detected as early as 6 hr after EP, and had already peaked at 12 hr (Fig. 1F). Finally, we noticed that the efficiency of transgene expression estimated by immunofluorescence (IF) largely depends on the DNA concentration used for injection, with 5 ยตg being close to saturation (Fig. 1G). Thus, we optimized the in vivo EP method applicable for shot-term transgene expression into mouse testes.
Fig. 1. Optimization of EP procedures.
A, Diagram of in vivo EP procedures for mouse testis highlighting the injection of a DNA solution into the rete testis and the application of an electric pulse. Detailed procedures are shown in S1, S2 Figures. B, Testes from mice of the indicated postnatal ages. The volume of DNA solution and the voltage of the electric pulse are indicated. C, Progression of spermatogenesis analyzed by flow cytometry. Peaks correspond roughly to mitotic cells (2n), spermatocytes (4n) and post-meiotic haploid cells (1n). D, The average GFP-SYCE3 expression efficiencies in testes from mice of the indicated ages. GFP positive cells were counted among the SCP1 positive cell populations (>1000 cells). The right graph indicates the distribution of prophase I sub-stages within testis cell suspensions from mice of the indicated ages. nโ=โ248 (17 dpp), 330 (30 dpp) and 306 cells (60 dpp). The sub-stages are defined by SCP3 and SCP1 stainings. Lep, leptotene; Zyg, zygotene; Pac, pachytene; Dip, diplotene; M I, metaphase I. E, The average GFP-SYCE3 expression efficiencies after EP with various lag times between injection and electroporation examined as in D. Mice aged 17 dpp were used. F, The average GFP-SYCE3 expression efficiencies at various time points after EP. Mice aged 17 dpp were used. G, The localizations of GFP fusion proteins expressed by in vivo EP. Testis cell suspensions were stained with SCP3 (for MIS12, KASH5, SCP3 and RAD21L) or SCP1 (for SYCE3) in red, GFP in green and DAPI in blue. The graph shows the average GFP expression efficiencies as examined by immunofluorescence at the indicated DNA concentrations. GFP positive cells were counted among the SCP3 (for MIS12, KASH5, SCP3 and RAD21L) or SCP1 (for SYCE3) positive cell populations (>1000 cells). Mice aged 17 dpp were used. H, Western-blotting analysis of testis extracts after EP (17 dpp). Asterisks indicate the specific bands corresponding to each fusion protein. ฮฑ-Tubulin and REC8 were the loading controls. I, Spermatocytes showing diffusive GFP-SCP3 signals stained for SCP3 (red), GFP (green) and DAPI (blue). Each column represents the average of three independent experiments; error bars represent S.E.M. Statistical significance (TTEST, two-tailed) was assessed (*P<0.05, **P<0.005, ***P<0.0005). Bars, 5 ยตm (unless otherwise indicated).
To explore the variation in the EP efficiencies of several proteins, we further examined MIS12 (kinetochore), KASH5 (telomere/NE), SCP3 (axial element) and RAD21L (cohesin/axial element), and compared the results with those of SYCE3 , , , , , , , . As a result, GFP signals for each protein were detected on specific chromosomal parts as endogenous proteins (Fig. 1G), although the efficiencies varied among the inserted genes. To explore this variation, transgene expressions were analyzed by Western blot (WB) (Fig. 1H). Consistent with the results of IF, expressions of GFP-SYCE3 and MIS12 were detected by WB. In contrast, GFP-RAD21L expression was hardly detectable by either WB or IF, suggesting the protein expression/stability is rate-limiting in this case. The expression of GFP-SCP3, however, was comparable to that of GFP-MIS12 in WB, while the IF of GFP-SCP3 was much weaker. A number of cells with nucleoplasmic GFP-SCP3 signals without axial element localization were observed (Fig. 1I), suggesting that the turnover efficiencies of endogenous proteins might also be important for proper localization. Collectively, these data suggest that in vivo EP is applicable for various transgenes, and that the expression efficiency varies dependent, most likely, on protein stability and turnover.
We next examined the functionality of the transgenes in testis. The inner nuclear membrane protein SUN1 is required for the nuclear peripheral distribution of meiotic telomeres, and the disruption of Sun1 prevents homologous pairing/synapsis due to the loss of meiotic chromosome movements , . We confirmed that telomeres, represented by TRF1 foci, were partly detached from the NE in spermatocytes from Sun1โ/โ mice (15 internal telomeres/cell) (Fig. 2A). Strikingly, the exogenous expression of SUN1-MYC protein by in vivo EP largely restored the telomere attachment defects in Sun1โ/โ testes (1โ2 internal telomeres/cell) (Fig. 2A).
Fig. 2. Complementation assay by in vivo EPs.
A, Equator images of Sun1โ/โ spermatocytes expressing GFP-SUN1 or SUN1-MYC stained for telomere TRF1 (green), GFP or MYC (blue) and SCP3 (red). The graph shows the number of internal telomeres (TRF1 foci) in wild type (zygotene to pachytene), Sun1โ/โ and Sun1โ/โ expressing exogenous SUN1 protein. B, Quantification of TRF1 foci number in wild type, Sun1โ/โ spermatocytes and Sun1โ/โ spermatocytes expressing exogenous SUN1 protein. C, Representative pictures of Sun1โ/โ spermatocytes or Sun1โ/โ spermatocytes expressing SUN1-MYC stained for SCP3 (red), SCP1 (green) and MYC (blue). The median numbers are shown in the graphs. Bars, 5 ยตm.
To assess the homolog pairing/synapsis states, we quantified the number of TRF1 foci in Sun1โ/โ spermatocytes. Theoretically, there are 80 and 40 TRF1 foci before and after homolog pairing/synapsis, respectively (the number of chromosome in mice is 2nโ=โ40). While WT spermatocytes gradually achieved homolog pairing/synapsis from leptotene to pachytene stage, Sun1โ/โ spermatocytes largely failed to complete homolog pairing/synapsis even in the proceeding zygotene-like stage (>70 TRF1 foci) (Fig. 2B). Again, the exogenous expression of the SUN1-MYC protein partly rescued the telomere-pairing defects of Sun1โ/โ spermatocytes (57 TRF1 foci) (Fig. 2B). Consistently, the subsequent homolog synapsis process, assessed by the loading of a synaptonemal complex protein SCP1, was also restored by the expression of the SUN1-MYC protein (Fig. 2C). We also performed complementation assays using another meiotic mutant mouse, Rad21lโ/โ, and confirmed that the expression of GFP-RAD21L restored the pairing/synapsis defects and telomere aggregation phenotypes observed in Rad21lโ/โ (S4 Figure) , . Notably, however, GFP-Sun1 EP failed to rescue Sun1โ/โ phenotypes at all, even though GFP-SUN1 itself successfully targeted to NE proximal telomeres (Fig. 2AโB). It is assumed that because the N-terminal domain of SUN1 interacts with telomeres through binding to TERB1 , the N terminus GFP-tagging of SUN1 might impair its meiotic functions. Collectively, complementation assays are useful to validate the functionality of tagged proteins and further molecular analysis in vivo.
To dissect the meiotic chromosome movements in live spermatocytes, we subjected simultaneous EPs of GFP-Scp3 and GFP-Trf1 transgenes to wild type testis (20 dpp) to visualize chromosome axes and telomeres, respectively, as we demonstrated in the previous study . At 24 hr after EPs, cell suspensions were diluted in Hoechst 33342-containing medium to visualize DNA, the cells were attached to the dishes with Cell-Tak (BD Bioscience) to avoid cell movements, and the cells were then subjected to time-lapse analysis. Consistent with our previous results, we can reproducibly observe the rapid movement of chromosomes within pachytene nuclei (Fig. 3A), that comprise two superimposed types of chromosome movement, random telomere movement and unidirectional rotation of the entire nucleus (rotation is highlighted with trajectories in Fig. 3A). Both of these movements were again significantly suppressed by the addition to the medium of nocodazole, an MT-destabilizing drug, (Fig. 3A, bottom, and S1, S2 Movies), confirming the previously established notion that meiotic chromosome movements in mammals depend totally on the MT polymerization activity, as is the case in S. pombe, C. elegans and perhaps some plant species, but not in S. cerevisiae , , , , .
Fig. 3. Visualization of stage-specific chromosome movement in live spermatocytes.
A, Time-lapse images (30 sec intervals) of pachytene spermatocytes (from 21 dpp male mouse testis) expressing GFP-TRF1 and GFP-SCP3 with or without nocodazole. Asterisks indicate identical heterochromatin. The trajectories indicate the movements of heterochromatin during the indicated time frame. Whole images are in S1, S2 Movies. B, Time-lapse images (14 sec intervals) of spermatocytes expressing GFP-TRF1 and GFP-SCP3. Leptotene/zygotene spermatocytes were from 14 dpp and pachytene to diplotene spermatocytes were from 21 dpp male mice. Asterisks indicate identical heterochromatin. The trajectories indicate the movements of heterochromatin during the indicated time frame. Whole images are in S5 Figure and S3, S4, S5 Movies. C, Equatorial images of time-lapse observations (7 sec intervals). Arrows indicate identical telomeres. Whole images are in S5 Figure and S3, S4, S5 Movies. D, Quantification of telomere velocities in various meiotic sub-stages. 5 telomeres were traced for 10 continuous time-points (7 sec intervals) for each cell (nโ=โ5 cells), and the 3-dimensional velocities for each time-point interval are plotted. The bars represent average values. Statistical significance (TTEST, two-tailed) was assessed (*P<0.0005). E, Trajectories of a telomere (time point 0:00โ3:30) overlaid on a projection of the final time points. F, Spermatocytes stained for SCP3 (blue), ฮณ-Tubulin (red) and SUN1 (green). Bars, 5 ยตm.
To examine the stage specific properties of chromosome movement throughout meiotic prophase I, we prepared spermatocytes from 14 dpp (dominantly in leptotene to zygotene) and 21 dpp (dominantly in pachytene to diplotene) male mice after subjecting them to GFP-Trf1 and GFP-Scp3 EPs. Because endogenous TRF1 and SCP3 were intact and spermatocytes expressing GFP-TRF1 and GFP-SCP3 developed normally at least until diplotene stage (see below), we reasoned that the transgenic spermatocytes might behave as wild-type. At 14 dpp, most of the GFP-positive spermatocytes showed faint chromosome axis signals (represented by GFP-SCP3) and more than 40 telomeres (represented by GFP-TRF1), suggesting that these spermatocytes are in leptotene/zygotene stages (Fig. 3B, top). In contrast, at 21 dpp, there are two types of GFP-positive spermatocytes. One showed about 40 GFP-TRF1 foci with intense GFP-SCP3 signals along the chromosome axes, corresponding to pachytene spermatocytes (Fig. 3B, middle), while the other showed GFP-SCP3 signals less on the chromosome axes (because of desynapsis) but more accumulated at the edge of chromosome axes, corresponding to diplotene spermatocytes (Fig. 3B, bottom). Diplotene spermatocytes are also distinguishable by their expanded and rather distorted nuclear shape compared to the earlier stage (Fig. 3B, bottom) (Whole images in S5 Figure and S3, S4, S5 Movies).
First, we observed overall chromosome movement by tracing pericentromeric heterochromatin, regions intensely stained by Hoechst 33342, and found the presence of unidirectional rotations not only in pachytene but also leptotene/zygotene spermatocytes (n>10 cells for each stages) (Fig. 3B, top and middle). In contrast, the rotary chromosome movements almost ceased in diplotene spermatocytes (n>10 cells) (Fig. 3B, bottom). Further detailed observations of time-lapse images taken at short intervals (7 sec intervals) allowed us to track identical GFP-TRF1 foci for several continuous time-points and to quantitatively calculate the 3-dimensional telomere velocities (Fig. 3C and S5 Figure and S3, S4, S5 Movie). As a result, it is estimated that the average velocities of telomeres are almost the same in leptotene/zygotene (0.12 ยตm/sec) and in pachytene (0.13 ยตm/sec) spermatocytes, while those in diplotene spermatocytes are drastically reduced (0.083 ยตm/sec) (Fig. 3D). The trajectories of GFP-TRF1 foci also confirmed the rapid telomere movement accompanying rotary motion in leptotene/zygotene and pachytene and its diminishment in diplotene stage (Fig. 3E). These observations suggest that both telomere movements and subsequent rotary chromosome movements persist throughout early meiotic prophase I, and are significantly down-regulated in diplotene spermatocytes. While an old observation of rat spermatocytes also hinted at the cessation of nuclear rotation in late prophase I , our results, with GFP-SCP3 and GFP-TRF1 EPs, have, for the first time, defined the precise meiotic sub-stages in live-cells, and verified that chromosome movements operate in a stage-specific manner.
To provide mechanistic insight into this phenomenon, we examined the spatiotemporal localization of SUN1 in fixed spermatocytes (Fig. 3F) because SUN1 accumulation to meiotic telomeres, regulated by TERB1, is essential for MT-dependent chromosome movements in mice , . As reported, SUN1 is accumulated to telomeres throughout meiotic prophase I as punctate signals. However, specifically in late pachytene to diplotene stages, SUN1 gradually diminishes from telomeres and aggregates on the nuclear surface. Notably, SUN1 aggregation always occurs near ฮณ-Tubulin signals, representing the position of the MTOC/centrosome (Fig. 3F). This SUN1 aggregation is sensitive to hypotonic and detergent treatments, suggesting it is chromatin-unbound unstable population. Thus, telomere-freed SUN1 might be polarized to the MT-minus end likely through the activity of minus end directed motors such as the dynein-dynactin complex. The down-regulation of telomeric SUN1 pools may explain the reduced chromosome movements observed in late meiotic prophase I in our time-lapse observation.
Our time-lapse imaging of diplotene spermatocytes showed that some chromosome ends accompanied intense GFP accumulations and formed clusters on pericentromeric heterochromatin, regions intensely stained by Hoechst 33342 (Fig. 3B bottom). These sites may correspond to centromeres, because previous fixed cell observations also reported the accumulation of SCP3 at short-arm ends, centromeres, and the inter-centromere connections in late diplotene stage , . In our case, spermatocytes express both GFP-SCP3 and GFP-TRF1, and mouse chromosome is telocentric, the intense GFP signals associating with heterochromatin in diplotene stage may compose both centromere-specific accumulation of GFP-SCP3 and the proximal short-arm GFP-TRF1 foci (hereafter we refer these signals as GFP-TRF1 for simplicity).
To dissect the different nature of short-arm and long-arm telomeres in diplotene stage, we traced a pair of GFP-TRF1 foci co-localizing with pericentromeric heterochromatin (at short-arm) and not co-localizing with pericentromeric heterochromatin (at long-arm) in the same diplotene cells (Fig. 4A). We found that these pairs of GFP-TRF1 foci move in coordination maintaining a distance within 4.5 ยตm, implying that these pairs of GFP-TRF1 foci correspond to telomeres of homologous chromosomes, which are physically connected by a chiasmata (Fig. 4A, B, C). The tracing of GFP-TRF1 foci revealed that a pair of heterochromatin-associated telomeres draws parallel trajectories while heterochromatin-unassociated telomeres draws rather disordered ones, suggesting that the heterochromatin-associated telomeres are more tightly connected and move in greater coordination than the heterochromatin-unassociated ones (Fig. 4A, B and original images in S5D and S6 Figures). The quantification of 3-dimensional distances between a pair of GFP-TRF1 foci further confirmed the stable and close association between heterochromatin-associated telomeres (<1 ยตm) and a rather loose association between heterochromatin-unassociated telomeres (<4.5 ยตm) (Fig. 4C). The tight association of telomeres on heterochromatin observed in our time-lapse imaging likely reflects the presence of the inter-centromere connection seen in fixed diplotene cells, which might facilitate the correct co-orientation of homolog centromeres and the subsequent disjunction of homologous chromosomes in anaphase I , .
Fig. 4. Inter-centromere connection observed in live-diplotene cells.
A, Diplotene spermatocytes (from 21 dpp male mouse testis) expressing GFP-TRF1 and GFP-SCP3 with the trajectories of pairs of telomeres shown by red and green (time 0:00โ3:30 min), overlaid on a projection of the first (0:00) and last (3:30) time points. The arrows indicate the pericentromeric heterochromatin, on which the marked short-arm telomeres are co-localized. Magnified images show the original images of marked pairs of telomeres. Whole images are in S5D Figure and S5 Movie. B, Trajectories of pairs of telomeres shown in A at the indicated time points. The original and overlaid images are shown in S6 Figure. C, The interpretation of long-arm and short-arm telomere dynamics in diplotene stage (top). Quantification of the 3D-distances between homolog telomeres throughout the time-lapse analysis in the cell shown in A (bottom). 3 pairs of telomeres (shown as blue, red and green) were traced for 3.5 minutes (7 sec intervals) for both long-arm and short-arm telomeres. The inter-telomere distances were calculated from the original 3-dimensional data for each time-points. Whole images are in S5D Figure and S5 Movie. Bars, 5 ยตm (unless otherwise indicated).
During the course of time-lapse imaging, telomeres and heterochromatin gathered in a limited region on the NE, forming a โbouquet-likeโ arrangement (Fig. 5A and S6 Movie). The mobilities of clustered telomeres were apparently diminished, while cluster-free telomeres still moved rapidly in the same cell (Fig. 5A, right) (S5B Figure and S8 Movie) suggesting that telomere movements are locally constrained. Further, the polarized asymmetric distribution of telomeres and heterochromatin in bouquet stage persists throughout the time-lapse analysis, suggesting that the overall rotational movement is also largely suppressed (Fig. 5A, S5B Figure and S6 and S8 Movies). These results contrast with those for S. pombe, in which all telomeres are clustered near the spindle pole body (SPB/centrosome) forming bouquet-like arrangements, and the entire nucleus moves rapidly accompanying the bouquet arrangements throughout meiotic prophase I , .
Fig. 5. Stable MTOCs positioning during rapid chromosome movements.
A, Time-lapse images (30 sec intervals) of spermatocytes (17 dpp) expressing GFP-TRF1 and GFP-SCP3 showing the โbouquet-likeโ configuration. Whole images are in S6 Movie. The graph shows the quantification of telomere velocities in bouquet stage (S5B Figure and S8 Movie). Three clustered and 10 cluster-free telomeres were traced for 10 continuous time-points, and the 3-dimensional velocities for each time-point interval are plotted. The bars represent average values. Statistical significance (TTEST, two-tailed) was assessed (*P<0.0005). B, Spermatocytes stained for SCP3 (blue), ฮณ-Tubulin (green) and TRF1 (red). C, Time-lapse images (30 sec intervals) of spermatocytes expressing GFP-ฮณ-Tubulin. Arrowheads indicate the positions of punctate GFP-ฮณ-Ttubulin. Asterisks indicate identical heterochromatin. Whole images are in S7 Movie. Bars, 5 ยตm.
To examine the spatiotemporal distribution of the mouse microtubule organizing center (MTOC)/centrosome, a cell organelle corresponding to yeast SPB, we carried out immunostaining for ฮณ-Tubulin using fixed spermatocyte samples. As a result, ฮณ-Tubulin appeared as punctate signals localizing to the cytoplasmic side of the nuclear periphery throughout meiotic prophase I and at spindle poles in metaphase I (Fig. 3F and Fig. 5B). In line with observations reported in other model systems , , , , but in contrast to an atypical case in S. pombe , telomeres appear to be randomly distributed on the NE regardless of ฮณ-Tubulin position and transiently assembled near the ฮณ-Tubulin signal only in bouquet stage (Fig. 5B). The abolishment of coordination between MTOC and telomere position in most stages, other than bouquet stage is likely for dynamic chromosome movements accompanying rotary movements of the entire nucleus.
In S. pombe, the movement of SPB/MTOC drives the chromosome movements throughout prophase I with accompanying drastic deformation of the entire nuclear shape. In contrast, a study in budding yeast visualized the stable positioning of SPB/MTOC during rapid chromosome movements .
To verify the mammalian case in which characteristic rotary movement of the whole nucleus dominates, we visualized MTOC in live pachytene spermatocytes by GFP-ฮณ-Tubulin EP to testes of 17 dpp mice. At 17 dpp, a majority of spermatocytes are in pachytene stage, showing clustered and peripherally distributed heterochromatin (Fig. 1D and Fig. 5C). By following identical heterochromatin during time-lapse imaging (asterisk in Fig. 5C), we traced the unidirectional rotation of chromosomes. GFP-ฮณ-Tubulin showed intense punctate signals at the nuclear surface as observed in fixed cells, suggesting that GFP-ฮณ-Tubulin assembles to the centrosome in the endogenous form (arrowhead in Fig. 5C). Clearly, the position of GFP-ฮณ-Tubulin remains fairly stable during rapid rotational movement of chromosomes (Fig. 5C and S7 Movie), suggesting that the rotational movement is not driven by MTOC movements themselves. This reinforces the aforementioned conclusion that the coordination between MTOC and telomeres is lost during rapid chromosome movements other than at bouquet stage.
Although the inhibition of MT polymerization by Nocodazole leads to the almost complete cessation of rapid chromosome movements in mouse spermatocytes (Fig. 3A), there remains a possibility that this is an indirect effect caused by the global destruction of cytoskeletal networks including that of actin followed by MT depolymerization. To address this possibility, we made the same time-lapse observations in the presence of cytochalasin D, an actin depolymerization drug, in the medium. As a result, in contrast to nocodazole addition, we still observed the rapid chromosome movements, including rotary motion of heterochromatin (Fig. 6A) and rapid telomere motion (Fig. 6B) even in the presence of cytochalasin D, suggesting that the rapid chromosome movements in mammals depends solely on MTs, but not actin (S9, S10, S11, S12 Movies).
Fig. 6. The different contributions of tubulin and actin to meiotic nuclear dynamics.
A, Time-lapse images (30 sec intervals) of pachytene spermatocytes (from 17 dpp male mouse testis) expressing GFP-TRF1 and GFP-SCP3 with DMSO, nocodazole, cytochalasin D or both. Asterisks indicate identical heterochromatin. The trajectories indicate the movements of heterochromatin during the indicated time frame. Whole images are in S9, S10, S11, S12 Movies. AT indicates the binary image of the DNA shape at any indicated time point. XOR (AT, AT+1) indicates the binary image of the change in nuclear shape between any indicated time point, AT and AT+1. B, Trajectories of a telomere (time point 0:00โ3:30) overlaid on a projection of the last time point. C, Quantification of the relative change in the nuclear area (XOR (AT, AT+1)/AT) (10 continuous time points from 5 independent cells for each culture condition). The bars represent average values. D, Histological sections of testes from 60 dpp male mice stained for SCP3 (red), phalloidin (green) and DNA (blue). The magnified pictures show zygotene and pachytene spermatocytes. E, Zygotene and pachytene spermatocytes stained for SCP3 (red), phalloidin (green) and DAPI (blue). Cells were prepared without hypotonic treatment and then fixed without Triton-X100. F, Pachytene spermatocyte stained for SCP3 (red), phalloidin (green) and DAPI (blue). Cells were prepared with mild hypotonic treatment and then fixed with 0.1%Triton-X100. Bars, 5 ยตm (unless otherwise indicated).
However, we noticed that the nuclear shape, as visualized by the 2D projective image of Hoechst 33342 signals, was oscillating during the time course even in the presence of nocodazole, but that this was largely suppressed in the presence of cytochalasin D (Fig. 6A). We captured this nuclear oscillation in a quantitative manner as followed: 1) convert the nuclear 2D projection into a binary image; 2) calculate the binary area at each time point (AT); 3) calculate the change in the binary area at each time (XOR (AT, AT+1)); 4) divide XOR (AT, AT+1) by AT. These quantifications represent the relative change in the nuclear area and demonstrate a drastic reduction in nuclear oscillation in the presence of cytochalasin D, less reduction in the presence of nocodazole, and the further synthetic reduction in the presence of both cytochalasin D and nocodazole, where both nuclear oscillation and rapid chromosome movements are lost (Fig. 6C). These data suggest that actin is required for the oscillation of nuclear shape, but not for the rapid chromosome movements driven by telomeres, for which MTs are largely responsible.
We then examined the localization of actin in mouse testis. Fluorescently labeled phalloidin, a chemical that binds specifically to fibrous actin (F-actin), demonstrated F-actin localization on the cell cortex uniformly in zygotene and in a rather polarized manner in pachytene spermatocytes in testis histological sections (Fig. 6D). Staining spread spermatocytes confirmed the same F-actin localization patterns on the cell cortex (Fig. 6E). After hypotonic and permeabilization treatments, a cloudy F-actin signal was also visible in the cytoplasm surrounding the nucleus (Fig. 6F). These actin structures might somehow regulate the oscillation of nuclear shape during meiotic chromosome movements (see Discussion).
To obtain mechanical insight into the MT structures responsible for the rapid chromosome movement in mammalian meiosis, we examined the distribution of ฮฑ-Tubulin by immunostaining fixed-pachytene spermatocytes. Under native staining conditions, ฮฑ-Tubulin was observed on the cell membrane as densely networked filaments (Fig. 7A, top). After hypotonic treatment and permeabilization with Triton-X100, we could observe ฮฑ-Tubulin filaments in the cytoplasm and also at the nuclear periphery (Fig. 7A, middle). In extensively permeabilized cells (see Materials and Methods), the cytoplasmic MTs were mostly washed out while the dense MT cables surrounding the NE remained (Fig. 7A, bottom). These dense MT cables were observed throughout meiotic prophase I (S7 Figure). Intriguingly, telomeres were frequently placed on this MT structure (Fig. 7B).
Fig. 7. MTs dynamics in spermatocytes.
A, Pachytene spermatocytes stained for SCP3 (red), ฮฑ-Tubulin (green) and DAPI (blue). Cells were prepared without hypotonic treatment and then fixed without Triton-X100 (-). Or, cells were prepared with mild (mild extraction) or severe (severe extraction) hypotonic treatment and then fixed in Triton-X100. B, Single sections of spermatocytes near the nuclear periphery stained for TRF1 (red), ฮฑTubulin (green) and SCP3 (blue). Arrows indicate TRF1 signals on the MT cables. The graph indicates the average ratio of TRF1 foci on the nuclear periphery, which localize on the MT cables (379 telomeres from nโ=โ15 zygotene cells for WT and 536 telomeres from nโ=โ21 zygotene-like cells for Sun1โ/โ). Error bars represent the S.D. Statistical significance (TTEST, two-tailed) was assessed (*P<0.0005). C, Schematic images of meiotic chromosome movement in mammals. Bars, 5 ยตm.
Since SUN1 is required for the stable association between telomeres and the NE (Fig. 2) and the accumulation of MT-dependent cytoplasmic motors to meiotic telomeres , , we hypothesized that the telomere/MT cable interaction might also be mediated by SUN1. To test this possibility, we examined the distribution of MTs and telomeres in Sun1โ/โ spermatocytes. Although the cable-like MT structures were present in Sun1โ/โ spermatocytes as in wild type spermatocytes and a portion of the telomeres still located on the NE, the colocalization of telomeres and MT cables was detectably impaired in the absence of SUN1 (74% in WT and 45% in Sun1โ/โ, Fig. 7B). These data suggest that the rapid chromosome movements during meiotic prophase are mediated by the rail tracking movement of telomeres along MT cables, and that they are connected in part by SUN1 (Fig. 7C).
The development of mammalian meiocytes requires the help of supporting somatic cells so that, if meiocytes are isolated, it is technically difficult to culture them long term in vitro , . Most genetic manipulations are suitable for cultured cells and not easily applicable to tissues in vivo because manipulations in tissues require laborious processes, namely, raising genetically engineered mice as done in the current convention. In other biological fields such as neuroscience, however, in vivo gene expression systems by electroporation (EP) have been established, and these work as powerful tools for in vivo genetic analysis . In the field of mammalian meiosis, there are a few reports of success in reporter GFP expression, but this expression has never been applied to any practical analysis because of its low efficiency , .
To overcome these difficulties, we have established a highly efficient DNA EP method for live mouse testis , . In this study, we further optimized EP efficiency (Fig. 1 and S1, S2 Figures), and succeeded in demonstrating the short-term expressions of various transgenes, such as GFP-SYCE3, MIS12, KASH5, SCP3 and RAD21L, all of which localize to specific chromosomal parts as endogenous proteins. Our comprehensive assays suggest that DNA concentration, mouse age, and the lag time from DNA injection to EP are critical factors for efficient transgene expression (Fig. 1). We also demonstrate that transgenes are, in principle, sufficiently functional (Fig. 2 and S4 Figures), suggesting that the EP technique is useful for molecular analysis in vivo.
The regulation of chromosome movements in prophase I is one of the most intriguing aspects of meiosis. For the sake of physical access to the correct homolog partners, meiotic chromosomes tethered to the NE through telomeres (or pairing centers in nematodes) move rapidly along the NE. The responsible driving forces are diverse among organisms, such as actin in S. cerevisiae, and MTs in S. pombe, C. elegans and probably plants , , , , . Recent studies in mice demonstrated that MTs are responsible for telomere-driven chromosome movement, although the mechanical properties have been poorly understood , , .
Here, we applied an in vivo electroporation technique to visualize and comprehensively dissect chromosome movements in different sub-stages during meiotic prophase I in mice (Fig. 3). We defined leptotene/zygotene, pachytene and diplotene spermatocytes according to GFP-TRF1 and GFP-SCP3 signals in live spermatocytes. Our assays reveal that the rapid chromosome movements that accompany random telomere motion and unidirectional chromosome movement persist through leptotene/zygotene to pachytene, and then diminish in diplotene spermatocytes. This observation is consistent with the earlier findings, which depicted rotational motion of rat spermatocytes and its cessation in late prophase , , . Our current study goes beyond the previous studies by precisely defining meiotic sub-stages in live cells according to GFP-TRF1 and GFP-SCP3 signals, and quantitatively determining telomere motions by tracing GFP-TRF1 signals.
Further, we discovered the gradual liberation of the SUN1 protein from telomeres in late prophase, which might explain the reduction in chromosome movements in this stage (Fig. 3F). It is reported that the telomere localization of the meiosis-specific telomere binding protein TERB1, which is responsible for SUN1 accumulation at telomeres, is down-regulated as well during diplotene, presumably by CDK1-Cyclin B dependent phosphorylation . Thus, the temporal release of SUN1 from meiotic telomeres during diplotene might be the consequence of the loss of TERB1 from the telomeres. Notably, also in C.elegans, chromosome movements drastically decline in late prophase concomitant with the dispersal of the SUN-1 protein from pairing centers, uncovering the conserved molecular regulations defining the stage-specific properties of chromosome movements in different eukaryotic species .
In the diplotene stage, homologous chromosomes are physically connected by chiasmata, and the large chromosomal arm regions, including telomeres at long-arms, lose their tight association mediated by the synaptonemal complex. However, earlier studies using fixed cells found that centromeric regions are tightly connected even in late diplotene stage, suggesting there might be some chiasmata-independent homolog associations at centromeres in this stage , .
In the current study, we carried out time-lapse imaging of diplotene cells to show that the homolog telomeres at short-arms are more tightly connected and move with greater coordination than at long-arms reflecting the presence of inter-centromere connections in live-cells as well (Fig. 4). Furthermore, our time-lapse imaging also implies that there might be physical connections between pericentromeric heterochromatin because the short-arm telomeres form several clusters on pericentromeric heterochromatin, and these clusters also seems to move in coordination.
The molecular mechanism of the inter-centromere connection remains controversial. Because a portion of the synaptonemal complex is retained specifically at centromeres even after desynapsis in early diplotene stage, the synaptonemal complex may play a role , . However, because the synaptonemal complex is finally dissociated, if not completely, from centromeres in late-diplotene stage, concomitant with the gradual accumulation of axial elements (SCP3) at centromeres, there might be some unknown mechanism to keep homolog centromeres together in this stage.
Our time-lapse observations of pachytene spermatocytes revealed unexpected outputs following the inhibition of actin polymerization during chromosome movement (Fig. 6). Our data suggest that the rapid chromosome movement is essentially regulated by MTs, but that actin also contributes to the oscillation of nuclear shape during movement. Indeed, our cytological observations of testis sections and spread cells identified F-actin localization on both the cell cortex and around the nucleus of spermatocytes; probably either structure or both is responsible for actin-dependent nuclear shape oscillations. Notably, the analogous phenomenon, the reduction in nuclear shape change after actin depolymerization during meiotic chromosome movement, was also found in S. cerevisiae, although in this case the shape change might be an indirect consequence of the reduction in telomere-mediated chromosome movements, which is also under the regulation of actin in this model system , . Though we cannot address the role of actin mediated nuclear oscillation in meiotic progression or chromosomal regulation in this study, further detailed dissection of chromosome movements or analysis of the terminal meiotic phenotype after actin depolymerization will answer this question in the future.
