gebhart/patrepeval huggingface dataset:
Characterization of specific and distinct patient types in clinical trials of acute schizophrenia using an uncorrelated PANSS score matrix transform (UPSM) (2020)

Understanding the specificity of symptom change in schizophrenia can facilitate the evaluation antipsychotic efficacy for different symptom domains. Previous work identified a transform of PANSS using an uncorrelated PANSS score matrix (UPSM) to reduce pseudospecificity among symptom domains during clinical trials of schizophrenia. Here we used UPSM-transformed factor scores to identify 5 distinct patient types, each having elevated and specific severity among each of 5 symptom domains. Subjects from placebo-controlled clinical trials of acute schizophrenia were clustered (baseline) and classified (post-baseline) by a machine-learning algorithm. At baseline, all 5 patient types were similar in PANSS total score. Post-baseline, subjects' memberships among the 5 UPSM patient types were relatively stable over treatment duration and were relatively insensitive to overall improvements in symptoms, in contrast to other methods based on untransformed PANSS items. Using UPSM-transformed PANSS, drug treatment effect sizes versus placebo were doubly-dissociated for specificity across symptom domains and within specific patient types. This approach illustrates how broader clinical trial populations can nevertheless be utilized to characterize the specificity of new mechanisms across the dimensions of schizophrenia psychopathology.
Venous thromboembolism and cancer (2017)

Venous thromboembolism (VTE) is a collective term for deep vein thrombosis and pulmonary embolism. VTE is a common cause of mortality and morbidity in patients with cancer, and may also be the first sign of an underlying malignancy. The first aim of this thesis was to investigate the risk of incident and recurrent VTE in active cancer compared to a cancer-free reference population and to explore the influence of genetic risk factors on cancer-related VTE. Secondly, we aimed to investigate the association between plasma D-dimer levels at VTE and the subsequent risk of cancer. \n\tAll four papers in this thesis utilize the Tromsø Study. The first survey of the Tromsø Study was conducted in 1974 and, thus far, seven surveys have been completed. Our study populations were recruited from the Tromsø 4 and 6 surveys for Paper I, and Tromsø 1 to 6 surveys for Papers III and IV. Participants were followed from 1994, when the VTE registry was established in Tromsø, throughout 2012. Paper II was based on the Scandinavian Thrombosis and Cancer (STAC) cohort, which comprises individual data from the Tromsø 4 survey, the second Nord-Trøndelag Health Study (HUNT2) and the Danish Diet, Cancer and Health (DCH) Study. Validated VTE events and cancer diagnoses were registered from inclusion (1993 to 1997) to the end of follow-up (2007 to 2012).\n\tWe found a joint effect between two single nucleotide polymorphisms (SNPs) in the F5 gene (F5 rs6025 (Factor V Leiden) and F5 rs4524) and active cancer on the risk of VTE. The incidence of cancer-related VTE increased considerably in the six months following a cancer diagnosis, and especially so in patients with risk alleles at these SNPs. \nFurther, cancer-related factors consistently demonstrated a strong influence on incident and recurrent VTE. In traditional analysis, the risk of VTE was highest in the first 6 months after cancer diagnosis and the risk declined markedly thereafter. However, when mortality was taken into account, the risk of VTE was equal in the 6 months before and 6 months after a cancer diagnosis, which suggests that cancer itself is a major contributor to the VTE risk. The risk of VTE by cancer sites was greatly influenced by mortality and the time since cancer diagnosis. We found that patients with an occult cancer-related incident VTE had a higher rate of VTE recurrence than those with overt cancer and those without cancer. Patients with occult cancer-related incident VTE who experienced a VTE recurrence more often had prothrombotic and advanced cancers at the time of cancer diagnosis. The majority of VTE recurrences were not related to cancer treatment as they occurred prior to cancer diagnosis. \nFinally, we found that plasma D-dimer levels above 5000 ng/ml at incident VTE were associated with an increased risk of subsequent cancer at one and two years. Patients with higher D-dimer levels at incident VTE had more advanced cancers at the time of diagnosis and mortality was greater among these patients.
Cold Plasma Decontamination of Foods (2012)

