gebhart/patrepeval huggingface dataset:
An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld s ) mouse (1998)

Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wlds) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wlds among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences ("illegitimate" or "nonhomologous" recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wlds mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.
Nanoparticle Surface Charges Alter Blood–Brain Barrier Integrity and Permeability (2004)

(1) Neutral NPs and low concentration anionic NPs can be utilized as colloidal drug carriers to brain, (2) cationic NPs have an immediate toxic effect at the BBB and (3) NP surface charges must be considered for toxicity and brain distribution profiles.
Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. (1975)

About 300 carcinogens and non-carcinogens of a wide variety of chemical types have been tested for mutagenicity in the simple Salmonella/microsome test. The test uses bacteria as sensitive indicators for DNA damage, and mammalian liver extracts for metabolic conversion of carcinogens to their active mutagenic forms. Quantitative mutagenicity data from linear dose-response curves are presented: potency varies over a 10(6)-fold range. There is a high correlation between carcinogenicity and mutagenicity: 90% (156/174) of carcinogens are mutagenic in the test and despite the severe limitations inherent in defining non-carcinogenicity, few "non-carcinogens" show any degree of mutagenicity. The results also demonstrate the great utility, and define the limitations, of the test in detecting environmental carcinogens.
Common-Case Computation: A High-Level Energy and Performance Optimization Technique (2004)

This paper proposes a novel circuit design methodology, called common-case computation (CCC)-based design, and new design automation algorithms for optimizing energy consumption and performance. The proposed techniques are applicable in conjunction with any high-level design methodology, where a structural register-transfer level (RTL) description and its corresponding scheduled behavioral (cycle-accurate functional) description are available. It is a well-known fact that in behavioral descriptions of hardware circuits (and also in software programs), a small set of computations often account for most of the computational complexity. However, in the hardware implementations (structural RTL or lower level), the common cases and the remaining computations are typically treated alike. This paper shows that identifying and exploiting common cases during the design process can lead to implementations that are much more efficient in terms of energy consumption and performance.
Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. (1993)

We measured changes in basal release of nitric oxide and its effect on polymorphonuclear leukocyte (PMN) adherence to endothelial cells (ECs) in a feline model of myocardial ischemia (90 minutes) and reperfusion. Basal release of nitric oxide from the left anterior descending coronary artery (LAD) after myocardial ischemia/reperfusion and from the control left circumflex coronary artery (LCX) was assessed by NG-nitro L-arginine methyl ester (L-NAME)-induced vasocontraction. L-NAME induced a significant EC-dependent vasocontraction in control LCX rings (0.28 +/- 0.04 g), which was fully reversed by L-arginine but not D-arginine. L-NAME-induced vasocontraction of LAD rings was not significantly changed after 90 minutes of myocardial ischemia without reperfusion. However, 10 minutes of reperfusion reduced the L-NAME-induced vasocontraction to 0.13 +/- 0.04 g (p < 0.05), and this was restored by addition of 3 mM L-arginine but not D-arginine. Longer periods of reperfusion progressively decreased L-NAME-induced vasocontraction. After 270 minutes of reperfusion, L-NAME-induced vasocontraction was virtually abolished. Myocardial ischemia without reperfusion did not increase PMN adherence to ECs. However, PMN adherence to LAD ECs was significantly increased after 20 minutes of reperfusion (39 +/- 6 to 105 +/- 9 PMNs/mm2, p < 0.01), and incubation of LAD segments with L-arginine significantly attenuated this increase in PMN adherence. After 270 minutes of reperfusion, PMN adherence to LAD ECs was further increased to 224 +/- 10 PMNs/mm2 (p < 0.001). This increase in PMN adherence was almost completely blocked by MAb R15.7, a monoclonal antibody against CD18 of PMNs, and was significantly attenuated by MAb RR1/1, a monoclonal antibody against intercellular adhesion molecule-1 of ECs (p < 0.01). These results indicate that decreased basal release of endothelium-derived relaxing factor after myocardial ischemia/reperfusion precedes enhanced PMN adherence to the coronary endothelium, which may lead to PMN-induced myocardial injury.
IMPORTANCE OF ANTIGEN SPECIFICITY FOR COMPLEMENT‐MEDIATED LYSIS BY MONOCLONAL ANTIBODIES (1988)

