gebhart/patrepeval huggingface dataset:
Preliminary characterization of a transformed cell strain derived from human trabecular meshwork (1994)

Cells isolated from the trabecular meshwork (TM) of a male glaucoma patient were transformed by transfection with an origin defective mutant of SV40 virus. Transformation dramatically increased the growth rate of these cells (designated HTM-3 cells), allowing biochemical and pharmacological characterization. The HTM-3 cells had cytoskeletal components that were reported to be present in TM tissue and non-transformed TM cells. Vimentin, tubulin and smooth muscle specific alpha-actin, but not desmin, were localized in these cells by immunocytochemistry. The extracellular matrix components collagen types I, III and IV, fibronectin and laminin were found in HTM-3 cells as well as their non-transformed parental cells. As predicted, the protein profile of the HTM-3 cells revealed by two-dimensional gel electrophoresis was different from that of the non-transformed cells, probably due to the enhanced growth characteristics of these cells. Furthermore, HTM-3 cells had various intracellular second messenger systems that responded to pharmacological agents. Forskolin, prostaglandin E2, beta-adrenergic and adenosine A2 agonists stimulated the adenylyl cyclase in these cells, whereas muscarinic, serotonergic, dopaminergic and other agonists were ineffective. Sodium nitroprusside increased the intracellular concentration of cGMP, demonstrating the presence of a functional guanylyl cyclase. Phospholipase C activity in these cells was also detected. Muscarinic agonists, histamine and bradykinin, but not adrenergic, serotonergic agonists or prostaglandins, increased phosphoinositide turnover. These drug responses of HTM-3 cells agree with published data on primary TM cells and TM tissues, suggesting that the transformed cells may be a valid substitute for certain pharmacological studies of TM.
A Novel Electrode Array for Diameter-Dependent Control of Axonal Excitability: A Simulation Study (2004)

Electrical extracellular stimulation of peripheral nerve activates the large-diameter motor fibers before the small ones, a recruitment order opposite the physiological recruitment of myelinated motor fibers during voluntary muscle contraction. Current methods to solve this problem require a long-duration stimulus pulse which could lead to electrode corrosion and nerve damage. The hypothesis that the excitability of specific diameter fibers can be suppressed by reshaping the profile of extracellular potential along the axon using multiple electrodes is tested using computer simulations in two different volume conductors. Simulations in a homogenous medium with a nine-contact electrode array show that the current excitation threshold (Ith) of large diameter axons (13-17 microm) (0.6-3.0 mA) is higher than that of small-diameter axons (2-7 microm) (0.4-0.7 mA) with 200-microm axon-electrode distance and 10-micros stimulus pulse. The electrode array is also tested in a three-dimensional finite-element model of the sacral root model of dog (ventral root of S3). A single cathode activates large-diameter axons before activating small axons. However, a nine-electrode array activates 50% of small axons while recruiting only 10% of large ones and activates 90% of small axons while recruiting only 50% of large ones. The simulations suggest that the near-physiological recruitment order can be achieved with an electrode array. The diameter selectivity of the electrode array can be controlled by the electrode separation and the method is independent of pulse width.
The selective androgen receptor modulator GTx‐024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double‐blind, placebo‐controlled phase II trial (2011)

BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.
Long‐term in vivo transduction of neurons throughout the rat central nervous system using novel helper‐dependent CAV‐2 vectors (2003)

Numerous genetic and environmental causes, variable pathophysiologies, and the blood-brain barrier create a formidable challenge for the study and treatment of neurodegenerative diseases affecting the central nervous system. Although there are many intracellular strategies to address neurodegeneration, for example, which transgene to use, one fundamental criterion for the long-term survival of neurons may be their genetic modification. Here, we describe the generation and in vivo efficacy of helper-dependent canine adenovirus (CAV-2) vectors that preferentially transduced neurons and efficiently trafficked via axonal retrograde transport. We used a flexible strategy and the synergy between Cre/loxP and nonlethal packaging-defective helper vectors to generate high titer helper-dependent vector stocks. One year after striatal injections in the rat brain, we found stable, high-level expression in striatal neurons, ~50% of the dopaminergic neurons of the substantia nigra, and the cholinergic neurons in the basal nuclei of Meynert. Due to the intrinsic properties of helper-dependent CAV-2 vectors (27-kb cloning capacity; low preexisting, innate, and induced immunogenicity; retrograde transport; and long-term transgene expression), they will aid fundamental and applied studies in neurobiology. Moreover, helper-dependent CAV-2 vectors may be clinically relevant for the treatment of many neurodegenerative diseases.
A comparison of hemagglutination inhibition and neutralization assays for characterizing immunity to seasonal influenza A (2016)

