gebhart/patrepeval huggingface dataset:
Stochastic Video Generation with a Learned Prior (2018)

Generating video frames that accurately predict future world states is challenging. Existing approaches either fail to capture the full distribution of outcomes, or yield blurry generations, or both. In this paper we introduce an unsupervised video generation model that learns a prior model of uncertainty in a given environment. Video frames are generated by drawing samples from this prior and combining them with a deterministic estimate of the future frame. The approach is simple and easily trained end-to-end on a variety of datasets. Sample generations are both varied and sharp, even many frames into the future, and compare favorably to those from existing approaches.
Cancer BiomarkersAn Invitation to the Table (2006)

The allure of the emerging genomic technologies in cancer is their ability to generate new biomarkers that predict how individual cancer patients will respond to various treatments. However, productive implementation of cancer biomarkers into patient care will require fundamental changes in how we consider approvals for cancer indications and how we track patient responses. Here we briefly describe ongoing efforts to identify and to validate cancer biomarkers, discuss the technological hurdles that lie ahead, and then focus on the more pressing political and cultural issues that, if left unheeded, could derail many of the anticipated benefits of biomarker research.
Emerging Research: A View from One Research Center (2001)

The Health Management Research Center at the University of Michigan has assembled a database on health risks, medical care costs, an in some cases, productivity measures for over 2,000,000 individuals. For employees of its corporate consortium members, the database contains seven to eighteen years of data. Working with this data, the research team has observed a number of emerging trends. These trends have been stable in this data set for a number of years, but some of them are yet to be subjected to rigorous external peer review. The trends are summarized below. 1) Annual participation rates of 20% to 30% in Health Risk Appraisal are typical; over 10 years, 80% participate at least once, 60% at least twice and 40% at least three times. 2) Among the employers in the data base, excess risk factors account for 21% to 31% of medical care costs, with a mean of 25%. 3) Medical care costs increase as the number risk factors and age increase. As risk factors increase, medical costs increase; as risk factors decrease, medical care costs decrease. The mean cost increase per risk factor increased ($350) may be more than double the mean cost decrease per risk factor decreased ($150). 4) Cost savings greatest among those who participate in programs multiple times. 5) Absenteeism seems to be higher and other measures of productivity lower for those with health risk factors. 6) Programs designed to keep healthy people healthy in addition to reducing the risks of those with multiple risks will probably provide the greatest return to the employers. 7) Best results may be achieved by focusing efforts on employees who have clusters of risk factors associated with low perceived health status. 8) A corporate wellness score which combines risk factor levels and participation rates may provide a "corporate wellness score" which can be used to compare health status across employer. 9) Increased use of longitudinal data sets, fuzzy cut points for data categories and data mining techniques may allow breakthroughs in future analysis efforts.
Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation (2003)

MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the ORF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms.
Selection of peptides binding to the alpha 5 beta 1 integrin from phage display library. (1993)

The alpha 5 beta 1 integrin binds fibronectin through the integrin recognition sequence Arg-Gly-Asp (RGD). We have used a 6-amino acid peptide library expressed on filamentous phage to identify peptide ligands for alpha 5 beta 1. We found that this integrin selectively binds RGD-containing peptides from the library. Of the 32 different sequences obtained, 28 had the RGD motif, 3 contained sequences related to RGD, and only 1 had a clearly different sequence. One of the RGD-containing phage encoded a potentially cyclic insert CRGDCL. The cyclic peptide GAC*RGDC*LGA (where * denotes cysteines forming a disulfide bond) was 10-fold more efficient than any of the linear RGD-containing hexapeptides in inhibiting the binding of RGD-expressing phage to alpha 5 beta 1 or the attachment of alpha 5 beta 1-expressing cells to fibronectin. This peptide also inhibited cell attachment mediated by the alpha v beta 1, alpha v beta 3, and alpha v beta 5 integrins with about 10-fold higher efficiency than linear GRGDSP. One peptide containing an RGD-related sequence, NGRAHA, was also found to inhibit phage attachment and cell adhesion, especially adhesion mediated by the alpha v beta 5 integrin. These results indicate that novel and high affinity ligands for integrins can be isolated from a random peptide library.
Control of Rhizoctonia solani on Cotton Seedlings with Pseudomonas fluorescens and With an Antibiotic Produced by the Bacterium (2008)

