gebhart/patrepeval huggingface dataset:
Development and testing of improved suicide functions for biological containment of bacteria (1995)

We have developed very efficient suicide functions for biological containment based on the lethal Escherichia coli relF gene. The suicide functions are placed in duplicate within a plasmid and arranged to prevent inactivation by deletion, recombination, and insertional inactivation. The efficiency of this concept was tested in a plasmid containment system that prevents transfer of plasmids to wild-type bacteria. Protection against plasmid transfer was assayed in test tubes and in rat intestine. Protection was efficient and refractory to inactivation by mutation and transposons. The efficiency of the suicide system was also tested in soil and seawater. We show that unprecedented suicide efficiency can be achieved in soil and seawater after suicide induction by IPTG (isopropyl-beta-D-thiogalactopyranoside). More than 7 orders of magnitude reduction in suicide bacteria was achieved.
Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells (2001)

Melanoma and renal cell carcinoma (RCC) are considered to be the most immunogenic tumors in humans. To generate conditions to induce primary T-cell responses against RCC and to allow further expansion of tumor-specific cytotoxic T lymphocytes (CTL) for adoptive transfer, peripheral blood mononuclear cells from RCC patients were stimulated with primary autologous tumor cells or monocyte-derived dendritic cells (DC) loaded with either tumor lysate (TU-LY) or apoptotic tumor cells (TU-AP). Whereas repetitive stimulation (4x) with tumor cells alone induced a predominant population of CD3(-) natural killer cells, 4 weeks of stimulation with tumor-loaded DC favored induction and expansion of CD4+ T cells (>80%). However, 2 weekly stimulation cycles with tumor-loaded DC followed by restimulation with autologous irradiated tumor cells alone were optimal for induction of tumor-specific CTL responses in vitro. Using these culture conditions a marked increase of CD4+ T cells was observed during the first 2 weeks of stimulation with tumor-loaded DC. Subsequent restimulation with autologous tumor cells alone gave rise to 500-fold expansion of CD8+ T cells. These CD8+ T cells were shown to exhibit strong major histocompatibility complex class I-restricted cytotoxic activity against the autologous tumor. Comparison of TU-LY and TU-AP as a source of tumor antigen for loading DC did not show any difference in stimulating tumor-specific CTL. Length pattern analysis of the complementary determining region 3 (CDR3) of the T-cell receptor Vbeta chain revealed expansion of oligoclonal CTL populations with outgrowth of 1 or 2 clones after prolonged stimulation with autologous tumor cells. Our study demonstrated an efficient method for generating tumor-specific CTL in vitro that may be used to identify tumor cell antigens or that can be expanded for adoptive T-cell transfer in tumor immunotherapy.
MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism (2015)

The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of MYC or any other oncogene in the initiation or maintenance of kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that the MYC oncogene, but not the RAS oncogene, initiates and maintains RCC. Desorption electrospray ionization-mass-spectrometric imaging was used to obtain chemical maps of metabolites and lipids in the mouse RCC samples. Gene expression analysis revealed that the mouse tumors mimicked human RCC. The data suggested that MYC-induced RCC up-regulated the glutaminolytic pathway instead of the glycolytic pathway. The pharmacologic inhibition of glutamine metabolism with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide impeded MYC-mediated RCC tumor progression. Our studies demonstrate that MYC overexpression causes RCC and points to the inhibition of glutamine metabolism as a potential therapeutic approach for the treatment of this disease.
Surface hydrophobicity and intracellular degradation of proteins. (1997)

Cellular proteins turn over with rates varying more than 1000 fold and all organelles are involved in this process of renewal. Although the surface of protein molecules bears many peptide bonds, which could be potential cleavage sites for proteases, only a small fraction of all cellular proteins is subject to very rapid turnover, with half-lives of less than one hour in mammalian cells. Many of these proteins play key roles in basic regulatory mechanisms. One of the features that make proteins short-lived is surface hydrophobicity which is increased in nascent polypeptide chains before association with chaperones, in oligomeric proteins before the association of the monomers, and in many enzymes in absence of their substrates. Cellular proteases tend to act most rapidly on peptide bonds involving (or near to) apolar amino acids. A striking correlation has been found between the half-lives of cellular proteins and their surface hydrophobicity. Clusters of hydrophobic residues appear to be necessary for ubiquitination. Apolar amino acid residues that are hidden can be exposed after oxidation of proteins or after binding of ubiquitin molecules. Additionally, tetraubiquitin exposes many hydrophobic residues which are essential for targeting of the ubiquitinated substrate proteins to a 50 kDa-subunit of the 26S-protease.
Non-Zinc Mediated Inhibition of Carbonic Anhydrases: Coumarins Are a New Class of Suicide Inhibitors (2009)

