gebhart/patrepeval huggingface dataset:
Mechanisms Underlying Chemotherapy-Induced Neurotoxicity and the Potential for Neuroprotective Strategies (2008)

Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life. The incidence of chemotherapy-induced neurotoxicity appears critically related to cumulative dose and infusion duration, while individual risk factors may also influence the development and severity of neurotoxicity. Differences in structural properties between chemotherapies further contribute to variations in clinical presentation. The mechanisms underlying chemotherapy-induced neurotoxicity are diverse and include damage to neuronal cell bodies in the dorsal root ganglion and axonal toxicity via transport deficits or energy failure. More recently, axonal membrane ion channel dysfunction has been identified, including studies in patients treated with oxaliplatin which have revealed alterations in axonal Na(+) channels, suggesting that prophylactic pharmacological therapies aimed at modulating ion channel activity may prove useful in reducing neurotoxicity. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity will inevitably assist in the development of future neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.
The Effects of Atypical Antipsychotic Drugs on Neurocognitive Impairment in Schizophrenia: A Review and Meta-analysis (1999)

Cognitive deficits are a fundamental feature of the psychopathology of schizophrenia. Yet the effect of treatment on this dimension of the illness has been unclear. Atypical antipsychotic medications have been reported to reduce the neurocognitive impairment associated with schizophrenia. However, studies of the pattern and degree of cognitive improvement with these compounds have been methodologically limited and have produced variable results, and few findings have been replicated. To clarify our understanding of the effects of atypical antipsychotic drugs on neurocognitive deficits in patients with schizophrenia, we have (1) reported on newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia, (2) reviewed the literature on this topic and determined the extent to which 15 studies on the effect of atypical antipsychotics met these standards, (3) performed a meta-analysis of the 15 studies, which suggested general cognitive enhancement with atypical antipsychotics, and (4) described the pharmacological profile of these agents and considered the pharmacological basis for their effects on neurocognition. Finally, we suggest directions for the development of new therapeutic strategies.
Pneumococcal vaccine after 15 years of use. Another view (1994)

IN A recent Commentary, Hirschmann and Lipsky<sup>1</sup>reviewed pneumococcal vaccine after 15 years of use in the United States. Following their evaluation of prospective vaccine trials, retrospective studies, and projections of vaccine effectiveness, they stated that "no conclusive evidence has yet emerged that the pneumococcal vaccine is effective in<i>any</i>group in the United States." In their judgment, "the evidence justifies not vaccinating immunocompromised or elderly populations" with pneumococcal vaccine. While most observers would agree that the available evidence on the clinical effectiveness of pneumococcal vaccination is incomplete, the evidence has been the subject of ongoing critical review by several expert groups, including the Advisory Committee on Immunization Practices,<sup>2</sup>the American College of Physicians/ Infectious Diseases Society of America Task Force on Adult Immunization,<sup>3</sup>the National Advisory Committee on Immunization in Canada,<sup>4</sup>and a Technical Advisory Group to the World Health Organization Regional Office for Europe.<sup>5</sup>
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action? (2002)

A range of target-based agents for the treatment of solid tumors are in development. The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB-2, ErbB-3, and ErbB-4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR-TKIs), of which ZD1839 ('Iressa') is an example. In Phase II monotherapy trials, oral ZD1839 was well tolerated and demonstrated clinically meaningful antitumor activity and symptom relief in pretreated patients with advanced NSCLC. Preclinical studies have suggested that the antitumor activity of ZD1839 does not depend on the level of EGFR expression. Furthermore, in addition to an effect on EGFR signaling, treatment with ZD1839 as well as with other quinazoline EGFR-TKIs, may also affect signaling of other ErbB family members. EGFR-TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents.
Full Parallax 3-D TV with Programmable Display Parameters (2011)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. Martínez-Corral, H. Navarro, R. Martínez-Cuenca, G. Saavedra, and B. Javidi, "Full Parallax 3-D TV with Programmable Display Parameters," Optics & Photonics News 22(12), 50-50 (2011) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Chlamydomonas reinhardtii Phosphoribulokinase (1990)

