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We use cookies to customise content for your subscription and for analytics.If you continue to browse Lexology, we will assume that you are happy to receive all our cookies. For further information please read our Cookie Policy. Citizens Suits have played an important role in the enforcement of both the Clean Water Act (CWA) and the Clean Air Act (CAA), and all permittees of wastewater discharge permits and air quality permits should be aware of the significance of these Congressionally-approved remedies. While they have broad application to many routine industrial discharges, there also are limited conditions placed on their use. For instance, the CWA Citizen Suit provision, 33 U.S.C. § 1365, requires plaintiffs to provide the alleged violator 60 days’ notice before filing a lawsuit. In addition, the text of the provision of the CWA limits its application to violations of “effluent standards or limitations,” which the CWA also carefully defines by reference to Sections 1311, 1312, 1316. 1317, 1341, and 1342 of the CWA. If the subject matter of the alleged violation is not covered by these provisions, the case will usually be dismissed. Recently, the U.S. Court of Appeals for the Sixth Circuit, in Askins v. Ohio Department of Agriculture, et al., affirmed the lower court’s dismissal of a CWA Citizen Suit filed against the Ohio Department of Agriculture, the Ohio EPA and the U.S. EPA alleging that these agencies violated the CWA’s agency permitting procedures when the Ohio EPA delegated administration of the concentrated animal feeding operations (CAFOs) permitting process to the Ohio Department of Agriculture. The Court of Appeals expressed the view that the Citizen Suits are limited in scope because they principally serve as an adjunct to the plenary authority of federal and state regulatory agencies. In addition, the Court of Appeals ruled that EPA did not have a non-discretionary duty to conduct a hearing into complaints as to the administration of the program in Ohio. Plaintiffs’ claims arose in connection with water pollution generated by large animal feeding operations in Ohio. EPA authorized the Ohio EPA to administer the state National Pollutant Discharge Elimination System (NPDES) permitting program, and the CAFO-permitting programs were later delegated to the Ohio Department of Agriculture without obtaining EPA’s contemporaneous authorization. The plaintiffs filed administrative appeals with regard to some CAFO permits, and then filed this federal lawsuit complaining that the lack of approval of the Ohio EPA’s delegation to the Ohio Department of Agriculture violated the CWA, justifying the filing of the lawsuit under the Citizen Suit provisions of the CWA. The district court dismissed these claims on the basis that the plaintiffs failed to establish that they were authorized to file this private cause of action, and on the ground that the plaintiffs failed to allege that EPA had violated a non-discretionary duty in its administration of the Ohio state program. The Court of Appeals affirmed the district court’s holding that none of these alleged procedural violations of Section 1314 of the CWA were actionable as a Citizen Suit because they were not specified by the Congress as sections of the CWA subject to the precise formulation of the Citizen Suit provisions. Compare jurisdictions: Arbitration “I find the newsfeeds to be extremely helpful and relevant to my practice area and to the issues facing my company. As I am extremely happy with the newsfeed (it is one of the best I receive) I have no suggestions at this time for improvement.”
Lt Gov say Duck Dynasty important to La. tourism, offers to help family find new producers This undated image released by A&E shows brothers Silas "Uncle Si" Robertson, left, and Phil Robertson from the popular series "Duck Dynasty." Phil Robertson was suspended last week for comments he made to GQ magazine about gay people. A&E, Zach Dilgard, Associated Press Summary Louisiana's lieutenant governor says the "Duck Dynasty" reality TV show is important to state tourism — and he could help connect the Robertson family with new producers if they cannot reach agreement with the A&E network. “If the Robertson family cannot come to an agreement with A&E and wants to continue the show, Louisiana already has the infrastructure in place to maintain their record-breaking program.” La. Lt. Governor Jay Dardenne NEW ORLEANS — Louisiana's lieutenant governor says the "Duck Dynasty" reality TV show is important to state tourism — and he could help connect the Robertson family with new producers if they cannot reach agreement with the A&E network. The network suspended patriarch Phil Robertson last week for telling GQ magazine that gays are sinners akin to adulterers and swindlers. "Regardless of one's views on Phil Robertson's statements, Duck Dynasty has been an important representation of the state of Louisiana, inspiring prospective visitors and investors since its debut," Lt. Governor Jay Dardenne said in a statement emailed Saturday. The show is produced around the Robertson family's home base in Ouachita Parish. KNOE-TV of Monroe reported in February that the show was bringing people from around the country who wouldn't otherwise stop in northeast Louisiana. The Duck Commander warehouse has become a tourist attraction, said Alana Cooper, director of the Monroe-West Monroe Visitors and Convention Bureau. Dardenne, whose job includes running the Department of Culture, Recreation and Tourism, said the audience of tens of millions is eager to visit Louisiana. "If the Robertson family cannot come to an agreement with A&E and wants to continue the show, Louisiana already has the infrastructure in place to maintain their record-breaking program," he wrote. The lieutenant governor did not immediately answer a request for comment Sunday. Dardenne, who authored the state's film and TV tax credit program, said he would use his influence in the state's industry to help the Robertsons. Gov. Bobby Jindal said Thursday that everyone is entitled to express their opinions. More than 1.7 million fans have liked an impromptu Facebook page titled "Boycott A&E Until Phil Robertson Is Put Back On Duck Dynasty" — one of numerous pages with similar names, though none of the others has even 1 percent as many "likes." "Duck Dynasty" is on hiatus until Jan. 15. A network spokesman told the AP on Thursday that nine of next season's 10 episodes have already been filmed. That means Robertson likely isn't needed in front of the camera before next March. Popular Comments I'm waiting for the backlash from the "tolerance" crowd against Charlie Sheen and his hate-filled comments regarding Duck Dynasty. What he said was far far worse than what Phil Robertson said but I'm guessing we won't hear much More.. 3:34 p.m. Dec. 22, 2013 Top comment CAAZFR MESA, AZ Regarding entertainers, sports stars, commentators, politicians:In 2013 they cannot, on TV, offer an unflattering personal opinion about gays, and mention the Bible in the same paragraph.In the near-future it won't be tolerated to More.. 3:29 p.m. Dec. 22, 2013 Top comment Happy Valley Heretic Orem, UT Why anyone would care what he or charlie sheen says, is beyond me.You are free to say what ever you want, this does not relieve you of the consequences of those action.
The disclosure of Japanese Patent Application No. 2001-367231 filed on Nov. 30, 2001, and No. 2002-341644 filed on Nov. 26, 2002, each including the specification, drawings and abstract is incorporated herein by reference in its entirety. 1. Field of the Invention The present invention relates generally to a contact lens and a method of designing the same, and is concerned with techniques for providing a contact lens that is satisfactory in shape stability and that is thin and comfortable to wear. More particularly, the present invention is concerned with a novelly shaped contact lens suitably applicable to soft contact lenses, and capable of establishing an easiness of handling and an easiness of differentiating between a front surface and a back surface thereof with the help of its shape stability, while ensuring its suitable wearing comfort as felt by a lens wearer. The present invention is also concerned with a novel method of designing the contact lens. 2. Description of the Related Art Generally, contact lenses require to be excellent in (a) lens wearing comfort as felt by a lens wearer, and to be easy of (b) handling by fingers of the lens wearer. In order to improve the former requirement, i.e., the lens wearing comfort, it is desirable to sufficiently reduce a thickness of a contact lens (hereinafter referred to as a xe2x80x9clens thicknessxe2x80x9d where appropriate) while assuring a minimum lens thickness determined by a selected lens material, with production efficiency and durability of the contact lens taken into consideration. Such a thin contact lens is also excellent in oxygen permeability. The thin contact lens, however, may be deteriorated in its shape stability. In the case of a thin soft contact lens, particularly, it is likely that the soft contact lens, when being placed on a finger of the lens wearer to be worn on or removed from a cornea, clings to a surface of the finger of the lens wearer. This makes it difficult to handle the contact lens by the fingers and to differentiate between a front surface and a back surface of the contact lens, resulting in cumbersome operations in wearing and removal of the contact lens. To cope with these problems, a number of solutions have been suggested. For instance, a lens thickness of a contact lens is increased by an amount enough to ensure a good handling thereof based on its good shape stability. Alternatively, an identification mark is provided on a surface of the contact lens for allowing the wearer to differentiate between the front surface and the back surface of the contact lens. The latter one enables the contact lens to be made thin with a great regard for the lens wearing comfort, while coping with the problem of insufficiency in the shape stability of the contact lens. However, these solutions are still in a level of compromises in which any one of the wearing comfort and the shape stability (or the handling of the contact lens) is sacrificed or ignored, and are not what can be called fundamental solutions. In particular, a number of specific manufacturing process and workings are needed to form the identification mark on the surface of the contact lens, undesirably pushing a manufacturing cost. In order to achieve both of the excellent lens wearing comfort and the good handling of the contact lens, JP-A-8-286155 discloses a contact lens design wherein a peripheral zone has a lens thickness of not less than 1.2 times a lens thickness as measured at a central portion of the lens, and a front junction of an optical zone with a peripheral zone on a front surface (or a front curve surface) of the lens is offset radially outwardly from a back junction of an optical zone with a peripheral zone on a back surface (or a base curve surface) of the lens, so as to increase the thickness of the peripheral zone. Further, JP-A-11-52304 and JP-A-2000-214417 disclose another contact lens design wherein there are determined a lens thickness as measured at its central portion and a lens thickness at and a position of a part of a peripheral portion where the thickness dimension is maximized. These contact lens designs disclosed in the above-indicated documents are unsatisfactory in achieving both of the lens wearing comfort and good handling of the contact lens. In this respect, these conventional contact lens designs are basically concerned with the lens thickness as measured at around the front junction on the front surface of the contact lens where the optical zone and the peripheral zone join together, and determine the lens thickness at around the front junction to be made larger enough to exhibit its good shape stability, but not cause considerable deterioration of the lens wearing comfort as felt by the wearer. The increase in the lens thickness at around the front junction inevitably restricts a design of optical characteristics of the optical zone, resulting in a relatively low degree of freedom in designing lens forms and powers. Upon designing a contact lens, generally, a radius of curvature of a back surface of the lens is determined as a base curve to approximately correspond to a shape of a surface of the cornea of the lens wearer so that the contact lens is comfortable to wear and is positioned on the cornea with high stability. Then, a front surface of the lens is designed so as to give a desirable optical power to an optical zone of the lens, and so as to permit the optical zone to have a minimum thickness of the lens determined by selected materials. Since the lens thickness as measured at around an outer peripheral portion of a front optical zone of the contact lens is dimensioned to a specific value, according to the above-described documents, the thickness of the optical zone is entirely restricted or affected by the thickness of the outer peripheral portion of the optical zone, thus limiting a degree of freedom in designing the contact lens and a power of the lens. It is therefore an object of the invention to provide a contact lens which is novel in configuration and which is capable of highly ensuring both of lens wearing comfort and shape stability, while providing a high degree of freedom in designing the contact lens. It is another object of the present invention to provide a novel method of designing such a contact lens. The above and/or optical objects of this invention may be attained according to at least one of the following modes of the invention. Each of those modes of the invention is numbered like the, appended claims and depending from the other mode or modes, where appropriate, to indicate possible combinations of elements or technical features of the invention. It is to be understood that the principle of the invention is not limited to these modes of the invention and combinations of the technical features, but may otherwise be recognized based on the teachings of the present invention disclosed in the entire specification and drawings or that may be recognized by those skilled in the art in the light of the present disclosure in its entirety. (1) A contact lens comprising: a central optical zone including a front optical zone and a back optical zone; and a peripheral zone surrounding the optical zone and including a front peripheral zone and a back peripheral zone, wherein the contact lens is provided with a dioptric power P ranging from xe2x88x9210 to 0 diopters (xe2x88x9210xe2x89xa6Pxe2x89xa60), wherein the front optical zone and the front peripheral zone join together at a front junction, and the back optical zone and the back peripheral zone join together at a back junction that is located outward of the front junction in a diametric direction of the contact lens orthogonal to a center axis of the contact lens, and wherein the contact lens has a central lens thickness TC ranging from 0.03 to 0.50 mm as measured along the center axis thereof, a front junction lens thickness TFJ of not less than 0.05 mm as measured at the front junction, and a back-junction lens thickness TBJ as measured at the back junction, the back-junction lens thickness TBJ is determined depending upon the dioptric power P so as to satisfy a following expression: xcexa3(Aixc2x710xe2x88x92ixc2x7Pi)xe2x89xa6TBJ/TFJxe2x89xa6xcexa3(Bixc2x710xe2x88x92ixc2x7Pi) where, A0=+1.2382 A1=xe2x88x920.1741 A2=xe2x88x921.4711 A3=xe2x88x920.9355 B0=+1.4699 B1=xe2x88x920.2523 B2=xe2x88x921.9897 B3=xe2x88x921.2603 In order to accomplish this mode of the invention, an extensive analysis or study was made by the inventors on their new finding that a shape stability of a contact lens owing to an optical zone varies depending upon a shape of a front surface of the contact lens that is determined by a dioptric power of the lens. A result of the analysis has revealed that when the front junction and the back junction are spaced away from each other in the diametric direction orthogonal to the center axis of the lens, a suitable adjustment of a ratio TBJ/TFJ of the back junction lens thickness TBJ to the front junction lens thickness TFJ depending upon the dioptric power P of the lens makes it possible to effectively ensure a desired shape stability of the contact lens at the optical zone. In this respect, the ratio TBJ/TFJ is adjusted to meet the specific condition as represented by the expression depending upon the dioptric power of the optical zone, thus making it possible to provide the contact lens that is well comfortable to wear and is fully satisfactory in its shape stability. This mode of the present invention has been accomplished based on the above-described knowledge of the present inventors. According to this mode of the invention, moreover, the back junction formed between the back optical zone and the back peripheral zone is located radially outward of the front junction formed between the front optical zone and the front peripheral zone with a radial spacing therebetween. This arrangement makes it possible to adjust the ratio TBJ/TFJ, which is determined depending upon the dioptric power of the lens, by only shifting a position of the back junction relative to the front junction. In other words, this arrangement makes it possible to improve the shape stability of the contact lens to a required level by suitably adjusting the back junction lens thickness, while desirably determining the front junction lens thickness TFJ in order to establish required optical characteristics in the optical zone of the lens, and while eliminating adverse effect on the optical characteristics of the optical zone. The central lens thickness TC of the contact lens is held within a range of 0.03-0.50 mm, more preferably 0.05-0.50 mm, while the front junction lens thickness TFJ where the front optical zone and the front peripheral zone join together is not smaller than 0.05 mm more preferably not smaller than 0.10 mm. This arrangement enables the contact lens to have the approximately same form and lens thickness in its optical zone, depending upon its dioptric power, thus making it possible to systematically and accurately recognize shape stability generated in the optical zone based on the dioptric power of the contact lens. Therefore, shape stability to be generated in the peripheral zone can be determined while taking into account the shape stability of the optical zone, thus enabling the contact lens to stably establish a desired shape stability in its entirety, which is enough to ensure a good handling of the contact lens. Therefore, the contact lens constructed according to this mode of the invention can effectively establish a preferable shape stability in its entirety that is determined with the shape stability of the optical zone taken into consideration, thus eliminating the conventionally experienced problems that an excessively large lens thickness causes an excessively increased shape stability of the lens and a resultant deterioration in lens wearing comfort, and adverse effects on optical characteristics of the lens. For this reason, the contact lens according to this mode of the invention is superiorly comfortable to wear and excellent in handling as well. A type and a material of the contact lens according to this mode of the invention are not particularly limited, and the principle of the present mode of the invention may be applicable to various types of known contact lenses including contact lenses for treating myopia, presbyopia, and astigmatism. The term xe2x80x9clens thicknessxe2x80x9d should be interpreted to mean a thickness of a contact lens measured in a radial direction at an optional measuring point. In the case where a contact lens has a spherical back optical zone, the lens thickness of the contact lens is defined by a thickness of the lens as measured along a straight line extending through a center of the spherical back optical zone and a measuring point, for example. In the case where a contact lens has an aspherical back optical zone, the lens thickness is defined by a thickness of the lens as measured along a straight line including a center of a vertex sphere as a starting point. The reasons why the present mode of the invention is directed to contact lenses having dioptric powers within a range of xe2x88x9210-0 diopters (xe2x88x9210xe2x89xa6Pxe2x89xa60) are that a great demand exists for these contact lenses usable for treating myopia, and that these contact lenses can be supplied to the market as a design family of contact lenses whose dioptric powers vary from one another at given equal intervals. (2) A contact lens comprising: a central optical zone including a front optical zone and a back optical zone; and a peripheral zone surrounding the optical zone and including a front peripheral zone and a back peripheral zone, wherein the contact lens is provided with a dioptric power P ranging from xe2x88x926 to 0 diopters (xe2x88x926xe2x89xa6Pxe2x89xa60), wherein the front optical zone and the front peripheral zone join together at a front junction, and the back optical zone and the back peripheral zone join together at a back junction that is located outward of the front junction in a diametric direction of the contact lens orthogonal to a center axis of the contact lens, and wherein the contact lens has a central lens thickness TC ranging from 0.03 to 0.50 mm, more preferably 0.05 to 0.50 mm, as measured along the center axis thereof, a front junction lens thickness TFJ of not less than 0.05 mm as measured at the front junction between the front optical zone and the front peripheral zone, and a back-junction lens thickness TBJ as measured at the back junction is determined so as to satisfy a following expression: TBJ/TFJxe2x89xa71 Like the above-indicated mode (1) of the invention, the principle of this mode of the invention has been accomplished as a result of the extensive analysis or study conducted by the inventors based on the technical concept that a suitable adjustment of the ratio TBJ/TFJ of the back junction lens thickness TBJ to the front junction lens thickness TFJ depending upon the dioptric power of the lens permits the contact lens to effectively establish its overall shape stability, while eliminating the problem of deterioration of the lens wearing comfort due to the excessive enlargement of the lens thickness. More particularly, the principle of this mode of the invention has been developed based on a new finding that the contact lens provided with the dioptric power P ranging from xe2x88x926 to 0 diopters (xe2x88x926xe2x89xa6Pxe2x89xa60) may suffer from difficulty in exhibiting an effective shape stabilizing characteristics or capability in its optical zone, when being provided with a suitable form and thickness at its optical zone. The reasons why the present mode of the invention is directed to contact lenses having dioptric powers within a range of xe2x88x926-0 diopters (xe2x88x926xe2x89xa6Pxe2x89xa60) are that a great demand exists for these contact lenses usable for treating myopia, and that the present inventors have paid their attention to a new finding that the contact lenses having dioptric powers within a range of xe2x88x926-0 diopters, among the contact lenses having the dioptric powers within a range of xe2x88x9210-0 diopters (xe2x88x9210xe2x89xa6Pxe2x89xa60), especially suffer from their common difficulty in establishing a desired shape stability in their optical zones. Described in detail, in each of the contact lenses having the dioptric powers ranging from xe2x88x926 to 0 diopters, the optical zone has a relatively small difference between its minimum thickness and its maximum thickness, so that the optical zone is capable of ensuring a lens wearing comfort, but is incapable of exhibiting a desired shape stability, if the minimum thickness of the optical zone is set to a minimum value required for ensuring strength and durability of the contact lens. In the contact lens constructed according to this mode of the invention, the back junction lens thickness TBJ as a lens thickness measured at the back junction is made larger than the front junction lens thickness TFJ as a lens thickness measured at the front junction, while the optical zone is desirably designed in terms of its shape and a thickness dimension. While the desirably shaped optical zone of the contact lens is prone to be insufficient in its shape stability, the peripheral zone of the contact lens where the lens thickness is made larger at the back junction rather than at the front junction, can effectively compensate the insufficient shape stability of the contact lens. Thus, the contact lens of this mode of the invention is able to establish a desired shape stability in its entirety and a resultant good handling thereof, while being highly satisfactory in terms of its optical characteristics and its wearing comfort with the help of a reduced thickness of the optical zone. In this respect, an upper limit of the ratio TBJ/TFJ is determined while taking into account lens wearing comforts as felt by lens wearers, and a variation in sensitivities or the like of individual wearers. In general, the front and back junction lens thicknesses TFJ. TBJ have respective minimum values restricted by required lens strength and durability varying depending upon a material of the contact lens, and respective maximum values restricted by the lens wearing comfort not to be larger than 1.0 mm. For this reason, there is no need to especially consider the upper limit of the ratio TBJ/TFJ. (3) A contact lens according to the above-indicated mode (1) or (2), wherein the front junction has a diameter within a range of 55-85% of a diameter of the contact lens, and the back junction has a diameter within a range of 70-90% of the diameter of the contact lens. Upon setting a variety of dioptric power of the contact lens, this arrangement ensures the contact lens to establish a desired shape stability in its entirety, since one or both of the shape stabilities exhibiting in the optical zone and the peripheral zone can be compensated by the other or with each other. (4) A contact lens comprising: a central optical zone including a front optical zone and a back optical zone; and a peripheral zone surrounding the optical zone and including a front peripheral zone and a back peripheral zone, wherein the contact lens is provided with a dioptric power P not larger than xe2x88x9210 diopters (P less than xe2x88x9210), wherein the front optical zone and the front peripheral zone join together at a front junction, and the back optical zone and the back peripheral zone join together at a back junction that is located outward of the front junction in a diametric direction of the contact lens orthogonal to a center axis of the contact lens, and wherein the contact lens has a central lens thickness TC ranging from 0.03 to 0.50 mm as measured along the center axis thereof, a front junction lens thickness TFJ of not less than 0.05 mm as measured at the front junction, and a back-junction lens thickness TBJ as measured at the back junction, the back-junction lens thickness TBJ is determined depending upon the dioptric power P so as to satisfy a following expression: (a) where the front optical zone has a diameter DFOZ of smaller than 7.0 mm (DFOZ less than 7.0 mm), 0.877xe2x89xa6TBJ/TFJxe2x89xa60.993 (b) where the front optical zone has a diameter DFOZ of not smaller than 7.0 mm (DFOZxe2x89xa77.0 mm), xcexa3(Aixc2x710xe2x88x92ixc2x7Pi)xe2x89xa6TBJ/TFJxe2x89xa6xcexa3(Bixc2x710xe2x88x92ixc2x7Pi) where, A0=+1.7980 A1=+1.4330 A2=+0.5824 A3=+0.0814 B0=+2.0184 B1=+1.5827 B2=+0.6298 B3=+0.0871 According to this mode of the invention, a so-called xe2x80x9chigh-minus lensxe2x80x9d provided with a negative refractive power larger than xe2x88x9210 diopters can exhibit an excellent shape stability in its entirety, like in the above-indicated mode (1), since a shape stability generated in the optical zone can be recognized and effectively compensated by a shape stability generated in the peripheral zone with the recognized shape stability of the optical zone utilized. In addition, the peripheral zone is shaped so as to meet specific conditions selected based on the dioptric power given to the optical zone, thus making it possible to establish the excellent shape stability of the contact lens, while assuring a sufficient degree of freedom in designing the optical characteristics of the optical zone, and an excellent lens wearing comfort. It should be appreciated that the peripheral zone is shaped with the diameter DFOZ of the front optical zone taken into consideration, making it possible to suitably compensate the shape stability generated in the optical zone by the peripheral zone with the help of the accurate recognition of the shape stability in the optical zone, without causing an excessive increase in the thickness of the peripheral zone. Thus, the contact lens constructed according to this mode of the invention is capable of exhibiting the excellent shape stability in its entirety and the excellent lens wearing comfort, as well. More specifically described, in the case where the optical zone of the contact lens has a relatively large diameter DFOZ, the thickness of a peripheral portion of the optical zone is inevitably made large sufficiently, since the negative refractive power given to the optical zone is great. Thus, the contact lens can be designed so as to exhibit its entire shape stability by utilizing the shape stability eventually generated in the optical zone, and so as to establish the excellent lens wearing comfort without needing the excessive increase in the thickness of the peripheral zone, which is likely to be caused. In the case where the optical zone of the contact lens has a relatively small diameter DFOZ, on the other hand, the contact lens can be designed such that a tendency of lacking in the shape stability generated in the optical zone can be compensated by the peripheral zone. (5) A contact lens comprising: a central optical zone including a front optical zone and a back optical zone; and a peripheral zone surrounding the optical zone and including a front peripheral zone and a back peripheral zone, wherein the contact lens is provided with a dioptric power P larger than 0 diopters (0 less than P), wherein the front optical zone and the front peripheral zone join together at a front junction, and the back optical zone and the back peripheral zone join together at a back junction that is located outward of the front junction in a diametric direction of the contact lens orthogonal to a center axis of the contact lens, and wherein the contact lens has a central lens thickness TC ranging from 0.03 to 0.50 mm as measured along the center axis thereof, a front junction lens thickness TFJ of not less than 0.05 mm as measured at the front junction, and a back-junction lens thickness TBJ as measured at the back junction, the back-junction lens thickness TBJ is determined depending upon the dioptric power P so as to satisfy a following expression: (a) where the front optical zone has a diameter DFOZ of smaller than 7.0 mm (DFOZ less than 7.0 mm), 1.238xe2x89xa6TBJ/TFJxe2x89xa61.470 (b) where the front optical zone has a diameter DFOZ of not smaller than 7.0 mm (DFOZxe2x89xa77.0 mm), xcexa3(Aixc2x710xe2x88x921xc2x7Pi)xe2x89xa6TBJ/TFJxe2x89xa6xcexa3(Bixc2x710xe2x88x92ixc2x7Pi) where, A0=+1.2066 A1=xe2x88x920.0398 A2=xe2x88x920.1341 A3=+0.0139 B0=+1.4328 B1=xe2x88x920.0516 B2=xe2x88x920.1436 B3=+0.0153 According to this mode of the invention, a so-called xe2x80x9cplus lensxe2x80x9d provided with a positive refractive power larger than 0 diopter can exhibit an excellent shape stability in its entirety, like in the above-indicated mode (1), since the shape stability generated in the optical zone can be recognized and effectively compensated by the shape stability generated in the peripheral zone with the recognized shape stability in the optical zone utilized. In addition, the peripheral zone is shaped so as to meet specific conditions selected based on the dioptric power given to the optical zone, thus making it possible to establish the excellent shape stability of the contact lens, while assuring a sufficient degree of freedom in designing the optical characteristics of the optical zone, and an excellent lens wearing comfort. It should be appreciated that the peripheral zone is shaped with the diameter DFOZ of the front optical zone taken into consideration, like in the above-indicated mode (2), making it possible to suitably arrange the shape stability generated in the peripheral zone depending upon the shape stability generated in the optical zone, permitting the contact lens to exhibit both of the excellent shape stability and lens wearing comfort in its entirety. More specifically described, in the case where the optical zone of the contact lens has a relatively large diameter DFOZ, the thickness of a central portion of the optical zone is inevitably made larger sufficiently, since the positive refractive power given to the optical zone is great. Thus, the contact lens can be designed so as to exhibit its entire shape stability by effectively utilizing the shape stability generated in the optical zone, and so as to establish the excellent lens wearing comfort without needing the excessive increase in the thickness of the peripheral zone, which is likely to be caused. In the case where the optical zone of the contact lens has a relatively small diameter DFOZ, on the other hand, the contact lens can be designed such that a tendency of lacking in the shape stability generated in the optical zone can be compensated by the peripheral zone. (6) A contact lens according to any one of the above indicated modes (1)-(5), wherein at least one of the front junction and the back junction is formed by a connecting surface joined to the optical zone along junctions lying on tangents common to curves of the optical zone and the connecting surface, and to the peripheral zone along junctions lying on tangents common to curves of the peripheral zone and the connecting surface, as seen in diametrical cross section, the connecting surface being a smoothly continuous surface interposed between the optical zone and the peripheral zone and lying on tangents whose slopes are continuously changed over an entire width thereof. According to this mode of the invention, at least one of the front surface and the back surface of the contact lens is arranged such that the optical zone and the peripheral zone can smoothly join together at their junction with the help of the connecting surface interposed therebetween with a given radial width, although the optical zone and the peripheral zone are provided with different shapes in diametrical cross section so as to meet their different optical characteristics, respectively. Thus, the presence of the connecting surface makes it possible to smoothly join the optical zone and the peripheral zone together with no adverse influence on the shape or the optical characteristics of the optical zone and the peripheral zone, thereby effectively eliminating a possible problem of deterioration in lens wearing comfort due to an edge or angle formed at the junction between the optical zone and the peripheral zone on the at least one of the front and back surfaces of the contact lens. The contact lens of the present invention may have the following structure other than the structure defined by the above-indicated mode (6) for a smooth connection between the optical zone and the peripheral zone. In the case where the peripheral zone of the contact lens has a relatively high degree of freedom in its shape design, at least one of the front and back surfaces of the contact lens is arranged such that an inner circumferential edge of the peripheral zone is shaped to have an angle value equal to an angle value of an outer circumferential edge of the optical zone. This arrangement permits at least one of the front and back surfaces of the contact lens that the optical zone and the peripheral zone directly and smoothly join together along junctions lying on tangents common to curves of the optical zone and the peripheral zone. The contact lens constructed as described above can provide a further improved lens wearing comfort as felt by the lens wearer, like in the above-indicated mode (6) of the invention. (7) A contact lens according to any one of the above-indicated modes (1)-(6), wherein the front peripheral zone has a diametrical cross sectional shape represented by at least one of a polynomial of not less than second order, a conic section and a spline curve. According to this mode of the invention, the front peripheral zone can be designed to be a smooth surface with a high degree of freedom. This makes it possible to easily shape the front peripheral zone of the contact lens, for example, such that the front peripheral zone is joined to the front optical zone along junctions lying on tangents common to curves of the front optical zone and the front peripheral zone, and is smoothly joined to an outermost edge of the contact lens, while permitting the contact lens to have a desired lens thickness as measured at the back junction where the back optical zone and the back peripheral zone join together. (8) A contact lens according to any one of the above-indicated modes (1)-(7) wherein the back peripheral zone at least partially has an arcuate shape in diametrical cross section. This arrangement permits a relatively easy designing of the back peripheral zone of the contact lens. Preferably, the back peripheral zone is designed to have a radius of curvature larger than that of the back optical zone. In this respect, the back peripheral zone may consist of at least two parts that have arcuate forms in diametrical cross section with different radius of curvatures, and that join together in the radial direction of the contact lens. In this respect, the radius of curvature of the radially outer one of the two parts of the back peripheral zone is preferably made larger than that of the radially inner one of the two parts of the back peripheral zone. (9) A contact lens according to any one of the above-indicated modes (1)-(8), wherein the contact lens comprises a soft contact lens formed of a soft material. According to this mode of the invention, the principle of the present invention is applied to a soft contact lens, so that the soft contact lens is accurate in its dioptric power, thin enough to assure a high gas permeability, and is able to effectively establish its shape stability that has been widely required. The soft contact lens of this mode of the invention can eliminate the conventionally experienced problem that a soft contact lens, when being placed on a finger of the lens wearer for wearing the contact lens, clings to a surface of the finger of the lens wearer. Therefore, the soft contact lens of this mode of the invention is excellent in its handling and easy to differentiate between the front surface and the back surface of the contact lens. All of the above-described modes (1)-(8) of the invention may be applicable not only to a variety of soft contact lenses of high, medium and low hydrophilic types but to hydrophobic or hard contact lenses as well. These contact lenses according to any one of the above-indicated modes (1)-(8) of the invention can be provided with a relatively small lens thickness, each being satisfactory in its strength and deformation stability in its entirety, whereby these contact lenses can satisfactory provide required optical characteristics and can improve lens wearing comfort and handling, and their overall strength. (10) A method of designing a contact lens including: a central optical zone having a front optical zone and a back optical zone; and a peripheral zone surrounding the optical zone and having a front peripheral zone and a back peripheral zone, the method comprising the steps of: positioning a back junction where the back optical zone and back peripheral zone join together is located radially outward of a front junction where the front optical zone and the front peripheral zone join together; and adjusting a ratio TBJ/TFJ of a back junction lens thickness TBJ to a front junction lens thickness TFJ to be held within a tolerable range predetermined depending upon a dioptric power P provided to the optical zone. This method of designing a contact lens has been accomplished based on the technical concept as described above with respect to a contact lens according to the present invention. Namely, the back junction where the back optical zone and the back peripheral zone join together is located radially outward of the front junction where the front optical zone and the front peripheral zone join together and the lens thickness at the back junction is suitably adjusted, thus making it possible to establish a desirable shape stability of the contact lens with no adverse influence on the optical characteristics of the contact lens. It should be noted that the configuration of the contact lens is determined based on the dioptric power of the optical zone. This makes it possible to compensate the shape stability at the optical zone by enhancing the shape stability at the peripheral zone, when the shape stability of the optical zone is considered to be insufficient. Accordingly, the present method makes it possible to effectively and easily design a desired lens configuration that allows the contact lens to exhibit desired shape stability in its entirety with a relatively small lens thickness, by adjusting a shape stability generated in the peripheral zone depending upon a shape stabilizing effect generated in the optical zone, with required optical characteristics of the optical zone provided highly precisely. That is, the method according to this mode of the invention makes it possible to easily provide a contact lens that is remarkably improved both in its handling and wearing comfort while maintaining its accurate optical characteristics. This method may preferably be usable for designing a variety of soft contact lenses of high, medium and low hydrous types, and for designing hard contact lenses as well, thereby allowing each obtained contact lens to be improved in its wearing comfort and its overall handling and strength, while being satisfactory in its optical characteristics. (11) A method of designing a contact lens according the above-indicated mode (10), further comprising the step of designing a form of the optical zone such that a central lens thickness measured along a center axis of the contact lens is held within a range of 0.03-0.50 mm, more preferably 0.05-0.50 mm, and a peripheral lens thickness measured at the front junction is not less than 0.05 mm, more preferably, 0.10 mm. This method makes it possible to more sufficiently achieve both requirements, i.e., the thinned optical zone and the lens shape stability. (12) A method of designing a contact lens according to the above-indicated mode (10) or (11), wherein when a dioptric power P is held within a range from 0 diopter to xe2x88x926 diopters, the ratio of TBJ/TFJ is adjusted according to a condition expression that a ratio of the back-junction lens thickness TBJ to the front-junction lens thickness TFJ is held within a tolerable range of not less than 1. As discussed above with respect to the above-indicated mode (2), when the contact lens has a dioptric power ranging from 0 diopter to xe2x88x926 diopters, the optical zone is likely to be insufficient in its shape stabilizing effect so as to be suitably designed in its shape and thickness. This insufficient shape stability generated in the optical zone can be compensated with the shape stability generated in the peripheral zone. Thus, the present method easily permits a design of the contact lens that is excellent in handling with the help of the excellent shape stability in its entirety, while highly ensuring desired optical characteristics of the optical zone and a lens wearing comfort with the help of a relatively thin lens thickness. (13) A method of designing a contact lens according to any one of the above indicted modes (10)-(12), wherein the tolerable range of the ratio TBJ/TFJ of the back-junction lens thickness TBJ to the front-junction lens thickness TFJ comprises options represented by the expressions with respect to the ratio TBJ/TFJ recited in the above indicated modes (1),(3) and (4), selectable depending upon the dioptric power P given to the optical zone and the diameter DFOZ of the optical zone. The present method of this mode of the invention makes it possible to design and provide contact lenses constructed according to the present invention and capable of exhibiting a variety of excellent technical effects or advantages of the invention. The contact lens designed according to any one of the above-indicated method of the invention, may be manufactured according to any known methods of producing contact lenses, which may be selected with a material and a dioptric power of the lens taken into consideration. For instance, the contact of the present invention may be formed of polymer by cutting and polishing, or alternatively may be manufactured by injecting and polymerizing a monomer composition in a mold having a mold cavity whose form corresponds to a desired form of the contact lens. Also, the contact lens of the invention may be manufactured by forming one of opposite surfaces thereof upon polymerizing a material in a suitable mold cavity and by cutting and polishing the other surface thereof. Further, the contact lens of the invention may be formed by spin casting wherein a monomer composition is injected into a rotatable mold and shaped by utilizing an effect of a centrifugal force.
IN THE COURT OF CRIMINAL APPEALS OF TEXAS NO. 2189-01 HAROLD WAYNE BAILEY, Appellant v. THE STATE OF TEXAS ON APPELLANT'S PETITION FOR DISCRETIONARY REVIEW FROM THE FOURTEENTH COURT OF APPEALS HARRIS COUNTY Keasler, J., filed this dissenting opinion. DISSENTING OPINION The Court concludes that Bailey's judgment was not complete until the March 12th hearing and, therefore, that this case is not controlled by Basaldua v. State. (1) I disagree. Facts The record includes a judgment which convicts Bailey of failure to stop and render assistance and sentences him to five years in prison, probated for 10 years. The judgment is signed by the judge and dated February 12, 2001. Attached to the judgment is a document entitled "Conditions of Community Supervision," setting out 24 conditions. None of these conditions provide for restitution. This document is also signed by the judge and dated February 12, 2001. The next document in the record is entitled "Conditions of Community Supervision 1st Amended." Condition 12 requires Bailey to make restitution. This document is signed by the judge and dated March 12, 2001. The docket sheet indicates that on February 12, 2001, Bailey "pleaded guilty," that the court "found the defendant guilty" and "assessed the punishment," and that imposition "of sentence [was] suspended and [the] Defendant [was] placed on Probation for . . . 10 years." The docket sheet reflects the case was "r/s," which presumably means "reset," for "3/12/01, Restitution Hearing." The next entry is partially illegible due to a copying error. What is legible reflects that on some date (presumably March 12, 2001), there was a hearing with testimony and argument, and the court ordered Bailey to pay restitution. It also states that Bailey, through his attorney, gave notice of appeal at that time. In Bailey's notice of appeal, he sought to appeal "the judgment and sentence in the above cause, in addition to the Court's appealable orders concerning restitution and probationary conditions." Analysis In Basaldua, the defendant was placed on probation in July of 1975. In November, the defendant filed a motion to modify the probation conditions which the trial court denied. The defendant appealed that ruling. We held that no appeal was allowed from the trial court's order. (2) We explained that we could find "neither constitutional nor statutory authority which would confer jurisdiction on this court to hear an appeal from an order. . . altering or modifying probationary conditions or an order, as in the instant case, refusing to alter or modify such conditions." (3) We then proceeded to hear the defendant's complaint, at his request, pursuant to our original habeas jurisdiction. (4) The facts of Basaldua are nearly identical to those in this case. The only distinguishing factor is that in this case Bailey appeals the judge's order modifying his probation conditions, while in Basaldua the defendant appealed the judge's ruling denying a motion to modify a probation condition. Nevertheless, this distinction is meaningless because both appeals are impermissible for the same reason, as we explained in Basaldua - there is no authority for appealing either an order modifying probation conditions or an order refusing to do so. The majority finds Basaldua distinguishable because, according to the majority, the instant case does not involve a modification of probation. Instead, the majority contends, in this case the judgment was incomplete until the March 12th hearing. It bases this conclusion on its belief that a judgment is incomplete until restitution is ordered. This holding raises significant problems. First, the majority's authority for this conclusion is weak. It relies on Art. 42.037(e), which states that "[t]he imposition of the [restitution] order may not unduly complicate or prolong the sentencing process." The Court says that this statement "essentially" includes restitution within sentencing and therefore "implies" that "restitution is imposed as part of the original sentence, and that the sentence is not complete until restitution is imposed." (5) That is quite a leap. Nothing in the text of the statute states that a judgment is "incomplete" until restitution is ordered. Instead, the statute seems to acknowledge that as a general rule, restitution will be part of the sentencing process. The statute does not foresee a case in which the restitution order is not entered until a later date. The Court also relies on Art. 42.01, § 1(25), which says that the judgment "should" reflect the amount of restitution. But saying that the judgment should reflect that amount does not mean that this judgment did so. Regardless of the mandates of Art. 42.01, Bailey's February 12th judgment did not contain restitution. Nothing in Art. 42.01 states that a judgment is incomplete until restitution is ordered. Finally, the majority relies on Arguijo v. State. (6) Of course, Arguijo is distinguishable because in that case, the judge failed to enter any conditions of probation at the time the defendant was placed on probation. The court of appeals held that the judgment was not complete until the later hearing when all the probation conditions were entered. (7) This case is different because here, the trial court did impose conditions of probation - 24 of them -- at the first hearing. The only thing the judge added at the later hearing was the restitution. This was an amendment of the previously ordered probation conditions. The judge could have, and possibly even should have, waited until the March 12th hearing to enter the judgment against Bailey, but she did not do so. Instead, she entered a judgment of conviction on February 12th and set forth probation conditions. Later, she entered a "1st Amended" list of probation conditions. The very fact that the judge titled the list "1st Amended" demonstrates the parties' understanding that the judgment was complete on February 12th but was amended on March 12th. If the judgment were incomplete on February 12th, there would have been nothing to "amend" on March 12th. And since the March 12th order "amended" the previous judgment, this case falls directly under the ambit of Basaldua, which prevents an appeal from such an order. Indeed, even Bailey himself recognized this in his notice of appeal. He specifically sought to appeal the judgment "in addition to the court's appealable order[] concerning restitution." If the judgment were incomplete until March 12th, there would be no need to appeal both the restitution order and the judgment - an appeal of simply the judgment would have been sufficient. Finally, under the Court's rationale, anytime a judgment omits one of the requirements of Art. 42.01, it is incomplete. And since Art. 42.01, § 1 (10), requires the judgment to set forth the conditions of probation, anytime a judge amends conditions of probation after sentencing, the judgment will be entered anew at that time. So no judgment is ever really complete, because we never know when a trial judge may amend the conditions of probation. This will wreak havoc on the law. Perhaps most troubling about the Court's opinion is that it is so unnecessary. The Court seems worried that Bailey will have no recourse if we do not allow his appeal, but this is just not true. His remedy is to file an application for a writ of habeas corpus attacking the probation condition. (8) The remedy is most certainly not to create a body of law unsupported by statute or case law, as the majority has done in this case. I dissent. DATE FILED: March 24, 2004 PUBLISH 1. 558 S.W.2d 2 (Tex. Crim. App. 1977). 2. Id. at 5. 3. Ibid. 4. Id. at 5-7. 5. Ante, slip op. at 9. 6. 738 S.W.2d 367 (Tex. App. - Corpus Christi 1987, no pet.). 7. Id. at 369. 8. See Ex parte Alakayi, 102 S.W.3d 426 (Tex. App. - Houston [14th Dist.] 2003, no pet.); Ex parte Renfro, 999 S.W.2d 557 (Tex. App. - Houston [14th Dist.] 1999, pet. ref'd).
Comparative enantiocontrol with allyl phenyldiazoacetates in asymmetric catalytic intramolecular cyclopropanation. Dirhodium(II) azetidinone-carboxylates are effective asymmetric catalysts for diazo decomposition of allyl diazoacetates and their subsequent intramolecular cyclopropanations. The effect of alkene substituents on enantiocontrol has been examined and modest selectivities have been achieved. Steric influences from substituents on the diazo carbon are seen to diminish enantioselectivities.
Q: Multiple Parameters in URL I have a search form with multiple search filters. I followed the tutorial example https://dev.to/gaels/an-alternative-to-handle-global-state-in-react-the-url--3753 It works fine with one search filter, input textbox or checkbox. But now both. The URL looks like this https://apiurl/?keyword=xxx&checkbox= OR https://apiurl/?keyword=&checkbox=item1. I have no idea how to update both parameter state. Any suggestion? Should I use query parameter object like state={ query:{keyword:'', checkbox:[]}} or just state={keyword:'', checkbox:[]} and how to update URL for multiple parameters? Thanks. A: function getParams(location) { const searchParams = new URLSearchParams(location.search); return { keyword: searchParams.get('keyword') \|\| '', checkbox: searchParams.get('checkbox') \|\| '', }; } function setParams({keyword = "", checkbox = ""}) { const searchParams = new URLSearchParams(); searchParams.set("keyword", keyword); searchParams.set("checkbox", checkbox ); return searchParams.toString(); } state = { keywordValue: "", checkboxValue: "" }; updateKeywordValue = e => this.setState({ keywordValue: e.target.value }); updateCheckboxValue = e => this.setState({ updateCheckboxValue : e.target.value }); use these functions instead of updateInputValue and then create another function, which is triggered on click of a button, that calls the setParams function. Now calling this.props.history.push(?`${url}\`); will push the values to both the query params to get the params, you have to do const {keyword, checkbox} = getParams(location);
The redshirt sophomore has really come on this season since Montee Ball's departure. Gordon has rushed for 1,466 yards on just 181 carries, good for an outstanding 8.1 YPC and 12 touchdowns. Gordon’s draft profile is intriguing based on several factors. For one, Gordon hails from “Offensive Line University” where pro-caliber offensive linemen seem to grow on trees. This has hurt the image of Wisconsin running backs in terms of their pro potential due to coming from such a great system. Current Denver Broncos rookie running back Montee Ball – a former Badger – has done an admirable job in spot-duty so far this season and can help buck this trend if his production continues to rise. Ball was a second-round pick last year and Gordon has more physical talent. If Gordon can prove that his estimated 4.4 speed is legit at the NFL Combine, the end of the second-round should serve as the worst-case scenario for his draft position. Another compelling aspect of Gordon’s draft profile is the fact that Wisconsin has two dynamic ball-carriers; James White and Gordon. This has enabled Gordon to be stashed away like grain for the winter, leaving him with a lot of tread left on his tires. NFL teams take notice of how many hits running backs are exposed to more than any other position and Gordon hasn’t taken very many. Gordon possesses the best size/speed combination out of any running back in this year’s draft (assuming Gordon declares). There have been recent rumors that Gordon will stay in school for a chance at the Heisman Trophy next season – a distinct possibility – but if he chooses to leave, Gordon should be the first running back taken. Lache Seastrunk/RS Junior – 5'10", 210 pounds - Baylor The former Oregon Duck who transferred to Baylor in 2011 has lit up the Big-12 this season. Owning a staggering 7.8 YPC average on the season (to go along with 982 yards and 11 touchdowns) is telling in regards to the sort of big-play ability Seastrunk possesses. With a compact frame to go along with incredible agility and quickness, scouts have fallen in love with Seastrunk’s potential as a dynamic offensive piece on the pro level. The one area of concern for Seastrunk is in his pass-blocking abilities, or lack thereof. Because Seastrunk plays in the system he plays in – one where the offense throws around 35-40 times a game – this aspect of his game has been put on full-display and the results haven’t been up to par. The NFL is a league of details, especially for the running back. Pass-blocking is one of those overlooked aspects of earning playing time on a pro field, and is one of the skills Seastrunk hasn’t developed enough yet. In the grand scheme of his skill-set, this isn’t a major weakness, but it is the biggest concern with regards to his draft status. It should be noted that Seastrunk has zero catches on the season and while the running backs don’t get targeted much in Baylor’s offense, the stat is still somewhat disconcerting. Overall, Seastrunk’s big-play ability and freakish athleticism put him in serious consideration for the first running back taken in the 2014 NFL Draft. Ka’Deem Carey/Junior – 5'10", 196 pounds – Arizona Carey has had an extremely productive and underrated career for the Wildcats but is widely regarded as the most NFL-ready tailback in the nation. The junior is the school’s all-time leader in virtually every single-season and career rushing record as well as the Pac-12 all-time leader in others. As a sophomore in 2012, Carey was a first-team All-American while rushing for 1,929 yards and 6.4 yards per carry average (YPC), to go along with 23 touchdowns. Carey had some monster games last year but none more so than a game against Colorado in which he became the Pac-12’s all-time leader for rushing yards in a single game with 25 rushes, 366 yards, 14.6 YPC, and 5 TDs. Carey has carried over that incredible production into this season in which he has accounted for 1,716 yards, 5.3 YPC, and 17 touchdowns. Carey has rushed 100+ yards in 15 straight games, a Pac-12 record. Most impressively was when Arizona took on No. 5 Oregon and Carey carried them to a victory with an epic 48-carry, 206-yard, 4-TD masterpiece, demonstrating the ability to gain tough yards despite his size. At 5'10", 196 pounds, Carey possesses adequate enough size but plays with a ton of heart and is one of the most challenging backs in the nation to bring down with just one defender. Carey is constantly breaking tackles and runs like a player who is much more physically-imposing. Possessing great leg-drive and excellent durability, Carey is a relentless runner who also displays patience to let plays develop. This combination is extremely rare and invokes first-round credentials. The one area that remains a question-mark for Carey is his straight-line, breakaway speed. Once the NFL Combine rolls around and the running backs run their 40-yard dash, no runner will have more on the line than Carey. If he can run under a 4.6 that should be good enough to solidify his place with the top dogs of this year’s class come draft time. Bishop Sankey/Junior – 5'10", 200 pounds – Washington No running back on this list has had a more productive season than Sankey who broke Corey Dillon’s school-record for most rushing yards in a season (1,695) with 1,775. Sankey also has 18 rushing touchdowns, giving him 35 for his career, also a school-record. Sankey’s size enables him to maintain excellent leverage which combined with his aggressive running style and excellent lateral movement skills, makes him a legit workhorse runner. These skills plus his underrated catching ability (58 catches, 547 yards over the last two seasons) translate very well to the pro-level. The most underrated skill that Sankey has is his vision and endurance. This makes the best fit for him in a zone-blocking scheme, a scheme that would utilize his patience as a runner to a tee, enabling Sankey to have a very long and very productive pro career. Charles Sims/Senior – 6', 213 pounds – West Virginia Not only the darkhorse of the group, Sims is also the best all-around running back on this list mostly due to his excellent pass-catching ability. Sims transferred from the University of Houston this past season so his polished skills could be put on further display in West Virginia’s spread system. Sims hasn’t disappointed and has rushed 208 times, 1,095 yards, 5.3 YPC, 11 touchdowns to go along with 45 receptions, 401 yards, and 3 TDs. Sims is a real weapon out of the backfield who has been overlooked the entire season due to West Virginia’s disappointing 4-8 record. With his size/speed combo (with an estimated 4.45 40-yard dash) and excellent hands, scouts have already compared him to Bears RB Matt Forte because of his versatility and size. The do-it-all back will be in contention for the first running back taken and as the off-season draft preparations progress, could separate himself from the pack entirely.
A Guelph woman alleged she was discriminated against on the basis of disability and age Deputy CAO Colleen Clack says the city will immediately implement orders made against it during a recent Human Rights Tribunal of Ontario decision. The City of Guelph was found to have contravened the terms of settlement of a 2015 Human Rights Tribunal of Ontario application after Guelphite Eileen LaBerge alleged the city discriminated against her on the basis or disability and age through incidents which occurred on Guelph Transit buses. The main complaint, said adjudicator Dawn J. Kershaw in the Oct. 31 decision, was that LaBerge said she had altercations with other passenger on Guelph Transit buses because they wanted her to move out of the priority seating she requires so they could sit there with their strollers. LaBerge, who identifies as being disabled, said people continue to harass her on city buses while she is seated in the priority section. “(LeBerge) states that the tribunal should tell the respondent not to aid and abet criminal behaviour,” said Kershaw. On July 22, 2015, the City and LaBerge entered into a Minutes of Settlement (MOS) in relation to the allegations, after which the city was to install revised signage on all of its conventional buses, conduct a public awareness campaign relating to priority seating and complete refresher training for all 150 of its bus operators. The city admitted the revised signage had not been installed by the end of 2015, as required by the MOS, but was complete by the time of the Aug. 17, 2017 hearing. Kershaw said it was clear the City did not fulfill this term of the MOS. The refresher training for bus operators was to be carried out by March of 2016, but in LaBerge’s view it had not occurred people would not have continued to harass her on City buses while she was seated in priority seating, said Kershaw. A new module called May I Help You? has been added to the Accessibility for Ontarians with Disabilities Act (AODA) training, in which operators are trained they can not always tell if a person has a disability and to not ask questions. Organizational-wide changes within Guelph Transit prevented the completion of the refresher training before the deadline. As a result of Kershaw’s findings, the city is ordered to train the remaining bus operators within six months of their returning to work and to remind all bus operators within 10 days of the order to implement the terms of the training they received with respect to educating other passengers who take exception with a person sitting in priority seating that not all disabilities are visible ones. The city complied with the public awareness component of the MOS, Kershaw said. LaBerge did not ask for, nor did she receive any financial compensation for the complaint and Kershaw said the HRTO does not have the power to order the city to cease, in LaBerge's words, aiding and abetting criminal behaviour. In an email sent to GuelphToday on Tuesday, Deputy CAO Colleen Clack said the city will ‘immediately implement’ the orders in the Oct. 31 HRTO decision.
1. Field of the Invention One or more embodiments relate to sulfonated poly(arylene sulfone), a cross-linked material thereof, a clay nanocomposite including the same, and a fuel cell including the same. 2. Description of the Related Art Fuel cells may be classified according to the kind of electrolyte used. For example, fuel cells may be classified as polymer electrolyte membrane fuel cells (PEMFCs), phosphoric acid fuel cells, molten carbonate electrolyte fuel cells, and solid oxide fuel cells. A PEMFC includes an anode, a cathode, and a polymer electrolyte membrane disposed therebetween. The anode includes a catalyst layer that promotes oxidation of a fuel, and the cathode includes a catalyst layer that promotes reduction of an oxidizer. The polymer electrolyte membrane of the PEMFC functions not only as an ion conductor for the movement of protons from the anode towards the cathode, but also as a separation layer preventing mechanical contact between the anode and the cathode. Thus, it is desirable for the polymer electrolyte membrane to have excellent ion conductance, electrochemical stability, high mechanical strength, high heat resistance, and film formation properties. As disclosed in Japanese Patent Laid-Open Publication No. 9-245818, an example of a material used to form a polymer electrolyte membrane is sulfonated polysulfone. However, the mechanical strength of this material is typically less than desired for functioning as a polymer electrolyte membrane.
