gebhart/patrepeval huggingface dataset:
An efficient T-cell epitope discovery strategy using in silico prediction and the iTopia assay platform (2012)

Functional T-cell epitope discovery is a key process for the development of novel immunotherapies, particularly for cancer immunology. In silico epitope prediction is a common strategy to try to achieve this objective. However, this approach suffers from a significant rate of false-negative results and epitope ranking lists that often are not validated by practical experience. A high-throughput platform for the identification and prioritization of potential T-cell epitopes is the iTopia(TM) Epitope Discovery System(TM), which allows measuring binding and stability of selected peptides to MHC Class I molecules. So far, the value of iTopia combined with in silico epitope prediction has not been investigated systematically. In this study, we have developed a novel in silico selection strategy based on three criteria: (1) predicted binding to one out of five common MHC Class I alleles; (2) uniqueness to the antigen of interest; and (3) increased likelihood of natural processing. We predicted in silico and characterized by iTopia 225 candidate T-cell epitopes and fixed-anchor analogs from three human tumor-associated antigens: CEA, HER2 and TERT. HLA-A2-restricted fragments were further screened for their ability to induce cell-mediated responses in HLA-A2 transgenic mice. The iTopia binding assay was only marginally informative while the stability assay proved to be a valuable experimental screening method complementary to in silico prediction. Thirteen novel T-cell epitopes and analogs were characterized and additional potential epitopes identified, providing the basis for novel anticancer immunotherapies. In conclusion, we show that combination of in silico prediction and an iTopia-based assay may be an accurate and efficient method for MHC Class I epitope discovery among tumor-associated antigens.
Adenovirus‐mediated gene therapy of experimental gliomas (1994)

The efficacy of adenovirus (ADV)-mediated gene therapy to treat brain tumors was tested in a syngeneic glioma model. Tumor cells were transduced in situ with a replication-defective ADV carrying the herpes simplex virus thymidine kinase (HSV-tk) gene controlled by the Rous sarcoma virus promoter. Expression of the HSV-tk gene enables the transduced cell to convert the drug ganciclovir to a form that is cytotoxic to dividing cells. Tumors were generated in Fischer 344 rats by stereotaxic implantation of 9L gliosarcoma cells into the caudate nucleus. Eight days later, the tumors were injected either with the ADV carrying the HSV-tk (ADV-tk) gene or a control ADV vector containing the beta-galactosidase (ADV-beta gal) gene and the rats were treated with either ganciclovir or saline. Tumor size was measured 20 days after implantation of 9L cells or at death. Rats treated with ADV-beta gal and ganciclovir or with ADV-tk and saline had large tumors. No tumors were detected in animals treated with ADV-tk and with ganciclovir at doses > or = 80 mg/kg. An infiltrate of macrophages and lymphocytes at the injection site in animals treated with ADV-tk and ganciclovir indicated an active local immune reaction. In survival studies, all animals treated with ADV-tk and ganciclovir have remained alive longer than 80 and up to 120 days after tumor induction whereas all untreated animals died by 22 days. These results demonstrate that ADV-mediated transfer of HSV-tk to glioma cells in vivo confers sensitivity to ganciclovir, and represents a potential method of treatment of brain tumors.
High Overall In Vitro Efficiency of Porcine Handmade Cloning (HMC) Combining Partial Zona Digestion and Oocyte Trisection with Sequential Culture (2005)

