gebhart/patrepeval huggingface dataset:
Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. (2000)

Coordinated presentation of antigen and costimulatory molecules has been shown to result in the induction of an antigen-specific T-cell response rather than the development of anergy. This study evaluated the vaccine ALVAC-CEA B7.1, a canary pox virus that has been engineered to encode the gene for the tumor-associated antigen carcinoembryonic antigen (CEA) and B7.1, a T-cell costimulatory molecule. Patients with CEA-expressing tumors were immunized with 2.5 x 10(7) (n = 3), 1.0 x 10(8) (n = 6), and 4.5 x 10(8) (n = 30) plaque-forming units intradermally every other week for 8 weeks. Patients with stable or responding disease received monthly boost injections. Biopsies of vaccine sites were obtained 48 h after vaccination to evaluate leukocytic infiltration and CEA expression. Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-gamma. Therapy was well tolerated, without significant toxicity attributable to vaccine. All patients had evidence of leukocytic infiltration and CEA expression in vaccine biopsy sites. Six patients with elevated serum CEA values at baseline had declines in their levels lasting 4-12 weeks. These patients all had stable disease after four vaccinations. After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA-specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline. The number of prior chemotherapy regimens was inversely correlated with the ability to generate a T-cell response. ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, and it is associated with the induction of a CEA-specific T-cell response.
Panel-Type Semiconductor Optical Modulator Using Electron Depleting Absorption Control (1993)

Operation of a newly proposed panel-type (or surface-illuminated-type) semiconductor optical modulator based on absorption control by electron depletion around the p-n junctions is demonstrated. Performance of a 61% on/off extinction ratio for 5.5 V variation of the applied voltage was obtained in a device having 39 p-n junctions.
Characterization of HIV Isolates Arising After Prolonged Zidovudine Therapy (1992)

Human immunodeficiency virus type 1 (HIV-1) was isolated from five patients with late-stage disease treated with zidovudine (ZDV) for more than 1 year. Peripheral blood mononuclear cells (PBMCs) were used for all virus isolations and to assay for drug resistance. The isolates exhibited a 10- to 100-fold decrease in ZDV susceptibility compared to pretreatment isolates. Multiple clones of a 618 bp segment of the HIV reverse transcriptase gene encompassing codons 60-250 were sequenced for each isolate. The association of alterations at codons Asp67----Asn, Lys70----Arg, Thr215----Phe or Tyr, and Lys219----Gln with ZDV resistance has been previously noted (ref. 5). In this study, the most frequent alterations was Thr215----Tyr although genotypic mixtures of Thr/Tyr and Phe/Tyr were also observed. One isolate with a Tyr215 alteration and unaltered codons at 67, 70, and 219 had high-level ZDV resistance. Alterations at codons 67, 70, and 219 did not appear to increase resistance when seen in combination with Tyr215. Virus isolates obtained from each patient by cultivation with either 0 or 4 microM ZDV were compared and found to have similar alterations at codons 67, 70, 215, and 219, although one instance of apparent in vitro selection for Tyr215 over Phe215 was observed. Assays using PBMCs for virus propagation will permit susceptibility testing of HIV isolates from most patients on antiretroviral drugs to investigate the clinical significance of drug resistance.
Detection of cytotoxic T lymphocytes specific for synthetic peptides of gp160 in HIV-seropositive individuals (1991)

Four synthetic peptides corresponding to the IIIB sequence of gp160 of HIV were recently reported to stimulate Th cell function by PBL from HIV-infected, asymptomatic patients. In the present report, we used these same peptides to demonstrate CTL activity in a similar patient population. EBV-transformed B-cell lines from asymptomatic, HIV seropositive and seronegative control donors were pre-incubated with the peptides. Fresh PBL from 19 (76%) of 25 HIV seropositive donors lysed autologous targets pulsed with at least one of the four peptides. Autologous targets pulsed with two non-immunogenic peptides were not lysed. PBL from none of the eight HIV seronegative controls lysed peptide-preincubated autologous targets. The CTL activity was mediated by T cells, was predominantly MHC class I restricted, and was increased by in vitro restimulation of PBL with the peptides. HLA A-2 was identified as a restricting element for all four peptides in different patients, and for three of the peptides in the same donor. HLA-A1 or -B8 may also present some of the peptides. Thus, the same peptides can be recognized by human Th cells and class I MHC-restricted CTL.
The Many Roles of Computation in Drug Discovery (2004)

