Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogeography of the Spring and Fall Waves of the H1N1/09 Pandemic Influenza Virus in the United States

ABSTRACT Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers.
Charges in the hydrophobic interior of proteins

Charges are inherently incompatible with hydrophobic environments. Presumably for this reason, ionizable residues are usually excluded from the hydrophobic interior of proteins and are found instead at the surface, where they can interact with bulk water. Paradoxically, ionizable groups buried in the hydrophobic interior of proteins play essential roles, especially in biological energy transduction. To examine the unusual properties of internal ionizable groups we measured the pKa of glutamic acid residues at 25 internal positions in a stable form of staphylococcal nuclease. Two of 25 Glu residues titrated with normal pKa near 4.5; the other 23 titrated with elevated pKa values ranging from 5.2–9.4, with an average value of 7.7. Trp fluorescence and far-UV circular dichroism were used to monitor the effects of internal charges on conformation. These data demonstrate that although charges buried in proteins are indeed destabilizing, charged side chains can be buried readily in the hydrophobic core of stable proteins without the need for specialized structural adaptations to stabilize them, and without inducing any major conformational reorganization. The apparent dielectric effect experienced by the internal charges is considerably higher than the low dielectric constants of hydrophobic matter used to represent the protein interior in electrostatic continuum models of proteins. The high thermodynamic stability required for proteins to withstand the presence of buried charges suggests a pathway for the evolution of enzymes, and it underscores the need to mind thermodynamic stability in any strategy for engineering novel or altered enzymatic active sites in proteins.
Robot-mediated therapy for paretic upper limb of chronic patients following neurological injury.

OBJECTIVE To evaluate the effectiveness of robot-mediated therapy targeted at the motor recovery of the upper limb in chronic patients following neurological injury. DESIGN Pre-post treatment study. SUBJECTS Twenty patients were enrolled in the study. METHODS Robot-mediated therapy was provided to chronic hemiparetic patients (acute event had occurred at least one year prior to the study), 3 times a week, for 6 weeks. The therapy consisted of goal-directed, planar reaching tasks that exercised the hemiparetic shoulder and elbow. The items for the shoulder and elbow of Motor Status Score, Modified Ashworth Scale and range of motion were used as outcome measures. RESULTS Statistically significant improvements before and after treatment were found in each outcome measure. A 3-month follow-up evaluation indicated that patients maintained the improvements. CONCLUSION The results confirm that robot-mediated therapy, through short-term, but intensive, repetitive and goal-directed trials, contributes to a decrease in the upper limb's motor disability in people with a chronic neurological injury by reducing motor impairment and shoulder pain. The treatment was well accepted and tolerated by patients. No adverse events occurred.
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury

Through undefined mechanisms, dominant mutations in (Cu/Zn) superoxide dismutase‐1 (mSOD1) cause the non‐cell‐autonomous death of motoneurons in inherited amyotrophic lateral sclerosis (ALS). Microgliosis at sites of motoneuron injury is a neuropathological hallmark of ALS. Extracellular mutant SOD1 (mSOD1) causes motoneuron injury and triggers microgliosis in spinal cord cultures, but it is unclear whether the injury results from extracellular mSOD1 directly interacting with motoneurons or is mediated through mSOD1‐activated microglia. To dissociate these potential mSOD1‐mediated neurotoxic mechanisms, the effects of extracellular human mSOD1G93A or mSOD1G85R were assayed using primary cultures of motoneurons and microglia. The data demonstrate that exogenous mSOD1G93A did not cause detectable direct killing of motoneurons. In contrast, mSOD1G93A or mSOD1G85R did induce the morphological and functional activation of microglia, increasing their release of pro‐inflammatory cytokines and free radicals. Furthermore, only when microglia was co‐cultured with motoneurons did extracellular mSOD1G93A injure motoneurons. The microglial activation mediated by mSOD1G93A was attenuated using toll‐like receptors (TLR) 2, TLR4 and CD14 blocking antibodies, or when microglia lacked CD14 expression. These data suggest that extracellular mSOD1G93A is not directly toxic to motoneurons but requires microglial activation for toxicity, utilizing CD14 and TLR pathways. This link between mSOD1 and innate immunity may offer novel therapeutic targets in ALS. © 2009 Wiley‐Liss, Inc.
Finite Size Corrections and Likelihood Ratio Fluctuations in the Spiked Wigner Model

