gebhart/patrepeval huggingface dataset:
Diphenylmethanofullerenes: New and Efficient Acceptors in Bulk‐Heterojunction Solar Cells (2005)

Abstract A novel fullerene derivative, 1,1‐bis(4,4′‐dodecyloxyphenyl)‐(5,6) C 61 , diphenylmethanofullerene (DPM‐12), has been investigated as a possible electron acceptor in photovoltaic devices, in combination with two different conjugated polymers poly[2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐ para ‐phenylene vinylene] (OC 1 C 10 ‐PPV) and poly[3‐hexyl thiophene‐2,5‐diyl] (P3HT). High open‐circuit voltages, V OC = 0.92 and 0.65 V, have been measured for OC 1 C 10 ‐PPV:DPM‐12‐ and P3HT:DPM‐12‐based devices, respectively. In both cases, V OC is 100 mV above the values measured on devices using another routinely used fullerene acceptor, [6,6]‐phenyl‐C 61 butyric acid methyl ester (PCBM). This is somewhat unexpected when taking into account the identical redox potentials of both acceptor materials at room temperature. The temperature‐dependent V OC reveals, however, the same effective bandgap (HOMO Polymer –LUMO Fullerene ; HOMO = highest occupied molecular orbital, LUMO = lowest unoccupied molecular orbital) of 1.15 and 0.9 eV for OC 1 C 10 ‐PPV and P3HT, respectively, independent of the acceptor used. The higher V OC at room temperature is explained by different ideality factors in the dark‐diode characteristics. Under white‐light illumination (80 mW cm –2 ), photocurrent densities of 1.3 and 4.7 mA cm –2 have been obtained in the OC 1 C 10 ‐PPV:DPM‐12‐ and P3HT:DPM‐12‐based devices, respectively. Temperature‐dependent current density versus voltage characteristics reveal a thermally activated (shallow trap recombination limited) photocurrent in the case of OC 1 C 10 ‐PPV:DPM‐12, and a nearly temperature‐independent current density in P3HT:DPM‐12. The latter clearly indicates that charge carriers traverse the active layer without significant recombination, which is due to the higher hole‐mobility–lifetime product in P3HT. At the same time, the field‐effect electron mobility in pure DPM‐12 has been found to be μ e = 2 × 10 –4 cm 2 V –1 s –1 , that is, forty‐times lower than the one measured in PCBM (μ e = 8 × 10 –3 cm 2 V –1 s –1 ).
SHP-1 and SHP-2 Associate with Immunoreceptor Tyrosine-Based Switch Motif of Programmed Death 1 upon Primary Human T Cell Stimulation, but Only Receptor Ligation Prevents T Cell Activation (2004)

To study the cis- and trans-acting factors that mediate programmed death 1 (PD-1) signaling in primary human CD4 T cells, we constructed a chimeric molecule consisting of the murine CD28 extracellular domain and human PD-1 cytoplasmic tail. When introduced into CD4 T cells, this construct mimics the activity of endogenous PD-1 in terms of its ability to suppress T cell expansion and cytokine production. The cytoplasmic tail of PD-1 contains two structural motifs, an ITIM and an immunoreceptor tyrosine-based switch motif (ITSM). Mutation of the ITIM had little effect on PD-1 signaling or functional activity. In contrast, mutation of the ITSM abrogated the ability of PD-1 to block cytokine synthesis and to limit T cell expansion. Further biochemical analyses revealed that the ability of PD-1 to block T cell activation correlated with recruitment of Src homology region 2 domain-containing phosphatase-1 (SHP-1) and SHP-2, and not the adaptor Src homology 2 domain-containing molecule 1A, to the ITSM domain. In TCR-stimulated T cells, SHP-2 associated with PD-1, even in the absence of PD-1 engagement. Despite this interaction, the ability of PD-1 to block T cell activation required receptor ligation, suggesting that colocalization of PD-1 with CD3 and/or CD28 may be necessary for inhibition of T cell activation.
Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice. (1996)

Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from transgenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight was comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, and 300 days, respectively, after birth. At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and control mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.
Overexpression of Insulin-Like Growth Factor Binding Protein-5 Helps Accelerate Progression to Androgen-Independence in the Human Prostate LNCaP Tumor Model through Activation of Phosphatidylinositol 3′-Kinase Pathway* (2000)

Although insulin-like growth factor (IGF) binding protein-5 (IGFBP-5) is highly up-regulated in normal and malignant prostate tissues after androgen withdrawal, its functional role in castration-induced apoptosis and androgen-independent progression remains undefined. To analyze the functional significance of IGFBP-5 overexpression in IGF-I-mediated mitogenesis and progression to androgen-independence, IGFBP-5-overexpressing human androgen-dependent LNCaP prostate cancer cells were generated by stable transfection. The growth rates of IGFBP-5-transfected LNCaP cells were significantly faster, compared with either the parental or vector-only transfected LNCaP cells in both the presence and absence ofdihydrotestosterone. IGFBP-5-induced increases in LNCaP cell proliferation occurs through both IGF-I-dependent and -independent pathways, with corresponding increases in the cyclin D1 messenger RNA expression and the fraction of cells in S + G2/M phases of the cell cycle. Changes in Akt/protein kinase B, a downstream component of phosphatidylinositol 3'-kinase (PI3K) pathway, in the LNCaP sublines also paralleled changes in their growth rates. Although treatment with a PI3K inhibitor induced apoptosis in both control and IGFBP-5-overexpressing LNCaP cells, this PI3K inhibitor-induced apoptosis was prevented by exogenous IGF-I treatment only in IGFBP-5 transfectants, suggesting that IGFBP-5 overexpression can potentiate the antiapoptotic effects of IGF-I. Furthermore, tumor growth and serum prostate-specific antigen levels increased several fold faster in mice bearing IGFBP-5-transfected LNCaP tumors after castration, despite having similar tumor incidence and tumor growth rates with controls when grown in intact mice before castration. Collectively, these data suggest that IGFBP-5 overexpression in prostate cancer cells after castration is an adaptive cell survival mechanism that helps potentiate the antiapoptotic and mitogenic effects of IGF-I, thereby accelerating progression to androgen independence through activation of the PI3K-Akt/ protein kinase B signaling pathway.
Mouse major histocompatibility class I gene expression begins at midsomite stage and is inducible in earlier-stage embryos by interferon. (1985)

To determine the timing of major histocompatibility complex class I gene expression during embryonic development, binding of anti-class I antibodies and appearance of class I gene transcripts were examined in mouse embryos from the egg-cylinder stage through day 16 of gestation. By using two series of monoclonal antibodies reactive with monomorphic and polymorphic determinants of class I antigens, it was found that cell-surface expression of the antigens becomes detectable at a low level only after midsomite stage on gestation day 10, at a time when embryos are developed beyond primordial organogenesis and have partial blood circulation. In agreement with the above finding, a low level of class I mRNA became detectable in day 9 and older embryos in blot hybridization. The level of class I transcripts in embryos at least to day 13 remained less than 1/50th that in adult spleen cells. Cells from head-fold stage embryos (gestation day 8), which otherwise do not have an appreciable amount of class I mRNA or surface antigens, begin to express a high level of antigens upon treatment with mouse alpha/beta or gamma interferon. This induction of class I antigen expression appears to be stage specific in that embryos in an earlier egg-cylinder stage (day 6) failed to express the antigens after interferon treatment. A possible role of interferons in activating class I genes during in vivo embryonic development is suggested.
Flea Repellents for Use on Clothing1 (1946)

Journal Article Flea Repellents for Use on Clothing Get access J. P. Linduska, J. P. Linduska U.S.D.A., Agr. Res. Adm., Bureau of Entomology and Plant Quarantine. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Cochran, J. H. Cochran U.S.D.A., Agr. Res. Adm., Bureau of Entomology and Plant Quarantine. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. A Morton F. A Morton U.S.D.A., Agr. Res. Adm., Bureau of Entomology and Plant Quarantine. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 39, Issue 6, 1 December 1946, Pages 767–769, https://doi.org/10.1093/jee/39.6.767 Published: 01 December 1946
Transferrin Trojan Horses as a Rational Approach for the Biological Delivery of Therapeutic Peptide Domains (1999)

