gebhart/patrepeval huggingface dataset:
Generation of murine tumor cell lines deficient in MHC molecule surface expression using the CRISPR/Cas9 system (2017)

In this study, the CRISPR/Cas9 technology was used to establish murine tumor cell lines, devoid of MHC I or MHC II surface expression, respectively. The melanoma cell line B16F10 and the murine breast cancer cell line EO-771, the latter stably expressing the tumor antigen NY-BR-1 (EO-NY), were transfected with an expression plasmid encoding a β2m-specific single guide (sg)RNA and Cas9. The resulting MHC I negative cells were sorted by flow cytometry to obtain single cell clones, and loss of susceptibility of peptide pulsed MHC I negative clones to peptide-specific CTL recognition was determined by IFNγ ELISpot assay. The β2m knockout (KO) clones did not give rise to tumors in syngeneic mice (C57BL/6N), unless NK cells were depleted, suggesting that outgrowth of the β2m KO cell lines was controlled by NK cells. Using sgRNAs targeting the β-chain encoding locus of the IAb molecule we also generated several B16F10 MHC II KO clones. Peptide loaded B16F10 MHC II KO cells were insusceptible to recognition by OT-II cells and tumor growth was unaltered compared to parental B16F10 cells. Thus, in our hands the CRISPR/Cas9 system has proven to be an efficient straight forward strategy for the generation of MHC knockout cell lines. Such cell lines could serve as parental cells for co-transfection of compatible HLA alleles together with human tumor antigens of interest, thereby facilitating the generation of HLA matched transplantable tumor models, e.g. in HLAtg mouse strains of the newer generation, lacking cell surface expression of endogenous H2 molecules. In addition, our tumor cell lines established might offer a useful tool to investigate tumor reactive T cell responses that function independently from MHC molecule surface expression by the tumor.
Modulation of intercellular adherens-type junctions and tyrosine phosphorylation of their components in RSV-transformed cultured chick lens cells. (1991)

Transformation of cultured chick lens epithelial cells with a temperature-sensitive mutant of Rous sarcoma virus (tsRSV) leads to radical changes in cell shape and interactions. When cultured at the restrictive temperature (42 degrees C), the transformed cells largely retained epithelial morphology and intercellular adherens junctions (AJ), whereas on switch to the permissive temperature (37 degrees C) they rapidly became fibroblastoid, their AJ deteriorated, and cell adhesion molecules (A-CAM) (N-cadherin) largely disappeared from intercellular contact sites. The microfilament system that was primarily associated with these junctions was markedly rearranged on shift to 37 degrees C and remained associated mainly with cell-substrate focal contacts. These apparent changes in intercellular AJ were not accompanied by significant alterations in the cellular content of several junction-associated molecules, including A-CAM, vinculin, and talin. Immunolabeling with phosphotyrosine-specific antibodies indicated that both cell-substrate and intercellular AJ were the major cellular targets for the pp60v-src tyrosine-specific protein kinase. It was further shown that intercellular AJ components serve as substrates to tyrosine kinases also in nontransformed lens cells, because the addition of a combination of vanadate and H2O2--which are potent inhibitors of protein tyrosine phosphatases--leads to a remarkable accumulation of immunoreactive phosphotyrosine-containing proteins in these junctions. This finding suggests that intercellular junctions are major sites of action of protein tyrosine kinases and that protein tyrosine phosphatases play a major role in the regulation of phosphotyrosine levels in AJ of both normal and RSV-transformed cells.
Depletion of serum methionine by methioninase in mice. (1993)

Methionine dependence is a tumor-specific metabolic defect found in human cancer cell lines as well as in fresh human tumor specimens. Methionine dependent tumors cease growing when deprived of methionine, unlike normal cells which can substitute homocysteine for methionine for their growth requirement. We have previously purified a stable, endotoxin-free methioninase from the bacterium, Pseudomonas putida. We demonstrate in this report that purified methioninase can lower the serum levels of methionine in normal and nude mice from 60 microM to approximately 5 microM within 1 hour. The circulating half-life of methioninase is approximately 100 minutes in mice after i.v. injection. The enzyme therefore seems to be a good candidate as an antitumor agent for methionine-dependent tumors.
Free-space micromachined optical switches for optical networking (1999)