The X-ray crystal structure of the adduct between the zinc metalloenzyme carbonic anhydrase II (CA, EC 4.2.1.1) with the recently discovered natural product coumarin derivative 6-(1S-hydroxy-3-methylbutyl)-7-methoxy-2H-chromen-2-one showed the coumarin hydrolysis product, a cis-2-hydroxy-cinnamic acid derivative, and not the parent coumarin, bound within the enzyme active site. The bound inhibitor exhibits an extended, two-arm conformation that effectively plugs the entrance to the enzyme active site with no interactions with the catalytically crucial zinc ion. The inhibitor is sandwiched between Phe131, with which it makes an edge-to-face stacking, and Asn67/Glu238sym, with which it makes several polar and hydrogen bonding interactions. This unusual binding mode, with no interactions between the inhibitor molecule and the active site metal ion is previously unobserved for this enzyme class and presents a new opportunity for future drug design campaigns to target a mode of inhibition that differs substantially from classical inhibitors such as the clinically used sulfonamides and sulfamates. Several structurally simple coumarin scaffolds were also shown to inhibit all 13 catalytically active mammalian CA isoforms, with inhibition constants ranging from nanomolar to millimolar. The inhibition is time dependent, with maximum inhibition being observed after 6 h.
Transgenic Animal Technology: A Laboratory Handbook (2014)

Section One Overview. Introduction to transgenic animals. Section Two Transgenic animal production focusing on the mouse model. Transgenic animal production using DNA microinjection. Factors affecting transgenic animal production. Gene targeting in embryonic stem cells I: History and methodology. Gene targeting in embryonic stem cells II. Conditional technologies. Retrovirus-mediated gene transfer. Nuclear transfer technologies. Section Three Production of transgenic laboratory and domestic animal species. Production of transgenic rats. Production of transgenic rabbits. Production of transgenic fish. Production of transgenic poultry. Production of transgenic swine by DNA Microinjection. Production of transgenic ruminants by DNA Microinjection. Production of transgenic non-human primates. Retrovirus-mediated gene transfer into oocytes. Section Four: Molecular biology, analyses and enabling technologies Vector design for Transgene Expression. Analysis of transgene integration. PCR optimization for Detection of Transgenic Integration. Evaluation of Transgene Expression. Control of gene expression (from standard gain/loss of function to anti-sense to PNAs). Enabling technologies:Cryopreservation of gametes. Enabling technologies:Embryo culture considerations. Databases, Internet Resources and Genetic Nomenclature.
Human pain in a dish: Native DRG neurons and differentiated pluripotent stem cells (2014)

Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, CT 06516, USA *Address: Center for Neuroscience and Regeneration Research, 127A, Bldg 34, VA Connecticut Healthcare System, 950 Campbell Ave, West Haven, CT 06516, USA. Tel.: +1 (203) 937 3802; fax: +1 (203) 937 3801. E-mail: [email protected]
Semantic Parsing via Staged Query Graph Generation: Question Answering with Knowledge Base (2015)

Wen-tau Yih, Ming-Wei Chang, Xiaodong He, Jianfeng Gao. Proceedings of the 53rd Annual Meeting of the Association for Computational Linguistics and the 7th International Joint Conference on Natural Language Processing (Volume 1: Long Papers). 2015.
Cyanines during the 1990s:  A Review (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyanines during the 1990s: A ReviewAmaresh Mishra, Rajani K. Behera, Pradipta K. Behera, Bijaya K. Mishra, and Gopa B. BeheraView Author Information Centre of Studies in Surface Science and Technology, Department of Chemistry, Sambalpur University, Jyoti Vihar 768 019, Orissa, India Cite this: Chem. Rev. 2000, 100, 6, 1973–2012Publication Date (Web):May 9, 2000Publication History Received27 January 1999Published online9 May 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/cr990402thttps://doi.org/10.1021/cr990402tresearch-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views15036Altmetric-Citations1310LEARN 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 SUBJECTS:Absorption,Dyes and pigments,Fluorescence,Molecules,Solvents Get e-Alerts
Combined effects of the signal sequence and the major chaperone proteins on the export of human cytokines in Escherichia coli (1996)

