Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of Foot-and-Mouth Disease Virus Mutant Polymerases with Reduced Sensitivity to Ribavirin

ABSTRACT Passage of poliovirus (PV) or foot-and-mouth disease virus (FMDV) in the presence of ribavirin (R) selected for viruses with decreased sensitivity to R, which included different mutations in their polymerase (3D): G64S located in the finger subdomain in the case of PV and M296I located within loop β9-α11 at the active site in the case of FMDV. To investigate why disparate substitutions were selected in two closely related 3Ds, we constructed FMDVs with a 3D that included either G62S (the equivalent replacement in FMDV of PV G64S), M296I, or both substitutions. G62S, but not M296I, inflicts upon FMDV a strong selective disadvantage which is partially compensated for by the substitution M296I. The corresponding mutant polymerases, 3D(G62S), 3D(M296I), and 3D(G62S-M296I), were analyzed functionally and structurally. G62S in 3D impairs RNA-binding, polymerization, and R monophosphate incorporation activities. The X-ray structures of the 3D(G62S)-RNA, 3D(M296I)-RNA, and 3D(G62S-M296I)-RNA complexes show that although the two positions are separated by 13.1 Å, the loops where the replacements reside are tightly connected through an extensive network of interactions that reach the polymerase active site. In particular, G62S seems to restrict the flexibility of loop β9-α11 and, as a consequence, the flexibility of the active site and its ability to bind the RNA template. Thus, a localized change in the finger subdomain of 3D may affect the catalytic domain. The results provide a structural interpretation of why different amino acid substitutions were selected to confer R resistance in closely related viruses and reveal a complex network of intra-3D interactions that can affect the recognition of both the RNA template and incoming nucleotide.
Power management of hybrid DRAM/PRAM-based main memory

Hybrid main memory consisting of DRAM and non-volatile memory is attractive since the non-volatile memory can give the advantage of low standby power while DRAM provides high performance and better active power. In this work, we address the power management of such a hybrid main memory consisting of DRAM and phase-change RAM (PRAM). In order to reduce DRAM refresh energy which occupies a significant portion of total memory energy, we present a runtime-adaptive method of DRAM decay. In addition, we present two methods, DRAM bypass and dirty data keeping, for further reduction in refresh energy and memory access latency, respectively. The experiments show that by reducing DRAM refreshes, we can obtain 23.5%∼94.7% reduction in the energy consumption with negligible performance overhead compared with the conventional DRAM-only main memory.
Nerve Growth Factor- and Neurotrophin-3-Induced Changes in Nociceptive Threshold and the Release of Substance P from the Rat Isolated Spinal Cord

Acute superfusion of nerve growth factor (NGF; 1–100 ng/ml) through a naive rat spinal cord preparation did not alter basal or electrically evoked release of substance P-like immunoreactivity (SP-LI). In contrast, neurotrophin-3 (NT-3; 1–100 ng/ml), although not modifying SP-LI basal outflow, dose-dependently inhibited the electrically evoked, but not capsaicin (10 nm)-induced, release of the peptide. This NT-3 (10 ng/ml)-induced inhibition persisted even in the presence of 100 ng/ml NGF in the perfusion fluid and was still significant when the evoked release of SP-LI was enhanced by a prolonged in vivo treatment with NGF. Co-superfusion with naloxone (0.1 μm), but not CGP 36742 (100 μm), a GABAB antagonist, prevented NT-3 (10 ng/ml) inhibition of SP-LI release. Basal and electrically evoked release of SP-LI from the rat spinal cord in vitro was not modified 24 hr after single systemic injection of either NGF (1 mg/kg) or NT-3 (10 mg/kg). At these time intervals from administration, NGF had induced thermal and mechanical hyperalgesia in the rat hindpaw, and NT-3 had induced mechanical, but not thermal, hypoalgesia. NT-3 administered six times over a 2 week period (at 1 mg/kg) did not alter thermal threshold but significantly reduced electrically evoked release of SP-LI from the spinal cord. An identical treatment regimen with 1 mg/kg NGF induced a significant increase in evoked release of SP-LI. However, this was not associated with a significant hyperalgesia. Although finding that NGF-induced hyperalgesia does not clearly correlate with changes in the release of SP-LI in the spinal cord, this study shows that NT-3 is an inhibitor of SP-LI release and suggests that this mechanism may be responsible for NT-3-induced antinociception.
Specific Serological Diagnosis of Leprosy with a Recombinant Mycobacterium leprae Protein Purified from a Rapidly Growing Mycobacterial Host

