gebhart/patrepeval huggingface dataset:
Distinct class of putative “non-conserved” promoters in humans: Comparative studies of alternative promoters of human and mouse genes (2007)

Although recent studies have revealed that the majority of human genes are subject to regulation of alternative promoters, the biological relevance of this phenomenon remains unclear. We have also demonstrated that roughly half of the human RefSeq genes examined contain putative alternative promoters (PAPs). Here we report large-scale comparative studies of PAPs between human and mouse counterpart genes. Detailed sequence comparison of the 17,245 putative promoter regions (PPRs) in 5463 PAP-containing human genes revealed that PPRs in only a minor fraction of genes (807 genes) showed clear evolutionary conservation as one or more pairs. Also, we found that there were substantial qualitative differences between conserved and non-conserved PPRs, with the latter class being AT-rich PPRs of relative minor usage, enriched in repetitive elements and sometimes producing transcripts that encode small or no proteins. Systematic luciferase assays of these PPRs revealed that both classes of PPRs did have promoter activity, but that their strength ranges were significantly different. Furthermore, we demonstrate that these characteristic features of the non-conserved PPRs are shared with the PPRs of previously discovered putative non-protein coding transcripts. Taken together, our data suggest that there are two distinct classes of promoters in humans, with the latter class of promoters emerging frequently during evolution.
A specifier's introduction to formal methods (1990)

Formal methods used in developing computer systems (i.e. mathematically based techniques for describing system properties) are defined, and their role is delineated. Formal specification languages, which provide the formal method's mathematical basis, are examined. Certain pragmatic concerns about formal methods and their users, uses, and characteristics are discussed. Six well-known or commonly used formal methods are illustrated by simple examples. They are Z, VDM, Larch, temporal logic, CSP, and transition axioms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of metal salts on poly(DL-lactide-co-glycolide) polymer hydrolysis (1997)

The effects of encapsulated metal salts on poly(DL-lactide-co-glycolide) (PLGA) water uptake and degradation properties were investigated in this work. Salts of varying aqueous solubility characteristics were incorporated into PLGA films either as particles or by codissolution in polymer solutions. Polymer films were characterized with respect to the kinetics of water uptake, morphology changes, degradation, and weight loss after hydration. It was found that these properties are strongly influenced by the presence and nature of encapsulated salts. Effects range from minor changes in water uptake profile with no significant difference in degradation kinetics to major alterations in water uptake kinetics together with a several-fold decrease in the polymer degradation rate. Possible mechanistic explanations for the observed effects are discussed.
Human Anti-IgG1 Hinge Autoantibodies Reconstitute the Effector Functions of Proteolytically Inactivated IgGs (2008)

A number of proteases of potential importance to human physiology possess the ability to selectively degrade and inactivate Igs. Proteolytic cleavage within and near the hinge domain of human IgG1 yielded products including Fab and F(ab')(2) possessing full Ag binding capability but absent several functions needed for immune destruction of cellular pathogens. In parallel experiments, we showed that the same proteolytically generated Fabs and F(ab')(2)s become self-Ags that were widely recognized by autoantibodies in the human population. Binding analyses using various Fab and F(ab')(2), as well as single-chain peptide analogues, indicated that the autoantibodies targeted the newly exposed sequences where proteases cleave the hinge. The point of cleavage may be less of a determinant for autoantibody binding than the exposure of an otherwise cryptic stretch of hinge sequence. It was noted that the autoantibodies possessed an unusually high proportion of the IgG3 isotype in contrast to Abs induced against foreign immunogens in the same human subjects. In light of the recognized potency of IgG3 effector mechanisms, we adopted a functional approach to determine whether human anti-hinge (HAH) autoantibodies could reconstitute the (missing) Fc region effector functions to Fab and F(ab')(2). Indeed, in in vitro cellular assays, purified HAH autoantibodies restored effector functions to F(ab')(2) in both Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays. The results indicate that HAH autoantibodies selectively bind to proteolytically cleaved IgGs and can thereby provide a surrogate Fc domain to reconstitute cell lytic functions.
Bacteriophage T7 late promoters with point mutations: quantitative footprinting andin vivoexpression (1988)