The sequence and kinetic properties of phosphoribulokinase purified from Chlamydomonas reinhardtii were determined and compared with the spinach (Spinacea oleracea) enzyme. Chlamydomonas phosphoribulokinase was purified to apparent homogeneity, with a specific activity of 410 micromoles per minute per milligram. Polyclonal antibodies to the purified protein were used to isolate a Chlamydomonas cDNA clone, which, upon sequencing, was found to contain the entire coding region. The transit peptide cleavage site was determined by Edman analysis of the mature protein. The precursor protein consists of a 31 amino acid transit peptide and a 344 amino acid mature polypeptide. The mature polypeptide has a calculated molecular weight of 38.5 kilodaltons and a pl of 5.75. The V(max) of the purified enzyme was 465 micromoles per minute per milligram, with apparent K(m) values of 62 micromolar ATP and 56 micromolar ribulose 5-phosphate. Immunoblot analysis indicated antigenic similarity and a similar subunit size for the enzyme from five higher plant species and Chlamydomonas. Southern blot analysis of Chlamydomonas genomic DNA indicated the presence of a single phosphoribulokinase gene. Comparison of the mature proteins from Chlamydomonas and spinach revealed 86 amino acid differences in primary structure (25% of the total) without a major difference in kinetic properties. The transit peptides of the spinach and Chlamydomonas proteins possessed little sequence homology.
Screening of yeasts for production of xylitol fromd-xylose and some factors which affect xylitol yield inCandida guilliermondii (1988)

The ability to convert D-xylose to xylitol was screened in 44 yeasts from five genera. All but two of the strains produced some xylitol with varying rates and yields. The best xylitol producers were localized largely in the species Candida guilliermondii and C. tropicalis. Factors affecting xylitol production by a selected C. guilliermondii strain, FTI-20037, were investigated. The results showed that xylitol yield by this strain was affected by the nitrogen source. Yield was highest at 30 35~ and could be increased with decreasing aeration rate. Using high cell density and a defined medium under aerobic conditions, xylitol yield by C. guilliermondii FTI-20037 from 104 g/1 D-xylose was found to be 77.2 g/1. This represented a yield of 81% of the theoretical value, which was computed to be 0.9 mol xylitol per tool D-xylose.
Integrating Fracture Mapping Technologies To Improve Stimulations in the Barnett Shale (2005)

Summary A large hydraulic-fracture diagnostic project was undertaken in the summer of 2001 that integrated fracture-diagnostic technologies, including tiltmeter (i.e., surface and downhole) and microseismic mapping. The extensive data gathered resulted in a much clearer understanding of the highly complex fracture behavior in the Barnett shale of north Texas. The detailed fracture-mapping results allowed construction of a calibrated 3D fracture simulator that better reflects the observed mechanics of fracturing in this fractured-shale reservoir. More than just simple calibration was required. Indeed, a whole new understanding of fracture growth was developed. The Barnett shale has seen a rebirth of drilling and refracturing activity in recent years because of the success of waterfracture, or "light-sand," fracturing treatments. This extremely low-permeability reservoir benefits from fracture treatments that establish long and wide fracture "fairways," which result in connecting very large surface areas of the formation with an extremely complex fracture network. Understanding the created-fracture geometry is key to the effectiveness of any stimulation program or infill-drilling program, particularly in this area, with its nonclassical fracture networks. Integrated-fracture diagnostics have led to the identification of new fracturing techniques, as well as additional refracturing and infill-drilling candidates. A new method for evaluating large microseismic data sets was developed. Combining the microseismic analysis with surface- and downhole-tilt fracture mapping allowed characterization of the created-fracture networks. Correlations between production response and various fracture parameters will be presented along with a discussion of methods for calibrating a fracture model to the observed fracture behavior.
Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry (1991)

Four-color flow cytometry was used with a cocktail of antibodies to identify and isolate CD34+ hematopoietic progenitors from normal human peripheral blood (PB) and bone marrow (BM). Mature cells that did not contain colony forming cells were resolved from immature cells using antibodies for T lymphocytes (CD3), B lymphocytes (CD20), monocytes (CD14), and granulocytes (CD11b). Immature cells were subdivided based on the expression of antigens found on hematopoietic progenitors (CD34, HLA-DR, CD33, CD19, CD45, CD71, CD10, and CD7). CD34+ cells were present in the circulation in about one-tenth the concentration of BM (0.2% v 1.8%) and had a different spectrum of antigen expression. A higher proportion of PB-CD34+ cells expressed the CD33 myeloid antigen (84% v 43%) and expressed higher levels of the pan leukocyte antigen CD45 than BM-CD34+ cells. Only a small fraction of PB-CD34+ cells expressed CD71 (transferrin receptors) (17%) while 94% of BM-CD34+ expressed CD71+. The proportion of PB-CD34+ cells expressing the B-cell antigens CD19 (10%) and CD10 (3%) was not significantly different from BM-CD34+ cells (14% and 17%, respectively). Few CD34+ cells in BM (2.7%) or PB (7%) expressed the T-cell antigen CD7. CD34+ cells were found to be predominantly HLA-DR+, with a wide range of intensity. These studies show that CD34+ cells and their subsets can be identified in normal PB and that the relative frequency of these cells and their subpopulations differs in PB versus BM.
Becoming a Wise Giver (2012)

