Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in the Vasopressin Prohormone Involved in Diabetes Insipidus Impair Endoplasmic Reticulum Export but Not Sorting*

Familial neurohypophysial diabetes insipidus is characterized by vasopressin deficiency caused by heterozygous expression of a mutated vasopressin prohormone gene. To elucidate the mechanism of this disease, we stably expressed five vasopressin prohormones with a mutation in the neurophysin moiety (NP14G→R, NP47E→G, NP47ΔE, NP57G→S, and NP65G→V) in the neuroendocrine cell lines Neuro-2A and PC12/PC2. Metabolic labeling demonstrated that processing and secretion of all five mutants was impaired, albeit to different extents (NP65G→V ≥ NP14G→R > NP47ΔE ≥ NP47E→G > NP57G→S). Persisting endoglycosidase H sensitivity revealed these defects to be due to retention of mutant prohormone in the endoplasmic reticulum. Mutant prohormones that partially passed the endoplasmic reticulum were normally targeted to the regulated secretory pathway. Surprisingly, this also included mutants with mutations in residues involved in binding of vasopressin to neurophysin, a process implicated in targeting of the prohormone. To mimick the high expression in vasopressin-producing neurons, mutant vasopressin prohormones were transiently expressed in Neuro-2A cells. Immunofluorescence displayed formation of large accumulations of mutant prohormone in the endoplasmic reticulum, accompanied by redistribution of an endoplasmic reticulum marker. Our data suggest that prolonged perturbation of the endoplasmic reticulum eventually leads to degeneration of neurons expressing mutant vasopressin prohormones, explaining the dominant nature of the disease.
Computationally-effective wideband worst-case model of transmission line radiation

The analytical model for radiation of a rectilinear uniform transmission line placed above a conducting screen is proposed. The model is intended for diagnostics (express analysis) of unintentional interference in large complexes of radio and electronic equipment. The model makes it possible to compute the envelopes of the amplitude-frequency characteristics for electric and magnetic fields in any spatial point above the screen. Single wire above ground plane, coaxial and triaxial lines with various grounding configurations are considered. The model is based on replacement of the complicated transmission line by an equivalent (in terms of the radiated field) single wire over ground plane. Correctness of the proposed model was verified by comparison with numerical simulation results in the frequency band from 10 kHz to 2 GHz for lines of length from 5 cm to 10 m with various load and source impedances, the line height above the ground plane was varied from the radius of the line to 5 m, the observation point position was up to 5 m away from the center of the line in arbitrary direction.
The Parental Antagonism Theory of Language Evolution: Preliminary Evidence for the Proposal

Abstract Language as with most communication systems likely evolved by means of natural selection. Accounts for the genetieal selection of language can usually be divided into two scenarios, either of which used in isolation of the other appear insufficient to explain the phenomena: (1) there are group benefits from communicating, and (2) there are individual benefits from being a better communicator. In contrast, it is hypothesized that language phenotypes emerged during a coevolutionary struggle between parental genomes via genomic imprinting, which is differential gene expression depending on parental origin of the genetic element. It is hypothesized mat relaiedness asymmetries differentially selected for patrigene-caused language phenotypes to extract resources from mother (early in development) and matrigene-caused language phenotypes to influence degree of cooperativeness among asymmetric kin (later in development), This paper reports that imprinted genes have a high frequency of involvement in language phenotypes (∼36%), considering their presumed rarity in the human genome (∼2%). For example, two well-studied genes associated with language impairments (FOXP2 and UBE3A) exhibit parent-of-origin effects. Specifically, FOXP2 is putatively paternally expressed, whereas UBE3A is a maternally expressed d imprinted gene, it is also hypothesized that the more unique and cooperative aspects of human language emerged to the benefit of matrilineal inclusive fitness. Consistent with this perspective, it is reported here that the X-chromosome has higher involvement in loci that have associations with language than would be expected by chance. It is also reported, for the first time, that human and chimpanzee maternally expressed overlapping imprinted genes exhibit greater evolutionary divergence (in terms of the degree of overlapping transcripts) than paternally expressed overlapping imprinted genes. Finally, an analysis of global language patterns reveals that paternally but not maternally silenced Alu elements are positively correlated with language diversity. Furthermore, there is a much higher than expected frequency of Alu elements inserted into the protein-coding machinery of imprinted and X-chromosomal language loci compared with nonimprinted language loci. Taken together these findings provide some support for parental antagonism theory. Unlike previous theories for language evolution, parental antagonism theory generates testable predictions at the proximate (e.g., neurocognitive areas important for social transmission and language capacities), ontogenetic (e.g., the function of language at different points of development), ultimate (e.g., inclusive fitness), and phylogenetic levels (e.g., the spread of maternally derived brain components in mammals, particularly in the hominin lineage), thus making human capacities for culture more tractable than previously thought.
Incretin mimetics as a novel therapeutic option for hepatic steatosis