Cold plasma is a novel nonthermal food processing technology that uses energetic, reactive gases to inactivate contaminating microbes on meats, poultry, fruits, and vegetables. This flexible sanitizing method uses electricity and a carrier gas, such as air, oxygen, nitrogen, or helium; antimicrobial chemical agents are not required. The primary modes of action are due to UV light and reactive chemical products of the cold plasma ionization process. A wide array of cold plasma systems that operate at atmospheric pressures or in low pressure treatment chambers are under development. Reductions of greater than 5 logs can be obtained for pathogens such as Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus. Effective treatment times can range from 120 s to as little as 3 s, depending on the food treated and the processing conditions. Key limitations for cold plasma are the relatively early state of technology development, the variety and complexity of the necessary equipment, and the largely unexplored impacts of cold plasma treatment on the sensory and nutritional qualities of treated foods. Also, the antimicrobial modes of action for various cold plasma systems vary depending on the type of cold plasma generated. Optimization and scale up to commercial treatment levels require a more complete understanding of these chemical processes. Nevertheless, this area of technology shows promise and is the subject of active research to enhance efficacy.
Neuropilin-1 Upholds Dedifferentiation and Propagation Phenotypes of Renal Cell Carcinoma Cells by Activating Akt and Sonic Hedgehog Axes (2008)

Expression of neuropilin-1 (NRP-1) has been shown in many cancer cells, but its molecular effect on tumorigenesis is largely unknown. In this report, we show that in aggressive types of renal cell carcinoma (RCC), NRP-1 is expressed at a high level. We show that after knockdown of NRP-1 by short hairpin RNA, RCC cells express significantly lower levels of MDM-2 and p63 proteins but higher levels of p53, and exhibit reduced migration and invasion. When implanted in mice, RCC cells with a reduced NRP-1 level have a statistically significant smaller tumor-forming ability than control cells. Also, NRP-1 knockdown RCC cells exhibit a more differentiated phenotype, as evidenced by the expression of epithelial-specific and kidney-specific cadherins, and the inhibition of sonic hedgehog expression participated in this effect. Inhibition of sonic hedgehog expression can be reversed by DeltaNp63alpha overexpression. Our study reveals that NRP-1 helps maintain an undifferentiated phenotype in cancer cells.
Efficient total syntheses of the oligopeptide antibiotics netropsin and distamycin (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEfficient total syntheses of the oligopeptide antibiotics netropsin and distamycinJ. William Lown and Krzysztof KrowickiCite this: J. Org. Chem. 1985, 50, 20, 3774–3779Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/jo00220a019https://doi.org/10.1021/jo00220a019research-articleACS PublicationsRequest reuse permissionsArticle Views619Altmetric-Citations74LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Overexpression of NBS1 Contributes to Transformation through the Activation of Phosphatidylinositol 3-Kinase/Akt (2005)

Nijmegen breakage syndrome (NBS) is a chromosomal instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1 (p95) or nibrin, is a part of the hMre11 complex, a central player associated with double strand break repair. We previously demonstrated that c-Myc directly activates NBS1 expression. Here we have shown that constitutive expression of NBS1 in Rat1a and HeLa cells induces/enhances their transformation. Repression of endogenous NBS1 levels using short interference RNA reduces the transformation activity of two tumor cell lines. Increased NBS1 expression is observed in 40-52% of non-small cell lung carcinoma, hepatoma, and esophageal cancer samples. NBS1 overexpression stimulates phosphatidylinositol (PI) 3-kinase activity, leading to increased phosphorylation levels of Akt and its downstream targets such as glycogen synthase kinase 3beta and mammalian target of rapamycin in different cell lines and tumor samples. Transformation induced by NBS1 overexpression can be inhibited by a PI3-kinase inhibitor (LY294002). Repression of endogenous Akt expression by short interference RNA decreases the transformation activity of Rat1a cells overexpressing NBS1. These results indicate that overexpression of NBS1 is an oncogenic event that contributes to transformation through the activation of PI3-kinase/Akt.
Multilineage engraftment in NOD/LtSz-scid/scid mice from mobilized human CD34+ peripheral blood progenitor cells. (1997)

