gebhart/patrepeval huggingface dataset:
Bevacizumab (B) plus gemcitabine (G) in patient (pts) with advanced pancreatic cancer (PC): Updated results of a multi-center phase II trial (2004)

4009 Background: Vascular endothelial growth factor (VEGF) and its receptors are overexpressed in PC. In preclinical models, anti-VEGF antibodies suppress PC growth and potentiate the activity of gemcitabine. High VEGF expression correlates with advanced stage and decreased survival in PC pts. These data suggest that anti-VEGF therapy may have utility in PC. Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to VEGF. Methods: We are conducting a phase II trial of BG in advanced PC pts at 8 centers. Eligible pts have no prior chemotherapy (except 5-FU as a radiosensitizer); PS 0–2; measurable disease; no tumor invasion of major vessels; no bleeding or thrombosis. G 1000 mg/m2 is given over 30 minutes days (D) 1, 8, 15 every 28 D. B 10 mg/kg is given D 1, 15 every 28D. CT scans are obtained every 2 cycles. Plasma VEGF levels are obtained pretreatment. 45 pts enrolled 11/01–12/03. Pt characteristics: male 47%; median age 61 (range 42–83); PS: 0/1/2: 62%/36%/2%; stage IV 100%; liver metastases 80%; prior radiation 18%. Results: 182 cycles of BG have been administered (median 3, range <1–11). 42 pts are currently evaluable for response in this ongoing trial (median follow-up 5.7 months). There are 9 confirmed partial responses (21% PR) lasting a median of 9.4 months. 19 pts (45%) had stable disease lasting a median of 5.4 months. Median time to progression is 5.8 months (95% CI: 4.8, 9.1). Median survival is 9.0 months (95% CI: 7.4, 12.4); 6-month survival is 74%. Grade ¾ toxicities (% pts): neutropenia 33%; leukopenia 30%; thrombocytopenia 7%; thrombosis 12%; bowel perforation 5%; hypertension, proteinuria, and headache 2% each. Grade 5 toxicities: 1 gastrointestinal bleed, 1 bowel perforation. Pretreatment plasma VEGF levels in 32 pts (range 0–586 pg/ml) showed no correlation with either response (Fisher's exact test p=1.00) or survival (Log rank test p=0.70). Conclusion: BG is active and well-tolerated in advanced PC. The median survival of 9.0 months and the 74% 6-month survival are encouraging. A randomized phase III trial of BG vs. G is in development in the Cancer and Leukemia Group B. Supported by NCI grant N01-CM-17102. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Lilly Oncology Genentech Lilly Oncology Lilly Oncology
Microvascular corrosion casting in the study of tumor vascularity: a review. (1995)

Tumor blood flow is dependent on the structure and three-dimensional (3-D) architecture of the vascular network. The latter can be best studied by scanning electron microscopy of microvascular corrosion casts. However, literature reviews show that nearly all studies using this technique render comparisons of different tumors more difficult since they are mainly based on descriptive terms that might lead to misunderstandings. Qualitative comparisons of 13 experimental and 3 human primary tumors of different origin show a high degree of similarity in the vasculature. Quantitative analysis of these casts reveals similar ranges of parameters such as diameters, intervascular and interbranching distances. Diameters of vessels with capillary wall structure range from 6 micron m to 55 micron m in the human primary tumors (renal clear cell carcinoma, basalioma), and from 5 micron m to 80 micron m in xenografted tumors (sarcomas, colon carcinoma). Intervascular distances in the human primary tumors range from 2 micron m to 52 micron m, and from 11 micron m to 105 micron m in the xenografts. Interbranching distances range from 34 micron m to 258 micron m in the former, and from 11 micron m to 160 micron m in the latter. Both qualitative and quantitative analyses of tumor microvascular corrosion casts enable pathophysiological conclusions to be drawn and contribute to a better understanding of tumor vascularity.
Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer (2011)

