gebhart/patrepeval huggingface dataset:
Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. (1991)

In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.
High-mobility p-channel metal-oxide-semiconductor field-effect transistor on strained Si (1993)

An enhancement-mode p-channel metal-oxide-semiconductor field-effect transistor (PMOSFET) is fabricated on a strained Si layer for the first time. A biaxial strain in a thin Si layer is produced by pseudomorphically growing this layer on a Ge0.25Si0.75 buffer layer which is grown on a Si substrate. At higher magnitude of gate bias, channel mobility of a strained Si PMOSFET has been found to be 50% higher than that of an identically processed conventional Si PMOSFET.
Reciprocal antagonism of steroid hormones and BZLF1 in switch between Epstein-Barr virus latent and productive cycle gene expression (1992)

BZLF1 repression of transcription from the Epstein-Barr virus BC-R2 promoter (Cp) was shown to require a glucocorticoid response element in cis and glucocorticoids in trans. The mechanism of the repression is indirect and involves up regulation of the cellular c-fos proto-oncogene. Glucocorticoids maintain Epstein-Barr virus latency, and removal of glucocorticoids from the cell culture medium results in activation of the productive cycle. This inverse regulation of the expression of latent and productive cycle genes contributes to the switch between virus latency and the productive cycle. Glucocorticoid control of BC-R2 might also provide a mechanism for EBNA promoter switching during early infection and in development of the restricted latent pattern of gene expression.
Disruption of cysteine-rich repeats of the p75 nerve growth factor receptor leads to loss of ligand binding (1991)

Nerve growth factor (NGF) binds to a low affinity cell surface receptor (p75NGFR) which contains four extracellular repeats, rich in cysteine residues and negatively charged. We have made mutations in the receptor cDNA by inserting linkers in specific domains of the receptor. Nearly all the mutations caused a change in the predicted charge, and resulted in either an insertion or deletion in the primary sequence. Stably transfected fibroblasts were assayed for NGF binding by affinity cross-linking with 125I-NGF. Appropriate expression of the mutated receptors was monitored by rosetting with monoclonal antibodies and by metabolic labeling followed by immunoprecipitation. Although the mutant receptors were recognized by monoclonal antibodies, insertions and deletions in the third and fourth cysteine-rich regions of the receptor had a detrimental effect upon NGF binding. Insertions made outside the cysteine-rich region or in the cytoplasmic domain did not inhibit the ability of 125I-NGF to bind to the receptor, as assessed by affinity cross-linking. A chimeric human-rat NGF receptor transfected into fibroblasts indicates that NGF binding and monoclonal antibody recognition sites are separated but contained within the four cysteine repeats.
The development of anti-inflammatory drugs for infectious diseases. (2010)

Traditionally, disease is thought to result from an insufficient response of the host to infection, leading to increased replication of microorganisms and consequently disease. However, infection may not necessarily lead to disease and disease is not only the result of uncontrolled replication of a microorganism. Indeed, the inflammatory response triggered by certain infections is frequently the cause of tissue damage and death. The present review argues that it is possible to separate mechanisms necessary for the host response to deal with infection from those which cause unwanted inflammation and drive disease. By understanding mechanisms which drive disease and where/how interaction leads to disease, we may be able to devise novel therapies to alleviate suffering of patients. Below, we will describe three situations--influenza, dengue and sepsis--in which unwanted (excessive, misplaced or altered) inflammation is responsible for disease induction. In these three situations, we will also describe some examples of molecules which have been found to drive disease but appear not to be essential for the ability of the host to control infection.
Conversion of [(tBuCH2)2TaN]5 to Cubic TaN:  Related Syntheses, EHMO Calculations, and MAS and Spin Echo 15N NMR Spectroscopies (1996)

