Miracle-dz/UniFAR-FTUs huggingface dataset:
Boron-Slow Neutron Capture Therapy of Gliomas

The most favorable among 140 boron compounds studied in mice, bearing gliomas, were checked for their toxicity in larger animals, and of these the six best were finally assayed in man for use in neutron capture therapy by analyses of tissue uptake during craniotomy and by toxicity and excretion studies in terminal glioma patients. An initial series of 16 patients were irradiated, using intravenous injection of paracarboxybenzene boronic acid made wiih boron-10. Dosimetric and operative techniques are described. Treatment of a second series has begun, Using an even less toxic compound, containing far more boron and suitable for intracarotid injection following temporary occlusion of both the common carotid arteries. (auth)
Perceived resistance, user resistance and managers' performance in the Malaysian port industry

Purpose – Using the extended task‐technology fit (TTF) model, this paper attempts to determine whether task‐technology fit, perceived resistance, user resistance and usage influence managers' performance.Design/methodology/approach – The study was conducted on 150 middle managers from various organisations in Malaysia's port industry.Findings – The structural equation modelling results reveal that task‐technology fit is significantly related to usage and perceived resistance, and that perceived resistance is a predictor of usage. Usage predicts performance, but not user resistance. There is no relationship between usage and user resistance, and vice versa.Research limitations/implications – The study focuses on Malaysia's port industry and concentrates only on the management perspective of intranet usage.Practical implications – The results provide insights into how the Malaysian port industry and other organisations of a similar structure could enhance their intranet usage.Originality/value – This study .
Sinusoidal high‐intensity exercise does not elicit ventilatory limitation in chronic obstructive pulmonary disease

• What is the central question of this study? Is it possible for patients with chronic obstructive pulmonary disease to avoid ventilatory limitation during high‐intensity exercise by using a fast‐fluctuating sinusoidal exercise task? • What is the main finding and its importance? Sinusoidal exercise, with a cycle time of 60 s superimposed upon a mean work rate at critical power, resulted in minimal fluctuations in the exercise ventilation. Thus, high‐intensity exercise, with excursions well above peak aerobic power, was sustained for up to 20 min in chronic obstructive pulmonary disease patients, and the end‐exercise ventilation was less than peak. This exercise protocol may prove beneficial in rehabilitative exercise training programmes where large gains in skeletal muscle adaptation are the goal.
Treatment of muscle mechanoreflex dysfunction in hypertension: effects of L‐arginine dialysis in the nucleus tractus solitarii

• What is the central question of this study? Does increasing NO production within the nucleus tractus solitarii (NTS) affect mechanoreflex function in normotensive and hypertensive rats? • What is the main finding and its importance? Dialysis of 1 μm l‐arginine, an NO precursor, within the NTS significantly attenuated the pressor response to muscle stretch in normotensive and hypertensive rats. In contrast, 10 μm l‐arginine had no effect in normotensive animals, while increasing and decreasing the pressor and tachycardic responses to stretch, respectively, in hypertensive rats. This suggests that increasing NO within the NTS using lower doses of l‐arginine can partly normalize mechanoreflex overactivity in hypertensive rats, whereas the effects of larger doses are equivocal.
Proteome of brain glia: The molecular basis of diverse glial phenotypes

Several different types of nonneuronal glial cells with diverse phenotypes are present in the CNS, and all have distinct indispensible functions. Although glial cells primarily provide neurons with metabolic and structural support in the healthy brain, they may switch phenotype from a “resting” to a “reactive” state in response to pathological insults. Furthermore, this reactive gliosis is an invariant feature of the pathogeneses of CNS maladies. The glial proteome serves as a signature of glial phenotype, and not only executes physiological functions, but also acts as a molecular mediator of the reactive glial phenotype. The glial proteome is also involved in intra‐ and intercellular communications as exemplified by glia–glia and neuron–glia interactions. The utilization of authoritative proteomic tools and the bioinformatic analyses have helped to profile the brain glial proteome and explore the molecular mechanisms of diverse glial phenotypes. Furthermore, technologic innovations have equipped the field of “glioproteomics” with refined tools for studies of the expression, interaction, and function of glial proteins in the healthy and in the diseased CNS. Glioproteomics is expected to contribute to the elucidation of the molecular mechanisms of CNS pathophysiology and to the discovery of biomarkers and theragnostic targets in CNS disorders.
Use of genetic models of idiopathic hypogonadotrophic hypogonadism in mice and men to understand the mechanisms of disease

