gebhart/patrepeval huggingface dataset:
Interwoven Ubiquitination Oscillators and Control of Cell Cycle Transitions (2004)

Ubiquitin-mediated proteolysis has emerged as a paramount mechanism for regulating the cell division cycle. Changes in the activities of certain E3 ligases can promote the interconversion of cell cycle states or transitions. Recent studies have revealed how distinct E3 ligases control the activity of other E3 ligases and how the interplay between these degradation machines sets up the timing of cell cycle transitions. For example, during G1, the anaphase-promoting complex in conjunction with Cdh1 (APC(Cdh1)) catalyzes destruction of the S-phase activator Skp2, helping to define the G1 state. In response to poorly defined signals, APC(Cdh1) activity is reduced, allowing accumulation of Skp2 and therefore entry into S phase. In many cases, E3 ligases also function to ubiquitinate proteins that negatively regulate cell cycle transitions. Recent work indicates that cyclin-dependent kinase 2 and Polo kinase collaborate to phosphorylate Wee1, thereby promoting its ubiquitination by SCF(beta-TRCP). Thus, activation of the mitotic transition produces feedback signals that help to turn off the negative upstream pathway to further reenforce the transition.
Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012. (2015)

4502 Background: Pembrolizumab, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in patients with recurrent or metastatic PD-L1–positive urothelial cancer enrolled in the phase 1b KEYNOTE-012 study (NCT01848834). We present updated efficacy and safety data for these patients, as well as an analysis of the relationship between PD-L1 expression and ORR. Methods: Eligible patients had recurrent, metastatic, or persistent urothelial cancer of the bladder, renal pelvis, ureter, or urethra. Patients received pembrolizumab 10 mg/kg every 2 weeks until complete response, progression, or unacceptable toxicity. PD-L1 expression was evaluated in baseline tumor samples at a central laboratory. Patients were enrolled if there were ≥1% PD-L1–positive cells in tumor nests or a PD-L1–positive band in stroma by a prototype immunohistochemistry assay. Samples were also analyzed with the clinical trial immunohistochemistry assay. Response was evaluated every 8 weeks per RECIST v1.1 by central review. Results: Thirty-three patients were enrolled (median age, 70 years; ≥3 prior therapies, 33%; visceral or osseous metastases, 66%). Median follow-up duration was 13 months (range, 1-16). Grade 3-4 drug-related adverse events occurred in 5 (15%) patients. In the 28 patients with measurable disease at baseline, ORR was 25% (95% CI 11-45), with 3 (11%) complete and 4 (14%) partial responses per central review. At the time of analysis, median duration of response had not been reached (range, 16-50+ weeks). The 12-month PFS rate was 19%. ORR in patients with tumors positive for PD-L1 expression as assessed with the clinical trial assay was 38%. Conclusions: Pembrolizumab demonstrates durable antitumor activity in patients with advanced urothelial cancer. A higher response rate was seen in patients with PD-L1 expression. Further analysis of the relationship between response and predictive biomarkers is ongoing. Clinical trial information: NCT01848834.
A Comparison of Field Drilling Experience with Low-Viscosity Mineral Oil and Diesel Muds (1992)

ABSTRACT Diesel has been the most widely used base-oil for oil muds. Mineral oil muds have found some application where operators wished to drill with an oil mud but wanted lower aromatic exposure to workers and the environment. Regulations have now been established that increase the difficulty of using diesel in drilling muds. From a human health, safety, and environmental issues perspective, alternates to diesel mud have merit. This paper will describe laboratory and field performance data comparing diesel oil muds with a low-viscosity, low-aromatic, low-toxicity oil or enhanced mud oil (EMO), an improvement over the early mineral oils. The physical, compositional, environmental, and human health differences between diesel and the EMO are discussed. Field data are presented which show that EMO muds have improved rate of penetration over diesel muds when used under similar conditions by 23 to 54 %.
Ionophores and Their Structures (1981)