ABSTRACT In this report we demonstrate the utility of an monoclonal antibody inhibition enzyme-linked immunosorbent assay based on theMycobacterium leprae 35-kDa protein, purified from the rapidly growing host Mycobacterium smegmatis, for the serodiagnosis of multibacillary leprosy. The assay proved highly specific (97.5%) and sensitive (90%) and compared favorably with two other established methods routinely utilized for leprosy serodiagnosis.
Improving physicians’ HIV risk-assessment skills using announced and unannounced standardized patients

AbstractOBJECTIVES: To evaluate feasibility of and to validate a rating scale for two educational programs that use standardized patient-instructors (SPIs) in the office setting to improve physicians’ HIV risk communication skills. DESIGN: Pilot randomized trial of announced and unannounced SPIs. PARTICIPANTS/SETTINGS: Twenty four primary care physicians in the Rochester, NY, area. MEASUREMENTS: The Rochester HIV Interview Rating Scale (RHIRS), HIV test ordering, physician satisfaction questionnaire. RESULTS: Physicians found the intervention useful, and predicted a positive effect on their future HIV-related communication. HIV test ordering and RHIRS scores increased similarly in both intervention groups. Announced SPI visits were more convenient and preferred by physicians. Cost for each SPI visit was $75. CONCLUSIONS: A brief office-based intervention using SPIs was feasible, well-accepted, convenient, and inexpensive. Announced SPIs were preferred to unannounced SPIs. Pilot results suggesting improvement in HIV-related communication should be confirmed in a larger randomized trial.
Ergodic mutual information of full-duplex MIMO radios with residual self-interference

We study the theoretical performance of a full-duplex multiple-input multiple-output (MIMO) bi-directional communication system. We focus on the effect of the residual self-interference due to channel estimation errors and transmitter impairments. We assume that the instantaneous channel state information (CSI) at the transmitting nodes is not known and the CSI at the receiving nodes is imperfect. To maximize the system ergodic mutual information, which is a non-convex function of power allocation vectors at the nodes, a gradient projection (GP) algorithm is developed to optimize the power allocation vectors. This algorithm exploits both spatial and temporal freedoms of the source covariance matrices of the MIMO links between the nodes to achieve higher sum ergodic mutual information. It is observed through the simulations that the algorithm reduces to a full-duplex scheme when the nominal residual self-interference is low, or to a half-duplex scheme when the nominal residual self-interference is high.
Mobile Scheduling for Spatiotemporal Detection in Wireless Sensor Networks

Wireless sensor networks (WSNs) deployed for mission-critical applications face the fundamental challenge of meeting stringent spatiotemporal performance requirements using nodes with limited sensing capacity. Although advance network planning and dense node deployment may initially achieve the required performance, they often fail to adapt to the unpredictability and variability of physical reality. This paper explores efficient use of mobile sensors to address limitations of static WSNs for target detection. We propose a data-fusion-based detection model that enables static and mobile sensors to effectively collaborate in target detection. An optimal sensor movement scheduling algorithm is developed to minimize the total moving distance of sensors while achieving a set of spatiotemporal performance requirements including high detection probability, low system false alarm rate, and bounded detection delay. The effectiveness of our approach is validated by extensive simulations based on real data traces collected by 23 sensor nodes.
Lateral mixing in the equatorial Pacific: The importance of inertial instability

Mixing in the ocean plays a key role in the ocean's dynamics and thermodynamics and how the ocean interacts with the atmosphere. Here we focus on lateral mixing in the equatorial ocean, and in particular the part played by inertial instability. We demonstrate the effectiveness of the instability in promoting mixing in the equatorial thermocline, that is sufficient to affect the large scale structure of the equatorial ocean, and which rectifies problems in existing ocean models. The spatial and temporal variability of the process is likely to impinge on interannual variations of the ocean and El Niño.
Dispensing of non-prescribed antibiotics in Jordan