Abstract: Background: Fat accumulation in the liver or non‐alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes.
Therapy of acute hepatitis C

Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow‐up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta‐analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover.
Adverse drug reactions reporting: a questionnaire-based study on Egyptian pharmacists' attitudes following an awareness workshop.

RATIONALE, AIMS AND OBJECTIVES Hospital pharmacists can promote medication safety through spontaneous reporting of adverse drug reactions (ADRs). However, different educational interventions and different factors (socio-demographic and professional) have been implicated to influence the reporting process. The aims of this study were to assess the impact of pharmacovigilance awareness workshop on knowledge of hospital pharmacists; and to identify the main factors and barriers that influence ADRs reporting. METHODS Two validated self-administered questionnaires were distributed to pharmacists attending an awareness workshop (pre and post); and a telephone survey was completed three months after the workshop. ADR reports (yellow cards) received from participating pharmacists were monitored for six months, and analysed for quality (validity and seriousness) and reporter demographic and professional factors. RESULTS Two hundred and eighty-one pharmacists (95.25%) and 270 pharmacists (91.52%) completed pre- and post-workshop questionnaires respectively. A comparison of their knowledge of ADRs to report before and after the workshop showed significant difference (Wilcoxon test P < 0.05). Two hundred and four pharmacists (72.6%) completed the follow-up questionnaire, with lack of time, administrative barriers and inability to complete patient details being the most frequent reasons for not reporting. A total of 163 yellow cards were received from 49 pharmacists (17.44%) over 6 months, of which 126 reports (77.3%) were serious ADRs. Demographics of reporting pharmacists showed significance for completion of post-graduate studies, ministry of health hospitals and pharmacist post in hospital. CONCLUSION Despite pharmacists' adequate knowledge after the workshop, they failed to maintain consistent reporting. Addressing the barriers to reporting and the personal factors influencing the process may be needed.
GNU Radio Beacon Receiver (GRBR) observations of large-scale wave structure (LSWS) and equatorial spread F (ESF)

“GNU Radio Beacon Receiver (GRBR) is a new digital receiver based on GNU Radio and USRP (Universal Software Radio Peripheral) [Yamamoto, 2008]. In this paper, the GRBR observations of large-scale wave structure (LSWS) and the subsequent development of equatorial spread F (ESF) using total electron content (TEC) derived from the ground based reception of signals from the radio beacon on board C/NOFS (Communications/Navigation Outage Forecasting System) satellite are presented. The other evidences of LSWS include the ‘satellite traces’ observed in ionograms. These observations show that LSWS appears to play an important role in the development of ESF.
QoS-Enabled Improvements for the Network Mobility Protocol

The aim of this article is to introduce an approach to providing connectivity on public transport connecting to the wider Internet via heterogeneous networks and prioritizing traffic according to service classes. We present a packet prioritization for each service class: premium, intermediate and default. A railway scenario is considered as our case study to evaluate the prioritization mechanisms. Experiments using the NS-2 simulator are to implement and evaluate the model. Results are presented to show the effectiveness of the model for network mobility in heterogeneous environments.
Antioxidant Activity of Kohlrabi Leaf and Tuber