Our cytological observations further confirmed that the positions of MTOC and telomeres are mostly irrelevant, and that they are in transient juxtaposition on the nuclear surface only during the bouquet stage (Fig. 5), which might be a general feature of eukaryotic meiosis other than an atypical case reported in S. pombe , . Because the dynein-dynactin complex localizes to meiotic telomeres in a SUN1-KASH5 dependent manner , , , dynein-dynactin dependent telomere movement toward the minus-end of MTs might drive the transient juxtaposition of telomeres and MTOC in the bouquet stage. However, since the dynein-dynactin complex continuously localizes to meiotic telomeres throughout prophase I, it is still unclear how telomeres are gathered to the MTOC only in the bouquet stage and then released thereafter. It is plausible that counteracting motors, such as MT plus-end directed motors, might also regulate the prophase chromosome movements as in S. pombe , and that the temporal changes in the force balances between these counteracting motors may define the stage specific distribution of meiotic telomeres and chromosome movements. Also, the contribution of the chromosome axis, SCP3, to the proper exit from bouquet stage is implicated . It is also noteworthy that a transient bouquet configuration has also been observed in plant meiosis where a defined MTOC โcentrosomeโ is absent. Probably, alternative regulations may ensure the bouquet formation without centrosomes, such as the temporal polarization and clustering of multiple MTOCs or the asymmetric redistributions of the NE component as discussed extensively in previous studies , , , .
Our live-observations, combined with GFP-ฮณ-Tubulin EP, further demonstrate that the position of GFP-ฮณ-Tubulin (MTOC) remains stable even during rapid rotational chromosome movement in pachytene spermatocytes (Fig. 5C). This observation is in line with the case in budding yeast, where a fluorescent-tagged SPB component, SPC42, shows stable positioning during the chromosome movements . Our assays further reveal that MTs are densely located on the nuclear surface as a cable-like fibrous structure, and that telomeres are frequently placed on the MT cables in a partially SUN1-dependent manner, suggesting that the dynamic chromosome movements are produced by a rail-racking mechanism (Fig. 7). The presence of MT around meiotic nuclei and the MT organizing activity on the NE surface have also been reported in plants , , , although the cable-like structures were not observed in these reports. In budding yeast, actin instead of MTs forms an intense cable-like structure surrounding meiotic nuclei . These issues implicate the analogous reformations of cytoskeletal networks taking place on the NE for meiotic chromosome movements in multiple eukaryotic species.
Collectively, our results obtained using a cutting-edge EPs technique describe for the first time prophase chromosome movements and their responsible cytoskeletal structures comprehensively in mammals, and show that these largely fit the general models observed in a variety of eukaryotic species (Fig. 7C).
Animal experiments were approved by the Institutional Animal Care and Use Committee (approval #2512, #2608).
The following antibodies were used: rabbit polyclonal antibodies against GFP (Invitrogen), SCP1 (Abcam), SCP3 (Abcam), ฮฑ-Tubulin (Abcam) and ฮณ-Tubulin (Abcam); mouse polyclonal antibodies against MYC (MBL), SCP3, TRF1, SCP1 ; and rat polyclonal antibody against SCP3 . F-actin was stained by phalloidin (life technologies; A12379).
Plasmid DNAs (CAG or CMV promoter) were extracted from E. coli DH5a by alkaline lysis (MAXI-KIT; QIAGEN) and solubilized in HBS buffer (2% HEPES, 0.8% NaCl, 5 mM KCl, 0.7 mM Na2HPO4, 0.1% glucose). For efficient electroporation, we prepared a 5 ยตg/ยตl DNA solution, which was stored until use at โ80ยฐC. For injection (testis from 17 dpp ICR mice), 9 ยตl of DNA solution was mixed with 1 ยตl of 0.1% FastGREEN (SIGMA: #F7258).
Glass capillaries (NARISHIGE: Model GD-1, 1ร90 mm 500 pcs) (S1A Figure) were heated and pulled under gravity with a PC-10 puller (NARISHIGE) (S1B Figure). To obtain the appropriate sharpness, the tip of the glass capillary was cut (S1C Figure). The appropriate sharpness was about 0.05โ0.1 mm (S1 Figure).
Male mice of various ages were anesthetized by an intraperitoneal injection of 0.5% pentobarbital sodium salt solution (NACALAI #26427-14) (S2A Figure). The solution was stored at room temperature. The appropriate volume of 0.5% pentobarbital sodium salt solution was experimentally estimated to be 12 ยตl/weight (g). Mice were anesthetized for 1 to 5 hr depending on age.
The testes of male mice under anesthesia were pulled from the abdominal cavity (S2B Figure). 9 ยตl of plasmid DNA solution (5 ยตg/ยตl) was injected into the rete testis using a mouth pipette equipped with a glass capillary by breath pressure under a stereomicroscope (Leica; M165C) (S2C-D Figure). 1 hr after injection, the testes were held between a pair of tweezer-type electrodes (BEX: LF650P5) (S2E Figure), and electric pulses were applied four times, and then four times in the reverse direction at 30 V for 50 ms at 950 ms intervals per pulse using an electroporator (BEX: CUY 21 EDIY-TYPE) (S2F Figure). The testes were then returned to the abdominal cavity, and the abdominal wall and skin were closed with sutures. Immunostaining or time lapse analysis was performed 24 hr after electroporation. In complementation assays using Sun1โ/โ and Rad21lโ/โ mice, immunostaining was performed 72 hr after electroporation.
For live-imaging of spermatocytes, pCAG-GFP plasmids harboring ฮณ-Tubulin cDNA or a mixture of pCAG-GFP plasmids harboring Trf1 cDNA and Scp3 cDNA were electroporated into wild type testes. After 24 hr, GFP-positive cells were imaged in phenol red-free Leibovitz's L-15 medium (Gibco) supplemented with 400 ng/ml Hoechst 33342 (Wako Chemicals USA) at 33ยฐC with or without 5 ยตM nocodazole and 10 ยตM cytochalasin D. To avoid rotation of the spermatocytes in the medium, dishes were pre-treated with Cell-Tak (BD Biosciences) for 30 min before cell spread. Exposures of 0.15 sec (for GFP) and 0.025 sec (for Hoechst 33342) were acquired every 30 or 7 sec using a 100ร NA 1.40 objective on a microscope (Olympus lV-X71 Delta Vision). Stacks of 7โ12 optical sections with 1 ยตm spacing were acquired. The nuclear area and the telomere-trajectory were analyzed using ImageJ software.
Immunostaining of chromosome spreads from spermatocytes was performed based on a previous study with modifications . Briefly, testes were incubated in trypsin-EDTA solution at 37ยฐC for 15 min, and washed briefly in PBS. The trypsinized testes were pipetted repeatedly and centrifuged. The cell pellets were washed several times with PBS. For native staining conditions (Fig. 6E and Fig. 7A top), cells were fixed by adding the same volume of fixation buffer (1% PFA). For mild extraction (Fig. 6F and Fig. 7A middle), cells were suspended in hypotonic buffer (30 mM Tris PH 7.5, 17 mM Tris Sodium Citrate, 5 mM EDTA, 50 mM Sucrose) for 5 min at room temperature and then fixed by adding the same volume of fixation buffer with detergent (1% PFA, with 0.1% Triton X-100). For more severe extraction (Fig. 7A bottom, Fig. 7B and S7 Figure), the former hypotonically-treated cells were sedimented and then suspended sequentially in alternative hypotonic buffer (200 mM Sucrose) for 5 min at room temperature, and then fixed by adding the same volume of fixation buffer with detergent. The fixed cell suspensions were placed on slides and air-dried. For immunostaining, the slides were incubated with primary antibodies in PBS containing 3% BSA for 2 hr, and then with Alexa Fluor 488, 568, 647 (Invitrogen) secondary antibodies (1โถ1,000 dilution) for 1 hr at room temperature. The slides were washed with PBS, and mounted using VECTASHIELD medium with DAPI (Vector Laboratories).
Testes were scraped and digested with 100 ยตg/ml collagenase and 100 ยตg/ml DNase I for 15 min at 37ยฐC, and then filtered through a 40 ยตm cell strainer (FALCON). The testicular cells were fixed in 70% ethanol and brought to a concentration of 1โ2ร106 cells/ml in propidium iodide/RNase solution (BD Biosciences 550825). Cells were analyzed by a Becton, Dickinson (Rutherford, NJ) FACSort instrument equipped with an argon laser.
Images were taken on a microscope (Olympus IL-X71 Delta Vision; Applied Precision) equipped with 100รNA 1.40 and 60รNA 1.42 objectives, a camera (CoolSNAP HQ; Photometrics), and softWoRx 5.5.5 acquisition software (Delta Vision). Acquired images were processed with Photoshop (Adobe).
1. HiraokaY, DernburgAF (2009) The SUN rises on meiotic chromosome dynamics. Dev Cell 17: 598โ605.
2. KoszulR, KlecknerN (2009) Dynamic chromosome movements during meiosis: a way to eliminate unwanted connections? Trends Cell Biol 19: 716โ724.
3. ChikashigeY, TsutsumiC, YamaneM, OkamasaK, HaraguchiT, et al. (2006) Meiotic proteins bqt1 and bqt2 tether telomeres to form the bouquet arrangement of chromosomes. Cell 125: 59โ69.
4. WanatJJ, KimKP, KoszulR, ZandersS, WeinerB, et al. (2008) Csm4, in collaboration with Ndj1, mediates telomere-led chromosome dynamics and recombination during yeast meiosis. PLoS Genet 4: e1000188.
5. Trelles-StickenE, AdelfalkC, LoidlJ, ScherthanH (2005) Meiotic telomere clustering requires actin for its formation and cohesin for its resolution. J Cell Biol 170: 213โ223.
6. ConradMN, LeeCY, ChaoG, ShinoharaM, KosakaH, et al. (2008) Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination. Cell 133: 1175โ1187.
7. JosephI, JiaD, LustigAJ (2005) Ndj1p-dependent epigenetic resetting of telomere size in yeast meiosis. Curr Biol 15: 231โ237.
8. KosakaH, ShinoharaM, ShinoharaA (2008) Csm4-dependent telomere movement on nuclear envelope promotes meiotic recombination. PLoS Genet 4: e1000196.
9. PenknerA, TangL, NovatchkovaM, LadurnerM, FridkinA, et al. (2007) The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. elegans meiosis. Dev Cell 12: 873โ885.
10. PenknerAM, FridkinA, GloggnitzerJ, BaudrimontA, MachacekT, et al. (2009) Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1. Cell 139: 920โ933.
11. BaudrimontA, PenknerA, WoglarA, MachacekT, WegrostekC, et al. (2010) Leptotene/zygotene chromosome movement via the SUN/KASH protein bridge in Caenorhabditis elegans. PLoS Genet 6: e1001219.
12. WynneDJ, RogO, CarltonPM, DernburgAF (2012) Dynein-dependent processive chromosome motions promote homologous pairing in C. elegans meiosis. J Cell Biol 196: 47โ64.
13. SatoA, IsaacB, PhillipsCM, RilloR, CarltonPM, et al. (2009) Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell 139: 907โ919.
14. YaoKT, EllingsonDJ (1969) Observations on nuclear rotation and oscillation in Chinese hamster germinal cells in vitro. Exp Cell Res 55: 39โ42.
15. EllingsonDJ, YaoKT (1970) Growth and observations of Chinese hamster seminiferous epithelium in vitro. J Cell Sci 6: 195โ205.
16. ParvinenM, SoderstromKO (1976) Chromosome rotation and formation of synapsis. Nature 260: 534โ535.
17. DingX, XuR, YuJ, XuT, ZhuangY, et al. (2007) SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev Cell 12: 863โ872.
18. MorimotoA, ShibuyaH, ZhuX, KimJ, IshiguroK, et al. (2012) A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis. J Cell Biol 198: 165โ172.
19. ShibuyaH, IshiguroK, WatanabeY (2014) The TRF1-binding protein TERB1 promotes chromosome movement and telomere rigidity in meiosis. Nat Cell Biol 16: 145โ156.
20. ShibuyaH, WatanabeY (2014) The meiosis-specific modification of mammalian telomeres. Cell Cycle 13: 2024โ8.
21. SchrammS, FrauneJ, NaumannR, Hernandez-HernandezA, HoogC, et al. (2011) A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet 7: e1002088.
22. GoshimaG, KiyomitsuT, YodaK, YanagidaM (2003) Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J Cell Biol 160: 25โ39.
23. PolakovaS, CipakL, GreganJ (2011) RAD21L is a novel kleisin subunit of the cohesin complex. Cell Cycle 10: 1892โ1893.
24. LeeJ, HiranoT (2011) RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis. J Cell Biol 192: 263โ276.
25. HerranY, Gutierrez-CaballeroC, Sanchez-MartinM, HernandezT, VieraA, et al. (2011) The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility. EMBO J 30: 3091โ3105.
26. Gutierrez-CaballeroC, HerranY, Sanchez-MartinM, SujaJA, BarberoJL, et al. (2011) Identification and molecular characterization of the mammalian alpha-kleisin RAD21L. Cell Cycle 10: 1477โ1487.
27. YuanL, LiuJG, ZhaoJ, BrundellE, DaneholtB, et al. (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5: 73โ83.
28. HornHF, KimDI, WrightGD, WongES, StewartCL, et al. (2013) A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. J Cell Biol 202: 1023โ1039.
29. IshiguroK, KimJ, ShibuyaH, Hernandez-HernandezA, SuzukiA, et al. (2014) Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes. Genes Dev 28: 594โ607.
30. SalonenK, ParankoJ, ParvinenM (1982) A colcemid-sensitive mechanism involved in regulation of chromosome movements during meiotic pairing. Chromosoma 85: 611โ618.
31. DingDQ, ChikashigeY, HaraguchiT, HiraokaY (1998) Oscillatory nuclear movement in fission yeast meiotic prophase is driven by astral microtubules, as revealed by continuous observation of chromosomes and microtubules in living cells. J Cell Sci 111 (Pt 6) 701โ712.
32. CowanCR, CandeWZ (2002) Meiotic telomere clustering is inhibited by colchicine but does not require cytoplasmic microtubules. J Cell Sci 115: 3747โ3756.
33. KoszulR, KimKP, PrentissM, KlecknerN, KameokaS (2008) Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope. Cell 133: 1188โ1201.
34. QiaoH, ChenJK, ReynoldsA, HoogC, PaddyM, et al. (2012) Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis. PLoS Genet 8: e1002790.
35. BisigCG, GuiraldelliMF, KouznetsovaA, ScherthanH, HoogC, et al. (2012) Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes. PLoS Genet 8: e1002701.
36. HarperL, GolubovskayaI, CandeWZ (2004) A bouquet of chromosomes. J Cell Sci 117: 4025โ4032.
37. ScherthanH (2001) A bouquet makes ends meet. Nat Rev Mol Cell Biol 2: 621โ627.
38. von WettsteinD (1984) The synaptonemal complex and genetic segregation. Symp Soc Exp Biol 38: 195โ231.
39. ZicklerD, KlecknerN (1998) The leptotene-zygotene transition of meiosis. Annu Rev Genet 32: 619โ697.
40. ZicklerD (2006) From early homologue recognition to synaptonemal complex formation. Chromosoma 115: 158โ174.
41. McKeeBD (2004) Homologous pairing and chromosome dynamics in meiosis and mitosis. Biochim Biophys Acta 1677: 165โ180.
42. Trelles-StickenE, DresserME, ScherthanH (2000) Meiotic telomere protein Ndj1p is required for meiosis-specific telomere distribution, bouquet formation and efficient homologue pairing. J Cell Biol 151: 95โ106.
43. MosesMJ (1969) Structure and function of the synaptonemal complex. Genetics 61: Suppl: 41โ51.
44. SatoT, KatagiriK, GohbaraA, InoueK, OgonukiN, et al. (2011) In vitro production of functional sperm in cultured neonatal mouse testes. Nature 471: 504โ507.
45. SatoT, KatagiriK, KubotaY, OgawaT (2013) In vitro sperm production from mouse spermatogonial stem cell lines using an organ culture method. Nat Protoc 8: 2098โ2104.
46. SaitoT (2006) In vivo electroporation in the embryonic mouse central nervous system. Nat Protoc 1: 1552โ1558.
47. MatsudaT, CepkoCL (2004) Electroporation and RNA interference in the rodent retina in vivo and in vitro. Proc Natl Acad Sci U S A 101: 16โ22.
48. ShojiM, ChumaS, YoshidaK, MoritaT, NakatsujiN (2005) RNA interference during spermatogenesis in mice. Dev Biol 282: 524โ534.
49. ScherthanH, WangH, AdelfalkC, WhiteEJ, CowanC, et al. (2007) Chromosome mobility during meiotic prophase in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 104: 16934โ16939.
50. YoshidaM, KatsuyamaS, TatehoK, NakamuraH, MiyoshiJ, et al. (2013) Microtubule-organizing center formation at telomeres induces meiotic telomere clustering. J Cell Biol 200: 385โ395.
51. LiebeB, AlsheimerM, HoogC, BenaventeR, ScherthanH (2004) Telomere attachment, meiotic chromosome condensation, pairing, and bouquet stage duration are modified in spermatocytes lacking axial elements. Mol Biol Cell 15: 827โ837.
52. CarltonPM, CowanCR, CandeWZ (2003) Directed motion of telomeres in the formation of the meiotic bouquet revealed by time course and simulation analysis. Mol Biol Cell 14: 2832โ2843.
53. BassHW, MarshallWF, SedatJW, AgardDA, CandeWZ (1997) Telomeres cluster de novo before the initiation of synapsis: a three-dimensional spatial analysis of telomere positions before and during meiotic prophase. J Cell Biol 137: 5โ18.
54. VantardM, LevilliersN, HillAM, AdoutteA, LambertAM (1990) Incorporation of Paramecium axonemal tubulin into higher plant cells reveals functional sites of microtubule assembly. Proc Natl Acad Sci U S A 87: 8825โ8829.
55. CowanCR, CarltonPM, CandeWZ (2002) Reorganization and polarization of the meiotic bouquet-stage cell can be uncoupled from telomere clustering. J Cell Sci 115: 3757โ3766.
56. PetersAH, PlugAW, van VugtMJ, de BoerP (1997) A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res 5: 66โ68. |
0.999621 | Do you know the Greek names of the Planets? The names of the planets are given by more or less famous astronomers who discovered them throughout the years.
The planets in our solar system got their names mostly from the Greek Mythology and the Roman nomenclature.
Here we will present the Greek names of the planets, as they were given by the ancient Greeks and modern astronomers.
There are also several astronomical terms with a Greek origin. For instance, the word Galaxy comes from the Greek Galaxias, the Greek name for Chaos is Haos, while the word planet comes from the Greek word Planitis.
We chose to present the planets according to their distance from the sun.
Helios is the Greek name of the Sun, the center of our solar system.
Gaia was the great mother of all, creator and giver of birth to the Earth and all the Universe, the heavenly gods, the Titans, and the Giants. The gods were born from her union with Uranus (the sky), while the sea-gods were born from her union with Pontus (the sea).
Ermis is the Greek name of the planet Mercury, which is the closest planet to the sun. It is named after the Greek God of commerce, Ermis or Hermes, who was also the messenger of the Ancient Greek gods.
Aphrodite is the Greek name of the planet Venus, which is named after Aphrodite, the goddess of Love.
Aris is the Greek name of the planet Mars, the fourth planet from the sun, also known as the Red planet. Aris or Ares was the Greek god of War.
Jupiter, the fifth planet from the sun, is the largest planet in our solar system. In Greek the name of the planet Jupiter is Dias, the Greek name of god Zeus.
Jupiter has many moons orbiting around the planet. The largest one is Ganymede and it is named after Ganymedes, the hero of the Greek mythology.
Saturn is the second largest planet of our system and the sixth planet from the sun. The Greek name of the planet Saturn is Kronos. The Titan Cronus was the father of Zeus, while Saturn was the Roman God of agriculture.
Ouranos is the Greek name of the planet Uranus, the seventh planet from the sun. This planet is named after the creator of the sky, God Uranus or Ouranos, which means sky in the Greek language. He was the father of Cronus and the Titans, as well as of the Cyclopes.
Neptune or Poseidon as is its Greek name, was the God of the Seas. It is the eight planet from the sun, and its predominant color is blue, which makes its name a rather excellent choice.
The god of the Underworld, Pluto or Pluton in Greek is the farthest planet from the sun and one of the least observed planets in our solar system.
Cerberus. The three headed dog โ guardian of the gates of the Underworld, known with the name Kerveros in Greek, is given to the large black spot on the surface of planet Mars.
On Mars, there is also the Olympus Mons, the largest volcano of the planet, referring to Mount Olympus or Olympos in Greek, the mountain of the gods in the Greek mythology.
Planet Venus also has its volcano, named Rhea Mons, after Rhea or Rea, the mother of Zeus, daughter of Uranus and Gaia.
i love it, Greek myth is my favorite thing to learn, but i though Apollo was the god of the sun?
Helios is the Greek name of the sun, but Apollo is the god of the sun.
its good want to learn more about greek mythology. i love to know more about greek history. i wanna know it in a beautiful way. |
0.968906 | Two men imprisoned in Canada are accused of playing a leadership role from behind bars in what American authorities are calling one of the world's most prolific fentanyl-trafficking and money-laundering operations.
The U.S. Justice Department says customers bought pure fentanyl and other dangerous drugs online directly from Chinese factories, and inexperienced users would overdose because they didn't realize the potency of the opioids.
``The investigations of Yan and Zhang revealed a new and disturbing facet of the opioid crisis in America: Fentanyl and fentanyl analogues are coming into the United States in numerous ways, including highly pure shipments of fentanyl from factories in China directly to U.S. customers who purchase it on the internet,'' the U.S. Justice Dept. said in a statement.
Federal agents were able to identify more than 100 distributors of synthetic opioids involved with Yan's networks, they said.
``Xiaobing Yan, Jian Zhang and their respective associates represent one of the most significant drug threats facing the country _ overseas organized crime groups capable of producing nearly any synthetic drug imaginable, including fentanyl, and who attempt to hide their tracks with web-based sales, international shipments and cryptocurrency transactions,'' said Robert Patterson, acting administrator of the U.S. Drug Enforcement Administration.
``To hide their financial transactions, co-conspirators used off-shore accounts, anonymous virtual currency transactions, and third parties to move money, as well as using encrypted communication applications to discuss financial transactions,'' the indictment states. |
0.999998 | Context: Why ELLs in Philadelphia?
On March 15, 2018, Philadelphia Superintendent Helen Gym held a roundtable with students in the Philadelphia public school district to find out from them what they saw as the biggest issues in their schools. She publicized this roundtable on Twitter, posting updates from the discussion using the hashtag #PHLedroundtable. Scrolling through this hashtag, there are several consistent themes that the students brought up. Among these was the lack of support for English Language Learners. The tweet below, among others, was a source of inspiration to undertake this project, which is why the photo from this tweet is featured in this websiteโs header image. The students of Philadelphia have spoken, and support for ELLs is a major issue that they are struggling with on a daily basis. My hope is that this website can give some insight into this issue and how it can be addressed.
Note: BCAs are Bilingual Counselor Assistants, support staff in schools who can help students and families with translating and navigating the school system. |
0.908416 | On June 11, 2008, On August 24, 2006, the International Astronomical Union (IAU) voted at the meeting of its Executive Committee to establish bright "dwarf planets beyond the orbit of Neptune as a new class of substellar objects in the Solar System called "plutoids" (IAU press release). According to the IAU, these plutoids "are celestial bodies in orbit around the Sun at a distance greater than that of Neptune that have sufficient mass for their self-gravity to overcome rigid body forces so that they assume a hydrostatic equilibrium (near-spherical) shape, and that have not cleared the neighbourhood around their orbit. Satellites of plutoids are not plutoids themselves, even if they are massive enough that their shape is dictated by self-gravity. The two known and named plutoids are Pluto and Eris [formerly 2003 UB313]." In addition, "it was decided that, for naming purposes, any Solar System body having (a) a semimajor axis greater than that of Neptune, and (b) an absolute magnitude brighter than H = +1 (magnitude will, for the purpose of naming, be considered to be a plutoid," so that many large and relatively round Edgeworth-Kuiper ice bodies may eventually be designated as plutoids, including 2004 XR190.
On August 24, 2006, the IAU voted to establish a new category of Solar System objects called "dwarf planets." 2003 XR190 is probably large enough to have a spherical shape and so is a candidate for IAU designation as a dwarf planet.
On December 13, 2005, a team of astronomers (led by Lynne Allen) announced the discovery of a new planetary body between one-fifth to one half the size of Pluto, found during routine operation of the Canada-France Ecliptic Plane Survey (CFEPS) as part of the Legacy Survey on the Canada France Hawaii Telescope (CFEPS press release). The object's brightness indicates that it is likely to be between 500 and 1,000 kilometers (300 to 600 miles) in diameter. Currently designated 2004 XR190 (or XR 190) but nicknamed "Buffy," the object takes about 440 years to move around the Sun at an average distance (semi-major axis) of 57.4 AUs in a relatively circular orbit (e=0.11) that is inclined about 46.7๏ฟฝ to the ecliptic. It is the first known object with a relatively circular but highly tilted orbit beyond Neptune and Pluto. This orbit is hard to explain using existing models of Edgeworth-Kuiper Belt formation (more technical details).
In late 2005, 2004 XR190's highly circular orbit was considered to be unusual for the icy objects found in the outer Solar System. At that time, only one other detected object, Sedna, remains further than 50 AUs from the Sun throughout its entire orbit. Moreover, Sedna has a highly eccentric orbit that takes inward as close as 76 AUs before moving back beyond 900 AUs. In contrast, Buffy stays in a comparative narrow orbital region between 52 and 62 AUs from the Sun. Although astronomers have detected other EKOs whose orbits lie mostly 50 AUs, these objects have very eccentric orbits, and almost all eventually move inward to within 38 AUs of the Sun, which place them within Neptune's gravitational reach and so these EKOs are generally thought to have been scattered out to their present orbits by a gravitational slingshot with Neptune to become part of the "Scattered Disk."
As of late 2005, only a few other EKOs were known to have orbits that stay mostly beyond 50 AUs. Unlike Scattered Disk objects, these EKOs do not move inward within Neptune's gravitational reach of Neptune but have named members of the "Extended Scattered Disk." Two of these objects (1995 TL8 and 2000 YW134) move inward to within to 40 AUs of the Sun but have fairly elliptical orbits that take them back out beyond 60 AUs.
ยฉ 2005-2008 Sol Company. All Rights Reserved. |
0.715457 | Native Americans of the St. Lawrence, Ohio, Mississippi, and Mohawk River valleys played an important role during the century of warfare from the 1680s to the 1780s, when the French, English, and Americans fought for control of North America. During the last great contest, the War for American Independence (1775โ1783), most Indian tribes allied with the English. This opposition to the American patriots was true of the Six Nations of the Iroquois. The Treaty of Paris of 1783 ending the war gave the new United States control of the region from the Appalachian Mountains to the Mississippi River, which included countless Indian villages and thousands of warriors. The new government of the United States organized under the Articles of Confederation gave Congress the power to make treaties with Indian nations. In 1784, Congress appointed Oliver Wolcott, Richard Butler, and Arthur Lee to negotiate a treaty with the defeated Cayuga, Seneca, Mohawk, Oneida, Tuscarora, and Onondaga tribes of upstate New York. The resulting treaty, signed by the American commissioners and representatives of the tribes, set forth the boundaries of the Indian nations, demanded Indian hostages be turned over to American authorities, and agreed to bring supplies to the beleaguered natives. This treaty, like many treaties before and after signed by the United States and North American Indian tribes, would be short-lived. War would again occur during the next ten years until the Indians were soundly defeated at Fallen Timbers in 1794.
See also Indian Treaties ; Iroquois .
Six hostages shall be immediately delivered to the commissioners by the said nations, to remain in possession of the United States, till all the prisoners, white and black, which were taken by the said Senecas, Mohawks, Onondagas and Cayugas, or by any of them, in the late war, from among the people of the United States, shall be delivered up.
A line shall be drawn, beginning at the mouth of a creek about four miles east of Niagara, called Oyonwayea, or Johnston's Landing-Place, upon the lake named by the Indians Oswego, and by us Ontario; from thence southerly in a direction always four miles east of the carrying-path, between Lake Erie and Ontario, to the mouth of Tehoseroron or Buffaloe Creek on Lake Erie; thence south to the north boundary of the state of Pennsylvania; thence west to the end of the said north boundary; thence south along the west boundary of the said state, to the river Ohio; the said line from the mouth of the Oyonwayea to the Ohio, shall be the western boundary of the lands of the Six Nations, so that the Six Nations shall and do yield to the United States, all claims to the country west of the said boundary, and then they shall be secured in the peaceful possession of the lands they inhabit east and north of the same, reserving only six miles square round the fort of Oswego, to the United States, for the support of the same.
The Commissioners of the United States, in consideration of the present circumstances of the Six Nations, and in execution of the humane and liberal views of the United States upon the signing of the above articles, will order goods to be delivered to the said Six Nations for their use and comfort.
SOURCE: "Treaty with the Six Nations, 1784." In Indian Treaties, 1778โ1883. Edited by Charles J. Kappler. Washington, DC: 1904.
"Treaty with the Six Nations (1784)." Dictionary of American History. . Encyclopedia.com. 24 Apr. 2019 <https://www.encyclopedia.com>. |
0.871668 | More than 40 high-level people have fled or been fired from the trump administration in its first year, and even more are headed for the exits. They know whatโs up. Heโs dirty. Heโs guilty. Thereโs no use in sticking around.
Writing a novel Joe? A couple of lines from a paper and the summary made up by yourself. Trump-sleuth โ go get him tiger.
Eyes wide open, Maureen, eyes wide open.
A trifecta of events had set him off in a way that two officials said they had not seen before: Hope Hicksโ testimony to lawmakers investigating Russiaโs interference in the 2016 election, conduct by his embattled attorney general and the treatment of his son-in-law by his chief of staff.
Trump, the two officials said, was angry and gunning for a fight, and he chose a trade war.
Unglued? Angry? Gunning for a fight? Thankfully he chose a trade war and not the big red nuclear buttonโฆ but what about the next time he becomes unstuck?
Itโs all blow, youโd do better following what heโs doing, rather than what โsourcesโ are saying about him. Trump is a ring master, and the clowns are frenzied.
Some ringmaster โ no amount of spin from his supporters changes the reality that trumpโs administration is in utter self-inflicted chaos. And if you seriously believe that trump is ring-masterly in his behaviour then youโre as deluded as Alan and David.
Hereโs some evidence of Russian collusion โ oops, the โevidenceโ is against the Democrats .. who would have thought?
you have to laugh reallyโฆโlaissez faireโ Capitalism,free trade ,transparency,accountability,integrity โฆ.all in ..tatters. |
0.999999 | Toulmin Outline for Classical ArgumentShopping at Wal-Mart is good for the consumerClaim: People should shop at Wal-MartReason: It domesticates the prices of basic commodities.Grounds: Evidence that Wal-Mart has numerous branches across the United States and offers a uniform set of prices in every branch[The standardized pricing scheme for products sold at Wal-Mart allows consumers to buy certain goods that are normally expensive in other stores.
]Warrant: People should exercise wise spending when shopping.Backing: Argument showing why practicality is an important reason.[The prices of domestically manufactured goods differ from those of goods manufactured in other places, thus, the wide array of goods and services sold by Wal-Mart allow consumers to purchase local and transported products in relatively similar prices: Thereby giving more variety to consumers.]Questioning the stated reason and grounds:The price domestication exercised by Wal-Mart marginalizes the consumer options. |
0.999674 | Most people who come in to see me have heard that student loans can't be discharged in bankruptcy. That's not quite right. Student loans can be forgiven in bankruptcy, but it is hard to do so. The bankruptcy law says that, unlike other types of debts, student loans can only be forgiven if the borrower can show the judge that it would be an "undue hardship" to pay them back. Most judges have set a very high standard; usually the borrower has to be disabled or unable to work. Your lawyer is best able to tell you if your situation gives you a shot at discharge. If it does, you sue the student loan lender during your bankruptcy case (the lawsuit is called an "adversary proceeding") and have a hearing in front of a judge.
Most people won't be able to do this, and so in those cases, it makes sense to think about repayment plans. If you have federal student loans, it's a good idea to look into consolidation and income-based repayment plans. |
0.948579 | How is your blog performing and what can you do to improve it?
One of the best ways of answering both of the above questions is to conduct a content audit on your blog. While it may not be the most appealing task out there, it is worth every second of your time. In this blog, I will be running you through the most important things you need to account for when it comes to auditing the content contained in your blog.
To figure out these numbers, you will likely need to use a combination of metrics software such as Google Analytics and some manual perusing through the actual blogs you're looking to assess the performance of. In terms of SEO measurements, software/programs like Moz, HubSpot or certain SEO-focused plugins can paint a picture of how well optimised the page is. While you can test a blog page's SEO via manual searches on Google to a certain degree, the results aren't as definitive and unambiguous as those provided by SEO software.
It's important to note that Google Analytics is free, whereas Moz and HubSpot do have subscription fees. While Moz is purely focused on SEO, HubSpot is a more extensive package comprising blogging, SEO, lead capturing and nurturing, email marketing, and social media marketing/listening. When you create your blog via the HubSpot platform, it will allow you to more easily measure all key performance indicators in terms of whether or not your blog is succeeding as desired.
How much of your blog do you want to audit? If you've been at it for a few years and have hundreds of blogs, doing a full audit of everything you've posted is going to take a considerable amount of time.
