gebhart/patrepeval huggingface dataset:
Sialylation enhancement of CTLA4‐Ig fusion protein in Chinese hamster ovary cells by dexamethasone (2010)

The importance of glycoprotein sialic acid levels is well known, as increased levels have been shown to increase in vivo serum half-life profiles. Here we demonstrate for the first time that dexamethasone (DEX) was capable of improving the sialylation of a CTLA4-Ig fusion protein produced by Chinese hamster ovary (CHO) cells. DEX was shown to enhance the intracellular addition of sialic acid by sialyltransferases as well as reduce extracellular removal of sialic acid by sialidase cleavage. We illustrated that DEX addition resulted in increased expression of the glycosyltransferases alpha2,3-sialyltransferase (alpha2,3-ST) and beta1,4-galactosyltransferase (beta1,4-GT) in CHO cells. Based upon our previous results showing DEX addition increased culture cell viability, we confirmed here that cultures treated with DEX also resulted in decreased sialidase activity. Addition of the glucocorticoid receptor (GR) antagonist mifepristone (RU-486) was capable of blocking the increase in sialylation by DEX which further supports that DEX affected sialylation as well as provides evidence that the sialylation enhancement effects of DEX on recombinant CHO cells occurred through the GR. Finally, the effects of DEX on increasing sialylation were then confirmed in 5-L controlled bioreactors. Addition of 1 microM DEX to the bioreactors on day 2 resulted in harvests with average increases of 16.2% for total sialic acid content and 15.8% in the protein fraction with N-linked sialylation. DEX was found to be a simple and effective method for increasing sialylation of this CTLA4-Ig fusion protein expressed in CHO cells.
Translational Repression of MCL-1 Couples Stress-induced eIF2α Phosphorylation to Mitochondrial Apoptosis Initiation (2007)

The integrated stress response (ISR) integrates a broad range of environmental and endogenous stress signals to the phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2 alpha). Although intense or prolonged activation of this pathway is known to induce apoptosis, the molecular mechanisms coupling stress-induced eIF2 alpha phosphorylation to the cell death machinery have remained incompletely understood. In this study, we characterized apoptosis initiation in response to classical activators of the ISR (tunicamycin, UVC, elevated osmotic pressure, arsenite). We found that all applied stress stimuli activated a mitochondrial pathway of apoptosis initiation. Rapid and selective down-regulation of the anti-apoptotic BCL-2 family protein MCL-1 preceded the activation of BAX, BAK, and caspases. Stabilization of MCL-1 blocked apoptosis initiation, while cells with reduced MCL-1 protein content were strongly sensitized to stress-induced apoptosis. Stress-induced elimination of MCL-1 occurred with unchanged protein turnover and independently of MCL-1 mRNA levels. In contrast, stress-induced phosphorylation of eIF2 alpha at Ser(51) was both essential and sufficient for the down-regulation of MCL-1 protein in stressed cells. These findings indicate that stress-induced phosphorylation of eIF2 alpha is directly coupled to mitochondrial apoptosis regulation via translational repression of MCL-1. Down-regulation of MCL-1 enables but not enforces apoptosis initiation in stressed cells.
Properties of GaN tunneling MIS light-emitting diodes (1978)

MIS structures on GaN consisting of Au-NaI-GaN or Au-Al2O3-GaN with insulator thickness &amp;lt;100 Å have been fabricated with the aim of producing light-emitting diodes with emission in the uv and blue spectral region at low bias. I-V characteristics are consistent with a tunneling carrier transport mechanism, and light emission typically occurs for voltages 2–3 V. The spectral behavior of electroluminescence (EL) is in good agreement with photoluminescence (PL) data in the uv and blue spectral region. Suggestions for further work to improve radiant power output from such devices are presented.
Public Outreach Report: Templeton Planning and Design Studies Fall 2012 (2013)

This Public Outreach Report provides a summary of community outreach efforts done as part of the process to develop a community shared vision for the future development of Templeton. This planning effort was conducted as a class project by fourth year students in the City and Regional Planning Department at California Polytechnic State University over a five months period during the academic year of 2012-2013.
Ethyl Octylphosphonofluoridate and Analogs: Optimized Inhibitors of Neuropathy Target Esterase (1995)

The relation between organophosphorus-induced delayed neuropathy (OPIDN) and brain neuropathy target esterase (NTE) inhibition is further examined in hens by structure-activity studies leading to the most potent in vitro NTE inhibitors known, which are then examined for their neuropathic effects in vivo in hens. The principal compounds studied are alkyl alkylphosphonofluoridates and dialkyl phosphorofluoridates. Potencies that exceed those of any previous inhibitors under the standard in vitro NTE assay condition are achieved with alkyl octylphosphonofluoridates (ethyl, isopropyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, and 3-iodopropyl), 2-iodoethyl hexylphosphonofluoridate, and dialkyl phosphorofluoridates [ethyl, nonyl; di(2-iodoethyl); di(3-iodopropyl); dipentyl]. The concentration for 50% NTE inhibition (I50) of these compounds is 0.04-0.14 nM. Thirty-eight less active analogs including aryl phosphonates and aryl phosphates give I50s of 0.27-4730 nM. For highest potency the summation of length of the alkyl and alkoxy groups on phosphorus should be 12-16 atoms (carbons, oxygens, and phosphorus) (a terminal iodo substituent in this relationship is equivalent to a propyl group). In general, the phosphonofluoridates and phosphorofluoridates are more active than analogs with leaving groups other than fluorine, i.e., phenoxy, 4-nitrophenoxy, 4-cyanophenoxy, 3,4-dichlorophenoxy, and 4H-1,3,2-benzodioxaphosphorin. Considering the exceptional potencies of ethyl and 2-iodoethyl octylphosphonofluoridates (I50s of 0.04 and 0.09 nM, respectively), it is not surprising that at ip doses of 10-30 mg/kg they inhibit brain NTE by 82-97% 48 h after treatment. However, unexpectedly, only the ethyl but not the 2-iodoethyl compound induces OPIDN, possibly associated with the greater ease of aging for NTE inhibited with the ethyl than the 2-iodoethyl compound (as observed in vitro both spontaneously and on induction by potassium fluoride). The high potency of ethyl octylphosphonofluoridate and several analogs as NTE inhibitors suggests that they are useful probes in determining the toxicological features of this secondary lesion for organophosphorus poisoning.
Conformational Behavior of Grafted Weak Polyelectrolyte Chains: Effects of Counterion Condensation and Nonelectrostatic Anion Adsorption (2011)