• What is the topic of this review? This review discusses the genetics of idiopathic hypogonadotrophic hypogonadism, with a focus on how deficiencies in the kisspeptin and neurokinin B pathways result in reproductive dysfunction in both mice and men. • What advances does it highlight? In humans, deficiencies in kisspeptin signalling lead to a sustained absence of puberty. Mutations in the neurokinin B pathway are also associated with an initial absence of pubertal development, but the hypogonadotrophism can improve later in life with spontaneous activation of the hypothalamic–pituitary–gonadal cascade. Mouse models with mutations in each of these pathways recapitulate many of the features observed in human patients. Spontaneous recovery of gonadotrophin‐releasing hormone secretion, termed ‘reversal’, indicates that the hypothalamic–pituitary–gonadal axis may be capable of awakening in the setting of neurokinin B signalling abnormalities.
Comparative proteomic analysis of early salt stress responsive proteins in roots and leaves of rice

Growth and productivity of rice (Oryza sativa L.) are severely affected by salinity. Understanding the mechanisms that protect rice and other important cereal crops from salt stress will help in the development of salt‐stress‐tolerant strains. In this study, rice seedlings of the same genetic species with various salt tolerances were studied. We first used 2DE to resolve the expressed proteome in rice roots and leaves and then used nanospray liquid chromatography/tandem mass spectrometry to identify the differentially expressed proteins in rice seedlings after salt treatment. The 2DE assays revealed that there were 104 differentially expressed protein spots in rice roots and 59 in leaves. Then, we identified 83 proteins in rice roots and 61 proteins in rice leaves by MS analysis. Functional classification analysis revealed that the differentially expressed proteins from roots could be classified into 18 functional categories while those from leaves could be classified into 11 functional categories. The proteins from rice seedlings that most significantly contributed to a protective effect against increased salinity were cysteine synthase, adenosine triphosphate synthase, quercetin 3‐O‐methyltransferase 1, and lipoxygenase 2. Further analysis demonstrated that the primary mechanisms underlying the ability of rice seedlings to tolerate salt stress were glycolysis, purine metabolism, and photosynthesis. Thus, we suggest that differentially expressed proteins may serve as marker group for the salt tolerance of rice.
Resolution of hyposmotic stress in isolated mouse ventricular myocytes causes sealing of t‐tubules

• What is the central question of this study? The t‐tubules of ventricular myocytes are critical elements in excitation–contraction coupling. They become disorganized or even lost in various cardiac pathologies. However, the mechanisms leading to disruption of t‐tubules are essentially unknown. This study was designed to identify physiologically relevant processes that underlie remodelling of t‐tubules. • What is the main finding and its importance? We show that the resolution of physiologically relevant hyposmotic swelling, not the application of osmotic shock itself, leads to dramatic t‐tubular remodelling, including the sealing of individual t‐tubules. The results point to an important and probably general mechanism of acute and fast stress‐induced t‐tubular remodelling that may underlie various relevant pathologies of the heart.
Proteomic analysis of human substantia nigra identifies novel candidates involved in Parkinson's disease pathogenesis