All morning, my Facebook feed has been inundated with links to a disturbing new infographic about the toxic ingredients in our personal care products. Lead. Aluminum. Heavy metals. In baby shampoo. FACT: Adults are exposed to an average 126 chemical ingredients daily through the use of personal care products. 61% of top-brand lipsticks contain cancer-causing heavy metals, 82% of children’s shampoos contain formaldehyde, and 89% of ingredients in products currently sold on the market have never been tested for safety. Surprised? Not me. I stumbled into this information on the web a couple years ago, on a blog called No More Dirty Looks. I was so aghast at the findings of those clinical studies when I read them that I tossed out every make-up product I owned. I wondered why it wasn’t being talked about on Good Morning America, in the New York Times, on Capitol Hill for heaven’s sake. I thought of all the women in my family who had died of cancer. I felt betrayed. Why hadn’t I been told? As a woman, I feel like I’ve been taught my entire life that first appearances are everything: You have to wear mascara to be professional, lip gloss to make you feel sexy, a mask on your face to be beautiful. I remember as a young child sitting inside my mother’s bathroom sink, watching her apply thick black coats of paint to her long lashes. “Whatcha doing, momma?” She smiled. “Putting on my face.” This issue isn’t just relevant to women, either. If you wear deodorant, use shaving cream, wash you hands with soap… sorry guys, it effects you too. Without regulation, companies can to some extent put whatever cheap, nasty preservatives into personal care products they want (the FDA requires testing on the products, not ingredients). This especially important for parents to know, as the developing bodies of children are even more susceptible to the negative effects of ingesting these toxins. The first step in making any significant personal or societal change, in my opinion, is awareness. Become aware of your own beliefs about beauty, about the ingredients in products you purchase, about the ways companies treat the workers they employ. And then take action, choose a path that will bestow greater health and wellbeing to yourself (first) and the community at large. Maybe that means purchasing organic, fair-trade personal care products. Maybe it means reducing the number of products you use to a bare (pun intended) minimum. I’m struck by the fact that this topic is very much a 1st world issue. What a luxury it is that we even be outraged about the toxic ingredients in our personal care products, that we can afford to lather body creams and eye shadows on our skin to begin with. Perhaps this is an opportunity for us to acknowledge that and consider how the development of the products impact people who aren’t so lucky. It’s not just what’s in those products that matters. I’m more concerned with how they’re produced (forced labor, toxic work environments, etc) and the cultural conditioning that tells us they’re necessary to begin with. I began this blog with a fact, I leave you with a suggestion for action. I would love to hear your thoughts in the comments. ACTION: Read through the infographic below, then check out Skin Deep, a website that provides safety ratings for 63,509 products on the market. Know what’s in the products you’re using, then let your dollars be your vote. Thanks to Mind Body Green & Dr. Frank Lipman for sharing this informative infographic from cosmetologyschool.org
Victoria police are asking for help locating a missing 13-year-old girl, Bailey Smith, who has last seen in the 900 block of Kings Road Thursday night. Missing Victoria teen Bailey Smith was last seen on Thursday, July 21, 2016. (Victoria Police Department) "Bailey is described as a young Caucasian female with a slim build, weighing about 110 pounds and standing about five feet, two inches tall," said a release from the Victoria Police Department on Saturday. Smith has blue eyes and brown hair, with auburn highlights. She was last seen wearing a red baseball cap, black leggings and black Nike suede shoes with a distinctive white "swoosh". Bailey may also be wearing a pair of white Puma runners. Police say a friend had lent her a dark, charcoal grey hoodie to wear as she did not have a jacket of her own at the time. Police say missing Victoria teen Bailey Smith recently added auburn highlights to her brown hair. (Victoria Police Department)
Abstract OBJECTIVE—We investigated the impact of active smoking and exposure to passive smoke on the risk of developing diabetes. RESEARCH DESIGN AND METHODS—Data were analyzed from a cohort of participants in the High-Risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP) conducted in Japan from 1999 to 2004. Active and passive smoking status in the workplace was evaluated at baseline. RESULTS—Of 6,498 participants (20.9% women), a total of 229 diabetes cases were reported over a median 3.4 years of follow-up. In the workplace, compared with zero-exposure subjects, the multivariable-adjusted hazard ratios of developing diabetes were 1.81 (95% CI 1.06–3.08, P = 0.028) for present passive subjects and 1.99 (1.29–3.04, P = 0.002) for present active smokers. CONCLUSIONS—In this cohort, exposure to passive smoke in the workplace was associated with an increased risk of diabetes after adjustment for a large number of possible confounders. A positive association between active smoking and the incidence of diabetes has been identified (1–3). Only one study has shown a significant association between passive smoke and impaired glucose tolerance (4), and the association between exposure to passive smoke and the risk of developing diabetes has not been fully investigated. Here, we examine the relationship between exposure to passive smoke in the workplace or at home and the risk of developing diabetes in a large sample from a nonrandomized health promotion intervention study conducted at workplaces in Japan. RESEARCH DESIGN AND METHODS Analyses were performed using baseline and annual follow-up data from the High-Risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP) conducted between 1999 and 2004 at 12 large-scale companies, excluding prevalent diabetes cases or those who did not report active or passive smoking status at baseline. Full-time employees at the worksites were enrolled, and then the worksites were nonrandomly assigned to either the intervention or control groups (13–20). All participants underwent an annual health check including blood testing at baseline and thereafter. A history of diabetes as well as lifestyle variables such as daily alcohol intake and smoking habits were evaluated using a self-administered questionnaire (5–7). We constructed the following four categories by combining active smoking status and passive smoking status at workplace or at home as follows: 1) “zero exposure” included those who never smoked and were not currently exposed to passive smoke; 2) “past active only” included those who had smoked in the past but did not currently smoke and were not currently exposed to passive smoke; 3) “present passive” included those currently exposed to passive smoke but who did not actively smoke, irrespective of past smoking; and 4) “present active” included those who currently smoke irrespective of exposure to passive smoke. A subject was considered diabetic if at least one of the following parameters was met: fasting blood glucose level ≥126 mg/dl (≥7.0 mmol/l), random plasma glucose level ≤200 mg/dl (≥11.1 mmol/l), or treatment with hypoglycemic medication (insulin or oral hypoglycemic agent). A self-reported history of diabetes was also accepted, since self-reported diagnosis of diabetes has been shown to be reliable (8) and has been used in many cohort studies (9,10). Statistical analyses We used the Cox proportional hazards model to analyze the association between passive smoking and incident diabetes cases. Person-time was calculated from the return of the baseline questionnaire until the date of the annual health check, at which the diagnosis of diabetes was confirmed, or the end of the follow-up, whichever occurred first. We evaluated the effect of active smoking and exposure to passive smoke on the risk of developing diabetes in a multivariable-adjusted model, adjusting for all variables listed in Table 1. Likelihood ratio tests were used to test statistical interactions between passive smoking status and sex, BMI, or assigned intervention. RESULTS Of the 6,498 participants (20.9% women), 44.6% were current smokers (average of 19.6 cigarettes smoked per day), while 12.6% reported exposure to passive smoke in the workplace. Approximately 32% of participants dropped out during the follow-up. CONCLUSIONS— In this 4-year prospective study conducted in the workplace, self-reported exposure to environmental tobacco smoke in the workplace and current active smoking at baseline were positively associated with an increased risk of developing diabetes, even after adjustment for a large number of possible confounders. To our knowledge, only one study has explored the association between exposure to passive smoke and subsequent risk of diabetes, which yielded similar results to our study, although not statistically significant (4). A possible limitation of our study is that the results might be underestimated by time-dependent confounding by smoking status; in fact, exposure to passive smoke in the workplace was not associated with the risk of diabetes in the intervention group, possibly due to lowered exposure to passive smoke by intervention. These findings add new evidence to support the need for measures to lessen environmental tobacco smoke in the workplace, especially in Asian populations, in which both the genetic susceptibility to diabetes (11,12) and smoking rate (13) are generally high. Acknowledgments The HIPOP-OHP study was funded by research grants from the Ministry of Health and Welfare, Japan (H10-12, no. 063, Research on Health Services, Health Sciences Research Grant; and H13, no. 010, Medical Frontier Strategy Research, Health Sciences Research Grant), the Ministry of Health, Labor and Welfare, Japan (H14-16, no. 010, Clinical Research for Evidenced-Based Medicine, Health and Labor Sciences Research Grant), and the Japan Arteriosclerosis Prevention Fund 2000 and 2004. We thank Toshimi Yoshida, Department of Health Sciences, Shiga University of Medical Science, for excellent clerical support in this research. Footnotes ↵* A complete list of the members of the HIPOP-OHP Research Group can be found in the appendix. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
This invention relates to an improvement in a dual spark plug internal combustion engine having two spark plugs in each combustion chamber thereof, which is provided with an EGR (Exhaust Gas Recirculation) system for recirculating a considerably large amount of exhaust gases back to the combustion chamber. In connection with the control of nitrogen oxides (NOx) formed in automotive internal combustion engines, a dual spark plug internal combustion engine provided with an EGR system has been proposed as disclosed in the pending application of Yasuo Nakajima et al., U.S. Pat. Ser. No. 815,449, filed on July 13, 1977 and entitled "Multiple Spark Ignition Internal Combustion Engine with Exhaust Gas Recirculation", now abandoned. In such an engine, two spark plugs are located relatively separate from each other in each combustion chamber. They ignite the air-fuel mixture which is mixed with exhaust gases recirculated back into the engine intake air at a relatively high EGR rate (the volume rate of recirculated exhaust gases relative to engine intake air), for example, about 30%. By virtue of the dual spark plug ignition, fast burn is achieved in the combustion chamber even though the air-fuel mixture is mixed with a considerably large amount of inert exhaust gases. NOx formation is greatly lowered without degradation of engine stability, resulting in an improvement in the driveability of a motor vehicle on which the engine is mounted. The engine of this type requires operation on a single spark plug ignition in which one of the two spark plugs in each combustion chamber is put into inoperative condition during high power output engine operating condition. If dual spark plug ignition is continued during high power output engine operation, combustion pressure in the combustion chamber is excessively raised, shortening the life of the engine and increasing engine noise. This excessive rise in combustion pressure results from improved combustion in the combustion chamber, which is caused by the fact that charging efficiency of the engine is improved and EGR rate is decreased to a great extent from view points of engine power output and fuel economy during high power output engine operation. In view of the above, it has also been proposed, as disclosed in the pending application of Shigeo Muranaka et al, U.S. Pat. Ser. No. 787,211, filed on Apr. 13, 1977 and entitled "Improved Dual Spark Plug Ignition Engine", now U.S. Pat. No. 4,144,860, that one of two spark plugs in each combustion chamber is rendered inoperative upon sensing a low intake vacuum which represents the high power output engine operation. However, such an engine has encountered the problem in which dual spark plug ignition is not operable during engine starting even though dual spark plug ignition is necessary for effectively initiating ignition of the air-fuel mixture. This results from the fact that the intake vacuum is very low or close to atmospheric pressure because of very low engine speed during cranking by the starting motor.
Baby Polar Bear Found Wandering 450 Miles South Of Arctic Baby Polar Bear Found Wandering 450 Miles South Of Arctic This adorable little floofer with a dangerous case of wanderlust has been found roaming nearly 450 miles south of her natural habitat in the Arctic. A polar bear, believed to be just nine months old, has travelled a remarkable 700 kilometres south of the icy tundra and taken up residence in the autumnal wilds by the Kolyma River in north-eastern Siberia. Locals named her Umka, after feeding her from their throwaway fishing hauls, and the cub has befriended both the people and their pooches. The things she must have seen! Ministry of Nature Protection of Yakutia Although the Kolyma region has a subarctic climate with very cold winters lasting up to six months of the year, covered in permafrost, the little polar bear looks more than a little lost amid the green and brown lush foliage. Experts presume she lost her mother for unknown reasons but are genuinely puzzled how she came to be so far away from her natural territory. It is not clear whether her wandering have any relation to the ongoing destruction of the polar ice caps at the hands of climate change and global warming. Ministry of Nature Protection of Yakutia Umka, who will now probably be renamed, is too young to be released alone into the wild and has had too much contact with the indigenous people to survive on her own. Yet this only adds to the mystery of how she came this far south. One theory is that her mother was killed by poachers and they took the orphaned cub live with them south from the Arctic coast, releasing her when she got too large. But there is no evidence for the fate of the mother. Now a rescue mission is underway to ensure the cub’s safety, so far away from home. Ministry of Nature Protection of Yakutia The rescue team was led by the head of the Central Kolyma Inspectorate for Nature Protection, Ivan Belonogov, who said she would now go to Yakutsk zoo Orto Doidu. The cub is not afraid of people, since the fishermen who found the bear fed her with fish. For now the condition of the cub is satisfactory, her appetite is good. Ministry of Nature Protection of Yakutia The cub has to be tranquillised and transported in a crate via river to nearby Srednekolymsk, and will sadly be taken into captivity for her own safety; an unfortunate but necessary solution. The little lost cub has since proved quite a hit online, with many admiring her intrepid nature, and her cute little nose, and musing over the mystery of how she managed to travel 700 kilometres alone. During the Pleistocene era, the ecology of the Kolyma region was quite different to its modern environment, with the extinct wooly mammoth and the wooly rhinoceros present. Interestingly, the polar bear most likely evolved here. Maybe she was just heading back to her roots on a early-life gap year adventure to try and find herself.
Q: Displaying a content managed image in a Umbraco 6 MVC website I'm working on my first Umbraco 6 MVC website, its just took me about an hour to work out how to display a content managed image in a razor view. It cant be that hard, I must be missing something... This is what I ended up with... @inherits Umbraco.Web.Mvc.UmbracoTemplatePage @{ Layout = null; } <!Doctype HTML> <html> <head> <title>blah</title> </head> <body> <header> <img src="@Umbraco.TypedMedia(Int32.Parse(Model.Content.GetPropertyValue("siteLogo").ToString())).GetPropertyValue("umbracoFile")"/> </header> </body> </html> ... which seems overly complicated to just display an image? Surely this cant be best practice using razor? A: Two things here: You don't need to cast the property value to an Int32, as TypeMedia() accepts a string or object id parameter. You can use the Url property of the IPublishedContent instead of GetPropertyValue("umbracoFile") So it becomes: <img src="@Umbraco.TypedMedia(Model.Content.GetPropertyValue("siteLogo")).Url"/> Which is much nicer isn't it? There are obviously many ways to shortne this, extension methods but one that a friend showed me recently was uMapper which allows you to create strongly typed objects corresponding to your document types, working much like AutoMapper. For a little leg work up front, your code can become much more understandable and concise.
Dumbo (2019) type Movie genre Family Dumbo is back and flying high in the first trailer for Tim Burton’s live-action re-imagining of Disney’s 1941 animated movie, in a tale of family, loss, a struggling circus, and an oddly unique baby elephant that brings hope and inspiration to those he meets. The film stars Colin Farrell as Holt Farrier, a former horse showman who returns from the war a widower to his two children and a circus struggling to survive. The circus’ owner, Max Medici (Danny DeVito), buys a pregnant elephant, and thus Dumbo enters their lives and “awakens everybody to their better selves,” Farrell told EW. The first look at the film shows Holt and his two children Milly (Nico Parker) and Joe (Finley Hobbins) meet Dumbo, Colette swinging across the circus arena, a glimpse of a pink elephant bubble (taken from the animated film’s famous pink elephant dream sequence) and finally, Dumbo soaring through the circus crowd. The trailer is accompanied by a new rendition of the classic film’s Oscar-nominated song Baby Mine, sung by Norwegian singer-songwriter Aurora. From Edward Scissorhands to Alice in Wonderland, Burton is known for constructing lavish, whimsical worlds, and with Dumbo he delivered some vast, intricately designed, meticulous sets that Michael Keaton — who reunites with his Batman Returns (1992) collaborators Burton and DeVito on Dumbo — said left him almost speechless. “The physical space was so enormous, it’s the largest set I’ve ever been on in my life,” he said. “Literally, a chill went up the back of my neck.” Keaton, who plays V.A. Vandevere, the owner of a successful attraction called Dreamland whose attention is piqued by the news of a flying elephant, said he enjoyed playing the antagonist in a story that’s ultimately about love and acceptance. Dumbo’s story has transcended generations because, Keaton said, “there’s a real elemental thing about family and what it means, and what it means to be a part of something.” “My sense is we’re on the cusp… of a re-emergence of consideration,” Keaton said. “People are worn out, not just by cruelty, but judgment and discrimination and inequality.” Dumbo will fly into theaters in March 2019. See the first trailer above.
“Captain Marvel” Has $455M Global Debut Attempts to sink the launch of Marvel Studios’ “Captain Marvel” appeared to have had no impact – the film beat expectations to deliver a massive box office weekend. The film had become something of a lightning rod for online vitriol following some out of context quotes by star Brie Larson about wanting more diversity amongst film critics, said quotes fuelled the flames of a “Captain Marvel has an anti-white male agenda” screed flooding message boards and preview/review sites. It got bad enough that “Star Wars: The Last Jedi” filmmaker Rian Johnson joked that attempts by ‘review bombers’ to drop the Rotten Tomatoes Audience Score could well be considered the new “Certified Fresh”. When actual critics reviews came out they were pretty damn good, not great but solid enough and now the film’s box-office numbers are in with the movie pulling in an estimated $153 million domestically, a number that could rise to $157 million after official stats are released. That’s the seventh best debut for a Marvel Studios film, and the third for a March release. On top of that, the film generated a further $302 million overseas including a strong $89.3 million from China. Its overall global haul of $455 worldwide is the second best superhero debut of all time (behind only “Avengers: Infinity War” with $630 million), the sixth highest opening weekend of all time and the biggest worldwide box office debut record for a female-led film. It almost certainly guarantees the film will break the $1 billion mark. With no other wide releases in the United States, understandably the rest of the box-office dropped by around 50% aside from doco “Apollo 11” which held strong with only a 19% fall. In limited release, the Julianne Moore-led “Gloria Bell’ opened on five screens to a per-theater-average of $30,955. As for the online backlash? As a recent article by AV Club sums up the problem and paints the fact this sort of thing is unlikely to go away anytime soon. Also “Fantastic Four” reboot director Josh Trank had the best response someone who said this morning that “No superhero movie fails” to which he replied: “Hold my beer.”
Q: How to form a given list of elements in python to create another set of lists from it? List1 =['000095', '000094', '000092', '000101', '000099', '000096', '000095'] def makecycle(list, startElement): A loop which forms the bottom list which is made from the upper one's elements! if i pass that function the start element and the list it shoul print like this: makecycle(list1, 000094) it should print: ['000094', '000092', '000101', '000099', '000096', '000095', '000094'] and if pass makecycle(list1, 000101) it should print: ['000101', '000099', '000096', '000095', '000094', '000092', '000101'] and if pass makecycle(list1, 000092) it should print: ['000092', '000101', '000099', '000096', '000095', '000094', '000092'] i know its kinda not clear enough but thats all i can point! A: def makecycle(list1,startElement): ind = list1.index(startElement) l = len(list1) i = ind list2 = [] while ind < (l-1): list2.append(list1[ind]) ind = ind + 1 for x in range(i): if list1[x] not in list2: list2.append(list1[x]) print(list2)
This Tutorial contains following Attachments This Tutorial contains 2 Answers Origins of Psychology and Research Methods Worksheet Part l: Origins of Psychology The seven major perspectives In modern psychology are psychoanalytic. behavionst. humanist. oognitlve. neuroscientific/ biopsychological. evolutionary. and sociocultural. Describe the perspectives using two to three sentences each. Select one major ﬁgure associated with one of the perspectives and describe hls or her world in two to three sentences. Type your response in the space below. Within psychology, there are several perspectives used to describe predict. and explain human behaviour. Part 2: Research Methods Describe research methods used in psychology by completing the following table. Then. select two of the research methods, and compare and contrast them. Your response must be at least T5 words. Case Study Longitudinal Describe one ethical issue related to research. Why Is informed consent necessary for ethical research? Naturalistic Observation Part 3: The Brain Studying the functions and elements of the brain Is essential to understanding human behavior. 1. Why do psychologists study twins? Why do psychologists study children who have been adopted? What can be learned from these types of studies? 2. What are the functions of neurotransmitters and hormones? How do they influence the brain and behavior? Some psychologists specialize in the study and treatment of psychological disorders, such as schizophrenia, mood disorder, eating disorders, and anxiety disorders. For your Learning Team presentation, research and explain various elements that influence physical and mental health and b.. Developmental psychology seeks to address various aspects of human development, including physical, cognitive, social, moral, and personality development. Discuss the influences on physical and cognitive development in a 1,050- to 1,400-word paper. Select one of the following stages of develo.. Create an outline for Week Five’s Influences on Behavior and Psychological Disorders Presentation. Include the following: Introduction Include all introductory points. Include a thesis statement. Body of presentation Address all main topics and subtopics in the body of the.. Write a 700- to 1,050-word paper describing a single, informal learning experience that someone could have. o You may describe, for example, how someone could become afraid of heights, why a particular food or smell moves him/her emotionally, or why he/she dislikes elevators. The exper.. Write a 700- to 1,050-word paper describing a single, informal learning experience that someone could have. o You may describe, for example, how someone could become afraid of heights, why a particular food or smell moves him/her emotionally, or why he/she dislikes elevators. The exper.. Write a 700- to 1,050-word paper describing a single, informal learning experience that someone could have. o You may describe, for example, how someone could become afraid of heights, why a particular food or smell moves him/her emotionally, or why he/she dislikes elevators. The exper.. This Tutorial contains 2 Answers Origins of Psychology and Research Methods Worksheet Part l: Origins of Psychology The seven major perspectives In modern psychology are psychoanalytic. behavionst. humanist. oognitlve. neuroscientific/ biopsychological. evolutionary. and sociocultural. Descri.. This Tutorial contains 2 Presentations Learning Team Assignment: Influences on Behavior and Psychological Disorders Presentation Some psychologists specialize in the study and treatment of psychological disorders, such as schizophrenia, mood disorder, eating disorders, and anxiety disorders. F.. This Tutorial contains 2 Set of Answers Remembering, Feeling, and Thinking Worksheet Part I: Motivation, Emotion, and Behavior Explain the relationships between motivation, emotion, and behavior. How does emotion affect motivation? Provide an example of a specific behavior, and the motiva.. This Tutorial contains 2 Papers Write a 700- to 1,050-word paper describing an informal learning experience you have had. You may describe, for example, how you became afraid of heights, why a particular food or smell moves you emotionally, or why you dislike elevators. The experience must be c..
In his latest essay, Emmet Scott explores the parallels between the barbarian invasions of Rome in the 4th century A.D. with the migrant invasions of Europe in the 21st century. The Barbarians Who Sacked Rome Came Into the Empire as Refugees by Emmet Scott Over the past century many commentators have remarked on the parallels between the modern West and ancient Rome in its period of decadence and decline. The most influential proponent of the idea, perhaps, has been Oswald Spengler, whose Decline of the West is now widely viewed as a classic of conservative thought. As might be imagined, “progressives” have consistently sneered at the idea, but, then again, they would scarcely be progressives if they didn’t. One is reminded of the Chinese saying: “When a fool sees the Tao [Truth] he laughs. If he did not laugh it would not be the Tao.” The parallels between decadent Rome and the modern West are actually there. And they are uncanny, and they are becoming more numerous by the day. In 410 A.D. the walls of Rome were breached and the city plundered by a barbarian army under the leadership of Alaric the Goth. This was the first time since the Gallic sack of the city around 390 B.C. that the imperial metropolis had been entered by a hostile enemy. The fall of Rome shocked the world at the time, but what is not generally known nowadays is that the Gothic army that carried out the atrocity had entered the Empire thirty years earlier as refugees. Until the second half of the fourth century the Goths had inhabited a vast swathe of territory taking what now comprises Romania as well as the Ukraine. In 375, however, they were attacked by the Huns, a tribe of nomad warriors from central Asia who had been moving steadily westwards during the preceding century and a half. In the ensuing war the Goths suffered a crushing defeat and large numbers of them fled westwards towards the Roman Empire. By the summer of 376 an enormous host of Goths, generally estimated at around 100,000, arrived at the River Danube and pleaded with the Roman authorities to be allowed into the Empire. The Eastern Emperor Valens, at that moment stationed in Antioch, eventually gave permission for the Therving tribe, which comprised about half the total number of Gothic refugees, to be ferried across the river. For at least two centuries prior to this the Romans had actively recruited barbarians into the army (necessary because of Rome’s abysmally low birth-rate) and Valens reasoned that the Goths would provide a valuable pool of new and cheap recruits. The operation to ferry these people across the Danube was an enormous and costly one and took several weeks to complete and, as Ammianus Marcellinus sarcastically comments, “diligent care was taken that no future destroyer of the Roman state should be left behind, even if he were smitten by a fatal disease.” Unsurprisingly, within a few weeks of their entry into the Empire, the first clashes with the Roman authorities occurred, and by the end of the summer the Goths were at war with Rome. After several military disasters, the Emperor Valens made a hasty return to Constantinople to personally take charge of the campaign, and was killed in battle at Adrianople in 378 — just two years after he had sanctioned the mass immigration. But worse was to come. A decade and a half of uneasy peace was terminated in 395 by a renewed Gothic war, this time under the leadership of Alaric. Commanding an enormous host of warriors (who were in fact officially soldiers in the Roman army) Alaric moved south from Thrace into Greece, a land which he proceeded to devastate. City after city was taken, its male population massacred, its female population raped and sold into slavery, and its wealth plundered. Finally, in 396 the Western Empire bestirred itself and its greatest general Stilicho was dispatched with a sizeable force to the relief of Hellas. After a lengthy game of cat and mouse around the Peloponnesian Peninsula the Goths were trapped by the superior science and tactics of the Roman general. Unfortunately, however, Stilicho did not prosecute the siege to its conclusion and the Goths effected a daring escape and made their way to Epirus. At this moment a Greek political philosopher named Synesius published a widely-discussed treatise on the present emergency and the measures that needed to be taken. He exhorted the emperor to, “revive the courage of his subjects by the example of manly virtue; to banish luxury from the court and from the camp; to substitute, in the place of barbarian mercenaries, an army of men in the defence of their laws and of their property … to rouse the indolent citizen from his dream of pleasure. … At the head of such troops who might deserve the name, and would display the spirit, of Romans, he [encouraged the emperor] never to lay down his arms till he had chased them [the barbarians] far away into the solitudes of Scythia, or had reduced them to the state of ignominious servitude …” In the words of Gibbon, “The court of [Emperor] Arcadius indulged the zeal, applauded the eloquence, and neglected the advice of Synesius.” Instead of exile in the solitudes of Scythia, Alaric was actually promoted to the rank of master-general of the province of Eastern Illyricum, and the Roman provincials, remarks Gibbon, “were justly indignant that the ruin of Greece and Epirus should be so liberally rewarded.” Does all of this sound eerily familiar? Yet even worse was to come; for the patriot who had saved Greece from Alaric, the general Stilicho, was himself only a decade later denounced by the Roman ruling class and murdered, along with his entire family. This was after Stilicho had saved Italy from a second attack by Alaric, as well as from another barbarian host led by one Rhadagastus which had crossed the Alps and devastated the Po Valley. What kind of society brings in barbarians who cannot be assimilated in order to replace the children it refused to have; which excuses and rewards the horrific crimes of those barbarians; and which punishes patriots who try to stop the depredations of the said barbarians? Previous posts by Emmet Scott:
Post-traumatic thumb reconstruction with radial forearm flap. The study described a case of a 37-year-old patient, who had undergone avulsion amputation of the thumb, and was subject to a primary thumb reconstruction by means of thumb reconstruction with radial forearm flap, with the use of osseous fragments of the amputated thumb parts.
(CNN) Handwashing with soap and warm water for 20 seconds -- along with staying home and standing six feet apart from others -- is the best weapon we have against the novel coronavirus that has infected almost 800,000 people around the world. However, there's one big yet little discussed difference when it comes to this essential personal hygiene habit: Women are hands down better handwashers than men. Years of surveys, observations and research have found that women are more likely to wash their hands, use soap and scrub for a longer period of time than men after using the restroom. However, there's still a surprisingly large portion of both sexes who don't wash their hands at all. People lie about washing their hands Researchers have had to come up with clever ways to collect this data, since most people will tell you that they think handwashing after using the bathroom is important . That's even if they don't actually do it. Carl Borchgrevink, director of the School of Hospitality at Michigan State University in East Lansing, takes this kind of survey data with a pinch of salt. "If you're at a restroom at an airport, for example, and when you come out someone [asks] you 'Did you wash your hands?' And what are you going to say? Yes, of course," said Borchgrevink. When researchers only ask about people's handwashing habits, "we found that the data that people were reporting seemed to be too high," he said. Borchgrevink tasked 12 research assistants at Michigan State University with the job of surreptitiously hanging out in four different restrooms on and off campus to record what 3,749 men and women actually did. The To dig deeper into what people really do after using the bathroom,Borchgrevink tasked 12 research assistants at Michigan State University with the job of surreptitiously hanging out in four different restrooms on and off campus to record what 3,749 men and women actually did. The results of the 2013 study were shocking to the researchers. Few people wash their hands correctly Some 15% of men didn't wash their hands at all, compared with 7% of women. When they did wash their hands, only 50% of men used soap, compared with 78% of women. Overall, only 5% of people who used the bathroom washed their hands long enough to kill the germs that can cause infections. A bigger study published in 2009 that used more high tech methods at a busy highway rest stop in the UK was equally, if not more, damning. With the use of wireless devices to record how many people entered the restroom and used the pumps of the soap dispensers, researchers were able to collect data on almost 200,000 restroom trips over a three-month period. The found that only 31% of men and 65% of women washed their hands with soap. It's a big gap -- clearly twice as many women as men were washing their hands," said Susan Michie, health psychology professor and director of the Centre for Behaviour Change at the Department of Clinical, Educational and Health Psychology at University College London. "Another interesting result was that the more people were in the toilet area the more they were likely to wash their hands," said Michie, who was an author of the study. "If there were no people around, people tended to zap out with no one noticing." There's little to suggest that men in the UK and US are unsual in their handwashing (or lack thereof). hand-washing, mask-wearing and surface cleaning in the context of an epidemic, like flu. review published on the subject in 2016 looked at research from dozens of different countries, and found that women were 50% more likely than men to practice, or increase, protective behavior like properhand-washing, mask-wearing and surface cleaning in the context of an epidemic, like flu. Why is there a gender gap? There's been far less research done on why there is such a gap between the sexes when it comes to hand-washing. Michie said it was likely socially programmed behavior, not genetic. "Women are more focused on care than men -- childcare, household care, personal care," she said. Similarly, Borchgrevink said that while his study didn't look at why men didn't wash their hands as much as women, he suggested that it could be down to a sense that men were too macho to fear germs. "We did talk to some of (the men) and ask, 'why didn't wash your hands?'" Borchgrevink said. "And they would look at us indignantly and say, 'I'm clean, I don't need to wash my hands.' They had a sense of invincibility." Nancy Tomes, a history professor at Stony Brook University and the author of "The Gospel of Germs: Men, Women and the Microbe in American Life," says the hand-washing gender gap has a long history dating back to when the germ theory of disease took hold in the public consciousness in the Victorian era -- that certain diseases were caused by microorganisms that invaded the body rather than bad air or miasma. An unidentified Red Cross nurse teaches a class on home hygiene and care for the sick to a group of women of various ages, 1920. "This changed the definition of cleanliness," she said, and women especially were told their family's health depended on the highest level of hygiene. "Of course, there had been definitions of what was clean and unclean before the germ theory came along, but it injected a level of specificity and also upped the ante. If you made a mistake in your cleanliness, you could die, your family could die. "And that message of, 'make a mistake and your kid will die' resonates like a megaphone in the lives of mothers (even today)," Tomes said. Motivating men to wash their hands Michie's research at the highway rest stop in the UK looked at what kind of public health messaging would improve handwashing rates by using a sign that illuminated with different messages as people entered the restroom. While the findings weren't conclusive, the study suggested that men and women responded to different types of messaging around handwashing. Messages that triggered disgust ("Soap it off or eat it later") resonated with men, while women were more motivated to wash by messages that activated knowledge, such as "Water doesn't kill germs, soap does." Michie said she wasn't aware of any public health campaigns that had focused their efforts on men in light of their handwashing lapses, but said this was the perfect moment to try. "It's an excellent idea to target men. It could be really helpful. If women knew men weren't doing it, they'd get on to them."
Hungarian NGO Law Cracks Down on Civil Society and Inches Closer to Authoritarianism Washington, D.C.—Human Rights First today condemned the Hungarian parliament’s passage of a law that will stigmatize and severely restrict the ability of nongovernmental organizations to operate. Passed under the pretense of increasing transparency and combating the funding of terrorism, the new law is widely seen as another step in Prime Minister Orban’s self-declared effort to erode the rule of law and silence critics of the Hungarian government. “By moving to silence community groups that work to expose corruption, promote the rule of law, and protect the vulnerable, Prime Minister Orban took yet another step today on the path toward Russian-style despotism,” said Human Rights First’s Rob Berschinski. “Orban’s plan is clear. He intends to undermine every potential check on his power, whether that be independent courts, a free media, strong educational institutions, or, in this case, non-profit groups that work to the benefit of Hungarian citizens. The only question now is, will the United States and Europe stand up to an authoritarian in their midst?” In recent years the Hungarian government has targeted nearly 60 NGOs in an attempt to intimidate and harass dissidents through paralyzing tax investigations. In 2015, United Nations Special Rapporteur on Human Rights Defenders Michel Forst visited Hungary and urged the authorities not to undermine “peaceful and legitimate activities through criminal defamation and excessive administrative and financial pressure.” Today’s passage indicates that Orban’s government has chosen to ignore Forst’s recommendation in what will be a severe setback for civil society in Hungary. The law closely resembles legislation passed in Russia in 2012 known as the “foreign agents” law, adding to growing concerns that the Kremlin’s influence is growing in Hungary. The label of "foreign agent" carries a debilitating stigma rooted in Cold War terminology, associated with foreign spies. Combined with the overbearing operational costs of complying with the law, many organizations in Russia have weighed the option of shutting down entirely rather than being labeled as foreign agents.
Pastor Robert Morris has reportedly contracted pneumonia, the latest in a series of medical emergencies for the Dallas-based megachurch pastor. In a series of Instagram posts, his wife Debbie told followers that Morris "has pneumonia but we have aggressively started treating it." Morris was airlifted to the hospital earlier this week after suffering internal bleeding, a complication of hernia surgery. He went through two rounds of emergency surgery plus an angiogram on Sunday and Monday. He was reportedly stable and recovering until Wednesday evening, when Debbie announced he had pneumonia. Despite this news, doctors are reportedly pleased with Morris' recovery progress. Morris will reportedly get a chance to walk today, his first time standing since the airlift. In her two most recent updates, Debbie asked believers to pray "for renewed strength," for "antibiotics [to] work to destroy infection," "for his levels to continue to improve" and "for no setbacks." 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Introduction {#Sec1} ============ MS is a chronic inflammatory disease of the CNS in which both the innate and adaptive immune system are involved. The immune system of MS patients displays a disrupted balance favoring pro-inflammatory responses. T cells have long been considered as the most important players although the emergence of B cell depleting treatment has emphasized the importance of B cells in MS pathogenesis^[@CR1],[@CR2]^. Adaptive immune cell subtypes involved in the pathological processes during MS are memory T cells (CD45RO^+^CD45RA^−^) and more specifically C-C chemokine receptor type 7 (CCR7)^−^ effector memory T cells, CD8^+^ T cells and memory (CD27^+^) B cells^[@CR3]--[@CR8]^. CD4^+^ T helper (Th) 1 and Th17 cells produce pro-inflammatory cytokines including interferon-γ (IFN-γ), interleukin-17 (IL-17) and granulocyte macrophage colony-stimulating factor (GM-CSF) while Th2 and regulatory T (Treg) cells produce anti-inflammatory IL-4 and IL-10^[@CR1],[@CR9]^. Double negative (DN, IgD^−^CD27^−^) B cells with a pro-inflammatory cytokine profile are described to be increased in a proportion of MS patients^[@CR10]^. For the innate immune system, monocytes (CD14^+^), neutrophils and natural killer (NK) cells, including CD56^dim^ and CD56^bright^ NK cells, are involved in MS pathogenesis^[@CR11]--[@CR14]^. Dimethyl fumarate (DMF, Tecfidera^®^) was licensed as an oral first-line treatment for MS in 2013. Two phase III clinical trials, DEFINE and CONFIRM, demonstrated clinical efficacy of DMF in relapsing-remitting (RR) MS^[@CR15],[@CR16]^. DMF reduced the annualized relapse rate and reduced the mean number of new or enlarging MRI lesions throughout the course of the study^[@CR15],[@CR16]^. Earlier studies have demonstrated that DMF and its active metabolite monomethyl fumarate (MMF) exert neuroprotective and immunomodulatory effects through the activation of transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and via the suppression of transcription factor nuclear factor kappa b (NF-kB)^[@CR17],[@CR18]^. A number of studies investigated the effect of DMF on certain subtypes of disease-related immune cells^[@CR19],[@CR20]^. Nevertheless, the working mechanism of DMF is multifactorial and the pathogenesis of MS is directed by interplay between different immune cell subtypes. Previous studies were limited by a cross-sectional design, limited follow-up to 6 months only, a focus on 1 immune cell subtype or the inclusion of patients who were previously treated with second-line therapies. Therefore, we performed an extensive immunophenotypic analysis of the innate and adaptive immune system of RRMS patients under DMF treatment using 3 study designs: a 12 month (m) follow-up study, a cross-sectional study and an in vitro study. In this way we further explored changes of several immune cell types over a longer period in a cause-and-effect way in untreated MS patients or in MS patients previously treated with first-line treatments. Results {#Sec2} ======= Clinical characteristics {#Sec3} ------------------------ In the follow-up study, 16 RRMS patients were enrolled and peripheral blood was collected before treatment, after 3 m and after 12 m of DMF treatment. Twelve of the 16 MS patients finished the total duration of the study (Table [1](#Tab1){ref-type="table"}), while 4 MS patients dropped out of the study, with 2 due to side effects (gastrointestinal and flushing), 1 due to pregnancy and 1 due to other medication use. Eight of the 12 DMF treated MS patients underwent MRI before and after 12 m of DMF treatment. In all patients, no new or enlarged lesions were detected. Furthermore, 4 of these 8 MS patients showed lesions that were decreased in volume or were less pronounced compared to baseline. Although not significant, EDSS decreased from 2.8 at baseline to 2.3 after 12 m of DMF treatment (p = 0.0547, Table [2](#Tab2){ref-type="table"}). When considering individual MS patients, EDSS improved for 6 patients, remained stable for 4 patients and increased for 2 patients who were clinical responders. Interestingly, a significantly improved cognitive function measured by the PASAT was observed after 3 m of DMF treatment (p \< 0.05). Other clinical measures remained stable over the course of the study (Table [2](#Tab2){ref-type="table"}).Table 1Characteristics of study subjects.GroupNAge^a^Female % (F/M)^b^EDSS^c^Previous treatmentFollow-up studyRRMS DMF-treated1234 ± 1258 (7/5)2.8 ± 1.2UT: 8, IFN: 4Cross-sectional studyHC1030 ± 660 (6/4)N.A.N.A.RRMS UT2536 ± 1172 (18/7)2.5 ± 1UT: 19, IFN: 4, GA: 2RRMS DMF-treated 0--5 m2337 ± 961 (14/9)2.1 ± 1.2UT: 15, IFN: 5, TF: 3RRMS DMF-treated 6--12 m2336 ± 1070 (16/7)1.7 ± 1.2UT: 10, IFN: 10, GA: 1, TF: 1RRMS DMF-treated \> 12 m1835 ± 1072 (13/5)1.6 ± 1.4UT: 3, IFN: 12, GA: 2, TF: 1*In vitro* study[Costimulatory molecules]{.ul} HC937 ± 1255 (5/4)N.A.N.A. RRMS UT745 ± 1157 (4/3)2.8 ± 1.8UT: 6, IFN: 1[Apoptosis]{.ul} HC1234 ± 1167 (8/4)N.A.N.A. RRMS UT645 ± 866 (4/2)2.8 ± 1.9UT: 4, IFN: 2[BAFFR]{.ul} HC1433 ± 1171 (10/4)N.AN.A. RRMS UT645 ± 866 (4/2)2.8 ± 1.9UT: 4, IFN: 2[Breg frequency]{.ul} RRMS UT538 ± 1380 (4/1)2 ± 0.8UT: 5^a^Mean age in years; ^b^number of female (F) and male (M) individuals; ^c^mean Expanded Disability Status Scale (EDSS); IFN = interferon-β, RRMS = relapsing-remitting multiple sclerosis, DMF = dimethyl fumarate, HC = healthy control, m = months, Breg = regulatory B cell, N.A. = not applicable, UT = untreated, TF = teriflunomide, GA = glatiramer acetate.Table 2Clinical tests and absolute numbers of immune cells after DMF treatment.Clinical testBaseline mean ± SD3 m DMF mean ± SD12 m DMF mean ± SDEDSS2.8 ± 1.32.7 ± 1.62.3 ± 1.7^§^PASAT50 ± 453 ± 353 ± 4^\^NHPT dominant hand20.6 s ± 520 s ± 419 s ± 3NHPT non-dominant hand20.3 s ± 420 s ± 319.8 s ± 4T25FW4.9 s ± 25.5 s ± 35.5 s ± 3FSMC (motor)31 ± 731 ± 731 ± 6FSMC (cognitive)30 ± 931 ± 1032 ± 11Absolute number (x10* ^3^ /ml) ^a^ (clinic)Leukocytes7984 ± 18627180 ± 29056397 ± 1754^\^Lymphocytes2494 ± 7462019 ± 8091346 ± 289^\^Monocytes488 ± 137501 ± 96453 ± 84Neutrophils4826 ± 13024514 ± 19624470 ± 1616Absolute number (x10 ^3^ /ml) ^a^ (calculated)CD56^dim^ NK cells160 ± 77156 ± 112111 ± 53^\^CD56^+^ NK cells16 ± 920 ± 1419 ± 8^\^T cells (CD3^+^)1857 ± 6691520 ± 604974 ± 270^\^CD4^+^ T cells1072 ± 268955 ± 379623 ± 197^\^Naive CD4^+^ T cells (CD4^+^CD45RO^−^CD45RA^+^)439 ± 246453 ± 226340 ± 195Memory CD4^+^ T cells (CD4^+^CD45RO^+^CD45RA^−^)623 ± 156523 ± 295279 ± 153^\^Regulatory T cells (CD4^+^CD25^+^CD127^low^)53 ± 1444 ± 2027 ± 10^\^IL-17^+^ CD4^+^ T cells6 ± 44 ± 33 ± 2GM-CSF^+^ CD4^+^ T cells65 ± 3349 ± 4619 ± 14^\^IFN-γ^+^ CD4^+^ T cells99 ± 3366 ± 4331 ± 14^\^IL-4^+^ CD4^+^ T cells34 ± 1125 ± 1418 ± 10^\^IL-10^+^ CD4^+^ T cells3 ± 35 ± 52 ± 3^\^CD8^+^ T cells618 ± 452447 ± 261254 ± 117^\^Naive CD8^+^ T cells (CD8^+^CD45RO^−^CD45RA^+^)402 ± 366281 ± 191211 ± 104Memory CD8^+^ T cells (CD8^+^CD45RO^+^CD45RA^−^)210 ± 180164 ± 17642 ± 23^\^B cells (CD19^+^)295 ± 165187 ± 132142 ± 47^\^Transitional B cells (CD19^+^CD27^−^CD38^+^)8 ± 58 ± 47 ± 4Naive B cells (CD19^+^CD27^−^IgD^+^)185 ± 140120 ± 90102 ± 46Non class-switched memory B cells (CD19^+^CD27^+^IgD^+^)38 ± 2418 ± 817 ± 8^\^Class-switched memory B cells (CD19^+^CD27^+^IgD^−^)41 ± 1324 ± 1615 ± 4^\^Double negative B cells (CD19^+^CD27^−^IgD^−^)12 ± 58 ± 46 ± 2^\^DMF = dimethyl fumarate, m = months, ^§^p = 0.05, ^\^p \< 0.05 12 m compared to baseline.^a^Absolute numbers of immune cells were available from 7 of the 12 DMF-treated MS patients, EDSS was available from all DMF-treated MS patients while FSMC and NHPT was available from 9/12 DMF-treated MS patients and PASAT and T25FW was available from 8/12 DMF-treated MS patients. Absolute numbers of immune cells {#Sec4} -------------------------------- Absolute immune cell numbers of leukocytes, lymphocytes, monocytes and neutrophils were obtained from standard clinical lab tests for 7 DMF-treated MS patients. A significant decrease in the absolute leukocyte (20%) and lymphocyte (46%) numbers was measured after 12 m of DMF treatment (p = 0.0313, Table [2](#Tab2){ref-type="table"}). Grade 3 lymphopenia (absolute lymphocyte numbers \<0.5 × 10^9^ cells/L) was not observed in this patient cohort. Absolute monocyte and neutrophil numbers remained stable. Specific cell subtypes of both the innate and adaptive immune system, calculated as described in the methods section, showed significantly reduced numbers after 12 m but not after 3 m of DMF treatment. The absolute number of CD56^dim^ NK cells was significantly reduced (p = 0.0156), while CD56^bright^ NK cell numbers were significantly increased (p = 0.0469). The absolute numbers of T cells (CD3^+^) and all T cell subtypes were significantly decreased (p \< 0.05), except for naive T cells (p = 0.1563 for CD4^+^CD45RO^−^CD45RA^+^ and p = 0.0781 for CD8^+^CD45RO^−^CD45RA^+^) and IL-17^+^ CD4^+^ T cells (p = 0.1094). Within the B cell population, the absolute numbers of total B cells (CD19^+^) and all B cell subtypes were decreased (p \< 0.05) except for transitional B cells (p = 0.6875) and naive B cells (p = 0.0781), which were not affected. In conclusion, most immune cell subtypes showed decreased circulating absolute numbers following 12 m of DMF treatment. Therefore, it was important to investigate the remaining peripheral blood immune cell population by determining immune cell subtype percentages. Percentages of innate immune cell subtypes {#Sec5} ------------------------------------------ When analyzing innate immune cell subtypes (gated as in Fig. [1a](#Fig1){ref-type="fig"}), increased percentages of monocytes (p = 0.0005), CD56^+^ (p = 0.0005) and CD56^dim^ (p = 0.0269) NK cells were detected after 12 m (Fig. [1b](#Fig1){ref-type="fig"}), but not after 3 m (Supplementary Fig. [1](#MOESM1){ref-type="media"}) of DMF treatment. Thus, DMF treatment increased the percentages of all analyzed innate immune cell subtypes.Figure 1DMF treatment increased frequencies of monocytes and NK cells. (a) A representative analysis of innate immune cell subtypes is shown. Single cells were selected using forward scatter (FSC) area and width. Lymphocytes were gated in the singlet gate using FSC and side scatter (SSC) parameters. CD56^dim^ NK cells (CD3^−^CD16^+^CD56^dim^) and CD56^+^ NK cells (CD3^−^CD16^+^CD56^+^) were gated from lymphocytes and the CD3- cell population. Monocytes (CD14^+^) were gated from monocyte gate. (b) Frequency of monocytes and NK cells at baseline and after 12 m of DMF treatment in RRMS patients (n = 12). Each line represents an individual patient and average values are depicted as histograms. Wilcoxon matched-pairs signed rank test was used to determine p values. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001. NK = natural killer, m = months. Percentages of adaptive immune cell subtypes {#Sec6} -------------------------------------------- After 12 m of DMF treatment, T cell percentages decreased, although not significantly (data not shown). Within the T cell population (gated as in Fig. [2a](#Fig2){ref-type="fig"}), CD4^+^ T cells remained stable, while CD8^+^ T cells decreased (p = 0.0034, Fig. [2b](#Fig2){ref-type="fig"}). Most importantly, a decrease in the percentages of memory and effector memory CD4^+^ and CD8^+^ T cells was evident (p \< 0.01) while naive CD4^+^ and CD8^+^ T cell percentages increased (p \< 0.01). No effect of DMF treatment was observed on Treg percentages (Supplementary Fig. [1](#MOESM1){ref-type="media"}). When analyzing cytokine-expressing CD4^+^ T cells (gating shown in Supplementary Fig. [2](#MOESM1){ref-type="media"}), decreased percentages of pro-inflammatory IFN-γ^+^ (p = 0.0015), GM-CSF^+^ (p = 0.0005) and IL-17^+^ (p = 0.0488) CD4^+^ T cells (Fig. [3a](#Fig3){ref-type="fig"}) were detected and anti-inflammatory IL-4^+^ and IL-10^+^ CD4^+^ T cells were unchanged (Fig. [3b](#Fig3){ref-type="fig"}, Supplementary Fig. [2](#MOESM1){ref-type="media"}).Figure 2DMF treatment reduced (effector) memory T cell frequencies after 12 m of treatment in MS patients. (a) A representative analysis of T cell subtypes is shown. Single cells were selected using FSC area and width. Lymphocytes were gated within the singlet gate using FSC and SSC parameters. Next, CD4^+^ T cells and CD8^+^ T cells were gated from lymphocytes. Naive T cells (CD45RA^+^CD45RO^−^), memory T cells (CD45RA^−^CD45RO^+^) and effector memory T cells (CD45RA^−^CCR7^−^) were gated from the CD4^+^ or CD8^+^ T cell population. (b) Frequency of T cell subtypes at baseline and after 12 m of DMF treatment in RRMS patients (n = 12). Each line represents an individual patient and average values are depicted as histograms. Wilcoxon matched-pairs signed rank test was used to determine p values. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001. m = months.Figure 3Reduction in the frequency of T cells expressing pro-inflammatory cytokines after 12 m of DMF treatment. Frequency of CD4^+^ T cells expressing pro-inflammatory cytokines (a), including IFN-γ, GM-CSF, IL-17 or anti-inflammatory cytokines (b), including IL-4 and IL-10, in RRMS patients at baseline and after 12 m of DMF treatment (n = 12). Each line represents an individual patient and average values are depicted as histograms. Wilcoxon matched-pairs signed rank test was used to determine p values. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001. IFN-γ = interferon γ, GM-CSF = granulocyte macrophage colony-stimulating factor, IL-17 = interleukin-17, IL-4 = interleukin-4, IL-10 = interleukin-10, m = months. Furthermore, B cell percentages were not affected by DMF treatment (Fig. [4](#Fig4){ref-type="fig"}). Within the B cell population (gated as in Fig. [4a](#Fig4){ref-type="fig"}), percentages of transitional and naive B cells increased (Fig. [4b](#Fig4){ref-type="fig"}). Further, DMF treatment resulted in decreased percentages of DN (p = 0.0161), class-switched memory (p = 0.0034) and non class-switched memory (p = 0.0161) B cells. After 3 m of DMF treatment, no significant differences were observed in the percentages of all adaptive immune cell subtypes (Supplementary Fig. [1](#MOESM1){ref-type="media"}).Figure 4DMF treatment reduced memory and DN B cell subtypes after 12 m of treatment in MS patients. (a) A representative analysis of B cell subtypes is shown. Single cells were selected using FSC area and width. Lymphocytes were gated in the singlet gate using FSC and SSC parameters. B cells (CD19^+^) were gated from lymphocytes followed by analysis of transitional B cells (CD27^−^CD38^high^), naive B cells (CD27^−^IgD^+^), non class-switched memory B cells (CD27^+^IgD^+^), class-switched memory B cells (CD27^+^IgD^−^) and DN B cells (CD27^−^IgD^−^). (b) B cell subtypes at baseline and after 12 m of DMF treatment in RRMS patients (n = 12). Each line represents an individual patient and average values are depicted as histograms. Wilcoxon matched-pairs signed rank test was used to determine p values. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001. DN = double negative, m = months. In vitro* treatment of B cells from 5 untreated RRMS patients with DMF or MMF indicated that DMF induced a trend towards an increased regulatory B cell (Breg) percentage (p = 0.06, Supplementary Fig. [3](#MOESM1){ref-type="media"}). MMF decreased the percentage of TNF-α^+^ B cells, although not significantly (p = 0.06). Together, these results indicate that 12 m DMF treatment reduced percentages of pro-inflammatory and memory T and B cell subtypes and increased percentages of naive T and B cells and transitional B cells. T cell subtypes in a cross-sectional study {#Sec7} ------------------------------------------ Since 3 m DMF treatment only partly reflected changes reported at 12 m, additional time points were included in a cross-sectional study to identify how soon the reported effect was found after treatment (Table [1](#Tab1){ref-type="table"}). Memory CD4^+^ and CD8^+^ T cell percentages were reduced, while naive CD4^+^ and CD8^+^ T cell percentages were increased after 6 m of DMF treatment compared to untreated MS patients (Fig. [5](#Fig5){ref-type="fig"}). Furthermore, percentages of memory CD8^+^ T cells were decreased, while naive CD8^+^ T cells were increased after 6--12 m compared with 1--5 m of DMF treatment. After prolonged treatment (\>12 m), memory and naive CD4^+^ and CD8^+^ T cell percentages remained stable. Thus, DMF is fully effective after 6 m of treatment.Figure 5DMF treatment is fully effective on immune cells after 6 m of treatment. Frequencies of naive and memory CD4^+^ and CD8^+^ T cells in HC (n = 10), untreated RRMS patients (n = 25), 1--5 m DMF-treated RRMS patients (n = 23), 6--12 m DMF-treated RRMS patients (n = 23), \>12 m DMF-treated MS patients (n = 18). A Kruskal-Wallis one-way ANOVA was used to compare the different groups. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001, ^\\\\^p \< 0.0001. HC = healthy control, DMF = dimethyl fumarate, m = months. Direct effect of DMF on B cell apoptosis {#Sec8} ---------------------------------------- We next investigated induction of apoptosis as one of the underlying mechanisms of the drop in absolute lymphocyte numbers. Previously, in vitro studies showed that DMF induced T cell apoptosis with a preferential effect on memory T cells^[@CR21]^. Since DMF treatment decreased the percentage of memory B cells while increasing naive B cells, we investigated whether DMF induced apoptosis of B cells and whether naive B cells showed a lower vulnerability to DMF-induced apoptosis. Here, the direct effect of DMF and MMF on B cell apoptosis was investigated (Table [1](#Tab1){ref-type="table"}). In HC, DMF induced B cell apoptosis at 25 µM (p \< 0.05) and 50 µM (p \< 0.001) compared to baseline (Fig. [6](#Fig6){ref-type="fig"}). In untreated MS patients, apoptosis was induced with 50 µM DMF (p \< 0.01), although late B cell apoptosis was already induced at 25 µM (p \< 0.05). In HC, late apoptosis was only induced at 50 µM DMF (p \< 0.001). MMF treatment did not induce B cell apoptosis (Supplementary Fig. [4](#MOESM1){ref-type="media"}) and no difference was detected between memory and naive B cells (data not shown). In summary, DMF induced concentration-dependent apoptosis of B cells from HC and MS patients with B cells of MS patients appearing to be more vulnerable.Figure 6DMF induces apoptosis in B cells in a concentration-dependent manner. Purified B cells of HC and untreated RRMS patients were treated in vitro with the following concentrations of DMF: 10 µM (HC: n = 12, MS: n = 5), 16 µM (HC: n = 10, MS: n = 4), 25 µM (HC: n = 8, MS: n = 6) and 50 µM (HC: n = 7, MS: n = 5) or left untreated (HC: n = 12, MS: n = 6). (a) Frequency of live B cells (Annexin V^−^7-AAD^−^), (b) apoptotic B cells (Annexin V^+^7-AAD^−^), (c) late apoptotic B cells (Annexin V^+^7-AAD^+^) and (d) necrotic B cells (Annexin V^−^7-AAD^+^) of HC and MS patients. A Kruskal-Wallis one-way ANOVA was used to compare the different groups. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001. HC = healthy control, MS = multiple sclerosis, DMF = dimethyl fumarate. Direct effect of DMF on functional markers of B cells {#Sec9} ----------------------------------------------------- We previously demonstrated the potential of MS B cells to induce autoreactive T cell responses via antigen presentation and increased costimulatory molecule expression on MS B cells^[@CR4]^. As immunomodulatory treatment abrogated these effects^[@CR4]^, we investigated whether in vitro treatment with DMF directly decreased the expression of antigen presentation and costimulatory molecules (Table [1](#Tab1){ref-type="table"}). DMF, but not MMF, directly decreased B cell expression of HLA-DR/DP/DQ and CD40 in HC (p = 0.0234 and p = 0.0078, respectively) and untreated MS patients (p = 0.0313 and p = 0.0313, respectively, Fig. [7A](#Fig7){ref-type="fig"}, Supplementary Fig. [5](#MOESM1){ref-type="media"}). In contrast, DMF increased CD80 expression on B cells of untreated MS patients (p = 0.0469), while no effect was detected in HC or on CD86 expression. However, DMF had no effect on the percentage of CD80^+^ B cells while it decreased the percentage of CD86^+^ B cells in HC.Figure 7DMF downregulates the expression of antigen-presentation molecules, costimulatory molecule CD40 and survival marker BAFFR on B cells. (A) Purified B cells of HC and untreated RRMS patients were treated in vitro with 10 µM DMF or were left untreated. Expression (MFI) of HLA-DR/DP/DQ (HC: n = 8, MS: n = 7), CD40 (HC: n = 8, MS: n = 7), CD80 (HC: n = 9, MS: n = 7) and CD86 (HC: n = 9, MS: n = 7) on B cells and % CD80^+^ (HC: n = 8, MS: n = 7) and % CD86^+^ (HC: n = 9 MS: n = 7) B cells is depicted for HC and MS patients. (B) Purified B cells of HC and untreated RRMS patients were treated in vitro with the following concentrations of DMF: 10 µM (HC: n = 14, MS: n = 5), 16 µM (HC: n = 11, MS: n = 4), 25 µM (HC: n = 9, MS: n = 6) and 50 µM (HC: n = 7, MS: n = 5), or with MMF: 50 µM (HC: n = 9, MS: n = 4) or were left untreated (HC: n = 14 and MS: n = 5). (C) Plasma BAFF levels of RRMS patients at baseline (n = 11), 3 m of DMF treatment (n = 9) and 12 m of DMF treatment (n = 11) and expression (MFI) of BAFFR on B cells of RRMS patients at baseline and 12 m of DMF treatment (n = 12). A Kruskal-Wallis one-way ANOVA was used to compare the different groups and a Wilcoxon matched-pairs signed rank test was used to determine p values between two groups. ^\^p \< 0.05, ^\\^p \< 0.01, ^\\\^p \< 0.001, ^\\\\^p \< 0.0001. HLA-DR/DP/DQ = human leukocyte antigen, HC = healthy control, MS = multiple sclerosis, DMF = dimethyl fumarate, MFI = mean fluorescence intensity, BAFF(R) = B cell activating factor (receptor), pos = positive. B cell survival was further investigated via BAFFR expression. DMF, but not MMF, directly decreased BAFFR expression on B cells in vitro, already at 10 µM (HC: p \< 0.05; MS: p = 0.0625) with stronger effects using higher DMF concentrations (p \< 0.01, Fig. [7B](#Fig7){ref-type="fig"}). An increased baseline BAFFR expression level was observed on MS B cells compared to HC (p \< 0.0001). In our follow-up study, an increased BAFFR expression was detected after 12 m of DMF treatment and no effect was measured on BAFF plasma levels (Fig. [7C](#Fig7){ref-type="fig"}). This suggests that DMF treatment has a direct effect on B cell survival by decreasing BAFFR expression and an indirect effect ex vivo due to a shift in B cell subtypes. Discussion {#Sec10} ========== In 2013, DMF (Tecfidera^®^), was licensed as an oral first-line treatment for RRMS^[@CR15],[@CR16]^. However, its mechanism of action is still not fully elucidated. Here, we used 3 study designs and demonstrated that DMF treatment induced a persistent change of both the innate and adaptive immune system of MS patients. Furthermore, DMF directly induced concentration-dependent apoptosis and reduced expression of functional markers of B cells. Next to the immunological findings, clinical parameters were analyzed in the 12 m follow-up study. DMF treatment improved cognitive function (PASAT) and showed a trend towards improved EDSS of MS patients. Cognitive decline is a serious complication in MS that is characterized by deficits in (non)verbal memory, information processing speed and sustained attention^[@CR22]^. However, validation in a larger cohort of DMF-treated MS patients is needed. We further showed that DMF treatment selectively targets or has a stronger effect on particular immune cell subtypes, since it decreased total leukocyte and lymphocyte numbers without affecting monocytes, neutrophils and anti-inflammatory subtypes such as CD56^+^ NK cells and transitional B cells. Absolute numbers in this study are comparable to others^[@CR21],[@CR23]--[@CR25]^. The B cell subtype numbers are in line with Li et al. where DMF preferentially decreased mature B cells without affecting transitional B cells after at least 3 m of treatment^[@CR20]^. However, our study reinforced this by showing a persistent change after 12 m. We further confirmed the preferential loss of CD8^+^ T cells (58%) versus CD4^+^ T cells (41%) and additionally indicated that this loss was persistent after 12 m of treatment. However, in our study none of the DMF-treated MS patients showed a decline of CD4^+^ T cells below the lower limit of normal (LLN, 400/µl) and only 14% of the patients showed a decline of CD8^+^ T cells below the LLN (200/µl), which is in contrast with other studies^[@CR24],[@CR25]^. This could be due to the difference in patient numbers and inclusion criteria. After 3 m of DMF treatment, no significant changes were observed in the number of innate and adaptive immune cell subtypes, which is in agreement with Spencer et al.^[@CR25]^. As the absolute numbers of almost all immune cell subtypes decreased, it was important to consider their percentages to elucidate which subtypes were preferentially affected by DMF treatment. We showed that innate immune cell percentages (monocytes and NK cells) increased, implying that DMF prevails normal innate immune function. The relative increase in monocytes could be the result of the decreased absolute lymphocyte number, as the absolute monocyte number did not change. CD56^+^ NK cells were increased after DMF treatment, while CD56^dim^NK cells increased to a lesser extent. Medina et al. demonstrated an increase of CD56^+^ NK cells after 6 m of DMF treatment, but we reinforced this result by showing its persistence after 12 m of DMF treatment^[@CR26]^. Furthermore, Chaves et al. and Medina et al. did not find a change in total NK cell percentages which indicates that it is important to investigate NK cell subtypes since CD56^+^ and CD56^dim^ NK cells were described to have different functions^[@CR26],[@CR27]^. CD56^+^ NK cells were first considered regulatory NK cells by Cooper et al. due to a reduced cytotoxicity and an increased production of cytokines compared to cytotoxic CD56^dim^ NK cells^[@CR28]^. Further, NK cells have become increasingly important as players in MS pathogenesis, as the expansion of CD56^+^ NK cells was previously correlated with the efficacy of daclizumab in MS patients^[@CR29]^. Regulatory NK cells cytolyze activated T cells in a comparable way as cytotoxic NK cells, whereas they have no cytotoxicity towards resting T cells^[@CR29]^. Since regulatory NK cells cytolyze activated T cells and their expansion is linked with the disease activity of MS patients, regulatory NK cells are clearly important in MS. As with daclizumab, the increase in regulatory NK cells is one of the beneficial mechanisms of DMF. Other mechanisms of DMF, including T cell apoptosis and inhibition of dendritic cell maturation, might indirectly be a consequence of this finding^[@CR21],[@CR30]^. Within the adaptive immune system, DMF treatment reduced percentages of pro-inflammatory immune cell subtypes such as (effector) memory (CD4^+^ and CD8^+^) T cells and (non) class-switched memory and DN B cells in the follow-up study. Furthermore, DMF treatment increased naive T and B cells and transitional B cells. This switch from a pro-inflammatory profile into an anti-inflammatory profile is in line with other studies^[@CR19],[@CR26],[@CR31],[@CR32]^. Since the same results are obtained in different study populations of different countries (Spain, Germany, USA and Belgium) it appears that DMF has a rather stable immunological effect, although it has many mechanisms of action. In addition, our cross-sectional study emphasizes the long-lasting effect of DMF. Medina et al. and Smith et al. reported a reduction of memory B cells and the latter also reported an increase in naive B cells at 6 m of treatment^[@CR26],[@CR33]^. Our study additionally indicated a persistent effect of DMF after 12 m treatment on naive and memory B cells. In contrast to others, who reported no effect of DMF on transitional and Breg cells after 6 m of treatment^[@CR26],[@CR33]^, we detected an increase in transitional B cells. This could indicate that the effect of DMF on transitional B cells is only detectable after a longer treatment period, which was confirmed by Lundy et al., who showed increased Breg cells in 4 of the 8 MS patients after 12 m of DMF treatment compared to 4--6 m of DMF treatment^[@CR34]^. Furthermore, we can speculate that transitional and naive B cells are more resistant to DMF treatment than memory B cells, although we demonstrated that DMF directly induced B cell apoptosis without a preferential effect on memory or naive B cells. Indirect effects, such as the interplay between immune cells or the output of new B cells from the bone marrow, could be responsible for the findings of the follow-up study. Transitional B cells are enriched for Breg which could have beneficial effects in MS^[@CR3]^. Furthermore, results from in vitro treatment of B cells with DMF induced increased Breg percentages, although not significantly. In addition, MMF induced a trend towards a decreased percentage of TNF-α^+^ B cells. Thus, the increased Breg percentage^[@CR34]^ and decreased percentage of TNF-α^+^ B cells^[@CR20],[@CR33]^ that were previously described after DMF treatment could be regulated in a direct manner. As Breg are known to suppress Th1 and Th17 differentiation while inducing Treg generation^[@CR35]^, the decreased IFN-γ^+^ and IL-17^+^ CD4^+^ T cells after DMF treatment in the follow-up study could be an indirect consequence of an increase in Breg. When considering CD4^+^ T cells expressing the anti-inflammatory cytokines IL-4 and IL-10, we could not find a difference after treatment with DMF. One explanation could be the great patient diversity in IL-4^+^ and IL-10^+^ CD4^+^ T cells. Because of this variety a population-wide conclusion about the effect of DMF on IL-4^+^ and IL-10^+^ CD4^+^ T cells cannot be made. Other studies also did not detect a difference in the percentage of IL-4^+^ or IL-10^+^ CD4^+^ T cells^[@CR19],[@CR26],[@CR36]^. In contrast, Wu et al. detected an increase in IL-4^+^ T cells, although the percentage of IL-4^+^ T cells was much lower than detected in other studies^[@CR32]^. One of the limitations of our study is that we did not include memory CD4^+^ cytokine expressing cells. Since we observed a decrease in pro-inflammatory cytokine expressing CD4^+^ cells it is still possible that this reduction is due to the reduction of memory CD4^+^ cells observed in the follow-up study. Furthermore, it would have been interesting to assess CD8^+^ cytokine expressing T cells. The direct effect of DMF on B cells was studied in more detail. Gillard et al. demonstrated that DMF and MMF are active between 5.5 and 50 µM and 50 and 150 µM, respectively. Therefore, DMF was used at different concentrations between 10 µM and 50 µM, while 50 µM of MMF was used^[@CR37]^. DMF induced concentration-dependent B cell apoptosis in HC and untreated RRMS patients starting from a concentration of 25 µM DMF. As MMF did not have an effect on B cell apoptosis, DMF is responsible for the full effect on the reduction of B cell numbers. Although DMF could not be detected in serum of HC, a degree of systemic penetrance of DMF has been reported with DMF-glutathione conjugates found in urine of DMF-treated psoriasis patients^[@CR38]^. Furthermore, Litjens et al. demonstrated that DMF could be taken up by lymphocytes and monocytes^[@CR39]^. Due to the fact that the exact concentration of DMF in the circulation or in immune cells of RRMS patients is not known and cannot be determined exactly, it is important to investigate the direct effects of DMF on B cells in low concentrations in vitro. Since Blewett et al. demonstrated that DMF directly interacts with cysteine residues of T cells in concentrations between 10 and 50 µM and that this is mechanistically relevant to the immunosuppressive activity of the drug and since we have demonstrated that no apoptosis is induced in concentrations below 25 µM, we examined whether DMF also exerted a direct effect on functional markers of B cells at a concentration of 10 µM^[@CR40]^. In this study, we demonstrated that DMF directly decreased B cell expression of antigen presentation HLA-DR/DP/DQ and costimulatory molecule CD40. This could lead to reduced T cell activation, since B cells are critical antigen presenting cells in MS that can stimulate T cell proliferation to foreign or neuro-antigens^[@CR4]^. Previous reports demonstrated increased CD40 ligand on MS T cells and hyper-responsiveness of MS memory B cells to CD40 stimulation^[@CR41],[@CR42]^. Therefore, we suggest that the decreased B cell CD40 expression induced by DMF will result in disrupted B cell activation and thus B cell mediated pathology. Furthermore, these results could explain the decrease in memory T cells and reduced T cell proliferation and activation following DMF treatment^[@CR23],[@CR27],[@CR31],[@CR32],[@CR43]^. DMF directly reduced B cell expression of the survival marker BAFFR. However, BAFF serum levels were unchanged and B cell BAFFR expression was increased in the follow-up study. The latter effect could be due to increased transitional and naive B cells after DMF treatment. BAFF has been described to play a dual role in MS pathology including both pathological effects^[@CR44]^ and positive effects on treatment outcome and detrimental effects of BAFF antagonists^[@CR45]^. Interestingly, BAFFR expression was increased on B cells of untreated MS patients compared to HC. An increased BAFFR mRNA level was previously demonstrated in MS patients^[@CR46]^. BAFF is important for maintaining antibody-producing plasma cells and the direct effect of DMF on BAFFR expression could be beneficial for MS pathogenesis. In conclusion, this study shows that DMF treatment persistently changes the immune balance of MS patients and illustrates the multifactorial working mechanism of DMF. The effects of DMF elucidated here could help explain its therapeutic efficacy in MS. Methods {#Sec11} ======= Study subjects {#Sec12} -------------- RRMS patients and healthy controls (HC) were recruited at the Zuyderland Medical Center (Sittard, The Netherlands), Rehabilitation & MS-Center (Overpelt, Belgium) and Biomedical Research Institute (Diepenbeek, Belgium). All experimental protocols and methods were conducted in accordance with institutional guidelines and regulations and was approved by the institutes' ethics committees (METC14-T-96, 15.143/neuro15.12) and all study subjects gave written informed consent. For the follow-up study, peripheral blood was collected before, after 3 m and 12 m of DMF treatment. Clinical outcome measures including the Expanded Disability Status Scale (EDSS) and the Fatigue Scale for Motor and Cognitive Functions (FSMC) were analyzed. Furthermore, the timed 25-foot walk (T25FW), the Paced Auditory Serial Addition Test (PASAT-3″) and the Nine Hole Peg test (NHPT) were analyzed according to the Multiple Sclerosis Functional Composite (MSFC). All samples were stored in the University Biobank Limburg. Further clinical details and numbers of MS patients and HC are provided in Table [1](#Tab1){ref-type="table"}. In all analyses, HC were matched to MS patients as closely as possible with regard to age and sex. Cell isolation {#Sec13} -------------- Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by Ficoll density gradient centrifugation (Lympholyte, Cedarlane Laboratories, Uden, The Netherlands). PBMC of MS patients and HC were cryopreserved and thawed before use, unless stated otherwise. PBMC collected at different time points during the follow-up study were simultaneously thawed to exclude inter-assay variation. PBMC were cryopreserved in 10% dimethyl sulfoxide (DMSO, Sigma Aldrich, Overijse, Belgium) and fetal bovine serum (FBS, Life Technologies, Gent, Belgium) using a slow temperature-lowering method (Coolcell®, VWR, Haasrode, Belgium). After 24 h, cryovials were transferred to liquid N~2~ until analysis. PBMC were thawed by bringing the temperature of the cryovials to 0 °C in a water bath (37 °C). Hereafter, cold thawing medium consisting of 20% FBS in RPMI 1640 (Lonza, Basel, Switzerland) was added and PBMC were centrifuged at 4 °C. PBMC were suspended in thawing medium in a concentration of 10 × 10^6^ cells/1000 µl containing DNAse (1/100) and incubated at 37 °C for 10 minutes. Subsequently, cells were washed twice. Median cell recovery was 76 ± 18%. B cells were purified from freshly isolated PBMC by negative magnetic selection (STEMCELL Technologies SARL, Grenoble, France). Purity of B cells was routinely ≥98.4%. Flow cytometry {#Sec14} -------------- In the follow-up study, PBMC were stained with anti-human CD14 PerCP, CD16 FITC, CD56 PE-Cy7 (BD Biosciences, Erembodegem, Belgium) and CD3 APC-Cy7 (BioLegend, Antwerp, Belgium). B cell subtypes were analyzed using anti-human CD19 PE-Cy7, immunoglobulin (Ig)M PerCP-Cy5.5 (BioLegend), CD27 APC, IgD PE-CF594, IgG FITC (BD Biosciences), CD38 APC-ef780 (eBioscience, San Diego, USA) and IgA PE (Miltenyi Biotec, Leiden, The Netherlands). T cell subtypes were analyzed with anti-human CD4 APC (BioLegend), CD45RA APC-ef780, CD127 PE, CD25 PE-Cy7 (eBioscience), CD45RO PE-CF594, CD8 FITC and CCR7 PerCP-Cy5.5 (BD Biosciences). Expression of B-cell activating factor receptor (BAFFR) on B cells was assessed using CD19 PE-Cy7, CD268 APC-Cy7 (BAFFR) (BioLegend). For intracellular T cell cytokine analysis, PBMC were stimulated with phorbol 12-myristate 13-acetate (PMA, 50 ng/ml) and calcium ionomycin (1 µg/ml, Sigma-Aldrich, Overijse Belgium) in the presence of Golgistop (BD Biosciences) for 4 h. PBMC were fixed and permeabilized using Cytofix/Cytoperm (BD Biosciences) and stained with anti-human IL-10 PE-Cy7, GM-CSF APC, CD4 PE-Cy5 (BioLegend), IL-4 PE, IL-17 FITC (eBioscience) and IFN-γ PE-CF594 (BD Biosciences). Freshly isolated PBMC were analyzed in the cross-sectional study using anti-human CD4 APC, CD8 PE, CD45RO (BD Biosciences). Apoptosis and BAFFR expression of in vitro cultured B cells was measured using anti-human CD19 PE-Cy7, CD268 APC-Cy7 (BioLegend), CD27 APC, IgG PE, IgD PE-CF594 (BD Biosciences), annexin V FITC and 7-AAD (eBioscience). Expression of costimulatory and antigen presentation molecules was assessed using anti-human CD19 PerCP-Cy5.5, CD27 APC, CD80 PE, CD86 PE-CF594, HLA-DR/DP/DQ FITC (BD Biosciences) and CD40 PE-Cy7 (eBioscience). When analyzing frequency of Breg and pro-inflammatory B cells, B cells were restimulated during the last 4 h with PMA (50 ng/ml) and calcium ionomycin (1 µg/ml, both Sigma-Aldrich) in the presence of GolgiStop (BD Biosciences). Fixation and permeabilization were done using Cytofix/Cytoperm (BD Biosciences). The antibodies used were anti-human CD19 BV421, CD24 PE-Cy7, IL-10 Brilliant Violet 711 (all from BD Biosciences), CD38 APC-ef780, Fixable Viability Dye-eFluor506 (all from eBioscience) and TNF-α PerCP-Cy5.5 (BioLegend). All flow cytometry was performed on a FACSAria II or LSRFortessa flow cytometer using FACSDiva software (BD Biosciences). Absolute numbers of leukocytes, lymphocytes, monocytes and neutrophils were obtained from standard clinical lab tests for 7 DMF-treated MS patients. Absolute numbers of lymphocyte subtype populations were calculated as follows: absolute lymphocyte number (10^9^/l) × percentage of lymphocyte subtype population × 10. In vitro B cell cultures {#Sec15} -------------------------- B cells were cultured in 96-well round-bottom plates (Greiner Bio-One B.V., Alphen aan den Rijn, The Netherlands) at 3 × 10^5^ cells in RPMI 1640 (Lonza, Basel, Switzerland) with 10% fetal bovine serum (FBS, Life Technologies, Gent, Belgium), 50 U/ml penicillin, 50 mg/ml streptomycin (Invitrogen, Carlsbad, CA), 0.1 mM nonessential amino acids and 1 mM sodium pyruvate (Sigma-Aldrich). For analysis of B cell apoptosis, survival marker and expression of costimulatory and antigen presentation molecules, B cells were treated during 24 h with DMF (10 µM--50 µM), MMF (50 µM) or were left untreated (DMSO). After 1 h, B cells were stimulated with 2 µg/ml CpG2006 (ODN2006, Invivogen, Toulouse, France) for the following 23 h. When measuring the frequency of Breg and pro-inflammatory B cells, purified B cells were treated during 48 h with DMF (10 µM), MMF (50 µM) or were left untreated in the presence of 1 µg/ml soluble CD40 ligand together with 2 µg/ml CpG2006. ELISA {#Sec16} ----- BAFF plasma levels were quantified before and after 12 m of DMF treatment using a commercial ELISA kit according to the manufacturer's protocol (R&D systems, Abingdon, United Kingdom). Statistics {#Sec17} ---------- Statistical analyses were performed using Graphpad Prism 6. Wilcoxon matched-pairs signed rank test was used for comparison of variables at baseline and follow-up and for comparing cells with or without DMF treatment (in vitro). When comparing multiple groups, one-way ANOVA (Kruskal-Wallis) was used. A p value less than 0.05 was considered statistically significant. Electronic supplementary material ================================= {#Sec18} Supplementary information Electronic supplementary material Supplementary information accompanies this paper at 10.1038/s41598-018-26519-w. Publisher\'s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We thank Igna Rutten and Kim Ulenaers (Hasselt University, Biomedical Research Institute and UBilim), Rehabilitation & MS Center (Overpelt), Sandra Liedekerken, Tiny Kempkens, Judith Poeth, Lianne van Gennip and all MS nurses at Zuyderland Medisch Centrum (Sittard) for patient recruitment and sample collection. We thank prof. dr. Niels Hellings for critical reading. This work was supported by Hasselt University and Maastricht University. Funding was provided via an investigator-initiated trial grant from Biogen. J. Fraussen is a postdoctoral fellow of the Fund for Scientific Research, Flanders. Conceived and designed the experiments: G.M.D., J.F., V.S. Performed the experiments and analyzed the data: G.M.D. Contributed reagents/materials/analysis tools: R.H., B.V.W. Wrote the paper: G.M.D., J.F., B.V.W., R.H., V.S. Competing Interests {#FPar1} =================== The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: G.M.D., J.F., V.S.: nothing to disclose; B.V.W.: received Research and Travel Grants, Honoraria for MS-Expert Advise and Speakers Fees from Bayer-Schering, Biogen, Sanofi Genzyme, Merck-Serono, Novartis, Roche and TEVA; R.H.: received research grants and honoraria for advisory boards from BIOGEN, Merck and Sanofi-Genzyme.
