gebhart/patrepeval huggingface dataset:
Spontaneous planarization of nanoscale phase separated thin film (2002)

Structure of complex fluid at mesoscales is influenced by interfacial effects. We describe the dynamic response in such films to sudden change in interfacial tension. In a self-assembled block copolymer film, the monolayer of 15 nm diam cylindrical discrete phases close to the surface commence to sink at an average rate of 0.16 nm/day in response to the interfacial tension change. Surprisingly, this spontaneous planarization occurs, even though the cylinders are covalently stitched to the matrix. A simple model explains the observed behavior. The observation may lead to approaches to tailor the structure of mesoscale thin films of complex fluids for long-range order that are desirable for nanoscale device fabrication.
In vitro experiments on axonal guidance and growth-cone collapse (1990)

In the retinotectal projection, nasal retinal axons project to posterior tectum, while temporal axons project to the anterior part of the tectum. In in vitro experiments, a similar specificity can be observed: the nasal and temporal retinal axons can be guided by tectal membrane components so that, for example, temporal retinal axons, when growing on a striped substratum consisting of anterior and posterior tectal membranes, express a very strong preference for the anterior stripes. This preference is not due to attractivity of anterior membranes but rather to avoidance of posterior material, although the pure posterior membranes are a very good substratum for growth of temporal axons. The repellent guidance molecule has been identified. Interestingly, besides guidance this molecule causes another reaction: when growing temporal axons are exposed to medium containing either posterior membranes or artificial lipid vesicles containing the repellent guidance molecule, the axonal growth cones collapse. As in guidance, there is a clear regional specificity: e.g. the repellent guidance molecule derived from posterior tectum induces collapse of temporal but not of nasal axons. Since the guiding and the collapse-inducing activity are expressed by one and the same glycoprotein molecule (Mr 33 x 10(3), linked to the membrane by phosphatidylinositol) and since another molecule has been identified by Keynes' group which also expresses both guiding and collapse-inducing activity, one might speculate that axonal guidance and axonal collapse have something in common. Models of axonal guidance will be discussed.
Linking radiology equipment service and medical physics survey databases. (2004)

During the performance of medical physics surveys on diagnostic imaging equipment, it is not unusual to find problems requiring service. In the work described in this article, two existing and separate databases, one for radiology equipment maintenance and the other for medical physics surveys were linked. By linking the two databases we have closed the loop in our documentation. The two databases are integrated so that when logging a survey, a single mouse click will allow the user to initiate a service call and link it to the survey. In addition, any survey linked to a service call permits the user to view the service record with a single mouse click. This allows us within the medical physics database to document the resolution of problems as well as to keep track of the status of service calls initiated as a result of medical physics surveys.
Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2 (2001)

Remarkable progress has been made recently in identifying a new gene family related to the capsaicin (vanilloid) receptor, VR1. Using a combination of in silico analysis of expressed sequence tag (EST) databases and conventional molecular cloning, we have isolated a novel vanilloid-like receptor, which we call VRL-2, from human kidney. The translated gene shares 46% and 43% identity with VR1 and VRL-1, respectively, and maps to chromosome 12q23-24.1, a locus associated with bipolar affective disorder. VRL-2 mRNA was most strongly expressed in the trachea, kidney, and salivary gland. An affinity-purified antibody against a peptide incorporating the COOH terminal of the receptor localized VRL-2 immunolabel in the distal tubules of the kidney, the epithelial linings of both trachea and lung airways, serous cells of submucosal glands, and mononuclear cells. Unlike VR1 and VRL-1, VRL-2 was not detected in cell bodies of dorsal root ganglia (DRG) or sensory nerve fibers. However, VRL-2 was found on sympathetic and parasympathetic nerve fibers, such as those innervating the arrector pili smooth muscle in skin, sweat glands, intestine, and blood vessels. At least four vanilloid receptor-like genes exist, the newest member, VRL-2 is found in airway and kidney epithelia and in the autonomic nervous system.
Precise Gene Deletion and Replacement Using the CRISPR/Cas9 System in Human Cells (2014)

