gebhart/patrepeval huggingface dataset:
The Integrator complex terminates promoter-proximal transcription at protein-coding genes (2019)

SUMMARY The transition of RNA polymerase II (Pol II) from initiation to productive elongation is a central, regulated step in metazoan gene expression. At many genes, Pol II pauses stably in early elongation, remaining engaged with the 25-60 nucleotide-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, a number of genes display highly unstable promoter Pol II, suggesting that paused polymerase might dissociate from template DNA at these promoters and release a short, non-productive mRNA. Here, we report that paused Pol II can be actively destabilized by the Integrator complex. Specifically, Integrator utilizes its RNA endonuclease activity to cleave nascent RNA and drive termination of paused Pol II. These findings uncover a previously unappreciated mechanism of metazoan gene repression, akin to bacterial transcription attenuation, wherein promoter-proximal Pol II is prevented from entering productive elongation through factor-regulated termination. Highlights The Integrator complex inhibits transcription elongation at ∼15% of mRNA genes Integrator targets promoter-proximally paused Pol II for termination The RNA endonuclease of Integrator subunit 11 is critical for gene attenuation Integrator-repressed genes are enriched in signaling and growth-responsive pathways
Autogenous Formation of Gold on Layered Black Phosphorus for Catalytic Purification of Waste Water (2020)

Layered black phosphorus (BP) is a member of a layered material family with anisotropic properties and layer-dependent band gaps that can be exfoliated down to single-layered phosphorene. Compared with graphene, few-layered BP and its single-layer phosphorene are significantly more reactive, and this reactivity can be applied for the autogenous reduction of gold ions to metallic gold nanoparticles supported by few-layered BP (Au/BP). Few-layered BP and gold are well-known oxidation catalysts important in organic synthesis and also in the catalytic treatment and purification of industrial wastewater. The treatment of organic contamination present in industrial wastewater presents serious problems and is an important issue for current catalysis. Here, we show the high catalytic activity of the gold supported on few-layered black phosphorus (Au/BP) for wet oxidation of acrylic acid, including samples of industrial wastewater with complex composition. The catalyst Au/BP exhibits high stability, which allows utilization of its easily accessible 2D surface for the preparation of 2D material-supported metal catalysts.
Minimal criteria for placement of adults on the liver transplant waiting list: A report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases (1997)

This report summarizes a recent meeting cosponsored by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases to formulate minimal criteria by which patients with severe liver disease will be placed on the waiting list for liver transplantation. The participants agreed that only patients in immediate need of liver transplantation should be placed on the waiting list. Patients should not be placed in anticipation of some future need for such therapy. It was agreed that minimal criteria could assist but not replace the clinical judgment of the transplant professionals at individual centers. The criteria will be summarized below for adult patients with acute or chronic liver disease. The most important non-disease-specific criterion for placement on the transplant waiting list was an estimated 90% chance of surviving 1 year. This translated into a Child-Pugh score of > or = 7 for patients with cirrhosis which places the patient in Child-Pugh class B or C. Cirrhotic patients who have experienced gastrointestinal bleeding caused by portal hypertension or a single episode of spontaneous bacterial peritonitis would meet the minimal criteria irrespective of their Child-Pugh score. There were disease-specific criteria also. These include a sole minimal criterion for patients with fulminant hepatic failure regardless of etiology of the onset of stage 2 hepatic encephalopathy. A requirement for 6 months abstinence from alcohol before placement on the transplant waiting list was considered appropriate for most patients with alcoholic liver disease. Exceptional cases could get access to the waiting list through a regional review process. Chronic cholestatic diseases present difficulties because of a different natural history than that of chronic hepatocellular diseases. The use of specific risk scores for primary biliary cirrhosis and primary sclerosing cholangitis will likely replace Childs-Pugh classification as the scoring systems become refined. Minimal criteria for any patient with a primary hepatocellular cancer would admit any patient with a tumor confined to the liver irrespective of size or number of tumors, after careful investigation had failed to show spread to lymph nodes, the portal vein, or distant organs. Unusual or rare indications for liver transplantation, including Budd-Chiari syndrome, Wilson's disease, and other hereditary disorders, were also discussed. Finally, it was agreed that there should be no absolute contraindications to placement of patients on the liver transplant waiting list. These criteria should be open to regular review to accommodate advances in the field.
Abstract 1264: Mutated CD80 may facilitate T-cell activation by inhibiting PDL1-PD1 suppression and by costimulating. (2013)