/* * Licensed to the Apache Software Foundation (ASF) under one or more * contributor license agreements. See the NOTICE file distributed with * this work for additional information regarding copyright ownership. * The ASF licenses this file to You under the Apache License, Version 2.0 * (the "License"); you may not use this file except in compliance with * the License. You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. */ package tests.support; public class Support_TestResource_fr_FR_VAR extends java.util.ListResourceBundle { @Override protected Object[][] getContents() { Object[][] contents = { { "parent4", "frFRVARValue4" }, { "child1", "frFRVARChildValue1" }, { "child2", "frFRVARChildValue2" }, { "child3", "frFRVARChildValue3" }, }; return contents; } }
Q: Primefaces file uploader doesn't call the handler method I have a problem with primefaces file uploader, when the uploading finish the handler method in the fileUploadListener doesn't called i placed a break point in the method start and the execution proceeds normally as it's not exists, there are no exceptions occurred: this is my file uploader: <h:form enctype="multipart/form-data"> <p:fileUpload fileUploadListener="#{fileUploadController.handleFileUpload}" mode="advanced" update="messages" sizeLimit="100000" allowTypes="/(\.\|\/)(gif\|jpe?g\|png)$/" <h:message style="color:red;margin:8px;"/> <p:growl id="messages" showDetail="true" /> </h:form> and this is the handler: @ManagedBean(name="fileUploadController") @SessionScoped public class FileUploadController { public void handleFileUpload(FileUploadEvent event) { FacesMessage msg = new FacesMessage("Succesful", event.getFile().getFileName() + " is uploaded."); FacesContext.getCurrentInstance().addMessage(null, msg); } } web.xml <?xml version="1.0" encoding="UTF-8"?> <web-app xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://java.sun.com/xml/ns/javaee" xmlns:web="http://java.sun.com/xml/ns/javaee/web-app_2_5.xsd" xsi:schemaLocation="http://java.sun.com/xml/ns/javaee http://java.sun.com/xml/ns/javaee/web-app_3_0.xsd" id="WebApp_ID" version="3.0"> <display-name>Ga</display-name> <welcome-file-list> <welcome-file>pages/HomePage.jsf</welcome-file> </welcome-file-list> <filter> <filter-name>PrimeFaces FileUpload Filter</filter-name> <filter-class>org.primefaces.webapp.filter.FileUploadFilter</filter-class> </filter> <filter-mapping> <filter-name>PrimeFaces FileUpload Filter</filter-name> <servlet-name>Faces Servlet</servlet-name> </filter-mapping> <filter-mapping> <filter-name>PrimeFaces FileUpload Filter</filter-name> <servlet-name>Faces Servlet</servlet-name> </filter-mapping> <servlet> <servlet-name>Faces Servlet</servlet-name> <servlet-class>javax.faces.webapp.FacesServlet</servlet-class> <load-on-startup>1</load-on-startup> </servlet> <servlet-mapping> <servlet-name>Faces Servlet</servlet-name> <url-pattern>*.jsf</url-pattern> </servlet-mapping> <context-param> <description>State saving method: 'client' or 'server' (=default). See JSF Specification 2.5.2</description> <param-name>javax.faces.STATE_SAVING_METHOD</param-name> <param-value>client</param-value> </context-param> <context-param> <param-name>javax.servlet.jsp.jstl.fmt.localizationContext</param-name> <param-value>resources.application</param-value> </context-param> <listener> <listener-class>com.sun.faces.config.ConfigureListener</listener-class> </listener> A: You should add the following filter to the web.xml : <filter> <filter-name>PrimeFaces FileUpload Filter</filter-name> <filter-class>org.primefaces.webapp.filter.FileUploadFilter</filter-class> </filter> <filter-mapping> <filter-name>PrimeFaces FileUpload Filter</filter-name> <servlet-name>Faces Servlet</servlet-name> </filter-mapping> EDIT1 : Also this question can be helpful ;) EDIT2 : Dear friend please eliminate one of the filter mapping in your web.xml, it's duplicated.
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589568 0 0 ( 2 22 -128 ) ( 5 26.5 -128 ) ( 2 22 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 5 26.5 -128 ) ( 9.5 29.5 -128 ) ( 5 26.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 9.5 29.5 -128 ) ( 16 31 -128 ) ( 9.5 29.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 16 31 -128 ) ( 22 29.5 -128 ) ( 16 31 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 22 29.5 -128 ) ( 26.5 26.5 -128 ) ( 22 29.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 26.5 26.5 -128 ) ( 29.5 22 -128 ) ( 26.5 26.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 29.5 22 -128 ) ( 31 16 -128 ) ( 29.5 22 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 31 16 -128 ) ( 30 11 -128 ) ( 31 16 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 30 11 -128 ) ( 26.5 5.5 -128 ) ( 30 11 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 26.5 5.5 -128 ) ( 22 2.5 -128 ) ( 26.5 5.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 22 2.5 -128 ) ( 16 1 -128 ) ( 22 2.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 16 1 -128 ) ( 10.5 2 -128 ) ( 16 1 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 10.5 2 -128 ) ( 5 5.5 -128 ) ( 10.5 2 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 5 5.5 -128 ) ( 2 10 -128 ) ( 5 5.5 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 ( 2 10 -128 ) ( 0.5 16 -128 ) ( 2 10 0 ) tex_common/lightclip 0 0 0 0.25 0.25 589568 0 0 } } // entity 3 { "classname" "func_group" // brush 0 { ( 25 6 10 ) ( 25 26 10 ) ( 5 26 10 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 4 26 37 ) ( 24 26 37 ) ( 24 6 37 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 25 16 24 ) ( 25 16 4 ) ( 25 6 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 24 12 24 ) ( 24 12 4 ) ( 20 3 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 9 24 ) ( 22 9 4 ) ( 15 2 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 19 7 24 ) ( 19 7 4 ) ( 10 3 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 15 6 24 ) ( 15 6 4 ) ( 5 6 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 11 7 24 ) ( 11 7 4 ) ( 2 11 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 9 24 ) ( 8 9 4 ) ( 1 16 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 12 24 ) ( 6 12 4 ) ( 2 21 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 16 24 ) ( 5 16 4 ) ( 5 26 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 20 24 ) ( 6 20 4 ) ( 10 29 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 23 24 ) ( 8 23 4 ) ( 15 30 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 11 25 24 ) ( 11 25 4 ) ( 20 29 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 15 26 24 ) ( 15 26 4 ) ( 25 26 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 19 25 24 ) ( 19 25 4 ) ( 28 21 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 23 24 ) ( 22 23 4 ) ( 29 16 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 24 20 24 ) ( 24 20 4 ) ( 28 11 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 1 { ( 35 32 11 ) ( 35 0 11 ) ( 3 32 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0 0 4 ) ( 32 0 4 ) ( 0 32 4 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0.5 16 -128 ) ( 2 22 -128 ) ( 0.5 16 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 22 -128 ) ( 5 26.5 -128 ) ( 2 22 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 26.5 -127.5 ) ( 9.5 29.5 -127.5 ) ( 5 26.5 0.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 9.5 29.5 -127.5 ) ( 16 31 -127.5 ) ( 9.5 29.5 0.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 31 -128 ) ( 22 29.5 -128 ) ( 16 31 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 29.5 -128 ) ( 26.5 26.5 -128 ) ( 22 29.5 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 26.5 -128 ) ( 29.5 22 -128 ) ( 26.5 26.5 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 29.5 22 -128 ) ( 31 16 -128 ) ( 29.5 22 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 31 16 -128 ) ( 30 11 -128 ) ( 31 16 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 30 11 -128 ) ( 26.5 5.5 -128 ) ( 30 11 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 5.5 -128 ) ( 22 2.5 -128 ) ( 26.5 5.5 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 2.5 -128 ) ( 16 1 -128 ) ( 22 2.5 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 1 -127.5 ) ( 10.5 2 -127.5 ) ( 16 1 0.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 10.5 2 -127.5 ) ( 5 5.5 -127.5 ) ( 10.5 2 0.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 5.5 -128 ) ( 2 10 -128 ) ( 5 5.5 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 10 -128 ) ( 0.5 16 -128 ) ( 2 10 0 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 2 { ( 5 18 36 ) ( 5 16 36 ) ( 3 18 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 17 20 ) ( 3 17 20 ) ( 5 17 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 17 20 ) ( 5 17 17 ) ( 5 15 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 3 15 11 ) ( 5 15 11 ) ( 3 17 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 3 15 18 ) ( 3 15 21 ) ( 5 15 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 3 15 17 ) ( 3 17 17 ) ( 3 15 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 3 { ( 8 26 36 ) ( 8 24 36 ) ( 6 26 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 25 20 ) ( 6 25 20 ) ( 8 25 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 25 20 ) ( 8 25 17 ) ( 8 23 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 23 11 ) ( 8 23 11 ) ( 6 25 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 23 18 ) ( 6 23 21 ) ( 8 23 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 23 17 ) ( 6 25 17 ) ( 6 23 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 4 { ( 8 9 36 ) ( 8 7 36 ) ( 6 9 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 8 20 ) ( 6 8 20 ) ( 8 8 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 8 8 20 ) ( 8 8 17 ) ( 8 6 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 6 11 ) ( 8 6 11 ) ( 6 8 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 6 18 ) ( 6 6 21 ) ( 8 6 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 6 6 17 ) ( 6 8 17 ) ( 6 6 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 5 { ( 16 30 36 ) ( 16 28 36 ) ( 14 30 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 29 20 ) ( 14 29 20 ) ( 16 29 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 29 20 ) ( 16 29 17 ) ( 16 27 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 27 11 ) ( 16 27 11 ) ( 14 29 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 27 18 ) ( 14 27 21 ) ( 16 27 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 27 17 ) ( 14 29 17 ) ( 14 27 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 6 { ( 25 26 36 ) ( 25 24 36 ) ( 23 26 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 25 25 20 ) ( 23 25 20 ) ( 25 25 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 25 25 20 ) ( 25 25 17 ) ( 25 23 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 23 11 ) ( 25 23 11 ) ( 23 25 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 23 18 ) ( 23 23 21 ) ( 25 23 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 23 17 ) ( 23 25 17 ) ( 23 23 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 7 { ( 28 18 36 ) ( 28 16 36 ) ( 26 18 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 28 17 20 ) ( 26 17 20 ) ( 28 17 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 28 17 20 ) ( 28 17 17 ) ( 28 15 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26 15 11 ) ( 28 15 11 ) ( 26 17 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26 15 18 ) ( 26 15 21 ) ( 28 15 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26 15 17 ) ( 26 17 17 ) ( 26 15 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 8 { ( 25 10 36 ) ( 25 8 36 ) ( 23 10 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 25 9 20 ) ( 23 9 20 ) ( 25 9 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 25 9 20 ) ( 25 9 17 ) ( 25 7 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 7 11 ) ( 25 7 11 ) ( 23 9 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 7 18 ) ( 23 7 21 ) ( 25 7 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 23 7 17 ) ( 23 9 17 ) ( 23 7 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 9 { ( 16 6 36 ) ( 16 4 36 ) ( 14 6 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 5 20 ) ( 14 5 20 ) ( 16 5 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 5 20 ) ( 16 5 17 ) ( 16 3 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 3 11 ) ( 16 3 11 ) ( 14 5 11 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 3 18 ) ( 14 3 21 ) ( 16 3 18 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 14 3 17 ) ( 14 5 17 ) ( 14 3 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 10 { ( 35 32 31 ) ( 35 0 31 ) ( 3 32 31 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0 0 27 ) ( 32 0 27 ) ( 0 32 27 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0.5 16 -105 ) ( 2 22 -105 ) ( 0.5 16 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 22 -104.5 ) ( 5 26.5 -104.5 ) ( 2 22 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 26.5 -104.5 ) ( 9.5 29.5 -104.5 ) ( 5 26.5 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 9.5 29.5 -104.5 ) ( 16 31 -104.5 ) ( 9.5 29.5 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 31 -108 ) ( 22 29.5 -108 ) ( 16 31 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 29.5 -105 ) ( 26.5 26.5 -105 ) ( 22 29.5 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 26.5 -105 ) ( 29.5 22 -105 ) ( 26.5 26.5 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 29.5 22 -105 ) ( 31 16 -105 ) ( 29.5 22 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 31 16 -105 ) ( 30 11 -105 ) ( 31 16 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 30 11 -105 ) ( 26.5 5.5 -105 ) ( 30 11 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 5.5 -105 ) ( 22 2.5 -105 ) ( 26.5 5.5 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 2.5 -108 ) ( 16 1 -108 ) ( 22 2.5 20 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 1 -104.5 ) ( 10.5 2 -104.5 ) ( 16 1 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 10.5 2 -104.5 ) ( 5 5.5 -104.5 ) ( 10.5 2 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 5.5 -104.5 ) ( 2 10 -104.5 ) ( 5 5.5 23.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 10 -105 ) ( 0.5 16 -105 ) ( 2 10 23 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 11 { ( 35 32 43 ) ( 35 0 43 ) ( 3 32 43 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0 0 36 ) ( 32 0 36 ) ( 0 32 36 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0.5 16 -96 ) ( 2 22 -96 ) ( 0.5 16 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 22 -95.5 ) ( 5 26.5 -95.5 ) ( 2 22 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 26.5 -95.5 ) ( 9.5 29.5 -95.5 ) ( 5 26.5 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 9.5 29.5 -95.5 ) ( 16 31 -95.5 ) ( 9.5 29.5 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 31 -96 ) ( 22 29.5 -96 ) ( 16 31 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 29.5 -96 ) ( 26.5 26.5 -96 ) ( 22 29.5 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 26.5 -96 ) ( 29.5 22 -96 ) ( 26.5 26.5 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 29.5 22 -96 ) ( 31 16 -96 ) ( 29.5 22 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 31 16 -96 ) ( 30 11 -96 ) ( 31 16 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 30 11 -96 ) ( 26.5 5.5 -96 ) ( 30 11 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 5.5 -96 ) ( 22 2.5 -96 ) ( 26.5 5.5 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 2.5 -96 ) ( 16 1 -96 ) ( 22 2.5 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 1 -95.5 ) ( 10.5 2 -95.5 ) ( 16 1 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 10.5 2 -95.5 ) ( 5 5.5 -95.5 ) ( 10.5 2 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 5.5 -95.5 ) ( 2 10 -95.5 ) ( 5 5.5 32.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 10 -96 ) ( 0.5 16 -96 ) ( 2 10 32 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } // brush 12 { ( 35 32 21 ) ( 35 0 21 ) ( 3 32 21 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0 0 17 ) ( 32 0 17 ) ( 0 32 17 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 0.5 16 -115 ) ( 2 22 -115 ) ( 0.5 16 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 22 -114.5 ) ( 5 26.5 -114.5 ) ( 2 22 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 26.5 -114.5 ) ( 9.5 29.5 -114.5 ) ( 5 26.5 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 9.5 29.5 -114.5 ) ( 16 31 -114.5 ) ( 9.5 29.5 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 31 -118 ) ( 22 29.5 -118 ) ( 16 31 10 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 29.5 -115 ) ( 26.5 26.5 -115 ) ( 22 29.5 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 26.5 -115 ) ( 29.5 22 -115 ) ( 26.5 26.5 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 29.5 22 -115 ) ( 31 16 -115 ) ( 29.5 22 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 31 16 -115 ) ( 30 11 -115 ) ( 31 16 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 30 11 -115 ) ( 26.5 5.5 -115 ) ( 30 11 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 26.5 5.5 -115 ) ( 22 2.5 -115 ) ( 26.5 5.5 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 22 2.5 -118 ) ( 16 1 -118 ) ( 22 2.5 10 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 16 1 -114.5 ) ( 10.5 2 -114.5 ) ( 16 1 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 10.5 2 -114.5 ) ( 5 5.5 -114.5 ) ( 10.5 2 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 5 5.5 -114.5 ) ( 2 10 -114.5 ) ( 5 5.5 13.5 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 ( 2 10 -115 ) ( 0.5 16 -115 ) ( 2 10 13 ) tex_common/nodraw 0 0 0 0.25 0.25 0 128 0 } }
Interbroker ICAP, has released electronic trading volume figures for the month of June. Among all of its platforms, averaged daily volumes (ADV) were $731.1B, a 14% decline from the same period last year, but up 6% from May. In FX, trading on the EBS platform showed slight improvement from May, rising 5% to $77B ADV. The figures though were well below 2013, having declined by 40% since the same period last year, even as volumes now include activity from ICAP’s relationship-based liquidity platform, EBS Direct. Volumes last year were assisted by strength in Japanese yen activity, which had been the most volatile major currency for the first half of 2013. Known as an FX spot venue ‘of last resort’ for the yen, due to the platform’s deep liquidity, EBS briefly halted its multi-year downtrend in volumes growth in the H1 2013. However, with yen volatility having dipped over the past 12 months, it has affected EBS activity negatively. Suggested articles Looking ahead, volume figures are expected to be released soon from Thomson Reuters. Like EBS, Thomson Reuters has seen a decline in activity on its FX matching platform, having been surpassed by its FXall unit which includes both ECN and relationship pricing. However, like EBS, the Thomson Reuters platform dominates ECNs for several currencies, including the British pound and Chinese yuan where they provide leading pools of liquidity depth. As such, after pound volumes led CME activity higher in June, Thomson Reuters may also have experienced a sharp increase in volumes for the month thanks to the currency.
Sussex Taps Product Catalog Water is one of our most fundamental needs. But at Sussex we believe the tap that conveys it should satisfy our appetite for aesthetic perfection. Each Sussex tap is therefore an exquisite object, finely honed by the artisans in our Melbourne workshop to express your individual tastes. The result is a classic piece that brings you pleasure each time you experience its timeless beauty. The journey from a solid block of recycled brass to precision-crafted masterpiece is a slow and careful one. Each component passes through the knowing hands of a seasoned craftsman and beneath the watchful eye of an exacting quality evaluator. Only the most perfect work leaves our workshop bearing the Sussex signature of approval.
News Takeover Rumors Send Delia’s (DLIA) Stock Soaring The teenage girl-targeted mall clothing chain Delia’s (DLIA) saw shares jump more than 35 percent at one point after receiving several unspecified takeover offers. While details on any deal remain vague, any massive change in leadership for this troubled company in a troubled industry is being welcomed by the market. Delia’s has struggled alongside most mall retailers, as more and more shoppers migrate online, and the brick-and-mortar stalwarts like Delia’s struggle to adapt. While this is not to say Delia’s online presence is non-existent; it is limited, especially compared to behemoths like Amazon (AMZN) . Delia’s is much like comparable niche retailers who saw business boom in the 90s, only to watch that business evaporate as mall shopping culture continued to go the way of the dodo. Compatriots like Abercrombie and Fitch (ANF) have likewise struggled, as numbers continue to stagnate while their online-focused brethren surge. But Delia’s is perhaps the worst of the lot: their Q1 earnings report showed an astounding comparable store sales drop-off of 23.8 percent. A&F does not find themselves in nearly the same situation as Delia’s, whose stock has languished well under a dollar a share for most of 2014. Internal turnaround efforts have so far failed to right the ship, and the company risked going insolvent unless a drastic change was to take place. What change? That has, and continues to so far be, unclear. But in many cases, the market responds enthusiastically to any change in leadership, like the mere mention that former Microsoft CEO Steve Ballmer was stepping down that sent shares of the tech giant soaring. In tis case, it’s the mere fact that somebody, no matter who, is going to take the Delia’s brand and do something with it besides lose money. Delia’s has been scrambling, replacing their CFO in June in a bid to mitigate their rapid decline and possible delistment from the NYSE. The plans for Delia’s remain murky. Even if a buyout will indeed take place is far from certain. But the possibility of any change to stop the plunging of a stock that has lost 72 percent of its value in 2014 look to be more than enough to get investors excited, or at least to believe that Delia’s isn’t completely down yet. DISCLOSURE: The views and opinions expressed in this article are those of the authors, and do not represent the views of equities.com. Readers should not consider statements made by the author as formal recommendations and should consult their financial advisor before making any investment decisions. To read our full disclosure, please go to: http://www.equities.com/disclaimer
Q: Apache access logs request I'm seeing some requests for "GET / HTTP/1.1" and they're showing a 200 result-- is this the root of the vhost, or the web root?? Thanks! A: GET / is a request for the vHost (website) root, for example https://serverfault.com/ A 200 response indicates success.
Yes, the news broke this week that President Trump asked an aide to look into whether the U.S. could purchase Greenland—a country that is literally melting—and on Sunday night, comedian John Oliver had a field day with the news. “Yeah, of course he fucking did. Of course he did,” offered Oliver on Last Week Tonight. “Greenland is icy, distant, and semi-autonomous—it’s exactly Trump’s type,” he added, before throwing to a picture of the president’s third wife, Melania Trump. “Now, speculation on Trump’s comments rose to such a point this week that Greenland’s premier had to issue a statement saying, ‘Greenland is not for sale,’” the HBO host continued, “so, if you had 2 1/2 years in your office pool of ‘when a world leader would have to tell Trump you can’t buy our country,’ congratulations, you’re a big winner.” Later on, Oliver took issue with Trump’s idiotic response to the ongoing protests in Hong Kong over an extradition bill that could strip the people of their autonomy. “Trump not only barely seems aware of what’s going on there, he also essentially gave China a green light to do whatever they want,” Oliver said. He then played a clip of Trump breaking down the protests: “Well, something’s probably happening with Hong Kong… because when you look at, you know, what’s going on, they’ve had riots for a long period of time, and I don’t know what China’s attitude is,” Trump said. “Somebody said that at some point they’re going to want to stop that, but that’s between Hong Kong and that’s between China, because Hong Kong is a part of China.” Hong Kong is a part of China. Brilliant stuff. “I will say this: ‘They’re gonna want to stop that’ is exactly the wrong message to send to China right now,” Oliver argued. “Trump effectively giving China a tacit endorsement to use force against protesters is unfortunately not remotely surprising—he sends the wrong signals to other countries all the time. And until his term ends, we’re all just going to have to live with the fact that we now have a president who looks at America’s allies and says, ‘Go fuck yourselves’; looks at Russia’s interference in our election and says, ‘No big deal’; and looks at Greenland and says, ‘Two hundred dollars and Don Jr.—final offer.’”
The vagus nerve slow heart rate in part by activating a cardiac potassium (K+) channel, I/KACH- Activated muscarinic receptors release the G protein Gbetagamma dimer which dramatically increases channel activity by up to 1,000-fold. We showed that I/KACH was composed of two distinct inwardly rectifying K+ channel subunits, KIRK1 (Kir3.1) and GIRK4 (KIR 3.4). In this proposal we outline the experiments that over the next five years will reveal the assembly expression, and stabilization of the cardiac I/KACh channel. First, we will use a combination of electrophysiology, biochemistry, and molecular biology to study how the GIRK1/GIRK4 subunits assembly and determine proteins associating with the final complex. In particular we are interested in how a particular receptor maintains its specificity of activation of the channel. Second, evidence indicates that key lipids are important to the regulation and stability of the final channel complex once it has reached the plasma membrane. We will refine our understanding of the role of Gbetagamma and phosphatidylinositols in the regulation of the functional GIRK1/GIRK4 complex. Finally, we will characterize the promoters of GIRK channel subunits in preparation for defining transcriptional control of their expression. One major question is why IKACh is preferentially expressed in pacing tissues and atria, but not ventricle. If we can understand the details of expression, assembly, and regulation of this channel, it may someday be possible to selectively express and activate it in order to terminate firing of excitable cells in arrhythmias.