ER-negative breast cancers with high levels of TIL have heightened sensitivity to anthracycline-based chemotherapy, as assessed by the immediate response to neoadjuvant therapy and long-term outcome following adjuvant therapy. Investigations of TIL-based predictive tests to identify patients likely to benefit from anthracycline-based treatments are warranted.
Influenza vaccines: present and future (2002)

The future of vaccine designThe impact of influenza on individuals and on society remains underappreciated.Up to 20% of the population may develop influenza in any given year, and epidemics of influenza are responsible -on average -for 20,000 deaths per year in the US.In some epidemics, this number may climb to more than 40,000 deaths, with over 300,000 influenza-related hospitalizations in a single winter season (1).By far the most catastrophic impact of influenza during the past 100 years was the pandemic of 1918, which cost more than 500,000 lives in the United States (2) and lowered the average life expectancy by almost 10 years.
A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells (2006)

Tissue hypoxemia is common in several pathological diseases, including vaso-occlusion in sickle cell disease and myocardial infarction. One finds increased presence of leukocytes during lung injury and at sites of inflammation in vascular endothelium. In this study, we used human pulmonary microvascular endothelial cells and human dermal microvascular endothelial immortalized cell line to delineate the cellular signaling mechanism of hypoxia- and CoCl2 (a mimetic of hypoxia)-induced IL-8 expression, and the latter's role in chemotaxis of polmorphonuclear neutrophils. We show that hypoxia- and CoCl2-induced IL-8 mRNA and protein expression involved activation of PI3K/Akt and p38 MAPK, but not MEK kinase. Analysis of some transcription factors associated with IL-8 promoter revealed that hypoxia and CoCl2 increased DNA-binding activity of hypoxia-inducible factor-1alpha (HIF-1alpha), NF-kappaB, and AP-1. In addition, we show that hypoxia- and CoCl2-induced IL-8 expression requires activation of HIF as demonstrated by the following: 1) EMSA; 2) transfection studies with IL-8 promoter reporter constructs with mutation in HIF-1alpha binding site; 3) attenuation of IL-8 expression by both HIF-1alpha small interfering RNA and R59949; 4) augmentation of IL-8 expression by either transfection with HIF-prolyl hydroxylase-2 small interfering RNA or overexpression of HIF-1alpha; and 5) chromatin immunoprecipitation analysis. Moreover, conditioned medium from hypoxia-treated endothelial cells augmented chemotaxis of neutrophils, due to release of IL-8. These data indicate that hypoxia-induced signaling in vascular endothelium for transcriptional activation of IL-8 involves PI3K/Akt, p38 MAPK, and HIF-1alpha. Pharmacological agents, which inhibit HIF-1alpha, may possibly ameliorate inflammation associated with hypoxia in pathological diseases.
Low-Latency Successive-Cancellation Polar Decoder Architectures Using 2-Bit Decoding (2014)

<?Pub Dtl=""?> Polar codes have emerged as important error correction codes due to their capacity-achieving property. Successive cancellation (SC) algorithm is viewed as a good candidate for hardware design of polar decoders due to its low complexity. However, for <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(n, k)$</tex></formula> polar codes, the long latency of SC algorithm of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(2n-2)$</tex></formula> is a bottleneck for designing high-throughput polar decoder. In this paper, we present a novel reformulation for the last stage of SC decoding. The proposed reformulation leads to two benefits. First, critical path and hardware complexity in the last stage of SC algorithm is significantly reduced. Second, 2 bits can be decoded simultaneously instead of 1 bit. As a result, this new decoder, referred to as 2b-SC decoder, reduces latency from <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(2n-2)$</tex> </formula> to <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(1.5n-2)$</tex> </formula> without performance loss. Additionally, overlapped-scheduling, precomputation and look-ahead techniques are used to design two additional decoders referred to as 2b-SC-Overlapped-scheduling decoder and 2b-SC-Precomputation decoder, respectively. All three architectures offer significant advantages with respect to throughput and hardware efficiency. Compared to known prior least-latency SC decoder, the 2b-SC-Precomputation decoder has 25% less latency. Synthesis results show that the proposed (1024, 512) 2b-SC-Precomputation decoder can achieve at least 4 times increase in throughput and 40% increase in hardware efficiency.
WIDENING ACCESS TO UNIVERSITY EDUCATION (1988)