Abstract CD80 functions as a costimulatory signal to activate T cells when it binds to CD28 or as an apoptotic signal when it binds to CTLA4. We recently identified another function for CD80 and showed that co-expression of CD80 by Program Death Ligand-1+ (PDL1+) human tumor cells prevents PDL1 binding to its receptor PD1 on activated T cells, and enhances activation of tumor-reactive T cells. To distinguish if CD80 is facilitating T cell activation by preventing PDL1-PD1 interactions and/or by functioning as a costimulatory molecule, we have generated a recombinant CD80 molecule that does not bind to CD28. Since we hypothesize that CD80 may be a therapeutic for inhibiting tumor-mediated immune suppression via PDL1-PD1 interactions, the recombinant CD80 is also designed to not interact with CTLA4. Using site directed mutagenesis we generated CD80 with the following mutations: H96A, L97A, and E99A (CD8096,97,99). CD28 and CTLA4 bind to 35.3% and 37.4%, respectively, of tumor cells expressing wild type CD80. In contrast, only 1.2% and 1.4% of tumor cells expressing CD8096,97,99 bind CD28 and CTLA4, respectively, demonstrating that the mutant CD80 does not bind to CD28 or CTLA4. Previous studies demonstrated that CD80 prevents PDL1-PD1 interactions by binding to PDL1 and obscuring its detection. Only 7.05% of CD8096,97,99 mutants have detectable PDL1 (vs. 98% of untransfected parental human tumor cells), demonstrating that the CD8096,97,99 mutant does not bind CD28 or CTLA4, but retains the ability to inhibit PDL1-PD1 interactions. We are also generating a soluble form of CD8096,97,99 (sCD8096,97,99) that could be administered to cancer patients to prevent tumor cell-mediated PDL1 immune suppression. The construct for the soluble form was generated by ligating the two extracellular domains of CD80 containing the 96,97,99 mutations to the Fc region of human IgG1, followed by incorporation into the Pet21a+ plasmid containing the T7 promoter. Recombinant protein will be isolated from transformed E. coli using a protein G affinity column, and tested in functional experiments with PDL1+ tumor cells to determine if CD80 increases T-cell activation by inhibiting PDL1-PD-1 immune suppression and/or by facilitating costimulation. This work was funded, in part, by grants from the HHMI Precollege and Undergraduate Science Education Program (52006949), CBI (T32 GM066706), and NIH (R01CA84232 and RO1CA115880). Citation Format: Sonia P. Dalal, Samuel Haile, Preethi Somasundaram, Suzanne Ostrand-Rosenberg. Mutated CD80 may facilitate T-cell activation by inhibiting PDL1-PD1 suppression and by costimulating. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1264. doi:10.1158/1538-7445.AM2013-1264
A Scenario-Based Mobile Application for Robot-Assisted Smart Digital Homes (2010)

Smart homes are becoming more popular, as every day a new home appliance can be digitally controlled. Smart Digital Homes are using a server to make interaction with all the possible devices in one place, on a computer or webpage. In this paper we designed and implemented a mobile application using Windows Mobile platform that can connect to the controlling server of a Smart Home and grants the access to the Smart Home devices and robots everywhere possible. UML diagrams are presented to illustrate the application design process. Robots are also considered as devices that are able to interact to other object and devices. Scenarios are defined as a set of sequential actions to help manage different tasks all in one place. The mobile application can connect to the server using GPRS mobile internet and Short Message System (SMS). Interactive home map is also designed for easier status-checking and interacting with the devices using the mobile phones.
Phase Transformation Behavior of Oxide Scale on Plain Carbon Steel Containing 0.4 wt.% Cr during Continuous Cooling (2018)