We have studied the export of two human proteins in the course of their production in Escherichia coli. The coding sequences of the granulocyte-macrophage colony-stimulating factor and of interleukin 13 were fused to those of two synthetic signal sequences to direct the human proteins to the bacterial periplasm. We found that the total amount of protein varies with the signal peptide-cytokine combination, as does the fraction of it that is soluble in a periplasmic extract. The possibility that the major chaperone proteins such as SecB and the GroEL-GroES and DnaK-DnaJ pairs are limiting factors for the export was tested by overexpressing one or the other of these chaperones concomitantly with the heterologous protein. The GroEL-GroES chaperone pair had no effect on protein production. Overproduction of SecB or DnaK plus DnaJ resulted in a marked increase of the quantity of human proteins in the periplasmic fraction, but this increase depends on the signal peptide-heterologous protein-chaperone association involved.
Decoding by Linear Programming (2005)

This paper considers a natural error correcting problem with real valued input/output. We wish to recover an input vector f/spl isin/R/sup n/ from corrupted measurements y=Af+e. Here, A is an m by n (coding) matrix and e is an arbitrary and unknown vector of errors. Is it possible to recover f exactly from the data y? We prove that under suitable conditions on the coding matrix A, the input f is the unique solution to the /spl lscr//sub 1/-minimization problem (/spl par/x/spl par//sub /spl lscr/1/:=/spl Sigma//sub i/|x/sub i/|) min(g/spl isin/R/sup n/) /spl par/y - Ag/spl par//sub /spl lscr/1/ provided that the support of the vector of errors is not too large, /spl par/e/spl par//sub /spl lscr/0/:=|{i:e/sub i/ /spl ne/ 0}|/spl les//spl rho//spl middot/m for some /spl rho/>0. In short, f can be recovered exactly by solving a simple convex optimization problem (which one can recast as a linear program). In addition, numerical experiments suggest that this recovery procedure works unreasonably well; f is recovered exactly even in situations where a significant fraction of the output is corrupted. This work is related to the problem of finding sparse solutions to vastly underdetermined systems of linear equations. There are also significant connections with the problem of recovering signals from highly incomplete measurements. In fact, the results introduced in this paper improve on our earlier work. Finally, underlying the success of /spl lscr//sub 1/ is a crucial property we call the uniform uncertainty principle that we shall describe in detail.
Phosphorylation and Activation of Cell Division Cycle Associated 8 by Aurora Kinase B Plays a Significant Role in Human Lung Carcinogenesis (2007)

Through genome-wide gene expression analysis of lung carcinomas, we detected in the great majority of lung cancer samples cotransactivation of cell division cycle associated 8 (CDCA8) and aurora kinase B (AURKB), which were considered to be components of the vertebrate chromosomal passenger complex. Immunohistochemical analysis of lung cancer tissue microarrays showed that overexpression of CDCA8 and AURKB was significantly associated with poor prognosis of lung cancer patients. AURKB directly phosphorylated CDCA8 at Ser(154), Ser(219), Ser(275), and Thr(278) and seemed to stabilize CDCA8 protein in cancer cells. Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. In addition, functional inhibition of interaction between CDCA8 and AURKB by a cell-permeable peptide corresponding to 20-amino acid sequence of a part of CDCA8 (11R-CDCA8(261-280)), which included two phosphorylation sites by AURKB, significantly reduced phosphorylation of CDCA8 and resulted in growth suppression of lung cancer cells. Our data imply that selective suppression of the CDCA8-AURKB pathway could be a promising therapeutic strategy for treatment of lung cancer patients.
Transformation-Based Error-Driven Parsing (1993)

In this paper we describe a new technique for parsing free text: a transformational grammar 1 is automatically learned that is capable of accurately parsing text into binarybranching syntactic trees. The algorithm works by beginning in a very naive state of knowledge about phrase structure. By repeatedly comparing the results of bracketing in the current state to proper bracketing provided in the training corpus, the system learns a set of simple structural transformations that can be applied to reduce the number of errors. After describing the algorithm, we present results and compare these results to other recent results in automatic grammar induction. 1 INTRODUCTION There has been a great deal of interest of late in the automatic induction of natural language grammar. Given the difficulty inherent in manually building a robust parser, along with the availability of large amounts of training material, automatic grammar induction seems like a path worth pursuing. A number of syste...
Molecular Signatures Distinguish Human Central Memory from Effector Memory CD8 T Cell Subsets (2005)

Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naive central memory (T(CM)), effector memory (T(EM)), and effector memory RA (T(EMRA)) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that T(CM) have a gene expression and cytokine signaling signature that lies between that of naive and T(EM) or T(EMRA) cells, whereas T(EM) and T(EMRA) are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that T(EM) and T(EMRA) cells strongly express genes with known importance in CD8 T cell effector function. In contrast, T(CM) are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish T(CM) and T(EM)/T(EMRA) at the molecular level and are consistent with the concept that T(CM) represent memory stem cells.
Defects in functional expression of an influenza virus hemagglutinin lacking the signal peptide sequences. (1983)

We have investigated the requirement of the signal sequence for expression of influenza virus hemagglutinin (HA). For this purpose we used a recombinant prepared from a late-region deletion mutant of simian virus 40 (SV40) and cloned influenza HA DNA; the influenza DNA was inserted into the late region of SV40 previously occupied by the deleted sequences coding for SV40 capsid proteins. A simple in-phase deletion was made in the HA DNA, resulting in loss of 11 internal amino acids from the 16 amino acid signal peptide. This deletion HA recombinant was then used to infect African green monkey kidney cells. Mutant HA was not detected on the cell surface but stably accumulated in the cytoplasm at a level similar to that of wild-type HA. NaDodSO4/polyacrylamide gel analysis of lysates from infected cells showed that mutant HA was not glycosylated. Significantly, the amount of mutant HA synthesized was not affected by tunicamycin. In contrast, wild-type HA was decreased more than 90% by tunicamycin. These findings suggest that mutant polypeptide is synthesized on free polyribosomes rather than on membrane-bound polyribosomes. The mutant HA failed to agglutinate erythrocytes, probably due to a defect directly or indirectly associated with the lack of carbohydrate side chains.
Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure (2003)

Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow-derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.
How much is there really? Why stereology is essential in lung morphometry (2006)

Quantitative data on lung structure are essential to set up structure-function models for assessing the functional performance of the lung or to make statistically valid comparisons in experimental morphology, physiology, or pathology. The methods of choice for microscopy-based lung morphometry are those of stereology, the science of quantitative characterization of irregular three-dimensional objects on the basis of measurements made on two-dimensional sections. From a practical perspective, stereology is an assumption-free set of methods of unbiased sampling with geometric probes, based on a solid mathematical foundation. Here, we discuss the pitfalls of lung morphometry and present solutions, from specimen preparation to the sampling scheme in multiple stages, for obtaining unbiased estimates of morphometric parameters such as volumes, surfaces, lengths, and numbers. This is demonstrated on various examples. Stereological methods are accurate, efficient, simple, and transparent; the precision of the estimates depends on the size and distribution of the sample. For obtaining quantitative data on lung structure at all microscopic levels, state-of-the-art stereology is the gold standard.
Limitations on subdiffraction imaging with a negative refractive index slab (2003)

A planar slab of material, for which both the permittivity and permeability have the values of −1, can bring not only the propagating fields associated with a source to a focus, but can also refocus the nonpropagating near fields, thereby achieving resolution beyond the diffraction limit. We study the sensitivity of this subwavelength focus to the slab material properties and periodicity, and note the connection to slab surface plasmon modes. We conclude that significant subwavelength resolution is achievable with a single negative index slab, but only over a restrictive range of parameters.
Wound bed preparation: a systematic approach to wound management (2003)

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or "stuck" at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; the current status of wound bed preparation; an analysis of the acute and chronic wound environments; how wound healing can take place in these environments; the role of wound bed preparation in the clinic; the clinical and cellular components of the wound bed preparation concept; a detailed analysis of the components of wound bed preparation.
Method of growing ofp-type GaN in nonequilibrium conditions (1977)

Using Van Vechten's theory, the displacement energy for Ga in GaN is calculated to be 25.5 eV. This relatively high energy makes it possible to adapt the indirect doping technique on GaN crystal growth, in order to obtain $p$-type GaN.