gebhart/patrepeval huggingface dataset:
The Effect of Calcium-Regulating Hormones and Prostaglandins on Bone Resorption by Osteoclasts Disaggregated from Neonatal Rabbit Bones* (1985)

It has previously only been possible to assess osteoclastic bone resorption in intact bone, where other cell types may modify or mediate osteoclastic responses to environmental agents. We have recently developed techniques which enable us to measure bone resorption by osteoclasts extracted from bone and have used these techniques to assess the effects of prostaglandins (PGs) and calcium-regulating hormones on bone resorption by these cells. Osteoclasts were mechanically disaggregated from neonatal rabbit long bones and cultured on slices of devitalized cortical bone for 8 or 24 h. After this time, osteoclasts were associated with the appearance in the scanning electron microscope of characteristic resorption pits, the volume of which was calculated by computer-assisted morphometric and stereophotogrammetric techniques after removal of cells. Salmon calcitonin inhibited osteoclastic bone resorption at concentrations of 1 pg/ml and above, while PTH and 1,25-dihydroxyvitamin D3 were without significant effect. This suggests that the latter hormones do not increase bone resorption in intact bone through a direct effect on osteoclasts. PGI2, PGE1, and PGE2, all of which are known to stimulate resorption when added to intact bone, paradoxically reduced resorption in our cultures. It appears likely that PGs act as direct inhibitors of osteoclastic bone resorption but have an additional effect on other cells in bone, which are induced by PGs to cause osteoclastic stimulation.
Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of Current Hurdles (2017)

MRgFUS is a promising new surgical approach with a number of unknowns and unsolved issues. It represents a valuable option particularly for patients who refused or could not be candidates for other procedures, deep brain stimulation in particular.
A Convenient Synthesis of 2-Arylindazol-3-Ones (1991)

Abstract The reductive cyclisation of o-nitrobenzanilides with zinc and sodium hydroxide in aqueous methanol provides a convenient source of 2-arylindazol-3-ones.
Dynamic Changes in Clinical Features and Cytokine/Chemokine Responses in Sars Patients Treated with Interferon Alfacon-1 plus Corticosteroids (2005)

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged in early 2003 as a major international health crisis. We report on serum cytokine levels, viral load and clinical parameters over the course of the disease in a cohort of nine adult SARS patients treated with steroids and interferon alfacon-1 at North York General Hospital in Toronto, Ontario. Considerable variation among SARS patients with respect to circulating viral load and patterns of SARS-CoV-evoked cytokine responses was recorded. No single cytokine profile was observed in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels during the course of the disease in all patients. Expression levels for IL-10, IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL-12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently highest within 5 days of peak viral load. These results suggest that elevated levels of inflammatory cytokines are sensitive correlates of disease severity, including lung abnormalities and viral load in serum, and may provide a tool for monitoring disease progression in affected individuals.
Crystal Structure of Histidine Ammonia-Lyase Revealing a Novel Polypeptide Modification as the Catalytic Electrophile, (1999)

Histidine ammonia-lyase (EC 4.3.1.3) catalyzes the nonoxidative elimination of the alpha-amino group of histidine and is closely related to the important plant enzyme phenylalanine ammonia-lyase. The crystal structure of histidase from Pseudomonas putida was determined at 2.1 A resolution revealing a homotetramer with D2 symmetry, the molecular center of which is formed by 20 nearly parallel alpha-helices. The chain fold, but not the sequence, resembles those of fumarase C and related proteins. The structure shows that the reactive electrophile is a 4-methylidene-imidazole-5-one, which is formed autocatalytically by cyclization and dehydration of residues 142-144 with the sequence Ala-Ser-Gly. With respect to the first dehydration step, this modification resembles the chromophore of the green fluorescent protein. The active center is clearly established by the modification and by mutations. The observed geometry allowed us to model the bound substrate at a high confidence level. A reaction mechanism is proposed.
Phorbol ester-induced differentiation of human T-lymphoblastic cell line HPB-ALL. (1982)

12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, induced phenotypic differentiation in the human thymic acute lymphocytic leukemia cell line, HPB-ALL. Within 30 min of seeding in the presence of TPA, the cells formed a smooth round shape. After a 7-day exposure to TPA, most of the cells became smaller and reminiscent of large or atypical lymphocytes. Electron microscopic analysis evidenced morphological differentiation in TPA-treated HPB-ALL cells. Thymic antigens stained with monoclonal antibody OKT6 were dramatically reduced while Leu2a-positive cells were increased in the TPA-treated HPB-ALL cells. However, OKT3-positive cells did not appear in these TPA-treated cells for up to 7 days. Upon TPA-induced phenotypic differentiation, the growth rate of cells was significantly inhibited, their ability to incorporate DNA and RNA via 3H-labeled precursors was reduced, their ability to bind sheep red blood cell rosettes was significantly increased, and the proportion of terminal deoxynucleotidyl transferase-positive cells was decreased.
Effects of acidic and basic fibroblast growth factors (aFGF, bFGF) on glial precursor cell proliferation: Age dependency and brain region specificity (1992)

Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) are present in high levels in most areas of the embryonic rodent brain. To begin to understand the role of these growth factors in brain development, the effects of aFGF and bFGF on dissociated cell cultures prepared from embryonic and neonatal rat brain were studied. Addition of aFGF and heparin or bFGF alone to serum-free cultures of the dissociated Embryonic Day (E) 14.5 mesencephalon stimulates cell proliferation, as judged by [3H]thymidine autoradiography, leading to a maximal 75-fold increase in the total number of cells. This effect is dose-dependent with half-maximal increases at concentrations of about 5-6 ng/ml of aFGF or bFGF and is inhibited by the FGF antagonist HBGF-1U. The effect of aFGF on cell proliferation in cultures prepared from E14.5 mesencephalon is similar to that in cultures prepared from E14.5 cortex. However, in cultures prepared from E14.5 rhombencephalon or diencephalon, the proliferative effect of aFGF is much reduced. In all brain areas studied, the proliferative effect of aFGF declines with increasing age. Immunocytochemical analysis of E14.5 mesencephalic cultures demonstrated that the aFGF-induced increase in cell number is due to the proliferation of A2B5-immunoreactive (IR) glial precursor cells, but not of neuronal precursors, fibroblasts, or microglial cells. Moreover, differentiated glial fibrillary acidic protein-IR astrocytes and 2',3'-cyclic nucleotide 3'-phosphohydrolase-IR oligodendrocytes were not observed in cultures continuously treated with aFGF or bFGF, but were observed in high numbers after removal of the growth factors. These results suggest (1) that aFGF and bFGF are potent mitogens for glial precursor cells in all embryonic brain regions, (2) that the magnitude of the effects of aFGF depends on embryonic age and brain region, and (3) that both growth factors inhibit the differentiation of astrocyte or oligodendrocyte precursors. These observations made in vitro strongly support the hypothesis that FGF plays a critical role in gliogenesis and the timing of glial differentiation in the brain.
Antibody-directed enzyme prodrug therapy (ADEPT) with mustard prodrugs. (1995)

Antibody-directed enzyme prodrug therapy (ADEPT) is a two-step targeting procedure designed to improve the selectivity of anti-tumour agents. The approach is based on the activation of specially designed prodrugs by enzyme-antibody conjugates targeted to tumour-associated antigens. This review concerns ADEPT using nitrogen mustard prodrugs and carboxypeptidase G2 (CPG2) as the activating enzyme. The specific structural features required of the nitrogen mustard prodrugs, their design, syntheses, physicochemical properties, biological characteristics and activation to the corresponding drugs are reviewed. The ADEPT clinical trial with a nitrogen mustard prodrug is also discussed.
Ascending‐Dose Study of Controlled‐Release Ketamine Tablets in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability (2020)

Parenteral ketamine has fast-onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled-release ketamine tablets would improve safety and tolerability compared with injected ketamine by reducing peak ketamine exposures compared with dosing by injection. In this randomized, placebo-controlled ascending-dose study, ketamine doses of 60, 120, or 240 mg or matching placebo (single dose followed by every-12-hours dosing for 5 doses) were given to 24 healthy volunteers. Pharmacokinetics, pharmacodynamics (brain-derived neurotropic factor), adverse events, and vital signs were assessed up to 72 hours. Drug release occurred over ∼10 hours, with most drug substance present as norketamine (∼90%). Area under the concentration-time curve and peak concentration were dose proportional. Elimination half-life was prolonged (7-9 hours) compared with published data from immediate-release oral formulations. There were no changes in blood pressure or heart rate after any dose. Mild dissociation was reported after 240 mg but not lower doses; mean dissociation ratings in this group were minimal (1-2/76). There were no clinically significant changes in ECGs or safety laboratory tests at any time. Compared with injected ketamine, oral controlled-release ketamine tablets did not increase blood pressure or heart rate, and only at doses of 240 mg was dissociation of mild intensity reported. Reducing and delaying ketamine peak concentration by oral dosing with controlled-release ketamine tablets improve this drug's tolerability for patients with depression/anxiety.
The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation (2001)

Atherosclerosis causes most acute coronary syndromes and strokes.The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells.CD44 is an adhesion protein expressed on inflammatory and vascular cells.CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells.Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells.To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice.We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates.We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions.Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1.Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation.We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.
Test program generation for functional verification of PowerPC processors in IBM (1995)

