Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of chloride-depleted human sulfite oxidase by EPR spectroscopy: experimental evidence for the role of anions in product release

The Mo(V) state of the molybdoenzyme sulfite oxidase (SO) is paramagnetic and can be studied by electron paramagnetic resonance (EPR) spectroscopy. Vertebrate SO at pH < 7 and pH > 9 exhibits characteristic EPR spectra that correspond to two structurally different forms of the Mo(V) active center referred to as the low-pH ( lpH ) and high-pH ( hpH ) forms, respectively. Both EPR forms have an exchangeable equatorial OH ligand, but its orientation in the two forms is different. It has been hypothesized that the formation of the lpH species is dependent upon the presence of chloride. In this work we have prepared and purified samples of wild type and various mutants of human SO that are depleted in chloride. These samples do not exhibit the typical lpH EPR spectrum at low pH, but rather show spectra that are characteristic of the blocked species that contains an exchangeable equatorial sulfate ligand. Addition of chloride to these samples results in the disappearance of the blocked species and the formation of the lpH species. Similarly, if chloride is added before sulfite, the lpH species is formed instead of the blocked one. Qualitatively similar results were observed for samples of sulfite oxidizing enzymes from other organisms that were previously reported to form a blocked species at low pH. However, the depletion of chloride has no effect upon the formation of the hpH species.
Long-term Course of Pediatric Obsessive-Compulsive Disorder: Three Years of Prospective Follow-up

, Abstract Objective— This study assesses the long-term course of treatment-seeking youth with a primary diagnosis of DSM-IV OCD. Method— Sixty youth and their parents completed intake interviews and annual follow-up interviews for three years using the youth version of the Longitudinal Interval Follow-up Evaluation (Y-LIFE) and Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Remission was defined as no longer meeting DSM-IV criteria for OCD for 8 weeks or more, and recurrence was defined as meeting full criteria for OCD for 4 consecutive weeks after having achieved symptom remission. Remission rates for youth were compared to rates of adults participating in the same study. Results— The probability of achieving partial remission of OCD was 0.53 and the probability of achieving full remission was 0.27. Among the 24 youth participants who achieved remission: 79% stayed in remission throughout the study (mean of 88 weeks of follow-up) and 21% experienced a recurrence of symptoms. Better functioning at intake and a shorter latency to initial OCD treatment were associated with faster onset of remission (P < .001). Conclusions— Remission is more likely among youth versus adults with OCD. Treatment early in the course of illness and before substantial impact on functioning predicted a better course.
Avaliação funcional de idoso vítima de fraturas na hospitalização e no domicílio

Trauma is often related to functional impairment, representing an important social, economic and health issue. This study intended to evaluate the functional independence of aged individuals with fractures, at admission, discharge and after one month from their regressing home. Furthermore, this study also intended to verify the relationship between functional independence and demographic and health variables. Thirty-four aged individuals hospitalized at the Orthopedics and Traumatology Institute of the University of Sao Paulo Faculty of Medicine were interviewed and submitted to the application of the Functional Independence Measure (FIM). Among all fractures, 67.6% were femur fractures. The motor and total FIM scores increased at discharge; on the other hand, the total FIM score decreased one month after their returning home. Functional impairment increased with age and also with longer length of stay. Hypothyroidism was related to cognitive impairment, while dementia and depression were related to motor impairment.
Characterization of Si‐BCB transmission line at millimeter‐wave frequency by compact fractional‐order equivalent circuit model

In this article, fractional‐order calculus is introduced to characterize Si‐BCB transmission line up to millimeter‐wave frequency region. Direct calculation method is employed to build this compact fractional‐order equivalent circuit model. Measured results have confirmed that the proposed fractional‐order model is capable of accurately describing the behavior of BCB‐Si T‐Line over a large range of frequencies up to 110 GHz.
Primary and Secondary Dimer Interfaces of the FGFR3 Transmembrane Domain: Characterization via Multiscale Molecular Dynamics Simulations

