gebhart/patrepeval huggingface dataset:
Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery (2022)

Neurodegenerative diseases represent a formidable challenge to global health. As advances in other areas of medicine grant healthy living into later decades of life, aging diseases such as Alzheimer's disease (AD) and other neurodegenerative disorders can diminish the quality of these additional years, owed largely to the lack of efficacious treatments and the absence of durable cures. Alzheimer's disease prevalence is predicted to more than double in the next 30 years, affecting nearly 15 million Americans, with AD-associated costs exceeding $1 billion by 2050. Delaying onset of AD and other neurodegenerative diseases is critical to improving the quality of life for patients and reducing the burden of disease on caregivers and healthcare systems. Significant progress has been made to model disease pathogenesis and identify points of therapeutic intervention. While some researchers have contributed to our understanding of the proteins and pathways that drive biological dysfunction in disease using <i>in vitro</i> and <i>in vivo</i> models, others have provided mathematical, biophysical, and computational technologies to identify potential therapeutic compounds using <i>in silico</i> modeling. The most exciting phase of the drug discovery process is now: by applying a target-directed approach that leverages the strengths of multiple techniques and validates lead hits using Drosophila as an animal model of disease, we are on the fast-track to identifying novel therapeutics to restore health to those impacted by neurodegenerative disease.
Human Red Blood Cells-1 (2013)

Biochemists and cell biologists, who are interested in membranes, tend to regard the human red blood cell ambivalently. On one hand, red blood cells lack nuclei and the various intracellular organelles, yet that are highly specialized for a particular respiratory function. On the other hand, the human red blood cell presents an excellent model for membrane transport function.
Chemical control of optical damage in lithium niobate (1978)

A new chemical process has been developed that significantly affects the susceptibility of LiNbO3 crystals and optical waveguiding layers to the laser-induced effects known as optical damage. The process involves controlling the nonstoichiometry of LiNbO3 by diffusion of lithium oxide. Susceptibility to optical damage in bulk crystals was reduced by increasing the nonstoichiometry (out-diffusion) and enhanced by decreasing the nonstoichiometry (in-diffusion). Typically, low-loss optical waveguides formed by the process supported one or more TE modes and tolerated more than 10 kW/cm2 laser transmission at 488.0 nm without inducing any measurable beam profile distortion.
Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells (2013)

Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases such as cancer and pulmonary arterial hypertension. We have synthesized inhibitors that are selective for the two isoforms of sphingosine kinase (SK1 and SK2) that catalyze the synthesis of S1P. A thiourea adduct of sphinganine (<b>F02</b>) is selective for SK2 whereas the 1-deoxysphinganines <b>55-21</b> and <b>77-7</b> are selective for SK1. (2<i>S</i>,3<i>R</i>)-1-Deoxysphinganine (<b>55-21</b>) induced the proteasomal degradation of SK1 in human pulmonary arterial smooth muscle cells and inhibited DNA synthesis, while the more potent SK1 inhibitors <b>PF-543</b> and <b>VPC96091</b> failed to inhibit DNA synthesis. These findings indicate that moderate potency inhibitors such as <b>55-21</b> are likely to have utility in unraveling the functions of SK1 in inflammatory and hyperproliferative disorders.
Deformation invariant image matching by spectrally controlled diffeomorphic alignment (2009)

We present a new approach to deformation invariant image matching. Our matcher (a) aligns templates to targets over a broad range of nonlinear deformations, (b) factors the total deformation into spectral categories, where low wavenumber deformations are smooth and global and high wavenumbers are turbulent and local, and (c) weighs the reduction in template-target misfit within each category to differentiate between relevant and irrelevant deformations. It accomplishes this by aligning images in a scale-cascaded fashion, with more complex, local deformations following simpler, more global ones. Each step of the cascade involves finding an iterative solution to a nonlinear optimization problem using a Gabor deformation basis. Cascaded alignment makes deformation invariant matching feasible and efficient. Our approach is applied to recognize the flexible bodies of salamanders from a large database; results indicate that the method is very promising.
Through‐Bond Energy Transfer Cassettes with Minimal Spectral Overlap between the Donor Emission and Acceptor Absorption: Coumarin–Rhodamine Dyads with Large Pseudo‐Stokes Shifts and Emission Shifts (2009)

