title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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N-alkynyl derivatives of 5-fluorouracil: susceptibility to palladium-mediated dealkylation and toxigenicity in cancer cell culture. | Palladium-activated prodrug therapy is an experimental therapeutic approach that relies on the unique chemical properties and biocompatibility of heterogeneous palladium catalysis to enable the spatially-controlled in vivo conversion of a biochemically-stable prodrug into its active form. This strategy, which would allow inducing local activation of systemically administered drug precursors by mediation of an implantable activating device made of Pd(0), has been proposed by our group as a way to reach therapeutic levels of the active drug in the affected tissue/organ while reducing its systemic toxicity. In the seminal study of such an approach, we reported that propargylation of the N1 position of 5-fluorouracil suppressed the drug's cytotoxic properties, showed high stability in cell culture and facilitated the bioorthogonal restoration of the drug's pharmacological activity in the presence of extracellular Pd(0)-functionalized resins. To provide additional insight on the properties of this system, we have investigated different N1-alkynyl derivatives of 5-fluorouracil and shown that the presence of substituents near the triple bond influence negatively on its sensitivity to palladium catalysis under biocompatible conditions. Comparative studies of the N1- vs. the N3-propargyl derivatives of 5-fluorouracil revealed that masking each or both positions equally led to inactive derivatives (>200-fold reduction of cytotoxicity relative to the unmodified drug), whereas the depropargylation process occurred faster at the N1 position than at the N3, thus resulting in greater toxigenic properties in cancer cell culture. | 25,121,087 | [
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A synchronous-asynchronous particle swarm optimisation algorithm. | In the original particle swarm optimisation (PSO) algorithm, the particles' velocities and positions are updated after the whole swarm performance is evaluated. This algorithm is also known as synchronous PSO (S-PSO). The strength of this update method is in the exploitation of the information. Asynchronous update PSO (A-PSO) has been proposed as an alternative to S-PSO. A particle in A-PSO updates its velocity and position as soon as its own performance has been evaluated. Hence, particles are updated using partial information, leading to stronger exploration. In this paper, we attempt to improve PSO by merging both update methods to utilise the strengths of both methods. The proposed synchronous-asynchronous PSO (SA-PSO) algorithm divides the particles into smaller groups. The best member of a group and the swarm's best are chosen to lead the search. Members within a group are updated synchronously, while the groups themselves are asynchronously updated. Five well-known unimodal functions, four multimodal functions, and a real world optimisation problem are used to study the performance of SA-PSO, which is compared with the performances of S-PSO and A-PSO. The results are statistically analysed and show that the proposed SA-PSO has performed consistently well. | 25,121,109 | [
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Locked mouths: Tooth loss in a women's prison in northeastern Brazil. | Prisoners, in general, exhibit unsatisfactory oral conditions, especially with regard to the large number of missing teeth and with untreated caries. The aim of this study was to assess tooth loss, use of and need for prosthetic rehabilitation, and use of dental services among inmates. A cross-sectional study involving 65 inmates was developed at the Regional Women's Prison of Campina Grande, Brazil. Data regarding sociodemographic and sentencing profile, use of dental services, dental morbidity, and self-perceived oral health impacts were investigated. Chi-square, Pearson, and Kruskal-Wallis (P < 0.05) statistical tests were used. The mean tooth loss was 11.3 teeth. Significant association between tooth loss and oral health satisfaction (P = 0.049), self-perceived need for dental prosthesis (P < 0.001), uncomfortable teeth brushing (P = 0.005), difficult speaking (P = 0.002), and difficulty in performing routine tasks (P = 0.025) was observed. It was observed that 29.2% of inmates were using some type of prosthesis, all deemed unsuitable for use, and 78.5% of inmates needed prosthetic rehabilitation. The oral health condition of the population studied was found to be poor, and prisoners showed significant tooth loss and need for dentures, with the aggravation of having tooth extraction as the major reason for seeking dental care. | 25,121,127 | [
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A note on parametric surfaces in Minkowski 3-space. | With the help of the Frenet frame of a given pseudo null curve, a family of parametric surfaces is expressed as a linear combination of this frame. The necessary and sufficient conditions are examined for that curve to be an isoparametric and asymptotic on the parametric surface. It is shown that there is not any cylindrical and developable ruled surface as a parametric surface. Also, some interesting examples are illustrated about these surfaces. | 25,121,129 | [
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On the open problem related to rank equalities for the sum of finitely many idempotent matrices and its applications. | Tian and Styan have shown many rank equalities for the sum of two and three idempotent matrices and pointed out that rank equalities for the sum P₁ + ⋯+P k with P₁,…, P k be idempotent (k > 3) are still open. In this paper, by using block Gaussian elimination, we obtained rank equalities for the sum of finitely many idempotent matrices and then solved the open problem mentioned above. Extensions to scalar-potent matrices and some related matrices are also included. | 25,121,133 | [
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Generalized equilibrium problem with mixed relaxed monotonicity. | We extend the concept of relaxed α-monotonicity to mixed relaxed α-β-monotonicity. The concept of mixed relaxed α-β-monotonicity is more general than many existing concepts of monotonicities. Finally, we apply this concept and well known KKM-theory to obtain the solution of generalized equilibrium problem. | 25,121,137 | [
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Antibiotic therapy for acute appendicitis in adults. Fewer immediate complications than with surgery, but more subsequent failures. | Appendectomy is the standard treatment for acute appendicitis. Since the 1990s, antibiotic therapy has sometimes been proposed as an alternative to immediate appendectomy. How effective are antibiotics in adults with uncomplicated acute appendicitis, and what is the risk of complications? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. A systematic review with meta-analysis included four randomised trials of antibiotics versus immediate appendectomy, in 900 patients hospitalised with uncomplicated appendicitis. The studies included only patients with few severe symptoms, thus undermining the strength of the results. Antibiotic therapy was usually administered intravenously first, then orally. The antibiotics used were amoxicillin + clavulanic acid, cefotaxime, or a fluoroquinolone. Metronidazole or tinidazole was often added. The total duration of antibiotic treatment was 8 to 15 days. The overall incidence of complications of appendicitis (perforation, peritonitis and surgical wound infections) was 25% in the immediate appendectomy group versus 18% in the antibiotic group. The frequency of perforations and peritonitis did not differ between the groups. All symptoms of appendicitis disappeared, without relapse or rehospitalisation during the first month, in 78% of patients in the antibiotic group. After one year of follow-up, 63% of patients treated with antibiotics were asymptomatic and had no complications or recurrences. In another systematic review of five randomised trials, outcome at one year was optimal in 73% of patients treated with antibiotics alone versus 97% of patients who had immediate appendectomy. In practice, in early 2014, appendectomy remains the first-line treatment for uncomplicated acute appendicitis. In some still poorly characterised patients, the harm-benefit balance of antibiotic therapy is probably better than that of immediate appendectomy. When informed of the risks, some patients are likely to choose antibiotic therapy. | 25,121,154 | [
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Baseline extracellular potassium level as an indicator of the rate of increase of the same on further storage in CPDA-1 whole blood units: a potential approach to complement FIFO system for prioritisation of blood bags for release from blood-banks. | Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects. Within a 19-month period, baseline and weekly samples from 15 CPDA-1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin. One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0·50, P < 0·01) of storage; four units increase at 2 weeks (r2 = 0·64, P < 0·001) and 3 weeks (r2 = 0·51, P < 0·01) of storage; six units at 4 weeks (r2 = 0·53, P < 0·01) of storage. Baseline whole blood haemoglobin showed a moderate association with baseline potassium (r2 = 0·36, P < 0·05) and 2-week potassium (r2 = 0·35, P < 0·05) values. For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the ‘first-in-first-out’ (FIFO) policy with ‘early release of blood-bags with high initial potassium’ might be helpful in improving the release of suitable blood units from blood-banks. | 25,121,159 | [
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Job satisfaction, organisation commitment and retention in the public workforce: a survey among pharmacists in Malaysia. | The aims of the study were to assess job satisfaction and organisational commitment among pharmacists working in the public sector and its influence on their likelihood to stay within the public workforce. A cross-sectional survey was conducted among all fully registered pharmacists (FRPs) in the northern states of Malaysia in 2009 (n = 467). The questionnaire consisted of three sections to capture the demographic characteristics of the respondents, assess job satisfaction and organisational commitment of the respondents and their likelihood of staying in public service. A total of 247 FRPs (response rate 52.9%) in the northern region of Malaysia participated in this survey. Majority of the respondents were women (n = 205, 83.0%), of Chinese ethnicity (n = 155, 62.8%), graduates from public universities (n = 173, 70.0%), single (n = 172, 69.6%), with a median age of 27 years (interquartile range (IQR) 2.0) and had worked with the Ministry of Health for a median of 2.75 years (IQR 1.63). The mean job satisfaction and organisational commitment score were 58.09 (standard deviation (SD) 11.83) and 53.46 (SD 6.65) respectively out of a maximum possible score of 90. Majority of the respondents claimed that they were likely to stay in public service (n = 176, 71.3%). Their likelihood of staying in public service was affected by respondents’ gender, ethnicity, job satisfaction and organisational commitment. The findings from this study provide stakeholders with evidence on factors and issues affecting pharmacists’ job satisfaction and commitment in the public workforce as well as the likely turnover rate with an early cohort of pharmacists affected by the compulsory service. | 25,121,161 | [
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Objective and subjective socioeconomic status and health symptoms in patients following hematopoietic stem cell transplantation. | Recent research indicates that subjective socioeconomic status (SES) – the perception of one's own SES compared with other people – is an important predictor of cancer-related health outcomes. Subjective SES may function as a psychosocial mechanism by which objective SES affects health, well-being, and, more broadly, quality of life among cancer survivors. This study tested whether the association between objective SES and indicators of quality of life was mediated by subjective SES in a sample of cancer survivors who had undergone hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation survivors (N=268) completed measures of objective and subjective SES, along with four measures related to quality of life (depressive symptoms, health-related quality of life, symptoms of generalized distress, and posttraumatic stress disorder symptoms). Higher objective SES was associated with greater quality of life across all four measures. Subjective SES mediated the relationship between objective SES and depressive symptoms (total indirect effect b=-0.09, 95% confidence interval [CI] [-0.15, -0.05]), generalized distress (total indirect effect b=-0.08, 95% CI [-0.13, -0.04]), health-related quality of life (total indirect effect b=0.10, 95% CI [0.06, 0.17]), and posttraumatic stress disorder (total indirect effect b=-0.08, 95% CI [-0.14, -0.04]). Findings extend work on subjective SES to cancer and suggest that SES gradients in patient outcomes after cancer may reflect not only material resources but also psychosocial factors related to rank within social hierarchies. Further research may provide insights useful for reducing disparities in this population | 25,121,168 | [
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NMR, calorimetry, and computational studies of aqueous solutions of N-methyl-2-pyrrolidone. | N-Methyl-2-pyrrolidone (NMP) is a solvent with applications in different industrial fields. Although largely employed in aqueous mixtures, little is known on the structural and dynamic properties of this system. In order to improve the knowledge on NMP aqueous solutions, useful to the development of their applications, NMR spectroscopy, calorimetric titration, and puckering analysis of molecular dynamics (MD) simulations were employed in this work. Our calorimetric study evidenced the presence of strong interactions between NMP and water and revealed that, under comparable conditions, the solvation of NMP by water results in an interaction stronger than the solvation of water by NMP. Overall, the changes of (1)H and (13)C chemical shifts and 2D ROESY spectra upon dilution suggested a preferential location of water nearby the carbonyl group of NMP and the formation of hydrogen bonding between these two molecules. In parallel, observation of correlation times by (13)C NMR spectroscopy evidenced a different dynamic behavior moving from the NMP-rich region to the water-rich region, characterized by a maximum value at about 0.7 water mole fraction. MD simulations showed that the NMP conformation remains the same over the whole concentration range. Our results were discussed in terms of changes in the NMP assembling upon dilution. | 25,121,346 | [