Provides a comprehensive survey of the three-dimensional structure of ionophores. Supplements the stereoscopic picture of the molecule with a list of orthogonal coordinates for constituent atoms. Discusses the action of ionophores (complexing of metal ions, selectivity of complex formation, and mode of transport across membranes) as a consequence of their three-dimensional form.
Experimental analysis of a portable atmospheric water generator by thermoelectric cooling method (2017)

A portable water generator (7 kg) with two thermoelectric coolers (TECs) was designed and experimentally investigated in this study. Different inlet air relative humidity (RH) and air flow rates were investigated to obtain their impacts on the amount of generated water and condensation rate. The amount of generated water and condensation rate increased with the RH rose. The amount of generated water increased with air flow rates rose but the condensation rate had opposite trend. The maximum amount of generated water was 25.1 g each hour with 0.216 m2 condensation surface and 58.2 W input power. This system had small size and could work at small air flow rates which was suitable for outdoor use. This study had a guiding role in designing and optimizing a high-efficient portable water generator.
Transmucosal Potential Difference as an Index of Esophageal Mucosal Integrity (1995)

All the epithelia lining the gastrointestinal (GI) tract, including that of the esophagus, exhibit a transmucosal electrical potential difference (PD). The luminal surface of the GI mucosa is indeed electrically negative when compared with the serosal one. Although it was initially felt that the body of the esophagus exhibits a PD near 0 or slightly positive, recent studies, using parenteral reference electrodes, have shown a negative PD of around -15 mV. Measurement of esophageal PD has been mainly used to locate both the lower and the upper esophageal sphincters but very rarely to evaluate esophageal mucosal integrity in clinical settings, most probably due to the difficulties encountered during measurement of mucosal PD. Reliable techniques to measure esophageal PD simultaneously with esophageal pressure or mucosal pH are now available. Application of these recently developed methodologies showed that measurement of esophageal PD during either manometry or endoscopy provides meaningful information about mucosal integrity. Indeed, tissue injury, either neoplastic of inflammatory, usually results in a less negative PD. In contrast, an abnormally high negative PD is very often observed in patients with columnar-lined lower esophagus. In patients with microscopic reflux esophagitis, PD exhibits less negative values which are significantly correlated with the degree of the mucosal damage. Normalization of the altered PD after either medical or surgical treatment makes it an additional parameter to evaluate the effect of a given therapy.
Analysis of HLA-DQ Genotypes and Susceptibility in Insulin-Dependent Diabetes Mellitus (1990)

There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles. Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P less than 0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ("dominant protection"). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/DQw8 haplotype ("dominant susceptibility"). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8. We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.
Adenovirus type 2 mRNA in transformed cells: map positions and difference in transport time (1978)

Adenovirus type 2 rat transformed cells produced two polyadenylic acid-terminated mRNA's with approximate coordinates 1.5-4.4 and 4.4-11.0 on the physical map of the adenovirus type 2 genome. These mRNA's were also formed early during lytic infection in addition to one or more smaller mRNA's from the 4.4-11.0 region. In transformed cells, the 1.5-4.4 mRNA appeared in the cell cytoplasm without detectable lag, whereas the 4.4-11.0 mRNA required at least 20 to 30 min for the maximal rate of accumulation.
Atom transfer radical polymerization of methyl methacrylate catalyzed by cobalt catalyst system (2005)

Abstract A new catalyst system, CoCl 2 /tris(2‐(dimethyl amino) ethyl)amine (Me 6 TREN), was used to catalyze the polymerization of methyl methacrylate (MMA) successfully through atom transfer radical polymerization mechanism. The control over the polymerization was not ideal, the molecular weight distribution of the resulting polymer (PMMA) was relatively broad ( M w / M n = 1.63–1.80). To improve its controllability, a small amount of hybrid deactivator (FeBr 3 /Me 6 TREN or CuBr 2 /Me 6 TREN) was added in the cobalt catalyst system. The results showed that the level of control over the polymerization was significantly improved with the hybrid cobalt–iron (or cobalt–copper) catalyst system; the polydispersity index of the resulting polymer was reduced to a low level ( M w / M n = 1.15–1.46). Furthermore, with the hybrid cobalt–iron catalyst, the dependence of the propagation rate on the temperature and the copolymerization of methacrylate (MA) with PMMA‐Br as macroinitiator were also investigated. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5207–5216, 2005
Dehydroepiandrosterone Augmentation in the Management of Negative, Depressive, and Anxiety Symptoms in Schizophrenia (2003)

