gebhart/patrepeval huggingface dataset:
Arginine Deiminase as a Novel Therapy for Prostate Cancer Induces Autophagy and Caspase-Independent Apoptosis (2009)

Arginine deprivation as an anticancer therapy has historically been met with limited success. The development of pegylated arginine deiminase (ADI-PEG20) has renewed interest in arginine deprivation for the treatment of some cancers. The efficacy of ADI-PEG20 is directly correlated with argininosuccinate synthetase (ASS) deficiency. CWR22Rv1 prostate cancer cells do not express ASS, the rate-limiting enzyme in arginine synthesis, and are susceptible to ADI-PEG20 in vitro. Interestingly, apoptosis by 0.3 microg/mL ADI-PEG20 occurs 96 hours posttreatment and is caspase independent. The effect of ADI-PEG20 in vivo reveals reduced tumor activity by micropositron emission tomography as well as reduced tumor growth as a monotherapy and in combination with docetaxel against CWR22Rv1 mouse xenografts. In addition, we show autophagy is induced by single amino acid depletion by ADI-PEG20. Here, autophagy is an early event that is detected within 1 to 4 hours of 0.3 microg/mL ADI-PEG20 treatment and is an initial protective response to ADI-PEG20 in CWR22Rv1 cells. Significantly, the inhibition of autophagy by chloroquine and Beclin1 siRNA knockdown enhances and accelerates ADI-PEG20-induced cell death. PC3 cells, which express reduced ASS, also undergo autophagy and are responsive to autophagy inhibition and ADI-PEG20 treatment. In contrast, LNCaP cells highly express ASS and are therefore resistant to both ADI-PEG20 and autophagic inhibition. These data point to an interrelationship among ASS deficiency, autophagy, and cell death by ADI-PEG20. Finally, a tissue microarray of 88 prostate tumor samples lacked expression of ASS, indicating ADI-PEG20 is a potential novel therapy for the treatment of prostate cancer
The Use of Amino Acid Oxidases for the Small-scale Preparation of the Optical Isomers of Amino Acids (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Use of Amino Acid Oxidases for the Small-scale Preparation of the Optical Isomers of Amino AcidsJekishan R. Parikh, Jesse P. Greenstein, Milton Winitz, and Sanford M. BirnbaumCite this: J. Am. Chem. Soc. 1958, 80, 4, 953–958Publication Date (Print):February 1, 1958Publication History Published online1 May 2002Published inissue 1 February 1958https://pubs.acs.org/doi/10.1021/ja01537a052https://doi.org/10.1021/ja01537a052research-articleACS PublicationsRequest reuse permissionsArticle Views154Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Hypersensitivity and Hyperreactivity in the Irritable Bowel Syndrome: An Opportunity for Drug Discovery (1999)

The gastrointestinal tract of many patients with irritable bowel syndrome (IBS) is hypersensitive to different stimuli. The mechanisms of this hypersensitivity are unclear, but could involve enteric, visceral afferent/efferent, spinal and/or central nervous systems. Such complexity, the absence of animal models or anatomical, molecular or genetic markers of IBS, means that it is difficult to create new types of drugs which specifically treat the condition of IBS. To help in this process, current pre-clinical and early-clinical approaches are evaluated in terms of their ability to intervene within the gut-spinal cord/brain axis and inhibit gastrointestinal 'hypersensitivity' and 'hyperreactivity'. Thus, by developing a rational process the pharmaceutical industry may better understand how to design truly effective drugs for the treatment of IBS.
The Novel Trk Receptor Tyrosine Kinase Inhibitor CEP‐701 (KT‐5555) Exhibits Antitumor Efficacy against Human Pancreatic Carcinoma (Panc1) Xenograft Growth and In Vivo Invasiveness (1999)