Receptor tyrosine kinases are single pass membrane proteins which form dimers within the membrane. The interactions of their transmembrane domains (TMDs) play a key role in dimerization and signaling. The fibroblast growth factor receptor 3 (FGFR3) is of interest as a G380R mutation in its TMD is the underlying cause of ~99% of cases of achondroplasia, the most common form of human dwarfism. The structural consequences of this mutation remain uncertain: the mutation shifts the position relative of the TMD relative to the lipid bilayer but does not alter the association free energy. We have combined coarse-grained and all-atom molecular dynamics simulations to study the dimerization of wild-type, heterodimer, and mutant FGFR3 TMDs. The simulations reveal that the helices pack together in the dimer to form a flexible interface. The primary packing mode is mediated by a Gx 3 G motif. There is also a secondary dimer interface which is more highly populated in heterodimer and mutant configurations which may feature in the molecular mechanism of pathology. Both coarse-grained and atomistic simulations reveal a significant shift of the G380R mutant dimer TMD relative to the bilayer so as to enable interactions of the arginine sidechain with lipid head group phosphates.
Intramolecular Heme Ligation of the CYP2C9 R108H Mutant Demonstrates Pronounced Conformational Flexibility of the B-C Loop Region: Implications for Substrate Binding

A previous study (i.e. Dickmann, L., et al. (2004) Mol. Pharmacol . 65, 842-850. ) revealed some unusual properties of the R108H mutant of cytochrome P450 2C9 (CYP2C9), including elevated thermostability relative to CYP2C9, as well as a UV-visible absorbance spectrum that was indicative of nitrogenous ligation to the heme iron. In the present study, size-exclusion chromatography and UV-visible absorbance spectroscopy of CYP2C9 R108H monomers demonstrated that nitrogen ligation is indeed intramolecular. Pulsed electron paramagnetic resonance of CYP2C9 R108H monomers showed that a histidine is most likely bound to the heme as previously hypothesized. An energy-minimized model of the R108H mutant maintained a CYP fold, despite substantial movement of several loop regions of the mutant and, therefore, represents an extreme example of a closed conformation of the enzyme. Molecular dynamics (MD) simulations of CYP2C9 were performed in order to study the range of energetically accessible CYP2C9 conformations. These in silico studies showed that the B-C loop region of CYP2C9 moves away from the heme to a position resembling the putative open conformation described for rabbit CYP2B4. A model involving the movement of the B-C loop region and R108 between the open and closed conformations of CYP2C9 is presented, which helps to explain the enzyme’s ability to regio- and stereo-specifically metabolize some ligands, while allosterically activating others. using the
Enhanced ROCK Activation in Patients with Systemic Lupus Erythematosus

Objective— Rho-kinases (ROCKs) have been implicated in the pathogenesis of cardiovascular and renal disorders. We recently showed that ROCKs could regulate the differentiation of murine T H 17 cells and production of IL-17 and IL-21, two cytokines associated with SLE. The goal of this study was to assess ROCK activation in human T H 17 cells and evaluate ROCK activity in SLE patients. Methods— An ELISA-based ROCK activity assay was employed to evaluate ROCK activity in human cord blood CD4 + T cells differentiated under T H 0 or T H 17 conditions. We then performed a cross-sectional analysis of 28 SLE patients and 25 healthy matched controls. ROCK activity in peripheral blood mononuclear cell (PBMC) lysates was assessed by ELISA. Cytokine and chemokine profiles were analyzed via ELISA. Results— Human cord blood CD4 + T cells differentiated under T H 17 conditions expressed higher levels of ROCK activity than CD4 + T cells stimulated under T H 0 conditions. Production of IL-17 and IL-21 was furthermore inhibited by addition of a ROCK inhibitor. SLE PBMCs expressed significantly higher levels of ROCK activity as compared to healthy controls, 1.25 vs. 0.56, respectively (p=0.0015). Sixteen (57%) SLE patients expressed high ROCK levels (OD450>1). Disease duration, lymphocyte count, and azathioprine use were significant independent predictors of ROCK activity in multivariable analyses. Conclusions— Consistent with previous results in the murine system, increased ROCK activation was associated with T H 17 differentiation. Enhanced ROCK activity was furthermore observed in a subgroup of SLE patients. These data support the concept that the ROCK pathway could represent an important therapeutic target for SLE.
Role of Wnt/Beta-Catenin Signaling in Liver Metabolism and Cancer