The prokaryotic type II CRISPR/Cas9 system has been adapted to perform targeted genome editing in cells and model organisms. Here, we describe targeted gene deletion and replacement in human cells via the CRISPR/Cas9 system using two guide RNAs. The system effectively generated targeted deletions of varied length, regardless of the transcriptional status of the target gene. It is notable that targeted gene deletions generated via CRISPR/Cas9 and two guide RNAs resulted in the formation of correct junctions at high efficiency. Moreover, in the presence of a homology repair donor, the CRISPR/Cas9 system could guide precise gene replacement. Our results illustrate that the CRISPR/Cas9 system can be used to precisely and effectively generate targeted deletions or gene replacement in human cells, which will facilitate characterization of functional domains in protein-coding genes as well as noncoding regulatory sequences in animal genomes.
Ketoconazole Effectively Reverses Multidrug Resistance in Highly Resistant KB Cells (1994)

The antifungal agent ketoconazole was found to overcome resistance to vinblastine and doxorubicin in multidrug resistant KB-V1 cells in vitro. These cells are several hundred-fold more resistant than the parental cell line KB-3-1. Ketoconazole had little or no effect on the parental KB-3-1 cells. The concentrations used to overcome drug resistance in vitro have already been safely used in vivo for treatment of fungal infections and in the monotherapy of hormone independent prostate carcinomas to block adrenal androgen production. Because of a possible beneficial effect of a combination of ketoconazole and a chemotherapeutic drug in multidrug resistant cancers, we examined a panel of 11 prostate carcinoma tissues for the expression of the MDR1 gene by an RNA-PCR assay. MDR1 expression was detectable, albeit at low levels, in 8 of the 11 tumors, suggesting a possible role of this gene in the drug resistance of prostate carcinomas. Our data suggest that ketoconazole might be useful in overcoming multidrug resistance in concentrations that are achievable in humans.
Oil reservoir production forecasting with uncertainty estimation using genetic algorithms (2003)

A genetic algorithm is applied to the problem of conditioning the petrophysical rock properties of a reservoir model on historic production data. This is a difficult optimization problem where each evaluation of the objective function implies a flow simulation of the whole reservoir. Due to the high computing cost of this function, it is imperative to make use of an efficient optimization method to find a near optimal solution using as few iterations as possible. We have applied a genetic algorithm to this problem. Ten independent runs are used to give a prediction with an uncertainty estimate for the total future oil production using two different production strategies.
Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. (1998)

Members of the phosphatidylinositol-3 kinase related kinase (PIKK) family function in both cell cycle progression and DNA damage-induced cell cycle checkpoints. The fungal metabolite, wortmannin, is an effective radiosensitizer that irreversibly inhibits certain members of the PIKK family. Based on their roles in DNA damage responses, several PIKKs, DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM) and the ataxia- and Rad3-related protein (ATR), are potential targets for the radiosensitizing effect of wortmannin. In this report, we demonstrate that wortmannin is a relatively potent inhibitor of DNA-PK (IC50, 16 nM) and ATM (IC50, 150 nM) activities, whereas ATR activity is significantly less sensitive to this drug (IC50, 1.8 microM). In intact A549 lung adenocarcinoma cells, wortmannin inhibited both DNA-PK and ATM at concentrations that correlated closely with those required for radiosensitization. Furthermore, pretreatment of A549 cells with wortmannin resulted in radioresistant DNA synthesis, a characteristic abnormality of ATM-deficient cells. These results identify wortmannin as an inhibitor of ATM activity and suggest that ATM and DNA-PK are relevant targets for the radiosensitizing effect of this drug in cancer cells.
Superiority of Tandem Autologous Transplantation Over Standard Therapy for Previously Untreated Multiple Myeloma (1997)

Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. "Total Therapy" (TT) consisting of noncross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m2 subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM.
Vaccination of Metastatic Renal Cancer Patients with MVA-5T4: A Randomized, Double-Blind, Placebo-Controlled Phase III Study (2010)

MVA-5T4 in combination with SOC was well tolerated, but no difference in survival was observed in the overall study population. Exploratory analyses indicate that there may be subsets of patients who could gain significant benefit from MVA-5T4, but such results would need to be confirmed in future randomized clinical studies.
TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells (2017)

Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. <i>Cancer Res; 77(21); e108-10. ©2017 AACR</i>.
Function of Neisserial Outer Membrane Phospholipase A in Autolysis and Assessment of Its Vaccine Potential (2005)

