gebhart/patrepeval huggingface dataset:
Computing Jacobians and compliance matrices for externally loaded continuum robots (2011)

Kinematic models that account for deformation due to applied loads have recently been developed for a variety of continuum robots. In these cases, a set of nonlinear differential equations with boundary conditions must often be solved to obtain the robot shape. Thus, computing manipulator Jacobians and compliance matrices efficiently is not straight forward. In this paper, we propose a method for obtaining an arc length parametrized Jacobian and compliance matrix. Our approach involves obtaining an augmented Jacobian by propagating the necessary partial derivatives through the model equations, resulting in a new set of differential equations. These equations can be solved as an initial value problem, via a single numerical integration. Our method can be generally applied to various continuum robot architectures, regardless of the specific actuation system used. We provide a specific case study using this method to obtain the Jacobian for a concentric-tube robot.
Interleukin-8 Mediates Resistance to Antiangiogenic Agent Sunitinib in Renal Cell Carcinoma (2010)

The broad spectrum kinase inhibitor sunitinib is a first-line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients develop sunitinib resistance and progressive disease after about 1 year of treatment. In this study, we evaluated the mechanisms of resistance to sunitinib to identify the potential tactics to overcome it. Xenograft models were generated that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, indicating that an escape from antiangiogenesis occurred. Notably, escape coincided with increased secretion of interleukin-8 (IL-8) from tumors into the plasma, and coadministration of an IL-8 neutralizing antibody resensitized tumors to sunitinib treatment. In patients who were refractory to sunitinib treatment, IL-8 expression was elevated in ccRCC tumors, supporting the concept that IL-8 levels might predict clinical response to sunitinib. Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy.
Translational pathophysiology: a novel molecular mechanism of human disease (2000)

In higher eukaryotes, the expression of about 1 gene in 10 is strongly regulated at the level of messenger RNA (mRNA) translation into protein. Negative regulatory effects are often mediated by the 5'-untranslated region (5'-UTR) and rely on the fact that the 40S ribosomal subunit first binds to the cap structure at the 5'-end of mRNA and then scans for the first AUG codon. Self-complementary sequences can form stable stem-loop structures that interfere with the assembly of the preinitiation complex and/or ribosomal scanning. These stem loops can be further stabilized by the interaction with RNA-binding proteins, as in the case of ferritin. The presence of AUG codons located upstream of the physiological start site can inhibit translation by causing premature initiation and thereby preventing the ribosome from reaching the physiological start codon, as in the case of thrombopoietin (TPO). Recently, mutations that cause disease through increased or decreased efficiency of mRNA translation have been discovered, defining translational pathophysiology as a novel mechanism of human disease. Hereditary hyperferritinemia/cataract syndrome arises from various point mutations or deletions within a protein-binding sequence in the 5'-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinemia and severity of cataract in affected individuals. Hereditary thrombocythemia (sometimes called familial essential thrombocythemia or familial thrombocytosis) can be caused by mutations in upstream AUG codons in the 5'-UTR of the TPO mRNA that normally function as translational repressors. Their inactivation leads to excessive production of TPO and elevated platelet counts. Finally, predisposition to melanoma may originate from mutations that create translational repressors in the 5'-UTR of the cyclin-dependent kinase inhibitor-2A gene.
A multilevel security model for a distributed object-oriented system (2002)

Distributed systems are vulnerable to a number of security attacks. The authors look at the security problems of object-based distributed systems, and propose a model based on labelling for multilevel security. The purpose of this model is to preserve the information flow security in a distributed object-oriented system. The authors consider the basic concepts of the object paradigm, and also the security threats to such systems. They postulate various modelling possibilities, and produce a specific set of security properties which describe a multilevel secure object model. This particular model should not be considered as a panacea, but rather should demonstrate how the various modelling decisions are reflected in an actual model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family (1996)

The mouse brachypodism locus encodes a bone morphogenetic protein (BMP)-like molecule called growth/differentiation factor 5 (GDF5). Here we show that Gdf5 transcripts are expressed in a striking pattern of transverse stripes within many skeletal precursors in the developing limb. The number, location and time of appearance of these stripes corresponds to the sites where joints will later form between skeletal elements. Null mutations in Gdf5 disrupt the formation of more than 30% of the synovial joints in the limb, leading to complete or partial fusions between particular skeletal elements, and changes in the patterns of repeating structures in the digits, wrists and ankles. Mice carrying null mutations in both Gdf5 and another BMP family member, Bmp5, show additional abnormalities not observed in either of the single mutants. These defects include disruption of the sternebrae within the sternum and abnormal formation of the fibrocartilaginous joints between the sternebrae and ribs. Previous studies have shown that members of the BMP family are required for normal development of cartilage and bone. The current studies suggest that particular BMP family members may also play an essential role in the segmentation process that cleaves skeletal precursors into separate elements. This process helps determine the number of elements in repeating series in both limbs and sternum, and is required for normal generation of the functional articulations between many adjacent structures in the vertebrate skeleton.
TGF-β is important in determining the in vivo patterns of susceptibility or resistance in mice infected with Candida albicans (1995)