While we found high overall correspondence of titers between NT and HI assays for seasonal influenza A, no exact equivalence between assays could be determined. This was further complicated by correspondence between titers changing with age. These findings support generalized comparison of results between assays and give further support for use of the hemagglutination inhibition assay over the more resource intensive viral neutralization assay for seasonal influenza A, although attention should be given to the effect of age on these assays.
Phenyl−Carbonyl Coupling Reactions Promoted by Samarium Diiodide and Hexamethylphosphoramide (1997)

By mediation of samarium diiodide and hexamethylphosphoramide, benzaldehydes and acetophenones underwent self- and cross-couplings to give the products having linkages at the para-carbons of phenyl rings and the carbonyl groups. The phenyl−carbonyl coupling of 2,5-dimethoxybenzaldehyde generated a Sm(III)−enolate intermediate, which was trapped by alkyl halides in a stereospecific manner to give uncommon 1,4-dialkyl-2,5-cyclohexadiene-1-carboxaldehydes. The benzaldehydes bearing tethered carbonyl chains proceeded with intramolecular phenyl−carbonyl couplings to afford fused benzocycles.
Chitosan as a Polymer for pH-Induced DNA Capture in a Totally Aqueous System (2006)

A novel DNA solid-phase extraction protocol based on the pH-dependent charge of chitosan was developed specifically for low-volume DNA extraction on microchips. The method uses chitosan-coated beads to extract DNA at pH 5 and release it from the chitosan at pH 9. DNA extraction efficiency as high as 92% could be attained, even from complex samples such as human blood containing significant amounts of protein. Using this method, PCR inhibitors that are typically used in DNA extraction procedures (e.g., chaotropic salts, 2-propanol) can be avoided, making the method more conducive to downstream sample processing using PCR. A high-density multichannel microchip device was then fabricated and the microchannels coated with chitosan for DNA extraction in an open channel configuration without the need for an additional stationary phase. This design provided a relatively high surface area-to-volume ratio for extraction, while retaining the low flow resistance commensurate with open channels. With a flow rate of approximately 1 microL/min during the extraction, the total extraction time was less than 10 min, with most of the DNA recovered in the first 2 microL of elution buffer. Using the microchip device, extraction efficiencies for lambda-phage DNA and human genomic DNA were as high as 67 and 63%, respectively. Human genomic DNA from whole blood samples could be extracted in 10 min with an extraction efficiency of 75 +/- 4% (n = 3), and the purified DNA was suitable for PCR amplification of a fragment of the gelsolin gene. The combination of an entirely aqueous DNA extraction method with a high-density, low-flow resistance microchannel pattern sets the stage for future integration into microfluidic genomic analysis devices.
Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. (1988)

The ras oncogene products require membrane localization for their function, and this is thought to be accomplished by the addition of a palmitoyl group to a cysteine residue near the carboxyl terminus of the nascent chain. A lipidated carboxyl-terminal cysteine residue is also found in sequence-related yeast sex factors, and in at least two cases, the alpha-carboxyl group is also methyl esterified. To determine if ras proteins are themselves modified by a similar type of methylation reaction, we incubated rat embryo fibroblasts transformed with p53 and activated Ha-ras oncogenes with L-[methyl-3H]methionine under conditions in which the isotope was converted to the methyl donor S-adenosyl-L-[methyl-3H]methionine. By using an assay that detects methyl ester linkages, we found that immunoprecipitated ras proteins are in fact esterified and that the stability of these esters is consistent with a carboxyl-terminal localization. This methylation reaction may be important in regulating the interaction of ras proteins with plasma membrane components. The presence of analogous carboxyl-terminal tetrapeptide sequences in other proteins may provide a general recognition sequence for lipidation and methylation modification reactions.
C5a-Mediated Leukotriene B4-Amplified Neutrophil Chemotaxis Is Essential in Tumor Immunotherapy Facilitated by Anti-Tumor Monoclonal Antibody and β-Glucan (2005)

Intravenous and orally administered beta-glucans promote tumor regression and survival by priming granulocyte and macrophage C receptor 3 (CR3, iC3bR and CD11b/CD18) to trigger the cytotoxicity of tumor cells opsonized with iC3b via anti-tumor Abs. Despite evidence for priming of macrophage CR3 by oral beta-glucan in vivo, the current study in C57BL/6 and BALB/c mice showed that granulocytes were the essential killer cells in mAb- and oral beta-glucan-mediated tumor regression, because responses were absent in granulocyte-depleted mice. Among granulocytes, neutrophils were the major effector cells, because tumor regression did not occur when C5a-dependent chemotaxis was blocked with a C5aR antagonist, whereas tumor regression was normal in C3aR(-/-) mice. Neutrophil recruitment by C5a in vivo required amplification via leukotriene B(4), because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B(4)R-deficient (BLT-1(-/-)) mice.
Transdermal secretin for autism - a case report. (2001)

