gebhart/patrepeval huggingface dataset:
All Models are Wrong, but Many are Useful: Learning a Variable's Importance by Studying an Entire Class of Prediction Models Simultaneously. (2019)

Variable importance (VI) tools describe how much covariates contribute to a prediction model's accuracy. However, important variables for one well-performing model (for example, a linear model <i>f</i> (x) = x <sup><i>T</i></sup> <i>β</i> with a fixed coefficient vector <i>β</i>) may be unimportant for another model. In this paper, we propose model class reliance (MCR) as the range of VI values across <i>all</i> well-performing model in a prespecified class. Thus, MCR gives a more comprehensive description of importance by accounting for the fact that many prediction models, possibly of different parametric forms, may fit the data well. In the process of deriving MCR, we show several informative results for permutation-based VI estimates, based on the VI measures used in Random Forests. Specifically, we derive connections between permutation importance estimates for a <i>single</i> prediction model, U-statistics, conditional variable importance, conditional causal effects, and linear model coefficients. We then give probabilistic bounds for MCR, using a novel, generalizable technique. We apply MCR to a public data set of Broward County criminal records to study the reliance of recidivism prediction models on sex and race. In this application, MCR can be used to help inform VI for unknown, proprietary models.
A Randomized, Placebo-controlled Study of Fentanyl Buccal Tablet for Breakthrough Pain in Opioid-treated Patients With Cancer (2006)

FBT is efficacious and safe in the treatment of cancer-related BTP.
The Future Promises of Xenotransplantation a,b (1998)

The use of animals as a source of organs and tissues for humans has been an enduring goal of transplantation. Xenotransplantation, as such, would overcome a shortage of human donors and allow for biochemical or genetic approaches to modification of transplants. The use of animal organs and tissue, however, is hindered by an intense immune response of the recipient against the graft. The molecular basis for this immune response has recently been elucidated, at least in part, and specific approaches to therapy, including the genetic engineering of source animals, have been developed. Other hurdles, including the physiologic limitations of the transplant and the possibility of transferring infectious agents from the transplant into the host, may also be important. The development of specific therapies and the application of genetic engineering to overcome these problems can now be envisioned. As the immunologic, physiologic, and infectious hurdles to xenotransplantation are addressed, new efforts will focus on the use of the transplant to impart novel functions to answer the therapeutic needs of the transplant recipient.
Searching for three-dimensional secondary structural patterns in proteins with ProSMoS (2007)

We developed ProSMoS--a Protein Structure Motif Search program that emulates an expert. Starting from a spatial structure, the program uses previously delineated secondary structural elements. A meta-matrix of interactions between the elements (parallel or antiparallel) minding handedness of connections (left or right) and other features (e.g. element lengths and hydrogen bonds) is constructed prior to or during the searches. All structures are reduced to such meta-matrices that contain just enough information to define a protein fold, but this definition remains very general and deviations in 3D coordinates are tolerated. User supplies a meta-matrix for a structural motif of interest, and ProSMoS finds all proteins in the protein data bank (PDB) that match the meta-matrix. ProSMoS performance is compared to other programs and is illustrated on a beta-Grasp motif. A brief analysis of all beta-Grasp-containing proteins is presented. Program availability: ProSMoS is freely available for non-commercial use from ftp://iole.swmed.edu/pub/ProSMoS.
Adenoviral Gene Therapy (2002)

As of May 2001, 532 gene therapy protocols had been approved for evaluation in clinical trials; however, only five of those had been evaluated in phase III clinical trials. Among the most commonly used vectors for the delivery of genetic material into human cells are the adenoviruses. Remarkable progress has been made with these vectors in the last decade, but some shortcomings continue to challenge investigators. The newly acquired knowledge of the adenoviral life cycle and the positive outcomes from phase II clinical trials have led to the application of vectors engineered to selectively target tumor tissue under controlled promoters.
Mammalian cell cultures. Part II: Genetic engineering, protein glycosylation, fermentation and process control. (1993)

