gebhart/patrepeval huggingface dataset:
Trans-activation of the Mouse Cartilage-Derived Retinoic Acid-Sensitive Protein Gene by Sox9 (1999)

The transcription factor Sox9 is capable of enhancing type II collagen gene expression and may play a crucial role in chondrogenesis. To determine whether Sox9 is an inducer of the chondrocyte phenotype, we investigated the role of Sox9 in transcription of another cartilage gene encoding the cartilage-derived retinoic acid-sensitive protein (CD-RAP). CD-RAP is specifically expressed during chondrogenesis. We show here that Sox9 protein is able to bind to a SOX consensus sequence in the CD-RAP promoter. Mutation of the SOX motif led to decreased transcription of a CD-RAP promoter construct in chondrocytes. Overexpression of SOX9 resulted in a dose-dependent increased activity of CD-RAP promoter-driven reporter gene in both chondrocytes and nonchondrogenic cells. A truncated SOX9, which contains a binding domain but no trans-activation function, inhibited CD-RAP promoter activity. Overexpression of SOX9 increased the level of endogenous CD-RAP mRNA in chondrocytes, but was unable to induce endogenous gene expression in 10T1/2 mesenchymal cells or BALB/c-3T3 fibroblasts. These results suggest that Sox9 is a general transcriptional regulator of cartilage-specific genes. However, Sox9 does not appear to be able to induce the chondrocyte phenotype in nonchondrogenic cells, implying that other factors are involved in chondrogenesis.
DNA amplification is rare in normal human cells. (1990)

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10(8) cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of oncogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency.
Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS- derived leukemia (1993)

The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty-four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS.
Evolution of the microstructure in microcrystalline silicon prepared by very high frequency glow-discharge using hydrogen dilution (2000)

A series of samples was deposited by very high frequency glow discharge in a plasma of silane diluted in hydrogen in concentrations SiH4/(SiH4+H2) varying from 100% to 1.25%. For silane concentrations below 8.4%, a phase transition between amorphous and microcrystalline silicon occurs. Microcrystalline silicon has been characterized by transmission electron microscopy (TEM) and x-ray diffraction. The medium-resolution TEM observations show that below the transition, the microstructure of microcrystalline silicon varies in a complex way, showing a large variety of different growth structures. For the sample close to the phase transition, one observes elongated nanocrystals of silicon embedded in an amorphous matrix followed at intermediate dilution by dendritic growth, and, finally, at very high dilution level, one observes columnar growth. X-ray diffraction data evidence a (220) crystallographic texture; the comparison of the grain sizes as evaluated from TEM observations and those determined using Scherrer’s equation illustrates the known limitations of the latter method for grain size determination in complex microstructures.
Neuropathology of Cognitively Normal Elderly (2003)

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.
Metabolism of bovine parathyroid hormone. Immunological and biological characteristics of fragments generated by liver perfusion. (1975)

The metabolism of bovine parathyroid hormone (PTH) by the perfused rat liver was studied. Labeled hormone, with or without cold hormone, was infused into the circulating perfusion medium containing various calcium concentrations. Pefusate samples at various time periods after the introduction of PTH into the system were chromatographed on Bio-gel P-10; radioactivity and/or immunoreactivity were measured in eluted fractions. Before the perfusion, all immuno- and radioactivity eluted in a single peak, with an apparent mol wt of 9,500 (peak I). After perfusion for 15 min, two other peaks with approximate mol wt of 7,000 (peak II) and 3,500 (peak III) were discernible. Peak I contained both NH2-terminal and COOH-terminal immunoreactivity and was biologically active at all time periods tested. The relative contribution of NH2-terminal and COOH-terminal immunoreactivity to the total immunoreactivity remained constant in this peak throughout the perfusion. In every respect, peak I had the characteristics of intact hormone. At all times, peak II consisted of only COOH-terminal immunoreactivity and was biologically inactive. At early time periods, peak III contained predominantly NH2-terminal immunoreactivity and was biologically active. With time, the relative contribution of NH2-terminal immunoreactivity decreased strikingly while that of COOH-terminal immunoreactivity increased. The three peaks identified in these experiments were analogous in size, biological activity, and immunological characteristics to those we have previously described for fractionated human hyperparathyroid serum. The rate of metabolism of PTH appeared to be regulated by the calcium concentration in the medium. At a high concentration of calcium (greater than 11 mg/100 ml), PTH metabolism was greatly retarded. At a low concentration of calcium (smaller than 5 mg/100 ml), the rate of metabolism was greatly increased. The physiological significance of our observations on the metabolism of PTH by isolated perfused rat liver is not known. However, since such metabolism results in a biologically active fragment, it is suggested that metabolism of intact hormone may be required before full biological expression is possible.
Nonpeptide angiotensin II antagonists derived from 1H-pyrazole-5-carboxylates and 4-aryl-1H-imidazole-5-carboxylates (1993)