Not only will you need to look at every single blog individually (and list the name, URL and word count of each blog as a reference point), but then you'll have to factor in the above insights for each post. Is a specific blog helping you rank well for specific keywords, how much traffic does it have, does it bring in a desirable number of visitors, has anyone commented on it, where is the traffic to this blog coming from (did they find you via Google, social media, another website, etc.), is it a top perfoming blog post, does it have a good overall SEO score?
You have to do this for every single individual blog post you choose to audit. The good news is you can search specific pages via software like Google Analytics and HubSpot. The bad news, however, is that even when you do, there are plenty of other variables you'll need to adjust and account for.
While you may get the overview of pageviews in Google Analytics, it's a difficult task to actually associate which keywords people searched in Google to come across a particular page - let alone a blog page.
The important point is that collating all of this information is time-consuming and will require patience. So if you feel a full audit of every single blog you've ever posted would simply be too much, opt for a limited audit instead. This could be auditing a particular month that you found performed well for you. Auditing the blogs that were published during this time could give you an idea of what made that monthly stretch excel over others.
If you host your blog through something such as HubSpot, it's easier to see track your pageviews and the sources (including keywords).
You can also get an idea of how any blog is perfoming SEO-wise.
The findings you gain via your blog audit will allow you to make informed decisions about the future content you create and publish. For example, if you find blogs that focus on a specific topic tend to perform poorly (e.g. minimal views and sharing), then it may be best to turn your attention away from them.
Similarly, if you've found your SEO efforts are lacking on previous blogs, you should jump in and amend as many of these issues as possible to improve your search engine discoverability. And be sure to embrace these steps with every new blog you create.
Other variables, such as word count, can play a role in your blog's performance, too. Does yours benefit more when the word count is large or small? Craft future posts that adhere to the word count bracket that's earned you the best results in the past.
The reason a blog audit is so valuable is because every blog is different. What works for one blog may not necessarily work for yours. But taking the time out to conduct an audit (be it assessing every single blog or a sample of blogs throughout a specific time frame) grants you the ability to know what is and isn't working for yours, and you can refine your blogging efforts accordingly. |
0.99404 | The construction of a meaningful graph plays a crucial role in the success of many graph-based representations and algorithms for handling structured data, especially in the emerging field of graph signal processing. However, a meaningful graph is not always readily available from the data, nor easy to define depending on the application domain. In particular, it is often desirable in graph signal processing applications that a graph is chosen such that the data admit certain regularity or smoothness on the graph. In this paper, we address the problem of learning graph Laplacians, which is equivalent to learning graph topologies, such that the input data form graph signals with smooth variations on the resulting topology. To this end, we adopt a factor analysis model for the graph signals and impose a Gaussian probabilistic prior on the latent variables that control these signals. We show that the Gaussian prior leads to an efficient representation that favors the smoothness property of the graph signals. We then propose an algorithm for learning graphs that enforce such property and is based on minimizing the variations of the signals on the learned graph. Experiments on both synthetic and real world data demonstrate that the proposed graph learning framework can lead to efficiently inferring meaningful graph topologies from signal observations under the smoothness prior. |
0.989972 | Add this film to William H. Macy's ever-lengthening resumรฉ of sad sack roles. In The Cooler he plays Bernie, a character so down on his luck that it's actually contagious. Working in a Las Vegas casino, his services are called upon whenever a gambler hits a hot streak. Bernie pays the player a tableside visit and buys him a drink, or pats him on the shoulder, and the dice go cold, the cards turn mean and the house saves a pile of dough.
The plot gets going when Bernie informs casino owner Shelly Kaplow (Alec Baldwin) that, in one week's time, he's leaving town. Shelly doesn't want to lose his ace in the hole and employs new waitress Natalie (Maria Bello) to seduce Bernie and keep him in Vegas. Sure enough, Bernie falls for her and then she falls for him. And nobody in love can be unlucky. Now Bernie has somebody who wants to leave town with him and he's no longer souring the worldยs milk.
From here the story takes a couple of turns; fortune, which is what this movie is supposed to be about, slides from one character to the next, leading to a completely untenable conclusion in the desert.
Macy's very sympathetic, Bello conveys some mileage and Baldwin hefts good weight as the malevolent old school casino mobster. The plot's a little self-conscious and flabby but the characters are compelling enough to keep it from being painful. The idea of a realistic, magic film noir is appealing but, as The Cooler proves, it's not easy to pull off. |
0.958669 | Fantasy Football Mock Draft Pick 12 of 12 Teams I purposely chose the 12th pick of a 12 team, PPR league. I wanted to focus on strong wide receiver depth, then work on my running backs. Here are the results. 1.12 Brandon Marshall, Wide Receiver, Chicago Bears He's a no-brainer WR1 even with the emergence of Alshon Jeffery. 2.1 Julio Jones, Wide Receiver, Atlanta Falcons The best guys to get things done in Atlanta. He's a beast on the field, proving it last year with 41 catches in just five games. That would have put him on course for well over 100 receptions had he finished the season. 3.12 Bishop Sankey, Running Back, Tennessee Titans This might be risky, but Sankey looks to be the team's starter over weathered Shonn Greene. Coming off of 3,300-plus rushing yards at Washington, I'm impressed. 4.1 Ryan Mathews, Running Back, San Diego Chargers The Chargers saying they're going with Mathews as their starter, expected to receive the majority of the carries. Fingers crossed he stays healthy.
5.12 Emmanuel Sanders, Wide Receiver, Denver Broncos Just listened to Sanders interview and he's amped to play for Peyton. Coming off of 67 catches and six touchdowns under Big Ben, Sanders should make a great flex WR. 6.1 Matt Ryan, Quarterback, Atlanta Falcons I love having one duo from the same team. Bring it this year, Ryan and Jones. Despite all the Falcons' losses, Ryan passed for over 4,500 yards and had a passer rating of 67.4 percent. 7.12 Darren Sproles, Running Back, Philadelphia Eagles He's always been versatile and Sproles will be used to keep LeSean McCoy fresh.
8.1 Kyle Rudolph, Tight End, Minnesota Vikings Norv Turner loves to utilize tight ends.
9.12 Tre Mason, Running Back, St. Louis Rams Watch out, Zac Stacy, because Mason is faster than your 3.9 yards per carry. Mason could be a sleeper for 2014. 10.1 Anquan Boldin, Wide Receiver, San Francisco 49ers Boldin is a devout veteran who remains sold in any offense he plays. In fact he crossed the 1,000-plus yard mark with his new team, something he hasn't done since 2009. 11.12 LeGarrette Blount, Running Back, Pittsburgh Steelers I'm sure Blount will be used for some goal line work after showing off in last season's playoffs while with the Patriots. |
0.999962 | One of the most widely used models for specifying functional requirements is a use case model. The viewpoint of the use case model that views a system as a black box focuses on descriptions of external interactions between the system and related environments. However, for embedded systems that do not disclose most implementation logics outside the system, black box-based use case models may experience the drawback that considerable information that must be defined for system developments is omitted. To solve this shortcoming, several studies have been proposed on the use of kind of white box technique in which the dynamic behaviors of embedded systems are defined first using a state diagram and the results are reflected in the requirement specifications. However, white box-based modeling has not been widely adopted by developers due to tasks that require a lot of time in the requirement analysis phase in the initial phase of the software development life cycle. This study proposes a gray box-based requirement specification method as a trade-off between two contradictory elements (the amount of information required to develop an embedded system and the cost of the effort required during the requirement analysis phase) in terms of the two approaches, the black and the white box-based models. The proposed method suggests that an appropriate depth level of embedded system modeling is required to define the requirements. This study also proposes a mechanism that automatically generates an application programming interface for each component based on the created model. The proposed method was applied to the development of a camera sensor controller in a mobile phone, and the case results proved the feasibility of the method through discussion of the application results.
Embedded software refers to software that controls specific functions embedded in electronic products, from small appliances, such as mobile phones, digital cameras, and MP3 players, to digital control systems, such as vehicles and airplanes . For the requirement specifications of embedded software, most embedded system development organizations have used a scenario-based specification method from a black box perspective; this method has been widely employed in existing business applications. One of the most widely used scenario-based methods for specifying the functionality of a system is a use case model [2,3], which focuses on descriptions of interactions occurring between the system and the user. However, most implementation logics in embedded systems start with interactions either with hardware inside the system or with other external software products rather than with interactions between the system and external users.
The use case model in Figure 1 is a specification describing a use case diagram in relation to camera video shooting among the software functions embedded in a mobile phone and the requirements of the system. The four sentences in the specifications in Figure 1 provide information that explains how to use the system from the userโs standpoint. However, from the viewpoint of embedded software developers, the information that can be extracted only includes the fact that an interface with internal components such as a camsensor and a microphone is needed, as suggested in Figure 1.
As described above, when a use case model is used for functional requirement specifications, the information provided to developers by the requirement specifications is not sufficient. To solve this problem, several studies have been proposed in which a state diagram is created in advance during business application development that identifies the systemโs state, the behaviors of the system that correspond to events occurring inside and outside the system, and the stateโs transitions; this information is reflected in the requirement specification. As the depth of the state diagram becomes deeper, it can provide a clearer implementation guide for developers. However, a method that identifies levels up to individual class levels inside the component, that is, a white box-based method that describes the requirements completely, experiences the problem that it requires excessive time in the initial phase of the software development cycle.
To overcome this problem, this study proposes a gray box-based requirement specification method that can provide an appropriate level of requirement specification depth in consideration of two issues: (1) the limitation of the information in the requirement specifications involved in the black box-based method; and (2) an excessive initial cost during the extraction of requirements in the white box-based method. Through the extension of the black box-based requirement specification method and the specification of collaboration between components that make up the system, developers are not provided with information for system implementation that was not previously expressed by use case specifications. To compensate for the time cost required to create state and sequence diagrams during the requirement analysis phase, a mechanism is suggested that generates requirement specifications automatically from the created model.
This paper is organized as follows. Section 2 investigates the trend of existing studies. Section 3 describes the embedded software requirement specification method, based on a gray box, proposed in this study. Section 4 discusses a development case for mobile phone camera sensor controllers using the automatic generation mechanism of the proposed specification. Finally, in Section 5, the contribution of this study is proven through verification of the effect of automatically-generated requirement specifications on the reduction of software development time.
The gray box-based requirements in this paper are defined as requirements that describe interactions between the system and the environment where the system is utilized and the collaboration between internal components in the system that produces the interactions. According to this definition, model-based requirement specification methods that visualize internal operations in the system are deemed to belong to the category of โgray box-based requirement specifications.โ Model-based methods refer to software development in which developers discover the main characteristics of the software and allow them to be independent from implementations at the lower-level source code . One of the well-known model-based embedded software development methodologies is Gomaaโs Concurrent Object Modeling and architectural design method (COMET) . In addition, the Object Modeling Technique (OMT) and Octopus methodologies that model a system by differentiating structural, functional, and dynamic models provide guidelines for embedded software development.
There have been a number of studies on the application of the above general model-based specification methodologies to the embedded software domain [6,7,8,9]. In , a method that specified requirements based on the states of the system components was proposed, and proposed concentrated specifications among three main components (controller, actuator, and sensor) of a controller that controlled the entire system. In contrast, divided an analysis model into an E-Level, which represents a systemโs external structure and behaviors, and an S-Level, which indicates a conceptual model of the inside of the system. This study showed the characteristics of using state diagrams and activity diagrams for specifications and analysis of the E-Level process. In , a relationship between an actual object and a system state was identified to specify the requirements of the embedded system, and then the relationship was made into a hierarchy to redefine the relationship with a state diagram.
However, although most results in these studies [6,7,8,9] proposed a requirement specification method for each development phase, as shown in Table 1, they did not provide a guideline for the degree of detail in each diagram needed to utilize the proposed modeling methodologies for the task of creating the requirement specifications. That is, they only vaguely mentioned that the degree of detail in the diagrams could be increased through iterative applications. Since they also did not support an automatic creation assistance mechanism for requirement specification, there were no compensation methods regarding the cost of the effort required for model creation.
As mentioned above, in previous studies, guidelines about the degree of detail needed during diagram creation for the requirement specification of embedded systems were not sufficient. Thus, this study proposes and divides into two depths the guidelines about the degree of detail.
Guideline 1: A state diagram of the controller that is identified in the uppermost level is created.
In accordance with the definition in , this study divided the components that make up a system into a controller, an actuator, and a sensor. Among these, the controller was assigned as the main actor of the system state, because it presides over the behavior of the sensor and the actuator and accounts for most of the implementation code during the embedded system development. The state diagram of the controller can also increase its depth while nesting continuously into inner space. However, the goal of the state diagram creation during the requirement analysis phase is to define the requirement specifications of the components that will be developed by developers rather than to obtain the design model that can be directly interlinked with the real development code. Thus, the state diagram needed for the requirement specification defines the behavior of the controller and limits the scope of creation as a top level of the state diagram.
Guideline 2: A sequence diagram, including the state transition information of the controller, is created.
The state diagram of the controller shows how the controller state transitions according to specific events. However, it cannot describe the order in which the events occur as time flows. Thus, it is necessary for developers to provide a sequence diagram that can describe the sequential development logic. It proposes an additional display of the controllerโs state information identified in the state diagram prior to the basic sequence diagrams in the lifeline of the controllerโs sequence diagram. While elements that express the state of objects were already added in UML 2.0 or later versions, a UML 1.4 version supported by most UML-related tools is used, and the state of the controllerโs objects are represented using the note considering the high resistance against design tasks using UML by embedded developers.
The development requirement specification method of embedded systems based on the gray box, including the above two core guidelines, consists of eight substeps, as depicted in Figure 2.
Steps 1โ3 in the gray box-based requirement specification method are the same as those in the existing use case specification creation methods. Since the gray box-based method aims to complement the specifications of the inside of the system, which are not represented using specification methods via the black box, there is no change in the scope of the specification method covered by the existing use case specifications.
Utilizing the use case specifications created through Step 3, and using the domain knowledge in the corresponding embedded system, the state diagram of the controller is created in Step 4. According to Guideline 1, mentioned earlier, only the states of the uppermost level in the controller are identified. Figure 3 shows an example of state diagrams that identify only the uppermost level states in the CameraController.
Once all the states of the controller are identified in Step 4, Step 5 is the creation of a sequence diagram according to the flow of time to describe how the controller controls the actuator in response to stimulation sensed by the sensor or to outside events occurring through the user interface in Step 5. A part of the sequence diagrams related to the state transition, marked by the shade in Figure 3, can be found in Figure 4b. Steps 4 and 5 create an analysis model that corresponds to a source for the creation of requirement specifications, which can be generated overhead and newly compared to the creation of existing use case specifications.
To trade off the new overhead increase during the development process, a development specification generator (DSG) was developed as a tool to create the following three specifications automatically: External interaction scenario specifications made by the extraction of information in the already created UML-based analysis model, an intercomponent specification, and a unit component specification. The three specifications are explained in Section 4, using the example of a mobile phone camera, through the mapping process with the analysis model. The DSG identified the XML Metadata Interchange (XMI) structure of the UML model file and employed a method of mapping to each item, described in the three predefined specifications. The current implementation version supports the creation of specifications in the MS Word format from the open source StarUML. In addition to the toolโs reduction in development time, the time cost overhead required to create a part of the analysis model during the requirement analysis phase can be sufficiently compensated for through the three additional specifications providing information about the inside of the system for developers. The reduction effect of the development time due to the use of the created specifications is discussed through the experimental results in Section 5.
Once the created analysis model is inputted to the DSG, the DSG reads the XML that contains the information for the sequence diagram through the mapping process depicted in Figure 4. It outputs the results to appropriate items in the predefined Word template, thereby automatically creating the requirement specification that defines the internal and external interactions of the system. The information marked by the dotted lines in Figure 4b is mapped to the first row in the external interaction scenario specification in Figure 4a. That is, startCamera() transforms the state of the system from โIdleโ to โInitializedโ by the external stimulation, and the related components are PanelFORM, CameraController, and Camsensor_IF. The intercomponent collaboration specification in Figure 4c describes the collaboration and state transition in the system inside until Figure 4a occurs, and the content in the area marked by the solid line in Figure 4b is mapped to the intercomponent collaboration specification. The components corresponding to the destination of the message, located in the far right column in Figure 4c, refer to components whose mission is to implement the message. In other words, a set of messages whose destination is the same corresponds to the Application Programming Interface (API) set that should be implemented by specific components. Thus, operations whose destination is the same in Figure 4c can be collected, and unit specifications of the components that correspond to the destination can be extracted. An example of the unit component specification is shown in Figure 6c. In contrast with the other two specifications, the unit component specification is distributed to developers as the development specification. Thus, accurate header information about operations in each of the APIs is stated.
Figure 5 shows the existing use case specification and Figure 6 shows the specifications automatically created by the DSG, based on the analysis model as a source, according to the guidelines proposed in this study. Figure 6aโc show the content that corresponds to the basic event flow among the contents in the โvideo shootingโ use case specification. As shown in the figures, the use case specification concentrates on descriptions of the interaction between the system and the environment, whereas the intercomponent collaboration specification in Figure 6b shows the collaborations between the software components and the state changes inside the system until the external interaction occurs. The specification in Figure 6b has the advantage that not only can it be a source of the unit component specification in Figure 6c, as explained above, but it can also be utilized as a test case for integration between components after system implementation.
A comparison between Figure 1, which shows the video shooting use case specification for the development of a mobile phone camera sensor using the black box-based method described in the introduction, and Figure 4, which shows the requirement specification related to video shooting that is created or automatically generated using the gray box-based method proposed in this study, verifies that the amount of additional information provided through the proposed method can be measured in a fragmentary way.
This study conducted an experiment with 38 fourth-year undergraduate students to measure the effect on the improvement in the productivity of a quantitative increase in the requirement specifications for the development of an embedded system during actual embedded software development. Considering that embedded software developers in the software industry have a low overall level of knowledge about UML, the fourth-year undergraduate students were selected because they were capable of development language programming to some extent, but their level of knowledge about UML was relatively low. The target system was a function of โdetection and bypassing obstacles and intruders during robot runningโ of the patrolling robot. The patrolling robot system is also one of the embedded system categories, consisting of a sensor, a controller, and an actuator.
This study divided the participatory students into two groups. In order not to make a meaningful difference in the average capability of the two groups, I organized each team with reference to the grades of each student in the programming subject. While the use case diagrams and specifications of the existing black box-based requirement specifications were provided to both group 1 and group 2, the automatically-generated requirement specifications proposed in this paper were provided only to group 2. Then, I had each student in each group implement the function of "detection and bypassing obstacles and intruders during robot running", according to the different requirement specification artifacts. The time taken for each development phase was filled in, in the time recording log (C16) sheet of the personal software process (PSP), for two weeks .
The results showed that group 2 reduced the development time in all phases except for the planningโestablishment phase, as shown in Figure 7. In particular, group 2 shortened the time of the design phase by about 31% and of the implementation phase by about 28%, compared to group 1. To verify that the reduction effect between groups was not caused by a difference in individual abilities, regression analysis was conducted with individual academic grades and development times. The analysis results showed that the determination coefficient R-Square was 0.01, which verified that the effect of individual abilities was not significant in the reduction in development time. Thus, group 2โs reduction effect on development time throughout the design, implementation, test, and maintenance phases, as shown in Figure 7, can be analyzed as being due to the additional requirement specification method proposed in this study.
This study proposed a guideline for developers by setting the optimum level of requirement specification that can be utilized as a development convention in order to overcome the limitation of information that occurs when using use case specifications for documenting functional requirements of embedded software. The proposed gray box-based requirement specification method has the same context as the gray box testing technique in order to leverage the pros of the white box testing and the black box testing approaches. The study also developed a tool that can extract requirement specifications automatically from the analysis model in order to compensate for the effort needed to create the analysis model during the requirement analysis phase, and it applied the tool to real system developments. This study also visibly and quantitatively proved the effectiveness of the proposed method through an experiment with actual embedded system development.
However, like the use case model, the proposed method guides the specification of functional requirements among the taxonomy of software requirements. To develop highly-qualified embedded software, the specification of non-functional requirements (e.g., performance, usability, reliability, security, etc.) is as important as the functional requirements. I am currently working on finding a more effective way than the existing models to extend the proposed method to the non-functional requirements of embedded software.
Whatโs Wrong with Use Cases? Available online: https://pythonconquerstheuniverse.wordpress.com/2009/10/17/whats-wrong-with-use-cases/ (accessed on 15 January 2019).
Broy, M.; Stauner, T. Requirements engineering for embedded systems. In Proceedings of the FemSysโ97; Available online: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.10.5614&rank=1. (accessed on 15 January 2019).
Figure 1. Use case model describing โmobile phone video shootingโ.
Figure 2. The embedded system analysis and development requirement specification process.
Figure 3. State diagram in the camera controller.
Figure 4. Automatic creation process of development requirement specification from the gray box-based analysis model.
Figure 5. The โMobile phone camera video shootingโ use case specification.
Figure 6. (a) External collaboration scenario specifications, (b) Intercomponent collaboration specifications, (c) Unit component specification that corresponds to the โMobile phone camera video shootingโ use case.
Figure 7. Results of comparison experiments on productivity during embedded software development.
Table 1. Comparison of gray box-based requirement specification methods. |
0.998246 | This is how you shorten a string with PHP.
echo shortenString('Test.', 20); // Test. |
0.999769 | Why is picking a strong, memorable brand name so important?
When most people think of high quality sedans, they immediately start to think of cars like Mercedes Benz, Toyota Corolla, Honda Accord (and usually in that order).
Even a minor car accident can cause thousands of dollars in damage and lead to significant injuries. Therefore, it is important to understand the cause of car crashes and what you can do to avoid them. Let's take a look at some specific ways in which you can stay safe while on the road. |
0.997638 | You are currently being governed by a party who refuse to abide by the democratic process, and who are seeking to overthrow the sovereignty of Parliament. This state of affairs has a name. Tyranny.
If "race traitor" means someone who thinks people of other ethnicities than their own deserve equal treatment with them, then I'm proud to be one. And frankly, the fact that you see it as a war is deeply disturbing.
No, the referendum was not an instruction. It was plainly and clearly described as being advisory in nature. Personally, I think it should have taken a super-majority to make a Leave result count even as advice, but that's water under the bridge. As of this moment, I do not personally favour a campaign to avoid brexit. I reserve the right to change this opinion if and when the government actually lives up to its democratic duty and says something concrete about the terms it is considering accepting, thereby giving me the chance to judge their worth.
No, the will "expressed by the people" was not that we should leave the Single Market. The Market was not mentioned on the ballot slip. The only question asked was "Should the UK leave the European Union?" I don't care what you, personally, read into that, or that you claim to know what all the other Leave voters read into it. You, I, and everyone else who voted, were asked one, very specific, question. Anything else you read into it was nothing but supposition on your part, and unfounded insinuation on the part of the lying press barons and dirty politicians who led us into this mess.
Yes, brexit means brexit. And dog means dog, but you'd probably want to consider such questions as "Rottweiler or toy poodle?" before buying one sight-unseen, yes?
Please explain to me how I can be a working-class socialist, currently unemployed man, who lives nowhere near London, and at the same time be a member of the champagne-quaffing, liberal, luvvie, metropolitan รฉlite which all Remain voters are allegedly members of. Really, I desperately need an answer to this apparent paradox.
No, we really have not had a left-wing government in this country since 1979. Just because the word "labour" is present in the name "New Labour," does not mean that the monstrosity foisted upon us by the class traitors Tony Blair and Gordon Brown ever actually represented the working classes, or followed any truly left-wing ideals.
And finally, no, my ability to string a properly-formed sentence togetherโand one which contains "posh" words no lessโdoes not make a lie of my claim to be of the working class. Y'see, back when I was young, we had this thing called the National Curriculum. Well, we still do, but when I was a kid, it still applied to the vast majority of schools. And it stipulated that all pupils should reach adulthood with a good grounding in, amongst other things, the use of the English language. Furthermore, if you actually look into the history of the working classes in the twentieth century, you'll find that a large amount of pride was taken, in unionist, socialist and communist circles, in self-improvement and the negation of the snobbish idea that people born into the working class are inherently stupid, uneducable, and cultureless. So stick your reverse-snobbery in your smoke, old chap, and pipe it.
That's the lot for now. I may add more to the list as the argument rolls interminably along.
Daz, you have made some interesting and valid points โ though I feel the people they are addressed to would not take heed unless you wrote them on the side of a big red bus.
I think the problem lies with the media. People now are more informed about current affairs, but seem to have less understanding of what that information actually means. What now passes for news is really little more than opinion, and written to confirm the prejudices of the target audience โ often resulting in such shameful tabloid headlines as the recent ones calling the judges enemies of the people.
I happen to think that the judges were wrong on both points of their decision.
I believe prerogative can be used to trigger Article 50 โ they should not have distinguished Rees-Mogg (their doing so does seem to create a legal absurdity). And triggering Article 50 would not take away rights from the British people.
Though this is merely my own opinion I base it on years of study (Constitutional Law and European Community Law were compulsory subjects when I read law at University two decades ago, and I have kept up to date), rather than just regurgitating the opinion of some tabloid hack. Whether the Supreme court agrees with me is another matter, but I fully expect there to be some degree of dissent so I shall be glued to the live feed come December.
David Cameron could not carry out his democratic duty regarding the referendum result so had to step down. If he had merely ignored the result (perhaps by claiming it was only advisory) he would certainly have faced a vote of no confidence, quite possibly triggering a general election.
The are a couple of minor quibbles. That was not the question on the ballot paper. The Electoral Commission had rejected a leading question in favour of the more politically neutral one actually used.
And, lastly, there was no National Curriculum when you were at school. You and I are the same age. We both left school in 1982. The National Curriculum was introduced in the Education Reform Act .
Is there anybody left on the Internet whoโs not a fascist?
donotwash. Thankfully yes. Iโm happy to say that I have come across very few fascists, either online or socially. Though I should qualify that by admitting that I tend to interact with people who share a similar ethos to my own โ socialist, anti-referendum, pro-immigration, Corbyn Labour not Blair Labour, liberal not authoritarian. There is a certain comfort in familiarity.
I do try to see the best in people, especially when their opinion differs from my own. I would prefer to find that people are either misguided or misinformed rather than possessed of any deep seated hatred. If I engage with such a person I would try to persuade them of the argument from my point of view โ and likewise I am open to persuasion from their side.
That being said, I have noticed a recent rise in vilification on the internet. Cries of โAnyone who disagrees with me is literally Hitlerโ, and โFacts are fascistโ. Such people do so because either they donโt have anything valid to add to the debate, or are simply trolling. I find it easier to just ignore them.
There are genuine fascists out there but, fortunately, they are few in number. They attract attention because repugnant views stand out more than mainstream ones. And they tend to shout louder.
Getting to the stage with me that I cannot access the internet without wanting to commit murder. Perhaps I need to throw my computer out of the window.
Donโt despair, donotwash. I share your frustration. The best solution is to simply not visit sites that incur your wrath. Just stick to safe site like this one.
I have been following The Dixie Flatline for many years and have yet to see any pro-Brexit comments, let alone anything right wing. I think anyone contemplating expressing such views would realise, from the comment history, that theyโd be asked to justify them โ and very often they canโt.
We do get the odd, often very odd, drive-by evangelist, but they are always quickly dispatched with a good dose of facts and reason. Of course they never admit they may be wrong, they just stop commenting. And that is where, I feel, the frustration lies. There is no closure.
For instance, elsewhere I was engaging with a Brexiter. When asked why they had voted to leave they gave the usual pat answer โ immigrants, scroungers, draining the economy etc. And the source of their information โ Littlejohn, Daiy Mail, my mate said etc. I pointed them to official data that showed immigrants actually make a net contribution to the economy. And that was it. No refutation, no yes-buts. Nothing, they simply stopped commenting. It is annoying sometimes.
There is a way to relieve this frustration, though it may seem odd โ role play. Get a friend, or someone on the internet, to play the part of the other person (the one with the views opposite to yours) and take the argument to its logical conclusion. It is remarkable effective.
I would be more than happy to oblige you. Or perhaps barriejohn. He is both well informed and pretty thick-skinned. Iโm sure he would be up for a placebo argument.
Remigius, I remember we had a regular Christian fundamentalist, self proclaimed, and regular poster a year or so back, although she was quite pleasant, albeit sadly deluded and refusing to accept things may be other than the stuff she had been brainwashed with. I feel very sorry for people like that as they are obviously decent to a point but cannot escape the tyranny of religion and, as such, help promote it.
She did, I missed that. Hopefully she is OK and just got fed up with us, she often posted music videos in the Friday Night etc threads.
OK, Iโll bite. I voted Leave โ but first Iโd like to thank Daz for clarifying the current legal situation back there in the OP.
Years ago, I voted for us to go IN to the EEC as it then was, as it seemed to be a brilliant idea. European countries co-operating instead of fighting each other as they have done for so long. Loss of our sovereignty didnโt bother me; if the French, Germans and the rest could live with it, so should we. I even looked forward to the distant day when we might all have the same currency. I was younger then, of course.
Unfortunately, the Eurozone seems doomed to disaster (ask a Greek or an Italian) and itโs this that could well unravel the whole European Dream. Time to jump ship, I reckoned, so I voted Leave in the referendum. That, and the almost complete absence of anything positive from the Remain camp.
My only reservation was that, if Leavers were in the majority, there didnโt seem to be any plan for what would happen next. It now seems that no-one in Westminster had thought that far ahead.
Daz is annoyed at being numbered among โthe champagne-quaffing, liberal, luvvie, metropolitan รฉliteโ just because he wishes us to Remain. I, for my part, donโt like being considered part of a racist, ignorant, Farage-worshipping mob because I voted Leave.
And finally . . . in politics, Iโm middle oโtโroad, so sometimes I agree with Daz and sometimes I donโt, so I read what he has to say and think about it. If I wanted a political argument Iโd go to the pub. |
0.973808 | Story 1: Transmit your will.
You can convert your "will" into LOGOS-WAVE and transmit it into space-time.
You can make original program files in natural language format (i.e. words and sentences).
The text you input is automatically converted to LOGOS data so that LOGOSTRON can transmit it.
You can also select pre-programmed files from the list of basic program files with just one click.
This system also offers template program files. You can easily make a program file just by filling in the blanks.
LOGOSTRON L transmits LOGOSTRON frequencies consisting of sine waves.
In particular, the role of the receiver, or the user who uses LOGOSTRON, is important as he/she is incorporated as part of the whole system. |
0.999797 | Here are three code samples that illustrate some of the most common mistakes people make when using C++ library containers, iterators, and algorithms. Do you see what's wrong with each one?
These fragments are wrong for different reasons. Fragment 1 is merely a careless typographical error: writing sort(v1.begin(), v2.end()) instead of sort(v1.begin(), v1.end()). It's an error because sort's arguments first and last are supposed to be a valid range, and v1.begin() and v2.end() do not form a valid range. They're iterators from two different containers, and if you try to step from v1.begin() to v2.end() you'll end up stepping through memory you don't own. Calling a standard algorithm with iterators from two different containers is an easy mistake; it will probably cause your program to crash or to go into an infinite loop. If your program is crashing and you're looking over your code to find the cause, this should be one of the first things you look for.
The vector still has five elements, just as it did before.
The problem is a conceptual mismatch between the goal (performing an operation on a container) and the means (performing an operation on a range of values). There's no way for remove_if to change the number of elements in a vector, because it never sees a vector. All it sees is a range of iterators that point to values. It can examine those values, it can copy a value from one location to another, but it can't change the number of locations themselves. If you think about this the right way, it becomes obvious: Pointers into a C array are iterators, and you can't very well change the number of elements in a C array.
The correct equivalent of remove_if for a set is more complicated.
where previous isn't the beginning of the container but the end point of an earlier search.
Generic algorithms such as find are possible because iterators have a well-defined interface: You can use find with any iterator type that satisfies the input iterator requirements described in Table 72 of the C++ Standard. Containers, though, also have a well-defined interface: The container requirements are Table 65 of the C++ Standard. There are no container-based algorithms in the C++ Standard Library, but the container requirements make it possible to write such algorithms.
it's impossible for you to make the first of the three mistakes I showed at the beginning of this column. The more interesting container-based algorithms, though, are the ones that use the container interface to do things that containers on ranges can't.
As before, these are thin wrappers around existing Standard Library algorithms.
CONTAINER TRAITS This still isn't quite right: Our remove and remove_if algorithms aren't as general as they ought to be. Naturally, it doesn't make sense to talk about removing elements from any arbitrary container type; it only makes sense for container types that allow you to delete elements.ย As defined, however, these algorithms are even more restrictive.
The C++ Standard defines two categories of variable-size containers: sequences, such as vector and list, and associative containers, such as set and map. Our versions of remove and remove_if are, as the name of the first template parameter suggests, appropriate for sequences; the erase member function is part of the sequence requirements. These algorithms are not, however, appropriate for associative containers. We've already seen the problem: std::remove and std::remove_if work by assigning one element to another, and that's not something you can do with the elements of an associative container.
Writing remove_if is slightly trickier, but only slightly: We use linear search to find the elements we want to remove, and then erase them one at a time.
would be ambiguousยthere's nothing to tell the compiler which version you mean. We could distinguish the two versions by name (remove_if_seq and remove_if_assoc, perhaps), or we could leave out support for associative containers altogether, but neither of those options is satisfactory.