We investigated the in vitro developmental competence of porcine embryos produced from in vitro matured (IVM) oocytes by improved HMC and parthenogenetic activation (PA). Embryos were cultured in a modified North Carolina State University (NCSU37) medium. Firstly, we compared the developmental competence between oocytes from sows and gilts by zona-intact (ZI) and zona-free (ZF) PA. Significantly higher (p < 0.05) blastocyst rates were obtained from sow oocytes (42 +/- 4% for ZF and 55 +/- 6% for ZI) than gilt oocytes (20 +/- 2% for ZF and 26 +/- 5% for ZI). Secondly, sow oocytes were used to establish the modified HMC that was based on a modified enucleation with partial zona digestion and trisection of porcine oocytes and the use of three cytoplasts and one somatic cell for embryo reconstruction. In vitro fertilization (IVF) and in parallel ZF PA were used as the control systems. After oocyte trisection, >90% of oocyte fragments were recovered, resulting in an average of 37 reconstructed embryos from 100 oocytes. Blastocyst rates of HMC, IVF, and ZF PA embryos were 17 +/- 4%, 30 +/- 6%, and 47 +/- 4%, respectively. Our results prove that HMC in pigs may result in high in vitro efficiency up until the blastocyst stage. In vivo developmental competence will be confirmed in embryo transfer experiments.
Metabolic Responses of Mesophytes to Plant Water Deficits (1982)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
OpenCFU, a New Free and Open-Source Software to Count Cell Colonies and Other Circular Objects (2013)

Counting circular objects such as cell colonies is an important source of information for biologists. Although this task is often time-consuming and subjective, it is still predominantly performed manually. The aim of the present work is to provide a new tool to enumerate circular objects from digital pictures and video streams. Here, I demonstrate that the created program, OpenCFU, is very robust, accurate and fast. In addition, it provides control over the processing parameters and is implemented in an intuitive and modern interface. OpenCFU is a cross-platform and open-source software freely available at http://opencfu.sourceforge.net.
Philosophy and the Cognitive Sciences (1994)

Online collection of papers by Devitt, Dretske, Guarino, Hochberg, Jackson, Petitot, Searle, Tye, Varzi and other leading thinkers on philosophy and the foundations of cognitive Science. Topics dealt with include: Wittgenstein and Cognitive Science, Content and Object, Logic and Foundations, Language and Linguistics, and Ontology and Mereology.
Relationship Between the Lethal Yellow (<italic>A</italic><sup><italic>y</italic></sup>) Gene of the Mouse and Susceptibility to Induced Pulmonary Tumors (1942)

Relationship Between the Lethal Yellow (A y ) Gene of the Mouse and Susceptibility to Induced Pulmonary Tumors Get access W. E. Heston W. E. Heston geneticist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 3, December 1942, Pages 303–308, https://doi.org/10.1093/jnci/3.3.303 Published: 01 December 1942
Unifying mechanism for Aplysia ADP-ribosyl cyclase and CD38/NAD+ glycohydrolases (2000)

Highly purified Aplysia californica ADP-ribosyl cyclase was found to be a multifunctional enzyme. In addition to the known transformation of NAD+ into cADP-ribose this enzyme is able to catalyse the solvolysis (hydrolysis and methanolysis) of cADP-ribose. This cADP-ribose hydrolase activity, which becomes detectable only at high concentrations of the enzyme, is amplified with analogues such as pyridine adenine dinucleotide, in which the cleavage rate of the pyridinium-ribose bond is much reduced compared with NAD+. Although the specificity ratio Vmax/Km is in favour of NAD+ by 4 orders of magnitude, this multifunctionality allowed us to propose a ‘partitioning’ reaction scheme for the Aplysia enzyme, similar to that established previously for mammalian CD38/NAD+ glycohydrolases. This mechanism involves the formation of a single oxocarbenium-type intermediate that partitions to cADP-ribose and solvolytic products via competing pathways. In favour of this mechanism was the finding that the enzyme also catalysed the hydrolysis of NMN+, a substrate that cannot undergo cyclization. The major difference between the mammalian and the invertebrate enzymes resides in their relative cyclization/hydrolysis rate-constant ratios, which dictate their respective yields of cADP-ribose (ADP-ribosyl cyclase activity) and ADP-ribose (NAD+ glycohydrolase activity). For the Aplysia enzyme's catalysed transformation of NAD+ we favour a mechanism where the formation of cADP-ribose precedes that of ADP-ribose; i.e. macroscopically the invertebrate ADP-ribosyl cyclase conforms to a sequential reaction pathway as a limiting form of the partitioning mechanism.
Impaired Retinal Angiogenesis in Diabetes (2005)