For expression of human genes in mammalian cell culture regulatory sequences such as promotor or terminator region of viral origin are required. The most widely used expression system uses dihydrofolic acid reductase (DHFR) as a selection marker in conjunction with a DHFR deficient Chinese hamster ovary (CHO) cell using methotrexate as selection pressure. Alternatively the glutamine synthetase amplification system seems to be one of the most efficient expression systems using methionine sulphoximine (MSX) as selection pressure. Folding and glycosylation takes place in mammalian cell cultures at the sites of endoplasmatic reticulum and the Golgi apparatus and is comparable to synthesis in human cells. Most large scale manufacturing processes for products derived from mammalian cell cultures are fed batch suspension culture processes up to 15,000 l. Important factors for productivity are media composition and feeding strategies. Sterility of the entire system during the fermentation period is a decisive factor for success rate. Because mammalian cell cultures reacting very sensitive to small changes in temperature, pH, osmolality and agitation the fermentation system requires a reliable process control system. Validation of the entire manufacturing process is required to ensure consistent product quality which meets predetermined specifications and to provide a basis for an economic process. In a joint effort equipment qualification, process validation, in-process controls and quality controls provide the basis for product consistency from batch to batch.
Enantiospecific synthesis of D-myo-inositol 1,4,5-trisphosphate from (-)-quinic acid (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantiospecific synthesis of D-myo-inositol 1,4,5-trisphosphate from (-)-quinic acidJ. R. Falck and Pendri YadagiriCite this: J. Org. Chem. 1989, 54, 25, 5851–5852Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/jo00286a011https://doi.org/10.1021/jo00286a011research-articleACS PublicationsRequest reuse permissionsArticle Views252Altmetric-Citations34LEARN 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 Get e-Alerts
Select Bibliography (2012)

A summary is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Unidirectional Reconstitution into Detergent-destabilized Liposomes of the Purified Lactose Transport System of (1996)

The lactose transport protein (LacS) of Streptococcus thermophilus was amplified to levels as high as 8 and 30% of total membrane protein in Escherichia coli and S. thermophilus, respectively. In both organisms the protein was functional and the expression levels were highest with the streptococcal lacS promoter. Also a LacS deletion mutant, lacking the carboxyl-terminal regulatory domain, could be amplified to levels >20% of membrane protein. Membranes from S. thermophilus proved to be superior in terms of efficient solubilization and ease and extent of purification of LacS; >95% of LacS was solubilized with relatively low concentrations of Triton X-100, n-octyl-beta-D-glucoside, n-dodecyl-beta-D-maltoside, or C12E8. The LacS protein carrying a poly-histidine tag was purified in large quantities (approximately 5 mg/liter of culture) and with a purity >98% in a two-step process involving nickel chelate affinity and anion exchange chromatography. The membrane reconstitution of LacS was studied systematically by stepwise solubilization of preformed liposomes, prepared from E. coli phospholipid and phosphatidylcholine, and protein incorporation at the different stages of liposome solubilization. The detergents were removed by adsorption onto polystyrene beads and H+-lactose symport and lactose counterflow were measured. Highest transport activities were obtained when Triton X-100 was used throughout the solubilization/purification procedure, whereas activity was lost irreversibly with n-octyl-beta-D-glucoside. For reconstitutions mediated by n-dodecyl-beta-D-maltoside, C12E8, and to a lesser extent Triton X-100, the highest transport activities were obtained when the liposomes were titrated with low amounts of detergent (onset of liposome solubilization). Importantly, under these conditions proteoliposomes were obtained in which LacS was reconstituted in an inside-out orientation, as suggested by the outside labeling of a single cysteine mutant with a membrane impermeable biotin-maleimide. The results are consistent with a mechanism of reconstitution in which the hydrophilic regions of LacS prevent a random insertion of the protein into the membrane. Consistent with the in vivo lactose/galactose exchange catalyzed by the LacS protein, the maximal rate of lactose counterflow was almost 2 orders of magnitude higher than that of H+-lactose symport.
Unique Tumor Antigens: Evidence for Immune Control of Genome Integrity and Immunogenic Targets for T Cell–Mediated Patient-Specific Immunotherapy (2006)

Abstract The molecular identification and characterization of antigenic epitopes recognized by T cells on human cancers has rapidly evolved since the cloning in 1991 of MAGEA1, the first gene reported to encode a CTL-defined human tumor antigen. In the expanding field of human tumor immunology, unique tumor antigens constitute a growing class of T cell–defined epitopes that exhibit strong immunogenicity. Some of these antigens, which often derive from mutation of genes that have relevant biological functions, are less susceptible to immunoselection and may be retained even in advanced tumors. Immunogenicity and constitutive expression of the unique tumor antigens provide a strong rationale for the design of novel, patient-tailored therapies that target such determinants. Here we discuss the immunologic relevance of unique tumor antigens in the light of the prospects for exploiting such epitopes as targets for patient-specific immune intervention strategies.
Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1 (2012)

An unresolved issue about many neurodegenerative diseases is why neurons are particularly sensitive to defects in ubiquitous cellular processes. One example is Niemann Pick type C1, caused by defects in cholesterol trafficking in all cells, but where neurons are preferentially damaged. Understanding this selective failure is limited by the difficulty in obtaining live human neurons from affected patients. To solve this problem, we generated neurons with decreased function of NPC1 from human embryonic stem cells and used them to test the hypothesis that defective cholesterol handling leads to enhanced pathological phenotypes in neurons. We found that human NPC1 neurons have strong spontaneous activation of autophagy, and, contrary to previous reports in patient fibroblasts, a block of autophagic progression leading to defective mitochondrial clearance. Mitochondrial fragmentation is an exceptionally severe phenotype in NPC1 neurons compared with fibroblasts, causing abnormal accumulation of mitochondrial proteins. Contrary to expectation, these abnormal phenotypes were rescued by treatment with the autophagy inhibitor 3-methyladenine and by treatment with the potential therapeutic cyclodextrin, which mobilizes cholesterol from the lysosomal compartment. Our findings suggest that neurons are especially sensitive to lysosomal cholesterol accumulation because of autophagy disruption and accumulation of fragmented mitochondria, thus defining a new route to effective drug development for NPC1 disease.
Phosphorylation of Sendai Virus Phosphoprotein by Cellular Protein Kinase C ζ (1997)

