gebhart/patrepeval huggingface dataset:
Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease (2016)

Alpha-1 antitrypsin (AAT) deficiency, characterized by low plasma levels of the serine protease inhibitor AAT, is associated with emphysema secondary to insufficient protection of the lung from neutrophil proteases. Although AAT augmentation therapy with purified AAT protein is efficacious, it requires weekly to monthly intravenous infusion of AAT purified from pooled human plasma, has the risk of viral contamination and allergic reactions, and is costly. As an alternative, gene therapy offers the advantage of single administration, eliminating the burden of protein infusion, and reduced risks and costs. The focus of this review is to describe the various strategies for AAT gene therapy for the pulmonary manifestations of AAT deficiency and the state of the art in bringing AAT gene therapy to the bedside.
Completions and Stimulations for Coalbed Methane Wells (1995)

Abstract Amoco is producing coalbed methane from several hundred wells in both San Juan and Warrior basins. These wells were completed/stimulated in one of two ways: (1) openhole cavity completions, (2) hydraulic fracture stimulations through perforations in casing. Cavity operations are described, and new data from several cavity completions is presented and analyzed. The latest geomechanics modeling of the formation of cavities in coalbeds is presented. The model allows the growth of a cavity as tensile failure occurs, and computes increases in permeability in a stress-relief zone that extends tens of feet from the well. Critical parameters are given for the success of cavity completions. A pulse interference analysis is discussed: as well as interwell permeability, this can provide information on stress-dependent permeability. Finally, some wells which were originally cavitated did not perform up to expectation, and have been recavitated with remarkable success – these are also examined. Amoco has tried several different kinds of hydraulic fracturing treatments. Results of comparisons between foam fracture, slick water fracture, and gel fracture treatments are presented. Statistical comparisons are given for regions outside of the fairway zone in the San Juan Basin. In the Warrior Basin, water fracture treatments with and without sand have been compared. Lastly, foamed water cleanouts, without sand, have been deployed, and their success is reviewed.
The CpG island searcher: a new WWW resource. (2003)

Clusters of CpG dinucleotides in GC rich regions of the genome called "CpG islands" frequently occur in the 5' ends of genes. Methylation of CpG islands plays a role in transcriptional silencing in higher organisms in certain situations. We have established a CpG-island-extraction algorithm, which we previously developed [Takai and Jones, 2002], on a web site which has a simple user interface to identify CpG islands from submitted sequences of up to 50kb. The web site determines the locations of CpG islands using parameters (lower limit of %GC, ObsCpG/ExpCpG, length) set by the user, to display the value of parameters on each CpG island, and provides a graphical map of CpG dinucleotide distribution and borders of CpG islands. A command-line version of the CpG islands searcher has also been developed for larger sequences. The CpG Island Searcher was applied to the latest sequence and mapping information of human chromosomes 20, 21 and 22, and a total of 2345 CpG islands were extracted and 534 (23%) of them contained first coding exons and 650 (28%) contained other exons. The CpG Island Searcher is available on the World Wide Web at http://www.cpgislands.com or http://www.uscnorris.com/cpgislands/cpg.cgi.
Mortalities associated with use of a commercial suspension of polyvinyl alcohol. (1989)

Two cases of symptomatic neonatal hepatic arteriovenous malformation (AVM) are presented. Both were treated with percutaneous transcatheter embolization and a commercially available polyvinyl alcohol suspension. Both infants died soon after AVM embolization. The results of laboratory examination of particle-size homogeneity of this commercial suspension demonstrate marked inhomogeneity of particle size very probably contributed to the death of these patients. A protocol has been developed to help determine appropriate particle size in individual cases; this may help prevent such catastrophic results during transcatheter embolization.
ChemInform Abstract: The Synthesis of A‐ and B‐Ring Fluorinated Analogues of Cholesterol. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies. (1992)

This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type III collagen was very similar to that of type I, and type VI collagen appeared together with these two types of collagen in the thickened intimas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions.
Structural basis of albumin–thyroxine interactions and familial dysalbuminemic hyperthyroxinemia (2003)

Human serum albumin (HSA) is the major protein component of blood plasma and serves as a transporter for thyroxine and other hydrophobic compounds such as fatty acids and bilirubin. We report here a structural characterization of HSA-thyroxine interactions. Using crystallographic analyses we have identified four binding sites for thyroxine on HSA distributed in subdomains IIA, IIIA, and IIIB. Mutation of residue R218 within subdomain IIA greatly enhances the affinity for thyroxine and causes the elevated serum thyroxine levels associated with familial dysalbuminemic hyperthyroxinemia (FDH). Structural analysis of two FDH mutants of HSA (R218H and R218P) shows that this effect arises because substitution of R218, which contacts the hormone bound in subdomain IIA, produces localized conformational changes to relax steric restrictions on thyroxine binding at this site. We have also found that, although fatty acid binding competes with thyroxine at all four sites, it induces conformational changes that create a fifth hormone-binding site in the cleft between domains I and III, at least 9 A from R218. These structural observations are consistent with binding data showing that HSA retains a high-affinity site for thyroxine in the presence of excess fatty acid that is insensitive to FDH mutations.
Distribution and Regulation of the Mobile Genetic Element-Encoded Phenol-Soluble Modulin PSM-mec in Methicillin-Resistant Staphylococcus aureus (2011)

The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.
Evaluation of a Unique Oral Contraceptive in the Treatment of Premenstrual Dysphoric Disorder (2001)

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.
A Coupled Reservoir and Geomechanical Simulation System (1998)

Summary Current simulation models do not account for the interactions among the geomechanical behavior, formation fracturing and multiphase flow, and heat transfer in porous media. This paper describes a method for modular coupling of a commercial reservoir simulator with a three-dimensional (3D) stress code and fracture-propagation model. The iteratively coupled system is equivalent to a fully coupled solution of flow and stress. The iterative method is very robust. An experience with acceleration of the iteration is described, and the utility of the method is demonstrated on examples. The comparison with an uncoupled solution shows that significantly different (and more realistic) answers are obtained with the coupled modeling. The current limitations and future work are also discussed.
Evaluation of Doxorubicin Cardiotoxicity in Patients Treated Intermittently with Beta-Methyldigoxin (1982)

Twenty-one patients with various advanced neoplasms were treated with 60 to 75 mg/m2 of doxorubicin every 3 to 4 weeks and monitored by ECG and systolic time intervals (PEP/LVET) with the aim to establish whether a pretreatment with beta-methyldigoxin, administered intermittently, could prevent doxorubicin-induced cardiotoxicity. It was found that until patients received digitalis pretreatment the PEP/LVET ratio did not change significantly from mean basal values even after the highest cumulative dosages of doxorubicin. However, after interruption of the therapy with both drugs, PEP/LVET increased reaching a value not significantly different from that observed in a comparable group of patients treated only with doxorubicin. Moreover, of 9 patients who reached the cumulative limiting dose, 2 developed congestive heart failure. These results question the possibility that digitalis administered according to an intermittent treatment scheme may prevent doxorubicin cardiomyopathy.
Microelectronic circuits (1982)

Devices and basic circuits -- Signals and amplifiers -- Operational amplifiers -- Semiconductors -- Diodes -- Mos field-effect transistors (MOSFETS) -- Bipolar junction transistors (BJTS) -- Transistor amplifiers -- Analog integrated circuits -- Building blocks of integrated-circuit amplifiers -- Differential and multistage amplifiers -- Frequency response -- Feedback -- Output stages and power amplifiers -- Operational amplifier circuits -- Filters -- Oscillators -- Digital integrated circuits -- Cmos digital logic circuits -- Digital Design: Power, Speed, and Area -- Memory and Clocking Circuits -- Appendices
Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. (1991)

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.
The Blind Watchmaker (1986)

***30th Anniversary Edition*** Cover note: Each copy of the anniversary edition of The Blind Watchmaker features a unique biomorph. No two covers are exactly alike. Acclaimed as the most influential work on evolution written in the last hundred years, The Blind Watchmaker offers an inspiring and accessible introduction to one of the most important scientific discoveries of all time. A brilliant and controversial book which demonstrates that evolution by natural selection - the unconscious, automatic, blind yet essentially non-random process discovered by Darwin - is the only answer to the biggest question of all: why do we exist?
Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects (2015)

Certain class II MHC (MHCII) alleles in mice and humans confer risk for or protection from type 1 diabetes (T1D). Insulin is a major autoantigen in T1D, but how its peptides are presented to CD4 T cells by MHCII risk alleles has been controversial. In the mouse model of T1D, CD4 T cells respond to insulin B-chain peptide (B:9-23) mimotopes engineered to bind the mouse MHCII molecule, IA(g7), in an unfavorable position or register. Because of the similarities between IA(g7) and human HLA-DQ T1D risk alleles, we examined control and T1D subjects with these risk alleles for CD4 T-cell responses to the same natural B:9-23 peptide and mimotopes. A high proportion of new-onset T1D subjects mounted an inflammatory IFN-γ response much more frequently to one of the mimotope peptides than to the natural peptide. Surprisingly, the control subjects bearing an HLA-DQ risk allele also did. However, these control subjects, especially those with only one HLA-DQ risk allele, very frequently made an IL-10 response, a cytokine associated with regulatory T cells. T1D subjects with established disease also responded to the mimotope rather than the natural B:9-23 peptide in proliferation assays and the proliferating cells were highly enriched in certain T-cell receptor sequences. Our results suggest that the risk of T1D may be related to how an HLA-DQ genotype determines the balance of T-cell inflammatory vs. regulatory responses to insulin, having important implications for the use and monitoring of insulin-specific therapies to prevent diabetes onset.
In vitro formation and characterization of a perfusable three-dimensional tubular capillary network in microfluidic devices (2012)