Cassette recording: A new class of coumarin–rhodamine through-bond energy-transfer (TBET) cassettes with minimal spectral overlap between the donor emission and the acceptor absorption (see picture) show large pseudo-Stokes shifts (up to 230 nm) and emission shifts (up to 170 nm). The utility of this TBET platform for TBET-based probe development was demonstrated by a new ratiometric fluorescence pH probe. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A multi-perforation staged fracturing experimental study on hydraulic fracture initiation and propagation (2020)

Hydraulic fracture initiation and propagation are extremely important on deciding the production capacity and are crucial for oil and gas exploration and development. Based on a self-designed system, multi-perforation cluster-staged fracturing in thick tight sandstone reservoir was simulated in the laboratory. Moreover, the technology of staged fracturing during casing completion was achieved by using a preformed perforated wellbore. Three hydraulic fracturing methods, including single-perforation cluster fracturing, multi-perforation cluster conventional fracturing and multi-perforation cluster staged fracturing, were applied and studied, respectively. The results clearly indicate that the hydraulic fractures resulting from single-perforation cluster fracturing are relatively simple, which is difficult to form fracture network. In contrast, multi-perforation cluster-staged fracturing has more probability to produce complex fractures including major fracture and its branched fractures, especially in heterogeneous samples. Furthermore, the propagation direction of hydraulic fractures tends to change in heterogeneous samples, which is more likely to form a multi-directional hydraulic fracture network. The fracture area is greatly increased when the perforation cluster density increases in multi-perforation cluster conventional fracturing and multi-perforation cluster-staged fracturing. Moreover, higher perforation cluster densities and larger stage numbers are beneficial to hydraulic fracture initiation. The breakdown pressure in homogeneous samples is much higher than that in heterogeneous samples during hydraulic fracturing. In addition, the time of first fracture initiation has the trend that the shorter the initiation time is, the higher the breakdown pressure is. The results of this study provide meaningful suggestions for enhancing the production mechanism of multi-perforation cluster staged fracturing.
Scheduling jobs across geo-distributed datacenters (2015)

With growing data volumes generated and stored across geo-distributed datacenters, it is becoming increasingly inefficient to aggregate all data required for computation at a single datacenter. Instead, a recent trend is to distribute computation to take advantage of data locality, thus reducing the resource (e.g., bandwidth) costs while improving performance. In this trend, new challenges are emerging in job scheduling, which requires coordination among the datacenters as each job runs across geo-distributed sites. In this paper, we propose novel job scheduling algorithms that coordinate job scheduling across datacenters with low overhead, while achieving near-optimal performance. Our extensive simulation study with realistic job traces shows that the proposed scheduling algorithms result in up to 50% improvement in average job completion time over the Shortest Remaining Processing Time (SRPT) based approaches.
Hypermutation targets a green fluorescent protein-encoding transgene in the presence of immunoglobulin enhancers (1999)

Hypermutation introduces point mutations into the gene segments encoding immunoglobulin variable regions at a rate that is a million-fold higher than the spontaneous mutation rate in most of the genome. Because Ig enhancers are required to target hypermutation, transcription appears to play a critical role for the hypermutation mechanism. We have developed a novel system for detecting mutations that enables us to determine the influence of expression levels on the mutability of a transgene. This system utilizes a green fluorescent protein receptor gene and the powerful enumeration and quantification properties of flow cytometry. We have tested this system with several constructs bearing Ig enhancers in cell lines with active and inactive hypermutation systems.
Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-<i>ras</i> gene than in control non-transgenic mice (1996)

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.
A new high-performance liquid chromatographic procedure to quantitate hemoglobin A1c and other minor hemoglobins in blood of normal, diabetic, and alcoholic individuals. (1983)

