Miracle-dz/UniFAR-FTUs huggingface dataset:
Reevaluation of Neurodegeneration in lurcher Mice: Constitutive Ion Fluxes Cause Cell Death with, Not by, Autophagy

The lurcher (Lc) mice have served as a valuable model for neurodegeneration for decades. Although the responsible mutation was identified in genes encoding δ2 glutamate receptors (GluD2s), which are predominantly expressed in cerebellar Purkinje cells, how the mutant receptor (GluD2Lc) triggers cell death has remained elusive. Here, taking advantage of recent knowledge about the domain structure of GluD2, we reinvestigated Lc-mediated cell death, focusing on the “autophagic cell death” hypothesis. Although autophagy and cell death were induced by the expression of GluD2Lc in heterologous cells and cultured neurons, they were blocked by the introduction of mutations in the channel pore domain of GluD2Lc or by removal of extracellular Na+. In addition, although GluD2Lc is reported to directly activate autophagy, mutant channels that are not associated with n-PIST (neuronal isoform of protein-interacting specifically with TC10)–Beclin1 still caused autophagy and cell death. Furthermore, cells expressing GluD2Lc showed decreased ATP levels and increased AMP-activated protein kinase (AMPK) activities in a manner dependent on extracellular Na+. Thus, constitutive currents were likely necessary and sufficient to induce autophagy via AMPK activation, regardless of the n-PIST–Beclin1 pathway in vitro. Interestingly, the expression of dominant-negative AMPK suppressed GluD2Lc-induced autophagy but did not prevent cell death in heterologous cells. Similarly, the disruption of Atg5, a gene crucial for autophagy, did not prevent but rather aggravated Purkinje-cell death in Lc mice. Furthermore, calpains were specifically activated in Lc Purkinje cells. Together, these results suggest that Lc-mediated cell death was not caused by autophagy but necrosis with autophagic features both in vivo and in vitro.
Evaluation of Ophthacare® eye drops—a herbal formulation in the management of various ophthalmic disorders

An open prospective multicentre clinical trial was conducted in patients suffering from various ophthalmic disorders namely, conjunctivitis, conjunctival xerosis (dry eye), acute dacryocystitis, degenerative conditions (pterygium or pinguecula) and postoperative cataract patients with a herbal eye drop preparation (Ophthacare®) containing basic principles of different herbs which have been conventionally used in the Ayurvedic system of medicine since time immemorial. These include Carum copticum, Terminalia belirica, Emblica officinalis, Curcuma longa, Ocimum sanctum, Cinnamomum camphora, Rosa damascena and meldespumapum. These herbs reportedly possess antiinfective and antiinflammatory properties. The present study was undertaken to elucidate the role of this herbal product in a variety of eye ailments. Side effects, if any, were noted during the study. An improvement was observed with the treatment of the herbal eye drop treatment in most cases.
Molecular genetic prenatal diagnosis for a case of autosomal recessive spondylocostal dysostosis

Autosomal recessive spondylocostal dysostosis type 1 (ARSCD1) is a member of the heterogeneous group of disorders termed the spondylocostal dysostoses that are characterized by multiple vertebral segmentation defects and rib anomalies. In these patients, the entire vertebral column is malformed and is replaced by multiple hemivertebrae giving rise to truncal shortening, abdominal protrusion and non‐progressive spinal curvature. Genetic studies have shown that some cases of ARSCD are due to mutations in the somitogenesis gene, Delta‐like 3 (DLL3), that encodes a ligand for the Notch signalling pathway—ARSCD type 1. To date, 17 different DLL3 gene mutations have been reported. A consanguineous family of Turkish origin with ARSCD type 1 due to a homozygous DLL3 mutation requested genetic prenatal diagnosis. Using DNA from a chorionic villus sample, both linkage analysis of the DLL3/19q region and direct sequencing for the familial mutation demonstrated that the unborn fetus was an unaffected carrier. This is the first case of molecular genetic prenatal diagnosis in any form of SCD. Copyright © 2003 John Wiley & Sons, Ltd.
Comparative evaluation of lesion detectability for 6 PET imaging platforms using a highly reproducible whole-body phantom with (22)Na lesions and localization ROC analysis.