Secretin hormone given daily in transdermal cream was associated with marked and sustained developmental progress in an aphasic two-and-a-half year old child diagnosed with autism.
Cecal Ligation and Puncture (2010)

The cecum contains a high concentration of microbes, which are a combination of Gram-negative and Gram-positive flora. These bacteria range from anaerobic to facultative aerobic to aerobic organisms. In the procedure described in this unit, the ligation of the cecum produces a source of ischemic tissue as well as polymicrobial infection. This combination of ischemic/necrotic tissue and microbial infection distinguishes this multifactorial model from a number of other bacterial sepsis models, including but not limited to: bacteremia secondary to intravenous or intraperitoneal administration; fecal administration or intraperitoneal administration of fecal or bacterial plugs; colonic stents; and bacterial abscess formation.
Nuclear factor‐κB regulates seizure threshold and gene transcription following convulsant stimulation (2007)

We evaluated a role for the nuclear factor-kappa B (NF-kappaB) pathway in the regulation of seizure susceptibility and transcriptional activation during prolonged, continuous seizures (status epilepticus). Using two functionally distinct NF-kappaB inhibitors we observed a decrease in latency to onset of kainate-induced seizures and status epilepticus. To assess NF-kappaB transcriptional activation, we evaluated inhibitor kappa B alpha (IkappaBalpha) and brain-derived neurotrophic factor (bdnf) gene targets. Inhibition of the NF-kappaB signaling pathway significantly attenuated the increases in IkappaBalpha and bdnf mRNA levels that occurred during prolonged seizure activity, suggesting that the NF-kappaB pathway was involved in the up-regulation of these transcripts during status epilepticus. DNA-binding studies and chromatin immunoprecipitation assays using hippocampal extracts from animals with status epilepticus revealed that NF-kappaB subunits were associated with the candidate kappaB-binding elements within promoter 1 of the bdnf gene. The pattern of association was different for the p50 and p65 subunits supporting complex NF-kappaB modifications within promoter 1. In summary, our findings provide additional insights into the role of NF-kappaB transcriptional regulation in hippocampus following status epilepticus and suggest that NF-kappaB pathway activation contributes to seizure susceptibility.
Maximum-likelihood synchronization of a single user for code-division multiple-access communication systems (1998)

Code-division multiple access (CDMA) has emerged as an access protocol well-suited for voice and data transmission. One significant limitation of the conventional CDMA system is the near-far problem where strong signals interfere with the detection of a weak signal. Multiuser detectors assume knowledge of all of the modulation waveforms and channel parameters, and exploit this information to eliminate multiple-access interference (MAI) and to achieve near-far resistance. A major problem in practical application of multiuser detection is the estimation of the signal and channel parameters in a near-far limited system. We consider maximum-likelihood estimation of users delay, amplitude, and phase in a CDMA communication system. We present an approach for decomposing this multiuser estimation problem into a series of single-user problems. In this method the interfering users are treated as colored non-Gaussian noise. The observation vectors are preprocessed to be able to apply a Gaussian model for the MAI. The maximum-likelihood estimate (MLE) of each user's parameters based on the processed observation vectors becomes tractable. The estimator includes a whitening filter derived from the sample covariance matrix which is used to suppress the MAI, thus yielding a near-far resistant estimator.
Experimental demonstration of pulse shaping and shortening by spatial filtering of an induced-phase-modulated probe wave (1997)

An asymmetrically induced phase modulation resulting in an intensity-dependent spatial beam deflection and a subsequent spatial filtering have been used for all-optical pulse shaping and shortening. A compression factor of eight and controllable symmetrical super-Gaussian pulses and pulse trains have been observed in a good agreement with previous analyses in a pump-probe beam configuration.
Development of Monoclonal Antibodies for an Assay of Cardiac Troponin-I and Preliminary Results in Suspected Cases of Myocardial Infarction (1992)