Resistance and susceptibility of mice to systemic infection with the fungus Candida albicans are associated with the preferential expansion of Th1 and Th2 cells, respectively. In this study, endogenous production of TGF-beta was found to be increased soon after infection of healer mice with a live vaccine strain of the fungus, but down-regulated in nonhealer mice with virulent yeast challenge. Although not affecting the outcome of primary challenge, serologic ablation of TGF-beta in the former animals abrogated development of acquired resistance and resulted in impaired production of IL-12/IFN-gamma and higher expression of IL-4/IL-10 at the time of reinfection with virulent yeast. A CD4+ population expressing the memory phenotype, CD44highMEL-14low, which appeared to be expanded by yeast infection of nonhealer mice, was similarly increased in the healer mice by anti-TGF-beta treatment. In vitro rTGF-beta impaired the candidacidal function of IFN-gamma-activated macrophages. Yet in nonhealer mice infected with virulent C. albicans, administration of rTGF-beta delayed progression of the disease, which was concomitant with the detection of lower levels of IL-4. In addition to previous evidence for an obligatory role of IFN-gamma and IL-12 in Candida-driven Th1 cell differentiation in vivo, the present data establish TGF-beta as a third cytokine, the presence of which may be required for optimal Th1 development leading to long-lived anticandidal resistance.
Mutation and killing of Escherichia coli expressing a cloned Bacillus subtilis gene whose product alters DNA conformation (1992)

Expression of the Bacillus subtilis gene coding for SspC, a small, acid-soluble protein, caused both killing and mutation in a number of Escherichia coli B and K-12 strains. SspC was previously shown to bind E. coli DNA in vivo, and in vitro this protein binds DNA and converts it into an A-like conformation. Analysis of revertants of nonsense mutations showed that SspC caused single-base changes, and a greater proportion of these were at A-T base pairs. Mutation in the recA gene abolished the induction of mutations upon synthesis of SspC, but the killing was only slightly greater than in RecA+ cells. Mutations in the umuC and umuD genes eliminated most of the mutagenic effect of SspC but not the killing, while the lexA mutation increased mutagenesis but did not appreciably affect the killing. Since there was neither killing nor mutation of E. coli after synthesis of a mutant SspC which does not bind DNA, it appears likely that the binding of wild-type SspC to DNA, with the attendant conformational change, was responsible for the killing and mutation. A strain containing the B. subtilis gene that is constitutive for the RecA protein at 42 degrees C showed a lower frequency of mutation when that temperature was used to induce the RecA protein than when the temperature was 30 degrees C, where the RecA level is low, suggesting that at the elevated temperature the high RecA level could be inhibiting binding of the B. subtilis protein to DNA.
Lethal Effects of Heat on Bacterial Physiology and Structure (2003)

High temperatures have profound effects on the structural and physiological properties of sporulating and non-sporulating bacteria, with membranes, RNA, DNA, ribosomes, protein and enzymes all affected. Nevertheless, it is apparent that no one single event is responsible for cell death. The induction of intracellular heat-shock proteins and the activation of extracellular alarmones in vegetative cells exposed to mildly lethal temperatures are important cell responses. In bacterial spores, several factors contribute to the overall resistance to moist (wet) and dry heat; the latter, but not the former, induces mutations. Heat resistance develops during sporulation, when spore-specific heat-shock proteins are also produced. Heat sensitivity is regained during germination of spores.
Multiple Genetic Alterations Cause Frequent and Heterogeneous Human Histocompatibility Leukocyte Antigen Class I Loss in Cervical Cancer (2000)

The nature and frequency of human histocompatibility leukocyte antigen (HLA) class I loss mechanisms in primary cancers are largely unknown. We used flow cytometry and molecular analyses to concurrently assess allele-specific HLA phenotypes and genotypes in subpopulations from 30 freshly isolated cervical tumor cell suspensions.Tumor-associated HLA class I alterations were present in 90% of the lesions tested, comprising four altered pheno/genotype categories: (a) HLA-A or -B allelic loss (17%), mostly associated with gene mutations; (b) HLA haplotype loss, associated with loss of heterozygosity at 6p (50%). This category included cases with additional loss of a (third) HLA-A or -B allele due to mutation, as well as one case with an HLA class I-negative tumor cell subpopulation, caused by a beta2-microglobulin gene mutation; (c) Total HLA class I antigen loss and retention of heterozygosity (ROH) at 6p (10%); and (d) B locus or HLA-A/B downregulation associated with ROH and/or allelic imbalance at 6p (10%). Normal HLA phenotypes and ROH at 6p were observed in 10% of the cases. One case could not be classified (3%). Altered HLA class I antigen expression occurs in most cervical cancers, is diverse, and is mainly caused by genetic changes. Combined with widespread tumor heterogeneity, these changes have profound implications for natural immunity and T cell-based immunotherapy in cervical cancer.
Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity (1997)