Fiber-optic switches with high port count have emerged as leading candidates for deployment in future optical transport networks, where restoration and provisioning in the optical layer will become increasingly important. This paper reviews the principle and performance of free-space micromachined optical switches (FS-MOS) featuring free-rotating hinged micromirrors. A single-chip FS-MOS that implements the critical function of bridging-essential for restoration in core optical networks is also proposed and demonstrated. The scalability of FS-MOS devices, and the dependence of their insertion losses on mirror-angle, are estimated theoretically. Simulation results suggest that the FS-MOS approach holds considerable promise for being expandable to the port-count values that will be needed in future core-transport lightwave networks.
A Conceptual Framework for Caring for Families of Hospice Patients (1990)

Hospice caregivers are usually family-focused in their practice with individual clients. Less often is the entire family as a unit considered the client. The authors present a conceptual framework for working with hospice families as clients. Their perspective incorporates concepts of the family as a system, the family life cycle, and the components of professional practice. Clinical examples illustrate the application of the framework in practice.
Inhibition of ADP-induced P-selectin Expression and Platelet-Leukocyte Conjugate Formation by Clopidogrel and the P2Y12 Receptor Antagonist AR-C69931MX but not Aspirin (2002)

Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activation, aggregation and other responses induced by numerous platelet agonists. We studied the effects of clopidogrel and aspirin on ADP-induced platelet-leukocyte conjugate formation and P-selectin expression in healthy volunteers. The effects of clopidogrel and AR-C69931MX administered to patients with ischaemic heart disease were also assessed. AR-C69931MX and aspirin were also studied in vitro. Clopidogrel and AR-C69931MX suppressed ADP-induced platelet aggregation, P-selectin expression and platelet-leukocyte conjugate formation whereas aspirin had no inhibitory effect. These effects of clopidogrel and AR-C69931MX may confer therapeutic benefits in the management of acute coronary syndromes.
Comparative Study of DNA Enzymes and Ribozymes against the Same Full-length Messenger RNA of the Vanilloid Receptor Subtype I (2002)

The efficiencies of 32 antisense oligodeoxynucleotides, 35 DNA enzymes and 6 ribozymes to bind and cleave the full-length messenger RNA of the vanilloid receptor subtype I were analyzed. Systematic screening of the mRNA revealed that good accessibility of a putative cleavage site for antisense oligodeoxynucleotides is a necessary but not a sufficient prerequisite for efficient DNA enzymes. Comparison of DNA enzymes and ribozymes against the same target sites revealed: 1) DNA enzymes were more active with longer recognition arms (9 nucleotides on either side), whereas ribozymes revealed higher activities with shorter recognition arms (7 nucleotides on either side). 2) It does not only depend on the target site but also on the enzyme sequence, whether a DNA enzyme or a ribozyme is more active. 3) The most efficient DNA enzyme found in this study had an approximately 15-fold higher reaction rate, k(react), and a 100-fold higher k(react)/K(m) under single turnover conditions compared with the fastest ribozyme. DNA enzymes as well as ribozymes showed significant activity under multiple turnover conditions, the DNA enzymes again being more active. We therefore conclude that DNA enzymes are an inexpensive, very stable and active alternative to ribozymes for the specific cleavage of long RNA molecules.
Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells. (1996)