An overview is given on the diverse uses of computational chemistry in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding.
d-δ-Tocotrienol-Mediated Suppression of the Proliferation of Human PANC-1, MIA PaCa-2, and BxPC-3 Pancreatic Carcinoma Cells (2009)

Suppression of mevalonate pathway activities, be it by modulators of HMG CoA reductase (statins, tocotrienols, and farnesol), farnesyl transferase (farnesyl transferase inhibitors), and/or mevalonate pyrophosphate decarboxylase (phenylacetate) activity, may have a potential in pancreatic cancer chemotherapy.
An Internal Ribosome Entry Site (IRES) Mutant Library for Tuning Expression Level of Multiple Genes in Mammalian Cells (2013)

A set of mutated Encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) elements with varying strengths is generated by mutating the translation initiation codons of 10(th), 11(th), and 12(th) AUG to non-AUG triplets. They are able to control the relative expression of multiple genes over a wide range in mammalian cells in both transient and stable transfections. The relative strength of each IRES mutant remains similar in different mammalian cell lines and is not gene specific. The expressed proteins have correct molecular weights. Optimization of light chain over heavy chain expression by these IRES mutants enhances monoclonal antibody expression level and quality in stable transfections. Uses of this set of IRES mutants can be extended to other applications such as synthetic biology, investigating interactions between proteins and its complexes, cell engineering, multi-subunit protein production, gene therapy, and reprogramming of somatic cells into stem cells.
Under the following conditions (2010)

the manner specified by the author or licensor (but not in any way that suggests that they endorse you or your use of the work). Noncommercial. You may not use this work for commercial purposes. No Derivative Works. You may not alter, transform, or build upon this work. • For any reuse or distribution, you must make clear to others the license terms of this work. The best way to do this is with a link to this web page. • Any of the above conditions can be waived if you get permission from the copyright holder. • Nothing in this license impairs or restricts the author&amp;apos;s moral rights. Download the Legal Code for this Licence at:
Blood-Brain Barrier Penetration and in Vivo Activity of an NGF Conjugate (1993)

Nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons of the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant of dementia in these patients and may therefore suggest a therapeutic role for NGF. However, NGF does not significantly penetrate the blood-brain barrier, which makes its clinical utility dependent on invasive neurosurgical procedures. When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection. This conjugated NGF increased the survival of both cholinergic and noncholinergic neurons of the medial septal nucleus that had been transplanted into the anterior chamber of the rat eye. This approach may prove useful for the treatment of Alzheimer's disease and other neurological disorders that are amenable to treatment by proteins that do not readily cross the blood-brain barrier.
The localization of Thy-1.1, MRC OX 2 and Ia antigens in the rat ovary and fallopian tube. (1983)

The localization of Thy-1, MRC OX 2 and Ia antigens as defined by monoclonal antibodies MRC OX 7, MRC OX 2 and MRC OX 6 was determined by an indirect immunoperoxidase technique on cryostat sections of rat ovaries. Thy-1 antigen was present significantly in the theca interna of growing antral follicles. Developing corpora lutea exhibited an increasing presence of Thy-1 antigen and it was still present in degenerating ones. Thy-1 antigen was constantly present in fallopian tube tunica propria. The MRC OX 2 antigen was expressed most on ovarian structures that do not develop further, i.e. granulosa of degenerating antral follicles and third generation of corpora lutea. MRC OX 2 antibody stained the capillaries of the fallopian tube; the most heavily MRC OX 2+ were the cells of ovarian germinal epithelium. The Ia+ cells were occasionally found within the growing ovarian structures but they were more frequent in degenerating ones. Rare or no la+ cells within the ovary and heavily Ia-depleted thymus medulla and Ia areas in the spleen were, however, observed in some rats. The role of these antigens with respect to the structures they label is discussed.
Allopurinol hypersensitivity syndrome: a preventable severe cutaneous adverse reaction? (2008)

