gebhart/patrepeval huggingface dataset:
β-Adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells (2000)

beta-Adrenergic receptor (betaAR) activation and/or increases in cAMP regulate growth and proliferation of a variety of cells and, in some cells, promote cell death. In the current studies we addressed the mechanism of this growth reduction by examining betaAR-mediated effects in the murine T-lymphoma cell line S49. Wild-type S49 cells, derived from immature thymocytes (CD4(+)/CD8(+)) undergo growth arrest and subsequent death when treated with agents that increase cAMP levels (e.g., betaAR agonists, 8-bromo-cAMP, cholera toxin, forskolin). Morphological and biochemical criteria indicate that this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells, which lack G(s)alpha and functional protein kinase A (PKA), respectively, betaAR activation of G(s)alpha and cAMP action via PKA are critical steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cAMP-induced apoptosis. We conclude that betaAR activation induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while overexpression of Bcl-2 prevents cell death. betaAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.
Automatic Real-Time Music Generation for Games (2015)

Music composition can be a challenge for many small- to medium-sized game companies, largely due to the expense and difficulty in creating original music for each level of a game. To address this, we developed a tool that automatically generates original music, by training a music generator on pieces whose style the game designer wishes to imitate. The generator then creates original music in that style in real-time, and switches between styles when signaled by the game. This software has been refined to produce music that is coherent and imitates a composer’s larger music structure.
Immunoglobulin secretion by peripheral blood and bone marrow B cells in patients with multiple myeloma. Studies by the reverse haemolytic plaque assay. (1984)

The reverse haemolytic plaque assay (RHPA) was used to enumerate circulating and bone marrow (BM) immunoglobulin secreting cells (ISC) in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), as well as in normal controls. Significantly greater quantities of plaque forming cells (PFC) secreting the same isotype of the serum M component were detected in the peripheral blood of MM patients than in the blood of MGUS patients or normal subjects. Comparative analysis of the numbers of monoclonal PFC in both peripheral blood (PB) and BM at diagnosis usually showed a higher number as well as more precocious chemotherapy-induced variations of ISC in the BM compartment than in the PB. Although large individual variations were observed during follow-up studies of MM patients, persistently increased or decreased levels of monoclonal PFC were often found to accompany (and sometimes to precede by months) the phases of relapse or remission, respectively. Similarly to IgG-MGUS patients, a distorted ratio of IgG kappa to IgG lambda secreting cells was consistently detected in patients with smouldering MM, although the total number (IgG kappa plus IgG lambda) of ISC appeared within normal limits. It is suggested that, in addition to other clinical and laboratory criteria, the RHPA may be of value in the diagnosis and follow-up of patients with monoclonal gammopathies.
Comparative reactivity of thiophene and 3,4-(ethylenedioxy)thiophene as terminal electropolymerizable units in bis-heterocycle arylenes (1997)

The monomers bis(2-thienyl)-9,9-didecylfluorene, BTDF, and bis(3,4-(ethylenedioxy)thien-2-yl)-9,9-didecylfluorene, BEDOT-DF, have been synthesized and electropolymerized to the corresponding conducting polymers. The potential for the electropolymerization of BTDF was found to be dependent on the solvent composition. In CH2Cl2, polymer film deposition is achieved only at potentials higher than 1.3 V vs. Ag/Ag+, while in a 30/70 mixture of CH2Cl2/CH3CN the polymerization is efficient at 0.9 V. BEDOT-DF polymerizes at significantly lower potentials and more rapidly than BTDF. The electron-donating alkoxy substituents of the EDOT units lead to stabilization of the cation radical intermediates allowing the electropolymerization to proceed at 0.55 V. The neutral polymers are insoluble in common organic solvents and are stable to 300°C under nitrogen. Upon oxidation, both polymers show two intragap transitions at intermediate doping levels due to the formation of bipolaronic states and the oxidized polymers exhibit conductivities up to 10−4 S/cm. The redox-stimulated ion transport characteristics, studied by the electrochemical quartz crystal microbalance (EQCM) indicates that the electrolyte anions are the dominant mobile species. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 3627–3636, 1997
The Aβ Hypothesis: Leading Us to Rationally-Designed Therapeutic Strategies for the Treatment or Prevention of Alzheimer Disease (2006)

