gebhart/patrepeval huggingface dataset:
Sir Victor Horsley at the birth of neurosurgery (2015)

In 1886, Victor Horsley was appointed to the first neurosurgery post in the UK. On the centenary of his death, Powell describes the life of one of the leading clinical neuroscientists of his era, his scientific achievements including the forerunner of the stereotactic frame and his innovative surgery.
Audio Watermarking and Fingerprinting: For Which Applications? (2003)

Although not a new issue, music piracy has acquired a new status in the digital era, as recordings can be easily copied and distributed. Watermarking has been proposed as a solution to this problem. It consists in embedding into the audio signal an inaudible mark containing copyright information. A different approach, called fingerprinting, consists in extracting a ?fingerprint? from the audio signal. In association with a database, this fingerprint can be used to identify a recording, which is useful, for example, to monitor audio excerpts played by broadcasters and webcasters. There are far more applications to watermarking and fingerprinting. After a brief technical review, this article describes potential applications of both methodologies, showing which one is more suitable for each application.
Phospholamban: Protein Structure, Mechanism of Action, and Role in Cardiac Function (1998)

A comprehensive discussion is presented of advances in understanding the structure and function of phospholamban (PLB), the principal regulator of the Ca2+-ATPase of cardiac sarcoplasmic reticulum. Extensive historical studies are reviewed to provide perspective on recent developments. Phospholamban gene structure, expression, and regulation are presented in addition to in vitro and in vivo studies of PLB protein structure and activity. Applications of breakthrough experimental technologies in identifying PLB structure-function relationships and in defining its interaction with the Ca2+-ATPase are also highlighted. The current leading viewpoint of PLB's mechanism of action emerges from a critical examination of alternative hypotheses and the most recent experimental evidence. The potential physiological relevance of PLB function in human heart failure is also covered. The interest in PLB across diverse biochemical disciplines portends its continued intense scrutiny and its potential exploitation as a therapeutic target.
Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels (1995)

The loss of ovarian follicles through atresia, which accounts for greater than 99% of postnatal female germ cell depletion, is mediated through apoptotic cell death. Although recent data have shown that apoptosis in granulosa cells of ovarian follicles can be hormonally manipulated, the molecular mechanisms responsible for transducing external signals remain to be elucidated. Herein we have characterized changes in the expression of the bcl-2 protooncogene (an inhibitor of apoptosis), the bax gene (an inducer of apoptosis), and the bcl-x gene (which encodes both bcl-xlong, an inhibitor of apoptosis, and bcl-xshort, an inducer of apoptosis) during gonadotropin-stimulated follicular development in vivo and during atresia of antral follicles incubated in vitro. Complementary DNA fragments corresponding to rat bcl-2, rat bax, and rat bcl-x coding sequences were obtained by the reverse transcription-polymerase chain reaction (RT-PCR) technique using total RNA prepared from immature rat ovaries. Northern blot analysis of steady-state bcl-2, bax, and bcl-x messenger RNA (mRNA) levels in total RNA prepared from ovaries of immature rats before and after in vivo priming with 10 IU equine CG (eCG) revealed that eCG-induced follicular growth and survival were associated with a relatively constitutive level of bcl-2 and bcl-x expression but markedly reduced levels of bax mRNA (29 +/- 5% of saline-treated control animals). Using the RT-PCR technique coupled with Southern blot hybridization analysis to distinguish the long vs. short forms of bcl-x (which differ in size by 189 base pairs), it was determined that bcl-xlong was the predominant message expressed by granulosa cells of eCG-primed ovaries. The eCG-mediated decrease in bax expression, coupled with a maintenance of bcl-2 and bcl-xlong mRNA levels, were associated with a pronounced reduction in the extent of granulosa cell apoptosis. In contrast, the induction of apoptosis in a homogeneous population of healthy antral follicles by incubation in vitro without tropic support was associated with an significant increase in bax mRNA levels to 220 +/- 10% of those detected in freshly isolated, healthy follicles. Moreover, bcl-xlong message levels were significantly reduced in follicles incubated for 24 h to 69 +/- 4% of those levels detected in freshly isolated, healthy follicles. However, no significant change in the level of bcl-2 mRNA was detected.
Characterization of microRNA expression profiles in normal human tissues (2007)

Measuring the quantity of miRNAs in tissues of different physiological and pathological conditions is an important first step to investigate the functions of miRNAs. Matched samples from normal state can provide essential baseline references to analyze the variation of miRNA abundance. We provided expression data of 345 miRNAs in 40 normal human tissues, which identified universally expressed miRNAs, and several groups of miRNAs expressed exclusively or preferentially in certain tissue types. Many miRNAs with co-regulated expression patterns are located within the same genomic clusters, and candidate transcriptional factors that control the pattern of their expression may be identified by a comparative genomic strategy. Hierarchical clustering of normal tissues by their miRNA expression profiles basically followed the structure, anatomical locations, and physiological functions of the organs, suggesting that functions of a miRNA could be appreciated by linking to the biologies of the tissues in which it is uniquely expressed. Many predicted target genes of miRNAs that had specific reduced expression in brain and peripheral blood mononuclear cells are required for embryonic development of the nervous and hematopoietic systems based on database search. We presented a global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures. We also described evidence from the cis-regulatory elements and the predicted target genes of miRNAs to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.
Reactive Oxygen Species and the Pathogenesis of Radiocontrast-Induced Nephropathy (2010)