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Outcomes of surgical site infections in orthopedic trauma surgeries in a tertiary care centre in India. | Surgical site infections (SSIs) still cause significant morbidity and mortality despite advances in trauma care. We have studied in this paper the rate of SSIs, their outcomes in patients undergoing interventions for trauma and SSI trends in developing countries. A 16-month study (May, 2011- August, 2012) was carried out. Patients undergoing interventions for orthopedic trauma were followed and assessed for SSIs and their outcomes and antimicrobial sensitivity patterns of the micro-organisms isolated were noted and correlated. A total of 40 (4.4%) confirmed cases of SSIs were identified among 852 patients of orthopedic trauma. Based on the new CDC criteria, after ruling out cellulitis, only 24 (2.6%) were found to have SSIs. A total of 12.5% of the SSIs were detected during follow-up. Acinetobacter baumannii was the predominant organism as also Staphylococcus aureus. Outcomes observed included changes in antibiotic regime, revision surgery, readmission to hospital and deaths. SSI is prevalent in orthopaedic trauma patients and an active surveillance program will help in early management and prevention. | 25,121,363 | [
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Lower levels of serum high-density lipoprotein cholesterol are associated with a worse Duke treadmill score in men but not in women. | High-density lipoprotein cholesterol (HDL-C) levels are inversely related to the atherosclerotic burden and are higher in women than in men. We aimed to investigate the sex-specific relationship between serum HDL-C levels and the Duke treadmill score (DTS) in this study. A total of 111 patients (59 men, 42 women) with suspected coronary artery disease (CAD) who underwent exercise treadmill test (EST) were included. Fasting blood samples were obtained for the assessment of serum lipid levels. DTS was calculated for each patient based on EST findings including ST segment deviation and symptoms. Patients were categorized into a moderate to high risk group based on the DTS score (group-I: 38 patients) and a low risk group (group-II: 63 patients). There was a significant positive correlation between serum HDL-C levels and DTS (r = 0.230; P=0.021). The mean HDL-C level was significantly higher in group-II relative to group-I (49.25 ±11.21 vs. 44.43 ± 11.18, respectively, P = 0.04). An HDL-C level less than the cut-off value of 41.39 mg/dL predicted a moderate to severe risk DTS with 65% sensitivity and 69% specificity in men (area under curve = 0.732, P = 0.004), but not in women (area under curve = 0.505, P = 0.958). After adjustment for traditional CAD risk factors (age, sex, and smoking status), the relationship of DTS to HDL-C remained significant. (P = 0.030; adjusted OR = 0.948 [95% CI, 0.904-0.995]). Low HDL-C levels may be associated with a moderate to high risk Duke treadmill score in men, but not in women. Further research is required to clarify the sex-specific relationship between HDL-C and DTS. | 25,121,364 | [
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ProSeal Laryngeal Mask Airway Attenuates Systemic and Cerebral Hemodynamic Response During Awakening of Neurosurgical Patients: A Randomized Clinical Trial. | Extubation and emergence from anesthesia may lead to systemic and cerebral hemodynamic changes that endanger neurosurgical patients. We aimed to compare systemic and cerebral hemodynamic variables and cough incidence in neurosurgery patients emerging from general anesthesia with the standard procedure (endotracheal tube [ETT] extubation) or after replacement of the ETT with a laryngeal mask airway (LMA). Forty-two patients undergoing supratentorial craniotomy under general anesthesia were included in a randomized open-label parallel trial. Patients were randomized (sealed envelopes labeled with software-generated randomized numbers) to awaken with the ETT in place or after its replacement with a ProSeal LMA. We recorded mean arterial pressure as the primary endpoint and heart rate, middle cerebral artery flow velocity, regional cerebral oxygen saturation, norepinephrine plasma concentrations, and coughing. No differences were found between groups at baseline. All hemodynamic variables increased significantly from baseline in both groups during emergence. The ETT group had significantly higher mean arterial pressure (11.9 mm Hg; 95% confidence interval [CI], 2.1-21.8 mm Hg) (P=0.017), heart rate (7.2 beats/min; 95% CI, 0.7-13.7 beats/min) (P=0.03), and rate-pressure product (1045.4; 95% CI, 440.8-1650) (P=0.001). Antihypertensive medication was administered to more ETT-group patients than LMA-group patients (9 [42.9%] vs. 3 [14.3%] patients, respectively; P=0.04). The percent increase in regional cerebral oxygen saturation was greater in the ETT group by 26.1% (95% CI, 9.1%-43.2%) (P=0.002), but no between-group differences were found in MCA flow velocity. Norepinephrine plasma concentrations rose in both groups between baseline and the end of emergence: LMA: from 87.5±7.1 to 125.6±17.3 pg/mL; and ETT: from 118.1±14.1 to 158.1±24.7 pg/mL (P=0.007). The differences between groups were not significant. The incidence of cough was higher in the ETT group (87.5%) than in the LMA group (9.5%) (P<0.001). Replacing the ETT with the LMA before neurosurgical patients emerge from anesthesia results in a more favorable hemodynamic profile, less cerebral hyperemia, and a lower incidence of cough. | 25,121,397 | [
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Custom-modified three-dimensional periodic microstructures by pattern-integrated interference lithography. | By combining interference lithography and projection photolithography concurrently, pattern-integrated interference lithography (PIIL) enables the wafer-scale, rapid, and single-exposure fabrication of multidimensional periodic microstructures that integrate arbitrary functional elements. To date, two-dimensional PIIL has been simulated and experimentally demonstrated. In this paper, we report new simulated results of PIIL exposures for various custom-modified three-dimensional (3D) periodic structures. These results were generated using custom PIIL comprehensive vector modeling. Simulations include mask-integrated and mask-shaped 3D periodic arrangements as well as microcavities on top of or fully embedded within 3D periodic structures. These results indicate PIIL is a viable method for making versatile 3D periodic microstructures. | 25,121,439 | [
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Nonparaxial propagation and focusing properties of azimuthal-variant vector fields diffracted by an annular aperture. | Based on the vectorial Rayleigh-Sommerfeld integrals, the analytical expressions for azimuthal-variant vector fields diffracted by an annular aperture are presented. This helps us to investigate the propagation behaviors and the focusing properties of apertured azimuthal-variant vector fields under nonparaxial and paraxial approximations. The diffraction by a circular aperture, a circular disk, or propagation in free space can be treated as special cases of this general result. Simulation results show that the transverse intensity, longitudinal intensity, and far-field divergence angle of nonparaxially apertured azimuthal-variant vector fields depend strongly on the azimuthal index, the outer truncation parameter and the inner truncation parameter of the annular aperture, as well as the ratio of the waist width to the wavelength. Moreover, the multiple-ring-structured intensity pattern of the focused azimuthal-variant vector field, which originates from the diffraction effect caused by an annular aperture, is experimentally demonstrated. | 25,121,455 | [
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Copper clusters as novel fluorescent probes for the detection and photocatalytic elimination of lead ions. | A new homogeneous assay for a fast, selective and sensitive detection and elimination of lead ions has been developed using copper clusters as novel fluorescent probes in aqueous solutions. At the same time, their elimination is achieved using the efficient photocatalytic activity of such clusters. Both effects are explained in terms of an efficient electron transfer due to the LUMO energy of the cluster overlapping with the ion redox potential. The mechanism, which allows the explanation of previously reported results for different types of metal clusters, is further confirmed using smaller and larger Cu clusters displaying non-selective and non-quenching luminescence in the presence of different cations. | 25,121,465 | [
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Contact tracing investigation after professional exposure to tuberculosis in a Swiss hospital using both tuberculin skin test and IGRA. | A 950 bed teaching hospital in Switzerland. To describe the result of a contact investigation among health care workers (HCW) and patients after exposure to a physician with smear-positive pulmonary tuberculosis in a hospital setting using standard tuberculin skin tests (TST) and Interferon-gamma release assay (IGRA). HCW with a negative or unknown TST at hiring had a TST two weeks after the last contact with the index case (T0), repeated six weeks later if negative (T6). All exposed HCW had a T-SPOT.TB at T0 and T6. Exposed patients had a TST six weeks after the last contact, and a T-SPOT.TB if the TST was positive. Among 101 HCW, 17/73 (22%) had a positive TST at T0. TST was repeated in 50 at T6 and converted from negative to positive in eight (16%). Twelve HCW had a positive T-SPOT.TB at T0 and ten converted from negative to positive at T6. Seven HCW with a positive T-SPOT.TB reverted to negative at T6 or at later controls, most of them with test values close to the cut-off. Among 27 exposed patients tested at six weeks, ten had a positive TST, five of them confirmed by a positive T-SPOT.TB. HCW tested twice after exposure to a case of smear-positive pulmonary TB demonstrated a possible conversion in 10% with T-SPOT and 16% with TST. Some T-SPOT.TB reverted from positive to negative during the follow-up, mostly tests with a value close to the cut-off. Due to the variability of the test results, it seems advisable to repeat the test with values close to the cut-off before diagnosing the presence of a tuberculous infection. | 25,121,477 | [
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Performance assessment of time-domain optical brain imagers, part 1: basic instrumental performance protocol. | Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m² sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation. | 25,121,479 | [
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Compromised dynamic cerebral autoregulation in patients with a right-to-left shunt: a potential mechanism of migraine and cryptogenic stroke. | The relationship between right-to-left shunts (RLS) and migraine and cryptogenic stroke is not well understood. In this study, we investigated whether RLS are associated with impairment of dynamic cerebral autoregulation (dCA), which may play a role in migraine and cryptogenic stroke. Sixty-six migraineurs were enrolled in the study, including 36 non-RLS patients and 30 RLS patients. Non-invasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each patient by using transcranial Doppler and servo-controlled plethysmograph, respectively. Transfer function analysis was applied to derive autoregulatory parameters of gain, phase difference (PD), and autoregulation index. The PD in migraineurs with RLS was 50.6 ± 22.9 degrees, which was significantly lower than that observed in the non-RLS group (67.2 ± 18.2 degrees, P<0.001). The PD in the large RLS group (45.4 ± 22.6 degrees) was significantly lower than that of the small RLS group (64.9 ± 17.1 degrees, P<0.01) and non-RLS group (P<0.001); however, the PD in the small RLS group was similar to that of the non-RLS group. The PD in the permanent group (48.8 ± 19.9 degrees) was similar to that of the latent group (52.6 ± 26.1 degrees), and both were significantly lower than that of the non-RLS group (P<0.05). The autoregulation index results were similar to the PD findings. dCA is impaired in migraineurs with large RLS, and this may represent a potential mechanism linking RLS, migraine, and cryptogenic stroke. | 25,121,485 | [
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Altered resting-state FMRI signals in acute stroke patients with ischemic penumbra. | Identifying the ischemic penumbra in acute stroke subjects is important for the clinical decision making process. The aim of this study was to use resting-state functional magnetic resonance singal (fMRI) to investigate the change in the amplitude of low-frequency fluctuations (ALFF) of these subjects in three different subsections of acute stroke regions: the infarct core tissue, the penumbra tissue, and the normal brain tissue. Another aim of this study was to test the feasilbility of consistently detecting the penumbra region of the brain through ALFF analysis. Sixteen subjects with first-ever acute ischemic stroke were scanned within 27 hours of the onset of stroke using magnetic resonance imaging. The core of infarct regions and penumbra regions were determined by diffusion and perfusion-weighted imaging respectively. The ALFF were measured from resting-state blood oxygen level dependent (BOLD) fMRI scans. The averaged relative ALFF value of each regions were correlated with the time after the onset of stroke. Relative ALFF values were significantly different in the infarct core tissue, penumbra tissue and normal brain tissue. The locations of lesions in the ALFF maps did not match perfectly with diffusion and perfusion-weighted imagings; however, these maps provide a contrast that can be used to differentiate between penumbra brain tissue and normal brain tissue. Significant correlations between time after stroke onset and the relative ALFF values were present in the penumbra tissue but not in the infarct core and normal brain tissue. Preliminary results from this study suggest that the ALFF reflects the underlying neurovascular activity and has a great potential to estimate the brain tissue viability after ischemia. Results also show that the ALFF may contribute to acute stroke imaging for thrombolytic or neuroprotective therapies. | 25,121,486 | [