Allopurinol hypersensitivit y syndrome is a life-threatening cutaneous adverse reaction. Allopurinol should be initiated under clear indications with appropriate dosages. Potential associations with this syndrome include the Chinese race, the elderly, and patients with underlying renal impairment.
An optimal scheduling technique for dual-arm robots in cluster tools with residency constraints (2002)

Discusses a scheduling technique, for cluster tools, that addresses post-processing residency constraints and throughput requirements. The residency constraints impose a limit on the post-processing time that a material unit spends in a processing module. The technique searches in the time and resource domains for a feasible schedule with a maximum throughput. Several heuristics are designed and added to reduce the complexity of the scheduling algorithm. The resulting schedules are deadlock free, since resources are scheduled according to the times that they are available. Analytical and experimental analyses demonstrate the correctness and efficiency of our proposed technique.
Frontotemporal and motor neurone degeneration with neurofilament inclusion bodies: additional evidence for overlap between FTD and ALS (2003)

We present the case of a patient who had clinical frontal lobe dementia without apparent motor neurone disease (MND), with pathologic findings not typical of any single currently classified frontotemporal degeneration (FTD). At autopsy, the brain had frontal and temporal atrophy with neuronal loss, gliosis, and superficial spongiosis, typical of all FTDs. There were at least three different morphologic types of intracytoplasmic neuronal inclusions in a variety of brain and brainstem regions, including the hippocampal dentate gyrus and pyramidal neurones, the neocortex (in particular, the motor cortex), basal ganglia, thalamus, subthalamic nucleus, basis pontis, and inferior olivary nuclei. Inclusions had the morphologies of Pick-like bodies, pleomorphic inclusions, and hyaline conglomerate (HC)-like inclusions. None of these were positive with tau immunostains. Pick-like bodies in the dentate gyrus were labelled with ubiquitin. The pleomorphic inclusions in the neocortex and dentate gyrus and the HC-like inclusions in the motor and parietal cortex were strongly positive with immunostains for neurofilament. We discuss the differential diagnosis and compare this case with those disorders to which it is most similar. In particular, we compare the unique neurofilament-positive inclusions to the inclusions of FTD-MND, to Pick bodies, and to the basophilic and HC inclusions that are occasionally seen in amytrophic lateral sclerosis (ALS). Although FTD-MND may be found in ALS, the findings in this case may have additional implications for a link between FTD and ALS.
Depth from Defocus of Structured Light (1990)

We propose a new range sensing technique that uses defocus of structured light to measure depth. The technique is an extension of the original passive depth-from-defocus idea to an active, structured-light system. Depth from defocus of structured light has similar properties as structured light triangulation, but it avoids the &quot;missing parts problem&quot; and the &quot;correspondence problem&quot; by eliminating the parallax between the structured light source and the camera. We propose refinements to the technique, using either an anisotropic aperture or astigmatic optics for the light source. Both refinements use an isotropic structured light pattern and compare blur in two orthogonal directions. We point out different ways to remove the ambiguity between objects behind and in front of the plane of best focus.
Antimicrobial proteins in sterilised human milk. (1977)