This paper describes the in vitro formation and characterization of perfusable capillary networks made of human umbilical vein endothelial cells (HUVECs) in microfluidic devices (MFDs). Using this platform, an array of three-dimensional (3D) tubular capillaries of various dimensions (50-150 μm in diameter and 100-1600 μm in length) can be formed reproducibly. To generate connected blood vessels, MFDs were completely filled with fibrin gel and subsequently processed to selectively leave behind gel structures inside the bridge channels. Following gel solidification, HUVECs were coated along the gel walls, on opposite ends of the patterned 3D fibrin gel. After 3-4 days, HUVECs migrating into the fibrin gel from opposite ends fused with each other, spontaneously forming a connected vessel that expressed tight junction proteins (e.g., ZO-1), which are characteristic of post-capillary venules. With ready access to a perfusable capillary network, we demonstrated perfusion of the vessels and imaged red blood cells (RBCs) and beads flowing through them. The results were reproducible (∼50% successful perfusable capillaries), consistent, and could be performed in a parallel manner (9 devices per well plate). Additionally, compatibility with high resolution live-cell microscopy and the possibility of incorporating other cell types makes this a unique experimental platform for investigating basic and applied aspects of angiogenesis, anastomosis, and vascular biology.
Optogenetic Mimicry of the Transient Activation of Dopamine Neurons by Natural Reward Is Sufficient for Operant Reinforcement (2012)

Activation of dopamine receptors in forebrain regions, for minutes or longer, is known to be sufficient for positive reinforcement of stimuli and actions. However, the firing rate of dopamine neurons is increased for only about 200 milliseconds following natural reward events that are better than expected, a response which has been described as a "reward prediction error" (RPE). Although RPE drives reinforcement learning (RL) in computational models, it has not been possible to directly test whether the transient dopamine signal actually drives RL. Here we have performed optical stimulation of genetically targeted ventral tegmental area (VTA) dopamine neurons expressing Channelrhodopsin-2 (ChR2) in mice. We mimicked the transient activation of dopamine neurons that occurs in response to natural reward by applying a light pulse of 200 ms in VTA. When a single light pulse followed each self-initiated nose poke, it was sufficient in itself to cause operant reinforcement. Furthermore, when optical stimulation was delivered in separate sessions according to a predetermined pattern, it increased locomotion and contralateral rotations, behaviors that are known to result from activation of dopamine neurons. All three of the optically induced operant and locomotor behaviors were tightly correlated with the number of VTA dopamine neurons that expressed ChR2, providing additional evidence that the behavioral responses were caused by activation of dopamine neurons. These results provide strong evidence that the transient activation of dopamine neurons provides a functional reward signal that drives learning, in support of RL theories of dopamine function.
Organic Thin-Film Transistors as Plastic Analytical Sensors (2005)

ADVERTISEMENT RETURN TO ISSUEPREVFeaturesNEXTOrganic Thin-Film Transistors as Plastic Analytical SensorsLuisa Torsi and Ananth DodabalapurCite this: Anal. Chem. 2005, 77, 19, 380 A–387 APublication Date (Web):October 1, 2005Publication History Published online1 October 2005Published inissue 1 October 2005https://pubs.acs.org/doi/10.1021/ac053475nhttps://doi.org/10.1021/ac053475nnewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2375Altmetric-Citations132LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (1 MB) Get e-Alertsclose SUBJECTS:Plastics,Sensors,Transistors Get e-Alerts
Thermal expression of intersubjectivity offers new possibilities to humanâ€“machine and technologically mediated interactions (2014)

The evaluation of the psychophysiological state of the interlocutor is an important element of interpersonal relationships and communication. Thermal infrared (IR) imaging has proved to be a reliable tool for non-invasive and contact-less evaluation of vital signs, psychophysiological responses, and emotional states. This technique is quickly spreading in many fields, from psychometrics to social and developmental psychology; and from the touch-less monitoring of vital signs and stress, up to the human-machine interaction. In particular, thermal IR imaging promises to be of use for gathering information about affective states in social situations. This paper presents the state of the art of thermal IR imaging in psychophysiology and in the assessment of affective states. The goal is to provide insights about its potentialities and limits for its use in human-artificial agent interaction in order to contribute to a major issue in the field: the perception by an artificial agent of human psychophysiological and affective states.