Ovarian cancers have a high ability to invade the peritoneal cavity and some are stimulated by estrogens. In an attempt to understand the mode of action of estrogens on these cancer cells and to develop new markers, we have characterized estrogen-regulated proteins. This study was aimed at identifying a protein secreted by ovarian cancer cells whose level was increased by estradiol [Galtier-Dereure, F., Capony, F., Maudelonde, T. & Rochefort, H. (1992) J. Clin. Endocrinol. Metab. 75, 1497-1502]. By using microprotein sequencing, the 110-kDa protein was identified as fibulin-1, a protein of the extracellular matrix that binds to fibronectin, laminin, and nidogen. The amount of immunoprecipitated fibulin-1 secreted into the medium and present in the cell extract was increased up to 10-fold by estradiol in three estrogen-responsive ovarian cancer cell lines. By immunohistochemistry fibulin-1 was located in the stroma of several ovarian cancers and cysts. The findings highlight a potential role for fibulin-1 in the spread of ovarian cancer in the peritoneal cavity and/or in distal metastases.
Selenium status of cats in four regions of the world and comparison with reported incidence of hyperthyroidism in cats in those regions (2001)

Cats have higher Se concentrations in plasma, compared with values for other species. However, Se status alone does not appear to affect the incidence of hyperthyroidism in cats. High Se concentrations may have implications for health of cats if such concentrations are influenced by the amount of that micronutrient included in diets.
Bioerodible polyanhydrides as drug‐carrier matrices. II. Biocompatibility and chemical reactivity (1986)

The biocompatibility of bioerodible polyanhydrides and toxicology of the polymer breakdown products were assessed. Poly-[bis (p-carboxy-phenoxy) propane anhydride] (PCPP), Poly(terephthalic acid anhydride) (PTA), and their copolymers with sebacic acid were tested. The polymers did not provoke inflammatory responses in the corneas of rabbits over a six week implantation period. Subcutaneous implantation studies of PCPP in rats over a six month period showed no evidence of inflammatory cells and only slight tissue encapsulation by layers of fibroblastic cells. The degradation products of the polymers were nonmutagenic, noncytotoxic, and had a low teratogenic potential. The in vitro growth of mammalian cells on the polymers was unaffected as measured by cell morphology and cell growth rate. The chemical reactivity of the polyanhydrides with reactive model drugs, para substituted anilines, was also examined. Amides were formed when the drugs were injection molded with the polyanhydrides at 120 degrees C. However, no reaction was observed using compression molding at room temperature. No reaction occurred between the polymer and the drug during the hydrolytic degradation of the matrix at 37 degrees C.
Creating Vulnerability Signatures Using Weakest Preconditions (2007)

Signature-based tools such as network intrusion detection systems are widely used to protect critical systems. Automatic signature generation techniques are needed to enable these tools due to the speed at which new vulnerabilities are discovered. In particular, we need automatic techniques which generate sound signatures -- signatures which will not mistakenly block legitimate traffic or raise false alarms. In addition, we need signatures to have few false negatives and will catch many different exploit variants. We investigate new techniques for automatically generating sound vulnerability signatures with fewer false negatives than previous research using program binary analysis. The key problem to reducing false negatives is to consider as many as possible different program paths an exploit may take. Previous work considered each possible program path an exploit may take separately, thus generating signatures that are exponential in the size of the number of branches considered. In the exact same scenario, we show how to reduce the overall signature size and the generation time from exponential to polynomial. We do this without requiring any additional assumptions, or relaxing any properties. This efficiency gain allows us to consider many more program paths, which results in reducing the false negatives of generated signatures. We achieve these results by creating algorithms for generating vulnerability signatures that are based on computing weakest preconditions (WP). The weakest precondition for a program path to a vulnerability is a function which matches all exploits that may exploit the vulnerability along that path. We have implemented our techniques and generated signatures for several binary programs. Our results demonstrate that our WP-based algorithm generates more succinct signatures than previous approaches which were based on forward symbolic execution.
Acute Opioid Tolerance (2000)

Relatively large-dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.
Learning Bayesian Network Structure from Massive Datasets: The "Sparse Candidate" Algorithm (1999)