Outer membrane phospholipase A (OMPLA) is an outer membrane-localized enzyme, present in many gram-negative bacterial species. It is implicated in the virulence of several pathogens. Here, we investigated the presence, function, and vaccine potential of OMPLA in the human pathogen Neisseria meningitidis. Immunoblot analysis showed the presence of OMPLA in 28 out of 33 meningococcal strains investigated. The OMPLA-negative strains all contained a pldA gene, but these alleles contained premature stop codons. All six Neisseria gonorrhoeae strains tested, but only two out of seven commensal neisserial strains investigated, expressed OMPLA, showing that OMPLA is expressed by, but not limited to, many pathogenic neisserial strains. The function of OMPLA was investigated by assessing the phenotypes of isogenic strains, expressing no OMPLA, expressing wild-type levels of OMPLA, or overexpressing OMPLA. OMPLA exhibited phospholipase activity against endogenous phospholipids. Furthermore, OMPLA was characterized as an autolysin that acted under specific conditions, such as prolonged growth of the bacteria. The vaccine potential of the protein was investigated by immunizing mice with in vitro refolded, recombinant OMPLA. High levels of antibody titers were obtained, but the murine sera were neither bactericidal nor protective. Also, convalescent patients and vaccinee sera did not contain detectable levels of anti-OMPLA antibodies, indicating that OMPLA may not be sufficiently immunogenic to be included in a meningococcal vaccine.
ARC discharge supply component protection circuitry (1976)

In a mercury bombardment ion engine, the discharge supply is a high current, low voltage supply that maintains an arc or discharge inside the engine. The output of the power supply is commandable and the response to this command is current, Ina 30 cm ion engine the supply provides up to 45 volts at ~13 amperes and is referenced at ~1100 volts above ground. Due to the engine discharge characteristics, a very slow feedback control loop is required. A high speed current limit must therefore be used to protect the components in the power conditioner, in this case a pulse width modulated bridge inverter. A high speed cycle-bycycle current limit circuit which allows the inverter to continue running in an overcurrent condition is used to protect the inverter. The high speed current sensing allows the inverter to be turned off each half cycle before the current in the primary of the inverter exceeds a safe level. This permits the inverter to continue to provide current into a discharge or a fault condition, until the feedback control system can actively control the current.
The dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors: a new class of oral therapy for patients with type 2 diabetes mellitus (2007)

Abstract The observation that an oral glucose load is more effective at releasing insulin, compared with the same amount of glucose given intravenously, has been called the incretin effect, and is due to the augmentation of glucose‐stimulated insulin secretion by intestinally derived peptides. Glucagon‐like peptide‐1 (GLP‐1), in particular, has been shown to stimulate insulin release in a glucose‐dependent manner in humans, but it is rapidly metabolised by dipeptidyl‐peptidase‐4 (DPP‐4). Inhibition of DPP‐4 activity enhances fasting and post‐prandial GLP‐1 which, in turn, improves glycaemic control by increasing glucose‐dependent insulin secretion and by decreasing glucagon concentration. Current oral antidiabetic drugs (OADs) for type 2 diabetes are limited by adverse effects such as gastrointestinal problems, weight gain, oedema, or hypoglycaemia. In addition, there are recent concerns about rosiglitazone and cardiovascular outcomes, and with the thiazolidinediones in general regarding excess fracture rate in women and increased risk of heart failure. Thus the introduction of a new class of OADs, the DPP‐4 inhibitors, is welcome. This review article discusses the most clinically relevant data published on DPP‐4 inhibitors based on Medline literature searches (1966 to August 2007) and posters and oral presentations from the American Diabetes Association Scientific Sessions in 2006 and 2007. We have concentrated our review on two DPP‐4 inhibitors: sitagliptin (Januvia) and vildagliptin (Galvus). Copyright © 2007 John Wiley &amp; Sons.
A universal data compression system (1983)

A universal data compression algorithm is described which is capable of compressing long strings generated by a "finitely generated" source, with a near optimum per symbol length without prior knowledge of the source. This class of sources may be viewed as a generalization of Markov sources to random fields. Moreover, the algorithm does not require a working storage much larger than that needed to describe the source generating parameters.
Plasma MMP1 and MMP8 expression in breast cancer: Protective role of MMP8 against lymph node metastasis (2008)

In summary, we observed differences in MMP1 and MMP8 plasma levels between healthy controls and breast cancer patients as well as between breast cancer patients. Interestingly, our results suggest that MMP8 may affect the metastatic behaviour of breast cancer cells through protection against lymph node metastasis, underlining the importance of anti-target identification in drug development.
Idiopathic left ventricular tachycardia with dual electrocardiogram morphologies in a single patient (2009)