Fortunately, this is a well-known problem and there's a well-known solution. Some of the algorithms in the C++ Standard Library already present exactly the same difficulty. Consider, for example, the generic algorithm advance, which takes an iterator i and a number n, and increments i n times. There's an obvious implementation when i is a forward iterator (a loop with ++i in its body), and there's an equally obvious implementation when i is a random access iterator (i += n). Again this is vaguely like overloading, but not in a sense that the C++ overload resolution mechanism can work with. Overloading in C++ works with types, not with abstract requirements such as forward iterator and random access iterator.
The solution in the Standard Library is to represent these abstract descriptions within the C++ type system, thus allowing us to use overload resolution. First we define a set of tag classes, input_iterator_tag, output_iterator_tag, forward_iterator_tag, bidirectional_iterator_tag, and random_access_iterator_tag, and then we define a mechanism so that every iterator type is associated with one of those tag classes. For example, int* and std::vector<bool>::const_iterator are associated with the tag class random_access_iterator_tag, while std::list<std::string> is associated with the tag class bidirectional_iterator_tag.
Finally, then, we write several versions of advance overloaded on an iterator tag argument, and write a wrapper that dispatches to one of them using iterator_traits. The dispatch takes place at compile time, so there is no performance penalty.
The "..." is because we have to specialize container_traits for every container type we want to work with. If we fail to specialize it for some container type then that type will be tagged as a general container, not as a sequence or an associative container; a generic algorithm operating on that type won't be able to use any member functions from the sequence or associative container requirements.
CONCLUSION This isn't finished work. Traits are an important general mechanism. The C++ Standard Library includes iterator_traits so that we can write generic algorithms that depend on the properties of specific iterators, and perhaps a future version of the Standard Library will include something like container_traits so that we can more easily write generic algorithms that operate on containers. Is the minimal version of container_traits we've presented here sufficient, or should it be something more extensive? Might it be, for example, that the kind of algorithm one writes for linked lists (algorithms based on splicing list nodes) is fundamentally different from the kind of algorithm one writes for vectors, and that this difference should be reflected in container_traits? Should container_traits provide information about iterator invalidation guarantees, and about exception safety?
At present the C++ community has very little experience with container-based generic algorithms, so we can't do much more than speculate. Container-based generic algorithms are certainly useful, though, and some version of container_traits will surely be an important tool for writing them.
* It's not yet clear which kind of implementation is correctยthere's a slight defect in this part of the C++ Standard, and the standardization committee hasn't yet decided how to fix it. There's no doubt, though, that it's wrong to arbitrarily assign a new value to an element of a set, or to use algorithms, such as remove or reverse, that perform such assignments. The only disagreement is about whether this error should be caught at compile time or at runtime.
ย Warning: This involves a language feature called partial ordering of function templates. There are two overloaded function templates with the same number of arguments, and the compiler chooses the most specialized version whenever find is invoked. Partial ordering is part of the C++ Standard (ยง14.5.5.2), but some compilers still don't support it. If you're using a compiler that doesn't support it yet, there's no really good way to define a container-based version of find. The lack of widespread support for partial ordering of function templates is the only reason I didn't add container-based algorithms to the SGI STL years ago.
ย All of the predefined containers in the C++ Standard Library happen to be variable-size, but nothing in the container requirements says they have to be. A fixed-size container can conform to all of the requirements in Table 65 of the Standard. I describe a fixed-size container, block, in my book, and Bjarne Stroustrup describes a very similar fixed-size container, c_array, in The C++ Programming Language. |
0.94396 | The 1964 Afghanistan Constitution was the constitution of Afghanistan from 1964 to 1977. It was drafted by a committee of foreign-educated Afghans appointed for the task by Mohammed Zahir Shah. The primary goals of the Constitution were to prepare the government and the people for gradual movement toward democracy and socio-economic modernization. A Loya Jirgah (grand council of notables) had debated, modified and approved its innovations, which included a bill or rights for all Afghans, explicitly including women. After public review the constitution was put into effect in October 1964.
A new parliament was created, dominated by its lower house (the Wolesi Jirgah), which was to be elected through universal suffrage. It had the power to reject royal appointments to the cabinet and to dismiss it by a vote of no confidence. Laws passed by parliament were to have constitutional precedence over traditional Islamic law (the Sharia). Parliament was to meet regularly, not at royal pleasure as before. It could refuse budget increases, but could not reduce appropriations below the level of the previous year. Its members had control over the organization of parliament and enjoyed legal immunity for what they said in debate. Members had the right to form political parties, but their formation required legislation acceptable to the cabinet and, hence, the king.
The Constitution of Afghanistan is the supreme law of the state Afghanistan, which serves as the legal framework between the Afghan government and the Afghan citizens. Although Afghanistan (Afghan Empire) was made a state in 1747 by Ahmad Shah Durrani, the earliest Afghan constitution was written during the reign of Emir Abdur Rahman Khan in the 1890s followed by the 1923 version.
The current Afghan constitution was approved by the consensus in January 2004 after the 2003 loya jirga. The Constitution consists of 162 articles and was officially signed by Hamid Karzai on January 26, 2004. It evolved out of the Afghan Constitution Commission mandated by the Bonn Agreement. The constitution provides for an elected President and National Assembly. The transitional government of interim president Hamid Karzai was put in place after the June 2002 loya jirga. The first presidential elections after the new constitution was in effect, took place in October 2004, and Karzai was elected to a five-year term. The first elections for the National Assembly were delayed until September 2005. |
0.947668 | Christopher Columbus was born on October 31, 1441 in Genoa, Italy. Christopher embarked on his first ship when he was just fourteen years old. After settling on the island of Madeira, Columbus soon began hearing rumors of the New World. Before long, Christopher decided that he wanted to take an expedition himself, but lacked the money. Eventually, King Ferdinand and Queen Isabella elected to finance the journey. They were hoping that great riches could be found. Isabella became so supportive that she sold some of her most precious jewels to finance the trip. At the time, the Spanish had been engaged in numerous conflicts and the costs associated with war had placed the government under intense financial pressure. The monarchy hoped to strike it rich in newly conquered lands.
Columbus obtained three caravels, the Nina, the Pinta, and the Santa Maria. All three were about the same size. They were all approximately eighty feet in length and twenty five feet in width. Columbus left on August 3, 1492. He believed that they would arrive somewhere in Asia. However, after traveling more than three thousand miles the crew began to give up. Then suddenly, on October 12, 1492, and they sighted and island that Columbus named El Salvador. This discovery was followed by the discovery of the island of Cuba on October 28, and Haiti and the Dominican Republic on December 5th. Then on Christmas night the Santa Maria was wrecked on a sandbar. Columbus was forced to leave behind approximately forty men in the Dominican Republic. Before he left, they constructed, La Navidad, the first Spanish settlement in the New World.
Once back in Spain, Columbus was greeted by King Ferdinand and Queen Isabella. Walking in front of Columbus was entourage of a half-dozen indigenous people from the New World. They dazzled the Spanish royalty by wearing huge gold ornaments and carrying spears and arrows. Columbus also brought with him forty beautiful parrots, and a five foot iguana.
Columbus would make three more voyages. The second lasted from September, 1493 to March, 1496. He would return to La Navidad and find that all of the men had perished, killed by the local natives. Next, he would then discover Puerto Rico and Jamaica.
On April 8, 1494, Antonio de Torres, one of Columbus's captains, would return to Spain with the first slaves from the New World. Columbus claimed they were cannibals, and they may have been. A year later in February 1495, Torres would again return to Castille, Spain with 500 more slaves. Before long, slave ships would shift away the sights away from Africa and instead focus of the New World. Island after island was wiped clean of its inhabitants.
The third voyage lasted from January. 1498 to October, 1500 AD. On this voyage Columbus would finally discover the mainland of the America's or Tierra Firme (firm ground) as it would soon be known. Here he would realize that he had discovered an enormous continent. The fourth voyage would make contact with the Mayans. Near the island of Guanaja off the coast of northern Honduras he encountered a canoe carrying traders who told the Spaniards that they were Maia or Maiam. It is from these names that the word Maya evolved. Columbus died on May 20, 1506 in Valladoid, Spain. Upon his death he held the titles of Viceroy of the Indies, and Admiral of the Ocean. |
0.999747 | A handful of 2020 presidential candidates share common support with former Vice President Joe Biden.
Biden has been the subject of controversy over the past week, with women alleging he inappropriately touched them and invaded their personal space.
If Biden were to decide against running for president or face dwindling support, several candidates could capitalize.
WASHINGTON โ With former Vice President Joe Biden's recent controversies, in which multiple women have accused him of inappropriately touching them and invading their personal space, there could be an opening for one of the savvy 2020 presidential candidates to court some of the voters poised to back his looming White House bid.
According to polling from INSIDER examining which candidates have shared blocks of supporters, Biden either choosing not to run or losing traction could dramatically shift which candidates gain support in the growing field of Democrats eyeing the presidency.
Biden has strong name recognition, with 82% of likely Democratic primary voters having heard of him. In a crowded field of candidates, being well-known is a key component of maintaining a campaign.
According to INSIDER polling, 52% of Democratic primary voters who'd be satisfied in the event Biden was nominee would also be satisfied see Vermont Sen. Bernie Sanders as the Democratic nominee. According to the latest numbers, following Sanders are California Sen. Kamala Harris at 43% satisfaction among Biden backers, Massachusetts Sen. Elizabeth Warren at 42%, and former Texas Rep. Beto O'Rourke sharing 37% of Biden backers.
When looking at how other candidates share support with Biden, it becomes clear whose base may be jeopardized in the event Biden runs.
For example, 72% of those satisfied with New York Sen. Kirsten Gillibrand atop the ticket would also be satisfied with Biden as the nominee. Gillibrand supporters are more inclined to want Biden as the nominee than the entire Democratic voting block, where 66% would be satisfied with Biden winning the primaries, a nearly 6% difference.
While he is fairly late to jump into the race compared to the more than a dozen who have already announced their candidacies, Biden is reportedly moving "full steam ahead."
Biden has been embroiled by accusations that he has inappropriately touched women. While the former Delaware senator has denied any knowledge of making the women in question feel uncomfortable, his spokesman has made it clear he empathizes with them.
"Neither then, nor in the years since, did he or the staff with him at the time have an inkling that Ms. Flores had been at any time uncomfortable, nor do they recall what she describes," said Biden spokesman Bill Russo. "But Vice President Biden believes that Ms. Flores has every right to share her own recollection and reflections, and that is a change for better in our society that she has the opportunity to do so. He respects Ms. Flores as a strong and independent voice in our politics and wishes her only the best."
But Biden's team has also pushed back on other instances, including condemning the use of certain images of him appearing to be too close for comfort with women.
In one instance, during the 2015 swearing-in ceremony for then-Defense Secretary Ashton Carter, Biden is seen with his hands over the shoulders of Carter's wife, Stephanie Carter. In a Medium post, Carter adamantly denied she in any felt violated or uncomfortable.
And Biden's spokesman characterized the repeated use of such images as a deliberate conspiracy and troll effort from the far right and elsewhere. |
0.967885 | Canards are special solutions of slow/fast systems that spend long times near repelling sets. They are ubiquitous in applications and have been used to explain the firing patterns of electrically excitable cells in neuroscience, the sudden change in amplitude and period of oscillatory behaviour in chemical reactions, and the anomalous delays in response to exogenous pulses of inositol triphosphate in calcium signalling. In this talk, we survey some of the exciting new developments in canard theory and its applications to bursting in nerve and endocrine cells. In particular, we devise analytic criteria for the detection and classification of a new class of singularities for differential equations, which act as organizing centers for complex oscillatory behaviour. We demonstrate our theory in a model for intracellular calcium dynamics, where we discover a new class of bursting rhythms and explain the mechanisms that underlie them.
Methods of data assimilation, such as the ensemble Kalman filter, have recently been applied to tracking neuronal network structure parameters. This is a particularly challenging domain for parameter estimation due to the strongly non-linear models combined with large observation noise, a high-dimensional parameter space, and model uncertainty. We discuss recent practical improvements in adaptive filtering, and alternative approaches when model error is large or parts of the model are unknown. In the extreme case that no model is available, we propose a method using delay coordinate reconstruction that merges Kalman filtering with Takens' work on nonlinear data analysis.
Perceptual bistability arises from ambiguous stimuli that our brain cannot recognise univocally. Under a steady sensory input, subjects usually report alternation of percepts resulting in a sequence of single-percept time intervals that typically follow a Gamma distribution. Different models have been proposed to account for this statistics of dominance times, most of them containing few variables that represent key features of the main involved areas and, eventually, some slow adaptation processes. Two-attractor models have been extensively studies but, recently, heteroclinic networks have successfully been applied to model this phenomenon, see [Ashwin and Lavric, Physica D (2010)]. The mechanisms that allow to match heteroclinic networks with the statistics of dominance times rely on the fact that their trajectories are characterized by spending long periods in neighbourhoods of saddle points from which they escape thanks to noise. In fact, in all the bistable perception models, noise plays a leading role to explain the statistics of dominance times of percepts observed in experiments. Noise is meant to model a diversity of inputs impinging on the areas represented in the model. Despite of being such a cornerstone, including noise is somehow a vague form to account for generic inputs since it considers inputs spanning a continuum of frequencies (the spectrum of the noise); it is, then, natural to think that perception transitions could be driven by less sophisticated inputs. With this idea, in this lecture we consider quasiperiodic perturbations of heteroclinic networks, assuming that our cognitive system (the featured areas of the model) is receiving events, either internal or from other brain areas, that include only a finite number of (non-resonant) frequencies. We show how these systems can achieve good agreement with Gamma distributions of the dominance times observed in bistable perception, and we compare these results with those obtained with noise. Moreover, we have adapted the well-known tool of separatrix map to the quasiperiodically perturbed heteroclinic networks. We then substitute the numerical integration by an iteration of maps which, at the end, provides a new (discrete) model for bistable perception. In addition, this approach allows to avoid numerical unstability when integrating close to saddle points.
This is joint work with Amadeu Delshams and Gemma Huguet (UPC).
Oscillations occur in virtually all spatial and temporal scales, performing crucial roles in biological systems. Yet, their precise function is often elusive and even dismissed as epiphenomenon. My work comprises mathematical and computational approaches to three oscillatory systems with distinct functional hypotheses: (1) inter-oscillator coupling provides response to seasonality in circadian systems (2) circadian phase clustering in the hippocampus underlie functions in memory processes (3) membrane potential oscillations coordinate cell polarity, growth and guidance in pollen tubes (the focus of this talk). Among the fastest growing cells in nature, pollen tubes sustain a highly polarized apical growth and are able to follow cues towards the ovule to perform fertilization. They show remarkable spontaneous oscillations in vitro involving multiple cellular processes such as growth, extracellular ion fluxes, and cytosolic ion concentrations. However, their function and underlying mechanism remain unknown, being limited by the availability of quantitative methods to characterize and model the different dynamic regimes observed. I will present a โComputational Heuristics for Understanding Kymographs and aNalysis of Oscillations Relying on Regression and Improved Statisticsโ, or CHUKNORRIS, which allowed to detect and quantify spiking behavior upon growth arrest and synchronized oscillations with growth and all ions studied (Ca2+, Cl- and H+). Conductance based models will be developed to predict the effect of these different regimes in polarity establishment, growth and guidance.
Mathematical biology and pharmacology models are increasingly utilized in the pharmaceutical industry, recognizing the need for improving the probability of success or reducing the cost of drug development. More mechanistic, quantitative systems pharmacology (QSP) models are being leveraged to aid in the identification of novel targets in early research, in the translational medicine activities for bringing molecules into the clinic, and for achieving proof of mechanism, and understanding variability in response to novel compounds in later clinical development.
During forward swimming, pairs of crayfish swimmerets (limbs) exhibit a robust pattern, moving rhythmically in a back to front metachronal wave with neighbors delayed by approximately 25% of the period. We study the mechanism responsible for this coordinated limb behavior using a model which represents the underlying neural circuitry as a chain of coupled oscillators. Previous modeling efforts have only considered the effects of nearest neighbor coupling, ignoring the presence of longer range connections in the system.
In this talk, I'll address how long-range coupling affects this mechanism, using an oscillator chain whose architecture reflects the known neural circuitry in the swimmeret system. I'll present analytical arguments and numerical simulations that indicate that long-range coupling tends to speed up the metachronal wave. Combined with insights from a computational fluid dynamics model, we suggest that this coupling may ensure maximal swimming efficiency.
In addition to the widely-used ability to selectively target specific cell types, Optogenetics and other emerging strategies for remote stimulation also offer an exciting path towards spatio-temporally-controlled targeting. For example, projected patterns of light can be used to selectively and flexibly control or image activity patterns distributed across entire populations of neurons.
The talk will present an overview of our recent work on distributed neuronal interfacing with large populations of neurons using optical and acoustic approaches. Our results demonstrate that patterned computer-generated holographic stimulation can achieve high temporal precision at multiple different scales, and can be effectively coupled with neuro-imaging and behaving animal paradigms. I will then describe a rational approach to quantitative understanding and design of next-generation neural interfaces using novel biophysical models, particularly the emerging Neural Intramembrane Cavitation framework for elucidating the biophysical basis of neuro-acoustic excitation. I will how insights provided from mathematical modeling may be opening new windows towards noninvasive neuromodulation with potential basic science and medical applications. |
0.969219 | How do you avoid this common kitchen cry-fest?
Chop off the two ends of the onion.
Lightly tap your knife on the onion to score it, then peel off the first layer.
Slice down the middle of a peeled onion, pole-to-pole.
Lay one half down on its flat side and slice through. Repeat with the other half.
Tip: Leaving out the root of the onion will result to a sweeter-tasting and more aromatic dish.
Slice a peeled onion in half, pole-to-pole.
Lay half down on its flat side. Slice through horizontally twice, until you reach the root.
Flip the onion perpendicularly and slice through vertically.
To mince, run your knife through the onions until very fine. |
0.955515 | Kavala was called Neapolis in antiquity. Its modern name appeared during the Turkish occupation and, specifically, at the end of the 15th century.
The exact date of the founding of ancient Neapolis is not known, just like the descent of its first inhabitants. From the archaeological evidence, we come to think that the area was first colonized by the Thassians between 650 and 625 BC.
Although information about Neapolis is scarce, the multitude of pottery found in the city bears witness to the extent of trading it carried out with the rest of Greece, which trading was facilitated by its harbour.
Neapolis gained its autonomy from the Thassians only during the last part of the 6th century BC. After the Persian wars, Neapolis became a member of the Delian Alliance in 454. During the Peloponnesian War, Neapolis remained a faithful ally to Athens.
In 411, the Spartans led by general Eteonikos and with the aid of the Thassians, laid siege to Neapolis, but the Athenean Thracyboulos hurried to put an end to the siege. Neapolis was a member of the second Athenian alliance.
When Phillip appeared in the horizon, Neapolis came under his power in about 340. Not only did Neapolis lose its autonomy, it also lost its importance as a city and came to be the port of Philippi. |
0.854125 | Although most asteroids travel in fairly circular orbits, there are notable exceptions.
In addition to the near-Earth asteroids, discussed above, some objects are known to travel in orbits that extend far inside or outside the main belt. One of the most extreme is (3200) Phaethon, the first asteroid to be discovered by a spacecraft (the Infrared Astronomical Satellite in 1983). Phaethon approaches to within 0.14 AU of the Sun, well within the perihelion distance of 0.31 AU for Mercury, the innermost planet. By contrast, Phaethon's aphelion distance of 2.4 AU is in the main asteroid belt. This object is the parent body of the Geminid meteor stream, the concentration of meteoroids responsible for the annual Geminid meteor shower seen on Earth each December.
Asteroids traditionally have been distinguished from comets by characteristics based on physical differences, location in the solar system, and orbital properties. An object is classified as a comet when it displays "cometary activity"โi.e, a coma, or tail, or any evidence of gas or dust coming from it. In addition, any object on a nonreturning orbit (a parabolic or hyperbolic orbit, rather than an elliptical one) is generally considered to be a comet.
Although these distinctions apply most of the time, they are not always sufficient to classify an individual object as an asteroid or a comet. For example, an object found to be receding from the Sun on a nonreturning orbit and displaying no cometary activity could be a comet, or it could be a planet-crossing asteroid being ejected from the solar system after a close encounter with a planet, most likely Jupiter. Unless such an object reveals itself by displaying cometary activity, there is usually no way to determine its origin and thus to classify it unequivocally. The object may have formed as an icy body, as comets do, but lost its volatile materials during a series of passes into the inner solar system. Its burned-out remnant of rocky material would presently have more physical characteristics in common with asteroids than with other comets.
a defunct cometโone that has lost its volatile materials and no longer displays the classic cometary features of a nebulous coma and a tail. Another asteroid, (944) Hidalgo, is also thought by some to be a defunct comet because of its unusual orbit. This object, discovered in 1920, travels sunward as near as 2.02 AU, which is at the inner edge of the main asteroid belt, and as far as 9.68 AU, which is just beyond the orbit of Saturn, at 9.54 AU. |
0.967328 | Hejblum G, et al. "Comparison of routine and on-demand prescription of chest radiographs in mechanically ventilated adults: a multicentre, cluster-randomised, two-period crossover study". The Lancet. 2009. 374(9702):1687-1693.
For mechanically ventilated patients, are daily chest radiographs necessary or should they be ordered only when a patient's clinical status changes?
For mechanically ventilated adult ICU patients, using an on-demand strategy for CXRs reduces the number of CXRs overall by 32% compared to routine daily CXRs, without having any deleterious effect on patient safety or clinical outcome measures in the ICU.
Chest radiographs are common in critically ill, intubated, mechanically ventilated patients. Professional society recommendations had supported the practice of routine daily radiographs, though some questioned the utility in detecting changes like displaced endotracheal tubes compared to bedside examination. Radiographs have significant consequences of cost, radiation, and results of unexpected findings which may or may not have clinical significance.
Earlier single-center studies had favoured on-demand strategies, but only two, with a total of 259 patients, focused on mechanically ventilated patients (Graat et al., Crit Care 2006; Clec'h et al., Intensive Care Med 2008). This study was much larger, including nearly 850 patients across 21 ICUs, using a cluster-randomized crossover design to control for variation in practice between ICUs. Patients in an ICU using the routine strategy received daily CXRs during morning rounds, while those in the on-demand strategy received them only when clinical examination suggested the need for one.
This study showed a reduction of daily CXRs by an average of 32% (from 1.09 to 0.75 CXRs per day), consistent with findings in the smaller studies. The number of images leading to diagnostic or therapeutic interventions were similar between both strategies, indicating that few if any important abnormalities were missed. Further, key ICU clinical outcomes of days on mechanical ventilation, ICU length of stay, and ICU mortality were similar between the groups, suggesting that the on-demand strategy is both safe and effective.
Setting: 21 closed, adult ICUs (13 medical, 2 surgical, 6 mixed ICUs) of a research network in Paris, France.
Enrollment: 2006-2007, median duration of study at each ICU was 131 days.
Follow-up: Until discharge from ICU or 30 days of mechanical ventilation.
Primary outcome: Mean number of chest radiographs per patient-day of mechanical ventilation.
Secondary outcomes: Days of mechanical ventilation, length of stay in the ICU, and mortality of patients during ICU stay.
Adult patients in a study ICU.
Receiving mechanical ventilation during morning rounds.
Mechanically ventilated for less than 2 days.
Routine Strategy: ventilated patients received daily chest radiographs.
On-Demand Strategy: ventilated patients receive on-demand chest radiographs.
Number of chest radiographs, a reason for doing each radiograph, new findings leading to diagnostic procedures or therapeutic interventions, days of mechanical ventilation, length of stay in the ICU, and mortality of patients were recorded for each patient.
After the washout period, each ICU began the other strategy for the Second Treatment period with an enrollment goal of 20 patients.
Comparisons are Routine Strategy vs. On-Demand Strategy.
On-demand strategy associated with fewer chest radiographs than routine strategy in every ICU.
Both strategies had a similar number of diagnostic procedures or therapeutic interventions driven by new findings on chest radiograph, both overall (824 vs. 834 procedures or interventions (p=0.77)), and the types of interventions were similar between groups except for an increased number of changes in vent settings in the on-demand strategy.
All ICUs were closed with patients managed by dedicated intensivists, limiting its generalizability to ICUs with other staffing models.
Workflow and efficiency differences between the two strategies for clinicians and technicians were not assessed.
No data is provided to guide how long patients can be safely managed without a CXR if no clinical indications are present.
Actions based on negative CXR findings were not documented.
No subgroup analysis by patient type was done.
Study funded by a grant for research on standard care procedures from Assistance Publique-Hopitaux de Paris.
A 2012 systematic review and meta-analysis pooled 3 RCTs and 6 before-after observational studies. The authors found no evidence of harm, but noted limitations in assessing any consequences of missed findings on routine CXRs: Ganapathy A, Adhikari N, Spiegelman J, Scales DC. "Routine Chest x-rays in intensive care units: a systematic review and meta-analysis." Crit Care. 2012; 16(2): R68.
This page was last modified on 17 November 2015, at 01:04. |
0.999868 | 1. Joseph Waring, Mobile World Live: To kick this off, it will be great if you can give a little background on how your experience in military shapes your management style with Huawei. And the tie with that is, now that Huawei is under a bit of scrutiny worldwide, how are those ties with the military impacting Huawei's future as it continues to grow?
Mr. Ren: I joined the military during China's Cultural Revolution. At that time, there was chaos almost everywhere, including in agriculture and the industry. The country was facing very difficult times. These difficulties were reflected in people's diets and clothing. I remember that, back then, at the most difficult of times, every Chinese person was allotted only one-third of a meter of cloth. That amount could be used only for patching. So I never wore clothes without patches when I was young.
When we just arrived at the site, it was dozens of square kilometers, and there was no housing at all. So everyone slept on the grass. Later, the factory got some funding and built some shabby housing that provided little shelter from the rain and wind. It was minus 20-something degrees Celsius outside. You can image how harsh the conditions were. If you ask me how I felt back then, I would say: First, we had been given access to the world's most advanced technology. That French company had a very high level of automated controls that no Chinese companies had. This was the first time that I had learned what the world's most advanced technology looked like.
Second, we learned to endure hardship. Our housing was very shabby, so we constantly felt cold as it couldn't protect us from the wind. Just imagine, the temperature could drop to minus 28 degrees Celsius. China was facing huge economic challenges at that time. The supply of meat and cooking oil was very limited. For ordinary people living in Northeastern China, their monthly supply of cooking oil was around 150g. There was no supply of fresh vegetables at all, so we had to pickle some vegetables like cabbages and radishes we got in autumn in large concrete pots, and rely on pickled foods for six months at a time. Our staple food was sorghum. It was far from delicious. So in a nutshell, we learned from the world's most advanced technology while living a life that could be seen as primitive. That's how I felt back then.
But I was happy then, because if you read too many books in other parts of the country, you could get criticized. The factory was probably one of the few places that people could read. We had to read to understand how this modern equipment worked. At the time, I was a technician of a company in the military, and then I became a deputy director of a small construction research institute with just twenty plus people. That's actually a title equivalent to a deputy-regimental level. My dream back then was to reach the military rank of Lieutenant-Colonel before China disbanded its military forces. Unfortunately, that did not happen. So I'm just a veteran without a military rank.
2. Yuan Yang, Financial Times: I'm with the Financial Times, and I have a question regarding your personal experience. It is reported that you participated in the National Congress of the Communist Party of China back in 1982. How come you attended that conference, and what is the relationship between Huawei and the Communist Party of China today?
That's also the time when the "Gang of Four" was smashed and the country was trying to find readily available examples to demonstrate that science and technology were valuable. My little invention was exaggerated into something really big and it was promoted in various media outlets, including newspapers, magazines, movies, etc. And because of such massive publicity, luckily I was chosen to be a member of the National Science Conference.
If you are aware, that's a time when you had to be a CPC member even to become the head of a cooking team in the military. I was selected to attend the National Science Conference, but I was not a CPC member. My supervisor felt that was really strange, so with the help of party organizations, I became a CPC member. The reason I was not a member was not because I didn't do my job well enough. It was because of my family background.
My father was labeled as a "capitalist roader". For this, he was actually locked up in a cow barn at one point in time. You know, for an educated person back then, an intellectual, his or her background or history would be much more complicated than that of a cadre among farmers and workers. It was because of such close scrutiny of my father that he was in such a difficult situation for over 10 years before his name was cleared. And because of this family connection, there was no possibility for me at the time to become a CPC member.
After I joined the party in 1978, China encouraged leaders to have "four qualities": young, professional, educated, and revolutionary. I happened to meet the requirements, and was recommended to be a member of the 12th National Congress of the Communist Party of China. And in the end, I was selected. Unfortunately, I was too young to truly understand what the big reform was all about in that historical moment. That was really a pity. I was a complete technical geek back then. Today, I still love my country. I support the Communist Party of China. But I will never do anything to harm any other nation.
3. Joe McDonald, Associated Press: As I understand, over the last few weeks or months, it must have been very stressful for you. Thank you for taking the time to talk with us today. I want to ask a question about security. Security incidents occur a lot recently. The security concerns raised by governments such as the US and Australia are not about the capabilities of Huawei's technologies. These governments appear to be concerned that every company in China, fundamentally Huawei, is under the authority of the Communist Party of China. If the Communist Party requires Huawei to do something, the company has to obey. I'm wondering, what assurances can you give foreign customers that Huawei is able to protect the safety of their networks or protect the confidentiality of information? Under the legal circumstances of China, what can Huawei say to customers about the limits of its abilities to give assurances about that?
Mr. Ren: The first point I want to make is that over the past 30 years, our products have been used in more than 170 countries and regions, serving more than 3 billion users in total. We have maintained a solid track record in security. Huawei is an independent business organization. When it comes to cyber security and privacy protection, we are committed to siding with our customers. We will never harm any nation or any individual. Secondly, China's Ministry of Foreign Affairs has officially clarified that no law in China requires any company to install backdoors. Neither Huawei, nor I personally, have ever received any requests from any government to provide improper information.
Joe McDonald, Associated Press: Pardon me. I'm not arguing with you. Any government, the United States or Australia, would say you are a company that sells networks. A customer has to trust a vendor with the most secret information about how a national telecommunications network operates. Suppose, for instance, the Ministry of State Security were to come to Huawei to ask Huawei to give information about a foreign country to the Ministry of State Security. Legally, there's nothing Huawei can do to refuse. Huawei must obey. So what can and will Huawei do to reassure customers?
Mr. Ren: Can I sell Huawei to you?
Joe McDonald, Associated Press: Yes, I did just buy a Huawei product.
Mr. Ren: If you cannot afford [to buy Huawei], I would probably have to shut the company down. Customer-centricity has been at the very core of Huawei's business operations since our founding. We will never do anything to harm the interests of our customers. Apple is an example we look up to in terms of privacy protection. We will learn from Apple. We would rather shut Huawei down than do anything that would damage the interests of our customers in order to seek our own gains.
4. Dan Strumpf, Wall Street Journal: I was hoping to ask you about your daughter, Meng. It's been just more than one month since she was detained in Canada. I was just wondering how you're feeling knowing this was an [extradition] request? And tell me if you feel that your daughter has been targeted because she is your family member and because of her position in Huawei?
Mr. Ren: As you must be aware, the case of Meng Wanzhou right now is in legal proceedings. So, we'd rather leave it to legal proceedings. I won't provide much comment about it here.
As Meng Wanzhou's father, I miss her very much. And I'm deeply grateful to the fairness of the Honorable Justice, William Ehrcke. I'm also much grateful to Prosecutor John Gibb-Carsley and Prosecutor Kerri Swift. I also thank the Alouette Correctional Centre for Women for its humane management. Thanks to Meng Wanzhou's cellmates, for treating her kindly.
5. Gao Yuan, Bloomberg: You are the father of Ms. Meng. And now your daughter has been treated like this. You mentioned just now you trust the legal proceedings. But is it because Meng is part of your family that she is being targeted by US and Canada? What's your personal feeling?
6. Arjun Kharpal, CNBC: Thank you for taking the time, Mr. Ren. I just want to follow up on the answer you gave to Joseph in which you mentioned Apple, in your response. You were referring to the case when Apple was asked to hand over evidence from an iPhone and they took it to court. Is that what you will do if there was a request from the Chinese government for data from the networks? Just a second one, let's say, topic. What kind of correspondence do you have with the US authorities around some of the other engagements that may let you back in the market? What have the conversations been? And what is coming up for the very thing?
Mr. Ren: We don't have any channels for communicating with the US government, and, honestly, we don't know much about each other. Regarding what would happen if the implied cyber-security case occurred, I believe I have made myself very clear: We will never harm the interests of our customers.
7. Eamon Barrett, Fortune: Thank you Mr. Ren for talking to us today. A couple of points have been raised already regarding issues which foreign nations may consider as causes of concern for Huawei, namely military background, affiliations with the communist party, etc. Another primary concern foreign nations have is that the government somehow has ownership for Huawei. Huawei claims to be an employee-owned company, but the exact way that the shares are spread out among its employees is still secret. If you were to make that information public or even make Huawei public, you would surely have resolved all the suspicious, so why do you keep the shareholding structure private.