Ethanol, methanol, acetone and water extract of the leaves and tuber of fresh kohlrabi were evaluated their total phenolic contents and antioxidant activities. Total phenolic contents of leaf and tuber extracts ranged from 16.473-27.582 and 7.3223-8.303 mg GAE/g extract, respectively. The leaf extracts showed higher activity than tuber extracts at all antioxidant activity assays. The EC50 values of DPPH scavenging activity varied within 9.04−12.94 μg/mL for ethanol, methanol and acetone extracts of leaf while they varied within 16.69−21.93 μg/mL for tuber, respectively. However the leaf water extract was most effective extract with 80 %, 70 % and 65 % activities at 750 μg/mL extract concentration in terms of ferrous ion chelating ability, β-carotene bleaching activity and superoxide radical scavenging activity, respectively. The results obtained in this study indicate that kohlrabi leaf extracts are more potential source than tuber extracts as natural antioxidant.
PI-RADS Version 2: Detection of Clinically Significant Cancer in Patients With Biopsy Gleason Score 6 Prostate Cancer.

OBJECTIVE The purpose of this study was to analyze the utility of the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) in the detection of a clinically significant cancers in patients with prostate cancers with a biopsy Gleason score of 6. MATERIALS AND METHODS A group of 182 consecutively registered patients with biopsy-proven prostate cancer with a Gleason score of 6 underwent MRI and radical prostatectomy. Clinically significant cancer was surgically defined as Gleason score of 7 or greater, tumor volume of 0.5 cm3 or greater, or tumor category T3 or greater. Clinical parameters (prostate-specific antigen level, greatest percentage of biopsy core, and percentage of positive cores) and the PI-RADSv2 ratings by three independent readers (experienced readers 1 and 2, inexperienced reader 3) were investigated. Cutoffs and the diagnostic performance of PI-RADSv2 for clinically significant cancer were analyzed. RESULTS Clinically significant cancer was found in 87.4% (159/182) of patients. The cutoff PI-RADSv2 score for clinically significant cancer was 4 for readers 1 and 2 and 5 for reader 3. The AUCs were 0.829 and 0.853 for readers 1 and 2 (p < 0.001) and 0.602 for reader 3 (p = 0.067). For reader 1, sensitivity was 89.9% (143/159); specificity, 69.6% (16/23); positive predictive value, 95.3% (143/150); negative predictive value, 50.0% (16/32); and accuracy, 87.4% (159/182). The corresponding values for reader 2 were 81.1% (129/159), 82.6% (19/23), 97.0% (129/133), 38.8% (19/49), and 81.3% (148/182). For the experienced readers, 66.7-81.3% of patients with false-negative results had clinically significant cancers with tumor volume less than 1 cm3. CONCLUSION PI-RADSv2 may help experienced readers identify clinically significant prostate cancers in patients with a biopsy Gleason score of 6. However, some small (< 1 cm3) clinically significant cancers can be missed when PI-RADSv2 is used.
Interval Arithmetic for Pattern Tolerance Analysis of Parabolic Reflectors

An innovative analytic strategy for the estimation of the average pattern behavior of reflector antennas when surface deformations are present on the parabolic disc is proposed. Since measuring the surface deviations from a reference ideal shape is a complex task, the root-mean-square (rms) surface deformations are modeled as intervals and their impact on the power pattern as well as the sensitivity of the beam features is efficiently predicted by exploiting the rules of the interval arithmetic throughout interval analysis (IA). The result is the definition of closed-form relationships between the bounds (upper and lower values) of the radiated power pattern and the rms interval surface deformations. Uniformly and non-uniformly distributed perturbations of the ideal surface are analyzed to assess the effectiveness of proposed approach. Comparisons with state-of-the-art solutions are also carried out by varying the deformation thickness as well as the reflector geometry and illumination.
Issues Relating to the Usage and Conceptualization of Mental Health Constructs Employed by Gerontologists