A new HPLC procedure is described for the separation and quantitation of minor human Hb variants. The cation exchanger, Synchropak CM 300, is a silica support with a bonded polymeric coating of carboxylic acid residues. The chromatogram is developed with 0.03M Bis-Tris-KCN buffers, pH 6.40, and a Na-acetate gradient increasing from 0 to 0.1125M. As many as 11 minor Hbs (including Hb A2) can be isolated. Some of these have been identified through rechromatography of the minor Hb zones obtained by Bio-Rex-70 chromatography. Quantitation of Hb A1c and Hb A2 is readily accomplished. Hb F0 and an unidentified minor Hb often observed in red cells of alcoholics co-chromatograph with Hb A1c. The method has been applied to blood samples of 10 normal adults, 13 diabetic patients, and nine alcoholic subjects. An excellent correlation exists between the Hb A1c percentages and the levels of Hb A1 determined by microcolumn chromatography. Some other minor Hbs, identified as components 9 and 10, which are (at least in part) Hb A0 with glucose attached to the alpha chains, are present in increased amounts in the blood of diabetic patients and others may be observed in patients who subject themselves to (severe) alcohol abuse. It is suggested that the new procedure is well-suited for detailed studies of the minor Hbs in patients with various abnormalities in carbohydrate metabolism.
Helicobacter pylori infection and blood groups. (1996)

Positivity for H. pylori was not associated with blood group O. Our observation does not support the conclusion that the receptor for H. pylori in the gastric mucosa is the blood group antigen Lewis b.
The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task (1994)

1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 micrograms) and SCH39166 (1-5 micrograms) and/or the nonselective dopamine antagonist haloperidol (10-100 micrograms) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location.(ABSTRACT TRUNCATED AT 400 WORDS)
Synthesis of microstrip antenna arrays for optimum near-field patterns via steepest decent method (2011)

This paper employs the steepest decent method (SDM) to synthesize the phases of an array of antennas to radiate an optimum field pattern in the near-zone of antenna aperture. The synthesized phases are implemented to design a microstrip antenna array, which is operated at 24 GHz band and can be used for the vital-sign detection with a higher resolution.
Ventilator-associated Pneumonia or Endotracheal Tube-associated Pneumonia? (2009)

Ventilator-associated pneumonia is the most common nosocomial infection in the intensive care unit, and it is associated with prolonged hospitalization, increased health care costs, and high attributable mortality. During the past several decades, numerous studies focused on the crucial role of the endotracheal tube (ETT) in the pathogenesis of ventilator-associated pneumonia. Tracheal intubation thwarts the cough reflex, compromises mucocilliary clearance, injures the tracheal epithelial surface, provides a direct conduit for rapid access of bacteria from upper into the lower respiratory tract, and allows the formation of biofilm on the ETT surface. The combination of these factors puts the mechanically ventilated patient at great jeopardy of developing ventilator-associated pneumonia. Many preventive strategies have arisen from this understanding: control of intracuff pressure, aspiration of subglottic secretions, decontamination of subglottic area, use of antiseptic impregnated ETTs, and elimination or prevention of the ETT biofilm formation. The authors review the role of ETT management for the prevention of the ventilator-associated pneumonia.
O Atual Currículo do Curso de Geologia - USP e a Demanda de Profissionais Geólogos para a Atuação em Projetos de Áreas Contaminadas (2007)

This article aims to present a contribution to the debate regarding curricular reform of the undergraduate course of Geology-USP, based on the recent employment of geologists in projects regarding investigation and remediation of contaminated sites. This area is experiencing considerable expansion, especially after the enforcement of the Federal Law 9605, regarding Environmental Crimes, in 1999. Even after all efforts in the conduction and completion of the existing cases of contamination, it is recognized that most of such environmental problems still remain unknown, which leads one to believe that there will be a tendency for growth in the demand for new professionals to work in this area at the long term. Considering that the geologist performs a vital and notable role in the characterization of geology, hydrogeology and contamination in an investigation and remediation project, it is believed that some courses should be adjusted to meet some of the professional activities mentioned in the CONFEA Resolution 1010, which regulates the professional activities of the geologist. Besides this, a re-evaluation of the duration, content and sequencing of some of the fundamental geological disciplines is believed to be necessary. This will result in benefits which affect not only the action of the geologist in projects on contaminated areas, but also in other areas of applied geology.
Mining concepts from code with probabilistic topic models (2007)