Suppression of angiogenesis during diabetes is a recognized phenomenon but is less appreciated within the context of diabetic retinopathy. The current study has investigated regulation of retinal angiogenesis by diabetic serum and determined if advanced glycation end products (AGEs) could modulate this response, possibly via AGE-receptor interactions. A novel in vitro model of retinal angiogenesis was developed and the ability of diabetic sera to regulate this process was quantified. AGE-modified serum albumin was prepared according to a range of protocols, and these were also analyzed along with neutralization of the AGE receptors galectin-3 and RAGE. Retinal ischemia and neovascularization were also studied in a murine model of oxygen-induced proliferative retinopathy (OIR) in wild-type and galectin-3 knockout mice (gal3(-/-)) after perfusion of preformed AGEs. Serum from nondiabetic patients showed significantly more angiogenic potential than diabetic serum (P < 0.0001) and within the diabetic group, poor glycemic control resulted in more AGEs but less angiogenic potential than tight control (P < 0.01). AGE-modified albumin caused a dose-dependent inhibition of angiogenesis (P < 0.001), and AGE receptor neutralization significantly reversed the AGE-mediated suppression of angiogenesis (P < 0.01). AGE-treated wild-type mice showed a significant increase in inner retinal ischemia and a reduction in neovascularization compared with non-AGE controls (P < 0.001). However, ablation of galectin-3 abolished the AGE-mediated increase in retinal ischemia and restored the neovascular response to that seen in controls. The data suggest a significant suppression of angiogenesis by the retinal microvasculature during diabetes and implicate AGEs and AGE-receptor interactions in its causation.
Electrochemical Probing of DNA Based on Oligonucleotide-Functionalized Polypyrrole (2001)

We have developed a new type of electrochemical biosensor based on oligonucleotide-functionalized polypyrrole. At first, we analyzed the experimental conditions necessary for building such modified electrodes that show a high electroactivity in aqueous media. We developed a precursor polymer bearing an easy leaving ester group on which amino-labeled oligonucleotides with various sequence lengths were directly substituted. The electrochemical response of the modified electrode was analyzed in various aqueous media containing either complementary or noncomplementary oligonucleotides. Results show that the cyclic voltammogram of oligonucleotide-functionalized polypyrrole is not modified when in the presence of a noncomplementary oligonucleotide in solution. On the other hand, a significant modification of the voltammogram is observed upon addition of a complementary oligonucleotide "target" to the electrolytic medium, which can be quantitatively determined by amperometric methods. The detection limit of this electrochemical biosensor is about 10(-11) mol, without any signal processing.
Breeding Opportunities for Increasing the Efficiency of Water Use and Crop Yield in Temperate Cereals (2002)

Genetic advances in grain yield under rainfed conditions have been achieved by empirical breeding methods. Progress is slowed, however, by large genotype x season and genotype x location interactions arising from unpredictable rainfall, which is a feature of dry environments. A good understanding of factors limiting and/or regulating yield now provides us with an opportunity to identify and then select for physiological and morphological traits that increase the efficiency of water use and yield under rainfed conditions. The incorporation of these traits into breeders' populations should broaden their genetic base. It also may lead to faster selection methods and selection for the traits may result in correlated gains in yield. Here, we undertake a review of factors that limit yield in rainfed environments and discuss genetic opportunities and genetic progress in overcoming them. The examples given are for wheat (Triticum aestivum L.), but the principles apply to all cereal crops grown in dry environments.
Structural, optical and electrical properties of ZnO thin films grown by radio frequency (rf) sputtering in oxygen atmosphere (2011)

Growth conditions for ZnO thin films were found for their potential use as a buffer layer in CdTe/CdS solar cells. Electrical, optical and structural properties were investigated as a function of the oxygen pressure during the growth of ZnO by radio frequency (rf) sputtering. The electrical behavior is explained in terms of the structural properties. Our results suggest that optimal oxygen partial pressure is 4 Pa for attaining a ZnO thin film as a buffer layer, with resistivity on the order of 103 W cm and an average of optical transmission of 89%.

