gebhart/patrepeval huggingface dataset:
Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins (2011)

Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50 % of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management.
The Turnover Kinetics of Major Histocompatibility Complex Peptides of Human Cancer Cells (2005)

Peptides presented by the major histocompatibility complex (MHC) are derived from the degradation of cellular proteins. Thus, the repertoire of these peptides (the MHC peptidome) should correlate better with the cellular protein degradation scheme (the degradome) than with the cellular proteome. To test the validity of this statement and to determine whether the majority of MHC peptides are derived from short lived proteins, from defective ribosome products, or from regular long lived cellular proteins we analyzed in parallel the turnover kinetics of both MHC peptides and cellular proteins in the same cancer cells. The analysis was performed by pulse-chase experiments based on stable isotope labeling in tissue culture followed by capillary chromatography and tandem mass spectrometry. Indeed only a limited correlation was observed between the proteome and the MHC peptidome observed in the same cells. Moreover a detailed analysis of the turnover kinetics of the MHC peptides helped to assign their origin to normal, to short lived or long lived proteins, or to the defective ribosome products. Furthermore the analysis of the MHC peptides turnover kinetics helped to direct attention to abnormalities in the degradation schemes of their source proteins. These observations can be extended to search for cancer-related abnormalities in protein degradation, including those that lead to loss of tumor suppressors and cell cycle regulatory proteins.
Hands‐On Defibrillation Has the Potential to Improve the Quality of Cardiopulmonary Resuscitation and Is Safe for Rescuers— A Preclinical Study (2012)

Background Recently, it has been demonstrated that rescuers could safely provide a low, static downward force in direct contact with patients during elective cardioversion. The purpose of our experimental study was to investigate whether shock delivery during uninterrupted chest compressions may have an impact on cardiopulmonary resuscitation ( CPR ) quality and can be safely performed in a realistic animal model of CPR . Methods and Results Twenty anesthetized swine were subjected to 7 minutes of ventricular fibrillation followed by CPR according to the 2010 A merican H eart A ssociation G uidelines. Pregelled self‐adhesive defibrillation electrodes were attached onto the torso in the ventrodorsal direction and connected to a biphasic defibrillator. Animals were randomized either to (1) hands‐on defibrillation, where rescuers wore 2 pairs of polyethylene gloves and shocks were delivered during ongoing chest compressions, or (2) hands‐off defibrillation, where hands were taken off during defibrillation. CPR was successful in 9 out of 10 animals in the hands‐on group (versus 8 out of 10 animals in the hands‐off group; not significant). In the hands‐on group, chest compressions were interrupted for 0.8% [0.6%; 1.4%] of the total CPR time (versus 8.2% [4.2%; 9.0%]; P =0.0003), and coronary perfusion pressure was earlier restored to its pre‐interruption level ( P =0.0205). Also, rescuers neither sensed any kind of electric stimulus nor did H olter ECG reveal any serious cardiac arrhythmia. Conclusions Hands‐on defibrillation may improve CPR quality and could be safely performed during uninterrupted chest compressions in our standardized porcine model.
Impact of elevated cytosolic and apoplastic invertase activity on carbon metabolism during potato tuber development (2000)

During tuberization in Solanum tuberosum var. Desirée maximal catalytic activities of invertase(s) and sucrose synthase are inversely correlated. During the early stages, invertase activity is high and declines during maturation. The decrease in invertase activity is accompanied by a decrease in the hexose to sucrose ratio and an increase in sucrose synthase activity. This switch is paralleled by the onset of the storage phase as shown by the accumulation of starch and storage proteins. Biochemical and genetic evidence suggests that sucrose synthase activity is positively correlated with sink strength. To explore the possibility of enhancing sink strength in potato tubers by elevating the sucrolytic capacity, transgenic potato plants expressing either cytosolic or apoplastic yeast invertase in their tubers were made. Surprisingly, cytosolic invertase led to a decrease and apoplastic invertase to an increase in tuber yield. To understand the causes of the observed phenotypes, carbon metabolism in tubers of transgenic and control plants was analysed during different stages of tuber development. Both cytosolic and apoplastic invertase resulted in decreased sucrose and elevated glucose contents, indicating that sucrose is accessible in both compartments. Metabolic perturbation, however, was found to be compartment specific. Elevated cytosolic invertase activity led to increased carbon flux towards glycolysis and accumulation of phosphorylated intermediates. The phosphorylated intermediates were not used to build up starch. In contrast, apoplastic invertase does not lead to a significant increase in hexose phosphates compared to untransformed controls. Thus, hexoses originating in the apoplast are not efficiently phosphorylated during potato tuber development, which might be explained by an endocytotic uptake of sucrose and/or hexoses from the apoplast into the vacuole bypassing the cytosolic compartment.
Drew Heywood's Windows 2000 Network Services (2001)

From the Publisher:
Drew Heywood's Networking Windows 2000 highlights the crucial aspects of networking - such as hardware configuration and the core Windows 2000 networking issues - so the reader can successfully and efficiently setup and administer a Windows 2000 network. This book is a reference for the networking professional who needs to learn how to anticipate and solve problems before they happen.