Wnt/ β -catenin signaling is known for its role in embryogenesis as well as carcinogenesis. In the liver, it plays many critical roles during hepatic development and regeneration, and its dysregulation is evident in aberrant hepatic growth during various liver tumors. Its chief cellular roles in the liver include regulation of processes of cell proliferation, apoptosis, oxidative stress and differentiation, which in turn contributes to hepatic growth, zonation, xenobiotic metabolism and other metabolic processes inherent to the liver. Most of these functions of the Wnt/ β -catenin signaling are dictated through the highly temporal and tissue-specific or non-specific transcriptional targets of the pathway. In addition, some of the critical functions such as cell-cell adhesion and perhaps maintenance of various junctions that are critical from an epithelial cell biology perspective are also a function of β -catenin, which is the central component of the canonical Wnt pathway. Various animal models and clinical studies have demonstrated the spectra of Wnt/ β -catenin signaling in liver health and disease. Thus therapeutic modulation of this pathway for improved hepatic health is inevitable in the future. The current review discusses the advances in our understanding of the Wnt/ β -catenin signaling in liver physiology and pathology especially in hepatic metabolism and various tumors in adult liver and goes on to extrapolate the preclinical significance and possible translational implications of such findings.
Enteral Nutrition for TBI Patients in the Rehabilitation Setting: Associations with Patient Pre-injury and Injury Characteristics and Outcomes

Objective—To determine the association of enteral nutrition (EN) with patient pre-injury and injury characteristics and outcomes for patients receiving inpatient brain injury rehabilitation. Design—Prospective observational study using propensity scores to isolate the effect of EN Setting—9 rehabilitation centers in the US Participants—Patients (n=1701) admitted for first full inpatient rehabilitation after a TBI index injury Interventions—Not applicable Main Outcome Measures—Functional Independence Measure (FIM) at rehabilitation discharge, length of stay (LOS), weight loss, and presence of infections. Results—There were many significant differences in pre-injury and injury characteristics for patients who received EN compared to patients who did not. After matching patients with a propensity score >40% for the likely use of EN, patients with greater than 25% of their rehabilitation stay receiving EN with either standard or high protein formulas (greater than 20% of calories coming from protein) had better FIM Motor and FIM Cognitive scores at rehabilitation discharge and less weight loss than similar patients not receiving EN. Corresponding author: Susan D. Horn, PhD, University of Utah School of Medicine, Department of Population Health Sciences, Health System Innovation and Research Program, Williams Building, Rm. 1N461, 295 Chipeta Way, Salt Lake City, Utah 84108. susan.horn@hsc.utah. edu cell 801-718-9149. Reprints will not be available. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Arch Phys Med Rehabil. Author manuscript; available in PMC 2016 August 01. Published in final edited form as: Arch Phys Med Rehabil. 2015 August ; 96(8 0): S245–S255. doi:10.1016/j.apmr. 2014.06. 024. A uhor M anscript
Role of the TGF- b /Alk5 Signaling Pathway in Monocrotaline-induced Pulmonary Hypertension

Rationale : Pulmonary arterial hypertension is a progressive disease characterized by an elevation in the mean pulmonary artery pressure leading to right heart failure and a signiﬁcant risk of death. Alterations in two transforming growth factor (TGF) signaling pathways, bone morphogenetic protein receptor II and the TGF- b receptor I, Alk1, have been implicated in the pathogenesis of pulmonary hypertension (PH). However, the role of TGF- b family signalinginPHandpulmonaryvascularremodelingremainsunclear. Objectives : To determine whether inhibition of TGF- b signaling will attenuate and reverse monocrotaline-induced PH (MCT-PH). Methods : We have used an orally active small-molecule TGF- b receptor I inhibitor, SD-208, to determine the functional role of this pathway in MCT-PH. Measurements and Main Results : The development of MCT-PH was associated with increased vascular cell apoptosis, which paralleled TGF- b signalingasdocumentedbypsmad2expression.Inhibitionof TGF- b signaling with SD-208 signiﬁcantly attenuated the develop- ment of the PH and reduced pulmonary vascular remodeling. These effects were associated with decreased early vascular cell apoptosis, adventitial cell proliferation, and matrix metalloproteinase expression. Inhibition of TGF- b signaling with SD-208 in established MCT-PH resulted in a small but signiﬁcant improvement in hemodynamic parameters and medial remodeling. Conclusions : These ﬁndings provide evidence that increased TGF- b signaling participates in the pathogenesis of experimental severe PH.
On the self‐resonant frequency reduction of closed‐ and open‐bifilar coils

In this work we present the electrical characterization of closed‐ and open‐bifilar solenoid coils by comparing their self‐capacitance, self‐inductance, and self‐resonant frequency (SRF). The analysis is done by relating these parameters with those of a conventional solenoid coil with same dimensions and number of turns. It is shown that bifilar coils have a greater self‐capacitance and lower SRF when compared with the respective conventional coil and that this relation can be expressed only in terms of the number of turns of the coils. Therefore, these components have a potential use in applications that need to avoid the use of a real capacitor and need to operate in a smaller resonant frequency, such as in wireless power transfer systems, for example. In a similar way, the self‐inductances of closed‐ and open‐bifilar coils are also compared with those of conventional coils with the same dimensions. It is also shown that the SRF of closed‐ and open‐bifilar coils are approximately the same for practical values of the quality factor and that their impedance behaves as series and parallel RLC circuits. Practical experiments are conducted validating the developed theory.
Informatics in Radiology Problem-centric Organization and Visualization of Patient Imaging and Clinical Data 1

A patient’s electronic medical record contains a large amount of un-structured textual information. As patient records become increasingly dense owing to an aging population and increased occurrence of chronic diseases, a tool is needed to help organize and navigate patient data in a way that facilitates a clinician’s ability to understand this information and that improves efficiency. A system has been developed for physicians that summarizes clinical information from a patient record. This system provides a gestalt view of the patient’s record by organizing information about each disease along four dimensions (axes): time (eg, disease progression over time), space (eg, tumor in left frontal lobe), existence (eg, certainty of existence of a finding), and causality (eg, response to treatment). A display is generated from information provided by radiology reports and discharge summaries. Natural language processing is used to identify clinical abnormalities (problems, symptoms, findings) from these reports as well as associated properties and relationships. This information is presented in an integrated format that organizes extracted findings into a problem list, depicts the information on a timeline grid, and provides direct access to relevant reports and images. The goal of this system is to improve the structure of clinical information and its presentation to the physician, thereby simplifying the information retrieval and knowledge discovery necessary to bridge the gap between acquiring raw data and making an informed diagnosis.
Nerve Growth Factor Regulates the Expression and Activity of p33Cdl and p34cd' Kinases in PC12 Pheochromocytoma Cells

In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels Of p33cdk2 and p34cdc2, two key regulators of cell cycle progression. The decrease in p33Cd 2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA p34Cdc2, cyclinB-p34cdc2, cyclinE-p33c ,2 and cyclinA-p33cdk2 kinases. The decline in p33Cdk and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140rk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of pl4 Ok and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33Cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation.
Cooperative Position Prediction: Beyond Vehicle-to-Vehicle Relative Positioning

Reliable and accurate relative position prediction techniques are vital to the integrity of cooperative intelligent transportation systems (C-ITS) because most C-ITS safety applications should constantly access a (relative-) localization mechanism that satisfies not only a certain (relative-) position accuracy range but also a minimal computational complexity. A global navigation satellite system (GNSS) coupled with dedicated short-range communications (DSRC) links is a candidate for the localization system required for vehicular relative positioning. The vehicle-to-vehicle (V2V) exchange of safety-related data such as raw GNSS measurements, as accurate and frequent as possible, via DSRC links allows the vehicular localization mechanism to maintain real-time relative positioning (RRP) vectors. However, V2V DSRC safety messages may include inaccurate positioning data or may fast become outdated, and/or DSRC links may occasionally fail due to various adverse scenarios including network overheads that drop the bandwidth of vehicular ad-hoc networks. Hence, each DSRC-enabled vehicle may not necessarily know the latest positioning data of neighboring vehicles. This calls upon reliable and accurate relative position prediction mechanisms to cover the DSRC-related deficiencies of relative positioning. This paper, at first, studies the benefits of a terrestrial communications system complementing DSRC-based V2V RRP and then considers position prediction techniques suitable for V2V RRP and examines a few existing solutions and makes a detailed comparison based on a set of required positioning performance parameters for vehicle safety application.