	 

	Key words: Zinc oxide, transparent conducting oxide, buffer layer, solar cell, electrical resistance, optical transmission.
Self-precharge of floating capacitors in a five-level ANPC inverter (2012)

Five-level active neutral-point-clamped (ANPC) converter is a newly emerging topology which can overcome the drawbacks of traditional neutral-point-clamped and flying-capacitor multilevel converters. During the start-up of the converter, it must be ensured that the switches and capacitors cannot be overvoltage and overcurrent due to the uncharged floating capacitors. In this paper, a floating capacitor self-precharge method is proposed which, by transferring the circuit into a booster, charges the floating capacitors to the reference voltage with a very small average load current. Simulation and experimental results are presented to verify the validity of this method.
Lipid Nanoparticles for the Delivery of Biopharmaceuticals (2015)

Biopharmaceuticals comprise therapeutic protein-based, nucleic acids and cell-based products. According to their therapeutic success, the clinical use of these products has been growing. Therefore, the development of efficient biopharmaceuticals delivery systems, which overcome their limitations for administration, remains an excellent prospect for pharmaceutical technologists. In this area, lipid nanoparticles have been increasingly recognized as one of the most promising delivery systems, due to their exclusive advantages. However, no clinical biopharmaceutical lipid nanoparticle-based products are yet available. This fact could be explained by the lack or failure of in vivo studies, regarding stability and toxicological concerns, and also by the complex regulatory issues that must be accomplished. The present review article focuses on the different classes of biopharmaceuticals, their characteristics and limitations for administration. A state of the art regarding the use of lipid nanoparticles to improve biopharmaceuticals delivery is presented and a critical prospect of the future directions that should be addressed by pharmaceutical technologists is also discussed.
Purification and characterization of other distinct bone-inducing factors. (1988)

We purified a factor that induces bone formation greater than 300,000-fold from guanidinium chloride extracts of demineralized bone. Fifty nanograms of highly purified protein was active in an in vivo cartilage and bone-formation assay. The activity resided in a single gel band, corresponding to a molecular mass of approximately 30 kDa, which yielded proteins of 30, 18, and 16 kDa on reduction. The partial amino acid sequence obtained from these proteins confirmed our identification of specific factors that induce new bone formation in vivo.
Isolation of a cDNA from the Virus Responsible for Enterically Transmitted Non-A, Non-B Hepatitis (1990)

Major epidemic outbreaks of viral hepatitis in underdeveloped countries result from a type of non-A, non-B hepatitis distinct from the parenterally transmitted form. The viral agent responsible for this form of epidemic, or enterically transmitted non-A, non-B hepatitis (ET-NANBH), has been serially transmitted in cynomolgus macaques (cynos) and has resulted in typical elevation in liver enzymes and the detection of characteristic virus-like particles (VLPs) in both feces and bile. Infectious bile was used for the construction of recombinant complementary DNA libraries. One clone, ET1.1, was exogenous to uninfected human and cyno genomic liver DNA, as well as to genomic DNA from infected cyno liver. ET1.1 did however, hybridize to an approximately 7.6-kilobase RNA species present only in infected cyno liver. The translated nucleic acid sequence of a portion of ET1.1 had a consensus amino acid motif consistent with an RNA-directed RNA polymerase; this enzyme is present in all positive strand RNA viruses. Furthermore, ET1.1 specifically identified similar sequences in complementary DNA prepared from infected human fecal samples collected from five geographically distinct ET-NANBH outbreaks. Therefore, ET1.1 represents a portion of the genome of the principal viral agent, to be named hepatitis E virus, which is responsible for epidemic outbreaks of ET-NANBH.
Diltiazem-like Calcium Entry Blockers:  A Hypothesis of the Receptor-Binding Site Based on a Comparative Molecular Field Analysis Model (1997)