We develop and apply statistical topic models to software as a means of extracting concepts from source code. The effectiveness of the technique is demonstrated on 1,555 projects from SourceForge and Apache consisting of 113,000 files and 19 million lines of code. In addition to providing an automated, unsupervised, solution to the problem of summarizing program functionality, the approach provides a probabilistic framework with which to analyze and visualize source file similarity. Finally, we introduce an information-theoretic approach for computing tangling and scattering of extracted concepts, and present preliminary results
Cleavable hairpin beacon-enhanced fluorescence detection of nucleic acid isothermal amplification and smartphone-based readout (2020)

Fluorescence detection of nucleic acid isothermal amplification utilizing energy-transfer-tagged oligonucleotide probes provides a highly sensitive and specific method for pathogen detection. However, currently available probes suffer from relatively weak fluorescence signals and are not suitable for simple, affordable smartphone-based detection at the point of care. Here, we present a cleavable hairpin beacon (CHB)-enhanced fluorescence detection for isothermal amplification assay. The CHB probe is a single fluorophore-tagged hairpin oligonucleotide with five continuous ribonucleotides which can be cleaved by the ribonuclease to specifically initiate DNA amplification and generate strong fluorescence signals. By coupling with loop-mediated isothermal amplification (LAMP), the CHB probe could detect Borrelia burgdorferi (B. burgdorferi) recA gene with a sensitivity of 100 copies within 25 min and generated stronger specific fluorescence signals which were easily read and analysed by our programmed smartphone. Also, this CHB-enhanced LAMP (CHB-LAMP) assay was successfully demonstrated to detect B. burgdorferi DNA extracted from tick species, showing comparable results to real-time PCR assay. In addition, our CHB probe was compatible with other isothermal amplifications, such as isothermal multiple-self-matching-initiated amplification (IMSA). Therefore, CHB-enhanced fluorescence detection is anticipated to facilitate the development of simple, sensitive smartphone-based point-of-care pathogen diagnostics in resource-limited settings.
Alternating-Phase-Focused Linac with Interdigital H-Mode Structure for Medical Injector (2006)

A compact injector consisting of a Radio Frequency Quadrupole (RFQ) linac and Interdigital H-mode Drift Tube Linac (IH-DTL) for medical accelerators was designed. A model cavity of IH-DTL was constructed and electric field distributions were measured. The measured distributions were compared with those calculated by a three dimensional field solver. With the comparison, accuracy of the solver was discussed. The RFQ linac has been constructed. The final design of IH-DTL is in progress. Construction of the entire compact injector will be completed by the end of this year, and a beam test will be performed.
Adhesive and sealant interfaces for general surgery applications (2015)

The main functions of biological adhesives and sealants are to repair injured tissues, reinforce surgical wounds, or even replace common suturing techniques. In general surgery, adhesives must match several requirements taking into account clinical needs, biological effects, and material features; these requirements can be fulfilled by specific polymers. Natural or synthetic polymeric materials can be employed to generate three-dimensional networks that physically or chemically bind to the target tissues and act as hemostats, sealants, or adhesives. Among them, fibrin, gelatin, dextran, chitosan, cyanoacrylates, polyethylene glycol, and polyurethanes are the most important components of these interfaces; various aspects regarding their adhesion mechanisms, mechanical performance, and resistance to body fluids should be taken into account to choose the most suitable formulation for the target application. This review aims to describe the main adhesives and sealant materials for general surgery applications developed in the past decades and to highlight the most important aspects for the development of future formulations.