gebhart/patrepeval huggingface dataset:
Hematopoietic Progenitor Kinase 1 Is a Negative Regulator of Dendritic Cell Activation (2009)

Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 kinases that acts as a negative regulator of T cell functions through the AP-1, NFAT, and NFkappaB pathways. Using HPK1-deficient (HPK1(-/-)) mice, we report in this study a novel role for HPK1 in dendritic cells (DCs). Specifically, we observed that matured HPK1(-/-) bone marrow-derived DCs (BMDCs) are superior to their wild-type (WT) counterpart in stimulating T cell proliferation in vivo and in vitro. Several characteristics of HPK1(-/-) BMDCs may account for this enhanced activity: Matured HPK1(-/-) BMDCs express higher levels of costimulatory molecules CD80, CD86, and I-A(b) as well as produce more proinflammatory cytokines IL-12, IL-1beta, TNF-alpha, and IL-6 than their WT littermates. The role of HPK1 as a proapoptotic molecule was assessed post activation with LPS, and results indicated that HPK1(-/-) BMDCs are significantly resistant to LPS-induced apoptosis. Our results led us to investigate the role of HPK1(-/-) BMDCs in tumor immunotherapy. Using a s.c. murine model of Lewis Lung Carcinoma, we found that HPK1(-/-) BMDCs eliminate established s.c. Lewis Lung Carcinoma more efficiently than their WT counterpart. Our data reveal a novel role for HPK1 as a negative regulator of DC functions, identifying its potential as a molecular target for DC-based immunotherapy against cancers.
TheChlamydomonas reinhardtiiPlastid Chromosome (2002)

Chlamydomonas reinhardtii is a unicellular eukaryotic alga possessing a single chloroplast that is widely used as a model system for the study of photosynthetic processes. This report analyzes the surprising structural and evolutionary features of the completely sequenced 203,395-bp plastid chromosome. The genome is divided by 21.2-kb inverted repeats into two single-copy regions of approximately 80 kb and contains only 99 genes, including a full complement of tRNAs and atypical genes encoding the RNA polymerase. A remarkable feature is that >20% of the genome is repetitive DNA: the majority of intergenic regions consist of numerous classes of short dispersed repeats (SDRs), which may have structural or evolutionary significance. Among other sequenced chlorophyte plastid genomes, only that of the green alga Chlorella vulgaris appears to share this feature. The program MultiPipMaker was used to compare the genic complement of Chlamydomonas with those of other chloroplast genomes and to scan the genomes for sequence similarities and repetitive DNAs. Among the results was evidence that the SDRs were not derived from extant coding sequences, although some SDRs may have arisen from other genomic fragments. Phylogenetic reconstruction of changes in plastid genome content revealed that an accelerated rate of gene loss also characterized the Chlamydomonas/Chlorella lineage, a phenomenon that might be independent of the proliferation of SDRs. Together, our results reveal a dynamic and unusual plastid genome whose existence in a model organism will allow its features to be tested functionally.
DAOmap: a depth-optimal area optimization mapping algorithm for FPGA designs (2005)

In This work we study the technology mapping problem for FPGA architectures to minimize chip area, or the total number of lookup tables (LUTs) of the mapped design, under the chip performance constraint. This is a well-studied topic and a very difficult task (NP-hard). The contributions of This work are as follows: (i) we consider the potential node duplications during the cut enumeration/generation procedure so the mapping costs encoded in the cuts drive the area-optimization objective more effectively; (ii) after the timing constraint is determined, we will relax the non-critical paths by searching the solution space considering both local and global optimality information to minimize mapping area; (iii) an iterative cut selection procedure is carried out that further explores and perturbs the solution space to improve solution quality. We guarantee optimal mapping depth under the unit delay model. Experimental results show that our mapping algorithm, named DAOmap, produces significant quality and runtime improvements. Compared to the state-of-the-art depth-optimal, area minimization mapping algorithm CutMap (Cong and Hwan, 1995), DAOmap is 16.02% better on area and runs 24.2X faster on average when both algorithms are mapping to FPGAs using LUTs of five inputs. LUTs of other inputs are also used for comparisons.
A Trial of a 9-Valent Pneumococcal Conjugate Vaccine in Children with and Those without HIV Infection (2003)

Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection.
A Cost-based Optimizer for Gradient Descent Optimization (2017)