Objective Current regulations in Jordan state that antibiotics cannot be sold without a medical prescription. This study aimed to assess the percentage of pharmacies that dispense antibiotics without a medical prescription in the Kingdom of Jordan and identify and highlight the extent and seriousness of such practices among Jordanian pharmacies. Methods A prospective study was performed, and five different clinical scenarios were simulated at pharmacies investigated including sore throat, otitis media, acute sinusitis, diarrhea, and urinary tract infection in childbearing-aged women. Three levels of demand were used to convince the pharmacists to sell an antibiotic. Results A total of 202 total pharmacies in Jordan were visited in the present study. The majority of pharmacies (74.3%) dispensed antibiotics without prescription with three different levels of demand. The percentage of pharmacies dispensing antibiotics without a prescription for the sore throat scenario was 97.6%, followed by urinary tract infection (83.3%), diarrhea (83%), and otitis media (68.4%). The lowest percentage of antibiotic dispensing was for the acute sinusitis simulation at 48.5%. Among the pharmacies that dispensed antibiotics, the pharmacists provided an explanation as the number of times per day the drug should be taken in 95.3% of the cases, explained the duration of treatment in 25.7%, and inquired about allergies prior to the sale of the antibiotic in only 17.3%. Only 52 pharmacies (25.7%) refused to dispense any kind of antibiotics, the majority (61.5%) of this refusal response came from acute sinusitis cases, while the minority (2.4%) came from the sore throat cases. Conclusion The results of this study demonstrate that antibiotics continue to be dispensed without prescription in Jordan in violation with national regulations regarding this practice. The findings of this study could provide a layout for governmental health authorities to implement strict enfrorcment of national regulations regarding antibiotic dispensing in order to avoid the serious complications that could arise in the future as a result of such practices.
Fluctuations in nonequilibrium statistical mechanics: models, mathematical theory, physical mechanisms

The fluctuations in nonequilibrium systems are under intense theoretical and experimental investigation. Topical ‘fluctuation relations’ describe symmetries of the statistical properties of certain observables, in a variety of models and phenomena. They have been derived in deterministic and, later, in stochastic frameworks. Other results first obtained for stochastic processes, and later considered in deterministic dynamics, describe the temporal evolution of fluctuations. The field has grown beyond expectation: research works and different perspectives are proposed at an ever faster pace. Indeed, understanding fluctuations is important for the emerging theory of nonequilibrium phenomena, as well as for applications, such as those of nanotechnological and biophysical interest. However, the links among the different approaches and the limitations of these approaches are not fully understood. We focus on these issues, providing: (a) analysis of the theoretical models; (b) discussion of the rigorous mathematical results; (c) identification of the physical mechanisms underlying the validity of the theoretical predictions, for a wide range of phenomena.
Effect of inhomogeneities and substrate on the dynamics of the metal-insulator transition in VO 2 thin films

We study the thermal relaxation dynamics of VO$_2$ films after the ultrafast photo-induced metal-insulator transition for two VO$_2$ film samples grown on Al$_2$O$_3$ and TiO$_2$ substrates. We find two orders of magnitude difference in the recovery time (a few ns for the VO$_2$/Al$_2$O$_3$ sample vs. hundreds of ns for the VO$_2$/TiO$_2$ sample). We present a theoretical model that accurately describes the MIT thermal properties and interpret the experimental measurements. We obtain quantitative results that show how the microstructure of the VO$_2$ film and the thermal conductivity of the interface between the VO$_2$ film and the substrate affect long time-scale recovery dynamics. We also obtain a simple analytic relationship between the recovery time-scale and some of the film parameters.
The importance of immunohistochemical analyses in evaluating the phenotype of Kv channel knockout mice

To gain insights into the phenotype of voltage‐gated potassium (Kv)1.1 and Kv4.2 knockout mice, we used immunohistochemistry to analyze the expression of component principal or α subunits and auxiliary subunits of neuronal Kv channels in knockout mouse brains. Genetic ablation of the Kv1.1 α subunit did not result in compensatory changes in the expression levels or subcellular distribution of related ion channel subunits in hippocampal medial perforant path and mossy fiber nerve terminals, where high levels of Kv1.1 are normally expressed. Genetic ablation of the Kv4.2 α subunit did not result in altered neuronal cytoarchitecture of the hippocampus. Although Kv4.2 knockout mice did not exhibit compensatory changes in the expression levels or subcellular distribution of the related Kv4.3 α subunit, we found dramatic decreases in the cellular and subcellular expression of specific Kv channel interacting proteins (KChIPs) that reflected their degree of association and colocalization with Kv4.2 in wild‐type mouse and rat brains. These studies highlight the insights that can be gained by performing detailed immunohistochemical analyses of Kv channel knockout mouse brains.
Academic procrastination in college students: The role of self-reported executive function

Procrastination, or the intentional delay of due tasks, is a widespread phenomenon in college settings. Because procrastination can negatively impact learning, achievement, academic self-efficacy, and quality of life, research has sought to understand the factors that produce and maintain this troublesome behavior. Procrastination is increasingly viewed as involving failures in self-regulation and volition, processes commonly regarded as executive functions. The present study was the first to investigate subcomponents of self-reported executive functioning associated with academic procrastination in a demographically diverse sample of college students aged 30 years and below (n = 212). We included each of nine aspects of executive functioning in multiple regression models that also included various demographic and medical/psychiatric characteristics, estimated IQ, depression, anxiety, neuroticism, and conscientiousness. The executive function domains of initiation, plan/organize, inhibit, self-monitor, working memory, task monitor, and organization of materials were significant predictors of academic procrastination in addition to increased age and lower conscientiousness. Results enhance understanding of the neuropsychological correlates of procrastination and may lead to practical suggestions or interventions to reduce its harmful effects on students' academic performance and well-being.
Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone

Objectives The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE). Materials and Methods This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11β-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure. Results and Discussion PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 μg/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 μg/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11β-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were lower than those from uncomplicated pregnancies, although only when the babies were born prematurely. Children born at term to normotensive mothers or mothers suffering from PE had comparable birth weights.
Slow mixing of Glauber dynamics for the hard-core model on the hypercube

For λ > 0, let π<inf>λ</inf> be the probability measure on the independent sets of the hypercube {0,1}<sup><i>d</i></sup> in which <i>I</i> is chosen with probability proportional to λ<sup>|<i>I</i>|</sup>. We study the Glauber dynamics, or single-site-update Markov chain, whose stationary distribution is π<inf>λ</inf>, and show that for values of λ tending to 0 as <i>d</i> grows, the convergence to stationarity is exponentially slow in the volume of the cube. The proof combines a conductance argument with combinatorial enumeration methods.
Cell-Free Urinary MicroRNA-99a and MicroRNA-125b Are Diagnostic Markers for the Non-Invasive Screening of Bladder Cancer

Background Evidence implicated the diagnostic significance of microRNAs in whole urine/urine sediments in urothelial carcinoma of the bladder (UCB). However, the contaminated blood cells in patients with haematouria significantly altered the expression profiles of urinary microRNA, influencing the test accuracy. Methods MicroRNA profiles of the urine supernatants of UCB patients and controls without any malignancy and profiles of malignant and corresponding normal mucosa tissues from the patients were determined by microRNA microarray and compared to identify differentially expressed microRNAs. The differential expression was verified in the tissues of an independent patient cohort by RT-qPCR. The diagnostic significance of selected microRNAs as biomarkers in the urine supernatant was investigated in the expanded cohorts. Results MicroRNA-99a and microRNA-125b were down-regulated in the urine supernatants of UCB patients. The degree of down-regulation was associated with the tumor grade. A diagnostic model was developed using a combined index of the levels of microRNA-99a and microRNA-125b in the urine supernatant with a sensitivity of 86.7%, a specificity of 81.1% and a positive predicted value (PPV) of 91.8%. Discriminating between high- and low-grade UCB, the model using the level of microRNA-125b alone exhibited a sensitivity of 81.4%, a specificity of 87.0% and a PPV of 93.4%. Conclusions The results revealed a unique microRNA expression signature in the urine supernatants of UCB patients for the development of molecular diagnostic tests. An effective cell-free urinary microRNA-based model was developed using a combined index of the levels of microRNA-99a and microRNA-125b to detect UCB with good discriminating power, high sensitivity and high specificity.
Anatomic mapping of neuronal odor responses in the developing rat olfactory bulb

Behavioral evidence indicates that altricial mammals possess olfactory function at early developmental ages, before the olfactory bulb has matured anatomically. We monitored the early anatomic and functional development of the olfactory bulb in rat pups stimulated with odors using in situ localization of c‐fos mRNA to identify responsive postsynaptic neurons. Odor‐specific spatial patterns of neuronal activation in the glomerular layer were evident from birth, were sharply defined rather than diffuse, and remained relatively unchanged in terms of their bulbar distribution during the first 3 postnatal weeks. In neonates, focal postsynaptic responses in the glomerular layer occurred in the form of clusters of activated tufted neurons. Broad zones of activated mitral cells were located beneath these cell clusters, with scattered neurons in the underlying granule cell layer also expressing c‐fos. The cellular composition of these functional neuronal groups shifted from predominantly output neurons at the earliest ages, to increasing incorporation of interneurons as they developed postnatally. The characteristic distribution of activated neurons in the mature glomerular layer, in which the boundaries of individual glomeruli are precisely defined by cells expressing c‐fos, emerged near the end of the first week. Broad zones of cRNA hybridization in the mitral cell layer became increasingly restricted as the size of the activated granule cell population increased postnatally, correlating with the functional maturation of inhibitory circuitry. These results provide evidence that the types and distributions of neurons collectively activated by sensory input to glomeruli change as the rat olfactory bulb matures and that distinct, functional odor maps in the glomerular layer are established from birth. J. Comp. Neurol. 455:56–71, 2003. © 2002 Wiley‐Liss, Inc.