/* * Copyright (c) 2004 Topspin Communications. All rights reserved. * Copyright (c) 2005 Voltaire, Inc. All rights reserved. * Copyright (c) 2005 Sun Microsystems, Inc. All rights reserved. * Copyright (c) 2008 Cisco. All rights reserved. * * This software is available to you under a choice of one of two * licenses. You may choose to be licensed under the terms of the GNU * General Public License (GPL) Version 2, available from the file * COPYING in the main directory of this source tree, or the * OpenIB.org BSD license below: * * Redistribution and use in source and binary forms, with or * without modification, are permitted provided that the following * conditions are met: * * - Redistributions of source code must retain the above * copyright notice, this list of conditions and the following * disclaimer. * * - Redistributions in binary form must reproduce the above * copyright notice, this list of conditions and the following * disclaimer in the documentation and/or other materials * provided with the distribution. * * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, * EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF * MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND * NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS * BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN * ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN * CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE * SOFTWARE. / #define pr_fmt(fmt) "user_mad: " fmt #include <linux/module.h> #include <linux/init.h> #include <linux/device.h> #include <linux/err.h> #include <linux/fs.h> #include <linux/cdev.h> #include <linux/dma-mapping.h> #include <linux/poll.h> #include <linux/mutex.h> #include <linux/kref.h> #include <linux/compat.h> #include <linux/sched.h> #include <linux/semaphore.h> #include <linux/slab.h> #include <asm/uaccess.h> #include <rdma/ib_mad.h> #include <rdma/ib_user_mad.h> MODULE_AUTHOR("Roland Dreier"); MODULE_DESCRIPTION("InfiniBand userspace MAD packet access"); MODULE_LICENSE("Dual BSD/GPL"); enum { IB_UMAD_MAX_PORTS = 64, IB_UMAD_MAX_AGENTS = 32, IB_UMAD_MAJOR = 231, IB_UMAD_MINOR_BASE = 0 }; / * Our lifetime rules for these structs are the following: * device special file is opened, we take a reference on the * ib_umad_port's struct ib_umad_device. We drop these * references in the corresponding close(). * * In addition to references coming from open character devices, there * is one more reference to each ib_umad_device representing the * module's reference taken when allocating the ib_umad_device in * ib_umad_add_one(). * * When destroying an ib_umad_device, we drop the module's reference. / struct ib_umad_port { struct cdev cdev; struct device dev; struct cdev sm_cdev; struct device sm_dev; struct semaphore sm_sem; struct mutex file_mutex; struct list_head file_list; struct ib_device ib_dev; struct ib_umad_device umad_dev; int dev_num; u8 port_num; }; struct ib_umad_device { int start_port, end_port; struct kobject kobj; struct ib_umad_port port[0]; }; struct ib_umad_file { struct mutex mutex; struct ib_umad_port port; struct list_head recv_list; struct list_head send_list; struct list_head port_list; spinlock_t send_lock; wait_queue_head_t recv_wait; struct ib_mad_agent agent[IB_UMAD_MAX_AGENTS]; int agents_dead; u8 use_pkey_index; u8 already_used; }; struct ib_umad_packet { struct ib_mad_send_buf msg; struct ib_mad_recv_wc recv_wc; struct list_head list; int length; struct ib_user_mad mad; }; static struct class umad_class; static const dev_t base_dev = MKDEV(IB_UMAD_MAJOR, IB_UMAD_MINOR_BASE); static DEFINE_SPINLOCK(port_lock); static DECLARE_BITMAP(dev_map, IB_UMAD_MAX_PORTS); static void ib_umad_add_one(struct ib_device device); static void ib_umad_remove_one(struct ib_device device); static void ib_umad_release_dev(struct kobject kobj) { struct ib_umad_device dev = container_of(kobj, struct ib_umad_device, kobj); kfree(dev); } static struct kobj_type ib_umad_dev_ktype = { .release = ib_umad_release_dev, }; static int hdr_size(struct ib_umad_file file) { return file->use_pkey_index ? sizeof (struct ib_user_mad_hdr) : sizeof (struct ib_user_mad_hdr_old); } / caller must hold file->mutex / static struct ib_mad_agent __get_agent(struct ib_umad_file file, int id) { return file->agents_dead ? NULL : file->agent[id]; } static int queue_packet(struct ib_umad_file file, struct ib_mad_agent agent, struct ib_umad_packet packet) { int ret = 1; mutex_lock(&file->mutex); for (packet->mad.hdr.id = 0; packet->mad.hdr.id < IB_UMAD_MAX_AGENTS; packet->mad.hdr.id++) if (agent == __get_agent(file, packet->mad.hdr.id)) { list_add_tail(&packet->list, &file->recv_list); wake_up_interruptible(&file->recv_wait); ret = 0; break; } mutex_unlock(&file->mutex); return ret; } static void dequeue_send(struct ib_umad_file file, struct ib_umad_packet packet) { spin_lock_irq(&file->send_lock); list_del(&packet->list); spin_unlock_irq(&file->send_lock); } static void send_handler(struct ib_mad_agent agent, struct ib_mad_send_wc send_wc) { struct ib_umad_file file = agent->context; struct ib_umad_packet packet = send_wc->send_buf->context[0]; dequeue_send(file, packet); ib_destroy_ah(packet->msg->ah); ib_free_send_mad(packet->msg); if (send_wc->status == IB_WC_RESP_TIMEOUT_ERR) { packet->length = IB_MGMT_MAD_HDR; packet->mad.hdr.status = ETIMEDOUT; if (!queue_packet(file, agent, packet)) return; } kfree(packet); } static void recv_handler(struct ib_mad_agent agent, struct ib_mad_recv_wc mad_recv_wc) { struct ib_umad_file file = agent->context; struct ib_umad_packet packet; if (mad_recv_wc->wc->status != IB_WC_SUCCESS) goto err1; packet = kzalloc(sizeof packet, GFP_KERNEL); if (!packet) goto err1; packet->length = mad_recv_wc->mad_len; packet->recv_wc = mad_recv_wc; packet->mad.hdr.status = 0; packet->mad.hdr.length = hdr_size(file) + mad_recv_wc->mad_len; packet->mad.hdr.qpn = cpu_to_be32(mad_recv_wc->wc->src_qp); packet->mad.hdr.lid = cpu_to_be16(mad_recv_wc->wc->slid); packet->mad.hdr.sl = mad_recv_wc->wc->sl; packet->mad.hdr.path_bits = mad_recv_wc->wc->dlid_path_bits; packet->mad.hdr.pkey_index = mad_recv_wc->wc->pkey_index; packet->mad.hdr.grh_present = !!(mad_recv_wc->wc->wc_flags & IB_WC_GRH); if (packet->mad.hdr.grh_present) { struct ib_ah_attr ah_attr; ib_init_ah_from_wc(agent->device, agent->port_num, mad_recv_wc->wc, mad_recv_wc->recv_buf.grh, &ah_attr); packet->mad.hdr.gid_index = ah_attr.grh.sgid_index; packet->mad.hdr.hop_limit = ah_attr.grh.hop_limit; packet->mad.hdr.traffic_class = ah_attr.grh.traffic_class; memcpy(packet->mad.hdr.gid, &ah_attr.grh.dgid, 16); packet->mad.hdr.flow_label = cpu_to_be32(ah_attr.grh.flow_label); } if (queue_packet(file, agent, packet)) goto err2; return; err2: kfree(packet); err1: ib_free_recv_mad(mad_recv_wc); } static ssize_t copy_recv_mad(struct ib_umad_file file, char __user buf, struct ib_umad_packet packet, size_t count) { struct ib_mad_recv_buf recv_buf; int left, seg_payload, offset, max_seg_payload; / We need enough room to copy the first (or only) MAD segment. / recv_buf = &packet->recv_wc->recv_buf; if ((packet->length <= sizeof (recv_buf->mad) && count < hdr_size(file) + packet->length) \|\| (packet->length > sizeof (recv_buf->mad) && count < hdr_size(file) + sizeof (recv_buf->mad))) return -EINVAL; if (copy_to_user(buf, &packet->mad, hdr_size(file))) return -EFAULT; buf += hdr_size(file); seg_payload = min_t(int, packet->length, sizeof (recv_buf->mad)); if (copy_to_user(buf, recv_buf->mad, seg_payload)) return -EFAULT; if (seg_payload < packet->length) { / * Multipacket RMPP MAD message. Copy remainder of message. * Note that last segment may have a shorter payload. / if (count < hdr_size(file) + packet->length) { / * The buffer is too small, return the first RMPP segment, * which includes the RMPP message length. / return -ENOSPC; } offset = ib_get_mad_data_offset(recv_buf->mad->mad_hdr.mgmt_class); max_seg_payload = sizeof (struct ib_mad) - offset; for (left = packet->length - seg_payload, buf += seg_payload; left; left -= seg_payload, buf += seg_payload) { recv_buf = container_of(recv_buf->list.next, struct ib_mad_recv_buf, list); seg_payload = min(left, max_seg_payload); if (copy_to_user(buf, ((void ) recv_buf->mad) + offset, seg_payload)) return -EFAULT; } } return hdr_size(file) + packet->length; } static ssize_t copy_send_mad(struct ib_umad_file file, char __user buf, struct ib_umad_packet packet, size_t count) { ssize_t size = hdr_size(file) + packet->length; if (count < size) return -EINVAL; if (copy_to_user(buf, &packet->mad, hdr_size(file))) return -EFAULT; buf += hdr_size(file); if (copy_to_user(buf, packet->mad.data, packet->length)) return -EFAULT; return size; } static ssize_t ib_umad_read(struct file filp, char __user buf, size_t count, loff_t pos) { struct ib_umad_file file = filp->private_data; struct ib_umad_packet packet; ssize_t ret; if (count < hdr_size(file)) return -EINVAL; mutex_lock(&file->mutex); while (list_empty(&file->recv_list)) { mutex_unlock(&file->mutex); if (filp->f_flags & O_NONBLOCK) return -EAGAIN; if (wait_event_interruptible(file->recv_wait, !list_empty(&file->recv_list))) return -ERESTARTSYS; mutex_lock(&file->mutex); } packet = list_entry(file->recv_list.next, struct ib_umad_packet, list); list_del(&packet->list); mutex_unlock(&file->mutex); if (packet->recv_wc) ret = copy_recv_mad(file, buf, packet, count); else ret = copy_send_mad(file, buf, packet, count); if (ret < 0) { /* Requeue packet / mutex_lock(&file->mutex); list_add(&packet->list, &file->recv_list); mutex_unlock(&file->mutex); } else { if (packet->recv_wc) ib_free_recv_mad(packet->recv_wc); kfree(packet); } return ret; } static int copy_rmpp_mad(struct ib_mad_send_buf msg, const char __user buf) { int left, seg; / Copy class specific header / if ((msg->hdr_len > IB_MGMT_RMPP_HDR) && copy_from_user(msg->mad + IB_MGMT_RMPP_HDR, buf + IB_MGMT_RMPP_HDR, msg->hdr_len - IB_MGMT_RMPP_HDR)) return -EFAULT; / All headers are in place. Copy data segments. / for (seg = 1, left = msg->data_len, buf += msg->hdr_len; left > 0; seg++, left -= msg->seg_size, buf += msg->seg_size) { if (copy_from_user(ib_get_rmpp_segment(msg, seg), buf, min(left, msg->seg_size))) return -EFAULT; } return 0; } static int same_destination(struct ib_user_mad_hdr hdr1, struct ib_user_mad_hdr hdr2) { if (!hdr1->grh_present && !hdr2->grh_present) return (hdr1->lid == hdr2->lid); if (hdr1->grh_present && hdr2->grh_present) return !memcmp(hdr1->gid, hdr2->gid, 16); return 0; } static int is_duplicate(struct ib_umad_file file, struct ib_umad_packet packet) { struct ib_umad_packet sent_packet; struct ib_mad_hdr sent_hdr, hdr; hdr = (struct ib_mad_hdr ) packet->mad.data; list_for_each_entry(sent_packet, &file->send_list, list) { sent_hdr = (struct ib_mad_hdr ) sent_packet->mad.data; if ((hdr->tid != sent_hdr->tid) \|\| (hdr->mgmt_class != sent_hdr->mgmt_class)) continue; /* * No need to be overly clever here. If two new operations have * the same TID, reject the second as a duplicate. This is more * restrictive than required by the spec. / if (!ib_response_mad((struct ib_mad ) hdr)) { if (!ib_response_mad((struct ib_mad ) sent_hdr)) return 1; continue; } else if (!ib_response_mad((struct ib_mad ) sent_hdr)) continue; if (same_destination(&packet->mad.hdr, &sent_packet->mad.hdr)) return 1; } return 0; } static ssize_t ib_umad_write(struct file filp, const char __user buf, size_t count, loff_t pos) { struct ib_umad_file file = filp->private_data; struct ib_umad_packet packet; struct ib_mad_agent agent; struct ib_ah_attr ah_attr; struct ib_ah ah; struct ib_rmpp_mad rmpp_mad; __be64 tid; int ret, data_len, hdr_len, copy_offset, rmpp_active; if (count < hdr_size(file) + IB_MGMT_RMPP_HDR) return -EINVAL; packet = kzalloc(sizeof packet + IB_MGMT_RMPP_HDR, GFP_KERNEL); if (!packet) return -ENOMEM; if (copy_from_user(&packet->mad, buf, hdr_size(file))) { ret = -EFAULT; goto err; } if (packet->mad.hdr.id >= IB_UMAD_MAX_AGENTS) { ret = -EINVAL; goto err; } buf += hdr_size(file); if (copy_from_user(packet->mad.data, buf, IB_MGMT_RMPP_HDR)) { ret = -EFAULT; goto err; } mutex_lock(&file->mutex); agent = __get_agent(file, packet->mad.hdr.id); if (!agent) { ret = -EINVAL; goto err_up; } memset(&ah_attr, 0, sizeof ah_attr); ah_attr.dlid = be16_to_cpu(packet->mad.hdr.lid); ah_attr.sl = packet->mad.hdr.sl; ah_attr.src_path_bits = packet->mad.hdr.path_bits; ah_attr.port_num = file->port->port_num; if (packet->mad.hdr.grh_present) { ah_attr.ah_flags = IB_AH_GRH; memcpy(ah_attr.grh.dgid.raw, packet->mad.hdr.gid, 16); ah_attr.grh.sgid_index = packet->mad.hdr.gid_index; ah_attr.grh.flow_label = be32_to_cpu(packet->mad.hdr.flow_label); ah_attr.grh.hop_limit = packet->mad.hdr.hop_limit; ah_attr.grh.traffic_class = packet->mad.hdr.traffic_class; } ah = ib_create_ah(agent->qp->pd, &ah_attr); if (IS_ERR(ah)) { ret = PTR_ERR(ah); goto err_up; } rmpp_mad = (struct ib_rmpp_mad ) packet->mad.data; hdr_len = ib_get_mad_data_offset(rmpp_mad->mad_hdr.mgmt_class); if (ib_is_mad_class_rmpp(rmpp_mad->mad_hdr.mgmt_class) && ib_mad_kernel_rmpp_agent(agent)) { copy_offset = IB_MGMT_RMPP_HDR; rmpp_active = ib_get_rmpp_flags(&rmpp_mad->rmpp_hdr) & IB_MGMT_RMPP_FLAG_ACTIVE; } else { copy_offset = IB_MGMT_MAD_HDR; rmpp_active = 0; } data_len = count - hdr_size(file) - hdr_len; packet->msg = ib_create_send_mad(agent, be32_to_cpu(packet->mad.hdr.qpn), packet->mad.hdr.pkey_index, rmpp_active, hdr_len, data_len, GFP_KERNEL); if (IS_ERR(packet->msg)) { ret = PTR_ERR(packet->msg); goto err_ah; } packet->msg->ah = ah; packet->msg->timeout_ms = packet->mad.hdr.timeout_ms; packet->msg->retries = packet->mad.hdr.retries; packet->msg->context[0] = packet; / Copy MAD header. Any RMPP header is already in place. / memcpy(packet->msg->mad, packet->mad.data, IB_MGMT_MAD_HDR); if (!rmpp_active) { if (copy_from_user(packet->msg->mad + copy_offset, buf + copy_offset, hdr_len + data_len - copy_offset)) { ret = -EFAULT; goto err_msg; } } else { ret = copy_rmpp_mad(packet->msg, buf); if (ret) goto err_msg; } / * Set the high-order part of the transaction ID to make MADs from * different agents unique, and allow routing responses back to the * original requestor. / if (!ib_response_mad(packet->msg->mad)) { tid = &((struct ib_mad_hdr ) packet->msg->mad)->tid; tid = cpu_to_be64(((u64) agent->hi_tid) << 32 \| (be64_to_cpup(tid) & 0xffffffff)); rmpp_mad->mad_hdr.tid = tid; } if (!ib_mad_kernel_rmpp_agent(agent) && ib_is_mad_class_rmpp(rmpp_mad->mad_hdr.mgmt_class) && (ib_get_rmpp_flags(&rmpp_mad->rmpp_hdr) & IB_MGMT_RMPP_FLAG_ACTIVE)) { spin_lock_irq(&file->send_lock); list_add_tail(&packet->list, &file->send_list); spin_unlock_irq(&file->send_lock); } else { spin_lock_irq(&file->send_lock); ret = is_duplicate(file, packet); if (!ret) list_add_tail(&packet->list, &file->send_list); spin_unlock_irq(&file->send_lock); if (ret) { ret = -EINVAL; goto err_msg; } } ret = ib_post_send_mad(packet->msg, NULL); if (ret) goto err_send; mutex_unlock(&file->mutex); return count; err_send: dequeue_send(file, packet); err_msg: ib_free_send_mad(packet->msg); err_ah: ib_destroy_ah(ah); err_up: mutex_unlock(&file->mutex); err: kfree(packet); return ret; } static unsigned int ib_umad_poll(struct file filp, struct poll_table_struct wait) { struct ib_umad_file file = filp->private_data; / we will always be able to post a MAD send / unsigned int mask = POLLOUT \| POLLWRNORM; poll_wait(filp, &file->recv_wait, wait); if (!list_empty(&file->recv_list)) mask \|= POLLIN \| POLLRDNORM; return mask; } static int ib_umad_reg_agent(struct ib_umad_file file, void __user arg, int compat_method_mask) { struct ib_user_mad_reg_req ureq; struct ib_mad_reg_req req; struct ib_mad_agent agent = NULL; int agent_id; int ret; mutex_lock(&file->port->file_mutex); mutex_lock(&file->mutex); if (!file->port->ib_dev) { dev_notice(file->port->dev, "ib_umad_reg_agent: invalid device\n"); ret = -EPIPE; goto out; } if (copy_from_user(&ureq, arg, sizeof ureq)) { ret = -EFAULT; goto out; } if (ureq.qpn != 0 && ureq.qpn != 1) { dev_notice(file->port->dev, "ib_umad_reg_agent: invalid QPN %d specified\n", ureq.qpn); ret = -EINVAL; goto out; } for (agent_id = 0; agent_id < IB_UMAD_MAX_AGENTS; ++agent_id) if (!__get_agent(file, agent_id)) goto found; dev_notice(file->port->dev, "ib_umad_reg_agent: Max Agents (%u) reached\n", IB_UMAD_MAX_AGENTS); ret = -ENOMEM; goto out; found: if (ureq.mgmt_class) { memset(&req, 0, sizeof(req)); req.mgmt_class = ureq.mgmt_class; req.mgmt_class_version = ureq.mgmt_class_version; memcpy(req.oui, ureq.oui, sizeof req.oui); if (compat_method_mask) { u32 umm = (u32 ) ureq.method_mask; int i; for (i = 0; i < BITS_TO_LONGS(IB_MGMT_MAX_METHODS); ++i) req.method_mask[i] = umm[i * 2] \| ((u64) umm[i * 2 + 1] << 32); } else memcpy(req.method_mask, ureq.method_mask, sizeof req.method_mask); } agent = ib_register_mad_agent(file->port->ib_dev, file->port->port_num, ureq.qpn ? IB_QPT_GSI : IB_QPT_SMI, ureq.mgmt_class ? &req : NULL, ureq.rmpp_version, send_handler, recv_handler, file, 0); if (IS_ERR(agent)) { ret = PTR_ERR(agent); agent = NULL; goto out; } if (put_user(agent_id, (u32 __user ) (arg + offsetof(struct ib_user_mad_reg_req, id)))) { ret = -EFAULT; goto out; } if (!file->already_used) { file->already_used = 1; if (!file->use_pkey_index) { dev_warn(file->port->dev, "process %s did not enable P_Key index support.\n", current->comm); dev_warn(file->port->dev, " Documentation/infiniband/user_mad.txt has info on the new ABI.\n"); } } file->agent[agent_id] = agent; ret = 0; out: mutex_unlock(&file->mutex); if (ret && agent) ib_unregister_mad_agent(agent); mutex_unlock(&file->port->file_mutex); return ret; } static int ib_umad_reg_agent2(struct ib_umad_file file, void __user arg) { struct ib_user_mad_reg_req2 ureq; struct ib_mad_reg_req req; struct ib_mad_agent agent = NULL; int agent_id; int ret; mutex_lock(&file->port->file_mutex); mutex_lock(&file->mutex); if (!file->port->ib_dev) { dev_notice(file->port->dev, "ib_umad_reg_agent2: invalid device\n"); ret = -EPIPE; goto out; } if (copy_from_user(&ureq, arg, sizeof(ureq))) { ret = -EFAULT; goto out; } if (ureq.qpn != 0 && ureq.qpn != 1) { dev_notice(file->port->dev, "ib_umad_reg_agent2: invalid QPN %d specified\n", ureq.qpn); ret = -EINVAL; goto out; } if (ureq.flags & ~IB_USER_MAD_REG_FLAGS_CAP) { dev_notice(file->port->dev, "ib_umad_reg_agent2 failed: invalid registration flags specified 0x%x; supported 0x%x\n", ureq.flags, IB_USER_MAD_REG_FLAGS_CAP); ret = -EINVAL; if (put_user((u32)IB_USER_MAD_REG_FLAGS_CAP, (u32 __user ) (arg + offsetof(struct ib_user_mad_reg_req2, flags)))) ret = -EFAULT; goto out; } for (agent_id = 0; agent_id < IB_UMAD_MAX_AGENTS; ++agent_id) if (!__get_agent(file, agent_id)) goto found; dev_notice(file->port->dev, "ib_umad_reg_agent2: Max Agents (%u) reached\n", IB_UMAD_MAX_AGENTS); ret = -ENOMEM; goto out; found: if (ureq.mgmt_class) { memset(&req, 0, sizeof(req)); req.mgmt_class = ureq.mgmt_class; req.mgmt_class_version = ureq.mgmt_class_version; if (ureq.oui & 0xff000000) { dev_notice(file->port->dev, "ib_umad_reg_agent2 failed: oui invalid 0x%08x\n", ureq.oui); ret = -EINVAL; goto out; } req.oui[2] = ureq.oui & 0x0000ff; req.oui[1] = (ureq.oui & 0x00ff00) >> 8; req.oui[0] = (ureq.oui & 0xff0000) >> 16; memcpy(req.method_mask, ureq.method_mask, sizeof(req.method_mask)); } agent = ib_register_mad_agent(file->port->ib_dev, file->port->port_num, ureq.qpn ? IB_QPT_GSI : IB_QPT_SMI, ureq.mgmt_class ? &req : NULL, ureq.rmpp_version, send_handler, recv_handler, file, ureq.flags); if (IS_ERR(agent)) { ret = PTR_ERR(agent); agent = NULL; goto out; } if (put_user(agent_id, (u32 __user )(arg + offsetof(struct ib_user_mad_reg_req2, id)))) { ret = -EFAULT; goto out; } if (!file->already_used) { file->already_used = 1; file->use_pkey_index = 1; } file->agent[agent_id] = agent; ret = 0; out: mutex_unlock(&file->mutex); if (ret && agent) ib_unregister_mad_agent(agent); mutex_unlock(&file->port->file_mutex); return ret; } static int ib_umad_unreg_agent(struct ib_umad_file file, u32 __user arg) { struct ib_mad_agent agent = NULL; u32 id; int ret = 0; if (get_user(id, arg)) return -EFAULT; mutex_lock(&file->port->file_mutex); mutex_lock(&file->mutex); if (id >= IB_UMAD_MAX_AGENTS \|\| !__get_agent(file, id)) { ret = -EINVAL; goto out; } agent = file->agent[id]; file->agent[id] = NULL; out: mutex_unlock(&file->mutex); if (agent) ib_unregister_mad_agent(agent); mutex_unlock(&file->port->file_mutex); return ret; } static long ib_umad_enable_pkey(struct ib_umad_file file) { int ret = 0; mutex_lock(&file->mutex); if (file->already_used) ret = -EINVAL; else file->use_pkey_index = 1; mutex_unlock(&file->mutex); return ret; } static long ib_umad_ioctl(struct file filp, unsigned int cmd, unsigned long arg) { switch (cmd) { case IB_USER_MAD_REGISTER_AGENT: return ib_umad_reg_agent(filp->private_data, (void __user ) arg, 0); case IB_USER_MAD_UNREGISTER_AGENT: return ib_umad_unreg_agent(filp->private_data, (__u32 __user ) arg); case IB_USER_MAD_ENABLE_PKEY: return ib_umad_enable_pkey(filp->private_data); case IB_USER_MAD_REGISTER_AGENT2: return ib_umad_reg_agent2(filp->private_data, (void __user ) arg); default: return -ENOIOCTLCMD; } } #ifdef CONFIG_COMPAT static long ib_umad_compat_ioctl(struct file filp, unsigned int cmd, unsigned long arg) { switch (cmd) { case IB_USER_MAD_REGISTER_AGENT: return ib_umad_reg_agent(filp->private_data, compat_ptr(arg), 1); case IB_USER_MAD_UNREGISTER_AGENT: return ib_umad_unreg_agent(filp->private_data, compat_ptr(arg)); case IB_USER_MAD_ENABLE_PKEY: return ib_umad_enable_pkey(filp->private_data); case IB_USER_MAD_REGISTER_AGENT2: return ib_umad_reg_agent2(filp->private_data, compat_ptr(arg)); default: return -ENOIOCTLCMD; } } #endif / * ib_umad_open() does not need the BKL: * * - the ib_umad_port structures are properly reference counted, and * everything else is purely local to the file being created, so * races against other open calls are not a problem; * - the ioctl method does not affect any global state outside of the * file structure being operated on; / static int ib_umad_open(struct inode inode, struct file filp) { struct ib_umad_port port; struct ib_umad_file file; int ret = -ENXIO; port = container_of(inode->i_cdev, struct ib_umad_port, cdev); mutex_lock(&port->file_mutex); if (!port->ib_dev) goto out; ret = -ENOMEM; file = kzalloc(sizeof file, GFP_KERNEL); if (!file) goto out; mutex_init(&file->mutex); spin_lock_init(&file->send_lock); INIT_LIST_HEAD(&file->recv_list); INIT_LIST_HEAD(&file->send_list); init_waitqueue_head(&file->recv_wait); file->port = port; filp->private_data = file; list_add_tail(&file->port_list, &port->file_list); ret = nonseekable_open(inode, filp); if (ret) { list_del(&file->port_list); kfree(file); goto out; } kobject_get(&port->umad_dev->kobj); out: mutex_unlock(&port->file_mutex); return ret; } static int ib_umad_close(struct inode inode, struct file filp) { struct ib_umad_file file = filp->private_data; struct ib_umad_device dev = file->port->umad_dev; struct ib_umad_packet packet, tmp; int already_dead; int i; mutex_lock(&file->port->file_mutex); mutex_lock(&file->mutex); already_dead = file->agents_dead; file->agents_dead = 1; list_for_each_entry_safe(packet, tmp, &file->recv_list, list) { if (packet->recv_wc) ib_free_recv_mad(packet->recv_wc); kfree(packet); } list_del(&file->port_list); mutex_unlock(&file->mutex); if (!already_dead) for (i = 0; i < IB_UMAD_MAX_AGENTS; ++i) if (file->agent[i]) ib_unregister_mad_agent(file->agent[i]); mutex_unlock(&file->port->file_mutex); kfree(file); kobject_put(&dev->kobj); return 0; } static const struct file_operations umad_fops = { .owner = THIS_MODULE, .read = ib_umad_read, .write = ib_umad_write, .poll = ib_umad_poll, .unlocked_ioctl = ib_umad_ioctl, #ifdef CONFIG_COMPAT .compat_ioctl = ib_umad_compat_ioctl, #endif .open = ib_umad_open, .release = ib_umad_close, .llseek = no_llseek, }; static int ib_umad_sm_open(struct inode inode, struct file filp) { struct ib_umad_port port; struct ib_port_modify props = { .set_port_cap_mask = IB_PORT_SM }; int ret; port = container_of(inode->i_cdev, struct ib_umad_port, sm_cdev); if (filp->f_flags & O_NONBLOCK) { if (down_trylock(&port->sm_sem)) { ret = -EAGAIN; goto fail; } } else { if (down_interruptible(&port->sm_sem)) { ret = -ERESTARTSYS; goto fail; } } ret = ib_modify_port(port->ib_dev, port->port_num, 0, &props); if (ret) goto err_up_sem; filp->private_data = port; ret = nonseekable_open(inode, filp); if (ret) goto err_clr_sm_cap; kobject_get(&port->umad_dev->kobj); return 0; err_clr_sm_cap: swap(props.set_port_cap_mask, props.clr_port_cap_mask); ib_modify_port(port->ib_dev, port->port_num, 0, &props); err_up_sem: up(&port->sm_sem); fail: return ret; } static int ib_umad_sm_close(struct inode inode, struct file filp) { struct ib_umad_port port = filp->private_data; struct ib_port_modify props = { .clr_port_cap_mask = IB_PORT_SM }; int ret = 0; mutex_lock(&port->file_mutex); if (port->ib_dev) ret = ib_modify_port(port->ib_dev, port->port_num, 0, &props); mutex_unlock(&port->file_mutex); up(&port->sm_sem); kobject_put(&port->umad_dev->kobj); return ret; } static const struct file_operations umad_sm_fops = { .owner = THIS_MODULE, .open = ib_umad_sm_open, .release = ib_umad_sm_close, .llseek = no_llseek, }; static struct ib_client umad_client = { .name = "umad", .add = ib_umad_add_one, .remove = ib_umad_remove_one }; static ssize_t show_ibdev(struct device dev, struct device_attribute attr, char buf) { struct ib_umad_port port = dev_get_drvdata(dev); if (!port) return -ENODEV; return sprintf(buf, "%s\n", port->ib_dev->name); } static DEVICE_ATTR(ibdev, S_IRUGO, show_ibdev, NULL); static ssize_t show_port(struct device dev, struct device_attribute attr, char buf) { struct ib_umad_port port = dev_get_drvdata(dev); if (!port) return -ENODEV; return sprintf(buf, "%d\n", port->port_num); } static DEVICE_ATTR(port, S_IRUGO, show_port, NULL); static CLASS_ATTR_STRING(abi_version, S_IRUGO, __stringify(IB_USER_MAD_ABI_VERSION)); static dev_t overflow_maj; static DECLARE_BITMAP(overflow_map, IB_UMAD_MAX_PORTS); static int find_overflow_devnum(struct ib_device device) { int ret; if (!overflow_maj) { ret = alloc_chrdev_region(&overflow_maj, 0, IB_UMAD_MAX_PORTS 2, "infiniband_mad"); if (ret) { dev_err(&device->dev, "couldn't register dynamic device number\n"); return ret; } } ret = find_first_zero_bit(overflow_map, IB_UMAD_MAX_PORTS); if (ret >= IB_UMAD_MAX_PORTS) return -1; return ret; } static int ib_umad_init_port(struct ib_device device, int port_num, struct ib_umad_device umad_dev, struct ib_umad_port port) { int devnum; dev_t base; spin_lock(&port_lock); devnum = find_first_zero_bit(dev_map, IB_UMAD_MAX_PORTS); if (devnum >= IB_UMAD_MAX_PORTS) { spin_unlock(&port_lock); devnum = find_overflow_devnum(device); if (devnum < 0) return -1; spin_lock(&port_lock); port->dev_num = devnum + IB_UMAD_MAX_PORTS; base = devnum + overflow_maj; set_bit(devnum, overflow_map); } else { port->dev_num = devnum; base = devnum + base_dev; set_bit(devnum, dev_map); } spin_unlock(&port_lock); port->ib_dev = device; port->port_num = port_num; sema_init(&port->sm_sem, 1); mutex_init(&port->file_mutex); INIT_LIST_HEAD(&port->file_list); cdev_init(&port->cdev, &umad_fops); port->cdev.owner = THIS_MODULE; port->cdev.kobj.parent = &umad_dev->kobj; kobject_set_name(&port->cdev.kobj, "umad%d", port->dev_num); if (cdev_add(&port->cdev, base, 1)) goto err_cdev; port->dev = device_create(umad_class, device->dma_device, port->cdev.dev, port, "umad%d", port->dev_num); if (IS_ERR(port->dev)) goto err_cdev; if (device_create_file(port->dev, &dev_attr_ibdev)) goto err_dev; if (device_create_file(port->dev, &dev_attr_port)) goto err_dev; base += IB_UMAD_MAX_PORTS; cdev_init(&port->sm_cdev, &umad_sm_fops); port->sm_cdev.owner = THIS_MODULE; port->sm_cdev.kobj.parent = &umad_dev->kobj; kobject_set_name(&port->sm_cdev.kobj, "issm%d", port->dev_num); if (cdev_add(&port->sm_cdev, base, 1)) goto err_sm_cdev; port->sm_dev = device_create(umad_class, device->dma_device, port->sm_cdev.dev, port, "issm%d", port->dev_num); if (IS_ERR(port->sm_dev)) goto err_sm_cdev; if (device_create_file(port->sm_dev, &dev_attr_ibdev)) goto err_sm_dev; if (device_create_file(port->sm_dev, &dev_attr_port)) goto err_sm_dev; return 0; err_sm_dev: device_destroy(umad_class, port->sm_cdev.dev); err_sm_cdev: cdev_del(&port->sm_cdev); err_dev: device_destroy(umad_class, port->cdev.dev); err_cdev: cdev_del(&port->cdev); if (port->dev_num < IB_UMAD_MAX_PORTS) clear_bit(devnum, dev_map); else clear_bit(devnum, overflow_map); return -1; } static void ib_umad_kill_port(struct ib_umad_port port) { struct ib_umad_file file; int id; dev_set_drvdata(port->dev, NULL); dev_set_drvdata(port->sm_dev, NULL); device_destroy(umad_class, port->cdev.dev); device_destroy(umad_class, port->sm_cdev.dev); cdev_del(&port->cdev); cdev_del(&port->sm_cdev); mutex_lock(&port->file_mutex); port->ib_dev = NULL; list_for_each_entry(file, &port->file_list, port_list) { mutex_lock(&file->mutex); file->agents_dead = 1; mutex_unlock(&file->mutex); for (id = 0; id < IB_UMAD_MAX_AGENTS; ++id) if (file->agent[id]) ib_unregister_mad_agent(file->agent[id]); } mutex_unlock(&port->file_mutex); if (port->dev_num < IB_UMAD_MAX_PORTS) clear_bit(port->dev_num, dev_map); else clear_bit(port->dev_num - IB_UMAD_MAX_PORTS, overflow_map); } static void ib_umad_add_one(struct ib_device device) { struct ib_umad_device umad_dev; int s, e, i; if (rdma_node_get_transport(device->node_type) != RDMA_TRANSPORT_IB) return; if (device->node_type == RDMA_NODE_IB_SWITCH) s = e = 0; else { s = 1; e = device->phys_port_cnt; } umad_dev = kzalloc(sizeof umad_dev + (e - s + 1) * sizeof (struct ib_umad_port), GFP_KERNEL); if (!umad_dev) return; kobject_init(&umad_dev->kobj, &ib_umad_dev_ktype); umad_dev->start_port = s; umad_dev->end_port = e; for (i = s; i <= e; ++i) { umad_dev->port[i - s].umad_dev = umad_dev; if (ib_umad_init_port(device, i, umad_dev, &umad_dev->port[i - s])) goto err; } ib_set_client_data(device, &umad_client, umad_dev); return; err: while (--i >= s) ib_umad_kill_port(&umad_dev->port[i - s]); kobject_put(&umad_dev->kobj); } static void ib_umad_remove_one(struct ib_device device) { struct ib_umad_device umad_dev = ib_get_client_data(device, &umad_client); int i; if (!umad_dev) return; for (i = 0; i <= umad_dev->end_port - umad_dev->start_port; ++i) ib_umad_kill_port(&umad_dev->port[i]); kobject_put(&umad_dev->kobj); } static char umad_devnode(struct device dev, umode_t mode) { return kasprintf(GFP_KERNEL, "infiniband/%s", dev_name(dev)); } static int __init ib_umad_init(void) { int ret; ret = register_chrdev_region(base_dev, IB_UMAD_MAX_PORTS 2, "infiniband_mad"); if (ret) { pr_err("couldn't register device number\n"); goto out; } umad_class = class_create(THIS_MODULE, "infiniband_mad"); if (IS_ERR(umad_class)) { ret = PTR_ERR(umad_class); pr_err("couldn't create class infiniband_mad\n"); goto out_chrdev; } umad_class->devnode = umad_devnode; ret = class_create_file(umad_class, &class_attr_abi_version.attr); if (ret) { pr_err("couldn't create abi_version attribute\n"); goto out_class; } ret = ib_register_client(&umad_client); if (ret) { pr_err("couldn't register ib_umad client\n"); goto out_class; } return 0; out_class: class_destroy(umad_class); out_chrdev: unregister_chrdev_region(base_dev, IB_UMAD_MAX_PORTS * 2); out: return ret; } static void __exit ib_umad_cleanup(void) { ib_unregister_client(&umad_client); class_destroy(umad_class); unregister_chrdev_region(base_dev, IB_UMAD_MAX_PORTS * 2); if (overflow_maj) unregister_chrdev_region(overflow_maj, IB_UMAD_MAX_PORTS * 2); } module_init(ib_umad_init); module_exit(ib_umad_cleanup);
New housebuilding must be more considered - analyst - Mortgage Solutions Any increase in housebuilding must be done in a considered fashion in order to create a sustainable future for the housing market, BLP Insurance chief executive officer Kim Vernau has said. Vernau said plans to create new houses must not be rushed through and government must make sure the quality of the build and the impact on local communities are considered. "We urgently need to provide additional housing to meet the increasing demand that we are seeing for property in the UK," she said. "It is, however, vitally important that we are considered and legislate properly if that property is going to be both sustainable and cost effective. Producing housing that fails to meet these criteria is not a solution as it becomes a problem over time. "This starts from the planning stage in terms of the quality of the build. Furthermore, we need to consider the effects on local communities and ensure that new housing developments have the right infrastructure available to support them and provide residents with enough schools and hospitals." Vernau said that schemes involving the local community were most likely to succeed: "A considered and effective neighbourhood plan with buy-in from all affected parties is key to the success of such development. The current lack of available land is a big problem. "We endorse the government's initiative to enable communities to improve their local area by giving them the right to ask that under-used or unused land owned by Public Bodies be brought back into use." She later added changes to Capital Gains Tax (CGT) could scare buyers away from the London market. "The recent changes to CGT in respect of foreign buyers announced by the Chancellor earlier this month could scare the horses and stop foreign investors from bringing their investment to the UK. We would not wish to see such a measure dissuade foreign investors from investing their money here by creating an atmosphere of uncertainty in respect of taxation. "The government intends to conduct a thorough investigation of this measure early in the New Year and we hope they consider the dangerous signal this move would send to foreign investors."
Q: OrderBy used with LINQ returns no rows in DOcumentDb I have been trying to use OrderBy in LINQ i have changed several fields but it always returns null (no rows) while my documents are present in the collection. Here's my simple query- var rests = _client.CreateDocumentQuery<Restraunt>(_collectionUri) .OrderBy(x => x.RestName); A: You have to create an indexing policy with a range index on the type of the property you use in the order by (here I assume a string). If you let the default policy, the order by return no result. You need a sorting policy like that : restrauntsCollection.IndexingPolicy.IncludedPaths.Add( new IncludedPath { Path = "/RestName/?", Indexes = new Collection<Index> { new RangeIndex(DataType.String) { Precision = -1 } } }); See this page for more information: https://azure.microsoft.com/en-us/documentation/articles/documentdb-orderby/ Hope this helps
Wisconsin vs. Illinois: Game preview, prediction Jeff Potrykus \| Milwaukee Journal Sentinel TEAMS: Wisconsin Badgers (4-1, 2-1 Big Ten) vs. Illinois Fighting Illini (3-3, 1-2). TIME: 11 a.m. Saturday WHERE: Camp Randall Stadium TV: FS1 with Justin Kutcher (play-by-play), Demarco Murray (analysis) and Petros Papadakis (sideline). RADIO: AM-920 in Milwaukee and a state network with Matt Lepay (play-by-play) and Mike Lucas (analysis). TICKETS: Available. LINE: Wisconsin by 26. SERIES: UW leads, 41-36-7. COACHES: UW's Paul Chryst (38-9, third season; 57-28 overall); vs. Illinois’ Lovie Smith (8-22, third season overall). LIVE COVERAGE: Follow our live coverage from the press box SCOUTING REPORT:Illinois at a glance STATS, ROSTERS: Wisconsin \| Illinois LIVE SCOREBOARD: NCAA football schedule, box scores FOUR THINGS TO WATCH ON FIRE OR FLAT? The loss to Michigan ended any talk of UW making a run at the College Football Playoff. The UW players said all the right things this week, noting the loss wouldn’t affect their drive to win the Big Ten West Division title. It is human nature, however, to sag a bit after such a loss. Watch to see how hard and physical UW plays early against Illinois. That will be a good indicator of how well the players prepared this week. “We don’t want to hang our heads just because we lost two games,” wide receiver Kendric Pryor said. “We went undefeated until the Big Ten (title) game last year so it is weird that we’ve lost two games. We still want to win every game. We’re not going to mope through the rest of the season...we’ve still got half a season left to play.” READ YOUR KEYS: Illinois quarterback AJ Bush Jr. generally won’t burn teams with his arm. He has completed a modest 54.8% of his passes (40 of 73) for 482 yards with one touchdown and one interception. Bush is most dangerous running the zone read or scrambling after a play breaks down. Tailbacks Reggie Corbin (7.4-yard average) and Mike Epstein (6.8) and Bush (4.4) have combined for 1,163 rushing yards and 11 touchdowns. UW defenders must stick to their assignments or they’ll get burned for long runs. UW OFFENSE SHOULD THRIVE: During the week the UW coaches and players during saluted how hard members of the Illinois defense compete play after play. Yet, the numbers reveal the Illini are struggling to contain opponents on the ground or through the air. Illinois is last in the Big Ten in total defense, allowing an average of 504.7 yards per game. The Illini no doubt will sell out to slow tailback Jonathan Taylor and test UW’s passing game. UW still might be able to find creases in a unit that is allowing 199.5 rushing yards per game, and play-action passes should be effective. GET AFTER THE QUARTERBACK: UW entered the Michigan game with three sacks in its first five games. The Badgers recorded three sacks against the Wolverines and with outside linebacker Andrew Van Ginkel (ankle) getting healthier could be on the verge of a breakout. It won’t hurt that Illinois has allowed 17 sacks in six games, most in the Big Ten. HISTORY LESSON Illinois limited UW’s offense to 303 yards and four scoring drives in 11 possessions in the teams’ meeting last season. But the Illini could not contain offensive lineman Michael Deiter, who was UW’s No. 1 left tackle at the time. It was Deiter’s 4-yard touchdown run that helped UW take a 24-3 lead with 3 minutes 54 seconds left in the game and spark a wild end-zone celebration. UW faced third and goal at the 4 when quarterback Alex Hornibrook rolled right and threw a backward pass to the left side, to Deiter. Deiter caught the ball at the 15 and followed a trio of blockers into the end zone. DID YOU KNOW? Senior linebacker T.J. Edwards has compiled a total of 17 tackles, including five for loss, in UW’s last two games. Three of the tackles for loss were sacks. Edwards is second on the team in tackles (36), one behind fellow senior Ryan Connelly. Edwards leads the team in sacks (three) and tackles for loss (8½). JEFF POTRYKUS' PREDICTION Illinois has accumulated some nice young talent and battled Penn State for three quarters before losing big in the Big Ten opener. Nevertheless, the Illini were outclassed at home by Purdue last week and don’t have the talent across the board to match up with UW for four quarters. UW will control the line of scrimmage and extend its winning streak against West Division foes to 16 with a 35-10 decision.
Masterworks of art and chronic illness experiences in the elderly. This article presents findings of a qualitative study, conducted between 1997 and 2000, to investigate the plausibility of integrating masterworks of art with care of the chronically ill elderly, and to analyse perceptions about chronic illness among three groups: registered nurses, nursing students, and the elderly. Statistically the incidence of chronic illness increases in the elderly. Although pathophysiology of chronic illness is increasingly understood, few studies explore the experience of living with chronicity from the perspective of the elderly. Understanding and intervening appropriately for the elderly with chronic illness may contribute significantly to improving quality of life for this growing population. The study was approved through an Institutional Review Board. Facility permission and participant informed consent were obtained. Anonymity and confidentiality were protected. Using hermeneutic phenomenology and masterworks of art as a centre point for dialogue, the investigators explored the perceptions of nurses, students, and the elderly about living with a chronic illness. A purposive sample of 65 participants made up seven focus groups with which group interviews were conducted. Themes were explicated and analysed from audiotaped interviews until data saturation was reached. Content analysis of focus group interviews revealed themes of social isolation, inevitable role change, and inertia-movement. Only the elderly acknowledged hope and a steadfast refusal to give up, while nurses and students viewed chronicity more negatively. Themes of social isolation and role change are consistent with other studies of the elderly. A paradox of inertia-movement in the chronically ill elderly has not been reported in the nursing literature. Paradoxical tension of inertia-movement in the chronically ill elderly appears to be linked to the broader concept of energy in nursing science, and to Parse's theory of human becoming. Masterworks of art can generate energy exchange between the elderly and caregivers, providing a plausible catalyst for meaningful interventions that transcend age and practice settings.
/**************************************************************** * Licensed to the Apache Software Foundation (ASF) under one * * or more contributor license agreements. See the NOTICE file * * distributed with this work for additional information * * regarding copyright ownership. The ASF licenses this file * * to you under the Apache License, Version 2.0 (the * * "License"); you may not use this file except in compliance * * with the License. You may obtain a copy of the License at * * * * http://www.apache.org/licenses/LICENSE-2.0 * * * * Unless required by applicable law or agreed to in writing, * * software distributed under the License is distributed on an * * "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY * * KIND, either express or implied. See the License for the * * specific language governing permissions and limitations * * under the License. * ****************************************************************/ package org.apache.james.mailbox.events; import static org.apache.james.backends.rabbitmq.Constants.AUTO_DELETE; import static org.apache.james.backends.rabbitmq.Constants.DURABLE; import static org.apache.james.backends.rabbitmq.Constants.EMPTY_ROUTING_KEY; import static org.apache.james.backends.rabbitmq.Constants.EXCLUSIVE; import static org.apache.james.backends.rabbitmq.Constants.REQUEUE; import static org.apache.james.backends.rabbitmq.Constants.deadLetterQueue; import static org.apache.james.mailbox.events.RabbitMQEventBus.MAILBOX_EVENT; import static org.apache.james.mailbox.events.RabbitMQEventBus.MAILBOX_EVENT_DEAD_LETTER_EXCHANGE_NAME; import static org.apache.james.mailbox.events.RabbitMQEventBus.MAILBOX_EVENT_EXCHANGE_NAME; import java.nio.charset.StandardCharsets; import java.util.Objects; import java.util.Optional; import java.util.function.Predicate; import org.apache.james.backends.rabbitmq.ReactorRabbitMQChannelPool; import org.apache.james.backends.rabbitmq.ReceiverProvider; import org.apache.james.event.json.EventSerializer; import org.apache.james.util.MDCBuilder; import org.slf4j.Logger; import org.slf4j.LoggerFactory; import com.google.common.base.Preconditions; import reactor.core.Disposable; import reactor.core.publisher.Mono; import reactor.core.scheduler.Schedulers; import reactor.rabbitmq.AcknowledgableDelivery; import reactor.rabbitmq.BindingSpecification; import reactor.rabbitmq.ConsumeOptions; import reactor.rabbitmq.QueueSpecification; import reactor.rabbitmq.Receiver; import reactor.rabbitmq.Sender; import reactor.util.retry.Retry; class GroupRegistration implements Registration { static class WorkQueueName { static WorkQueueName of(Group group) { return new WorkQueueName(group); } static final String MAILBOX_EVENT_WORK_QUEUE_PREFIX = MAILBOX_EVENT + "-workQueue-"; private final Group group; private WorkQueueName(Group group) { Preconditions.checkNotNull(group, "Group must be specified"); this.group = group; } String asString() { return MAILBOX_EVENT_WORK_QUEUE_PREFIX + group.asString(); } } private static final Logger LOGGER = LoggerFactory.getLogger(GroupRegistration.class); static final String RETRY_COUNT = "retry-count"; static final int DEFAULT_RETRY_COUNT = 0; private final ReactorRabbitMQChannelPool channelPool; private final MailboxListener.ReactiveMailboxListener mailboxListener; private final WorkQueueName queueName; private final Receiver receiver; private final Runnable unregisterGroup; private final Sender sender; private final EventSerializer eventSerializer; private final GroupConsumerRetry retryHandler; private final WaitDelayGenerator delayGenerator; private final Group group; private final RetryBackoffConfiguration retryBackoff; private final MailboxListenerExecutor mailboxListenerExecutor; private Optional<Disposable> receiverSubscriber; GroupRegistration(ReactorRabbitMQChannelPool channelPool, Sender sender, ReceiverProvider receiverProvider, EventSerializer eventSerializer, MailboxListener.ReactiveMailboxListener mailboxListener, Group group, RetryBackoffConfiguration retryBackoff, EventDeadLetters eventDeadLetters, Runnable unregisterGroup, MailboxListenerExecutor mailboxListenerExecutor) { this.channelPool = channelPool; this.eventSerializer = eventSerializer; this.mailboxListener = mailboxListener; this.queueName = WorkQueueName.of(group); this.sender = sender; this.receiver = receiverProvider.createReceiver(); this.retryBackoff = retryBackoff; this.mailboxListenerExecutor = mailboxListenerExecutor; this.receiverSubscriber = Optional.empty(); this.unregisterGroup = unregisterGroup; this.retryHandler = new GroupConsumerRetry(sender, group, retryBackoff, eventDeadLetters, eventSerializer); this.delayGenerator = WaitDelayGenerator.of(retryBackoff); this.group = group; } GroupRegistration start() { receiverSubscriber = Optional .of(createGroupWorkQueue() .then(retryHandler.createRetryExchange(queueName)) .then(Mono.fromCallable(() -> this.consumeWorkQueue())) .retryWhen(Retry.backoff(retryBackoff.getMaxRetries(), retryBackoff.getFirstBackoff()).jitter(retryBackoff.getJitterFactor()).scheduler(Schedulers.elastic())) .block()); return this; } private Mono<Void> createGroupWorkQueue() { return channelPool.createWorkQueue( QueueSpecification.queue(queueName.asString()) .durable(DURABLE) .exclusive(!EXCLUSIVE) .autoDelete(!AUTO_DELETE) .arguments(deadLetterQueue(MAILBOX_EVENT_DEAD_LETTER_EXCHANGE_NAME)), BindingSpecification.binding() .exchange(MAILBOX_EVENT_EXCHANGE_NAME) .queue(queueName.asString()) .routingKey(EMPTY_ROUTING_KEY)); } private Disposable consumeWorkQueue() { return receiver.consumeManualAck(queueName.asString(), new ConsumeOptions().qos(EventBus.EXECUTION_RATE)) .publishOn(Schedulers.parallel()) .filter(delivery -> Objects.nonNull(delivery.getBody())) .flatMap(this::deliver) .subscribe(); } private Mono<Void> deliver(AcknowledgableDelivery acknowledgableDelivery) { byte[] eventAsBytes = acknowledgableDelivery.getBody(); int currentRetryCount = getRetryCount(acknowledgableDelivery); return deserializeEvent(eventAsBytes) .flatMap(event -> delayGenerator.delayIfHaveTo(currentRetryCount) .flatMap(any -> runListener(event)) .onErrorResume(throwable -> retryHandler.handleRetry(event, currentRetryCount, throwable)) .then(Mono.<Void>fromRunnable(acknowledgableDelivery::ack))) .onErrorResume(e -> { LOGGER.error("Unable to process delivery for group {}", group, e); return Mono.fromRunnable(() -> acknowledgableDelivery.nack(!REQUEUE)); }); } private Mono<Event> deserializeEvent(byte[] eventAsBytes) { return Mono.fromCallable(() -> eventSerializer.fromJson(new String(eventAsBytes, StandardCharsets.UTF_8)).get()) .subscribeOn(Schedulers.parallel()); } Mono<Void> reDeliver(Event event) { return retryHandler.retryOrStoreToDeadLetter(event, DEFAULT_RETRY_COUNT); } private Mono<Void> runListener(Event event) { return mailboxListenerExecutor.execute( mailboxListener, MDCBuilder.create() .addContext(EventBus.StructuredLoggingFields.GROUP, group), event); } private int getRetryCount(AcknowledgableDelivery acknowledgableDelivery) { return Optional.ofNullable(acknowledgableDelivery.getProperties().getHeaders()) .flatMap(headers -> Optional.ofNullable(headers.get(RETRY_COUNT))) .filter(object -> object instanceof Integer) .map(Integer.class::cast) .orElse(DEFAULT_RETRY_COUNT); } @Override public void unregister() { receiverSubscriber.filter(Predicate.not(Disposable::isDisposed)) .ifPresent(Disposable::dispose); receiver.close(); unregisterGroup.run(); } }
// Copyright 2014 The Chromium Authors. All rights reserved. // Use of this source code is governed by a BSD-style license that can be // found in the LICENSE file. #include "base/bind.h" #include "base/location.h" #include "base/macros.h" #include "base/memory/ptr_util.h" #include "base/single_thread_task_runner.h" #include "base/threading/thread_task_runner_handle.h" #include "components/gcm_driver/gcm_driver.h" #include "components/invalidation/impl/gcm_invalidation_bridge.h" #include "components/signin/core/browser/profile_oauth2_token_service.h" #include "components/signin/core/browser/signin_manager.h" #include "google_apis/gaia/gaia_constants.h" #include "google_apis/gaia/identity_provider.h" namespace invalidation { namespace { // For 3rd party developers SenderId should come from application dashboard when // server side application is registered with Google. Android invalidations use // legacy format where gmail account can be specificed. Below value is copied // from Android. const char kInvalidationsSenderId[] = "ipc.invalidation@gmail.com"; // In Android world AppId is provided by operating system and should // match package name and hash of application. In desktop world these values // are arbitrary and not verified/enforced by registration service (yet). const char kInvalidationsAppId[] = "com.google.chrome.invalidations"; // Cacheinvalidation specific gcm message keys. const char kContentKey[] = "content"; const char kEchoTokenKey[] = "echo-token"; } // namespace // Core should be very simple class that implements GCMNetwrokChannelDelegate // and passes all calls to GCMInvalidationBridge. All calls should be serialized // through GCMInvalidationBridge to avoid race conditions. class GCMInvalidationBridge::Core : public syncer::GCMNetworkChannelDelegate, public base::NonThreadSafe { public: Core(base::WeakPtr<GCMInvalidationBridge> bridge, scoped_refptr<base::SingleThreadTaskRunner> ui_thread_task_runner); ~Core() override; // syncer::GCMNetworkChannelDelegate implementation. void Initialize(ConnectionStateCallback connection_state_callback, base::Closure store_reset_callback) override; void RequestToken(RequestTokenCallback callback) override; void InvalidateToken(const std::string& token) override; void Register(RegisterCallback callback) override; void SetMessageReceiver(MessageCallback callback) override; void RequestTokenFinished(RequestTokenCallback callback, const GoogleServiceAuthError& error, const std::string& token); void RegisterFinished(RegisterCallback callback, const std::string& registration_id, gcm::GCMClient::Result result); void OnIncomingMessage(const std::string& message, const std::string& echo_token); void OnConnectionStateChanged(bool online); void OnStoreReset(); private: base::WeakPtr<GCMInvalidationBridge> bridge_; scoped_refptr<base::SingleThreadTaskRunner> ui_thread_task_runner_; MessageCallback message_callback_; ConnectionStateCallback connection_state_callback_; base::Closure store_reset_callback_; base::WeakPtrFactory<Core> weak_factory_; DISALLOW_COPY_AND_ASSIGN(Core); }; GCMInvalidationBridge::Core::Core( base::WeakPtr<GCMInvalidationBridge> bridge, scoped_refptr<base::SingleThreadTaskRunner> ui_thread_task_runner) : bridge_(bridge), ui_thread_task_runner_(ui_thread_task_runner), weak_factory_(this) { // Core is created on UI thread but all calls happen on IO thread. DetachFromThread(); } GCMInvalidationBridge::Core::~Core() {} void GCMInvalidationBridge::Core::Initialize( ConnectionStateCallback connection_state_callback, base::Closure store_reset_callback) { DCHECK(CalledOnValidThread()); connection_state_callback_ = connection_state_callback; store_reset_callback_ = store_reset_callback; // Pass core WeapPtr and TaskRunner to GCMInvalidationBridge for it to be able // to post back. ui_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::CoreInitializationDone, bridge_, weak_factory_.GetWeakPtr(), base::ThreadTaskRunnerHandle::Get())); } void GCMInvalidationBridge::Core::RequestToken(RequestTokenCallback callback) { DCHECK(CalledOnValidThread()); ui_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::RequestToken, bridge_, callback)); } void GCMInvalidationBridge::Core::InvalidateToken(const std::string& token) { DCHECK(CalledOnValidThread()); ui_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::InvalidateToken, bridge_, token)); } void GCMInvalidationBridge::Core::Register(RegisterCallback callback) { DCHECK(CalledOnValidThread()); ui_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Register, bridge_, callback)); } void GCMInvalidationBridge::Core::SetMessageReceiver(MessageCallback callback) { message_callback_ = callback; ui_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::SubscribeForIncomingMessages, bridge_)); } void GCMInvalidationBridge::Core::RequestTokenFinished( RequestTokenCallback callback, const GoogleServiceAuthError& error, const std::string& token) { DCHECK(CalledOnValidThread()); callback.Run(error, token); } void GCMInvalidationBridge::Core::RegisterFinished( RegisterCallback callback, const std::string& registration_id, gcm::GCMClient::Result result) { DCHECK(CalledOnValidThread()); callback.Run(registration_id, result); } void GCMInvalidationBridge::Core::OnIncomingMessage( const std::string& message, const std::string& echo_token) { DCHECK(!message_callback_.is_null()); message_callback_.Run(message, echo_token); } void GCMInvalidationBridge::Core::OnConnectionStateChanged(bool online) { if (!connection_state_callback_.is_null()) { connection_state_callback_.Run(online); } } void GCMInvalidationBridge::Core::OnStoreReset() { if (!store_reset_callback_.is_null()) { store_reset_callback_.Run(); } } GCMInvalidationBridge::GCMInvalidationBridge( gcm::GCMDriver* gcm_driver, IdentityProvider* identity_provider) : OAuth2TokenService::Consumer("gcm_network_channel"), gcm_driver_(gcm_driver), identity_provider_(identity_provider), subscribed_for_incoming_messages_(false), weak_factory_(this) {} GCMInvalidationBridge::~GCMInvalidationBridge() { if (subscribed_for_incoming_messages_) { gcm_driver_->RemoveAppHandler(kInvalidationsAppId); gcm_driver_->RemoveConnectionObserver(this); } } std::unique_ptr<syncer::GCMNetworkChannelDelegate> GCMInvalidationBridge::CreateDelegate() { DCHECK(CalledOnValidThread()); return base::MakeUnique<Core>(weak_factory_.GetWeakPtr(), base::ThreadTaskRunnerHandle::Get()); } void GCMInvalidationBridge::CoreInitializationDone( base::WeakPtr<Core> core, scoped_refptr<base::SingleThreadTaskRunner> core_thread_task_runner) { DCHECK(CalledOnValidThread()); core_ = core; core_thread_task_runner_ = core_thread_task_runner; } void GCMInvalidationBridge::RequestToken( syncer::GCMNetworkChannelDelegate::RequestTokenCallback callback) { DCHECK(CalledOnValidThread()); if (access_token_request_ != NULL) { // Report previous request as cancelled. GoogleServiceAuthError error(GoogleServiceAuthError::REQUEST_CANCELED); std::string access_token; core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::RequestTokenFinished, core_, request_token_callback_, error, access_token)); } request_token_callback_ = callback; OAuth2TokenService::ScopeSet scopes; scopes.insert(GaiaConstants::kChromeSyncOAuth2Scope); access_token_request_ = identity_provider_->GetTokenService()->StartRequest( identity_provider_->GetActiveAccountId(), scopes, this); } void GCMInvalidationBridge::OnGetTokenSuccess( const OAuth2TokenService::Request* request, const std::string& access_token, const base::Time& expiration_time) { DCHECK(CalledOnValidThread()); DCHECK_EQ(access_token_request_.get(), request); core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::RequestTokenFinished, core_, request_token_callback_, GoogleServiceAuthError::AuthErrorNone(), access_token)); request_token_callback_.Reset(); access_token_request_.reset(); } void GCMInvalidationBridge::OnGetTokenFailure( const OAuth2TokenService::Request* request, const GoogleServiceAuthError& error) { DCHECK(CalledOnValidThread()); DCHECK_EQ(access_token_request_.get(), request); core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::RequestTokenFinished, core_, request_token_callback_, error, std::string())); request_token_callback_.Reset(); access_token_request_.reset(); } void GCMInvalidationBridge::InvalidateToken(const std::string& token) { DCHECK(CalledOnValidThread()); OAuth2TokenService::ScopeSet scopes; scopes.insert(GaiaConstants::kChromeSyncOAuth2Scope); identity_provider_->GetTokenService()->InvalidateAccessToken( identity_provider_->GetActiveAccountId(), scopes, token); } void GCMInvalidationBridge::Register( syncer::GCMNetworkChannelDelegate::RegisterCallback callback) { DCHECK(CalledOnValidThread()); // No-op if GCMClient is disabled. if (gcm_driver_ == NULL) return; std::vector<std::string> sender_ids; sender_ids.push_back(kInvalidationsSenderId); gcm_driver_->Register(kInvalidationsAppId, sender_ids, base::Bind(&GCMInvalidationBridge::RegisterFinished, weak_factory_.GetWeakPtr(), callback)); } void GCMInvalidationBridge::RegisterFinished( syncer::GCMNetworkChannelDelegate::RegisterCallback callback, const std::string& registration_id, gcm::GCMClient::Result result) { DCHECK(CalledOnValidThread()); core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::RegisterFinished, core_, callback, registration_id, result)); } void GCMInvalidationBridge::Unregister() { DCHECK(CalledOnValidThread()); // No-op if GCMClient is disabled. if (gcm_driver_ == NULL) return; gcm_driver_->Unregister( kInvalidationsAppId, base::Bind(&GCMInvalidationBridge::UnregisterFinishedNoOp)); } // static void GCMInvalidationBridge::UnregisterFinishedNoOp( gcm::GCMClient::Result result) { // No-op. } void GCMInvalidationBridge::SubscribeForIncomingMessages() { // No-op if GCMClient is disabled. if (gcm_driver_ == NULL) return; DCHECK(!subscribed_for_incoming_messages_); gcm_driver_->AddAppHandler(kInvalidationsAppId, this); gcm_driver_->AddConnectionObserver(this); core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::OnConnectionStateChanged, core_, gcm_driver_->IsConnected())); subscribed_for_incoming_messages_ = true; } void GCMInvalidationBridge::ShutdownHandler() { // Nothing to do. } void GCMInvalidationBridge::OnStoreReset() { core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::OnStoreReset, core_)); } void GCMInvalidationBridge::OnMessage(const std::string& app_id, const gcm::IncomingMessage& message) { gcm::MessageData::const_iterator it; std::string content; std::string echo_token; it = message.data.find(kContentKey); if (it != message.data.end()) content = it->second; it = message.data.find(kEchoTokenKey); if (it != message.data.end()) echo_token = it->second; core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::OnIncomingMessage, core_, content, echo_token)); } void GCMInvalidationBridge::OnMessagesDeleted(const std::string& app_id) { // Cacheinvalidation doesn't use long lived non-collapsable messages with GCM. // Android implementation of cacheinvalidation doesn't handle MessagesDeleted // callback so this should be no-op in desktop version as well. } void GCMInvalidationBridge::OnSendError( const std::string& app_id, const gcm::GCMClient::SendErrorDetails& send_error_details) { // cacheinvalidation doesn't send messages over GCM. NOTREACHED(); } void GCMInvalidationBridge::OnSendAcknowledged( const std::string& app_id, const std::string& message_id) { // cacheinvalidation doesn't send messages over GCM. NOTREACHED(); } void GCMInvalidationBridge::OnConnected(const net::IPEndPoint& ip_endpoint) { core_thread_task_runner_->PostTask( FROM_HERE, base::Bind( &GCMInvalidationBridge::Core::OnConnectionStateChanged, core_, true)); } void GCMInvalidationBridge::OnDisconnected() { core_thread_task_runner_->PostTask( FROM_HERE, base::Bind(&GCMInvalidationBridge::Core::OnConnectionStateChanged, core_, false)); } } // namespace invalidation
Questions about Fused Silica Mainly, grades are classified by inclusion class and degree of homogeneity. Different grades have varying purity and/or hydroxide content which may affect transmittance at certain wavelengths. What are the differences between fused silica and fused quartz? Both Fused Silica and Fused Quartz are extremely pure materials featuring very low thermal expansion and excellent optical qualities. They both work well in areas that require good chemical resistance. Unlike fused quartz, which originates from mined, natural quartz or silica sand, fused silica is produced synthetically by the vapor phase hydrolysis of a silicon halide. The resulting product is vitreous, non-crystalline, of the highest purity and one of the most transparent glasses made. Its transmission and homogeneity exceed those of crystalline quartz without the problems of orientation and temperature instability inherent in the crystalline form. Fused silica, with a softening temperature of around 1,600 degrees Celsius, a very low coefficient of thermal expansion and resistance to thermal shock and effects of radiation, is the material of choice for various applications. We use cookies to provide you with the best experience. To learn more about how we use cookies please read our Privacy Policy. By continuing to use the website, you agree and consent to our policy.Got it!
Q: How can I pass Cursor to another Activity? I need to pass Cursor object to another activity, what is the best way to do it? A: You can share you Cursor object using Application class, but it is not entertain because it is recommended not to use static reference much, So its Better to create cursor with a new query in another activity.
'Smurfing' suspect charged in Germaine Road fire February 14, 2018News Extra A purported meth lab “cook” recently popped up on law enforcement radar. Investigators were locked on William E. Burke, 38, of Winfield Township, who they suspect was “smurfing,” that is, using others to buy Sudafed pills from pharmacies. The medicine, a must-have for meth-makers, was turned over to Burke. He was using it, authorities believe, for a “one pot” or “shake and bake” portable — and potentially volatile — methamphetamine lab in Butler Township. Just two weeks after state and county narcotics officers began investigating Burke, he was badly burned in a fire Feb. 3 that destroyed a home on typically peaceful Germaine Road. From the confines of a Pittsburgh hospital, investigators said, he later admitted the fire started while he was cooking up the synthetic stimulant.
Posts in the ‘Recipes’ Category Looking for an inexpensive alternative to cake pops? Try making these pink sprinkle Oreo pops instead. Shauna at Ella and Annie Magazine put together this quick and easy tutorial for making them. These are perfect as birthday treats on a dessert table, party favors dressed in little cellophane bags, and Valentine's Day treats. What kid wouldn't want this colorful cookie treat at a birthday or on Valentines day!? They are easy to make and super fun. Raspberry Jello Shots Recipe As the holidays approach, Strongbow hard cider asked us to come up with a second party food pairing (our first pairing was our quick and easy aioli recipe). We chose to pair our pepper parmesan crisps recipe with the hard cider because we love the combination of apples and cheese. The cider brings a tangy, tart, appley-flavor, and the cheese brings a salty, unctuous richness that stands up well to the sharpness in the cider. Both play off each other effortlessly. Need some last-minute Christmas dessert ideas? Below are 9 of our favorite recipes for you to whip up this holiday! We've got yummy cookies, brownies, cupcakes, cakes, and even peppermint bark. These have all been tested for ease and deliciousness. So spend less time baking and more time enjoying your holiday with friends and family! I was asked by Strongbow to come up with a recipe that would pair well with the flavors in their hard apple cider. When I think of drinking hard ciders, with their warm apple-y bite, I think about hanging out with friends on a winter day in big, bulky sweaters (maybe that's what I'm thinking about right now because it's cold and cloudy here in Northern California). So I wanted to come up with something that would work well for a casual winter get-together. I love serving French fries when I entertain because... everyone loves French fries. Honestly, do you know anyone who doesn't? But to elevate them, I like to serve them with unique and flavorful dipping sauces. So enter my quick and easy aioli recipe! We were asked by DeKuyper to come up with a signature cocktail that would be fun to serve during the holidays. Most people think of eggnog or peppermint as their Christmas flavors of choice, but when I think winter... I think citrus! If you're serving cake this holiday, and need to save time, do what I did here. Buy a white cake at the grocery store, and add some homemade touches like candied orange slices and I promise your guests will be impressed. Making these candied orange slices was super easy. The only thing you need to be aware of is that your orange slices need time to dry, like two hours in a warm oven. Other than that, there's really nothing to it and the candied orange slices were delicious -- sweet, tangy, and chewy. They're definitely great for cake decorating, but you can serve them on their own as a candied treat, and your guests will eat them up! Here's a delicious and easy peppermint bark recipe from Shauna at Ella and Annie Magazine that is a fun treat to serve at your holiday parties or as part of a Christmas gift basket! With the holidays fast approaching, I am getting all my recipes in order for our gift baskets. Ever since I was a little girl I have watched my mother bake. Christmas time for our family is a special time of year. We bake. We bake for family and friends. If you are looking for last-minute and delicious Thanksgiving dessert ideas, we've got them! Here are 9 of my favorite desserts to give you some ideas beyond the usual fare. I've created each recipe myself, so I know they how easy and tasty each one is, I promise you won't be disappointed. And if you make one of these =, please email me a photo to jillian(at)catchmyparty(dot)com. I'd love to see how yours turned out!
