gebhart/patrepeval huggingface dataset:
Sulfasalazine for brain cancer fits (2012)

Recent research has identified an important role for a cystine-glutamate antiporter (system Xc) in the biology of malignant brain tumors. This transporter is effectively inhibited by sulfasalazine, a drug widely used to treat a number of chronic inflammatory conditions such as Crohn's disease. Preclinical data show that sulfasalazine is an effective inhibitor of tumor growth and tumor-associated seizures. These studies suggest that the cystine-glutamate antiporter is a valuable drug target for which tumor-specific drugs can be generated. In the meantime, sulfasalazine may be considered as adjuvant treatment for malignant gliomas.
Discovery of High Potency, Single-Chain Insulin Analogs with a Shortened B-Chain and Nonpeptide Linker (2013)

A series of novel, single chain insulin analogs containing polyethylene glycol based connecting segments were synthesized by native chemical ligation and tested for biological activity. While the full length single chain insulin analogs exhibited low potency, deletion of amino acids B26-B30 unexpectedly generated markedly higher activity. This observation is unprecedented in all previous studies of single chain insulin analogs and is consistent with the presumption that in the native hormone this sequence must translocate to achieve high potency insulin receptor interaction. Optimization of the sequence yielded an insulin analog with potency and selectivity comparable to that of native insulin. These results establish a basis for discovery of novel higher potency, single chain insulin analogs of shortened length.
Strategic Service Pricing and Yield Management (1999)

The authors investigate pricing strategies based on yield management systems (YMS), such as early discounting, overbooking, and limiting early sales, for capacity-constrained services. They find that YMS work best when price-insensitive customers prefer to buy later than price-sensitive consumers. The authors also identify other conditions favoring the use of YMS.
Demonstration of a Genetic Factor Influencing Spontaneous Release of a Xenotropic Virus of Mouse Cells (1974)

There is increasing evidence that mouse cells of different strains contain different numbers and biologic classes of naturally-integrated type-C RNA viruses. The present studies have examined the cellular regulation of one class of virus, xenotropic in host range, which is common to mice of NIH Swiss and NZB strains. This virus is spontaneously released at high level by NZB embryo cells but its production by NIH Swiss embryo cells is below detectable levels. Quantitative analysis of the chronic level of virus release by embryo cell lines established in tissue culture from genetic crosses of NIH and NZB strains has demonstrated the existence of a partially dominant gene influencing virus release. Evidence is presented indicating that this gene may act to provide a factor necessary for expression of a specific class of endogenous virus.
Adjuvant Cationic Liposomes Presenting MPL and IL-12 Induce Cell Death, Suppress Tumor Growth, and Alter the Cellular Phenotype of Tumors in a Murine Model of Breast Cancer (2014)

Dendritic cells (DC) process and present antigens to T lymphocytes, inducing potent immune responses when encountered in association with activating signals, such as pathogen-associated molecular patterns. Using the 4T1 murine model of breast cancer, cationic liposomes containing monophosphoryl lipid A (MPL) and interleukin (IL)-12 were administered by intratumoral injection. Combination multivalent presentation of the Toll-like receptor-4 ligand MPL and cytotoxic 1,2-dioleoyl-3-trmethylammonium-propane lipids induced cell death, decreased cellular proliferation, and increased serum levels of IL-1β and tumor necrosis factor (TNF)-α. The addition of recombinant IL-12 further suppressed tumor growth and increased expression of IL-1β, TNF-α, and interferon-γ. IL-12 also increased the percentage of cytolytic T cells, DC, and F4/80(+) macrophages in the tumor. While single agent therapy elevated levels of nitric oxide synthase 3-fold above basal levels in the tumor, combination therapy with MPL cationic liposomes and IL-12 stimulated a 7-fold increase, supporting the observed cell cycle arrest (loss of Ki-67 expression) and apoptosis (TUNEL positive). In mice bearing dual tumors, the growth of distal, untreated tumors mirrored that of liposome-treated tumors, supporting the presence of a systemic immune response.
An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs (2013)

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.
GCN5-Related N-Acetyltransferases: A Structural Overview (2000)

Hundreds of acetyltransferases exist. All use a common acetyl donor--acetyl coenzyme A--and each exhibits remarkable specificity for acetyl acceptors, which include small molecules and proteins. Analysis of the primary sequences of these enzymes indicates that they can be sorted into several superfamilies. This review covers the three-dimensional structures of members of one of these superfamilies, now referred to in the literature as the GCN5-related N-acetyltransferases (GNAT), reflecting the importance of one functional category, the histone acetyltransferases. Despite the diversity of substrate specificities, members of the GNAT superfamily demonstrate remarkable similarity in protein topology and mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic mechanism.
On the orthogonal transformation used for structural comparisons (1989)

