gebhart/patrepeval huggingface dataset:
A Comparison of the Interaction of Shc and the Tyrosine Kinase ZAP-70 with the T Cell Antigen Receptor ζ Chain Tyrosine-based Activation Motif (1995)

Tyrosine-based activation motifs (TAMs) define a conserved signaling sequence, EX2YX2L/IX7YX2L/I, that couples the T cell antigen receptor to protein tyrosine kinases and adapter molecules. The present study shows that phosphorylation of both tyrosines within the motif is required for high affinity binding of the tyrosine kinase ZAP-70 whereas phosphorylation of the single COOH-terminal tyrosine within the motif is optimal for the binding of the adapter Shc. There were also quantitative differences in the ZAP-70 and Shc association with the zeta 1-TAM since nM concentrations of the doubly phosphorylated zeta 1-TAM are sufficient for ZAP-70 recruitment whereas micromolar levels of singly phosphorylated TAMs are necessary for Shc binding. Shc is tyrosine phosphorylated in antigen receptor-activated T cells and can potentially form a complex with the adapter molecule Grb2 and could thus recruit the Ras guanine nucleotide exchange protein Sos into the antigen receptor complex. The present data show that Grb2 can bind to the phosphorylated TAM, but this binding is independent of Shc and there is no formation of zeta 1-TAM.Shc.Grb2.Sos complexes in antigen receptor-activated cells. Accordingly, Shc function should not be considered in the context of Grb2/Sos recruitment to the T cell antigen receptor complex.
Correction: Involvement of Dynamin-Related Protein 1 in Free Fatty Acid-Induced INS-1-Derived Cell Apoptosis (2013)

Elevated extracellular free fatty acids (FFAs) can induce pancreatic beta cell apoptosis, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2D). Mitochondrial dysfunction has been implicated in FFA-induced beta cell apoptosis. However, molecular mechanisms linking mitochondrial dysfunction and FFA-induced beta cell apoptosis are not clear. Dynamin-related protein 1 (DRP-1) is a mitochondrial fission modulator. In this study, we investigated its role in FFAinduced INS-1 beta cell apoptosis. DRP-1 protein was promptly induced in INS-1 cells and rat islets after stimulation by FFAs, and this DRP-1 upregulation was accompanied by increased INS-1 cell apoptosis. Induction of DRP-1 expression significantly promoted FFA-induced apoptosis in DRP-1 WT (DRP-1 wild type) inducible INS-1-derived cell line, but not in DRP-1K38A (a dominant negative mutant of DRP-1) inducible INS-1-derived cell line. To validate these in vitro results, we transplanted DRP-1 WT or DRP-1 K38A cells into renal capsules of streptozotocin (STZ)-treated diabetic mice to study the apoptosis in xenografts. Consistent with the in vitro results, the over-expression of DRP-1 led to aggravated INS-1-derived cell apoptosis triggered by FFAs. In contrast, dominant-negative suppression of DRP-1 function as represented by DRP-1 K38A significantly prevented FFA-induced apoptosis in xenografts. It was further demonstrated that mitochondrial membrane potential decreased, while cytochrome c release, caspase-3 activation, and generation of reactive oxygen species (ROS) were enhanced by the induction of DRP-1WT, but prevented by DRP-1 K38A in INS-1-derived cells under FFA stimulation. These results indicated that DRP-1 mediates FFA-induced INS-1-derived cell apoptosis, suggesting that suppression of DRP-1 is a potentially useful therapeutic strategy for protecting against beta cell loss that leads to type 2 diabetes.
Varying the concentration of single walled carbon nanotubes in thin film polymer composites, and its effect on thermoelectric power (2011)

Resistivity and thermoelectric power (TEP) measurements were conducted on single walled carbon nanotube (SWNT), polyvinylidene fluoride composite thin films of varying SWNT concentrations. This heterogeneous material was used in order to utilize the good electrical conductance of the nanotubes and the poor thermal conductance of the polymer to increase the figure of merit (ZT). As the nanotube weight percent decreased from 100% to 5%, the beneficial effects of the TEP increase and thermal conductivity decrease outweighed the negative effect of decreased electrical conductivity, resulting in an increase in ZT by a factor of 100.
Innate immune functions of microglia isolated from human glioma patients (2006)