Peripheral blood progenitor cells (PBPCs) are now the most widely used source for hematopoietic support of patients in the autologous transplant setting and are increasingly being used for allogeneic transplantation. A reliable model to characterize the in vivo potential of various PBPC subpopulations could be valuable as a preclinical assay to predict the hematopoietic performance in humans of these populations and of products resulting from their manipulations ex vivo. We have used immunocompromised nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice to engraft human CD34+ PBPCs and to study the repopulation characteristics of this progenitor cell fraction. Following myeloablation, intravenous infusion of CD34+ cells consistently produced engraftment and development in mice. Multilineage development occurred in all mice with CD34+ cells, erythroid precursors, and the most immature populations of myeloid cells and B lymphocytes restricted to the mouse bone marrow (BM). More mature populations of myeloid cells and B lymphocytes were peripheralized to the spleen and blood of the animals. This finding suggests that human hematopoiesis in the mice may recapitulate hematopoietic recovery in humans. The provision of human growth factors was not necessary for either engraftment or development of CD34+ cells. When mice were supplemented with growth factors, engraftment levels were unaffected but development was biased toward myeloid production. These findings indicate that providing nonphysiological levels of human growth factors may obscure or enhance the developmental potential of particular progenitor cell populations in this model. Cells capable of initiating colony formation in vitro were maintained in BM during the engraftment period (up to 17 weeks), suggesting that continuous production of myeloid and erythroid precursors occurred from more primitive hematopoietic cells subsequent to engraftment. In comparing results from this study with previous results, it was found that in this model the engraftment potential of CD34+ umbilical cord blood cells is greater than that described here for CD34+ PBPCs. In summary, this model may provide a reliable assay to predict the hematopoietic potential of progenitor cell populations in humans if a correlation for engraftment of identical cell fractions can be established between the two species.
A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI / Funktionelle Magnetresonanztomographie zeigt Aktivierungen des Hirnstamms und weiterer zerebraler Strukturen unter transkutaner Vagusnervstimulation (2008)

The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP are discussed and new possibilities of tVNS are hypothesised.
GENEEXPRESSION INNEMATODEFEEDINGSITES (2002)

The feeding sites induced by sedentary root-endoparasitic nematodes have long fascinated researchers. Nematode feeding sites are constructed from plant cells, modified by the nematode to feed itself. Powerful new techniques are allowing us to begin to elucidate the molecular mechanisms that produce the ultrastructural features in nematode feeding cells. Many plant genes that are expressed in feeding sites produced by different nematodes have been identified in several plant species. Nematode-responsive plant genes can now be grouped in categories related to plant developmental pathways and their roles in the making of a feeding site can be illuminated. The black box of how nematodes bring about such elaborate cell differentiation in the plant is also starting to open. Although the information is far from complete, the groundwork is set so that the functions of the plant and nematode genes in feeding site development can begin to be assessed.
High power cw operation of GaAs/GaAlAs surface-emitting lasers mounted in the junction-up configuration (1991)

High power cw operation of horizontal cavity monolithic GaAs/GaAlAs surface-emitting lasers with all dry etched micromirrors in the junction-up configuration has been demonstrated for the first time. The 45° and 90° mirrors of the devices were fabricated by ion beam etching and reactive ion etching techniques, respectively. Typical threshold current densities of less than 360 A/cm2, external differential efficiencies of 22% (0.34 W/A) from the emitting facet, and output powers in excess of 280 mW were achieved under cw operation.
Interfacial Catalysis: the Mechanism of Phospholipase A 2 (1990)