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Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome. | Rituximab has emerged as an important medication for patients with steroid-dependent or steroid-resistant nephrotic syndrome. We report the efficacy and safety of therapy with intravenous rituximab, administered once weekly for 2-4 doses, in 193 patients (mean age 10.9, range 2.2-18.7 years) with difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI)-dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n = 58) managed at this center during 2006-13. Therapy in patients with steroid dependence and CNI-dependent steroid resistance led to significantly reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2 relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P < 0.0001). This resulted in a significant reduction in steroid requirement (mean difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend to improved standard deviation scores for height (P = 0.069) and body mass index (P = 0.029). Remission was longer in patients with steroid dependence compared with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001). Prior response to cyclophosphamide predicted a lower risk of relapse in the former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P = 0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to occurrence of relapse; redosing (n = 42 patients) was safe and effective. Response to therapy was unsatisfactory in patients with steroid- and CNI-resistant nephrotic syndrome, with remission in 29.3%. Focal segmental glomerulosclerosis was associated with higher odds of non-response (odds ratio 11.1; P = 0.028) and lack of response was associated with progressive chronic kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse effects or infections were noted in 19 (9.8%) patients. Therapy with rituximab is effective and safe in reducing relapse rates and need for immunosuppressive medications in patients with steroid-dependent and CNI-dependent steroid-resistant nephrotic syndrome. | 25,121,488 | [
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Distribution of schistosomiasis and soil transmitted helminthiasis in Zimbabwe: towards a national plan of action for control and elimination. | Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe. | 25,121,489 | [
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Hyperglycemia and blood pressure treatment goal: a cross sectional survey of 18350 patients with type 2 diabetes in 77 tertiary hospitals in China. | To investigate the association of hyperglycemia with blood pressure control goal in the patients with type 2 diabetes (T2D) cared by tertiary hospitals in China. A cross sectional survey of 29442 patients was conducted in 77 tertiary hospitals in 4 major cities in China in 2011 and 18350 of them without known hypertension were used in the analysis. Univariable and multivariable logistic regression analysis stratified on cities and hospitals was performed to obtain odds ratio of factors of interest for achievement of the blood pressure treatment goal, i.e., 140/80 mmHg as recommended by American Diabetes Association (ADA). Sensitivity analysis was performed after re-inclusion of 11902 patients with diagnosed hypertension. Findings from were further replicated in patients with T2D recruited using the same protocol from tertiary hospitals located in other central cities in China. The mean age was 58.2 (SD: 11.3) years and 53.3% were male, with a median of 4 years of disease duration. A total of 12129 patients (58.2%) did not achieve the ADA recommended goal for BP control. After adjusting for covariables, hyperglycemia was associated with failure to achieve the BP goal (OR of HbA1c at 6.5%-6.9% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.39; OR of 7.0%-7.0% vs. <6.0%: 1.37, 1.21 to 1.54 and OR of ≥ 8.0% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.38). The sensitivity analysis and the replication analysis showed similar results. Hyperglycemia defined as HbA1c ≥ 6.5% increased the risk of failure to achieve the BP goal in T2D patients. | 25,121,493 | [
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Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment. | Transcriptional/translational feedback loops drive daily cycles of expression in clock genes and clock-controlled genes, which ultimately underlie many of the overt circadian rhythms manifested by organisms. Moreover, phosphorylation of clock proteins plays crucial roles in the temporal regulation of clock protein activity, stability and subcellular localization. dCLOCK (dCLK), the master transcription factor driving cyclical gene expression and the rate-limiting component in the Drosophila circadian clock, undergoes daily changes in phosphorylation. However, the physiological role of dCLK phosphorylation is not clear. Using a Drosophila tissue culture system, we identified multiple phosphorylation sites on dCLK. Expression of a mutated version of dCLK where all the mapped phospho-sites were switched to alanine (dCLK-15A) rescues the arrythmicity of Clk(out) flies, yet with an approximately 1.5 hr shorter period. The dCLK-15A protein attains substantially higher levels in flies compared to the control situation, and also appears to have enhanced transcriptional activity, consistent with the observed higher peak values and amplitudes in the mRNA rhythms of several core clock genes. Surprisingly, the clock-controlled daily activity rhythm in dCLK-15A expressing flies does not synchronize properly to daily temperature cycles, although there is no defect in aligning to light/dark cycles. Our findings suggest a novel role for clock protein phosphorylation in governing the relative strengths of entraining modalities by adjusting the dynamics of circadian gene expression. | 25,121,504 | [
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Changes in corneal deformation parameters after lenticule creation and extraction during small incision lenticule extraction (SMILE) procedure. | To investigate the effects of lenticule creation and subsequent corneal lenticule extraction on corneal deformation parameters during small incision lenticule extraction (SMILE) procedure. In this prospective study, 18 eyes of 10 patients (27.90 ± 7.11 years, -5.64 ± 2.45 diopters) scheduled for SMILE procedure were enrolled. Changes in the corneal deformation parameters, including deformation amplitude (DA), applanation time(AT1 and AT2), applanation length(AL1 and AL2), corneal velocity(CV1 and CV2), peak distance(P.Dist.), radius and intraocular pressure values were measured preoperatively, immediately after lenticule creation and subsequent to corneal lenticule extraction in all eyes with the Corvis Scheimpflug Technology (Corvis ST, OCULUS, Wetzlar, Germany). Repeated measures analysis of variance (ANOVA) with bonferroni-adjusted post hoc comparisons was performed to investigate changes following each step of the procedure. All surgical procedures were uneventful. A significant difference was detected among the three time points (pre-operation, post-lenticule creation and post lenticule extraction) for AT1 (P<0.001), AT2 (P = 0.001), DA(P<0.001), and IOP(P = 0.002). Bonferroni-adjusted post hoc comparisons indicated that there was no significant change in AT1, AT2, DA, or IOP after lenticule creation (post hoc P>0.05), but there was a significant change in these parameters following subsequent corneal lenticule extraction (post hoc P<0.01), when compared to values obtained pre-operatively. The scheimpflug camera of the Corvis ST demonstrated the intralamellar small gas bubbles formed from the vaporisation of tissue after lenticule creation and a gray zone was observed between the cap and the residual stromal bed after lenticule extraction. There is a significant change in corneal deformation parameters following SMILE procedure. The changes may be caused predominantly by stromal lenticule extraction, while lenticule creation with femtosecond laser may not have an obvious effect on corneal deformation properties. | 25,121,508 | [
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Comparing interferon-gamma release assays to tuberculin skin test in Thai children with tuberculosis exposure. | Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB. Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings. | 25,121,513 | [
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Optical phase under deep turbulence conditions. | The Markov approximation for waves in random media specifies that, under strong scintillation conditions, the optical field of unbounded waves has a normal probability distribution with zero mean. Using the coherence function provided by the Markov approximation, we calculate statistics of the phase of the optical field that accounts for the presence of multiple phase dislocations. We also develop and test a Monte Carlo model that generates the phase samples obeying these statistics. In contrast to numerous phase models described in the literature, this model generates discontinuous phase samples that contain optical vortices. | 25,121,533 | [
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Plasmonic corrugated cylinder-cone terahertz probe. | The spoof surface plasmon polariton (SPP) effect on the electromagnetic field distribution near the tip of a periodically corrugated metal cylinder-cone probe working at the terahertz regime was studied. We found that radially polarized terahertz radiation could be coupled effectively through a spoof SPP into a surface wave and propagated along the corrugated surface, resulting in more than 20× electric field enhancement near the tip of probe. Multiple resonances caused by the antenna effect were discussed in detail by finite element computation and theoretical analysis of dispersion relation for spoof SPP modes. Moreover, the key figures of merit such as the resonance frequency of the SPP can be flexibly tuned by modifying the geometry of the probe structure, making it attractive for application in an apertureless background-free terahertz near-field microscope. | 25,121,543 | [
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Introducing the concept of anisotropy at different scales for modeling optical turbulence. | In this paper, the concept of anisotropy at different atmospheric turbulence scales is introduced. A power spectrum and its associated structure function with inner and outer scale effects and anisotropy are also shown. The power spectrum includes an effective anisotropic parameter ζ(eff) to describe anisotropy, which is useful for modeling optical turbulence when a non-Kolmogorov power law and anisotropy along the direction of propagation are present. | 25,121,545 | [
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Photochemical tyrosine oxidation in the structurally well-defined α3Y protein: proton-coupled electron transfer and a long-lived tyrosine radical. | Tyrosine oxidation-reduction involves proton-coupled electron transfer (PCET) and a reactive radical state. These properties are effectively controlled in enzymes that use tyrosine as a high-potential, one-electron redox cofactor. The α3Y model protein contains Y32, which can be reversibly oxidized and reduced in voltammetry measurements. Structural and kinetic properties of α3Y are presented. A solution NMR structural analysis reveals that Y32 is the most deeply buried residue in α3Y. Time-resolved spectroscopy using a soluble flash-quench generated [Ru(2,2'-bipyridine)3](3+) oxidant provides high-quality Y32-O• absorption spectra. The rate constant of Y32 oxidation (kPCET) is pH dependent: 1.4 × 10(4) M(-1) s(-1) (pH 5.5), 1.8 × 10(5) M(-1) s(-1) (pH 8.5), 5.4 × 10(3) M(-1) s(-1) (pD 5.5), and 4.0 × 10(4) M(-1) s(-1) (pD 8.5). k(H)/k(D) of Y32 oxidation is 2.5 ± 0.5 and 4.5 ± 0.9 at pH(D) 5.5 and 8.5, respectively. These pH and isotope characteristics suggest a concerted or stepwise, proton-first Y32 oxidation mechanism. The photochemical yield of Y32-O• is 28-58% versus the concentration of [Ru(2,2'-bipyridine)3](3+). Y32-O• decays slowly, t1/2 in the range of 2-10 s, at both pH 5.5 and 8.5, via radical-radical dimerization as shown by second-order kinetics and fluorescence data. The high stability of Y32-O• is discussed relative to the structural properties of the Y32 site. Finally, the static α3Y NMR structure cannot explain (i) how the phenolic proton released upon oxidation is removed or (ii) how two Y32-O• come together to form dityrosine. These observations suggest that the dynamic properties of the protein ensemble may play an essential role in controlling the PCET and radical decay characteristics of α3Y. | 25,121,576 | [
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Reduction-sensitive dual functional nanomicelles for improved delivery of paclitaxel. | We have developed a dual-functional nanocarrier composed of a hydrophilic polyethylene glycol (PEG) and a hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist), which is effective in delivery of hydrophobic anticancer drug, paclitaxel (PTX). To facilitate the retention of the therapeutic activity of the carrier, FTS was coupled to PEG via a reduction-sensitive disulfide linkage (PEG5k-S-S-FTS2). PEG5k-S-S-FTS2 conjugate formed uniform micelles with very small size (∼30 nm) and the hydrophobic drug PTX could be readily incorporated into the micelles. Interestingly, inclusion of a disulfide linkage into the PEG5k-FTS2 micellar system resulted in a 4-fold decrease in the critical micelle concentration (CMC). In addition, the PTX loading capacity and colloidal stability of PTX-loaded micelles were improved. HPLC-MS showed that parent FTS could be more effectively released from PEG5k-S-S-FTS2 conjugate in tumor cells/tissues compared to PEG5k-FTS2 conjugate in vitro and in vivo. PEG5k-S-S-FTS2 exhibited a higher level of cytotoxicity toward tumor cells than PEG5k-FTS2 without a disulfide linkage. Furthermore, PTX-loaded PEG5k-S-S-FTS2 micelles were more effective in inhibiting the proliferation of cultured tumor cells compared to Taxol and PTX loaded in PEG5k-FTS2 micelles. More importantly, PTX-loaded PEG5k-S-S-FTS2 micelles demonstrated superior antitumor activity compared to Taxol and PTX formulated in PEG5k-FTS2 micelles in an aggressive murine breast cancer model (4T1.2). | 25,121,577 | [
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Loop-Closure and Gaussian Models of Collective Structural Characteristics of Capped PEO Oligomers in Water. | Parallel-tempering MD results for a CH3(CH2-O-CH2)mCH3 chain in water are exploited as a database for analysis of collective structural characteristics of the PEO globule with a goal of defining models permitting statistical thermodynamic analysis of dispersants of Corexit type. The chain structure factor, relevant to neutron scattering from a deuterated chain in null water, is considered specifically. The traditional continuum-Gaussian structure factor is inconsistent with the simple k → ∞ behavior, but we consider a discrete-Gaussian model that does achieve that consistency. Shifting and scaling the discrete-Gaussian model helps to identify the low-k to high-k transition near k ≈ 2π/0.6 nm when an empirically matched number of Gaussian links is about one-third of the total number of effective atom sites. This short distance-scale boundary of 0.6 nm is directly verified with the r space distributions, and this distance is thus identified with a natural size for coarsened monomers. The probability distribution of Rg(2) is compared with the classic predictions for both the Gaussian model and freely jointed chains. ⟨Rg(2)(j)⟩, the contribution of the jth chain segment to ⟨Rg(2)⟩, depends on the contour index about as expected for Gaussian chains despite significant quantitative discrepancies that express the swelling of these chains in water. Monomers central to the chain contour occupy the center of the chain globule. The density profiles of chain segments relative to their center of mass can show distinctive density structuring for smaller chains due to the close proximity of central elements to the globule center. However, that density structuring washes out for longer chains where many chain elements additively contribute to the density profiles. Gaussian chain models thus become more satisfactory for the density profiles for longer chains. | 25,121,580 | [
