gebhart/patrepeval huggingface dataset:
A Phase II Randomized Study of HIV-Specific T-Cell Gene Therapy in Subjects with Undetectable Plasma Viremia on Combination Antiretroviral Therapy (2002)

Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels in plasma, but it is unlikely to eradicate cellular reservoirs of virus. Immunotherapies that are cytolytic may be useful adjuncts to drug therapies that target HIV replication. We have generated HIV-specific CD4(+) and CD8(+) T cells bearing a chimeric T-cell receptor (CD4zeta) composed of the extracellular and transmembrane domain of human CD4 (which binds HIVgp120) linked to the intracellular-zeta signaling chain of the CD3 T-cell receptor. CD4zeta-modified T cells can inhibit viral replication, kill HIV-infected cells in vitro, and survive for prolonged periods in vivo. We report the results of a phase II randomized trial of CD4zeta gene-modified versus unmodified T cells in 40 HIV-infected subjects on HAART with plasma viral loads <50 copies/ml. Serial analyses of residual blood and tissue HIV reservoirs were done for 6 months postinfusion. No significant between-group differences were noted in viral reservoirs following therapy. However, infusion of gene-modified, but not unmodified, T cells was associated with a decrease from baseline in HIV burden in two of four reservoir assays and a trend toward fewer patients with recurrent viremia. Both groups experienced a treatment-related increase in CD4(+) T-cell counts.
Bacterial display using circularly permuted outer membrane protein OmpX yields high affinity peptide ligands (2006)

A bacterial display methodology was developed for N- and C-terminal display and demonstrated to enable rapid screening of very large peptide libraries with high precision and efficiency. To overcome limitations of insertional fusion display libraries, a new scaffold was developed through circular permutation of the Escherichia coli outer membrane protein OmpX that presents both N and C termini on the external cell surface. Circularly permuted OmpX (CPX) display was directly compared to insertional fusion display by screening comparable peptide libraries in each format using magnetic and fluorescence activated cell sorting. CPX display enabled in situ measurement of dissociation rate constants with improved accuracy and, consequently, improved affinity discrimination during screening and ranking of isolated clones. Using streptavidin as a model target, bacterial display yielded the well-characterized HP(Q)/(M) motif obtained previously using several alternative peptide display systems, as well as three additional motifs (L(I)/(V) CQNVCY, CGWMY(F)/(Y)xEC, ERCWYVMHWPCNA). Using CPX display, a very high affinity streptavidin-binding peptide was isolated having a dissociation rate constant k(off) = 0.002sec(-1) even after grafting to the C terminus of an unrelated protein. Comparison of individual clones obtained from insertional fusion and terminal fusion libraries suggests that the N-terminal display yields sequences with greater diversity, affinity, and modularity. CPX bacterial display thus provides a highly effective method for screening peptide libraries to rapidly generate ligands with high affinity and specificity.
An Introduction to PCR Techniques (2006)

The polymerase chain reaction (PCR) is a method for the enzymatic amplification of DNA and has revolutionised our approach to both diagnostics and research, permitting the amplification of small amounts of genetic material, either derived from genomic (chromosomal DNA) or RNA via reverse transcription to cDNA. This chapter gives a primer of methods for the preparation of materials for PCR and some advice on the requirements for the PCR itself.
Effect of electrolyte concentration on axial anion ligation in manganese(III) meso-tetraphenylporphyrin chlorides (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of electrolyte concentration on axial anion ligation in manganese(III) meso-tetraphenylporphyrin chloridesGarry J. Foran, Robert S. Armstrong, Maxwell J. Crossley, and Peter A. LayCite this: Inorg. Chem. 1992, 31, 8, 1463–1470Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://pubs.acs.org/doi/10.1021/ic00034a029https://doi.org/10.1021/ic00034a029research-articleACS PublicationsRequest reuse permissionsArticle Views162Altmetric-Citations12LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts
CRISPR Genome Editing Made Easy Through the CHOPCHOP Website (2021)

