gebhart/patrepeval huggingface dataset:
Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II (2017)

Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. H2O2-sensitive Cys residues in the zincbinding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding. [BMB Reports 2017; 50(8): 391-392].
DeltaNI (2013)

Main-memory database systems are emerging as the new backbone of business applications. Besides flat relational data representations also hierarchical ones are essential for these modern applications; therefore we devise a new indexing and versioning approach for hierarchies that is deeply integrated into the relational kernel.
A CT assisted method for absolute quantitation of internal radioactivity (1996)

A method is described for the determination of radioactivity (microCi or MBq) at an organ site within an object or patient. Using both anatomic image data (CT or MRI scans) and planar gamma camera images, activity at depth is determined using a matrix inversion method based on least squares. The result of the inversion analysis was the unknown set of n linear (uniform) activity densities representative of each organ within the phantom or patient. The problem was overdetermined since the number of unknown activity densities (microCi/cm) was much less than the number of analysis points (N) within the nuclear image. This method, defined as the CT assisted matrix inversion (CAMI) technique, was accurate to within 15% for a three "organ" plastic phantom, wherein the organs were right circular cylinders having activities of 74 to 508 microCi (or 2.74 MBq to 18.8 MBq). This accuracy included image quantitation effects, particularly assumptions concerning attenuation correction. The average absolute percent error of the estimated activity in four distinct radioactive volumes in the phantom was 9.8%. It was found that the background activity within the phantom was estimated to be too high if sampling regions near strong sources were used in the analysis (scatter effect). This was minimized by going at least 2 cm away from such sources. By applying the method to a monoclonal antibody clinical study, activities within the patient's major organs such as liver, spleen, and kidney could be estimated, even in cases where the organ could not be visualized. Here, the CAMI algorithm gave internally consistent results for the patient's left and right lung linear activity concentrations. The CAMI technique resolves the problem of tissue superimposition using depth information from 3-D CT and is applicable in cases where a number of organs overlap in the gamma camera image. Thus, the method should be generally useful to nuclear image quantitation and the estimation of absorbed radiation doses in patients. One particular application is the estimation of radiation doses in radioimmunotherapy (RIT).
Extremum Seeking Based Control Strategy for a Chilled-Water Plant With Parallel Chillers (2015)

Chilled-water plants with multiple chillers are the backbone of ventilation and air conditioning (VAC) systems for commercial buildings. A penalty function based multivariate extremum seeking control (ESC) strategy is proposed in this paper for maximizing the energy efficiency in real time for a variable primary flow (VPF) chilled-water plant with parallel chillers. The proposed ESC algorithm takes the total power consumption (chiller compressors + cooling tower fan + condenser water pumps + penalty terms if inputs saturation occurs) as feedback, and tower fan air flow, condenser water flows and evaporator leaving chilled-water temperature setpoint as plant inputs (ESC outputs). A band-pass filter array is used in place of the conventional high-pass filter at the plant output so as to reduce the cross-channel interference. Chiller sequencing is also enabled with input saturation related signals. A Modelica based dynamic simulation model is developed for a chilled-water plant with two parallel chillers, one cooling tower, one air-handling unit and one zone. Simulation results under several testing conditions validate the effectiveness of the proposed model-free control strategy, as well as the significant energy saving.
Nicotine Free Herbal Composition for Smoking De-Addiction - A Placebo Controlled, Double Blind, Randomized, Multi-centric Clinical Study (2022)

Abstract Background: Smoking is a major predisposing factor for many health problems including Cancers, Vascular disorders etc. Quitting smoking is the only solution to prevent them. Various medicinal and non-medicinal methods are used for the same. Hypothesis/Purpose : The purpose of the present study was to evaluate the efficacy of a nicotine free herbal formulation (Smotect tablets) containing ingredients like Mucuna pruriens, Withania somnifera, Bacopa monnieri etc. for cessation of smoking and its effects on other health parameters related to smoking. Study Design: The present study was a placebo controlled, double blind, randomized, multi-centric clinical study conducted at three clinical sites in India. Methods: After ethical approval and informed consent, all participants were given nicotine free herbal composition - Smotect Tablets or Placebo tablets in a dose of 2 tablets twice daily for 90 days. A total of 103 Participants (52 in trial group and 51 in placebo group) completed the study. Evaluation of cessation of smoking was done along with other parameters like measurement of lung capacity, clinical assessment and laboratory investigations at baseline and at regular intervals till the end of the study. Results: A significant reduction in smoking as well as in the CO and COHb levels was observed with the use of Smotect tablets as compared to placebo over a period of 90 days. Significant improvement was also observed in quality of life, energy and stamina levels, reduction of stress level. Smotect tablets were found to be safe without causing any adverse effects. Conclusion: Smotect tablets, a nicotine free herbal composition, can be recommended as a safe and effective remedy for de-addiction of smoking along with improving health related problems arising due to smoking.
Calculation and measurement of acoustic scatter to assess fragmentation in shock wave lithotripsy (2006)