Parkinson's disease (PD) pathology spreads throughout the brain following a region‐specific process predominantly affecting the substantia nigra (SN) pars compacta. SN exhibits a progressive loss of dopaminergic neurons responsible for the major cardinal motor symptoms, along with the occurrence of Lewy bodies in the surviving neurons. To gain new insights into the underlying pathogenic mechanisms in PD, we studied postmortem nigral tissues dissected from pathologically confirmed PD cases (n = 5) and neurologically intact controls (n = 8). Using a high‐throughput shotgun proteomic strategy, we simultaneously identified 1795 proteins with concomitant quantitative data. To date, this represents the most extensive catalog of nigral proteins. Of them, 204 proteins displayed significant expression level changes in PD patients versus controls. These were involved in novel or known pathogenic processes including mitochondrial dysfunction, oxidative stress, or cytoskeleton impairment. We further characterized four candidates that might be relevant to PD pathogenesis. We confirmed the differential expression of ferritin‐L and seipin by Western blot and demonstrated the neuronal localization of gamma glutamyl hydrolase and nebulette by immunohistochemistry. Our preliminary findings suggest a role for nebulette overexpression in PD neurodegeneration, through mechanisms that may involve cytoskeleton dynamics disruption. All MS data have been deposited in the ProteomeXchange with identifier PXD000427 (http://proteomecentral.proteomexchange.org/dataset/PXD000427).
Initial experience with partial liquid ventilation in adult patients with the acute respiratory distress syndrome

Objective. —To evaluate the safety and efficacy of partial liquid ventilation (PLV). Design. —Before-after trial. Setting. —The surgical intensive care unit at the University of Michigan, Ann Arbor, from April to December 1994. Patients. —A consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory distress syndrome who were receiving extracorporeal life support. Intervention. —Perflubron was administered into the trachea until the dependent zone of the lung was filled. Gas ventilation of the perflubron-filled lung was then performed (PLV). Volatilized perflubron replacement was repeated daily for from 1 to 7 days with a median cumulative dose of 38 mL/kg (range, 15 to 62 mL/kg). Main Outcome Measures. —Physiologic shunt and static pulmonary compliance. Results. —Physiologic shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21 to 0.96) over the 72 hours following initiation of PLV (P=.01 by repeated measures analysis of variance). Static pulmonary compliance corrected for patient weight increased from a median of 0.16 mL/cm H2O per kilogram (range, 0.01 to 0.48 mL/cm H2O per kilogram) to 0.27 mL/cm H2O per kilogram (range, 0.05 to 1.11 mL/cm H2O per kilogram) over the same time period (P=.04 by repeated measures analysis of variance). Overall survival was five (50%) of 10 patients. Complications that were potentially associated with PLV included pneumothorax development in one patient and mucus plug formation in one patient. Conclusions. —Perflubron may be safely administered into the lungs of patients with severe respiratory failure receiving extracorporeal life support and may be associated with improvement in gas exchange and pulmonary compliance. (JAMA. 1996;275:383-389)
Acute effect of dietary fatty acid composition on postprandial metabolism in women

What is the central question of this study? We wanted to determine the effect of three high‐fat meals enriched with different fatty acids [monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs) or saturated fatty acids (SFAs)] on diet‐induced thermogenesis and substrate oxidation in premenopausal women of normal weight. What is the main finding and its importance? We found that a PUFA‐rich high‐fat meal led to a greater diet‐induced thermogenesis in normal‐weight premenopausal women compared with SFA‐ or MUFA‐rich high‐fat meals. The greater diet‐induced thermogenesis for PUFA‐rich meals could contribute to differences in long‐term overall energy balance, and thus, weight maintenance. Substrate utilization was not different between treatments.
Proteomic identification of rainbow trout sperm proteins

Proteomics represents a powerful tool for the analysis of fish spermatozoa, since these cells are transcriptionally inactive. The aim of the present study was to generate an inventory of the most prominent rainbow trout sperm proteins by SDS‐PAGE prefractionation combined with nano‐LC‐MS/MS based identification. This study provides the first in‐depth analysis of the rainbow trout sperm proteome, with a total of 206 identified proteins. We found that rainbow trout spermatozoa are equipped with functionally diverse proteins related to energetic metabolism, signal transduction, protein turnover, transport, cytoskeleton, oxidative injuries, and stress and reproduction. The availability of a catalog of rainbow trout sperm proteins provides a crucial tool for the understanding of fundamental molecular processes in fish spermatozoa, for the ongoing development of novel markers of sperm quality and for the optimization of short‐ and long‐term sperm preservation procedures. The MS data are available at ProteomeXchange with the dataset identifier PXD000355 and DOI 10.6019/PXD000355.
Elongator and SPT4/SPT5 complexes as proxy to study RNA polymerase II transcript elongation control of plant development