UNLABELLED The lesion detectability performance of 6 PET imaging platforms has been compared using a highly reproducible whole-body phantom and localization receiver operating characteristic (LROC) analysis. METHODS A realistic whole-body phantom consisting of brain, thorax with lungs and liver, and pelvis with bladder was assembled and outfitted with 27 semipermanent (22)Na lesions of various sizes and activity concentrations. The background compartments were reproducibly filled with (18)F solutions. The phantom was imaged under the condition of equal emission scan time on 7 PET platforms: Advance, HR+, HR961, C-PET, IRIX, MCD, and AXIS. Imaging data were processed using manufacturer-supplied software and defaults, and LROC evaluation was performed using 11 human observers. RESULTS Near-nominal counting rates were obtained for the NaI systems, and the bismuth germanate (BGO) systems were operated well below nominal counting rates. The BGO systems provided the highest lesion detection performance, followed by the large-area dedicated NaI system, and hybrid PET gamma cameras. Lesion detectability was highly dependent on lesion size, with all systems exhibiting similar performance for 16-mm lesions but differentiated performance for lesions < or =12 mm. CONCLUSION Reconstruction methodology can have a significant effect on lesion detectability. PET lesion detectability performance is correlated with system cost and imaging characteristics. For a particular imaging task, care should be taken to ensure that the scanner being used is appropriate and that the scan time is adjusted accordingly to ensure good lesion detectability.
Preservice Teachers

Abstract This study sought to understand how a group of preservice teachers, before and after participating in an innovative technology component of a teacher preparation program, envisioned the use of technology within their future classroom. Secondly, this study sought to understand preservice teachers’ ability to identify content-based technology uses for their anticipated teaching position, after completion of student teaching. The results showed that preservice teachers developed, to a limited extent, a “thinking with technology” perspective. Issues that pertained to the limited development of this perspective in the majority of the participants included: (a) the role of cooperating teachers, (b) the availability of technology integration models, (c) the participants’ abilities to generate technology-supported lessons, (d) instructional approaches to technology integration, and (e) their inclination to teach technology-supported lessons without a thorough understanding of the technology.
Gender and bipolar illness.

BACKGROUND For major depression and schizophrenia, gender differences have been reported in symptom expression and course of illness. Gender differences in bipolar disorder are becoming increasingly apparent, but have been less studied. Research data on these differences will help determine whether gender is important in influencing illness variables such as course, symptom expression, and likelihood of comorbidity. METHOD Charts of 131 patients (63 women and 68 men) with a DSM-IV diagnosis of bipolar disorder admitted to the University of California Los Angeles Mood Disorders Program over a 3-year period were reviewed to gather data on demographic variables and course of illness and to assess differences in the illness across genders. RESULTS No significant gender differences were found in the rate of bipolar I or bipolar II diagnoses, although women were overrepresented in the latter category. Also, no significant gender differences emerged in age at onset, number of depressive or manic episodes, and number of hospitalizations for depression. Women, however, had been hospitalized significantly more often than men for mania. Further, whereas bipolar men were significantly more likely than bipolar women to have a comorbid substance use disorder, women with bipolar disorder had 4 times the rate of alcohol use disorders and 7 times the rate of other substance use disorders than reported in women from community-derived samples. CONCLUSION For bipolar disorder, course of illness variables such as age at onset and number of affective episodes of each polarity do not seem to differ across genders. Women, however, may be more likely than men to be hospitalized for manic episodes. While both men and women with the illness have high rates of comorbidity with alcohol and other substance use disorders, women with bipolar disorder are at a particularly high risk for comorbidity with these conditions.
THE INFLUENCE OF RESOURCE LOSS, SOCIAL SUPPORT, AND SELF ESTEEM ON THE SEXUAL RISK BEHAVIORS OF LOW INCOME URBAN AFRICAN AMERICAN WOMEN WITH HISTORIES OF ABUSE