Here, I also have a piece of information to share with you. We have 96,768 shareholding employees. Just a few days ago on January 12, we completed the election of the new representatives of shareholding employees at 416 polling stations across over 170 countries and regions. The entire process of this election lasted about one year. We first communicated our Articles of Governance to all employees. Through those efforts, our employees became more familiar with how the corporate governance structure of this company works.
On January 12, we completed the voting โ the election โ of our shareholding employee representatives around the world. Over the past few days, our messengers around the world have been taking those votes back to Shenzhen. We are going to calculate the votes on our electronic platform, and audit the authenticity of those votes. Eventually, we will come up with 115 representatives for all shareholding employees. The Representatives' Commission, consisting of these 115 employees, is the highest decision-making authority in Huawei, and the company is owned by our 96,768 shareholding employees.
Our shareholding employees are currently working at Huawei or are retired former employees who have worked at Huawei for years. There is no single individual that owns even one cent of Huawei's shares without working at Huawei. There is no external institution or government department that owns our shares, not even one cent's worth. We have a shareholding registry that lists the shares held by our shareholding employees. Journalists who are interested are welcome to take a look at it.
8. Yuan Yang, Financial Times: Last year, it was reported that the African Union said there was infiltration from the Chinese side on their equipment based in Ethiopia. And we also learned that some of the equipment used by the African Union was provided by Huawei. Do you have any comment on that? You have said that Huawei will never harm the interest of any customer or individual. Suppose one, either Chinese or foreigner did something illegal here in China, and they left some trace on their Huawei smartphone, for example. Huawei, just like any other company, is supposed to provide support and cooperate with public security authorities because it is required by the law. Then in that case, would Huawei cooperate? Then, imagine that one Chinese or one foreigner committed a crime in countries outside of China, what would be Huawei's actions in those cases?
Mr. Ren: For Huawei employees, whether they are Chinese or non-Chinese, if they violate local laws, we'll always cooperate with the investigations. We stand strongly against any behavior that violates laws and regulations. Within Huawei, we have a very sound internal and external compliance management system. The idea is to prevent those wrongdoings or bad things from happening. Those who commit violations will be disciplined by our compliance department. Huawei may grow even bigger in the future. In the cloud era, our society is becoming more and more complex. If we do not govern our behavior through discipline, we might get overwhelmed.
9. Eamon Barrett, Fortune: Following up on that and about how Huawei implements its disciplinary actions, just last week, a member of Huawei's staff was arrested in Poland on suspicion of spying. Huawei has fired that employee already without waiting for the trial, without waiting for the evidence to move forward. Whereas in Canada, where Meng Wanzhou was arrested in December, Huawei appears to at least stand by her and is still, in a sense, putting trust in her innocence. So why was the decision made to fire the employee in Poland? Why has that action not been taken in Canada?
Mr. Ren: Both cases are in the judicial process, and I'm not in a position to make further comments other than the information available from our official statements.
10. Gao Yuan, Bloomberg: My question is more related to Huawei's business. In light of recent developments, especially where some European countries have also stopped using Huawei's equipment based on the concerns on cyber security. What impacts will this have on Huawei's business? What actions and plans does Huawei have in mind or what do you think Huawei should be doing to address this kind of situation and to sustain its business in those markets, like Europe, US, and other Five Eyes countries?
Mr. Ren: First, it has always been the case that some customers accept Huawei and others don't. This is nothing new at all. If only a handful of congressmen decide that Huawei should not be accepted, then that does not represent the entire government. We can reach out to talk with the right stakeholders. If those individual opinions become orders coming from a government, then we may have to stop our sales there.
One of the major topics currently in question is 5G. If you look at 4G, I do not believe there was any controversy or debate about it. So, for products where there is no such debate, we will continue working to drive our sales. Some countries have decided not to buy equipment from Huawei. Therefore, we can shift our focus to better serve countries that welcome Huawei. We can build high-quality networks in those countries to prove that we are trustworthy. Therefore, it's like a peaceful race from a technical point of view, and I think that's fair.
11. Joe McDonald, Associated Press: Chinese foreign minister arrested two Canadian citizens on national security charges. Yesterday, a court pronounced a death sentence for a Canadian who was accused of drug charges. Some people outside of China suggested that these two Canadians were detained basically as hostages in connection with the arrest of Meng Wanzhou in Canada, and the drug case might have been influenced by that case. How do you feel having people say this sort of thing about your company or that you are personally connected to Chinese government taking hostages to help you or that there might be some political influence on this drug case to help your company? How does that make you feel?
Mr. Ren: First, I don't know the whole story about this case, and it is not related to Huawei in any way.
12. Dan Strumpf, Wall Street Journal: I was wondering about the rollout of 5G networks in coming years. There are a number of countries taking a lead from apparently the United States to put new restrictions on Huawei's participation in 5G, and perhaps even more broad restrictions on top of that. I was just wondering, last week Polish officials stated they would like a unified position with NATO with regards to Huawei. In light of these new potential restrictions, what does this mean for Huawei knowing that it might be effectively locked out from a significant chunk of the world's telecommunications networks in the future, both from a business sense and a reputational sense? And how will Huawei contend with these restrictions?
Mr. Ren: To start with, I'm not sure how far this proposal will go, and whether or not Poland is able to push it through. I think countries like France and Germany might have a greater say in NATO.
So I'm not sure if Poland can get its proposal accepted. Even if they get what they want, it does not matter so much to Huawei. Because, as you know, we are not a public company โ we aren't overly concerned about beautiful numbers, or a nice-looking balance sheet. If we are not allowed to sell our products in certain markets, we would rather scale down a bit. As long as we can feed our employees, I believe there will always be a future for Huawei.
So we are the strongest in terms of telecommunications capabilities. I believe people will make their own comparison in the end between countries that choose Huawei and countries that don't work with Huawei. Of course, there is no way we can control their choice.
If your products are not good, no matter how strong you go for publicity, nobody will buy them. So what matters to Huawei more is working to streamline our internal management, improve our products, and improve our services. I think that's what we should work on to address the challenges of this changing world.
There are only several companies in the world working on 5G infrastructure equipment, and not many companies are engaged in microwave technology. Huawei is the only company in the world that can integrate 5G base stations with the most advanced microwave technology. With that capability, our 5G base stations don't even need fiber connections. Instead, they can use superfast microwave to support ultra-wide bandwidth backhauls. This is a compelling solution that makes a lot of economic sense. It works best for sparsely populated rural areas.
13. Arjun Kharpal, CNBC: Mr. Ren, I just want to go back to a point you made earlier. You said that if there was a request by the government to access data, to create backdoors and networks, then you would deny it. You would not comply. Considering that you are a member of the Communist party, how could you deny what they are asking for? What means do you have to actually fight against any request from the Chinese government to do any of these things? What assurance would you be able to give to your customers that if there was a request for something along those lines you would actually be able to fight it?
Mr. Ren: We are a company, and we are a business entity. The values of a business entity are such that it must be customer-centric and the customer always comes first. We are a business organization, so we must follow business rules. Within that context, I can't see close connections between my personal political beliefs and the business actions we are going to take as a business entity. I think I already made myself very clear earlier. We will certainly say no to any such request. After writing this quote in your story, maybe 20 or 30 years down the road, if I am still alive, people will consider this quote and check my behavior against it, as well as the behavior of our company.
Arjun Kharpal, CNBC: This one just follows up the previous one asked. Like you mentioned, Apple went to court against the government. Is there a system here such that you can take the government to court to fight such requests?
Mr. Ren: If I or Huawei deny those requests, I think it should be the government in question that files litigation against Huawei, not the other way around. Whether or not the government would file such litigation, I don't know.
14. Joseph Waring, Mobile World Live: The trade war developing with the US seems to have moved beyond just a trade war, and the term "cold war" has come up a bit. Looking at the technology camps โ GSM and CDMA, years ago I participated in CDMA. What are your thoughts on the two technology camps? Do the US and China lead these camps in technology, which is facing tailwinds similar to what we see in mobile platforms like Android and iOS?
15. Josh Chin, Wall Street Journal: I'd like to follow up my colleague from Associated Press's question on the detained Canadians and the case of the Canadian who was just sentenced to death. I know some of these cases don't have anything to do with Huawei, but the perception is that they do have a connection to Huawei. I'm wondering if you could comment on whether you think this helps or hurts Madam Meng's chances for her release. And then, on that, I just wanted to talk a little bit about your personal relationship with Madam Meng, as your daughter, and how that's translated into the workplace at Huawei.
Mr. Ren: Personally, I don't see any connection between those cases and the case of Meng. In Meng's case, I believe we just need to leave the outcome to the proper legal proceedings.
As far as the relationship between me and Meng as father and daughter, I would say, it's a close relationship in some aspects and not so close in others.
Why do I say it's not so close? Throughout her childhood, I was in the military, which means that each year I was away for 11 months, spending one month with my family. Meng had to go to school, and after school, she had to do her homework. Therefore, our connection during her childhood and adolescence was not that strong. In addition, when I started Huawei, I had to fight for the survival of this company, spending 16 hours a day in the office. I have one son and two daughters, and I do not think my relationship with them was very close. As a father, I feel indebted to them. I once talked to all of them, asking if they would prefer we spent more time together as a family. The alternative I gave them was that I would build a platform upon which they could grow. Their response was, alright, we would choose a platform for our professional development.
Within Huawei, Huawei's management system is one based on processes. Processes are cold things, and I do not directly supervise Ms. Meng's responsibilities, so we don't have a strong connection in the workplace, either. Of course, maybe after my retirement in the future, I will try my best to compensate for these things.
16. Gao Yuan, Bloomberg: Follow-up question on that: You talked about retirement. Do you have any plan right now to retire? And the two other questions are related to the United States. You mentioned earlier that you do not have access or channels to talk to the US government. Right now we have so many foreign media outlets and journalists here. What is the message that you want to communicate through us to the US government? Trump also mentioned or tweeted that he could intervene in Meng's case if that would serve the trade negotiations with China. What would you say about that? And how do you feel about Donald Trump as a person?
Mr. Ren: To your first question, the timing of my retirement will depend on when Google can invent a new medicine that will allow people to live forever. I'm waiting for that medicine.
To your second question, the message to the US that I want to communicate is collaboration and shared success. In our high-tech world, it is increasingly impossible for any single company or even any single country to do the whole thing.
As for your third question, for President Trump's comment that he might intervene in the case of Meng Wanzhou, we need to wait and see whether he acts upon this. Right now I can't make a judgment about that.
And then for President Trump as a person, I still believe he's a great president, in the sense that he was bold to slash taxes. I think that's conducive to the development of industries in the U.S.
Reducing taxes is conducive to encouraging investment. It is like digging a trench in the ground, which makes it easy for water to flow into that trench. However, it's also important to treat all countries and all companies โ which are potential investors โ nicely, so that they will proactively invest. Benefits from increased investment can offset loss of revenue from tax cuts for the government.
If countries or companies are frightened, let's say, by the detention of certain individuals, then those potential investors might be scared away, and the favorable environment created by tax cuts will not perform to expectations.
17. Yuan Yang, Financial Times: Many people are saying that the suspicion around Huawei's 5G in Europe and the United States is not all about technology. It is about politics as well. Some people even argue that Huawei perfectly embodies the cold war going on between China and the US. What do you have to say about that?
Mr. Ren: First, I would say Huawei is not that important. We are like a small sesame seed, stuck in the middle of conflict between two great powers. What role can we play? The trade conflict between China and the US has not had a major impact on our business. We are expected to continue our growth in 2019, but that growth won't be greater than 20%.
Second, some people in the West believe that Huawei's equipment is stamped with some sort of ideology. That's as silly as people smashing textile machines back during the industrial revolution, as they thought advanced textile machines would disrupt the world. We only provide equipment to telecom operators, and that equipment doesn't have an ideology. It is controlled by telecom operators, not by Huawei. So I definitely hope that people do not go back to the old days of the industrial revolution when textile machines were being smashed.
18. Eamon Barrett, Fortune: Thank you. You were talking earlier about the need for the telecom industry worldwide to be integrated and be interconnected. Let's look at what happened to your state-owned rival ZTE last year when sanctions of America shut down the company's production. Are you worried that something similar might happen to Huawei if the US were to impose sanctions? Will it stifle Huawei's business? Secondly, I read that when Huawei was still young, and just a manufacturer of telephone switches, you had a meeting with Jiang Zemin when you told him that telephone switches were related to national security, and that a country without its own telephone switches is a country without its own military. I just want to ask, what do you mean by that? Maybe you still think domestically producing telecoms equipment is vital to China's national security?
We're able to do these things partly because we are not a public company, so we can work truly for our ideals, and for the greater good of society. Public companies tend to focus more on their financial numbers. So no matter how harsh the conditions are, we have committed ourselves to working for the bigger ideals of human society.
I also visited a village near Mount Everest at an altitude of 5,200 meters, as well as the base stations nearby. I told everyone that, if I'm personally afraid of death, how could I motivate my people to charge forward?
If Huawei were a public company, I think a lot of behavior that I shared with you just now would not have been possible. Over the past 30 years, Huawei has made very admirable contributions to the progress of people around the world, especially people living in poor and remote areas. Some of our people have even sacrificed their lives. Those people should never be forgotten. Likewise, we should not forget the contributions that Huawei has made to human society. More importantly, we shouldn't allow suspicion to confuse the facts.
19. Josh Chin, Wall Street Journal: Who do you have in mind to succeed you as the CEO of Huawei? The second question is about your roles in setting Huawei's culture, which is known for, it's very aggressive, with high standards, and is described by people as "wolf culture". What's your role in shaping Huawei's culture? Why Huawei's culture is important?
The company cannot place its future squarely on the shoulders of any single individual. If this person runs into trouble, then wouldn't that mean our company's operations would halt? In light of the future uncertainties in the environment where we survive and thrive, we must stick to collective leadership so that we can overcome one difficulty after another, and continually achieve success.
Apart from the rotating chairmen, we also have a Chairman of the Board. The Chairman of the Board chairs the Representatives' Commission to ensure rules set out in the Articles of Governance are followed by the Executive Committee and the whole Board of Directors.
We also have the Supervisory Board, which supervises the behavior of board members. So to your question, I don't know exactly who my successor will be. Successors will naturally appear during this circulation, and this process of renewing authority. It's not someone that I appoint. I am not a king.
20. Arjun Kharpal, CNBC: I just want to ask about your business outlook for the year. I notice this is not typically being the method for Huawei's business, but how much is at the front of your mind, given that some of your European competitors are struggling, the likes of Ericsson for example? Would that help you to diversify your business? Can you give us your revenue outlook for 2019 that you are targeting?
Mr. Ren: In 2019, we might face challenges and difficulties in the international market. That's why I said earlier that our growth next year would be less than 20%, and I think our annual revenue for 2019 will probably be around 125 billion US dollars. We will not take advantage of the difficulties that our peers like Nokia and Ericsson are facing, in order to seize their market shares. I also think that the macro environment is in their favor, because there are restrictions on Huawei in some countries, but there are no restrictions on those companies. Therefore, I believe they may have more opportunities than Huawei.
21. Yuan Yang, Financial Times: Several questions related to the PLA. What is the relationship between Madam Sun Yafang and Chinese Ministry of State Security, and how does that relate to Huawei? Second, what is your business collaboration with the PLA, or PLA-related institutions? If yes, what type of products do you provide to them? Third, is there any R&D collaboration or partnerships between Huawei and PLA-affiliated institutions?
Mr. Ren: For the first question, the biography of Madam Sun Yafang is available on Huawei's website. Second, we are probably selling a small amount of civilian products to the PLA, but I don't know the exact number, because it is not our major customer. Third, we don't have any R&D collaboration or partnerships with the PLA-affiliated institutions.
22. Josh Chin, Wall Street Journal: Just ask a general question. You were talking about President Donald Trump and the investment environment in the US. What are your views on the issues of trade war which is the access of American companies to the Chinese market? Currently foreign investment in the sector where Huawei is involved, which is cloud, is quite restricted. Do you think China should open up the access for foreign companies, and what impacts will this have on Chinese technology companies?
Mr. Ren: I'm a person that always advocates open policies; however, I'm not the one who is making decisions.
I can share several stories with you. In 2003, there was litigation between Huawei and Cisco that drew wide attention at the time. Back then, Huawei was still a fairly small company. That was, I would say, an overwhelming case that we had to deal with, and I personally felt enormous pressure, which was mainly attributable to a lack of experience. However, even back then, I didn't try to win the case by inciting nationalistic sentiments against Cisco. Several years later at an airport meeting that I had with John Chambers, he told me that he was aware of Huawei's attitude towards Cisco at the time. This is because we believe that China, as a nation, would only have hope once it opens up and implements reform. The country should not close its door simply because of one company, Huawei.
When unexpected huge incidents happened, like US companies that suddenly decided to stop buying Huawei phones, some people in China said we should do the same to Apple's iPhones in China. My opinion was that the Chinese government should not take similar measures against Apple in China. The national interests or policies around economic reform and opening up cannot be sacrificed for the benefit of Huawei. Even in light of the recent setbacks we encountered in some Western countries, we still support China, as a country, to become even more open. I think China can become more prosperous only when it becomes more open, and continues to press ahead with its reform agenda.
I also believe there will be future opportunities for us to meet with each other. Maybe we can deep dive into some of your questions in the future. I think today we covered a lot of topics, and by asking broader questions, I think you have done me a favor. I'm usually more concerned about interrogation-type questions with many follow-up questions. After our meeting today, I think we can drink coffee together some time and have some more casual talks. However, please don't make those casual talks into headlines. I believe we will have more heart-to-heart talks. Once again, my sincerest thanks to all of you. |
0.932187 | ARM Holdings PLC, Cambridge, England was originally founded as Advanced RISC Machines (hence ARM) in 1990 by Acorn Computers, Apple and VLSI Technology. A "reduced instruction set computer" (RISC) design approach means ARM processors have a simpler instruction set and require significantly fewer transistors than "complex instruction set computers" (CISC) such as the Intel x86 series processors used in most desktop and super computers.
The RISC approach reduces costs, heat and power. These reductions are highly desirable traits for light, portable, battery powered devices such as smartphones, tablets, notepads and embedded products such as set-top remote controllers. A simpler design makes multi-core computers more efficient with lower costs saving critical power in the server market.
ARM Holdings develops the instruction set and architecture for ARM based products, but does not manufacture the semiconductors. ARM Holdings licenses the chip design IP (intellectual property) and the instruction set architecture IP to third parties who then design their own products.
Some of the companies that manufacture chips that implement an ARM architecture include Apple, AppliedMicro, Broadcom, Cypress Semiconductor, Freescale Semiconductor, Nvidia, Qualcomm, Samsung Electronics, ST Microelectronics and Texas Instruments. ARM licenses processor designs to fabless companies such as Qualcomm and Nvidia, who then get their chips made by contract manufacturers like TSMC. Licensed companies are allowed to incorporate some of their their own unique design features. ARM periodically releases updates to its cores.
ARM processor architectures are designated by the prefix "ARM" and one or two digits, such as ARM7 or ARM15. Product designs have a name such as Cortex-A7, where the last digit(s) indicate the version. Current cores from ARM Holdings support both 32-bit and 64-bit address spaces.
Globally ARM is the most widely used instruction set architecture in terms of the chip quantity produced. The low power consumption of ARM processors has made them extremely popular. As of the end of 2014 over 50 billion ARM processors have been produced.
In early 1992 the Apple ARM collaboration evolved into the ARM6. Apple used the ARM6 based ARM610 as the basis for their Newton personal digital assistant (PDA), the forerunner to the smartphone. In 1994, Acorn used the ARM610 as the main central processing unit (CPU) for their RiscPC computers. DEC licensed the ARM6 architecture and produced the StrongARM. At 233 MHz, this CPU drew only one watt.
The StrongARM work was later passed to Intel as a part of a lawsuit settlement, and Intel took the opportunity to supplement their i960 line with the StrongARM. Intel later developed its own high performance implementation named XScale, which it sold to Marvell.
Transistor count of the ARM core remained essentially the same size throughout these changes. ARM2 had 30,000 transistors, while ARM6 grew to only 35,000.
The ARM Cortex series is a group of 32-bit and 64-bit RISC processor cores licensed by ARM Holdings. The 32-bit ARM Cortex-A cores implement the ARMv7 architecture. The 64-bit ARM Cortex-A cores implement the ARMv8 architecture. These architectures have evolved over time.
A-Profile -- the "Application" profile, implemented by cores in the Cortex-A series.
R-Profile -- the "Real-time" profile, implemented by cores in the Cortex-R series.
M-Profile -- the "Micro-controller" profile, implemented by cores in the Cortex-M series.
The ARM Cortex-A series of "application" processors provide a range of solutions for devices undertaking complex compute tasks, such as hosting complicated operating systems. Cortex-A processors scale efficiently across a wide range of performance in consumer, embedded and enterprise devices. These include smartphones, mobile computing platforms, digital TVs, set-top boxes, from Internet-of-Things (IoT) devices to enterprise, networking and server solutions. See the Android "Google" image to the left.
In an increasingly energy conscious landscape, the low power of Cortex-A processors provide a significant advantage. Device manufacturers can custom design their products for higher clock speeds, very low power consumption, instruction set extensions, size optimization, etc.
The Cortex-R series processors provide fast time-to-market devices through proven "real-time" technologies found in billions of products. They leverage the ARM ecosystem with local language and 24/7 support services to ensure rapid low-risk development. Cortex-R processors have key features that are demanded by deeply embedded, real-time markets such as automotive and wireless baseband.
The Cortex-M series is a group of processors that are intended for "micro-controller" use. The Cortex-M family is a range of scalable, energy efficient, easy to use processors designed to help developers meet the needs of connected embedded applications. The demands include delivering features at a low cost, with increasing connectivity and improved energy efficiency.
The Cortex-M family is optimized for cost, power, and mixed-signal devices. Major applications are: the Internet of Things (IoT), connectivity, motor control, smart metering, human interface devices, industrial control systems, domestic household appliances, consumer products and medical instruments. |
0.999974 | We analyzed a scene from Batman Begins. Batman is attempting to stop a moving car three stories beneath him in a parking structure. As the car is driving down the ramp, Batman falls and aims to hit the vehicle as it passes under him. In the scene. He begins with an initial velocity of zero and accelerates at 9.8m/s/s due to gravity. When we froze the scene to count the levels in the parking structure, there were three levels, which is approximately 30 feet or 9 meters. At ten feet a story, or thirty feet, falling with a mass of around 190 pounds, Batman's velocity would amount to 13.622 m/s. |
0.99968 | How do i calibrate a remote microphone system?
Condenser microphones are extremely stable and sensitive transducers when used in their normal operating conditions. When used for long-term noise monitoring, they can be exposed to more extreme environments (e.g. high temperatures, high windspeeds, moisture, etc) which may cause a change in sensitivity, and even damage. The nature of this type of monitoring often precludes a site visit to calibrate the microphone in the normal way, such as using a sound level calibrator or pistonphone mounted directly on the microphone capsule.
We therefore need a method of checking that all is well at the microphone end, so this article describes two methods that can be used.
The first is SysCheck from GRAS, which simply injects an electrical signal into the microphone circuit, via the preamplifier, to check the signal path integrity. This includes the microphone capsule itself, which means that any change in the resulting measured signal can be used to deduce if the microphone capacitance has changed, which might be an indicator of damage (e.g. damage or corrosion on the diaphragm, or physical damage). A similar method is also called charge injection calibration (CIC).
Itโs important to note that this is not a โcalibrationโ as such, it is simply a means to check that nothing has changed out of tolerances, which can be preset by the measuring system. It is not an acoustical signal.
In order to inject the signal, an additional connection is required on the preamplifier, and this is normally available via an industry standard 7-pin Lemo connector, used by many GRAS power supplies, such as 12AK, 12AA etc. These power supplies include the signal generator, and will activate the signal when the Syscheck button is pressed, or remotely by software trigger.
microphone, such as IEPE, which is used solely to provide power to the preamplifier, and return the measured signal. Some front-ends have Syscheck built-in, such as Apollo from Sinus, where the Samurai software can provide the necessary signal on the correct pin of the Lemo connector.
For this method, a suitable preamplifier must be used, such as the 26AJ from GRAS, and this feature is also built-in to the GRAS 41AC-2 Environmental Microphone.
A more stable and repeatable calibration can be achieved by using an electrostatic actuator mounted on the microphone itself. This takes the form of a plate mounted very close to the microphone diaphragm, and normally replaces the standard protection grid.
Some microphones incorporate the actuator in the weather protection system (e.g. rain cover). A variant is to electrically isolate the top plate of the standard microphone grille, so this doubles as the actuator (e.g. the MK255 capsule in the Svantek SV200). |
0.999918 | The Maldives are an island chain nation that sits between the Arabian Sea and the Indian Ocean. The country has no land borders, although just to the country's northeast is India.
The entire country of the Maldives is simply coral reefs and atolls with the country's highest point being only six feet (two meters) above sea level.
The Maldives has a fairly consistent weather pattern throughout the year. Temperatures rarely get below 75ยฐ F (24ยฐ C) and rarely get above about 90ยฐ F (32ยฐ C). What does change though is the humidity and rain. The humidity is always somewhat high, but during the months of October and November it tends to decrease a bit as rain is rare. From about December to March the humidity and rain tends to be the heaviest, although both can arrive or leave at any time during the year.
Due to its very geography, the wildlife in the Maldives is limited and that begins with the mammal population, which is scarce at best. Only the flying fox and shrew are native to the islands, although numerous other animals have since been introduced by people. Opposite of this limitation is the sea life. In the surrounding oceans there are mammals, like the whale and dolphin, but also thousands of fish, shellfish and other animals like mollusks and coral. Some of the more common animals in these waters are rays, sharks, eels, tilapia, clams, squid, octopuses, lobsters, crabs, and starfish among others.
The bird life is also impressive, but is primarily limited to water fowls. The heron, frigate bird, and moorhen are all common. The reptile life is, like the mammals, also limited, but there are geckos, lizards, snakes, turtles, and crocodiles. The amphibians are more varied as there are numerous frogs and toads among others. There are also a decent number of insects and other small animals like spiders and scorpions. |
0.960311 | Can I retrofit my halogen headlamps with an after-market HID headlamp system such as Xenon lights?
In general,we do not allow the retrofitting of HID lamp systems on existing vehicles, unless it is duly certified by the vehicle manufacturers.
This is because converting the existing headlamps to HID headlamps would require the entire headlamp assembly, including the electrical system, to be replaced as the reflectors and lenses are different from those in a conventional halogen headlamp.
In addition, the wiring of the existing headlamp system would not be able to handle the much higher starting current required for a HID headlamp system. This could cause extensive damage to the headlamp assembly and electrical system and therefore could pose a fire hazard to road users. |
0.999188 | Why should you care about the benefits of essential oils? What are essential oils? How can they help you in your daily life? Essential oils can be beneficial for many things. One reason I include essential oils is because I was able to see firsthand the side effects pharmaceutical medication can have. Iโm not saying do not take prescribed medicine because they can be very beneficial. I just prefer a more natural route with less side effects. This includes natural immune boosting items and remedies. One of the ways I use a holistic approach is through essential oils. I have a few favorite recipes including ones for stress and anxiety and a homemade bath salts with.
Essential oils are compounds extracted from plants. The oil is extracted through distillation using steam,water, or by mechanical methods such as cold pressing. Once the oil is derived it is combined with a carrier oil to make the oil ready for use.
They are most commonly used by inhaling them or rubbing them on the body. If using them directly on the skin always make sure to dilute with a carrier oil. These oils can reduce symptoms of depression and anxiety, balance out hormone levels, heal digestive disorders, disinfect, and aid in reducing cold and allergy symptoms.
Inhaling essential oils triggers powerful brain responses. Similarly, topical application allows the oils to quickly enter the bloodstream by being absorbed through skin tissue. I have found that applying topically with a carrier oil is great for muscle strain. Another excellent use of is for reducing congestion One recipe I use is a homemade bath salts with essential oils added recipe. It not only aids with achy muscles but opens up the sinuses to reduce congestion.
Vaporizing bath slats with essential oils. Good for relieving sinus congestion and sore achy muscles.
1. Add the epson salts and baking soda to a medium mixing bowl. Whisk to combine.
2. Add the essential oils and stir well to distribute.
3. Mix in the soap colorants and stir until your desired shade of green is achieved.
4. Transfer to an airtight glass container and store in a cool and dry place.
1. Add 1/4 cup of the vaporizing bath salts to your warm bath water.
2. Use your hand to circulate the bath salts around in the water and to activate the essential oils.
3. Sit back and enjoy the vaporizing effects of the peppermint, eucalyptus and rosemary essential oils. These bath salts are perfect for relieving sinus congestion and to ease sore and achy muscles.
You can also pack the mix in ice cube maker containers and freeze. Then pop a cube out to place in the shower or bath and let the aromas work.
Here are step by step pics to go with the above instructions.
Using essential oils can help in many aspects of life including cleaning, stress relief, disinfectant, and more. Stay tuned for more recipes I use in my daily life. What do you use in your life?
I Have used a few essential oils but mainly when I was pregnant. This sounds really cool!
I love DIY project and making your own bath salts is a great idea. Very simple and you get to control the essential oil mixtures that you put together! Healthy and homemade, thats how we like it!
Iโve heard about essential oils, but never really took the time read up on the benefits of them. Thanks for sharing. This makes me want to look into it more. Especially considering itโs potential for helping with stress and so forth.
I love DIY projects! Making bath salts sounds really simple and we love essential oils in our house! I will have to give this a try.
I just used some bath salts with oils in them the other day. These had lavender in them, so I put them in my boysโ bathtub on a crazy night and they loved it! I didnโt realize it was so easy to make, Iโll have to make more myself soon.
These look great, and a great gift for the holidays, too!
I love these! Not only would they be great for pampering myself, but they also make perfect gifts!
The more I hear about the wonders of essential oils, the more I want to try them! With the cold months coming, Iโm definitely going to make those decongestant bath salts. Sounds like a total game changer!
I have been wanting to make my own bath salts mix. Think Iโll be starting out with this formula of yours to get me started in the right direction. Plus essential oils are amazing.
Iโve made a sugar scrub using essential oils but not bath salts! What a great idea I will definitely try this out!
I love sugar scrubs too especially for my face but the bath salts are great for soaking in.
I totally need to pick up a rosemary essential oil! This sounds so much better than buying lush bath bombs that keep staining my tub!!
Oh, I need this in my life! Iโm training a lot and my muscles need some relief from a wamr bath with essential oils. |
0.998554 | It has been said that only two equally powerful emotions drive our behavior โ fear and love. I believe thatโs true. The most common questions people ask me come down to some form of this: How can I get over my fear and take a chance?
Anger, resentment and our need to control everything around us are all different forms of fear that we sometimes adopt as defense mechanisms to keep us in our comfort zone. In order to create and live a life that you love, you need to take some risks, step out of familiar territory and face your fears. Growth, self-knowledge and a life well-lived begin at the end of your comfort zone. But you must be willing to take risks to get there. Some people are natural risk-takers. Other people are content to stay where they are because it's comfortable, even if it means settling for a life of mediocrity and unfulfilled dreams.
The next time fear stops you from taking action, consider this radical notion: What if there is no such thing as failure? Then entertain this idea instead: I cannot fail - I only produce results. Failure is simply a judgment we place on a given outcome. We cannot choose our facts, but we can choose to look at them in a different light. As Wayne Dyer often said, change the way you look at things and the things you look at change.
Nothing thatโs truly valuable was ever achieved by playing it safe. Itโs better to jump in and experience life than to stand on the sidelines fearing that something might go wrong. You donโt need to know it all in advance. No one, not even the greatest achievers in the world, ever does. You just need to know enough to get the ball rolling, and learn โthe restโ by taking action. Taking action will do more for your learning than planning and thinking alone ever will.
The central idea of the Law of Attraction is โenergy flows where attention goesโ, or whatever you focus on, expands. It applies to things you feel good about that enhance your self-image, as well as to negative, self-destructive thoughts. In other words, you can attract more of what you want - and less of what you donโt want - into your life by shifting your attention in a positive direction. A simple 3-step practice that has been around for years can help you do just that.
1. At the end of each day, write down three accomplishments from the day in a journal, either electronically or on paper.
2. At the end of each week, review your 21 accomplishments and write down your top 3.
3. Then, at the end of the month select the top 3 accomplishments for the month and celebrate by treating yourself to something you love.
To make this exercise even more effective, try doing it with a friend or group and share your accomplishments with each other. That way youโll hold each other accountable to send the list daily, weekly, and monthly.
This is a big improvement over just looking at a long list of tasks ahead or concentrating on all of the things you havenโt gotten done. Creating a written record of your successes, large and small, consistently builds your confidence and self-esteem. But the biggest benefit is that it helps you to be more present, more effective, and happier in your daily life.
The desire for perfection can motivate us to achieve the grandest and most sublime goals. But when it turns into perfectionism, it can just as easily be the biggest obstacle to our dreams we face.
Bob Proctor likes to say, โThere is no RIGHT way to do anything. It can be a good way. It can even be a valid way, but clearly understand there is always a better way. And with the right attitude you will find it.โ Waiting for the perfect time and state of readiness before trying anything all but guarantees that true opportunities for success will go unrecognized.
Remember that youโre only human, and humans make mistakes. We ALL make mistakes in life. The difference is that some people learn from them and use them as stepping stones to greater achievement, while others let their mistakes consume them.