The elongation phase of the RNA polymerase II (RNAPII) transcription process is dynamic and regulated. Elongator and SUPPRESSOR OF Ty4 (SPT4)/SPT5 are transcript elongation factors that contribute to the regulation of mRNA synthesis by RNA polymerase II in the chromatin context. Recently, the Elongator complex consisting of six subunits and the SPT4/SPT5 heterodimer were isolated from Arabidopsis. Mutant plants affected in the expression of Elongator or SPT4/SPT5 share various auxin‐signaling phenotypes. In line with that observation, auxin‐related genes are prominent among the genes differentially expressed in these mutants. Exemplified by Elongator and SPT4/SPT5, we discuss here the role that transcript elongation factors may play in the control of plant growth and development.
Quantitative phosphoproteomics of Alzheimer's disease reveals cross‐talk between kinases and small heat shock proteins

Abnormal phosphorylation contributes to the formation of neurofibrillary tangles in Alzheimer's disease (AD), but may play other signaling roles during AD pathogenesis. In this study, we employed IMAC followed by LC‐MS/MS to identify phosphopeptides from eight individual AD and eight age‐matched control postmortem human brain tissues. Using this approach, we identified 5569 phosphopeptides in frontal cortex across all 16 cases in which phosphopeptides represented 80% of all peptide spectral counts collected following IMAC enrichment. Marker selection identified 253 significantly altered phosphopeptides by precursor intensity, changed by at least 1.75‐fold relative to controls, with an empirical false discovery rate below 7%. Approximately 21% of all significantly altered phosphopeptides in AD tissue were derived from tau. Of the other 142 proteins hyperphosphorylated in AD, membrane, synapse, cell junction, and alternatively spliced proteins were overrepresented. Of these, we validated differential phosphorylation of HSP 27 (HSPB1) and crystallin‐alpha‐B (CRYAB) as hyperphosphorylated by Western blotting. We further identified a network of phosphorylated kinases, which coenriched with phosphorylated small HSPs. This supports a hypothesis that a number of kinases are regulating and/or regulated by the small HSP folding network.
Automated classification of web pages in hierarchical browsing

Purpose – The purpose of this study is twofold: to investigate whether it is meaningful to use the Engineering Index (Ei) classification scheme for browsing, and then, if proven useful, to investigate the performance of an automated classification algorithm based on the Ei classification scheme.Design/methodology/approach – A user study was conducted in which users solved four controlled searching tasks. The users browsed the Ei classification scheme in order to examine the suitability of the classification systems for browsing. The classification algorithm was evaluated by the users who judged the correctness of the automatically assigned classes.Findings – The study showed that the Ei classification scheme is suited for browsing. Automatically assigned classes were on average partly correct, with some classes working better than others. Success of browsing showed to be correlated and dependent on classification correctness.Research limitations/implications – Further research should address problems of d.
Active dendrites mediate stratified gamma‐range coincidence detection in hippocampal model neurons

Quantitative metrics for the temporal window of integration/coincidence detection, based on the spike‐triggered average, were employed to assess the emergence and dependence of gamma‐range coincidence detection in hippocampal pyramidal neurons on various ion channel combinations. The presence of hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels decreased the coincidence detection window (CDW) of the neuronal compartment to the gamma frequency range. Interaction of HCN channels with T‐type calcium channels and persistent sodium channels further reduced the CDW, whereas interaction with A‐type potassium channels broadened the CDW. When multiple channel gradients were co‐expressed, the high density of resonating conductances in the distal dendrites led to a slow gamma CDW in the proximal dendrites and a fast‐gamma CDW in the distal dendrites. The presence of resonating and spike‐generating conductances serve as a mechanism underlying the emergence of stratified gamma‐range coincidence detection in the dendrites of CA1 pyramidal neurons, enabling them to perform behaviour‐ and state‐dependent gamma frequency multiplexing.
Enhanced BDNF signalling following chronic hypoxia potentiates catecholamine release from cultured rat adrenal chromaffin cells