The phosphoproteins (P) of nonsegmented negative strand RNA viruses are viral RNA polymerase subunits involved in both transcription and replication during the virus life cycle. Phosphorylation of P proteins in several negative strand RNA viruses by specific cellular kinases was found to be required for P protein function. In the present study, using bacterially expressed unphosphorylated P protein of Sendai virus, a mouse parainfluenza virus, we have shown that the major cellular kinase that phosphorylates P protein in vitro is biochemically and immunologically indistinguishable from protein kinase C (PKC) zeta isoform. PKC zeta was packaged into the Sendai virion and remained associated with purified viral ribonucleoprotein, where it phosphorylated both the P and the nucleocapsid protein in vitro. When PKC zeta-specific inhibitory pseudosubstrate peptide was introduced into LLC-MK2 cells prior to Sendai virus infection, production of progeny virus was dramatically attenuated, and kinetic analysis revealed that primary transcription was repressed. These data indicate that phosphorylation of the Sendai virus P protein by PKC zeta plays a critical role in the virus life cycle.
How Coil-Cortex Distance Relates to Age, Motor Threshold, and Antidepressant Response to Repetitive Transcranial Magnetic Stimulation (2000)

Repetitive transcranial magnetic stimulation (rTMS) is a tool with antidepressant potential that uses a coil placed on the scalp to produce a powerful magnetic field that directly stimulates only the outermost cortex. MRI scans were obtained in 29 depressed adults involved in an rTMS antidepressant clinical treatment. These scans were analyzed to investigate the effect of distance from coil to cortex on clinical parameters. Longer motor cortex distance, but not prefrontal distance, strongly correlated with increased motor threshold (P<0.01). Clinical antidepressant response did not correlate with either distance. The rTMS antidepressant responders, however, were significantly younger (t=–2.430, P<0.05), and there appears to be a maximum threshold of age and distance to prefrontal cortex for response.
Improved radioimmunoimaging of human tumor xenografts by a mixture of monoclonal antibody F(ab')2 fragments. (1986)

F(ab')2 fragments of monoclonal antibodies (MAbs) GA 73-3 and CO 29.11, with specific binding reactivity in vitro to human tumors of the gastrointestinal tract, were radioiodinated and injected into nude mice bearing human colon carcinoma xenografts. Fragments of both MAbs preferentially localized in tumor tissue compared with normal mouse tissue, as determined by differential tissue counting of radioactivity. The fragments localized specifically only in those tumors to which they bind in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus MAb did not localize in the tumors. Whole-body scintigraphy demonstrated tumor localization with 131I-labeled fragments without background subtraction. Best tumor contrast, as quantitated by analyzing digital computer scans, was obtained between Days 2 and 5 after injection. Tumor contrast was significantly enhanced when a mixture of both MAb F(ab')2 fragments was used. The biologic half-life of the MAb mixture in the tumor was significantly greater than that of either MAb alone, suggesting the use of the MAb mixture in radioimmunotherapy.
Molecular Cloning and Nucleotide Sequence of cDNA Coding for Rat Brain Cholecystokinin Precursor (1984)

A mixture of 14-mer oligodeoxynucleotides was used for the screening of a cDNA clone coding for a cholecystokinin (CCK) precursor from a cDNA library for rat brain microsomal poly(A)RNA. The longest insert is 718 bp long which was verified to contain a nearly full-length cDNA sequence coding for rat CCK precursor, because the size of CCK mRNA was estimated to be about 850 bases long by Northern blotting analysis. Sequence analysis revealed 110 bp in the 5'-untranslated region, 345 bp in the amino acid coding region corresponding to the CCK precursor and 263 bp in the 3'-noncoding region which contains polyadenylation signal AUUAAA and the poly(A) sequence. The precursor may contain a 28 amino acid signal peptide and 12 additional amino acids at the carboxyl terminus.
Variation in cuff blood pressure in untreated urban outpatients with mild hypertension in Harare, Zimbabwe--implications for the diagnosis of hypertension. (1991)