Two series of potential angiotensin II antagonists derived from carboxyl-functionalized "diazole" heterocycles have been prepared and evaluated. Initially, a limited investigation of 4-arylimidazole-5-carboxylates led to 2-n-butyl-4-(2-chlorophenyl)-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-y l] methyl]-1H-imidazole-5-carboxylic acid (12b), which was found to be a highly potent antagonist of the rabbit aorta AT1 receptor (IC50 0.55 nM). In conscious, normotensive rats, 12b at 0.1 mg/kg iv inhibited the pressor response to AII by 88%, with a duration of > 6 h. More extensively studied was an isosteric series of 3-alkyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazole -5- carboxylates bearing aryl, alkyl, or aralkyl substituents at N1. These compounds were available in highly regioselective fashion via condensation of a substituted hydrazine hydrochloride with a 2-(methoxyimino)-4-oxoalkanoate intermediate. In vitro, the most potent pyrazolecarboxylic acids had n-butyl at C3 and were substituted at N1 by such groups as 2,6-dichlorophenyl (19h), 2-(trifluoromethyl)phenyl (19k), benzyl (19t), and phenethyl (19u), all with IC50 values of 0.18-0.24 nM. Although less potent in the receptor assay, 3-n-propylpyrazolecarboxylic acids were at least as effective as their butyl counterparts in vivo. Several of the pyrazolecarboxylic acid derivatives demonstrated potent, long-lasting oral activity in rats. At 1 mg/kg po, the 1-benzyl-3-butyl (19t), 1-(2,6-dichlorophenyl)-3-propyl (19v), 3-propyl-1-(2,2,2-trifluoroethyl) (19y), and 1-benzyl-3-propyl (19z) analogues all gave > or = 75% inhibition of the AII pressor response in the rat model, with duration of action > 23 h.
12 W broad area semiconductor amplifier with diffraction limited optical output (1991)

Broad area travelling wave GaAlAs SQW optical amplifiers have been fabricated and characterised. Using a 600 μm wide and a 1000 μm long double pass amplifier, 12 W of peak pulsed output power was achieved with a 0.08° wide diffraction limited far-field lobe. Small signal gain of 31 dB was measured in a 400 μm wide active area device.
The Efficacy of Alefacept in the Treatment of Chronic Plaque Psoriasis (2004)

With the completion of several phase 2 and phase 3 clinical studies, the efficacy and tolerability of alefacept in patients with chronic plaque psoriasis is now well studied. The majority of patients treated with a single course of intravenous or intramuscular alefacept experienced a clinically meaningful response. The efficacy of alefacept correlated with its ability to selectively target and reduce the number of pathogenic memory T cells. A second course of alefacept resulted in further clinical improvement, with increasing response rates and prolonged response duration following treatment cessation. Subpopulation analyses demonstrated that alefacept is effective in a broad spectrum of patients with psoriasis, regardless of disease severity, history of and response to prior antipsoriatic treatment, or whether patients are refractory to or have contraindications to other systemic psoriasis therapies or phototherapy.
Immunodeficiency and immunotherapy in multiple myeloma (2007)

Multiple myeloma is a malignant tumour of plasma cells that remains incurable for the vast majority of patients, with a median survival of 2-3 years. It is characterized by the patchy accumulation of tumour cells within bone marrow leading to variable anaemia, bone destruction, hypercalcaemia, renal failure and infections. Immune dysfunction is an important feature of the disease and leads to infections that are both a major cause of morbidity and mortality and may promote tumour growth and resistance to chemotherapy. Numerous defects of the immune system have been described in multiple myeloma although the relative clinical importance of these remains elusive. There has been considerable interest in the identification of an autologous response against myeloma. Although T cells and humoral responses directed against myeloma-associated antigens have been described, it is uncertain if the immune system plays a role in preventing or controlling myeloma cell growth. There is increasing interest in the potential role of immunotherapy but the success of these interventions is likely to be modified by the immunologically hostile environment associated with multiple myeloma. This review attempts to summarize the current knowledge relating to the immune defects found in multiple myeloma.
Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary Dengue‐3 Virus Infections (2002)

Dengue hemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage, thrombocytopenia, and hepatic inflammation. The interrelationships among virus burden, immune activation, and development of DHF were examined in 54 children with secondary dengue-3 virus infections participating in a prospective, hospital-based study. DHF was associated with higher mean plasma viremia early in illness and earlier peak plasma interferon-gamma levels. Maximum plasma viremia levels correlated with the degree of plasma leakage and thrombocytopenia. Maximum plasma levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II correlated with the degree of thrombocytopenia, independently of viremia levels. Hepatic transaminase elevation correlated with plasma soluble IL-2 receptor levels and not with viremia levels. Quantitative differences in virus burden and host immune responses, and the timing of type 1 cytokine responses, have differing influences on the severity of disease manifestations during secondary dengue-3 virus infections.
Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction. (1988)