As the use of machine learning (ML) permeates into diverse application domains, there is an urgent need to support a declarative framework for ML. Ideally, a user will specify an ML task in a high-level and easy-to-use language and the framework will invoke the appropriate algorithms and system configurations to execute it. An important observation towards designing such a framework is that many ML tasks can be expressed as mathematical optimization problems, which take a specific form. Furthermore, these optimization problems can be efficiently solved using variations of the gradient descent (GD) algorithm. Thus, to decouple a user specification of an ML task from its execution, a key component is a GD optimizer. We propose a cost-based GD optimizer that selects the best GD plan for a given ML task. To build our optimizer, we introduce a set of abstract operators for expressing GD algorithms and propose a novel approach to estimate the number of iterations a GD algorithm requires to converge. Extensive experiments on real and synthetic datasets show that our optimizer not only chooses the best GD plan but also allows for optimizations that achieve orders of magnitude performance speed-up.
A Comparison of the Self-association Behavior of the Plant Cyclotides Kalata B1 and Kalata B2 via Analytical Ultracentrifugation (2003)

The recently discovered cyclotides kalata B1 and kalata B2 are miniproteins containing a head-to-tail cyclized backbone and a cystine knot motif, in which disulfide bonds and the connecting backbone segments form a ring that is penetrated by the third disulfide bond. This arrangement renders the cyclotides extremely stable against thermal and enzymatic decay, making them a possible template onto which functionalities can be grafted. We have compared the hydrodynamic properties of two prototypic cyclotides, kalata B1 and kalata B2, using analytical ultracentrifugation techniques. Direct evidence for oligomerization of kalata B2 was shown by sedimentation velocity experiments in which a method for determining size distribution of polydisperse molecules in solution was employed. The shape of the oligomers appears to be spherical. Both sedimentation velocity and equilibrium experiments indicate that in phosphate buffer kalata B1 exists mainly as a monomer, even at millimolar concentrations. In contrast, at 1.6 mm, kalata B2 exists as an equilibrium mixture of monomer (30%), tetramer (42%), octamer (25%), and possibly a small proportion of higher oligomers. The results from the sedimentation equilibrium experiments show that this self-association is concentration dependent and reversible. We link our findings to the three-dimensional structures of both cyclotides, and propose two putative interaction interfaces on opposite sides of the kalata B2 molecule, one involving a hydrophobic interaction with the Phe6, and the second involving a charge-charge interaction with the Asp25 residue. An understanding of the factors affecting solution aggregation is of vital importance for future pharmaceutical application of these molecules.
Abstract 4281: Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human, Cynomolgus Monkey and Mouse (2015)

Abstract RDB 1450 is an engineered fusion protein designed to selectively activate the intermediate-affinity IL-2 receptor versus the high-affinity IL-2 receptor. The potencies of RDB 1450 and IL-2 for activation of distinct subsets of effector and regulatory lymphocytes from murine, non-human primate and human donors were determined. Splenocytes isolated from mice or leukocytes isolated from human or cyno blood were stimulated with either RDB 1450 or IL-2. Multicolor flow cytometry was used to identify distinct subpopulations and the extent of phosphorylation of STAT5 was measured. Whereas IL-2 is 2-3 orders of magnitude more potent on immunosuppressive Tregs relative to NK cells and memory CD8 T cells, RDB 1450 induces activation of NK cells, memory CD8 T cells and Tregs at comparable concentrations within each species. The non-differentiated potency of RDB 1450 on the lymphocyte subpopulations examined suggests that its effects are mediated through the intermediate affinity receptors even on CD25-expressing Tregs. The preferential activation of Tregs by IL-2 may lead to immunosuppression and limit its antitumor efficacy. In contrast, RDB 1450 does not exhibit the same preference for Treg activation and is expected to be more effective in driving antitumor immune responses. These results highlight the differentiated immunological profile of RDB 1450 and support its potential as a novel human immunotherapy. Citation Format: Emily E. Rosentrater, Heather Flick, Jared E. Lopes, Heather C. Losey, Chunhua Wang, Juan C. Alvarez. Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human, Cynomolgus Monkey and Mouse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4281. doi:10.1158/1538-7445.AM2015-4281
Release Behavior of Thin-Walled Microcapsules Composed of Polyelectrolyte Multilayers (2001)

