gebhart/patrepeval huggingface dataset:
Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity in this syndrome. (1988)

The cloning of a cDNA for the human androgen receptor gene has resulted in the availability of cDNA probes that span various parts of the gene, including the entire steroid-binding domain and part of the DNA-binding domain, as well as part of the 5' region of the gene. The radiolabeled probes were used to screen for androgen receptor mutations on Southern blots prepared by restriction endonuclease digestion of genomic DNA from human subjects with complete androgen insensitivity syndrome (AIS). In this investigation, we considered only patients presenting complete AIS and with the androgen receptor (-) form as the most probable subjects to show a gene deletion. One subject from each of six unrelated families with the receptor (-) form of complete AIS and 10 normal subjects (6 females and 4 males) were studied. In the 10 normal subjects and in 5 of the 6 patients, identical DNA restriction fragment patterns were observed with EcoRI and BamHI. In one affected individual, a partial deletion of the androgen receptor gene involving the steroid-binding domain was detected. Analysis of other members of this family confirmed the apparent gene deletion. Our data provide direct proof that complete AIS in some families can result from a deletion of the androgen receptor structural gene. However, other families do not demonstrate such a deletion, suggesting that point mutations (or small, undetectable deletions) may also result in the receptor (-) form of complete AIS, adding further to the genetic heterogeneity of this syndrome.
Identification of the Potassium Channel Opener Site on Sulfonylurea Receptors (1999)

Diversity of sulfonylurea receptor (SUR) subunits underlies tissue specific pharmacology of K(ATP) channels, which represent critical regulators of electrical activity in numerous cells. Notably, the neuronal/pancreatic beta-cell receptor, SUR1, imparts high sensitivity to hypoglycemic sulfonylureas (SUs; e.g. glibenclamide) and low to potassium channel openers (KCOs; e.g. P1075), whereas the opposite drug sensitivities are conferred by cardiovascular receptors, SUR2A and SUR2B. By exchanging domains between SUR1 and SUR2B, we identify two regions (KCO I: Thr(1059)-Leu(1087) and KCO II: Arg(1218)-Asn(1320); rat SUR2 numbering) within the second set of transmembrane domains (TMDII) as critical for KCO binding. Swapping both regions reconstitutes KCO affinities and sensitivities of the donor SUR isoform. High glibenclamide affinity of SUR1 is not reduced by transfer of KCO I plus II from SUR2B, demonstrating that high SU and KCO affinity can coexist in the same SUR molecule. Consistently, high SU affinity was imparted on SUR2B by substituting the region separating KCO I and II (Ile(1088)-Val(1217)) with the corresponding domain of SUR1. We infer the receptor sites for KCOs and SUs to be closely associated within a regulatory domain (Thr(1059)-Asn(1320)) in TMDII of SURs.
A distinct cyclin-dependent kinase-activating kinase of Arabidopsis thaliana (1998)

The activation of cyclin-dependent kinases (CDKs) requires phosphorylation of a threonine residue within the T-loop catalyzed by CDK-activating kinases (CAKs). Thus far no functional CAK homologue has been reported in plants. We screened an Arabidopsis cDNA expression library for complementation of a budding yeast CAK mutant. A cDNA, cak1At, was isolated that suppressed the CAK mutation in budding yeast, and it also complemented a fission yeast CAK mutant. cak1At encodes a protein related to animal CAKs. The CAK similarity was restricted to the conserved kinase domains, leading to classification of Cak1At as a distinct CDK in the phylogenetic tree. Immunoprecipitates with the anti-Cak1At antibody phosphorylated human CDK2 at the threonine residue (T160) within the T-loop and activated its activity to phosphorylate histone H1. Whereas CAKs in animals and fission yeast are involved in regulation of the cell cycle and basal transcription by phosphorylating the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II, Cak1At did not phosphorylate the CTD. An Arabidopsis CTD-kinase isolated separately from Cak1At was shown to interact with the yeast protein p13(suc1), but it had no CDK2-kinase activity. Therefore, the CTD of RNA polymerase II is probably phosphorylated by a Cdc2-related kinase distinct from Cak1At. cak1At is a single-copy gene in Arabidopsis and is highly expressed in proliferating cells of suspension cultures.
A Schrödinger cat living in two boxes (2016)

