Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental change in GABAA receptor desensitization kinetics and its role in synapse function in rat cortical neurons

We examined the maturation of GABAA receptor synapses in cortical pyramidal neurons cultured from embryonic rats. The decay kinetics of GABAA receptor‐mediated miniature postsynaptic currents (mPSCs) were compared with those of responses evoked by GABA in excised membrane patches. Fast perfusion of 1 or 10 mM GABA on membrane patches evoked currents with different desensitizing time courses in young and old neurons. For neurons older than 4 days in vitro (DIV), GABAA currents had a fast component of desensitization (median ≈ 3 ms) seldom seen in patches from younger neurons. In contrast, mPSCs exhibited a substantial fast component of decay at 2–4 DIV that became more prominent with further development although the median value of its time constant remained unchanged. The selective α3 subunit positive modulator SB‐205384 had no effect on mPSCs at any time in vitro but potentiated extrasynaptic activity. This suggests that synapse maturation does not proceed by a gradual exchange of early embryonic GABAA receptor subforms for adult forms. At all ages, the kinetic properties of mPSCs were heterogeneous. This heterogeneity extended to the level of mPSCs from single neurons and may be a normal aspect of synaptic functioning. These results suggest that inhibitory synapses in developing neurons are capable of selectively capturing GABAA receptors having fast desensitization kinetics. This functional preference probably reflects the developmental turning point from an inwardly looking trophic capacity of embryonic GABAA receptors to a role concerned with information processing.
Growth of Science How the Growth of Science Ended Theory Change

This paper outlines a defense of scientific realism against the pessimistic meta-induction which appeals to the phenomenon of the exponential growth o f science. Here, scientific realism is defined as the view that our current successful scientific the ories are mostly approximately true, and pessimistic meta-induction is the argument that projects th e occurrence of past refutations of successful theories to the present concluding that many or mos t current successful scientific theories are false. The defense starts with the observation that at lea s 80% of all scientific work ever done has been done since 1950, proceeds with the claim that pract ically all of our most successful theories were entirely stable during that period of time, and con cludes that the projection of refutations of successful theories to the present is unsound. In addi tion to this defense, the paper offers a framework through which scientific realism can be compared wi th two types of anti-realism. The framework is also of help to examine the relationships between t h se three positions and the three main arguments offered respectively in their support (No-mir acle argument, pessimistic meta-induction, underdetermination).
Autoantibody Against ICA512 Did Not Improve Test Sensitivity for Slowly Progressive IDDM in Adults

only 1) if symptoms suggestive of hypoglycemia were of sufficient severity to seek medical advice; 2) if whole venous blood glucose levels were <2.5 mmol/1 at the time of symptoms; 3) if symptoms were relieved by eating carbohydrate. Of the 162 nondiabetic twins, 5 sought medical advice with hypoglycemic symptoms relieved by carbohydrate; hypoglycemia was confirmed on extensive testing in only 3 of them. All 3 subjects were twins of IDDM patients, 2 of these 3 twins subsequently developed diabetes. However, in one (S.C.), hypoglycemia was probably due to self-injection of insulin since she was admitted unconscious to the hospital at age 15 years with a blood glucose of 0.9 mmol/1 and normal serum Cpeptide level (0.049 nmol/1), despite an extremely high serum insulin level (1,380 pmol/1) indicating an exogenous source of insulin. This twin already had impaired glucose tolerance, islet cell antibodies (ICA), and glutamic acid decarboxylase 65 (GAD65) antibodies but had no insulin autoantibodies; IDDM developed at age 19 years. Thus, spontaneous clinical hypoglycemia was detected in just 1 of the 55 twins who developed diabetes under observation. This twin (VS.), started having symptomatic hypoglycemia after large meals (blood glucose on three occasions of 2.0 mmol/1) at age 34 years. She developed diabetes 4 years later with GAD65 antibodies and decreased first-phase insulin response. Her diabetes is controlled by diet alone at present. The third twin (C.A.) with documented hypoglycemia (blood glucose on three occasions <2.5 mmol/1) remains nondiabetic without antibodies and is, we estimate, unlikely to develop diabetes. Symptoms of hypoglycemia before the onset of NIDDM have been reported to be common (5) but alone are not sufficient to establish the diagnosis. Furthermore, low blood glucose levels may occur without symptoms (6). By strict diagnostic criteria, spontaneous hypoglycemia occurred in only 2 of 162 twins (1.2%) and then only in twins of IDDM patients. Extrapolating from our observations in twins, we conclude that clinical hypoglycemia, whether fictitious or real, is not a feature of the prediabetic period.
Angina and Other Risk Factors in Patients With Cardiac Diseases Undergoing Noncardiac Operations