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Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data. | Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart-enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes), as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS). Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin) was targeted by transcriptional activators CLOCK and BMAL1 by showing 1) Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2) cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3) Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(Δ19/Δ19) hearts; 4) BMAL1 bound to the Tcap promoter by ChIP assay; 5) BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6) CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function. | 25,121,604 | [
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Temperature and food influence shell growth and mantle gene expression of shell matrix proteins in the pearl oyster Pinctada margaritifera. | In this study, we analyzed the combined effect of microalgal concentration and temperature on the shell growth of the bivalve Pinctada margaritifera and the molecular mechanisms underlying this biomineralization process. Shell growth was measured after two months of rearing in experimental conditions, using calcein staining of the calcified structures. Molecular mechanisms were studied though the expression of 11 genes encoding proteins implicated in the biomineralization process, which was assessed in the mantle. We showed that shell growth is influenced by both microalgal concentration and temperature, and that these environmental factors also regulate the expression of most of the genes studied. Gene expression measurement of shell matrix protein thereby appears to be an appropriate indicator for the evaluation of the biomineralization activity in the pearl oyster P. margaritifera under varying environmental conditions. This study provides valuable information on the molecular mechanisms of mollusk shell growth and its environmental control. | 25,121,605 | [
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Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study. | The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Blood samples were collected prospectively from healthy women (n = 21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk. | 25,121,606 | [
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Cadherin cytoplasmic domains inhibit the cell surface localization of endogenous E-cadherin, blocking desmosome and tight junction formation and inducing cell dissociation. | The downregulation of E-cadherin function has fundamental consequences with respect to cancer progression, and occurs as part of the epithelial-mesenchymal transition (EMT). In this study, we show that the expression of the Discosoma sp. red fluorescent protein (DsRed)-tagged cadherin cytoplasmic domain in cells inhibited the cell surface localization of endogenous E-cadherin, leading to morphological changes, the inhibition of junctional assembly and cell dissociation. These changes were associated with increased cell migration, but were not accompanied by the down-regulation of epithelial markers and up-regulation of mesenchymal markers. Thus, these changes cannot be classified as EMT. The cadherin cytoplasmic domain interacted with β-catenin or plakoglobin, reducing the levels of β-catenin or plakoglobin associated with E-cadherin, and raising the possibility that β-catenin and plakoglobin sequestration by these constructs induced E-cadherin intracellular localization. Accordingly, a cytoplasmic domain construct bearing mutations that weakened the interactions with β-catenin or plakoglobin did not impair junction formation and adhesion, indicating that the interaction with β-catenin or plakoglobin was essential to the potential of the constructs. E-cadherin-α-catenin chimeras that did not require β-catenin or plakoglobin for their cell surface transport restored cell-cell adhesion and junction formation. | 25,121,615 | [
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Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience. | Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer. | 25,121,637 | [
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Control of chromaticity by phosphor in glasses with low temperature sintered silicate glasses for LED applications. | Phosphor-in-glass (PiG) color converters for LED applications were fabricated with a mixture of phosphors, Y₃Al₅O₁₂:Ce³⁺ (yellow) and CaAlSiN₃:Eu²⁺ (red). The low sintering temperature (550°C) of SiO₂-Na₂O-RO (R=Ba, Zn) glass powder enabled the inclusion of CaAlSiN₃:Eu²⁺ (red) phosphor which cannot be embedded with conventional glass powders for PiGs. By simply varying the mixing ratio of glass to phosphors as well as the ratio of yellow to red phosphors, the facile control of the CIE chromaticity coordinates and correlated color temperature of the LED following the Planckian locus has been achieved. Phosphors were well distributed within the glass matrix without noticeable reactions, preserving the enhanced thermal quenching property of the PiG compared to those with silicone resins, for LEDs. | 25,121,657 | [
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Flexible operability and amplification of gray pulses. | We have investigated experimentally the flexible production and amplification of gray pulses for the first time to our knowledge. Switchable wavelengths, tunable pulse-widths, and adjustable contrasts have all been obtained in a fiber laser. Amplification of gray pulses was also experimentally investigated in detail. The contrast of the pulses could also be increased in an amplifier. The robust stability that results from the interactions between adjacent harmonic mode locking counterparts of gray pulses was found to last for up to ten hours. To the best of our knowledge, the gray pulses trains we have generated are the most stable achieved to date in an all-fiber laser system. This finding can be used as a guide for the establishment of robust gray pulses as laser sources. | 25,121,665 | [
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Surface and thickness profile measurement of a transparent film by three-wavelength vertical scanning interferometry. | We have developed a novel areal film thickness and topography measurement method using three-wavelength interferometry. The method simultaneously estimates the profiles of the front and back surfaces and the thickness distribution of a transparent film by model-based separation of two overlapped signals in an interferogram. The validity of the proposed method is demonstrated using computer simulations and actual experiments. | 25,121,679 | [
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Incoherent-light temporal stretching of high-speed intensity waveforms. | We propose and demonstrate experimentally the first incoherent-light scheme for temporal imaging (magnification) of intensity waveforms. The scheme is based on a time-domain equivalent of a pinhole camera under incoherent illumination, involving two dispersive lines and temporal intensity modulation with a short gate. We report incoherent-light temporal stretching of radiofrequency waveforms by a magnification factor of 2.86, with a time-bandwidth product exceeding 160, i.e., a resolution of ~50 ps over a temporal aperture of ~8 ns, totally avoiding the use of chirp-controlled pulsed lasers. This work opens up new perspectives for realization of many critical high-speed signal-processing modules using practical incoherent light-wave schemes. | 25,121,697 | [
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Heterodyne-detected and ultrafast time-resolved second-harmonic generation for sensitive measurements of charge transfer. | In organic photovoltaics many key ultrafast processes occur at the interface between electron donor and acceptor molecules. Traditional ultrafast spectroscopies, such as pump-probe or time-resolved fluorescence, are not ideal for studying the interface because most of their signal is from the bulk material. Time-resolved second-harmonic generation (TRSHG) spectroscopy solves this problem by only generating signal from the interface. We demonstrate an optically heterodyned TRSHG to reduce the impact of stray light, enhance sensitivity, and detect the full complex signal field. | 25,121,705 | [
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Experimental study on the dynamics of polarized strong optical injection in 1550 nm VCSELs. | We have experimentally analyzed the dynamics of polarized strong optical injection in 1550 nm vertical-cavity surface-emitting lasers (VCSELs). The locking ranges of optical injection-locked (OIL) VCSELs are experimentally measured in different states of polarized strong optical injection. Based on our novel ellipse model, the influence of the polarization state of strong injection light is quantitatively studied for the first time. | 25,121,707 | [
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On resilience and acceptance in the transition to palliative care at the end of life. | Specialist palliative care is a prominent and expanding site of health service delivery, providing highly specialised care to people at the end of life. Its focus on the delivery of specialised life-enhancing care stands in contrast to biomedicine's general tendency towards life-prolonging intervention. This philosophical departure from curative or life-prolonging care means that transitioning patients can be problematic, with recent work suggesting a wide range of potential emotional, communication and relational difficulties for patients, families and health professionals. Yet, we know little about terminally ill patients' lived experiences of this complex transition. Here, through interviews with 40 inpatients in the last few weeks of life, we explore their embodied and relational experiences of the transition to inpatient care, including their accounts of an ethic of resilience in pre-palliative care and an ethic of acceptance as they move towards specialist palliative care. Exploring the relationship between resilience and acceptance reveals the opportunities, as well as the limitations, embedded in the normative constructs that inflect individual experience of this transition. This highlights a contradictory dynamic whereby participants' experiences were characterised by talk of initiating change, while also acquiescing to the terminal progression of their illness. | 25,121,725 | [
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Hematology as a diagnostic tool in bovine medicine. | The objective of the current review is to provide the reader with an overview of the bovine hematological profile. Sample collection, bovine reference ranges, and cattle-specific characteristics of erythrocyte, leukocyte, and platelet parameters are reviewed. Furthermore, diseases associated with abnormalities in the complete blood cell count of cattle are discussed. | 25,121,728 | [
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Systematic comparison of non-invasive measures for the assessment of atrial fibrillation complexity: a step forward towards standardization of atrial fibrillation electrogram analysis. | To present a comparison of electrocardiogram-based non-invasive measures of atrial fibrillation (AF) substrate complexity computed on invasive animal recordings to discriminate between short-term and long-term AF. The final objective is the selection of an optimal sub-set of measures for AF complexity assessment. High-density epicardial direct contact mapping recordings (234 leads) were acquired from the right and the left atria of 17 goats in which AF was induced for 3 weeks (short-term AF group, N = 10) and 6 months (long-term AF group, N = 7). Several non-invasive measures of AF organization proposed in the literature in the last decade were investigated to assess their power in discriminating between the short-term and long-term group. The best performing measures were identified, which when combined attained a correct classification rate of 100%. Their ability to predict standard invasive AF complexity measures was also tested, showing an average R(2) of 0.73 ± 0.04. An optimal set of measures of the AF substrate complexity was identified out of the set of non-invasive measures analysed in this study. These measures may contribute to improve patient-tailored diagnosis and therapy of sustained AF. | 25,121,730 | [
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A role for H2S in the microcirculation of newborns: the major metabolite of H2S (thiosulphate) is increased in preterm infants. | Excessive vasodilatation during the perinatal period is associated with cardiorespiratory instability in preterm neonates. Little evidence of the mechanisms controlling microvascular tone during circulatory transition exists. We hypothesised that hydrogen sulphide (H2S), an important regulator of microvascular reactivity and central cardiac function in adults and animal models, may contribute to the vasodilatation observed in preterm newborns. Term and preterm neonates (24-43 weeks gestational age) were studied. Peripheral microvascular blood flow was assessed by laser Doppler. Thiosulphate, a urinary metabolite of H2S, was determined by high performance liquid chromatography as a measure of 24 hr total body H2S turnover for the first 3 days of postnatal life. H2S turnover was greatest in very preterm infants and decreased with increasing gestational age (p = 0.0001). H2S turnover was stable across the first 72 hrs of life in older neonates. In very preterm neonates, H2S turnover increased significantly from day 1 to 3 (p =0.0001); and males had higher H2S turnover than females (p = 0.04). A significant relationship between microvascular blood flow and H2S turnover was observed on day 2 of postnatal life (p = 0.0004). H2S may play a role in maintaining microvascular tone in the perinatal period. Neonates at the greatest risk of microvascular dysfunction characterised by inappropriate peripheral vasodilatation--very preterm male neonates--are also the neonates with highest levels of total body H2S turnover suggesting that overproduction of this gasotransmitter may contribute to microvascular dysfunction in preterms. Potentially, H2S is a target to selectively control microvascular tone in the circulation of newborns. | 25,121,737 | [