We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.
Improving Reinforcement Learning Based Image Captioning with Natural Language Prior (2018)

Recently, Reinforcement Learning (RL) approaches have demonstrated advanced performance in image captioning by directly optimizing the metric used for testing. However, this shaped reward introduces learning biases, which reduces the readability of generated text. In addition, the large sample space makes training unstable and slow. To alleviate these issues, we propose a simple coherent solution that constrains the action space using an n-gram language prior. Quantitative and qualitative evaluations on benchmarks show that RL with the simple add-on module performs favorably against its counterpart in terms of both readability and speed of convergence. Human evaluation results show that our model is more human readable and graceful. The implementation will become publicly available upon the acceptance of the paper 1 .
Neuronal responses to myelin are mediated by rho kinase (2006)

CNS myelin inhibits axon growth due to the expression of several growth-inhibitory proteins, including myelin-associated glycoprotein, oligodendrocyte myelin glycoprotein and Nogo. Myelin-associated inhibitory proteins activate rho GTPase in responsive neurons. Rho kinase (ROCK) has been implicated as a critical rho effector in this pathway due to the ability of the pharmacological inhibitor Y-27632 to circumvent myelin-dependent inhibition. Y-27632, however, inhibits the activity of additional kinases. Using three independent approaches, we provide direct evidence that ROCKII is activated in response to the myelin-associated inhibitor Nogo. We demonstrate that Nogo treatment enhances ROCKII translocation to the cellular membrane in PC12 cells and enhances ROCKII kinase activity towards an in vitro substrate. In addition, Nogo treatment enhances phosphorylation of myosin light chain II, a known ROCK substrate. Further, we demonstrate that primary dorsal root ganglia neurons can be rendered insensitive to the inhibitory effects of myelin via infection with dominant negative ROCK. Together these data provide direct evidence for a rho-ROCK-myosin light chain-II signaling cascade in response to myelin-associated inhibitors.
Electronic and magnetic metal–metal interactions in dinuclear oxomolybdenum(V) complexes across bis-phenolate bridging ligands with different spacers between the phenolate termini: ligand-centred vs. metal-centred redox activity (2001)

A series of dinuclear complexes has been prepared in which two {MoV(TpMe,Me)(O)Cl} fragments (abbreviated as Mo; TpMe,Me = tris(3,5-dimethylpyrazol-1-yl)hydroborate) are attached to either end of a bis-p-phenolate bridging ligand [(4,4′-OC6H4)–X–(4,4′-C6H4O)]2−. The complexes are Mo2(CC) (X = CHCH), Mo2(CC)2 (X = CHCH–CHCH), Mo2(CC)3 (X = CHCH–CHCH–CHCH), Mo2(th) (X = 2,5-thiophenediyl), Mo2(th)2 (X = 2,5:2′,5′-bithiophenediyl), Mo2(th)3 (X = 2,5:2′,5′:2″,5″-terthiophenediyl), Mo2(CC) (X = CC), Mo2(NN) (X = NN), Mo2(CO) [X = C(O)] and Mo2(C2ΦC2) [X = CHCH(1,4-C6H4)CHCH]. Electrochemical, UV/VIS/NIR spectroelectrochemical and magnetic measurements have been carried out in order to see how effectively the different spacer groups X mediate electronic and magnetic interactions between the two redox-active, paramagnetic, Mo centres. The electronic interactions were determined from the redox separation between the two successive one-electron oxidations which are formally Mo(VI)–Mo(V) couples; it was found that thienyl units in the bridging ligand are much more effective at maintaining electronic communication over long distances than p-phenylene or ethenyl spacers of comparable lengths. The azo (NN) linkage afforded a much weaker electronic interaction than the ethenyl or ethynyl spacers. UV/VIS/NIR spectroelectrochemical studies showed that whereas the first oxidation is metal-centred to give Mo(VI)–Mo(V) species with characteristic intense phenolate→Mo(VI) LMCT transitions in the near-IR region, the spectra of the doubly oxidised complexes are characteristic of quinones: thus, the sequence of species formed on oxidation is [Mo(V)(μ-diolate)Mo(V)]0 → [Mo(V)(μ-diolate)Mo(VI)]+ → [Mo(V)(μ-quinone)Mo(V)]2+, with an internal charge redistribution associated with the second oxidation. Semi-empirical ZINDO calculations provide some support for this. Magnetic susceptibility measurements on Mo2(CC), Mo2(th), Mo2(NN) and Mo2(CC) show that all are weakly antiferromagnetically coupled, as expected on the basis of a spin-polarisation picture, with the order of strength of the magnetic interaction being the reverse of the order for electronic coupling, such that Mo2(th) affords the strongest electronic interaction but the weakest magnetic interaction.
Immunization of Cancer Patients Using Autologous Cancer Cells Modified by Insertion of the Gene for Interleukin-2 (National Institutes of Health) (1992)