Rotation matrices that minimize or maximize the sum of the squared distances between corresponding atoms for two structures are found using a constrained least-squares procedure solved analytically as an eigenvalue problem in quaternion parameters.
Interleukin-15 and Its Receptor Augment Dendritic Cell Vaccination against theneuOncogene through the Induction of Antibodies Partially Independent of CD4 Help (2010)

Interleukin-15 (IL-15) stimulates the diffrentiation and proliferation of T, B, and natural killer cells; enhances CD8(+) cytolytic T-ceII activity; helps maintain CD44(hi)CD8(+) memory T cells; and stimulates immunoglobulin synthesis by B cells. IL-15 is trans-presented to effector cells by its receptor, IL-15Ralpha, expressed on dendritic cells (DC) and monocytes. We examined the antitumor effect of adenoviral-mediated gene transfer of IL-15 and IL-15Ralpha to augment a DC vaccine directed against the NEU (ErbB2) oncoprotein. Transgenic BALB-neuT mice vaccinated in late-stage tumor development with a DC vaccine expressing a truncated NEU antigen, IL-I5, and its receptor (DC(Ad.Neu+Ad_mIL-15+Ad.mlL-15Ralpha)) were protected from mammary carcinomas, with 70% of animals tumor-free at 30 weeks compared with none of the animals vaccinated with NEU alone (DC(Ad.Neu)). The combination of neu, IL-15, and IL-15Ralpha gene transfer leads to a significaintly greater anti-NEU antibody response compared with mice treated with DC(Ad.Neu) or DC(Ad.Neu) combined with either IL-15 (DC(Ad.Neu+Ad.mlL-15)) or lL-15Ralpha (DC(Ad.Neu+Ad.mlL-15Ralpha)). The antitumor effect was antibody mediated and involved modulation of NEU expression and signaIing. Depletion of CD4(+) cells did not abrogate the antitumor effect of the vaccine, nor did it inhibit the induction of anti-NEU aritibodies. Coexpression of IL-15 and IL-15Ralpha in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4(+) T-helper function.
The Development of Downdrift Erosion: an Update of Paper in JCR, Vol. 11(4) (2001)

Leeside-erosion is the terminology for the adverse effect on shore stability occurring on the downdrift side of a littoral drift barrier. Paper by BRUUN titled The Development of Downdrift Erosion published by the Journal of Coastal Research, vol. 14(4), 1995, explains that leeside erosion may have a short-range as well as a long-range effect, the latter being caused by the former. Between the two effects one may in some cases find an area of relatively less erosion making it protruding somewhat from the adjoining shorelines. In this paper more examples are given. It is concluded that the only fully reliable answer to the extent of the leeside erosion downdrift can only be obtained by qualitative research which will probably reveal that the leeside effect extends further down drift than indicated by shoreline developments on the downdrift side.
Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications (2014)

The rate of transcription elongation plays an important role in the timing of expression of full-length transcripts as well as in the regulation of alternative splicing. In this study, we coupled Bru-seq technology with 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) to estimate the elongation rates of over 2000 individual genes in human cells. This technique, BruDRB-seq, revealed gene-specific differences in elongation rates with a median rate of around 1.5 kb/min. We found that genes with rapid elongation rates showed higher densities of H3K79me2 and H4K20me1 histone marks compared to slower elongating genes. Furthermore, high elongation rates had a positive correlation with gene length, low complexity DNA sequence, and distance from the nearest active transcription unit. Features that negatively correlated with elongation rate included the density of exons, long terminal repeats, GC content of the gene, and DNA methylation density in the bodies of genes. Our results suggest that some static gene features influence transcription elongation rates and that cells may alter elongation rates by epigenetic regulation. The BruDRB-seq technique offers new opportunities to interrogate mechanisms of regulation of transcription elongation.
Expression and characterization of Edg‐1 receptors in rat cardiomyocytes (2000)

Recent evidence indicates that sphingolipids are produced by the heart during hypoxic stress and by blood platelets during thrombus formation. It is therefore possible that sphingolipids may influence heart cell function by interacting with G-protein-coupled receptors of the Edg family. In the present study, it was found that sphingosine 1-phosphate (Sph1P), the prototypical ligand for Edg receptors, produced calcium overload in rat cardiomyocytes. The cDNA for Edg-1 was cloned from rat cardiomyocytes and, when transfected in an antisense orientation, effectively blocked Edg-1 protein expression and reduced the Sph1P-mediated calcium deregulation. Taken together, these results demonstrate that cardiomyocytes express an extracellular lipid-sensitive receptorsystem that can respond to sphingolipid mediators. Because the major source of Sph1P is from blood platelets, we speculate that Edg-mediated Sph1P negative inotropic and cardiotoxic effects may play important roles in acute myocardial ischemia where Sph1P levels are probably elevated in response to thrombus.
High Q-factor CMOS-MEMS inductor (2008)