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Neck circumference and body mass index as independent predictors of hypertension misclassification in patients suspected of having obstructive sleep apnea. | Twenty-four-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate way of diagnosing hypertension in patients with obstructive sleep apnea (OSA). However, this diagnostic tool is expensive and time-consuming and is therefore not used routinely. We aimed to find baseline predictors that enable the identification of patients who misclassify themselves as nonhypertensive to optimize the use of ABPM. Clinically suspected OSA patients (n=369) were enrolled and underwent overnight polysomnography and 24-h ABPM, and completed a data collection form. Anthropometric measurements were assessed. Generalized additive models, the minimum P-value approach, and logistic regression models were used for data analysis. Results were considered significant when α is equal to 0.05. One hundred and twenty-two patients who were not on antihypertensive medication did not report hypertension, but according to ABPM data, 43.4% (n=53) of them had misclassified themselves as nonhypertensive. These patients had a significantly higher apnea-hypopnea index (P<0.001), ABPM variables (P<0.001), BMI (P=0.002), and neck circumference (NC) (P=0.002) than nonhypertensive patients (n=69). BMI and NC emerged as independent predictors of hypertension misclassification. The cut-off points that best discriminated the two groups of patients were 27 kg/m and 39 cm for BMI and NC, respectively. The resulting binary BMI and NC remained independent predictors of hypertension misclassification in the final model (odds ratio: 3.2, P=0.010; odds ratio: 2.4, P=0.038). Our findings emphasize the importance of ABPM for the diagnosis of hypertension in patients suspected of having OSA with a BMI and NC above 27 kg/m and 39 cm, respectively. | 25,121,756 | [
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Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. | Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution. Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival. The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% (n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location (P < .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not by radiation (P < .01), as significantly increasing risk of early progression. We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies. | 25,121,770 | [
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The Staurotypus turtles and aves share the same origin of sex chromosomes but evolved different types of heterogametic sex determination. | Reptiles have a wide diversity of sex-determining mechanisms and types of sex chromosomes. Turtles exhibit temperature-dependent sex determination and genotypic sex determination, with male heterogametic (XX/XY) and female heterogametic (ZZ/ZW) sex chromosomes. Identification of sex chromosomes in many turtle species and their comparative genomic analysis are of great significance to understand the evolutionary processes of sex determination and sex chromosome differentiation in Testudines. The Mexican giant musk turtle (Staurotypus triporcatus, Kinosternidae, Testudines) and the giant musk turtle (Staurotypus salvinii) have heteromorphic XY sex chromosomes with a low degree of morphological differentiation; however, their origin and linkage group are still unknown. Cross-species chromosome painting with chromosome-specific DNA from Chinese soft-shelled turtle (Pelodiscus sinensis) revealed that the X and Y chromosomes of S. triporcatus have homology with P. sinensis chromosome 6, which corresponds to the chicken Z chromosome. We cloned cDNA fragments of S. triporcatus homologs of 16 chicken Z-linked genes and mapped them to S. triporcatus and S. salvinii chromosomes using fluorescence in situ hybridization. Sixteen genes were localized to the X and Y long arms in the same order in both species. The orders were also almost the same as those of the ostrich (Struthio camelus) Z chromosome, which retains the primitive state of the avian ancestral Z chromosome. These results strongly suggest that the X and Y chromosomes of Staurotypus turtles are at a very early stage of sex chromosome differentiation, and that these chromosomes and the avian ZW chromosomes share the same origin. Nonetheless, the turtles and birds acquired different systems of heterogametic sex determination during their evolution. | 25,121,779 | [
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Effectiveness of prophylactic antibiotics in outpatient plastic surgery. | The effectiveness of prophylactic antibiotics has not been established for patients who undergo plastic surgery as outpatients, and consensus guidelines for antibiotic administration in clean-contaminated plastic surgery are not available. In a retrospective study of outpatients, the authors examined preoperative timing of prophylactic antibiotics, whether postoperative antibiotics were administered, and whether any correlations existed between these practices and surgical complications. The medical records of 468 plastic surgery outpatients were reviewed. Collected data included preoperative antibiotic timing, postoperative antibiotic use, comorbidities, and complications. Rates of complications were calculated and compared with other data. All 468 patients received antibiotics preoperatively, but only 93 (19.9%) received them ≥1 hour before the initial incision. Antibiotics were administered 15 to 44 minutes before surgery in 217 patients (46.4%). There was no significant difference in complication rates between the 315 patients who received postoperative prophylactic antibiotics (16.2%) and the 153 who did not (20.9%). Comorbidities had no bearing on postoperative complications. Postoperative antibiotic prophylaxis may be unnecessary for outpatient plastic surgery patients. 3. | 25,121,784 | [
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An approach toward constructing the trioxadispiroketal core in the DEF-ring of (+)-spirastrellolide A. | A concise and stereoselective synthesis of the trioxadispiroketal motif that embodies the DEF-ring of the marine macrolide (+)-spirastrellolide A is described. The synthetic approach features a sequence of cyclic acetal tethered ring-closing metathesis and Suárez oxidative cyclization, thereby constituting a viable strategy for constructing the Northern Half. | 25,121,803 | [
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Role of desorption kinetics in the rhamnolipid-enhanced biodegradation of polycyclic aromatic hydrocarbons. | The main aim of this study was to investigate the effect of a rhamnolipid biosurfactant on biodegradation of (14)C-labeled phenanthrene and pyrene under desorption-limiting conditions. The rhamnolipid caused a significant solubilization and enhanced biodegradation of PAHs sorbed to soils. The enhancement was, however, negatively influenced by experimental conditions that caused an enrichment of slow desorption fractions. These conditions included aging, a higher organic matter content in soil, and previous extraction with Tenax to remove the labile-desorbing chemical. The decline in bioavailability caused by aging on sorbed (14)C-pyrene was partially reversed by rhamnolipids, which enhanced mineralization of the aged compound, although not so efficiently like with the unaged chemical. This loss in biosurfactant efficiency in promoting biodegradation can be explained by intra-aggregate diffusion of the pollutant during aging. We suggest that rhamnolipid can enhance biodegradation of soil-sorbed PAHs by micellar solubilization, which increase the cell exposure to the chemicals in the aqueous phase, and partitioning into soil organic matter, thus enhancing the kinetics of slow desorption. Our study show that rhamnolipid can constitute a valid alternative to chemical surfactants in promoting the biodegradation of slow desorption PAHs, which constitutes a major bottleneck in bioremediation. | 25,121,829 | [
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Designing metal hemispheres on silicon ultrathin film solar cells for plasmonic light trapping. | We systematically investigate the design of two-dimensional silver (Ag) hemisphere arrays on crystalline silicon (c-Si) ultrathin film solar cells for plasmonic light trapping. The absorption in ultrathin films is governed by the excitation of Fabry-Perot TEMm modes. We demonstrate that metal hemispheres can enhance absorption in the films by (1) coupling light to c-Si film waveguide modes and (2) exciting localized surface plasmon resonances (LSPRs). We show that hemisphere arrays allow light to couple to fundamental TEm and TMm waveguide modes in c-Si film as well as higher-order versions of these modes. The near-field light concentration of LSPRs also may increase absorption in the c-Si film, though these resonances are associated with significant parasitic absorption in the metal. We illustrate how Ag plasmonic hemispheres may be utilized for light trapping with 22% enhancement in short-circuit current density compared with that of a bare 100 nm thick c-Si ultrathin film solar cell. | 25,121,839 | [
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152 W average power Tm-doped fiber CPA system. | A high-power thulium (Tm)-doped fiber chirped-pulse amplification system emitting a record compressed average output power of 152 W and 4 MW peak power is demonstrated. This result is enabled by utilizing Tm-doped photonic crystal fibers with mode-field diameters of 35 μm, which mitigate detrimental nonlinearities, exhibit slope efficiencies of more than 50%, and allow for reaching a pump-power-limited average output power of 241 W. The high-compression efficiency has been achieved by using multilayer dielectric gratings with diffraction efficiencies higher than 98%. | 25,121,845 | [
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Nonlinear switching in a two-concentric-core chalcogenide glass optical fiber for passively mode-locking a fiber laser. | We propose an all-fiber mode-locking device, which operates based on nonlinear switching in a novel two-concentric-core fiber structure. The design is particularly attractive given the ease of fabrication and coupling to other components in a mode-locked fiber laser cavity. The nonlinear switching in this coupler is studied, and the relative power transmission is obtained. The analysis shows that this nonlinear switch is practical for mode-locking fiber lasers and is forgiving to fabrication errors. | 25,121,846 | [
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Photo-aligned ferroelectric liquid crystals in microchannels. | In this Letter we disclose a method to realize a good alignment of ferroelectric liquid crystals (FLCs) in microchannels, based on photo-alignment. The sulfonic azo dye used in our research offers variable anchoring energy depending on the irradiation energy and thus provides good control on the FLC alignment in microchannels. The good FLC alignment has been observed only when anchoring energy normalized to the capillary diameter is less than the elastic energy of the FLC helix. The same approach can also be used for the different microstructures viz. photonic crystal fibers, microwaveguides, etc. which gives an opportunity for designing a photonic devices based on FLC. | 25,121,847 | [
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Controllable continuous-wave Nd:YVO₄ self-Raman lasers using intracavity adaptive optics. | A controllable self-Raman laser using an adaptive optics (AO)-based control loop featuring an intracavity deformable mirror is reported. This method has the potential to alleviate thermal lensing within the Raman and laser gain media, and enable solid-state Raman lasers to reach new power levels. A proof-of-concept experiment using a Nd:YVO4 self-Raman laser and resulting in 18% enhancement of the first Stokes output power is reported. Moreover, wavelength selection between two Raman laser outputs (λ=1109 and 1176 nm) emanating from the 379 and 893 cm(-1) Raman shifts of YVO4, respectively, was achieved using this AO technique. | 25,121,868 | [
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3D-printed miniature gas cell for photoacoustic spectroscopy of trace gases. | A new methodology for the development of miniature photoacoustic trace gas sensors using 3D printing is presented. A near-infrared distributed feedback (DFB) laser is used together with a polymer-based gas cell, off-the-shelf fiber optic collimators, and a microelectromechanical system (MEMS) microphone to measure acetylene at 1532.83 nm. The resonance behavior of the miniature gas cell is analyzed using a theoretical and experimental approach, with a measured resonance frequency of 15.25 kHz and a Q-factor of 15. A minimum normalized noise equivalent absorption of 4.5×10(-9) W cm(-1) Hz(-1/2) is shown together with a 3σ detection limit of 750 parts per billion (ppb) for signal averaging times of 35 s. The fiber-coupled delivery and miniature cost-effective cell design allows for use in multipoint and remote detection applications. | 25,121,877 | [
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Interferometric fiber-optic bending/nano-displacement sensor using plastic dual-core fiber. | We demonstrate an interferometric fiber-optic bending/nano-displacement sensor based on a plastic dual-core fiber. The light coupled into the two fiber cores is first guided along the fiber, and then reflected by the mirror coated at the fiber end. Reflected light coming out of the fiber produces interference that shifts as the fiber bends. The interference shift is interrogated using a slit and a photodetector. The resolution of our sensor is ∼3×10(-4) m(-1) for sensing the bending curvature, and ∼70 nm for sensing the displacement. | 25,121,887 | [
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Narrow-linewidth quantum cascade laser at 8.6 μm. | We report on a narrow-linewidth distributed-feedback quantum cascade laser at 8.6 μm that is optical-feedback locked to a high-finesse V-shaped cavity. The spectral purity of the quantum cascade laser is fully characterized using a high-sensitivity optical frequency discriminator, leading to a 1 ms linewidth of less than 4 kHz and a minimum laser frequency noise spectral density as low as 0.01 Hz2/Hz for Fourier frequencies larger than 100 kHz. The cumulative standard deviation of the laser intensity is better than 0.1% over an integration bandwidth from 2 Hz to 100 MHz. | 25,121,915 | [
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Polarization-diversified photonic comb filter with independently tunable free spectrum range. | A polarization-diversified photonic comb filter with tunable free spectrum range (FSR) is proposed using two variable differential group delay (DGD) elements in a loop configuration. Two different cosine transfer functions could be simultaneously realized on orthogonal polarization states. Experimental demonstrations also verify feasibilities in various reconfigurable transfer functions. | 25,121,921 | [
