gebhart/patrepeval huggingface dataset:
InP HBT integrated circuit technology with selectively implanted subcollector and regrown device layers (2004)

We describe a quasi-planar HBT process using a patterned implanted subcollector with a regrown MBE device layer. Using this process, we have demonstrated discrete SHBT with f/sub t/>250 GHz and DHBT with f/sub t/>230 GHz. The process eliminates the need to trade base resistance for extrinsic base/collector capacitance. Base/collector capacitance was reduced by a factor of 2 over the standard mesa device with a full overlap between the heavily doped base and subcollector regions. The low proportion of extrinsic base/collector capacitance enables further vertical scaling of the collector even in deep submicrometer emitters, thus allowing for higher current density operation. Demonstration ring oscillators fabricated with this process had excellent uniformity and yield with gate delay as low as 7 ps and power dissipation of 6 mW/CML gate. At lower bias current, the power delay product was as low as 20 fJ. To our knowledge, this is the first demonstration of high-performance HBTs and integrated circuits using a patterned implant on InP.
Barcoded Primers Used in Multiplex Amplicon Pyrosequencing Bias Amplification (2011)

ABSTRACT “Barcode-tagged” PCR primers used for multiplex amplicon sequencing generate a thus-far-overlooked amplification bias that produces variable terminal restriction fragment length polymorphism (T-RFLP) and pyrosequencing data from the same environmental DNA template. We propose a simple two-step PCR approach that increases reproducibility and consistently recovers higher genetic diversity in pyrosequencing libraries.
TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure (2009)

This trial will test whether torasemide-PR possesses antifibrotic properties, which may provide an additional benefit beyond diuresis in patients with chronic heart failure.
Metabolic effects of tamoxifen in postmenopause. (1995)

Tamoxifen is actually considered the drug of choice for the hormonal treatment of early and metastatic breast cancer due to its efficacy and low toxicity. In addition, clinical trials of adjuvant therapy have demonstrated a 35% decrease in controlateral breast cancer in women receiving tamoxifen compared with controls, suggesting a potential role for this drug in chemoprevention of breast cancer in healthy women at increased risk of disease. Although tamoxifen is usually classified as an estrogen antagonist it also has partial estrogenic effects in some tissues such as liver, bone and uterus. The estrogenic action of tamoxifen on lipid metabolism and bone mineral density suggests additional benefits in protection against cardiovascular diseases and osteoporosis in postmenopausal women. Of particular interest could be the use of tamoxifen as an alternative to traditional estrogen replacement therapy in postmenopausal women previously treated for breast cancer or at increased risk of disease due to family history or histology on breast biopsy. The potential adverse effects of tamoxifen are partially similar to those of ERT and includes an increased risk of endometrial cancer, hepatic diseases, thromboembolic alterations and ocular toxicity. The mechanism of action of tamoxifen is briefly examined and the potential toxic effects and benefits of tamoxifen treatment are discussed.
Long-term up to 24-month efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients (2010)

NCT00903409.
A112, a tamibarotene dimethylaminoethyl ester, may inhibit human leukemia cell growth more potently than tamibarotene (2011)