A strain of <i>Pseudomonas fluorescens</i> antagonistic to <i>Rhizoctonia solani</i> was isolated from the rhizosphere of cotton seedlings. An antibiotic strongly inhibitory to <i>R. solani</i> was isolated from <i>P. fluorescens</i> cultures and identified as pyrrolnitrin (3-chloro-4-[2'-nitro-3'-chlorophenyl]-pyrrole). The antibiotic also inhibited growth of other fungi associated with the cotton seedling disease complex including: <i>Thielaviopsis basicola, Alternaria</i> sp., and <i>Verticillium dahliae.</i> A <i>Fusarium</i> sp. was only partially inhibited and <i>Pythium ultimum</i> was unaffected. Treating cottonseed with <i>P. fluorescens</i> or pyrrolnitrin at time of planting in <i>R. solani</i>-infested soil increased seedling survival from 30 to 79% and from 13 to 70%, respectively. Pyrrolnitrin persisted for up to 30 days in moist nonsterile soil with no measurable loss in activity.
Interactions between the mannose receptor and thyroid autoantigens (2004)

Thyroid autoantigens require internalization and processing by antigen-presenting cells to induce immune responses. Besides pinocytosis, antigen uptake can be receptor-mediated. The mannose receptor (ManR) has a cysteine rich domain (CR) and eight carbohydrate recognition domains (CRD) that bind glycosylated proteins. The TSH receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) are glycoproteins. To investigate a role for the ManR in thyroid autoimmunity, we tested the interaction between these autoantigens and chimeric ManRs. Plasmids encoding the CR-domain linked to IgG-Fc (CR-Fc) and CDR domains 4-7 linked to IgG-Fc (CDR4-7-Fc) were expressed and purified with Protein A. Enzyme-linked immunosorbent assay (ELISA) plates were coated with human thyroid autoantigens and CR-Fc or CRD4-7-Fc binding detected with peroxidase-conjugated anti-IgG-Fc. CRD4-7-Fc binding was highest for the TSHR, followed by Tg and was minimal for TPO. CR-Fc bound to Tg but not to TSHR or TPO. The interaction between the TSHR and CRD-Fc was calcium-dependent; it was inhibited by mannose (not galactose), and required a glycosylated TSHR A-subunit. Moreover, precomplexing the TSHR A-subunit with CRD-Fc (but not CR-Fc), or adding mannose (but not galactose), decreased in vitro responses of splenocytes from TSHR-immunized mice. Our data indicate that the ManR may participate in autoimmune responses to Tg and the TSHR but not to TPO. Most important, ManR binding of heavily glycosylated TSHR A-subunits suggests a mechanism by which the minute amounts of A-subunit protein shed from the thyroid may be captured by antigen-presenting cells located in the gland or in draining lymph nodes.
Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer (2017)

Purpose Trop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an antibody-drug conjugate, targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan. Patients and Methods We evaluated sacituzumab govitecan in a single-arm, multicenter trial in patients with relapsed/refractory metastatic TNBC who received a 10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles. The primary end points were safety and objective response rate; secondary end points were progression-free survival and overall survival. Results In 69 patients who received a median of five prior therapies (range, one to 12) since diagnosis, the confirmed objective response rate was 30% (partial response, n = 19; complete response, n = 2), the median response duration was 8.9 (95% CI, 6.1 to 11.3) months, and the clinical benefit rate (complete response + partial response + stable disease ≥ 6 months) was 46%. These responses occurred early, with a median onset of 1.9 months. Median progression-free survival was 6.0 (95% CI, 5.0 to 7.3) months, and median overall survival was 16.6 (95% CI, 11.1 to 20.6) months. Grade ≥ 3 adverse events included neutropenia (39%), leukopenia (16%), anemia (14%), and diarrhea (13%); the incidence of febrile neutropenia was 7%. The majority of archival tumor specimens (88%) were moderately to strongly positive for Trop-2 by immunohistochemistry. No neutralizing antibodies to the ADC or antibody were detected, despite repeated cycles developed. Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC. As a therapeutic target and predictive biomarker, Trop-2 warrants further research.
A Comparison of the Bronchodilating Effects of a Beta-2 Adrenergic Agent (Albuterol) and an Anticholinergic Agent (Ipratropium Bromide), Given by Aerosol Alone or in Sequence (1986)

We evaluated the effect of anticholinergic and beta-adrenergic inhaled bronchodilators, alone or in sequence, in 11 patients with chronic obstructive pulmonary disease. We compared the agents albuterol and ipratropium bromide when each was used as a single aerosol in the maximal dose. After giving a maximal dose of one agent, we compared the effect of adding the other with that of adding a placebo. When used alone, both bronchodilators significantly increased airflow and relieved hyperinflation, and there was no significant difference between the two. After the improvement with the initial bronchodilator, the subsequent effect of a second inhaled bronchodilator was not greater than that of placebo. These results suggest that in the treatment of chronic obstructive pulmonary disease, these two aerosols are usually equipotent in maximal doses and the addition of a second agent is of no practical value. The data support the prescription of a single inhaled agent in most cases but do not rule out the value of combinations of agents under special circumstances.
Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. (1995)