Six hundred eighty-eight consecutive patients with cardiac diseases or who wer, ′older than 70 yr of age, all of whom were undergoing noncardiac operations, were studied. Twenty-four preopeiative risk factors were analyzed for the outcome of perioperative myocardial infarction (PMI) or cardiac death using stepwise logistic regression. Old age, emergency operation, angina, previous myocardial infarction, electrocardiographic signs of ischemia, type of surgical procedure, and hypokalemia were identified as individual factors useful in predicting outcome. Thirty-two patients (4.65%) developed PMI. Seven of these 32 patients (21.9%) and eight more patients without PMI—a total of 15 patients (2.2%)—died a cardiac death. Nonfatal but serious complications occurred in 23% of the patients. Patients undergoing emergency operations and patients with chronic stable angina, previous myocardial infarction, and electrocardio- graphic signs of ischemia were found to be at increased risk for PMI and cardiac death.
Resiliency and success in adults with Moebius syndrome.

OBJECTIVE This study asked selected mature individuals with Moebius syndrome to discuss the sources of strength and resiliency that allowed them to achieve professional and personal success. DESIGN Adults with Moebius syndrome were selected in a nonrandom manner based primarily on their affiliation with the Moebius Syndrome Foundation. Following a letter from the author describing the objective, the subjects were interviewed by telephone and were encouraged to respond at length. PARTICIPANTS Eighteen adults (aged 29 to 70 years) responded. All were or had been gainfully employed in a variety of professional or vocational positions. RESULTS The respondents reported the following as major sources of resiliency and success: family support, faith, humor, sense of self, special skills, determination, and networking. CONCLUSIONS The recognition and reinforcement of strengths and resiliences in younger patients may help maximize their professional and personal success as adults.
The role of reactive oxygen and nitrogen species in cellular iron metabolism

The catalytic role of iron in the Haber–Weiss chemistry, which results in propagation of damaging reactive oxygen species (ROS), is well established. In this review, we attempt to summarize the recent evidence showing the reverse: That reactive oxygen and nitrogen species can significantly affect iron metabolism. Their interaction with iron-regulatory proteins (IRPs) seems to be one of the essential mechanisms of influencing iron homeostasis. Iron depletion is known to provoke normal iron uptake via IRPs, superoxide and hydrogen peroxide are supposed to cause unnecessary iron uptake by similar mechanism. Furthermore, ROS are able to release iron from iron-containing molecules. On the contrary, nitric oxide (NO) appears to be involved in cellular defense against the iron-mediated ROS generation probably mainly by inducing iron removal from cells. In addition, NO may attenuate the effect of superoxide by mutual reaction, although the reaction product—peroxynitrite—is capable to produce highly reactive hydroxyl radicals.
Creation of an above-the-knee amputation stump after hip disarticulation for severe periprosthetic infection and fracture. A report of two cases.