Pre-oxidation in air at 750°C for 10 min, the plain carbon steels without Cr and containing 0.4 wt.% Cr tended to rapidly form oxide scale composed of outer Fe3O4 layer and inner FeO layer. Moreover, a FeCr2O4 layer was observed at the FeO/substrate interface on the steel containing Cr. A comparative study was carried out between the scales on the two steels in inert gas cooled from 350–600°C to room temperature at the cooling rate range of 1–40°C/min, to determine the effect of low concentration Cr addition on the phase transformation of FeO. Based on the cross-sectional morphologies of oxide scale during various cooling conditions, the relationship between cooling rate and start cooling temperature were constructed, and the area fraction of eutectoid structure was analyzed. The result shows that the transformation rate and area fraction of eutectoid structure in oxide scale on steel containing Cr were greater than that on steel without Cr, and then the nucleation, growth and 100% transformation region of eutectoid structure in oxide scale on steel without Cr were delayed. This study proposed two mechanisms to discuss the experimental results. Firstly, the formation of FeCr2O4 layer reduced the consumption of O, and then prevented short-range uphill diffusion of Fe from FeO to substrate. Secondly, combined with the lamellar spacing in eutectoid structure and the Fe–Cr–O equilibrium phase diagram, the Cr addition increased the formation temperature of FeO in oxide scale, which provided sufficient driving force for eutectoid transformation during continuous cooling.
Enhanced CMOS for analog-digital power IC applications (1986)

Elementary process additions to 2-3-µm polygate CMOS provide enhanced high-voltage MOSFET's and broadband complimentary bipolars. This allows monolithic integration of a modern logic family and quality analog function with high-voltage high-current buffers and drivers. The technology is suitable for data conversion, telecommunication, analog switch, and industrial IC applications where low-voltage digital and analog control circuitry must be interfaced to high-voltage high-current outputs.
Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome (2004)

This review failed to show any long-term effect of immunosuppressive treatment on patient and/or renal survival. There was an increased number of discontinuations due to adverse events in immunosuppressive treatment groups. Within the class of alkylating agents there is weak evidence supporting the efficacy of cyclophosphamide as compared to chlorambucil. On the other hand, cyclophosphamide had fewer side effects leading to patient withdrawal than chlorambucil.
Radiation can inhibit tumor growth indirectly while depleting circulating leukocytes. (1996)

The growth of certain UV-radiation-induced tumors is suppressed by T lymphocytes, but it has been proposed that non-T lymphocytes stimulate the growth of several of these tumors. In this study, the indirect effects of X irradiation on the growth of one such tumor in T-cell-deficient nude mice was tested. Even when the site of tumor cell injection was shielded, whole-body irradiation with 6 Gy before tumor challenge inhibited subsequent tumor growth significantly. The interval during which this indirect inhibition was observed correlated with the depletion of circulating leukocytes, which did not return to normal levels until 12-21 days after irradiation. These data are consistent with earlier results using an antibody to deplete Gr-1+ leukocytes and indicate that radiation can inhibit the growth of certain tumors indirectly without direct effects on the tumor cells or the tumor bed.
On the nature of the interaction between 4,4′‐diisothiocyanostilbene 2,2′‐disulfonic acid and microsomal glucose‐6‐phosphatase (1988)