Introduction {#Sec1} ============ It is becoming increasingly evident that in addition to being effector cells of the immune system, macrophages have vital homeostatic functions ranging from rather janitorial tasks, such as the clearance of cellular debris or the maintenance of erythrocyte turnover, to critical functions in wound healing, regeneration and tissue repair. This broad spectrum of activities is ensured by the notable plasticity that enables the physiology of these cells to be altered in response to environmental cues, producing different cell populations with distinct functions. To this end, macrophages are tightly interconnected with the surrounding cell populations via the controlled release and permanent sensing of intercellular communication signals. These signals include signaling peptides such as cytokines, chemokines, growth factors or arachidonic acid derivatives. In macrophages, at least in response to inflammatory pathogens, the expression of many of these mediators is controlled by the MAP kinase family member p38^MAPK^ and its downstream effector molecules. In addition to being critical for the initiation and establishment of the inflammatory response, this pathway is part of a signaling network that---in a cell type-dependent manner---modifies intracellular signal transduction and the cellular response towards cytokines such as IL-6 according to the context of coacting signals^[@CR1]--[@CR4]^. In addition, the p38^MAPK^ pathway has been recently demonstrated to mediate not only the release of inflammatory mediators but also the type I interferon-dependent release of IL-10 and the subsequent prolonged activation of signal transducer and activator of transcription (STAT)3^[@CR2],[@CR5],[@CR6]^. The latter protein is critical for the de-escalation and dissipation of the inflammatory response, indicating a key role of the p38^MAPK^ pathway in the orchestration of not only the induction but also the feedback control of the inflammatory response^[@CR2],[@CR7],[@CR8]^. An important part of the intracellular signal transduction elicited by p38^MAPK^ is mediated via the activation of the two downstream effector kinases of p38^MAPK^, MAPK-activated protein kinases (MAPKAPK or MK)2 and 3. These two kinases are highly critical for the control of the expression of a variety of intercellular communication signals, including various cytokines and chemokines such as TNF-α, IL-6, OSM, IFN-β, IL-10, CXCL2 and CXCL8. These two kinases are closely related isoenzymes and were initially demonstrated to cooperate in the regulation of inflammatory gene expression at the posttranscriptional level^[@CR9],[@CR10]^. However, previous evidence indicates that in addition to their cooperative action, these kinases exhibit distinct regulatory roles in gene expression. Thus, at least in the context of the macrophage inflammatory response^[@CR5]^, it has been demonstrated that MK3 exerts negative regulatory effects on lipopolysaccharide (LPS)-inducible gene expression in the absence of MK2. In particular, IκBβ protein levels and NFκB activation in response to LPS stimulation, as well as IRF3 expression, appear to be affected if only MK3 is present^[@CR5]^. Therefore, it is unclear to what degree the different IκBβ levels observable in macrophages deficient in MK2 alone or both MK2 and MK3 are due to reduced expression or enhanced degradation. Moreover, it is unknown, if these distinct regulatory effects of MK2 and MK3 described for the regulation of the IFN-β gene are true for LPS-inducible expression of only IFN-β or also of other genes. The present study aims to further characterize the differential impact of MK2 and MK3 on LPS-induced gene expression in macrophages. Results {#Sec2} ======= Deletion of MK2 or deletion of both MK2 and MK3 strongly alters gene expression in response to LPS {#Sec3} -------------------------------------------------------------------------------------------------- We previously demonstrated that in macrophages, the expression of the IL-10 gene in response to LPS requires MK2-mediated upregulation of IFN-β gene expression, activation of the IFN-α receptor (IFNAR) 1 and accumulation of the IL-10 transcript, which, in turn, is MK2/3-dependent^[@CR5]^. Consistent with these findings, sustained IL-10 expression in response to LPS was significantly downregulated in primary bone marrow-derived macrophages (BMDM) that lacked MK2, an effect that - at least during early time points - tended to be enhanced upon the additional deletion of MK3 in MK2/3^−/−^ BMDM (Fig. [1a](#Fig1){ref-type="fig"}). In contrast to this pattern but consistent with previous data from our group^[@CR5]^, the induction of IFN-β expression, which, in contrast to that of IL-10, occurs rapidly and is short-term, was impaired in MK2^−/−^ macrophages and restored upon the additional deletion of MK3 (MK2/3^−/−^; Fig. [1b](#Fig1){ref-type="fig"}) compared to that in wild-type control cells (wt BMDM). Notably, in macrophages that lack only MK3 (MK3^−/−^ BMDM), LPS-inducible expression of the IFN-β gene was not significantly affected (Supplemental Fig. [S1b](#MOESM1){ref-type="media"}), suggesting that MK3 only exerts its effects on the expression of genes such as IFN-β in the absence of MK2.Figure 1LPS-induced transcript expression of IL-10 and IFN-β is controlled by the interplay of MK2 and MK3. Bone marrow-derived macrophages (BMDM) were prepared from wild-type (wt), MK2-deficient (MK2^−/−^) and MK2/3-double-deficient (MK2/3^−/−^) mice and treated with 100 ng/ml LPS for the indicated durations. Total mRNA was extracted and analyzed using rtPCR. Data are presented as the means ± SEMs based on at least 5 replicates. Statistics were calculated by 2-way ANOVA with the Bonferroni test. A p-value of less than 0.05 was considered significant. The symbols indicate significance: \) wt vs. MK2^−/−^, ^+^) wt vs. MK2/3^−/−^ and ^x^) MK2^−/−^ vs. MK2/3^−/−^. There seems to be a complex interplay between MK2 and MK3, wherein MK2 neutralizes the negative regulatory effects of MK3 on LPS-induced IFN-β gene expression. However, it is not clear whether this effect is limited to IFN-β or is generally applicable to additional target genes. To answer this question, gene expression in response to LPS treatment was analyzed via whole genome array analyses in BMDM prepared from the bone marrow of MK2^−/−^ and MK2/3^−/−^ animals as well as from the corresponding control animals after 2 and 6 h of treatment with 100 ng/ml LPS. In this approach, the analysis was restricted to 33,325 out of 55,819 probes referring to genes related to NCBI listed accession numbers. Since several genes were proven by transcript expression with multiple probes, a total of 24,288 genes were included in the analysis. A response to LPS was considered relevant when the expression of the respective gene was significantly up- or downregulated, with a p-value of at least 0.05, upon treatment of the cells with LPS. Accordingly, after 2 h, a total of 11,768 genes and after 6 h, a total of 16,563 genes were significantly up- or downregulated independent of the genotype. Next, these genes were separated by genotype, and the results are presented in Venn diagrams (Fig. [2a,b](#Fig2){ref-type="fig"}). In wild-type macrophages, 6,580 transcripts (27% of the analyzed 24,288) exhibited a change in their expression after 2 h of treatment with 100 ng/ml LPS (Fig. [2a](#Fig2){ref-type="fig"}), while in MK2^−/−^ and MK2/3^−/−^ macrophages, 8,264 (34%) and 8,982 (37%) of the genes, respectively, were influenced in response to LPS treatment. The overall number of genes responsive to LPS increased to 10,081 (42%) in wt BMDM and to 13,311 (55%) or 12,962 (53%) in MK2^−/−^ or MK2/3^−/−^ BMDM, respectively (Fig. [2b](#Fig2){ref-type="fig"}), when stimulation with LPS was extended to 6 h.Figure 2LPS-responsive genes controlled by MK2 and/or MK2/3: Whole genome array and the top 25 MK2/3-dependent genes with the strongest induction. For (a,b), BMDM were isolated from wild-type (wt), MK2-deficient (MK2^−/−^) and MK2/3-double-deficient (MK2/3^−/−^) mice and treated with 100 ng/ml LPS for 2 (a) or 6 (b) h. Total mRNA was extracted and subjected to microarray analysis to determine the total transcript levels. In total, 24,288 genes with known functions were analyzed and integrated into Venn diagrams when significantly up- or downregulated upon LPS treatment (t-test, p \< 0.05). The numbers indicate the number of genes belonging to the indicated subset. The percentages reflect the ratio of the analyzed total genes. The red circles represent differentially regulated genes under wild-type conditions; blue, under MK2^−/−^ conditions; and green, under MK2/3^−/−^ conditions. From these genes, those with a minimum expression change of 4-fold from wild-type conditions were further analyzed after 2 (c) or 6 h (d) of LPS treatment. The top 25 differentially expressed genes with MK2- and/or MK2/3-dependency are listed. The three columns represent the relative LPS-induced expression level between the respective genotypes. wt vs. MK2^−/−^ indicates the level under wild-type conditions compared to that under MK2-deficient conditions. wt vs. MK2/3^−/−^ indicates the level under wild-type conditions compared to that under MK2/3 double-deficient conditions. MK2^−/−^ vs. MK2/3^−/−^ indicates the level under MK2-deficient conditions compared to that under MK2/3 double-deficient conditions. Therefore, the heat map color for each gene in each column reflects the degree of the difference between the expression levels of the respective genotypes. The red fields show enhanced expression in macrophages from the first listed genotype compared with the expression in the second genotype, whereas the blue fields show decreased expression in the first listed genotype compared with that in the second listed genotype. The white fields indicate no difference between the listed genotypes. Color transitions indicate patterns of differences in which at least one of the compared expression levels was significantly different (\p \< 0.05; \\p \< 0.01; \\\p \< 0.001). Notably, after 120 min or 360 min of treatment, a group of 5,188 or 6,482 genes, respectively, became LPS-responsive, but this effect occurred only if either MK2 or both MK2 and MK3 were deleted. Hence, these data indicate that, in addition to being critical for the regulation of gene expression in macrophages in response to LPS, MK2 and/or MK3 are required to prevent a large number of genes from being regulated by LPS or from contributing to feedback regulation of the LPS response (Fig. [2a,b](#Fig2){ref-type="fig"}). Analysis of the differential regulation of LPS-inducible gene expression in macrophages by MK2 and/or MK3 reveals six different modes of regulation {#Sec4} --------------------------------------------------------------------------------------------------------------------------------------------------- Next, we aimed to focus on the LPS-responsive genes that were upregulated in wt BMDM and differentially regulated in the absence of either MK2 alone and/or both MK2 and MK3. Thus, the number of transcripts analyzed was restricted to those that were significantly upregulated in response to LPS in wt BMDM by at least four-fold. Of the 24,288 genes analyzed after 120 min of LPS treatment, 682 were identified to meet these criteria, and this number increased to 1,065 genes after 360 min of stimulation with LPS. From these genes, identified as LPS-responsive, the expression level within each genotype (wt, MK2^−/−^, MK2/3^−/−^) was compared with the respective other two genotypes (wt vs. MK2^−/−^, wt vs. MK2/3^−/−^, MK2^−/−^ vs. MK2/3^−/−^). As a result 131 (120 min LPS incubation time) or 478 (360 min LPS) of the LPS-responsive genes were at least for one condition (wt vs. MK2^−/−^ or wt vs. MK2/3^−/−^ or MK2^−/−^ vs. MK2/3^−/−^) significantly changed and therefore were defined as MK2- and/or MK2/3-dependently regulated. The LPS-responsive genes determined by this procedure and considered to being MK2- and/or MK2/3-dependently regulated in BMDM are listed according to their relative expression level in the Supplemental Material (Supplemental Fig. [S2a,b](#MOESM1){ref-type="media"}, p-values are listed in [S2c,d](#MOESM1){ref-type="media"}). The top 25 of these genes are summarized as heat maps in Fig. [2c,d](#Fig2){ref-type="fig"} with Ifnb1* (gene symbol of IFN-β) as the factor, which is most prominently upregulated by LPS after 2 h (Fig. [2c](#Fig2){ref-type="fig"}) and Il19 (IL-19) as the gene with most prominent upregulation of gene expression after 6 h of LPS treatment (Fig. [2d](#Fig2){ref-type="fig"}). Compared to wt BMDM the abundance of both transcripts was significantly diminished upon deletion of MK2 (wt \> MK2^−/−^, Fig. [2c,d](#Fig2){ref-type="fig"} first column) and in the case of IL-19 transcript expression was also significantly reduced in MK2/3^−/−^ BMDM (Il19, Fig. [2d](#Fig2){ref-type="fig"} second column, wt \> MK2/3^−/−^) as suggested by the red color in the heat maps (wt \> MK2^−/−^ or wt \> MK2/3^−/−^). This indicates that in BMDM MK2 plays a critical role for the upregulation of these two genes in response to LPS. Contrariwise, when compared to MK2^−/−^ BMDM, additional deletion of MK3 in MK2/3^−/−^ BMDM results in an upregulation of the Ifnb1 transcript as indicated by the blue color (MK2^−/−^ \< MK2/3^−/−^). Although in the analysis of the array data this upregulation was not significant, it was consistent with the RT-qPCR data outlined above (Fig. [1b](#Fig1){ref-type="fig"}) indicating that LPS-inducible transcript expression of the IFN-β gene is strongly diminished upon deletion of MK2 in MK2^−/−^ BMDM, whereas, compared to MK2^−/−^ BMDM, IFN-β gene expression significantly increases again upon additional deletion of MK3 in MK2/3^−/−^ BMDM and time dependently even exceeds that observed in wt BMDM. In addition, the expression levels of these genes compared to the wild-type control are listed in the Supplemental Fig. [S2e1,f1](#MOESM1){ref-type="media"} with the wild-type control defined as 100% and those genes mentioned in the following text are also presented as bar charts (Supplemental Fig. [S2g--l](#MOESM1){ref-type="media"}). To identify genes that are differentially regulated regarding wt vs. MK2^−/−^, wt vs. MK2/3^−/−^ or MK2^−/−^ vs. MK2/3^−/−^ a variation of the mean values between the respective genotypes of \>20% (wt vs. MK2^−/−^ or wt vs. MK2/3^−/−^ or MK2^−/−^ vs. MK2/3^−/−^: \>or \<20%) was set as a threshold. Using this threshold, the heat maps further suggested that the regulatory pattern (wt \> MK2^−/−^, MK2/3^−/−^ \> MK2^−/−^) observed for Ifnb1 is not only the case for Ifnb1, but also for other genes including genes like Ccl12, Iigp1, Serpina3f and Serpina3g (Supplemental Fig. [S2g](#MOESM1){ref-type="media"}). The regulatory pattern suggested for this group of genes is summarized as group III in Fig. [3a](#Fig3){ref-type="fig"}. Contrariwise, in case of genes such as Adora2b, Cxcl2, Il2, Il10, Lcn2 or Saa2 the analysis reflected a different regulatory pattern (wt \> MK2^−/−^, MK2/3^−/−^ \< or = MK2^−/−^) similar to that seen for Il19 (Supplemental Fig. [S2h](#MOESM1){ref-type="media"}). These genes are summarized as group I in Fig. [3a](#Fig3){ref-type="fig"}. As it was the case for the Ifnb1 gene, the regulatory pattern identified for the regulation of the Il10 gene was in line with the RT-qPCR data outlined above (Fig. [1a](#Fig1){ref-type="fig"}) and with previous observations from our group^[@CR5]^.Figure 3Classification and allocation of the MK2/3-dependent genes by 6 different patterns of regulation and distribution of MK2- and MK2/3-regulated genes according to their expression pattern. The proposed 6 different patterns of regulation dependent on MK2 and MK3 are shown in (a) (groups I-VI). The long bars indicate high induction and the short bars indicate low induction of LPS-responsive genes. The red bars reflect the condition in wild-type macrophages, the blue bars reflect the MK2^−/−^ condition, and the green bars reflect the MK2/3^−/−^ condition. According to their expression patterns, all the analyzed genes listed in Supplemental Fig. [S2](#MOESM1){ref-type="media"}, of which the top 25 are listed in the heat maps in Fig. [2](#Fig2){ref-type="fig"} (c,d), were allocated to the 6 distinct groups and are shown in pie charts for the 2 h (b) and 6 h (c) treatments with 100 ng/ml LPS. The proportion of genes in each group is depicted in percentages. For the allocation, a minimum difference of 20% in LPS-induced gene expression between the genotypes was considered relevant (Supplemental Fig. [S3](#MOESM1){ref-type="media"}). Furthermore, the distinct genes summarized in these pie charts are shown in the scatter plot according to their relative expression value after 2 h (d) and 6 h (e) of treatment with 100 ng/ml LPS. The log-scaled x- and y-axis of the scatter plots indicates the relative expression level between the depicted genotypes with 0 meaning no difference, negative values meaning lower expression in MK2^−/−^ than in wt BMDM (wt vs. MK2^−/−^ on the y-axis) or in MK2/3^−/−^ than in MK2^−/−^ BMDM (MK2^−/−^ vs. MK2/3^−/−^ on the x-axis) and positive values meaning higher expression in MK2^−/−^ than in wt BMDM (wt vs. MK2^−/−^ on the y-axis) or in MK2/3^−/−^ than in MK2^−/−^ BMDM (MK2^−/−^ vs. MK2/3^−/−^ on the x-axis). Target genes that were analyzed further, as shown in Fig. [4](#Fig4){ref-type="fig"}, are depicted (d,e). In b to e, each group is identified by its distinct color, as shown in the figure legend. Interestingly, apart from these two groups the heat maps in Fig. [2c,d](#Fig2){ref-type="fig"} suggest additional groups with distinct regulatory patterns of LPS-induced gene expression. Thus, the genes Cd40, Gem, Fpr2, Il12b, Mab21l3, Sdc4 and Tcfec are enhanced in the absence of either MK2 alone (MK2^−/−^) or of both MK2 and MK3 (MK2/3^−/−^) (Supplemental Fig. [S2i](#MOESM1){ref-type="media"}), indicating that MK2 and/or MK2/3 restrict the LPS-inducible expression of these genes to lower levels (MK2^−/−^ \> WT, MK2/3^−/−^ \> WT; summarized in group II). In addition, another group of genes comprising Cxcl3, Csf2, Niacr1, Slc7a1 and Shisa3 appears to be MK3-dependently amplified in the absence of MK2 (summarized in group IV) since the enhancement of LPS-inducible gene expression is observable in MK2^−/−^ BMDM but does not occur upon combined deletion of MK2 and MK3 in MK2/3^−/−^ BMDM (MK2^−/−^ \> WT, MK2/3^−/−^ \< or = WT) (Supplemental Fig. [S2j](#MOESM1){ref-type="media"}). Furthermore, in some cases gene expression is only up- or down-regulated when both MK2 and MK3 are deleted, whereas deletion of MK2 alone appears to have no effect on gene expression. Thus, when compared to wt or MK2^−/−^ BMDM the expression of the genes Hdc, Il23a or Saa3 (summarized in group V) is diminished upon combined deletion of MK2 and MK3 (Supplemental Fig. [S2k](#MOESM1){ref-type="media"}), while the genes Cd69, Cxcl9, Cxcl10, Marcksl1, Mx2 or Socs1 are upregulated in the absence of both MK2 and MK3 in MK2/3^−/−^ BMDM (summarized in group VI) (Supplemental Fig. [S2l](#MOESM1){ref-type="media"}). Based on these six groups defined on the basis of the distinct regulation of LPS-inducible gene expression by the protein kinases MK2 and MK3 (Figs [2c,d](#Fig2){ref-type="fig"} and [S2a--d](#MOESM1){ref-type="media"}) the genes identified to be MK2- and/or MK2/3-dependently regulated by LPS were allocated to one of the six defined groups (Fig. [3a](#Fig3){ref-type="fig"}). Thereby, as outlined above, a gene was considered to be differentially regulated regarding wt vs. MK2^−/−^, wt vs. MK2/3^−/−^ or MK2^−/−^ vs. MK2/3^−/−^ respectively, when the mean values between the respective genotypes varied at least 20%, which was set as a threshold (wt vs. MK2^−/−^ or wt vs. MK2/3^−/−^ or MK2^−/−^ vs. MK2/3^−/−^: \>or \<20%). Using this approach the heatmap could be transformed into a map without any changes in the transition of color and assign a clear position for each gene within one of the six expression patterns (Supplemental Fig. [S3a,b](#MOESM1){ref-type="media"}). Based on this procedure, 31% of the 131 genes that were MK2- and/or MK2/3-dependently regulated after 2 h of LPS treatment, could be allocated to group II (Figs [3b](#Fig3){ref-type="fig"} and [S4a](#MOESM1){ref-type="media"}). Correspondingly, after 6 h of LPS treatment, 478 genes could be allocated to the six different expression patterns, with gene expression groups I and III as the biggest groups − 23% and 22%, respectively (Figs [3c](#Fig3){ref-type="fig"} and [S4b](#MOESM1){ref-type="media"}). Moreover, the proportion of LPS-inducible genes regulated by the interplay of MK2 and MK3 in the same way as Ifnb1 increased from 9% after 2 h to 22% after 6 h of LPS treatment. To demonstrate the relative strength of the influence of the respective knockout phenotype compared to the other genotypes on LPS-induced expression of the respective transcripts allocated to the six different groups in Fig. [3b,c](#Fig3){ref-type="fig"}, we further constructed a two-dimensional scatter plot (Fig. [3d,e](#Fig3){ref-type="fig"}). Based on these analyses, genes representative of one of the six defined groups were selected to further validate and corroborate the different regulatory patterns characterizing the six different groups. As the original aim of the study was primarily to test the hypothesis that genes other than Ifnb1 are also similarly regulated by the interplay of MK2 and MK3, three genes - complement component 1 r subcomponent A (Cr1a), the inflammasome-component nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and the serine peptidase inhibitor clade A member 3 F (Serpina3f) - were selected to further validate the regulatory pattern characteristic of group III. As demonstrated in Fig. [4a--c](#Fig4){ref-type="fig"}, LPS-inducible transcription of these three genes was reduced upon deletion of MK2 and, as is the case for IFN-β (Fig. [1b](#Fig1){ref-type="fig"}), the additional deletion of MK3 in MK2/3^−/−^ BMDM resulted in at least partial reconstitution of the transcript levels compared to those in wt BMDM. Similarly, the chemokine CXCL2 (Cxcl2), the IL4 receptor (IL4R)α (Il4ra) and IL-19 (Il19) (Fig. [4d--f](#Fig4){ref-type="fig"}) were chosen as three genes that are regulated in a similar way as IL-10 (Il10) (Fig. [1a](#Fig1){ref-type="fig"}) and belong to the same group of genes (group I), which has been previously described as being either mainly MK2-dependently regulated or cooperatively regulated by MK2 and MK3. Additionally, based on the results shown in Fig. [3](#Fig3){ref-type="fig"} for each of the other groups (II, IV, V and VI) defined in the present study, a representative gene was chosen, and its LPS-inducible expression was analyzed in wt BMDM, MK2^−/−^ BMDM and MK2/3^−/−^ BMDM using RT-qPCR for further validation. Consistent with the regulatory pattern described above for the genes summarized as group II, the LPS-induced accumulation of IL-12b transcripts was enhanced in MK2^−/−^ as well as in MK2/3^−/−^ BMDM compared to that in wt BMDM (Fig. [4g](#Fig4){ref-type="fig"}), corroborating the assumption that the LPS-inducible expression of these genes is limited by either MK2 alone or by MK2 and MK3 in cooperation. In contrast, the transcript level of the chemokine CXCL3 (Cxcl3) was enhanced in MK2^−/−^ BMDM but not in MK2/3^−/−^ BMDM compared to that in wt BMDM (Fig. [4h](#Fig4){ref-type="fig"}). Hence, as this gene is a member of group IV, its LPS-induced expression in BMDM lacking MK2 appears to be upregulated by MK3. In contrast, the transcript levels of genes such as HDC (Hdc) (group V) and CXCL9 (Cxcl9) (group VI) were either reduced (group V) or enhanced (group VI) in BMDM lacking both MK2 and MK3 (MK2/3^−/−^ BMDM) but not in wt BMDM or in MK2^−/−^ BMDM (Fig. [4i,j](#Fig4){ref-type="fig"}).Figure 4LPS-induced and MK2- and/or MK2/3-dependent expression of target genes and representatives of the 6 different types of regulation. Bone marrow-derived macrophages (BMDM) were prepared from wild-type (wt), MK2-deficient (MK2^−/−^) and MK2/3-double-deficient (MK2/3^−/−^) mice and treated with 100 ng/ml LPS for the indicated time points. Total mRNA was extracted and analyzed using rtPCR as specified in the methods section. C1rA, Nod1 and Serpina3f are representative target genes of group III (a--c), whereas CXCL2, IL-4Rα and IL-19 are representatives of group I (d--f). Group II is represented by IL-12b (g), group IV by CXCL3 (h), group V by HDC (i) and group VI by CXCL9 (j). Data are presented as the means ± SEMs based on at least 3 replicates per condition. Statistics were calculated by 2-way ANOVA with the Bonferroni test. A p-value of less than 0.05 was considered significant. The following symbols indicate significance: \) wt vs. MK2^−/−^, ^+^) wt vs. MK2/3^−/−^ and ^x^) MK2^−/−^ vs. MK2/3^−/−^. Notably, the LPS-inducible expression of none of the genes investigated in Fig. [1](#Fig1){ref-type="fig"} (IL-10 and IFN-β) and Fig. [4](#Fig4){ref-type="fig"} (Nod1, Cr1A, Serpina3f, CXCL2, IL-4Rα, IL-19, IL-12b, CXCL3, HDC and CXCL9) was significantly impaired in BMDM in which only MK3 was absent (Supplemental Figs [S1](#MOESM1){ref-type="media"} and [S5](#MOESM1){ref-type="media"}). Hence, these data indicate that in the presence of MK2, the function of MK3 may be replaceable or compensated by another, yet unidentified, molecule or process. As demonstrated recently for genes such as IL-10, tristetraprolin plays an important role in the regulation of genes summarized in group I {#Sec5} ------------------------------------------------------------------------------------------------------------------------------------------ In addition to being regulated at the transcriptional level, the accumulation of IL-10^[@CR11]--[@CR14]^ and CXCL2^[@CR9],[@CR11]^ transcripts is controlled at the level of mRNA stability. In this context, the mRNA binding factor tristetraprolin (TTP), which initiates mRNA degradation, is phosphorylated by MK2 and then disassociates from the target mRNA, leading to its stabilization^[@CR11],[@CR13],[@CR15]--[@CR17]^. Notably, the genes Cxcl1, Cxcl2* and Socs3 (Fig. [2c,d](#Fig2){ref-type="fig"}), as well as Cebpd and Zfp36 (Supplemental Fig. [S2](#MOESM1){ref-type="media"}), which were all defined as genes in group I (Supplemental Fig. [S4](#MOESM1){ref-type="media"}), were also identified among the top 25 target genes of TTP reported in another array-based study^[@CR18]^. Hence, it was conceivable that most of the group I genes are also targets of TTP, which was another common feature of the genes in this group. To investigate whether in addition to IL-10 and CXCL2, the IL-4Rα and IL-19 genes, which are representative members of group I, are also TTP target genes, we took advantage of immortalized TTP-deficient BMDM stably transfected with a vector encoding TTP or GFP under the control of a tetracycline-dependent promoter. In these cells, TTP expression can be reconstituted upon stimulation with doxycycline, allowing analysis of putative TTP target genes^[@CR19]^. Notably, doxycycline-inducible TTP expression was further enhanced upon costimulation with LPS (Fig. [5a](#Fig5){ref-type="fig"}). Consistently and in agreement with previous data, LPS-inducible IL-10 expression was substantially impaired upon reconstitution of TTP expression (Fig. [5b](#Fig5){ref-type="fig"}). Similarly, upregulated transcript expression of the α subunit of the IL-4 receptor was significantly reduced in response to LPS, if TTP expression was coinduced (Fig. [5c](#Fig5){ref-type="fig"}), indicating that its transcript expression is also controlled by TTP. In contrast, the upregulation of IL-19 transcription in response to LPS was not affected by TTP at early time points, while the decrease in the transcript abundance over time appeared to be accelerated if TTP was present (Fig. [5d](#Fig5){ref-type="fig"}). Hence, at least at later time points, the IL-19 transcript may also belong to the group of TTP-regulated transcripts.Figure 5The mRNA binding protein tristetraprolin (TTP) controls the transcript expression of the genes summarized in group I. Immortalized TTP^−/−^ bone marrow-derived macrophages (TTP^−/−^ BMDM^IM^) stably expressing a plasmid allowing tetracycline-inducible reconstitution of tristetraprolin (TTP^rec^) expression or GFP expression as the control were used. Cells were treated with 4 µg/ml doxycycline (DOX) for 2 h and were then stimulated with 100 ng/ml LPS for the indicated durations. The expression of TTP (a), IL-10 (b), IL-4Rα (c) or IL-19 (d) was analyzed using rtPCR. Data are presented as the means ± SEMs based on at least 3 replicates per condition. Statistics were calculated by 2-way ANOVA with the Bonferroni test. A p-value of less than 0.05 was considered significant, and the following symbols indicate significance: \) control vs. LPS and ^+^) GFP vs. TTP^rec^. Reconstitution of impaired NFκB activation in macrophages lacking MK2 upon the additional deletion of MK3 is due to accelerated ubiquitination and decay of IκBβ {#Sec6} ---------------------------------------------------------------------------------------------------------------------------------------------------------------- We previously demonstrated that in MK2^−/−^ BMDM, nuclear translocation of the p65 NFκB subunit was impaired due to enhanced expression of inhibitor of κB (IκB)β and increased binding of p65 to IκBβ^[@CR5]^. This impaired activation of NFκB in MK2^−/−^ BMDM has been demonstrated to be due to the action of MK3 in the absence of MK2. Since regular activation of NFκB is required for IFN-β gene expression, impaired NFκB activation was considered to be responsible for the reduced transcript expression observed in cells that lack MK2 (Fig. [1b](#Fig1){ref-type="fig"}). However, a more detailed analysis of the time dependency of NFκB subunit p65 appearance in nuclear extracts (Figs [6a](#Fig6){ref-type="fig"} and [S6a](#MOESM1){ref-type="media"}) and its accompanying disappearance from cytosolic lysates (Figs [6b](#Fig6){ref-type="fig"} and [S6b](#MOESM1){ref-type="media"}) in wt and MK2^−/−^ BMDM revealed that LPS-induced nuclear translocation of p65 is not completely abolished in MK2^−/−^ BMDM, but is diminished and delayed compared to that in wt BMDM. The additional deletion of MK3 in MK2/3^−/−^ BMDM contributed greatly to restoring the wild-type conditions with respect to the time course and extension of p65 nuclear translocation (Figs [6a,b](#Fig6){ref-type="fig"} and [S6a,b](#MOESM1){ref-type="media"}). Notably, inhibition of p38^MAPK^ using the small molecule compound SB203580 (Fig. [6c](#Fig6){ref-type="fig"}) as well as deletion of MK2 (MK2^−/−^ BMDM) or both MK2 and MK3 (MK2/3^−/−^ BMDM) (Fig. [6d,e](#Fig6){ref-type="fig"}) resulted in an increased abundance of IκBβ molecules, consistent with previous observations from our group^[@CR5]^. This increased availability of IκBβ molecules is considered to be responsible for the diminished and delayed release and nuclear translocation of the NFκB p65 subunit in MK2^−/−^ and in MK2/3^−/−^ BMDM compared to the wild-type conditions. Thereby, the kinetics of the decay of IκBβ as well as the time course of the phosphorylation of IκBβ at serines 19 and 23 upon stimulation with LPS did not significantly differ between wt and MK2^−/−^ BMDM (Fig. [6d,f](#Fig6){ref-type="fig"}). This pattern indicates that compared to wt BMDM, MK2^−/−^ BMDM exhibit increased IκBβ levels while the velocity of the decay of IκBβ remains equal to wild-type conditions. Interestingly, in accordance with the observation that in MK2/3^−/−^ BMDM, nuclear translocation of p65 in response to LPS treatment was almost restored to wild-type levels (Figs [6a](#Fig6){ref-type="fig"} and [S6a](#MOESM1){ref-type="media"}), the velocity of LPS-triggered IκBβ decay was substantially enhanced upon the additional deletion of MK3 in MK2/3^−/−^ BMDM compared to that in wt and MK2^−/−^ BMDM, resulting in accelerated disappearance of IκBβ (Fig. [6d,f](#Fig6){ref-type="fig"}). It is therefore suggested that the restoration of the nuclear translocation of p65 to wild-type levels upon the additional deletion of MK3 in MK2/3^−/−^ BMDM is due to an enhancement in the decay of IκBβ molecules in these cells (Fig. [6d,f](#Fig6){ref-type="fig"}) that otherwise would bind p65^[@CR5]^ and prevent its nuclear translocation. This enhancement was not accompanied by stronger or more prolonged Ser19/23 phosphorylation of IκBβ in MK2/3^−/−^ BMDM (Fig. [6d](#Fig6){ref-type="fig"}). In line with the increased velocity of IκBβ molecule decay, evidence is provided that compared to wild-type and MK2^−/−^ BMDM, MK2/3^−/−^ BMDM exhibit earlier ubiquitination of IκBβ (Figs [6g](#Fig6){ref-type="fig"} and [S6c](#MOESM1){ref-type="media"}) and that this ubiquitination can be reduced to wild-type or MK2^−/−^ levels if MK3 is reintroduced (Figs [6h](#Fig6){ref-type="fig"} and [S6d](#MOESM1){ref-type="media"}). Hence, in the absence of MK2, MK3 is responsible for delayed IκBβ ubiquitination. Our data suggest that the LPS-induced release of NFκB from IκBβ as well as the retention of NFκB in the cytosol by binding to IκBβ is controlled by the interplay of MK2 and MK3. In this case, MK2 suppresses the enhanced accumulation of IκBβ in the cytosol, whereas MK3 delays IκBβ ubiquitination and subsequent degradation to maintain temporally controlled LPS-induced NFκB release.Figure 6MK3 counteracts p65 NFκB nuclear translocation in the absence of MK2 by delaying the ubiquitination and subsequent degradation of the inhibitor of κB (IκB) β, whose protein accumulation is suppressed by MK2. For (a,b) and (e--h), immortalized bone marrow-derived macrophages (BMDM^IM^) were used. For (a), proteins in the nuclear extracts (NE) and for (b), proteins in the cytosolic lysates (CL) were prepared. For c and d, primary BMDM were prepared from wild-type (wt), MK2-deficient (MK2^−/−^) and MK2/3 double-deficient (MK2/3^−/−^) mice. For h, MK2/3^−/−^ BMDM^IM^ were stably transfected with a vector coexpressing MK3 or GFP as the control via an internal ribosomal reentry site (IRES) or with the same vector expressing only GFP as the control using retroviral gene transfer. Cells were treated with 100 ng/ml LPS for the indicated durations and (c), cells were treated with the p38^MAPK^ inhibitor SB203580 (5 µM) for 4 h prior to LPS treatment. Then, cells were harvested and further analyzed by immunoblotting using antibodies specifically recognizing the p65 subunit of the NFκB complex, producing a signal at a location corresponding to a molecular weight of 65 kDa according to the protein weight marker (a,b); nuclear full-length Lamin A/C, 70 kDa (a); IκBβ, 50 kDa (d--h); IκBβ phosphorylated at serine residues 19 and 23, 50 kDa (c,d); MK2, 40 and 50 kDa; MK3, 40 kDa (d); and GAPDH, 36 kDa (c,d). For (b), IκBβ and for (g,h), ubiquitin-ligated proteins were precipitated with polyubiquitin (PU) affinity beads and subjected to immunoblot analysis using antibodies specifically recognizing IκBβ, with a molecular weight of 50 kDa, or ubiquitinated proteins, from which the fraction containing proteins with a maximum molecular weight of 25 kDa is shown. (a--d,g,h) show samples from the same experiment, and the juxtaposed images show detections from different areas of the same blot or from the same area of different blots with the same samples, if the proteins of interest had approximately the same molecular weight. To set the focus on the individual antibody signals, images were cropped at the borders depicted with a black line. The time kinetics of IκBβ expression following LPS treatment shown in d were examined via densitometric analysis with n = 3 replicates, and data are presented as the means ± SEMs (e,f), demonstrating the basal expression (e) or time-dependent degradation of IκBβ (f). Statistics were calculated as described in the methods section; the following symbols indicate significance: \) wt vs. MK2^−/−^ or MK2/3^−/−^. Discussion {#Sec7} ========== Previous reports demonstrated that MK2 and MK3 control the expression of several mediators of inflammation, such as TNF-α, CXCL2 and IL-10, in a cooperative manner^[@CR5],[@CR9]^. Previous reports further suggested that MK2 and MK3 may also display distinct and, in part, contradictory regulatory effects on gene expression^[@CR5],[@CR20]^. Hence, as outlined above in macrophages, MK2 upregulates the transcription of IFN-β by neutralizing the negative regulatory effects of MK3, which impedes nuclear translocation of NFκB in the absence of MK2^[@CR5]^. Correspondingly, as shown previously^[@CR5]^ and confirmed herein, the expression of IFN-β mRNA is lower in MK2^−/−^ BMDM than in wild-type BMDM, an effect that at least in part can be neutralized by the additional deletion of MK3, as seen in MK2/3^−/−^ BMDM (Fig. [1b](#Fig1){ref-type="fig"}). Notably, deletion of MK3 alone in MK3^−/−^ BMDM had no effect on the LPS-inducible expression of IFN-β, indicating that MK3 exerts its negative regulatory effects on IFN-β gene expression only in the absence of MK2 (Supplemental Fig. [S1b](#MOESM1){ref-type="media"}). This behavior is in contrast to the LPS-inducible expression of IL-10, which was downregulated in MK2^−/−^ as well as in MK2/3^−/−^ BMDM (Fig. [1a](#Fig1){ref-type="fig"}) and tended to be reduced also in MK3^−/−^ BMDM (Supplemental Fig. [S1a](#MOESM1){ref-type="media"}) compared with that in wild-type BMDM. This finding supports recent observations that the regulation of IL-10 expression is governed by MK2 in cooperation with MK3^[@CR5],[@CR9]^. A major aim of the present study was to clarify whether MK2 also controls the LPS-inducible expression of genes other than IFN-β by neutralizing the inhibitory effects of MK3 on gene expression. As outlined above, we defined a group of genes (group III in Figs [3](#Fig3){ref-type="fig"} and [S4](#MOESM1){ref-type="media"}) regulated by the interplay of MK2 and MK3 in a similar way as IFN-β that, among others, includes the acute phase protein and serine peptidase inhibitor (Serpin)a3f and the pathogen recognition receptor Nod1 as well as the serine protease and component of the complement system C1rA (Fig. [4a--c](#Fig4){ref-type="fig"}). As with the IFN-β gene (Fig. [1b](#Fig1){ref-type="fig"}), the LPS-inducible expression of these genes was significantly diminished in BMDM lacking MK2 compared to that in wild-type control BMDM but was reconstituted or even enhanced upon the additional deletion of MK3 (Fig. [4a--c](#Fig4){ref-type="fig"}). These data suggest that as it does for the IFN-β gene, MK3 negatively affects the expression of these genes in the absence of MK2, which neutralizes the negative regulatory effects of MK3. Of note, as it is the case for IFN-β gene expression, deletion of MK3 alone in MK3^−/−^ BMDM does not affect the LPS-inducible expression of these genes, indicating that the negative regulatory effect of MK3 only becomes apparent in the absence of MK2 (Supplemental Fig. [S5a--c](#MOESM1){ref-type="media"}). Contrariwise, the LPS-inducible expression of genes summarized herein as group I (Fig. [3](#Fig3){ref-type="fig"}), including genes such as the chemokine CXCL2, the IL-4 receptor subunit (IL-4R)α and the cytokine IL-19 (Fig. [4d--f](#Fig4){ref-type="fig"}) is strongly impaired in MK2^−/−^ macrophages, an effect, which at least in part tends to be further enhanced upon additional deletion of MK3. Consistently, the data presented herein suggest that, although not significant, the LPS-inducible expression of these genes also tends to be impaired in the absence of MK3 (Supplemental Fig. [S5d--f](#MOESM1){ref-type="media"}). This type of regulation corresponds to that noted in previous reports demonstrating that MK2 and MK3 cooperate in upregulating the biosynthesis of genes such as IL-10 and TNF-α^[@CR5],[@CR9]^. Further studies as well as the results shown in Fig. [5](#Fig5){ref-type="fig"} demonstrate that the transcripts of these genes are targets of the RNA-binding protein TTP^[@CR13]--[@CR15],[@CR19],[@CR21]^. These findings suggest that at least some of the genes in group I are also target genes of TTP. Notably, the data presented herein suggest that in BMDM, the regulation of gene expression by the interplay of MK2 and MK3 in response to LPS is far more complex than the two regulatory patterns summarized as group I, or Il10-type, and group III, or Ifnb1-type. Hence, at least four additional regulatory patterns were identified based on the alteration of LPS-inducible gene expression in BMDM in response to deletion of MK2 or both MK2 and MK3 (Figs [3](#Fig3){ref-type="fig"} and [S4](#MOESM1){ref-type="media"}). These patterns suggest that in addition to cooperatively upregulating gene expression or neutralizing the negative regulatory effects of MK3, MK2 may either cooperate with MK3 to limit the upregulation of gene expression in response to LPS, as demonstrated for IL-12 subunit b (Fig. [4g](#Fig4){ref-type="fig"}, group II or Il12b-type), or counteract the enhancing effects of MK3, as demonstrated for CXCL3 (Fig. [4h](#Fig4){ref-type="fig"}, group IV or Cxcl3-type). In the latter case, gene expression was strongly enhanced in MK2^−/−^ BMDM compared with that in wild-type control cells, and this enhancement was reversed upon the additional deletion of MK3. In addition, as validated herein for the genes HDC (Fig. [4i](#Fig4){ref-type="fig"}) and CXCL9 (Fig. [4j](#Fig4){ref-type="fig"}), there are two groups - termed herein as groups V and VI (Figs [3](#Fig3){ref-type="fig"} and [S4](#MOESM1){ref-type="media"}) - in which gene expression was either diminished (group V or Hdc-type) or enhanced (group VI or Cxcl9-type) upon deletion of both MK2 and MK3, while deletion of MK2 alone did not significantly affect gene expression in response to LPS compared to that observed in wild-type BMDM. Notably, macropinocytosis of dendritic cells (DCs) in response to LPS treatment is diminished when both kinases are missing, whereas neither MK2 nor MK3 alone exert any influence on this particular function of DCs^[@CR22]^. These observations indicate that in some cases, MK2 and MK3 may thoroughly compensate for each other, whereas deletion of both causes drastic effects by unbalancing the cellular response to LPS. The underlying molecular mechanisms of the complex interplay by which the two kinases MK2 and MK3 achieve these different mechanisms of regulation of gene expression in response to LPS is largely unclear and must be the subject of future research. However, in this context, it is interesting to note that the negative regulatory effects of MK3 on IFN-β gene expression in the absence of MK2 are caused by delayed release of NFκB from its complex with IκBβ^[@CR5]^. Consistent with this observation, compared to wild-type controls, MK2^−/−^ BMDM exhibited impaired LPS-inducible nuclear translocation of the NFκB complex p65 subunit (Figs [6a](#Fig6){ref-type="fig"} and [S6a](#MOESM1){ref-type="media"}), coinciding with prolonged detectability of p65 in the cytoplasm (Figs [6b](#Fig6){ref-type="fig"} and [S6b](#MOESM1){ref-type="media"}). As suggested by previous data from immortalized BMDM cell lines, this delayed activation of NFκB in MK2^−/−^ BMDM is due to increased expression of the IκBβ protein in the absence of MK2^[@CR5]^. The latter observation was confirmed herein for primary BMDM, where IκBβ expression is also increased in cells lacking MK2 (Fig. [6d,e](#Fig6){ref-type="fig"}). The data presented indicate that upon additional deletion of MK3 in MK2/3^−/−^ BMDM, NFκB activation is reconstituted in these cells, although the basal IκBβ levels are increased due to an accelerated decay of IκBβ (Fig. [6d,f](#Fig6){ref-type="fig"}). Thereby, as demonstrated herein for the first time, in the absence of MK2, MK3 delays ubiquitination and subsequent degradation of IκBβ. This delay is circumvented upon additional MK3 deletion in MK2/3^−/−^ BMDM. Consistently, reconstitution of MK3 expression in MK2/3^−/−^ BMDM resulted in delayed IκBβ ubiquitination, which substantiates the hypothesis that MK3 is indeed responsible for hindering the degradation of IκBβ upon MK2 deficiency (Figs [6h](#Fig6){ref-type="fig"} and [S6d](#MOESM1){ref-type="media"}). Hence, we suggest that in BMDM lacking MK2 p65 translocation is delayed due to an increased abundance of IκBβ protein in the cytoplasm and a MK3-mediated delay of their ubiquitination resulting in a prolonged degradation of IκBβ. The molecular mechanism by which MK3 interferes with the ubiquitination and degradation of IκBβ in the absence of MK2 is unclear and remains to be established. However, in this context it may be interesting to note that previous work indicates that activation of MK2 is interlinked with regulation of ubiquitination. Hence, the endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 has been demonstrated to be a substrate of MK2 and MK2-dependent signaling^[@CR23]^ and may be involved in the regulation of proteasomal degradation of the ARE-mRNA decay factor AUF1^[@CR24]^. Methods {#Sec8} ======= Preparation and cultivation of murine bone marrow-derived macrophages {#Sec9} --------------------------------------------------------------------- The establishment, genotyping, and colony maintenance of mice deficient for MK2 or for MK3 have been described elsewhere^[@CR25],[@CR26]^. Wild-type bone marrow-derived macrophages (wt BMDM), MK2-deficient BMDM (MK2^−/−^ BMDM) and BMDM deficient in MK2 and 3 (MK2/3^−/−^ BMDM) were prepared and cultivated as recently described^[@CR12]^. The prepared BMDM were 96.7% (±3.6) F4/80-positive, 99.9% (±1.0) CD11b-positive and 71.3% (±2.5) CD11c-negative as assessed by flow cytometry analysis. The medium was changed to M-CSF-free culture medium 1 h before experiments were performed. Cells were used after a total differentiation period of 9 days. For experiments with immortalized murine bone marrow-derived macrophages (BMDM^IM^), cells described previously were used^[@CR5],[@CR12]^. Animals {#Sec10} ------- The MK2-, MK3- and MK2/3-deficient animals on a C57BL/6J background have been previously described^[@CR9],[@CR22],[@CR26]^. Animals were handled and housed under specific pathogen-free (SPF) conditions. Experiments were carried out in accordance with the German law for animal protection and were approved by the North-Rhine-Westphalia State Agency of Nature, Environment and Consumer Protection (LANUV) under the reference number 84-02.04.2013.A464. RNA isolation and real-time PCR {#Sec11} ------------------------------- RNA isolation and rtPCR were performed as described previously^[@CR5]^. The primers used are listed in Supplemental Table [1](#MOESM5){ref-type="media"}. The rtPCR specificity was controlled using controls lacking either template or reverse transcriptase. Semi-quantitative PCR results were analyzed using the ΔCT method, and the threshold values were normalized to the expression of hnSDHA. Preparation of total cell lysates, cytosolic lysates and nuclear extracts {#Sec12} ------------------------------------------------------------------------- The preparation of total cell lysates, cytosolic lysates (CL) and nuclear extracts (NE) from murine immortalized or primary BMDM, respectively, was performed as described previously^[@CR5]^. Immunoblotting, immunoprecipitation and immunodetection {#Sec13} ------------------------------------------------------- A total of 60 µg of protein extracts from cell culture lysates were subjected to SDS gel electrophoresis (8% PAA) and immunoblotted as described previously^[@CR5]^. For immunodetection, the following primary antibodies were used at a 1:2,000 dilution: rabbit polyclonal anti-IκBβ (Cat. No. DB076, Delta Biolabs, Gilroy, CA), anti-phospho-Ser19/23-IκBβ (Cat. No. 4921), anti-MK2 (Cat. No. 3042), anti-lamin A/C (Cat. No. 2032, Cell Signaling, Danvers, MA), and anti-ubiquitin (Cat. No. ab7780, Abcam, Cambridge, UK); mouse monoclonal anti-MK3 (Cat. No. H00007867-M01, Abnova, Taipei, Taiwan) and anti-p65 (Cat. No. sc-372, Santa Cruz, Dallas, TX); and mouse monoclonal anti-GAPDH (Cat. No. H86504M, Meridian Life Science, Memphis, TN). The immunoprecipitation protocol has been described previously^[@CR5]^. For the precipitation of polyubiquitinated proteins, a ubiquitinated protein enrichment kit (Cat. No. 662200, Merck, Darmstadt, Germany) was used according to the manufacturer's instructions. Equipment and settings for the detection of immunoblotted proteins {#Sec14} ------------------------------------------------------------------ Following an overnight incubation period at 4 °C with the appropriate primary antibody, immunoblots were incubated for 1 h with a 1:6,000 dilution of a horseradish peroxidase-conjugated secondary antibody (Dako/Agilent, Santa Clara, CA) reacting with either rabbit or mouse immunoglobulin. Next, immunoblots were washed 3 times and were then incubated for 1 min with Western Lightning Plus-ECL substrate (PerkinElmer, Waltham, MA). After immunoblots were sealed in a plastic sheet, they were exposed to film (Hyperfilm ECL, Amersham/GE Healthcare, Little Chalfont, UK) in the dark for between 10 sec and 3 min, depending on the signal intensity, for chemiluminescence detection. For this procedure, film sheets were cut into pieces covering the area on the immunoblot that included the size of the protein of interest according to the protein molecular weight marker (Precision Plus Protein Dual Color Standard, Bio-Rad, Munich, Germany). For film processing, a Curix 60 developer (Agfa, Mortsel, Belgium) was used according to the manufacturer's instructions. Next, developed films were scanned at a pixel intensity of at least 300 dpi using a Perfection 4990 Photo flatbed scanner (Epson, Suwa, Japan) and Epson Scan Software v3.04 G and were saved as JPEG files. The figures were cropped using XnView image viewer and editor software (Kolor, Francin, France) to set the focus on the protein of interest within the respective immunoblot area. There was no further image processing for brightness or contrast. Uncropped images of the scanned original films from respective immunoblots, which were cropped for Fig. [6](#Fig6){ref-type="fig"}, are presented in Supplemental Fig. [S7](#MOESM1){ref-type="media"}. Agilent gene chip analysis {#Sec15} -------------------------- Wild-type, MK2^−/−^ or MK2/3^−/−^ BMDM were stimulated with 100 ng/ml LPS for 120 min or 360 min. For both time points, four completely independent experiments were performed. The integrity of the isolated RNA was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies, Waldbronn, Germany). All samples in this study showed high-quality RNA integrity numbers (RIN 9,6 +/−0,08). RNA was quantified by photometric measurement on a NanoDrop (Thermo Fisher Scientific GmbH, Dreieich, Germany). Synthesis of cDNA and subsequent fluorescent labeling of cRNA was performed according to the manufacturer's protocol (One-Color Microarray-Based Gene Expression Analysis/Low Input Quick Amp Labeling; Agilent Technologies). Briefly, 100 ng of total RNA was converted to cDNA, followed by in vitro transcription and incorporation of Cy3-CTP into the newly synthesized cRNA. After fragmentation, labeled cRNA was hybridized to Agilent SurePrint G3 Mouse Gene Expression v2 8 × 60 K Microarrays (Agilent Technologies, Boeblingen, Germany) for 17 h at 65 °C and scanned as described in the manufacturer's protocol. Signal intensities on 20-bit TIFF images were calculated using Feature Extraction software (Agilent Technologies, Boeblingen, Germany). Data analyses were conducted with GeneSpring GX (Agilent Technologies, Boeblingen, Germany). Probe signal intensities were quantile normalized across all samples to reduce interarray variability^[@CR27]^. Input data preprocessing was concluded by baseline transformation to the median of all samples. Microarray analysis {#Sec16} ------------------- Data sets with 55,819 probe sets per array were compared using Microsoft Excel (Microsoft, Redmond, WA). To avoid negative ratios, average intensity differences of \<5 were first set to 5. Data were normalized by the mean using the untreated wild-type sample as the baseline in each experiment. To identify differentially expressed genes, we excluded all genes from the analysis that were absent in the test sample (for upregulated genes) or absent in the baseline sample (for downregulated genes) in one or both experiments. Fold changes were calculated separately for the experiments as the ratio of the normalized average intensity difference (test sample) to the normalized average intensity difference (baseline sample). Thresholds were set for the fold change (2-fold and greater, unless otherwise indicated) and absolute difference (at least 500) between the normalized average intensity differences. The consistency between experiments varied between samples depending on the treatment and time point. To minimize the number of false positives, only genes that reproducibly met all the thresholds described above in independent experiments were considered differentially expressed. Further analysis of microarray data to identify distinct gene expression patterns {#Sec17} --------------------------------------------------------------------------------- From the 55,819 measured probes, only those that corresponded to a gene of known function according to the NCBI database were further analyzed, restricting the dataset to 33,325 probes. If genes were proven by multiple probes, only the probe with the highest induction in wt BMDM after stimulation with 100 ng/ml LPS was selected for further analysis. Therefore, the expression levels of 24,288 genes in wt BMDM and in BMDM deficient in MK2 or both MK2 and MK3 were analyzed. Data were normalized to the mean expression value in untreated wt BMDM. Differential expression was assessed using the two-sample Student's t-test. All computations were conducted using MATLAB R2014a (The MathWorks, Inc., Natick, MA). Statistical evaluation and densitometry {#Sec18} --------------------------------------- Statistics were calculated using GraphPad Prism 6 software. Significance was calculated using two-way ANOVA with the Bonferroni test. p \< 0.05 was considered to be significant. Densitometric analyses of immunoblots were performed using ImageJ software 1.49 from the National Institutes of Health, USA. Immunoblot bands were marked using the selection mode of the software, and the analyze/measure option was selected to determine the mean signal intensity of the protein of interest (IκBβ) as well as that of the loading control (GAPDH) for normalization (Fig. [6e,f](#Fig6){ref-type="fig"}). Supplementary information ========================= {#Sec19} Supplemental figures Supplemental figure 2 Supplemental figure 3 Supplemental figure 4 Supplemental table 1 Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information ========================= Supplementary information accompanies this paper at 10.1038/s41598-019-46791-8. We thank Marijana Suzanj for excellent technical assistance and Manoj Menon for carefully reading the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft, in particular, through the collaborative research center SFB 974, project number 190586431 (JB and DH). Further funding came from projects of the Virtual Liver and the LiSyM Network (JB) founded by the German Federal Ministry of Education and Research and from intramural research funds of the medical faculty of the Heinrich-Heine-University in Düsseldorf (CE). C.E.: performance of experiments, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript J.R.: analysis and interpretation of data, critical revision of the manuscript U.A.: performance of experiments, critical revision of the manuscript R.D.: performance of experiments, analysis and interpretation of data, critical revision of the manuscript C.T.: performance of experiments K.K.: analysis and interpretation of data, critical revision of the manuscript O.S.: critical revision of the manuscript M.G.: interpretation of data, critical revision of the manuscript D.H.: interpretation of data, critical revision of the manuscript J.G.B.: study conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript. The datasets generated and analyzed during the current study are available in the GEO repository, <https://www.ncbi.nlm.nih.gov/geo/>, under accession number GSE123043. The authors declare no competing interests.
/* * Copyright (c) 2000, 2001 Fabrice Bellard * * This file is part of FFmpeg. * * FFmpeg is free software; you can redistribute it and/or * modify it under the terms of the GNU Lesser General Public * License as published by the Free Software Foundation; either * version 2.1 of the License, or (at your option) any later version. * * FFmpeg is distributed in the hope that it will be useful, * but WITHOUT ANY WARRANTY; without even the implied warranty of * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU * Lesser General Public License for more details. * * You should have received a copy of the GNU Lesser General Public * License along with FFmpeg; if not, write to the Free Software * Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA / #include "asf.h" const ff_asf_guid ff_asf_header = { 0x30, 0x26, 0xB2, 0x75, 0x8E, 0x66, 0xCF, 0x11, 0xA6, 0xD9, 0x00, 0xAA, 0x00, 0x62, 0xCE, 0x6C }; const ff_asf_guid ff_asf_file_header = { 0xA1, 0xDC, 0xAB, 0x8C, 0x47, 0xA9, 0xCF, 0x11, 0x8E, 0xE4, 0x00, 0xC0, 0x0C, 0x20, 0x53, 0x65 }; const ff_asf_guid ff_asf_stream_header = { 0x91, 0x07, 0xDC, 0xB7, 0xB7, 0xA9, 0xCF, 0x11, 0x8E, 0xE6, 0x00, 0xC0, 0x0C, 0x20, 0x53, 0x65 }; const ff_asf_guid ff_asf_ext_stream_header = { 0xCB, 0xA5, 0xE6, 0x14, 0x72, 0xC6, 0x32, 0x43, 0x83, 0x99, 0xA9, 0x69, 0x52, 0x06, 0x5B, 0x5A }; const ff_asf_guid ff_asf_audio_stream = { 0x40, 0x9E, 0x69, 0xF8, 0x4D, 0x5B, 0xCF, 0x11, 0xA8, 0xFD, 0x00, 0x80, 0x5F, 0x5C, 0x44, 0x2B }; const ff_asf_guid ff_asf_audio_conceal_none = { // 0x40, 0xa4, 0xf1, 0x49, 0x4ece, 0x11d0, 0xa3, 0xac, 0x00, 0xa0, 0xc9, 0x03, 0x48, 0xf6 // New value lifted from avifile 0x00, 0x57, 0xfb, 0x20, 0x55, 0x5B, 0xCF, 0x11, 0xa8, 0xfd, 0x00, 0x80, 0x5f, 0x5c, 0x44, 0x2b }; const ff_asf_guid ff_asf_audio_conceal_spread = { 0x50, 0xCD, 0xC3, 0xBF, 0x8F, 0x61, 0xCF, 0x11, 0x8B, 0xB2, 0x00, 0xAA, 0x00, 0xB4, 0xE2, 0x20 }; const ff_asf_guid ff_asf_video_stream = { 0xC0, 0xEF, 0x19, 0xBC, 0x4D, 0x5B, 0xCF, 0x11, 0xA8, 0xFD, 0x00, 0x80, 0x5F, 0x5C, 0x44, 0x2B }; const ff_asf_guid ff_asf_video_conceal_none = { 0x00, 0x57, 0xFB, 0x20, 0x55, 0x5B, 0xCF, 0x11, 0xA8, 0xFD, 0x00, 0x80, 0x5F, 0x5C, 0x44, 0x2B }; const ff_asf_guid ff_asf_command_stream = { 0xC0, 0xCF, 0xDA, 0x59, 0xE6, 0x59, 0xD0, 0x11, 0xA3, 0xAC, 0x00, 0xA0, 0xC9, 0x03, 0x48, 0xF6 }; const ff_asf_guid ff_asf_comment_header = { 0x33, 0x26, 0xb2, 0x75, 0x8E, 0x66, 0xCF, 0x11, 0xa6, 0xd9, 0x00, 0xaa, 0x00, 0x62, 0xce, 0x6c }; const ff_asf_guid ff_asf_codec_comment_header = { 0x40, 0x52, 0xD1, 0x86, 0x1D, 0x31, 0xD0, 0x11, 0xA3, 0xA4, 0x00, 0xA0, 0xC9, 0x03, 0x48, 0xF6 }; const ff_asf_guid ff_asf_codec_comment1_header = { 0x41, 0x52, 0xd1, 0x86, 0x1D, 0x31, 0xD0, 0x11, 0xa3, 0xa4, 0x00, 0xa0, 0xc9, 0x03, 0x48, 0xf6 }; const ff_asf_guid ff_asf_data_header = { 0x36, 0x26, 0xb2, 0x75, 0x8E, 0x66, 0xCF, 0x11, 0xa6, 0xd9, 0x00, 0xaa, 0x00, 0x62, 0xce, 0x6c }; const ff_asf_guid ff_asf_head1_guid = { 0xb5, 0x03, 0xbf, 0x5f, 0x2E, 0xA9, 0xCF, 0x11, 0x8e, 0xe3, 0x00, 0xc0, 0x0c, 0x20, 0x53, 0x65 }; const ff_asf_guid ff_asf_head2_guid = { 0x11, 0xd2, 0xd3, 0xab, 0xBA, 0xA9, 0xCF, 0x11, 0x8e, 0xe6, 0x00, 0xc0, 0x0c, 0x20, 0x53, 0x65 }; const ff_asf_guid ff_asf_extended_content_header = { 0x40, 0xA4, 0xD0, 0xD2, 0x07, 0xE3, 0xD2, 0x11, 0x97, 0xF0, 0x00, 0xA0, 0xC9, 0x5E, 0xA8, 0x50 }; const ff_asf_guid ff_asf_simple_index_header = { 0x90, 0x08, 0x00, 0x33, 0xB1, 0xE5, 0xCF, 0x11, 0x89, 0xF4, 0x00, 0xA0, 0xC9, 0x03, 0x49, 0xCB }; const ff_asf_guid ff_asf_ext_stream_embed_stream_header = { 0xe2, 0x65, 0xfb, 0x3a, 0xEF, 0x47, 0xF2, 0x40, 0xac, 0x2c, 0x70, 0xa9, 0x0d, 0x71, 0xd3, 0x43 }; const ff_asf_guid ff_asf_ext_stream_audio_stream = { 0x9d, 0x8c, 0x17, 0x31, 0xE1, 0x03, 0x28, 0x45, 0xb5, 0x82, 0x3d, 0xf9, 0xdb, 0x22, 0xf5, 0x03 }; const ff_asf_guid ff_asf_metadata_header = { 0xea, 0xcb, 0xf8, 0xc5, 0xaf, 0x5b, 0x77, 0x48, 0x84, 0x67, 0xaa, 0x8c, 0x44, 0xfa, 0x4c, 0xca }; const ff_asf_guid ff_asf_marker_header = { 0x01, 0xCD, 0x87, 0xF4, 0x51, 0xA9, 0xCF, 0x11, 0x8E, 0xE6, 0x00, 0xC0, 0x0C, 0x20, 0x53, 0x65 }; / I am not a number !!! This GUID is the one found on the PC used to generate the stream / const ff_asf_guid ff_asf_my_guid = { 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 }; const ff_asf_guid ff_asf_language_guid = { 0xa9, 0x46, 0x43, 0x7c, 0xe0, 0xef, 0xfc, 0x4b, 0xb2, 0x29, 0x39, 0x3e, 0xde, 0x41, 0x5c, 0x85 }; const ff_asf_guid ff_asf_content_encryption = { 0xfb, 0xb3, 0x11, 0x22, 0x23, 0xbd, 0xd2, 0x11, 0xb4, 0xb7, 0x00, 0xa0, 0xc9, 0x55, 0xfc, 0x6e }; const ff_asf_guid ff_asf_ext_content_encryption = { 0x14, 0xe6, 0x8a, 0x29, 0x22, 0x26, 0x17, 0x4c, 0xb9, 0x35, 0xda, 0xe0, 0x7e, 0xe9, 0x28, 0x9c }; const ff_asf_guid ff_asf_digital_signature = { 0xfc, 0xb3, 0x11, 0x22, 0x23, 0xbd, 0xd2, 0x11, 0xb4, 0xb7, 0x00, 0xa0, 0xc9, 0x55, 0xfc, 0x6e }; / List of official tags at http://msdn.microsoft.com/en-us/library/dd743066(VS.85).aspx / const AVMetadataConv ff_asf_metadata_conv[] = { { "WM/AlbumArtist" , "album_artist"}, { "WM/AlbumTitle" , "album" }, { "Author" , "artist" }, { "Description" , "comment" }, { "WM/Composer" , "composer" }, { "WM/EncodedBy" , "encoded_by" }, { "WM/EncodingSettings", "encoder" }, { "WM/Genre" , "genre" }, { "WM/Language" , "language" }, { "WM/OriginalFilename", "filename" }, { "WM/PartOfSet" , "disc" }, { "WM/Publisher" , "publisher" }, { "WM/Tool" , "encoder" }, { "WM/TrackNumber" , "track" }, { "WM/Track" , "track" }, // { "Year" , "date" }, TODO: conversion year<->date { 0 } }; int ff_put_str16_nolen(ByteIOContext s, const char tag) { const uint8_t q = tag; int ret = 0; while (q) { uint32_t ch; uint16_t tmp; GET_UTF8(ch, q++, break;) PUT_UTF16(ch, tmp, put_le16(s, tmp);ret += 2;) } put_le16(s, 0); ret += 2; return ret; }
Otherworlders Here is our third installment of the “Clockwork Mondays”, as we continue to take the primary character(s) from the Capes & Clockwork “Superheroes in the Age of Steam” anthologies and posting them here with Victorious game statistics, for you...