Journal Article Bacteriophage T7 late promoters with point mutations: quantitative footprinting and in vivo expression Get access Kenneth A. Chapman, Kenneth A. Chapman * McArdle Laboratory for Cancer Research, University of WisconsinMadison, WI 53706, USA + Present addresses: MSU-DOE Plant Reseach Laboratory, Michigan State University, East Lansing, MI 48824 * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Samuel I. Gunderson, Samuel I. Gunderson McArdle Laboratory for Cancer Research, University of WisconsinMadison, WI 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Anello, Michael Anello McArdle Laboratory for Cancer Research, University of WisconsinMadison, WI 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert D. Wells, Robert D. Wells McArdle Laboratory for Cancer Research, University of WisconsinMadison, WI 53706, USA § Department of Biochemistry, University of Alabama at Birmingham, Schools of Medicine and Dentistry Birmingham, AL 35294, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard R. Burgess Richard R. Burgess McArdle Laboratory for Cancer Research, University of WisconsinMadison, WI 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 10, 25 May 1988, Pages 4511–4524, https://doi.org/10.1093/nar/16.10.4511 Published: 25 May 1988 Article history Received: 12 January 1988 Revision received: 14 April 1988 Accepted: 14 April 1988 Published: 25 May 1988
Double fluorescent vital assay of phagocytosis by cultured retinal pigment epithelial cells. (1993)

This relatively simple new method is useful in that it uses inexpensive, readily available reagents, it enables real-time analysis of phagocytosis experiments, and it does not require termination of the cultures for analysis of phagocytic ability.
Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies. (2000)

Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor activity in murine tumor models. Putative mechanisms of action include activation of the transforming growth factor beta pathway and/or inhibition of p21ras signaling, leading to differentiation or apoptosis. In this Phase I trial, 17 patients took POH p.o. three times daily for 14 days of each 28-day cycle. The starting dose of POH was 1600 mg/m2/dose, with escalations to 2100 and 2800 mg/m2/dose in subsequent cohorts. Chronic nausea and fatigue were dose-limiting toxic effects at 2800 mg/m2. Grade 1-2 hypokalemia was common at 2100 and 2800 mg/m2. Although POH could not be detected in plasma, two of its metabolites, dihydroperillic acid (DHPA) and perillic acid (PA), were measured in plasma and urine on days 1 and 15 after the first and last doses of POH, respectively. Both area under the concentration versus time curve and peak plasma concentration (Cmax) values increased with dose and exhibited high intersubject variability. Day 15 DHPA Cmax values ranged from a mean +/- SD of 22.6+/-12 microM at 1600 mg/m2/dose to 42.4+/-15.24 microM at 2800 mg/m2/dose. Corresponding mean +/- SD Cmax values for PA were 433.2+/-245.8 and 774.1+/-439.6 microM. One patient treated at the 2800 mg/m2/dose had markedly prolonged plasma levels of both PA and DHPA and developed grade 3 mucositis. POH treatment did not consistently alter the expression of p21ras, rap1, or rhoA in peripheral blood mononuclear cells obtained from patients treated at the highest dose level. The metabolites PA and DHPA did not change expression or isoprenylation of p21ras in MCF-7 breast or DU145 prostate carcinoma cells at concentrations that exceeded those achieved in patient plasma after POH treatment. We conclude that POH at 1600-2100 mg/m2 p.o. three times daily is well tolerated on a 14-day on/14-day off dosing schedule. Inhibition of p21ras function in humans is not likely to occur after POH administration at safe doses of the present oral formulation.
Research on generalized random petri net GSPN-based methods of safety analysis (2007)