The conversion of pentamer [(tBuCH2)2TaN]5 (2) and ammonia to cubic TaN0.8 (5) proceeds via precipitate 1/n[TaC1.41H3.90N1.90]n (3) and amorphous TaN (4). Precursors other than (tBuCH2)3TaCHtBu (1) and NH3, which provided 2, such as Ta(NMe2)5 (7) and NH3, (Me2N)3TaNtBu (9) and NH3, also afforded 5. Extended Hückel molecular orbital calculations were conducted to examine the electronic changes that appear upon oligomerization of hypothetical Me2TaN to (Me2TaN)∞, as a model for pentamer 2 formation. The relationship between pentamer 2 and the remaining nitrides, 3−5 was probed via magic angle spinning (MAS) and spin-echo solid-state 15N NMR experiments that probe the local environments of the various nitrogen atoms. In combination with 15N-labeling studies, the spin-echo spectra were used in an effort to analyze the possibility of a direct relationship between the 2-dimensional Ta2N2 “squares” of the pentamer (2) and the 3-dimensional Ta4N4 “cubes” of the ultimate product, cubic TaN0.8 (5).
Band gap discontinuity in Ga0.9In0.1N0.027As0.973−xSbx∕GaAs single quantum wells with ⩽x&lt;0.06 studied by contactless electroreflectance spectroscopy (2006)

Contactless electroreflectance (CER) spectroscopy has been applied to study optical transitions in Ga0.9In0.1N0.027As0.973−xSbx∕GaAs single quantum well (QW) with antimony content varying from 0% to 5.4%. CER features related to optical transitions between the ground and excited states have been clearly observed. Energies of the QW transitions have been matched with those obtained from theoretical calculations. It has been determined that the conduction band offset decreases from ∼55% to ∼45% with the increase in Sb content from 0% to 5.4%. This result demonstrates that the band gap discontinuity for Ga0.9In0.1N0.027As0.973−xSbx∕GaAs system can be simply tuned by a change in antimony content.
Characterization of Coliphage PR772 and Evaluation of Its Use for Virus Filter Performance Testing (2004)

Virus filtration is a key clearance unit operation in the manufacture of recombinant protein, monoclonal antibody, and plasma-derived biopharmaceuticals. Recently, a consensus has developed among filter manufacturers and end users about the desirability of a common nomenclature and a standardized test for classifying and identifying virus-retentive filters. The Parenteral Drug Association virus filter task force has chosen PR772 as the model bacteriophage to standardize nomenclature for large-pore-size virus-retentive filters (filters designed to retain viruses larger than 50 to 60 nm in size). Previously, the coliphage PR772 (Tectiviridae family) has been used in some filtration studies as a surrogate for mammalian viruses of around 50 to 60 nm. In this report, we describe specific properties of PR772 critical to the support of its use for the standardization of virus filters. The complete genomic sequence of virulent phage PR772 was determined. Its genome contains 14,946 bp with an overall G+C content of 48.3 mol%, and 32 open reading frames of at least 40 codons. Comparison of the PR772 nucleotide sequence with the genome of Tectiviridae family prototype phage PRD1 revealed 97.2% identity at the DNA level. By dynamic light-scattering analysis, its hydrodynamic diameter was measured as 82 +/- 6 nm, consistent with use in testing large-virus-retentive filters. Finally, dynamic light-scattering analysis of PR772 preparations purified on CsCl gradients showed that the phage preparations are largely monodispersed. In summary, PR772 appears to be an appropriate model bacteriophage for standardization of nomenclature for larger-pore-size virus-retentive filters.
Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated (1995)

Expression of the agouti gene from two different promoters, one active at the midpoint of the hair cycle and the other specific for the ventrum, is responsible for generating a range of mammalian pigmentation patterns. We demonstrate that in postnatal mice transcripts from both promoters are confined to the dermal papilla of hair follicles, as predicted by classical transplantation experiments. Transcripts from the hair cycle promoter are detected in the embryonic whisker plate but not in other regions of the body before birth, whereas ventral-specific transcripts are detected in the ventral trunk of the embryo as well as ventral whisker plate. To investigate further the embryonic origins of adult pigmentation patterns, we carried out a detailed analysis of agouti expression in the embryo. The ventral-specific agouti isoform is first expressed at E10.5 in neural crest-derived ventral cells of the second branchial arch, in anterior regions of the forelimb buds and in a narrow stripe of ventral mesenchyme. By E14.5 a continuous layer of expression is observed in the upper cells of the dermis, including cells of the developing dermal papillae, and covering the entire ventral surface of the head and trunk and dorsal surfaces of the distal forelimb and hindlimb. This expression pattern reflects the domain of yellow coloration evident in adult animals and suggests that the agouti gene is regulated in part by factors responsible for establishing differences between the dorsal and ventral surfaces of the body during embryogenesis. To test the hypothesis that agouti is a paracrine signaling molecule that can influence pigment production by hair follicle melanocytes when expressed by either dermis or epidermis, as suggested by recombination and transplantation experiments, we created transgenic animals in which agouti is expressed in basal cells of the epidermis. These animals display stripes of yellow hairs corresponding to regions of epidermal agouti expression, confirming that agouti signals melanocytes to synthesize yellow pigment and providing direct evidence that it functions in a paracrine manner with a restricted radius of action.
An Extended Genetic Linkage Map for Watermelon Based on a Testcross and a BC&lt;sub&gt;2&lt;/sub&gt;F&lt;sub&gt;2&lt;/sub&gt; Population (2011)