Mindful givers take time to clear their own lenses, to see what's best for themselves and for their recipients. To “know thyself” in this context involves asking how much you want to live on, how much you want to give away during your life, and how much you want to leave at death. Doing so helps avoid guilt giving or grantor's remorse. This chapter also recommends taking the approach of “nothing too much” in giving to family.
A Role of the Mitochondrial Apoptosis-Inducing Factor in Granulysin-Induced Apoptosis (2001)

Granulysin is a cytolytic molecule released by CTL via granule-mediated exocytosis. In a previous study we showed that granulysin induced apoptosis using both caspase- and ceramide-dependent and -independent pathways. In the present study we further characterize the biochemical mechanism for granulysin-induced apoptosis of tumor cells. Granulysin-induced death is significantly inhibited by Bcl-2 overexpression and is associated with a rapid (1-5 h) loss of mitochondrial membrane potential, which is not mediated by ceramide generation and is not inhibited by the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide generation induced by granulysin is a slow event, only observable at longer incubation times (12 h). Apoptosis induced by exogenous natural (C(18)) ceramide is truly associated with mitochondrial membrane potential loss, but contrary to granulysin, this event is inhibited by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide-induced apoptosis is also completely prevented by Bcl-2 overexpression. The nuclear morphology of cells dying after granulysin treatment in the presence of caspase inhibitors suggested the involvement of mitochondrial apoptosis-inducing factor (AIF) in granulysin-induced cell death. We demonstrate using confocal microscopy that AIF is translocated from mitochondria to the nucleus during granulysin-induced apoptosis. The majority of Bcl-2 transfectants are protected from granulysin-induced cell death, mitochondrial membrane potential loss, and AIF translocation, while a small percentage are not protected. In this small percentage the typical nuclear apoptotic morphology is delayed, being of the AIF type at 5 h time, while at longer times (12 h) the normal apoptotic morphology is predominant. These and previous results support a key role for the mitochondrial pathway of apoptosis, and especially for AIF, during granulysin-induced tumoral cell death.
Molecular evolution of the vertebrate blood coagulation network (2003)

In mammalian blood coagulation 5 proteases, factor VII (FVII), factor IX (FIX), factor X (FX), protein C (PC) and prothrombin act with two cofactors factor V and factor VIII to control the generation of fibrin. Biochemical evidence and molecular cloning data have previously indicated that blood coagulation involving tissue factor, prothrombin and fibrinogen is present in all vertebrates. Using degenerate RT-PCR we have isolated and characterized novel cDNAs with sequence identity to the blood coagulation serine proteases and cofactors from chicken and the puffer fish (Fugu rubripes). Sequence alignments, phylogenetic and comparative sequence analysis all support the existence of the Gla-EGF1-EGF2-SP domain serine proteases FVII, FIX, FX, PC and the A1-A2-B-A3-C1-C2 domain protein cofactors FV and FVIII in these species. These results strongly suggest that the blood coagulation network is present in all jawed vertebrates and evolved before the divergence of tetrapods and teleosts over 430 million years ago; and that vertebrate blood coagulation may have benefited from two rounds of gene or whole genome duplication. Sequences identified in Fugu coding for additional FVII-like, FIX-like and PC-like sequences support the possibility of further tandem and large-scale duplications in teleosts. Comparative sequence analyses of amino acid residues in the active site region suggest these additional sequences have evolved new and as yet unknown functions.
Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) (2010)

Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcare-associated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.
Radioreceptor Assay for α;-Msh Using Mouse B16 Melanoma Cells (1988)