The purpose of this study was to examine the relationship between resource loss, social support, self esteem, and the sexual risk behaviors of low income urban African American women with abuse histories. The present study was a secondary data analysis from an experimental HIV prevention intervention with low income urban women with abuse histories in a mid-western US city and only examined data collected from African American women at pretest and posttest between 2002 and 2004. Participants in this sample (n = 442) were sexually active low income urban African American women between ages 16-29 with histories of abuse (adult rape, childhood physical abuse, and childhood sexual abuse). Participants were recruited from two women‘s health clinics serving low income urban women and answered questions about their levels of resource loss, social support, self esteem, sexual behaviors, childhood and adult abuse histories, drug and alcohol use, their perception of AIDS risk, levels of depression and post traumatic disorder, and socio demographic characteristics. SPSS was used to analyze the data in this study. The instrument data were analyzed using hierarchical multiple regression and binary logistic regression. Eight predictors were used to predict sexual risk behavior represented by percentage condom use and having a recent STD in the past three months. Hierarchical regression results
Demonstration of Low $V_{t}$ Ni-FUSI N-MOSFETs With SiON Dielectrics by Using a $\hbox{Dy}_{2}\hbox{O}_{3}$  Cap Layer

This letter reports a novel approach to achieve low threshold voltage (Vt) Ni-fully-silicide (FUSI) nMOSFETs with SiON dielectrics. By using a dysprosium-oxide (Dy<sub>2</sub>O<sub>3</sub>) cap layer with a thickness of 5 Aring on top of the SiON host dielectrics, V<sub>t,lin</sub> of 0.18 V for long-channel devices (L<sub>g</sub> = 1 mum) using NiSi-FUSI electrode is obtained, satisfying the high-performance device requirements. The Vt modulation due to the Dy<sub>2</sub>O<sub>3</sub> cap layer is also maintained in the short-channel devices (with an L<sub>g,min</sub> of 90 nm as demonstrated in this letter). In particular, approximately 150times reduction in gate leakage current is seen while preserving the dielectric capacitance equivalent thickness after adding the Dy<sub>2</sub>O<sub>3</sub> cap layer on SiON dielectrics, likely due to a high-k layer (DySiON) formation during device source/drain activation process. We also report that the Dy<sub>2</sub>O<sub>3</sub> layer does not vitally degrade the device reliability, such as positive-bias temperature instability and time-dependant dielectrics breakdown.
Improvement of extraction and processing of RNA from renal biopsies.

BACKGROUND Assessment of mRNA levels has the potential to predict renal outcome. The objective of this study was to optimize several steps in the protocol for obtaining cDNA from routine clinical kidney biopsy material. METHODS RNA integrity was compared between different methods for extraction of RNA, synthesis of cDNA, and storage of renal tissue. Hereby, RNAlater, an RNA-preserving compound, was tested for implementation in a protocol for renal biopsies that combines routine histology and RNA expression studies. Gel electrophoresis and real-time polymerase chain reactions (PCR) were outcome parameters for assessment of RNA integrity. RESULTS The Trizol method rendered higher RNA yields from fresh renal tissue than the NP40 method and RNeasy spin columns. RNA yields were not affected when renal tissue was stored at -70 degrees C for up to 2 months in phosphate-buffered saline (PBS). cDNA levels obtained using avian myeloblastosis virus (AMV) reverse transcriptase (RT) were at least twice as high as those obtained with Sensiscript and Superscript RT. RNAlater maintained RNA integrity in whole renal cortex stored at 4 degrees C for up to 3 months. Dissection of small biopsies in RNAlater rendered similar RNA yields in comparison with dissection in PBS, but the yield of glomeruli from the cortices was 50% lower (P < 0.005). Integrity of RNAlater-treated tissue, evaluated by light microscopy and immunofluorescence, was diminished. CONCLUSION This study shows optimization of several steps in the protocol for extraction and handling of RNA in renal cortical tissue. RNA extraction and cDNA synthesis can be optimized by the use of the Trizol method and AMV RT, respectively. RNAlater is beneficial for preserving RNA integrity in whole renal cortex during storage and processing, but is not suitable for implementation in routine diagnostic histologic stainings combined with RNA expression studies in dissected biopsy material.
Cirrus parametrization and the role of ice nuclei