In 1934, the Romanian-Jewish scholar Valeriu Marcu penned a book about the Spanish Inquisition, “The Expulsion of the Jews From Spain.” Officially banned in Germany because its author was Jewish, the book still found its way into the hands of German and German-Jewish intellectuals, and was widely read. Three years later, the Jewish Museum Berlin opened an exhibition on Isaac Abravanel, a 15th-century Portuguese rabbi and scholar who rose to prominence during the Spanish Inquisition. Although Kristallnacht (the “Night of Broken Glass”) was still a year away, this seemingly obscure museum attraction drew great interest, and not just among Jews. Carl Schmitt, a leading Nazi theorist who became known as “the crown jurist of the Third Reich,” found the exhibition fascinating. According to Eugene Sheppard, associate professor of modern Jewish history and thought, the Inquisition was the historical time period German and German-Jewish intellectuals in the 1930s thought most comparable to their own. Like people throughout history, they looked to the past as a way of understanding their present. Sheppard has uncovered a sudden proliferation of references to the Inquisition in German writings from that time. Years before the Final Solution began, German Jews clearly faced an ominous future under Hitler. They believed their fate would be similar to that of the Jews in medieval Spain — expulsion from their home country. Such an outcome, Sheppard says, was judged disastrous. In retrospect, it seems like wishful thinking. German Jews “get that something catastrophic is about to happen,” he says. “The problem is that the Spanish model was not catastrophic enough.” Marcu’s book, published a year before the Nuremberg Laws stripped German Jews of their citizenship, is filled with historical errors and disproven assumptions. But that’s not the point, says Sheppard. “Marcu wrote in a way that made it obvious to every German reader that he was really writing about the present,” he says. The epigraph in Marcu’s book quotes 19th-century German historian Leopold von Ranke on the Inquisition: “In no country have the prejudices concerning a distinction between pure and impure blood become so firmly implanted as in Spain. […] To [the Spanish people] it appeared as much an error of blood not to be of the pure Catholic faith as an error of opinion, hence the value they attributed to purity of blood, to limpieza.” Substitute a few words, and von Ranke could be describing Nazi Germany. Marcu was also interested in Abravanel, who had offered the Spanish monarchy a large sum of money to rescind the order expelling Jews. Though Abravanel wasn’t successful, Sheppard says German Jews still hoped a similar approach might work with the Nazis. Abravanel gave German Jews further cause for optimism. After he was driven out of Spain, he moved to Italy, where he managed to regain some of his prominence and wealth. German Jews in the 1930s didn’t know where they would wind up if Hitler expelled them, but they could at least cling to the hope that they might thrive there. Sheppard has found that Schmitt, the Nazi legal scholar, became bizarrely obsessed with Abravanel’s apocalyptic prophecies. In his writings, Abravanel predicted a climactic clash between civilizations, symbolized by a battle between the biblical monsters Leviathan and Behemoth, who would fight each other to a draw, then be slain by the Messiah. Afterward, men and women would gather to eat the monsters. “The Lord of hosts shall make unto all people […] a feast of fat things, of fat things full of marrow,” the religious scholar wrote. Schmitt convinced himself Leviathan and Behemoth represented England and Germany, destined to go to war against each other. He worried that if Germany exiled its Jews, the Messiah would come, and the Jews would get revenge by devouring whatever was left of the two countries. In a time with truly no precedent, both the Germans and the Jews got their predictions terribly wrong. Again and again, Sheppard’s research shows how tenuous a guide to the future history can be.
Q: Golang dependency management on windows does not work (GOPATH error) I try to use to different dependency management tools: godep and dep. And both fail with similar error. How should i set enviroument and where should I put sources? dep PS D:\Work\Golang\src\ChrBack> dep init root project import: D:\Work\Golang\src\ChrBack is not within any GOPATH/src godep PS D:\Work\Golang\src\ChrBack> godep save godep: [WARNING]: godep should only be used inside a valid go package directory and godep: [WARNING]: may not function correctly. You are probably outside of your $GOPATH. godep: [WARNING]: Current Directory: D:\Work\Golang\src\ChrBack godep: [WARNING]: $GOPATH: D:\Work\Golang\src godep: Unable to find SrcRoot for package . Go env $ D:\Work\Golang\Go\bin\go.exe version go version go1.9.1 windows/amd64 $ D:\Work\Golang\Go\bin\go.exe env set GOARCH=amd64 set GOBIN=D:\Work\Golang\src\bin set GOEXE=.exe set GOHOSTARCH=amd64 set GOHOSTOS=windows set GOOS=windows set GOPATH=D:\Work\Golang\src set GORACE= set GOROOT=D:\Work\Golang\Go set GOTOOLDIR=D:\Work\Golang\Go\pkg\tool\windows_amd64 set GCCGO=gccgo set CC=gcc set GOGCCFLAGS=-m64 -mthreads -fmessage-length=0 set CXX=g++ set CGO_ENABLED=1 set CGO_CFLAGS=-g -O2 set CGO_CPPFLAGS= set CGO_CXXFLAGS=-g -O2 set CGO_FFLAGS=-g -O2 set CGO_LDFLAGS=-g -O2 set PKG_CONFIG=pkg-config A: Try to set GOPATH=D:\Work\Golang Then create folders like src\github.com\user\repo and keep you in them.
Q: MYSQLI mysqli_real_escape_string and PHP problems Hey What's up Everybody… I am having a lot of trouble with this script. I guess it is standard PHP MYSQLI stuff. It was working until I tried to add the mysqli_real_escape string parts. Any ideas? <?php require_once 'connect.php'; $name = ($_POST['name']); $address = ($_POST['address']); $city = ($_POST['city']); $state = ($_POST['state']); $zip = ($_POST['zip']); $persons = ($_POST['persons']); $damages = ($_POST['damages']); $complaint = ($_POST['complaint']); $safename = mysqli_real_escape_string($connection, $name); $safeaddress = mysqli_real_escape_string($connection, $address); $safecity = mysqli_real_escape_string($connection, $city); $safestate = mysqli_real_escape_string($connection, $state); $safezip = mysqli_real_escape_string($connection, $zip); $safedate = mysqli_real_escape_string($connection, $date); $safepersons = mysqli_real_escape_string($connection, $persons); $safedamages = mysqli_real_escape_string($connection, $damages); $safecomplaint = mysqli_real_escape_string($connection, $complaint); $query = "INSERT INTO blacklisted ( name, address, city, state, zip, date, persons, damages, complaint ) VALUES ( ".$safename.", ".$safeaddress.", ".$safecity.", ".$safestate.", ".$safezip.", ".$safedate.", ".$safepersons.", ".$safedamage.", ".$safecomplaint." )"; $result = mysqli_query($connection, $query); mysqli_free_result($result); mysqli_close($connection); ?> I was under the impression everything would be fine but I am now confused. A: String values in SQL queries must be quoted. You are just escaping the data and them dumping it into the string. (I don't understand why you are concatenating all your strings instead of using variable interpolation there either). You shouldn't be mashing user input into strings of SQL anyway. Use prepared statements.
Patient characteristics and inequalities in doctors' diagnostic and management strategies relating to CHD: a video-simulation experiment. Numerous studies examine inequalities in health by gender, age, class and race, but few address the actions of primary care doctors. This factorial experiment examined how four patient characteristics impact on primary care doctors' decisions regarding coronary heart disease (CHD). Primary care doctors viewed a video-vignette of a scripted consultation where the patient presented with standardised symptoms of CHD. Videotapes were identical apart from varying patients' gender, age (55 versus 75), class and race, thereby removing any confounding factors from the social context of the consultation or other aspects of patients' symptomatology or behaviour. A probability sample of 256 primary care doctors in the UK and US viewed these video-vignettes in a randomised experimental design. Gender of patient significantly influenced doctors' diagnostic and management activities. However, there was no influence of social class or race, and no evidence of ageism in doctors' behaviour. Women were asked fewer questions, received fewer examinations and had fewer diagnostic tests ordered for CHD. 'Gendered ageism' was suggested, since midlife women were asked fewest questions and prescribed least medication appropriate for CHD. Primary care doctors' behaviour differed significantly by patients' gender, suggesting doctors' actions may contribute to gender inequalities in health.
That Boy You know, being friends with two cute boys does have its benefits. There's Danny. Danny is a golden boy in every way. He has dreamy blue eyes and blonde hair that always looks perfect, even when it's windblown or been stuck under a football helmet. He's the boy every girl crushes on. The boy I get into trouble with, the boy I fight with, the hot quarterback no girl can resist, not even me. Being with Danny is like being on an adventure. He has a bright, contagious smile and abs to die for. He's pretty much irresistible. I adored this book: the story, the characters, the narrator, etc. But there was one thing about the audiobook that drove me nuts and for that reason alone I feel like I had to post this in the hopes that it doesn't happen on other audiobooks. I listen to a lot of audiobooks and it made me crazy that every chapter ran right into the next. There was no pause, no breath, no nothing. I like being able to have a moment to digest what just happened in the previous chapter, even if it's for a moment, and there was NO pause at all between the final words of the previous chapter and the first ones of the next. I know that it seems picky, but it seriously bothered me enough to give the performance a 4-star rating instead of a 5. I know this isn't the narrator's fault, and I thought she was stellar, but whoever produced this needs to keep it in mind in the future. Otherwise, it was an amazing book and I highly recommend it! Rant over! 2 of 2 people found this review helpful Report Inappropriate Content If you find this review inappropriate and think it should be removed from our site, let us know. This report will be reviewed by Audible and we will take appropriate action. Your report has been received. It will be reviewed by Audible and we will take appropriate action. Can't wait to hear more from this listener? You can now follow your favorite reviewers on Audible. When you follow another listener, we'll highlight the books they review, and even email* you a copy of any new reviews they write. You can un-follow a listener at any time to stop receiving their updates. * If you already opted out of emails from Audible you will still get review emails by the listeners you follow.
Q: ioctl call program compiling error I want to call kernel module driver.ko ioctl from user space with c program. when compiling I got this error header.h:13:38: error: expected expression before ‘char’ #define IOCTL_CMD _IORW(MAGIC_NO, 0, char ) by definition I put the right arguments : _IORW(int type, int number, data_type) main.c #include <stdio.h> #include <fcntl.h> #include <string.h> #include "header.h" int main() { int fd; char msg = "5"; fd = open(DEVICE_PATH, O_RDWR); ioctl(fd, IOCTL_CMD, msg); printf("ioctl executed\n"); close(fd); return 0; } header.h #include <linux/ioctl.h> #include <linux/kdev_t.h> /* for MKDEV / #define DEVICE_NAME "driver" #define DEVICE_PATH "/dev/driver" #define WRITE 0 static int major_no; #define MAGIC_NO '4' / * Set the message of the device driver / #define IOCTL_CMD _IORW(MAGIC_NO, 0, char ) A: The macro _IORW doesn't seem to exist in the Linux headers, try using _IOWR instead. Also I don't think you're use of char * is correct here. That would imply the last parameter to ioctl is the address of a char * variable, not a string.
$43K Eco-Friendly Tiny House Set to Change the Face of Real Estate February 3, 2018Brent Furdyk Anyone looking to build a small home on an even smaller budget will want to investigate M.A.DI., a prefabricated home that is assembled on-site in as little as six hours — at an affordable cost that could be a game-changer for many aspiring homeowners. Real Estate $43K Eco-Friendly Tiny House Set to Change the Face of Real Estate February 3, 2018 Brent Furdyk Anyone looking to build a small home on an even smaller budget will want to investigate M.A.DI., a prefabricated home that is assembled on-site in as little as six hours — at an affordable cost that could be a game-changer for many aspiring homeowners. M.A.DI. 1/14 M.A.DI. "M.A.DI. is an unfoldable modular living unit," states <a href="https://www.madihome.com/" rel="noopener" target="_blank">the M.A.Di website</a>. "Using an unfolding technique, this construction system allows [the construction of] earthquake-resistant buildings for residential, leisure and hospitality. M.A.DI. can be also used to set-up of temporary villages for sports, fairs and first aid facilities in case of natural disasters." Real Estate$43K Eco-Friendly Tiny House Set to Change the Face of Real Estate M.A.DI. PHOTO 1 of 14 READ LESS - "M.A.DI. is an unfoldable modular living unit," states <a href="https://www.madihome.com/" rel="noopener" target="_blank">the M.A.Di website</a>. "Using an unfolding technique, this construction system allows [the construction of] earthquake-resistant buildings for residential, leisure and hospitality. M.A.DI. can be also used to set-up of temporary villages for sports, fairs and first aid facilities in case of natural disasters." A Tiny Home with a Difference A Tiny Home with a Difference Tapping into the tiny home trend, these modular homes are available in a variety of sizes. Prices begin at €28,000 (about $43,000 Canadian) for the smallest one, which hosts 290 square feet of living space. The largest model retails for €62,000 (approximately $95,000 Canadian), measuring 904 square feet. Real Estate$43K Eco-Friendly Tiny House Set to Change the Face of Real Estate A Tiny Home with a Difference PHOTO 7 of 14 READ LESS - Tapping into the tiny home trend, these modular homes are available in a variety of sizes. Prices begin at €28,000 (about $43,000 Canadian) for the smallest one, which hosts 290 square feet of living space. The largest model retails for €62,000 (approximately $95,000 Canadian), measuring 904 square feet. Expandable Expandable Another benefit of these modular homes is that they can be modified to be larger. If you wind up requiring more space, there’s no need to move — you can actually buy more modules that can be added to the home to increase the living area. Each additional module costs €16,000 (approximately $25,000 Canadian) while an extra staircase will set you back €2,000 (about $3,000 Canadian dollars). Real Estate$43K Eco-Friendly Tiny House Set to Change the Face of Real Estate Expandable PHOTO 9 of 14 READ LESS - Another benefit of these modular homes is that they can be modified to be larger. If you wind up requiring more space, there’s no need to move — you can actually buy more modules that can be added to the home to increase the living area. Each additional module costs €16,000 (approximately $25,000 Canadian) while an extra staircase will set you back €2,000 (about $3,000 Canadian dollars).
An Insider's Guide to Nashville's 10 Best Museums From music to sports, you're sure to find a museum that piques your interest If you're making a list of things to see while in Nashville, be sure to include some of these top museums. In addition to the well-known Parthenon, you can also explore museums specializing in visual arts, trains, and Tennessee state history. There are also several hall-of-fame museums that honor musicians and sports figures. Cheekwood Botanical Garden and Museum of Art is a 55-acre cultural attraction completed in 1932 by the Cheek family. It is located eight miles from downtown Nashville. The estate features 11 specialty gardens, paintings, and sculptures. Come in spring when more than 100,000 tulips are in bloom. Cheekwood plans many classes, workshops, and festivals appealing to all ages. The Country Music Hall of Fame and Museum is one of Nashville's most famous museums. Located in the heart of downtown Nashville's entertainment district, the museum is 40,000 square feet of pure country music history and memorabilia, right down to Webb Pierce's Silver Dollar Cadillac. Located downtown on Broadway in Nashville's historic Art Deco post office building, the popular Frist Center is a cultural hub of the community. The Frist Center features some of the world's greatest art, plus an array of films, lectures, music events and family activities. Visitors age 18 and younger get in free. The Lane Motor Museum displays 150 cars and motorcycles not typically seen in the United States. In fact, it houses the country's largest collection of European vehicles. Discover amphibious vehicles, competition cars, alternative fuel vehicles, microcars, military vehicles, motorcycles, and prototypes. This is not your typical car museum The Musicians Hall of Fame and Museum covers all genres of music including country, rhythm and blues, soul, funk, jazz, rock, and pop. It provides an inside look at the musicians and instruments that helped produce some of the greatest recordings of all time. It's located on the first floor of the Nashville Municipal Auditorium. The Tennessee Central Railway Museum is dedicated to the preservation of Tennessee's railroad heritage. TCRM is home to a unique collection of historic equipment such as passenger cars, cabooses, and freight cars. The museum also operates passenger excursions in Middle Tennessee, providing a unique opportunity for everyone to experience the joys of rail travel. The Tennessee Sports Hall of Fame is a 7,200-square foot facility located in the Bridgestone Arena. Honorees include athletes, coaches and sports writers who have made a mark in Tennessee sports history. It also features interactive games such as a virtual reality, one-on-one basketball, a strength-training apparatus used by Olympic swimmers, college football, and basketball exhibits, NASCAR video games and more. This Nashville museum is one of the largest state museums in the nation. The Tennessee State Museum features exhibits with Native American artifacts dating back 15,000 years as well as more modern state history. Located in downtown's James K. Polk Cultural Center, the museum offers free admission to all permanent exhibits. Built in 1897, The Parthenon is a full-size replica of the Parthenon in Athens, Greece, and like the original structure also centers around a large statue of the goddess Athena. Its impressive art collection contains paintings by 19th and 20th century American artists. Read more about the history of Nashville's Parthenon. The Upper Room Chapel hosts more than 25,000 visitors each year. The focal point is a woodcarving of Leonardo da Vinci's painting “The Last Supper”, sculpted by Ernest Pellegrini. Visitors also enjoy the Upper Room Museum, whose permanent collection reflects an international, interracial and interdenominational nature.
New atom-type-based AI topological indices: application to QSPR studies of aldehydes and ketones. Multiple linear regression (MLR) analysis based on a combined use of the modified Xu index and the atom-type based AI indices is performed to construct quantitative structure-property models on several data sets of organic compounds including aliphatic aldehydes and/or ketones. For each of the physical properties (the normal boiling points, molar refractions, gas heat capacities at 25 degrees C, water solubility at 25 degrees C, and n-octanol/water partition coefficient at 25 degrees C), high quality QSPR models are obtained, particularly the decrease in the standard error is within the range of 23.6-75.9% relative to the linear models with the modified Xu index alone. For individual subsets containing only aldehydes or ketones, in the majority of cases the quality of the model can be further improved. The significant improvement verifies the efficiency of the present approach and also indicates the usefulness of these indices for application to a wide range of physical properties. The results indicate that the physical properties studied are dominated by molecular size but atom types have smaller influences, especially the oxygen atom seems to be most important due to intermolecular polar interactions. The final models are validated to be statistically reliable using the leave-one-out cross-validation and/or an external test set.
Can we look past people's race? The effect of combining race and a non-racial group affiliation on holistic processing. Face memory is worse for races other than one's own, in part because other-race faces are less holistically processed. Both experiential factors and social factors have been suggested as reasons for this other-race effect. Direct measures of holistic processing for race and a non-racial category in faces have never been employed, making it difficult to establish how experience and group membership interact. This study is the first to directly explore holistic processing of own-race and other-race faces, also classed by a non-racial category (university affiliation). Using a crossover design, White undergraduates (in Australia) completed the part-whole task for White (American) and Black South African faces attributed to the University of Western Sydney (own) and University of Sydney (other). Black South African undergraduates completed the same task for White and Black South African faces attributed to the University of Cape Town (own) and Stellenbosch University (other). It was hypothesised that own-race faces would be processed more holistically than other-race faces and that own-university faces would be processed more holistically than other-university faces. Results showed a significant effect of race for White participants (White faces were matched more accurately than Black faces), and wholes were matched more accurately than parts, suggesting holistic processing, but only for White faces. No effect of university was found. Black South African participants, who have more experience with other-race faces, processed wholes better than parts irrespective of race and university category. Overall, results suggest that experiential factors of race outweigh any effects of a non-racial shared group membership. The quality of experience for the named populations, stimuli presentation, and degree of individuation are discussed.
Technical Field The present invention relates to a shovel that includes an excavation attachment moved by a hydraulic cylinder, and to a method of controlling the shovel. Description of Related Art An overload prevention device for hydraulic power shovels has been known. This overload prevention device prevents, during excavation work of a power shovel, a lift of front wheels by detecting a reaction force from the ground as a holding hydraulic pressure in the head-side oil chamber of a boom cylinder and opening a relief valve when the holding hydraulic pressure reaches a predetermined pressure. Furthermore, the lift of front wheels is prevented by automatically causing a boom, an arm and a bucket to operate by putting a boom main operation valve, an arm main operation valve, and a bucket main operation valve into operation, instead of opening the relief valve.
Case: 17-11113 Document: 00514701356 Page: 1 Date Filed: 10/29/2018 IN THE UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT United States Court of Appeals Fifth Circuit No. 17-11113 FILED October 29, 2018 Lyle W. Cayce In the Matter of: PROVIDER MEDS, L.L.C., Clerk Debtor RPD HOLDINGS, L.L.C., Appellant v. TECH PHARMACY SERVICES, doing business as Advanced Pharmacy Services, Appellee Appeal from the United States District Court for the Northern District of Texas Before HIGGINBOTHAM, SMITH, and GRAVES, Circuit Judges. PATRICK E. HIGGINBOTHAM, Circuit Judge: RPD Holdings, L.L.C. claims that it purchased a patent license from multiple debtors in bankruptcy sales of their estates. Tech Pharmacy Services argues that RPD does not have rights under the license to Tech Pharm’s patented invention. Concluding that the patent license was a rejected executory contract and could not have been transferred by the bankruptcy sales in question, we agree with Tech Pharm and affirm the decision of the district court. Case: 17-11113 Document: 00514701356 Page: 2 Date Filed: 10/29/2018 No. 17-11113 I This appeal emerges from a series of bankruptcy cases involving “OnSite.” The entities involved in operating OnSite, the “OnSite parties,” placed dispensing machines with long-term care facilities, then used proprietary OnSite software to remotely dispense pharmaceuticals from the machines to nurses in the facilities. They had a joint corporate parent, OnSiteRx, but functioned as independent business entities 1—and, when the time came to file for bankruptcy, filed separate bankruptcy cases. A The story begins before the OnSite parties filed for bankruptcy. Tech Pharm holds a patent on a system, software, and related methods of remote pharmaceutical dispensing. 2 In 2010, it sued multiple defendants in the Eastern District of Texas—including several OnSite parties—for infringing this patent by using their own remote pharmaceutical dispensing machines. 3 The OnSite parties counterclaimed challenging Tech Pharm’s patent. The parties agreed to settle the litigation, entering into a “Compromise, Settlement, Release, and License Agreement” (the “License Agreement”), granting a “non-exclusive perpetual license” to all but one of the OnSite parties for “so long as the Patent or Patents are valid and enforceable.” The OnSite parties agreed to pay a one-time licensing fee of $4,000 for each OnSite machine placed into operation after the execution of the agreement, and to provide quarterly reports reflecting all new machines placed in service. All parties also agreed to release any and all claims they “may have or claim to have . . . which relate to or could have been claimed in the Litigation, or that 1 See CERx Pharm. Partners, LP v. RPD Holdings, LLC, No. 13-30678-BJH, 2014 WL 4162870, at 3 (Bankr. N.D. Tex. Aug. 20, 2014). 2 U.S. Patent No. 7,698,019 (filed Sept. 20, 2004). 3 Tech Pharm included other, non-OnSite defendants in the same suit, but their involvement is not relevant to this case. 2 Case: 17-11113 Document: 00514701356 Page: 3 Date Filed: 10/29/2018 No. 17-11113 relate to the [Patents] or any alleged infringement [or invalidity] of same, except for the obligations specifically called for under this Agreement.” Following the settlement agreement, the district judge in the Eastern District of Texas dismissed all claims with prejudice. B Beginning in 2012 and continuing into 2013, the six OnSite parties relevant to this appeal filed separate Chapter 11 bankruptcy cases in the Northern District of Texas. 4 Each case was later converted to Chapter 7. Five of the six OnSite debtors were also parties to the Tech Pharm License Agreement. Despite the bankruptcy requirement that they schedule all assets and creditors, however, none of the debtors listed the License Agreement or Tech Pharm on their schedules. RPD had a security interest in the OnSite debtors’ collateral. It agreed to purchase its collateral from three of the bankruptcy estates—ProvideRx of Grapevine, LLC (“Grapevine”), ProvideRx of Waco, LLC (“Waco”), and W. Pa. OnSiteRx, LLC (“Western Pennsylvania”)—instead of litigating its liens. RPD and each estate laid out the terms of each sale in a separate asset purchase agreement, the APA, and each sale was approved by the bankruptcy court in a separate sale order. No APA explicitly referenced the License; instead, each APA covered certain categories of subject property. In turn, the sale orders approved the sale of the subject property in each APA—providing that to the extent that any of the subject property was an executory contract, it was “hereby ASSUMED by the Estate and immediately ASSIGNED to RPD under the applicable provisions of section 365 of the Bankruptcy Code.” The parties have stipulated that RPD was not aware of the License until after all three sale motions and APAs were filed with the bankruptcy court, but that it 4 There were ten related OnSite debtors in total. 3 Case: 17-11113 Document: 00514701356 Page: 4 Date Filed: 10/29/2018 No. 17-11113 became aware of the License before the bankruptcy court entered the last of the sale orders, the Waco sale order. Shortly after the bankruptcy court approved the last of these sales, the trustees from the other estates—Provider Meds, LP (“Provider Meds”), OnSiteRx, Inc. (“OnSite”), and ProvideRx of San Antonio, LLC (“San Antonio”)—entered into a settlement agreement, the “global agreement,” with RPD and CERx, a competing secured party. The global agreement provided for RPD and CERx to severally own the OnSite source code, and divided other assets between them. RPD avers that because it was aware of the License at this point, it believed that it had purchased the License under the terms of the Grapevine, Western Pennsylvania, and Waco APAs and sale orders. As a result, the global agreement provided that the Provider Meds and San Antonio trustees would transfer their Tech Pharm licenses to CERx, but that “RPD is entitled to all remaining available Tech Pharm licenses (such as those otherwise acquired from ProvideRx of Grapevine, LLC; W Pa OnsiteRx, LLC; and ProvideRx of Waco, LLC).” C Almost a year after the bankruptcy court approved the global agreement, Tech Pharm filed a petition in Texas state court against several defendants, including the Waco and San Antonio debtors, alleging that the defendants had failed to comply with their obligations under the License Agreement to provide quarterly reports and pay licensing fees for new machines. RPD intervened and removed the proceeding to the bankruptcy court, arguing that one or more of the debtor estates had assigned or otherwise transferred the License to RPD. The bankruptcy court held that RPD did not have rights under the License Agreement for either of two reasons: RPD had not purchased the License under any of the OnSite sales and, regardless of the terms of the sales, the License Agreement was an executory contract that was rejected by 4 Case: 17-11113 Document: 00514701356 Page: 5 Date Filed: 10/29/2018 No. 17-11113 operation of law prior to any alleged transfer. 5 It also determined that RPD had not gained rights under the License Agreement by purchasing OnSite machines from the debtors. 6 RPD appealed to the district court, which concluded that the License was a rejected executory contract and affirmed. 7 RPD now appeals the decision of the district court affirming the bankruptcy court. It claims that its rights under the License Agreement were established by final and non-appealed bankruptcy court orders, so any determination to the contrary would constitute an impermissible collateral attack. It also argues that the bankruptcy and district courts erred on the merits in determining RPD has no rights under the License Agreement. D In reviewing a decision of the district court affirming the bankruptcy court, we apply “the same standard of review to the bankruptcy court that the district court applied,” reviewing findings of law de novo and findings of fact for clear error. 8 We conclude that the License Agreement was an executory contract that was deemed rejected by operation of law prior to the bankruptcy sales where RPD allegedly purchased the License. Because the License was not part of the bankruptcy estates at the time of the relevant sales, the bankruptcy court’s final orders did not effect a transfer of the License from the OnSite debtors to RPD. II Section 365 of Title 11 of the United States Code addresses the ability of bankruptcy trustees to assume or reject executory contracts and unexpired 5 See Tech Pharm. Servs., Inc. v. RPD Holdings, LLC (In re Provider Meds, LLC), No. 13-30678, 2017 WL 213814, at 10–11, 12–18 (Bankr. N.D. Tex. Jan. 18, 2017). 6 See id. at 11–12 ¶¶5–11. 7 Tech Pharm. Servs., Inc. v. RPD Holdings, LLC (In re Provider Meds, LLC), No. 3:17- CV-0441-D, 2017 WL 3764630 (N.D. Tex. Aug. 31, 2017). 8 Galaz v. Katona (In re Galaz), 841 F.3d 316, 321 (5th Cir. 2016). 5 Case: 17-11113 Document: 00514701356 Page: 6 Date Filed: 10/29/2018 No. 17-11113 leases. This provides a way for “a trustee to relieve the bankruptcy estate of burdensome agreements which have not been completely performed.” 9 Once a trustee assumes an executory contract, a trustee may generally also assign the contract, even where legal or contractual provisions would otherwise prohibit assignment. 10 An executory contract must be assumed or rejected in its entirety, 11 and rejection may be treated as a breach of contract. 12 Under most bankruptcy chapters, the trustee may assume or reject an executory contract at any point before the plan is confirmed, 13 but the rule is different for Chapter 7 cases. Section 365(d)(1) provides that in Chapter 7 cases, if the trustee does not assume or reject an executory contract or unexpired lease of residential real property or of personal property of the debtor within 60 days after the order for relief, or within such additional time as the court, for cause, within such 60-day period, fixes, then such contract or lease is deemed rejected. 14 Here, if the License Agreement was an executory contract, the sixty-day time period started when the cases were converted to Chapter 7 and would have expired before the first of the bankruptcy sales. 15 The trustees did not assume the License Agreement within the required period. RPD contends that the bankruptcy and district courts erred in concluding that the License Phoenix Exploration, Inc. v. Yaquinto (In re Murexco Petroleum, Inc.), 15 F.3d 60, 62 9 (5th Cir. 1994) (per curiam). 10 See 11 U.S.C. § 365(f)(1). 11 See Stewart Title Guar. Co. v. Old Republic Nat’l Title Ins. Co., 83 F.3d 735, 741 (5th Cir. 1996) (per curiam). 12 11 U.S.C. § 365(g). 13 See id. § 365(d)(2); Stumpf v. McGee (In re O’Connor), 258 F.3d 392, 400 (5th Cir. 2001). 14 11 U.S.C. § 365(d)(1). 15 As the bankruptcy court explained, the latest any of the trustees had to assume the License Agreement was November 3, 2013, but the earliest sale motion was filed on November 22, 2013. See In re Provider Meds, 2017 WL 213814, at 6 ¶ 49. 6 Case: 17-11113 Document: 00514701356 Page: 7 Date Filed: 10/29/2018 No. 17-11113 Agreement was an executory contract. It further argues that even if the License Agreement is an executory contract, section 365(d)(1)’s time limit should not apply where the debtors failed to schedule the License and the trustees therefore were unaware of its existence. We disagree. A Our first inquiry is whether the License Agreement was an executory contract. The Bankruptcy Code does not define the term “executory contract,” 16 but we have concluded that a contract is executory if “performance remains due to some extent on both sides” and if “at the time of the bankruptcy filing, the failure of either party to complete performance would constitute a material breach of the contract, thereby excusing the performance of the other party.” 17 We must therefore determine whether both sides—Tech Pharm and each of the OnSite parties—owed additional performance under the License Agreement, and whether any party’s failure to perform would constitute a material breach excusing the other side’s performance. The bankruptcy court held, and the district court affirmed, that Tech Pharm had an ongoing obligation under the License Agreement to refrain from suing its counterparties for patent infringement for machines placed into service after execution of the Agreement. 18 It further concluded that the OnSite 16 See In re Murexco Petroleum, 15 F.3d at 62. 17 Id. at 62–63; accord Ocean Marine Servs. P’ship No. 1 v. Digicon, Inc. (In re Digicon, Inc.), No. 03-20121, 2003 WL 21418127, at 5 (5th Cir. 2003) (per curiam) (approving of district court language adopting this definition). This follows the “Countryman” definition of an executory contract, which is widely—though not universally—adopted by our fellow circuits. 18 See In re Provider Meds, 2017 WL 3764630, at 2 (district court opinion); In re Provider Meds, 2017 WL 213814, at 14–15 ¶¶ 22–26 (bankruptcy court opinion). As we discuss, Tech Pharm dismissed its claims against the OnSite debtors with prejudice in the 2010 lawsuit, so it was already precluded from suing for patent infringement concerning machines in existence at the time of that lawsuit. The License Agreement separately provided that Tech Pharm would release the OnSite parties from claims “that relate to the [Patents] or any alleged infringement of same, except for the obligations specifically called for under this Agreement.” We agree with the bankruptcy and district 7 Case: 17-11113 Document: 00514701356 Page: 8 Date Filed: 10/29/2018 No. 17-11113 licensees had ongoing material obligations because they were required to provide quarterly reports as to new machines, pay a one-time licensing fee of $4,000 to Tech Pharm for each new machine, and refrain from making public statements about the settled lawsuit. 19 1 RPD does not dispute that these reciprocal requirements would typically be enough to render the License Agreement executory, but argues instead that unique features of the License Agreement make it non-executory. RPD’s principal contention is that because the License Agreement came hand in hand with a settlement agreement to dismiss Tech Pharm’s patent infringement suit against the OnSite debtors with prejudice, Tech Pharm’s sole executory obligation under the License Agreement—to refrain from suing the OnSite debtors for patent infringement involving future machines—was illusory. Claim preclusion “bars the litigation of claims that either have been litigated or should have been raised in an earlier suit.” 20 Our analysis is most closely governed by principles of claim preclusion as they apply to patent infringement suits. 21 The Federal Circuit has held that claim preclusion does courts that this contemplated an ongoing obligation not to sue the OnSite debtors for future patent infringement, even when such claims could not have been brought in the initial litigation. In other words, if Tech Pharm sued the OnSite parties for patent infringement even though they complied with the terms of the License Agreement, it would breach the contract. 19 In re Provider Meds, 2017 WL 213814, at 16 ¶ 27. 20 Duffie v. United States, 600 F.3d 362, 372 (5th Cir. 2010). “The test for claim preclusion has four elements: (1) the parties in the subsequent action are identical to, or in privity with, the parties in the prior action; (2) the judgment in the prior case was rendered by a court of competent jurisdiction; (3) there has been a final judgment on the merits; and (4) the same claim or cause of action is involved in both suits.” Id. 21 Because Federal Circuit law would govern any potential future patent infringement suit Tech Pharm could bring against the OnSite parties, we look to the Federal Circuit to see if principles of claim preclusion would bar a particular cause of action in a patent case. The Federal Circuit applies its own law on issues of claim preclusion specific to patent law. See Mentor Graphics Corp. v. EVE-USA, Inc., 851 F.3d 1275, 1298 (Fed. Cir. 2017); see also SimpleAir, Inc. v. Google LLC, 884 F.3d 1160, 1165–66 (Fed. Cir. 2018) (applying general 8 Case: 17-11113 Document: 00514701356 Page: 9 Date Filed: 10/29/2018 No. 17-11113 not bar patent infringement allegations “with respect to accused products that were not in existence at the time of the [previous actions,] for the simple reason that [claim preclusion] requires that in order for a particular claim to be barred, it is necessary that the claim either was asserted, or could have been asserted, in the prior action.” 22 As a result, claim preclusion solely encompasses “the particular infringing acts or products that are accused in the first action or could have been made subject to that action.” 23 This is consistent with the Supreme Court’s decision in Lawlor v. National Screen Service Corp., an antitrust case holding that even where two suits involved “essentially the same course of wrongful conduct,” the later suit was not barred by claim preclusion because the prior judgment “[could] not be given the effect of extinguishing claims which did not even then exist and which could not possibly have been sued upon in the previous case.” 24 RPD argues that these general principles apply differently to method patent claims than to other claims for patent infringement. It contends that under a method patent, the determinative question is whether a particular process infringed on the method 25—so once a claim for method patent infringement is dismissed with prejudice, any future challenge to the use of the same process is barred by claim preclusion. Under RPD’s view, once Tech Pharm dismissed with prejudice its claim that the OnSite parties’ process infringed its method patent, it could never again sue the OnSite parties for Fifth Circuit principles of claim preclusion, but Federal Circuit law on whether “a particular cause of action in a patent case is the same as or different from another cause of action”). 22 Aspex Eyewear, Inc. v. Marchon Eyewear, Inc., 672 F.3d 1335, 1342 (Fed. Cir. 2012). 23 Id. at 1343. 24 349 U.S. 322, 327–28 (1955); see also Aspex Eyewear, 672 F.3d at 1342–43 (citing Lawlor). 25 See Joy Techs., Inc. v. Flakt Inc., 6 F.3d 770, 773 (Fed. Cir. 1993). 9 Case: 17-11113 Document: 00514701356 Page: 10 Date Filed: 10/29/2018 No. 17-11113 using that same process, even if the OnSite parties used the process after the termination of the lawsuit to place new machines into operation. We disagree, finding recent Federal Circuit case law conclusive on this point. Mentor Graphics Corp. v. EVE-USA, Inc. is particularly instructive. 26 There, the relevant parties had previously litigated two method and logic system patents, 27 but—as in this case—the patentholder dismissed its infringement claims with prejudice and granted a license to the asserted patents. 28 When another company acquired the licensee, the license automatically terminated. 29 The acquiring company then sued the patentholder for a declaratory judgment of non-infringement, and the patentholder counterclaimed for infringement. 30 The Federal Circuit flatly held that because the infringement claims were based on acts that occurred after the initial lawsuit, they were not precluded by the initial suit’s dismissal with prejudice. 31 Following Lawlor, it emphasized that where infringement allegations could not have previously been brought in an initial suit because the alleged infringing act had not yet occurred, claim preclusion would not apply even where the alleged infringement was “essentially the same” as that litigated in the prior action. 32 Especially relevant here, the court observed that 26 Mentor Graphics, 851 F.3d 1275. 27 See U.S. Patent No. 6,009,531 (filed May 27, 1997); U.S. Patent No. 5,649,176 (filed Aug. 10, 1995). 28 Mentor Graphics, 851 F.3d at 1297–98. 29 Id. at 1298. 30 Id. 31 Id. at 1299. 32 Id. at 1299–1301 (“The present lawsuit is based on post-license conduct, so the alleged infringement did not exist during the previous action . . . Because the allegations could not have been brought in the first action, we need not determine whether the newly accused products are ‘essentially the same’ as the products litigated in the first action.”) (discussing Lawlor v. Nat’l Screen Serv. Corp., 349 U.S. 322, 328 (1955); Aspex Eyewear, 672 F.3d at 1342; and Brain Life, LLC v. Elekta Inc., 746 F.3d 1045, 1052 (Fed. Cir. 2014)). In Mentor Graphics, the Federal Circuit also observed that under the Supreme Court’s decision in Kessler v. Eldred, 206 U.S. 285 (1907), an adjudicated non-infringer may be 10 Case: 17-11113 Document: 00514701356 Page: 11 Date Filed: 10/29/2018 No. 17-11113 if such claims were instead barred by claim preclusion, “any licensee holding a license obtained through litigation could breach that license, yet prevent the patentee from asserting infringement against new products not covered by the license.” 33 By holding that future infringement claims were not barred by claim preclusion, the Mentor Graphics decision avoided that counterintuitive result. The Federal Circuit has reached similar results concerning other method patent claims. Mentor Graphics relied in part on the court’s previous decision in Brain Life, LLC v. Elekta Inc., which straightforwardly held that claim preclusion would not bar claims for method patent infringement “relating to acts of infringement that postdate [the prior] judgment” because the patentee could not have asserted claims in the first lawsuit for acts of infringement that occurred after the judgment in that suit. 34 Similarly, in Asetek Danmark A/S v. CMI USA Inc., the Federal Circuit addressed an injunction predicated on a jury finding of liability for infringement of two system and method patents. 35 The patentholder dismissed with prejudice its claims against one of the defendants prior to trial, 36 but after the jury found liability, the district court enjoined both original defendants—including the dismissed party. 37 The court shielded from future lawsuits involving the same allegedly infringing activity, even where such lawsuits would not be barred by claim or issue preclusion. See Mentor Graphics, 851 F.3d at 1301. While the Kessler doctrine may cushion the effect of these claim preclusion principles where a court conclusively establishes non-infringement, the Mentor Graphics panel explained that it does not apply where a party received a license to the patent and the patentholder dismissed its claims with prejudice, as is the case here. See id. at 1297–98, 1301. 33 Id. at 1300. 34 Brain Life, 746 F.3d at 1053–54. 35 852 F.3d 1352, 1355 (Fed. Cir. 2017). Asetek Danmark was initially decided prior to Mentor Graphics, and Mentor Graphics cited the initial opinion as one of several cases supporting its conclusion. See Mentor Graphics, 851 F.3d at 1299. The Federal Circuit subsequently vacated its original Asetek Danmark opinion and issued a new opinion, but its discussion of claim preclusion remained unchanged. Compare Asetek Danmark A/S v. CMI USA Inc., 842 F.3d 1350, 1362–63 (Fed. Cir. 2016), with Asetek Danmark, 852 F.3d at 1365. 36 Asetek Danmark, 852 F.3d at 1355. 37 Id. at 1358. 11 Case: 17-11113 Document: 00514701356 Page: 12 Date Filed: 10/29/2018 No. 17-11113 concluded that the injunction against the dismissed party addressing its future conduct was not barred by claim preclusion, because “[i]t is well established . . . that the difference in timing means that the two situations do not involve the same ‘claim’ for claim-preclusion purposes, even if all the conduct is alleged to be unlawful for the same reason.” 38 Although the court ultimately remanded for a more thorough determination of whether the injunction was permissible against the dismissed party, 39 it made clear that principles of claim preclusion standing alone would not have barred the injunction—even though the system and method infringement claims had previously been dismissed with prejudice. 40 RPD’s reliance on the Federal Circuit’s earlier decision in Hallco Manufacturing Co. v. Foster is unpersuasive. 41 Hallco held that because a party had dismissed its patent invalidation claim with prejudice in earlier litigation, it was potentially barred from suing the patentholder to invalidate the same patent or from seeking a declaratory judgment that a redesigned device did not infringe the patent. 42 While Hallco’s language may be read more broadly, we take the Federal Circuit to have since clarified that the case does not govern preclusion of infringement claims brought by the patentholder, which were not at issue in Hallco. 43 The other cases we have discussed are more representative of whether claim preclusion would prevent Tech Pharm 38 Id at 1365 (citing, e.g., Aspex Eyewear, 672 F.3d at 1343). 39 See id. at 1368–69. 40 See id. at 1370. 41 256 F.3d 1290 (Fed. Cir. 2001). 42 Id. at 1293. The court remanded for a determination of whether the devices at issue were sufficiently different that principles of claim preclusion would not apply. See id. at 1298. 43 See Mentor Graphics, 851 F.3d at 1299–1300 (“Neither [of the Foster v. Hallco Manufacturing] cases addressed whether a patentee could bring new infringement allegations based on conduct occurring after a previous litigation ended. This is the precise issue addressed in Aspex Eyewear and Brain Life and the precise issue now before us.”). While the patentholder brought a counterclaim in the Hallco case, it was for breach of the settlement agreement, not for infringement. See Hallco Mfg., 256 F.3d at 1293. 12 Case: 17-11113 Document: 00514701356 Page: 13 Date Filed: 10/29/2018 No. 17-11113 from suing the OnSite debtors over new machines—and they indicate that it would not. In sum, but for the License Agreement, Tech Pharm would not be barred from suing the OnSite debtors for patent infringement stemming from their introduction of new OnSite machines—even if those machines used the same process at issue in the settled 2010 litigation. Tech Pharm had an ongoing material obligation under the License Agreement to refrain from suing the debtors. 2 The OnSite debtors also had corresponding material obligations under the License Agreement. The License Agreement straightforwardly obligated the debtors to take certain ongoing actions, such as filing quarterly reports and not discussing the settled lawsuit. 44 RPD claims, however, that because the License Agreement granted a “perpetual” license for so long as the Tech Pharm patent was valid and enforceable, Tech Pharm would be prohibited from suing the debtors for patent infringement even if they breached their side of the agreement—and so any debtor obligations would not be material, as required by our definition of an executory contract. 45 It points to cases holding that where a license is both “irrevocable” and “perpetual,” the licensor may not revoke the license even when the licensee breaches. 46 But the cases RPD cites do not stand for the proposition that a merely “perpetual” license is itself irrevocable in the face of material breach. Rather, 44 We have suggested in an unpublished opinion that “[a] contract is not executory if the only performance required by one side is the payment of money.” In re Digicon, Inc., 2003 WL 21418127, at 5 (adopting language from district court opinion). Because the OnSite debtors were required to undertake other performance under the License Agreement, we do not need to resolve this issue here. 45 See In re Murexco Peroleum, 15 F.3d at 62–63. 46 See Nano-Proprietary, Inc. v. Canon, Inc., 537 F.3d 394 (5th Cir. 2008); Timeline, Inc. v. Proclarity Corp., No. C05-1013-JLR, 2007 WL 1574069 (W.D. Wash. May 29, 2007). 13 Case: 17-11113 Document: 00514701356 Page: 14 Date Filed: 10/29/2018 No. 17-11113 they hold that when a license uses the terms “irrevocable” and “perpetual,” “irrevocable” must mean something beyond “not revocable at will,” since otherwise the use of both “irrevocable” and “perpetual” would be superfluous. 47 Both cases explain that the use of “perpetual” indicates that the license may not be revoked at will; the use of “irrevocable” goes one step further and indicates that the license may not be revoked for any reason, even a breach by the other side. RPD is arguably correct that because the License granted under the License Agreement was “perpetual,” under Texas law, it was therefore not revocable at will. 48 This does not mean, though, that Tech Pharm would not be excused from its obligations if the OnSite debtors were to materially breach the License Agreement. RPD has offered no authority holding that a license that is only “perpetual,” and not “perpetual and irrevocable,” is irrevocable in the face of material breach—and, indeed, the cases it presents suggest the opposite. 47 See Nano-Proprietary, 537 F.3d at 400 (“Based upon the unambiguous meaning of ‘irrevocable,’ we find that the PLA could not be terminated, notwithstanding a material breach of the agreement. Otherwise, the terms ‘irrevocable’ and ‘perpetual’ would be rendered superfluous, in contravention of established rules of contract interpretation.”); Timeline, 2007 WL 1574069, at 4 (“Despite the ordinary meaning of the term, Timeline suggests that ‘irrevocable’ is used in the contract to convey that the licenses are not terminable at will and should not be interpreted to restrict Timeline’s ability to terminate the licenses due to a material breach. As Microsoft notes, however, the licenses would not have been terminable at will even if the agreement had excluded the term ‘irrevocable.’ . . . As Microsoft suggests, the use of the word ‘perpetual’ would also be sufficient to express an intent that the licenses were not terminable at will.”). 48 Texas law “disfavors” perpetual contracts, but will typically treat a contract as perpetual—and therefore not revocable at will—if it offers a definite endpoint for the party’s obligation. See, e.g., Kirby Lake Dev., Ltd. v. Clear Lake City Water Auth., 320 S.W.3d 829, 842 (Tex. 2010). Here, indexing the License Agreement to the duration of the patent generated a definite endpoint. As we explain, however, we do not need to determine whether the License Agreement was in fact perpetual—even if it was perpetual, that still does not mean that it was irrevocable in the face of a material breach. 14 Case: 17-11113 Document: 00514701356 Page: 15 Date Filed: 10/29/2018 No. 17-11113 We therefore conclude that both sides had ongoing material obligations under the terms of the License Agreement, making it an executory contract. Having established that the License Agreement was executory, we must address whether it was rejected by operation of law. B As we have explained, 11 U.S.C. section 365(d)(1) imposes a sixty-day deadline for a bankruptcy trustee to assume an executory contract, starting here with the cases’ conversion from Chapter 11 to Chapter 7. After that deadline passes, the contract will be deemed rejected by operation of law. Because we have concluded that the License Agreement was executory, it appears that it was deemed rejected when each of the bankruptcy estates failed to assume it prior to the expiration of the sixty-day period. But RPD urges us to read an implicit exception into section 365(d)(1) for when a bankruptcy debtor fails to schedule the executory contract and the trustee was unaware of the contract within the sixty-day period. Like most circuits, we have not spoken directly to this issue. Both parties point to the sparse array of applicable case law from other courts, though there appears to be no clear consensus. Some courts have held that a contract will not be deemed rejected by operation of law where a debtor intentionally conceals the existence of the contract from a trustee. 49 That is not at issue here, where the License Agreement was a matter of public record, listed on the docket of the 2010 patent litigation between Tech Pharm and the OnSite 49 See Strohbeck v. Zuniga (In re Zuniga), 287 B.R. 201, 206 (Bankr. E.D. Mo. 2001) (finding an executory contract was not deemed rejected under § 365(d)(1) where the debtor had engaged in an overt pattern of misrepresentation about her bankruptcy in order to obtain a loan, and failed to disclose the loan contract to the trustee); see also Texas W. Fin. Corp. v. McCraw Candies, Inc., 347 F. Supp. 445, 449 (N.D. Tex. 1972) (finding no rejection under an applicable provision of the Bankruptcy Act where “the transaction had been deleted from [the debtor’s] business records and was not listed as an asset on the schedule . . . . [so there was no evidence] that the trustee had knowledge of the claim or could have obtained it”). 15 Case: 17-11113 Document: 00514701356 Page: 16 Date Filed: 10/29/2018 No. 17-11113 debtors. When there is no intentional concealment, several courts have held that failure to schedule an executory contract will not prevent it from being deemed rejected, 50 though at least one court appears to have broadly concluded that failure to schedule the contract should always toll the deadline. 51 While most of these decisions do not extensively discuss the issue, we find persuasive analysis in a Ninth Circuit decision addressing a similar provision under the earlier Bankruptcy Act. 52 That court held that under the Bankruptcy Act, “a trustee has an affirmative duty to investigate for unscheduled executory contracts or unexpired leases,” and that “[t]he statutory presumption of rejection by the trustee’s nonaction within the sixty day period following his qualification is a conclusive presumption.” 53 The Ninth Circuit’s decision took place in a different statutory landscape, but its reasoning still applies. 54 The Bankruptcy Code places an affirmative duty on the trustee to “investigate the financial affairs of the debtor.” 55 And, more to the point, section 365(d)(1) does not impose an actual or constructive notice requirement 50 See Permacel Kansas City, Inc. v. Kohler Co., No. 08-00804-CV-W-FJG, 2010 WL 2516924, at 3-4 (W.D. Mo. June 14, 2010); Carrico v. Tompkins (In re Tompkins), 95 B.R. 722, 724 (B.A.P. 9th Cir. 1989); Hoffman v. Vecchitto (In re Vecchitto), 235 B.R. 231, 236 (Bankr. D. Conn. 1999), aff’d, No. 00-5010, 2000 WL 1508872 (2d Cir. Oct. 11, 2000). 51 See Medley v. Dish Network, LLC, No. 8:16-CV-2534-T-36TBM, 2018 WL 4092120, at 5 (M.D. Fla. Aug. 27, 2018). 52 See Cheadle v. Appleatchee Riders Ass’n (In re Lovitt), 757 F.2d 1035 (9th Cir. 1985) (discussing 11 U.S.C. § 110(b) (1970)). 53 Id. at 1040–42. 54 Cases decided under the modern Bankruptcy Code have looked to In re Lovitt approvingly. See In re Tompkins, 95 B.R. at 724; Corp. Prop. Investors v. Chandel Enters. (In re Chandel Enters.), 64 B.R. 607, 610 (Bankr. C.D. Cal. 1986). RPD argues that it is no longer applicable because it was decided under the Bankruptcy Act’s rule that “executory contracts and leases—unlike all other assets—do not vest in the trustee as of the date of the filing of the bankruptcy petition . . . . [, but] only upon the trustee’s timely and affirmative act of assumption.” In re Lovitt, 757 F.2d at 1041. But we agree with Tech Pharm that the Lovitt conclusion regarding unscheduled contracts did not hinge on this presumption. 55 11 U.S.C. § 704(a)(4); see also id. § 704(a)(1) (requiring the trustee to “collect and reduce to money the property of the estate”). 16 Case: 17-11113 Document: 00514701356 Page: 17 Date Filed: 10/29/2018 No. 17-11113 for when the sixty-day deadline applies. We will not read such a requirement into the statute when doing so is not supported by the statutory text. Nor do we agree with RPD’s other arguments for a narrower application of section 365(d)(1)’s deadline. There is no conflict with 11 U.S.C. sections 554(c) and (d), which provide that scheduled but non-administered property is abandoned to the debtor but property of the estate that is neither abandoned nor administered remains within the estate. The rejection of an executory contract places that contract outside of the bankruptcy estate 56—so section 554 does not apply. Similarly, we disagree with RPD’s suggestion that even where a contract has been rejected under section 365, a trustee can sell the contract pursuant to section 363. Because a rejected contract ceases to be property of the bankruptcy estate, it cannot be sold under a provision that authorizes a trustee to sell “property of the estate.” 57 In any event, we cannot approve of the use of a “sale” under section 363 to avoid the requirement that an executory contract be assumed and assigned under section 365. 58 56 See, e.g., Eastover Bank for Savings v. Sowashee Venture (In re Austin Dev. Co.), 19 F.3d 1077, 1081 (5th Cir. 1994) (observing that deemed rejection of a lease under § 365(d)(4) “did not terminate the lease but merely placed the trustee’s obligation to perform under the leasehold outside of the bankruptcy administration without destroying the leasehold estate” (citing Comm. Trading Co. v. Lansburgh (In re Garfinkle), 577 F.2d 901, 904 (5th Cir. 1978)); In re Scharp, 463 B.R. 123, 129 (Bankr. C.D. Ill. 2011) (“The primary effect of rejection is to abandon the lease from the estate so that it reverts back to the debtor’s control outside of bankruptcy. Assumption and rejection are bankruptcy concepts that determine whether the estate will administer the lease; rejection merely removes it from the property of the estate.” (citations omitted)); cf. Kane v. Nat’l Union Fire Ins. Co., 535 F.3d 380, 384–86 (5th Cir. 2008) (explaining that a trustee may abandon property of the estate, but may not administer property that was abandoned to the debtor pursuant to a different provision). 57 See 11 U.S.C. § 363(b)–(c). 58 See Cinicola v. Scharffenberger, 248 F.3d 110, 124 (3d Cir. 2001) (“[T]he sale of an executory contract triggers the protections afforded sales of bankruptcy estate property but also requires satisfaction of the requirements for assuming and/or assigning the same executory contract.”); In re Access Beyond Techs., Inc., 237 B.R. 32, 47 (D. Del. Bankr. 1999) (“A debtor cannot avoid the requirements of section 365 by saying it is ‘selling’ a lease or executory contract, rather than assuming and assigning it.”). 17 Case: 17-11113 Document: 00514701356 Page: 18 Date Filed: 10/29/2018 No. 17-11113 We therefore hold that the License Agreement was deemed rejected by operation of law when each trustee failed to assume it within the sixty-day period. At a minimum, the statutory presumption of rejection after sixty days is conclusive where there is no suggestion that the debtor intentionally concealed a contract from the estate’s trustee. 59 III With this groundwork laid, that the bankruptcy court did not engage in an impermissible collateral attack on its previous orders becomes clear. RPD argues that two sets of final bankruptcy court orders established that it purchased the License Agreement from the Grapevine, Waco, and Western Pennsylvania estates. The first were the sale orders from the Grapevine, Waco, and Western Pennsylvania estates. As we have explained, each of those sale orders ordered the transfer of the subject property defined in the relevant asset purchase agreement, and included a provision stating that to the extent that any of the transferred subject property was an executory contract, “the same [was] hereby ASSUMED by the Estate and immediately ASSIGNED to RPD under the applicable provisions of section 365 of the Bankruptcy Code.” RPD argues that even if these provisions providing for assumption and assignment were erroneous, they are nonetheless entitled to protection against collateral attack. But by the time each of these sale orders was finalized, the sixty-day deadline had passed for each estate, and the License Agreement had already been deemed rejected. As we have explained, when an executory contract is rejected, it exits the bankruptcy estate. It was therefore outside the power of the bankruptcy trustees to include the License Agreement within the subject 59 We do not decide here whether this rule might shift if a debtor is shown to have hidden assets from a trustee. 18 Case: 17-11113 Document: 00514701356 Page: 19 Date Filed: 10/29/2018 No. 17-11113 property, or to attempt to assume and assign it to RPD. We do not read any of the bankruptcy court’s sale orders as providing for the estates to assume and assign contracts that were outside the relevant estate at the time of sale. 60 This is not a matter of collateral attack, but merely an interpretation of the bankruptcy court’s orders. 61 RPD also points to the bankruptcy court’s order effectuating the global agreement. It argues that the sale order explicitly incorporated all terms of the global agreement, including the portion of that agreement providing that “RPD is entitled to all remaining available Tech Pharm licenses (such as those otherwise acquired from ProvideRx of Grapevine, LLC; W Pa OnSiteRx, LLC; and ProvideRx of Waco, LLC).” 62 Standing alone, however, this could not conclusively establish that RPD had acquired the License through the Grapevine, Western Pennsylvania, and Waco sales. RPD did not actually purchase the License from any of those debtors—as an executory contract deemed rejected, it had already passed out of their estates—and the bankruptcy court’s attenuated incorporation of a statement to the contrary does not establish otherwise. 63 Ultimately, RPD’s collateral attack argument hinges on the assumption that the License was still part of the bankruptcy estates at the time of each of 60 Here, not only did the relevant sale orders not reference the License, but they also ordered the transfer of the subject property only to the extent that the debtor and estate had a right, title, or interest in the property. We cannot read the sale orders as ordering the License assumed and assigned even though it had already passed out of the relevant bankruptcy estates. 61 See United States v. 115.27 Acres of Land, 471 F.2d 1287, 1290 (5th Cir. 1973). 62 The bankruptcy court approved the global agreement in a sale order stating that “ALL terms of the Agreement are incorporated herein by reference.” 63 At a minimum, as Tech Pharm observes, only a Chapter 7 trustee may sell an estate’s property, and so RPD and CERx could not by fiat establish that the Waco, Grapevine, and Western Pennsylvania trustees had transferred the license to RPD when those trustees were not parties to the global agreement. See In re Gonzales, No. 10-35766-SGJ-7, 2010 WL 4340936, at 2 (Bankr. N.D. Tex. Oct. 27, 2010). 19 Case: 17-11113 Document: 00514701356 Page: 20 Date Filed: 10/29/2018 No. 17-11113 the Grapevine, Western Pennsylvania, and Waco sales. It was not, and the bankruptcy court’s sale orders did not hold differently. Our decision today therefore does not affirm a collateral attack on those sale orders. * * Because the License Agreement was an executory contract deemed rejected by operation of law, RPD could not and did not acquire the License from any of the Grapevine, Western Pennsylvania, and Waco estates—and no bankruptcy court order held otherwise. This resolves the heart of the dispute, so we do not need to resolve several other issues raised by the parties, such as whether RPD actually purchased the License under the terms of the relevant APAs and sale orders. IV We pause to briefly address a final issue. The parties stipulated before the bankruptcy court that its scope of decision making would be limited to “whether [RPD] validly acquired, by way of sale and assignment, all rights and obligations under [the License Agreement].” At trial, RPD’s counsel argued that even if RPD had not purchased or been assigned the License, it had a right to use the OnSite machines it had purchased from two of the debtor estates, under a provision of the License Agreement granting limited rights to third parties to operate OnSite machines. 64 When the bankruptcy judge observed that the issue had not been briefed and was not necessarily encompassed by the stipulated issues, RPD’s counsel argued that the question was necessarily connected to whether RPD had acquired rights under the License Agreement. 64 The relevant portion of the License Agreement provided that “If an Onsite Machine is used in a long-term care facility (‘LTCF’) as permitted by an Onsite party pursuant to this License, the Onsite party may sell the Onsite Machine to that LTCF or to a third party purchaser of the Onsite Machine who is not the LTCF. The LTCF (or a third party purchaser of the Onsite Machine who is not the LTCF) can continue to operate that Onsite Machine currently in place at the time of purchase of said Onsite Machine . . . .” 20 Case: 17-11113 Document: 00514701356 Page: 21 Date Filed: 10/29/2018 No. 17-11113 The bankruptcy court therefore assessed whether RPD had acquired limited rights under this provision, and concluded that it had not because it failed to prove that it had purchased specific machines encompassed by the License Agreement. 65 The court additionally concluded that under the terms of the License Agreement, RPD could only use any machines covered by the Agreement in the same long term care facility in which they were used at the time the Agreement was finalized, and that RPD had not shown that it had done so. 66 RPD now contends that this issue was not within the scope of the parties’ stipulation or briefing, and that the bankruptcy court lacked jurisdiction to address it regardless; Tech Pharm responds that RPD raised the issue of its own volition, and should suffer the consequences. Based on the facts presented to us, we conclude that the bankruptcy court did not exceed its authority in addressing RPD’s rights through purchase of the OnSite machines. Nor do we find that the bankruptcy court erred in reading the License Agreement to require that third parties operate OnSite machines in the same locations where they were placed at the time of sale. V We affirm the district court’s judgment. 65In re Provider Meds, 2017 WL 213814, at 11 ¶ 9. Specifically, the court noted that RPD had “failed to introduce evidence of the serial numbers of the 15 ADS Machines it purchased under the Grapevine APA and the Grapevine Sale Order,” id., and concluded the same regarding a machine purchased from the W. Pa. estate, id. at 12 ¶ 10. 66 Id. at *11 ¶¶ 8–9. 21
The characteristics of corneal staining in successful daily and extended disposable contact lens wearers. PURPOSE: The aim of this investigation was to measure levels of corneal staining in successful daily and extended wearers of disposable hydrogel contact lenses. METHODS: Twenty-four subjects on a daily wear (DW) schedule and 20 subjects on an extended wear (EW) schedule were examined at six-monthly intervals over a two-year period. Subjects wore two types of disposable hydrogel lenses. Measurements were taken from the eye wearing an etafilcon A contact lens only. The cornea was divided into five equally sized zones and the extent and depth of corneal staining were assessed on a zero to four scale. RESULTS: The overall levels of corneal staining were low with median values below or equal to grade 0.5 in all groups. There was no difference in the extent, depth or geographical distribution of corneal staining between the DW and EW groups. Staining was more frequently recorded in the superior and inferior areas of the cornea than in the central, nasal or temporal regions (Pearson's Chi-Square, p < 0.10). CONCLUSIONS: The mode of wear with disposable contact lenses is not a contributing factor to the amount of corneal staining seen in successful wearers. Low levels of corneal staining should be expected in successful DW and EW wearers.