Learning Bayesian networks is often cast as an optimization problem, where the computational task is to find a structure that maximizes a statistically motivated score. By and large, existing learning tools address this optimization problem using standard heuristic search techniques. Since the search space is extremely large, such search procedures can spend most of the time examining candidates that are extremely unreasonable. This problem becomes critical when we deal with data sets that are large either in the number of instances, or the number of attributes. In this paper, we introduce an algorithm that achieves faster learning by restricting the search space. This iterative algorithm restricts the parents of each variable to belong to a small subset of candidates. We then search for a network that satisfies these constraints. The learned network is then used for selecting better candidates for the next iteration. We evaluate this algorithm both on synthetic and real-life data. Our results show that it is significantly faster than alternative search procedures without loss of quality in the learned structures.
Optimising inter-view prediction structure for multiview video coding with minimum spanning tree (2007)

A new systematic method to construct a near-optimal inter-view prediction structure for multiview video coding is proposed based on the directed minimum spanning tree of inter-view prediction cost graph. The method is applicable to arbitrary irregular and dynamic changing camera arrangements. Results show that the generated structure achieves better compression efficiency than the reference structure of the joint multiview video model.
Instability of electromagnetic oscillations of the millimeter wave range specified by injection of charge carrier in inhomogeneous semiconductor structures (1989)

Present-day technology allows to develop a semiconductor plasma of limited sizes in which a ballistic (collisionless) charge transfer is realized [1]-[3].
Diazonium−Protein Adducts for Graphite Electrode Microarrays Modification:  Direct and Addressed Electrochemical Immobilization (2005)

Diazonium cation electrodeposition was investigated for the direct and electro-addressed immobilization of proteins. For the first time, this reaction was triggered directly onto diazonium-modified proteins. Screen-printed (SP) graphite electrode microarrays were studied as active support for this immobilization. A 10-microelectrode (eight working electrodes, 0.2 mm2 each; one reference; and one auxiliary) setup was used to study the addressing possibilities of the method. These electrode microarrays were shown to be able to covalently graft diazonium cations through electrochemical reduction. Cyclic voltammetry and X-ray photoelectron spectroscopy were used to characterize the electrochemical grafting onto our SP graphite surface and suggested that a diazonium monolayer was deposited. Rabbit and human immunoglobulins (IgGs) were then chemically coupled to an aniline derivative (4-carboxymethylaniline), followed by diazotation to form an aryl diazonium function available for the electrodeposition. These modified proteins were both successfully electro-addressed at the surface of the graphite electrodes without cross-talk or interference. The immuno-biochip obtained using this novel approach enabled the specific detection of anti-rabbit IgG antibodies with a detection limit of 50 fmol of protein. A promising strategy to immobilize markedly different biological entities was then presented, providing an excellent spatial specificity of the electro-addressing.
Rotational Acetabular Osteotomy for Advanced Osteoarthritis Secondary to Dysplasia of the Hip (2007)

Rotational acetabular osteotomy for advanced osteoarthritis secondary to dysplasia of the hip in properly selected patients can improve clinical scores and is associated with a lack of radiographic signs of progression of osteoarthritis in most patients.
Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells (2012)

Together with peptides, T lymphocytes respond to hydrophobic molecules, mostly lipids, presented by the non-classical CD1 family (CD1a-e). These molecules have evolved complex and diverse binding grooves in order to survey different cellular compartments for self and exogenous antigens, which are then presented for recognition to T-cell receptors (TCRs) on the surface of T cells. In particular, most CD1d-presented antigens are recognized by a population of lymphocytes denominated natural killer T (NKT) cells, characterized by a strong immunomodulatory potential. Among NKT cells, two major subsets (type I and type II NKT cells) have been described, based on their TCR repertoire and antigen specificity. Here we review recent structural and biochemical studies that have shed light on the molecular details of CD1d-mediated antigen recognition by type I and II NKT cells, which are in many aspects distinct from what has been observed for peptide major histocompatibility complex-reactive TCRs.
Select Nutrients in the Ovine Uterine Lumen. I. Amino Acids, Glucose, and Ions in Uterine Lumenal Flushings of Cyclic and Pregnant Ewes1 (2008)