The Council for Industry and Higher Education, a remarkable body of over two dozen Company Chairmen, leavened by another dozen Vice‐Chancellors and Directors of Polytechnics, came into being to help develop a common voice. It has enabled some of our intellectual and business leaders to begin to mark out their common interests. We want to find a common language in which to contribute to higher education's important thinking about its future place in our economic life.
Prospective Randomized Study Comparing Docetaxel, Estramustine, and Prednisone With Docetaxel and Prednisone in Metastatic Hormone-Refractory Prostate Cancer (2008)

The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.
Expressions of vascular endothelial growth factor in cirrhotic tissues and their relations to proto-oncogene c-fos, c-myc. (2002)

The protein level of VEGF can reflect the compensation status of cirrhosis patients and may act as an anti-cirrhotic factor. The proto-oncogene c-fos, c-myc and VEGF may have different mechanisms in the course of cirrhosis or hepatic tumorigenesis.
Comparison of the vasoconstrictor effects of the selective 5‐HT1D‐receptor agonist L‐775,606 with the mixed 5‐HT1B/1D‐receptor agonist sumatriptan and 5‐HT in human isolated coronary artery (2000)

The selective 5-HT1D-receptor agonist L-775,606 has less propensity towards vasoconstriction in human isolated coronary artery (endothelium-denuded) than was mixed 5-HT1B/1D-receptor agonist sumatriptan. The contractions produced were at concentrations where L-775,606 would be expected to occupy 5-HT1B-receptors.
Carbohydrate Recognition in Water by a Tricyclic Polyamide Receptor (2004)

A sweet center: Most carbohydrates are supremely comfortable in water. Can they be tempted to leave? Yes, if their new home satisfies all their needs. The water-soluble receptor 1 (R=polycarboxylate) provides hydrophobic surfaces (purple) for CH groups and amide groups (red) for polar substituents. Equatorial substitution is especially well accommodated, and the system duly favors β-glucosyl (2). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z461409_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Production of Cellulase in Solid-State Fermentation with Trichoderma reesei MCG 80 on Wheat Straw (1996)

It is an accepted fact that ethanol production from lignocellulosic materials is not economical as yet because of the high cost of cellulase production. To reduce the cost of cellulase production, lignocellulosic material (wheat straw EWS]), a comparatively much cheaper substrate, was used instead of costly substrates (pure cellulose or lactose). A pan bioreactor was developed for solid-state fermentation (SSF) that required a small capital investment. High yields of complete cellulase system were obtained compared to that in the liquid-state fermentation (LSF) from WS, when treated with 4.25% NaOH at 121°C for 1 h and mixed with Mandels’ medium. A complete cellulase system is defined as one in which the ratio of ßglucosidase activity to filter paper activity in the enzyme solution is close to 1.0. The cellulase system derived from SSF using the pan bioreactor gave more than 85% hydrolysis of delignified WS. The prototype pan bioreactor requires further improvements so that optimum quantity of substrate can be fermented to obtain high yields of complete cellulase system per unit space. The SSF process provides a means for the production of complete cellulase system for the economical bioconversion of renewable biomass into ethanol.
Definition, detection, and recovery of single-page failures, a fourth class of database failures (2012)

The three traditional failure classes are system, media, and transaction failures. Sometimes, however, modern storage exhibits failures that differ from all of those. In order to capture and describe such cases, single-page failures are introduced as a fourth failure class. This class encompasses all failures to read a data page correctly and with plausible contents despite all correction attempts in lower system levels. Efficient recovery seems to require a new data structure called the page recovery index. Its transactional maintenance can be accomplished writing the same number of log records as today's efficient implementations of logging and recovery. Detection and recovery of a single-page failure can be sufficiently fast that the affected data access is merely delayed, without the need to abort the transaction.
Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway (2015)