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Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase signaling in human eosinophils. | Eosinophils function contributes to human allergic and autoimmune diseases, many of which currently lack curative treatment. Development of more effective treatments for eosinophil-related diseases requires expanded understanding of eosinophil signaling and biology. Cell signaling requires integration of extracellular signals with intracellular responses, and is organized in part by cholesterol rich membrane microdomains (CRMMs), commonly referred to as lipid rafts. Formation of these organizational membrane domains is in turn dependent upon the amount of available cholesterol, which can fluctuate widely with a variety of disease states. We tested the hypothesis that manipulating membrane cholesterol content in primary human peripheral blood eosinophils (PBEos) would selectively alter signaling pathways that depend upon membrane-anchored signaling proteins localized within CRMMs (e.g., mitogen activated protein kinase [MAPK] pathway), while not affecting pathways that signal through soluble proteins, like the Janus Kinase/Signal Transducer and Activator of Transcription [JAK/STAT] pathway. Cholesterol levels were increased or decreased utilizing cholesterol-chelating methyl-β-cyclodextrin (MβCD), which can either extract membrane cholesterol or add exogenous membrane cholesterol depending on whether MβCD is preloaded with cholesterol. Human PBEos were pretreated with MβCD (cholesterol removal) or MβCD+Cholesterol (MβCD+Chol; cholesterol delivery); subsequent IL-5-stimulated signaling and physiological endpoints were assessed. MβCD reduced membrane cholesterol in PBEos, and attenuated an IL-5-stimulated p38 and extracellular-regulated kinase 1/2 phosphorylation (p-p38, p-ERK1/2), and an IL-5-dependent increase in interleukin-1β (IL-1β) mRNA levels. In contrast, MβCD+Chol treatment elevated PBEos membrane cholesterol levels and basal p-p38, but did not alter IL-5-stimulated phosphorylation of ERK1/2, STAT5, or STAT3. Furthermore, MβCD+Chol pretreatment attenuated an IL-5-induced increase in cell survival at 48 hours, measured as total cellular metabolism. The reduction in cell survival following cholesterol addition despite unaltered STAT phosphorylation contradicts the current dogma in which JAK/STAT activation is sufficient to promote eosinophil survival, and suggests an additional, unidentified mechanism critically regulates IL-5-mediated human PBEos survival. | 25,121,926 | [
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Registered nurses, nurse specialists and physicians have a neutral to moderately positive view on nurse prescribing, though physicians still have patient safety concerns. | Implications for practice and research: The process of assigning medical roles to nurses has to be gradual and stepwise. The influence of this process on the consequences for the nursing and medical professions, and for the quality of care, should be investigated further. | 25,121,933 | [
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Magnetic reflectometry of heterostructures. | Measuring the magnetic configuration at complex buried layers and interfaces is an important task, which requires especially a non-destructive probing technique. X-ray resonant magnetic reflectometry (XRMR) combines the non-destructive depth profiling potential of x-ray reflectometry with the excellent sensitivity for magnetic phenomena, utilizing the x-ray magnetic circular dichroism effect. It provides the magnetic spatial distribution with a precision down to the angstrom scale, combined with element and symmetry specificity, sub-monolayer sensitivity, and the possible separation of spin and orbital magnetic moments. This review provides an overview to the XRMR technique in a tutorial way. We focus on the introduction to the theory, measurement types, and data simulation. We provide related experimental examples and show selected applications. | 25,121,937 | [
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Coronal fracture of the scaphoid--a case report and literature review. | Coronal fracture of the scaphoid is a rare configuration of scaphoid fracture. Only three cases have been found to be reported in English literature. In our case, a 25-year-old man sustained right wrist injury after a fall with an outstretched hand, was suspected of suffering from a scaphoid fracture as shown on the pre-operative plain radiograph. Coronal fracture of the patient's scaphoid was found intra-operatively and was fixed with two headless compression screws in dorsal-to-volar direction. Post-operative outcome was clinically good as patient was symptom-free, and a computed tomography and radiograph showed complete healing of the fracture with no sign of avascular necrosis. | 25,121,939 | [
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Bilateral bipartite carpal scaphoid: a case report and literature review. | Congenital bipartite carpal scaphoid has been reported as an extremely rare congenital anomaly. We report a case of a 47-year-old man who was found with bilateral bipartite carpal scaphoids with no history of injury. Radiographs demonstrated symmetric findings of the distinct bipartition of the scaphoid without obvious degenerative change in both wrists. The patient complained of no other symptoms. The diagnostic differentiation of scaphoid bipartition from the pseudarthrosis of the scaphoid could be important in avoiding unnecessary surgery and inappropriate assessment in compensation cases. | 25,121,941 | [
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Associations between ulnar nerve strain and accompanying conditions in patients with cubital tunnel syndrome. | Pathophysiology of cubital tunnel syndrome (CubTS) is still controversial. Ulnar nerve strain at the elbow was measured intraoperatively in 13 patients with CubTS before simple decompression. The patients were divided into three groups according to their accompanying conditions: compression/adhesion, idiopathic, and relaxation groups. The mean ulnar nerve strain was 43.5 ± 30.0%, 25.5 ± 14.8%, and 9.0 ± 5.0% in the compression/adhesion, idiopathic, and relaxation groups respectively. The mean ulnar nerve strains in patients with McGowan's classification grades I, II, and III were 18.0 ± 4.2%, 27.1 ± 22.7%, and 33.7 ± 24.7%, respectively. The Jonckheere-Terpstra test showed that there were significant reductions in the ulnar nerve strain among the first three groups, but not in the three groups according to McGowan's classification. Our results suggest that the pathophysiology, not disease severity, of CubTS may be explained at least in part by the presence of ulnar nerve strain. | 25,121,945 | [
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Treatment of hook of the hamate fractures in adults using low-intensity pulsed ultrasound. | Two delayed unions and one nonunion of hook of the hamate fractures in adults aged 31-, 40-, and 41-years-old were treated with low-intensity pulsed ultrasound (LIPUS). Ultrasound treatment was started at three, four, and six months after injury and ultrasound exposure at the hook of the hamate in the hypothenar eminence was carried out for four to five months. During the management period, there was no immobilisation with a cast or brace and limited strain with only routine daily activities allowed. In all cases, bony union was confirmed on carpal tunnel radiographs or computed tomography at the final follow-up time of eight and 36 months after injuries. | 25,121,946 | [
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WW domain folding complexity revealed by infrared spectroscopy. | Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescence spectroscopy, to study the folding of the FBP28 WW domain. Laser-induced temperature jumps coupled with fluorescence or infrared spectroscopy have been used to probe changes in the peptide backbone on the submillisecond time scale. The relaxation dynamics of the β-sheets and β-turn were measured independently by probing the corresponding IR bands assigned in the amide I region. Using these wavelength-dependent measurements, we observe three kinetics phases, with the fastest process corresponding to the relaxation kinetics of the turns. In contrast, fluorescence measurements of the wild-type WW domain and tryptophan mutants exhibit single-exponential kinetics with a lifetime that corresponds to the slowest phase observed by infrared spectroscopy. Mutant sequences provide evidence of an intermediate dry molten globule state. The slowest step in the folding of this WW domain is the tight packing of the side chains in the transition from the dry molten globule intermediate to the native structure. This study demonstrates that using multiple complementary probes enhances the interpretation of protein folding dynamics. | 25,121,968 | [
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iNitro-Tyr: prediction of nitrotyrosine sites in proteins with general pseudo amino acid composition. | Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM's mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called "iNitro-Tyr" was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro-Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins. | 25,121,969 | [
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Who Seeks Cita Con El Doctor? Twelve Years of Spanish-Language Radio Program Targeting U.S. Latinos. | Spanish-dominant Latinos make up 13% of the U.S. population, and this group is poorer and faces multiple threats to health compared with the general population. Additionally, Spanish speakers face challenges accessing health information that is often not available in Spanish. This study provides a descriptive epidemiology of a unique, low-cost health information source: the longest-running U.S.-based Spanish-language call-in radio health education program. From the universe of all calls 1999 to 2011, stratified random sampling yielded 1,237 analyzed calls, which were manually coded for caller sex, age, proxy status, and health concern. Descriptive statistics were used to examine basic demographics of callers and call topics overall and by sex and proxy caller status. Among all calls, the top three call-generating health topics were specific symptoms/conditions, sexual/reproductive health, and gastrointestinal concerns. The top nine topics were consistent among women, men, and proxy callers; however, relative frequency of topics varied across groups. Nearly one quarter of calls were initiated on behalf of someone, generally a child, spouse or sibling, or parent. Sixty percent of callers were women; women made 70% of proxy calls. Understanding the differences in information seeking behaviors, information needs, and source preferences is important for determining where and how to disseminate health information and may help explain disparities in knowledge and health outcomes. The radio talk show format provides a uniquely personal, culturally sensitive channel for meeting health information needs of a vulnerable population while leveraging the cost-effectiveness and wide reach of a mass medium. | 25,121,981 | [
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Epoxy alcohol synthase of the rice blast fungus represents a novel subfamily of dioxygenase-cytochrome P450 fusion enzymes. | The genome of the rice blast fungus Magnaporthe oryzae codes for two proteins with N-terminal dioxygenase (DOX) and C-terminal cytochrome P450 (CYP) domains, respectively. One of them, MGG_13239, was confirmed as 7,8-linoleate diol synthase by prokaryotic expression. The other recombinant protein (MGG_10859) possessed prominent 10R-DOX and epoxy alcohol synthase (EAS) activities. This enzyme, 10R-DOX-EAS, transformed 18:2n-6 sequentially to 10(R)-hydroperoxy-8(E),12(Z)-octadecadienoic acid (10R-HPODE) and to 12S(13R)-epoxy-10(R)-hydroxy-8(E)-octadecenoic acid as the end product. Oxygenation at C-10 occurred by retention of the pro-R hydrogen of C-8 of 18:2n-6, suggesting antarafacial hydrogen abstraction and oxygenation. Experiments with (18)O2 and (16)O2 gas confirmed that the epoxy alcohol was formed from 10R-HPODE, likely by heterolytic cleavage of the dioxygen bond with formation of P450 compound I, and subsequent intramolecular epoxidation of the 12(Z) double bond. Site-directed mutagenesis demonstrated that the cysteinyl heme ligand of the P450 domain was required for the EAS activity. Replacement of Asn(965) with Val in the conserved AsnGlnXaaGln sequence revealed that Asn(965) supported formation of the epoxy alcohol. 10R-DOX-EAS is the first member of a novel subfamily of DOX-CYP fusion proteins of devastating plant pathogens. | 25,121,983 | [
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Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism. | Thyroid hormone (TH) is important for tissue repair because it regulates cellular differentiation. Intrahepatic TH activity is controlled by both serum TH levels and hepatic deiodinases. TH substrate (T4) is converted into active hormone (T3) by deiodinase 1 (D1) but into inactive hormone (rT3) by deiodinase 3 (D3). Although the relative expressions of D1 and D3 are known to change during liver injury, the cell types and signaling mechanisms involved are unclear. We evaluated the hypothesis that changes in hepatic deiodinases result from repair-related activation of the Hedgehog pathway in stromal cells. We localized deiodinase expression, assessed changes during injury, and determined how targeted manipulation of Hedgehog signaling in stromal cells impacted hepatic deiodinase expression, TH content, and TH action in rodents. Humans with chronic liver disease were also studied. In healthy liver, hepatocytes strongly expressed D1 and stromal cells weakly expressed D3. During injury, hepatocyte expression of D1 decreased, whereas stromal expression of D3 increased, particularly in myofibroblasts. Conditionally disrupting Hedgehog signaling in myofibroblasts normalized deiodinase expression. Repair-related changes in deiodinases were accompanied by reduced hepatic TH content and TH-regulated gene expression. In patients, this was reflected by increased serum rT3. Moreover, the decreases in the free T3 to rT3 and free T4 to rT3 ratios distinguished advanced from mild fibrosis, even in individuals with similar serum levels of TSH and free T4. In conclusion, the Hedgehog-dependent changes in liver stromal cells drive repair-related changes in hepatic deiodinase expression that promote intrahepatic hypothyroidism, thereby limiting exposure to T3, an important factor for cellular differentiation. | 25,121,996 | [