[Post-transplant hepatitis C. Immunosuppression and antiviral treatment]. There is always a second infection with HCV during the post-transplant period. Recurrence of the disease is one of the main present therapeutic challenges because there are still many questions to answer. Some transplant groups suggest that recurrence is earlier in certain circumstances, especially in face of repetitive episodes of acute rejection in the early post-transplant period. Different transplant centers have various approaches to minimize the risk of recurrence secondary to excessive immunosuppression. They go from absolute avoidance of steroids to single therapy with inhibitors of calcineurin. Some investigators advocate for a fast reduction in the dose of corticosteroids (in less than 3 months), elimination of steroids from the therapy or administration of a single steroid dose in the immediate post-transplant period. Some are trying to establish a regime based on a single inhibitor of calcineurin and supported with mofetil micofenolate if it's effective. There are other inhibitors being studied, like anti-CD25 antibodies. The goals of the treatment for HCV recurrence must be aimed at obtaining an effective therapy that may be able to prevent the damage and to inhibit the viral replication and subsequent inflammation on long term basis. Recently there have been reports about different schemes with IFN and ribavirin, either as single therapy or in combination, that showed modest advances in early viral elimination and delaying the recurrence of the disease. One of the risks of therapy with interferon that has immunomodulation properties, is organ rejection. Ribavirin administration as single therapy is contraindicated. There are still some unanswered questions, since nobody knows for sure how long therapy for HCV should be continued.
Q: React native Redux dispatch is not a function, dispatch is an instance of Object When dispatch is called I get an error - 'dispatch is not a funcion ... dispatch is an instance of Object' I have connected mapDispatchToProps and I don't know how to fix this (I am new to react and redux) Here is my code: import React from 'react'; import {Text, View} from 'react-native'; import Slider from 'react-native-slider'; import { connect } from "react-redux"; class SliderComponent extends React.Component{ constructor(props){ super(props) this.state={ sliderValue: this.props.val, type: this.props.sliderText, } } render(){ return( <View style={{alignContent: 'center', flexDirection: 'row', padding: 10, justifyContent: 'center'}}> <Text style={{color: 'white', flex: 1, alignContent: 'center', justifyContent: 'center', fontSize: 20, fontWeight: 'bold'}}>{this.state.type}</Text> <Slider style={{width: 300, padding: 30, flex: 4}} thumbTintColor='white' step={1} value={this.state.sliderValue} minimumValue={this.props.min} maximumValue={this.props.max} minimumTrackTintColor='#F87883' onValueChange={val => { this.setState({sliderValue: val}) } } onSlidingComplete={ val => this.props.changeSliderValue(this.state.type, this.state.sliderValue) } > </Slider> <Text style={{color: 'white', flex: 1, alignContent: 'center', justifyContent: 'center', fontSize: 20, fontWeight: 'bold'}}>{this.state.sliderValue}</Text> </View> ) } }; const mapDispatchToProps = (dispatch) => { return{ changeSliderValue: (type, value) => { dispatch({type: type, value: value}) } } } export default connect( mapDispatchToProps )(SliderComponent); A: connect is implemented in the wrong way, your actual code is const mapDispatchToProps = (dispatch) => { return { changeSliderValue: (type, value) => { dispatch({type: type, value: value}); } } } export default connect(mapDispatchToProps)(SliderComponent); but the actual syntax for connect is, 1st parameter mapStateToProps function and 2nd parameter is mapDispatchToProps. Please change connect code as below. const mapDispatchToProps = (dispatch) => { return { changeSliderValue: (type, value) => { dispatch({type: type, value: value}); } } } const mapStateToProps = (state) => null; export default connect(mapStateToProps, mapDispatchToProps)(SliderComponent);
Q: Best way to center some images using iOS autolayout I am doing this and I am curious whether it is the best way, or a dumb way! I have a bunch of 40 pixel wide images, each one is like a Scrabble tile. My app wants to display some and center them on the screen. Only it don't know how many there are going to be! Could be between 3 and 10. So I think best thing is if I count how many, multiple by 40, so I know how many pixels wide the whole thing will be, and then let's pretend it's 280 pixels - I will create a 280 px wide UIView, stick all the tiles in there, and then use Autolayout to center that UIView on the device. That way if user rotates device, no problem! Is this the best way? Also I am going to need to let the user drag the tiles out of that UIView and into another place on screen. Will that be possible? A: Three approaches leap out at me: I think your solution of using a container view is perfectly fine. But, you don't have to mess around with determining the size of the images. You can just define the relation between the container and the image views, and it will resize the container to conform to the intrinsic size of the image views (or if you explicitly define the size of the image views, that's fine, too). And you can then center the container (and not give it any explicit width/height constraints): // create container UIView containerView = [[UIView alloc] init]; containerView.backgroundColor = [UIColor clearColor]; containerView.translatesAutoresizingMaskIntoConstraints = NO; [self.view addSubview:containerView]; // create image views UIImageView imageView1 = [[UIImageView alloc] initWithImage:[UIImage imageNamed:@"1.png"]]; imageView1.translatesAutoresizingMaskIntoConstraints = NO; [containerView addSubview:imageView1]; UIImageView imageView2 = [[UIImageView alloc] initWithImage:[UIImage imageNamed:@"2.png"]]; imageView2.translatesAutoresizingMaskIntoConstraints = NO; [containerView addSubview:imageView2]; NSDictionary views = NSDictionaryOfVariableBindings(containerView, imageView1, imageView2); // define the container in relation to the two image views [containerView addConstraints:[NSLayoutConstraint constraintsWithVisualFormat:@"H:\|[imageView1]-[imageView2]\|" options:0 metrics:nil views:views]]; [containerView addConstraints:[NSLayoutConstraint constraintsWithVisualFormat:@"V:\|-[imageView1]-\|" options:0 metrics:nil views:views]]; [containerView addConstraints:[NSLayoutConstraint constraintsWithVisualFormat:@"V:\|-[imageView2]-\|" options:0 metrics:nil views:views]]; // center the container [self.view addConstraint:[NSLayoutConstraint constraintWithItem:containerView attribute:NSLayoutAttributeCenterX relatedBy:NSLayoutRelationEqual toItem:containerView.superview attribute:NSLayoutAttributeCenterX multiplier:1.0 constant:0]]; [self.view addConstraint:[NSLayoutConstraint constraintWithItem:containerView attribute:NSLayoutAttributeCenterY relatedBy:NSLayoutRelationEqual toItem:containerView.superview attribute:NSLayoutAttributeCenterY multiplier:1.0 constant:0]]; Another common solution with constraints is to create two extra UIView objects (sometimes called "spacer views"), for which you'll specify a background color of [UIColor clearColor], and put them on the left and right of your image views, and define them to go to the margins of the superview, and define the right view to be the same width of the left view. While I'm sure you're building your constraints as you're going along, if we were going to write the visual format language (VFL) for two imageviews to be centered on the screen, it might look like: @"H:\|[leftView][imageView1]-[imageView2][rightView(==leftView)]\|" Alternatively, you could eliminate the need for the container view or the two spacer views on the left and right by creating NSLayoutAttributeCenterX constraints using constraintWithItem, and specifying multiplier for the various image views so that they're spaced the way you want. While this technique eliminates the need for these two spacer views, I also think it's a little less intuitive. But it might look like: [imageViewArray enumerateObjectsUsingBlock:^(UIView view, NSUInteger idx, BOOL stop) { NSLayoutConstraint constraint = [NSLayoutConstraint constraintWithItem:view attribute:NSLayoutAttributeCenterX relatedBy:NSLayoutRelationEqual toItem:view.superview attribute:NSLayoutAttributeCenterX multiplier:2.0 (idx + 1) / ([imageViewArray count] + 1) constant:0]; [view.superview addConstraint:constraint]; }]; This admittedly employs a slightly different spacing of the image views, but in some scenarios it's fine. Personally, I'd lean towards the first approach, but any of these work.
ounded to 5 decimal places? -0.00013 Let w = 753782.07176 - 11.07176. Let t = w - 753763.6000107. Let a = t + -7.4. What is a rounded to six dps? -0.000011 Let y = -0.7 - -0.8. Let m = y + -1.7. Let g = 14.9 + m. Round g to 0 dps. 13 Let q = -2706.6984203 + 2706.7. What is q rounded to 4 dps? 0.0016 Let b = -268.9954 + -0.0046. Let f = -268.679 - b. What is f rounded to two dps? 0.32 Suppose 5k - 2y - 58247250 = -0k, 0 = -2k - y + 23298909. Let w = -228819 + k. Let z = 3020633 - w. Round z to the nearest 1000000. -8000000 Suppose 8g - 28228873 = 65611127. What is g rounded to the nearest 1000000? 12000000 Let p = -122 - -122.00302. What is p rounded to 3 decimal places? 0.003 Let b = 1958457.4519 + -1959312.5. Let t = b + 855. Round t to 2 dps. -0.05 Let a = -314.451 + 0.451. Let n = a - -313.99999697. What is n rounded to 7 decimal places? -0.000003 Let g(r) = -r3 - 11r*2 + 12r + 28. Let j be g(-23). Round j to the nearest one thousand. 6000 Let h = 311.99999574 + -312. Round h to six decimal places. -0.000004 Let d be 2/42 + -1. Suppose x + dx = -23753943. Let w = 2253943 + x. What is w rounded to the nearest one million? -22000000 Suppose 2u + 15 = 5u, -2284975 = -5z + 5u. Round z to the nearest ten thousand. 460000 Let r = 8088145.73508744 + -87921.87508004. Let q = r - 8000314.86. Let d = q - -91. Round d to 6 dps. 0.000007 Suppose -137r + 134r = -2757000. What is r rounded to the nearest 100000? 900000 Let m be 2/(1(-8)/(-12)). Suppose mz = 3t - 1278 - 30, 1338 = -3z - 3t. Let f = -648 - z. Round f to the nearest ten. -210 Let c = 427.00391 - 427. Round c to 3 dps. 0.004 Suppose 3r - 7 = 2. Suppose rw - 5w + 10 = 0. Let z be (2/w)/((-11)/(-4510)). What is z rounded to the nearest 10? 160 Suppose 2j + 17 = -3a, 7j - 2a = 2j + 5. Let u = j + 1. Suppose 2800000 = -n - un. Round n to the nearest one hundred thousand. -2800000 Let o = 111979713 + -706379799. Let c = o + 594399824.000123. Let t = 262 + c. Round t to five decimal places. 0.00012 Let j = -127 - -163. Let c = j + -35.999836. What is c rounded to 4 dps? 0.0002 Let x = -0.21 + -17.79. Let i = x - -18.072. Let r = -0.072074 + i. Round r to 5 decimal places. -0.00007 Let c = -10.7958 + -0.1442. Round c to the nearest ten. -10 Let x(m) = -6m2 - 8m - 14. Let a = 46 - 52. Let i be x(a). What is i rounded to the nearest ten? -180 Let s = 21 - 18. Suppose -sp - 3218495 = -848495. Round p to the nearest 100000. -800000 Let z = -420 - -155. Let x = -77 - z. Let w = 189.07 - x. Round w to one decimal place. 1.1 Let q = -108 - -43. Let r = q + 65.39. Let s = r + -0.352. What is s rounded to two decimal places? 0.04 Suppose 2o - 2u = 3o - 3881, 0 = 4o - u - 15506. Suppose -9m + 3323 + o = 0. Round m to the nearest one hundred. 800 Let q = -19.40256 - 5.52109. Let i = q - -22.523. Let y = -2.4 - i. What is y rounded to four decimal places? 0.0007 Let g(c) = -719c - 1. Let v be g(-2). Suppose v = 2x - 1639. Let l be (-14)/91 + x/26. What is l rounded to the nearest ten? 60 Let c(q) = q - 5. Let j be c(8). Suppose 2k - 3h - 233 = 0, jk + 0k = 3h + 357. Let p = -200 + k. What is p rounded to the nearest 10? -80 Let i = 6449333 - 4304523. Suppose -i = -8s + 4255190. Round s to the nearest one million. 1000000 Let k(y) = y3 + y2 - y - 1. Let c be k(-1). Let f be c + (3 - 0) + 0. Suppose 3q - 77 = 4q + fl, -8 = 4l. What is q rounded to the nearest ten? -70 Let h be (-86)/(-16) - 33/88. Let u(f) = -2 + 2 - 103f - 1 + h. Let s be u(3). What is s rounded to the nearest ten? -310 Let c = 0.1375 + 7.2525. Round c to one decimal place. 7.4 Suppose 2l + l = 459. Suppose -5x = -3n - 231, 5x - 175 = -3n + 44. Suppose -l = m + x. What is m rounded to the nearest 10? -200 Let n = 30.79971 - 30.8. What is n rounded to 4 decimal places? -0.0003 Suppose 5j = m + 20, -6m = -m - 4j + 16. Suppose ms + 5s - 34800025 = 5v, 0 = 5s - 25. Round v to the nearest 1000000. -7000000 Let u = 0.44 + -0.381. Let p = u + 0.291. Round p to 2 dps. 0.35 Let i = -277348 - -277084.918. Let s = -0.082 - i. Let z = 263.0000129 - s. Round z to 6 decimal places. 0.000013 Let j = -37 + 36.12. Let z = 0.5 - -1.1. Let l = z + j. What is l rounded to one dp? 0.7 Let v = 145 - 144.9999472. Round v to five decimal places. 0.00005 Let s(h) = -h2 + 6h + 10. Let g be s(7). Suppose 0 = -gi - 20552 + 158906. Let w = -24118 + i. Round w to the nearest ten thousand. 20000 Let d be 0 + 3 + -10 + -3 + 453410. What is d rounded to the nearest one hundred thousand? 500000 Let v = -1103945 - -1103991.7501. Let n = -46.8 + v. Let r = -0.05 - n. Round r to four dps. -0.0001 Suppose 3u = 4f - 229 - 509, f - 1247 = 5u. Let b = 496 + u. Round b to the nearest 10. 250 Let k = 5.03 + -5. Let l = k - -42.97. Let m = l + -42.9966. Round m to 3 dps. 0.003 Let d = 844.665086 + -787.9918677. Let x = d - 34.67321918. Let k = x + -22. Round k to seven dps. -0.0000009 Let r = 0.34 - -0.06. Let c = r + -0.28. Let a = -0.08 + c. Round a to 1 dp. 0 Let x be 2 - 10116/((-108)/12). Round x to the nearest one hundred. 1100 Let h = -34 - -35. Let c be (4/14 + 3368/(-28))/h. What is c rounded to the nearest 10? -120 Suppose 82316 = -x + 4p, 0 = -3p + 6 + 6. Round x to the nearest ten thousand. -80000 Let z = -2.9441 + 15.733. Let d = 12.8 - z. Round d to 3 dps. 0.011 Suppose 5p - 20 = 5j, 4 = 3p - 11. Suppose -3s - j = -7. Suppose 4i + 2874 = sy, 3y - 542 + 4151 = -5i. What is i rounded to the nearest one hundred? -700 Let o(a) = a*2 - 5a + 1. Let m = -8 + 10. Let l be o(m). Let f be (-55299)/(-7) - l/35. What is f rounded to the nearest 1000? 8000 Let x = -89 + 88.83. Let b = x - -0.2124. Round b to 3 dps. 0.042 Let j = -10254.8534 - -10254. Round j to one decimal place. -0.9 Let b = 143.882 - 144. Let w = 0.11707 + b. What is w rounded to 4 decimal places? -0.0009 Let a = -1679273 + 1681464.342. Let o = -2196 + a. Let p = -0.058 - o. Round p to the nearest integer. 5 Suppose r + 1 = 0, -2198 = 2u - 2r - 0r. Round u to the nearest 100. -1100 Let x = 3791657.02 + -3791607.0199987. Let y = x - 50. Round y to six decimal places. 0.000001 Let a = -3634 + 1244. Let b be 4/(-6) - a/30. Let q = b - 679. Round q to the nearest one hundred. -600 Let a = 70.02 + -352.92. Let h = 297 + a. Round h to zero dps. 14 Let v = 31 + -30.08. Let o = v - 0.9263. Let u = -0.0063311 - o. What is u rounded to 6 dps? -0.000031 Let p = -2239 + 2098.7. Let z = 106 + p. What is z rounded to zero dps? -34 Let b = -1.645 - -1.6. Let g = b - -0.016. What is g rounded to 2 decimal places? -0.03 Let n = 55 - 48. Suppose 0 = -nr + 9r + 53400. What is r rounded to the nearest one thousand? -27000 Let x = -9.2 - 80.8. Let k = x - -87.97. What is k rounded to 1 decimal place? -2 Let s = -89 + 12. Let k = s - -77.0047. Round k to four dps. 0.0047 Let y = -52201197 + 52201218.0000008. Let j = y + -21. Round j to 6 decimal places. 0.000001 Let t = -85 + 105.68. Let j = -20 + t. Round j to one decimal place. 0.7 Let h = 24.4 - 64. Let j = -39.600000371 - h. Round j to seven dps. -0.0000004 Let d = 5.536 - 5.5. Let h = d + 0.044. What is h rounded to one dp? 0.1 Let p = 864921 + -864924.99759. Let r = p - -4. What is r rounded to 4 decimal places? 0.0024 Let n = -386 - -113. Let i = 115 + n. Let z = -157.99869 - i. Round z to 4 decimal places. 0.0013 Let m = -17396714 + 26746714. Round m to the nearest 1000000. 9000000 Let q = -198.41983309 + 198.42. What is q rounded to five dps? 0.00017 Let c = 16 - 10. Suppose -l + cl = -135. Let n be 20/((l/(-690))/(-9)). Round n to the nearest 1000. -5000 Let f = 123.02 - 123. What is f rounded to 3 decimal places? 0.02 Let p = -2620693.0057 - -2620569. Let u = p - -124. What is u rounded to 3 dps? -0.006 Let m = 410 + -250. Let n = m - 146.6. Round n to 0 decimal places. 13 Let n = -75.6046095 + 20.604604. Let x = n + 55. What is x rounded to six dps? -0.000006 Suppose -h + 125855 = -95964. Suppose -7*i + 562881 + h = 0. Round i to the nearest ten thousand. 110000 Let s = 880 + -880.0000635. What is s rounded to five decimal places? -0.00006 Let s = 105.24 - 119. Let z = -32 - s. Let j = z + 18. What is j rounded to 1 decimal place? -0.2 Let i = -6488685.299991 - -6488692. Let w =
574 F.2d 637 187 U.S.App.D.C. 426 Leev.Senate Motors, Inc. No. 77-1495 United States Court of Appeals, District of Columbia Circuit 3/2/78 1 D.C.D.C. AFFIRMED
Trifluoromethylations of Alkenes Using PhICF3Cl as Bifunctional Reagent. We described a trifluoromethylation of alkenes using PhICF3Cl as bifunctional reagent. Chlorotrifluoromethylated products were obtained when nonconjugated alkenes were treated with PhICF3Cl in 1,4-dioxane at 60 °C, while vinyl C-H trifluoromethylated products were obtained by further elimination of hydrochloride in the case of those conjugated alkene substrates in DMF. Broad substrate scope, especially including complex alkenes bearing biological active motifs, suggests that this mild reaction is feasible for late-stage modification in drug discovery.
The Securitate was, in proportion to Romania's population, one of the largest secret police forces in the Eastern bloc.[2] The first budget of the Securitate in 1948 stipulated a number of 4,641 positions, of which 3,549 were filled by February 1949: 64% were workers, 4% peasants, 28% clerks, 2% persons of unspecified origin, and 2% intellectuals.[citation needed] By 1951, the Securitate's staff had increased fivefold, while in January 1956, the Securitate had 25,468 employees.[4] At its height, the Securitate employed some 11,000 agents and had a half-million informers[2] for a country with a population of 22 million by 1985.[3] Under Ceaușescu, the Securitate was one of the most brutal secret police forces in the world, responsible for the arrests, torture and deaths of thousands of people.[2] The General Directorate for the Security of the People (Romanian initials: DGSP, but more commonly just called the Securitate) was officially founded on August 30, 1948, by Decree 221/30 of the Presidium of the Great National Assembly.[4] However, it had precursors going back to August 1944, following King Michael's Coup.[4] Its stated purpose was to "defend democratic conquests and guarantee the safety of the Romanian Peoples' Republic against both internal and external enemies."[citation needed] The Securitate was created with the help of SMERSH, the NKVD counter-intelligence unit. The SMERSH operation in Romania, called Brigada Mobilă ("The Mobile Brigade"), was led until 1948 by NKVD colonel Alexandru Nicolschi.[citation needed] The first Director of the Securitate was NKVD general Gheorghe Pintilie (born Panteleymon Bondarenko, nicknamed "Pantiuşa"). Alexandru Nicolschi (by then a general) and another Soviet officer, Major GeneralVladimir Mazuru, held the deputy directorships. Wilhelm Einhorn was the first Securitate secretary. As Vladimir Tismăneanu says, "If one does not grasp the role of political thugs such as the Soviet spies Pintilie Bondarenko (Pantiușa) and Alexandru Nikolski in the exercise of terror in Romania during the most horrible Stalinist period, and their personal connections with Gheorghe Gheorghiu-Dej and members of his entourage, it is difficult to understand the origins and the role of the Securitate".[5] Initially, many of the agents of the Securitate were former Royal Security Police (named General Directorate of Safety Police—Direcția Generală a Poliției de Siguranță in Romanian) members. However, before long, Pantiușa ordered anyone who had served the monarchy's police in any capacity arrested, and in the places of the Royal Security Policemen, he hired ardent members of the Romanian Communist Party, to ensure total loyalty within the organization. In the 1980s, the Securitate launched a massive campaign to stamp out dissent in Romania, manipulating the country's population with vicious rumors (such as supposed contacts with Western intelligence agencies), machinations, frameups, public denunciations, encouraging conflict between segments of the population, public humiliation of dissidents, toughened censorship and the repression of even the smallest gestures of independence by intellectuals. Often the term "intellectual" was used by the Securitate to describe dissidents with higher education, such as college and university students, writers, directors and scientists who opposed the philosophy of the Romanian Communist Party. Assassinations were also used to silence dissent, such as the attempt to kill high-ranking defector Ion Mihai Pacepa, who received two death sentences from Romania in 1978, and on whose head Ceauşescu decreed a bounty of two million US dollars. Yasser Arafat and Muammar al-Gaddafi each added one more million dollars to the reward.[7] In the 1980s, Securitate officials allegedly hired Carlos the Jackal to assassinate Pacepa.[8] Forced entry into homes and offices and the planting of microphones was another tactic the Securitate used to extract information from the general population. Telephone conversations were routinely monitored, and all internal and international fax and telex communications were intercepted. After coal miners' unions went on strike and several leaders died prematurely, it was later discovered that Securitate doctors had subjected them to five-minute chest X-rays in an attempt to have them develop cancer.[9] After birth rates fell, Securitate agents were placed in gynecological wards while regular pregnancy tests were made mandatory for women of child-bearing age, with severe penalties for anyone who was found to have terminated a pregnancy.[9] The Securitate's presence was so ubiquitous that it was believed one out of four Romanians was an informer. In truth, the Securitate deployed one agent or informer for every 43 Romanians, which was still large enough to make it all but impossible for dissidents to organize. The regime deliberately fostered this sense of ubiquity, believing that the fear of being watched was sufficient to bend the people to Ceauşescu's will. For example, one shadow group of dissidents limited itself to only three families; any more than that would have attracted Securitate attention.[10] In truth, the East GermanStasi was even more ubiquitous than the Securitate; counting informers, the Stasi had one spy for every 6.5 East Germans.[11] The General Directorate for Technical Operations was a key part of the Securitate. Created with Soviet assistance in 1954, it monitored all voice and electronic communications in and out of Romania. They bugged telephones and intercepted all telegraphs and telex messages, as well as placing microphones in both public and private buildings. The Directorate for Counterespionage surveyed all foreigners in Romania, and did their utmost to impede contact between foreigners and Romanians. Contact that was impossible to stop was instead monitored. It enforced a variety of measures to prevent Romanians living with foreign nationals, one of these being the requirement to report any known foreigners to the Securitate within 24 hours. One of the tasks of this Directorate was to stop Romanians from seeking asylum in foreign embassies. The Directorate for Foreign Intelligence conducted Romania's espionage operations in other countries, such as those of Western Europe. Among those operations sanctioned by the Communist government were industrial espionage to obtain nuclear technology, and plots to assassinate dissidents, such as Matei Pavel Haiducu was tasked with, though he informed French authorities, faking the assassinations before defecting to France. The Directorate for Penitentiaries operated Romania's prisons, which were notorious for their horrendous conditions. Prisoners were routinely beaten, denied medical attention, had their mail taken away from them, and sometimes even administered lethal doses of poison.[citation needed] The Directorate for Internal Security was originally given the task of monitoring the activities going on in the Romanian Communist Party (PCR). But after Ion Mihai Pacepa's defection in 1978 and his exposing details of the Ceauşescu regime, such as the collaboration with Arab radical groups, massive espionage on American industry targets and elaborate efforts to rally Western political support, international infiltration and espionage in the Securitate only increased, much to Ceauşescu's anger. In order to solve this problem the entire Division was reorganized and was charged with rooting out dissent in the PCR. A top secret division of this Directorate was formed from forces loyal only to Ceauşescu and charged with monitoring the Securitate itself.[citation needed] It acted almost as a Securitate for the Securitate, and was responsible for bugging the phones of other Securitate officers and PCR officials to ensure total loyalty. The National Commission for Visas and Passports controlled all travel and immigration in and out of Romania. In effect, traveling abroad was all but impossible for anyone but highly placed Party officials, and any ordinary Romanian who applied for a passport was immediately placed under surveillance. Many Jews and ethnic Germans were given passports and exit visas through tacit agreements with the Israeli and West German governments.[12] The Directorate for Security Troops acted as a 20,000-strong paramilitary force for the government, equipped with artillery and armoured personnel carriers. The security troops selected new recruits from the same annual pool of conscripts that the armed services used. The police performed routine law enforcement functions including traffic control and issuance of internal identification cards to citizens. Organized in the late 1940s to defend the new regime, in 1989 the security troops had 20,000 soldiers. They were an elite, specially trained paramilitary force organized like motorized rifle (infantry) units equipped with small arms, artillery, and armored personnel carriers, but their mission was considerably different.[13] The security troops were directly responsible through the Minister of the Interior to Ceaușescu. They guarded important installations including PCR judet and central office buildings and radio and television stations. The Ceaușescu regime presumably could call the security troops into action as a private army to defend itself against a military coup d'état or other domestic challenges and to suppress antiregime riots, demonstrations, or strikes.[13] To ensure total loyalty amongst these crack troops, there were five times as many political officers in the Directorate for Security Troops than there were in the regular army.[13] They adhered to stricter discipline than in the regular military, but they were rewarded with special treatment and enjoyed far superior living conditions compared to their countrymen.[13] They guarded television and radio stations, and PCR buildings and in the event of a coup, would have been called in to protect the regime. After the Revolution, the Directorate for Security Troops was disbanded and replaced first by the Guard and Order Troops (Trupele de Pază şi Ordine), and in July 1990 by the Gendarmerie.
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Q: How to convert number in UITextField and pass it to UILabel in UITableViewCell? First, I want to build my app like this money converter. Cell for Row 0 will have a UITextLabel as a subview of UITableViewCell, which gets a number from users. Cell for Row 2 will have a UILabel as a subview of UITableViewCell, which will shows the calculated number. Cell for Row 3 will have a UILabel as a subview of UITableViewCell, which will shows the calculated number. But this number would be different from the number at Row 2. So I made 3 classes, for 'UITextField', 'UILabel', 'UITableViewController' Here is the 'UITableViewController' class code. class TableViewController: UITableViewController, UITextFieldDelegate { let fruitsComponents: [String] = ["Apple", "Banana", "Grape", "Pear"] let cellReuseidentifier = "cell" let anotherCellReuseidentifier = "anotherCell" override func viewDidLoad() { super.viewDidLoad() tableView.register(FruitTableViewCell.self, forCellReuseIdentifier: cellReuseidentifier) tableView.register(AnotherFruitTableViewCell.self, forCellReuseIdentifier: anotherCellReuseidentifier) } override func numberOfSections(in tableView: UITableView) -> Int { return 1 } override func tableView(_ tableView: UITableView, numberOfRowsInSection section: Int) -> Int { return fruitsComponents.count } override func tableView(_ tableView: UITableView, cellForRowAt indexPath: IndexPath) -> UITableViewCell { if indexPath.row == 0 { let cell = tableView.dequeueReusableCell(withIdentifier: cellReuseidentifier, for: indexPath) as! FruitTableViewCell cell.textLabel?.text = fruitsComponents[indexPath.row] return cell } else { let cell = tableView.dequeueReusableCell(withIdentifier: anotherCellReuseidentifier, for: indexPath) as! AnotherFruitTableViewCell cell.textLabel?.text = fruitsComponents[indexPath.row] return cell } } } I can get a number from UITextField and calculate it in UITextLabel subclass file. Or, I can do this in cellForRow syntex in UITableViewController class by making UITextLabel instance directly. But the problem is, I cannot pass the calculated data to UILabel. Because, TableViewCell was made by 'dequeue' method. I cannot pass the calculated data because the cells which contains UILabel subview were not made. Even if the cells are made, I cannot pass the data in 'cell' to 'cell', because both 'cell' and 'cell' was made by 'dequeue' method using same 'let cell'. Of course, I cannot differentiate the cell at Row2 and the cell at Row 3. Because of this, now, I cannot make a function that converts UILabel layout after receiving the data from UITextField. How to convert number in UITextField and pass it to UILabel in UITextViewCell? -------- Updates --------- 'FruitsTableViewCell' subclass code class FruitTableViewCell: UITableViewCell, UITextFieldDelegate { var numberTextField = UITextField() let toolBarKeyBoard = UIToolbar() let flexibleSpace = UIBarButtonItem(barButtonSystemItem: .flexibleSpace, target: nil, action: nil) lazy var doneButton = UIBarButtonItem(barButtonSystemItem: .done, target: self, action: #selector(donePressed)) var result : String! override init(style: UITableViewCellStyle, reuseIdentifier: String?) { super.init(style: style, reuseIdentifier: reuseIdentifier) numberTextField.addTarget(self, action: #selector(valueChanged(_:)), for: .valueChanged) self.contentView.addSubview(numberTextField) } required init?(coder aDecoder: NSCoder) { fatalError("init(coder:) has not been implemented") } override func layoutSubviews() { super.layoutSubviews() numberTextField.frame = CGRect(x: 250, y: 7.5, width: 100, height: 30) numberTextField.keyboardType = .numberPad toolBarKeyBoard.sizeToFit() numberTextField.inputAccessoryView = toolBarKeyBoard toolBarKeyBoard.setItems([flexibleSpace, doneButton], animated: false) } @objc func valueChanged(_ textField: UITextField) { var dataDict: [String: Double] = [:] dataDict["amount"] = Double(numberTextField.text!) ?? 0 NotificationCenter.default.post(name: Notification.Name(rawValue: "AmountChanged"), object: nil, userInfo: dataDict) } @objc func donePressed() { numberTextField.resignFirstResponder() } } 'AnotherFruitTableViewCell' subclass code class AnotherFruitTableViewCell: UITableViewCell { var outputTextLabel = UILabel() override init(style: UITableViewCellStyle, reuseIdentifier: String?) { super.init(style: style, reuseIdentifier: reuseIdentifier) NotificationCenter.default.addObserver(self, selector: #selector(handleNewAmount(_:)), name: Notification.Name("AmountChanged"), object: nil) self.contentView.addSubview(outputTextLabel) } required init?(coder aDecoder: NSCoder) { fatalError("init(coder:) has not been implemented") } override func layoutSubviews() { super.layoutSubviews() outputTextLabel.frame = CGRect(x: 250.0, y: 7.5, width: 100.0, height: 30.0) } @objc func handleNewAmount(_ notification: Notification) { guard let userInfo = notification.userInfo, let amount = userInfo["amount"] as? Double else { return } let finalAmount = amount * 0.05 outputTextLabel.text = String(finalAmount) } } A: This is a perfect example for using Notifications. You should add observers to every cell which contains the label. I'm guessing AnotherFruitTableViewCell is the cell which contains the label and FruitTableViewCell is the one that contains text field. class AnotherFruitTableViewCell: UITableViewCell { // Initialization of label, country and other code override init(style: UITableViewCell.CellStyle, reuseIdentifier: String?) { super.init(style: style, reuseIdentifier: reuseIdentifier) NotificationCenter.default.addObserver(self, selector: #selector(handleNewAmount(_:)), name: Notification.Name("AmountChanged"), object: nil) } @objc func handleNewAmount(_ notification: Notification) { guard let userInfo = notification.userInfo, let amount = userInfo["amount"] as? Float else { return } let finalAmount = //Some formula //Make the necessary changes to amount based on the country label.text = finalAmount } } Note: If you need to calculate the amount for different countries, you would need something in the label cell to identify the country and handle that when you set the amount to the label from the notification. Now all you need to do is post a Notification from the text field cell when the value of the text field changes. class FruitTableViewCell: UITableViewCell, UITextFieldDelegate { // Initialization of text field and other code override init(style: UITableViewCell.CellStyle, reuseIdentifier: String?) { super.init(style: style, reuseIdentifier: reuseIdentifier) textField.addTarget(self, action: #selector(valueChanged(_:)), for: .editingChanged) } @objc func valueChanged(_ textField: UITextField) { var amount: [String: Float] = [:] amountDict["amount"] = Int(textField.text!) ?? 0 NotificationCenter.default.post(name: Notification.Name(rawValue: "AmountChanged"), object: nil, userInfo: amountDict) } } Edit: For done button click. Remove the target and implement the same thing in your button selector. @objc func donePressed() { numberTextField.resignFirstResponder() var amount: [String: Float] = [:] amountDict["amount"] = Int(numberTextField.text!) ?? 0 NotificationCenter.default.post(name: Notification.Name(rawValue: "AmountChanged"), object: nil, userInfo: amountDict) }
Q: Read Raw Data in with Mozilla Add-on I'm trying to read and write raw data from files using Mozilla's add-on SDK. Currently I'm reading data with something like: function readnsIFile(fileName, callback){ var nsiFile = new FileUtils.File(fileName); NetUtil.asyncFetch(nsiFile, function (inputStream, status) { var data = NetUtil.readInputStreamToString(inputStream, inputStream.available(),{charset:"UTF-8"}); callback(data, status, nsiFile); }); } This works for text files, but when I start messing with raw bytes outside of Unicode's normal range, it doesn't work. For example, if a file contains the byte 0xff, then that byte and anything past that byte isn't read at all. Is there any way to read (and write) raw data using the SDK? A: You've specified an explicit charset in the options to NetUtil.readInputStream. When you omit the charset option, then the data will be read as raw bytes. (Source) function readnsIFile(fileName, callback){ var nsiFile = new FileUtils.File(fileName); NetUtil.asyncFetch(nsiFile, function (inputStream, status) { // Do not specify a charset at all! var data = NetUtil.readInputStreamToString(inputStream, inputStream.available()); callback(data, status, nsiFile); }); } The suggestion to use io/byte-streams is OK as well, but keep in mind that that SDK module is still marked experimental, and that using ByteReader via io/file as the example suggests is not a good idea because this would be sync I/O on the main thread. I don't really see the upside, as you'd use NetUtil anyway. Anyway, this should work: const {ByteReader} = require("sdk/io/byte-streams"); function readnsIFile(fileName, callback){ var nsiFile = new FileUtils.File(fileName); NetUtil.asyncFetch(nsiFile, function (inputStream, status) { var reader = new ByteReader(inputStream); var data = reader.read(inputStream); reader.close(); callback(data, status, nsiFile); }); } Also, please keep in mind that reading large files like this is problematic. Not only will the whole file buffered in memory, obviously, but: The file is read as a char (byte) array first, so there will be a temporary buffer in the stream of at least file.size length (via asyncFetch). Both NetUtil.readInputStreamToString and ByteReader will use another char (byte) array to read the result into from the inputStream, but ByteReader will do that in 32K chunks, while NetUtil.readInputStreamToString, will use a big buffer of file.length. The data is then read into the resulting jschar/wchar_t (word) array aka. Javascript string, i.e. you need file.size * 2 bytes in memory at least. E.g., reading a 1MB file would require more than fileSize * 4 = 4MB memory (NetUtil.readInputStreamToString) and/or more than fileSize * 3 = 3MB memory (ByteReader) during the read operation. After the operation, 2MB of that memory will be still alive to store the resulting data in a Javascript string. Reading a 1MB file might be OK, but a 10MB file might be already problematic on mobile (Firefox for Android, Firefox OS) and a 100MB would be problematic even on desktop. You can also read the data directly into an ArrayBuffer (or Uint8Array), which has more efficient storage for byte arrays than a Javascript string and avoid the temporary buffers of NetUtil.readInputStreamToString and/or ByteReader. function readnsIFile(fileName, callback){ var nsiFile = new FileUtils.File(fileName); NetUtil.asyncFetch(nsiFile, function (inputStream, status) { var bs = Cc["@mozilla.org/binaryinputstream;1"]. createInstance(Ci.nsIBinaryInputStream); bs.setInputStream(inputStream); var len = inputStream.available(); var data = new Uint8Array(len); reader.readArrayBuffer(len, data.buffer); bs.close(); callback(data, status, nsiFile); }); } PS: The MDN documentation might state something about "iso-8859-1" being the default if the charset option is omitted in the NetUtil.readInputStreamToString call, but the documentation is wrong. I'll fix it.
Plenty more like this here! Author Comments Reviews Rated 5 / 5 stars2005-08-17 00:07:03 WOOO Mario you dumbass, Jerry Garcia was he leader of the Grateful Dead! You must be somethin like 12 to not know Garcia. DAMN! Well, this was a funnymovie. You know...4:20 is also Hitler's B-day...just a side note. Rated 5 / 5 stars2002-06-14 03:53:33 ..... wow... this movie was great i wish the weed i have down here was that good... mmmmm well i'm gonna have to smoke a bowl or twoand watch this agian abd agian and agian untill i get interested by the doorknob
United States Court of Appeals Fifth Circuit F I L E D August 25, 2003 IN THE UNITED STATES COURT OF APPEALS Charles R. Fulbruge III Clerk FOR THE FIFTH CIRCUIT No. 02-40561 UNITED STATES OF AMERICA, Plaintiff-Appellee, versus JAMES DANIEL CARMICHAEL, Defendant-Appellant, _________________________________ Consolidated with No. 02-21023 UNITED STATES OF AMERICA, Plaintiff-Appellee, versus GABRIEL BRANDON COLLINS, Defendant-Appellant. _________________________ Appeals from the United States District Court For the Southern District of Texas Before KING, Chief Judge, and HIGGINBOTHAM and STEWART, Circuit Judges. PATRICK E. HIGGINBOTHAM, Circuit Judge: Appellants Gabriel Collins and James Carmichael both pleaded guilty to federal bank robbery charges and are currently serving terms of confinement in federal prison facilities. Both have appealed their sentences because, pursuant to the DNA Analysis Backlog Elimination Act of 2000 (“the DNA Act”), the sentences require the collection of a DNA sample as a mandatory condition of supervised release, a provision appellants urge is unconstitutional. They further contend that an implied provision of their sentence was the requirement, pursuant to the DNA Act, that Bureau of Prison staff take DNA samples during their incarceration, also violative of their constitutional rights. For the following reasons we dismiss the appeal for failure to exhaust administrative remedies and for unripeness. I In 1994, Congress authorized the Federal Bureau of Investigation to create a national index of DNA samples taken from convicted offenders, crime scenes, and unidentified human remains which could be used by criminal justice agencies for law enforcement identification, in judicial proceedings, and for criminal defense purposes.1 As a result, the FBI established the Combined DNA Index System (CODIS), which allows state and local forensics laboratories to exchange and compare electronic DNA profiles in order to match crime scene evidence to convicted 1 H.R. REP. No. 106-900, at 8 (2000), reprinted in 2000 U.S.C.C.A.N. 2323, 2324; Violent Crime Control and Law Enforcement Act of 1994 § 210304, 42 U.S.C. § 14132(a), (b)(3). -2- offenders on file in the system.2 By 2000, all fifty states had enacted statutes requiring convicted offenders to provide DNA samples for analysis and entry into CODIS.3 Samples taken from federal offenders were not included in CODIS, however, “because the language of the 1994 act only authorized the creation of the CODIS system, and not the taking of samples from persons convicted of Federal crimes.”4 To fill the gap left by the absence of federal offenders’ DNA samples in CODIS, the FBI requested in 1998 that Congress “enact statutory authority to allow the taking of DNA samples from persons committing Federal crimes of violence, robbery, and burglary, or similar crimes in the District of Columbia or while in the military, and authorizing them to be included in CODIS.”5 In response to the perceived need for inclusion of federal offender samples in CODIS, in 2000 Congress passed the DNA Analysis Backlog Elimination Act, which granted authority for collection of these samples and also provided for federal grants to the states to assist in reducing the backlog of biological samples waiting to be analyzed in the state systems.6 2 H.R. REP. No. 106-900, at 8 (2000), reprinted in 2000 U.S.C.C.A.N. 2323, 2324. 3 Id. 4 Id. 5 Id. at 9, reprinted in 2000 U.S.C.C.A.N. 2323, 2324-25. 6 Id. -3- Two provisions of the Act relating to collection of federal offenders’ DNA are at issue in this appeal. The first provides that “[t]he Director of the Bureau of Prisons shall collect a DNA sample from each individual in the custody of the Bureau of Prisons [BOP] who is, or has been, convicted of a qualifying Federal offense ... or a qualifying military offense ....”7 Qualifying offenses include “murder; voluntary manslaughter; other homicide offenses; offenses relating to sexual abuse, sexual exploitation or other abuse of children, and transportation for illegal sexual activity; kidnapping; burglary; and any attempt or conspiracy to commit those crimes.”8 BOP policies provide that offenders in its custody are to be screened by local Community Corrections Management Offices to determine whether they are qualified offenders under the DNA Act.9 Once an inmate arrives at his designated correction facility, the facility’s Health Services staff will arrange to collect a DNA sample during the routine physical examination.10 The Act also amended statutes relating to a district court’s 7 42 U.S.C. § 14135a(a)(1); see also 28 C.F.R. § 28.12(a) (Department of Justice’s implementing regulations). 8 H.R. REP. No. 106-900, at 19 (2000), reprinted in 2000 U.S.C.C.A.N. 2323, 2334. 9 Memorandum from Michael B. Cooksey, Assistant Director, Correctional Programs Division, et al., to all Chief Executive Officers (Feb. 12, 2002). 10 Id. -4- sentencing of federal offenders to probation or supervised release, requiring district courts to impose as a mandatory condition that the defendant cooperate in the collection of a DNA sample.11 The amended supervised release provision reads, “[t]he court shall order, as an explicit condition of supervised release, that the defendant cooperate in the collection of a DNA sample from the defendant, if the collection of such a sample is authorized pursuant to ... the DNA Analysis Backlog Elimination Act of 2000.”12 The Administrative Office of the United States Courts has instructed probation officers that they should not require an offender on probation or supervised release to submit a sample if the BOP obtained one during the offender’s incarceration.13 The DNA Act makes the failure to cooperate in the taking of a sample a 11 18 U.S.C. §§ 3563(a)(9), 3583(d); H.R. REP. No. 106-900, at 21 (2000), reprinted in 2000 U.S.C.C.A.N. 2323, 2337 (“Section 7 of the bill amends section 3563 of title 18 of the United States Code to require Federal courts to order, as a condition of any imposed term of probation, that defendants cooperate in the collection of DNA samples authorized under the bill. It also amends section 3583 of title 18, United States Code, to require Federal courts to order, as a condition of any imposed term of supervised release, that defendants cooperate in the collection of DNA samples authorized under the bill.”). 12 § 3583(d); see also § 3563(a)(9) (“The [sentencing] court shall provide, as an explicit condition of a sentence of probation ... that the defendant cooperate in the collection of a DNA sample from the defendant if the collection of such a sample is authorized pursuant to ... the DNA Analysis Backlog Elimination Act of 2000.”). 13 Memorandum from the Administrative Office of the United States Courts, to all Chief Probation Officers (Dec. 14, 2001). -5- misdemeanor offense.14 II On November 8, 2001, James Carmichael robbed a bank in Brownsville, Texas. Armed with a .357 handgun which he pointed at a customer, he made off with approximately $17,000 in cash. When apprehended several hours later, he admitted having robbed the bank, and a search turned up the gun and the money. Carmichael was indicted on counts of aiding and abetting bank robbery and using a firearm during the commission of a bank robbery; he pleaded guilty to both charges. The district court sentenced Carmichael to 117 months’ imprisonment and three years’ supervised release, and ordered Collins to submit to DNA sampling in accordance with the DNA Act. On November 20, 2001, Gabriel Collins and an accomplice robbed a bank in Katy, Texas. They passed a note to the teller stating that they were armed and took $5,955 in cash. However, the cash was rigged with a dye pack and bait bills, and the police eventually tracked down Collins when he used dye-stained bills to pay for auto repairs. Collins confessed to the robbery and pleaded guilty to the single count of aiding and abetting bank robbery. The district court sentenced him to thirty-seven months’ imprisonment and three years’ supervised release, and required that pursuant to the DNA Act the probation officer be allowed to collect 14 42 U.S.C. § 14135a(a)(5); see also 28 C.F.R. § 28.12(c). -6- DNA from Collins as a mandatory condition of supervised release. Both Carmichael and Collins now appeal their sentences, alleging that they should not be required to provide a DNA sample, either in prison or on supervised release, because the DNA Act is unconstitutional. Their actions were consolidated into this single appeal. III Carmichael and Collins challenge the constitutionality of the DNA Act on two grounds. First, they argue that the Act is an unconstitutional exercise of congressional power; and, second, that the Act is unreasonable under the Fourth Amendment, both as to prisoners and as to criminals on supervised release. The Government asserts that the appellants’ constitutional claim relating to the DNA Act’s provision requiring collection of their DNA while they are incarcerated relates to “conditions of confinement,” which cannot be appealed on direct review but rather must be brought in a separate civil action. It further contends that the defendants’ claim regarding the portion of the Act requiring collection of the DNA while they are on supervised release is unripe for review, since the Act requires collection of the appellants’ DNA samples while they are incarcerated so in all likelihood they will not be asked to submit a sample while on supervised release. We find the Government’s arguments persuasive. A Collins and Carmichael brought this direct appeal of their -7- sentences under 18 U.S.C. § 3742, which authorizes, among other things, appeal of a sentence imposed “in violation of law.”15 The Government contends that the DNA’s mandate that the BOP collect DNA samples from qualified federal offenders is not part of the district court’s sentence. Rather, that portion of the Act operates independently from appellants’ sentences. Because the DNA Act is simply one of the myriad regulations of prison life, asserts the Government, it amounts to a condition of confinement, which Collins and Carmichael can challenge only in a separate civil action filed after exhausting their administrative remedies.16 Like the Government, we conclude that neither the text of the Act nor the legislative history suggests that district courts, at sentencing, are to play any part in the collection of DNA samples by BOP officials. The statute orders “[t]he Director of the Bureau of Prisons” to “collect a DNA sample from each individual in the custody of the Bureau of Prisons who is, or has been, convicted of a qualifying Federal offense.”17 This provision demonstrates that 15 18 U.S.C. § 3742(a)(1). 16 See 18 U.S.C. § 3626 (describing appropriate remedies with respect to prison conditions); 42 U.S.C. § 1997e(a) (Prison Litigation Reform Act) (“No action shall be brought with respect to prison conditions under section 1983 of this title, or any other Federal law, by a prisoner confined in any jail, prison, or other correctional facility until such administrative remedies as are available are exhausted.”); see also Groceman v. U.S. Dep’t of Justice, No. 3:01-CV-1619-G, 2002 WL 139559 (N.D. Tex. June 26, 2002) (civil action for injunctive relief brought by prisoners to prevent the BOP from taking DNA samples). 17 § 14135a(a)(1). -8- the BOP not only has power to take the samples, but is vested with the authority to determine who is eligible for DNA sampling. The legislative history reinforces this interpretation by explaining that the Act “direct[s] the Bureau of Prisons (BoP) to collect a DNA sample from each person in federal custody who has been convicted of certain felonies or sexual offenses.”18 That the Act took prison sampling out of the sentencing court’s hands is reinforced by its provisions relating to supervised release and probation, which in contrast “require Federal courts to order, as a condition of any imposed term of [probation or supervised release], that defendants cooperate in the collection of DNA samples authorized under the bill.”19 Collins and Carmichael argue that the DNA sampling requirement is no different than statutes requiring restitution, criminal forfeiture, or special assessments, which constitute part of a criminal sentence. However, each of these statutes provide that the district court “may” or “shall order” imposition of the sanction,20 while the portion of the DNA Act relating to collection 18 H.R. REP. No. 106-900, at 14 (2000), reprinted in 2000 U.S.C.C.A.N. 2323, 2329 (emphasis added). 19 Id. at 21, reprinted in 2000 U.S.C.C.A.N. 2323, 2337; see also id. at 14, reprinted in 2000 U.S.C.C.A.N. 2323, 2329 (“The bill would direct the Judiciary to collect a DNA sample from each person under federally supervised release who has been convicted of certain felonies or sexual offenses.” (emphasis added)). 20 18 U.S.C. § 3663 (“The court, when sentencing a defendant convicted of [certain offenses], may order, in addition to or, in -9- of DNA samples during incarceration lacks reference to any role a district court is to play in that process. We also reject their contention that suits challenging conditions of confinement relate only to complaints such as cell overcrowding and inadequate medical care. Rather, the Supreme Court has instructed that suits challenging conditions of confinement include prisoner petitions alleging not only “continuous conditions,” but “isolated episodes of unconstitutional conduct.”21 Stated another way, suits attacking conditions of confinement implicate “all inmate suits about prison life, whether they involve general circumstances or particular episodes, and whether they allege excessive force or some other wrong.”22 Accordingly, we hold that the DNA Act’s provision for the BOP’s collection of federal offenders’ DNA during incarceration is the case of a misdemeanor, in lieu of any other penalty authorized by law, that the defendant make restitution to any victim of such offense ....”); 18 U.S.C. § 3554 (“The court, in imposing a sentence on a defendant who has been found guilty of [certain offenses,] shall order ... that the defendant forfeit property to the United States ....”); 18 U.S.C. § 1467 (“The court shall order forfeiture of property ... if – (1) the trier of fact determines, beyond a reasonable doubt, that such property is subject to forfeiture ....”); 18 U.S.C. § 3013 (“The court shall assess on any person convicted of an offense against the United States ....”). 21 McCarthy v. Bronson, 500 U.S. 136, 139 (1991); see also Booth v. Churner, 206 F.3d 289, 294 (3d Cir. 2000) (“... [T]he unanimous Court interpreted the ... ‘conditions of confinement’ language – one half of the definition of ‘prison conditions’ in § 3626(g)(2) – to include all inmate petitions, not only those regarding ‘continuous conditions,’ but ‘isolated episodes of unconstitutional conduct,’ such as the petitioner’s claim of excessive force ....” (quoting McCarthy, 500 U.S. at 139)), aff’d, 532 U.S. 731 (2001). 22 Porter v. Nussle, 534 U.S. 516, 532 (2002). -10- not part of appellants’ sentence, but is rather a prison condition that must be challenged through a separate civil action after exhaustion of administrative remedies. B The Government concedes that the DNA Act’s provisions relating to collection of DNA samples during an offender’s probationary or supervised release period are part of the appellants’ sentences, because they require a sentencing court to impose DNA collection as a mandatory condition of probation or supervised release. However, the Government asserts that we must dismiss the remainder of the appeal for lack of jurisdiction because appellants’ constitutional claim regarding the DNA Act’s provisions for collection of the DNA during supervised release is not yet ripe. Only if the BOP fails to execute its statutorily-imposed duty to collect the sample will appellants be required to submit to sampling during supervised release. The Government posits that this renders the possibility of DNA sampling during supervised release speculative, and in this case ripeness considerations mitigate against premature adjudication since we are called upon by the defense to render an act of Congress unconstitutional. “Ripeness separates those matters that are premature because the injury is speculative and may never occur from those that are appropriate for judicial review.”23 A claim is not ripe for review 23 United Transp. Union v. Foster, 205 F.3d 851, 857 (5th Cir. 2000). -11- if “it rests upon contingent future events that may not occur as anticipated, or indeed may not occur at all.”24 The Government asserts that not only is it possible that the supervised release condition appellants complain of will never come to fruition, but it is likely, because unless the BOP “flouts the multiple layers of legal obligations placed upon it,” by the time the appellants are released it will already have collected a DNA sample from them in accordance with the Act. We agree. This scenario is distinct from those cases pointed to by appellants in which we have taken up objections to supervised release conditions on direct appeal of the sentence, because those related to conditions not contingent on future events.25 Here it is a matter of conjecture whether either Collins or Carmichael will be forced to submit to DNA sampling during supervised release. We therefore dismiss the remainder of this appeal for lack of jurisdiction. 24 Texas v. United States, 523 U.S. 296, 300 (1998) (internal quotation marks omitted). 25 See United States v. Warden, 291 F.3d 363, 365 (5th Cir. 2002) (addressing whether the district court’s oral pronouncement of supervised release conditions varied from its written pronouncement, and whether the probation officer could determine the defendant’s ability to pay for the court-ordered drug treatment and other programs); United States v. Paul, 274 F.3d 155, 164-66 (5th Cir. 2001) (addressing the defendant’s challenge to special conditions requiring him to avoid contact with minors, prohibiting him from engaging in any occupation or volunteer service that would expose him to minors, and instructing him to avoid places, establishments, and areas frequented by minors); United States v. Mills, 959 F.2d 516, 519 (1992) (evaluating a condition imposing an occupational restriction). -12- APPEAL DISMISSED. -13-
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd"> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <meta http-equiv="Content-Type" content="text/xhtml;charset=UTF-8"/> <meta http-equiv="X-UA-Compatible" content="IE=9"/> <meta name="generator" content="Doxygen 1.8.14"/> <meta name="viewport" content="width=device-width, initial-scale=1"/> <title>rllib: rlcontroller.h File Reference</title> <link href="tabs.css" rel="stylesheet" type="text/css"/> <script type="text/javascript" src="jquery.js"></script> <script type="text/javascript" src="dynsections.js"></script> <link href="search/search.css" rel="stylesheet" type="text/css"/> <script type="text/javascript" src="search/searchdata.js"></script> <script type="text/javascript" src="search/search.js"></script> <link href="doxygen.css" rel="stylesheet" type="text/css" /> </head> <body> <div id="top"><!-- do not remove this div, it is closed by doxygen! --> <div id="titlearea"> <table cellspacing="0" cellpadding="0"> <tbody> <tr style="height: 56px;"> <td id="projectalign" style="padding-left: 0.5em;"> <div id="projectname">rllib  <span id="projectnumber">1</span> </div> </td> </tr> </tbody> </table> </div> <!-- end header part --> <!-- Generated by Doxygen 1.8.14 --> <script type="text/javascript"> /* @license magnet:?xt=urn:btih:cf05388f2679ee054f2beb29a391d25f4e673ac3&dn=gpl-2.0.txt GPL-v2 / var searchBox = new SearchBox("searchBox", "search",false,'Search'); 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Meh, every useful library is still going to be written in English and there are a lot of programming concepts that need to be learned in English anyway before you can write anything useful in C. Creating some high-level scripting language like Python or Ruby would be better as an introduction to programming for Assyrians. But again, you would run into the issue of no libraries for general purpose programming Meh, every useful library is still going to be written in English and there are a lot of programming concepts that need to be learned in English anyway before you can write anything useful in C. Creating some high-level scripting language like Python or Ruby would be better as an introduction to programming for Assyrians. But again, you would run into the issue of no libraries for general purpose programming It's better to encourage people to use existing languages and frameworks to develop new innovate applications. Assyrians this way can learn something useful and potentially make a career out of it, empowering them. Also, Assyrians who actually start making money off of something they develop can hire outside help more easily if it's a language already standardized. If Assyrians waste their time writing libraries to just copy existing functionality and reproduce it for the sake of having different syntax...I just don't see it going anywhere. There's little value derived from it It's better to encourage people to use existing languages and frameworks to develop new innovate applications. Assyrians this way can learn something useful and potentially make a career out of it, empowering them. Also, Assyrians who actually start making money off of something they develop can hire outside help more easily if it's a language already standardized. If Assyrians waste their time writing libraries to just copy existing functionality and reproduce it for the sake of having different syntax...I just don't see it going anywhere. There's little value derived from it ok then by your idea, we should simply copy English C to Assyrian C by simply translating the libraries. I don't see what's so wrong with that. C is popular because of how low its abstraction is and how fast it is.