When tumor is resected from patients as part of the natural course of their treatment, an attempt will be made to establish a tissue culture line of the tumor. The gene coding for interleukin-2 will be introduced into these tumor cells and the integration and expression of this gene will be tested. Patients will become eligible for this study only if they develop metastatic cancer that has failed all standard effective treatment and have no other effective treatment options available to them. Tumor cells will be injected intradermally and subcutaneously into the thigh of these patients. The amount of tumor injected will be less than 1/50th the total tumor burden of that patient. In previous studies we have shown that these gene modified tumor cells are more immunogenic than the native unaltered tumor. Attempts will then be made to grow immune lymphocytes either from the tumor site or from the draining lymph nodes of these patients in order to use these lymphocytes for adoptive immunotherapy as detailed in previous protocols. The direct effect of the immunization with these immunogenic tumor cells will also be measured by assessing the impact on established tumor at other sites. Fifty patients receiving tumor inoculation will be included in this study.
The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. (1988)

The octamer motif ATGCAAAT is recognized indistinguishably by two mammalian transcription factors: one that is expressed ubiquitously and referred to here as Oct-1, and another, Oct-2, that is expressed in lymphoid cells. We report the cDNA cloning of the human oct-1 gene, which encodes Oct-1, by screening lambda gt11 recombinant phage in situ for octamer motif-specific DNA binding. One lambda gt11 recombinant expressed a beta-galactosidase-octamer-binding fusion protein with a DNA-binding specificity indistinguishable from human HeLa cell Oct-1 protein. As expected for a ubiquitously expressed protein, Oct-1 mRNA is expressed in all five human and two mouse cell lines tested. Polyclonal rabbit antiserum raised against the beta-galactosidase fusion protein shows that the DNA-binding domains of Oct-1 and Oct-2 proteins are related antigenically. Deletion analysis of the 743-amino-acid-long oct-1 open reading frame shows that the DNA-binding activity lies within a central highly charged domain of 160 amino acids. Comparison of the Oct-1 and Oct-2 sequences reveals that this domain is nearly identical between the two proteins. Highly similar domains are also present in the pituitary-specific transcription factor Pit-1 and the Caenorhabditis elegans unc-86 cell lineage gene product (see Herr et al. 1988). Within this shared POU (Pit-1, Oct-1 and Oct-2, unc-86) domain (pronounced 'pow') lie two subdomains: a POU-related homeo box and a POU-specific box. The Oct-1 protein is unique among the POU-related proteins and other homeo box proteins because it is expressed ubiquitously.
The kinetics of pre‐antral follicle development in ovaries of CBA/Ca mice during the first 14 weeks of life (1987)

The kinetics of ovarian follicle growth and death have been estimated in virgin inbred mice using a compartmental model and data obtained from differential follicle counts in histologically sectioned ovaries. The results showed that both growth and death rates are dependent on stage of development, defined by the compartments, and age, indicated in the model by step functions with transitions at 20 and 60 days of age. During the initial phase of postnatal ovarian development, large numbers of follicles disappeared from the non-growing reserve as a result of the combined effects of follicle death and recruitment into the growing population. The reduced death rate after 20 days led to a secondary peak in the numbers of follicles at intermediate stages. In contrast to these fluctuations, the number of large follicles, including pre-ovulatory types, were remarkably constant after this age and the rate of outflow stabilized at two to three follicles per day after an initially high value. This rate is sufficient for the normal ovulation rate in a 4-day oestrous cycle with a small surplus of follicles undergoing atresia. The rates of migration through successive stages of development decreased during ageing as large follicles began to emerge at the approach of puberty: this result may indicate that the recruitment of small growing follicles is influenced by a feedback effect.
Structure Activity Relationships and Differential Interactions and Functional Activity of Various Equine Estrogens Mediated via Estrogen Receptors (ERs) ERα and ERβ (2008)