Shock wave lithotripsy (SWL) is currently conducted with little feedback on whether kidney stones are breaking. To determine if fragmentation could be assessed, acoustic scatter from intact and fractured stone models was calculated numerically and measured in vitro. Acoustic scatter from the stones, which were modeled with glass spheres, was calculated numerically using a linear elastic model, initialized with known elastic constants, and propagated from the stone model surface using the Helmholtz-Kirchhoff integral. Experimentally, shock waves were generated with a research lithotripter and scatter was measured with a broadband, spherically focused receiver. Calculated and measured results agreed well in the time domain. In frequency, power spectra were integrated to find energy and showed that scatter from the fractured stone model had higher energy in specific frequency bands that were related to the reverberation period. High-speed photography indicated that cavitation did not adversely affect the analysis of scatter. In this work it was possible to distinguish between the intact and fractured stone models. This method could be applied to stones that fragment gradually under the application of shock waves and potentially be used to estimate fragment size, and therefore the endpoint of therapy. [Work supported by NSBRI SMS00402 and NIH DK43881.]
Comparison of<i>bcr-abl</i>Protein Expression and Philadelphia Chromosome Analyses in Chronic Myelogenous Leukemia Patients (1996)

The Philadelphia chromosome (Ph) is found in most chronic myelogenous leukemia (CML) patients. The bcr-abl oncoprotein (P210 or P185), the product of the fused bcr-abl gene produced by the Ph, is known to be the major factor in initiation and maintenance of the leukemic state in these types of leukemias. The authors have devised a Western blot test to detect and quantitate the bcr-abl oncoprotein in blood and bone marrow cells. The authors analyzed 1,155 peripheral blood samples from CML patients, for which there were same day Ph data, to determine if there was a correlation between bcr-abl protein levels and the percentage of Ph. A ratio of bcr-abl protein (P210 or P185) to normal abl protein (P145), the latter is ubiquitously expressed in all blood cells, has been established as a criterion for quantitating bcr-abl levels. The bcr-abl/abl protein ratio from 399 patient who were 100% Ph-positive had a mean of 2.47 (standard error [SE] of +/- 0.05); no false negatives were detected. A decreasing ratio was found in patients with decreasing percentages of Ph. The relationship between the ratio of bcr-abl/abl proteins to the percentage of Ph-positive cells was nearly linear in 392 patients with Ph percentages between 5% to 95% (r = 0.97, P < .001). For patients in remission with no detectable Ph, the bcr-abl/abl ratio had a mean of 0.01 (SE = 0 +/- 0.00). The level of bcr-abl expression in samples from peripheral blood and bone marrow also were compared. The results indicated that the amount of bcr-abl protein within peripheral blood is usually similar to that in marrow. In conclusion, quantitation of the bcr-abl oncoprotein in peripheral blood cells or marrow cells as measured by a Western blot assay provides reliable data for both diagnosis and monitoring patients with pH-chromosome positive leukemia.
The impact of budesonide/formoterol on the airway transcriptome in COPD (2014)

We have recently described COPD-associated gene-expression differences in bronchial airway epithelium that define a COPD field of injury. In this study, we sought to validate our COPD gene-expression signature and identify gene-expression changes associated with inhaled budesonide/formoterol (BUD/FORM; Symbicort ® ; 160/4.5 mcg x 2 puffs bid) in COPD patients. Methods: Current and former smokers with (n=15) and without (n=13) COPD were enrolled and underwent baseline collection of bronchial epithelium via bronchoscopy. Re-sampling was performed on 10 COPD subjects after initiation of BUD/FORM therapy (median 97 days). RNA was hybridized to arrays. A linear model adjusting for age was used to identify gene expression changes associated with baseline COPD status, while changes associated with therapy were found using a paired t-test within COPD subjects. Relationships with previously published signatures were assessed using GSEA. Results: Expression levels of 496 genes were altered at baseline in COPD subjects (p<0.05). Importantly, our previous 98-gene airway field of injury signature was enriched in this independent cohort (p<0.001). Expression levels of 896 genes were altered following BUD/FORM therapy (p<0.05). The 50 genes most repressed in COPD subjects were enriched in the group of genes increased by BUD/FORM (p<0.001). Conclusions: Our study shows that components of the COPD-associated alterations in airway gene-expression are reversible following short-term budesonide/formoterol treatment. This suggests that the airway field of injury in COPD is dynamic with therapy, raising the possibility that molecular profiles in the relatively accessible airway epithelium may serve as markers of therapeutic efficacy.
Discovery of an Oral Respiratory Syncytial Virus (RSV) Fusion Inhibitor (GS-5806) and Clinical Proof of Concept in a Human RSV Challenge Study (2015)

GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral efficacy in the cotton rat model of RSV infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a mean 4.2 log10 reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported.
Discovery of a PFKFB3 inhibitor for phase I trial testing that synergizes with the B-Raf inhibitor vemurafenib (2014)

Background In human cancers, loss of PTEN, stabilization of hypoxia inducible factor-1a, and activation of Ras and AKT converge to increase the activity of a regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). This enzyme synthesizes fructose-2,6-bisphosphate (F2,6BP), which is an activator of 6-phosphofructo1-kinase, a key step of glycolysis that is tightly controlled by multiple metabolic feedback mechanisms. We recently identified the first competitive small molecule inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), and have now sought to develop a more potent PFKFB3 inhibitor with improved PK properties for testing in clinical trials. Materials and methods Methods included recombinant PFKFB3 assays, PK studies using mass spectrometry, pre-clinical toxicity and efficacy studies, Western blot analyses for HIF-1a and PFKFB3 in A375 melanoma cells, F2,6BP assessments and flow cytometry for apoptosis. Results
A new integrated neutron/gamma radioisotope identification device evaluated under mixed radiation fields (2008)

Hand-Held RadioIsotope Identification Devices (HHRIID) are defined as a new class of portable neutron/gamma radiation detectors with specifications presented in the ANSI Standards N42.33 and N42.34. We have proposed a novel HHRIID design concept which uses a single photosensor to detect light emitted by two optically separated scintillator materials, one optimized for gamma detection and the other optimized for neutron detection. This work describes the performance of a modified charge integration discrimination method developed to test the viability of the new design. The scintillators chosen for the experiment were LYSO and ZnS:Ag/LiF.
Optimization of Cylindrical Hall Thrusters (2007)

The cylindrical Hall thruster features high ionization efficiency, quiet operation, and ion acceleration in a large volume-to-surface ratio channel with performance comparable with the state-of-the-art annular Hall thrusters. These characteristics were demonstrated in low and medium power ranges. Optimization of miniaturized cylindrical thrusters led to performance improvements in the 50-200W input power range, including plume narrowing, increased thruster efficiency, reliable discharge initiation, and stable operation. __________________________________________________
A 600-Mb/s encoder and decoder for low-density parity-check convolutional codes (2008)

A 600-Mb/s rate-1/2 (128,3,6) LDPC convolutional code encoder and decoder was implemented in a 90-nm CMOS process. The encoder operates at 1.1 GHz and includes built-in all-phase termination. The decoder design maximizes throughput while minimizing the number of memory banks and delivering an information throughput of 1 bit per clock cycle. The size of the decoder controller is minimized by sharing it among an arbitrary number of decoder processors. The decoder dissipates 0.61 nJ of energy per decoded information bit at an SNR of 2.0 and a throughput of 600 Mb/s. An integrated test system enables accurate power measurements for various SNR settings.
Power Engineering Letters Nighttime Application of PV Solar Farm as STATCOM to Regulate Grid Voltage (2009)

This letter presents a novel concept of utilizing pho- tovoltaic (PV) solar farm (SF) as a flexible ac transmission systems controller—static synchronous compensator, to regulate the point of common coupling voltage during nighttime when the SF is not producing any active power. This concept, although general, is pre- sented for the scenario of a distribution feeder, which has both PV solar and wind farms connected to it. The proposed control will en- able increased connections of renewable energy sources in the grid. A MATLAB/Simulink-based simulation study is presented under variable wind power generation and fault condition to validate the proposed concept. Index Terms—Distributed generation, flexible ac transmission systems (FACTS), solar energy, static synchronous compensator (STATCOM), voltage regulation, wind energy.
HIV-1 Nef targets calnexin: a novel mechanism behind Nef effects on host cell and viral proteins (2013)