In recent years the amyloid cascade hypothesis of Alzheimer disease (AD) has been increasingly referred to as the amyloid beta protein (Abeta) cascade hypothesis. This subtle rephrasing reflects the acknowledgment that there is debate within the field as to whether Abeta aggregates other than Abeta deposited as classic amyloid fibrils could trigger the pathological cascade that results in neuronal dysfunction and neurodegeneration. Despite this semantic shift, which highlights one enigmatic aspects of AD, the evidence supporting the Abeta hypothesis of AD is extensive. More importantly the Abeta hypothesis of AD has led and will continue to lead to the development of rationale therapeutic strategies that are likely to either prevent or treat this devastating disease. In this review, the evidence supporting the Abeta hypothesis and the recent advances in anti-Abeta therapy are discussed.
Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography (2012)

Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2.
Improved Efficiency and Pace of Generating Induced Pluripotent Stem Cells from Human Adult and Fetal Fibroblasts (2008)

It was reported recently that human fibroblasts can be reprogrammed into a pluripotent state that resembles that of human embryonic stem (hES) cells. This was achieved by ectopic expression of four genes followed by culture on mouse embryonic fibroblast (MEF) feeders under a condition favoring hES cell growth. However, the efficiency of generating human induced pluripotent stem (iPS) cells is low, especially for postnatal human fibroblasts. We started supplementing with an additional gene or bioactive molecules to increase the efficiency of generating iPS cells from human adult as well as fetal fibroblasts. We report here that adding SV40 large T antigen (T) to either set of the four reprogramming genes previously used enhanced the efficiency by 23-70-fold from both human adult and fetal fibroblasts. Discernible hES-like colonies also emerged 1-2 weeks earlier if T was added. With the improved efficiency, we succeeded in replacing MEFs with immortalized human feeder cells that we previously established for optimal hES cell growth. We further characterized individually picked hES-like colonies after expansion (up to 24 passages). The majority of them expressed various undifferentiated hES markers. Some but not all the hES-like clones can be induced to differentiate into the derivatives of the three embryonic germ layers in both teratoma formation and embryoid body (EB) formation assays. These pluripotent clones also differentiated into trophoblasts after EB formation or bone morphogenetic protein 4 induction as classic hES cells. Using this improved approach, we also generated hES-like cells from homozygous fibroblasts containing the sickle cell anemia mutation Hemoglobin Sickle. Disclosure of potential conflicts of interest is found at the end of this article.
COBRA combination therapy in patients with early rheumatoid arthritis: Long‐term structural benefits of a brief intervention (2002)

An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.
Novel Biological Response Modifiers Derived from Thalidomide (1998)

Thalidomide (N-alpha-phthalimidoglutarimide) was used widely as a hypnotic/sedative agent in the late 1950s and the early 1960s, but had to be withdrawn from the market because of its severe teratogenicity. In spite of this, there has been a resurgence of interest in the drug in recent years due to its potential usefulness for the treatment of various diseases, including acquired immunodeficiency syndrome (AIDS) and graft-versus-host disease (GVHD). The effectiveness of the drug in these diseases has been attributed to its specific inhibitory activity on tumor necrosis factor-alpha (TNF-alpha) production. Because TNF-alpha, a cytokine mediating host defence and immune regulation, with a wide range of activities, has deleterious pathophysiological effects in various diseases, including AIDS, tumors, rheumatoid arthritis and diabetes, its production-regulators are attractive lead compounds for novel biological response modifiers. The regulatory effect of thalidomide on TNF-alpha production has been found to be bidirectional, depending on both the cell-type and the TNF-alpha production-inducer; i.e., thalidomide possesses both enhancing and inhibiting activities on TNF-alpha production. Structural modification of thalidomide aiming at the creation of superior TNF-alpha production-regulators has afforded a number of phenyl- and benzylphthalimide analogs possessing more potent activity than thalidomide itself. The structure-activity relationships of these analogs has been investigated. The bidirectional TNF-alpha production-regulating activity is electronic state- and enantio-dependent, and both pure inhibitors and pure enhancers of TNF-alpha production has been obtained. Further structural development of the phthalimide analogs has yielded potent non-steroidal androgen antagonists.
Morphological Control for High Performance, Solution‐Processed Planar Heterojunction Perovskite Solar Cells (2013)

Organometal trihalide perovskite based solar cells have exhibited the highest efficiencies to‐date when incorporated into mesostructured composites. However, thin solid films of a perovskite absorber should be capable of operating at the highest efficiency in a simple planar heterojunction configuration. Here, it is shown that film morphology is a critical issue in planar heterojunction CH 3 NH 3 PbI 3‐ x Cl x solar cells. The morphology is carefully controlled by varying processing conditions, and it is demonstrated that the highest photocurrents are attainable only with the highest perovskite surface coverages. With optimized solution based film formation, power conversion efficiencies of up to 11.4% are achieved, the first report of efficiencies above 10% in fully thin‐film solution processed perovskite solar cells with no mesoporous layer.
Bimodal Activation of Different Neuron Classes with the Spectrally Red-Shifted Channelrhodopsin Chimera C1V1 in Caenorhabditis elegans (2012)