One novel approach for the biological delivery of peptide drugs is to incorporate the sequence of the peptide into the structure of a natural transport protein, such as human serum transferrin. To examine whether this is feasible, a peptide sequence cleavable by the human immunodeficiency virus type 1 protease (VSQNYPIVL) was inserted into various regions of human serum transferrin, and the resultant proteins were tested for function. Experimentally, molecular modeling was used to identify five candidate insertion sites in surface exposed loops of human serum transferrin that were distant from biologically active domains. These insertions were cloned using polymerase chain reaction mutagenesis, and the proteins were expressed using a baculovirus expression vector system. Analysis of the mutant proteins provided a number of important findings: (a) they retained native human serum transferrin function, (b) the inserted peptide sequence was surface exposed, and most importantly, (c) two of these mutants could be cleaved by human immunodeficiency virus-1 protease. In conclusion, this investigation has validated the use of human serum transferrin as a carrier protein for functional peptide domains introduced into its structure using protein engineering. These findings will be useful for developing a novel class of therapeutic agents for a broad spectrum of diseases.
Chitosan–cellulose composite for wound dressing material. Part 2. Antimicrobial activity, blood absorption ability, and biocompatibility (2014)

Chitosan (CS), a polysaccharide derived from chitin, the second most abundant polysaccharide, is widely used in the medical world because of its natural and nontoxic properties and its innate ability for antibacterial and hemostasis effects. In this study, the novel composites containing CS and cellulose (CEL) (i.e., [CEL + CS]), which we have previously synthesized using a green and totally recyclable method, were investigated for their antimicrobial activity, absorption of anticoagulated whole blood, anti-inflammatory activity through the reduction of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the biocompatibility with human fibroblasts. The [CEL + CS] composites were found to inhibit the growth of both Gram positive and negative micro-organisms. For examples, the regenerated 100% lyophilized chitosan material was found to reduce growth of Escherichia coli (ATCC 8739 and vancomycin resistant Enterococcus faecalis (ATCC 51299) by 78, 36, and 64%, respectively. The composites are nontoxic to fibroblasts; that is, fibroblasts, which are critical to the formation of connective tissue matrix were found to grow and proliferate in the presence of the composites. They effectively absorb blood, and at the same rate and volume as commercially available wound dressings. The composites, in both air-dried and lyophilized forms, significantly inhibit the production of TNF-α and IL-6 by stimulated macrophages. These results clearly indicate that the biodegradable, biocompatible and nontoxic [CEL + CS] composites, particularly those dried by lyophilizing, can be effectively used as a material in wound dressings.
Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group. (1991)

Thus, preoperative aspirin is associated with increased bleeding complications and offers no additional benefit in early vein graft patency compared with starting aspirin therapy 6 hours after operation. There was a trend, although not significant, toward improved early patency for Y grafts and internal mammary artery grafts with preoperative aspirin.
S-Adenosylmethionine and the Mechanism of Hydrogen Transfer in the Lysine 2,3-Aminomutase Reaction (1987)

Many enzymatic reactions involve chemical transformations that cannot be brought about by the catalytic actions of the functional groups in amino acids. The enzymes catalyzing these reactions exhibit extended catalytic capabilities by virtue of the actions of coenzymes or other cofactors, which lend specific and, in many cases, reasonably well-understood physicochemical properties to the catalytic process.
Electroporation-Enhanced Nonviral Gene Transfer for the Prevention or Treatment of Immunological, Endocrine and Neoplastic Diseases (2006)