HIV-1 Nef is a pleiotropic modulator of various cellular signaling proteins and cell surface receptors. It conditions cells for viral replication by aiding in immune evasion and priming T-cell activation, and also enhances HIV-1 infectivity by a poorly defined mechanism. Most of described effects of Nef, such as downregulation of CD4 and MHC I, involve Nef binding to the target protein and directing it to a degradation pathway. We have demonstrated previously that Nef causes degradation and functional impairment of ABCA1, the major cellular cholesterol transporter, an effect that likely contributes to low HDL levels and high risk of atherosclerosis in HIV-infected patients. Surprisingly, direct interaction between Nef and ABCA1 was not required for ABCA1 inactivation. Here we investigated the mechanism of this Nef activity using proteomics, co-immunoprecipitation, mutagenesis, confocal microscopy, and subcellular fractionation approaches. These studies identified calnexin, an endoplasmic reticulum (ER) resident lectin-like chaperone, as an essential partner of ABCA1 and a target of Nef, and characterized Nef- calnexin interaction and its effects on interactions between calnexin and its other partners, such as gp160. We demonstrated that Nef binds to calnexin and increases affinity and enhances interaction of calnexin with HIV-1 gp160, but disrupts calnexin interaction with ABCA1. Interaction with calnexin is essential for functionality of both these proteins, as knock-down of calnexin led to reduced infectivity of HIV-1, as well as to defective cholesterol efflux. However, gp160 and ABCA1 interacted with calnexin differently: while gp160 binding to calnexin was dependent on glycosylation, glycosylation was of little importance for interaction between ABCA1 and calnexin. Thus, Nef binding appears to induce a conformational change in calnexin that stimulates glycosylation-dependent interaction of calnexin with gp160 at the expense of glycosylation-independent interaction with ABCA1. This study identifies a novel mechanism for Nef-dependent inactivation of ABCA1, provides an additional explanation for the effect of Nef on HIV-1 infectivity, and suggests a number of other potential targets of this new Nef activity.
Advances in II-VI Blue-Green Laser Diodes (1993)

Significant progress toward the development of viable blue and green II-VI laser diodes (LDs) was made since the initial demonstration of these devices in our laboratory nearly 2 years ago [1]. Lasing was obtained in the pulsed mode at room temperature [2] with threshold current densities less than 1000 A/cm 2 and continuous wave devices have been operated at 80 K. It is also important to note that several other laboratories succeeded in confirming laser oscillation in related structures [4-10]. Some recent advances in II-VI laser diodes include the development of electrical contacts to p -type ZnSe with lower contact resistances, the growth of high quality lattice matched ternaries and the realization of increased efficiencies in Cd X Zn 1−X Se quantum wells grown by atomic layer epitaxy.
Internal Gas Composition and Pressure in As-drawn Hollow Core Optical Fibers (2022)

We present a study into the gas pressure and composition within a hollow core optical fiber immediately after fabrication. Results from three different experimental techniques indicate that the initial absolute pressure inside of the hollow core is significantly lower than atmospheric pressure. By measuring the equilibrium height to which water ingresses into the hollow core, we estimate the absolute internal gas pressure to be 20 kPa < <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{\boldsymbol{P}}_{\boldsymbol{i}}}$</tex-math></inline-formula> < 29 kPa for the fibers reported here that were fabricated using standard techniques. The initial gas composition within the hollow core was studied using Raman and absorption spectroscopy and the evolution of the gas composition provides indirect information about the condition of the silica surfaces inside the fiber. The measurements indicate that these internal surfaces become saturated with atmospheric water vapor as this is drawn into the open-ended fiber, initially due to a pressure gradient post-fabrication. Our findings are an essential foundation for the study of long-term optical and mechanical performance of hollow core fibers and important for accurate characterization of these specialty fibers. The first is becoming increasingly important as commercial applications of these fibers expand.
Design of virus-based nanomaterials for medicine, biotechnology, and energy (2016)

This review provides an overview of recent developments in "chemical virology." Viruses, as materials, provide unique nanoscale scaffolds that have relevance in chemical biology and nanotechnology, with diverse areas of applications. Some fundamental advantages of viruses, compared to synthetically programmed materials, include the highly precise spatial arrangement of their subunits into a diverse array of shapes and sizes and many available avenues for easy and reproducible modification. Here, we will first survey the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities. We will then examine the broad range of applications and implications of virus-based materials, focusing on the medical, biotechnology, and energy sectors. We anticipate that this field will continue to evolve and grow, with exciting new possibilities stemming from advancements in the rational design of virus-based nanomaterials.