The effects of acute global ischemia on cytosolic calcium transients were studied in perfused rabbit hearts loaded with the fluorescent calcium indicator indo 1. Indo 1-loaded hearts were illuminated at 360 nm, and fluorescence was recorded simultaneously at 400 and 550 nm from the epicardial surface of the left ventricle. The F400/F550 ratio was calculated by an analog circuit, which allowed cancellation of optical motion artifact. Resulting calcium transients demonstrated a rapid upstroke and slow decay similar to those recorded in isolated ventricular myocytes. Global ischemia rapidly suppressed contraction, but it produced a concurrent increase in the systolic and diastolic levels of the calcium transients, together with an increase in the duration of the peak. The effects of ischemia were reversed by reperfusion, inhibited by verapamil, and mimicked by perfusion of nonischemic hearts with acidified (CO2-rich) solution. In addition to elevation of the calcium transients, ischemia caused a pattern of intracellular calcium alternans that was discernible after 2-3 minutes. The pattern of alternans was stable at a given epicardial site, but it could be out of phase at different sites. Similar nonuniformities were observed in contraction strength and in the duration of monophasic action potentials recorded immediately adjacent to the fiber-optic probe. Abnormalities in intracellular calcium may be a causal factor in the loss of electrical and mechanical synchrony in the acutely ischemic heart.
Deferoxamine Enhances Bone Regeneration in Mandibular Distraction Osteogenesis (2014)

The authors' study demonstrates the effectiveness of deferoxamine treatment to enhance the number of osteocytes within the regenerate in a murine mandibular distraction osteogenesis model. Maintenance of full lacunae supports the authors' finding of a robust cellular response to deferoxamine therapy. These results suggest that the angiogenic capabilities of deferoxamine translate into an increase in the number of bone-forming cells in the regenerate. Deferoxamine may have utility in optimizing bone formation in distraction osteogenesis and lead to superior reconstructive capabilities for craniofacial surgeons in the future.
Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer (2008)

Novel transcriptional regulatory mechanisms involving Aurora kinase and survivin appear to contribute to cytotoxicity mediated by HDAC inhibitors in lung cancer cells.
A Method of Stress Reduction during Silicon Thinning (2011)

Abstract Post silicon validation techniques require backside sample preparation by silicon thinning techniques. The conventional fixture to this preparation on large die packages causes silicon to crack. A new “4-point bending” fixture was developed to reduce silicon bending strain during thinning to eliminate silicon cracking. This new fixture and technique improved remaining silicon thickness uniformity as well as process time.
Cancer Vaccines: Moving Beyond Current Paradigms (2007)

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. Although no therapeutic cancer vaccine has to date been approved by the Food and Drug Administration, several new paradigms are emerging from recent clinical findings both in the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and end point analyses. This article will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classic "tumor response" (Response Evaluation Criteria in Solid Tumors) criteria with "patient response" in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with "conventional" combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell--mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.
Flexoelectricity in nematic and smectic-A liquid crystals (1976)

Flexoelectric effects are observed in both the nematic and smectic-A phases of p-butoxybenzal-p- (β-methylbutyl) aniline (BBMBA) and p-cyano-benzylidine-p-octyloxyaniline (CBOOA). This is the first reported observation of flexoelectricity in smectic phases. The use of a symmetric interdigital electrode in the homeotropic geometry facilitated the unambiguous separation of linear and quadratic electro-optic effects. Both the interdigital electrodes and those liquid-crystal deformations that are quadratic in the voltage act as optical diffraction gratings with a spacing that corresponds to the repeat distance d for adjacent electrodes. In contrast linear electro-optic effects give rise to diffraction gratings with twice this spacing since adjacent electrodes have opposite voltages. Diffraction maxima due to the linear effects are halfway between the maxima due to the other effects. Using optical heterodyne detection, the intensity of the diffraction maxima believed to arise from the linear effect are indeed observed to be linear in the applied voltage V (ω). With homodyne detection the diffracted intensity is proportional to V (ω)2. Although previous discussions of flexoelectricity in nematics have been in terms of two flexoelectric coefficients e11 and e33, we present theoretical arguments that as long as ∇×E=0 there is only one true volume coefficient and that the other constant can always be included in surface effects. Our measurements of the volume coefficient f=e11+e33 are an order of magnitude larger than previously obtained values for e11 and e33. Measured values of f are also nearly independent of temperature, in contrast to previous theoretical models, and of similar magnitude in the smectic and nematic phases. Measurements of flexoelectric signals versus the frequency of the driving voltage obtain relaxation times for splaylike nematic fluctuations and undulation-type smectic fluctuations.
Spin immunoassay of opiate narcotics in urine and saliva (1972)

Free-radical technology can be combined with immunoassay to yield an entirely new system for detection and assay of small molecules in biologic fluids. The method, called "spin immunoassay," has substantial advantages over radioimmunoassay and standard procedures such as thin-layer and gas-liquid chromatography. The assay requires only a very small volume of the unknown solution (eg, urine, saliva), no chemical manipulations are needed, and the result is obtained by an instantaneous readout on the electron spin resonance spectrometer. This technique can be applied to the quantitative determination of opiate narcotics in urine and saliva.