Perfectionism does more than stop you from making progress. It can also derail you from living in the present moment and keep you from enjoying life while youโre working toward your goals. In fact, your imperfections are often your best qualities. They make you unique and what appears to be a flaw can be your most special attribute to use for your greatest good.
What Is Your Passion Anyway?
โThe only thing worse than being blind is having sight with no vision.
When creating a vision of your ideal life, have you ever asked yourself โWhat is my passionโ, and felt frustrated when you donโt know the answer?
Limiting Belief #1: Your passion is something that totally consumes you, and makes you feel like youโre practically on fire inside.
Many people get stuck when something theyโre interested in doesnโt make them burn with single-minded enthusiasm. They assume it must not really be a passion. But this couldnโt be further from the truth. Some people feel a deep sense of calm or inner peace when they are involved in a passionate pursuit. Others might feel love, completion or joy. Still others might experience that intense fiery feeling we recognize as โpassionโ. A true passion is nothing more than something that makes the everyday world seem to melt away when youโre engaged in it... and that can look different for different people.
Limiting Belief #2: Putting pressure on yourself to identify your single biggest lifelong passion.
The fact is that most of us have more than just ONE passion. I currently have at least 5 main passions โ and all of them are important to me. Chances are you have more than one thing that interests or inspires you too! So instead of putting pressure on yourself to identify just one passion, why not ask โwhat ARE my passionsโ instead of โwhat IS my passion.โ Give yourself the freedom to explore areas of life you may not have considered before, to add new interests and release outworn ones, and donโt feel like you have to commit yourself to just one โpassionโ forever.
Hereโs to living with passion! |
0.999887 | Follow these steps to create a practical, long-lasting and beautiful kitchen addition.
One of the most important features of any kitchen is the island. Not only does this structure serve to fill out the space, but it also offers a range of benefits for homeowners. These include an increase in available food preparation space as well as additional storage.
If you are planning on installing a functional island in your kitchen, follow this guide to create a long-lasting and beautiful addition.
Before you begin to build, itโs important to determine what your priorities are for your island. If storage is top-of-mind, plan for a taller and wider structure. This will allow you to increase the amount of shelving inside the unit and maximize its capacity. Need a little inspiration to help organize this space? Better Homes & Gardens offers a guide to several ideas for thinking outside the box, including a built-in microwave nook, hidden cabinets and storage cubbies.
If food preparation is the focus, consider installing a wet bar into the island itself. The addition of this small sink will reduce the number of trips between cooking stations, which will streamline the process and condense any messes you may make.
You do not want your island to dominate the entire kitchen. Measure out the available space in the room and from there, ensure that you will be allowing suitable aisle space between the structure and surrounding furniture and walls. If an island is created too large, it can cause a room to feel visually cramped and make it difficult to move around the room.
It may be necessary to add additional lighting to your kitchen after installing the island. If you want to make the unit the focal point of the room, a hanging lighting structure will help draw the eye to the center of the space. For a more subtle look, consider adding an ultra-thin ceiling light or an assortment of electronic candles.
Have you ever considered adding a wine fridge to your kitchen, but do not want to give up the square footage that it requires? An island is a perfect opportunity to install a unique element like this into a more compressed space, as the addition can be built around other features. Talk to your contractor early on in the planning process to learn how to best incorporate a unique touch.
You can never have too much seating, especially when it comes to entertaining! By extending the edge of your island countertop off of one side, you can create a simple ledge that is ideal for bar stools. This provides a less formal dining area, perfect for guests to gather around while you cook. When these stools are removed, it leaves additional counter space for preparing, storing or serving food. |
0.947201 | dhrig ivฤhฤ jฤซvanฤ jit har prฤซt n pฤi .
jit kanm har vฤซsarai dลซjai lagai jฤi .1.
aisฤ satigur sฤvฤซai manฤ jit sฤviai gลvid prฤซt ลซpajai avar visar sabh jฤi .
har sฤtฤซ chit gah rahai jarฤ kฤ bhau n hลvaฤซ jฤซvan padavฤซ pฤi .1. rahฤu .
gลbind prฤซt siu ik sahaj upajiฤ vฤkh jaisฤซ bhagat banฤซ .
ฤp sฤtฤซ ฤp khฤiฤ tฤ man niramal hลฤ jลtฤซ jลt samaฤซ .2.
bin bhฤgฤ aisฤ satigur n pฤฤซai jฤ lลchai sabh kลi .
kลซrai kฤซ pฤl vichah nikalai tฤ sadฤ sukh hลi .3.
nฤnak aisฤ satigur kฤซ kiฤ ลh sฤvak sฤvฤ karฤ gur ฤgai jฤซu dharฤi .
satigur kฤ bhฤnฤ chit karฤ satigur ฤpฤ kripฤ karฤi .4.1.3.
and accursed is the occupation in which God is forgotten and man becomes attached to duality.
O my soul, so serve the True Guru, by serving whom the Lord's love may be produced and all other be forgotten.
Thus the soul shall remain attached with God, there shall be no fear of old age and the man shall attain the immortal status. Pause.
See, as is the service performed so is a Divine peace, which springs from the Lord's love.
With self-effort, when I stilled my self-conceit, then my mind became pure and my light got blended with the Divine light.
Without Good fortune, such a True Guru cannot be obtained, however much all may long for him.
If the screen of falsehood is removed from within then an ever-lasting peace is obtained.
Nanak, what service can the servant perform for such a True Guru? He should lay down his very life for the Guru.
If the man attends to the True Guru's will, then the True Guru, himself shows him kindness.
Cursed is that life, in which the Lord's Love is not obtained.
Serve such a True Guru, O my mind, that by serving Him, God's Love may be produced, and all others may be forgotten.
A divine peace wells up from God's Love; behold, it comes from devotional worship.
Without good fortune, such a True Guru cannot be found, no matter how much all may yearn for Him.
O Nanak, what service can the servant perform for such a True Guru? He should offer his life, his very soul, to the Guru. |
0.986801 | How do I adjust my timestamp for Daylight Savings Time?
To adjust your timestamp to reflect Daylight Savings Time, Click on "My account" and "Select Timezone". Check the box labeled "Select to Observe DST". |
0.999386 | Flask-Diamond is a batteries-included Python Flask framework, sortof like Django but radically decomposable. Flask-Diamond offers some opinions about network information systems that process data. Using Flask-Diamond, you can scaffold a working application with sensible defaults, then easily override those defaults to meet your own goals. Flask-Diamond provides a shared vocabulary that helps teams coordinate as they scale up to develop multiple Flask applications while maintaining good code reuse and learning transfer. Flask-Diamond goes beyond a โproject scaffoldโ by providing a complete architecture and team solution, including documentation, tutorials, and other learning support.
Flask-Diamond is a batteries-included Flask framework. |
0.999095 | Working out hard to build abs? Read the following article that recommends some of the most healthy foods, which aid in fat burning, especially from the stomach.
In order to lose weight from your belly, you have to make a routine of exercising daily. Along with exercises, taking a proper diet is extremely essential. A healthy abs diet ensures that your body is energized to carry out the various exercises that you need to perform to lose belly fat. In addition, it aids in fat burning, too.
Your breakfast should be a must-have meal of the day. Never skip your breakfast as it provides you with the energy to keep going the whole day. Moreover, you must have seen that whenever you do not eat in the morning, you tend to eat whatever you can lay your hands on during the day. So, to avoid overeating and to keep yourself energized, eat a calcium and protein rich breakfast such as cereals with milk, a boiled egg, and perhaps, a glass of juice.
It is recommended that you give up processed foods, oily stuff, and junk food, especially burgers and pizzas, as these all add unnecessary layers of fat on the belly.
Have lots of fruits and vegetables. Make sure that you include fiber-rich foods such as apples, bananas, prunes, grapefruits, raspberries, oranges, almonds, green peas, avocados, sweet potatoes, broccoli, carrots, and sweet corn in your diet plan.
Although many diets recommend virtually giving up carbohydrates, it is not what you should aim for. However, what you should do is to take only those foods, which have complex carbohydrates, such as oatmeal, green leafy vegetables, legumes, brown rice, brown bread, and whole-wheat pasta. Researches have shown that complex carbohydrates are processed very easily by the body, and they, in fact, help in burning fat from all over the body.
Proper diet should include low-fat dairy products like yogurt and milk as researches show that dairy foods, especially low-fat milk, are one of the shocking foods that burn belly fat.
High-protein foods such as chicken and turkey are a must-have in any good diet for abs. High-protein foods improve upon the body's metabolism, thus leading to lesser weight gain. Eating fish such as salmon and tuna is recommended for men as these contain the omega-3 essential fatty acids, which are needed to keep the heart in good shape. Various nuts and seeds such as almonds and flax seeds are rich in such healthy fats too and so, should be taken every day.
Besides eating the right food, make sure that you drink enough water to keep your body hydrated. Ideally, two liters of water every day are suggested. However, if you are heavily into exercising and bodybuilding, drink a gallon. Water helps in better digestion and elimination of fats from the body.
As mentioned above, complement this diet with some effective cardiovascular exercises, as well as abdominal exercises. If you are able to stick to this plan and a regular exercise regimen, there are no two ways that soon you will experience fat loss from your entire body, including your stomach, thus revealing those much coveted abs. |
0.998736 | Have you ever felt overwhelmed? Here are some simple steps you can take to relieve the feeling of overwhelm.
Does overthinking get your head spinning, impact your decision making, and limit you? Here are some ways to stop overthinking.
Stop overthinking by retraining your brain - take chances, take risks, have fun, have gratitude, be spontaneous, and rewire your limiting beliefs.
Get in action mode to keep your mind busy and stop overthinking - have a positive place for your mind to go.
Spend time with positive people and influences who will help elevate your confidence, reduce insecurity, and believe in you.
Here's a simple exercise that helped me rewire my limiting beliefs and stop overthinking.
A list of books on overthinking from Amazon. |
0.998233 | Escribo para sujerir que todos los grupos nos reunamos pronto para empezar a planear lo que haremos para asegurar que el Condado de Humboldt se declare un Condado Sanctuario!
I'm writing to suggest that all the various groups get together to begin planning what we'll do to ensure that Humboldt County declares itself a Sanctuary County!
At least a couple of versions of the County Ordinance are floating around, including one proposed by the Human Rights Commission and another written by Eric Kirk (please see draft attached).
Por lo menos dos versiones de la Ordenanza estan flotando, incluyendo uno escrito por la Comision de Derechos Humanos y otro escrito por Eric Kirk (por favor encuentren el borrador aqui).
Let's come together on Sunday, June 11, 2:30, at Rohner Park, in Fortuna. We'll meet on the grassy area near the playground. This way, the kids can play while we talk. Bring your own lawn chairs. Among other ideas, we will consider holding a "community consultation" so that the community members may express their needs and wants.
Juntemonos el Domingo, Junio 11, 2:30, en Rohner Park, en Fortuna. Nos reuniremos en el pasto cerca de los juegos de los ninos. Asi, los ninos pueden jugar mientras platicamos. Por favor traigan sus propias sillas. Entre otras ideas, consideraremos organisar una "consulta comunitaria" para que miembros de la comunidad puedan expresar lo que quieren.
Please let me know if you'll be able to make it on June 11.
Por favor aviseme si podra llegar el 11 de Junio. |
0.98797 | So, what is a research design? The notion of research design usually refers to the general strategy that is applied by the individuals working on different case studies and experiments. Using a particular strategy, they can integrate all the elements of their research in a logical sequence. Moreover, these individuals are given the opportunity to structure their case studies in a coherent way.
In the most cases, the notion of research design is referred to an outline that determines three key elements of the research paper.The major components of any case study include three different stages. While the first one is known as data collection, the further two stages imply the processes of measurement and data analysis. Hence, it can be concluded that research design is a term used to denote a particular approach that is applied by the individuals in collecting and analyzing the materials needed for creating a case study.
The first and foremost thing that should be mentioned is the fact that the researchers should be able to select an adequate research design for writing their scientific paper. This issue is of great importance since, in the most cases, the inappropriate choice of the individuals may have a considerably negative impact on the validity of the results.
Additionally, it affects the reliability of the conclusions that can be observed in the paper. So, it is a high time to provide a detailed description of different types of research design.As it was already mentioned, there are four types of the research approaches. The scientists tend to claim that a list of these approaches includes exploratory research, descriptive research, explanatory research, and evaluation research.
When this type name is observed, it can be concluded that the main purpose of this particular research design is to explore the problem introduced in the paper. Indeed, this scientific approach is usually applied to study some issues that remain unclear as well as the ones that should be defined. For instance, in the case, if the researchers find an interesting hypothetical idea, they tend to use this type of research design to conduct a study. Thatโs the reason why such research papers do not provide any final offers related to the solution of the issue.
This notion is used to denote another type of the research approaches.
The initial purpose of this method can be grasped from its name. In this case, this approach is used when the researchers want to provide more details regarding a particular issue that was discussed earlier. Apart from an explicit description, descriptive research design is used to explain some things and validate them as well. The list of its key methods may include the observation, the numerous surveys, and a variety of case studies.
Explanatory research is the following type of the approaches used in creating a case study. The interesting thing is that such scientific papers explain different issues or phenomena as well as their causes and effects. Hence, while writing using this type of research design, the scientists attempt to provide the cause-effect analysis of the issue introduced in the paper. Thatโs the reason why this scientific approach may be called not only as the explanatory research but also as the causal one.
Evaluation research is the last but not least type of research designs.
The primary goal of such research is to measure the effectiveness of the program discussed in the paper.
This type of research is usually written on the basis of already existing data. Evidently, it is not required to include any hypothesis in the paper.
The correlational research presents two different variables, and the purpose of this paper is to identify whether they are related to each other in a particular way. Using a statistical review, the researchers observe every single variable.
In this case, the researchers attempt to establish the cause-effect relations between all the variables discussed in a case study.
This quantitative design is almost identical to the experimental research method. The only thing that differentiates these types of research designs is the use of accidental sampling while selecting different groups for creating a case study.While using a qualitative research design, the scientists do not attempt to forecast the results of the study. In turn, the researchers intend to explore the issue, and as a result, they try to understand and describe their findings.
How to Create a Research Design?
Identify the expected outcome of the potential research paper.
Try to pose a question that you want to discuss.
What kinds of measurement will you need?
Do not forget about selecting a population and identifying the method of data collection.
Develop the relevant interrelations between the variables.
Use the appropriate analysis technique.
Think about some possible distribution channels of the research paper. |
0.991515 | According to statistics, 46% of all Google searches are done in order to find local information, with 97% done to find a local business to visit in person.
This means that people use search engines more than ever to orient themselves and find retail stores and other places to visit. So with that in mind, how do you place your own establishment close to the top of the list? What kind of content do you have to create in order to boost your local search ranking and to help people find your brand more frequently than before?
The first step should be to claim your business pages on Google as soon as possible. Just as you are looking for visitors and customers for your business, those same people are looking for establishments that suit their interests. Depending on how specialized or niche your establishment is, this will allow you to reach a new audience fairly easily.
Once thatโs done, you should integrate those pages into your blog content and throughout the website youโve created for your business. Itโs worth noting that you should always use up-to-date contact and address information once you claim your Google pages. This will boost your SEO optimization and SERP ranking across the board, so make sure to integrate claimed links into your writing as organically as possible.
Every country, territory, and industry has certain keywords that are representative of that particular field. For example, a pizza establishment should use keywords related to different toppings, dough, flavors and other elements of the dish in their content.
In doing so, you will show up on Googleโs and other search engine result pages more frequently, especially for tourists and travelers. Tools such as Google Adwords and SEM Rush are perfectly suited to help you find local keywords to rely on, so make sure to spread them out evenly throughout your text.
When it comes to including local links in your content, you should generally avoid talking about or mentioning competitive brands and establishments. Not only is it not considered fair sportsmanship but it will also potentially drive your customers away to other businesses.
What you should do instead is mention local brands, companies, and businesses related to your industry. Coming back to the example of a pizza restaurant, you can mention businesses that offer sweets, local gyms, coffee shops, and other commonly-associated places. These links will help your pages rank higher in Googleโs search while also eliminating the possibility of confusing your business with another in the same industry.
Any written content should be legible and easy to read. This tool will quickly analyze your writing and provide constructive feedback on what you can do to make it more accessible to readers.
If you want to provide visibility for your establishment in terms of tourists and travelers, localization is a necessity. Content localization services will provide you with all the assistance you need in order to retrofit your content into different languages.
Proofreading and spellchecking are important aspects of content creation, especially in terms of SEO. Make sure to give this platform a shot before publishing any content aimed at boosting your local search ranking.
If you donโt have a suitable text editor already and want to use a cloud-based service to create your content, this is the perfect solution to your problems. The tool is designed with versatility and cross-platform synchronization in mind, meaning that you can write texts and articles through smart devices and desktops alike.
While this affects global SEO more than local, tagging and formatting your content is still very important for good ranking placement. Formatting your written content is fairly straightforward and CMSs such as WordPress offer very clear options for doing so. Just donโt forget to tag your headings, subheadings and other prominent elements on your website and landing page.
This tagging allows people who search for anything related to the content you wrote to find your website, especially if you are geographically close to where they are currently. Content tagging is a great strategy for gaining further local visibility when someone searches for businesses related to your industry, as well.
Multimedia content such as photos, videos, and customer testimonials will further boost your local (and global) search engine ranking. This is especially important for your blog, product portfolio (or menu, depending on the industry), and landing page.
The more visual information you provide for potential customers and visitors, the easier it will be for people to find your establishment. Donโt rely on stock photos or royalty-free photography found around the web. The more interesting and original your photos are, the more trust you will gain with anyone willing to give your products or services a go.
Googleโs review system is your best friend and worst enemy when it comes to local search ranking. According to published statistics, 74% of consumers trust businesses with positive reviews more than they would otherwise. This means that people often decide whether or not to visit an establishment based on what they read on Google. In order to make this system work in your advantage, you should encourage existing visitors to leave positive reviews on your behalf.
Emphasize the importance of Google reviews to your visitors through subtle calls to action in menus or business cards around the establishment. As a quick fix, you can even ask your employees or B2B network associates to leave some reviews to give you a search ranking bump. The best way to encourage positive Google reviews, however, is to provide quality services to your consumers and maintain the promises you set in your content, website and marketing materials.
Lastly, potential consumers and visitors will often message your business page directly through Google. These messages or comments will show up on your Google business listing but it is up to you to respond to them in a timely fashion. These posts are permanently kept online for every potential customer to see, so the way you treat comments and messages will reflect your business culture.
Make sure to be professional but casual and welcoming at the same time when answering questions on Google. Donโt leave your commenters hanging without an answer because it will reflect poorly on the way you treat your stakeholders. Be diplomatic and forthcoming, accept constructive criticism and invite people to visit your establishment in every answer you provide.
In the end, creating content aimed at local search ranking and SEO might seem tricky at first, especially if your business is in a populated area. Build your brand reputation through consistent, quality content with local links and Google business page updates. The right crowd will find its way to your business and you will soon find the time and resources youโve poured into your local search ranking to be worth it.
**About the Author: Kristin Savage nourishes, sparks and empowers using the magic of the word. Along with pursuing her degree in Creative Writing, Kristin has been gaining experience in the publishing industry, with a focus on marketing strategy for publishers and authors. You can find her on Facebook. |
0.993141 | Recent evidence demonstrates that American Sign Language (ASL) signs are active during print word recognition in deaf bilinguals who are highly proficient in both ASL and English. In the present study, we investigate whether signs are active during print word recognition in two groups of unbalanced bilinguals: deaf ASL-dominant and hearing English-dominant bilinguals. Participants judged the semantic relatedness of word pairs in English. Critically, a subset of both the semantically related and unrelated English word pairs had phonologically related translations in ASL, but participants were never shown any ASL signs during the experiment. Deaf ASL-dominant bilinguals (Experiment 1) were faster when semantically related English word pairs had similar form translations in ASL, but slower when semantically unrelated words had similar form translations in ASL, indicating that ASL signs are engaged during English print word recognition in these ASL-dominant signers. Hearing English-dominant bilinguals (Experiment 2) were also slower to respond to semantically unrelated English word pairs with similar form translations in ASL, but no facilitation effects were observed in this population. The results provide evidence that the interactive nature of lexical processing in bilinguals is impervious to language modality. |
0.999994 | A clock is set right at 5 a.m. The clock loses 16 minutes in 24 hours. What will be the true time when the clock indicates 10 p.m. on 4th day?
Answer : 4 11 p.m. |
0.754833 | The English word "tobacco" originates from the Spanish and Portuguese word "tabaco". The precise origin of this word is disputed, but it is generally thought to have derived at least in part, from Taino, the Arawakan language of the Caribbean. In Taino, it was said to mean either a roll of tobacco leaves (according to Bartolomรฉ de las Casas, 1552) or to tabago, a kind of L-shaped pipe used for sniffing tobacco smoke (according to Oviedo; with the leaves themselves being referred to as cohiba).
The earliest depiction of a European man smoking, from Tobacco by Anthony Chute, 1595.
An Indian man smoking Tobacco on hookah, Rajasthan, India.
Following the arrival of the Europeans to the Americas, tobacco became increasingly popular as a trade item. Hernรกndez de Boncalo, Spanish chronicler of the Indies, was the first European to bring tobacco seeds to the Old World in 1559 following orders of King Philip II of Spain. These seeds were planted in the outskirts of Toledo, more specifically in an area known as "Los Cigarrales" named after the continuous plagues of cicadas (cigarras in Spanish). Before the development of the lighter Virginia and white burley strains of tobacco, the smoke was too harsh to be inhaled. Small quantities were smoked at a time, using a pipe like the midwakh or kiseru or smoking newly invented waterpipes such as the bong or the hookah (see thuแปc lร o for a modern continuance of this practice). Tobacco became so popular that the English colony of Jamestown used it as currency and began exporting it as a cash crop; tobacco is often credited as being the export that saved Virginia from ruin.
Turkish tobacco is a sun-cured, highly aromatic, small-leafed variety (Nicotiana tabacum) grown in Turkey, Greece, Bulgaria, and North Macedonia. Originally grown in regions historically part of the Ottoman Empire, it is also known as "oriental". Many of the early brands of cigarettes were made mostly or entirely of Turkish tobacco; today, its main use is in blends of pipe and especially cigarette tobacco (a typical American cigarette is a blend of bright Virginia, burley, and Turkish).
Since 1947, the Indian government has supported growth in the tobacco industry. India has seven tobacco research centers, located in Tamil Nadu, Andhra Pradesh, Punjab, Bihar, Mysore, and West Bengal houses the core research institute.
As with all crops, tobacco crops extract nutrients (such as phosphorus, nitrogen, and potassium) from soil, decreasing its fertility.
Creamy snuff is tobacco paste, consisting of tobacco, clove oil, glycerin, spearmint, menthol, and camphor, and sold in a toothpaste tube. It is marketed mainly to women in India, and is known by the brand names Ipco (made by Asha Industries), Denobac, Tona, and Ganesh. It is locally known as mishri in some parts of Maharashtra.
Dokha is a middle eastern tobacco with high nicotine levels grown in parts of Oman and Hatta, which is smoked through a thin pipe called a medwakh. It is a form of tobacco which is dried up and ground and contains little to no additives excluding spices, fruits, or flowers to enhance smell and flavor.
Kreteks are cigarettes made with a complex blend of tobacco, cloves, and a flavoring "sauce". They were first introduced in the 1880s in Kudus, Java, to deliver the medicinal eugenol of cloves to the lungs.
Following the American Civil War, the use of tobacco, primarily in cigars, became associated with masculinity and power. Today, tobacco use is often stigmatized; this has spawned quitting associations and antismoking campaigns. Bhutan is the only country in the world where tobacco sales are illegal. Due to its propensity for causing detumescence and erectile dysfunction, some studies have described tobacco as an anaphrodisiacal substance.
Research on tobacco use is limited mainly to smoking, which has been studied more extensively than any other form of consumption. An estimated 1.1 billion people, and up to one-third of the adult population, use tobacco in some form. Smoking is more prevalent among men (however, the gender gap declines with age), the poor, and in transitional or developing countries.
Tobacco has a significant economic impact. The global tobacco market has been approximated to be US$760 billion (excluding China). Statistica estimates that in the U.S. alone the tobacco industry has a market of US$121 billion despite the fact the CDC reports that US smoking rates are declining steadily. In the US, the decline in the number of smokers, the end of the Tobacco Transition Payment Program in 2014, and competition from growers in other countries, made tobacco farming economics more challenging.
^ "Youth Tobacco Prevention: Underage Prevention Laws". Transform Tobacco. Archived from the original on 20 December 2016. Retrieved 4 December 2016. As of August 2014, all but eight states had laws prohibiting minors from purchasing tobacco: Alaska, Colorado, Massachusetts, Nevada, New Jersey, New York, Rhode Island, and West Virginia. All but eleven states had youth tobacco possession laws in place. These are Delaware, Hawaii, Massachusetts, Minnesota, Nevada, New Jersey, New Mexico, New York, North Carolina, Tennessee and Pennsylvania. There are still six states which prohibit youth from possessing tobacco, but allow for an exemption where parents or guardians give permission for that possession: Delaware, Georgia, Kentucky, Louisiana, Ohio, and Texas.
^ Rudgley, Richard. "Tobacco: from The Encyclopedia of Psychoactive Substances". Biopsychiatry. Little, Brown and Company (1998). Retrieved 26 November 2017.
^ "WHO Report on the global tobacco epidemic, 2008 (foreword and summary)" (PDF). World Health Organization. 2008: 8. Tobacco is the single most preventable cause of death in the world today.
^ "World Association of International Studies, Stanford University".
^ Ernst, A. (1889). "On the etymology of the word tobacco". The American Anthropologist. A2 (2): 133โ142. doi:10.1525/aa.1889.2.2.02a00020.
^ Lane's Lexicon. page 1879.
^ The word แนญubฤq no longer refers to various herbs, but has come to refer, in some dialects, specifically to tobacco. See Hans Wehr's Dictionary of Modern Written Arabic. page 647.
^ Goodman, Jordan. Tobacco in History and Culture: An Encyclopedia (Detroit: Thomson Gale, 2005).
^ "They smoke with excessive eagerness ... men, women, girls and boys, all find their keenest pleasure in this way." - Diรจreville describing the Mi'kmaq, circa 1699 in Port Royal.
^ Jack Jacob Gottsegen, Tobacco: A Study of Its Consumption in the United States, 1940, p. 107.
^ Appleby, Joyce (2010). The Relentless Revolution: A History of Capitalism. W.W. Norton & Company. p. 131.
^ Eric Burns, The Smoke of the Gods: A Social History of Tobacco (2006), A popular history focused on the US.
^ Jordan Goodman, Tobacco in History: The Cultures of Dependence (1993), A scholarly history worldwide.
^ "WHO | WHO Framework Convention on Tobacco Control (WHO FCTC)". Who.int. Retrieved 2008-09-18.
^ Lewis, Albert (1931). "Tobacco in New Guinea". The American Anthropologist. 33 (1): 134โ139. doi:10.1525/aa.1931.33.1.02a00290.
^ Elsey, K. D.; Rabb, R. L. (1967-12-01). "Biology of the Cabbage Looper on Tobacco In North Carolina1". Journal of Economic Entomology. 60 (6): 1636โ1639. doi:10.1093/jee/60.6.1636. ISSN 0022-0493.
^ "Inside the Tobacco Deal - interview with David Kessler". PBS. 2008. Retrieved 2008-06-11.
^ van Willigen, John; Eastwood, Susan (2015). Tobacco Culture: Farming Kentucky's Burley Belt. University Press of Kentucky. p. 91. ISBN 9780813148083. Retrieved 2 February 2018.
^ "Tobacco-growing states in the USA" (PDF). Campaign for Tobacco-Free Kids.
^ Cerami C, Founds H, Nicholl I, Mitsuhashi T, Giordano D, Vanpatten S, Lee A, Al-Abed Y, Vlassara H, Bucala R, Cerami A (1997). "Tobacco smoke is a source of toxic reactive glycation products". Proceedings of the National Academy of Sciences of the United States of America. 94 (25): 13915โ20. Bibcode:1997PNAS...9413915C. doi:10.1073/pnas.94.25.13915. PMC 28407. PMID 9391127.
^ "tobacco curing." The Hutchinson Unabridged Encyclopedia with Atlas and Weather guide. Abington: Helicon, 2010. Credo Reference. Web. 26 September 2012.
^ a b c Food and Agriculture Organization of the United Nations. "Projection of tobacco production, consumption and trade for the year 2010." Rome, 2003.
^ a b The Food and Agriculture Organization of the United Nations.Higher World Tobacco use expected by 2010-growth rates slowing down." (Rome, 2004).
^ Rowena Jacobs; et al. (2000). "The Supply-Side Effects Of Tobacco Control Policies". In Prabhat Jha; Frank J. Chaloupka (eds.). Tobacco Control in Developing Countries. New York: Oxford University Press. pp. 311ff. ISBN 978-0-19-263250-0.
^ Hu, T-W; Mao, Z; et al. (2006). "China at the Crossroads: The Economics of Tobacco and Health". Tobacco Control. 15: i37โi41. doi:10.1136/tc.2005.014621. PMC 2563551. PMID 16723674.
^ "FAOSTAT". Food And Agriculture Organization Of The United Nations. Retrieved 28 February 2017.
^ a b Food and Agriculture Organization of the United Nations. "Issues in the Global Tobacco Economy."
^ "People's Republic of China. "State Tobacco Monopoly Administration". Gov.cn. 2005-09-15. Retrieved 2013-10-03.
^ "Tobacco Board, Guntur". Tobaccoboard.com. Retrieved 2014-04-21.
^ Shoba, John and Shailesh Vaite. Tobacco and Poverty: Observations from India and Bangladesh. Canada, 2002.
^ "Tobacco Manufacturing in India".
^ 3.Food and Agriculture Organization of the United Nations. "Issues in the Global Tobacco Economy."
^ a b International Tobacco Growers' Association (n.d.). Tobacco farming: sustainable alternatives? Volume 2 (PDF). East Sussex: ITGA. ISBN 978-1872854021.
^ High Level Commission on Legal Empowerment of the Poor. "Report from South America." 2006.
^ The Campaign for Tobacco Free Kids (November 2001). "Golden Leaf, Barren Harvest: The Costs of Tobacco Farming" (PDF). Archived from the original (PDF) on 2013-04-06.
^ a b Taylor, Peter (September 1994). Smoke Ring: The Politics of Tobacco. London: Panos Briefing Paper.
^ FAO Yearbook, Production, Volume 48. 1995.
^ National Research Council (1995). Pesticides in the Diets of Infants and Children. National Academy Press.
^ a b World Health Organization. "Tobacco Free Initiative: Environmental issues".
^ Ganapathi TR; et al. (2004). "Tobacco (Nicotiana tabacum L.) โ A model system for tissue culture interventions and genetic engineering" (PDF). Indian Journal of Biotechnology. 3: 171โ184.
^ Fraley RT; et al. (1983). "Expression of bacterial genes in plant cells". Proc. Natl. Acad. Sci. U.S.A. 80 (15): 4803โ4807. Bibcode:1983PNAS...80.4803F. doi:10.1073/pnas.80.15.4803. PMC 384133. PMID 6308651.
^ "Science of Transgenic Cotton". Cottoncrc.org.au. Archived from the original on 2012-03-21. Retrieved 2013-10-03.
^ a b James, Clive (1996). "Global Review of the Field Testing and Commercialization of Transgenic Plants: 1986 to 1995" (PDF). The International Service for the Acquisition of Agri-biotech Applications. Retrieved 17 July 2010.
^ a b c "Tobacco". GMO Compass. Archived from the original on 2013-10-02. Retrieved 2013-10-03.
^ Conner AJ, Glare TR, Nap JP (Jan 2003). "The release of genetically modified crops into the environment. Part II. Overview of ecological risk assessment". Plant J. 33 (1): 19โ46. doi:10.1046/j.0960-7412.2002.001607.x. PMID 12943539.
^ Beverly Sparks, "Stinging and Biting Pests of People" Archived 2007-02-14 at the Wayback Machine Extension Entomologist of the University of Georgia College of Agricultural & Environmental Sciences Cooperative Extension Service.
^ Durkin Sarah; Brennan Emily; Wakefield Melanie (2012). "Mass media campaigns to promote smoking cessation among adults: an integrative review" (PDF). Tobacco Control. 21 (2): 127โ138. doi:10.1136/tobaccocontrol-2011-050345. PMID 22345235.
^ Mullin Sandra (2011). "Global anti-smoking campaigns urgently needed". The Lancet. 378 (9795): 970โ971. doi:10.1016/s0140-6736(11)61058-1. PMID 21741699.
^ Verze, Paolo, et al. "The link between cigarette smoking and erectile dysfunction: a systematic review." European urology focus 1.1 (2015): 39-46.
^ "Guindon & Boisclair" 2004, pp. 13-16.
^ Women and the Tobacco Epidemic: Challenges for the 21st Century 2001, pp.5-6.
^ Surgeon General's Report โ Women and Smoking 2001, p.47.
^ a b "WHO/WPRO-Tobacco". World Health Organization Regional Office for the Western Pacific. 2005. Archived from the original on 2009-02-11. Retrieved 2009-01-01.