Quantum superpositions of distinct coherent states in a single-mode harmonic oscillator, known as "cat states," have been an elegant demonstration of Schrödinger's famous cat paradox. Here, we realize a two-mode cat state of electromagnetic fields in two microwave cavities bridged by a superconducting artificial atom, which can also be viewed as an entangled pair of single-cavity cat states. We present full quantum state tomography of this complex cat state over a Hilbert space exceeding 100 dimensions via quantum nondemolition measurements of the joint photon number parity. The ability to manipulate such multicavity quantum states paves the way for logical operations between redundantly encoded qubits for fault-tolerant quantum computation and communication.
Promoter Elements Determining Weak Expression of the GAL4 Regulatory Gene of Saccharomyces cerevisiae (1993)

The GAL4 gene of Saccharomyces cerevisiae (encoding the activator of transcription of the GAL genes) is poorly expressed and is repressed during growth on glucose. To determine the basis for its weak expression and to identify DNA sequences recognized by proteins that activate transcription of a gene that itself encodes an activator of transcription, we have analyzed GAL4 promoter structure. We show that the GAL4 promoter is about 90-fold weaker than the strong GAL1 promoter and at least 7-fold weaker than the feeble URA3 promoter and that this low level of GAL4 expression is primarily due to a weak promoter. By deletion mapping, the GAL4 promoter can be divided into three functional regions. Two of these regions contain positive elements; a distal region termed the UASGAL4 (upstream activation sequence) contains redundant elements that increase promoter function, and a central region termed the UESGAL4 (upstream essential sequence) is essential for even basal levels of GAL4 expression. The third element, an upstream repression sequence, mediates glucose repression of GAL4 expression and is located between the UES and the transcriptional start site. The UASGAL4 is unusual because it is not interchangable with UAS elements in other yeast promoters; it does not function as a UAS element when inserted in a CYC1 promoter, and a normally strong UAS functions poorly in place of UASGAL4 in the GAL4 promoter. Similarly, the UES element of GAL4 does not function as a TATA element in a test promoter, and consensus TATA elements do not function in place of UES elements in the GAL4 promoter. These results suggest that GAL4 contains a weak TATA-less promoter and that the proteins regulating expression of this regulatory gene may be novel and context specific.
Gene of the month: KRAS (2013)

This is a general overview of KRAS, its structure and role in pertinent cancers. Also its role in determining adjuvant therapy is discussed.
Antibacterial properties of spinel ferrite nanoparticles (2013)

This book chapter is organized into four major parts. Firstly, it will cover an introduction of using spinel ferrite nanoparticles in biomedical applications, including the antibacterial properties. The second part will provide an overview of the structure and magnetism of spinel ferrites. The third part will focus on the preparation of cobalt ferrite and transition metal substituted cobalt ferrite nanoparticles by sol-gel methods. The last part will highlight the influence of transition metal concentration on the physical properties, and antibacterial property of transition metal substituted cobalt ferrite nanoparticles. A discussion on the mechanisms for the antibacterial properties will be presented.
Detecting drug-drug interactions between therapies for COVID-19 and concomitant medications through the FDA adverse event reporting system (2022)

<b>Background:</b> COVID-19 patients with underlying medical conditions are vulnerable to drug-drug interactions (DDI) due to the use of multiple medications. We conducted a discovery-driven data analysis to identify potential DDIs and associated adverse events (AEs) in COVID-19 patients from the FDA Adverse Event Reporting System (FAERS), a source of post-market drug safety. <b>Materials and Methods:</b> We investigated 18,589 COVID-19 AEs reported in the FAERS database between 2020 and 2021. We applied multivariate logistic regression to account for potential confounding factors, including age, gender, and the number of unique drug exposures. The significance of the DDIs was determined using both additive and multiplicative measures of interaction. We compared our findings with the Liverpool database and conducted a Monte Carlo simulation to validate the identified DDIs. <b>Results:</b> Out of 11,337 COVID-19 drug-Co-medication-AE combinations investigated, our methods identified 424 signals statistically significant, covering 176 drug-drug pairs, composed of 13 COVID-19 drugs and 60 co-medications. Out of the 176 drug-drug pairs, 20 were found to exist in the Liverpool database. The empirical <i>p</i>-value obtained based on 1,000 Monte Carlo simulations was less than 0.001. <i>Remdesivir</i> was discovered to interact with the largest number of concomitant drugs (41). <i>Hydroxychloroquine</i> was detected to be associated with most AEs (39). Furthermore, we identified 323 gender- and 254 age-specific DDI signals. <b>Conclusion:</b> The results, particularly those not found in the Liverpool database, suggest a subsequent need for further pharmacoepidemiology and/or pharmacology studies.
INNOVATIONS IN PALLADIUM MEMBRANE RESEARCH (2002)

This review highlights various aspects of current palladium membrane research and serves as a comprehensive bibliography covering palladium membrane preparation methods and applications. There are many promising uses for palladium membranes, although widespread use of the available technologies is constrained primarily by the high cost of palladium, lack of durability due to hydrogen embrittlement, and susceptibility to fouling. Various researchers in the field are tackling these problems and fabricating thinner palladium alloy composite membranes that better withstand contaminantion and thermal cycling. What has been accomplished to address these issues and the directions presently being explored are discussed.
BioBricks++: Simplifying Assembly of Standard DNA Components (2004)

Construction of complex biological systems can require assembling many modules together. However, existing assembly schemes are lacking in generality, ease of use, or power to perform some desirable operations. Currently, biological modules are most easily specified and manipulated as DNA sequences. A general system, called BioBricks++, for assembling and manipulating DNA modules is proposed. BioBricks++ was inspired by the BioBricks assembly scheme but provides for more possible module operations. BioBricks++ uses commercially available restriction enzymes and standard biological techniques for assembling modules. The key to the method is in the specification of the standard DNA module. Modules are packaged with a standard prefix and suffix DNA sequence containing several restriction enzyme sites, which are used for different module operations. The following operations can be performed on all BioBricks++ modules. The most fundamental operation is the arbitrary assembly of any two modules. In addition, the assembly of the two modules can be made seamless, with no extra intervening sequence inserted between the modules. Modules can also be easily reversed with no extra bases added during the operation. Another useful capability is being able to remove bases from either end of a module, allowing for operations such as protein fusions or addition of tags.
Using Address Independent Seed Encryption and Bonsai Merkle Trees to Make Secure Processors OS- and Performance-Friendly (2007)

In today's digital world, computer security issues have become increasingly important. In particular, researchers have proposed designs for secure processors which utilize hardware-based memory encryption and integrity verification to protect the privacy and integrity of computation even from sophisticated physical attacks. However, currently proposed schemes remain hampered by problems that make them impractical for use in today's computer systems: lack of virtual memory and inter-process communication support as well as excessive storage and performance overheads. In this paper, we propose 1) address independent seed encryption (AISE), a counter-mode based memory encryption scheme using a novel seed composition, and 2) Bonsai Merkle trees (BMT), a novel Merkle tree-based memory integrity verification technique, to eliminate these system and performance issues associated with prior counter-mode memory encryption and Merkle tree integrity verification schemes. We present both a qualitative discussion and a quantitative analysis to illustrate the advantages of our techniques over previously proposed approaches in terms of complexity, feasibility, performance, and storage. Our results show that AISE+BMT reduces the overhead of prior memory encryption and integrity verification schemes from 12% to 2% on average, while eliminating critical system-level problems.
A mathematical model for the growth of a single cell of E. coli on a glucose/glutamine/ammonium medium (1989)