There is limited genetic mapping data useful for breeding programs of watermelon. Introgression lines should be a use-ful tool for genetic studies and genetic enhancement of watermelon cultivars. In this study, we used an advanced re-combinant population (BC2F2) to identify and map chromosomal segments of the wild watermelon Citrullus lanatus var. citroides that were incorporated in the genome of the watermelon cultivar Crimson Sweet (Citrullus lanatus var. lana-tus). An advanced recombinant population (BC2F2) was constructed using a United States Plant Introduction (PI) 494817 (C. lanatus var. citroides) (known to have moderate resistance to bacterial fruit blotch) as a donor parent, and the elite watermelon cultivar Crimson Sweet (C. lanatus var. lanatus) as the recurrent parent. The genetic linkage map consists of 272 markers, including 89 sequence-related amplified polymorphism (SRAP), 72 targeted region amplifica-tion polymorphism (TRAP), and 111 high frequency oligonucleotide-targeting active gene (HFO-TAG) markers. The 272 markers were assembled into 51 linkage groups, covering a total genetic distance of 2162 cM, with an average genetic distance of 7.9 cM between markers. Also, we expended the genetic linkage map for watermelon derived from a testcross population {Griffin 14113 [C. lanatus var. citroide (L.H. Bailey) Mansf.] x watermelon cultivar New Hamp-shire Midget (C. lanatus var. lanatus)} x PI 386015 [C. colocynthis (L.) Schrad.]. The genetic linkage map based on the test cross population consists of 558 markers that cover a genetic distance of 2760.8 cM. This linkage map consists of 41 linkage group, including 10 large linkage groups (ranging from102-240 cM), nine intermediate size linkage groups (ranging from 62-93 cM), and 22 small linkage groups (ranging from 2-56 cM). Comparative mapping between these two linkage maps identified high consensus in 25 HFO-TAG markers and one TRAP marker that represent 8 linkage groups in the BC2F2 population and 9 linkage groups in the testcross population. These results indicate that HFO-TAG markers should be useful in comparative mapping. The extended genetic maps and the genetic population in this study should be useful in breeding programs using marker assisted selection and should serve as a platform for further de-velopment of introgression lines for watermelon.
Holographic Storage in Quadratic PLZT Ceramics (1974)

Photoinduced changes in refractive index in a quadratic electrooptic PLZT ceramic were observed. Thick‐phase holograms were recorded with high diffraction efficiency (η∼ 0.10 to 0.50). The dependencies of the diffraction efficiency on the density of light energy and applied field were determined. The observed amplification effect is explained in terms of photoinduced electrical field components and the quadratic electrooptic properties of the ceramic.
A Buried Polar Interaction Can Direct the Relative Orientation of Helices in a Coiled Coil (1998)