The survival rate for patients with pancreatic ductal adenocarcinoma (PDAC) is among the poorest for all cancers. The factors that contribute to this poor prognosis are lack of effective early detection, high rate of metastases and a generally refractory response to available treatment modalities. The most commonly used treatment methods--chemotherapy and radiation therapy--are mainly used for symptom palliation, with surgery being the only "curative" treatment option. The use of combinations of treatment modalities is the only therapy available to patients with locally advanced disease or that which is surgically unresectable. These options are still not sufficient to increase patient survival time significantly. The aggressive behavior and poor prognosis of this cancer is associated with an increased expression of many growth factors and their cognate receptors. We have demonstrated previously the aberrant expression of the Trk receptors (Trks A, B, and C) in PDAC specimens and human PDAC-derived cell lines and a biphasic, dose-dependent response of specific neurotrophic agents on the in vitro invasiveness of PDAC cells. Based on these data we have evaluated the therapeutic potential of inhibiting neurotrophin-Trk interactions using a selective Trk tyrosine kinase inhibitor (CEP-701) on subcutaneous (s.c.) and tracheal xenografts derived from the poorly differentiated PDAC cell line, Panc1. We demonstrate that CEP-701 administration at 10 mg/kg s.c. BID for 21 days inhibited tumor growth of the Panc1 s.c. xenografts in a statistically-significant manner (p < 0.01) compared to vehicle controls, in the absence of morbidity and mortality. A T/C value of 25% was observed for CEP-701-treated s.c. xenografts. In addition, CEP-701 administration inhibited tumor cell invasion in the s.c. tracheal xenograft model of in vivo invasiveness. Taken together, these data suggest that further studies are warranted to evaluate CEP-701 as a potential therapeutic agent in the treatment of PDAC.
On Integrated CMOS-MEMS System-on-Chip (2005)

The paper reviews the state-of-the-art in the field of CMOS-based microelectromechanical systems (MEMS). The different CMOS MEMS fabrication approaches, pre-CMOS, intermediate-CMOS, and post-CMOS, are summarized and examples are given.
Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites (2005)

Both Q-SiteFinder and Pocket-Finder have been made available online at http://www.bioinformatics.leeds.ac.uk/qsitefinder and http://www.bioinformatics.leeds.ac.uk/pocketfinder
Analysis of mismatch effects among A/D converters in a time-interleaved waveform digitizer (1991)

High-speed A/D conversion can be achieved by employing a parallel array of M A/D converters interleaved in time, each working at 1/Mth of the sampling rate. Theoretically, the resolution of the structure is given by the resolution of the A/D converters in the array (subconverters). In practice, however, mismatches among the subconverters lead to a decrease in the resolution. The effect of such mismatches is analyzed in terms of a signal-to-noise ratio defined as the ratio between the energy of the input analog signal and the energy of the error signal due exclusively to these mismatches. The analysis shows that the distortion is comparable to that generated by nonuniform sample timing in the analog demultiplexer when converting a single high-speed signal into several low-speed sampled-and-held signals. The results of the analysis can be used to specify the degree of precision to be achieved in an actual monolithic implementation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Brief Communication: Inhibition of Dimethylhydrazine-Induced Neoplasia of the Large Intestine by Disulfiram2 (1975)

Disulfiram added to the diet of female CF1 mice inhibited large-bowel neoplasia produced by repeated subcutaneous administrations of dimethylhydrazine (DMH). The mice on a control diet all showed multiple tumors of the large bowel after DMH treatments, whereas there was no evidence of neoplasia in mice given disulfiram.
Oxidative stability of soybean oils with altered fatty acid compositions (1992)

The oxidative stabilities of one canola oil and six soybean oils of various fatty acid compositions were compared in terms of peroxide values, conjugated dienoic acid values and sensory evaluations. Two of the soybean oils (Hardin and BSR 101) were from common commercial varieties. The other four soybean oils were from experimental lines developed in a mutation breeding program at Iowa State University that included A17 with 1.5% linolenate and 15.2% palmitate; A16 with 2% linolenate and 10.8% palmitate; A87‐191039 with 2% linolenate and 29.6% oleate; and A6 with 27.5% stearate. Seed from the soybean genotypes was cold pressed. Crude canola oil was obtained without additives. All oils were refined, bleached and deodorized under laboratory conditions with no additives and stored at 60°C for 15 days. The A17, A16, A87‐191039 and A6 oils were generally more stable to oxidation than the commercial soybean varieties and canola oil as evaluated by chemical and sensory tests. Canola oil was much less stable than Hardin and BSR 101 oils by both chemical and sensory tests. The peroxide values and flavor scores of oils were highly correlated with the initial amounts of linolenate (r=0.95, P=0.001). Flavor quality and flavor intensity had negative correlations with linolenate, (r=−0.89, P=0.007) and (r=−0.86, P=0.013), respectively.
Retroviral vector-mediated high-efficiency expression of adenosine deaminase (ADA) in hematopoietic long-term cultures of ADA-deficient marrow cells. (1989)

Two recombinant retroviral vectors encoding the cDNA of the human adenosine deaminase (ADA; EC 3.5.4.4) gene and the bacterial neomycin resistance (Neo) gene have been used to transduce bone marrow cells obtained from four patients affected by the ADA-deficient variant of severe combined immunodeficiency. By utilizing the long-term marrow culture system, freshly isolated bone marrow cells were subjected to multiple infection cycles with cell-free supernatants containing high titers of viral vector and then maintained in long-term marrow culture in the absence of any overt selection pressure. By using this experimental protocol, about 30-40% of the hematopoietic progenitors were productively transduced with the viral vector, as judged by the appearance of G418-resistant colonies derived from granulocyte/macrophage and multipotent hematopoietic progenitor cells. The vector-encoded human ADA gene was expressed efficiently in both the myeloid and lymphoid progeny of the cultured bone marrow cells, reaching levels between 15% and 100% as compared to the levels of ADA in normal bone marrow cells. The efficiency of gene transfer and ADA production was proportional to the number of infection cycles. Furthermore, transduction of the ADA vectors into the bone marrow cells derived from an ADA-deficient patient restored the capacity of the cells to respond to phytohemagglutinin and interleukin 2.
Radiology of lumbar vertebral pedicles: variants, anomalies and pathologic conditions. (1987)

Close scrutiny of the size, shape, density and margins of the pedicles may permit the clinical radiologist to suggest a wide variety of systemic diseases.
Induction of Bcl-xLExpression by Human T-Cell Leukemia Virus Type 1 Tax through NF-κB in Apoptosis-Resistant T-Cell Transfectants with Tax (1999)

Human T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play a pivotal role in immortalization of T cells. We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by interleukin-2 (IL-2) deprivation and converted its growth from being IL-2 dependent to being IL-2 independent. In this study, we demonstrate that constitutive expression of bcl-xl but not bcl-2, bcl-xs, bak, bad, or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax. Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax. Similar effects were observed in mutant Tax retaining transactivating ability through NF-kappaB. Deletion or substitution of a putative NF-kappaB binding site identified in the bcl-x promoter significantly decreased Tax-induced transactivation. This NF-kappaB-like element was able to form a complex with NF-kappaB family proteins in vitro. Furthermore, Tax-induced transactivation of the bcl-x promoter was also diminished by the mutant IkappaBalpha, which specifically inhibits NF-kappaB activity. Our findings suggest that constitutive expression of Bcl-x(L) induced by Tax through the NF-kappaB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation.
Phylogenetic Analysis and Structural Predictions of Human Adenovirus Penton Proteins as a Basis for Tissue-Specific Adenovirus Vector Design (2007)