A radioreceptor assay for alpha-MSH is described which is based on cultured mouse B16 melanoma cells and bioactive monoiodinated [Nle4]-alpha-MSH tracer. The assay was used (1) to study the binding characteristics of alpha-MSH to B16 cells, (2) to determine the relative binding activity of MSH peptides, and (3) to measure MSH in tissue extracts. The association of alpha-MSH to B16 cells reached a stable plateau after 3 h at 15 degrees C. At 25 degrees or 37 degrees C, the binding was transient and at 0-1 degree C, the association was very slow. The hormone-receptor complex was relatively stable between 0 degrees and 15 degrees C whereas a 50% dissociation was reached after 90 min at 25 degrees C and after 35 min at 37 degrees C. The mean KD for alpha-MSH of four saturation experiments was 1.3 nM and the number of receptors 9570 per cell. 1,10-Phenanthroline had a stabilizing effect in the binding assay when used at a 0.3 mM concentration. From the MSH peptides tested in the binding assay, some showed similar potencies in three bioassays (tyrosinase, melanin and Anolis skin), whereas others displayed considerably lower bioassay values than expected from the binding data. This shows that binding and bioactivity can be dissociated in some of the MSH peptides. The biological activity of MSH from the neurointermediate lobe of the rat pituitary as measured by its binding to B16 cells corresponds fairly well with RIA results; in the anterior lobe, alpha-MSH values are overestimated because of the large amount of ACTH present.
Positional Candidate Cloning of a QTL in Dairy Cattle: Identification of a Missense Mutation in the Bovine DGAT1 Gene with Major Effect on Milk Yield and Composition (2002)

We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition--particularly fat content--to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (1) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics.
Thermoacoustic and photoacoustic sensing of temperature (2009)

We present a novel temperature-sensing technique using thermoacoustic and photoacoustic measurements. This noninvasive method has been demonstrated using a tissue phantom to have high temporal resolution and temperature sensitivity. Because both photoacoustic and thermoacoustic signal amplitudes depend on the temperature of the source object, the signal amplitudes can be used to monitor the temperature. A temperature sensitivity of 0.15 degrees C was obtained at a temporal resolution as short as 2 s, taking the average of 20 signals. The deep-tissue imaging capability of this technique can potentially lead us to in vivo temperature monitoring in thermal or cryogenic applications.
Brain metabolism differs in Alzheimer's disease and Parkinson's disease dementia (2008)

Patients with AD and patients with PDD exhibited distinct brain metabolic MRS profiles. Findings suggest that comparison of brain MRS profiles across dementias provides useful direction for future study.
Amelioration of experimental colitis by thalidomide. (2001)

Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNF alpha, and should be further studied.
Interactions between L-arginine and L-glutamine change endothelial NO production. An effect independent of NO synthase substrate availability. (1995)

The effect of extracellular L-arginine and L-glutamine on nitric oxide (NO) release was studied in cultured bovine aortic endothelial cells and in rabbit aortic rings. Increasing L-arginine (0.01 to 10 mM) did not alter NO release from cultured endothelial cells or modify endothelium-dependent relaxation to acetylcholine in isolated vessels. L-Glutamine (0.6 and 2 mM) inhibited NO release from cultured cells (in response to bradykinin) and from aortic rings (in response to acetylcholine or ADP). L-Arginine (0.1-10 mM) dose-dependently reversed the L-glutamine inhibition of receptor-stimulated NO release in both models. In contrast to its inhibitory response to receptor-mediated stimuli, glutamine alone slightly potentiated NO release in both models when the calcium ionophore, A23187, was added. Furthermore, cultured cells incubated with L-arginine (0.01-10 mM), in the presence or absence of glutamine, released similar amounts of NO in response to A23187. L-Glutamine did not affect intracellular L-arginine levels. Neither D-glutamine nor D-arginine affected NO release or endothelium-dependent vascular relaxation. L-Glutamine had no effect on the activity of endothelial NOS assessed by L-arginine to L-citrulline conversion. These findings show that in the absence of L-glutamine, manipulating intracellular L-arginine levels over a wide range does not affect NO release. L-Glutamine in concentrations circulating in vivo may tonically inhibit receptor-mediated NO release by interfering with signal transduction. One mechanism by which L-arginine may enhance NO release is via reversal of the inhibitory effect of L-glutamine, but apparently independently of enhancing NO synthase substrate.