gebhart/patrepeval huggingface dataset:
Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model (2005)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which results from selective loss of upper and lower motor neurons. Mouse models of ALS, such as one carrying the G93A mutant of the human Cu-Zn superoxide dismutase gene[SOD1(G93A)], develop motor neuron pathology and clinical symptoms similar to those observed in ALS patients. There is compelling evidence that both direct and indirect glutamate toxicity contribute to the pathogenesis of motor neuron degeneration. However, the therapeutic effect of various glutamate receptor antagonists has not been clearly demonstrated. Memantine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It has been shown to protect neurons against NMDA- or glutamate-induced toxicity in vitro and in animal models of neurodegenerative diseases. In the current study, we have examined the therapeutic efficacy of memantine in an ALS mouse model carrying a high copy number of SOD1(G93A). Memantine treatment significantly delayed the disease progression and increased the life span of SOD1(G93A) mice, from 121.4 +/- 5.5 to 129.7 +/- 4.5 days (P = 0.032). Furthermore, NMDA receptor subunits were reliably detected in the spinal cord of SOD1(G93A) mice and their expression levels were similar to those in the wild-type littermate control. Therefore, the neuroprotective effect of memantine in SOD1(G93A) mice is most probably due to the inhibition of spinal cord NMDA receptors. In view of the long-term usage of memantine for dementia patients, with excellent tolerance and safety, these data suggest that memantine may be used in ALS patients alone or in combination with other therapies to prolong survival.
Molecular dynamics reveal a novel kinase–substrate interface that regulates protein translation (2014)

A key control point in gene expression is the initiation of protein translation, with a universal stress response being constituted by inhibitory phosphorylation of the eukaryotic initiation factor 2α (eIF2α). In humans, four kinases sense diverse physiological stresses to regulate eIF2α to control cell differentiation, adaptation, and survival. Here we develop a computational molecular model of eIF2α and one of its kinases, the protein kinase R, to simulate the dynamics of their interaction. Predictions generated by coarse-grained dynamics simulations suggest a novel mode of action. Experimentation substantiates these predictions, identifying a previously unrecognized interface in the protein complex, which is constituted by dynamic residues in both eIF2α and its kinases that are crucial to regulate protein translation. These findings call for a reinterpretation of the current mechanism of action of the eIF2α kinases and demonstrate the value of conducting computational analysis to evaluate protein function.
Effect of pulse shaping on defect reduction in pulsed laser welding (1992)

This paper describes the effectiveness of laser pulse shaping in eliminating weld defects such as porosity and cracking in pulsed Nd:YAG laser welding, as well as the influence of laser irradiation conditions on pulsed YAG laser melting tendency and great susceptibility of A5083P-0 to solidification cracking and porosity in laser weld metals.
A phase I study of TPI 287 in combination with temozolomide for patients with metastatic melanoma (2016)

TPI 287 is a synthetic taxane derivative with structural modifications allowing for central nervous system penetration and potential circumvention of multidrug resistance efflux pump mechanisms. The aim of this phase I study was to determine the maximum tolerated dose of the combination of TPI 287 and temozolomide in metastatic melanoma. Patients with stage IV unresectable or recurrent stage III melanoma were eligible. Stable untreated or treated brain metastases were allowed. Patients with previous taxane exposure were excluded. TPI 287 was administered intravenously on days 1, 8, and 15 and temozolomide was taken orally daily on days 1-5 of a 28-day cycle. Responses were assessed every two cycles according to WHO criteria. A total of 21 patients were enrolled. The maximum tolerated dose of the combination at this schedule was determined to be 125 mg/m intravenous of TPI 287 and 110 mg/m of oral temozolomide. The dose-limiting toxicity was neuropathy and six patients experienced grade III neuropathy. All patients were evaluable for tumor response. There were no complete responses; there were two partial responses and seven patients had stable disease (overall response rate 9.5% and disease control rate 42.9%). Three patients had stable disease in the brain despite progressive extracranial disease. The combination of TPI 287 and temozolomide is well tolerated in patients with metastatic melanoma, with the exception of neuropathy. The central nervous system penetration of both agents makes this a rational combination for further testing in primary and metastatic brain lesions.
HLA-B27 rats develop osteopaenia through increased bone resorption without any change in bone formation. (2009)