The C. elegans nervous system is particularly well suited for optogenetic analyses of circuit function: Essentially all connections have been mapped, and light can be directed at the neuron of interest in the freely moving, transparent animals, while behavior is observed. Thus, different nodes of a neuronal network can be probed for their role in controlling a particular behavior, using different optogenetic tools for photo-activation or -inhibition, which respond to different colors of light. As neurons may act in concert or in opposing ways to affect a behavior, one would further like to excite these neurons concomitantly, yet independent of each other. In addition to the blue-light activated Channelrhodopsin-2 (ChR2), spectrally red-shifted ChR variants have been explored recently. Here, we establish the green-light activated ChR chimera C1V1 (from Chlamydomonas and Volvox ChR1's) for use in C. elegans. We surveyed a number of red-shifted ChRs, and found that C1V1-ET/ET (E122T; E162T) works most reliable in C. elegans, with 540-580 nm excitation, which leaves ChR2 silent. However, as C1V1-ET/ET is very light sensitive, it still becomes activated when ChR2 is stimulated, even at 400 nm. Thus, we generated a highly efficient blue ChR2, the H134R; T159C double mutant (ChR2-HR/TC). Both proteins can be used in the same animal, in different neurons, to independently control each cell type with light, enabling a further level of complexity in circuit analyses.
Learning From Explanations Using Sentiment and Advice in RL (2016)

In order for robots to learn from people with no machine learning expertise, robots should learn from natural human instruction. Most machine learning techniques that incorporate explanations require people to use a limited vocabulary and provide state information, even if it is not intuitive. This paper discusses a software agent that learned to play the Mario Bros. game using explanations. Our goals to improve learning from explanations were twofold: (1) to filter explanations into advice and warnings and (2) to learn policies from sentences without state information. We used sentiment analysis to filter explanations into advice of what to do and warnings of what to avoid. We developed object-focused advice to represent what actions the agent should take when dealing with objects. A reinforcement learning agent used object-focused advice to learn policies that maximized its reward. After mitigating false negatives, using sentiment as a filter was approximately 85% accurate. object-focused advice performed better than when no advice was given, the agent learned where to apply the advice, and the agent could recover from adversarial advice. We also found the method of interaction should be designed to ease the cognitive load of the human teacher or the advice may be of poor quality.
Building interactive relationships : the risks, dilemmas and learning initiatives associated with partnerships with 'real' purpose (2003)

Many teachers already do all kinds of interesting and potentially useful data collection with their students but in a fridge door context the data is rarely kept, the analyses are rarely shared beyond the classroom (except on a family’s fridge door) and it is very rare that data is stored and added to over time. (Bigum, 2002)
The FLT3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro (1996)

The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony formation in combination with interleukin (IL) 3, granulocyte colony-stimulating factor (G-CSF), CSF-1, granulocyte macrophage (GM) CSF stem cell factor (SCF), and IL-6. FL and SCF were equally effective in stimulating colony formation in combination with IL-3. However, the tri-factor combination of FL + IL-3 + SCF stimulated 2.3-fold and 2.5-fold more colonies than FL + IL-3 and SCF + IL-3, respectively. These additional recruited progenitors appeared to be predominantly located in a primitive (CD71-) subset of the CD34+ progenitors, as 4.5-fold more colonies were formed by CD34+CD71- cells in response to FL + IL-3 + SCF than to FL + IL-3 or SCF + IL-3. Similar findings were observed in serum-containing and serum-deprived cultures. Whereas FL did not enhance burst-forming unit-erythroid (BFU-E) colony formation of CD34+ BM cells in the presence of serum, a low number of BFU-E colonies were formed in response to FL plus erythropoietin (Epo) under serum-deprived conditions. In addition, FL both in serum-containing and serum-deprived cultures stimulated colony formation of more committed myeloid progenitors in CD34+CD71+ BM cells. Thus, FL potently stimulates the growth of primitive and more committed human BM progenitor cells.
Nucleotide polymorphism in colicin E1 and Ia plasmids from natural isolates of Escherichia coli. (1994)