The method of safety analysis for the dynamic systems based on the generalized stochastic Petri nets(GSPN) has been systematically researched in this paper.Based on the basic principle of the Petri Net and GSPN models,a search algorithm of the critical state has been presented and the security simulation ana-lysis has been made.Applying Generalized Stochastic Petri Nets to security analysis domain can enrich the research method of dynamic security problem,which is of great significance to improving the security of our equipment model.
Intra-articular use of a medical device composed of hyaluronic acid and chondroitin sulfate (Structovial CS): effects on clinical, ultrasonographic and biological parameters (2012)

#ISRCTN91883031.
Galcanezumab in chronic migraine (2018)

This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.
Multi-View Stereo Revisited (2006)

We present an extremely simple yet robust multi-view stereo algorithm and analyze its properties. The algorithm first computes individual depth maps using a window-based voting approach that returns only good matches. The depth maps are then merged into a single mesh using a straightforward volumetric approach. We show results for several datasets, showing accuracy comparable to the best of the current state of the art techniques and rivaling more complex algorithms.
A convenient synthesis of nicotinate esters from 3‐cyanopyridones (1987)

Abstract A convenient synthesis of alkyl‐substituted ethyl nicotinates 8 was devised, using 3‐cyano‐2(1 H )‐pyridones 4. These were converted to the corresponding 2‐bromo‐3‐cyanopyridines 5 with boiling phosphorus tribromide. The resulting 5 were smoothly debrominated to 3‐cyanopyridines 6 with zinc dust in boiling ethanolic acetic acid. The nitrile function was hydrolyzed in boiling 6 N hydrochloric acid, and the resulting nicotinic acid hydrochlorides 7 esterified with refluxing triethyl orthoformate, to give the ethyl nicotinates 8. A modified formylation of 2‐butanone led to the sodium salt of 2‐methyl‐3‐oxobutanal ( 3a ) of enhanced purity.
Sn(OTf)2 and Sc(OTf)3: Efficient and versatile catalysts for the controlled polymerization of lactones (2000)

A general and novel method for the controlled synthesis of aliphatic polyesters is presented. The evaluation of stannous (II) trifluoromethane sulfonate [Sn(OTf)2] and scandium (III) trifluoromethane sulfonate [Sc(OTf)3] as catalysts for the ring-opening polymerization (ROP) of various lactones is described as a route to polyesters under mild and highly selective polymerization conditions. Size exclusion chromatograms of poly(ϵ-caprolactone) initiated from ethanol in the presence of either Sn(OTf)2 or Sc(OTf)3 demonstrate the facile synthesis of narrowly dispersed products. Predictable molecular weights, typical of a living or controlled polymerization, were obtained with high yields. These catalysts are versatile and applicable toward the ROP of other cyclic (di)esters, including β-butyrolactone, which produces the synthetic analogue of the biopolymer poly(β-hydroxybutyrate). © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2067–2074, 2000
Anatomic Suitability of the C1-C2 Complex for Pedicle Screw Fixation (2002)

C1-C2 pedicle screw fixation is a technique that appears to be widely applicable and may represent an alternative fixation technique in selected patients.
Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors (2007)

As discussed in Part I of this review, the geographic distribution of multiple sclerosis (MS) and the change in risk among migrants provide compelling evidence for the existence of strong environmental determinants of MS, where "environmental" is broadly defined to include differences in diet and other behaviors. As we did for infections, we focus here primarily on those factors that may contribute to explain the geographic variations in MS prevalence and the change in risk among migrants. Among these, sunlight exposure emerges as being the most likely candidate. Because the effects of sun exposure may be mediated by vitamin D, we also examine the evidence linking vitamin D intake or status to MS risk. Furthermore, we review the evidence on cigarette smoking, which cannot explain the geographic variations in MS risk, but may contribute to the recently reported increases in the female/male ratio in MS incidence. Other proposed risk factors for MS are mentioned only briefly; although we recognize that some of these might be genuine, evidence is usually sparse and unpersuasive.
MicroRNA Regulation and Role in Stem Cell Maintenance, Cardiac Differentiation and Hypertrophy (2013)