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A supersandwich electrochemiluminescence immunosensor based on mimic-intramolecular interaction for sensitive detection of proteins. | An electrochemiluminescence (ECL) immunoassay protocol was developed based on mimic-intramolecular interaction for sensitive detection of prostate specific antigen (PSA). It was constructed by integrating the ECL luminophore (tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)-ruthenium(ii)dichloride (Ru(dcbpy)3(2+))) and coreactant (histidine) into the supersandwich DNA structure. This strategy was more effective in amplifying the ECL signal by shortening the electronic transmission distance, improving the ECL luminous stability and enhancing the ECL luminous efficiency. The ECL matrices denoted as MWCNTs@PDA-AuNPs were fabricated through spontaneous oxidative polymerization of dopamine (DA) on multiwalled carbon nanotubes (MWCNTs) and reducing HAuCl4 to produce gold nanoparticles (AuNPs) by DA simultaneously. Then, the prepared matrices were applied to bind capture antibodies. Moreover, supersandwich Ab2 bioconjugate was designed using a PAMAM dendrimer to immobilize the detection antibody and supersandwich DNA structure. The PAMAM dendrimer, with a plurality of secondary and tertiary amine groups, not only facilitated high-density immobilization of the detection antibody and supersandwich DNA structure, but also greatly amplified the ECL signal of Ru(dcbpy)3(2+). The supersandwich DNA structure contained multiple Ru(dcbpy)3(2+) and histidine, further amplifying the ECL signal. The proposed supersandwich immunosensor showed high sensitivity with a detection limit of 4.2 fg mL(-1) and a wide linear range of 0.01 pg mL(-1)-40.00 ng mL(-1). With the excellent stability, satisfying precision and reproducibility, the proposed immunosensor indicates promising practicability for clinical diagnosis. | 25,122,008 | [
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Use of research evidence in state policymaking for childhood obesity prevention in Minnesota. | We describe how scientific evidence about obesity has been used in Minnesota legislative materials to understand how research evidence might more effectively be translated into policymaking. We selected 13 obesity-related bills introduced from 2007 to 2011 in Minnesota. Using state archives, we collected all legislative committee meeting materials and floor testimony related to each bill. We used a coding instrument to systematically analyze the content of a sample of 109 materials for their use of research evidence and non-research-based information. Research evidence was mentioned in 41% of all legislative materials. Evidence was often used to describe the prevalence or consequences of obesity or policy impacts but not to describe health disparities. In 45% of materials that cited evidence, no source of evidence was indicated. By contrast, 92% of materials presented non-research-based information, such as expert beliefs, constituent opinion, political principles, and anecdotes. Despite an abundance of available research evidence on obesity, less than half of legislative materials cited any such evidence in discussions around obesity-related bills under consideration in Minnesota. | 25,122,015 | [
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CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc prolongation. | Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome P450 system. We investigate associations between citalopram and escitalopram dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a retrospective chart review of citalopram or escitalopram patients with the inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and QTc interval on ECG. We further identified 42 citalopram users with citalopram serum concentration measurements and ECG. Regression and one-way ANOVA were used to examine the relationship between citalopram dose, citalopram serum concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients, the EM group had significantly shorter QTc intervals than a combined IM+PM group (427.1±23.6 ms vs. 440.1±26.6 ms, one-tailed t-test, p=0.029). In the 80 escitalopram cohort, there was no significant difference in QTc between phenotype groups. There was no statistical correlation between citalopram (p=0.62) or escitalopram (p=0.30) dose and QTc. QTc was not associated with citalopram serum level (p=0.45). In contrast to the FDA warning, this study found no association between citalopram/escitalopram dose and QTc. However, PM of the drug tended to have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in select patients may be helpful to guide medication optimization while limiting harmful effects. | 25,122,046 | [
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In vitro selection, characterization, and biosensing application of high-affinity cylindrospermopsin-targeting aptamers. | Contamination of freshwater with cyanotoxin cylindrospermopsin (CYN) represents a significant global concern for public health. The sensitive detection of CYN is necessary to effectively manage and control the treatment of water resources. Here we report a novel, highly sensitive label-free aptasensor for CYN analysis, using aptamers as specific receptors. We have selected the DNA aptamers from a diverse random library using the in vitro screening SELEX approach. The aptamers exhibited high affinity for CYN with Kd of nanomolar range. One aptamer exhibited conformational change upon CYN recognition (CD analysis) and was used to fabricate the label-free impedimetric aptasensor for CYN. A self-assembled monolayer from a disulfide-derivatized aptamer was formed on a gold electrode to fabricate the aptasensor. Upon CYN capturing to the aptasensor surface, a marked drop in the electron transfer resistance was obtained, which was used as the principle of detection of CYN. This resulted from the aptamer's conformational change induced by CYN recognition. The present aptasensor could detect CYN with the limit of detection as low as 100 pM and a wide linear range of 0.1 to 80 nM. When mounted on the gold surface, the aptamer exhibited a lower dissociation constant for CYN than that observed in the fluorescence assay, implying that the anchoring of the aptamer on the Au surface improved its affinity to CYN. Moreover, the aptasensor showed high specificity toward other coexistent cyanobacterial toxins of microcystin-LR and Anatoxin-a. Further biosensor designs will be generated using those aptamers for simple and sensitive CYN monitoring. | 25,122,072 | [
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Lower gastrointestinal bleeding associated with diclofenac topical patch in a patient with colonic mass and on antiplatelet therapy for atrial fibrillation. | Topical formulations of diclofenac, a nonsteroidal anti-inflammatory drug commonly prescribed to treat musculoskeletal complaints such as osteoarthritis, low back pain, and myofascial pain, are available in the form of a solution, gel, and patch. The topical application of diclofenac results in substantially lower systemic exposure to diclofenac compared with oral diclofenac, resulting in a more favorable side effect profile. To the authors' knowledge, this is the first case report of a lower gastrointestinal bleed associated with diclofenac topical patch use in a 77 yr-old-woman with a history of colonic mass and atrial fibrillation on antiplatelet therapy. | 25,122,100 | [
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The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations. | To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in "real-life" Chinese patients. A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM). LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m(2), female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001). The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations. | 25,122,123 | [
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Ways of coping with stress and perceived social support in gynecologic cancer patients. | Stress is commonly encountered among cancer patients and may be a challenge affecting immune system resistance. Social support may contribute positively to the health of cancer patients, playing a role in coping with stress. The aim of this study was to determine whether ways of coping are related to social support given to women with gynecologic cancer. The study was performed as a cross-sectional design in a university hospital in Istanbul, Turkey, with 221 women with gynecologic cancer; the data were collected via 3 questionnaires, the first with sociodemographic and clinical features, the second with multidimensional scale of perceived social support, and the third with the scale of ways of coping with stress. Women with gynecologic cancer who were employed and declared their incomes as balanced and reported more years of education were more likely to perceive higher social support and to use the ineffective coping ways with stress at a lower rate (P < .05) than other participants. Based on correlational analysis, effective coping ways with stress increase as perceived social support from family, friends, significant other, and total increases (P < .05). Social support from family members is the mainstay of coping with stress by women with gynecologic cancer. Nurses are indispensable in increasing social support required by women with gynecologic cancer. Well-trained clinical nurses via in-service programs should be experienced and aware of women diagnosed with gynecologic cancer in need of social support during hospital visits and provide necessary guidance. | 25,122,133 | [
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Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell-mediated antiviral defense. | TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF-family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR-/- mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses. | 25,122,141 | [
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0.1255307,
0.01743284,
0.1144885,
0.01204199,
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Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. | The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established. We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196. | 25,122,144 | [
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Feasibility study to quantify the auditory and social environment of older adults using a digital language processor. | To investigate the feasibility of using a digital language processor (DLP) to objectively quantify the auditory and social environment of older adults. Thirty-seven participants aged 64 to 91 years residing in a retirement community were asked to wear a DLP to record their auditory and language environment during 1 waking day. Recordings were analyzed with specialized software to derive quantitative estimates such as the number of spoken words heard and percentage of time spent around meaningful speech versus television/radio. Adequate DLP recordings that began before 10 AM and lasted for 10 hours or greater were collected from 24 participants. The mean duration of recording was 13 hours and 13 minutes, and individuals spent a mean of 26.7% (range, 4%-58%) of their waking day near a television or other electronic sounds. The projected mean word count over a maximum of 16 hours was 33,141 with nearly a 14-fold range between the lowest and highest observed values (range, 5120-77,882). High-quality objective data on the auditory environment of older adults can be feasibly measured with the DLP. Findings from this study may guide future studies investigating auditory and language outcomes in older adults. | 25,122,146 | [
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The Arabidopsis 14-3-3 protein RARE COLD INDUCIBLE 1A links low-temperature response and ethylene biosynthesis to regulate freezing tolerance and cold acclimation. | In plants, the expression of 14-3-3 genes reacts to various adverse environmental conditions, including cold, high salt, and drought. Although these results suggest that 14-3-3 proteins have the potential to regulate plant responses to abiotic stresses, their role in such responses remains poorly understood. Previously, we showed that the RARE COLD INDUCIBLE 1A (RCI1A) gene encodes the 14-3-3 psi isoform. Here, we present genetic and molecular evidence implicating RCI1A in the response to low temperature. Our results demonstrate that RCI1A functions as a negative regulator of constitutive freezing tolerance and cold acclimation in Arabidopsis thaliana by controlling cold-induced gene expression. Interestingly, this control is partially performed through an ethylene (ET)-dependent pathway involving physical interaction with different ACC SYNTHASE (ACS) isoforms and a decreased ACS stability. We show that, consequently, RCI1A restrains ET biosynthesis, contributing to establish adequate levels of this hormone in Arabidopsis under both standard and low-temperature conditions. We further show that these levels are required to promote proper cold-induced gene expression and freezing tolerance before and after cold acclimation. All these data indicate that RCI1A connects the low-temperature response with ET biosynthesis to modulate constitutive freezing tolerance and cold acclimation in Arabidopsis. | 25,122,152 | [
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Structure of chitosan determines its interactions with mucin. | Synthetic and natural mucoadhesive biomaterials in optimized galenical formulations are potentially useful for the transmucosal delivery of active ingredients to improve their localized and prolonged effects. Chitosans (CS) have potent mucoadhesive characteristics, but the exact mechanisms underpinning such interactions at the molecular level and the role of the specific structural properties of CS remain elusive. In the present study we used a combination of microviscosimetry, zeta potential analysis, isothermal titration calorimetry (ITC) and fluorescence quenching to confirm that the soluble fraction of porcine stomach mucin interacts with CS in water or 0.1 M NaCl (at c < c*; relative viscosity, η(rel), ∼ 2.0 at pH 4.5 and 37 °C) via a heterotypic stoichiometric process significantly influenced by the degree of CS acetylation (DA). We propose that CS-mucin interactions are driven predominantly by electrostatic binding, supported by other forces (e.g., hydrogen bonds and hydrophobic association) and that the DA influences the overall conformation of CS and thus the nature of the resulting complexes. Although the conditions used in this model system are simpler than the typical in vivo environment, the resulting knowledge will enable the rational design of CS-based nanostructured materials for specific transmucosal drug delivery (e.g., for Helicobacter pylori stomach therapy). | 25,122,160 | [
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0.002... |
ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term efficacy in primary acute promyelocytic leukemia. | The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4% ± 3.9% and 94.6 ± 3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL. | 25,122,165 | [
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MicroRNA-30e* suppresses dengue virus replication by promoting NF-κB-dependent IFN production. | MicroRNAs have been shown to contribute to a repertoire of host-pathogen interactions during viral infection. Our previous study demonstrated that microRNA-30e* (miR-30e*) directly targeted the IκBα 3'-UTR and disrupted the NF-κB/IκBα negative feedback loop, leading to hyperactivation of NF-κB. This current study investigated the possible role of miR-30e* in the regulation of innate immunity associated with dengue virus (DENV) infection. We found that DENV infection could induce miR-30e* expression in DENV-permissive cells, and such an overexpression of miR-30e* upregulated IFN-β and the downstream IFN-stimulated genes (ISGs) such as OAS1, MxA and IFITM1, and suppressed DENV replication. Furthermore, suppression of IκBα mediates the enhancing effect of miR-30e* on IFN-β-induced antiviral response. Collectively, our findings suggest a modulatory role of miR-30e* in DENV induced IFN-β signaling via the NF-κB-dependent pathway. Further investigation is needed to evaluate whether miR-30e* has an anti-DENV effect in vivo. | 25,122,182 | [