Nutrients in uterine secretions are essential for development and survival of conceptuses (embryo and associated extraembryonic membranes) during pregnancy; however, little is known about changes in the amounts of specific nutrients in the uterine fluids of cyclic and pregnant ruminants. This study determined quantities of glucose, amino acids, glutathione, calcium, sodium, and potassium in uterine lumenal fluid from cyclic (Days 3-16) and pregnant (Days 10-16) ewes. Total recoverable glucose, Arg, Gln, Leu, Asp, Glu, Asn, His, beta-Ala, Tyr, Trp, Met, Val, Phe, Ile, Lys, Cys, Pro, glutathione, calcium, and sodium were greater in the uterine fluid of pregnant compared with cyclic ewes between Days 10 and 16. In cyclic ewes, only modest changes in the total amounts of glucose, Asn, Cit, Tyr, Trp, Met, Val, Cys, glutathione, calcium, and potassium were detected between Days 3 and 16. However, in pregnant ewes, amounts of glucose, Arg, Gln, Glu, Gly, Cys, Leu, Pro, glutathione, calcium, and potassium in uterine fluids increased 3- to 23-fold between Days 10 and 14 and remained high to Day 16. Of particular interest were increases in glucose, Arg, Leu, and Gln in uterine flushings of pregnant ewes between Days 10 and 16 of pregnancy. Total amounts of His, ornithine, Lys, Ser, Thr, Ile, Phe, Trp, Met, and Cit in uterine fluids also increased, but to a lesser extent during early pregnancy. These novel results indicate activation of pregnancy-associated mechanisms for transport of nutrients into the uterine lumen, and they provide a framework for future studies of nutrients, including glucose, amino acids, and glutathione, required to activate nutrient-sensing cell signaling pathways for growth, development, and survival of conceptuses, as well as for optimization of culture media for in vitro studies of conceptus development.
The role of CTCF binding sites in the 3′ immunoglobulin heavy chain regulatory region (2012)

The immunoglobulin heavy chain locus undergoes a series of DNA rearrangements and modifications to achieve the construction and expression of individual antibody heavy chain genes in B cells. These events affect variable regions, through VDJ joining and subsequent somatic hypermutation, and constant regions through class switch recombination (CSR). Levels of IgH expression are also regulated during B cell development, resulting in high levels of secreted antibodies from fully differentiated plasma cells. Regulation of these events has been attributed primarily to two cis-elements that work from long distances on their target sequences, i.e., an ∼1 kb intronic enhancer, Eμ, located between the V region segments and the most 5' constant region gene, Cμ; and an ∼40 kb 3' regulatory region (3' RR) that is located downstream of the most 3' C(H) gene, Cα. The 3' RR is a candidate for an "end" of B cell-specific regulation of the Igh locus. The 3' RR contains several B cell-specific enhancers associated with DNase I hypersensitive sites (hs1-4), which are essential for CSR and for high levels of IgH expression in plasma cells. Downstream of this enhancer-containing region is a region of high-density CTCF binding sites, which extends through hs5, 6, and 7 and further downstream. CTCF, with its enhancer-blocking activities, has been associated with all mammalian insulators and implicated in multiple chromosomal interactions. Here we address the 3' RR CTCF-binding region as a potential insulator of the Igh locus, an independent regulatory element and a predicted modulator of the activity of 3' RR enhancers. Using chromosome conformation capture technology, chromatin immunoprecipitation, and genetic approaches, we have found that the 3' RR with its CTCF-binding region interacts with target sequences in the V(H), Eμ, and C(H) regions through DNA looping as regulated by protein binding. This region impacts on B cell-specific Igh processes at different stages of B cell development.