A112 is a tamibarotene dimethylaminoethyl ester considered a candidate compound for the treatment of acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML). Our goal in this study was to evaluate the efficacy of anti-cancer activity, beginning by studying its inhibitory effects on leukemia cells and then comparing it to tamibarotene. A112 effectively inhibited the growth of HL-60 and NB4 cells as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory effect of A112 was confirmed in mice in which A112 delayed the growth of HL-60 xenografts after 3 weeks' injection. The efficacy of A112 on leukemia cell growth was stronger than that of tamibarotene at the same dosage. The detection of A112 and tamibarotene in plasma of rats showed that A112 might sustain release of its hydrolysate tamibarotene, and the concentration was maintained at a higher level and for a longer time than that of tamibarotene injection. We studied the differentiation morphologies of leukemic cells exposed to A112 or tamibarotene. The number of differentiated NB4 cells was increased, suggesting that A112 possessed differentiation activity in the inhibition of leukemia growth. Further studies showed that the expression of CD11b, a marker of terminal granulocyte differentiation, was increased as estimated by flow cytometry with a direct immunofluorescence assay. A112 was found to induce the activation of CCAAT/enhancer-binding protein β (C/EBPβ) and cyclin-dependent kinase (CDK) inhibitors p21(Waf1/cip1) and p27(Kip1) while cell growth was inhibited. These activities of A112 were greater than those of tamibarotene. The higher efficacy of A112 was also evidenced by induction of apoptosis in leukemia cells. A112 induced a greater number of annexin V-positive cells than did tamibarotene as measured by flow cytometry analysis. Treatment of mice with A112 resulted in stronger terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in HL-60 xenografts. Western blot analysis revealed that A112 increased the expression of caspase-3, caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP) in leukemia cells both in vitro and in vivo, indicating that induction of apoptosis was involved in the inhibition of leukemia growth. Taken together, these results suggest that A112 is a highly effective derivative of trans retinoic acid and a potential candidate compound for the treatment of leukemia.
Xenopus sonic hedgehog as a potential morphogen during embryogenesis and thyroid hormone-dependent metamorphosis (1995)

The hedgehog family of proteins have been implicated as important signaling molecules in establishing cell positional information and tissue patterning. Here we present the cloning and characterization of a hedgehog homologue from Xenopus laevis similar to the sonic class of vertebrate hedgehog genes. We isolated Xenopus hedgehog (Xhh) from a subtractive hybridization screen designed to identify genes induced by thyroid hormone during metamorphosis of the X.laevis gastrointestinal tract. In the intestine, Xhh mRNA expression was up-regulated at the climax of metamorphosis (stage 62) when intestinal epithelium underwent morphogenesis. Treatment of pre-metamorphic tadpoles with exogenous thyroid hormone (TH) resulted in a similar pattern of Xhh induction. Furthermore, TH induction was resistant to inhibitors of protein synthesis suggesting that Xhh is a direct thyroid hormone response gene. The expression and TH regulation of Xhh was not limited to the intestine, but was also observed in the limb and a mixture of pancreas and stomach. Throughout development, Xhh mRNA was present at varying levels with the earliest expression being detected at neurula stage. The highest levels of Xhh were observed between stages 33 and 40 shortly before tadpole feeding begins. Whole mount in situ hybridization analysis of Xhh expression in pre-hatching, stage 32 tadpoles demonstrated staining in the notochord and floor plate similar to that observed for other vertebrate hedgehog genes. Together, these data suggest a putative role for Xhh in organ development during both amphibian embryogenesis and metamorphosis.
Emergence of Drug Tolerance in Cancer Cell Populations: An Evolutionary Outcome of Selection, Nongenetic Instability, and Stress-Induced Adaptation (2015)

In recent experiments on isogenetic cancer cell lines, it was observed that exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells, which display markers associated with stem cell-like cancer cells. After a period of time, some of the surviving cells were observed to change their phenotype to resume normal proliferation and eventually repopulate the sample. Furthermore, the drug-tolerant cells could be drug resensitized following drug washout. Here, we propose a theoretical mechanism for the transient emergence of such drug tolerance. In this framework, we formulate an individual-based model and an integro-differential equation model of reversible phenotypic evolution in a cell population exposed to cytotoxic drugs. The outcomes of both models suggest that nongenetic instability, stress-induced adaptation, selection, and the interplay between these mechanisms can push an actively proliferating cell population to transition into a weakly proliferative and drug-tolerant state. Hence, the cell population experiences much less stress in the presence of the drugs and, in the long run, reacquires a proliferative phenotype, due to phenotypic fluctuations and selection pressure. These mechanisms can also reverse epigenetic drug tolerance following drug washout. Our study highlights how the transient appearance of the weakly proliferative and drug-tolerant cells is related to the use of high-dose therapy. Furthermore, we show how stem-like characteristics can act to stabilize the transient, weakly proliferative, and drug-tolerant subpopulation for a longer time window. Finally, using our models as in silico laboratories, we propose new testable hypotheses that could help uncover general principles underlying the emergence of cancer drug tolerance.
Manganese binding and oxidation by spores of a marine bacillus (1982)