The human estrogen receptors (ERs) alpha and beta interact with 17beta-estradiol (17beta-E2), estrone, 17alpha-estradiol, and the ring B unsaturated estrogens, equilin, 17beta-dihydroequilin, 17alpha-dihydroequilin, equilenin, 17beta-dihydroequilenin, 17alpha-dihydroequilenin, Delta8-estrone, and Delta8, 17beta-E2 with varying affinities. In comparison to 17beta-E2, the relative binding affinities of most ring B unsaturated estrogens were 2- to 8-fold lower for ERalpha and ERbeta, however, some of these unique estrogens had two to four times greater affinity for ERbeta than ERalpha. The transcriptional activity of these estrogens in HepG2 cells transfected with ERalpha or ERbeta, or both, and the secreted-alkaline phosphatase gene showed that all estrogens were functionally active. 17beta-E2 induced the activity of secreted-alkaline phosphatase by ERalpha to a level higher than any other estrogen. Activity of other estrogens was 12-17% that of 17beta-E2. In contrast, 17beta-E2 stimulated the activity of ERbeta to a 5-fold lower level than that with ERalpha, whereas the activity of other estrogens was 66-290% that of 17beta-E2, with equilenin being the most active. The presence of both ER subtypes did not alter the functional activity of 17beta-E2, although it further enhanced the activity of 17beta-dihydroequilin (200%), 17beta-dihydroequilenin (160%), and Delta8, 17beta-E2 (130%). Except for 17beta-E2, no correlation was observed between the functional activities and their binding affinities for ER. In conclusion, our results show that the effects of ring B unsaturated estrogens are mainly mediated via ERbeta and that the presence of both ER subtypes further enhances their activity. It is now possible to develop hormone replacement therapy using selective ring B unsaturated estrogens for target tissues where ERbeta is the predominant ER.
α-Cyano-sulphonyl chlorides: their preparation and reactions with amines, alcohols, and enamines (1971)

Cyanomethanesulphonyl chloride has been prepared, and some aspects of its chemistry have been investigated. Reactions with primary and secondary amines led to the expected sulphonamides, but sulphonates derived from reactions with alcohols were in most cases too unstable to be isolated. Reactions with enamines gave either substituted thietan 1,1-dioxides or acyclic sulphones, depending upon whether the enamine was derived from an aldehyde or a cyclic ketone. Sulphonamides derived from cyanomethanesulphonyl chloride contain an acidic methylene group, and were found to condense with aldehydes and with isopentyl nitrite in the normal fashion to give, respectively, substituted olefins and an oxime. The course of the coupling reaction with diazonium salts, however, appeared to depend upon whether the sulphonamide was derived from a primary or a secondary amine. Homologues of cyanomethanesulphonyl chloride having an alkyl group attached to the α-carbon atom were markedly less reactive towards nucleophiles than was the parent compound, reactivity decreasing with increase in chain length. A number of sulphonamides were prepared from each homologue.
What are the best routes to effectively model human colorectal cancer? (2013)

Colorectal cancer (CRC) is the third most common cancer in the UK, with over 37,500 people being diagnosed every year. Survival rates for CRC have doubled in the last 30 years and it is now curable if diagnosed early, but still over half of all sufferers do not survive for longer than 5 years after diagnosis. The major complication to treating this disease is that of metastasis, specifically to the liver, which is associated with a 5 year survival of less than 5%. These statistics highlight the importance of the development of earlier detection techniques and more targeted therapeutics. The future of treating this disease therefore lies in increasing understanding of the mutations which cause tumourigenesis, and insight into the development and progression of this complex disease. This can only be achieved through the use of functional models which recapitulate all aspects of the human disease. There is a wide range of models of CRC available to researchers, but all have their own strengths and weaknesses. Here we review how CRC can be modelled and discuss the future of modelling this complex disease, with a particular focus on how genetically engineered mouse models have revolutionised this area of research.
Development and characterization of a mouse prostate adenocarcinoma cell line: Ductal formation determined by extracellular matrix (1998)

BACKGROUND Tumor vaccines show promise as a new approach for treating cancer. We have developed a murine prostate cancer cell line which can be used to study growth factor and extracellular matrix regulation of prostate differentiation and will be useful for generating tumor vaccines using the C3(1)/TAG transgenic model of prostate cancer. METHODS Pr-14 cells were established in defined growth media (GM) and grown in GM, GM + 2% fetal bovine serum (FBS) or DMEM + 10% FBS on plastic, collagen, or Matrigel. Immunofluorescence and Western blot analyses were performed using antibodies to cytokeratin, vimentin, SV40 large T-antigen, and androgen receptor (AR). RESULTS Pr-14 cells are cytokeratin-positive, vimentin-negative, and express SV40 large T-antigen. These cells are tumorigenic when injected into athymic nude mice and appear to be androgen-independent. Pr-14 cell lines are nontumorigenic when injected into syngeneic FVB/N mice, but form tumors in transgenic TAG-expressing FVB/N mice. Cell growth and morphology are dependent on media composition which determines whether ductal or acinar structures form when grown on Matrigel. CONCLUSIONS The mouse prostate adenocarcinoma cell line, Pr-14, undergoes alterations in the state of differentiation dependent upon serum concentration when grown on Matrigel. The Pr-14 cell line is a useful reagent to study prostate cell/extracellular matrix interactions, and for immunotherapy and cancer vaccine studies in C3(1)/TAG transgenic mice. Prostate 34:10–22, 1998. © 1998 Wiley-Liss, Inc.
A system for approximate tree matching (1994)

Ordered, labeled trees are trees in which each node has a label and the left-to-right order of its children (if it has any) is fixed. Such trees have many applications in vision, pattern recognition, molecular biology, programming compilation, and natural language processing. Many of the applications involve comparing trees or retrieving/extracting information from a repository of trees. Examples include classification of unknown patterns, analysis of newly sequenced RNA structures, semantic taxonomy for dictionary definitions, generation of interpreters for nonprocedural programming languages, and automatic error recovery and correction for programming languages. Previous systems use exact matching (or generalized regular expression matching) for tree comparison. This paper presents a system, called approximate-tree-by-example (ATBE), which allows inexact matching of trees. The ATBE system interacts with the user through a simple but powerful query language; graphical devices are provided to facilitate inputing the queries. The paper describes the architecture of ATBE, illustrates its use and describes some aspects of ATBE implementation. We also discuss the underlying algorithms and provide some sample applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Single stranded DNA SP6 promoter plasmids for engineering mutant RNAs and proteins: synthesis of a ‘stretched’ preproparathyroid hormone (1985)

The intergenic region of bacteriophage f1 has been subcloned into the bacteriophage SP6 promoter plasmids, pSP64 and pSP65, in both orientations. Coinfection of E. coli with these SP6 promoter/phage f1 chimeric plasmids and the interference resistance phage, IR1, results in the replication and secretion of the pSP6.f1 plasmids as single stranded DNA. Bovine preProPTH cDNAs in both the native form and a form containing an insertion of 117 base pairs in the protein coding region have been inserted in these plasmids. The RNA transcribed from the SP6.f1/preProPTH cDNA constructs was efficiently translated in the wheat germ or reticulocyte cell free systems without addition of a 7-methylguanosine cap to the RNA. In the presence of dog pancreatic or chicken oviduct microsomal membranes, conversion of the resultant pre-proteins to pro-proteins was observed. Confirmation of the "mutated" preProPTH cDNA was determined by dideoxyribonucleotide DNA sequencing of single stranded plasmid DNA. These vectors are suitable for the efficient biosynthesis of large amounts of single or double stranded DNA, and translationally active RNA. The combined properties of single stranded DNA replication and the SP6 promoter simplify the engineering of mutant RNAs and their corresponding proteins. In addition, single stranded DNA or RNA corresponding to either complementary strand may be synthesized as nucleic acid hybridization probes.
Temperature rise during photoradiation therapy of malignant tumors (1983)

This report discusses the optical and thermal distribution during photoradiation therapy of malignant tumors. Emphasis is put on the therapeutic procedure with the light dose delivered through an inserted optical fiber. Theoretical predictions and experimental results indicate that the temperature rise during the procedure may give rise to hyperthermal cell kill. The report discusses the extent of the regions with hyperthermal bioeffects in terms of tissue parameters as optical absorption and scattering, thermal conductivity, specific heat, blood flow, and optical dose parameters as optical power and exposure time.