A networking professional must understand the inner workings of Windows 2000 and how it relates to and communicates with other products, such as NetWare, UNIX, and Linux as network operating systems. To address these issues, the reader is presented with well-crafted coverage of the most vital networking components of the Windows 2000 family. Its detailed coverage will enable administrators to differentiate the features and technology changes from Windows NT 4.0 to Windows 2000.

This will be one of the first Windows 2000 networking titles that will be tested against the actual shipping product, versus the early books based on beta code and RC3. This allows the author to provide more accurate information based on real-world deployment case studies. 

Readers will benefit from the author's expert discussions of topics including:
Installation Planning and ExecutionTCP/IP ProtocolsDomain Name Services (DNS)Active DirectoryManaging DomainsDomain Host Configuration Protocol (DHCP)Windows Internet Name Service (WINS)Terminal Services and Thin ClientsInternet Information Services (IIS)
Intrauterine Growth Restriction Caused by Underlying Congenital Cytomegalovirus Infection (2014)

Congenital HCMV infection impairs placental development and functions and should be considered as an underlying cause of IUGR, regardless of virus transmission to the fetus.
Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. (1989)

We describe a general strategy for the genetic mapping in parallel of multiple restriction fragment length polymorphism (RFLP) loci. This approach allows the systematic identification for cloning of physical genetic loci within about 100 kb of any gene in Caenorhabditis elegans. We have used this strategy of parallel RFLP mapping to clone the heterochronic gene lin-14, which controls the timing and sequence of many C. elegans postembryonic developmental events. We found that of about 400 polymorphic loci in the C. elegans genome associated with the Tc1 family of repetitive elements, six are within 0.3 map unit of lin-14. The three closest lin-14-linked Tc1-containing restriction fragments were cloned and used to identify by hybridization an 830-kb region of contiguous cloned DNA fragments assembled from cosmid and yeast artificial chromosome libraries. A lin-14 intragenic recombinant that separated a previously cryptic lin-14 semidominant mutation from a cis-acting lin-14 suppressor mutation was used to map the location of the lin-14 gene to a 25-kb region of this 830-kb contig. DNA probes from this region detected lin-14 allele-specific DNA alterations and a lin-14 mRNA. Two lin-14 semi-dominant alleles, which cause temporally inappropriate lin-14 gene activity and lead to the reiterated expression of specific early developmental events, were shown to delete sequences from the lin-14 gene and mRNA. These deletions may define cis-acting sequences responsible for the temporal regulation of lin-14.
In vivo Evaluation of the Penetration of Topically Applied Drugs into Human Skin by Spectroscopic Methods (1993)

Spectroscopic techniques are reported on which allow to study in vivo the penetration behaviour of topically applied light-absorbing drugs into human skin. Remittance spectroscopy, a purely optical method, provides a good tool in both, skin adaptation by use of a remote viewing head coupled to the spectrometer via optical fibres, and adequate sensitivity for the detection of small amounts of the applied drugs. The measuring depth in the skin is determined by the wavelength-dependent optical penetration depth, which itself depends on light absorption and light scattering. In the UV-spectral region the optical penetration depth is of the order of the thickness of the stratum corneum (UV-A) or of only a superficial part of it (UV-B, UV-C). Fluorescence spectroscopy, another optical method, offers two kinds of drug detection, a direct one in case of self-fluorescent drugs or an indirect one being based on the light absorption of the drug, which may give rise to a screening of the self-fluorescence of the skin itself or of an applied marker. The measuring depth is comparable to that achieved with remittance spectroscopy. A third method is photothermal spectroscopy which is determined by thermal properties of the skin in addition to optical properties. Photothermal spectroscopy is unique in that it allows depth profiles of drug concentration to be measured non-invasively, as the photothermal measuring depth can be changed by varying the modulation frequency of the intensity-modulated incident light. Results of measurements demonstrating the potentials of these spectroscopic methods are presented.
Changes during lactation in ganglioside distribution in human milk from mothers delivering preterm and term infants. (1996)