Lysis of human lymphocytes by autologous complement had been studied using a range of monoclonal antibodies against different antigens. Antigen specificity (and not antibody isotype) was the most important factor which influenced cell lysis and this could not be accounted for merely by differences in surface density between antigens. Three antigens with comparable surface density were studied in detail: CAMPATH-1 (lytic), major histocompatibility complex class I (lytic) and leukocyte common antigen (poorly lytic). C1q binding was roughly proportional to antibody binding and dependent on antibody isotype. However, the lytic antibodies were much better able to bind and activate whole C1 than the poorly lytic ones. This result would not have been predicted from traditional concepts of complement activation but can be interpreted in the light of models for C1 activation which involve Fc-Fc interactions, Fc-C1r2s2 interactions and a critical C1q stem-arm angle for C1 binding and activation.
Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications (2010)

Locked Nucleic Acid (LNA) is a unique nucleic-acid modification possessing very high binding affinity and excellent specificity toward complementary RNA or DNA oligonucleotides. The remarkable properties exhibited by LNA oligonucleotides have been employed in different nucleic acid-based therapeutic strategies both in vitro and in vivo. Herein, we highlight the applications of LNA nucleotides for controlling gene expression.
Real-time microscopic visualization of tissue response to laser thermal therapy (2007)

We present methods for visualizing the dynamic response of biological samples to laser-induced heating. Our approach utilizes optical frequency-domain imaging to detect, spatially localize, and monitor unique dynamic signatures that arise within zones of active tissue denaturation. Since this information is precisely registered with high-resolution ( approximately 10 microm) cross sectional images, regions of thermally destroyed tissue can be mapped in relation to pre-existing morphology. Using porcine esophageal specimens ex vivo, we demonstrate that the extent and evolution of laser thermal damage can be assessed in real time.
Rapid, sensitive structure analysis of oligosaccharides (1997)

We have developed an efficient method for the derivatization of oligosaccharides, wherein the oligosaccharide is efficiently ligated to a basic aminooxyacetyl peptide by oxime formation. The resulting glycopeptide yields much higher sensitivity in matrix-assisted laser desorption/ionization mass spectrometry than does the underivatized oligosaccharide. Digestion of the glycopeptide by a exoglycosidase array and subsequent mass spectrometric assay of the digestion products provide a sensitive and rapid way to elucidate the structure of the oligosaccharide. In addition to oligosaccharide sequencing, the ligation reaction between an oligosaccharide and an aminooxyacetyl peptide also provides a potentially very convenient and efficient way for the synthesis of glycopeptides or glycoproteins.
DIETARY AND ENDOGENOUS CHOLESTEROL AND HUMAN CANCER (1984)

Recent questions about the role of cholesterol (particularly blood cholesterol) in human cancer have assumed considerable scientific and public health importance. This paper has reviewed the evidence relating human cancer to cholesterol, in diet, blood, and feces. With respect to dietary cholesterol, there is moderately consistent evidence, both descriptive and analytic, of a small-to-medium increase in risk of cancers of the colon and female breast in association with increased dietary cholesterol. However, the close correlation of cholesterol with other foods and nutrients precludes causal inference. The association of fecal cholesterol with large bowel cancer, in both descriptive and analytic studies, is inconsistent. However, there is some evidence that individuals with reduced degradation of fecal cholesterol are at increased risk of colon cancer. Other bile-derived fecal components, particularly the acid sterols, show a somewhat more consistent relationship with large bowel cancer. It may be of relevance to the findings on blood cholesterol that bile is produced from hepatic cholesterol which derives, in part, from blood cholesterol. Studies of blood cholesterol and cancer have been either experimental (intervention) or observational (primarily follow-up). Deliberate lowering of blood cholesterol, by either drugs or diet, does not appear to alter the risk of cancer, either overall or of specific types. The findings from 20 published follow-up studies, each initiated as a cardiovascular disease study, have been more varied. In 12 studies, an inverse association was observed between blood cholesterol level and overall cancer risk. Eight of those 12 were mortality studies, and in six, the inverse association was confined to deaths that occurred early in follow-up; this observation is consistent with lowered blood cholesterol having occurred as a metabolic response to a preclinical cancer. However, the results of the other two mortality studies do not exclusively support this interpretation. Furthermore, in three of the four incidence studies that reported an inverse association, the inverse association persisted for 10 or more years. This relationship was most marked for colon cancer in men and showed some evidence of being maximal in the proximal colon. The biologic plausibility of these particular observations on colon cancer risk in relationship to an antecedent naturally occurring low blood cholesterol gains some support from a body of epidemiologic, clinical, and experimental evidence.(ABSTRACT TRUNCATED AT 400 WORDS)
Uso de la vasopresina en el estado de choque (2004)