There are currently 1527 known microRNAs (miRNAs) in human, each of which may regulate hundreds or thousands of target genes. miRNA expression levels vary between cell types; for example, miR- 302 and miR-290 families are highly enriched in embryonic stem cells, while miR-1 is a muscle specific miRNA. miRNA biosynthesis and function are highly regulated and this regulation may be cell type specific. The processing enzymes and factors that recognize features in sequence and secondary structure of the miRNA play key roles in regulating the production of mature miRNA. Mature miRNA enriched in stem cells control stem cell self-renewal as well as their differentiation. Though specific miRNAs have been shown to control differentiation towards various lineages such as neural or skin cells, some of the most well characterized miRNAs have been found in promoting the formation of cardiac cells. In addition, miRNAs also play a critical role in cardiomyocyte hypertrophy, especially in a pathological context. Such miRNAs are predicted to be therapeutic targets for treating cardiovascular diseases. In this review we will discuss how miRNAs act to maintain the stem cell state and also explore the current knowledge of the mechanisms that regulate miRNAs. Furthermore, we will discuss the emerging roles of miRNAs using cardiomyocyte differentiation and maturation as a paradigm. Emphasis will also be given on some of the less ventured areas such as the role of miRNAs in the physiological maturation of cardiomyocytes. These potentially beneficial miRNAs are likely to improve cardiac function in both in vivo and in vitro settings and thus provide additional strategy to treat heart diseases and more importantly serve as a good model for understanding cardiomyocyte maturation in vitro.
HER2 Specific Tumor Targeting with Dendrimer Conjugated Anti-HER2 mAb (2006)

In the present study, we report the synthesis and human growth factor receptor-2 (HER2) specific tumor targeting properties of a dendrimer conjugated to anti-HER2 mAb (monoclonal antibody) conjugate. The polyamidoamine (PAMAM) dendrimer generation five (G5) was labeled with alexaFluor 488 and conjugated to anti-HER2 mAb. The binding and internalization of the antibody-conjugated dendrimer to HER2-expressing cells was evaluated by flow cytometry and confocal microscopy. Uniquely, the conjugate demonstrated cellular uptake and internalization in HER2-expressing cells as compared to free antibody. The time course of internalization and blocking experiments with free antibody suggest that the rapid and efficient cellular internalization of the dendrimer-antibody conjugate was achieved without alterations in specificity of targeting. Animal studies demonstrated that the conjugate targets HER2-expressing tumors.
Leukocyte Count as a Predictor of Cardiovascular Events and Mortality in Postmenopausal Women (2005)

The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.
ELIZA—a computer program for the study of natural language communication between man and machine (1966)

article Free Access Share on ELIZA—a computer program for the study of natural language communication between man and machine Author: Joseph Weizenbaum Massachusetts Institute of Technology, Cambridge Massachusetts Institute of Technology, CambridgeView Profile Authors Info & Claims Communications of the ACMVolume 9Issue 1Jan. 1966 pp 36–45https://doi.org/10.1145/365153.365168Published:01 January 1966Publication History 2,074citation19,466DownloadsMetricsTotal Citations2,074Total Downloads19,466Last 12 Months5,621Last 6 weeks843 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Determination of Anti-Adeno-Associated Virus Vector Neutralizing Antibody Titer with an In Vitro Reporter System (2015)

Adeno-associated virus (AAV) vectors are a platform of choice for in vivo gene transfer applications. However, neutralizing antibodies (NAb) to AAV can be found in humans and some animal species as a result of exposure to the wild-type virus, and high-titer NAb develop following AAV vector administration. In some conditions, anti-AAV NAb can block transduction with AAV vectors even when present at low titers, thus requiring prescreening before vector administration. Here we describe an improved in vitro, cell-based assay for the determination of NAb titer in serum or plasma samples. The assay is easy to setup and sensitive and, depending on the purpose, can be validated to support clinical development of gene therapy products based on AAV vectors.
DNA Cage Delivery to Mammalian Cells (2011)