Osteopaenia is a common complication of inflammatory bowel diseases (IBD). However, the mechanisms of bone loss are still the subject of debate. The aims of this study were to investigate bone loss in HLA-B27 transgenic rats, a spontaneous model of colitis and to compare the results provided by the usual markers of bone remodelling and by direct measurement of bone protein synthesis. Systemic inflammation was evaluated in HLA-B27 rats and control rats from 18 to 27 months of age. Then bone mineral density, femoral failure load, biochemical markers of bone remodelling and protein synthesis in tibial epiphysis were measured. Bone mineral density was lower in HLA-B27 rats than in controls. Plasma osteocalcin, a marker of bone formation, and fractional protein synthesis rate in tibial epiphysis did not differ between the two groups of rats. In contrast, urinary excretion of deoxypyridinoline, a marker of bone resorption, was significantly increased in HLA-B27 rats. The present results indicate that bone fragility occurs in HLA-B27 rats and mainly results from an increase in bone resorption. Systemic inflammation may be the major cause of the disruption in bone remodelling homeostasis observed in this experimental model of human IBD.
Clinical Follow-up of Patients Undergoing Percutaneous Mitral Balloon Valvotomy (1995)

The excellent intermediate long-term clinical follow-up of patients with echocardiographic score < or = 8 and no calcified mitral valves suggests that PMV may be the treatment of choice in this group of patients.
Highly efficient 2.2-GHz Si power MOSFETs for cellular base station applications (2003)

A 2.2-GHz Si power MOSFET with high output power and high drain efficiency has been developed for cellular base station applications. This device has an LDMOS structure with a sub-micron gate. Internal matched circuits for input and output impedance matching consist of MOS capacitor chips and Al bonding wires. In a push-pull configuration and 2.2-GHz operation, the MOSFET has output power of 120 W, power gain of 10.8 dB, and drain efficiency of 45%.
Application of photoelectric rotary encoder in flight simulation servo system (2004)

A new designing scheme of applying photoelectric rotary encoder to flight simulation servo system is introduced,and a realization method of servo system is proposed. The coding arithmetic principle of photoelectric rotary encoder is explained,then a fourfold-frequency direction-judgement circuit is designed. A triple close-loop control scheme is adopted in the flight simulation servo control system. The testing results show that the flight simulation servo systems which are adopted the proposed photoelectric rotary encoder and its related fourfold-frequency direction-judgement circuit can achieve a high control precision,excellent stability and strong robust.
Predicting arrhythmias in primary prevention heart failure patients: picking up the fragments (2022)

Identifying patients with high-risk heart failure (HF) who would benefit from an implantable cardioverter-defibrillator (ICD) remains controversial. A potential marker for arrhythmic sudden death is fragmented QRS (fQRS). fQRS is the notching and slurring of the QRS complex in a 12-lead ECG and it indicates abnormal ventricular depolarisation and myocardial scarring and fibrosis. However, before fQRS complex can be included into selection criteria for ICD therapy, more complete reporting is required on their association with malignant arrhythmias, left ventricular remodelling and myocardial scarring/fibrosis in patients with HF. The molecular basis of the fQRS-arrhythmia-fibrosis connection in HF also needs to be explored. It is not widely appreciated that changes in the QRS complex and phases 0 and 1 of the ventricular action potential occur before contraction and predetermine Ca 2+ release during contraction and later Ca 2+ sparks. It is currently not known whether the different zig-zag patterns of the QRS are associated with aberrant Ca 2+ cycling and arrhythmogenic sparks in patients with HF.
Multiple time scales for dispersals of bacterial disease over human history (2017)

Multiple microbial pathogens have spread geographically, sometimes with drastic impacts on the health of humans and their domesticated animals and crops due to epidemic outbreaks of disease. However, microbial pathogens do not leave fossils, and, until very recently, it has been difficult to reconstruct the causes of historical human diseases. For some bacterial pathogens, this situation is now changing due to recent advances in population genetics, DNA sequencing, and ancient DNA studies. This chapter illustrates these developments with an overview of the histories of three exemplary bacterial pathogens: Helicobacter pylori (a common cause of gastric ulcers), Yersinia pestis (the cause of plague), and Salmonella enterica serovar Agona (a common cause of gastroenteritis), with occasional references to other bacteria. These three pathogens have been inferred to have infected humans for very different time periods within the history of anatomically modern humans, ranging from 100,000 years down to 80 years.
Isolation, characterization, and in vitro expression of a cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase. (1991)

A cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase (pGA) was generated by recombination of two cDNAs that were isolated from a random-primed rat brain lambda gt11 library. pGA encodes 674 amino acids which includes an N-terminal sequence of 16 residues that should form an amphipathic helix, typical of a mitochondrial targeting sequence. Residues 73-90 correspond to the N-terminal sequence of the more abundant 65-kDa glutaminase peptide. In vitro transcription and translation of pGA yields a 72-kDa peptide that is immunoprecipitated with glutaminase-specific antibodies. Incubation of the glutaminase precursor with isolated mitochondria yields the 68- and 65-kDa peptides that are characteristic of the mature glutaminase. Thus, the two mature glutaminase peptides are synthesized from a single precursor. The complete 3' nontranslated region of the GA mRNA was characterized by sequencing a GA cDNA (pGA12) that was isolated from an oligo(dT)-primed rat kidney lambda gt10 library. This segment contains numerous AU-rich regions, four potential stem-loop structures, and a 48 base pair repeat of CA dinucleotides. Such domains may contribute to the increased stability of the GA mRNA that occurs in response to metabolic acidosis.
Quantification of regional variations in glenoid trabecular bone architecture and mineralization using clinical computed tomography images (2017)

The purpose of this study was to demonstrate feasibility of a clinical CT imaging and analysis technique to quantify regional variations in trabecular bone architecture and mineralization of glenoid bones. Specifically, our objective was to determine to what extent clinical CT imaging of intact upper extremities can describe variations of trabecular bone architectures at anatomic and peri-implant regions by comparing trabecular bone architectures as measured by high-resolution, micro CT imaging of same excised glenoid bones. Bone volume fraction (BVF), trabecular bone thickness (TbTh), number of trabecular bone (TbN), spacing (TbS), pattern factor (TbPf), bone surface area (BSA), and skeletal connectivity (Conn.), in addition to bone mineral content (BMC) and bone mineral density (BMD), were quantified from both clinical and micro CT images using whole bone, anatomic, and peri-implant bone masks. Strong correlations of BVF, TbTh, TbSp, BMC, and BMD were found between clinical CT and micro CT imaging methods. The variations in BVF, TbTh, TbSp, TbN, BMC, and BMD at anatomical and peri-implant regions were larger than those at whole bone regions. In this study, we have demonstrated that this clinical CT imaging methodology can be used to quantify variations of a patient's glenoid bone at anatomic and peri-implant levels. Statement of Clinical Significance. An in vivo quantitative assessment of glenoid trabecular bone architecture in the anatomic and peri-implant regions may improve our understanding on the role of bone quality on glenoid component loosening following total shoulder arthroplasty. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:85-96, 2018.
Heat shock factor 1 over-expression protects against exposure of hydrophobic residues on mutant SOD1 and early mortality in a mouse model of amyotrophic lateral sclerosis (2013)

Our results uncover the potential importance of changes in protein surface hydrophobicity of SOD1 and other non-SOD1 proteins in ALS, and how strategies that activate HSF1 are valid therapies for ALS and other age-associated proteinopathies.
Modeling of transmission line exposure to direct lightning strokes (1990)

A new model for assessing the exposure of free-standing structures and horizontal conductors above flat ground to direct lightning strokes is introduced. A recently developed criterion for positive leader inception modified to account for positive leaders initiated under the influence of a negative descending lightning stroke, is discussed. Subsequent propagation of the positive leader is analyzed to define the point of encounter of the two leaders which determines the attractive radius of a structure or the attractive lateral distance of a conductor. These parameters are investigated for a wide range of heights and return-stroke currents. A method for analyzing shielding failure and determining the critical shielding angle is also described. The predictions of the model are compared with field observations and previously developed models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Distilling the Knowledge of BERT for Sequence-to-Sequence ASR (2020)

Attention-based sequence-to-sequence (seq2seq) models have achieved promising results in automatic speech recognition (ASR). However, as these models decode in a left-to-right way, they do not have access to context on the right. We leverage both left and right context by applying BERT as an external language model to seq2seq ASR through knowledge distillation. In our proposed method, BERT generates soft labels to guide the training of seq2seq ASR. Furthermore, we leverage context beyond the current utterance as input to BERT. Experimental evaluations show that our method significantly improves the ASR performance from the seq2seq baseline on the Corpus of Spontaneous Japanese (CSJ). Knowledge distillation from BERT outperforms that from a transformer LM that only looks at left context. We also show the effectiveness of leveraging context beyond the current utterance. Our method outperforms other LM application approaches such as n-best rescoring and shallow fusion, while it does not require extra inference cost.
Special section on Breath Gas Analysis (2011)