In this paper we study principal components analysis in the regime of high dimensionality and high noise. Our model of the problem is a rank-one deformation of a Wigner matrix where the signal-to-noise ratio (SNR) is of constant order, and we are interested in the fundamental limits of detection of the spike. Our main goal is to gain a fine understanding of the asymptotics for the log-likelihood ratio process, also known as the free energy, as a function of the SNR. Our main results are twofold. We first prove that the free energy has a finite-size correction to its limit---the replica-symmetric formula---which we explicitly compute. This provides a formula for the Kullback-Leibler divergence between the planted and null models. Second, we prove that below the reconstruction threshold, where it becomes impossible to reconstruct the spike, the log-likelihood ratio has fluctuations of constant order and converges in distribution to a Gaussian under both the planted and (under restrictions) the null model. As a consequence, we provide a general proof of contiguity between these two distributions that holds up to the reconstruction threshold, and is valid for an arbitrary separable prior on the spike. Formulae for the total variation distance, and the Type-I and Type-II errors of the optimal test are also given. Our proofs are based on Gaussian interpolation methods and a rigorous incarnation of the cavity method, as devised by Guerra and Talagrand in their study of the Sherrington--Kirkpatrick spin-glass model.
A robust measurement placement method in distribution system state estimation

A robust measurement system can take account of the influence on Distribution System State Estimation (DSSE) caused by network reconfiguration. This paper proposes an optimization algorithm to determine the number and position of the measurement devices separately. The concept of measurement saturation is proposed, and the position of measurement devices is determined based on a heuristic algorithm constrained by the saturate number. Both network reconfiguration and the uncertainties introduced by the measurements are taken into account. The probabilities of different network configurations are given by Markov chain, and the uncertainties introduced by the measurements are simulated by Monte Carlo algorithm. The results obtained on IEEE33-bus system demonstrate that saturate number is usually one third of the number of nodes for a system, and the robust measurement placement method considering different network configurations can improve the precision of DSSE.
Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients.

The purpose of this trial was to evaluate the antihypertensive efficacy of the concomitant administration of selected doses of hydrochlorothiazide (HCTZ) on a background of losartan potassium (losartan) 50 mg, a selective angiotensin II receptor antagonist. Patients with essential hypertension ( > or = 95 mmHg inclusion criteria) with a mean sitting diastolic blood pressure (SiDBP) of 105 +/- 0.4 (S.E.) mmHg entered a 4-week, single-blind monotherapy period of losartan 50 mg once daily. At the end of the monotherapy period, patients whose blood pressure was adequately controlled were discontinued. Patients whose blood pressure was partially controlled based on a SiDBP > 92 mmHg entered a 12 week double-blind period and were randomly assigned to either receive placebo (n = 80), HCTZ 6.25 mg (n = 80), HCTZ 12.5 mg (n = 72) or HCTZ 25 mg (n = 80) in addition to losartan 50 mg. During the losartan monotherapy period, there was a 4 mmHg fall in SiDBP with a further fall of 5 mmHg after 12 weeks of double-blind therapy in the losartan/placebo control group. Based on the between group differences in BP change from the end of the losartan monotherapy period (baseline) to end of 12 weeks of double-blind, the concomitant administration of a very low dose of HCTZ (6.25 mg) with losartan did not significantly decrease SiDBP compared with the fall in blood pressure in the losartan/placebo control group (diff. between groups = -2 (95% C.I.[-4.1, +0.9] mmHg)). However, the concomitant administration of HCTZ 12.5 or 25 mg with losartan 50 mg resulted in significantly different (p < or = 0.05) reductions in diastolic blood pressure compared to the losartan/placebo group (diff. between groups = -4 (95% C.I. [-6.3, -1.1] mmHg) for 12.5mg combination group; -6 (95% C.I. [-8.3, -3.3]) mmHg for the HCTZ 25 mg combination group). The proportions of patients treated with losartan plus HCTZ 12.5 mg or 25 mg that achieved a trough SiDBP < 88 mmHg or a trough SiDBP > or = 88 mmHg but with a decrease of at least 5 mmHg were 71% and 83%, respectively. The percentage of clinical adverse experiences that were considered drug-related as assessed by the investigator were generally similar across all treatment groups. There were no reports of orthostatic hypotension in any of the treatment groups. Changes in serum glucose, potassium and uric acid were not appreciably different amongst the treatment groups. In summary, in patients with predominantly moderate to severe essential hypertension, the addition of HCTZ 12.5 mg or 25 mg to losartan 50 mg produced effective control of blood pressure in a substantial majority of patients who only partially responded to losartan monotherapy. There were no differences amongst the treatment groups with respect to drug-related adverse experiences in this trial.
High-Q Circular LTCC Resonator Using Zigzagged Via Posts and a  $\lambda/4$ Short Stub for Millimeter-Wave System-on-Package Applications