Experimental findings in vitro and in vivo illustrate enhanced hypoxia and the formation of reactive oxygen species (ROS) within the kidney following the administration of iodinated contrast media, which may play a role in the development of contrast media-induced nephropathy. Clinical studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetyl cysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging.
Direct Asymmetric Organocatalytic Michael Reactions of α,α-Disubstituted Aldehydes with β-Nitrostyrenes for the Synthesis of Quaternary Carbon-Containing Products (2004)

[reaction: see text] Direct asymmetric catalytic Michael reactions have been performed using chiral-amine/acid bifunctional catalysts. Performed with 0.3 equiv of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine and 0.3 equiv of trifluoroacetic acid as the catalyst, the reaction of alpha,alpha-dialkylaldehydes with (E)-beta-nitrostyrene provided the alpha,alpha-dialkyl Michael products in up to 96% yield with up to 91% ee. With respect to enantioselectivity, l-proline was a poor catalyst of this class of Michael reactions.
Cognitive Neural Prosthetics (2009)

The cognitive neural prosthetic (CNP) is a very versatile method for assisting paralyzed patients and patients with amputations. The CNP records the cognitive state of the subject, rather than signals strictly related to motor execution or sensation. We review a number of high-level cortical signals and their application for CNPs, including intention, motor imagery, decision making, forward estimation, executive function, attention, learning, and multi-effector movement planning. CNPs are defined by the cognitive function they extract, not the cortical region from which the signals are recorded. However, some cortical areas may be better than others for particular applications. Signals can also be extracted in parallel from multiple cortical areas using multiple implants, which in many circumstances can increase the range of applications of CNPs. The CNP approach relies on scientific understanding of the neural processes involved in cognition, and many of the decoding algorithms it uses also have parallels to underlying neural circuit functions.
Ibrutinib Resistance in Chronic Lymphocytic Leukemia (2014)

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is active in CLL, but resistance may emerge. The authors observed the emergence of a CLL clone with a cysteine-to-serine change in amino acid 481 of the target protein that substantially weakens drug binding and leads to resistance.
A practical method for uniform isotopic labeling of recombinant proteins in mammalian cells (1992)

A method to obtain uniformly isotopically labeled (15N and 15N/13C) protein from mammalian cells is described. The method involves preparation of isotopically labeled media consisting of amino acids isolated from bacterial and algal extracts supplemented with cysteine and enzymatically synthesized glutamine. The approach is demonstrated by producing 15N-labeled and 15N/13C-labeled urokinase from Sp2/0 cells and successfully growing Chinese hamster ovary (CHO) cells on the labeled media. Thus, using the procedures described, isotopically labeled proteins that have been expressed in mammalian cells can be prepared, allowing them to be studied by heteronuclear multidimensional NMR techniques.
Prolonged maintenance of 2,3‐diphosphoglycerate acid and adenosine triphosphate in red blood cells during storage (2008)

Resuspension of RBCs in our alkaline medium PAGGG-M resulted in a RBC unit of high quality during storage for up to at least 35 days, with 2,3-DPG levels of higher than 10 mumol per g Hb, hemolysis of less than 0.2 percent, and ATP levels of higher than 5 mumol per g Hb.
A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9 (2001)

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.
Enzymatic Hydrolysis of Poly(lactide)s:  Effects of Molecular Weight, l-Lactide Content, and Enantiomeric and Diastereoisomeric Polymer Blending (2001)

Nonblended poly(L-lactide) (PLLA) films having different molecular weights and nonblended poly(lactide) (PLA) films, enantiomeric blend films from PLLA and poly(D-lactide) (PDLA), and diastereoisomeric blend films of poly(DL-lactide) (PDLLA) with either PLLA or PDLA, having different L-lactide (LLA) contents (X(LLA)s) in the range of 0-0.99, were amorphous made by melt-quenching. The effects of molecular weight, X(LLA), and average L- and D-lactyl unit sequence length (l(L) and l(D), respectively) on the enzymatic hydrolysis of the films were investigated in the presence of proteinase K. The enzymatic hydrolysis rate (R(EH)) of PLLA estimated by gravimetry increased monotonically with the inverse of number-average molecular weight (M(n)). The extrapolation of R(EH) of PLLA to M(n)(-1) = 0, where no exo-chain-scission takes place, gave a positive R(EH) value (1.75 microg/(mm(2).h)), meaning that the enzymatic hydrolysis of PLLA proceeds via both endo- and exo-chain-scission. The R(EH) of the nonblended films as well as the enantiomeric and diastereoisomeric blend films decreased monotonically with the decease in X(LLA) and finally became zero for X(LLA) below 0.3. The R(EH) values of the blend films of PLLA and PDLLA with PDLA (l(D) = infinity) were lower than expected, while the R(EH) values of the blend films of PLLA with PDLLA (l(D) = 4) agreed completely with the expected values. These results reveal that the nonblended PLA films are enzymatically hydrolyzable when X(LLA) and l(L) are higher than 0.3 and 3, respectively, and l(D) is lower than 10 and that the presence of long D-lactyl unit sequences (l(D) > 4) as in PDLA hinders the enzymatic hydrolysis of long L-lactyl unit sequences even when long D- and L-lactyl unit sequences are present in the different molecules.
Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer (2020)