Nonviral gene transfer is markedly enhanced by the application of in vivo electroporation (also denoted electro-gene transfer or electrokinetic enhancement). This approach is safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. In this review, we address the principles of electroporation and demonstrate its effectiveness in disease models. Electroporation has been shown to be equally applicable to small and large animals (rodents, dogs, pigs, other farm animals and primates), and this addresses one of the major problems in gene therapy, that of scalability to humans. Gene transfer can be optimized and tissue injury minimized by the selection of appropriate electrical parameters. We and others have applied this approach in preclinical autoimmune and/or inflammatory diseases to deliver either cytokines, anti-inflammatory agents or immunoregulatory molecules. Electroporation is also effective for the intratumoral delivery of therapeutic vectors. It strongly boost DNA vaccination against infectious agents (e.g., hepatitis B virus, human immunodeficiency virus-1) or tumor antigens (e.g., HER-2/neu, carcinoembryonic antigen). In addition, we found that electroporation-enhanced DNA vaccination against islet-cell antigens ameliorated autoimmune diabetes. One of the most likely future applications, however, may be in intramuscular gene transfer for systemic delivery of either endocrine hormones (e.g., growth hormone releasing hormone and leptin), hematopoietic factors (e.g., erythropoietin, GM-CSF), antibodies, enzymes, or numerous other protein drugs. In vivo electroporation has been performed in humans, and it seems likely it could be applied clinically for nonviral gene therapy.
Scalable security and accounting services for content-based publish/subscribe systems (2005)

Content-based publish/subscribe systems offer an interaction scheme that is appropriate for a variety of large scale dynamic applications. However, widespread use of these systems is hindered by a lack of suitable security services. In this paper we present scalable solutions for confidentiality, integrity, and authentication for these systems. We also provide usage-based accounting services, which are required for e-commerce and e-business applications that use publish/subscribe systems. Our solutions are applicable in a setting where publishers and subscribers may not trust the publish/subscribe infrastructure.
The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells (2000)

Transport of lactate and other monocarboxylates in mammalian cells is mediated by a family of transporters, designated monocarboxylate transporters (MCTs). The MCT4 member of this family has recently been identified as the major isoform of white muscle cells, mediating lactate efflux out of glycolytically active myocytes [Wilson, Jackson, Heddle, Price, Pilegaard, Juel, Bonen, Montgomery, Hutter and Halestrap (1998) J. Biol. Chem. 273, 15920-15926]. To analyse the functional properties of this transporter, rat MCT4 was expressed in Xenopus laevis oocytes and transport activity was monitored by flux measurements with radioactive tracers and by changes of the cytosolic pH using pH-sensitive microelectrodes. Similar to other members of this family, monocarboxylate transport via MCT4 is accompanied by the transport of H(+) across the plasma membrane. Uptake of lactate strongly increased with decreasing extracellular pH, which resulted from a concomitant drop in the K(m) value. MCT4 could be distinguished from the other isoforms mainly in two respects. First, MCT4 is a low-affinity MCT: for L-lactate K(m) values of 17+/-3 mM (pH-electrode) and 34+/-5 mM (flux measurements with L-[U-(14)C]lactate) were determined. Secondly, lactate is the preferred substrate of MCT4. K(m) values of other monocarboxylates were either similar to the K(m) value for lactate (pyruvate, 2-oxoisohexanoate, 2-oxoisopentanoate, acetoacetate) or displayed much lower affinity for the transporter (beta-hydroxybutyrate and short-chain fatty acids). Under physiological conditions, rat MCT will therefore preferentially transport lactate. Monocarboxylate transport via MCT4 could be competitively inhibited by alpha-cyano-4-hydroxycinnamate, phloretin and partly by 4, 4'-di-isothiocyanostilbene-2,2'-disulphonic acid. Similar to MCT1, monocarboxylate transport via MCT4 was sensitive to inhibition by the thiol reagent p-chloromercuribenzoesulphonic acid.
Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents (2008)

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant hematological disease characterized by the expansion of hematopoietic stem cells (HSCs) and progeny mature cells, whose surfaces lack all the proteins linked through the glycosyl-phosphatidyl inositol anchor. This defect arises from an acquired somatic mutation in the X-linked phosphatidylinositol glycan class A gene, with subsequent clonal expansion of the mutated HSCs as a result of a concomitant, likely immune-mediated, selective pressure. The disease is characterized by complement-mediated chronic intravascular hemolysis, resulting in hemolytic anemia and hemosiderinuria; capricious exacerbations lead to recurrent gross hemoglobinuria. Additional cardinal manifestations of PNH are a variable degree of bone marrow failure and an intrinsic propensity to thromboembolic events. The disease is markedly invalidating, with chronic symptoms requiring supportive therapy - usually including periodical transfusions; possible life-threatening complications may also ensue. The biology of PNH has been progressively elucidated in the past few years, but therapeutic strategies remained unsatisfactory for decades, the only exception being stem cell transplantation, which is restricted to selected patients and retains significant morbidity and mortality. Recently, a biological agent to treat PNH has been developed - the terminal complement inhibitor eculizumab - which has been tested in a number of clinical trials, with exciting results. All the data from worldwide clinical trials confirm that eculizumab radically modifies the symptoms, the biology, and the natural history of PNH, strongly improving the quality of life of PNH patients.
Yeast Activity, Gas Production (2009)