DNA cages are nanometer-scale polyhedral structures formed by self-assembly from synthetic DNA oligonucleotides. Potential applications include in vivo imaging and the targeted delivery of macromolecules into living cells. We report an investigation of the ability of a model cage, a DNA tetrahedron, to enter live cultured mammalian cells. Cultured human embryonic kidney cells were treated with a range of fluorescently labeled DNA tetrahedra and subsequently examined using confocal microscopy and flow cytometry. Substantial uptake of tetrahedra into cells was observed both when the cells were treated with tetrahedra alone and when the cells were treated with a mixture of tetrahedra and a transfection reagent. Analysis of the subcellular localization of transfected tetrahedra using confocal microscopy and organelle staining indicates that the cages are located in the cytoplasm. FRET experiments indicate that the DNA cages remain substantially intact within the cells for at least 48 h after transfection. This is a first step toward the use of engineered DNA nanostructures to deliver and control the activity of cargoes within cells.
Formulation of carbetocin injection by lyophilization technique (2013)

The objective of this experiment is to formulate the Carbetocin injection by Lyophilization technique for betterstability by reducing Oxidative degradation, Hydrolytic degradation and alkaline degradation and for long term storage. Mannitol as bulking as well as isotonic agent, Glacial acetic acid as buffer and L-Methionine as Antioxidant were used with water for injection into 2 ml tubular vials with pre and post purging nitrogen. The filled vials were loaded into Lyophilizer and lyophilized them as per cycle. Different composition of additives was used and the different pH concentrations of 4.0, 4.5, 5.0, 5.5, 6.0 and 6.5 were adjusted with 1% Glacial Acetic acid were tried to formulate the formulation. The formulation F (3) which has been optimized, theresults of the cycle was observed to be optimized. Carbetocin was developed as lyophilized formulation for betterstability. The obtained results suggested that a stable formulation for drug Carbetocin was developed which wasComparable to reference listed product.
Overview of sleep & sleep disorders. (2010)

Sleep is defined on the basis of behavioural and physiological criteria dividing it into two states: non rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Circadian rhythm of sleep-wakefulness is controlled by the master clock located in the suprachiasmatic nuclei of the hypothalamus. The neuroanatomical substrates of the NREM sleep are located principally in the ventrolateral preoptic nucleus of the hypothalamus and those of REM sleep are located in pons. A variety of significant physiological changes occur in all body systems and organs during sleep as a result of functional alterations in the autonomic and somatic nervous systems. The international classification of sleep disorders (ICSD, ed 2) lists eight categories of sleep disorders along with appendix A and appendix B. The four major sleep complaints include excessive daytime sleepiness, insomnia, abnormal movements or behaviour during sleep and inability to sleep at the desired time. The most important step in assessing a patient with a sleep complaint is obtaining a detailed history including family and previous histories, medical, psychiatric, neurological, drug, alcohol and substance abuse disorders. Some important laboratory tests for investigating sleep disorders consist of an overnight polysomnography, multiple sleep latency and maintenance of wakefulness tests as well as actigraphy. General physicians should have a basic knowledge of the salient clinical features of common sleep disorders, such as insomnia, obstructive sleep apnoea syndrome, narcolepsy-cataplexy syndrome, circadian rhythm sleep disorders (e.g., jet leg, shift work disorder, etc.) and parasomnias (e.g., partial arousal disorders, REM behaviour disorder, etc.) and these are briefly described in this chapter. The principle of treatment of sleep disorders is first to find cause of the sleep disturbance and vigorously treat the co-morbid conditions causing the sleep disturbance. If a satisfactory treatment is not available for the primary condition or does not resolve the problem, the treatment should be directed at the specific sleep disturbance. Most sleep disorders, once diagnosed, can be managed with limited consultations. The treatment of primary sleep disorders, however, is best handled by a sleep specialist. An overview of sleep and sleep disorders viz., Basic science; international classification and approach; and phenomenology of common sleep disorders are presented.