070267125/2. -(x - 267)(x + 74885)3/6 What is n in -2n*5 - 794n*4/5 - 1126n*3 + 421274n*2/5 - 822432n/5 + 407592/5 = 0? -54, -222/5, 1, 17 Find q, given that 2q3 - 105588q*2 + 17696448q - 742658112 = 0. 84, 52626 Factor 436166t2/7 - 872044t/21 - 64/7. 2(3t - 2)(218083t + 48)/21 Factor 5s2 + 25530s - 10276875. 5(s - 375)(s + 5481) Factor -4i2 - 13220i - 10770144. -4(i + 1457)(i + 1848) Factor f*4 - 203f*3 - 496389f*2 + 4978615f - 12458600. (f - 809)(f - 5)2(f + 616) Suppose 5w3 + 92610w*2 + 450022125w + 656261900000 = 0. What is w? -11872, -3325 Factor 2y3 + 42770y*2 + 180135456y - 543978407808. 2(y - 1991)(y + 11688)*2 Factor -2l*3/7 - 10114l*2/7 - 2121466l - 4986246950/7. -2(l + 475)(l + 2291)2/7 What is q in q4/9 + 436q3/9 - 7915q*2/9 - 97462q/9 - 78520/3 = 0? -453, -5, -4, 26 Find i, given that 5i4/2 + 168335i*3/2 + 1262075i*2 + 4206500i = 0. -33652, -10, -5, 0 Factor -2o3/15 + 121748o*2/15 + 194816o/3 + 649408/5. -2(o - 60882)(o + 4)*2/15 Solve 3z*4 + 54963z*3 + 494484z*2 + 1098756z + 659232 = 0 for z. -18312, -6, -2, -1 Factor -s*3/4 - 1027s*2 + 136761s/4 + 111807. -(s - 36)(s + 3)(s + 4141)/4 What is a in a*2 - 509837a + 5608086 = 0? 11, 509826 Determine k so that 27k5/5 - 2079k*4/5 + 51837k*3/5 - 412869k*2/5 - 1152k + 9180 = 0. -1/3, 1/3, 17, 30 Find n, given that 2n5/7 - 36n*4/7 - 4924n*3/7 - 58176n*2/7 + 587834n/7 + 1047420 = 0. -23, -10, 11, 63 Factor 5w2 - 5143885w + 51438350. 5(w - 1028767)(w - 10) Suppose 3i2/2 + 143484i - 1434915/2 = 0. What is i? -95661, 5 Factor -2k2 + 961452k + 105783920. -2(k - 480836)(k + 110) Determine g so that 5g4 - 8680g*3 - 721065g*2 + 7498260g + 28749600 = 0. -88, -3, 12, 1815 Find r such that 3r4/2 - 17268r*3 - 380259r*2/2 = 0. -11, 0, 11523 Factor -3i*3 + 251451i*2 - 5349369645i + 3356595028725. -3(i - 41585)2(i - 647) Let -2x2/7 + 86820x/7 + 781542/7 = 0. What is x? -9, 43419 Suppose -w*4/2 - 5512w*3 - 13631886w*2 + 8801538112w - 17548504576 = 0. What is w? -5776, 2, 526 Find z, given that -3z3/2 + 14445z*2/2 + 2870457z - 5769792 = 0. -371, 2, 5184 Factor -o*2 - 4251830o + 97792619. -(o - 23)(o + 4251853) Let -d3/3 - 165d*2 + 17638d/3 + 426536 = 0. What is d? -524, -37, 66 Find w, given that 4w2 + 3696280w = 0. -924070, 0 Let c*4 + 199281c*3 + 9935897112c*2 + 763882997108c = 0. What is c? -99602, -77, 0 Factor -2v4/5 + 4888v*3 - 48872v*2/5. -2v*2(v - 12218)(v - 2)/5 Determine g, given that 3g*3/5 + 369447g*2/5 + 2274740592g - 34124433984/5 = 0. -61576, 3 What is u in -u*3 + 423045u*2 + 23693448u + 88005008 = 0? -52, -4, 423101 Factor -v*2/5 - 661v/5 + 290404. -(v - 919)(v + 1580)/5 Let 37v*3 - 1685v*2 - 3481v - 1759 = 0. What is v? -1, 1759/37 Determine l, given that -2l2 + 4328612l + 64929630 = 0. -15, 2164321 Suppose a*4 + 2273a*3 - 20559a*2 - 47677a + 559090 = 0. What is a? -2282, -5, 7 Solve -3u3/8 + 1041u*2/8 + 270609u/4 - 67782 = 0. -286, 1, 632 Solve -3n2/5 + 4719510n - 23597547/5 = 0. 1, 7865849 Determine q, given that -3q2 - 99817893q - 99817890 = 0. -33272630, -1 Solve o*4/4 - 397o*3/4 - 24011o*2/2 + 12697o + 72618 = 0. -98, -2, 3, 494 Let 5c3 - 63420545c*2 = 0. Calculate c. 0, 12684109 Determine s, given that 4s*5 + 26799628s*4 + 26799616s*3 - 53599248s*2 = 0. -6699906, -2, 0, 1 Factor -3a*3 + 20578581a*2 - 35289822708504a - 35289843287088. -3(a - 3429764)2(a + 1) Factor -4o3 - 7065808o*2 + 56526656o - 113053440. -4(o - 4)2(o + 1766460) Suppose -4m5 - 168m*4 + 16020m*3 - 313720m*2 + 1741104m + 2071008 = 0. What is m? -94, -1, 17, 18 Solve 39s3 + 65196s*2 + 1712121s - 532980 = 0. -1645, -27, 4/13 Determine i so that -5i2 - 142130i + 16840960 = 0. -28544, 118 What is h in -2h4 - 501h*3/7 + 1718h*2/7 - 1437h/7 + 234/7 = 0? -39, 3/14, 1, 2 Factor -18u3 - 130329622u*2 + 57924280u. -2u(u + 7240535)(9u - 4) Factor -r*3/3 - 13678r*2/3 + 123169r/3 - 191618/3. -(r - 7)(r - 2)(r + 13687)/3 Solve -33t3/7 + 9389496t*2/7 - 667899604605t/7 + 121435981350/7 = 0. 2/11, 142265 Factor d*2 - 1667101d - 10002642. (d - 1667107)(d + 6) Determine y so that -5y*5 - 6205y*4 - 325295y*3 + 1013165y*2 - 1025600y + 343940 = 0. -1186, -58, 1 Let 3y4 + 78294y*3 + 428422788y*2 - 1115705158776y = 0. Calculate y. -13998, 0, 1898 Let 3p4 + 1629p*3 - 241032p2 = 0. Calculate p. -664, 0, 121 Factor n5 + 34178n4 + 170871n*3 + 205034n*2 - 136700n - 273384. (n - 1)(n + 2)3(n + 34173) Find w such that 2w2/5 - 478616w/5 + 287166 = 0. 3, 239305 Factor -3n3 - 3573n*2 - 617100n + 3175200. -3(n - 5)(n + 216)(n + 980) Factor 3s*2/7 + 206652s/7 - 37086831/7. 3(s - 179)(s + 69063)/7 Factor 3b2/2 + 2629050b + 1151983983750. 3(b + 876350)2/2 Find g, given that -g4/7 + 174g*3/7 + 128g*2 - 174g/7 - 895/7 = 0. -5, -1, 1, 179 Let 15j5 - 27238675j*4 + 127113570j*3 - 145272570j*2 + 18159055j + 27238605 = 0. Calculate j. -1/3, 1, 3, 1815907 Solve v*5/4 - 99v*4/4 - 18906v*3 + 133126v*2 - 304860v + 228852 = 0 for v. -234, 2, 3, 326 Factor -d*3/3 - 2197229d2/3. -d2(d + 2197229)/3 Solve 2y*3/5 - 15731602y*2/5 - 8y/5 + 62926408/5 = 0. -2, 2, 7865801 Find o such that 3o4/2 + 11067o*3 + 21008154o*2 + 2178982740o = 0. -3634, -110, 0 Determine c, given that 3c2 - 111630c = 0. 0, 37210 Solve 14g4/25 + 278078g*3/25 + 1381223268g*2/25 + 749349576g/5 - 47330352 = 0. -9930, -3, 2/7 Let -z*3/4 + 308931z*2/4 + 1235772z + 4943152 = 0. Calculate z. -8, 308947 Determine g, given that -g*2/2 - 720621g/2 + 1441250 = 0. -720625, 4 Determine w, given that 2w5/11 + 6620w*4/11 - 26506w*3/11 + 19884w*2/11 = 0. -3314, 0, 1, 3 Factor -3o*5 - 765111o*4 + 42090180o*3. -3o*3(o - 55)(o + 255092) Find y, given that y3 + 24500y*2 + 1709804y - 7231280 = 0. -24430, -74, 4 Determine j, given that -5j3 - 141575j*2 - 25040130j + 50646600 = 0. -28137, -180, 2 Suppose -3m2/7 + 3814449m/7 + 38144790/7 = 0. What is m? -10, 1271493 Factor 63555f2 - 1525325f + 120. 5(f - 24)(12711f - 1) Suppose 4k*3/7 + 5876k*2/7 + 252160k/7 + 1938000/7 = 0. Calculate k. -1425, -34, -10 What is r in 5r5 - 42100r*4 - 506745r*3 + 6958820r*2 - 20407540r + 17707200 = 0? -21, 2, 5, 8432 Solve -5h3 + 13375h*2 - 1639510h - 6772360 = 0. -4, 133, 2546 Let 3a2 - 11252055a + 11252052 = 0. Calculate a. 1, 3750684 Solve 3k5 + 13599k*4 + 17941752k*3 + 5737058364k*2 + 536553349920k + 530834219712 = 0 for k. -2062, -204, -1 Suppose i*5 - 908i*4 - 49989i*3 + 65372i*2 + 832220i + 1017600 = 0. Calculate i. -53, -2, 5, 960 Determine k so that 104k2/5 + 22228938k - 6412194/5 = 0. -1068699, 3/52 Solve 2r4 - 1800r*3 - 2871802r*2 + 1800r + 2871800 = 0. -830, -1, 1, 1730 Determine y so that -5y4 + 444915y*3 - 9887449680y*2 - 445836644100y = 0. -45, 0, 44514 Suppose -15x5/2 - 22041x*4/2 + 946581x*3/2 + 5620593x*2/2 + 3178197x + 852204 = 0. What is x? -1511, -4, -1, -2/5, 47 Factor 1347p2 + 13473p/5 + 6/5. 3(p + 2)(2245p + 1)/5 Solve -5f*4 + 29930f*3 - 833745f*2 - 2236500f + 13405500 = 0. -5, 3, 30, 5958 Solve -p*3 - 3435p*2 - 61362p + 492048 = 0. -3417, -24, 6 Factor -5i2 + 236645i - 137418540. -5(i - 46741)(i - 588) Factor 102a3 + 213183a*2 + 111392820a + 3276075. 3(a + 1045)2(34a + 1) Determine s so that -52265088s*5 + 548762976s*4 + 7526387374s*3 + 17381086293s*2 + 6799248s + 665 = 0. -5, -7/2, -1/5112, 19 Find z such that -48z4 - 52703452z*3/7 - 4391924z*2/7 + 4391952z/7 = 0. -1097988/7, -1/3, 0, 1/4 Factor 2v2/9 - 3739624v/3 + 11218870/9. 2(v - 5609435)(v - 1)/9 Factor k*2/8 - 129831k/2 + 519323/8. (k - 519323)(k - 1)/8 Factor 2n*4/5 + 11098n*3/5 + 4455534n*2/5 + 464850774n/5. 2n(n + 213)*2(n + 5123)/5 Suppose 25q5 + 110790q*4 + 509155q*3 + 221310q*2 - 177080q = 0. What is q? -4427, -4, -1, 0, 2/5 Find v, given that 5v2 + 5226335v + 5226330 = 0. -1045266, -1 So
Tracking and attrition in longitudinal school-based smoking prevention research. Research in the development of school-based smoking prevention programs has resulted in a set of approaches of known short-term efficacy. Further evaluation of these approaches now requires long-term follow-up of participants. To minimize the problems caused by attrition in these longitudinal studies, investigators have developed techniques for tracking study participants. Based primarily on the use of the telephone, mail, and public documents, these methods require good background information on both the study participants and their parents. This article summarizes the experience of three teams of researchers engaged in such follow-up studies. These investigators have identified the types of background information most useful in long-term follow-up of participants, have developed a set of strategies to obtain such background information, and have developed methods for successfully tracking participants after a lapse of several years.
Q: Can you create a multitenant provider hosted app without using the office store? Stackexchange says this is a subjective question but I don't think it is. I am just trying to discover feasibility here. After a lot of reading online, I was able to successfully convert an app that was originally built using auto-hosted model to provider-hosted. I currently have it working in one sharepoint online site collection with the content being provided from an azure website. The steps to accomplish this involved registering the app/client id & secret on the sharepoint site where the app was to be deployed (using appregnew.aspx), and then putting these values into the web.config of the provider hosted part of the app. Now, say I want to publish this same app to another sharepoint online site. Would I need to create a completely different azure website (or other provider) for the new tenant? Since the azure web site contains the app/client ID and secret, I don't understand how this can be accomplished, since I assume that each sharepoint online site will need to generate and register a new id & secret for the provider. Is the only way to accomplish this by packaging the app for the office store? Update: I suppose I could keep a database of app/client ID's and secrets on the provider / azurewebsites side, keyed by SPHostUrl, and get at multiple tenants' auth info that way. Am testing this out now. However, the AppManifest would still have to change for each publish, since it will be different for different tenants. I suppose that's not too bad, and we might be able to automate that on a build server using some powershell... A: Well as for me you can always register the app for the first time on one of the tenants, use the registration data in Azure and in .app file and then, when installing the app on other tenants instead of clicking on generate button in appregnew.aspx, simply paste the client id and client secret you have generated when installing the app for the first time. Have tested it in Office365<->Azure environment and it is working. This way you use the same Azure site and the same .app file for every subsequent installation.
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Our line is used in a wide range of industries which include aggregates, landscaping, infrastructure and road building, construction and demolition Types of Crushers Mineral Processing &amp Metallurgy Crushers may be divided into three general classes, with respect to the manner in which they do their work: Pressure Crushers: This egory embraces the several types of gyratory crushers and jaw crushers, as well as the double crushing rolls, with either smooth or corrugated shells. Impact Crushers: This division is represented chiefly by the various styles of hammermill also by the cage Crusher Wikipedia Compound cone crusher (VSC series cone crusher) can crush materials of over medium hardness. It is mainly used in mining, chemical industry, road and bridge construction, building, etc. As for VSC series cone crusher, there are four crushing cavities (coarse, medium, fine and superfine) to choose. International International leads the screening and crushing industry with a complete line of equipment including: cone, jaw and impact crushers, vibrating screeners, trommels and stacking conveyors. Our line is used in a wide range of industries which include aggregates, landscaping, infrastructure and road building, construction and demolition images cone stone crusher supremewheels.co.za images cone stone crusher. used aggregate cone crushers price. About us. Our company independently,which is affiliated with Group,aims to provide a range of stone crushing and stone milling solutions to customers around the world,Which is our former brand .. ReadMore . 4 Cone Crusher YouTube What are the differences between a jaw crusher vs a cone Mar 04, 2017&nbsp· As is well known, Granite is one of the most using stone in aggregate crushing plant and artificial sand making line. Great Wall cone crusher and jaw crusher are frequently applied in granite crushing plant. 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Cone Crushers Mineral Processing &amp Metallurgy Cone crushers are used in AG and SAG grinding circuits to increase tonnage by effectively dealing with any pebble (critical size) buildup problem. Normally, heavy duty shorthead crushers are employed to crush pebbles. Power and crusher cavity level are the key variables for monitoring and controlling the crusher operation. Cone Crusher Maintenance Crushed Stone, Sand &amp Gravel Jul 01, 2012&nbsp· The type and condition of your lubriion oil is critical to successful operation of your cone crusher. Crushing with worn out oil or oil of the wrong specifiion can significantly reduce crusher life. Your crusher is designed to work with the lube oil in the range of 50 degrees F (10 degrees C) to 125 degrees F (51 degrees C). stone crusher machine price Alibaba A wide variety of stone crusher machine price options are available to you, There are 53,600 stone crusher machine price suppliers, mainly loed in Asia. 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David Fernandez Jr. Joins “Lowrider” Cast David Fernandez Jr. has been cast in Universal Pictures’ Lowriders where he joins a cast that includes Demian Bichir, Eva Longoria, and Theo Rossi a project from Universal Pictures, Imagine Entertainment and Blumhouse Productions. Fernandez, a San Diego native, is best known for the role of Spooky in the award-winning film End of Watch starring Jake Gyllenhaal and Michael Peña. David recently completed Atlas Entertainment’s The Hollow Point starring Patrick Wilson, John Leguizamo, and Jim Belushi which is set to be released in 2015. CineLatino TV Network is currently airing seven films featuring David. Fernandez has co-starred in USA Network’s original comedy series, Benched. Other TV credits include FX’s Sons of Anarchy and Justified, Showtime’s Weeds and Mystery Girls on ABC Family. Ricardo de Montreuil is directing the film which is currently shooting in Los Angeles, CA. Brian Grazer from Imagine will produce along with Jason Blum from Blumhouse. Kim Roth, Alexandre Dauman (Imagine) and Couper Samuelson (Blumhouse) will be overseeing the project. David is repped by Alicia Bravatti at Momentum Talent and Literary Agency.
How to process (smoke and dry) catfish using firewood and charcoal fuelled oven Processed catfish by Divine Fish Farm Processing catfish using firewood and charcoal fuelled oven gives the fish a unique taste that is reminicent of traditional home cooking. The process is meticulous and it results in smoked and dried catfish that attracts premium price from discerning consumers. What you need: 50 kilogrammes (kg) of live catfish 500 grammes (g) of table salt Two fish feed sacks (polythene type) Two large plastic basins/bowls A brick oven (powered by firewood and charcoal) Six bundles of firewood One big sack of charcoal Water Knife or razor blades Soap Day 1 Killing; Washing; Degutting; Firing the oven; Smoking; Day 2 – Drying Day 3 – Drying Day 4 – Drying You can enroll for a practical hands on training course with us at our farm. Alternatively, you can purchase an e-copy of our detailed instruction manual with photos to guide you on catfish processing. Contact us if you are interested in learning how to add value to fresh catfish by processing it. At At Divine Fish Farm we grow catfish to table-size using fresh water and high quality feed. We process our catfish by methodically smoking and drying them under hygienic conditions. Finally, we package and sell our processed catfish to customers near and far.
fresh potato chips making machine frozen french fries in Israel January 8, 2019 \| Food Timeline: history notes-pie & pastry 2015-2-21 · Pie crust In its most basic definition, pie crust is a simple mix of flour and water. The addition of fat makes it pastry. In all times and places, the grade of the ingredients depends upon the economic status of the cook. Burger King products - Wikipedia 2018-11-15 · When the predecessor of international fast food restaurant chain Burger King (BK) first opened in 1953, its menu predominantly consisted of hamburgers, French fries, soft drinks, milkshakes, and desserts. After being acquired by its Miami, Florida franchisees and renamed in 1954, BK began expanding its menu by adding the Whopper sandwich in ... The Food Timeline--history notes: muffins to yogurt 2015-1-8 · Mozzarella cheese In America today, mozzarella is the cheese of choice for pizza, lasagna & other baked Italian-American dishes. It Italy, mozzarella has a long and venerable tradition. Originally made by monks from buffalo milk, this soft cheese can also be made with cow's milk. Health \| Yahoo Lifestyle Awards entries – Onboard Hospitality American Airlines Cole Haan amenity kits Onboard supplier: Buzz Featured onboard: American Airlines Description: A custom bag designed by Cole Haan, the international First kit features perforated details and comes in six colours inspired by the ZerØGrand collection. The international Business kit is a versatile Cole Haan branded Dopp Kit design in eight colour combinations.
/////////////////////////////////////////////////////////////////////////////// // // AutobahnJava - http://crossbar.io/autobahn // // Copyright (c) Crossbar.io Technologies GmbH and contributors // // Licensed under the MIT License. // http://www.opensource.org/licenses/mit-license.php // /////////////////////////////////////////////////////////////////////////////// package io.crossbar.autobahn.wamp.exceptions; import java.util.List; import java.util.Map; public class ApplicationError extends Error { public final List<Object> args; public final Map<String, Object> kwargs; public ApplicationError(String message, List<Object> args, Map<String, Object> kwargs) { super(message); this.args = args; this.kwargs = kwargs; } public ApplicationError(String message) { super(message); this.args = null; this.kwargs = null; } }
--- title: Button 按钮 description: type: 0 group: null menuName: Button icon: order: 4 --- `form`中除了支持 [行为按钮](./action)以外，还支持一些特定的按钮。 ## 基本用法 ```schema:height="350" scope="body" { "type": "form", "api": "https://houtai.baidu.com/api/mock2/form/saveForm", "controls": [ { "type": "text", "name": "name", "label": "姓名：" }, { "type": "action", "actionType": "dialog", "label": "按钮", "dialog": { "title": "弹框标题", "body": "这是一个弹框" } } ] } ``` ## 提交表单请配置`"actionType": "submit"`或`"type": "submit"`按钮，可以触发表单提交行为， ```schema:height="350" scope="body" { "type": "form", "api": "https://houtai.baidu.com/api/mock2/form/saveForm", "controls": [ { "type": "text", "name": "name", "label": "姓名：" }, { "type": "submit", "label": "提交" } ] } ``` ## 重置表单请配置`"actionType": "reset"`或`"type": "reset"`按钮，可以触发表单提交行为。 ```schema:height="350" scope="body" { "type": "form", "api": "https://houtai.baidu.com/api/mock2/form/saveForm", "controls": [ { "type": "text", "name": "name", "label": "姓名：" }, { "type": "reset", "label": "重置" } ] } ``` ## 属性表见 [Action 行为按钮](../action)
A Persevering Champion After 17 years as a professional golfer, Sergio Garcia is a Masters Champion. This is the first time he’s won one of the four major golf championships, which include the Masters Tournament, the U.S. Open, the Open Championship, and the PGA Championship. The 37-year-old plays in both the PGA Tour and the European Tour, and has won 31 international tournaments as a professional. He has been in the Official World Golf Rankings top 10 for more than a decade, according to his website. Off the course, he has dedicated himself to making golf accessible to players of all ability-levels and backgrounds. In 2002, he founded the Sergio Foundation to promote, develop and fund golf clinics for disabled youth throughout Spain. Garcia recently partners with the American Junior Golf Association for the first Sergio Garcia Foundation Junior Championship, which will be held May 6-8 in Winter Garden, Florida. Since 2014, Garcia has also been the honorary chairman of the Junior PLAYERS Championship. In 2015, Garcia was featured in a commercial for The First Tee, titled “Better People.” As a player, he strives to instill values of perseverance and upstanding character in the young golfers he influences. After spitting into the hole during a third round of the CA Championship in 2007, many questioned his character and influence on the youth he wanted to impact. His past character flaws show that people can learn and change their behaviors to have better outcomes. This reversal of character, along with the dedication and hard work that resulted in his 2017 Masters win, make Garcia a great role model for our Gator Junior Golfers. He has continuously worked to make golf accessible and teach young people valuable life lessons through the sport, which align with the missions of Gator Junior Golf. “That's a big thing for me,” said executive director Sean Warner. “We've got to reduce the barriers to entry for the sport to truly be inclusive of all demographics. This includes access to equipment, ability to play and practice outside of class, and reduce the financial burdens for parents to play golf with their kids.” Gator Junior Golf is a non-profit youth development organization that uses the game of golf to help children succeed both on and off the golf course. Golf helps our students build character and teaches them the values that bridges success on the course into other walks of life. We currently partner with a local McDonald's to provide 28 students with scholarships for our program, totaling $1,500. In addition to these scholarships, we want to expand our fundraising infrastructure to accommodate more students and better serve the students we already have. Within the next year, Gator Junior Golf is opening an after-school day at Ironwood Golf Course to accommodate our students in east Gainesville. The long term goal is to have exclusive practice facilities for our students at golf courses in Gainesville so that we can provide the best learning environment possible. “If we want to make the golf course a home for these kids, we've got to give them a roof first,” Warner said.
Individuals hospitalized for community-acquired pneumonia (CAP) are at increased risk for sudden death as a result of adverse cardiac events. During hospitalization for CAP up to 1/5 of individuals >65 years of age experience some form of adverse cardiac event including arrhythmias, congestive heart failure, or myocardial infarction. Following successful resolution of the infection, individuals hospitalized for CAP remain at high-risk for sudden cardiac-related death for up to 1 year post-infection. Thus events occurring during pneumonia either aggravate existing cardiovascular conditions or directly affect cardiac function. Streptococcus pneumoniae (the pneumococcus) is the leading cause of CAP and infectious-related death among the elderly (>65 years). In past studies, we have determined that pneumococcal cell wall released during infection damages cardiomyocytes in a Platelet activating factor (PAFr)-dependent manner, inhibiting their ability to contract and leading to death of challenged mice. Recently, we have determined that statins (i.e. HMG-CoA reductase inhibitors) protect lung cells from damage during pneumonia by inhibiting PAFr expression and blocking lytic pore-formation by the pneumococcal toxin pneumolysin. For this reason, we hypothesize that statin therapy will also protect cardiomyocytes from cell wall and pneumolysin mediated damage during pneumonia and prevent the occurrence of adverse cardiac events. In support of this hypothesis we have collected data showing that statins reduced the ability of live bacteria and S. pneumoniae components to adhere to and kill vascular endothelial cells. Furthermore, that mice administered statins for 1 week were protected against heart failure and death following intravenous challenge with purified pneumococcal cell wall. Thus experimental evidence suggests that statins have strong potential to be used as a therapeutic agent against adverse cardiac events during pneumonia. To rigorously test whether statins protect cardiomyocyte function during pneumonia. We will: Aim 1: Determine impact of statin therapy on pneumolysin-mediated cardiomyocyte damage. We will examine the effect of statins on cardiomyocyte damage during infection with wild type and pneumolysin deficient bacteria, asses cardiomyocyte function in vivo and ex vivo following exposure to pneumolysin, and examine cardiomyocyte caspase-independent apoptosis, the pathway normally triggered by pneumolysin. Aim 2: Determine the impact of statin therapy on cardiomyocyte cell wall uptake. We will determine the impact of statins on cardiomyocyte PAFr expression and cell wall uptake in vitro and vivo, we will determine the impact of statin therapy on heart function following challenge with cell wall collected from wild type and ethanolamine grown bacteria, the latter which does not interact with PAFr, we will determine the impact of cell wall and statins on cardiomyocyte gene expression. PUBLIC HEALTH RELEVANCE: Individuals hospitalized for community-acquired pneumonia (CAP) are at increased risk for sudden death as a result of adverse cardiac events that are in part the result of noxious agents released by bacteria during the infection. Our published data suggests that statins are capable of protecting host cells against Streptococcus pneumoniae cell wall and the toxin pneumolysin. The goal of this proposal is to test if statins protect mice against heart damage during pneumonia.
The present invention generally relates to electrochemical cells. In particular, the present invention relates to a third electrode, charging electrode, or counter-electrode (hereinafter simply referred to as a third electrode) for a metal-air battery formed from a mixture of a lanthanum nickel compound and a conductive metal, and to a method for forming the same. Recently, in response to increasing environmental concerns, research into alternatively powered vehicles has increased. One area of research which has drawn particular interest is battery powered vehicles. Such vehicles are more environmentally friendly than conventionally powered gas or diesel vehicles because the amount of harmful emissions (e.g., CO2, NOx and hydrocarbons) is vastly reduced or eliminated. One type of battery that has drawn particular interest is metal-air cells. Metal-air cells are well known and desirable as light-weight sources of power. Metal-air cells utilize oxygen from ambient air as a reactant in an electrochemical reaction. Metal-air cells can include an air permeable electrode as a cathode and a metallic anode surrounded by an aqueous electrolyte. Metal-air cells function through the reduction of oxygen from ambient air which reacts with the metal to generate an electric current. For example, in a zinc-air cell, the anode contains zinc, and during operation, oxygen from the ambient air along with water and electrons present in the cell are converted at the cathode to hydroxyl ions. Conversely, at the anode zinc atoms and hydoxyl ions are converted to zinc oxide and water, which releases the electrons used at the cathode portion of the cell. Thus, the cathode and anode acting in concert generate electrical energy. Specifically, the reactions which take place at the cathode and anode are shown in detail below. Cathode Reaction: O2+2H2O+4exe2x88x92xe2x86x924OHxe2x88x92 Anode Reaction: 2Zn+4OHxe2x88x92xe2x86x92ZnO+2H2O+4exe2x88x92. Cells that are useful for only a single discharge cycle are called primary cells, and cells that are rechargeable and useful for multiple discharge cycles are called secondary cells. An electrically rechargeable metal-air cell is recharged by applying voltage between the anode and the cathode of the cell and reversing the electrochemical reaction. During recharging the cell discharges oxygen to the atmosphere through the air permeable cathode. There are two main types of rechargeable metal-air cells. The first type includes those with three electrodes (i.e., tricells), namely, an anode, a unifunctional cathode, and a counter-electrode (i.e. a third electrode). The unifunctional cathode is used during the discharge cycle of the metal-air and is incapable of recharging the cell. The counter-electrode is required to recharge the metal-air cell. The second type of metal-air cells include two electrodes. The bifunctional electrodes function in both the discharge mode and the recharge mode of the cell, thus eliminating the need for a third electrode. However, bifunctional electrodes suffer from a major drawback. That is, they do not last long because the recharging cycle deteriorates the discharge system (i.e., bifunctional cells suffer from decreasing performance as the number of discharge/recharge cycles increase). Thus, in view of the above, tricells are advantageous when compared to bifunctional cells in that they offer more stable performance over a greater number of discharge/recharge cycles. One of the important aspects of a metal-air cell is the two types catalysts used for oxygen reduction during discharge and for oxygen evolution during recharge. For example, catalysts which can be used for the oxygen reduction catalyst include silver, platinum, platinum-ruthenium, nickel spinel, nickel perovskites, and iron, nickel, or cobalt macrocyclics. On the other hand, oxygen evolution catalysts can include, for example, tungsten compounds such as CoWO4, WC, WS2, and WC containing fused cobalt. In addition, metal oxides such as LaNiO3, NiCo2O4 and Co3O4 are known to be useful as oxygen evolution catalysts. Furthermore, most metals and alloys, even platinum and other precious metals and alloys, are not good oxygen evolution catalysts in strong alkaline electrolytes. They either suffer from low activity or their activity fades quickly after just a small number of discharge/recharge cycles. In addition, some active metal/metal oxides such as Ru tend to dissolve in an alkaline system. Also, most if not all metal and alloys suffer from oxidation due to the high electrical potential generated in the metal-air cell. Metal oxides such LaNiO3, NiCo2O4 and Co3O4 have been bonded with TEFLON(copyright) (a tetrafluoroethylene fluorocarbon polymer) and tested as a third electrode in a tricell. Such third electrodes suffer from the problem that bonded oxides on the surface of the third electrode flake off (i.e., delaminate) during oxygen evolution tests. Due to delamination, such third electrodes lose their activity over time. One solution to the above problem is disclosed in U.S. Pat. No. 4,497,698 to Bockris et al. U.S. Pat. No. 4,497,698 discloses sintering pure LaNiO3 powder to a ceramic form, then binding the ceramic LaNiO3 to copper wire with a silver epoxy resin. Such an electrode, when tested, has been found to be stable for over 1000 hours of oxygen evolution. However, such a solid electrode is difficult to use as a third electrode in a secondary metal-air cell (i.e. a tricell), for example a zinc-air cell. This is because the solid electrode cannot be put between the metal electrode (e.g., the zinc electrode) and the air electrode (e.g., a platinum electrode) as there is no opening for the electrolyte (e.g., sodium hydroxide) to flow through the third electrode. Such a structure therefore restricts the flow of ions (e.g., hydroxyl ions) between the metal electrode and the air electrode. Additionally, it can be difficult to bind/adhere a LaNiO3 ceramic to metal to form an electrode. This is because the interface must be carefully protected with extra epoxy or the like, otherwise it will oxidize quickly. Also the silver in the epoxy used to bind the LaNiO3 ceramic to the metal can also oxidize. Finally, an electrode which utilizes silver epoxy to bind the LaNiO3 ceramic to the metal is thick and therefore contributes to an undesirable increase in both battery size and weight. This in turn leads to a decrease in battery performance. In view of the above, there is a need in the art for improved metal-air batteries. The present invention provides a third electrode (i.e. a counter-electrode) for use in a metal-air tricell battery formed from a mixture of an lanthanum nickel compound and at least one metal oxide, and support structure such as a mesh screen, a metal planar sheet or a series of rigid rods or wires, and to a method for forming the same. The present invention provides a third electrode that not only produces oxygen during recharge (or initial charge) for a metal-air tricell but also provides stable performance over a large number of discharge/recharge cycles. This in turn leads to improved metal-air batteries based on tricells which incorporate such a third electrode. In one embodiment, the present invention relates to a third electrode for use in a metal-air tricell comprising a support structure coated with a layer of a lanthanum nickel compound/at least one metal mixture, wherein the mixture is adhered to the support structure without the use of an adhesive. In another embodiment, the present invention relates to a metal-air tricell comprising: an air electrode; a metal electrode; and a third electrode, wherein the third electrode comprises a support structure coated with a mixture of a lanthanum nickel compound and at least one metal, wherein the mixture is adhered to the support structure without the use of an adhesive. In another embodiment, the present invention relates to a method of forming a third electrode for use in a metal-air tricell comprising the steps of: (A) applying a mixture of a lanthanum nickel compound and at least one metal oxide to a support structure, thereby yielding a coated support structure; and (B) heating the coated support structure in order to reduce the metal oxide present in the lanthanum nickel compound/metal oxide mixture to its corresponding metal and to adhere the lanthanum nickel compound/metal mixture to the support structure, thereby yielding a third electrode wherein the third electrode is free of an adhesive. In one embodiment, step (A) of the above mentioned method comprises: (A-1) mixing a lanthanum nickel compound, at least one metal oxide and at least one dispersant to form a lanthanum nickel compound/metal oxide suspension; and (A-2) applying the lanthanum nickel compound/metal oxide suspension to the support structure to yield a coated support structure. In one embodiment, step (B) of the above mentioned method comprises heating the coated support structure for about 5 to about 20 hours at a temperature in the range of 150xc2x0 C. to about 1350xc2x0 C. In another embodiment, step (B) of the above mentioned method comprises: (B-1) heating the coated support structure at a first temperature sufficient to reduce the metal oxide present in the lanthanum nickel compound/metal oxide mixture to its corresponding metal; and (B-2) heating the coated support structure at a second temperature sufficient to adhere the lanthanum nickel/metal mixture to the support structure without the use of an adhesive. In another embodiment, the present invention relates to a method of forming a third electrode for use in a metal-air tricell comprising the steps of: (A) forming a suspension of a lanthanum nickel compound, at least one metal oxide compound and at least one dispersant; (B) applying the lanthanum nickel compound/metal oxide suspension to a support structure, thereby yielding a coated support structure; (C) heating the coated support structure to drive off the dispersant, reduce the metal oxide present in the lanthanum nickel compound/metal oxide suspension to its corresponding metal and to adhere the resulting lanthanum nickel compound/metal mixture to the support structure, thereby yielding a third electrode wherein the third electrode is free of an adhesive.
Amount of Sleep Needed \| Health Blog Sleep and Stroke Risk People who typically sleep for longer than eight hours each night may have an elevated stroke risk compared to those who generally get less sleep. We all know how important it is to get sufficient sleep, and how awful we feel when we don’t. Adequate amounts of restful sleep help us perform optimally during the day and contribute to our overall health. Yet most of us constantly bemoan the fact that we just can’t find enough time to get the sleep we need. After all, sleeping for eight-and-a-half or nine hours a night practically sounds decadent. And if you could regularly get that kind of sleep, you would probably reap some significant health benefits, right? Not necessarily. In the case of stroke, at least, new research points to a higher risk in adults who sleep the most. The study, which was conducted at the University of Cambridge in England, found that people who typically sleep for longer than eight hours each night may have an elevated stroke risk compared to those who generally get less sleep.1 Doheny, Kathleen. “Sleeping too much could raise risk of stroke.” CBS News. 26 February 2015. Accessed 1 March 2015. http://www.cbsnews.com/news/sleeping-too-much-could-raise-risk-of-stroke The subjects were nearly 9,700 men and women taking part in the European Prospective Investigation into Cancer Study–Norfolk cohort. They were between the ages of 42 and 81 at the outset of the trial and were tracked for close to 10 years. The participants provided information on their sleep habits early in the study, from 1998 to 2000, then were interviewed again four years later to report on their sleep quality and duration at that point. The scientists also logged any occurrences of stroke among the volunteers during the decade-long research. The majority of the subjects, approximately 70 percent, said that they generally slept between six and eight hours per night. Only 10 percent reported sleeping more than eight hours most nights, and a very small percentage typically slept less than six hours a night. By the end of the study period, 346 of the participants had suffered a stroke. After analyzing the data, the scientists determined that the individuals who tended to sleep more than eight hours nightly had a 46 percent greater risk of stroke than those who slept six to eight hours. Those who slept the least, averaging less than six hours a night, also faced a greater stroke risk than those in the six-to-eight category, but their risk was increased by only 18 percent, which is considerably better than those who slept the most. However, because there were so few volunteers who fell into the group that slept less than six hours, the evidence of that link is somewhat more tenuous. There was no positive correlation to consistently being a “long sleeper,” reporting eight hours or more in both the initial and follow-up segments of the research, either. The subjects who slept more than eight hours in both time periods were found to have twice the stroke risk of their peers who slept six to eight hours. But a change in sleeping habits was even worse. Those who went from a typical sleeping schedule of less than six hours nightly to requiring in excess of eight hours a night had approximately four times the risk of suffering a stroke than did those who remained in the six-to-eight hours group throughout. The study was not designed to prove cause and effect, but only demonstrate an association between sleep duration and stroke risk. This leaves open several possibilities. It may be that too much sleep disrupts some function in the brain that increases the likelihood of stroke. There is also a chance that changes have taken place in the brain that result in greater sleep requirements as well as the occurrence of a stroke. Hopefully there will be research that can shed some light on this eventually. In the meantime, if you tend to sleep for only slightly more than eight hours a night, it’s probably not worth cutting back if you do not have other stroke risk factors. We do want to meet our requirements for health reasons, as a 2003 study at the University of Michigan School of Medicine in Ann Arbor found that getting enough sleep is essential to the immune system and the prevention of inflammation.2 Opp, MR and Toth, LA. “Neural-immune interactions in the regulation of sleep.” Frontiers in Bioscience. May 2003. Accessed 2 March 2015. http://www.ncbi.nlm.nih.gov/pubmed/12700057?dopt=Abstract If, however, you usually need considerably more than eight hours of sleep to feel refreshed, you might want to examine what might be causing this situation. The need for excessive sleep may be linked to depression, dementia, or a thyroid condition. Also, as we’ve discussed previously, studies have shown that those who sleep more than eight hours a night have a 12-percent increased mortality rate, and that risk escalates with each additional hour of sleep. For more information on the importance of getting the right amount of sleep and natural ways to sleep better, check out Jon Barron’s To Sleep Perchance To Dream. About Us Liability Statement The statements found within these pages have not been evaluated by the Food and Drug Administration. If a product or treatment is recommended in these pages, it is not intended to diagnose, treat, cure, or prevent any disease. The information contained herein is meant to be used to educate the reader and is in no way intended to provide individual medical advice. Medical advice must only be obtained from a qualified health practitioner.
Q: When I call an pre-existing event handler from a subroutine, it doesn't come back. VB I'm looking to call a pre-existing event handler subroutine from the form_Load event handler. But the below doesn't work because control doesn't come back and I want to do more. UPDATE: I'm new to this so I don't know what the proper protocol is but... The reason for the non-return was that a statement like the below ended the subroutines execution. If aLabel.Tag = 1... the fix was adding New to the declaration to create an instance of it, ie.. changing.... Dim aLabel As Label ... to ... Dim aLabel As New Label I'm surprised I didn't get a warning but instead they just abruptly stopped execution of the sub. That wasn't very helpful :) Thanks again for your time guys... (Maybe this question should be deleted now that it has served its purpose) @konrad @karl END OF UPDATE What doesn't work is.... Private Sub Form1_Load... button1_Click(sender, e) 'But Control doesn't come back. end sub Do I change the sender to something? Thanks in advance Dave A: Invoking event handlers like this is a bad idea, because you are trying to simulate the event context by making sender and/or EventArgs be something else. Instead, put the logic that you want to invoke into a Subroutine or Function and have your Form1_Load method call that; likewise if you really do have a real click event handler, then that handler code can call the method too, like this: Private Sub Form1_Load() DoSomeWork() End Sub Protected Sub button1_Click(ByVal sender As Object, ByVal e As EventArgs) DoSomeWork() End Sub Private Sub DoSomeWork() ' Put logic here that you want to do from form load and a button click End Sub This has the benefit of making the code cleaner, clearer and easier to maintain as you only need to change the logic in one place should you need to change the logic. Note: Obviously, you can pass parameters to the DoSomeWork method, if need be, and change it to a Function if you need it to return something.
Thomas Edge (footballer) Thomas Edge (born 6 April 1970) is a former association football player who represented New Zealand at international level. Edge made his full All Whites debut as a substitute in a 0–1 loss to Australia on 12 May 1991 and ended his international playing career with seven A-international caps to his credit, his final cap an appearance in a 0–3 loss to Australia on 15 November 1995. References External links Category:1970 births Category:Living people Category:New Zealand association footballers Category:New Zealand international footballers Category:Waitakere City F.C. players Category:Association footballers not categorized by position
Here we have provided the link to download GSEB SSC 10th Part- A MCQs Answers of Gujarati (First language) & English (FL) in PDF Format, So that Candidates Can Verify Answers by downloading this PDF File. Nibschool from Palanpur is Publishing Answer Key of GSEB SSC & HSC Examination Gujarati & English Medium on its website (answerkey.nibschool.com) 2017. Click here to download GSEB SSC Paper Solutions 2018 GSEB Official Website Anskwerkey 2017 @ www.gseb.org GSEB STD.10 Answer Key by answerkey.nibschool.com 2017 A Leading Coaching Institutes Like Nib School also Published On GSEB SSC Answer Key 2017 on its website which is nibschool.com.
Human hair morphology: a scanning electron microscopy study on a male Caucasoid and a computerized classification of regional differences. The present study was performed to provide a better understanding of the morphological variations of mammalian hair. Terminal hair samples were obtained from different regions of the body of the same Caucasian male. All hair samples were either cleaned or treated before being examined with scanning electron microscopy. As human scalp hair grew it appeared small like lanugo hair, but the increase in diameter appeared to have been relatively rapid. As hair increased in diameter the appearance of the scales changed. Neck hair was slightly smaller in diameter than scalp hair, and axillary hair was slightly smaller in diameter than neck hair. Nostril hair was larger than scalp or axillary hair. Eyelash hair was much smaller and much shorter than eyebrow hair. Neck hair, forearm hair, and shin hair were smaller than hair from most other regions of the body. Chest hair was similar in size to scalp hair, and pubic and sideburn hair were larger than scalp hair. A morphological feature called "steak-boning" was more characteristically present in whiskers of Caucasoids than Orientals or Blacks. "Steak-boning" occurred most frequently in hair of the mustache, followed by that of the chin, sideburn, cheek and under the chin. Cut surfaces of whiskers were different for electric as compared with straightedge razors. Hair morphology varied relative to the body region. Computer analysis of resin-embedded hair made it possible to classify arm, mustache, cheek, chin, head, shin, and pubic hair, and to quantify cross-sectioned differences.
Why the Cleveland Browns suck The Cleveland Browns have qualified for the NFL Playoffs once since being reformed as an NFL expansion team in 1999. Just two times in that near 20-year span has seen the Browns have a better than .500 record. No other NFL franchise has been as bad as the Browns in modern football. Cleveland’s ineptitude is reminiscent of the New Orleans Saints 20 years of failing from the 1960s to the 1980s along with the Tampa Buccaneers godawful 1970s and 1980s. However, the Browns have hit new lows that no other NFL franchise has experienced. Talented Teams and Inconsistency Despite being the NFL’s worst team, the Browns have had some very talented teams. Yet, the team’s player consistency has been one of the biggest problems that continues to set them back. Cleveland have played 30 different starting quarterbacks in 20 seasons. This year alone has seen the team play two different signal callers in four games. Tyrod Taylor has started three games while rookie No.1 pick Baker Mayfield has started once. Mayfield started the Browns 45-42 shootout loss to the Oakland Raiders in week 4. The loss came one week after Mayfield replaced an injured Taylor and led the Browns to a 21-17 win over the New York Jets. The win over the Jets ended Cleveland’s 19-game winless streak. Now, it looks like Mayfield is set to remain as the No. 1 quarterback on the depth chart. Meanwhile, Taylor isn’t ruling out a trade after playing just two full games with the Browns. This brings the Browns back to the lack of consistency they have had a quarterback. The franchise has chopped and changed signal callers when thing haven’t gone well in the past. The constant change has hurt the team over and over again. Now, the franchise is ready to put its future in the hands of yet another rookie. If things go wrong with Mayfield, it won’t be long again until the Browns make another change. The 2018 NFL Season Cleveland started the 2018 season well enough with Taylor under center. The rainy weather and wind caused poor play on opening day against the Pittsburgh Steelers. Taylor managed just 197 yards passing. Yet, the Browns played well enough and mounted a fourth quarter 14-point comeback to force overtime. The Browns couldn’t see out the game and win in the extra period. The game ended in a tie. Week 2 saw the Browns surrender a 12-3 fourth quarter lead to the New Orleans Saints. Drew Brees led the Saints back to win with a 44-yard field goal in the final 21 seconds. Both games should have ended in Saints wins. Against Oakland in week 4, Mayfield’s play still left plenty to be desired. He may have thrown for 295 yards and two scores, but he also threw two interceptions and fumbled twice. One interception was returned for an Oakland touchdown. Despite the mistakes, the Browns nearly pulled off a second win of the season. But the loss wasn’t entirely the team’s fault. In the wake of the Browns’ loss to Oakland, the NFL has admitted an officiating error that cost Cleveland the game. Cleveland’s luck just doesn’t seem to improve with age. In fact, the Browns had two calls wrongly called during the game. The first came when Oakland quarterback Derek Carr was tackled by Myles Garrett and Genard Avery. Carr lost the ball and it was picked up by Garrett and returned for a touchdown. The score would have sealed the game for the Browns, but it was overturned by the officials. NFL Senior Vice President of Officiating Al Riveron has publicly stated the call was wrong and the Browns’ touchdown should have stood. The second officiating error came on a Carlos Hyde run that was overturned by replay. The run, which resulted in a first down, should have stood. Head coach Hue Jackson then decided to punt on fourth down rather go for it on fourth and inches. Who’s to Blame for Cleveland’s Bad Performances? The fingers have been pointed for years. Who is the person or persons to blame for Cleveland’s continual bad play? Some must be laid at the feet of current coach Jackson. Now in his third season, Jackson has won just two games as Browns coach. But to blame him for everything would be foolish. The majority of blame in Cleveland must go on the franchise’s executives and front office. They are the ones who put Jackson in charge after one unsuccessful coaching season with the Oakland Raiders in 2011. It is the same front office who chose not the pursue Jimmy Garoppolo when the New England Patriots prepared to trade him a season ago. Regardless of the quality players available at Jackson’s disposal, the people on the sidelines and upstairs are preventing the Browns from moving forward on the field. Even though Cleveland Municipal Stadium is long gone, the Browns and their FirstEnergy Stadium are the new ‘mistake by the lake’.
Q: Merge SQL multiple insert statement is not an option So, the continaution of another question... I have merge which task is to create the junction table rows from an existing table which only can represent 1-1 connection between entities (PROJECT) and from a table which can represent N-1 connecton (worker) the junction table is (PROJECT-WORKER), everyproject should have a dedicated leaders, and every worker should have a project but now i should have an n-n connection... This merge would do the job: But unfortunately, multiple matched then insert branch is not a "feature" in sql, how can i workout this problem. The original query---) MERGE INTO WORKERPROJECT TARGET USING (SELECT distinct w.worker_id, w.worker_type, w.project_id worker_project_id, p.project_id project_project_id, p.dedicated_project_leader, p.dedicated_lead_developer, p.dedicated_lead_consultant, p.dedicated_supervisor from WORKER w join PROJECT p on w.project_id = p.project_id ) SOURCE ON (SOURCE.worker_type is null) WHEN NOT MATCHED THEN INSERT (TARGET.FK_WORKER_ID, TARGET.FK_PROJECT_ID,TARGET.IS_ACTIVE,POSITION) VALUES (SOURCE.WORKER_ID,SOURCE.worker_project_id,'ACTIVE',SOURCE.worker_type); WHEN NOT MATCHED THEN INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) VALUES (SOURCE.dedicated_project_leader,SOURCE.project_project_id,'ACTIVE','PROJECTVEZETŐ'); WHEN NOT MATCHED THEN INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) VALUES (SOURCE.dedicated_lead_developer,SOURCE.project_project_id,'ACTIVE','FEJLESZTŐVEZETŐ'); WHEN NOT MATCHED THEN INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) VALUES (SOURCE.dedicated_lead_consultant,SOURCE.project_project_id,'ACTIVE','KONZULENSVEZETŐ'); WHEN NOT MATCHED THEN INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) INSERT (FK_WORKER_ID, FK_PROJECT_ID,IS_ACTIVE,POSITION) VALUES (SOURCE.dedicated_supervisor,SOURCE.project_project_id,'ACTIVE','SUPERVISOR'); A: Actually you can. Thanks to the insert all http://docs.oracle.com/cd/B28359_01/server.111/b28286/statements_9014.htm#i2095116
Las redes sociales se han convertido en países digitales que aglutinan a decenas de millones de personas, sino cientos de millones que de alguna se identifican con la plataforma virtual a la que acceden, utilizando para ello un interfaz virtual a través de la que transmiten o se comunican en multitud de idiomas diferentes. Una de estas babilonias lingüísticas es la red de micro blog Twitter , tan solo se precisan 140 caracteres para que millones de usuarios expresen una idea común, pudiendo determinar la acción informativa del momento en términos globales. En la ultima infografía realizada por el cartógrafo Eric Fischer , detalla el grado de actividad de cada idioma en función de parámetros geograficos, para ello emplea un arco iris de colores que asocia a una determinada entidad idiomática, realizando una radiografia de la cantidad de idiomas en que transmiten sus mensajes.
Q: ActiveX component can’t create object : PCOMM.autECLConnList I am trying to automate the sending keystrokes to a mainframe application which is being connected using PCOMM iSeries emulator. I am not sure on what I am doing wrong here, as the same code works on a different machine. Below are the configurations, Working Machine : Windows 10 64 bit, Office 32-Bit Error Machine : Windows 7 64 bit, Office 64-Bit Below is the code On Error Resume Next Set autECLWinObj = CreateObject("PCOMM.autECLConnList") Set IA = CreateObject("PCOMM.autECLOIA") Set PS = CreateObject("PCOMM.autECLPS") PS.SetConnectionByName (Client) IA.SetConnectionByName (Client) autECLWinObj.SetConnectionByName (Client) Please help, i am new to this and stuck . P.S : Kindly don't duplicate the question as there are none specific to PCOMM. A: Changed MS Office 64 to MS Office 32 and it worked.
[Supervision in Psychiatric Training]. Psychotherapy is an essential component of psychiatric treatment. Although appropriate training including supervision is essential to become able to conduct psychotherapy skillfully, supervision has not been performed in the training of Japanese psychiatrists. In this article, we explain how to utilize supervision in psychiatric training.
Q: How to call shell script from perl script I'm trying to call already saved shell script from perl script, but it's not working . 1.pl: #!/usr/bin/perl #!/bin/csh -f use warnings; use Shell; system ("/bin/sh commands.sh"); commands.sh: #!/bin/csh -f echo "calling shell script from perl script"; A: If commands.sh is executable, then all you should need is: #!/usr/bin/perl system("/path/to/commands.sh") If commands.sh does not have the executable flag set, then #!/usr/bin/perl system("/bin/csh /path/to/commands.sh"); All of the other code appears to be superfluous.

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