^ "Who Fact Sheet: Tobacco". Who.int. 2013-07-26. Retrieved 2013-10-03.
^ "Cigarette Smoking Among Adults - United States, 2006". Cdc.gov. Retrieved 2013-10-03.
^ "WHO/WPRO-Smoking Statistics". Wpro.who.int. 2002-05-27. Retrieved 2014-04-21.
^ "WHO global burden of disease report 2008" (PDF). Retrieved 2013-10-03.
^ "WHO Report on the Global Tobacco Epidemic, 2008" (PDF). Retrieved 2013-10-03.
^ Le Foll, Bernard; Goldberg, Steven R. (1 April 2005). "Nicotine induces conditioned place preferences over a large range of doses in rats". Psychopharmacology. 178 (4): 481โ492. doi:10.1007/s00213-004-2021-5. ISSN 0033-3158. PMID 15765262.
^ Fischman, N; Mello, N. Testing for Abuse Liability of Drugs in Humans (PDF). 5600 Fishers Lane Rockville, MD 20857: U.S. Department of Health and Human Services Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse. p. 79. Archived from the original (PDF) on 2016-12-22.
^ "Tobacco Facts - Why is Tobacco So Addictive?". Tobaccofacts.org. Archived from the original on 2007-03-14. Retrieved 2008-09-18.
^ "Philip Morris Information Sheet". Stanford.edu. Archived from the original on 2008-04-05. Retrieved 2008-09-18.
^ Proctor Robert N (2012). "The history of the discovery of the cigarette-lung cancer link: evidentiary traditions, corporate denial, global toll" (PDF). Tobacco Control. 21 (2): 87โ91. doi:10.1136/tobaccocontrol-2011-050338. PMID 22345227.
^ Nutt, David J.; King, Leslie A.; Phillips, Lawrence D. (6 November 2010). "Drug harms in the UK: a multicriteria decision analysis". Lancet. 376 (9752): 1558โ1565. CiteSeerX 10.1.1.690.1283. doi:10.1016/S0140-6736(10)61462-6. ISSN 1474-547X. PMID 21036393.
^ Radford, Edward P.; Hunt, Vilma R. (1964). "Polonium-210: A Volatile Radioelement in Cigarettes". Science. 143 (3603): 247โ249. doi:10.1126/science.143.3603.247. JSTOR 1712451.
^ Sublette, Carey. "Polonium Poisoning".
^ "British American Tobacco - The global market". www.bat.com. Retrieved 2018-03-15.
^ "Tobacco: U.S. market value 2012-2017 | Statistic". Statista. Retrieved 2018-03-15.
^ Health, CDC's Office on Smoking and. "CDC - Trends in Current Cigarette Smoking - Smoking & Tobacco Use". Smoking and Tobacco Use. Archived from the original on 2018-03-07. Retrieved 2018-03-15.
^ Bomey, Nathan (September 2, 2015). "Thousands of farmers stopped growing tobacco after deregulation payouts". USA Today.
^ "Tobacco: Active and Passive Smoking". Greenfacts.org. Retrieved 5 July 2016.
G. Emmanuel Guindon; David Boisclair (2003). "Past, current and future trends in tobacco use" (PDF). Washington DC: The International Bank for Reconstruction and Development / The World Bank. Retrieved 2008-01-02.
The World Health Organization; The Institute for Global Tobacco Control, Johns Hopkins School of Public Health (2001). "Women and the Tobacco Epidemic: Challenges for the 21st Century" (PDF). World Health Organization. Archived from the original (PDF) on 2003-11-28. Retrieved 2009-01-02.
"Surgeon General's Report โ Women and Smoking". Centers for Disease Control and Prevention. 2001. Retrieved 2009-01-03.
Richard Peto; Alan D Lopez; Jillian Boreham; Michael Thun (2006). "Mortality from Smoking in Developed Countries 1950-2000: indirect estimates from national vital statistics" (PDF). New York, NY: Oxford University Press. Archived from the original (PDF) on 2005-02-24. Retrieved 2009-01-03.
"Cancer Facts & Figures 2015". American Cancer Society. Retrieved February 23, 2015.
Paul Lichtenstein; Niels V. Holm; Pia K. Verkasalo; Anastasia Iliadou; Jaakko Kaprio; Markku Koskenvuo; Eero Pukkala; Axel Skytthe; Kari Hemminki (2000). "Environmental and Heritable Factors in the Causation of Cancer โ Analyses of Cohorts of Twins from Sweden, Denmark, and Finland". New England Journal of Medicine. 343 (2): 78โ85. doi:10.1056/NEJM200007133430201. PMID 10891514.
Montesano, R.; Hall, J. (2001). "Environmental causes of human cancers". European Journal of Cancer. 37: 67โ87. doi:10.1016/S0959-8049(01)00266-0.
Janet E. Ash; Maryadele J. O'Neil; Ann Smith; Joanne F. Kinneary (June 1997) . The Merck Index (12 ed.). Merk and Co. ISBN 978-0-412-75940-6.
Charlton A (2004). "Medicinal uses of tobacco in history". J R Soc Med. 97 (6): 292โ6. doi:10.1258/jrsm.97.6.292. PMC 1079499. PMID 15173337. |
0.940461 | How to manage incomparable movement speeds in combat?
I'm playing a Shadow character in a campaign which is running for 2 year. Our party has reached a great amount gnosi (27), and we are all level 13.
The main features of my character is agility and speed movement. He can move 150m/turn at full speed (even more with Ki agumentation) and I cannot understand how to manage this in combat situation.
If he moves at full speed he can easily get out of close combat range.
If he uses Ki agumentation he can moves up to 25Km/turn at full speed, this should allow to enter/exit combat range with a simple partial movement (passive action).
How should I manage this great difference in speed during combat situations?
@IgneusJotunn the rest of the party moves normally (10 to 20 m/turn); they have other kind of special abilities. We all perform more or less the same number of attacks per turn (this number is determinated by the attack ability and not by the movement speed).
Also the enemies usually have other kind of peculiarities, so in normal situation my character goes as slow as he can in order to remain with the party. But a battle is a battle, so he uses all his power and moves as fast as he can. He has an Ars Magnus which allow him to appear at the back of his opponent and perform some attacks.
A problem is when someone perform an area attack, usually the range of the attach is much lower than his movement speed, so it should be able to evade them simply moving out of the range instead of performing a Dodge roll. But this seems to be a bit overpower because will ensure immunity to any kind of attacks simply by getting out of the range.
If Anima allows you to move/attack/move, then you can consider yourself the equivalent of a sniper with melee attacks. The enemy would have to figure out tactics that can trap/hurt you when you get in range. These might be readying to receive a charge or setting up tripwires.
In your case the Dodge skill would represent his ability to react to those area attacks in an appropriate manner. If he's there at the moment of the attack, that's where he is. The attacker has been leading him with a rocket launcher or he's just tripped a mine or whatever.
The logical reasoning behind this is that you have the ability to run very fast but it doesn't translate into making your arms move incredibly fast or increase the number of attacks you can have. For an example, check out the landlady chase scene in Kung Fu Hustle (which you should have watched as source material anyway :P).
If you're in open spaces, don't worry about staying on the map. Hit and run tactics are what you've chosen to focus on.
It isn't a problem that one of your players doesn't have to be on the map to attack people. He's constantly at long range. So what. It just means that to defeat him, people are going to have to find some interesting counters to his tactics. Counterattacks, land mines, slowing auras, tight quarters and so on.
Those will validate his choices and add challenge to the game.
Anima is not very known for its regards to physics... the setting runs on rool of cool, so things like acceleration, sound barrier and such are hand waved. At gnosis 27 you are barely human anyway so you can do inhuman things. You are also capable of inhuman things thanks to inhumanity and zen (that you need to do this stuff).
So yeah, a shadow level 13 with infinium (the ars magnus that lets you appear at the back of people is infinium right? I donโt have the book at handโฆ) can appear at your back from no were, attack, and move out the length of your sword. In the same turn. Before you have a chance to blink. Itโs a freaking shadow level 13, you will be glad if you can see him do that.
If you must combat that, you should treat it like a ranged character that happens to attack with melee weapons, but most of the time is at ranged distance. As mentioned you still have problems with couter-attacks, changing terrain, like landmines, but also other stuff like flying things, walls (not very much) or other things grabbing you (with your dex its going to be hard but possible).
In Anima at that levels you do crazy stuff all the time, I donโt see any problem in move-attack-move (beware of people charging at you!).
That said, I understand that a person moving at 25 km/h should not be hit easily. But the rules more or less say that when your turn comes, all other people/monsters/things are stationary when it comes to hit them. I mean in a โrealโ combat a fighter that moves incredibly more quickly than other can keep a distance with no problem, in Anima this is not the case, the same rules that let you move-attack-move, let other people move-attack you (or charge you) even if in more โrealisticโ settings they would have no chance in touching you.
I would interpret a failed dodge roll as "did not notice the attack in time to move fast out of the area" and a successful dodge roll as "avoided the attack, possibly by moving out of the area".
Not the answer you're looking for? Browse other questions tagged combat movement anima-beyond-fantasy or ask your own question.
Pathfinder house rules making movement similar to DnD 5e?
When a creature needs to hide only during some of its movement, how fast can it move?
What is combat or an encounter?
How do I ensure tactical combat is interesting for my large party?
How does the Dimensional Dervish feat work? |
0.996189 | Uzo Aduba, also known as Uzoamka Nwanneka is an award-winning actress, best-known for her performances in the series 'Orange is the New Black' where she plays 'Crazy Eyes' role. Her outstanding performances have earned her several awards and nominations such as the 2017 Primetime Emmy Awards as an excellent supporting Actress in a Drama Series. These awards have brought her fame and commendation.
Uzo Aduba was born on February 10, 1981, to Nigerian Parents of Igbo origin, in Boston Massachusetts. However, she was raised in Medfield and enrolled in Medfield High School where she graduated in 1999. Later on, Aduba joined the College of Fine Arts at Boston University where she studied classical voice and participated in track and field competitions.
While at the University, Uzo Aduba cultivated the love for acting because her teachers encouraged her more to pursue acting rather than a vocal career. Her interests in acting motivated her to move to New York to pursue her acting career. Interestingly, her family enjoys sports and her younger brother, Obi, played hockey in six professional seasons at the University of Massachusetts.
Uzo Aduba arrived in New York in early 2000 for her acting career and took outstanding performances. However, she started rising to fame in 2003 after her performance at Olney Theatre Center for the arts in โTranslations of Xhosaโ play, This play earned her a nomination award as the Outstanding Supporting Actress.
Remarkably, this performance opened doors to later opportunities such as 2006 performance at New York Theatre Workshop where she played the character Amphiarus followed by 2008 performance at Jolla Playhouse. Uzo Aduba also made other performances such as in โNotesโ of 2005 and โOver Thereโ of 2007. In the same year, she played Toby in 'Coram Boy' at Imperial Theatre.
Additionally, from 2011-2012, Uzo Aduba participated in the original cast of 'Godspell at Circle' in The Square Theatre where she sang โBy my Side.' During the same period, she made her first television appearance as a nurse on 'Blue Bloods' and also played as a mother character in 'Venice' at The Public Theater in New York.
In mid-2012, she auditioned for the Netflix series; โOrange is the New Black.' Fortunately, she got accepted for her role as โCrazy Eyesโ which won her several awards such as the 66th Primetime Creative Arts Emmy Awards, the 4th Critics Choice Television Awards, and the 18th Satellite Awards. Uzo Aduba made her season two performance of the series which led to several awards.
She was recognized as an Outstanding Female Actor in a Comedy Series and got nominated at the 72nd Golden Globe Awards as the Best Supporting Actress.
In 2015, Uzo Aduba won a second Primetime Emmy Award as the Outstanding Supporting Actress in a Drama Series, at the 67th Primetime Emmy Awards. Remarkably, her season three performance earned her more recognition as the Outstanding Female Actress in the 22nd Screen Actors Guild Awards and the best-supporting Actress at the 73rd Golden Globe Awards.
Besides her series performances, Uzo Aduba teamed up with Rachel Bay Jones in March 2014. They made a musical performance of the 'Lilyโs Eyes song' from 'The Secret Garden' at a benefit concert Broadway Cares/Equity Fight Aids. Later in April 2017, the Point Foundation awarded her with a Courage Award for unflinching support of the LGBT community.
Uzo Aduba has earned several awards and nominations including the 2013 Satellite Awards as the best-supporting actress in a series or television film. Additionally, she received a subsequent 'Critics Choice television award' for her performance as the best guest performer in a comedy series followed by Golden Globe Awards which recognized her as the best-supporting actress in a series, miniseries or television film.
In 2014, Uzo Aduba received three awards starting with the Primetime Emmy Awards as an Outstanding Guest Actress in a Comedy series. Screen Actors Guild Awards honored her for her outstanding Performance as a female actor and as an Ensemble in a comedy series. Finally, she received an NAACP Image Award as an Outstanding Actress in a comedy series.
Notably, In 2015, she earned her nomination for a comedy series โOrange is the New Black'. Additionally, she received several awards including the Primetime Emmy Awards as an outstanding supporting Actress in a drama series and the NAACP Image Awards as an exceptional actress in a comedy series.
In 2016, Uzo Aduba earned her awards; Screen Actors Guild Award, Golden Globe Awards and Glamour Awards for her outstanding performances in a comedy series.
In 2017, Uzo Aduba has also been recognized for her outstanding and supporting roles as an Actress in the comedy and drama series. The awards included the Screen Actors Guild Award, NAACP Image Award, and the Primetime Emmy Awards. |
0.997312 | Around Christmas in 1989 I was lying in bed awake and very sad,I had lost my father that year and missed him very much, he was a gentle kind soul and everyone that knew him spoke highly of him.
I suddenly heard this beautiful music and singing coming from my bedroom window, At first I thought maybe the neighbors were singing Christmas songs but as I listened closer I realized that it was no music from this world, it sounded wonderful. The angelic music was very comforting and it uplifted my grieving soul. At one point I was going to get up and peer out my bedroom window because I just knew that there were angels out there but a voice said "no" just listen so that it was I did.
I am a nurse and have told my angel story to several of my patients, two of my female patients said, "0h I wish the angels would sing to us!
All I know that it made me aware that Dad is in a better place and I felt much better that Christmas. I also had several dreams about him and in one dream I asked him how he was and it stated,"don't worry about me I'm having a great time".
People should know the importance of the education and they should have the confidence to learn essay writing service their education. The people should know the importance of the education and they should learn their education for their good future. |
0.954711 | When our feelings are denied, the fight and flight response or defence mechanisms become the main vehicle of communication and expression of ourselves. In this way, us as psychological individuals we become increasingly deformed. Some unhelpful responses are: giving advice, asking questions, judging, labelling, attacking, perfectionism/high standards, preoccupation with moral standards and avoiding. As these responses are activated automatically it is likely that we aren't aware of them, that we are blind to them. We never question the validity or helpfulness of what we do or say. We are more likely to pendulate between helpful and unhelpful ways of being with our close ones. It is a continuous journey of successes and failures to act in line with our goals and values.
Self-awareness is the key that unlocks this unhelpful pattern accompanied by being concerned with validating our and others' feelings.
What does it mean to validate/recognise feelings and how do we do that? It is easier than it sounds: by naming or having a good guess of what feelings we/others try to communicate. For example, the statement 'the boss was really unfair' sounds like 'I experienced my boss as unfair on this occasion'. Guessing the feeling: 'feeling angry and disappointed that he did not make it fair', 'a colleague does not work as much as I do', 'you/I see that the colleague does not have the same working ethics'.
Guessing a feeling brings people together. It generates an environment of compassion and understanding. It reduces the temptation to make it better or solve it for the other. Expressing opinions and views does not require problem solving. We can't problem solve with our views or opinions as most of them are not facts. This is really hard to remember at times. However with practice, a new emerging rule is that there isn't a threat between us: we are just individuals trying to help each other and that the more we validate/recognise each other's feelings the more care we take of ourselves. |
0.993945 | [[http://โwww.esp8266.com/โviewtopic.php?โf=6&โt=376|esp-httpd]] is a web server running directly on the ESP8266, created by [[User:โSprite_tm]]. [[http://โwww.esp8266.com/โviewtopic.php?โf=6&โt=376|esp-httpd]] is a web server running directly on the ESP8266, created by [[User:โSprite_tm]].
Let's use ESP8266. It makes things way easier. Let's use ESP8266. It makes things way easier. |
0.999986 | What are the pros and cons of a magistrate career? Get real job descriptions, career outlook and salary info to see if becoming a magistrate is right for you.
Magistrate professionals typically handle pretrial hearings and requests, try smaller civil and criminal cases or work in specific areas like family court. Review the following pros and cons to decide if being a magistrate is the right career path for you.
Sources: *U.S. Bureau of Labor Statistics, **American Judicature Society.
Magistrates work in federal district courts, as well as state and local courts. In the federal system, magistrate judges serve under district court judges. They hold initial proceedings and pretrial hearings. They can also try minor criminal cases or civil cases if the parties involved agree to it. U.S. magistrate judges are appointed by district court judges for eight-year terms if they work full-time, or four-year terms if part-time. The number of U.S. magistrate judgeships is determined by the Judicial Conference of the United States, a governing body of federal judges. There were 527 of these positions in 2011.
At the state level, magistrates' roles vary. For example, in North Carolina they may preside over proceedings and bond hearings, issue warrants and subpoenas, as well as handle traffic infractions, evictions and small claims cases. In Ohio, judges can appoint magistrates to preside in any civil or non-felony criminal case, although the parties may have to give consent. Magistrates may be appointed through elections and citizens' committees, as well as other government officials and judges.
Magistrates need to know the laws and procedures in their jurisdiction. They need to weigh conflicting claims and evidence without bias, or have the honesty to step aside when there is a conflict. Because magistrates make important decisions in the courtroom on a daily basis, they need to be effective deliberators with good reading and communication skills.
In May 2014, the U.S. Bureau of Labor Statistics (BLS) found that judges, magistrate judges and magistrates earned a median annual salary of about $115,000. Magistrates employed by state governments earned more than those employed by local governments. At the federal level, judges can earn more. In 2015, the Administrative Office of the U.S. Courts reported that district judges earned $201,000 and circuit judges earned more than $213,000. The BLS indicates that employment opportunities for these professionals were expected to increase two percent from 2012-2022. The slow growth is due to budgetary cuts and a low turnover rate.
Because qualifications for magistrate positions differ so much, you should begin with research into the requirements of the specific courts. Many states' court systems and state magistrates associations have websites with pages explaining what the magistrates of that state do and how to become one. U.S. magistrate judges have their own organization, the Federal Magistrate Judges Association. Once you know more about the specific jobs you may want, you can make educational and employment choices to gain legal knowledge and experience accordingly.
Typically, magistrates must have a bachelor's degree and workforce experience. However, some positions require a law degree and time spent in the legal practice. Federal magistrate judges must have at least five years experience as a lawyer and be in good standing with the state bar association. State-level requirements vary considerably. In Colorado, you need a J.D. degree and at least five years as an attorney in that state, while Delaware only requires you to be 25 years old and a state resident to take a screening exam. Every state has some kind of orientation process for new judges and magistrates, and many have continuing education requirements.
There were two magistrate judge openings in California, both requiring five years as a practicing attorney and a bar member in good standing. Candidates needed to be less than 70 years old. The appointee would be selected by the district court from a shortlist of five candidates screened by a committee of lawyers and others.
The Virginia Supreme Court's Executive Secretary sought to appoint a county-based magistrate. Qualifications were a bachelor's degree, firm grasp of the law and legal system, U.S. citizenship and state residency, plus strong communication, people and computer skills. Ideal candidates would be bilingual attorneys with experience in criminal justice. The job involved occasional duty on weekends and holidays.
Massachusetts had three clerk-magistrate positions open in state district courts, all by appointment of the governor on recommendations of the Judicial Nominating Commission. The requirements included a bachelor's degree, which could be substituted with 15 years working in the court system, state residency, and either three years as a practicing attorney and Massachusetts bar member or five years of other relevant work experience.
Even though minimum qualifications and hiring processes vary widely, there are some general qualities that those who screen judicial candidates seek. They look for evidence of commitment to public service and fairness, intellectual ability, industriousness and an even temperament. Volunteering in your community, especially for a legal services organization, may show your civic-mindedness and concern for equal justice for all.
If the entry requirements for magistrates seem forbidding but you're still keen to work in the courts, becoming a clerk may be a good alternative. Many of these positions do not require education past high school. Court clerks schedule dockets, make arrangements with parties to cases and handle the considerable paperwork involved in legal proceedings. In May 2011, the BLS indicated that clerks earn much less than magistrates, around $34,000. The BLS also indicated that employment opportunities were only expected to increase seven percent from 2010-2020.
If you are interested in a legal job without a law degree, you may consider becoming a paralegal. Most paralegals work in law firms, but many also work for government agencies or corporations. They do legal research, draft documents and other work to assist attorneys. As they gain experience, their responsibilities increase. Employers typically expect an associate's degree in paralegal studies or a bachelor's degree combined with a certificate in paralegal studies. The BLS expects employment of paralegals and legal assistants to increase 18% from 2010-2020, with a national median annual salary of almost $47,000 in May 2011.
If you wish to work in a different area of the criminal justice system, you may consider becoming a police officer or detective. Minimum qualifications range from a high school diploma for uniformed policing at the local level to a bachelor's degree and work experience for some federal detective roles. Police departments and investigative agencies generally screen for physical fitness, intelligence and integrity. The BLS predicts that employment opportunities for police and detectives were expected to increase just seven percent from 2010-2020, while detectives were expected to only see a three percent increase in the same period. In May 2011, the BLS reported that average salary for detectives and criminal investigators was $72,000 and $54,000 for police and sheriff's patrol officers. |
0.999999 | Did you know windshield wipers are among the most important safety features on your car? The number one job of a windshield wiper is to provide a clear unobstructed view while you are driving. To make sure your wiper blades stay in great shape you should clean them frequently to make sure they remain dirt free, also make sure to check them for dry, hard, brittle parts and be sure to replace them every 6-12 months depending on your climate and the use of your windshield wipers. |
0.964355 | Historically, over the last thirty-five or so years, the managed futures asset class has become synonymous with systematic trend-following CTA programs that actively trade futures or forward contracts. It is important to understand that not all futures-trading strategies fall under the managed futures umbrella as conventionally defined, and that even some well-known research and ratings agencies have on occasion ended up misclassifying some funds and strategies as managed futures. Conversely, some CTA programs that implement strategies other than systematic trend-following may still be legitimately classified as managed futures.
The program trades in multiple global futures markets (generally ranging from around 25-50 at the low end to more than 200), diversified across six major sectorsโstock indexes, fixed-income (including short-term interest rates and bonds), currencies, energy, metals, and agricultural commodities.
Trading is primarily systematic, although some discretionary traders do exist. Systematic trading is based on quantitative models and algorithms and generally involves very little if any manual intervention or decision-making, other than in extreme situations.
Trading is active in the sense that the models are generally run at least daily, if not more frequently, and positions are initiated, modified or closed out based on the outputs from the models.
The strategies employed are generally based on medium-term to long-term trend-following, but may include relative value trading, counter-trend or contrarian trading, mean reversion, pattern recognition, short-term trading, etc.
Our sample consists of sixteen CTA programs. The first eight among these are purely or primarily trend-following. The next two programs contain some element(s) or variant(s) of trend-following. For convenience, we refer to all ten of these programs as โtrendโ programs hereafter. Our sample of six โnon-trendโ CTA programs represent other trading styles such as spread or relative value trading, short-term trading, short-term pattern recognition, and discretionary and systematic global macro. Brief descriptions of all sixteen CTA programs are presented in the notes to the right of the correlation matrix. We also include in the correlation matrix five asset class indexes that are proxies for managed futures, US bonds, long-only commodities, US stocks, and world stocks.
Why do different CTA programs have different correlations with stocks or other asset classes?
We can identify some potential explanatory factors.
All CTA programs are not created equal. First and foremost, they can be broadly classified as systematic vs. discretionary, and trend vs. non-trend. The vast majority of CTA programs are based on systematic trend-following. However, the managed futures space includes several other trading styles: discretionary, global macro, relative value, mean reversion, pattern recognition, counter-trend, sector-specific, etc.3 A trend following CTA program is likely to have correlations to other asset classes that may be quite different from those of a relative value trading program.
Across CTA programs, and particularly within trend-following programs, trading or look back time horizons may range from short-term (2 days โ 2 weeks) to medium-term (2 weeks โ 2 months) to long-term (2 months โ 2 years). Again, the correlation of a short-term trading program to stocks, for example, may be very different from that of a longer-term program.
While the majority of CTA programs tend to be diversified across market sectors, and trade in multiple futures markets (quite often between 25 and 200), some sector-focused programs do exist. For example, there are CTA programs that focus on only physical commodities, others that may have a risk โoverweightโ to energy, and some (albeit fairly small) programs that may be even more narrowly focused on, for example, mainly meats and grains. The correlations of an energy-focused program with other asset classes are likely to be quite different from those of a broadly diversified CTA trading program.
1For more details, please see our Insight, โManaged Futures: Risk Management in CTA Programs,โ (2017).
2Pages 2-3 display CTA programs currently accessible through Equinox Funds.
3See our Insight, โPrincipal Component Analysis: A Tool for Analyzing and Describing CTA Programsโ (2016).
Diversification does not ensure profit or prevent losses. an investment in managed futures is speculative and involves a high degree of risk. You can lose money in a managed futures program. there is no guarantee that an investment in managed futures will achieve its objectives, goals, generate positive returns, or avoid losses. |
0.962385 | The efforts to develop technologies capable of pushing back the detection timeline to a stage that is even earlier than what is currently possible could provide new opportunities for early intervention, but such opportunities could also increase the difficulties associated with โoverdiagnosis.โ The underlying assumption in promoting early detection held by many investigators, most physicians, and almost all members of the lay population is that early detection provides an opportunity to reverse the malignancy process more effectively and perhaps with less toxicity than if the condition were identified later.
The notion that earlier detection is better requires the following three assumptions: (1) that development of carcinoma of the breast proceeds through a relatively orderly series of steps (Figure 1-6); (2) that this process includes an irreversible checkpoint (which may vary for different patients) and that once an individual is past this checkpoint the process steadily progresses so that only some sort of external intervention can prevent the ultimate inevitability of morbidity and mortality; and (3) that detection of this process before establishment of metastatic deposits will permit external intervention to prevent disease-specific morbidity and mortality more efficiently than after metastases are established. These points of detection are illustrated as A, B, C, and D, respectively by the vertical lines on Figure 1-6.
The fundamental support for these assumptions comes from the randomized clinical trials described earlier in this section, which showed that mammography screening of asymptomatic women results in early treatment of breast cancers that are detected and reduces disease-specific mortality by approximately 20 to 30 percent compared with that for women who have not been screened. Why is the decrease in mortality not greater? There are several possible answers to this question. Simply put, screening mammography is insufficiently sensitive in two ways: (1) it does not detect all cancers at point B, and (2) it does not detect any cancers at point C.
One might argue that improvements in imaging technologies might allow clinicians to increase the number of tumors detected at point B or even move detection to point C. However, a second reason that reductions in breast cancer mortality rates due to screening mammography are limited might be embedded in the biology of the cancer itself. Some cancers may metastasize at a time well before point B on the breast cancer continuum, whereas others may do so much later. Thus, the question of whether detection is early enough to allow effective intervention may vary from one woman to the next.
The assumptions presented above raise several considerations. A distinction should be made between screening for an asymptomatic but precise condition that is considered undesirable and establishing that the individual is at risk for such a condition but does not yet and may never have it. Indeed, taken to its extreme, this distinction is blurred and perhaps even abolished in the definition of โdisease.โ For example, most patients and physicians would consider a histological diagnosis of breast cancer, even when it is totally in situ, a โdisease.โ However, a more precise definition of disease is โa condition that causes morbidity and mortality.โ In this sense, breast cancer is only a disease when one of these two conditions exists. Morbidity and mortality occur almost exclusively in the setting of clinically detectable metastases.
FIGURE 1-6 Hypothetical illustration of breast cancer initiation and progression.
Although most patients and physicians would consider a histological diagnosis of breast cancer, even when it is totally in situ, a โdisease,โ a more precise definition of disease is โa condition that causes morbidity and mortality.โ In this sense, breast cancer is only a disease when one of these two conditions exists. Morbidity and mortality occur almost exclusively in the setting of clinically detectable metastases. Thus, all other stages of breast abnormalities are shown here as having variable levels of risk for the development of morbidity and mortality (i.e., disease). For more detail, refer to the section Dilemma of โEarlierโ Detection in the text.
Before the increased awareness of breast cancer and adoption of screening mammography, almost all patients who presented with breast cancer did so because the condition was at a stage at which it was truly a disease: it caused symptoms or even death. However, in more modern times, most patients are diagnosed with asymptomatic breast cancer. In this setting, almost all treatment for breast cancer (surgical removal of the primary tumor, local-regional radiation to sterilize the area, and adjuvant systemic therapy) could be considered prophylactic or preventive. Such treatments are applied to reduce the chances that the patient will develop morbidity or mortality (or โdiseaseโ). A substantial body of literature describing the results of randomized clinical trials demonstrates that each of these strategies does, in fact, reduce to some extent the individualโs chances of developing morbidity or mortality from breast cancer.
Why are these distinctions important? No single condition, other than actually having symptomatic disease, carries a 100 percent chance (or risk) of developing what is designated, in this discussion, disease. However, as one moves from left to right on the theoretical breast cancer continuum illustrated in Figure 1-6, an individualโs chances of ultimately developing morbidity and mortality increase. Estimating this risk is quite difficult because, at least in the last century, few patients were left untreated once they had a diagnosis of โbreast cancer,โ and therefore, it is impossible to determine what percentage of patients, if any, might never have progressed to experience morbidity or mortality from breast cancer if they were left untreated. |
0.970904 | The President of the Republic of Liberia is the head of state and government of Liberia. The president serves as the leader of the executive branch and as commander-in-chief of the Armed Forces of Liberia.
Prior to the independence of Liberia in 1847, executive power in the Commonwealth of Liberia was held by the Governor of Liberia, who was appointed by the American Colonization Society. The 1847 Constitution transferred the executive powers of the governorship to the presidency, which was largely modeled on the presidency of the United States.
Between 1847 and 1980, the presidency was exclusively held by Americo-Liberians, the original American settlers of Liberia and their descendants. The original two-party system, with the Republican Party and the True Whig Party, ended in 1878, when the election of Anthony W. Gardiner marked the beginning of 102 years of single-party rule by the True Whigs. Following a coup d'รฉtat by disgruntled army officers led by Samuel Doe in 1980, the presidency was vacated until the election of Doe in the 1985 general election. After the overthrow and murder of Doe in 1990, the presidency was again vacated for seven years during the First Liberian Civil War and again for two years following the conclusion of the Second Liberian Civil War in 2003.
Under the 1986 Constitution, the president is directly elected by eligible voters to a six-year term, which may be renewed once. Overall, 25 individuals have served as president, including Ellen Johnson Sirleaf, the first elected female head of state in Africa. On January 22, 2018, George Weah was sworn in as the twenty-fifth and current president of Liberia.
Following the establishment of the Commonwealth of Liberia in 1838, executive power was vested in the Governor of Liberia, who was appointed and served at the pleasure of the American Colonization Society. The first governor, Thomas Buchanan, served from 1838 until his death in 1841. He was succeeded by Joseph Jenkins Roberts, the first black governor of Liberia.
The presidency was vacant from 1980 to 1986, with executive power held by Doe as the head of the People's Redemption Council. Doe was later elected president in the 1985 general election, making him the first president outside of the Americo-Liberian elite. Doe was later overthrown and murdered in 1990 following the commencement First Liberian Civil War, during which the presidency remained vacant.
Following the 1997 general election, Charles Taylor held the presidency until his resignation on August 11, 2003 as part of a peace deal to end the Second Liberian Civil War. His successor, Moses Blah, ceded executive power on October 13 of that year to Gyude Bryant, the Chairman of the National Transitional Government of Liberia. The presidency was resumed on January 16, 2006 following the 2005 election of Ellen Johnson Sirleaf as the first female president.
George Weah was elected in 2017 as the 23rd President of Liberia. Incumbent President Ellen Johnson Sirleaf signed Executive Order No. 91, thus establishing a Joint Presidential Transition Team, due to the fact that Liberia had "not experienced the transfer of power from one democratically elected President to another democratically elected President for over 70 years [...]".
The presidency of Liberia is largely modeled on the presidency of the United States.
The 1986 Constitution gives the president the power to appoint all cabinet ministers, judges, ambassadors, sheriffs, county officials and military officers with the advice and consent of the Senate. Additionally, the president has the power to dismiss all appointees from office at his or her discretion. The president may also grant pardons or revoke sentences and fines. The president conducts all matters of foreign policy, though any treaties or international agreements must be ratified by both houses of the Legislature. Furthermore, the president serves as the commander-in-chief of the Armed Forces of Liberia.
The Constitution also grants the president the power to declare a state of emergency during times of war or civil unrest and suspend civil liberties during the emergency as necessary, with the exception of habeas corpus. Within seven days of the declaration, the president must state to the Legislature the reasons for the declaration, which both houses must then approve by a two-thirds majority. Otherwise, the president must repeal the state of emergency.