Duplicate measurements of BP were recorded at six visits in 32 male urban factory workers found to have raised BP (systolic blood pressure (SBP) greater than or equal to 160 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg) at the initial visit). A systematic decrease in both SBP and DBP occurred over the first three visits. The BP at visits 4-6 was not significantly different. Most of the decrease in BP occurred between the first and second visit (mean SBP decreased 8.5 mmHg and mean DBP decreased 11.1 mmHg). After 6 visits 66% of subjects could be classified into clear clinical groups (normotensive 53.5%, hypertensive 12.5%) but in 34% the variation in cuff BP precluded classification. In these subjects prolonged observation or home BP monitoring may be required before initiating lifelong treatment.
ChemInform Abstract: Targeting RNA with Conformationally Restricted Oligonucleotides (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Augmentation of the CD8+ T cell response by IFN-gamma in IL-12-deficient mice during Toxoplasma gondii infection. (1999)

The importance of IFN-gamma in regulating the host CD8+ T cell response during microbial infection has not been delineated. Mice deficient for the p40 chain of the IL-12 heterodimer have impaired IFN-gamma production and are susceptible to infection with the intracellular parasite Toxoplasma gondii. The administration of exogenous IFN-gamma to parasite-infected p40-/- mice increases survival and up-regulates the depressed CD8+ T cell response following infection. CD8+ T cells isolated from cytokine-treated p40-/- mice exhibit an increase in both precursor CTL frequency and IFN-gamma production compared with untreated controls. The enhancement of the CD8+ T cell response is independent of CD4+ T cell help. These CD8+ T cells induce protective immunity against a lethal challenge when adoptively transferred into naive p40-/- and IFN-gamma-/- mice. These observations indicate that IFN-gamma can regulate the CD8+ T cell response during T. gondii infection.
TCP onloading for data center servers (2004)

To meet the increasing networking needs of server workloads, servers are starting to offload packet processing to peripheral devices to achieve TCP/IP acceleration. Researchers at Intel Labs have experimented with alternative solutions that improve the server's ability to process TCP/IP packets efficiently and at very high rates.
The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. (1995)

The leukemogenic tyrosine kinase fusion protein Bcr-Abl activates a Ras-dependent pathway required for transformation. To examine subsequent signal transduction events we measured the effect of Bcr-Abl on two mitogen-activated protein kinase (MAPK) cascades--the extracellular signal-regulated kinase (ERK) pathway and the Jun N-terminal kinase (JNK) pathway. We find that Bcr-Abl primarily activates JNK in fibroblasts and hematopoietic cells. Bcr-Abl enhances JNK function as measured by transcription from Jun responsive promoters and requires Ras, MEK kinase (MAPK/ERK kinase kinase), and JNK to do so. Dominant-negative mutants of c-Jun, which inhibit the endpoint of the JNK pathway, impair Bcr-Abl transforming activity. These findings implicate the JNK pathway in transformation by a human leukemia oncogene.
Ventilation-perfusion studies in suspected pulmonary embolism (1979)

The results of ventilation-perfusion (V-Q) imaging and pulmonary angiography were retrospectively analyzed in 146 patients with suspected pulmonary embolism (PE) to define the frequency of PE associated with various scintigraphic patterns. When the radionuclide images demonstrated at least two moderate-sized or one large area of V-Q mismatch, the probability of PE was 92%. However, only one of three patients with a single moderate-sized V-Q mismatch had PE, while small V-Q mismatches were not associated with PE in any of 19 patients. Matched V-Q abnormalities in lung regions that were radiographically normal were infrequently due to PE (4.8%). When a perfusion defect was substantially smaller than a corresponding radiographic abnormality, the frequency of PE was low (7.7%). Conversely, when a perfusion defect was substantially larger than the corresponding radiographic abnormality, there was a high probability of PE (87%). Matched perfusion and radiographic abnormalities indicated an intermediate probability of PE (27%). Patients with suspected pulmonary embolism may be classified into groups with low, intermediate, or high probability of pulmonary embolism on the basis of size and number of perfusion defects and a careful comparison of perfusion defects with ventilatory and radiographic findings.
Targeted Degradation of Proteins by PROTACs (2010)

In recent years, small interference RNAs (siRNAs) have greatly enhanced our understanding of protein functions by allowing knockdown of targeted proteins at the mRNA level. Similarly, in an effort to achieve degradation of targeted proteins at the post-translational level, chimeric small molecules called "PROTACs" (PROteolysis TArgeting Chimeric molecules) have been developed. The PROTAC approach utilizes chimeric small molecules which recruit targeted proteins to the ubiquitin-proteasome pathway, a major intracellular protein degradation system. Unlike conventional small molecules that bind to protein and inhibit its function, the PROTAC approach induces destruction of target protein via the ubiquitin-proteasome system. This article presents a typical strategy for PROTAC design and preparation and biological characterization. Curr. Protoc. Chem Biol. 2:71-87. © 2010 by John Wiley & Sons, Inc.