To improve the specificity of biochemical markers of myocardial infarction (MI), we have developed a double monoclonal "sandwich" enzyme immunoassay to measure cardiac troponin-I (cTnI) in serum. We produced eight IgG monoclonal antibodies against human cardiac troponin-I (cTnI) and tested them against human and animal (canine, bovine, and rabbit) troponins. Five antibodies were cardiac-specific; none of the antibodies were species-specific. Two of the five cTnI-specific monoclonal antibodies were utilized in an immunoassay. Standards were made by adding purified human cTnI to affinity-stripped cTnI-free human sera to cover the range 0-100 micrograms/L for cTnI. The dose-response curve was nonlinear but reproducible. Total assay imprecision (CV) varied between 11% and 21%. The upper limit of the reference range (nonparametric 95% interval) was established as 3.1 micrograms/L by measuring cTnI concentration in sera of 159 hospitalized patients without evidence of cardiac disease. Purified human skeletal TnI up to 10,000 micrograms/L did not affect the assay (calculated cross-reactivity < 0.1%). Diagnostic sensitivities of creatine kinase MB isoenzyme (CK-MB) and cTnI were evaluated retrospectively in 49 consecutive patients with proven MI. In the 30 patients for whom sufficient information was available to establish an accurate time course, CK-MB was more sensitive during the first 4 h after the onset of chest pain, but thereafter the sensitivities were similar up to 48 h. However, cTnI is more cardiac-specific than is CK-MB and remains increased longer than does CK-MB.
Unsupervised Hebbian learning by recurrent multilayer neural networks for temporal hierarchical pattern recognition (2010)

Recurrent multilayer network structures and Hebbian learning are two essential features of biological neural networks. An artificial recurrent multilayer neural network that performs supervised Hebbian learning, called probabilistic associative memory (PAM), was recently proposed. PAM is a recurrent multilayer network of processing units (PUs), each processing unit comprising a group of novel artificial neurons, which generate spike trains. PUs are detectors and recognizers of the feature subvectors appearing in their receptive fields. In supervised learning by a PU, the label of the feature subvector is provided from outside PAM. Since the feature subvector may be shared by many causes and may contain parts from many causes, the label of the feature subvector is sometimes difficult to obtain, not to mention the cost, especially if there are many hidden layers and feedbacks. This paper presents an unsupervised learning scheme, which is Hebbian in the following sense: The strength of a synapse increases if the outputs of the presynaptic and postsynaptic neurons are identical and decreases otherwise. This unsupervised Hebbian learning capability makes PAM a good functional model of neuronal networks as well as a good learning machine for temporal hierarchical pattern recognition.
Heuristics of instability and stabilization in model selection (1996)

In model selection, usually a "best" predictor is chosen from a collection ${\hat{\mu}(\cdot, s)}$ of predictors where $\hat{\mu}(\cdot, s)$ is the minimum least-squares predictor in a collection $\mathsf{U}_s$ of predictors. Here s is a complexity parameter; that is, the smaller s, the lower dimensional/smoother the models in $\mathsf{U}_s$. If $\mathsf{L}$ is the data used to derive the sequence ${\hat{\mu}(\cdot, s)}$, the procedure is called unstable if a small change in $\mathsf{L}$ can cause large changes in ${\hat{\mu}(\cdot, s)}$. With a crystal ball, one could pick the predictor in ${\hat{\mu}(\cdot, s)}$ having minimum prediction error. Without prescience, one uses test sets, cross-validation and so forth. The difference in prediction error between the crystal ball selection and the statistician's choice we call predictive loss. For an unstable procedure the predictive loss is large. This is shown by some analytics in a simple case and by simulation results in a more complex comparison of four different linear regression methods. Unstable procedures can be stabilized by perturbing the data, getting a new predictor sequence ${\hat{\mu'}(\cdot, s)}$ and then averaging over many such predictor sequences.
Preparation and properties of anion exchange membranes having pyridinium or pyridinium derivatives as anion exchange groups (1998)

Anion exchange membranes with pyridinum groups and various pyridinium derivative groups were prepared from a copolymer membrane composed of chloromethylstyrene and divinylbenzene, and pyridine and pyridine derivatives. The anion exchange membranes obtained showed excellent electrochemical properties in electrodialysis. The transport numbers of sulfate ions, bromide ions, nitrate ions, and fluoride ions relative to chloride ions were evaluated in connection with the species of a substituent and the position of the substituent in the pyridinium groups. In general, when a hydrophilic substituent (methanol groups) existed at the 2-position of the pyridinium groups, nitrate ions and bromide ions, which are less hydrated, permeated through the membranes with difficulty, and sulfate ions permeated selectively through the membranes. On the other hand, when hydrophobic groups, for example, ethyl groups, existed at the 2-position of the pyridinium groups, bromide ions and nitrate ionspermeated selectively through the membranes and fluoride ions had difficulty permeating through the membranes. The carbon number of the alkyl chain of 4-alkyl pyridinium groups also affected permeation of nitrate ions and bromide ions due to the change in hydrophilicity of the membranes. Though the hydration of the anions and the species of the substituent at the 2-position of the pyridinium groups were related to selective permeation of the anion through the membranes, permeation of sulfate ions was not as sensitive to the hydrophilicity of the membranes. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 49–58, 1998