The penton base is a major capsid protein of human adenoviruses (HAdV) which forms the vertices of the capsid and interacts with hexon and fiber protein. Two hypervariable loops of the penton are exposed on the capsid surface. Sequences of these and 300 adjacent amino acid residues of all 51 HAdV and closely related simian adenoviruses were studied. Adjacent sequences and predicted overall secondary structure were conserved. Phylogenetic analysis revealed clustering corresponding to the HAdV species and recombination events in the origin of HAdV prototypes. All HAdV except serotypes 40 and 41 of species F exhibited an integrin binding RGD motif in the second loop. The lengths of the loops (HVR1 and RGD loops) varied significantly between HAdV species with the longest RGD loop observed in species C and the longest HVR1 in species B. Long loops may permit the insertion of motifs that modify tissue tropism. Genetic analysis of HAdV prime strain p17'H30, a neutralization variant of HAdV-D17, indicated the significance of nonhexon neutralization epitopes for HAdV immune escape. Fourteen highly conserved motifs of the penton base were analyzed by site-directed mutagenesis of HAdV-D8 and tested for sustained induction of early cytopathic effects. Thus, three new motifs essential for penton base function were identified additionally to the RGD site, which interacts with a secondary cellular receptor responsible for internalization. Therefore, our penton primary structure data and secondary structure modeling in combination with the recently published fiber knob sequences may permit the rational design of tissue-specific adenoviral vectors.
Peptide-based vaccines for cancer immunotherapy (2004)

One approach in the immunotherapy of cancer patients involves vaccination with peptides derived from tumour-associated antigens specifically designed to associate with T cells in the context of major histocompatibility complex (MHC) class I or II molecules. Several clinical trials in different tumour types have been conducted utilising this vaccination strategy. The majority of trials indicate that peptide vaccination has few toxicities associated with its administration, but disparities exist between in vitro and clinical responses. However, this represents an evolving field and, thus, it is difficult to draw firm conclusions concerning the efficacy of peptide-based vaccines for cancer immunotherapy. Improvements to peptide vaccination, including the addition of various adjuvants, the utilisation of peptide-pulsed dendritic cells, multipeptide vaccinations, the addition of helper peptides and peptide delivery through the use of mini-genes, are encouraging and serve as important guides for future research.
Biology of thrombopoiesis and the role of Mpl ligand in the production and function of platelets (1997)

(1997). Biology of thrombopoiesis and the role of Mpl ligand in the production and function of platelets. Platelets: Vol. 8, No. 5, pp. 319-332.
An 80-MHz 8-bit CMOS D/A converter (1986)

A high-speed 8-bit D/A converter has been fabricated in a 2-/spl mu/m CMOS technology. In order to achieve high accuracy, a current-cell matrix configuration and a switching sequence called symmetrical switching have been used. The mismatch problem of small-size transistors has been relaxed by this matrix configuration. The linearity error caused by an undesirable current distribution of the current sources has been reduced by symmetrical switching. A high-speed decoding circuit and a fast-setting current source have been developed. The experimental results show that the maximum conversion rate is 80 MHz, a typical DC integral linearity error is 0.38 LSB, a typical DC differential linearity error is 0.22 LSB, and the maximum power consumption is 145 mW. The chip size is 1.85 mm/spl times/2.05 mm.
[Studies on the sodium concentration of dialysate solution for continuous ambulatory peritoneal dialysis]. (1992)

Overloaded sodium(Na) induces the expansion of extracellular volume in case with severe renal insufficiency. Accordingly, in patients undergoing CAPD, the Na balance via trans-peritoneum is the critical determinant of fluid state. This study was performed to clarify the trans-peritoneal Na kinetics in patients using standard dialysate (Na: 132mEq/1,2-1), and to explore the clinical effects of lower Na concentration solution. Peritoneal dialysis effluent obtained from 87 patients was analysed [1.5% dextrose dialysate (D): 33 bags, 2.5%D: 54 bags]. In terms of net-Na removal, no significant relation was found with serum Na level. Whereas, a significant positive relation was found with ultrafiltration (UF) volume (p < 0.01). Net-Na removal was 10.0 +/- 3.3mEq in 1.5%D and 30.2 +/- 1.8 mEq in 2.5%D (mean +/- SEM). On the other hand, ultra low sodium concentration dialysate (ULNaD, Na level: 98mEq/1, Osm:340mOsm/1, 2l) was effectively used for the purpose of increasing Na removal. Net-Na removal was 78.1 +/- 5. 6mEq after 4-hr dwelling (n = 18). ULNaD was applied to ten patients who showed signs of overhydration, using once a day consecutively instead of standard one. After 9 days (mean) in this regimen, signs of overhydration were disappeared. Significant reductions in their body weight and fall in blood pressure were found compared to the periods before commencement of ULNaD, showing remarkable increase in Na removal (p < 0.01, respectively). No significant changes were found in serum Na level or UF volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Mental Stress of Long Duration: EMG Activity, Perceived Tension, Fatigue, and Pain Development in Pain‐Free Subjects (1997)