A series of 26 pyrrolo[2,1-c][1,4]benzothiazines, which have been already synthesized and reported to show calcium antagonist activity in both radioligand-binding assays and functional studies, were investigated using the comparative molecular field analysis (CoMFA) paradigm. Due to the lack of experimental structural data on these derivatives, the minimum energy conformers obtained by molecular mechanics calculations were used in the subsequent study. Structures were aligned following an alignment criterion based on the pharmacophoric groups of the studied compounds. The predictive ability of the CoMFA model was evaluated using a test set consisting of three representative compounds. The best 3D-quantitative structure-activity relationship model found yields significant cross-validated, conventional, and predictive r2 values equal to 0.703, 0.970, and 0.865, respectively, the average absolute error of predictions being 0.26 log unit. The predictive capability of this model was also tested on a further test set of molecules consisting of diltiazem and nine pyrrolo[2,1-d][1,5]benzothiazepines endowed with calcium antagonist activity. The accurate results obtained also in this case revealed the robustness of the model. On the basis of the same alignment, the structural moieties of the studied calcium entry blockers which are thought to contribute to the biological activity were identified, and a possible receptor-binding site for all these compounds is presented taking into account the information derived from the analysis of the steric and electrostatic CoMFA contour maps.
Safety Evaluation of Ocular Drug Delivery Formulations: Techniques and Practical Considerations (2008)

Development of new drug candidates and novel delivery techniques for treatment of ocular diseases has recently accelerated. Treatment of anterior-segment diseases has witnessed advances in prodrug formulations and permeability enhancers. Intravitreal, subconjunctival, and periocular routes of administration and sustained-release formulations of nanoparticles and microparticles, as well as nonbiodegradable and biodegradable implants to deliver drugs to the posterior segment of the eye, are becoming popular therapeutic approaches. Without adequate regulatory guidance for ocular drugs, such routes of administration and novel formulations can pose unique challenges to those involved in designing nonclinical programs, including considering clinical and nonclinical factors and choosing species, strains, and ocular toxicity parameters. Toxicologic pathologists also contribute practical experience to evaluating morphological effects of these novel formulations. Lastly, understanding species' anatomical differences is useful for interpreting toxicological and pathological responses to the eye and is important for human risk assessment of these important new therapies for ocular diseases.
The Self-Locking Metal Hip Prosthesis (1957)

Great judgment should be exercised in the selection of patients for replacement of the femoral head and a careful postoperative program should be planned. The importance of partial weight-bearing for a period of at least six months should be emphasized, with a gradual increase as roentgenograms show the reaction of bone about the prosthesis. New-bone formation takes place within the fenestrations of the prosthesis. Once this has occurred, the stem cannot be removed without chiseling away the new bone. The prosthesis becomes, literally, self-locking. It is very interesting to see, roentgenographically, the increasing density of bone in and under the prosthesis in the stress-bearing locations. If a prosthesis is to last indefinitely, it must be constructed in such a way that stress is distributed so as to produce a dynamic reaction, in accordance with Wolff's law. In this way, there gradually occurs a thickening of bone about the prosthesis enabling it to carry the normal load of weight and stress. The prosthesis becomes a part of the living bone. Five years ago a preliminary report was made of our experience with a self-locking Vitallium prosthesis in thirty-three patiensts2. The present report reviews the same experience in 153 patients and in 159 operations during a period of six years. There have been no fractures of the bone in applying the prosthesis, and no dislocations of the hip have occurred during the operation. Apparently Vitallium is insert in the tissues, and it is possible that the prosthesis may last indefinitely. Patients are made to understand that no artificial replacement can be expected to function as well as the normal hip and are urged to be careful. They are advised to always carry a cane or to use a light support. An attempt is being made to follow all patients. Time has already shown conclusively that transplanted cancellous bone in the medullary canal undergoes metaplastic changes and that the bone becomes progressively denser in the areas of stress. Time has also shown, as was anticipated, that there is hyperplasia of bone in, under, and about the prosthesis when weight-bearing is properly applied. Excessive weight-bearing stress or too short a stem results in pressure necrosis with a loose, clicking prosthesis and pain. With the stimulating stress of gradual weight-bearing, areas of increased density of bone appear about the prosthesis consistent with known mechanical and engineering principles. When patients have been properly selected and when operation has been correctly performed, and postoperative follow-up care has been conscientiously carried out, this prosthesis appears to become a part of the femur and to carry the normal stress load of weight-bearing with minimal degenerative changes and with minimal pain. The results so far are encouraging, and the increasing number of patients bears witness to growing confidence in the procedure. Final results can be known and a thorough evaluation of the method can be made only after many years of experience.