A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2S. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.
ChemInform Abstract: 2,3‐DISUBSTITUTED FURANS AND PYRROLES. XVIII. SYNTHESIS AND REARRANGEMENT OF 4H‐9,10‐DIHYDROBENZO(4.5)CYCLOHEPTA(1,2‐B)FURAN‐4‐ONES (1976)

Abstract Aus dem Phosphonat (I) werden durch Reaktion mit den entsprechenden Benzaldehyden und anschließende i katalytische Hydrierung die Ester (II) dargestellt, deren Säurechloride bei Behandlung mit AlCl 3 nur cyclisieren, wenn der Phenylring durch eine m‐Methoxygruppe aktiviert ist oder wenn die 5‐Stellung im Furanring durch einen Substituenten blockiert wird; von den aus (IIa) und (IIb) in zwei Schritten gewonnenen Säurechloriden (III) cyclisiert nur (IIIb) zu dem Tricyclus (IV).
Laser deposition of biaxially textured yttria-stabilized zirconia buffer layers on polycrystalline metallic alloys for high critical current Y-Ba-Cu-O thin films (1992)

Pulsed laser deposition of yttria-stabilized zirconia (YSZ) layers on polycrystalline metallic alloy substrates is used to produce an intermediate layer for YBa2Cu3O7−δ (YBCO) thin-film growth. The desired (001) YSZ texture is obtained at 1.0 mTorr oxygen pressure and 70 °C. Significant improvement in (001) texturing is demonstrated by using an ion beam to assist growth. Argon-ion-assisted growth produces layers with alignment of the in-plane crystal axes in addition to the (001)-normal texture. Highly c-axis-oriented biaxially aligned YBCO thin films can be deposited on these layers, with Tc(R=0)=92 K and Jc (77 K, B=0 T)=6×105 A/cm2 and Jc (77 K, 0.4 T)=8×104 A/cm2. With further improvement of the YSZ texture, the YBCO current-carrying capacity of films on polycrystalline metallic alloys may approach that of films on single-crystal substrates.
The IKKβ Subunit of IκB Kinase (IKK) is Essential for Nuclear Factor κB Activation and Prevention of Apoptosis (1999)

The IkappaB kinase (IKK) complex is composed of three subunits, IKKalpha, IKKbeta, and IKKgamma (NEMO). While IKKalpha and IKKbeta are highly similar catalytic subunits, both capable of IkappaB phosphorylation in vitro, IKKgamma is a regulatory subunit. Previous biochemical and genetic analyses have indicated that despite their similar structures and in vitro kinase activities, IKKalpha and IKKbeta have distinct functions. Surprisingly, disruption of the Ikkalpha locus did not abolish activation of IKK by proinflammatory stimuli and resulted in only a small decrease in nuclear factor (NF)-kappaB activation. Now we describe the pathophysiological consequence of disruption of the Ikkbeta locus. IKKbeta-deficient mice die at mid-gestation from uncontrolled liver apoptosis, a phenotype that is remarkably similar to that of mice deficient in both the RelA (p65) and NF-kappaB1 (p50/p105) subunits of NF-kappaB. Accordingly, IKKbeta-deficient cells are defective in activation of IKK and NF-kappaB in response to either tumor necrosis factor alpha or interleukin 1. Thus IKKbeta, but not IKKalpha, plays the major role in IKK activation and induction of NF-kappaB activity. In the absence of IKKbeta, IKKalpha is unresponsive to IKK activators.
Synthetic peptides corresponding to the site phosphorylated in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as substrates of cyclic nucleotide-dependent protein kinases. (1986)