We investigated the role of the neurotrophin BDNF signalling via the TrkB receptor in rat adrenomedullary chromaffin cells (AMCs) exposed to normoxia (Nox; 21% O2) and chronic hypoxia (CHox; 2% O2) in vitro for ∼48 h. TrkB receptor expression was upregulated in primary AMCs and in immortalized chromaffin (MAH) cells exposed to CHox; this effect was absent in MAH cells deficient in the transcription factor, hypoxia inducible factor (HIF)‐2α. Relative to normoxic controls, activation of the TrkB receptor in chronically hypoxic AMCs led to a marked increase in membrane excitability, intracellular [Ca2+], and catecholamine secretion. The BDNF‐induced rise of intracellular [Ca2+] in CHox cells was sensitive to the selective T‐type Ca2+ channel blocker TTA‐P2 and tetrodotoxin (TTX), suggesting key roles of low threshold T‐type Ca2+ and voltage‐gated Na+ channels in the signalling pathway.
Unravelling the proteome of degenerative human mitral valves

Degenerative mitral valve disease (DMVD), which includes the syndromes of mitral valve prolapse (MVP) and flail leaflet, is a common valvular condition which can be complicated by mitral regurgitation and adverse cardiovascular outcomes. Although several genetic and other studies of MVP in dog models have provided some information regarding the underlying disease mechanisms, the proteins and molecular events mediating human MVP pathogenesis have not been unraveled. In this study, we report the first large‐scale proteome profiling of mitral valve tissue resected from patients with MVP. A total of 1134 proteins were identified, some of which were validated using SWATH‐MS and western blotting. GO annotation of these proteins confirmed the validity of this proteome database in various cardiovascular processes. Among the list of proteins, we found several structural and extracellular matrix proteins, such as asporin, biglycan, decorin, lumican, mimecan, prolargin, versican, and vinculin, that have putative roles in the pathophysiology of MVP. These proteins could also be involved in the cardiac remodeling associated with mitral regurgitation. All MS data have been deposited in the ProteomeXchange with identifier PXD000774 (http://proteomecentral.proteomexchange.org/dataset/PXD000774).
Respiratory modulated sympathetic activity: a putative mechanism for developing vascular resistance?

Sympathetic activity exhibits respiratory modulation that is amplified in hypertensive rats. Respiratory modulated sympathetic activity produces greater changes in vascular resistance than tonic stimulation of the same stimulus magnitude in normotensive but not hypertensive rats. Mathematical modelling demonstrates that respiratory modulated sympathetic activity may fail to produce greater vascular resistance changes in hypertensive rats because the system is saturated as a consequence of a dysfunctional noradrenaline reuptake mechanism. Respiratory modulated sympathetic activity is an efficient mechanism to raise vascular resistance promptly, corroborating its involvement in the ontogenesis of hypertension.
An Infrared Thermal Image Processing Framework for Defect Detection of a Metal Part with Rough Surface

We propose an infrared thermal image processing framework based on a modified fuzzy c-means clustering algorithm with revised similarity measure in this paper. The framework can realize the defect detection of a metal part with rough surface. Firstly, a comprehensive method is used to preprocess infrared thermal image. Secondly, the preprocessed image is segmented using modified fuzzy c-means clustering algorithm with revised similarity measure. Finally, taking the average gray level of each cluster in the original gray scale image as a feature, defect cluster is recognized. Experimental result shows that the proposed framework has very promising performance and can obtain precise information of defects on a metal part with rough surface.
TRPM7 kinase activity regulates murine mast cell degranulation

The Mg2+ and Ca2+ conducting transient receptor potential melastatin 7 (TRPM7) channel–enzyme (chanzyme) has been implicated in immune cell function. Mice heterozygous for a TRPM7 kinase deletion are hyperallergic, while mice with a single point mutation at amino acid 1648, silencing kinase activity, are not. As mast cell mediators trigger allergic reactions, we here determine the function of TRPM7 in mast cell degranulation and histamine release. Our data establish that TRPM7 kinase activity regulates mast cell degranulation and release of histamine independently of TRPM7 channel function. Our findings suggest a regulatory role of TRPM7 kinase activity on intracellular Ca2+ and extracellular Mg2+ sensitivity of mast cell degranulation.