-0.2356715,
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0.1271736,
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0.1350664,
0.06695209,
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Inner and outer portions of colonic circular muscle: ultrastructural and immunohistochemical changes in rat chronically treated with otilonium bromide. | Rat colonic circular muscle, main target of otilonium bromide (OB) spasmolytic activity, is subdivided in an inner and outer portion. Since the inner one is particularly rich in organelles involved in calcium availability (caveolae, smooth endoplasmic reticulum, mitochondria), the expression of specific markers (Caveolin-1, eNOS, calreticulin, calsequestrin) in comparison with the outer portion was investigated. The possible changes of these organelles and related markers, and of muscarinic receptors (Mr2) were then studied after OB chronic exposition. Rats were treated with 2-20 mg/kg/OB for 10 or 30 days. Proximal colon was processed by electron microscopy, immunohistochemistry, and western blot. In colon strips the stimulated contractility response to muscarinic agonist was investigated. The inner portion showed a higher expression of Caveolin-1 and Mr2, but not of eNOS, calreticulin and calsequestrin, compared to the outer portion. Chronic OB treatment caused similar ultrastructural and immunohistochemical changes in both portions. Organelles and some related markers were increased at 10 days; Mr2 expression and muscle contractility induced by methacholine was increased at 30 days. The present findings: 1) provide new information on the immunohistochemical properties of the inner portion of the circular layer that are in favour of a role it might play in colonic motility distinct from that of the outer portion; 2) demonstrate that chronically administered OB interferes with cell structures and molecules responsible for calcium handling and storage, and modifies cholinergic transmission. In conclusion, chronic OB administration in the colonic circular muscle layer directly interacts with the organelles and molecules calcium-related and with the Mr2. | 25,122,192 | [
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A scalable and accurate targeted gene assembly tool (SAT-Assembler) for next-generation sequencing data. | Gene assembly, which recovers gene segments from short reads, is an important step in functional analysis of next-generation sequencing data. Lacking quality reference genomes, de novo assembly is commonly used for RNA-Seq data of non-model organisms and metagenomic data. However, heterogeneous sequence coverage caused by heterogeneous expression or species abundance, similarity between isoforms or homologous genes, and large data size all pose challenges to de novo assembly. As a result, existing assembly tools tend to output fragmented contigs or chimeric contigs, or have high memory footprint. In this work, we introduce a targeted gene assembly program SAT-Assembler, which aims to recover gene families of particular interest to biologists. It addresses the above challenges by conducting family-specific homology search, homology-guided overlap graph construction, and careful graph traversal. It can be applied to both RNA-Seq and metagenomic data. Our experimental results on an Arabidopsis RNA-Seq data set and two metagenomic data sets show that SAT-Assembler has smaller memory usage, comparable or better gene coverage, and lower chimera rate for assembling a set of genes from one or multiple pathways compared with other assembly tools. Moreover, the family-specific design and rapid homology search allow SAT-Assembler to be naturally compatible with parallel computing platforms. The source code of SAT-Assembler is available at https://sourceforge.net/projects/sat-assembler/. The data sets and experimental settings can be found in supplementary material. | 25,122,209 | [
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0... |
Scaling-up access to antiretroviral therapy for children: a cohort study evaluating care and treatment at mobile and hospital-affiliated HIV clinics in rural Zambia. | Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia. Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility. Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4(+) T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4(+) T-cell percentages. HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas. | 25,122,213 | [
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0.1375633,
-0.18484... |
Evidence for two types of lateral interactions in visual perception of temporal signals. | The aim of this work was to investigate the mechanisms of lateral interactions involved in flicker perception. Furthermore, the spatial properties of the monoptic and dichoptic components of these mechanisms were studied. We quantified the perceived flicker strength (PFS) in the center of a test stimulus, which was simultaneously modulated with a surround stimulus of variable size. The modulation depth of a separate stimulus, identical to the center test stimulus but without the surround, was determined using a two-alternative forced choice procedure. Using LCD goggles synchronized to the frame rate of a CRT screen, the center and surround of the test stimulus were presented either monoptically or dichoptically. In the monoptic condition, center-surround interactions have subcortical and cortical origins. In the dichoptic condition, center-surround interactions must have a cortical origin. The difference between the dichoptic and the monoptic data is an estimate of the contribution of the subcortical mechanisms. At each condition (surround stimulus size; monoptic or dichoptic presentation), the PFS was measured for phase differences between center and surround stimuli. The PFS changed systematically with phase difference. It also was observed that the PFS in the center stimulus changed merely be the presence of a surround stimulus independently of the center-surround phase difference. We propose that this is a phase-independent mechanism related to contrast adaptation owing to the presence of surround modulation. Our data suggest that both phase-dependent and -independent mechanisms have cortical and subcortical origins. There were no systematic differences between the spatial properties of subcortical and cortical components involved in PFS modulation. | 25,122,214 | [
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0.08471934,
-0.03345616,
0.2242285,
0.059... |
Consistent inference of a general model using the pseudolikelihood method. | Recently, a maximum pseudolikelihood (MPL) inference method has been successfully applied to statistical physics models with intractable likelihoods. We use information theory to derive a relation between the pseudolikelihood and likelihood functions. Furthermore, we show the consistency of the pseudolikelihood method for a general model. | 25,122,234 | [
0.1096364,
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0.3668348,
0.2344918,
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0.0157361,
0.1... |
Small-cluster renormalization group in Ising and Blume-Emery-Griffiths models with ferromagnetic, antiferromagnetic, and quenched disordered magnetic interactions. | The Ising and Blume-Emery-Griffiths (BEG) models' critical behavior is analyzed in two dimensions and three dimensions by means of a renormalization group scheme on small clusters made of a few lattice cells. Different kinds of cells are proposed for both ordered and disordered model cases. In particular, cells preserving a possible antiferromagnetic ordering under renormalization allow for the determination of the Néel critical point and its scaling indices. These also provide more reliable estimates of the Curie fixed point than those obtained using cells preserving only the ferromagnetic ordering. In all studied dimensions, the present procedure does not yield a strong-disorder critical point corresponding to the transition to the spin-glass phase. This limitation is thoroughly analyzed and motivated. | 25,122,256 | [
0.0910316,
0.22344,
0.1010392,
0.009762169,
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0.09129639,
0.1393996,
0.04879843,
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... |
Dynamic hysteretic features of Ising-type thin films. | In order to elucidate the nature of hysteresis characteristics in a magnetic Ising-type thin film with a certain thickness, such as types of frequency dispersion curves, decay of hysteresis loop area, corresponding coercive field and remanent magnetization values, etc., we investigate the hysteretic response of each layer within effective-field theory. Throughout the analysis, the best appropriate parameter values are chosen since they would allow us to observe the reversed magnetic hysteresis after a certain value of external field frequency. This eccentric phenomenon has prompted us to associate it to the domain nucleation and growth mechanism in the dynamic process. Exotic shapes of the response for different layer indices in two different regimes of modified surface exchange are particularly emphasized. | 25,122,273 | [
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0.3617271,
0.06511073,
-0.15... |
Rare regions and Griffiths singularities at a clean critical point: the five-dimensional disordered contact process. | We investigate the nonequilibrium phase transition of the disordered contact process in five space dimensions by means of optimal fluctuation theory and Monte Carlo simulations. We find that the critical behavior is of mean-field type, i.e., identical to that of the clean five-dimensional contact process. It is accompanied by off-critical power-law Griffiths singularities whose dynamical exponent z' saturates at a finite value as the transition is approached. These findings resolve the apparent contradiction between the Harris criterion, which implies that weak disorder is renormalization-group irrelevant, and the rare-region classification, which predicts unconventional behavior. We confirm and illustrate our theory by large-scale Monte Carlo simulations of systems with up to 70(5) sites. We also relate our results to a recently established general relation between the Harris criterion and Griffiths singularities [Phys. Rev. Lett. 112, 075702 (2014)], and we discuss implications for other phase transitions. | 25,122,283 | [
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0.07424202,
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0.1692887,
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0.03812296,
0.01948545,
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Work and efficiency of quantum Otto cycles in power-law trapping potentials. | We study the performance of a quantum Otto cycle operating in trapping potentials of different shapes. We show that, while both the mean work output and the efficiency of two Otto cycles in different trapping potentials can be made equal, the work probability distribution will still be strongly affected by the difference in structure of the energy levels. To exemplify our results, we study the family of potentials of the form V(t)(x) ∼ x(2q). This family of potentials possesses a simple scaling property that allows for analytical insights into the efficiency and work output of the cycle. We perform a comparison of quantum Otto cycles in various physically relevant scenarios and find that in certain instances, the efficiency of the cycle is greater when using potentials with larger values of q, while in other cases, the efficiency is greater with harmonic traps. | 25,122,289 | [
0.07711436,
0.3305011,
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0.06295091,
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0.1347174,
0.05898591,
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0.08634152,
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Heat transfer in the spin-boson model: a comparative study in the incoherent tunneling regime. | We study the transfer of heat in the nonequilibrium spin-boson model with an Ohmic dissipation. In the nonadiabatic limit we derive a formula for the thermal conductance based on a rate equation formalism at the level of the noninteracting blip approximation, valid for temperatures T>T(K), with T(K) as the Kondo temperature. We evaluate this expression analytically assuming either weak or strong couplings, and demonstrate that our results agree with exact relations. Far-from-equilibrium situations are further examined, showing a close correspondence to the linear response limit. | 25,122,292 | [
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0.02695594,
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0.1079614,
0.2100036,
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0.078... |
Effect of size polydispersity versus particle shape in dense granular media. | We present a detailed analysis of the morphology of granular systems composed of frictionless pentagonal particles by varying systematically both the size span and particle shape irregularity, which represent two polydispersity parameters of the system. The microstructure is characterized in terms of various statistical descriptors such as global and local packing fractions, radial distribution functions, coordination number, and fraction of floating particles. We find that the packing fraction increases with the two parameters of polydispersity, but the effect of shape polydispersity for all the investigated structural properties is significant only at low size polydispersity where the positional and/or orientational ordering of the particles prevail. We focus in more detail on the class of side/side contacts, which is the interesting feature of our system as compared to a packing of disks. We show that the proportion of such contacts has weak dependence on the polydispersity parameters. The side- side contacts do not percolate but they define clusters of increasing size as a function of size polydispersity and decreasing size as a function of shape polydispersity. The clusters have anisotropic shapes but with a decreasing aspect ratio as polydispersity increases. This feature is argued to be a consequence of strong force chains (forces above the mean), which are mainly captured by side-side contacts. Finally, the force transmission is intrinsically multiscale, with a mean force increasing linearly with particle size. | 25,122,294 | [
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0.4205335,
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