The specificities of cAMP-dependent and cGMP-dependent protein kinases were studied using synthetic peptides corresponding to the phosphorylation site in 6-phosphofructo-2-kinase/Fru-2,6-P2ase (Murray, K.J., El-Maghrabi, M.R., Kountz, P.D., Lukas, T.J., Soderling, T.R., and Pilkis, S.J. (1984) J. Biol. Chem. 259, 7673-7681) as substrates. The peptide Val-Leu-Gln-Arg-Arg-Arg-Gly-Ser-Ser-Ile-Pro-Gln was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase on predominantly the first of its 2 seryl residues. The Km (4 microM) and Vmax (14 mumol/min/mg) values were comparable to those for the phosphorylation of this site within native 6-phosphofructo-2-kinase/Fru-2,6-P2ase. An analog peptide containing only two arginines was phosphorylated with poorer kinetic constants than was the parent peptide. These results suggest that the amino acid sequence at its site of phosphorylation is a major determinant that makes 6-phosphofructo-2-kinase/Fru-2,6-P2ase an excellent substrate for cAMP-dependent protein kinase. Although 6-phosphofructo-2-kinase/Fru-2,6-P2ase was not phosphorylated by cGMP-dependent protein kinase, the synthetic peptide corresponding to the cAMP-dependent phosphorylation site was a relatively good substrate (Km = 33 microM, Vmax = 1 mumol/min/mg). Thus, structures other than the primary sequence at the phosphorylation site must be responsible for the inability of cGMP-dependent protein kinase to phosphorylate native 6-phosphofructo-2-kinase/Fru-2,6-P2ase. Peptides containing either a -Ser-Ser- or -Thr-Ser- moiety were all phosphorylated by cGMP-dependent kinase to 1.0 mol of phosphate/mol of peptide, but the phosphate was distributed between the two hydroxyamino acids. Substitution of a proline in place of the glycine between the three arginines and these phosphorylatable amino acids caused the protein kinase selectively to phosphorylate the threonyl or first seryl residue and also enhanced the Vmax values by 4-6-fold. These results are consistent with a role for proline in allowing an adjacent threonyl residue to be readily phosphorylated by cGMP-dependent protein kinase.
Association of Hypoadiponectinemia With Coronary Artery Disease in Men (2003)

Male patients with hypoadiponectinemia (<4.0 microg/mL) had a significant 2-fold increase in CAD prevalence, independent of well-known CAD risk factors.
Synthesis, cellular uptake and HIV-1 Tat-dependent trans-activation inhibition activity of oligonucleotide analogues disulphide-conjugated to cell-penetrating peptides (2005)

Oligonucleotides composed of 2'-O-methyl and locked nucleic acid residues complementary to HIV-1 trans-activation responsive element TAR block Tat-dependent trans-activation in a HeLa cell assay when delivered by cationic lipids. We describe an improved procedure for synthesis and purification under highly denaturing conditions of 5'-disulphide-linked conjugates of 3'-fluorescein labelled oligonucleotides with a range of cell-penetrating peptides and investigate their abilities to enter HeLa cells and block trans-activation. Free uptake of 12mer OMe/LNA oligonucleotide conjugates to Tat (48-58), Penetratin and R9F2 was observed in cytosolic compartments of HeLa cells. Uptake of the Tat conjugate was enhanced by N-terminal addition of four Lys or Arg residues or a second Tat peptide. None of the conjugates entered the nucleus or inhibited trans-activation when freely delivered, but inhibition was obtained in the presence of cationic lipids. Nuclear exclusion was seen for free delivery of Tat (48-58), Penetratin and R9 conjugates of 16mer phosphorothioate OMe oligonucleotide. Uptake into human fibroblast cytosolic compartments was seen for Tat, Penetratin, R9F2 and Transportan conjugates. Large enhancements of HeLa cell uptake into cytosolic compartments were seen when free Tat peptide was added to Tat conjugate of 12mer OMe/LNA oligonucleotide or Penetratin peptide to Penetratin conjugate of the same oligonucleotide.