The design of optimal guide RNA (gRNA) sequences for CRISPR systems is challenged by the need to achieve highly efficient editing at the desired location (on-target editing) with minimal editing at unintended locations (off-target editing). Although laboratory validation should ideally be used to detect off-target activity, computational predictions are almost always preferred in practice due to their speed and low cost. Several studies have therefore explored gRNA-DNA interactions in order to understand how CRISPR complexes select their genomic targets. CHOPCHOP (https://chopchop.cbu.uib.no/) leverages these developments to build a user-friendly web interface that helps users design optimal gRNAs. CHOPCHOP supports a wide range of CRISPR applications, including gene knock-out, sequence knock-in, and RNA knock-down. Furthermore, CHOPCHOP offers visualization that enables an informed choice of gRNAs and supports experimental validation. In these protocols, we describe the best practices for gRNA design using CHOPCHOP. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Design of gRNAs for gene knock-out Alternate Protocol 1: Design of gRNAs for dCas9 fusion/effector targeting Support Protocol: Design of gRNAs for targeting transgenic or plasmid sequences Basic Protocol 2: Design of gRNAs for RNA targeting Basic Protocol 3: Design of gRNAs for sequence knock-in Alternate Protocol 2: Design of gRNAs for knock-in using non-homologous end joining Basic Protocol 4: Design of gRNAs for knock-in using Cas9 nickases.
Dynamic Slicing of Java Bytecode Programs (2006)

A forward global method for obtaining backward dynamic slices of Java bytecode programs is presented. In contrast with existing published techniques that require either a customized Java compiler (which also implies access to the source code) or bytecode instrumentation and eventual manual dependency specifications, our approach was to produce an instrumented virtual machine for Java. This approach works with programs compiled with arbitrary third party compilers and does not require access to the source code during the slicing process. However, we still retain the ability to express the slicing criterion and the resulting slice in terms of source code locations using the supplemental information present in the compiled code. Our technique also handles advanced aspects of the Java environment, such as exception handling, multithreaded execution and, to a certain degree, the execution of native machine code linked with the Java classes.
Stimulatory effects of 4-hydroxytamoxifen on proliferation of human endometrial adenocarcinoma cells (Ishikawa line). (1989)

The effects of trans-4-hydroxytamoxifen (OHTam) on proliferation of cells of the Ishikawa human endometrial adenocarcinoma line were studied under serum-free, phenol red-free conditions and compared to those of estradiol. The addition of OHTam (1 microM) to basal medium (BM), consisting of equal parts of Dulbecco's modified Eagle's medium and Ham's F-12 with additional glutamine and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, resulted in significant increases in cell numbers relative to controls. These effects were even greater than those obtained with estradiol (10 nM-1 microM) or 1% charcoal-treated fetal bovine serum (ctFBS). Addition of 1% ctFBS to BM containing 1 microM OHTam further increased cell numbers whereas addition of estradiol (10 nM) did not do so. The stimulation of growth was positively correlated with OHTam concentrations in the range of 10 nM to 1 microM. Dissociation of estradiol and OHTam proliferative effects was observed in a variant of Ishikawa cells in which estradiol did not increase proliferation while OHTam had a strong stimulatory effect. The growth-promoting effects of OHTam were also observed in BM containing 5% or 15% ctFBS. In contrast, in parallel experiments in which BM was replaced by minimal essential medium (Eagle's) with Earle's salts, OHTam (1 microM) did not stimulate proliferation under these conditions and acted as an antiestrogen, inhibiting the proliferative effects of estradiol. These results illustrate marked effects of medium composition on proliferation and antiestrogenic actions of OHTam. Alkaline phosphatase activity was strongly stimulated by estradiol (10 nM) but only very weakly affected by OHTam (1 microM); at these concentrations, OHTam inhibited the effect of estradiol, both in serum-free BM and in minimal essential medium plus 15% ctFBS, demonstrating dissociation in its actions on proliferation and on enzymatic activity. These findings suggest that OHTam may stimulate the proliferation of particular clones of endometrial cancer cells in human tumors. They also suggest that OHTam can exert effects not mediated by the estrogen receptor system, or form OHTam-estrogen receptor agonistic complexes unlike those resulting from estradiol-estrogen receptor interactions. Clearly, Ishikawa cells provide a useful model to investigate mechanisms of action of antiestrogens.
Variation in gene expression patterns in follicular lymphoma and the response to rituximab (2003)

Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors.
Gene delivery to the heart in vivo and to cardiac myocytes and vascular smooth muscle cells in vitro using herpes virus vectors. (1996)