The president must sign all legislation passed by the House of Representatives and Senate. The president may choose to veto any legislation, which may be overturned by a two-thirds majority in both houses. Additionally, the president may exercise a pocket veto by refusing to sign legislation when the end of the twenty-day deadline for signing the bill falls during a recess of the legislature. The president may extend a legislative session past its adjournment date or call a special extraordinary session when he or she deems it necessary in the national interest. The president must also give an annual report to the Legislature on the state of the country.
have resided in Liberia for at least ten years.
Additionally, the president may not be from the same county as the Vice President of Liberia.
Under the original 1847 Constitution, the president was elected to a two-year term, which was increased to four years on May 7, 1907. Under this amendment, a new president would serve for eight years and could be re-elected to unlimited four-year terms. During the presidency of William Tolbert, the Constitution was amended to restrict the president to a single eight-year term; by 1976, voices in the Legislature were being raised in favor of returning to the previous system, but Tolbert proclaimed his support for the existing system and vowed to veto any constitutional amendments to remove term limits.
Currently, the president is elected by popular vote to a six-year term and is limited to two terms. Under the 1986 Constitution, presidential elections utilize a two-round system, wherein a second round of voting is held between the two candidates with the highest number of votes if no single candidate obtains a majority in the first round. Each term begins and ends at noon on the third working Monday in January of the year immediately following the elections. At the time of their inauguration, each president is required under the Constitution to take a presidential oath promising to preserve and defend the Constitution and faithfully execute the law. The oath is administered by the Chief Justice of Liberia in front of a joint session of the Legislature.
Since 2006, the Executive Mansion has been under renovations due to a fire that damaged parts of the building in July of that year. The office of the president was transferred to the nearby Foreign Ministry building as a result, where it currently hosts President George Weah.
(1809โ1876) January 3, 1848 January 7, 1856 Independent 1.
(1816โ1865) January 7, 1856 January 4, 1864 Independent 5.
(1815โ1880) January 4, 1864 January 6, 1868 Republican Party 9.
(1819โ1882) January 6, 1868 January 3, 1870 Republican Party 11.
(Deposed) True Whig Party 12.
(1819โ1882) January 3, 1876 January 7, 1878 Republican Party 15.
(Resigned) True Whig Party 16.
(1837โ1901) January 7, 1884 January 4, 1892 True Whig Party 19.
(Died) True Whig Party 23.
(1854โ1938) January 4, 1904 January 1, 1912 True Whig Party 29.
(1861โ1935) January 1, 1912 January 5, 1920 True Whig Party 32.
(Resigned) True Whig Party 34.
(Died) True Whig Party 39.
(Assassinated) National Democratic Party 47.
(Resigned) National Patriotic Party 48.
(1938โ) January 16, 2006 January 22, 2018 Unity Party 49.
(1966โ) January 22, 2018 Incumbent Congress for Democratic Change 51.
^ "President Sirleaf Issues Executive order No. 91 โ Establishing the Joint Presidential Transition Team of 2017". Executive Mansion. Retrieved December 29, 2017.
^ Starr, Frederick (1913). Liberia: Description, History, Problems. Chicago. p. 256.
^ "Pres. Tolbert Says 'No' To Evil Tradition: Vows to Veto Any Amendment To Keep Him In Office". [Monrovia] Sunday Express 1976-03-21: 1/2.
^ Daygbor, Nathaniel (September 20, 2010). "Mansion's Renovation Not Priority". The New Dawn.
Enno Schulz, "Presidents of Liberia. |
0.999965 | The given diagram illustrates the way in which waste glass bottles are recycled for reusing purpose.
" beginging" is a misspelled word. It should be "beginning" Overall, looking at the illustration, it is immediately evident that wasted glass bottle recycling is a manmade linear process.
In addition, there are 3main stages in the process beginging with the collection of used glass bottles and culminating in the finished items to their destinations.
"a bottles". The word "a" is a singular preposition but you place a plural noun after it.
The phrase should either read "a bottle" or "bottles"
"of recycling process". Missing word. It should be "of the recycling process". Afterwards, these processed bottles are Sorted out into three different group namely clear, green and brown before being moved to glass factory where they are broken into small pieces. After those pieces are heated at a higher temperature of 600 - 800o C in a furnace into recycled liquid glass which is mixed with new liquid glass.The mixture is shaped in a glass mould into a bottles. At the final stage of recycling process is finished bottles used for other products and ready for sales. |
0.999998 | Which is the best way to prepare coffee?
Always use fresh clean water.
Store coffee in an airtight container and consume within 2 months.
Do not boil your water and definitely never ever re-heat brewed coffee. |
0.999496 | Maasai villagers, Tehranians, Americansโeach is a society. But what does this mean? Exactly what is a society? In sociological terms, society refers to a group of people who live in a definable community and share the same culture. On a broader scale, society consists of the people and institutions around us, our shared beliefs, and our cultural ideas. Typically, more advanced societies also share a political authority.
Sociologist Gerhard Lenski (1924โ) defined societies in terms of their technological sophistication. As a society advances, so does its use of technology. Societies with rudimentary technology depend on the fluctuations of their environment, while industrialized societies have more control over the impact of their surroundings and thus develop different cultural features. This distinction is so important that sociologists generally classify societies along a spectrum of their level of industrialization, from preindustrial to industrial to postindustrial.
Throughout Northern Africa and the Arabian Peninsula live the Bedouin, modern-day nomads. While many different tribes of Bedouin exist, they all share similarities. Members migrate from one area to another, usually in conjunction with the seasons, settling near oases in the hot summer months. They tend to herds of goats, camels, and sheep, and they harvest dates in the fall (Kjeilen).
While pastoral and horticultural societies used small, temporary tools such as digging sticks or hoes, agricultural societies relied on permanent tools for survival. Around 3000 B.C.E., an explosion of new technology known as the Agricultural Revolution made farming possibleโand profitable. Farmers learned to rotate the types of crops grown on their fields and to reuse waste products such as fertilizer, leading to better harvests and bigger surpluses of food. New tools for digging and harvesting were made of metal, making them more effective and longer lasting. Human settlements grew into towns and cities, and particularly bountiful regions became centers of trade and commerce.
These individual pieces of land, known as fiefdoms, were cultivated by the lower class. In return for maintaining the land, peasants were guaranteed a place to live and protection from outside enemies. Power was handed down through family lines, with peasant families serving lords for generations and generations. Ultimately, the social and economic system of feudalism would fail, replaced by capitalism and the technological advances of the industrial era.
In the 18th century, Europe experienced a dramatic rise in technological invention, ushering in an era known as the Industrial Revolution. What made this period remarkable was the number of new inventions that influenced peopleโs daily lives. Within a generation, tasks that had until this point required months of labor became achievable in a matter of days. Before the Industrial Revolution, work was largely person- or animal-based, relying on human workers or horses to power mills and drive pumps. In 1782, James Watt and Matthew Boulton created a steam engine that could do the work of 12 horses by itself.
One of the results of increased productivity and technology was the rise of urban centers. Workers flocked to factories for jobs, and the populations of cities became increasingly diverse. The new generation became less preoccupied with maintaining family land and traditions, and more focused on acquiring wealth and achieving upward mobility for themselves and their family. People wanted their children and their childrenโs children to continue to rise to the top, and as capitalism increased, so did social mobility.
It was during the 18th and 19th centuries of the Industrial Revolution that sociology was born. Life was changing quickly and the long-established traditions of the agricultural eras did not apply to life in the larger cities. Masses of people were moving to new environments and often found themselves faced with horrendous conditions of filth, overcrowding, and poverty. Social scientists emerged to study the relationship between the individual members of society and society as a whole.
It was during this time that power moved from the hands of the aristocracy and โold moneyโ to business-savvy newcomers who amassed fortunes in their lifetimes. Families such as the Rockefellers and the Vanderbilts became the new power players, using their influence in business to control aspects of government as well. Eventually, concerns over the exploitation of workers led to the formation of labor unions and laws that set mandatory conditions for employees. Although the introduction of new technology at the end of the 19th century ended the industrial age, much of our social structure and social ideasโlike family, childhood, and time standardizationโhave a basis in industrial society.
Societies are classified according to their development and use of technology. For most of human history, people lived in preindustrial societies characterized by limited technology and low production of goods. After the Industrial Revolution, many societies based their economies around mechanized labor, leading to greater profits and a trend toward greater social mobility. At the turn of the new millennium, a new type of society emerged. This postindustrial, or information, society is built on digital technology and non-material goods.
In which type or types of societies do the benefits seem to outweigh the costs? Explain your answer, citing social and economic reasons. |
0.99999 | According to the CDC, respiratory syncytial virus (RSV) is a common respiratory virus that can affect people of all ages. In older children and adults, it causes mostly upper respiratory symptoms (colds), but it can cause a serious infection in the lungs (bronchiolitis or pneumonia) among infants and adults with serious underlying medical problems.
These symptoms usually appear in stages and not all at once. In very young infants with RSV, the only symptoms may be irritability, decreased activity, and breathing difficulties.
If my cold gets RSV, can my other children get it?
Yes, RSV is highly contagious. It is extremely important to prevent its spread to others. |
0.999509 | How do you solve a problem like Cristiano? For so much of his career, through his dramatic surge at Manchester United and his blossoming into the greatest goalscorer in Real Madridโs illustrious history, the answer has been to indulge him. He may be high-maintenance, but he has also been the perfect professional, his devotion to his craft unquestionable, perhaps even unmatched. Look after him, succumb to his every demand, and you will reap the rewards of his brilliance. |
0.95208 | ใHey Judeใ๋ ํด ๋งค์นดํธ๋๊ฐ ์๊ณกํ๊ณ ๋ ๋
ผ-๋งค์นดํธ๋ ๋ช
์๋ก ๋ฐํ๋ ์๊ตญ์ ๋ก ๋ฐด๋ ๋นํ์ฆ์ ๋
ธ๋๋ค. ์กด ๋ ๋
ผ์ ๊ทธ ๋น์ ์ ์์ ๋ ๋
ผ๊ณผ ์ดํผํ๊ณ ์ผ๋ณธ์ธ ์ค๋
ธ ์์ฝ์ ์ฌํผ์ ํ๋ค. ์ ์์์ ๋ ๋
ผ์ ์๋ค ์ค๋ฆฌ์ธ ๋ ๋
ผ์ ๋ถ์ํ๊ฒ ์ฌ๊ธด ๋งค์นดํธ๋๋ ์ค๋ฆฌ์ธ์ ์ํด ์ด ๊ณก์ ์๊ณกํ๋ค. ๊ทธ๋์ ์๋ ๊ณก์ ์ด๋ฆ์ ์ค๋ฆฌ์์ ์ ์นญ์ธ Julie, ์ฆ ใHey Julieใ์๋ค. ใHey Judeใ์ ๋์
๋ถ์ ๋ํ๋ ๋ฒ์ค-๋ธ๋ฆฌ์ง๋ ๋งค์นดํธ๋์ ๋ณด์ปฌ๊ณผ ํผ์๋
ธ ๋ฐ์ฃผ๊ฐ ๊ฒฐํฉ๋์ด ์๋ค. ๊ณก์ด ์งํ๋จ์ ๋ฐ๋ผ ๊ฐ๊ฐ์ง ์
๊ธฐ๊ฐ ์ถ๊ฐ๋๋ค. ๋ค ๋ฒ์งธ ๊ตฌ์ ์ดํ๋ก๋ ํ์ด๋์์ ์ฝ๋ค๋ก ์ ํฅํ์ฌ 4๋ถ๊ฐ ์ง์๋๋ค.
ใHey Judeใ๋ ์ฒ์ ์ ํ ๋ ์ฝ๋ ๋ ์ด๋ธ์ ๋ฌ๊ณ 1968๋
8์ ์ถ์๋์๋ค. 7๋ถ์ ๋๊ธฐ๋ ๊ณก์ ์ฌ์์๊ฐ ๋์ ๋น์ ์๊ตญ ์ฐจํธ ์ ์์ ์ค๋ฅธ ๊ณก ์ค ๊ฐ์ฅ ๊ธด ์ฌ์์๊ฐ์ ๋ณด์ ํ ๊ฒ์ผ๋ก ๊ธฐ๋ก๋์๋ค. ๋ํ ๋ฏธ๊ตญ์์๋ ์ด๋ค ๋นํ์ฆ ์ฑ๊ธ๋ ๋ฐ์ด๋์ง ๋ชปํ, 9์ฃผ ๋์ ์ ์์ ๋จธ๋ฌด๋ฅด๋ ๋์
์ ์ด๋ฃฉํ๋ค. ใHey Judeใ๋ ๋น์ ์๊ตญ ์ฐจํธ์์ ๊ฐ์ฅ ์ค๋ ๋จธ๋ฌด๋ฅธ ์ฑ๊ธ์ด์๋ค. ์ด ์ฑ๊ธ์ ๊ฑฐ์ 8๋ฐฑ๋ง ์ฅ์ด ํ๋ ค๋๊ฐ์ผ๋ฉฐ ํ๋ก ๊ฐ๊ฐ ์ ์ ํ ์ญ๋ ์ต๊ณ ๋
ธ๋ ๋ชฉ๋ก์ ๋จ๊ณจ๋ก ๋ฑ์ฅํ๋ค. 2013๋
, ๋น๋ณด๋๋ ์ญ๋ ๊ฐ์ฅ ์๋ํ ๊ณก์ 10์๋ก ๊ณก์ ์ ์ ํ๋ค.
1968๋
5์, ์กด ๋ ๋
ผ๊ณผ ๊ทธ์ ์๋ด ์ ์์ ๋ ๋
ผ์ ์ค๋
ธ ์์ฝ์ ์กด์ ์ธ๋๋ก ๋ณ๊ฑฐํ๋ค. ๋ค์ ๋ฌ, ํด ๋งค์นดํธ๋๋ ์จ์ด๋ธ๋ฆฌ์ง ์ผ์ฐ๋์ ์์นํ ์ ์์์ ์กด์ ์๋ค ์ค๋ฆฌ์ธ ๋ฐฉ๋ฌธ์ ์ํด ์ฐจ์ ์ฌ๋๋ค. ์ ์์๋ ๋ฐด๋๊ฐ 1963๋
๋ช
์ฑ์ ๋์ฌ๊ฐ๊ธฐ ์์ํ ๋๋ถํฐ ๋นํ์ฆ ์ฌ๊ต๊ณ์ ์ผ์์ด์๋ค. ๋งค์นดํธ๋๋ ๊ทธ๋
๊ฐ "์ข ๋๋ฌดํ๋ค ์ถ์ ์ ๋๋ก ๊ทธ๋ค๋ก๋ถํฐ ๋ฐ๋๋ฆผ ๋นํ์ผ๋ฉฐ ์ถ์์ ์ ์ธ๋์๋ค"๊ณ ๋ท๋ ํธ์ด๋์๋ค. ์ ์์๋ ๋งค์นดํธ๋์ ๊น์ง ๋ฐฉ๋ฌธ์ ์ด๋ ๊ฒ ํ์ํ๋ค. "์ฐ๋ฆฌ์ ์๋
์ ๊ธฐ์ํ๋ ๊ทธ์ ์ง์ค๋ ์ผ๋ ค๋ ์ ๋ง์์ ์ ๋ฟ์์ต๋๋ค. ... ๊ทธ๋ 'Hey Jude'๋ฅผ ์ฐจ๋ฅผ ์ด์ ํ๋ ์ฌํ๊ธธ ๋์ ์๊ณกํ์ฃ . ์ฐ๋ฆฌ๋ฅผ ์ํด ์์ค ํด์ ๊ทธ ์ ์ฌ๋ค์ด ๋ฐฐ๋ ค์ ์ผ๋ ค๋ฅผ ์ ๋ ์์ ์์ ๊ฒ๋๋ค."
ํด ๋งค์นดํธ๋๊ฐ ๊ณก์ ๋๋ถ๋ถ์ ๋ง๋ค์๋ค. ๊ทธ๋ ์กด๊ณผ ์ ์์ ๋ ๋
ผ์ด ํค์ด์ง ๋ค ๊ทธ์ ์๋ค ์ค๋ฆฌ์ธ์ ์ผ๋์ ๋๊ณ ์ด ๋
ธ๋๋ฅผ ์๊ณกํ๋ค. "๊ทธ ๊ฐ์กฑ์ ์น๊ตฌ๋ก์ ๊ทธ๋ค์๊ฒ ๋ค ์๋ ๊ฑฐ๋ผ๊ณ ๋งํด์ฃผ๋ ค๊ณ ์ฐจ๋ฅผ ํ๊ณ ์จ์ด๋ธ๋ฆฌ์ง์ ์๋ ์กด์ ์ง์ ๊ฐ๋ ๊ฒ ๊ฐ์ต๋๋ค." "ํ ์๊ฐ์ฏค ์ด์ ํ์ด์. (์ด์ ํ ๋๋ฉด) ์ ๋ ํญ์ ๋ผ๋์ค๋ฅผ ์ฐ๊ณ ๋
ธ๋๋ฅผ ๋ง๋ค์ด๋ณด๊ณค ํ์ฃ . ํน์ ๋ชจ๋ฅด๋๊น์."๋ผ๊ณ ๋งค์นดํธ๋๋ ํ์ํ๋ค. ๋ถ๋ชจ์ ์ดํผ์ผ๋ก ์คํธ๋ ์ค๋ฅผ ๊ฒช๋ ์ค๋ฆฌ์ธ์ ์๋กํ๊ธฐ ์ํด ๋งค์นดํธ๋๋ ใHey Julieใ๋ผ๋ ์ ๋ชฉ์ ์ฒ์ ๋ถ์๋ค.
ใ๋กค๋ง ์คํคใ์ง์์ ์ธํฐ๋ทฐ ๋์ค ๋งค์นดํธ๋๋ ์ด์ ํ ๋ ์ด ๊ณก์ด ์ด๋ป๊ฒ ๋ ์ฌ๋๋์ง ์ค๋ช
ํ๋ค. "์ ๋ ๋
ธ๋๋ฅผ ๋ถ๋ฅด๊ธฐ ์์ํ์ด์. '์ค์ค์ผ, ๋์๊ฒ๋ง ๋ณด์ง ๋ง.' ์ค๋ฆฌ์ธ์๊ฒ ์ ํ๋ ๋๊ด์ ์ด๊ณ ํฌ๋ง์ ์ธ ๋ฉ์์ง์์ฃ ." ๊ทธ๋ "์ฃผ๋๊ฐ ๋ ๋์ ์ด๋ฆ์ด๋ผ๋ ์๊ฐ"์์ ์ค์ค์์ ์ฃผ๋๋ก ๋ฐ๊ฟจ๋ค. ์ฌ๊ธฐ์ ์ฃผ๋๋ ๊ทธ๊ฐ ์ข์ํ ๋ฎค์ง์ปฌ ใ์คํด๋ผํธ๋ง!ใ์ ๋ฑ์ฅ์ธ๋ฌผ ์ด๋ฆ ์ ๋(Jud)์์ ๊ฐ์ ธ์๋ค. ๋งค์นดํธ๋๋ ์์ ์ด ์๊ฐํ ๊ตฌ์กฐ๋๋ก ๊ณก์ ๋ค ๋ถ๋ถ์ผ๋ก ๋๋ด๋ค.
ํ ๋ฒ ์๊ฐ์ ํด๋ด์ ... ๊ณง๋ฐ๋ก ์์ฝ์ ์ด๋ฏธ์ง๊ฐ ๊ทธ๋ ค์ง ๊ฒ๋๋ค. ๊ทธ๋ ์ด๋ ๊ฒ ๋งํ์ฃ . "์ด๋ด, ์ฃผ๋ โ ์ด๋ด, ์กด" ์ ๋ ์ ์์ ์ด ๊ณผ๋ ํด์ํ๋ ํฌ ๋ฌด๋ฆฌ์ฒ๋ผ ๋ค๋ฆฌ๋ ๊ฒ ์๋๋ค๋ง, ๋น์ ๋ ์ด ๊ณก์ด ์ ๋ฅผ ํฅํ ๊ฒ์์ "๋ค์" ์ ์์ด์. ... ๊ทธ๋ ์ ์ฌ์ ์ผ๋ก, ๋์๊ฐ๋ผ, ๋๋ฅผ ๋ด๋ฒ๋ ค ๋๋ผ๊ณ ๋งํฉ๋๋ค. ์์์ ์ธ ์ฐจ์์์๋ ์ ๊ฐ ๋์๊ฐ๊ธธ ์ํ์ง ์์์.
๋งค์นดํธ๋๋ ๋ ๋
ผ์๊ฒ ์ํ์ ์๊ฐํ ๋น์์ "๋น์ ์ด ํ์ํ ํ๋์ ๋น์ ์ด๊นจ์ ์์ด์(the movement you need is on your shoulder)"๋ฅผ ๋ ๋
ผ์ด "๋ฉ์ฒญํ ํํ์ด๊ตฐ. ์ต๋ฌด์๊ฐ์ ์๋ฆฌ์ผ"๋ผ๋ฉฐ ๊ณ ์น๋ ค๊ณ ํ๋ค๊ณ ์ฆ์ธํ๋ค. ๋ ๋
ผ์ ์ด๋ ๊ฒ ์์ํ๋ค. "๋ ์ง์ง ๊ทธ๋ฌ๊ธฐ์ผ. ๊ทธ๊ฑด ๊ณก์์ ์ต๊ณ ์ ๊ฐ์ฌ๋ผ๊ตฌ." ๋งค์นดํธ๋๋ ๊ฐ์ฌ๋ฅผ ๋ฐ๊พธ์ง ์๊ณ ์ ์งํ์๋ค. ํด์ "๊ทธ ๊ฐ์ฌ๋ ์กด์ ๋ ์ฌ๋ฆฌ๊ฒ ๋์. ๊ฐ๋ ๊ทธ ๋ถ๋ถ์ ๊ณต์ฐํ๊ฒ ๋๋ฉด ์กฐ๊ธ ๊ฐ์ ์ ์ด ๋์ฃ ."๋ผ๊ณ ๋งํ๋ค. ๋งค์นดํธ๋๊ฐ ๊ณก์ ์ค๋ฆฌ์ธ์ ์ํด ์ผ๋ค๊ณ ๋ ํ๋, ์กด ๋ ๋
ผ์ ๊ทธ๊ฒ์ด ์์ ์ ํฅํ ๊ณก์ด๋ผ๊ณ ์๊ฐํ๋ค. 1980๋
์ธํฐ๋ทฐ์์ ๋ ๋
ผ์ ์์ ์ด "๊ณก์ ๋ค์ ๋๋ง๋ค ์์ ์ ํฅํ ๊ฒ"์ผ๋ก ์๊ฐํ๋ค๋ฉด์ ์ด๋ค ๋ฉด์์ ๋งค์นดํธ๋๊ฐ ์์ ๊ณผ ์์ฝ์ ๊ด๊ณ๋ฅผ ์ถ๋ณตํ๋ ค๋ ์๋์๋ค๊ณ ๋ถ์ํ๊ณ , ๋ค๋ฅธ ํํธ์ผ๋ก ๋ ๋
ผ์ ์น๊ตฌ ์๋ฆฌ์, ๊ทธ๋ฆฌ๊ณ ์๊ณก ํํธ๋์ญ์ผ๋ก์ ๊ทธ๋ฅผ ์๊ฒ ๋ ์ค๋ง๊ฐ์ด ์กด์ฌํ๋ค๊ณ ์ฃผ์ฅํ๋ค.
์๊ฐ Mark Hertsgaard๋ "๊ณก์ ๊ฐ์ฌ ๋๋ค์๋ ๊ฐ๋ ฌํ ์ ์ฌ๋์ ์ฐพ๊ธฐ ์ง์ ์ ์ฑ์ธ์ ์ง์ ์ ์ผ๋ก ๊ฐ๋ฆฌํค๋ ๊ฒ ๊ฐ๋ค. ํนํ๋ ๊ฐ์ฌ '๊ทธ๋
๋ฅผ ์ฐพ์์ผ๋, ๊ฐ์ ๊ทธ๋
์ ์ฌ๊ท์ด์(you have found her now go and get her)' ๊ทธ๋ฆฌ๊ณ '๋น์ ์ ํจ๊ปํ ๋๊ตฐ๊ฐ๋ฅผ ๊ธฐ๋ค๋ฆฌ๊ณ ์์ด์(you're waiting for someone to perform with.)'์์ ํ์ ํ๋ค."๊ณ ์ ์ ํ๋ค. ์์
ํ๋ก ๊ฐ ๊ฒธ ์๊ฐ ํ ๋ผ์ผ๋ฆฌ๋ ์ด๋ ๊ฒ ์ ์๋ค. "๋ง์ฝ ๊ณก์ด ์ด๋ ค์์ ์ง๋ฉดํ ์๊ธฐ์กด์ค๊ณผ ์๊ธฐ์์์ ๋ํ ๊ฒ์ด๋ผ๋ฉด, ๋ณด์ปฌ ๊ณต์ฐ ๊ทธ ์์ฒด๋ ์ฌ์ ์ ์ ๋ฌํ๋ ๊ฒ์ ๊ฐ๊น๋ค. ๊ทธ๋ ๋๊ตฐ๊ฐ๋ฅผ ์๋กํ๊ธฐ ์ํด ๊ณก์ ๋ถ๋ฅด๊ธฐ ์์ํ๊ณ , ์งํ๋จ์ ๋ฐ๋ผ ๊ทธ๋ ์์ ์ ๊ฐ์ ์ด ๊ณก์ ์ํฅ์ ์ค์ ๋ฐ๊ฒฌํ๊ณ , ๋ง์ง๋ง์ผ๋ก ๋ฐ๋ณต๋๋ ํ๋ ด์์ ๊ทธ๋ ์์ ์ ๋ฏฟ๊ฒ ๋๋ค."
โ Griffith added that he and his fellow Iveys were "gobsmacked" by the performance.
โ In a 1971 interview with Jonathan Cott, Lennon recalled his and McCartney's conversation: "Ah, it's me! I said, it's me! He says, no it's me. I said, check, we're going through the same bit."
โ ๊ฐ ๋ ๋ค Womack 2014, 389์ชฝ.
โ โThe Beatles, 'Hey Jude'โ. ใRolling Stoneใ. 2011๋
4์ 7์ผ. 2007๋
8์ 14์ผ์ ํ์ธํจ.
โ Sounes 2010, 208, 221์ชฝ.
โ ๊ฐ ๋ Miles 1997, 465์ชฝ.
โ ๊ฐ ๋ ๋ค ๋ธ๋ผ์ด์ธ 2014, 230์ชฝ.
โ ๊ฐ ๋ Hunt, Chris (2003). ใHere Comes the Sonใ. ใMojo: The Beatles' Final Years Special Editionใ. London: Emap. 39์ชฝ.
โ ๊ฐ ๋ Cross 2005, 367์ชฝ.
โ ๊ฐ ๋ Sheff 2000, 186์ชฝ.
โ ๊ฐ ๋ The Beatles 2000, 297์ชฝ.
โ Harry, Bill (2000). ใThe Beatles Encyclopedia: Revised and Updatedใ. London: Virgin Publishing. 517์ชฝ. ISBN 0-7535-0481-2.
โ Unterberger, Richie. โHey Jude โ Song Reviewโ. AllMusic. All Media Network. 2006๋
1์ 20์ผ์ ํ์ธํจ.
โ Carr & Tyler 1978, 70์ชฝ.
โ Sounes 2010, 212โ13, 215์ชฝ.
โ ๊ฐ ๋ Hertsgaard 1995, 236์ชฝ.
Carr, Roy; Tyler, Tony (1978). ใThe Beatles: An Illustrated Recordใ. London: Trewin Copplestone Publishing. ISBN 0-450-04170-0.
Clayson, Alan (2003). ใRingo Starrใ. London: Sanctuary. ISBN 1-86074-488-5.
Cross, Craig (2005). ใThe Beatles: Day-by-Day, Song-by-Song, Record-by-Recordใ. Lincoln, NE: iUniverse. ISBN 0-595-34663-4.
Emerick, Geoff; Massey, Howard (2006). ใHere, There and Everywhere: My Life Recording the Music of The Beatlesใ. New York, NY: Gotham Books. ISBN 978-1-59240-269-4.
Everett, Walter (1999). ใThe Beatles as Musicians: Revolver Through the Anthologyใ. New York, NY: Oxford University Press. ISBN 0-19-509553-7.
Fletcher, Tony (2016). ใIn the Midnight Hour: The Life & Soul of Wilson Pickettใ. Oxford University Press. ISBN 978-0-19-025296-0.
Hertsgaard, Mark (1995). ใA Day in the Life: The Music and Artistry of The Beatlesใ. New York: Delacorte Press. ISBN 0-385-31377-2.
Leng, Simon (2006). ใWhile My Guitar Gently Weeps: The Music of George Harrisonใ. Milwaukee, WI: Hal Leonard. ISBN 978-1-4234-0609-9.
Lowry, Todd (2002). ใLennon and McCartney Hits: Keyboard Signature Licksใ. Hal Leonard. ISBN 0-634-03250-X.
Miles, Barry (1997). ใPaul McCartney: Many Years From Nowใ. New York, NY: Henry Holt and Company. ISBN 0-8050-5249-6.
O'Dell, Chris (2009). ใMiss O'Dell: My Hard Days and Long Nights with The Beatles, The Stones, Bob Dylan, Eric Clapton, and the Women They Lovedใ. New York, NY: Touchstone. ISBN 978-1-4165-9093-4.
Poe, Randy (2008). ใSkydog: The Duane Allman Storyใ. Backbeat Books. ISBN 978-1-61713-487-6.
Riley, Tim (2002). ใThe Beatles: Album By Album, Song By Song, the Sixties and Afterใ. Cambridge, MA: Da Capo Press. ISBN 0-306-81120-0.
Riley, Tim (2011). ใLennon: The Man, the Myth, the Music โ The Definitive Lifeใ. London: Random House. ISBN 978-0-7535-4020-6.
Ryan, Kevin; Kehew, Brian (2006). ใRecording the Beatles: The Studio Equipment and Techniques Used To Create Their Classic Albumsใ. Houston, TX: Curvebender Publishing. ISBN 0-9785200-0-9.
Schultheiss, Tom (1980). ใA Day in the Life: The Beatles Day-By-Dayใ. Ann Arbor, MC: Pierian Press. ISBN 0-87650-120-X.
Sheffield, Norman J (2013). ใLife On Two Legsใ. London: Trident Publishing. ISBN 0-9575133-0-5.
Simpson, Paul (2004). ใThe Rough Guide to Elvisใ. London: Rough Guides. ISBN 1-84353-417-7.
โHEY JUDE (Legal Title), BMI Work #562357โ. BMI. |
0.940039 | How can I filter the taxonomy terms by language?
I have searched a way to filter the taxonomy terms by language (as done for nodes), but I didn't find any way to do it.
Does the Views module support that filter in taxonomies too, or just in nodes?
By enabling the module Internationalization Views, the option to filter the taxonomy term by the language is available. Note that the version is currently in dev but it works like a charm.
You can use the Internationalization Views module in combination with the Taxonomy Translation module (which is part of Internationalization) to get a language filter for taxonomy terms.
Translate views using Internationalization. This is a work in progress and not all Views properties can be translated yet. Requires Internationalization 6.x-1.5 or newer.
The Views module doesn't allow to filter the taxonomy terms by the language associated with it, as Drupal only associate a language with nodes.
You can set the view to show only nodes with a predefined language, though.
Under "Filter criteria," select "Add"
in the next form, select "Content translation: Language"
the next form will allow you to select which language to use to filter the view content between "Select all," "Current user's language," "Default site language," "No language," and one of the languages enabled in the site.
I added this filter on the taxonomy term view that comes with the Views module, selecting English as language to filter the content, and I created two nodes: one in English, and one in Latin. I assigned to both the nodes the same taxonomy term, the one with ID equal to 22.
When I visited http://example.com/taxonomy/term/22, the view effectively shown just the content in English.
Language filtering for entity translation. A language filter in the view's "Filter Criteria" section is only needed if you use the node translation system. If instead you use the more modern Entity Translation system available for Drupal 7, just adapt the "Field Language" setting in the view's "Other" section.
How to do it for taxonomy terms. I tried this for taxonomy terms and it works. Just make sure you add the correct one of the two field instances for every translatable field, namely the one with a description of "Appears in: taxonomy-term:your-vocab-name". For details, see on issue #1841434.
* Views handler to filter language by term.
// '0' won't work as a key for checkboxes.
Clear All caches and New criterion will appear.
As I'm having some other issues with Internationalization Views module, namely that it seems to alter allready translated UI from views (pager directions, header / footer text etc.), I liftet the relevant code for creating the language filters out in a separate module. Replace MYMODULE below with the name of your module. Works as a charm for me!
* Registers views handlers with dependency to i18n_taxonomy.
// Add i18n language field to taxonomy_term_data. No clash.
* Field handler to provide simple renderer that shows term language.
* Argument handler to accept a language.
How to create something like a textual โadd other termโ for taxonomy terms?
How do I filter exposed taxonomy terms with other exposed taxonomy terms?
How Can I have Exposed filter for Taxonomy vocabulary in Heirarchical Select? |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.