We studied changes during lactation in the relative concentration of individual gangliosides in human milk from mothers delivering preterm and term infants. The relative content of G(D3) was higher in colostrum than in mature milk, and tended to be higher in preterm colostrum than in term colostrum, whereas the relative content of G(M3) was higher in mature milk than in colostrum, and was also higher in term than in preterm milk. As G(D3) is usually detected in developing tissues whereas G(M3) is more abundant in mature tissues, these results suggest a relationship between the presence of individual gangliosides in human milk and immaturity of the mammary gland in mothers of preterm infants.
A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens. (1993)

A discrete 10-kDa polypeptide (10K) is expressed from early stages in the embryonic chicken lens. Since this has potential as a marker for lens cell development, chicken 10K and its homologues from mouse and human lenses were identified by protein sequencing and cloning. Surprisingly, lens 10K proteins appear to be identical to a lymphokine, macrophage migration inhibitory factor (MIF), originally identified in activated human T cells. Using microdissection and PCR techniques, we find that expression of 10K/MIF is strongly correlated with cell differentiation in the developing chicken lens. Northern blot analysis shows that 10K/MIF is widely expressed in mouse tissues. These results suggest that proteins with MIF activity may have roles beyond the immune system, perhaps as intercellular messengers or part of the machinery of differentiation itself. Indeed, partial sequence of other small lens proteins identifies another MIF-related protein (MRP8) in calf lens. The relatively abundant expression of MIF in lens may have clinical significance, with the possibility of involvement in ocular inflammations that may follow damage to the lens.
In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. (1994)

IGF Binding Protein-3 (IGFBP-3), the major IGF carrier in the blood, undergoes limited proteolysis which reduces its affinity for IGFs, thus facilitating dissociation. The functional effects of this at the cellular level were studied by comparing two serum pools, one from healthy adults, one from women during late pregnancy when IGFBP-3 proteolysis is increased. Sera were mixed to yield identical IGF-I and IGF-II concentrations in the two pools. Western ligand and immunoblotting gave the characteristic IGFBP patterns for the two types of serum. Both pools dose-dependently stimulated DNA synthesis in cultured chick embryo fibroblasts. Stimulation by pregnancy serum was twice that by normal serum at 0.05-0.2% concentrations (P < 0.001). In the presence of excess monoclonal anti-IGF-I and -II antibodies, stimulation by both (0.1-0.2%) pools was 70-80% reduced and residual stimulation was similar. Addition of recombinant human (rh) IGFBP-3 dose-dependently depressed both pools' activity, more so for normal serum at 25 and 50 ng/ml, equally for each at 100 ng/ml. At the latter concentration, slight proteolysis of the rhIGFBP-3 was detectable in the presence of 0.2% pregnancy serum, but at 25 ng/ml, proteolysis was absent. These results suggest that IGFs are released more readily from pregnancy serum, accounting for the weaker inhibitory effect of low rhIGFBP-3 concentrations. For identical IGF concentrations, pregnancy serum's greater biological activity therefore reflects greater IGF availability to the cells. This study demonstrates the functional consequences at cellular level of serum IGFBP-3 proteolysis, underlining its significance in regulating serum IGF bioavailability.
A Strategy for the Stereoselective Preparation of Thymidine Phosphorothioates with the (R) or the (S) Configuration at the Stereogenic Phosphorus Atom and Their Application to the Synthesis of Oligodeoxyribonucleotides with Stereochemically Pure Phosphate/Phosphorothioate Chimeric Backbones (2006)

Abstract This paper describes a new method for the highly stereoselective preparation of dithymidine phosphorothioates (TpsT) with the ( R ) or the ( S ) configuration at the stereogenic phosphorus atom [( R p)‐ or ( S p)‐TpsT, respectively], together with the synthesis of oligodeoxyribonucleotides with stereochemically pure phosphate/phosphorothioate mixed backbones through the use of ( R p)‐ or ( S p)‐TpsT as building blocks.Stereochemically pure ( R p)‐ or ( S p)‐TpsT was produced through a five‐step process: 1) 1 H ‐tetrazole‐promoted thermodynamic equilibration of a diastereomeric mixture of allyl ( R p)‐ and ( S p)‐thymidine 3′,5′‐cyclic phosphate to give the ( S p) isomer as the major component, 2) stereospecific sulfurization of the allyl ( S p)‐thymidine 3′,5′‐cyclic phosphate to afford an allyl ( R p)‐thymidine 3′,5′‐cyclic phosphorothioate, 3) regioselective and stereoselective methanolysis of the allyl ( R p)‐thymidine 3′,5′‐cyclic phosphorothioate to provide an allyl methyl ( R p)‐thymidine 3′‐phosphorothioate as the main product, 4) stereospecific removal of the methyl group from the phosphorothioate moiety to give an allyl ( R p)‐5′‐ O ‐dimethoxytritylthymidine 3′‐phosphorothioate diester, or stereospecific removal of the allyl group from the phosphate moiety to form a methyl ( S p)‐5′‐ O ‐dimethoxytritylthymidine 3′‐phosphorothioate diester, and 5) stereospecific condensation of these ( R p)‐ and ( S p)‐diesters with a 5′‐ O ‐free thymidine in a Mitsunobu reaction to produce the allyl (3′–5′)‐linked ( S p)‐dithymidine phosphorothioate and the methyl (3′–5′)‐linked ( R p)‐dithymidine phosphorothioate, respectively. The resulting ( R p)‐ and ( S p)‐dithymidine phosphorothioates were converted into their 3′‐phosphoramidites. Oligodeoxyribonucleotides with stereochemically pure phosphate/phosphorothioate‐mixed backbones were then synthesized by use of these phosphoramidites as building blocks. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Heparin‐Binding Protein: An Early Marker of Circulatory Failure in Sepsis (2009)

