gebhart/patrepeval huggingface dataset:
Structure and Function of Glutamate Receptor Ion Channels (2004)

A vast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade.
UV laser diode with 350.9-nm-lasing wavelength grown by hetero-epitaxial-lateral overgrowth technology (2005)

We have demonstrated a UV-laser diode with a lasing wavelength of 350.9 nm, which has a GaN-AlGaN multiquantum-well (MQW) active layer and was grown on low-dislocation-density Al/sub 0.18/Ga/sub 0.82/N template. The Al/sub 0.18/Ga/sub 0.82/N template was produced by the hetero-epitaxial lateral overgrowth technology on the low-cost sapphire substrate, and has partially low-dislocation density of approximately 2/spl times/10/sup 7/ cm/sup -2/. The lasing operation under pulsed current injection was achieved with the threshold current density of 7.3 kA/cm/sup 2/ and the operating voltage of 10.4 V.
Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors (1992)

<h3>Objective.</h3> —To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence. <h3>Design.</h3> —In 1989, a self-administered questionnaire was sent to a sample of 15000 households. A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches. <h3>Setting.</h3> —A sample of households selected from a panel to be representative of the US population in terms of age, gender, household size, and geographic area. <h3>Participants.</h3> —After a single mailing, 20468 subjects (63.4% response rate) between 12 and 80 years of age responded to the survey. Respondents and non-respondents did not differ by gender, household income, region of the country, or urban vs rural status. Whites and the elderly were more likely to respond. Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria. <h3>Results.</h3> —17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. The prevalence of migraine varied considerably by age and was highest in both men and women between the ages of 35 to 45 years. Migraine prevalence was strongly associated with household income; prevalence in the lowest income group (&lt;$10 000) was more than 60% higher than in the two highest income groups (≥$30 000). The proportion of migraine sufferers who experienced moderate to severe disability was not related to gender, age, income, urban vs rural residence, or region of the country. In contrast, the frequency of headaches was lower in higher-income groups. Attack frequency was inversely related to disability. <h3>Conclusions.</h3> —A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition. (<i>JAMA</i>. 1992;267:64-69)
Passive bipedal running (1990)

Abstract Human-like running is a natural dynamic mode of a simple mechanical biped. Such a machine consists of two telescoping legs with linear springs, connected by a hip joint with a torsional spring. It will run passively; no pattern of forcing is required to generate the gait. With careful design its energy consumption can approach zero, but in any case the passive cycle can be ‘pumped' by various means to sustain running over a range of speeds and slopes. Passive running can also be realized over a wide range of mechanical design parameters. Some parameter sets produce cycles that are inherently stable; otherwise the mode can be actively stabilized by a simple control law. Thus the passive running model offers an effective foundation for design of practical running machines, and also provides an insight into the physics of human locomotion.
Bioavailability of enteral tramadol formulations. 1st communication: capsules. (1986)

The absolute bioavailability of tramadol hydrochloride (rac-1(e)-(m-methoxyphenyl)-2-(e)-(dimethylaminomethyl)cyclohexan- 1(a)-ol hydrochloride, CG 315) after the oral administration of Tramal capsules was determined in a balanced cross-over study in 10 male volunteers. Each volunteer received two single doses of 100 mg tramadol hydrochloride, one by oral (2 Tramal capsules) and one by intravenous route (2 ampoules of Tramal 50 solution for injection). The formulations were administered in the morning on an empty stomach, and the interval between the two applications was one week. Serum concentrations of tramadol were determined by gas chromatography-mass spectrometry and the bioavailability was ascertained by calculation of the areas under the serum concentration curves. The absolute bioavailability of tramadol in Tramal capsules was 68 +/- 13% (means +/- SD; n = 10) with a range of 41-84% and a 95% confidence interval of 55.0-79.2%. The areas under the serum concentration curves of tramadol hydrochloride (AUC) were 2488 +/- 774 ng X h/ml (p.o.) and 3709 +/- 977 ng X h/ml (i.v.). Peak serum concentrations of 280 +/- 49 ng/ml were reached 2 h after oral administration of two Tramal capsules; a serum concentration of 100 ng/ml (assumed as the threshold value for analgesic efficacy) was reached after 0.68 +/- 0.17 h and was maintained for 9.0 +/- 2.2 h. The half-life of absorption was 0.38 +/- 0.18 h and the lag-time 0.48 +/- 0.14 h. In the terminal phase the biological half-lives of tramadol were 5.1 +/- 0.8 h (p.o.) and 5.2 +/- 0.8 h (i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
Monoclonal Antibody First Dose Cytokine Release Syndromes–Mechanisms and Prediction (2008)

Acute cytokine release syndromes are associated with some therapeutic antibodies in man, leading to a spectrum of clinical signs from nausea, chills and fever to more serious dose limiting hypotension and tachycardia. When anticipated this syndrome is typically manageable, however this adverse reaction recently became headline news when a massive and unexpected cytokine release syndrome occurred within a few hours of dosing six healthy volunteers with a therapeutic antibody, putting their lives at risk due to multiple organ failure. Preclinical studies did not predict this adverse event, emphasising the need to compare the relative potency of the product in man and the chosen toxicology species, so that additional margins of safety can be applied when conducting first in man (FIM) studies if there is uncertainty over the predictability of the toxicology species. In vitro human PBMC and whole blood cultures may be useful for predicting cytokine release. However since cytokine release arises through at least two distinct mechanisms, it should be emphasised that the utility of these in vitro methods needs to be established for each antibody product.
Gene Therapy for Familial Hypercholesterolemia (2011)

Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of plasma low density lipoproteins (LDL) and an increased risk of premature atherosclerosis and coronary heart disease. LDL receptor (LDLr) deficiency is the most prevalent cause of FH. Therefore, hepatocyte-directed LDLr gene transfer constitutes an important strategy for the treatment of this monogenetic disease. Nowadays, homozygous FH patients are treated with lipid-lowering drugs complemented by plasma or LDL apheresis. Liver transplantation can restore metabolism of apolipoprotein B containing lipoproteins, but requires lifelong immunosuppression to prevent organ rejection. Recently, significant progress in gene transfer technology has encouraged investigators to further develop LDLr gene transfer approaches for the treatment of FH. In experimental animal models of FH, LDLr overexpression following viral vector-based gene transfer has been shown to be associated with long-term stable correction of hyperlipidemia, with attenuation of atherosclerosis progression, and in certain cases even with lesion regression. The first part of this review provides a thorough overview of familial hypercholesterolemia including its diagnosis, lipoprotein metabolism, and current management. In the second part, we critically review experimental LDLr gene transfer studies demonstrating the progress that has been made from the initial proof of principle studies to recent investigations showing dramatic regression of atherosclerosis in experimental models.
Recent Advances in Legume-Microbe Interactions: Recognition, Defense Response, and Symbiosis from a Genomic Perspective (2007)

The ability of legumes to form symbiotic mutualistic relationships with certain bacteria in the Rhizobiales (collectively called rhizobia) and harness the ability of the bacteria to fix atmospheric N2 into ammonia has a tremendous impact on natural and agricultural ecosystems. The interaction
Dog bone less osteogenetic than rat bone Bone-matrix transplants in nude rats (1989)

Demineralized bone matrix and bone-matrix gelatin prepared from cortical rat bone, and from cortical and cancellous canine bone were implanted into muscle pouches of nude rats for 6 weeks. Evaluation was done by histology, histomorphometry, and determination of alkaline phosphatase. Rat matrix consistently induced new bone and high phosphatase levels. Canine matrix induced but small amounts of bone and lower phosphatase levels, with cortical matrix somewhat more inductive than cancellous matrix; demineralized cancellous bone matrix from the dog was the only material tested not showing any inductivity. Irrespective of bone type or species, gelatin had clearly higher induction capacity than demineralized bone matrix.
A New Transgenic Rat Model of Hepatic Steatosis and the Metabolic Syndrome (2005)

Fatty liver is extremely common in insulin-resistant patients with either obesity or lipodystrophy and it has been proposed that hepatic steatosis be considered an additional feature of the metabolic syndrome. Although insulin resistance can promote fatty liver, excessive hepatic accumulation of fat can also promote insulin resistance and could contribute to the pathogenesis of the metabolic syndrome. We sought to create a new nonobese rat model with hypertension, hepatic steatosis, and the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein (SREBP-1a) in the spontaneously hypertensive rat (SHR). SREBPs are transcription factors that activate the expression of multiple genes involved in the hepatic synthesis of cholesterol, triglycerides, and fatty acids. The new transgenic strain of SHR overexpressing a dominant-positive form of human SREBP-1a under control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibited marked hepatic steatosis with major biochemical features of the metabolic syndrome, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Both oxidative and nonoxidative skeletal muscle glucose metabolism were significantly impaired in the SHR transgenic strain and glucose tolerance deteriorated as the animals aged. The SHR transgenic strain also exhibited reduced body weight and reduced adipose tissue stores; however, the level of hypertension in the transgenic SHR was similar to that in the nontransgenic SHR control. The transgenic SHR overexpressing SREBP-1a represents a nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension that may provide new opportunities for studying the pathogenesis and treatment of the metabolic syndrome associated with hepatic steatosis.
Interleukin-10 Functions In Vitro and In Vivo to Inhibit Bacterial DNA-Induced Secretion of Interleukin-12 (1997)

Bacterial DNA (bDNA) has a number of biologic properties, including the ability to induce interleukin-12 (IL-12) production by macrophages. We studied the role of the regulatory cytokine IL-10 as a potential inhibitor of bDNA-induced IL-12 production. IL-10 concentrations as low as 0.3 ng/ml profoundly inhibited bDNA-induced macrophage IL-12 production as measured by Elispot analysis of IL-12 p40-secreting cells. Additionally, we found that IL-10 inhibited bDNA-induced IL-12 secretion by the macrophage cell lines J774 and RAW 264. Preincubation of splenic adherent cells with IL-10 markedly reduced bDNA-induced transcription of IL-12 p40 mRNA. Interestingly, after 2 h of exposure, bDNA also induces transcription of IL-10 mRNA by splenic adherent cells. The importance of IL-10 in the in vivo regulation of bDNA-induced cytokine secretion was illustrated by the response of mice with disrupted IL-10 genes (IL-10 ko mice) to i.v. bDNA challenge. Compared to +/+ mice, IL-10 knockout (ko) mice exhibited increased numbers of IL-12 and interferon-gamma (IFN-gamma)-secreting cells following either single or repeated challenge with bDNA. These findings indicate that IL-10 plays a key role in regulating bDNA-induced production of inflammatory cytokines.
Neuropathology of inflicted head injury in children: II. Microscopic brain injury in infants (2001)

There are very few reports in the literature dealing with the neuropathology of infant head injury, and the question of whether diffuse traumatic brain damage [diffuse axonal injury (DAI)] occurs in such children has not yet been reliably established by detailed neuropathological studies. We report the findings in the brains of a series of 37 infants aged 9 months or less, all of whom died from inflicted head injuries, and 14 control infants who died of other causes. Axonal damage was identified using immunohistochemistry for beta-amyloid precursor protein. Full clinical details were available for each case, the most constant of which in the study cohort was an episode of significant apnoea at presentation, found to have been recorded in 75% of cases. Global hypoxic damage was the most common histological finding. Widespread axonal damage, interpreted as vascular, was present in 13 cases, but widespread traumatic axonal injury was found in only two children, both of whom had severe head injuries with multiple skull fractures. Epidural cervical haemorrhage and focal axonal damage to the brainstem and the spinal nerve roots, found in 11 cases but not in controls, indicate that the craniocervical junction is vulnerable in infant head injury, the neuropathology being that of stretch injury from cervical hyperextension/flexion. Damage to this region could account for the observed apnoea, which could in turn lead to hypoxic damage and brain swelling. The observation that the predominant histological abnormality in cases of inflicted head injury in the very young is diffuse hypoxic brain damage, not DAI, can be explained in one of two ways: either the unmyelinated axon of the immature cerebral hemispheres is relatively resistant to traumatic damage, or in shaking-type injuries the brain is not exposed to the forces necessary to produce DAI.
Enhancing the Hole-Conductivity of Spiro-OMeTAD without Oxygen or Lithium Salts by Using Spiro(TFSI)2 in Perovskite and Dye-Sensitized Solar Cells (2014)

2,2',7,7'-Tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD), the prevalent organic hole transport material used in solid-state dye-sensitized solar cells and perovskite-absorber solar cells, relies on an uncontrolled oxidative process to reach appreciable conductivity. This work presents the use of a dicationic salt of spiro-OMeTAD, named spiro(TFSI)2, as a facile means of controllably increasing the conductivity of spiro-OMeTAD up to 10(-3) S cm(-1) without relying on oxidation in air. Spiro(TFSI)2 enables the first demonstration of solid-state dye-sensitized solar cells fabricated and operated with the complete exclusion of oxygen after deposition of the sensitizer with higher and more reproducible device performance. Perovskite-absorber solar cells fabricated with spiro(TFSI)2 show improved operating stability in an inert atmosphere. Gaining control of the conductivity of the HTM in both dye-sensitized and perovskite-absorber solar cells in an inert atmosphere using spiro(TFSI)2 is an important step toward the commercialization of these technologies.
Construction and characterization of genomic libraries from specific human chromosomes. (1982)

Highly purified fractions of human chromosomes 21 and 22 were isolated from a suspension of metaphase chromosomes stained with ethidium bromide by using a fluorescence-activated cell sorter (FACS II). Two recombinant DNA libraries, representing chromosomes 21 and 22, were constructed by complete digestion of DNA from these fractions with EcoRI and insertion into the vector lambda gtWES lambda B. Twenty clones selected at random from the chromosome 22 library hybridized to EcoRI-digested human DNA, and five of these clones hybridized to single bands identical in size to the phage inserts. These five single-copy sequences and a clone coding for an 8S RNA isolated by screening the chromosome 22 library for expressed sequences were characterized in detail. Hybridization of all six clones to a panel of sorted chromosomes and hybrid cell lines confirmed the assignment of the sequences to chromosome 22. The sequences were localized to regions of chromosome 22 by hybridization to translocated chromosomes sorted from a cell line having a balanced translocation t(17;22)(p13;q11) and to hybrid cell lines containing the various portions of another translocation t(X;22)(q13;q112). Five clones reside on the long arm of chromosome 22 between q112 and pter, while one clone and an 18S rRNA gene isolated from the chromosome 22 library reside pter and g112. The construction of chromosome-specific libraries by this method has the advantage of being direct and applicable to nearly all human chromosomes and will be important in molecular analysis of human genetic diseases.
Management of the pelvic space with or without omentoplasty after abdominoperineal resection for carcinoma of the rectum: a prospective multicenter study. The French Association for Surgical Research. (1997)

Although this study was not randomised, the results suggest that omentoplasty to the pelvic space promotes perineal healing after abdominoperineal resection for carcinoma of the rectum by significantly reducing the need for secondary opening.
Spatial Sound Reproduction with Directional Audio Coding (2007)

Directional audio coding (DirAC) is a method for spatial sound representation, applicable for different sound reproduction systems. In the analysis part the diffuseness and direction of arrival of sound are estimated in a single location depending on time and frequency. In the synthesis part microphone signals are first divided into nondiffuse and diffuse parts, and are then reproduced using different strategies. DirAC is developed from an existing technology for impulse response reproduction, spatial impulse response rendering (SIRR), and implementations of DirAC for different applications are described.
Identification of Novel Virulence-Associated Genes via Genome Analysis of Hypothetical Genes (2004)

The sequencing of bacterial genomes has opened new perspectives for identification of targets for treatment of infectious diseases. We have identified a set of novel virulence-associated genes (vag genes) by comparing the genome sequences of six human pathogens that are known to cause persistent or chronic infections in humans: Yersinia pestis, Neisseria gonorrhoeae, Helicobacter pylori, Borrelia burgdorferi, Streptococcus pneumoniae, and Treponema pallidum. This comparison was limited to genes annotated as hypothetical in the T. pallidum genome project. Seventeen genes with unknown functions were found to be conserved among these pathogens. Insertional inactivation of 14 of these genes generated nine mutants that were attenuated for virulence in a mouse infection model. Out of these nine genes, five were found to be specifically associated with virulence in mice as demonstrated by infection with Yersinia pseudotuberculosis in-frame deletion mutants. In addition, these five vag genes were essential only in vivo, since all the mutants were able to grow in vitro. These genes are broadly conserved among bacteria. Therefore, we propose that the corresponding vag gene products may constitute novel targets for antimicrobial therapy and that some vag mutants could serve as carrier strains for live vaccines.
Antigen-specific tumor vaccines. Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy (1996)

The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression. In order to develop immunizing vectors for the treatment of patients with metastatic melanoma, replication-defective recombinant adenoviruses, Ad2CMV-MART1 and Ad2CMV-gp100, which encode these tumor Ags, have been generated. Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF. Sodium butyrate and TNF-alpha can further augment adenovirus-mediated transgene expression and increase recognition by specific CTLs. Although adenovirus-infected cells expressed the E3/19K protein at detectable levels, significant reduction of surface MHC class I expression was observed in only 3 of 10 tumor cell lines infected with either Ad2CMV-MART1 or Ad2CMV-gp100. Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally. Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect. The anti-gp100 T cells induced by Ad2CMV-gp100 vaccinated appeared to be responsible for the protection. Thus, these recombinant adenoviruses encoding tumor Ags may be useful as vaccines to induce specific T cell immunity for cancer therapy.
Tunable optical tweezers for wavelength-dependent measurements (2012)

Optical trapping forces depend on the difference between the trap wavelength and the extinction resonances of trapped particles. This leads to a wavelength-dependent trapping force, which should allow for the optimization of optical tweezers systems, simply by choosing the best trapping wavelength for a given application. Here we present an optical tweezer system with wavelength tunability, for the study of resonance effects. With this system, the optical trap stiffness is measured for single trapped particles that exhibit either single or multiple extinction resonances. We include discussions of wavelength-dependent effects, such as changes in temperature, and how to measure them.