Mature, dormant spores of a marine bacillus, SG-1, bound and oxidized (precipitated) manganese on their surfaces. The binding and oxidation occurred under dormant conditions, with mature spores suspended in natural seawater. These heat-stable spores were formed in the absence of added manganese in the growth medium. The rate and amount of manganese bound by SG-1 spores was a function of spore concentration. Temperatures greater than 45 degrees C, pH values below 6.5, or the addition of EDTA or the metabolic inhibitors sodium azide, potassium cyanide, and mercuric chloride inhibited manganese binding and oxidation. However, SG-1 spores bound and oxidized manganese after treatment with glutaraldehyde, formaldehyde, ethylene oxide gas, or UV light, all of which killed the spores. Manganese oxidation never occurred in the absence of manganese binding to spores. The data suggest that Mn2+ was complexed by a spore component, perhaps an exosporium or a spore coat protein: once bound, the manganese was rapidly oxidized.
Heterogeneous and monoclonal helper T cells induce similar anti‐(4‐hydroxy‐3‐nitrophenyl)acetyl (NP) antibody populations in the primary adoptive response I. Isotype distribution (1984)

In the response to NP-lipopolysaccharide or NP-Ficoll predominantly anti-NP antibodies of the IgM class are produced in mice with lower amounts of IgG3 and IgG2b but little or no IgG1 and IgG2a. In contrast, in the primary T-dependent response to NP-keyhole limpet hemocyanin (KLH) or NP-chicken gamma globulin high amounts of all IgG isotypes are induced. To investigate whether isotype-specific T cells are responsible for these differences we carried out cell transfer experiments using carrier-specific T cell lines. Two such lines were established and one of the two could be cloned. Upon activation by antigen the T cell lines induced unprimed syngeneic splenic B cells to proliferate and differentiate into antibody-secreting cells in vitro in an antigen-nonspecific way. Antigen-specific activation of unprimed B cells in a cell transfer system in vivo showed that high concentrations of hapten-specific antibodies of all IgG isotypes are induced through both carrier-specific T helper lines. The isotypic pattern of these antibodies is similar to that produced via heterogeneous splenic T cells in the cell transfer system, or in normal animals on immunization with the same antigen. These results suggest that isotype-specific T cells are not required for the production of IgG isotypes in a primary anti-NP response and thus not responsible for the differences seen in isotypic patterns between T-dependent and T-independent responses.
Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. (2002)

The WWOX (WW domain containing oxidoreductase) gene was recently identified as a candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans the common fragile site FRA16D. To evaluate the potential role of the WWOX gene in esophageal squamous cell carcinomas, we examined 36 tumors for genetic alterations of the WWOX gene. Loss of heterozygosity (LOH) at the WWOX locus was observed in 14 (39%) tumors. A tumor-specific missense mutation was found in one tumor, and LOH analysis had shown that the other allele was missing. Furthermore, we detected aberrant WWOX gene transcripts with absence of exons 6-8 in two tumors, and complete absence of transcript in one tumor. These results indicate that alteration and inactivation of the WWOX gene may play a role in esophageal squamous cell carcinogenesis.
The MELANIE project: From a biopsy to automatic protein map interpretation by computer (1991)

The goals of the MELANIE project are to determine if disease-associated patterns can be detected in high resolution two-dimensional polyacrylamide gel electrophoresis (HR 2D-PAGE) images and if a diagnosis can be established automatically by computer. The ELSIE/MELANIE system is a set of computer programs which automatically detect, quantify, and compare protein spots shown on HR 2D-PAGE images. Classification programs help the physician to find disease-associated patterns from a given set of two-dimensional gel electrophoresis images and to form diagnostic rules. Prototype expert systems that use these rules to establish a diagnosis from new HR 2D-PAGE images have been developed. They successfully diagnosed cirrhosis of the liver and were able to distinguish a variety of cancer types from biopsies known to be cancerous.
Programming mechanism of polysilicon resistor fuses (1982)

The programming characteristics of polysilicon resistor fuses were investigated. It was found that an open circuit occurs only after the fuse makes a transition to a second-breakdown state in which the current flow is mainly through a molten filament. Filamentary current flow is stable since the resistivity of silicon decreases abruptly upon melting. A simple model was developed which explains the observed <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I - V</tex> characteristics. Fuse opening occurs when the current in second breakdown exceeds a critical current I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</inf> which depends strongly on the fuse thickness and the presence or absence of a passivation layer over the fuse. The gap forms at the positive end, suggesting that the silicon ions move by drift in the applied electric field.
Multicolor Coding of Cells with Cationic Peptide Coated Quantum Dots (2004)

Quantum dots are a new class of fluorophores, whose more prominent characteristics include size-tunable, narrow, fluorescence emission bands and broad overlapping excitation spectra of multiple color dots. Here, we present an efficient, versatile, and gentle approach for intracellular delivery of quantum dots that is easily extended to multicolor optical coding of mammalian cells. In this method, a nine residue biotinylated l-arginine peptide is used to enhance delivery of streptavidin conjugated quantum dots into mammalian cells.
The mediamill large.lexicon concept suggestion engine (2006)

In this technical demonstration we show the current version of the MediaMill system, a search engine that facilitates access to news video archives at a semantic level. The core of the system is a lexicon of 436 automatically detected semantic concepts. To handle such a large lexicon in retrieval, an engine is developed which automatically selects a set of relevant concepts based on the textual query and example images. The result set can be browsed easily to obtain the final result for the query.
Experience with the Use of High-Dose Interleukin-2 in the Treatment of 652 Cancer Patients (1989)

We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients.
Improved Mammalian Expression Systems by Manipulating Transcriptional Termination Regions (2003)

Here we show that the transcriptional terminator element of human gastrin gene, which is the only element characterized to date in terms of its function in transcriptional termination, increases the transient expression levels of recombinant proteins. The expression of the beta-galactosidase gene was enhanced 3-4-fold in HeLa cells by inserting the terminator element of human gastrin gene at the 3'-side of the SV40 polyadenylation signal/cleavage site of the control vector (pSV-beta-gal). This effect of the terminator element is orientation-dependent but not cell-specific since a similar enhancement of beta-galactosidase gene expression was detected in COS.M6 and CHO DG44 cells. The increased level of beta-galactosidase gene expression by the transcriptional terminator element of human gastrin gene turned out to arise from elevated cellular mRNA levels, suggesting that the terminator element stabilizes mRNA by enhancing proper 3'-end processing of mRNA.
Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM (1993)

Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.
A Cold-Adapted Mutant of Parainfluenza Virus Type 3 Is Attenuated and Protective in Chimpanzees (1993)

A live attenuated cold-adapted parainfluenza virus type 3 (PIV-3) vaccine is being developed to prevent the serious lower respiratory tract disease caused by this virus in infants and young children. This cold-passaged mutant (cp45) was evaluated in seronegative chimpanzees and found to be highly attenuated in both the upper and lower respiratory tracts compared to its wild-type parent. Animals immunized with cp45 were also highly resistant to wild-type PIV-3 challenge. Stability of the attenuation phenotype was demonstrated by the administration to 2 additional chimpanzees of an isolate of cp45 obtained after 10 days of replication in a chimpanzee. It was attenuated in both the upper and lower respiratory tracts. The cp45 virus present in the respiratory tract secretions of chimpanzees retained the temperature-sensitive (ts) phenotype, but some loss of ts property was observed in the isolates. These results provide a basis on which to proceed to clinical trials in seronegative human infants and children.