A new methodology and test program generator have been used for the functional verification of six IBM PowerPC processors. The generator contains a formal model of the PowerPC architecture and a heuristic data-base of testing expertise. It has been used on daily basis for two years by about a hundred designers and testing engineers in four IBM sites. The new methodology reduced significantly the functional verification period and time to market of the PowerPC processors. Despite the complexity of the PowerPC architecture, the three processors verified so far had fully functional first silicon. 1 Introduction A new methodology and tool for functional test program generation has been used for several IBM PowerPC processors. The functional verification period and the processors time to market were reduced. Only one fifth of the simulation cycles needed to verify a RISC System/6000 processor with a previous generator was needed with the new methodology for a PowerPC processor. The new g...
Seizure-Like Events in Disinhibited Ventral Slices of Adult Rat Hippocampus (1999)

Epileptic discharges lasting 2-90 s, were studied in vitro in slices from the ventral hippocampus of adult rats, in which inhibition was blocked acutely with bicuculline methiodide (BMI, 5-30 microM) and potassium ([K(+)](o)) raised to 5 mM. These seizure-like events (SLEs) comprised three distinct phases, called here primary, secondary, and tertiary bursts. Primary bursts lasted 90-150 ms. Secondary bursts lasted a further 70-250 ms, comprising a short series of afterdischarges riding on the same depolarization as the primary burst. Finally a train of tertiary bursts started with a peak frequency of 5-10 Hz and could last >1 min. Slices from the ventral hippocampus showed significantly higher susceptibility to SLEs than did dorsal slices. SLEs proved sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. They were insensitive to N-methyl-D-aspartate (NMDA) receptor antagonists; 50 microl D-2-amino-5-phosphonopentanoic acid (D-AP5) did block the transient secondary bursts selectively. SLEs were restricted to the hippocampus proper even if the entorhinal cortex was present. Entorhinal bursts could last <2 s and were only coupled with hippocampal bursts in a minority of slices. Reentry of epileptic bursts occasionally occurred during interictal discharges, but not during the later stages of SLEs. Full-length SLEs always started in CA3 region and could be recorded in minislices containing CA3 plus dentate hilus. Ion-sensitive microelectrodes revealed that interictal discharges were followed by short (2-3 s) [K(+)](o) waves, peaking at approximately 7.5 mM. SLEs were always accompanied by increases in [K(+)](o) reaching approximately 8.5 mM at the start of tertiary bursts; [K(+)](o) then increased more slowly to a ceiling of 11-12 mM. After the end of each SLE, [K(+)](o) fell back to baseline within 10-15 s. SLEs were accompanied by significant increase in synaptic activity, compared with baseline and/or interictal activity, estimated by the variance of the intracellular signal in the absence of epileptic bursts and action potentials (0. 38 mV(2), compared with 0.13 mV(2), and 0.1 mV(2), respectively). No significant increases were observed in the interval preceding spontaneous interictal activity. These studies show that focal assemblies of hippocampal neurons, without long reentrant loops, are sufficient for the generation of SLEs. We propose that a key factor in the transition from interictal activity to SLEs is an increase in axonal and terminal excitability, resulting, at least in part, from elevations in [K(+)](o).
Turning Low-Molecular-Weight Drugs into Prolonged Acting Prodrugs by Reversible Pegylation: A Study with Gentamicin (2008)

Pegylation is a powerful technology to prolong the action of proteins in vivo, but it is impractical for low-molecular-weight (LMW) drugs, which are usually inactivated upon such modification. Here, we have applied a recently developed strategy of reversible pegylation to gentamicin, a LMW antibiotic. Variable length polyethyleneglycol (PEG-SH) chains were covalently linked to gentamicin using two heterobifunctional agents, each containing a spontaneously hydrolyzable bond. The inactive derivatives regained full antibacterial potency upon incubation under physiological conditions in vitro, and following systemic administration to rats, they released native active gentamicin with half-lives 7- to 15-fold greater than those of systemically administered nonderivatized gentamicin. In conclusion, reversibly pegylated prodrug derivatives of gentamicin were found to be capable of releasing gentamicin for prolonged periods in vivo. Most importantly, the major drawback of conventional pegylation, namely, the loss of pharmacological potency following irreversible derivatization, has been overcome.
Site-specifically radioiodinated antibody for targeting tumors. (1990)