This paper presents two high-Q circular resonators utilizing low temperature co-fired ceramic (LTCC) multilayer circuits for millimeter-wave system-on-package applications. A resonator including zigzagged dual-row via posts for tightly confining electromagnetic energy as a metallic boundary wall will be presented. Another resonator containing the zigzagged dual-row via posts and a lambda/4 short stub on a feeding via post in the circular resonator is used for transmitting energy in the resonator to output load without losses. Simple theories for obtaining high-Q factors using zigzagged dual-row via posts and the feeding technique with the lambda /4 short stub are derived. A total of four layers are used to construct the resonator with a height of 300 mu m (three layers); an additional layer is used for the probe excitation and signal feeding line. The signal feeding line is employed to connect a negative resistance generator monolithic microwave integrated circuit ((-)R MMIC) that consists of conductor backed coplanar waveguide (CBCPW), which is implemented on a layer. A CPW-type double bond wire connects the resonator and (-)R MMIC. The measurement results show that the first and second resonant modes are TM010 at 29.75 GHz and TE010 at 46.75 GHz, respectively. Although the unloaded Q value of the conventional resonator is 204, the proposed resonator with zigzagged dual-row via posts achieved an unloaded Q value of 249, which is a 22.1% improvement. Further, the new resonator with the lambda/4 short stub and zigzagged dual-row via posts yielded an unloaded Q of 296, an improvement of 45.1% for the first resonant mode. In order to verify the resonator performances, the oscillator integrating the proposed resonator is evaluated. The measured output power and phase noise of the oscillator is 18.8 dBm at 27 GHz and -104.67 dBc/Hz at 1 MHz offset, respectively. It can be implemented easily without requiring additional processes or any degradation of performance and therefore is suitable to implement in high integrated systems for millimeter-wave applications.
Anxiolytic and sedative-hypnotic activities of polygalasaponins from Polygala tenuifolia in mice

In the present study, the anxiolytic and sedative-hypnotic activities of polygalasaponins extracted from Polygala tenuifolia Willdenow (Polygalaceae) were determined in mice using hole-board, elevated plus maze, open field, and sodium pentobarbital-induced hypnosis tests. Moreover, the acute toxicity of polygalasaponins was also estimated in mice. Sixty minutes after p.o. administration of polygalasaponins (40, 80, 160 mg/kg) in mice, the central crossing counts and percentage of central/total ambulation significantly increased and the number of rearings and defecations was evidently inhibited in the open field test. Polygalasaponins also increased the head-dips of mice in the hole-board test and the time spent by mice in the open arms of the X-maze, prolonged sleep duration and shortened sleep latency in the test of synergetic effect on sodium pentobarbital (45 and 25 mg/kg, respectively). Acute toxic study showed the oral median lethal dose (LD50) of polygalasaponins was 3.95 g/kg and 0% lethal dose 2.6 g/kg. These results suggest that polygalasaponin possesses evident anxiolytic and sedative-hypnotic activities and has a relatively safe dose range, which supports the use of Polygala tenuifolia root as an anxiolytic and sedative-hypnotic drug in folk medicine.
Optimizing the Reflective Observer Role in High-Fidelity Patient Simulation.

BACKGROUND The purpose of this descriptive secondary analysis of qualitative data was to gain insights into the role and opportunities of the reflective observer in high-fidelity patient simulation (HFPS). Although the value of HFPS in nursing education has been documented, the reflective observer role in HFPS may not be used to its potential. METHOD This secondary data analysis of a broader study included qualitative interviews of those in observer roles (N = 23). This secondary analysis used content analysis to address research questions related to the reflective observer role. RESULTS Three themes emerged related to using the reflective observer role for self-assessment, peer review and debriefing, and team-focused learning. CONCLUSION Implications for nursing education, including orienting all HFPS participants to reflective observer roles and opportunities, are addressed. Further study of this important role for both individual and team learning is indicated. [J Nurs Educ. 2016;55(6):353-356. ].
A Comparison of the Psychosocial Environment of Two Types of Residences for Persons with Severe mental Illness: Small Congregate Community Residences and Psychiatric Inpatient Settings