La arginina-vasopresina (VP) tambien conocida como hormona antidiuretica es esencial para mantener el equilibrio hidrico. Su sintesis y liberacion depende de la interaccion de estimulos osmoticos, hipovolemicos, hormonales y no osmoticos. Se ha demostrado que en estados de choque es fundamental para mantener la homeostasis cardiovascular a traves de la regulacion del tono vasomotor, el cual determina las resistencias vasculares sistemicas y la presion arterial media, a traves de los receptores V1. El estado de choque con vasodilatacion refractaria que se presenta en sepsis, respuesta inflamatoria sistemica, hipovolemia, paro cardiaco, politraumatismo, etc... Se caracteriza por una fase inicial en la que hay liberacion y aumento en los niveles sericos de VP, esta es seguida por una segunda fase en la que se presentan niveles inapropiadamente bajos de la hormona y estos se asocian con refractariedad al manejo con volumen, inotropicos y vasopresores. Se ha demostrado, en estudios experimentales y clinicos, que en esta condicion el tratamiento con vasopresina exogena incrementa la resistencia vascular sistemica, la presion de perfusion y el aporte de oxigeno a los tejidos perifericos lo cual hace posible la disminucion y suspension de los vasopresores e incrementa la supervivencia
The scanned nanopipette: a new tool for high resolution bioimaging and controlled deposition of biomolecules (2005)

The boundary between the physical and biological sciences has been eroded in recent years with new physical methods applied to biology and biological molecules being used for new physical purposes. We have pioneered the application of a form of scanning probe microscopy based on a scanned nanopipette, originally developed by Hansma and co-workers, for reliable non-contact imaging over the surface of a live cell. We have found that the nanopipette can also be used for controlled local voltage-driven application of reagents or biomolecules and this can be used for controlled deposition and the local delivery of probes for mapping of specific species. In this article we review this progress, focussing on the physical principles and new phenomena that we have observed, and then outline the future applications that are now possible.
Oligomeric structure, enzyme kinetics, and substrate specificity of the phycocyanin alpha subunit phycocyanobilin lyase. (1994)

Phycobiliproteins carry linear tetrapyrrole chromophores (bilins) thioether-linked to specific cysteine residues. The process of bilin attachment to apoprotein in vivo has been characterized for only one bilin attachment site on one phycobiliprotein, that on the alpha subunit of phycocyanin (alpha PC). In the cyanobacterium Synechococcus sp. PCC 7002, the addition of phycocyanobilin to apo-alpha PC is catalyzed by the protein products of the cpcE and cpcF genes. We have purified and further characterized the recombinant CpcE and CpcF proteins. CpcE and CpcF form an enzymatically active 1:1 complex (CpcEF), stable to size exclusion chromatography. CpcEF causes a reduction in alpha PC fluorescence and strongly affects its absorption spectrum but has no effect on the beta subunit. The CpcEF bilin addition activity exhibits simple Michaelis-Menten kinetics with respect to the apo-alpha PC and to bilin. CpcEF also catalyzes the addition of phycoerythrobilin to apo-alpha PC; phycoerythrobilin is thought to be on the biosynthetic pathway of phycocyanobilin. CpcEF shows a preference for phycocyanobilin relative to phycoerythrobilin, both in binding affinity and in the rate of catalysis, sufficient to account for selective attachment of phycocyanobilin to apo-alpha PC.
Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention (2009)

Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or "atherogenic indices" have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.
Tumor Suppression by a Proapoptotic Calcium-activated Chloride Channel in Mammary Epithelium (2001)