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (<i>HER2</i>) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.
Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol (1998)

Scavenger receptor BI (SR-BI) is a cell surface receptor that binds high density lipoproteins (HDL) and mediates selective uptake of HDL cholesteryl esters (CE) in transfected cells. To address the physiological role of SR-BI in HDL cholesterol homeostasis, mice were generated bearing an SR-BI promoter mutation that resulted in decreased expression of the receptor in homozygous mutant (designated SR-BI att) mice. Hepatic expression of the receptor was reduced by 53% with a corresponding increase in total plasma cholesterol levels of 50-70% in SR-BI att mice, attributable almost exclusively to elevated plasma HDL. In addition to increased HDL-CE, HDL phospholipids and apo A-1 levels were elevated, and there was an increase in HDL particle size in mutant mice. Metabolic studies using HDL bearing nondegradable radiolabels in both the protein and lipid components demonstrated that reducing hepatic SR-BI expression by half was associated with a decrease of 47% in selective uptake of CE by the liver, and a corresponding reduction of 53% in selective removal of HDL-CE from plasma. Taken together, these findings strongly support a pivotal role for hepatic SR-BI expression in regulating plasma HDL levels and indicate that SR-BI is the major molecule mediating selective CE uptake by the liver. The inverse correlation between plasma HDL levels and atherosclerosis further suggests that SR-BI may influence the development of coronary artery disease.
A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection (2013)

ClinicalTrials.gov NCT00703469.
Measurement of the induced refractive index in a photothermorefractive glass by a liquid-cell shearing interferometer (2002)

A liquid-cell shearing interferometer was developed to measure refractive-index variations (delta n) in transparent materials. The cell was filled with a liquid having a matched refractive index. The achieved resolution was better than 1/1000 of a fringe shift and resulted in a delta n measurement sensitivity down to 10(-7) for 1-mm-thick samples. A refractive-index increment in photothermorefractive glass of up to 5 x 10(-6) was observed after UV exposure at 325 nm. A refractive-index decrement of up to 1 x 10(-3) was observed after thermal development of the exposed sample. It was proved that photothermorefractive glass obeys the reciprocity law; i.e., delta n depends on the UV dosage but does not depend on the irradiance.
Planning for PKI: Best Practices Guide for Deploying Public Key Infrastructure (2001)

From the Publisher:
An in-depth technical guide to the security technology driving Internet e-commerce. Planning for examines this cornerstone Internet security technology. Written by the architects of the Internet Public Key Infrastructure (PKI), this book provides authoritative technical guidance for network engineers, architects, and managers who need to implement the right PKI architecture for their organization. Readers will learn that building a successful PKI is an on going process, not a one-time event. The authors discuss results and lessons learned from three early PKI deployments, helping readers avoid the pitfalls and emulate the successes of early PKI adopters. Using plain and direct language, the authors share their extensive knowledge of PKI standards development in the Internet Engineering Task Force (IETF) and elsewhere. Subtle points about the Internet PKI standards are liberally sprinkled throughout the book. These nuggets provide insight into the intent of some of the esoteric topics in the standards, enabling greater interoperability. Planning for gathers the PKI state-of-the-art into one volume, covering everything from PKI history to emerging PKI-related technologies.
Strain‐ and region‐specific gene expression profiles in mouse brain in response to chronic nicotine treatment (2007)

A pathway-focused complementary DNA microarray and gene ontology analysis were used to investigate gene expression profiles in the amygdala, hippocampus, nucleus accumbens, prefrontal cortex (PFC) and ventral tegmental area of C3H/HeJ and C57BL/6J mice receiving nicotine in drinking water (100 mug/ml in 2% saccharin for 2 weeks). A balanced experimental design and rigorous statistical analysis have led to the identification of 3.5-22.1% and 4.1-14.3% of the 638 sequence-verified genes as significantly modulated in the aforementioned brain regions of the C3H/HeJ and C57BL/6J strains, respectively. Comparisons of differential expression among brain tissues showed that only a small number of genes were altered in multiple brain regions, suggesting presence of a brain region-specific transcriptional response to nicotine. Subsequent principal component analysis and Expression Analysis Systematic Explorer analysis showed significant enrichment of biological processes both in C3H/HeJ and C57BL/6J mice, i.e. cell cycle/proliferation, organogenesis and transmission of nerve impulse. Finally, we verified the observed changes in expression using real-time reverse transcriptase polymerase chain reaction for six representative genes in the PFC region, providing an independent replication of our microarray results. Together, this report represents the first comprehensive gene expression profiling investigation of the changes caused by nicotine in brain tissues of the two mouse strains known to exhibit differential behavioral and physiological responses to nicotine.
Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination (2000)

With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.