By transfection of COS cells with an expression vector containing CD70 cDNA we demonstrate that two previously described MoAbs (ED6 and LD6) recognize CD70. By means of these MoAbs, we show that the surface expression of CD70 inversely correlates with the expression of its receptor, CD27, on activated T and NK cell populations and clones, although a subpopulation of cells expressing low density of both molecules exists. In addition, culture in the presence of IL-4 significantly enhances CD27 and reduces CD70 surface expression in phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL), while tumour necrosis factor-alpha (TNF-alpha) displays opposite effects, indicating that receptor and ligand are reciprocally regulated by these cytokines. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CD27 and CD70 mRNA suggests a transcriptional control of CD27 antigen expression in T cell clones. In addition, we show by the use of a re-directed killing assay that in cytotoxic T cell receptor (TCR) alpha/beta+ T cell clones, CD27 molecule may be involved in the regulation of cytolytic functions and may act synergistically with CD2. Finally, CD70 also acts as a signal-transducing molecule in some activated CD70+ TCR gamma/delta+ T or NK cell clones. In conclusion, our data indicate that CD27 and CD70 molecules are differentially expressed and regulated on long term-activated T and NK cells and are involved in the control of cellular functions.
Noncoding regulatory RNAs database (2003)

The noncoding RNAs database is a collection of currently available sequence data on RNAs, which have no protein-coding capacity and have been implicated in regulation of cellular processes. The RNAs included in the database form very heterogenous group of molecules that act on different levels of information transmission in the cell. It includes RNAs acting on the level of chromatin structure, transcriptional and translational regulation of gene expression, modulation of protein function and regulation of subcellular distribution of RNAs and proteins. Those RNAs, with potential regulatory functions have been identified in prokaryotic, animal and plant cells. The database can be accessed at http://biobases.ibch.poznan.pl/ncRNA/.
The antitumor effect of Tiazofurin (TR) consists of anti-proliferative and anti-invasive elements. (1997)

We have studied the effects of the antimetabolite, Tiazofurin (TR-2-beta-D-furanosylthiazole-4-carboxamide), on the metastatization of HT168-M1 human melanoma cell line compared to 3LL-HH murine lung carcinoma. TR pretreatment of 3LL-HH cells, in a dose range 15-60 microM, caused inhibition of cell proliferation as well as adhesion to the EHS-matrix. TR inhibited the entry of adherent tumor cells to the S phase and accumulation in G1, however in non-adherent cells TR completely inhibited the entry of tumor cells to G2 phase. In contrast to these data TR treatment of HT168-M1 cells did not cause inhibition of cell proliferation, a change in cell cycle distribution or in the quantity of apoptotic cells. However, TR pretreatment did inhibit the adhesion to and migration through EHS-matrix of melanoma cells similar to 3LL-HH cells. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of HT168-M1 melanoma cells without major effects on the spleen primary tumor. Since in vivo TR treatment of HT168-M1 and 3LL-HH tumor bearing mice significantly decreased the number and incidence of liver metastases though there was a different effect on the in vitro/in vivo growth (lack of inhibitory effect in case of IIT168-M1 cells), we suggest that the antiproliferative and anti-metastatic effects of TR could be separated. We also suggest that the antimetastatic effects of TR are due to inhibition of adhesion and migration of tumor cells.
Design and Implementation of Mobile 3D Bluetooth Engine based on OpenGL-ES (2006)

This study focused on design and implementation of Mobile 3D Bluetooth Engine based on OpenGL-ES. In Mobile 3D network game so far, there is a form the mainstream of wireless internet game using WAP and VM. But, VM game are popular because of an excessive communication expense problem for this mobile network game that occur when connect to wireless internet as point out to problem by it, that is, stand-alone game are very popular. This study introduce a mobile 3D Bluetooth Engine which is based on mobile 3D standard using OpenGL-ES to solve a mobile network game generally that occurs when connect to take pleasure a wireless internet from some people into a short distance.
Multicentre surveillance of Pseudomonas aeruginosa susceptibility patterns in nosocomial infections (2003)

Resistance of P. aeruginosa to penicillins, cephalosporins, fluoroquinolones and aminoglycosides varies between hospitals, but is increasing.
Large-scale behavioral targeting (2009)