A major intention of the article was to delineate and clarify issues related to the usage and conceptualization of mental health constructs commonly utilized by gerontologists. Conclusions were drawn to the effect that (a) meanings of mental health constructs cluster differently depending on the type of analysis employed, (b) happiness may be considered the most apposite representative of the array of mental health constructs employed by gerontologists, (c) happiness has been conceptualized either as containing current affect and dispositional components or current affect components only, (d) contemporary models of happiness favour neither the expansionist nor contractionist positions as a means of attaining happiness and, (e) questions as to the relative contributions to happiness of the affective and dispositional components represents an important problem for future research. A final intention of the article was to provide a speculative reconceptualization of the happiness construct.
The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

Background The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. Methods A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. Results A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). Conclusions A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.
Engineered blood and lymphatic capillaries in 3‐D VEGF‐fibrin‐collagen matrices with interstitial flow

In vitro endothelial cell organization into capillaries is a long standing challenge of tissue engineering. We recently showed the utility of low level interstitial flow in guiding the organization of endothelial cells through a 3‐D fibrin matrix‐containing covalently bound vascular endothelial growth factor (VEGF). Here this synergistic phenomenon was extended to explore the effects of matrix composition on in vitro capillary morphogenesis of human blood versus lymphatic endothelial cells (BECs and LECs). Different mixtures of fibrin and collagen were used in conjunction with constant concentrations of matrix‐bound VEGF and slow interstitial flow over 10 days. Interestingly, the BECs and LECs each showed a distinct preference in terms of organization for matrix composition: LECs organized the most extensively in a fibrin‐only matrix, while BEC organization was optimized in the compliant collagen‐containing matrices. Furthermore, the BECs and LECs produced architecturally different structures; while BECs organized in thick, branched networks containing wide lumen, the LECs were elongated into slender, overlapping networks with fine lumen. These data demonstrate the importance of the 3‐D matrix composition in facilitating and coordinating BEC and LEC capillary morphogenesis, which is important for in vitro vascularization of engineered tissues. Biotechnol. Bioeng. 2007;96: 167–176. © 2006 Wiley Periodicals, Inc.
Microtubule orientation and spacing within bundles is critical for long‐range kinesin‐1 motility

Cells rely on active transport to quickly organize cellular cargo. How cells regulate transport is not fully understood. One proposed mechanism is that motor activity could be altered through the architecture of the cytoskeleton. This mechanism is supported by the fact that the cytoskeletal network is tightly regulated in cells and filament polarity within networks dictates motor directionality. For instance, axons contain bundles of parallel microtubules and all cargos with the same motor species will move in the same direction. It is not clear how other types of networks, such as antiparallel bundles in dendrites, can regulate motor transport. To understand how the organization of microtubules within bundles can regulate transport, we studied kinesin‐1 motility on three bundle types: random‐polarity bundles that are close‐packed, parallel polarity bundles, and antiparallel polarity bundles that are spaced apart. We find that close‐packed bundles inhibit motor motion, while parallel arrays support unidirectional motion. Spacing the microtubules with microtubule‐associated proteins enhances run lengths. Our results indicate that microtubule bundle architecture dictates the motion of single motors and could have effects on cargo transport. © 2014 Wiley Periodicals, Inc.
Activation of protein kinase A is a pivotal step involved in both BMP‐2‐ and cyclic AMP‐induced chondrogenesis

We studied the roles of protein kinase A (PKA) activation and cyclic AMP response element binding protein (CREB) phosphorylation in chondrogenesis using serum‐free chicken limb bud micromass cultures as a model system. We showed the following points: (1) in micromass cultures, activation of PKA enhances chondrogenesis and increases the phosphorylation of CREB; (2) BMP‐2, a chondrogenic stimulator, increases PKA activity and the level of phosphorylated CREB (P‐CREB); (3) H8, a PKA inhibitor, inhibits chondrogenesis; (4) the chondrogenic activities of BMP‐2 and cAMP are suppressed by H8; and (5) long‐term TPA treatment (a protein kinase C (PKC) modulator) inhibits chondrogenesis and decreases the levels of CREB and P‐CREB. These results suggest that activation of PKA is a physiological event during chondrogenesis that is involved in the chondrogenic effects of both BMP‐2 and cyclic AMP (cAMP)‐dependent pathways. J. Cell. Physiol. 170:153–165, 1997. © 1997 Wiley‐Liss, Inc.