The study examined the relationship between pain development in the shoulder, neck, and facial regions and the EMG activity of underlying muscles, during prolonged exposure to a mental stressor. The subjective perception of tension and fatigue was recorded. Thirty-six subjects were exposed to a two-choice reaction-time test for 1 hour. Electromyographic (EMG) recordings were performed bilaterally over the frontalis, temporalis, splenius, and trapezius muscles. Pain and perceived tension were scored on a visual analog scale, and fatigue on a Borg scale. Pain development was most pronounced in the shoulder and neck region. There was a weak tendency of those reporting pain in the shoulder region to generate higher EMG activity in the trapezius relative to those with no shoulder pain at the end of the test. No such relationship was observed for the other muscles. Perceived tension during the test was weakly related to pain and strongly related to fatigue at the end of the test, but not to EMG level. It is concluded that the mean level of the EMG response is of little consequence for pain development during stressful conditions. It is argued that other physiological responses such as prolonged activity in low-threshold motor units, whereby the surface EMG response can serve as a marker, can be important for shoulder pain originating in the trapezius muscle.
A biosynthetic pathway for anandamide (2006)

The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released "on demand" by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD). Here we document a biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages that involves the phospholipase C (PLC)-catalyzed cleavage of NAPE to generate a lipid, phosphoanandamide, which is subsequently dephosphorylated by phosphatases, including PTPN22, previously described as a protein tyrosine phosphatase. Bacterial endotoxin (LPS)-induced synthesis of anandamide in macrophages is mediated exclusively by the PLC/phosphatase pathway, which is up-regulated by LPS, whereas NAPE-PLD is down-regulated by LPS and functions as a salvage pathway of anandamide synthesis when the PLC/phosphatase pathway is compromised. Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.
TGF-β enhances macrophage ability to produce IL-10 in normal and tumor-bearing mice (1995)

In the present study, we demonstrate that TGF-beta is capable of enhancing macrophage ability to produce IL-10 in normal and EL4 tumor-bearing mice. We found the increase in IL-10 in ascitic fluid and IL-10 mRNA expression in macrophages in parallel with the TGF-beta level and tumor progression. The macrophage production of IL-10 in the tumor-bearing mice was significantly enhanced without LPS stimulation in vitro, compared with normal controls. To clarify the mechanism wherein increased IL-10 production was induced, anti-TGF-beta or anti-IL-10 Abs were administered to EL4-bearing mice. Administration of anti-TGF-beta Ab led to a reduction in the IL-10 contents in ascitic fluid of tumor-bearing mice; however, anti-IL-10 Ab administration did not prevent the increase in TGF-beta contents. Enhanced IL-10 production and mRNA expression of macrophages from the tumor-bearing mice were also reduced by anti-TGF-beta Ab administration. Both anti-TGF-beta and anti-IL-10 Ab administration restored the TNF-alpha production by macrophages in EL4-bearing mice. In normal macrophages, in vitro pretreatment with TGF-beta 1 potentiated IL-10 production, and when natural TGF-beta 1 was administered to normal mice, the recovered peritoneal macrophages showed enhanced IL-10 production. Based on the above findings it can be concluded that TGF-beta enhances macrophage ability to produce IL-10, which sheds a new light on the role of TGF-beta in the immune system.