In febrile patients, high plasma levels of HBP help to identify patients with an imminent risk of developing sepsis with circulatory failure.
Sialylation of glycoprotein oligosaccharides N-linked to asparagine. Enzymatic characterization of a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase and a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase from rat liver. (1982)

to homogeneity from rat liver (Weinstein, J.,
The surgeon as an endovascular interventionist. Why and how? (1996)

Catheter-based endovascular techniques have advanced significantly over the past three decades. It is only recently that surgeons have become more interested in these developments, and are now rapidly gaining in training and widening practice opportunities. Endovascular training and credentialing for the surgeon continue to be poorly-defined areas. Several pathways, albeit incomplete, are available for the incorporation of endoluminal/percutaneous skills into the surgical armamentarium. Ultimately, it can only be through established postgraduate residency and fellowship programs that the subspecialty of endovascular surgery can have a more universal applicability. The basic necessary catheter skills have been defined. Imaging requirements, both radiographic and endoscopic/ultrasonographic, are most significant and of great significance for the safe and successful performance of endoluminal vascular techniques. On balance, it is felt strongly that endoluminal catheter techniques are crucially important for the vascular surgeon of today and tomorrow.
Bacterial Resistance to β-Lactam Antibiotics:  Compelling Opportunism, Compelling Opportunity (2005)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity†Jed F. Fisher, Samy O. Meroueh, and Shahriar MobasheryView Author Information Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 Cite this: Chem. Rev. 2005, 105, 2, 395–424Publication Date (Web):February 9, 2005Publication History Received3 June 2004Published online9 February 2005Published inissue 1 February 2005https://pubs.acs.org/doi/10.1021/cr030102ihttps://doi.org/10.1021/cr030102iresearch-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views10570Altmetric-Citations746LEARN 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 SUBJECTS:Antimicrobial agents,Bacteria,Genetics,Monomers,Peptides and proteins Get e-Alerts
An Enzyme Library Approach to Biocatalysis:  Development of Nitrilases for Enantioselective Production of Carboxylic Acid Derivatives (2002)

The discovery, from Nature, of a large and diverse set of nitrilases is reported. The utility of this nitrilase library for identifying enzymes that catalyze efficient production of valuable hydroxy carboxylic acid derivatives is demonstrated. Unprecedented enantioselectivity and substrate scope are highlighted for three newly discovered and distinct nitrilases. For example, a wide array of (R)-mandelic acid derivatives and analogues were produced with high rates, yields, and enantiomeric excesses (95-99% ee). We also have found nitrilases that provide direct access to (S)-phenyllactic acid and other aryllactic acid derivatives, again with high yields and enantioselectivities. Finally, different nitrilases have been discovered that catalyze enantiotopic hydrolysis of 3-hydroxyglutaronitrile to afford either enantiomer of 4-cyano-3-hydroxybutyric acid with high enantiomeric excesses (>95% ee). The first enzymes are reported that effect this transformation to furnish the (R)-4-cyano-3-hydroxybutyric acid which is a precursor to the blockbuster drug Lipitor.
A new route for the preparation of pyrazolo[3,4‐c] pyridines (1979)

Abstract Catalytic reduction of the oximes of 4‐phenacyl‐3(5)R‐pyrazole‐4‐carboxylic acid esters ( 4a,b ) followed by cyclisalion constitutes a new appraoch to substituted pyrazolo[3,4‐ c ]pyridines. The starting materials 4a,b were prepared by reaction of ω‐bromoacetophenone oxime and sodium salts of oxalyl derivatives 2a,b and successive action of hydrazine on the obtained products 3a,b . Structural assignments rested upon correct elemental analysis and spectroscopic evidences.