A 29-year-old female with a documented ventricular tachycardia exhibiting two different electrocardiogram (ECG) morphologies in the precordial leads was referred for catheter ablation. We describe the mechanism of the dual ECG morphologies in this case.
Induction of antitumour immunity using survivin peptide‐pulsed dendritic cells in a murine lymphoma model (2003)

Survivin is overexpressed in several types of haematological malignancies making it an attractive target for therapeutic cytotoxic T-lymphocyte responses. Here, we identify two peptide epitopes derived from the murine survivin protein and demonstrate that Balb/c mice treated with syngeneic dendritic cells pulsed with the survivin epitopes were able to reject an otherwise lethal tumour inoculation of the A20 lymphoma. For the first time, these data provide evidence for the use of survivin peptide epitopes in T cell-based immunotherapeutic concepts against a B-cell lymphoma in vivo.
Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc. (1994)

We used an intracellular zinc-specific fluorophore, Zinquin, in conjunction with fluorescence video image analysis, to reveal labile zinc in pancreatic islet cells, which concentrate this metal for use in synthesis, storage, and secretion of insulin. Zinquin vividly demonstrated zinc in the islet cell secretory granules, which formed a brightly labeled crescent in the cytoplasm between one side of the nucleus and the plasma membrane. Lower but still appreciable amounts of zinc were detected in the remaining cytoplasm, but there was little labeling in the nucleus. Fluorescence intensity varied among islet cells, suggesting differences in zinc content. Their average fluorescence intensity greatly surpassed that of the surrounding pancreatic acinar cells in frozen sections of pancreas and in all other types of cell studied, including lymphocytes, neutrophils, fibroblasts, and erythrocytes. Less labile zinc was detected in cells of the mouse insulinoma cell line NIT-1, regardless of whether they were maintained in long-term culture in the presence or absence of exogenous extracellular zinc. Exposure of islet or insulinoma cells to a high concentration of glucose or other secretagogue decreased the content of labile zinc. Zinquin should be a useful probe for revealing changes in zinc homeostasis in islet B-cells that may be important in their dysfunction and death during diabetes.
Apolipoprotein E Isoforms Increase Intracellular Ca2+ Differentially Through a ω‐Agatoxin IVa‐Sensitive Ca2+‐Channel (1998)

Apolipoprotein E (apoE) is the major apolipoprotein in the brain and is known for its important role in plasticity and neurodegeneration. We show that apoE dose-dependently increases intracellular free Ca2+ in rat hippocampal astrocytes and neurons. This effect varies with isoforms in the order E4 > E3 > E2. It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein. ApoE evoked Ca2+-increases are blocked in zero [Ca]o and by the Ca-channel antagonists nickel and omega-Agatoxin-IVa but not by nifedipine and omega-Conotoxin-GVIa, demonstrating an isoform-specific activation of P/Q type Ca2+-channels. This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE epsilon-allelic variation (epsilon4 > epsilon3 > epsilon2).
Atomically controlled processing for future Si-based devices (2004)

One of the main requirements for Si-based ultrasmall devices is atomic-order control of process technology. Here we show the concept of atomically controlled processing, based on atomic-order surface reaction control. Self-limiting formation of 1-3 atomic layers of group IV or related atoms in the thermal adsorption and reaction of hydride gases (SiH/sub 4/, GeH/sub 4/, NH/sub 3/, PH/sub 3/, CH/sub 4/ and SiH/sub 3/CH/sub 3/) on Si(100) and Ge(100) are generalized, based on the Langmuir-type model. Si epitaxial growth over the N and P layer already-formed on the Si(100) surface is achieved. It is found that a higher level of electrical P atoms exist in such films, compared with doping under thermal equilibrium conditions. These results open the way to atomically controlled technology for ultralarge-scale integrations.
Multiple Constrained Folding of Programmable Logic Arrays: Theory and Applications (1983)

Programmable logic arrays are important building blocks of VLSI circuits and systems. We address the problem of optimizing the silicon area and the performances of large logic arrays. In particular, we describe a general method for compacting a logic array defined as multiple row and column folding and we address the problem of interconnecting a PLA to the outside circuitry. We define a constrained optimization problem to achieve minimal silicon area occupation with constrained positions of electrical inputs and outputs. We present a new computer program, PLEASURE, which implements several algorithms for multiple and/or constrained PLA folding.