Keywords: TGF-β, TGF-βRI kinase inhibitor, ALK5, galunisertib, LY2157299, cancer, clinical trials
Sperm mediated gene transfer in pig: Selection of donor boars and optimization of DNA uptake (2003)

Transgenic animals are produced primarily by microinjecting exogenous DNA into the male pronuclei of a zygote. Microinjection is successful in mice but not efficient in farm animals, limiting its general utility. We have pursued an alternative technology for producing transgenic animals: Sperm Mediated Gene Transfer (SMGT). Based on our finding that sperm cells bind and internalize exogenous DNA, we used sperm as a vector for transmitting, not only their own DNA, but also, the exogenously-introduced gene of interest to the zygote. SMGT is highly efficient (up to greater than 80%) and relatively inexpensive; it can be used in species refractory to microinjection, whenever reproduction is mediated by gametes. In this report, we describe the procedure for selection of sperm donors and optimization of DNA uptake that are the key steps for the successful outcome of SMGT. We found that the nominal parameters that boar sperm should possess to serve as a good vector for exogenous DNA are the quality of semen based on standard parameters used in conventional animal breeding programs (volume, concentration, presence of abnormal sperm cells, motility at time of collection, and high progressive motility after 2 hr) and the ability of the sperm cells to take up and internalize exogenous DNA. The results described provide significant advances in SMGT technology applied to pigs, so that transgenic pigs can be efficiently obtained. Mol.
Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne. (2008)

Talarozole, being developed by Barrier Therapeutics Inc under license from Johnson & Johnson, is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans retinoic acid for the treatment of psoriasis and acne. Phase II clinical trials of an oral formulation of talarozole in patients with psoriasis and with acne, and a phase I clinical trial of a topical formulation have been completed. At the time of publication, Barrier Therapeutics had suspended the development of talarozole as part of a series of cost-cutting initiatives; the company had also been acquired by Stiefel Laboratories Inc. No formal announcement had been made regarding the further development of talarozole.
Review: Bacteriocins of Lactic Acid Bacteria (2001)

During the last few years, a large number of new bacteriocins produced by lactic acid bacteria (LAB) have been identified and characterized. LAB-bacteriocins comprise a heterogeneous group of physicochemically diverse ribosomally-synthesized peptides or proteins showing a narrow or broad antimicrobial activity spectrum against Gram-positive bacteria. Bacteriocins are classified into separate groups such as the lantibiotics (Class I); the small (&lt;10 kDa) heat-stable postranslationally unmodified non-lantibiotics (Class II), further subdivided in the pediocin-like and anti Listeria bacteriocins (subclass IIa), the two-peptide bacteriocins (subclass IIb), and the sec-dependent bacteriocins (subclass IIc); and the large (&gt;30 kDa) heat-labile non-lantibiotics (Class III). Most bacteriocins characterized to date belong to Class II and are synthesized as precursor peptides (preprobacteriocins) containing an N-terminal double-glycine leader peptide, which is cleaved off concomitantly with externalization of biologically active bacteriocins by a dedicated ABC-transporter and its accessory protein. However, the recently identified sec-dependent bacteriocins contain an N-terminal signal peptide that directs bacteriocin secretion through the general secretory pathway (GSP). Most LAB-bacteriocins act on sensitive cells by destabilization and permeabilization of the cytoplasmic membrane through the formation of transitory poration complexes or ionic channels that cause the reduction or dissipation of the proton motive force (PMF). Bacteriocin producing LAB strains protect themselves against the toxicity of their own bacteriocins by the expression of a specific immunity protein which is generally encoded in the bacteriocin operon. Bacteriocin production in LAB is frequently regulated by a three-component signal transduction system consisting of an induction factor (IF), and histidine protein kinase (HPK) and a response regulator (RR). This paper presents an updated review on the general knowledge about physicochemical properties, molecular mode of action, biosynthesis, regulation and genetics of LAB-bacteriocins.
Immunotherapy for Targeting Tau Pathology in Alzheimer’s Disease and Tauopathies (2013)