R ecurrent infection at the site of a total joint replacement secondary to a highly resistant organism in combination with a periprosthetic fracture presents a treatment challenge. To salvage this situation, a hip disarticulation or a type-B-IIIb rotationplasty, as described by Winkelmann, are the only viable surgical techniques reported in the literature of which we are aware1,2. The purpose of our report is to present an alternative surgical technique for creating an above-the-knee stump with use of a modular proximal femoral replacement with a bipolar head after hip disarticulation. The procedure consists of two stages. Following implant removal and debridement, an antibiotic-impregnated polymethylmethacrylate spacer is implanted. After the proximal part of the femur is removed, the greater trochanter is fixed to the spacer to prevent shortening of the gluteal muscles. During this first stage, either an immediate hip disarticulation with reconstruction of an above-the-knee stump is performed (Case 1) or the extremity is preserved (Case 2). The former should be considered for a patient with a severe periprosthetic fracture, severe vascular compromise distally, or inadequate soft-tissue coverage. Following treatment with intravenous antibiotics, the patient is managed with reconstruction of an above-the-knee stump with use of a modular proximal femoral replacement implant (MUTARS; Implantcast, Buxtehude, Germany) and a bipolar head. In general, the original lateral incision is preferred and distally a fish-mouth skin incision is used for the amputation. The end of the reconstruction is covered with an anterior flap that is large enough so that the scar lies posteriorly. However, a reconstruction with use of a medial or an anterior flap is possible if the lateral soft tissues are severely scarred3. Depending on the quality of the soft-tissue coverage, every effort should be made to preserve a stump length of at least 25 cm, …
Understanding Attention-Deficit/Hyperactivity Disorder from Childhood to Adulthood

Abstract Attention deficit/hyperactivity disorder (ADHD) is among the most common neurobehavioral disorders requiring treatment in children and adolescents. The disorder is often chronic, with prominent symptoms and impairment spanning into adulthood. It is often associated with co-occurring disorders, including disruptive, mood, anxiety, and substance abuse disorders. The diagnosis of ADHD is clinically established by review of symptoms and impairment. The biological underpinning of the disorder is supported by genetic, neuroimaging, neurochemistry, and neuropsychological data. All aspects of an individual's life need to be considered in the diagnosis and treatment of ADHD. Multimodal treatment includes educational, family, and individual support. Psychotherapy alone and in combination with medication is helpful for treating patients with ADHD and comorbid disorders. Pharmacotherapy, including stimulants, noradrenergic agents, α-agonists, and antidepressants, plays a fundamental role in the long-term management of ADHD.
Writing ourselves into being: A review of the Canadian Journal for the Study of Adult Education/La Revue Canadianne pour l'Étude de l'Éducation des adultes

Examines and analyzes the 22-volume publication history of The Canadian Journal for the Study of Adult Education/la Revue canadianne pour l’etude de l’education des adultes (CJSAE/RCEEA). Three different approaches are applied: quantitative history of publication trends, e-mail interviews with five former editors, and analysis of Canadian Association for the Study of Adult Education (CASAE) documents relating to the journal. The author concludes that the journal has been shaped by different layers of expectations and influence, including three tensions of the United States vs. Canada, francophone vs. anglophone Canada, and east vs. west. Overall, the journal has contributed significantly to the formation of the academic field of adult education in Canada. Resume Cet article examine et analyse l'historique en 22 volumes de la CJSAE/RCEEA. Trois approches differentes sont employees a cet effet: l’analyse quantitative des tendances historiques de publication, l’analyse qualitative d’entretiens effectues par email avec 5 anciens editeurs, et l’etude de documents auxiliaires qui traitent de la revue, publies par la CASAE/ACEEA. L’auteur conclut que la revue a ete faconnee par des influences et attentes a des niveaux differents, comprenant, entre autres, trois tensions cles: la tension canado- americaine, la tension est-ouest et la tension anglophone- francophone. Dans l’ensemble, la revue a largement contribue a l’etablissement du domaine de recherche sur l’education des adultes au Canada
Changes in coping strategies, social support, optimism and health-related quality of life following traumatic brain injury: A longitudinal study