Extension of a single cell model of E. coli B/r to make predictions of culture response to variations in glutamine/glucose/ammonium ion concentrations is described. A biphasic glutamine transport system, a nitrogen metabolism scheme that includes glutamate dehydrogenase (GDH), glutamine synthetase/glutamate synthase (GS/GOGAT), the glutaminase routes, and a transaminase mechanism for glutamine carbon usage are added to the prototype model. The predictions of the extended model with regard to nutrient concentrations and cell size compare well with the experimental data and the prototype model predictions, demonstrating the capability of the integrated kinetic model to illustrate important enzymological interactions in a biological system. The discrepancies between the experimental data and the model predictions on growth yield suggest that a more detailed regulatory system of the TCA cycle is required for a more accurate energy budget.
Complete Deficiency of Plasminogen-Activator Inhibitor Type 1 Due to a Frame-Shift Mutation (1992)

THE process of plasminogen activation is considered a critical component of diverse biologic systems in humans. This reaction, which is catalyzed in vivo by tissue-type and urokinase-type plasminogen activators, results in the conversion of plasminogen to plasmin. Plasmin has an essential role in maintaining vascular patency by converting fibrin to soluble fibrin-degradation products. In addition, plasminogen activators have been implicated in the regulation of embryogenesis, angiogenesis, ovulation, inflammation, and tumor metastasis,1 suggesting that the plasminogen-activation system is an important mediator of tissue remodeling and cell migration. The activity of plasminogen activators is precisely regulated by several mechanisms.1 Critical among these . . .
Graphite‐Silicon‐Polyacrylate Negative Electrodes in Ionic Liquid Electrolyte for Safer Rechargeable Li‐Ion Batteries (2011)

Graphite/silicon composite electrodes are prepared with PANa polymer as a binder. Morphological characters and electrode performance are compared with those of PVdF. The PANa layer behaves like SEI at the interface with ionic liquid, resulting in the highly reversible electrode performance. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Three-dimensional integrated circuits for low-power, high-bandwidth systems on a chip (2002)

Shows the feasibility of stacking SOI circuits to build 3D-ICs with dense vertical interconnects; the results are being applied to develop higher performance systems. Low-power circuits with three metal levels are fabricated with a 0.25/spl mu/m fully-depleted SOI technology. Three or more circuit layers are stacked and connected with 3D vias whose size, pitch, and resistance will be decreased by replacing the adhesive process with low temperature oxide bonding and utilizing tungsten plugs to fill high-aspect-ratio vias.
Nonlinear Dynamics Forecasting of Obstructive Sleep Apnea Onsets (2016)

Recent advances in sensor technologies and predictive analytics are fueling the growth in point-of-care (POC) therapies for obstructive sleep apnea (OSA) and other sleep disorders. The effectiveness of POC therapies can be enhanced by providing personalized and real-time prediction of OSA episode onsets. Previous attempts at OSA prediction are limited to capturing the nonlinear, nonstationary dynamics of the underlying physiological processes. This paper reports an investigation into heart rate dynamics aiming to predict in real time the onsets of OSA episode before the clinical symptoms appear. A prognosis method based on a nonparametric statistical Dirichlet-Process Mixture-Gaussian-Process (DPMG) model to estimate the transition from normal states to an anomalous (apnea) state is utilized to estimate the remaining time until the onset of an impending OSA episode. The approach was tested using three datasets including (1) 20 records from 14 OSA subjects in benchmark ECG apnea databases (Physionet.org), (2) records of 10 OSA patients from the University of Dublin OSA database and (3) records of eight subjects from previous work. Validation tests suggest that the model can be used to track the time until the onset of an OSA episode with the likelihood of correctly predicting apnea onset in 1 min to 5 mins ahead is 83.6 ± 9.3%, 80 ± 8.1%, 76.2 ± 13.3%, 66.9 ± 15.4%, and 61.1 ± 16.7%, respectively. The present prognosis approach can be integrated with wearable devices, enhancing proactive treatment of OSA and real-time wearable sensor-based of sleep disorders.
Experimental rhinovirus infection in volunteers (1996)