Background: Legislation was passed in Sweden to stimulate the development of different housing solutions for persons suffering from severe mental illness. Among these solutions are small congregate residences built in the community to provide suitable housing and support for those not able or willing to live independently. Aims: The general aim of the present study was to compare the psychosocial environment of two types of residences for the persons with severe mental illness-congregate community residences and psychiatric inpatient settings. A specific aim was to see if the former provided higher levels of autonomy than the latter. Methods: In this cross-sectional study the real version of the Community Oriented Program Environmental Scale (COPES) was administered to residents, patients and staff members. Results: The study showed that the psychosocial environment differs between the two types of settings. Residents and staff in small congregate residences rated higher levels of Autonomy and lower levels of Practical Orientation, Anger and Aggression and Order and Organisation than patients and staff in inpatient settings. Conclusions: The psychosocial environment profiles for psychiatric settings in different phases of the care process may vary in terms of the aforementioned subscales.
Nuclear Morphology Measurements with Angle-Resolved Low Coherence Interferometry For Application To Cell Biology And Early Cancer Detection

The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents.
Competence regulation by oxygen in Streptococcus pneumoniae: involvement of ciaRH and comCDE

Anaerobic aerotolerant Streptococcus pneumoniae modulates its genetic transformability and its virulence in response to the oxygen concentration. The activity of a single protein encoded by nox and showing NADH oxidase activity is involved in these adaptive responses to O2. Northern blot analysis of wild‐type cultures grown under aerobic and microaerobic conditions indicated transcriptional control of comCDE by O2. An O2‐independent mutant strain carrying the gain‐of‐function mutation comE38KE was isolated and its analysis showed that ComE is a key point in competence stimulation by O2. Plasmid insertion mutations in ciaRH revealed that this two component signal‐transducing system negatively regulates comCDE transcription. The level of comCDE transcripts appears as a major control point in competence regulation by O2 and also by growth phase and cell density.
The Demographic and Medical Correlates of Plasma A&bgr;40 and A&bgr;42

Plasma amyloid &bgr;-42 (A&bgr;42) and A&bgr;42/A&bgr;40 are increasingly recognized as biomarkers for dementia, with low levels indicating increased risk. Little is known about the demographic and medical correlates of plasma A&bgr;40 or A&bgr;42. In 997 community-dwelling, nondemented older adults from the Health, Aging, and Body Composition Study, we determined the cross-sectional association between a wide range of demographic and medical variables with A&bgr;40 and A&bgr;42. In multivariate stepwise linear regression models, A&bgr;40 was significantly associated with race (&bgr;=−14.70, F=22.01, P<0.0001), age (&bgr;=1.34, F=6.39, P=0.01), creatinine (&bgr;=52.91, F=151.77, P<0.0001), and the serum brain-derived neurotrophic factor (&bgr;=−0.0004, F=7.34, P=0.007); A&bgr;42 was significantly associated with race (&bgr;=−3.72, F=30.83, P<0.0001), sex (&bgr;=1.39, F=4.32, P=0.04), education (&bgr;=1.50, F=4.78, P=0.03), apolipoprotein E e4 genotype (&bgr;=−2.82, F=16.57, P<0.0001), and creatinine (&bgr;=9.32, F=120.09, P<0.0001). These correlates should be considered as potential confounders in future studies investigating plasma A&bgr; as a biomarker of dementia. Understanding fully how these correlates mediate or modify the association between plasma A&bgr; and dementia will be a fundamental step in determining the biological pathways through which plasma A&bgr;40 and A&bgr;42 are associated with dementia, and in determining their full potential as biomarkers.
The Otsego-Schoharie healthy heart program: prevention of cardiovascular disease in the rural US

Objectives: To describe a rural, hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease (CVD) risk reduction using cross-sectional studies and a panel study. Methods: A rural population of 158,000 located in New York state comprised the intervention population. A similar but separate population was used for reference. A multifaceted, multimedia 5-year program provided health promotion and education initiatives to increase physical activity, decrease smoking, improve nutrition, and identify hypercholesterolemia and hypertension. To evaluate the effectiveness of the intervention, surveys were conducted at baseline in 1989 (cross-sectional) and at follow-up in 1994- 95 (cross-sectional and panel). For cross-sectional studies, a random sample of adults was obtained using a three-stage cluster design. Self-reported and objective risk factor measurements were obtained. Comparison of pre- to post- changes in intervention versus reference populations was done using 2× 2randomized block ANOVA, 2 × 2 mixed ANOVA, and extension of the McNemar test. Results: Smoking prevalence declined (from 27.9% to 17.6%) in the intervention population. Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides. Systolic blood pressure was reduced while diastolic blood pressure remained stable. Body mass index increased significantly in both populations. Conclusions: This rural, 5-year CVD community intervention program decreased smoking. The risk reduction may be attributable to tailoring of a multifaceted approach (multiple risk factors, multiple messages, and multiple population subgroups) to a target rural population. The study period was too short to identify changes in CVD morbidity and mortality.