The effect of 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) on microsomal glucose 6-phosphate hydrolysis has been reinvestigated and characterized in order to elucidate the topological and functional properties of the interacting sites of the glucose-6-phosphatase. The studies were performed on microsomal membranes, partially purified and reconstituted glucose-6-phosphatase preparations and show the following. (a) DIDS inhibits activity of the glucose-6-phosphatase of native microsomes as well as the partially purified glucose-6-phosphatase. (b) Inhibition is reversed when the microsomes and the partially purified phosphohydrolase, incorporated into asolectin liposomes, are modified with Triton X-114. (c) Treatment of native microsomes with DIDS and the following purification of glucose-6-phosphatase from these labeled membranes leads to an enzyme preparation which is labeled and inhibited by DIDS. (d) Preincubation of native microsomes or partially purified glucose-6-phosphatase with a 3000-fold excess of glucose 6-phosphate cannot prevent the DIDS-induced inhibition. (e) Inhibition of glucose-6-phosphatase by DIDS is completely prevented when reactive sulfhydryl groups of the phosphohydrolase are blocked by p-mecuribenzoate. (f) Reactivation of enzyme activity is obtained when DIDS-labeled microsomes are incubated with 2-mercaptoethanol or dithiothreitol. Therefore, we conclude that inhibition of microsomal glucose 6-phosphate hydrolysis by DIDS cannot result from binding of this agent to a putative glucose-6-phosphate-carrier protein. Our results rather suggest that inhibition is caused by chemical modification of sulfhydryl groups of the integral phosphohydrolase accessible to DIDS attack itself. An easy interpretation of these results can be obtained on the basis of a modified conformational model representing the glucose-6-phosphatase as an integral channel-protein located within the hydrophobic interior of the microsomal membrane [Schulze et al. (1986) J. Biol. Chem. 261, 16,571-16,578].
Synthesis and nucleophilic reactivity of a series of glutathione analogues, modified at the gamma-glutamyl moiety. (1988)

A series of GSH analogues with modifications at the gamma-glutamyl moiety was synthesized and purified by following peptide chemistry methodology. Benzyl, benzyloxycarbonyl and t-butyloxycarbonyl protective groups were used to protect individual amino acid functional groups. The formation of peptide bonds was accomplished through coupling of free amino groups with active esters, generated by reaction of the carboxylate functions with dicyclohexylcarbodi-imide and 1-hydroxybenzotriazole. The protecting groups in the tripeptides were removed in a single step by using Na in liquid NH3. Precautions were taken in order to prevent oxidation of the thiol function in the cysteine residue. Thus GSH analogues containing both L- and D-glutamic acid and L- and D-aspartic acid, coupled to cysteinylglycine through both the alpha- and the omega-carboxylate group, were synthesized. Also, decarboxy-GSH and deamino-GSH, lacking one functional group in the glutamate moiety, were prepared. The spontaneous non-enzyme-catalysed nucleophilic reaction of these GSH analogues with the electrophilic model substrate 1-chloro-2,4-dinitrobenzene showed appreciable rate differences, indicating the importance of intramolecular interactions in determining the nucleophilic reactivity of the thiol function in the cysteine residue. In particular, the free amino group in the gamma-L-glutamic acid residue appears to play a crucial role in activating the thiol group in GSH. In an adjacent paper [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724] these results are compared with those obtained in a study on the ability of these GSH analogues to act as a co-substrate in the glutathione S-transferase-catalysed conjugation reaction with 1-chloro-2,4-dinitrobenzene.
SU‐FF‐I‐126: Effect of Threshold Setting On 3D Visualization and Diameter Measurement Accuracy of Blood Vessels for CT Derived Images (2007)

Purpose: To investigate the effect on vessel sizing of varying the threshold in 3D volume‐rendered CT images and to verify the results with a 2D computer simulation. Method and Materials: 3D‐rendered images of a phantom with a vessel of varying diameter and of a patient with a basilar tip aneurysm were displayed on a Vitrea 2 workstation. Vessel diameters measured from the images were plotted as a function of gray‐scale threshold and actual vessel diameters measured directly from the phantom. A MatLab program was used to simulate different‐size vessel image models by convolving a rect function with a Gaussian point spread function (PSF) and to investigate the effect of threshold on sizing these vessels. Results: Plots of measured vessel diameter vs. threshold setting for varying real‐vessel diameter exhibit a monotonic decrease; with the slope decreasing both for low thresholds because of the extended tail of the PSF and for high thresholds where the vessel rapidly shrinks and then disappears as the threshold exceeds the vessel gray level. For intermediate thresholds there is a greater rate of fall‐off for smaller vessels below the width of the system PSF. Plots of measured diameter vs. real diameter intersect the 45 degree identity line at increasing diameters for increasing intermediate threshold. The crossing‐point indicates the point where the measured diameter equals the real diameter for the given threshold. Below the crossing point, these curves demonstrate reduced measured diameter for smaller vessels and, above the crossing‐point, larger values for larger vessels. The simplified 2D vessel‐model simulation and workstation data follow similar trends. Conclusion: A threshold set to accurately measure one rendered‐vessel diameter will inaccurately render vessels of other diameters. Using this threshold, smaller vessels will be inaccurately small or not be visualized and larger vessels will be too large. (Support: NIH R01‐NS43924, R01‐EB002873, Toshiba Corp.).
Therapeutic Potential of Ccr1 Antagonists for Multiple Myeloma (2011)