The release properties of the fluorescent probe pyrene, PYR, encapsulated in polyelectrolyte multilayer capsules were examined by fluorescence spectroscopy. PYR was encapsulated by the layer-by-layer deposition of oppositely charged polyelectrolytes onto PYR microcrystal templates, and its release was accomplished by exposing the polyelectrolyte-coated microcrystals to ethanol solutions. Solubilization of the hydrophobic probe by ethanol resulted in its expulsion from the core through the permeable polyelectrolyte multilayer shells. The PYR release rate, quantified by following the monomer fluorescence of the solubilized PYR as a function of time, decreased with increasing number of polyelectrolyte layers deposited onto the microcrystal cores. In addition, two amphiphiles (sodium dodecyl sulfate and dipalmitoyl-dl-α-phosphatidylcholine) used to disperse the microcrystals in aqueous solution prior to coating with polyelectrolytes significantly influenced the PYR release rate. The maximum release time, defined as the time required to achieve saturation release, could be varied by a factor of 2−5 depending on the nature of the first adsorbed layer and the number of polyelectrolyte layers composing the shell wall. The influence of flow (i.e., centrifugation vs magnetic stirring) as well as solvent on the PYR release rate is also discussed.
A program for aligning sentences in bilingual corpora (1991)

Researchers in both machine translation (e.g., Brown et al., 1990) and bilingual lexicography (e.g., Klavans and Tzoukermann, 1990) have recently become interested in studying parallel texts, texts such as the Canadian Hansards (parliamentary proceedings) which are available in multiple languages (French and English). This paper describes a method for aligning sentences in these parallel texts, based on a simple statistical model of character lengths. The method was developed and tested on a small trilingual sample of Swiss economic reports. A much larger sample of 90 million words of Canadian Hansards has been aligned and donated to the ACL/DCI.
On the Local and Superlinear Convergence of Quasi-Newton Methods (1973)

Journal Article On the Local and Superlinear Convergence of Quasi-Newton Methods Get access C. G. BROYDEN, C. G. BROYDEN Department of Computer Science, Cornell UniversityIthaca, N. Y. 15850, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J. E. DENNIS, Jr., J. E. DENNIS, Jr. Department of Computer Science, Cornell UniversityIthaca, N. Y. 15850, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar JORGE J. MORÉ JORGE J. MORÉ Department of Computer Science, Cornell UniversityIthaca, N. Y. 15850, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar IMA Journal of Applied Mathematics, Volume 12, Issue 3, December 1973, Pages 223–245, https://doi.org/10.1093/imamat/12.3.223 Published: 01 December 1973 Article history Received: 26 March 1973 Published: 01 December 1973
Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP‐1 and NFκB transcription factors (2007)

Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, contributing to the poor prognosis associated with these tumors. Over-expression of transcription factors such as NFkappaB and AP-1 contribute to the enhanced glioma survival, radioresistance, and chemoresistance. Curcumin, which may inhibit these pathways, was therefore investigated for a potential therapeutic role in glioma. The effect of curcumin on glioma survival was investigated in human (T98G, U87MG, and T67) and rat (C6) glioma cell lines. The ability of curcumin to overcome glioma cell radioresistance and chemoresistance was also explored. Curcumin reduced cell survival in a p53- and caspase-independent manner, an effect correlated with the inhibition of AP-1 and NFkappaB signaling pathways via prevention of constitutive JNK and Akt activation. Curcumin-sensitized glioma cells to several clinically utilized chemotherapeutic agents (cisplatin, etoposide, camptothecin, and doxorubicin) and radiation, effects correlated with reduced expression of bcl-2 and IAP family members as well as DNA repair enzymes (MGMT, DNA-PK, Ku70, Ku80, and ERCC-1). These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer.
A novel function forHedgehogsignalling in retinal pigment epithelium differentiation (2003)

Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog, related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2, Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus, suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.
Discovery of Dual Orexin Receptor Antagonists (DORAs) for the Treatment of Insomnia (2011)

Orexins are excitatory neuropeptides that have a critical role in maintaining wakefulness. Orexin receptor antagonists promote sleep in animals and humans. Indeed, small molecule orexin receptor antagonists have demonstrated clinical proof-of-concept in the treatment of primary insomnia. This review describes optimization of orexin receptor antagonists across diverse structural classes with a focus on how molecules were designed to optimize potency, physicochemical properties, pharmacokinetics, brain penetration, and in vivo activity.
ChemInform Abstract: Preparation of Fullerenol, Fullerenone, and Aminofullerene Derivatives Through Selective Cleavage of Fullerene C—H, C—C, C—N, and C—O Bonds in Fullerene‐Mixed Peroxide Derivatives. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Interferon gamma stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes. (1994)