Our preliminary observations report for the first time in double-blind fashion the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. The findings from this study raise important issues regarding the role of neurosteroids in general, and DHEA in particular, in the ongoing symptomatology and pharmacotherapy of schizophrenia.
ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism (2002)

Oxysterol binding protein (OSBP) related proteins (ORPs) constitute a family that has at least 12 members in humans. In the present study we characterize one of the novel OSBP homologs, ORP2, which we show to be expressed ubiquitously in mammalian tissues. The ORP2 cDNA encodes a deduced 55 kDa protein that lacks a pleckstrin homology (PH) domain, a feature found in the other family members. Sucrose gradient centrifugation analysis of Chinese hamster ovary (CHO) cell post-nuclear supernatant demonstrated that ORP2 is distributed in soluble and membrane-bound fractions. Immunofluorescence microscopy of the endogenous and overexpressed ORP2 in CHO cells suggested that the membrane-bound fraction of the protein localizes to the Golgi apparatus. Stably transfected CHO cells that overexpress ORP2 showed an increase in [14C]cholesterol efflux to serum, apolipoprotein A-I (apoA-I), and phosphatidyl choline vesicles. The proportion of cellular [14C]cholesterol that is esterified and the ACAT activity measured as [14C]oleyl-CoA conversion into cholesteryl [14C]oleate by the cellular membranes, were markedly decreased in the ORP2 expressing cells. Transient high level overexpression of ORP2 interfered with the clearance of a secretory pathway protein marker from the Golgi complex. The results implicate ORP2 as a novel regulator of cellular sterol homeostasis and intracellular membrane trafficking.
Deep convolutional neural networks for automatic segmentation of left ventricle cavity from cardiac magnetic resonance images (2017)

This work conducts a feasibility study of deep learning approaches for automatic segmentation of left ventricle (LV) cavity from cardiac magnetic resonance (CMR) images. Automatic LV cavity segmentation is a challenging task, partially due to the small size of the object as compared to the large CMR image background, especially at the apex. To cater for small object segmentation, the authors present a localisation‐segmentation framework, to first locate the object in the large full image, then segment the object within the small cropped region of interest. The localisation is performed by a deep regression model based on convolutional neural networks, while the segmentation is done by the deep neural networks based on U‐Net architecture. They also employ the Dice loss function for the training process of the segmentation models, to investigate its effects on the segmentation performance. The deep learning models are trained and evaluated by using public endocardium‐annotated CMR datasets from York University and MICCAI 2009 LV Challenge websites. The average dice metric values of the authors’ proposed framework are 0.91 and 0.93, respectively, on these two databases. These results are promising as compared to the best results achieved by the current state‐of‐art, which shows the potentials of deep learning approaches for this particular application.
Comparison of the configuration of the human anterior chamber angle, as determined by the Spaeth gonioscopic grading system and ultrasound biomicroscopy. (1995)

The SGGS appears to be an accurate method of characterizing the anatomic appearance of the anterior chamber angle in patients. It also provides a more comprehensive description of the angle that other grading systems.
ABIN-1 Binds to NEMO/IKKγ and Co-operates with A20 in Inhibiting NF-κB (2006)