Primary objective: To study longitudinal changes in psychological coping strategies, social support, life orientation and health-related quality of life in the late period after traumatic brain injury (TBI). Subjects: Thirty-one patients with TBI who were first investigated on average 2.3 years after injury and were prospectively followed on average 5.7 years later. Methods: Estonian versions of the COPE-D Test, the Brief Social Support Questionnaire, the Life Orientation Test and the RAND-36 questionnaire. Results: During the late follow-up period health-related quality of life and resuming work did not improve significantly. Persons with TBI reported an increase in seeking social/emotional support (p < 0.05), frequent use of avoidance-oriented styles and reduced use of task-oriented styles. This was accompanied by low social support and low satisfaction with support, both of which were associated with health-related quality of life and resuming work after TBI. Although the patients had become more optimistic (p < 0.05), this did not correlate with their health status and social well-being. Conclusions: This prospective study revealed maladaptive changes in the profile of coping strategies and an increase in optimism. As social support, satisfaction with support and health-related quality of life did not improve, then rehabilitation, social and psychological support are continuously needed.
Unique catalytic properties dictate the enhanced function of p59fynT, the hemopoietic cell-specific isoform of the Fyn tyrosine protein kinase, in T cells

As a result of alternative splicing, the fyn gene encodes two different tyrosine protein kinase isoforms. While one protein (p59fynB) is abundantly expressed in the brain, the alternative product (p59fynT) is contained only in cells of hemopoietic lineages, especially T lymphocytes. Sequence analyses have revealed that these two isoforms differ exclusively within a stretch of 52 amino acids which overlaps the end of the Src homology 2 (SH2) motif and the beginning of the catalytic domain. Consistent with the idea that FynT provides a specialized function in hemopoietic cells, we have previously shown that expression of activated FynT molecules, but not that of activated FynB polypeptides, enhanced the antigen responsiveness of a mouse T-cell line (BI-141) (D. Davidson, L. M. L. Chow, M. Fournel, and A. Veillette, J. Exp. Med. 175:1483-1492, 1992). In this study, we examined the basis for the distinct signalling capabilities of the two Fyn isoforms in T lymphocytes. Our biochemical analyses revealed that FynT is more adept than FynB at promoting antigen receptor-triggered calcium fluxes. This phenomenon likely contributes to the improved biological function of FynT during antigen stimulation, as the calcium ionophore ionomycin partially rescued the inability of FynB to enhance antigen-induced lymphokine secretion. To establish the structural basis for these observations, we also created and analyzed a series of chimeras of FynT and FynB. These studies demonstrated that the distinct catalytic domain of FynT, and not its altered SH2 motif, is responsible for the improved ability to augment antigen responsiveness. Similarly, this sequence enhances the ability to mobilize cytosolic calcium in response to antigen receptor stimulation. Taken together, these data show that the distinct biological impacts of FynT and FynB in T cells are related to limited structural differences in the amino-terminal portion of their catalytic domains and that they reflect, at least in part, the greater ability of FynT to mobilize cytoplasmic calcium.
High dose cyclophosphamide with carboplatin: a tolerable regimen suitable for dose intensification in children with solid tumors.

PURPOSE To determine the hematopoietic and nonhematopoietic toxicity of a novel dose-intensive chemotherapy regimen for the treatment of children with relapsed solid tumors. PATIENTS AND METHODS The time to hematopoietic recovery and toxicity experienced during 46 courses of high-dose cyclophosphamide (4.0 g/m2), MESNA, and carboplatin (400 mg/m2) with granulocyte colony stimulating factor (G-CSF) support in 14 children with recurrent solid tumors was reviewed. RESULTS All patients developed grade 4 neutropenia and thrombocytopenia. Recovery to an absolute neutrophil count (ANC) of 500/microliter and platelet count of 50,000/microliter occurred at a median of 15 days and 23 days respectively. Median time to ANC > 1,000/microliter and platelets > 100,000/microliter was 27 days. Hospitalization for fever and neutropenia occurred during 35 of 46 courses, with documented bacteremia in six courses. There was no grade II or greater nonhematopoietic organ toxicity. Responses (CR + PR) were observed in 6 of 11 evaluable patients. CONCLUSIONS These data suggest that this regimen is tolerable in heavily pretreated children with solid tumors with myelosuppression as the primary toxicity. Due to the lack of significant nonhematopoietic toxicity, this is a good candidate regimen for dose escalation using peripheral blood progenitor cell infusions and deserves further evaluation for efficacy in children with both recurrent and newly diagnosed high-risk solid tumors.
A rigorous statistical framework for spatio‐temporal pollution prediction and estimation of its long‐term impact on health