We have studied the cytotoxic activity of rat basophilic leukemia (RBL) cells transfected with cDNAs for the cytotoxic T lymphocyte (CTL) granule components, cytolysin (perforin), granzyme A, and granzyme B. With red cell targets, cytolysin expression conferred potent hemolytic activity, which was not influenced by coexpression of granzymes. With tumor targets, RBL cells expressing cytolysin alone were weakly cytotoxic, but both cytolytic and nucleolytic activity were enhanced by coexpression of granzyme B. RBL cells expressing all three CTL granule components showed still higher cytotoxic activities, with apoptotic target death. Analysis of the cytotoxic activity of individual transfectant clones showed that cytolytic and nucleolytic activity correlated with granzyme expression but was independent of cytolysin expression within the range examined. A synergism between granzymes A and B was apparent when the triple transfectant was compared with RBL cells expressing cytolysin and one granzyme. These data implicate granzymes as the major mediators of tumor target damage by cytotoxic lymphocytes.
Bit allocation for joint transcoding of multiple MPEG coded video streams (2001)

For the transcoding of pre-encoded video streams, certain useful picture statistics can be extracted from the input bit-streams to help bit-allocation. In this paper, a novel approach to estimate the picture-complexity of the transcoded output video streams from the input streams is proposed. Based on the picturecomplexity estimation, a bit-allocation strategy is presented for joint transcoding of multiple pre-encoded MPEG video streams. Simulation results show that our proposed algorithm can achieve better video quality compared to previously reported algorithms.
Monoclonal and Polyclonal Antibodies to Human Progesterone Receptor Peptide-(533-547) Recognize a Specific Site In Unactivated (8S) and Activated (4S) Progesterone Receptor and Distinguish between Intact and Proteolyzed Receptors* (1990)

We have synthesized three peptides with amino acid sequences corresponding to amino acids 533-547, 597-611, and 765-779 of the human progesterone receptor (hPR). These peptides were conjugated to keyhole limpet hemocyanin and injected into mice and rabbits to develop antibodies to hPR. Antibodies to the undenatured form of PR were elicited only by the peptide with amino acid sequence 533-547. Fusion of SP2/0 myeloma cells with spleen cells from mice immunized with this peptide produced several active clones. Rabbit sera from immunized animals produced one antiserum that reacted with the undenatured form of PR. One monoclonal antibody (PR-AT 4.14) and one antiserum (PR-AT533) raised against peptide-(533-547) were characterized. Binding of these antibodies to the undenatured form of PR was demonstrated by analysis of the antibody-receptor complexes on sucrose density gradients and by immunoprecipitation techniques. Binding of PR to the antibodies was inhibited by excess peptide. The antibodies did not react with estrogen, glucocorticoid, or androgen receptors, but recognized PR from human breast cancer as well as calf, rabbit, mouse, and rat uteri, indicating that this epitope was conserved among these species. Based on sucrose density gradient analysis of PR prepared and labeled in the presence of proteolysis inhibitors and sodium molybdate, the antibodies bound to a site on the intact undenatured PR, but failed to bind to partially degraded steroid-binding form of the receptor, suggesting that the antibody-binding domain is at or near a site sensitive to proteolysis.
On the search of the ideal barrier membrane for guided bone regeneration (2018)

It has been clearly described that biocompatibility is the most important requirement to take into account when choosing a membrane, but other factors such as space maintaining capacity, cell oclusiveness, easy handling and bioactivation friendly materials are the ones that will fulfill our necessities. <b>Key words:</b>Barrier membrane, guided bone regeneration, dental implantology, oral surgery, collagen membrane, biomaterial.
Dissecting the Role of Acyltransferase Domains of Modular Polyketide Synthases in the Choice and Stereochemical Fate of Extender Units (1999)