A parametrization of cirrus clouds formed by homogeneous nucleation is improved so that it can be used more easily in general‐circulation models (GCMs) and climate models. The improved parametrization is completely analytical and requires no fitting of parameters to models or measurements; it compares well with full microphysical model results even when monodisperse aerosol particles are used in the parametrization to determine cirrus ice‐crystal number densities. However, the presence of ice nuclei in the atmosphere can modify the formation of cirrus clouds. If sufficient ice particles have been generated by heterogeneous nucleation, the saturation ratio of the air parcel will never reach that required for homogeneous nucleation. We calculate the critical number density of ice nuclei, above which homogeneous nucleation will be suppressed. The critical number density depends on the temperature, the updraught velocity, and the supersaturation at which ice nuclei activate. The theory points to key uncertainties in our observations of ice nuclei in the upper troposphere; for ice nuclei that activate at relatively low supersaturations, number density is more important than a precise knowledge of the activation supersaturation. Overall, the theory provides a general framework within which to interpret observations and the results of full microphysical cloud models. The theory can provide analytical test cases as benchmarks for the testing of models in development, and can be implemented itself into larger‐scale atmospheric models, such as GCMs. Copyright © 2005 Royal Meteorological Society
Interpersonal strategy, attachment security and social status among Chinese children in the initial period of secondary school

This study examined the influences of peer interpersonal strategy and secure attachment on social status in peer contexts in the initial period of secondary school in China. Two hundred and thirty-one new students in secondary schools (grade 6) were recruited in the first semester to complete measures of interpersonal strategies in the peer group, secure attachment to mother, social dominance, and sociometric nomination. The results indicated that both prosocial strategies and attachment security were positively correlated with social dominance and peer preference in peer group, whereas the coercive strategies were not correlated with social status. Implications and limitations of findings were discussed.
Serum Metabolomic Profiling of Piglets Infected with Virulent Classical Swine Fever Virus

Classical swine fever (CSF) is a highly contagious swine infectious disease and causes significant economic losses for the pig industry worldwide. The objective of this study was to determine whether small molecule metabolites contribute to the pathogenesis of CSF. Birefly, serum metabolomics of CSFV Shimen strain-infected piglets were analyzed by ultraperformance liquid chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) in combination with multivariate statistical analysis. In CSFV-infected piglets at days 3 and 7 post-infection changes were found in metabolites associated with several key metabolic pathways, including tryptophan catabolism and the kynurenine pathway, phenylalanine metabolism, fatty acid and lipid metabolism, the tricarboxylic acid and urea cycles, branched-chain amino acid metabolism, and nucleotide metabolism. Several pathways involved in energy metabolism including fatty acid biosynthesis and β-oxidation, branched-chain amino acid metabolism, and the tricarboxylic acid cycle were significantly inhibited. Changes were also observed in several metabolites exclusively associated with gut microbiota. The metabolomic profiles indicate that CSFV-host gut microbiome interactions play a role in the development of CSF.
Perpendicular-magnetic-anisotropy CoFeB racetrack memory

Current-induced domain wall motion in magnetic nanowires drives the invention of a novel ultra-dense non-volatile storage device, called “racetrack memory. ” Combining with magnetic tunnel junctions write and read heads, CMOS integrability and fast data access speed can also be achieved. Recent experimental progress showed that perpendicular-magnetic anisotropy (PMA) CoFeB could be a good candidate to build up racetrack memory and promise high performance like high-density (e.g., ∼1 F2/bit), fast-speed, and low-power beyond classical spin transfer torque memories. In this paper, we first present the design of PMA CoFeB racetrack memory and a spice-compatible model to perform mixed simulation with CMOS circuits. Its area, speed, and power dissipation performance has been simulated and evaluated based on different technology nodes.
Clinical Teaching and OSCE in Pediatrics