Labeling of an antibody site specifically through its carbohydrate regions preserves its antigen-binding activity (Rodwell et al., Proc. Natl. Acad. Sci., 83: 2632, 1986). Previously site-specific labeling studies have conjugated antibodies with metallic radioisotopes or drugs. We now report site-specific labeling with a new radioiodinated compound, 2-hydroxy-5-iodo-3-methylbenzoyl hydrazide, whose synthesis we described earlier (Belinka et al., Biochemistry, 27: 3084, 1988). The compound is reacted with aldehyde groups produced by specific oxidation of the carbohydrate portion of the antibody with sodium m-periodate. Optimized conjugation conditions give good recovery of active antibody containing 10 groups per molecule. The conjugate is stable in solution for at least several weeks at both 4 and -70 degrees C. When injected into nude mice bearing LS174T human cancer xenografts, the conjugate of B72.3 antibody localizes well to tumor tissue, with low uptake by other organs. This biodistribution is similar to that of conjugate prepared by using solid-phase chloramine-T (Iodohead). There are only two significant differences. First, the carbohydrate conjugate is much less susceptible to dehalogenation, and thus shows much less thyroid uptake. Secondly, the biological half-life of the carbohydrate conjugate was about half that of the chloramine-T one. This could be due primarily to lysis of the hydrazine bond through which the antibody is attached to the compound, which would then be excreted rapidly by itself. The new reagent will be especially useful for antibodies which either cannot be labeled by chloramine-T methods, or whose activity is impaired by them.
3-D depth migration: Various methods andhow they perform on real data (1997)

3-D depth migration is one of the most active areas of research and development and it has been approached from different angles. An accurate algorithm which work" in the space-frequency domain was introduced by Blacquiere et al. (1989). Unfortunately, it is computationally very expensive and not suitable for solving real-life 3-D migration problems. This led to the development of an alternative scheme (Hale, 1990) which sacrifices some accuracy but is much more efficient. It is commonly referred to as the Hale-McClellan method. An alternative procedure known as reverse-time migration works in the space-time domain. It ;05 based on the full wave equation and yields by far the most accurate results, but it requires extremely large computer resources. However, a series of new developments (Mufti et al., 1996) have made this algorithm a very practical tool even for migrating large exploration-scale 3-D real data. We shall provide a comparative evaluation of the results obtained by this method with the corresponding resultsfrom Hale&apos;s algorithm. This will include a detailed investigation of the impulse response as well as migration of both synthetic and real poststack 3-D seismic data. We will not present any results based on prestack migration, but we will discuss a number of serious problems with the current technology developed for prestack migration as well as some food for thought.
Generation and Characterization of Human Induced Pluripotent Stem Cells (2009)

This unit describes how to generate human induced pluripotent stem (iPS) cells and evaluate the qualities of the generated iPS cells. The methods for establishment and maintenance of human iPS cells are similar to those for mouse iPS cells but not identical. In addition, these protocols include excellent procedures for passaging and cryopreservation of human iPS cells established by ES cell researchers, which result in an easy way to culture human iPS cells. Moreover, we include methods for characterizing iPS cells for further research. RT-PCR and immunocytochemistry for detection of pluripotent cell markers, embryoid body differentiation, and teratoma differentiation are used to determine pluripotency in vitro and in vivo, respectively.
CD Antigens 1996 (1997)

THE RESULTS OF THE 6th International Workshop on Human Leukocyte Differentiation Antigens were presented on November 10 through 14, 1996 at a conference held in Kobe, Japan. More than 500 laboratories worldwide participated in the evaluation of 1,152 antibodies and the characterization of more than
Status and potential of atmospheric plasma processing of materials (2011)

This paper is a review of the current status and potential of atmospheric plasma technology for materials processing. The main focus is the recent developments in the area of dielectric barrier discharges with emphasis in the functionalization of polymers, deposition of organic and inorganic coatings, and plasma processing of biomaterials. A brief overview of both the equipment being used and the physicochemical reactions occurring in the gas phase is also presented. Atmospheric plasma technology offers major industrial, economic, and environmental advantages over other conventional processing methods. At the same time there is also tremendous potential for future research and applications involving both the industrial and academic world.
VarScan: variant detection in massively parallel sequencing of individual and pooled samples (2009)

Massively parallel sequencing technologies hold incredible promise for the study of DNA sequence variation, particularly the identification of variants affecting human disease. The unprecedented throughput and relatively short read lengths of Roche/454, Illumina/Solexa, and other platforms have spurred development of a new generation of sequence alignment algorithms. Yet detection of sequence variants based on short read alignments remains challenging, and most currently available tools are limited to a single platform or aligner type. We present VarScan, an open source tool for variant detection that is compatible with several short read aligners. We demonstrate VarScan's ability to detect SNPs and indels with high sensitivity and specificity, in both Roche/454 sequencing of individuals and deep Illumina/Solexa sequencing of pooled samples.