This study investigates a high Q-factor spiral inductor fabricated by the CMOS (complementary metal oxide semiconductor) process and a post-process. The spiral inductor is manufactured on silicon substrate using the 0.35 mum CMOS process. In order to reduce the substrate loss and enhance the Q-factor of the inductor, silicon substrate under the inductor is removed using a post-process. The post-process uses RIE (reactive ion etching) to etch the sacrificial layer of silicon dioxide, and then TMAH (tetra methyl ammonium hydroxide) is employed to remove the underlying silicon substrate and obtain the suspended spiral inductor. The advantage of the post process is compatible with the CMOS process. The Agilent 8510 C network analyzer and a Cascade probe station are used to measure the performances of the spiral inductor. Experiments indicate that the spiral inductor has a Q-factor of 15 at 11 GHz, an inductance of 4 nH at 25.5 GHz and a self-resonance frequency of about 27 GHz.
Transient Ischemic Attacks in Patients With Atrial Fibrillation (2004)

Atrial fibrillation patients with TIA have a lower long-term risk of subsequent stroke than those with prior stroke, but their stroke risk during aspirin therapy is still high. For atrial fibrillation patients with either type of cerebral ischemia, recent or remote, secondary prevention with adjusted-dose warfarin instead of aspirin results in substantial absolute reductions in ischemic stroke.
Development and Use of IgM/J‐Chain Fusion Proteins for Characterization of Immunoglobulin Superfamily Ligand‐Receptor Interactions (2014)

Discovery of binding partners for immunoglobulin molecules expressed by cells of the immune system is an important topic of current research. However, many ligand-receptor interactions are of low affinity, and hence detection is refractory to most established protocols. We evaluated fusion proteins based on human IgM as high avidity probes to screen for ligand-receptor binding. We describe methods for cloning, expression, and quantification of IgM fusion proteins with J-chain. Furthermore, we outline protocols to assess binding of IgM fusion proteins to cells and to plate-bound proteins. Compared to standard IgG-fusion proteins, IgM + J chain increased binding of a test interaction, PD-L1 to PD-1, up to 1000-fold.
Comparison of the Anesthetic Effects of Oral Transmucosal Versus Injectable Medetomidine in Combination with Tiletamine-Zolazepam for Immobilization of Chimpanzees (Pan troglodytes) (2010)

Seventeen adult chimpanzees (Pan troglodytes) with an average age of 37 yr were immobilized with a combination of tiletamine-zolazepam (TZ) and medetomidine (MED) by one of two modes of delivery. Group A animals received the drug combination intramuscularly at 3 mg/kg and 0.05 mg/kg, respectively. Animals in group B received MED by oral transmucosal administration, meaning oral delivery with presumptive transmucosal absorption. MED at 0.1 mg/kg was mixed with marshmallow crème, and delivery was followed by 3 mg/kg of TZ intramuscularly. Chimpanzees from both groups were recovered after administration of atipamezole at 0.3 mg/kg intramuscularly. All chimpanzees were compliant with oral transmucosal drug administration, although two chimpanzees preferred oral MED mixed with applesauce. All animals exhibited some anxiety and excitatory behavior associated with darting, but this was reduced in group B, which was premedicated with oral transmucosal MED. The mean time from TZ administration to sedation sufficient for human contact was 16.4 and 14.7 min with and without oral transmucosal premedication, respectively. The mean time for recovery for those chimpanzees given oral transmucosal premedication was 13.8 min, which was significantly shorter than the time of recovery for the group not given oral premedication (P = 0.02). Oral transmucosal administration of MED provided light sedation in 16 of 17 chimpanzees to the level of arousable recumbency and a heavier sedation in one chimpanzee with no adverse side effects. TZ combined with MED by either oral transmucosal or injectable administration provided safe, heavy, long sedation with rapid, smooth, uneventful recoveries.
A few simple points about customary law and our legal system (2012)

The Tuhonohono gathering, held at Hopuhopu on the great awa Waikato of such importance to the Kingitanga and the Tainui tribes, brought together many knowledgeable participants to consider its central theme of customary law. It may be of some small use, therefore, if at the outset I try to discuss a few simple points about the place of customary law in our legal system, such as it is at the present time. Some of the points are dealt with more fully in the Introduction to Te Matapunenga: A Compendium of References to the Concepts and Institutions of Maori Customary Law, a draft of which was made available to participants and which, it is anticipated, will be published formally soon after this record of the Symposium proceedings.
Differential keratin gene expression in developing, differentiating, preneoplastic, and neoplastic mouse mammary epithelium. (1990)