The chemokine receptor CCR1 has been the target of intensive research for nearly two decades. Small-molecule antagonists were first reported in 1998 and, since then, many inhibitors for CCR1 have been brought forth. Yet, with all the money and time spent, to date, no small-molecule antagonists have successfully moved past Phase II clinical trials. With the current advancement of CCR1 antagonists by Bristol-Myers Squibb and Chemocentrix, there has been renewed interest. In this review, we present an overview of CCR1, its activating ligands, methods of signaling, and downstream response. We discuss studies that indicate CCR1 plays an important role in multiple myeloma and the underlying molecular mechanisms. Finally, we present an overview of the clinical and preclinical compounds for CCR1. We address individual structures, discuss their pharmacological précis, and summarize the published evidence to assess their value for use in multiple myeloma.
Diamminbis(1,5‐cyclooctadien)(μ‐1,4,10,13‐tetraoxa‐7,16‐diazacyclooctadecan‐N7,N16)dirhodium‐bis (hexafluorophosphat): Ein Makrocyclus als Ligand der ersten und zugleich der zweiten Koordinationssphäre (1985)

Im Rhodiumkomplex 1 fungiert erstmals ein stickstoffhaltiger Kronenether gegenüber einem Übergangsmetall als Ligand der ersten und zugleich der zweiten Koordinationssphäre. 1 weist ein kristallographisches Symmetriezentrum auf und wird durch intramolekulare Wasserstoffbrücken stabilisiert. magnified image
Paclitaxel-induced cell death (2000)

Advances in research of the cell cycle and apoptosis have extended our understanding of the mechanisms of paclitaxel-induced cell death. Further elucidation of resistance and enhancement of paclitaxel-induced apoptosis should expedite the development of better paclitaxel-based regimens for cancer therapy.
Data from A Pilot Study of MUC-1/CEA/TRICOM Poxviral-Based Vaccine in Patients with Metastatic Breast and Ovarian Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; PANVAC is a recombinant poxviral vaccine that contains transgenes for MUC-1, CEA, and 3 T-cell costimulatory molecules. This study was conducted to obtain preliminary evidence of clinical response in metastatic breast and ovarian cancer patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental design:&lt;/b&gt; Twenty-six patients were enrolled and given monthly vaccinations. Clinical and immune outcomes were evaluated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; These patients were heavily pretreated, with 21 of 26 patients having 3 or more prior chemotherapy regimens. Side effects were largely limited to mild injection-site reactions. For the 12 breast cancer patients enrolled, median time to progression was 2.5 months (1–37+) and median overall survival was 13.7 months. Four patients had stable disease. One patient had a complete response by RECIST and remained on study for 37 months or more, with a significant drop in serum interleukin (IL)-6 and IL-8 by day 71. Another patient with metastatic disease confined to the mediastinum had a 17% reduction in mediastinal mass and was on study for 10 months. Patients with stable or responding disease had fewer prior therapies and lower tumor marker levels than patients with no evidence of response. For the ovarian cancer patients (&lt;i&gt;n&lt;/i&gt; = 14), the median time to progression was 2 months (1–6) and median overall survival was 15.0 months. Updated data are presented here for one patient treated with this vaccine in a previous trial, with a time to progression of 38 months.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Some patients who had limited tumor burden with minimal prior chemotherapy seemed to benefit from the vaccine. Further studies to confirm these results are warranted. &lt;i&gt;Clin Cancer Res; 17(22); 7164–73. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;