Human milk contains factors such as IgA and lactoferrin that increase the newborn infant's resistance to infection. Preterm infants are fed pooled milk, which is normally sterilised by heating. After standard heat sterilisation IgA and lactoferrin were undetectable in milk samples. Pasteurisation also sterilised milk samples even after heavy artificial contamination and did not damage the proteins. Gamma-irradiation sterilised equally effectively but caused some denaturation of IgA and lactoferrin. Since most of the milk samples were sterile or had only light contamination with skin bacteria, there seems to be no need for routine sterilisation. If sterilisation is necessary, the method used should be chosen to minimise damage to milk proteins.
Use of Degenerate Oligonucleotide Primers and the Polymerase Chain Reaction to Clone Gene Family Members (2003)

As more and more genes are cloned and sequenced, it is apparent that nearly all genes are related to other genes. Similar genes are grouped into families. Examples of gene families include the collagen, globin, and myosin gene families. There are also gene superfamilies. Gene superfamilies are composed of genes that have areas of high homology and areas of high divergence. Examples of gene superfamilies include the oncogenes, homeotic genes, and a newly recognized gene superfamily of transmembrane proteins related to the lens fiber cells major intrinsic protein, or the MIP gene superfamily (1). In most cases, the different members of a gene family carry out related functions.
The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo (2009)

Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.
Skin tolerance: in search of the Holy Grail (2007)

In 1943, Gibson and Medawar opened the modern era of transplantation research with a paper on the problem of skin allograft rejection. Ten years later Billingham, Brent and Medawar demonstrated that it was possible to induce selective immune acceptance of skin grafts in mice, a state of tolerance. After over six decades, however, the precise mechanism of skin allograft rejection remains still ill-defined. Furthermore, it has not been possible to achieve reliably clinical tolerance allowing the widespread application of skin allotransplantation techniques. The first successful applications of skin allotransplantation have included the hand and face. However, complications from the chronic immunosuppression regimens limit the application of these techniques. Induction of tolerance to skin (and the other tissues in the allograft) would be the most effective way to overcome all these difficulties, but this is yet to be achieved reliably, stimulating some to look for other ways to surmount the current limitations. This paper summarizes alternatives to enlarge the scope of skin allotransplantation techniques, current understanding of mechanisms of skin rejection, and the utility and limitations of animal models used to study skin rejection and tolerance induction. Finally, manipulation strategies to achieve skin tolerance are outlined.
<title>Sizing of DNA fragments by flow cytometry</title> (1993)

Individual, stained DNA fragments were sized using a modified flow cytometer with high sensitivity fluorescence detection. The fluorescent intercalating dye ethidium homodimer was used to stain stoichiometrically lambda phage DNA and a Kpn I digest of lambda DNA. Stained, individual fragments of DNA were passed through a low average power, focused, mode-locked laser beam, and the fluorescence from each fragment was collected and quantified. Time-gated detection was used to discriminate against Raman scattering from the water solvent. The fluorescence burst from each fragment was related directly to its length, thus providing a means to size small quantities of kilobase lengths of DNA quickly. Improvements of several orders of magnitude in analysis time and sample size over current gel electrophoresis techniques were realized. Fragments of 17.1,29.9, and 48.5 thousand base pairs were well resolved, and were sized in 164 seconds. Less than one pg of DNA was required for analysis. We have demonstrated sizing of individual, stained DNA fragments with resolution approaching that of gel electrophoresis for moderately large fragments, but with significant reductions in the analysis time and the amount of sample required. Furthermore, system response is linear with DNA fragment length, in contrast to the logarithmic response in gel electrophoresis. There exists the potential to perform this sizing using relatively simple instrumentation, i.e. a continuous wave laser of low power and current mode detection.
Transcatheter occlusion of the persistently patent ductus arteriosus. Forty-month follow-up and prevalence of residual shunting. (1991)

Catheter occlusion will obviate the need for surgery in the majority of patients presenting with persistently patent ductus arteriosus. Reocclusion has been found feasible in those with continuous murmurs (nine of nine) and should be offered early because it is unlikely for spontaneous closure to occur in this group. It appears prudent to follow those with small residual shunting because further spontaneous closure can occur.
Effects of Electrical Stimulation at Different Frequencies on Regeneration of Transected Peripheral Nerve (2007)