The proteasome is a 700-kD multisubunit enzyme complex with several proteolytically active sites. The enzyme complex is involved in both ubiquitin-dependent and -independent protein degradation and may contribute to the processing of antigens presented by major histocompatibility complex (MHC) class I molecules. Here we demonstrate that treatment of mouse fibroblast cells with 20 U interferon gamma (IFN-gamma) for 3 d induces a change in the proteasome subunit composition and that the beta-type subunit LMP2, which is encoded in the MHC class II region, is incorporated into the enzyme complex. This is paralleled by reduction of the homologous delta-subunit. IFN-gamma stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected. When tested as a substrate a synthetic 25-mer polypeptide whose sequence covers the antigenic nonapeptide YPHFMPTNL of the MCMV pp89, 20S proteasomes of IFN-gamma-induced cells exhibit altered chymotrypsin-like cleavage site preferences. In the absence of IFN-gamma induction, the naturally processed nonamer peptide that is presented by MHC class I molecules appears as a minor cleavage product. IFN-gamma activation does not result in an increase of the final peptide but results in a different set of peptides. We hypothesize that these peptides represent precursor peptides that can be trimmed to final peptide size.
Proteolytic enzymes: a new treatment strategy for prosthetic infections? (1993)

Among the different mechanisms of bacterial resistance to antimicrobial agents that have been studied, biofilm formation is one of the most widespread. This mechanism is frequently the cause of failure in the treatment of prosthetic device infections, and several attempts have been made to develop molecules and protocols that are able to inhibit biofilm-embedded bacteria. We present data suggesting the possibility that proteolytic enzymes could significantly enhance the activities of antibiotics against biofilms. Antibiotic susceptibility tests on both planktonic and sessile cultures, studies on the dynamics of colonization of 10 biofilm-forming isolates, and then bioluminescence and scanning electron microscopy under seven different experimental conditions showed that serratiopeptidase greatly enhances the activity of ofloxacin on sessile cultures and can inhibit biofilm formation.
Study of persistent luminescence and thermoluminescence in SrSi2N2O2:Eu2+,M3+(M = Ce, Dy, and Nd) (2020)

The process of persistent luminescence or glow-in-the-dark, the delayed emission of light of irradiated substances, has long fascinated researchers, who have made efforts to explain the underlying physical phenomenon as well as put it to practical use. However, persistent luminescence is an elusive and difficult process, both in terms of controlling or altering its properties, as well as providing a quantitative description. In this paper, we used SrSi<sub>2</sub>N<sub>2</sub>O<sub>2</sub>:Eu<sup>2+</sup> as a model persistent phosphor, characterized by the broad distribution of structural defects and exhibiting long-lasting Eu<sup>2+</sup> luminescence that is visible for a few minutes after switching off UV light. We investigated the persistent luminescence process by two complementary methods, namely, thermoluminescence and temperature-dependent persistent luminescence decay measurements. Analysis of experimental data allowed us to determine the depth distribution of traps, and allowed us to distinguish two different mechanisms by which the emission is delayed. The first, the temperature-dependent mechanism, is related to trap activation, while the second, temperature-independent mechanism is related to carrier migration. Finally, we employed the strategy of the co-doping of the phosphor SrSi<sub>2</sub>N<sub>2</sub>O<sub>2</sub>:Eu<sup>2+</sup>,M<sup>3+</sup> (M = Ce, Nd, Dy) to modify the persistent luminescence properties.
Copy Number Lability and Evolutionary Dynamics of the Adh Gene Family in Diploid and Tetraploid Cotton (Gossypium) (2000)

Nuclear-encoded genes exist in families of various sizes. To further our understanding of the evolutionary dynamics of nuclear gene families we present a characterization of the structure and evolution of the alcohol dehydrogenase (Adh) gene family in diploid and tetraploid members of the cotton genus (Gossypium, Malvaceae). A PCR-based approach was employed to isolate and sequence multiple Adh gene family members, and Southern hybridization analyses were used to document variation in gene copy number. Adh gene copy number varies among Gossypium species, with diploids containing at least seven Adh loci in two primary gene lineages. Allotetraploid Gossypium species are inferred to contain at least 14 loci. Intron lengths vary markedly between loci, and one locus has lost two introns usually found in other plant Adh genes. Multiple examples of apparent gene duplication events were observed and at least one case of pseudogenization and one case of gene elimination were also found. Thus, Adh gene family structure is dynamic within this single plant genus. Evolutionary rate estimates differ between loci and in some cases between organismal lineages at the same locus. We suggest that dynamic fluctuation in copy number will prove common for nuclear genes, and we discuss the implications of this perspective for inferences of orthology and functional evolution.