Little is known of the roles played by ion channels in cancer. Here we describe a pair of closely related calcium-activated chloride channels whose differential regulation in normal, apoptotic, and transformed mouse cells suggests that channel function is proapoptotic and antineoplastic. While mCLCA1 predominates over mCLCA2 under normal physiological conditions, this relationship is reversed by apoptotic stress both in developing mammary gland and in cultured HC11 mammary epithelial cells. Consistent with an apoptosis-promoting role, splicing of mCLCA2 is disrupted in apoptosis-resistant tumor cell lines and in HC11 cells selected for resistance to detachment-induced apoptosis (anoikis). Unexpectedly, mCLCA1 message is also down-regulated in these cells by at least 30-fold. These results suggest that both genes antagonize survival of mammary tumor cells by sensitizing them to anoikis. When MCF7 or HEK293 tumor cells were transfected with plasmids encoding either mCLCA1 or mCLCA2, colony formation was greatly reduced relative to a vector-transfected control, demonstrating that calcium-sensitive chloride channel (CLCA) expression is deleterious to tumor cell survival. Furthermore, mammary epithelial cells overexpressing mCLCA2 had twice the rate of apoptosis of normal cells when subjected to serum starvation and formed multinuclear giants at a high frequency in normal culture, suggesting that mCLCA2 can promote either apoptosis or senescence.
Piribedil: Antiparkinsonian Properties and Potential Clinical Utility in Dopaminergic Disorders (2010)

Piribedil is a relatively unknown non-ergot dopamine agonist that has been in clinical use for over 3 decades for the symptomatic management of Parkinsons disease (PD). Piribedil is currently not approved for therapeutic use in the United States. It has unique pharmacological and pharmacokinetic attributes with a profile that is unlike many direct dopamine agonists. In addition to proven motor effects in PD, nonclinical and clinical evidence over the last few years indicate that piribedil may also exert beneficial non-motor effects such as in mild cognitive impairment and frontal cognitive dysfunctions prevalent in PD patients. This review presents the pharmaceutics, pharmacological pleiotropy, and clinical properties of piribedil with a focus on its utility in the therapy of motor and non-motor symptoms in PD and related dopaminergic disorders. The varied pharmacological, behavioral, and clinical properties of piribedil are related to current knowledge on its multifunctional pharmacology. Properties of piribedil that may differentiate it from other dopamine direct agonists are noted. As a partial agonist of dopamine D2 and D3 receptors with functional α2 adrenolytic activity, piribedil may be an alternative to the inherent anti-akinetic (beneficial) and dyskinetic (unwanted) effects of some dopamine replacement therapies. The activation of limbic dopamine receptors by piribedil and stimulation of acetylcholine release in the frontal cortex provide a basis for improving mood and cognitive disturbances. Additionally, α2 antagonism and weak 5-HT1A agonism may provide beneficial effects on dyskinesias, neuropsychiatric symptoms in PD, neurotrophic effects, and reduced sedation. The adverse effects of piribedil generally mirror its monoaminergic activity and include nausea, vomiting, abnormal sleep events, and psychiatric effects such as psychosis and compulsive disorders. While the therapeutic potential of piribedil may yet to be fully realized, investigations of its safety and toxicology under current standards of drug development are warranted before exposure to new patient populations.
Efficacy and Safety of Ferric Carboxymaltose and Other Formulations in Iron-Deficient Patients: A Systematic Review and Network Meta-analysis of Randomised Controlled Trials (2015)

All currently available intravenous iron preparations appear to be safe and effective, but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients.
Potent Neutralizing Serum Immunoglobulin A (IgA) in Human Immunodeficiency Virus Type 2-Exposed IgG-Seronegative Individuals (2004)

The mechanisms behind the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16 of 25 EGSN samples exhibited reactivity against whole HIV-2 antigen, 6 of 25 samples reacted with recombinant gp36 (rgp36), and 3 of 25 samples were positive against HIV-2 rgp105; no reactivity to native HIV-2 gp125 was detected. Purified serum IgA antibodies from both EGSN and HIV-2-positive individuals, but not that from the negative controls, exhibited neutralization of HIV-2(SBL6669). The most potent neutralization activity was exhibited by IgA purified from EGSN compared to infected individuals' IgA. The antigenic pattern of the HIV-2-positive partners showed that all serum IgA samples were reactive to whole HIV-2 antigen, and 14 of 15 reacted with rgp36. For rgp105 and gp125, 5 of 15 and 4 of 15 samples exhibited binding, respectively. The serum of the EGSN group had a higher mean IgA concentration than that of the negative controls (P < 0.05). Thus, we describe HIV-2-specific serum IgA antigen reactivity and show a more potent serum IgA-mediated HIV-2-neutralizing activity in EGSN individuals than in HIV-2-infected patients.