Abstract Emphasis is being given to early contact by medical students with patients, and curricula are being designed to address this trend. Although teaching of clinical skills mostly depends on the traditional “apprenticeship” model, there is insufficient supervision of students while they examine the patients. This leads to the lack of acquisition of good clinical skills and some patient-student frustrations during examination by inexperienced students. The problem is greater in pediatric departments. One way to overcome this is to observe the students while they take a history and do a physical examination and to give them feedback. On the other hand, objective structured clinical examinations (OSCEs) should be used more in pediatric examinations to make use of the steering effect such examinations have on student achievement. However, OSCEs should not be the only student assessment tool, but should be complemented by other examination methods.
Differential localization of carbachol‐ and bicuculline‐sensitive pontine sites for eliciting REM sleep‐like effects in anesthetized rats

Carbachol, a cholinergic agonist, and GABAA receptor antagonists injected into the pontine dorsomedial reticular formation can trigger rapid eye movement (REM) sleep‐like state. Data suggest that GABAergic and cholinergic effects interact to produce this effect but the sites where this occurs have not been delineated. In urethane‐anesthetized rats, in which carbachol effectively elicits REM sleep‐like episodes (REMSLE), we tested the ability of 10 nL microinjections of carbachol (10 mm) and bicuculline (0.5 or 2 mm) to elicit REMSLE at 47 sites located within the dorsal pontine reticular formation at the levels ‐8.00 to ‐10.80 from bregma (B) (Paxinos and Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego, 1997). At rostral levels, most carbachol and some bicuculline injections elicited REMSLE with latencies that gradually decreased from 242 to 12 s for carbachol and from 908 to 38 s for bicuculline for more caudal injection sites. As the latencies decreased, the durations of bicuculline‐elicited REMSLE increased from 104 s to over 38 min, and the effect was dose dependent, whereas the duration of carbachol‐elicited REMSLE changed little (104–354 s). Plots of REMSLE latency versus the antero‐posterior coordinates revealed that both drugs were maximally effective near B‐8.80. At levels caudal to B‐8.80, carbachol was effective at few sites, whereas bicuculline‐elicited REMSLE to at least B‐9.30 level. Thus, the bicuculline‐sensitive sites extended further caudally than those for carbachol and antagonism of GABAA receptors both triggered REMSLE and controlled their duration, whereas carbachol effects on REMSLE duration were small or limited by its concurrent REMSLE‐opposing actions.
Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms

Systemic inflammatory stimuli, such as infection, increase the risk of stroke and are associated with poorer clinical outcome. The mechanisms underlying the impact of systemic inflammatory stimuli on stroke are not well defined. We investigated the impact of systemic inflammation on experimental stroke and potential mechanisms involved. Focal cerebral ischemia was induced by intraluminal filament occlusion of the middle cerebral artery (MCAo). Brain damage and neurological deficit 24 h after MCAo were exacerbated by systemic lipopolysaccharide (LPS) administration. This exacerbation was critically dependent on interleukin (IL)-1, because coadministration of IL-1 receptor antagonist abolished the effect of LPS on brain damage. Systemic administration of IL-1 increased ischemic damage to a similar extent as LPS and also exacerbated brain edema. IL-1 markedly potentiated circulating levels of the acute phase proteins, serum amyloid A and IL-6, and the neutrophil-selective CXC chemokines, KC and macrophage inflammatory protein-2. Neutrophil mobilization and cortical neutrophil infiltration were aggravated by IL-1 before changes in ischemic damage. Neutropenia abolished the damaging effects of systemic IL-1. These data show for the first time that an acute systemic inflammatory stimulus is detrimental to outcome after experimental stroke and highlight IL-1 as a critical mediator in this paradigm. Our data suggest IL-1-induced potentiation of neutrophil mobilization via CXC chemokine induction is a putative mechanism underlying this effect. Our results may help to explain the poorer outcome in stroke patients presenting with infection and may have implications for neurodegenerative diseases involving neurovascular alterations, such as Alzheimer's disease, in which systemic inflammation can modulate disease progression.