Coiled coils consist of bundles of two or more alpha-helices that are aligned in a parallel or an antiparallel relative orientation. The designed peptides, Acid-p1 and Base-p1, associate in solution to form a parallel, heterodimeric two-stranded coiled coil [O'Shea, E. K., Lumb, K. J., and Kim, P. S. (1993) Curr. Biol. 3, 658]. The buried interface of this complex is formed by hydrophobic Leu residues, with the exception of an Asn residue from each strand that is positioned to engage in a buried polar interaction. Substitution of these buried Asn residues by Leu residues results in a loss of structural uniqueness, as evidenced by a lack of a particular helix orientation in the Acid-Base coiled-coil complex [Lumb, K. J., and Kim, P. S. (1995) Biochemistry 34, 8642]. Here, we alter the positions of the Asn residues in the Acid and Base peptides such that a buried polar interaction is only expected to occur when the helices are in an antiparallel orientation. The resulting peptides, Acid-a1 and Base-a1, associate to form a helical heterodimer, as shown by circular dichroism (CD) and equilibrium sedimentation centrifugation. The helix orientation preference has been measured using covalently linked, disulfide-containing heterodimers in which the constituent peptides are constrained to interact in either a parallel or an antiparallel orientation. Although both the parallel and antiparallel heterodimers form stable, helical structures, the antiparallel heterodimer is the predominant species at equilibrium when the heterodimers are allowed to undergo thiol-disulfide exchange. In addition, the antiparallel heterodimer is more stable to chemical denaturation than the parallel counterpart by approximately 2.3 kcal/mol. These results demonstrate that a single buried polar interaction in the interface between the helices of a coiled coil is sufficient to determine the relative orientation of its constituent helices.
Detection of Abundant Proteins in Multiple Myeloma Cells by Proteomics (2010)

Abundant proteins of human multiple myeloma (MM) were globally analyzed and identified by using two- dimensional gel electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry (MS). Spots of 517 corresponding to 268 different proteins were detected on 2DE gels of protein lysate from plasma cells isolated from eight newly diagnosed MM patients. These identified proteins were classified into different categories based on their molecular functions and biological processes. The detailed experimental procedures and MS spectra of all the identified proteins have been deposited in the Proteomics Identifications Database (PRIDE) (http://www.ebi.ac.uk/pride) with Accession No. 8846 & 8847. This 2DE map of MM proteins will be an invaluable resource for further proteomics research that investigates proteomic changes associated with biomarker identification and carcinogenesis analysis of multiple myeloma.
Palladium-Catalyzed Intermolecular Carbon−Oxygen Bond Formation:  A New Synthesis of Aryl Ethers (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPalladium-Catalyzed Intermolecular Carbon−Oxygen Bond Formation: A New Synthesis of Aryl EthersMichael Palucki, John P. Wolfe, and Stephen L. BuchwaldView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 1997, 119, 14, 3395–3396Publication Date (Web):April 9, 1997Publication History Received20 November 1996Published online9 April 1997Published inissue 1 April 1997https://pubs.acs.org/doi/10.1021/ja9640152https://doi.org/10.1021/ja9640152rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views7702Altmetric-Citations192LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Anions,Aromatic compounds,Ethers,Substitution reactions Get e-Alerts
Regulation of Phospholipase D Activity and Phosphatidic Acid Production after Purinergic (P2Y6) Receptor Stimulation (2013)

Phosphatidic acid (PA) is a lipid second messenger located at the intersection of several lipid metabolism and cell signaling events including membrane trafficking, survival, and proliferation. Generation of signaling PA has long been primarily attributed to the activation of phospholipase D (PLD). PLD catalyzes the hydrolysis of phosphatidylcholine into PA. A variety of both receptor-tyrosine kinase and G-protein-coupled receptor stimulations have been shown to lead to PLD activation and PA generation. This study focuses on profiling the PA pool upon P2Y6 receptor signaling manipulation to determine the major PA producing enzymes. Here we show that PLD, although highly active, is not responsible for the majority of stable PA being produced upon UDP stimulation of the P2Y6 receptor and that PA levels are tightly regulated. By following PA flux in the cell we show that PLD is involved in an initial increase in PA upon receptor stimulation; however, when PLD is blocked, the cell compensates by increasing PA production from other sources. We further delineate the P2Y6 signaling pathway showing that phospholipase Cβ3 (PLCβ3), PLCδ1, DGKζ and PLD are all downstream of receptor activation. We also show that DGKζ is a novel negative regulator of PLD activity in this system that occurs through an inhibitory mechanism with PKCα. These results further define the downstream events resulting in PA production in the P2Y6 receptor signaling pathway.
Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma (2013)

Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma.