gebhart/patrepeval huggingface dataset:
IL-9 strategy to perturb Treg function and enhance anti-tumor immunity (P4273) (2013)

Abstract IL-9 is a cytokine that is primarily associated with mast cells and airway inflammation, however it also plays a role in T regulatory cell (Treg) survival and recruitment to tumors. We previously reported that 4-1BB treatment of Tregs inhibits both Treg function and IL-9 secretion. Neutralization of IL-9 with an anti-IL-9 antibody inhibits the suppressive function of Tregs without affecting the function of CD4+ and CD8+ T effector cells. Furthermore, the combination of intra-tumoral CpG and anti-IL-9 induced tumor rejection in BALB-neuT and MUC1 tolerant transgenic mice. Here we show that the lack of IL-9 inhibits Treg suppression of T cell proliferation, using IL-9 knockout (IL-9ko) mice. Phenotypic analysis of Treg markers showed that tumor draining lymph nodes of 4T1 bearing mice contain fewer CTLA-4+ and CD103+ Tregs, and that these also have reduced of CTLA-4 and CD103 expression. We also observed that IL-9ko mice spontaneously reject TUBO and 4T1 mammary carcinoma cells and that rejection is abrogated by CD8+ T cell depletion. Finally, preliminary studies of human CD4+ T cell proliferation revealed that IL-9 neutralization led to greater proliferation than isotype control treated cells. Taken together our results suggest that IL-9 can have an immunosuppressive function that comes into play in the tumor microenvironment, and that the blockade of IL-9 could serve as a novel strategy to perturb the function of Tregs to enhance the antitumor effect of tumor vaccines.
Role of Steroidogenic Acute Regulatory Protein in Adrenal and Gonadal Steroidogenesis (1995)

Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with this disorder, steroidogenic acute regulatory protein, which enhances the mitochondrial conversion of cholesterol into pregnenolone, was mutated and nonfunctional, providing genetic evidence that this protein is indispensable normal adrenal and gonadal steroidogenesis.
Chemoradiotherapy after Surgery Compared with Surgery Alone for Adenocarcinoma of the Stomach or Gastroesophageal Junction (2001)

Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.
Antigen-specific T cell–mediated gene therapy in collagen-induced arthritis (2001)

Autoantigen-specific T cells have tissue-specific homing properties, suggesting that these cells may be ideal vehicles for the local delivery of immunoregulatory molecules. We tested this hypothesis by using type II collagen-specific (CII-specific) CD4(+) T hybridomas or primary CD4(+) T cells after gene transfer, as vehicles to deliver an immunoregulatory protein for the treatment of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). CII-specific T cells or hybridomas were transduced using retroviral vectors to constitutively express the IL-12 antagonist, IL-12 p40. Transfer of engineered CD4(+) T cells after immunization significantly inhibited the development of CIA, while cells transduced with vector control had no effect. The beneficial effect on CIA of IL-12 p40-transduced T cells required TCR specificity against CII, since transfer of T cells specific for another antigen producing equivalent amounts of IL-12 p40 had no effect. In vivo cell detection using bioluminescent labels and RT-PCR showed that transferred CII-reactive T-cell hybridomas accumulated in inflamed joints in mice with CIA. These results indicate that the local delivery of IL-12 p40 by T cells inhibited CIA by suppressing autoimmune responses at the site of inflammation. Modifying antigen-specific T cells by retroviral transduction for local expression of immunoregulatory proteins thus offers a promising strategy for treating RA.
[Hepatocellular carcinoma: treatment with arterial chemo-embolization]. (1994)

Due to extensive tumoural invasion, less than 10% of the patients with hepatocellular carcinoma can benefit from surgery. A variety of proposed palliative procedures, including general chemotherapy and radiotherapy, have given quite less than satisfactory results. Percutaneous alcoolization and hormone therapy are currently being evaluated. Increased use of intra-arterial embolization has developed over the last 10 years, initially in Asia and now in Europe. The aim of intra-arterial chemotherapy is to increase the concentration of anticancer agents within the tumour. Adding lipiodol with certain agents would increase the duration of cancer cell exposure. Arterial embolization aims at creating tumour necrosis by ischaemia and relies on the fact that the main blood supply from hepatocellular carcinomas comes from arteries while non-tumoural hepatic tissue is supplied by the portal vein. Numerous reports on intra-arterial treatment protocols combining chemotherapy and embolization have demonstrated that this technique can produce partial or total tumour necrosis. However, due to the variable nature of the natural history of hepatocellular carcinoma the clinically beneficial effect in terms of survival rate has not been established and would not appear to be highly significant, probably due to chemoresistance which cannot be overcome by intra-arterial administration. Indeed, the necrotic effect appears to result from hepatic embolization itself. In two randomized studies necrosis was significantly greater in patients who underwent repeated embolizations than in those receiving general or intra-arterial chemotherapy. It is generally accepted that intra-arterial chemoembolization is contraindicated in cases of portal thrombosis or major liver failure. In addition, each procedure requires at least one week hospitalization with the inherent effect on patient comfort and quality of life. Nevertheless, should intra-arterial, chemoembolization be abandoned? Probably not because there is no alternative method, at least for inoperable patients. Efforts should be made to improve the technique which should be reserved for carefully selected patients. New, more liposoluble drugs and possible combinations with glycoprotein inhibitors could be studied. Until an effective treatment for hepatocellular carcinoma has been developed, the role of palliative care must be evaluated in terms of survival rate, cost and quality of life.
The Rechargeable Li x TiS2 / LiAlCl4 / Li1 − x CoO2 Solid‐State Cell (1992)

An all solid‐state cell employing lithium tetrachloroaluminate as the lithium ion conducting solid electrolyte and using lithium intercalating compounds, titanium disulfide , and lithium cobalt (III) oxide , as the electroactive materials in the ldquo;rocking chair" configuration is described. Thin films of were prepared by chemical vapor deposition onto aluminum substrates while thin films of on aluminum were prepared by organometallic decomposition and used as the negative and positive electrodes, respectively. On charge, was delithiated and the lithium ions were transported through the solid electrolyte to the electrode where they were intercalated and formed lithiated titanium disulfide . On discharge, the electrode processes are reversed. The cell was operated at 100°C and exhibited an open‐circuit potential of 2.1 V in the charged state. The cell showed excellent discharge characteristics at current densities up to 0.1 mA/cm2 and also showed only a slight loss of capacity over one hundred charge‐discharge cycles.
Understanding the catalyst-free transformation of amorphous carbon into graphene by current-induced annealing (2013)

We shed light on the catalyst-free growth of graphene from amorphous carbon (a–C) by current-induced annealing by witnessing the mechanism both with in-situ transmission electron microscopy and with molecular dynamics simulations. Both in experiment and in simulation, we observe that small a–C clusters on top of a graphene substrate rearrange and crystallize into graphene patches. The process is aided by the high temperatures involved and by the van der Waals interactions with the substrate. Furthermore, in the presence of a–C, graphene can grow from the borders of holes and form a seamless graphene sheet, a novel finding that has not been reported before and that is reproduced by the simulations as well. These findings open up new avenues for bottom-up engineering of graphene-based devices.
Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110 (1994)

Flux balance models of metabolism use stoichiometry of metabolic pathways, metabolic demands of growth, and optimality principles to predict metabolic flux distribution and cellular growth under specified environmental conditions. These models have provided a mechanistic interpretation of systemic metabolic physiology, and they are also useful as a quantitative tool for metabolic pathway design. Quantitative predictions of cell growth and metabolic by-product secretion that are experimentally testable can be obtained from these models. In the present report, we used independent measurements to determine the model parameters for the wild-type Escherichia coli strain W3110. We experimentally determined the maximum oxygen utilization rate (15 mmol of O2 per g [dry weight] per h), the maximum aerobic glucose utilization rate (10.5 mmol of Glc per g [dry weight] per h), the maximum anaerobic glucose utilization rate (18.5 mmol of Glc per g [dry weight] per h), the non-growth-associated maintenance requirements (7.6 mmol of ATP per g [dry weight] per h), and the growth-associated maintenance requirements (13 mmol of ATP per g of biomass). The flux balance model specified by these parameters was found to quantitatively predict glucose and oxygen uptake rates as well as acetate secretion rates observed in chemostat experiments. We have formulated a predictive algorithm in order to apply the flux balance model to describe unsteady-state growth and by-product secretion in aerobic batch, fed-batch, and anaerobic batch cultures. In aerobic experiments we observed acetate secretion, accumulation in the culture medium, and reutilization from the culture medium. In fed-batch cultures acetate is cometabolized with glucose during the later part of the culture period.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasmid marker rescue transformation proceeds by breakage-reunion in Bacillus subtilis (1987)

Bacillus subtilis carrying a plasmid which replicates with a copy number of about 1 was transformed with linearized homologous plasmid DNA labeled with the heavy isotopes 2H and 15N, in the presence of 32Pi and 6-(p-hydroxyphenylazo)-uracil to inhibit DNA replication. Plasmid DNA was isolated from the transformed culture and fractionated in cesium chloride density gradients. The distribution of total and donor plasmid DNA was examined, using specific hybridization probes. The synthesis of new DNA, associated with the integration of donor moiety, was also monitored. Donor-specific sequences were present at a density intermediate between that of light and hybrid DNA. This recombinant DNA represented 1.4% of total plasmid DNA. The latter value corresponded well with the transforming activity (1.7%) obtained for the donor marker. Newly synthesized material associated with plasmid DNA at the recombinant density amounted to a minor portion of the recombinant plasmid DNA. These data suggest that, like chromosomal transformation, plasmid marker rescue transformation does not require replication for the integration of donor markers and, also like chromosomal transformation, proceeds by a breakage-reunion mechanism. The extent of donor DNA replacement of recipient DNA per plasmid molecule of 54 kilobases (27 kilobase pairs) was estimated as 16 kilobases.
Caprolactonic Poloxamer Analog:  PEG-PCL-PEG (2005)

The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (> 15. wt. %) undergoing "clear sol-gel-turbid sol" transition as the temperature increases from 20 to 60 degrees C has been developed. Light scattering and 13C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.
Expression of early transcription factors Oct-4, Sox-2 and Nanog by porcine umbilical cord (PUC) matrix cells (2006)

Cells isolated from PUC express three transcription factors found in pluripotent stem cell markers both at the mRNA and protein level. The presence of these transcription factors, along with the other characteristics of PUC cells such as their colony-forming ability, Hoechst dye-excluding side population and alkaline phosphatase expression, suggests that PUC cells have properties of primitive pluripotent stem cells. Furthermore, PUC cells are an easily and inexpensively obtained source of stem cells that are not hampered by the ethical or legal issues associated with ESCs. In addition, these cells can be cryogenically stored and expanded.
Combining Convergence and Diversity in Evolutionary Multiobjective Optimization (2002)

Over the past few years, the research on evolutionary algorithms has demonstrated their niche in solving multiobjective optimization problems, where the goal is to find a number of Pareto-optimal solutions in a single simulation run. Many studies have depicted different ways evolutionary algorithms can progress towards the Pareto-optimal set with a widely spread distribution of solutions. However, none of the multiobjective evolutionary algorithms (MOEAs) has a proof of convergence to the true Pareto-optimal solutions with a wide diversity among the solutions. In this paper, we discuss why a number of earlier MOEAs do not have such properties. Based on the concept of epsilon-dominance, new archiving strategies are proposed that overcome this fundamental problem and provably lead to MOEAs that have both the desired convergence and distribution properties. A number of modifications to the baseline algorithm are also suggested. The concept of epsilon-dominance introduced in this paper is practical and should make the proposed algorithms useful to researchers and practitioners alike.
Knowledge representation for syntactic/semantic processing (1980)

This paper describes the RUS framework for natural language processing, in which a parser incorporating a substantial ATN grammar for English interacts with a semantic interpreter to simultaneously parse and interpret input. The structure of that interaction is discussed, including the roles played by syntactic and semantic knowledge. Several implementations of the RUS framework are currently in use, sharing the same grammar, but differing in the form of their semantic component. One of these, the PSI-KLONE system, is based on a general object-centered knowledge representation system, called KL-ONE. The operation of PSI-KLONE is described, including its use of KL-ONE to support a general inference process called incremental description refinement. The last section of the paper discusses several important criteria for knowledge representation systems to be used in syntactic and semantic processing.
TGFBI protein high expression predicts poor prognosis in colorectal cancer patients. (2015)

Transforming growth factor-beta-induced (TGFBI) serves as a linker protein and plays a role in the activation of morphogenesis, cell proliferation, adhesion, migration, differentiation and inflammation. High expression levels of the human TGFBI gene are correlated with numerous human malignancies. In order to explore the roles of TGFBI in the tumor progression of colorectal cancer, colorectal cancer specimens from 115 patients with strict follow-up were selected for the analysis of TGFBI by immunohistochemistry. The correlations between TGFBI expression and the clinicopathological features of colorectal cancers were evaluated. In the colorectal cancer tissues, TGFBI was mainly localized in the cytoplasm and stroma and scarcely in the nucleus. TGFBI expression in the cytoplasm and stroma was not found to be associated with age, gender, tumor histopathological grading, PT category and tumor location (P > 0.05 for each). However, high TGFBI expression in the cytoplasm and stroma correlated with lymph node metastasis, distant metastasis and Dukes stage (P < 0.05 for each). The survival rate was significantly lower in patients with high TGFBI expression than in those with low TGFBI expression. Furthermore, we found that tumor node metastasis (TNM) staging (HR: 2.963; 95% CI: 1.573-1.664; P = 0.000), differentiation (HR: 1.574; 95% CI: 1.001-2.476; P = 0.049) and high TGFBI cytoplasmic expression (HR: 3.332; 95% CI: 1.410-7.873; P = 0.000) proved to be independent prognostic factors for survival in colorectal cancer. In conclusion, TGFBI plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor for colorectal cancer patients.
Hypothalamic Regulatory Hormones (1978)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Diameter-Controlled Synthesis of Carbon Nanotubes (2002)

Nearly monodisperse iron nanoclusters have been used to define the diameters of carbon nanotubes grown by chemical vapor deposition (CVD). Iron nanoparticles with average diameters of 3, 9, and 13 nm were used to grow carbon nanotubes with average diameters of 3, 7, and 12 nm, respectively. Transmission electron microscopy studies of the nanotubes show that the as-grown nanotubes are single-walled carbon nanotubes (SWNTs) or thin multiwalled carbon nanotubes (MWNTs) with 2 or 3 layers. Investigations of the growth conditions also demonstrate that the supply of carbon reactant is critical for enabling the growth of large diameter nanotubes from large iron nanoclusters, and that the growth temperature is especially important for achieving high-quality large diameter nanotubes. The implications of these results and possible applications of the nanotubes are discussed.
IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors (2016)

Many signal transduction inhibitors are being developed for cancer therapy target pathways that are also important for the proper function of antitumor lymphocytes, possibly weakening their therapeutic effects. Here we show that most inhibitors targeting multiple signaling pathways have especially strong negative effects on T-cell activation at their active doses on cancer cells. In particular, we found that recently approved MEK inhibitors displayed potent suppressive effects on T cells in vitro However, these effects could be attenuated by certain cytokines that can be administered to cancer patients. Among them, clinically available IL15 superagonists, which can activate PI3K selectively in T lymphocytes, synergized with MEK inhibitors in vivo to elicit potent and durable antitumor responses, including by a vaccine-like effect that generated resistance to tumor rechallenge. Our work identifies a clinically actionable approach to overcome the T-cell-suppressive effects of MEK inhibitors and illustrates how to reconcile the deficiencies of signal transduction inhibitors, which impede desired immunologic effects in vivo Cancer Res; 76(9); 2561-72. ©2016 AACR.
Effects of mixed solvent on gelation of poly(vinyl alcohol) solutions (2000)

The relationship between the polymer–solvent interaction and gelation behavior of poly(vinyl alcohol) (PVA) solutions prepared from ethylene glycol/water (EG/water) mixed solvents was investigated using a viscometer, light scattering, FTIR, X-ray, and pulsed NMR analyses. The viscometric result showed that the affinity to PVA for water is higher than that for EG. The light scattering result showed that the spinodal decomposition rate of the PVA solution decreases rapidly as the water content in the EG/water mixed solvent is increased. On the other hand, the FTIR and X-ray results both indicated that the crystallinity of the PVA gel decreases with water content. These results imply that the water molecules must improve the affinity of the solvent to PVA to inhibit the aggregation or crystallization of PVA chains. The pulsed NMR measurement results showed that the spin–spin relaxation times related to the polymer-rich and polymer-poor phases of the PVA gel increase, and the fractional amount of the polymer-poor phase increases while that of the polymer-rich phase decreases with increasing water content. These facts indicated that the increase in the mobility of PVA chains must give rise to the difficulty in chain aggregation of PVA solutions with increasing water content. Two transition temperatures were found in the phase transition of the polymer-rich phase. The lower transition temperature was attributed to the destruction of the denser chain entanglements in the polymer-rich phase and the higher transition temperature was mainly concerned with the melting of the crystallites. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1113–1120, 2001
Secondary metabolic gene cluster silencing in Aspergillus nidulans (2006)

In contrast to most primary metabolism genes, the genes involved in secondary metabolism and certain nutrient utilization pathways are clustered in fungi. Recently a nuclear protein, LaeA, was found to be required for the transcription of several secondary metabolite gene clusters in Aspergillus nidulans. Here we show that LaeA regulation does not extend to nutrient utilization or the spoC1 sporulation clusters. One of the secondary metabolite clusters regulated by LaeA contains the positive regulatory (i.e. aflR) and biosynthetic genes required for biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST gene cluster expression indicates LaeA regulation of the cluster is location specific as transcription of genes bordering the ST cluster are unaffected in a DeltalaeA mutant and placement of a primary metabolic gene, argB, in the ST cluster resulted in argB silencing in the DeltalaeA background. ST cluster gene expression was remediated when an additional copy of aflR was placed outside of the cluster but not when placed in the cluster. Site-specific mutation of an s-adenosyl methionine (AdoMet) binding site in LaeA generated a DeltalaeA phenotype suggesting the protein to be a methyltransferase.
Wilms Tumor Gene on X Chromosome (WTX) Inhibits Degradation of NRF2 Protein through Competitive Binding to KEAP1 Protein (2012)

WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the β-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor β-catenin, a key control point in the WNT/β-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of β-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and degradation of NRF2 and a reduced response to cytotoxic insult. These results expand our understanding of the molecular mechanisms of WTX and reveal a novel regulatory mechanism governing the antioxidant response.