Behavioral targeting (BT) leverages historical user behavior to select the ads most relevant to users to display. The state-of-the-art of BT derives a linear Poisson regression model from fine-grained user behavioral data and predicts click-through rate (CTR) from user history. We designed and implemented a highly scalable and efficient solution to BT using Hadoop MapReduce framework. With our parallel algorithm and the resulting system, we can build above 450 BT-category models from the entire Yahoo's user base within one day, the scale that one can not even imagine with prior systems. Moreover, our approach has yielded 20% CTR lift over the existing production system by leveraging the well-grounded probabilistic model fitted from a much larger training dataset.
The Hemoregulatory Peptide N-Acetyl-Ser-Asp-Lys-Pro Is a Natural and Specific Substrate of the N-terminal Active Site of Human Angiotensin-converting Enzyme (1995)

Angiotensin I-converting enzyme (ACE) is a zinc-dipeptidyl carboxypeptidase, which contains two similar domains, each possessing a functional active site. Respective involvement of each active site in the degradation of the circulating peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a negative regulator of hematopoietic stem cell proliferation, was studied by using wild-type recombinant ACE and two full-length mutants containing a single functional site. Both the N- and C-active sites of ACE exhibit dipeptidyl activity toward AcSDKP, with Km values of 31 and 39 microM, respectively. However, the N-active site hydrolyzes the peptide 50 times faster compared with the C-active site, with kcat/Km values of 0.5 and 0.01 microM-1.s-1, respectively. The predominant role of the N-active site in AcSDKP hydrolysis was confirmed by the inhibition of hydrolysis using a monoclonal antibody specifically directed against the N-active site. The N-domain specificity for AcSDKP will aid the identification of specific inhibitors for this domain. This is the first report of a highly specific substrate for the N-active site of ACE, with kinetic constants in the range of physiological substrates, suggesting that ACE might be involved via its N-terminal active site in the in vivo regulation of the local concentration of this hemoregulatory peptide.
New Multiple Somatic Mutations in the RET Proto-oncogene Associated with a Sporadic Medullary Thyroid Carcinoma (2006)

Medullary thyroid carcinoma (MTC) occurs mostly as a sporadic tumor or in connection with inherited cancer syndromes-multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in the RET proto-oncogene are found in most of the familial cases. Somatic mutations in the RET proto-oncogene are detected in 23%-69% of patients with sporadic MTC. The most frequent somatic mutation is Met918Thr in exon 16 and only a small percentage of mutations in other RET exons have been observed. In a very few cases double mutations were found. Genetic screening for somatic mutations in RET exons 10, 11, 13, 14, 15, and 16 in Czech patients with sporadic MTC was carried out by DNA sequencing. This study presents a new triplesomatic mutation Gly911Asp, Met918Thr, and Glu921Lys in exon 16 of the RET proto-oncogene detected in an 18-year-old Czech male patient. In the second case, a new double-somatic mutation Val591Ile in exon 10 with a concomitant somatic mutation Met918Thr in exon 16 was found in a 77-year-old Czech female patient. These both newly described somatic multiple mutations were revealed in a hemizygous status, the loss of heterozygosity in tumor tissues in comparison with germline DNA was confirmed.
Repurposing Drugs in Oncology (ReDO)—itraconazole as an anti-cancer agent (2015)

Itraconazole, a common triazole anti-fungal drug in widespread clinical use, has evidence of clinical activity that is of interest in oncology. There is evidence that at the clinically relevant doses, itraconazole has potent anti-angiogenic activity, and that it can inhibit the Hedgehog signalling pathway and may also induce autophagic growth arrest. The evidence for these anticancer effects, in vitro, in vivo, and clinical are summarised, and the putative mechanisms of their action outlined. Clinical trials have shown that patients with prostate, lung, and basal cell carcinoma have benefited from treatment with itraconazole, and there are additional reports of activity in leukaemia, ovarian, breast, and pancreatic cancers. Given the evidence presented, a case is made that itraconazole warrants further clinical investigation as an anti- cancer agent. Additionally, based on the properties summarised previously, it is proposed that itraconazole may synergise with a range of other drugs to enhance the anti-cancer effect, and some of these possible combinations are presented in the supplementary materials accompanying this paper.
Antigen-driven effector CD8 T cell function regulated by T-bet (2003)

Type 1 immunity relies on the differentiation of two major subsets of T lymphocytes, the CD4+ T helper (Th) cell and the CD8+ cytotoxic T cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. In contrast to CD4 cells, little is known about transcription factors that control the transition from the CD8 naïve to effector cell stage. Here, we report that the transcription factor T-bet, known to regulate Th cell differentiation, also controls the generation of the CD8+ cytotoxic effector cell. Antigen-driven generation of effector CD8+ cells was impaired in OT-I T cell receptor transgenic mice lacking T-bet, resulting in diminished cytotoxicity and a marked shift in cytokine secretion profiles. Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic choriomeningitis virus. T-bet is a key player in the generation of type 1 immunity, in both Th and T cytotoxic cells.