In Spring 2009 an idea was born to bring together the leading specialists from Germany and Austria working in the emerging field of breath gas research and its application for clinical diagnosis and therapeutic monitoring within an internationally open workshop. To bring this idea to fruition the first German–Austrian Workshop on Breath Gas Analysis was held in Greifswald, Germany, 7–9 June 2010. The conference was organized by the Leibniz Institute for Plasma Research and Technology (INP), Greifswald, in cooperation with the Institute of Community Medicine (ICM) of the University of Greifswald. The scientific program of the workshop covered all modern aspects of exhaled breath gas analysis ranging from sampling techniques and analytical approaches to pilot cases studies. The 54 participants came from nine European and non-European countries. The five invited speakers originated from Germany, Austria, Great Britain and the USA.
ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies (2016)

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies.
Fluorescence spectral characteristics of novel asymmetric monomethine cyanine dyes in nucleic acid solutions (1997)

Six new asymmetric monomethine cyanine dyes have been synthesized and their fluorescence characteristics in the presence of nucleic acids studied. The new dyes have no fluorescence of their own in water solutions upon excitation at 480 nm but they become strongly fluorescent in the presence of nucleic acids. The fluorescence maxima of the investigated dyes are found at 525-545 nm when bound to dsDNA and around 600 nm upon binding to RNA and ssDNA. Fluorescence quenching studies with increasing concentrations of NaCl indicate that the cyanine dyes have a mixed (intercalating and groove binding) type of interaction with dsDNA.
Characteristics of plant cell walls affecting intake and digestibility of forages by ruminants. (1995)

Even under the intensive concentrate feeding systems of ruminant animal production in the United States, forages continue to represent the single most important feed resource. Cell-wall concentration and digestibility limit the intake potential and energy availability of forage crops in beef and dairy production. Identification of cell-wall characteristics that should be targets of genetic modification is required if plant breeders and molecular biologists are to successfully improve forages for livestock feeding. As the forage plant cell develops, phenolic acids and lignin are deposited in the maturing cell wall in specific structural conformations, and in a strict developmental sequence. Lignin is the key element that limits cell-wall digestibility, but cross-linkage of lignin and wall polysaccharides by ferulic acid bridges may be a prerequisite for lignin to exert its affect. Lignin composition and p-coumaric acid in the wall are less likely to affect digestibility. Voluntary intake of forages is a critical determinant of animal performance and cell-wall concentration is negatively related to intake of ruminants consuming high-forage diets. Cell walls affect intake by contributing to ruminal fill. A simple model of cell-wall digestion and passage in which ruminal fill is a function of rates of digestion and passage, as well as the indigestible fraction of the cell-wall indicates that cell-wall concentration and rate of passage are the most critical parameters determining ruminal fill. Plant factors that affect rate of passage include those that affect particle size reduction by chewing and those that affect particle buoyancy in the rumen. The latter is primarily affected by 1) the ability of the particulate matter to retain gases, which is probably related to plant anatomy and rate of digestion of the plant tissue, and 2) the rate at which the gas is produced, which is affected by the potentially digestible fraction of the particulate matter and the rate of digestion of this fraction. Increasing rate of digestion should increase rate of passage by diminishing the gas produced and increasing density over time. A reduction in the indigestible cell-wall fraction is beneficial because this will decrease fill and increase digestibility. Animal production and economic benefits from reduced cell-wall concentration and increased digestibility are significant. Because of the high cell-wall concentration and large digestible cell-wall fraction of grasses, reduction in cell-wall concentration would probably be of greater value than improving digestibility in these species. Legumes represent the opposite situation and may benefit more from improvements in the digestibility of their cell walls.
"A Land without a People for a People without a Land": Civilizing Mission and American Support for Zionism, 1880s-1929 (2012)

This dissertation explores the origins of the "special relationship" between the United States and Israel
Mask-RCNN and U-Net Ensembled for Nuclei Segmentation (2019)

Nuclei segmentation is both an important and in some ways ideal task for modern computer vision methods, e.g. convolutional neural networks. While recent developments in theory and open-source software have made these tools easier to implement, expert knowledge is still required to choose the right model architecture and training setup. We compare two popular segmentation frameworks, U-Net and Mask-RCNN in the nuclei segmentation task and find that they have different strengths and failures. To get the best of both worlds, we develop an ensemble model to combine their predictions that can outperform both models by a significant margin and should be considered when aiming for best nuclei segmentation performance.
Speech and gesture are mediated by independent systems (2005)

Arbib suggests that language emerged in direct relation to manual gestural communication, that Broca's area participates in producing and imitating gestures, and that emotional facial expressions contributed to gesture-language coevolution. We discuss functional and structural evidence supporting localization of the neuronal modules controlling limb praxis, speech and language, and emotional communication. Current evidence supports completely independent limb praxis and speech/language systems.