Two keratins whose expression has been associated with proliferation (K14) and hyperproliferation (K6) in mouse epithelia were detected in normal, preneoplastic, and neoplastic mouse mammary tissues. K6 and K14 keratins were independently expressed in distinct epithelial cell populations in developing mammary anlage. K6 was confined to a small number of mammary epithelial cells associated with the growing end buds and among the proximal luminal epithelium, whereas K14 expression appeared in basally located fusiform cells that correspond to the location of mammary myoepithelial cells. This pattern was maintained in mature glands and through full functional differentiation with the exception that K6-positive cells were only rarely detectable. During lobuloalveolar growth in early pregnancy, K6 and K6/K14 coexpressing cells were observed among the luminal and suprabasal cells in the expanding lobular epithelium. This K6/K14 coexpressing epithelial subset persisted throughout pregnancy, lactation, and involution, albeit in much smaller numbers than observed in early pregnancy. Two patterns of K6 and K14 expression in preneoplastic and neoplastic lesions of mouse mammary glands were induced by various carcinogenic stimuli. In one, increased numbers of K6- or K14-positive cells were present in distinct cellular populations; in the other, coexpression of K6/K14 was found in a large subpopulation of both preneoplastic and neoplastic mammary epithelium. These observations suggest that expression of K6 and K14 keratins in the mouse mammary gland is associated with growth and expansion of specific mammary epithelial cell populations, and as such these keratins may be useful probes with which to identify mammary epithelium-specific primordial cells. In agreement with this possibility, K6/K14 expression was demonstrated within a distinct subset of morphologically distinct luminal mammary epithelial cells that have been reported to possess kinetic properties in vitro consistent with those expected of latent mammogenic stem cells.
bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. (1994)

Neutrophils, the most common inflammatory leukocytes, have the most limited life span of all blood cells. After they undergo apoptosis, they are recognized and engulfed by macrophages. bcl-2, a proto-oncogene rearranged and deregulated in B cell lymphomas bearing the t(14;18) translocation, is known to inhibit programmed death. bcl-2 expression is localized in early myeloid cells of the bone marrow but is absent in mature neutrophils. Transgenic mice that expressed bcl-2 in mature neutrophils showed that bcl-2 blocked neutrophil apoptosis. Despite this, homeostasis of neutrophil population is essentially unaffected. In fact, macrophage uptake of neutrophils expressing bcl-2 still occurred. This transgenic model indicates that the mechanism that triggers phagocytosis of aging neutrophils operates independently of the process of apoptosis regulated by bcl-2.
Liposomes, a Potential Immunoadjuvant and Carrier for a Cryptococcal Vaccine (1998)

Mice immunized with a cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund's adjuvant (CFA) develop an anticryptococcal cell-mediated immune response (CMI). CMI is detected by delayed-type hypersensitivity (DTH) reactions and by enhanced clearance of Cryptococcus neoformans from infected tissues. The objective of this research was to evaluate anticryptococcal DTH reactivity and clearance of cryptococci from groups of mice immunized with CneF encapsulated into liposomes (CneF-liposome) and compare the results to results from mice immunized with CneF-CFA. CBA/J mice were injected subcutaneously with vaccines or control formulations (saline-liposome or saline-CFA). Six days later the mice were footpad tested to assess their DTH response to CneF or the animals were challenged intravenously with 10(5) viable C. neoformans to determine clearance of infection. Clearance was evaluated 7 days later by enumeration of cryptococcal colony forming units (CFU) in lungs, spleens, livers, and brains of the infected mice. The CneF-liposome formulation induced a positive anticryptococcal DTH response and elicited increased clearance of C. neoformans from tissues as compared to mice treated with saline-liposome. Even though the CneF-liposome preparation did not induce as strong of a DTH response or as much protection as did CneF-CFA, our results indicate that liposomes are promising carriers for immunization with cryptococcal antigen and that such immunization can provide some protection to subsequent infection with C. neoformans.
off-State Degradation in Drain-Extended NMOS Transistors: Interface Damage and Correlation to Dielectric Breakdown (2007)

Off-state degradation in drain-extended NMOS transistors is studied. Carefully designed experiments and well-calibrated simulations show that hot carriers, which are generated by impact ionization of surface band-to-band tunneling current, are responsible for interface damage during off-state stress. Classical on-state hot carrier degradation has historically been associated with broken equivSi-H bonds at the interface. In contrast, the off-state degradation in drain-extended devices is shown to be due to broken equivSi-O- bonds. The resultant degradation is universal, which enables a long-term extrapolation of device degradation at operating bias conditions based on short-term stress data. Time evolution of degradation due to broken equivSi-O- bonds and the resultant universal behavior is explained by a bond-dispersion model. Finally, we show that, under off-state stress conditions, the interface damage that is measured by charge-pumping technique is correlated with dielectric breakdown time, as both of them are driven by broken equivSi-O- bonds.