Herpes simplex virus 1 (HSV1), while usually thought of as neurotrophic, can also efficiently infect a wide variety of non-neuronal cell types and so might be developed as a vector for gene delivery to non-neuronal as well as neuronal cells. Here we have tested three different disabled HSV vectors for their ability to deliver a lacZ gene to primary cardiac myocytes and vascular smooth muscle cells in vitro, and used the most efficient virus to transfect the rat heart in vivo. We also assessed the degree of cytopathic effect of the various viruses on the cardiac myocytes in vitro by testing the effects on the frequency of beating in synchronously beating myocyte cultures. While an HSV mutant in which the essential immediate-early gene IE2 had been deleted gave high efficiency gene transfer to the cardiac myocytes in vitro and the rat heart in vivo, viruses in which ICP34.5 or ICP34.5 and VMW65 were inactive (and which were also unable to replicate in these cells) gave a much lower efficiency of gene transfer, mirroring the degree of cytopathic effect observed in the beating myocyte cultures. Gene transfer to the vascular smooth muscle cells was considerably less efficient than to the myocytes in all cases. These results indicate that while HSV may be inappropriate for highly efficient gene transfer to the arterial wall, efficient gene transfer can be achieved in the myocardium, and thus that HSV vectors may be suitable for the alteration of cardiac cell physiology in vivo.
Nitrofuryltriazole derivatives as potential urinary tract antibacterial agents (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNitrofuryltriazole derivatives as potential urinary tract antibacterial agentsEva B. Akerblom and Dag E. S. CampbellCite this: J. Med. Chem. 1973, 16, 4, 312–319Publication Date (Print):April 1, 1973Publication History Published online1 May 2002Published inissue 1 April 1973https://pubs.acs.org/doi/10.1021/jm00262a002https://doi.org/10.1021/jm00262a002research-articleACS PublicationsRequest reuse permissionsArticle Views214Altmetric-Citations25LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts
Vapour sensing using hybrid organic–inorganic nanostructured materials (2000)

Small aromatic organothiol derivatives, with the structure HS–C6H4–X, have been used to stabilise gold nanoparticles. The nature of the functional group, X, is important for controlling the relative strength of the particle–particle and particle–solvent interactions and hence in determining the physical properties of these systems (e.g. solubility). Particles were stabilised with different ligands for which X=OH, –COOH, –NH2, and –CH3 and thin films of the particles were formed, by solution evaporation, on microelectrode patterned surfaces. The electronic behaviour indicates that conduction can be understood in terms of an activated electron tunnelling model. Finally, preliminary studies were carried out on the effect of exposure to different chemical vapours on the electronic transport properties.
Increasing protein O‐GlcNAc levels by inhibition of O‐GlcNAcase improves cardiac function following trauma hemorrhage and resuscitation in rat (2006)

Our previous studies have shown that administration of glucosamine during resuscitation following trauma‐hemorrhage (T‐H) improved cardiac output and organ perfusion. Glucosamine administration also increased levels of N‐acetyl‐glucosamine ( O ‐GlcNAc) on proteins in heart and brain. An alternative means of increasing O ‐GlcNAc levels is by inhibition of O ‐GlcNAcase, which catalyzes removal of GlcNAc from proteins with O ‐(2‐acetamido‐2‐deoxy‐d‐glucopyranosylidene) amino‐ N ‐phenylcarbamate (PUGNAc). The goal of this study therefore, was to determine whether PUGNAc administration following T‐H also improves recovery following T‐H. Fasted male rats were bled to and maintained at a mean arterial blood pressure of 40 mmHg for 90 min followed by fluid resuscitation. Administration of 300μ l of 20mM PUGNAc 30 min after the onset of resuscitation significantly improved cardiac output compared to the vehicle controls (14±2 vs. 26±2 mls/min/100g body wt; p&lt;0.05); decreased total peripheral resistance (6.2±0.9 vs. 3.7±3 mmHg/mls/min/100g body wt; p&lt;0.05), and increased perfusion of critical organs systems, including kidney, liver and brain, determined 2hrs after the end of resuscitation. PUGNAc also attenuated the T‐H induced increase in plasma IL‐6 levels (864±112 Vs 392±188 pmols/ml; p&lt;0.05). PUGNAc also significantly increased O ‐GlcNAc levels in heart, liver and skeletal muscle but not brain. Thus, PUGNAc, like glucosamine, improves cardiac function and organ perfusion and reduced the level of circulating IL‐6 following T‐H. The similar effects of glucosamine and PUGNAc suggest that this protection is mediated via increased protein O ‐GlcNAc levels. Supported by NIH grants RO1 HL076165‐01(RBM) and R37 GM39519 (IHC).
Contact Printing of Quantum Dot Light-Emitting Devices (2008)

We demonstrate a solvent-free contact printing process for deposition of patterned and unpatterned colloidal quantum dot (QD) thin films as the electroluminescent layers within hybrid organic-QD light-emitting devices (QD-LEDs). Our method benefits from the simplicity, low cost, and high throughput of solution-processing methods, while eliminating exposure of device structures to solvents. Because the charge transport layers in hybrid organic/inorganic QD-LEDs consist of solvent-sensitive organic thin films, the ability to avoid solvent exposure during device growth, as presented in this study, provides a new flexibility in choosing organic materials for improved device performance. In addition, our method allows us to fabricate both monochrome and red-green-blue patterned electroluminescent structures with 25 microm critical dimension, corresponding to 1000 ppi (pixels-per-inch) print resolution.
The vascular endothelial growth factor mRNA contains an internal ribosome entry site (1998)