Modular polyketide synthases (PKSs), such as the 6-deoxyerythronolide B synthase (DEBS), are large multifunctional enzyme complexes that are organized into modules, where each module carries the domains needed to catalyze the condensation of an extender unit onto a growing polyketide chain. Each module also dictates the stereochemistry of the chiral centers introduced into the backbone during the chain elongation process. Here we used domain mutagenesis to investigate the role of the acyl transferase (AT) domains of individual modules in the choice and stereochemical fate of extender units. Our results indicate that the AT domains of DEBS do not influence epimerization of the (2S)-methylmalonyl-CoA extender units. Hence, stereochemical control of the methyl-branched centers generated by DEBS most likely resides in the ketosynthase (KS) domains of the individual modules. In contrast, several recent studies have demonstrated that extender unit specificity can be altered by AT domain substitution. In some of these examples, the resulting polyketide was produced at considerably lower titers than the corresponding natural product. We analyzed one such attenuated mutant of DEBS, in which the methylmalonyl transferase domain of module 2 was replaced with a malonyl transferase domain. As reported earlier, the resulting PKS produced only small quantities of the expected desmethyl analogue of 6-deoxyerythronolide B. However, when the same hybrid module was placed as the terminal module in a truncated 2-module PKS, it produced nearly normal quantities of the expected desmethyl triketide lactone. These results illustrate the limits to modularity of these multifunctional enzymes. To dissect the role of specific amino acids in controlling AT substrate specificity, we exchanged several segments of amino acids between selected malonyl and methylmalonyl transferases, and found that a short (23-35 amino acid) C-terminal segment present in all AT domains is the principal determinant of their substrate specificity. Interestingly, its length and amino acid sequence vary considerably among the known AT domains. We therefore suggest that the choice of extender units by the PKS modules is influenced by a "hypervariable region", which could be manipulated via combinatorial mutagenesis to generate novel AT domains possessing relaxed or altered substrate specificity.
Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver (2008)

Although hepcidin expression was shown to be induced by the BMP/Smad signaling pathway, it is not yet known how iron regulates this pathway and what its exact molecular targets are. We therefore assessed genome-wide liver transcription profiles of mice of 2 genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts significantly modulated by the dietary iron content, 4 were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 all related to the Bmp/Smad pathway. As shown by Western blot analysis, variations in Bmp6 expression induced by the diet iron content have for functional consequence similar changes in Smad1/5/8 phosphorylation that leads to formation of heteromeric complexes with Smad4 and their translocation to the nucleus. Gene expression variations induced by secondary iron deficiency or iron overload were compared with those consecutive to Smad4 and Hamp1 deficiency. Iron overload developed by Smad4- and Hamp1-deficient mice also increased Bmp6 transcription. However, as shown by analysis of mice with liver-specific disruption of Smad4, activation of Smad7, Id1, and Atoh8 transcription by iron requires Smad4. This study points out molecules that appear to play a critical role in the control of systemic iron balance.
Poly-gate replacement through contact hole (PRETCH): a new method for high-K/metal gate and multi-oxide implementation on chip (2005)

We report on a new concept for an easy co-integration, on a same chip, of different MOSFET configurations (GP, LP, HS, buffer transistors) realized after the end of the standard FE process. This poly-gate replacement through contact hole (PRETCH) concept enables replacement of initial poly-silicon gate and/or gate oxide by any gate stack desired. PRETCH addresses multi-Vt control, multi-oxide realization and metal gate integration challenges. As PRETCH gate replacement takes place after PMD (beginning of BE), it is perfectly suitable for high-K integration, allowing low thermal budget (no source and drain anneal seen by HK) and no particular contamination issues. Large potential of PRETCH integration is confirmed by promising morphological results and by very good electrical characteristics of both nMOS and pMOS TiN 90nm gate length MOSFETs. Integration of TiN gate with three different oxide configurations is demonstrated: initial thermal oxide left, replaced by either slot plane antenna [SPA] oxide or high-K. PRETCH concept has also been validated on 3D architectures such as DG. Finally, functional TiN DG inverters and SRAMs are demonstrated.
A graphic interactive application monitor (1980)

With the graphic workstation and computer hardwaraev ailable at an attractive price today, graphic system development no longer has to concentrate onl ow-level optimization of application code. The main emphasis can now be put on ease of use, ease of programming, and ease of application system management and maintenance. The Graphic InteractiveA pplication Monitor, GIAM, has been developed to provide an intelligent graphic base system that can easily be used and customized by application programmers as well as by end users. It has been shown thabty proper structuring of a system andw ith the use of a high-level, pragmatic, and user-extendable language, a powerful and highly flexible graphic base system, which achieves excellent user productivity with a minimum of application program development, can be implemented.
Serial renal biopsy in systemic lupus erythematosus. (2000)

The major reason for repeat renal biopsy in patients with SLE was proteinuria. Renal morphology in patients with SLE can change with time, particularly in terms of chronicity and activity features. Repeat biopsies in patients with SLE appear to have clinical utility.
Cut and paste (1997)

The paper develops EDITOR, a language for manipulating semi-structured documents, such as the ones typically available on the Web. EDITOR programs allow to search and restructure a document. They are based on two simple ideas, taken from text editors: Search” instructions are used to select regions of interest in a document, and “cut &amp; paste” to restructure them. We study the expressive power and the complexity of these programs. We show that they are computationally complete, in the sense that any computable document restructuring can be expressed in EDITOR. We also study the complexity of a safe subclass of programs, showing that it captures exactly the class of polynomial-time restructurings. The language has been implemented in Java, and is used in the ARANEUS project to build database views over Web sites.