The drawbacks of amyloid immunotherapy, including the development of encephalitis, the lack of clinical improvement and of any effect on neurofibrillary tangles (NFTs), coupled with the central role of NFTs in dementia, may point that clearance of amyloid pathology is not sufficient for improving the dementia symptoms in Alzheimer's disease (AD) patients. This further supported the concept that immunotherapy targeting the NFT proteinous aggregates may be preferential. Yet, the encephalitogenicity of full-length tau protein under a proinflammatory CNS milieu, reported by us in immunized mice, demands to carefully and selectively target pathological tau, while not the normal functional tau, and assuring both efficacy (anti-NFT effect) as well as safety (free of encephalitis) of a potential vaccine. Accumulating evidence from animal studies shows that tau-immunotherapy, targeting selectively pathological tau, particularly the phosphorylated-tau isoforms, reduces the tau-pathology and improves the symptoms of dementia. These findings are based on studies from different research groups, including our laboratory, conducted in different animal models and using various immunization protocols. There is also evidence that the decrease in NFTs is antibody-mediated involving the endosomal/ lysosomal pathway. No adverse effects were reported by the research groups, including also our study in which mice were immunized with a single injection of phosphorylated-tau peptide under a CNS proinflammatory milieu. In this review, I discuss the studies reported in this field, focusing on different approaches, different immunization protocols and mechanistic aspects, with a focus on the promising efficacy of the tau-immunotherapy, while addressing the safety issues already in the preclinical stage, before progressing to clinical trials.
High-frequency regeneration in speech coding systems (2005)

The traditional method of high-frequency regeneration (HFR) of the excitation signal in baseband coders has been to rectify the transmitted baseband, followed by spectral flattening. In addition, a noise source is added at high frequencies to compensate for lack of energy during certain sounds. In this paper, we reexamine the whole HFR process. We show that the degree of rectification does not affect the output speech, and that, with proper processing, the high-frequency noise source may be eliminated. We introduce a new type of HFR based on spectral duplication of the baseband. Two types of spectral duplication are presented: spectral folding and spectral translation. Finally, in order to eliminate the problem of breaking the harmonic structure due to spectral duplication, we propose a pitch-adaptive spectral duplication scheme in the frequency domain by using adaptive transform coding to code the baseband.
Layer-by-Layer Assembly of Rectifying Junctions in and on Metal Nanowires (2001)

Alumina membranes containing 200 nm diameter pores were replicated electrochemically with metals (Au and Ag) to make free-standing nanowires several microns in length. Wet layer-by-layer assembly of nanoparticle (TiO2 or ZnO)/polymer thin films was carried out in the membrane between electrodeposition steps to give nanowires that contained rectifying junctions. Concentric structures with similar properties were prepared by first coating the membrane walls with multilayer films, and then growing nanowires inside the resulting tubules, or by growing films on the exposed surface of the nanowires after dissolution of the membrane. The I−V characteristics of nanowires prepared by either technique show current rectifying behavior. The electronic properties of Au(MEA)/(ZnO/PSS)19ZnO/Ag (MEA = mercaptoethylamine) devices indicate that rectification is determined by charge injection at the metal/ZnO/PSS-film interface rather than by a tunneling mechanism. In the case of Ag(TiO2/PSS)9TiO2/Au devices, switching behavior and hysteresis that could not be described by Schottky or Fowler−Nordheim characteristics was found. The combined replication/layer-by-layer synthetic approach allows one to control both the geometry and the chemical composition of diode nanowire devices.