Cereals & Grains Association is a nonprofit organization dedicated to advancing the knowledge and understanding of cereal grain science through research leadership, education, superior technical service, and advocacy.
One-Pot Synthesis of Carbon Nanofibers from CO2 (2015)

Carbon nanofibers, CNFs, due to their superior strength, conductivity, flexibility, and durability have great potential as a material resource but still have limited use due to the cost intensive complexities of their synthesis. Herein, we report the high-yield and scalable electrolytic conversion of atmospheric CO2 dissolved in molten carbonates into CNFs. It is demonstrated that the conversion of CO2 → CCNF + O2 can be driven by efficient solar, as well as conventional, energy at inexpensive steel or nickel electrodes. The structure is tuned by controlling the electrolysis conditions, such as the addition of trace transition metals to act as CNF nucleation sites, the addition of zinc as an initiator and the control of current density. A less expensive source of CNFs will facilitate its adoption as a societal resource, and using carbon dioxide as a reactant to generate a value added product such as CNFs provides impetus to consume this greenhouse gas to mitigate climate change.
Phase I trial of novel kinesin spindle protein (KSP) inhibitor SB-715992 IV Q 21 days (2004)

2078 Background: The mitotic kinesin KSP plays an exclusive and essential role in assembly and function of the mitotic spindle. KSP represents a novel target for development of therapeutics against cancer. SB-715992 is a unique and selective inhibitor of KSP, that is preferentially overexpressed in malignant cells, functions exclusively in mitosis, and is not expressed in terminally differentiated neurons. In pre-clinical studies in a broad range of human tumor xenografts, doses of SB-715992 below the MTD produced tumor regression and cures. Methods: A phase I study was conducted to determine the MTD, safety, and PK profile of SB-715992 Q 21 d IV.Results: 42 patients (pts) (M/F 31/11) with solid tumors were treated at doses of 1 to 21 mg/m2. Median age 61 years (range 37–85). Common tumor types included CRC (15), RCC (5) sarcoma (4), and lung (4). 2 pts developed DLT at 21 mg/m2 consisting of Grade (Gr) 4 neutropenia ≥ 5 days (1 pt) and Gr 4 neutropenic fever (1 pt). The 18 mg/m2dose level was expanded as a recommended phase II dose; 12 pts (18 cycles of safety data) have been treated. 2 DLTs have been observed at this dose level consisting of Gr 4 neutropenia ≥ 5 d; non-dose limiting Gr 3 or 4 neutropenia and Gr 4 leukopenia occurred in 7 (58%) and 1 (8%) pts. Neutropenic nadir occurred on day 8 and lasted 2–4 d. Common ≥ Gr 2 drug related toxicities at ≥ 6 mg/m2 included fatigue, leukopenia, and anemia. SD was observed for 5–11 cycles in 4 pts with CRC, HCC, SCCHN, & RCC. Increases in AUC0-∞and Cmax were dose-related. For the 18 mg/m2 dose level in Cycle 1, median PK values (n=6) were Cmax = 473 ng/mL; AUC0-∞= 5074 ng.h/mL; t1/2 = 33 hrs; CL = 6656 mL/hr; and Vss = 236 L. Monopolar mitotic spindles were observed in a tumor biopsy from a pt w/ SCCHN at 16 mg/m2.Conclusion: Based on the toxicities noted, 18 mg/m2 Q 21 d IV, which has been demonstrated to induce relevant biological effects in vivo, is recommended for phase II investigations. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytokinetics, Inc.