Electrical stimulation can have either a positive or negative impact on peripheral nerve regeneration. Clinical trials that combine stimulation with rehabilitation must determine the parameters that are most likely to be safe and effective.
Skin regeneration scaffolds: a multimodal bottom-up approach (2012)

Skin wounds are a major social and financial burden. However, current treatments are suboptimal. The gradual comprehension of the finely orchestrated nature of intercellular communication has stimulated scientists to investigate growth factor (GF) or stem cell (SC) incorporation into suitable scaffolds for local delivery into wound beds in an attempt to accelerate healing. This review provides a critical evaluation of the status quo of current research into GF and SC therapy and subsequent future prospects, including benefits and possible long-term dangers associated with their use. Additionally, we stress the importance of a bottom-up approach in scaffold fabrication to enable controlled factor incorporation as well as production of complex scaffold micro- and nanostructures resembling that of natural extracellular matrix.
Idioms (1994)

In the literature of generative grammar, idiomaticity has been widely identified with noncompositionality. Such a definition fails to recognize several important dimensions of idiomaticity, including, among others, conventionality and figuration. We propose to distinguish IDIOMATICALLY COMBINING EXPRESSIONS (e.g. take advantage, pull strings ), whose meanings—while conventional—are distributed among their parts, from IDIOMATIC PHRASES (e.g. kick the bucket, saw logs ), which do not distribute their meanings to their components. Most syntactic arguments based on idioms are flawed, we argue, because they treat all idioms as noncompositional. A careful examination of the semantic properties of idioms and the metaphors that many of them employ helps to explain certain intriguing asymmetries in the grammatical and thematic roles of idiomatic noun phrases.
Methodology Is Destiny: The Effect of Survey Prompts on Reported Levels of Giving and Volunteering (2004)

This article extends earlier methodological tests of giving and volunteering in Indiana to a large (N = 4,200) cross-sectional sample collected in the United States in the fall of 2001. The authors find that the results are consistent with those found in the earlier analyses, namely, that longer, more detailed prompts led respondents to recall giving and volunteering at higher incidence rates (proportion donating at all or volunteering at all) and at higher levels (dollars given or hours volunteered) than when compared to survey methodologies with fewer prompts.
Prodrugs : topical and ocular drug delivery (1992)

Penetration Enhancement: Physicochemical Considerations and Implications for Prodrug Design, Richard H. Guy and Jonathan Hadgraft Functional Group Considerations in the Development of Prodrug Approaches to Solving Topical Delivery Problems, Kenneth B. Sloan Prodrugs for Dermal Delivery: Solubility, Molecular Size, and Functional Group Effects, Gerald B. Kasting, Ronald L. Smith, and Bradley D. Anderson A Computational Method for Predicting Optimization of Prodrugs or Analogues Designed for Percutaneous Delivery, David W. Osborne and William J. Lambert Use of Solubility Parameters from Regular Solution Theory to Describe Partitioning-Driven Processes, Kenneth B. Sloan The Effect of Partitioning and Enzymatic Hydrolysis on the Percutaneous Transport of Lipophilic Prodrugs, Russell O. Potts Improved Ocular Drug Delivery with Prodrugs, Vincent H. L. Lee and Hans Bundgaard
Clinical, electrophysiologic, and pathologic evidence for sensory abnormalities in ALS (2007)

These data indicate that one third of patients with amyotrophic lateral sclerosis report sensory symptoms and sural sensory response amplitudes are reduced in a similar proportion of subjects. Pathologic evidence of sensory nerve pathology was present in 91% of patients who underwent sural nerve biopsy. The electrophysiologic and pathologic findings indicate a pattern of axonal loss that predominantly affects large-caliber myelinated fibers.