Experimental viral disease studies in volunteers have clarified many aspects of the pathogenesis of human viral disease. Recently, interest has focused on rhinovirus-associated asthma exacerbations, and new volunteer studies have suggested that airway responsiveness (AR) is enhanced during a cold. For scientific, ethical and safety reasons, it is important to use validated methods for the preparation of a virus inoculum and that the particular virological characteristics and host responses should not be altered. We have prepared a new human rhinovirus (HRV) inoculum using recent guidelines and assessed whether disease characteristics (for example, severity of colds or changes in AR) were retained. Studies were conducted in 25 clinically healthy volunteers using a validated HRV inoculum in the first 17 and a new inoculum in the subsequent eight subjects. Severity of cold symptoms, nasal wash albumin levels and airway responsiveness were measured, and the new inoculum was prepared from nasal washes obtained during the cold. The new inoculum was tested using standard virological and serological techniques, as well as a polymerase chain reaction for Mycoplasma pneumoniae. No contaminating viruses or organisms were detected and the methods suggested were workable. Good clinical colds developed in 20 of the 25 subjects and median symptom scores were similar in the validated and new inoculum groups (18 and 17.5, respectively; p=0.19). All subjects shed virus, and there were no differences noted in viral culture scores, nasal wash albumin and rates of seroconversion in the two groups. Although airway responsiveness increased in both groups (p=0.02 and p=0.05), the degree of change was similar. We have performed experimental rhinovirus infection studies and demonstrated similar clinical disease in two inoculum groups. Amplified airway responsiveness was induced; continuing studies will define the mechanisms and suggest modes of treatment.
Hydrogenation of p-type gallium nitride (1994)

Hole concentrations of up to 1019 cm−3 have been reported for GaN:Mg films grown by molecular beam epitaxy without any post-growth treatment. Comparing results from Hall measurements and secondary ion mass spectrometry, we observe doping efficiencies of up to 10% at room temperatures in such p-type material. By hydrogenating at temperatures above 500 °C, the hole concentration can be reduced by an order of magnitude. A new photoluminescence line at 3.35 eV is observed after this treatment, both in p-type and unintentionally doped n-type material, which suggests the introduction of a hydrogen-related donor level in GaN.
Increased Levels of Serum Interferon-gamma in Pulmonary Sarcoidosis and Relationship with Response to Corticosteroid Therapy (1991)

The aim of this study was to evaluate serum levels of the lymphokine interferon-gamma (IFNg) in patients with chronic pulmonary sarcoidosis, and to investigate its value as a predictive marker of clinical response to corticosteroid therapy. Twenty-five patients and 28 age-matched control subjects were studied. All the patients had parenchymal shadows (Stage II or Stage III) and none had clinical evidence of extrathoracic disease. Before therapy, serum IFNg levels were significantly higher in the patient group (p less than 0.001), and 20 (80%) had values above the normal range. After oral treatment with corticosteroids for a median 13 months (range, 3 to 49 months) the levels decreased significantly (p less than 0.01). However, the falls were less pronounced in patients who had a better outcome in terms of achieving complete radiographic resolution and in those who improved in forced vital capacity by greater than or equal to 10%. The prognostic value of the pretreatment serum IFNg was explored, and a significant relationship was found between higher pretreatment levels and lower grades or radiographic abnormality assessed 3 yr after commencement of treatment (p less than 0.01). In addition, the patients who had cleared completely while receiving steroids and remained in remission had significantly higher pretreatment serum IFNg levels than did those with incomplete resolution of parenchymal shadows or radiographic relapses (p less than 0.05). We conclude that elevated levels of circulating IFNg are detectable in most untreated patients with Stage II/III pulmonary sarcoidosis and that patients with the highest levels appear to have a better chance of achieving complete resolution with corticosteroid therapy.