Nuclear factor kappaB (NF-kappaB) plays a pivotal role in inflammation, immunity, stress responses, and protection from apoptosis. Canonical activation of NF-kappaB is dependent on the phosphorylation of the inhibitory subunit IkappaBalpha that is mediated by a multimeric, high molecular weight complex, called IkappaB kinase (IKK) complex. This is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, NEMO/IKKgamma. The latter protein is essential for the activation of IKKs and NF-kappaB, but its mechanism of action is not well understood. Here we identified ABIN-1 (A20 binding inhibitor of NF-kappaB) as a NEMO/IKKgamma-interacting protein. ABIN-1 has been previously identified as an A20-binding protein and it has been proposed to mediate the NF-kappaB inhibiting effects of A20. We find that both ABIN-1 and A20 inhibit NF-kappaB at the level of the IKK complex and that A20 inhibits activation of NF-kappaB by de-ubiquitination of NEMO/IKKgamma. Importantly, small interfering RNA targeting ABIN-1 abrogates A20-dependent de-ubiquitination of NEMO/IKKgamma and RNA interference of A20 impairs the ability of ABIN-1 to inhibit NF-kappaB activation. Altogether our data indicate that ABIN-1 physically links A20 to NEMO/IKKgamma and facilitates A20-mediated de-ubiquitination of NEMO/IKKgamma, thus resulting in inhibition of NF-kappaB.
Linker Architectures as Steric Auxiliaries for Altering Enzyme-Mediated Payload Release from Bioconjugates (2021)

Protease-activated prodrugs leverage the increased activity of proteases in the tumor microenvironment and the tight regulation in healthy tissues to provide selective activation of cytotoxins in the tumor while minimizing toxicity to normal tissues. One of the largest classes of protease-activated prodrugs are composed of therapeutic agents conjugated to macromolecular carriers via peptide motifs that are substrates for cathepsin B, and antibody-drug conjugates are one of the most successful designs within this class. However, many of these peptide motifs are also cleaved by extracellular enzymes such as elastase and carboxylesterase 1C. Additionally, some peptide sequences have little selectivity for other lysosomal cathepsins, which have also been found to have extracellular activity in normal physiological processes. A lack of selectivity or oversensitivity to other extracellular enzymes can lead to off-target release of the cytotoxic payload and subsequent toxicities. In this report, we describe an approach for modulating cathepsin-mediated release of the cytotoxic payload through steric shielding provided by the synergistic effects of appropriately designed hydrophilic linkers and the conjugated carrier. We prepared a fluorogenic model payload with a Val-Cit cleavable trigger and attached the trigger-payload to a variety of PEG-based linker architectures with different numbers of PEG arms (<i>y</i>), different numbers of ethylene oxide units in each arm (<i>n</i>), and different distances between the cleavable trigger and PEG branch point (<i>D</i>'). These linker-payloads were then used to prepare DAR2 conjugates with the cleavable triggers at three different distances (<i>D</i>) from the antibody, and cathepsin-mediated payload release was monitored with <i>in vitro</i> assays. The results show that structural variables of the linker architectures can be manipulated to effectively shield enzymatically labile trigger-payloads from enzymes with readily accessible binding sites, and may offer an additional strategy for balancing off-target and tumor-targeted payload release.
Identification of sound source in machine vision sequences using audio information (2004)

Identifying the sound source location in the acquired image for further processing is of concern in image/video processing especially when tracking objects of vibrating or sound making nature in the scene becomes necessary. On the other hand relying on the picture content to identify such objects is not an easy task especially when there are similar objects in the acquired image. In this paper, we present a technique for identifying the location of sound source using beam-forming techniques by means of an array of microphones based on the processing of audio from the source itself. Upon estimation of the location in 3-D space, a projection technique is used to accurately locate the position of sound source in 2-D image frame coordination.
Telnet end of record option (1983)

This RFC specifies a standard for the ARPA Internet community. Hosts on the ARPA Internet
Potentiale und Faltungsprodukte (1977)