&NA; In the United Kingdom, air pollution is linked to around 40000 premature deaths each year, but estimating its health effects is challenging in a spatio‐temporal study. The challenges include spatial misalignment between the pollution and disease data; uncertainty in the estimated pollution surface; and complex residual spatio‐temporal autocorrelation in the disease data. This article develops a two‐stage model that addresses these issues. The first stage is a spatio‐temporal fusion model linking modeled and measured pollution data, while the second stage links these predictions to the disease data. The methodology is motivated by a new five‐year study investigating the effects of multiple pollutants on respiratory hospitalizations in England between 2007 and 2011, using pollution and disease data relating to local and unitary authorities on a monthly time scale.
Going Unconstrained with Rolling Shutter Deblurring ( Supplementary Material )

As mentioned in section 1 in the main paper, our method advances the state-of-the-art in RS deblurring, as it can deal with wide-angle configuration, unconstrained ego-motion and unconstrained shutter, without the need for timing information. Here, we further elaborate the significance of these problems that we have addressed in our work. Unconstrained Focal-length: The PSFs provided in Fig. 2(b), which illustrates the importance of inplane rotations for wide-angle systems, is created using a focal length of 29 mm and real hand-held trajectory #39 in [6]. The full set of PSFs is provided in Fig. S1. We give in Fig. S2 focallength settings of some popular CMOS imaging devices. It is clearly evident from the figure that wide-angle configurations are indeed important in photography (and predominant in cell-phones and drone cameras). However, the state-ofthe-art RS-BMD [11] works only for narrow-angle settings. Hence, it is important to accommodate wide-angle settings. Unconstrained Ego-motion: Even though a polynomial function can reasonably model human camera shake, RS F o c a l le n g th ( 3 5 m m )
Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease.

BACKGROUND Vascular risk factors play a role in the development of dementia, including Alzheimer disease (AD). However, little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia. OBJECTIVE To investigate the relation between midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD. DESIGN AND SETTING Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years participated in the reexamination in 1998. MAIN OUTCOME MEASURES Dementia and AD. RESULTS Obesity at midlife (body mass index>30 kg/m2) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables (odds ratio [OR], 2.4 [95% confidence interval (CI), 1.2-5.1]). The association was somewhat modified by further adjusting for midlife blood pressure, total cholesterol level, and smoking (OR, 2.1 [95% CI, 1.0-4.6]) and also for apolipoprotein E genotype and history of vascular disorders (OR, 1.9 [95% CI, 0.8-4.6]). Midlife obesity, high total cholesterol level, and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor, and they increased the risk additively (OR, 6.2 for the combination). CONCLUSIONS Obesity at midlife is associated with an increased risk of dementia and AD later in life. Clustering of vascular risk factors increases the risk in an additive manner. The role of weight reduction for the prevention of dementia needs to be further investigated.
Reducing COD level on oily effluent by utilizing biosurfactant-producing bacteria

Two bacteria isolated from crude oil contaminated soil, Pantoea agglomerans and Planococcus citreus, produced biosurfactants utilizing 1.5% of kerosene and olive oil as the sole carbon sources, respectively. The bacteria and the biosurfactants produced were introduced to oily effluent, arising from margarine and soap industry. Emulsification activities were determined by increases in the absorbance of the oil-in-water emulsions at 610 nm, whereas the water-in-oil emulsions were expressed as the height (cm) of the emulsion layers formed. The 72 h incubation experiment resulted in a COD (Chemical Oxygen Demand) reduction of 76% with Planococcus citreus strain and 70% with Pantoea agglomerans.The COD reduction with bacterial biosurfactants was over 50% in 24 h of incubation. The COD reduction showed that these strains and the surfactants produced could be used in bioremediation processes.