Vascular endothelial growth factor (VEGF), an essential regulator of angiogenesis during early development as well as during the growth of solid tumours, bears an unusually large 5' untranslated region (5'-UTR) in the mRNA of over 1000 nucleotides. We found that the VEGF 5'-UTR, despite being GC-rich and containing an upstream short open reading frame, promotes efficient translation of a luciferase reporter. The VEGF 5'-UTR also allowed translation of luciferase from a dicistronic mRNA when placed between the two cistrons, demonstrating that it contains an internal ribosome entry site. Deletion analysis indicated that the IRES resides towards the 3' end of the 5'-UTR.
Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis. (2008)

The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA.
Genetic Engineering for Novel Fibres (2000)

Genetic engineering methods are being investigated for their potential to produce new kinds of textile fibres. The systems fall into two main groups. There are those systems that can produce monomeric protein molecules in solution from appropriately engineered genes and include expression in bacteria, cell cultures or in the milk of transgenic animals such as goats or sheep. The protein monomers are then isolated from the chosen system and spun and drawn into fibres. The other approach is to modify keratin fibres such as wool by expressing other proteins in the internal components by transgenesis. These systems are briefly reviewed with a discussion of the properties being sought and the progress to date including some changes to cellulose fibres.
A bridging model for parallel computation (1990)

The success of the von Neumann model of sequential computation is attributable to the fact that it is an efficient bridge between software and hardware: high-level languages can be efficiently compiled on to this model; yet it can be effeciently implemented in hardware. The author argues that an analogous bridge between software and hardware in required for parallel computation if that is to become as widely used. This article introduces the bulk-synchronous parallel (BSP) model as a candidate for this role, and gives results quantifying its efficiency both in implementing high-level language features and algorithms, as well as in being implemented in hardware.
Human resource development as an occupational culture through organizational stories (1994)

Abstract This study investigated HRD as an occupational culture. Cultural patterns were derived from the analysis of subject‐generated stories of workplace experiences. Data were collected from HRD professionals employed by Fortune 500 companies. Exploratory findings suggest that HRD is a cultural entity that is more concerned with employee development and work autonomy than with overall business agendas.
New Chemotherapeutic Advances in Pancreatic, Colorectal, and Gastric Cancers (2004)

Pancreatic, gastric, and colorectal cancers are major causes of morbidity and mortality worldwide. When curative surgical resection is not an option, these malignancies tend to respond very poorly to chemotherapy and carry a dismal prognosis. There is, therefore, an urgent need for novel treatment strategies for these cancers. Great strides have been made in colon cancer treatment with the recent introduction of several novel agents, including capecitabine, irinotecan, and oxaliplatin either alone or in combination regimens. Treatment of advanced colon cancer, however, remains essentially palliative, and treatment-related toxicity remains a significant problem. The treatment of advanced gastric and pancreatic cancer has also seen the introduction of new agents, such as gemcitabine and irinotecan; however, the impact of these agents on survival has been small, and toxicity continues to be a major obstacle. The search for new chemotherapeutic agents and treatment strategies will need to focus on improving outcomes and safety and tolerability profiles. To date, several new agents have shown promise, including pemetrexed, G17DT, bevacizumab, and other targeted agents. Further research into their optimal use either alone or in combination regimens should be a priority.
Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO (2001)

We have shown previously that at physiologically relevant oxygen tension (pO(2) approximately 10 mmHg), NO S-nitrosylates 1 of approximately 50 free cysteines per ryanodine receptor 1 (RyR1) subunit and transduces a calcium-sensitizing effect on the channel by means of calmodulin (CaM). It has been suggested that cysteine-3635 is part of a CaM-binding domain, and its reactivity is attenuated by CaM [Porter Moore, C., Zhang, J. Z., Hamilton, S. L. (1999) J. Biol. Chem. 274, 36831-36834]. Therefore, we tested the hypothesis that the effect of NO was mediated by C3635. The full-length RyR1 single-site C3635A mutant was generated and expressed in HEK293 cells. The mutation resulted in the loss of CaM-dependent NO modulation of channel activity and reduced S-nitrosylation by NO to background levels but did not affect NO-independent channel modulation by CaM or the redox sensitivity of the channel to O(2) and glutathione. Our results reveal that different cysteines within the channel have been adapted to serve in nitrosative and oxidative responses, and that S-nitrosylation of the cysteine-containing CaM-binding domain underlies the mechanism of CaM-dependent regulation of RyR1 by NO.