In diesem Paragraphen behandeln wir spezielle Fragen der Maß- und Integrationstheorie im R n , insbesondere die Konstruktion von Ausnahme-Mengen, die der Definition von Potentialen von Maßen bezüglich meßbarer Kerne angepaßt sind. Die Motivation für dieses Herangehen besteht in Sachverhalten der Potentialtheorie für den Laplace-Operator, die wir in Kapitel III ausführlich darstellen. Die Ausnahme-Mengen sind dabei die Mengen der Wienerschen Kapazität Null. Das hier gezeigte formale Herangehen, das auch von selbständigem Interesse ist, ermöglicht in Kapitel VIII die Einführung angepaßter Nullmengensysteme für elliptische Gleichungen höherer Ordnung. Mit diesem Gedanken, der von G. Anger [A 28], [A 33], [A 30] entwickelt worden war, befassen sich u. a. auch die Arbeiten [W 17], [W 25], [W 22], [W 21], [W 27], [S 14], [S 16], [S 17], wo diese Hilfsmittel weiterentwickelt und einige nichtklassische Anwendungen gegeben wurden ([S 12], [S 13], vgl. XI.4.). Ausnahmemengen in verschiedensten Zusammenhängen werden seit langem in der Literatur behandelt (vgl. Kapitel XI). Speziell für elliptische Gleichungen höherer Ordnung existieren auch andere Definitionen, auf die wir in Kapitel IX eingehen.
A Network of Hydrogen Bonds on the Surface of TLR2 Controls Ligand Positioning and Cell Signaling (2009)

TLR2 is a pattern recognition receptor that functions in association with TLR1 or TLR6 to mediate innate immune responses to a variety of conserved microbial products. In the present study, the ectodomain of TLR2 was extensively mutated, and the mutants were assessed for their ability to bind and to mediate cellular responses to triacylated lipopeptide Pam(3)CSK(4). This analysis provides evidence that the recently published crystal structure of the TLR2-TLR1-Pam(3)CSK(4) complex represents a functional signal-inducing complex. Furthermore, we report that extended H-bond networks on the surface of TLR2 are critical for signaling in response to Pam(3)CSK(4) and to other di- and tri-acylated TLR2-TLR6 and TLR2-TLR1 ligands. Based on this finding, we suggest a dynamic model for TLR2-mediated recognition of these ligands in which TLR2 fluctuates between a conformation that is more suitable for binding of the fatty acyl moieties of the ligands and a conformation that favors, via a specific orientation of the ligand head group, formation of a signal-inducing ternary complex.
Syntheses of (−)-Funebrine and (−)-Funebral, Using Sequential Transesterification and Intramolecular Cycloaddition of a Chiral Nitrone (2004)

The first syntheses of (-)-funebrine [(-)-1] and (-)-funebral [(-)-2] are described. The syntheses feature sequential formation of nitrone VI from methyl glyoxylate (5) with oxime 6, transesterification of nitrone VI with (E)-crotyl alcohol (4), and intramolecular cycloaddition of the resulting nitrone VII bearing crotyl ester to afford cycloadduct 7 as a major product. The adduct 7 was readily elaborated to amino lactone (-)-3, the key synthetic intermediate of (-)-1 and (-)-2.
An AOTV aeroheating and thermal protection study (1984)

The aerothermodynamics and thermal protection of aerobraking orbital transfer vehicles are studied with a view toward design methodology and technology requirements. A particular class of geometries is investigated: the ellipsoidally blunted raked-off elliptic cone. Discussed are the influence of various geometrical parameters on the trajectory and the heat flux as well as heating prediction methods ranging from an engineering correlation formula to computational solutions of the Navier-Stokes equations. Finite-rate catalytic thermal protection materials and gas radiation are considered. Estimates of the specific mass of possible thermal protection systems indicate that support structure is a large contributor to the aerobrake mass as compared with the thermal protection insulation itself. Sizing curves are included which enable the designer to estimate the size aerobrake required from heating considerations for different mass vehicles having aerobrakes of several specific masses.