We examined DNA sequence polymorphism for the colicin gene clusters of seven ColE1 and six ColIa plasmids obtained from natural isolates of Escherichia coli. These gene clusters harbor levels of nucleotide diversity ranging from 0.006 (ColIa) to 0.054 (ColE1). This level of diversity is similar to that observed for chromosomally encoded E. coli genes. However, the variance associated with these estimates is severalfold higher for the plasmid-encoded genes. This increased variance may be due to the differing plasmid population sizes. The pattern of colicin gene cluster polymorphism suggests that the two colicins are evolving in different fashions. ColE1 accumulates polymorphism at an elevated rate in the central domain of the colicin protein, while ColIa polymorphism is distributed evenly along the gene cluster. Comparison of the patterns of divergence between colicin and related proteins of ColIa and Ib and patterns of polymorphism within ColIa suggest that this gene cluster is not evolving in a neutral fashion. These data lend support to the hypothesis that colicin gene clusters may evolve under the influence of diversifying selection.
CCCL.—The structure of carbohydrates and their optical rotatory power. Part III. 4-Galactosido-α-mannose and its derivatives (1930)

W. N. Haworth, E. L. Hirst, M. M. T. Plant and R. J. W. Reynolds, J. Chem. Soc., 1930, 2644 DOI: 10.1039/JR9300002644
Low Coordinate Germanium(II) and Tin(II) Hydride Complexes: Efficient Catalysts for the Hydroboration of Carbonyl Compounds (2014)

This study details the first use of well-defined low-valent p-block metal hydrides as catalysts in organic synthesis. That is, the bulky, two-coordinate germanium(II) and tin(II) hydride complexes, L(†)(H)M: (M = Ge or Sn, L(†) = -N(Ar(†))(SiPr(i)3), Ar(†) = C6H2{C(H)Ph2}2Pr(i)-2,6,4), are shown to act as efficient catalysts for the hydroboration (with HBpin, pin = pinacolato) of a variety of unactivated, and sometimes very bulky, carbonyl compounds. Catalyst loadings as low as 0.05 mol % are required to achieve quantitative conversions, with turnover frequencies in excess of 13 300 h(-1) in some cases. This activity rivals that of currently available catalysts used for such reactions.
Unraveling the Swine Genome: Implications for Human Health (2015)

The pig was first used in biomedical research in ancient Greece and over the past few decades has quickly grown into an important biomedical research tool. Pigs have genetic and physiological traits similar to humans, which make them one of the most useful and versatile animal models. Owing to these similarities, data generated from porcine models are more likely to lead to viable human treatments than those from murine work. In addition, the similarity in size and physiology to humans allows pigs to be used for many experimental approaches not feasible in mice. Research areas that employ pigs range from neonatal development to translational models for cancer therapy. Increasing numbers of porcine models are being developed since the release of the swine genome sequence, and the development of additional porcine genomic and epigenetic resources will further their use in biomedical research.
Cationic Ruthenium(II) Catalysts for Oxidative C–H/N–H Bond Functionalizations of Anilines with Removable Directing Group: Synthesis of Indoles in Water (2012)

Cationic ruthenium(II) complexes enabled oxidative C-H bond functionalizations with anilines bearing removable directing groups. The C-H/N-H bond cleavages occurred most efficiently in water as a sustainable solvent and provided general access to various bioactive indoles. Mechanistic studies provided strong support for a novel reaction manifold.
Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver (1997)

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.
Papillomavirus virus‐like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells (2005)

Human papillomavirus (HPV) virus-like particles (VLP) are being extensively tested as vaccines for the prevention of HPV-associated cervical cancer. Dendritic cells (DC) acquire and present antigens, initiating innate and adaptive immune responses. It has been shown previously that DC of the myeloid lineage are capable of generating adaptive immune responses to HPV VLP in vitro. However, the capacity of plasmacytoid DC (pDC) to acquire HPV VLP and the nature of the immune response generated have not been reported. In this study we found that freshly isolated as well as CpG-matured pDC bind papillomavirus VLP and that internalization occurs preferentially in the immature pDC. In contrast to myeloid DC, pDC did not undergo phenotypic maturation upon exposure to HPV16 VLP. However, HPV16 VLP induced pDC to secrete of IFN-alpha and IL-6, both cytokines that play a role in the generation of antibody responses, as well as TNFalpha and IL-8. Given that VLP do not contain viral nucleic acids, these results indicate that viral capsids alone may be capable of inducing cytokine production by pDC. Finally, CpG-activated pDC, but not pDC exposed to HPV16 VLP, activated lymphocytes to secrete IL-10 and low levels of IFN-gamma. Together these findings suggest a possible immunogenic effect of pDC in the setting of VLP vaccination.