Poly[(2-dimethylamino)ethyl methacrylate] (PDEM) is completely charged, partially charged, and uncharged at pH 4, 7, and 10, respectively. We have investigated the salt effects on the conformational change of PDEM chains grafted on a surface at different pH by using quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance (SPR). The changes in frequency (Δf) and dissipation (ΔD) in QCM-D measurements demonstrate that the conformational behavior is governed by counterion condensation at pH 4 and 7 but by nonelectrostatic anion adsorption at pH 10. The addition of Na(2)SO(4) induces more collapse of the grafted layer than that of NaClO(3) at pH 4 and 7. However, they have a similar effect at pH 10. The shift of resonance unit (ΔRU) in SPR measurements reflects the changes of layer thickness and layer refractive index. At pH 4, ΔRU decreases with ionic strength in the presence of Na(2)SO(4), indicating the decrease of layer thickness or the chain collapse. However, ΔRU exhibits a minimum as the ionic strength increases in the case of NaClO(3). This is because the effects of the layer thickness and refractive index are dominant in the low and high ionic strength regimes, respectively. At pH 7, ΔRU slightly varies with ionic strength in the case of either Na(2)SO(4) or NaClO(3), indicating that the effects of the layer thickness and refractive index are comparable during the layer collapse. At pH 10, the shift in ΔRU suggests that the nonelectrostatic anion adsorption governs the conformational behavior of the PDEM chains.
Oxyrase, a method which avoids CO2 in the incubation atmosphere for anaerobic susceptibility testing of antibiotics affected by CO2 (1993)

The Oxyrase agar dilution method, with exclusion of CO2 from the environment, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibility of 51 gram-negative and 43 gram-positive anaerobes to azithromycin and erythromycin. With the Oxyrase method, anaerobiosis was achieved by incorporation of the O2-binding enzyme Oxyrase in addition to susceptibility test medium, antibiotic, and enzyme substrates into the upper level of a biplate. Plates were covered with a Brewer lid and incubated in ambient air. With azithromycin, Oxyrase yielded an MIC for 50% of strains tested (MIC50) and MIC90 of 2.0 and 8.0 micrograms/ml, compared to 8.0 and > 32.0 micrograms/ml in standard anaerobic conditions. At a breakpoint of 8.0 micrograms/ml, 90.4% of strains were susceptible to azithromycin with Oxyrase, compared to 53.2% in the chamber. The corresponding erythromycin MIC50 and MIC90 were 1.0 and 8.0 micrograms/ml with Oxyrase, compared to 4.0 and > 32.0 micrograms/ml by the reference method, with 89.3% of strains susceptible at a breakpoint of 4 micrograms/ml with Oxyrase, compared to 60.6% in CO2. Exclusion of CO2 from the anaerobic atmosphere when testing for susceptibility to azalides and macrolides yielded lower MICs, which may lead to a reconsideration of the role played by these compounds in treatment of infections caused by these strains.
Total Synthesis of the Potent Androgen Receptor Antagonist (−)-Arabilin: A Strategic, Biomimetic [1,7]-Hydrogen Shift (2011)

The first total synthesis of (-)-arabilin, a Streptomyces metabolite that inhibits hormone activation of the androgen receptor, has been completed. The key step, a [1,7]-hydrogen shift, establishes the enol ether-containing skipped-tetraene substructure. This nonenzymatic pericyclic reaction is considered to be biomimetic.
Image-to-Image Translation with Conditional Adversarial Networks (2017)

We investigate conditional adversarial networks as a general-purpose solution to image-to-image translation problems. These networks not only learn the mapping from input image to output image, but also learn a loss function to train this mapping. This makes it possible to apply the same generic approach to problems that traditionally would require very different loss formulations. We demonstrate that this approach is effective at synthesizing photos from label maps, reconstructing objects from edge maps, and colorizing images, among other tasks. Moreover, since the release of the pi×2pi× software associated with this paper, hundreds of twitter users have posted their own artistic experiments using our system. As a community, we no longer hand-engineer our mapping functions, and this work suggests we can achieve reasonable results without handengineering our loss functions either.
Virtualizing the VAX architecture (1991)

This paper describes modifications to the VAX architecture to support virtual machines. The VAX architecture contains several instructions that are sensitive but not privileged. It is also the first architecture with more than two protection rings to support virtual machines. A technique for mapping four virtual rings onto three physical rings, employing both software and microcode, is described. Differences between the modified and standard VAX architectures are presented. along with a description of the virtual VAX computer.
Enthalpy (ΔH) and Entropy (ΔS) for π-Stacking Interactions in Near-Sandwich Configurations:  Relative Importance of Electrostatic, Dispersive, and Charge-Transfer Effects (2007)

Interactions between two aromatic rings with various substituents in a near-sandwich configuration have been quantitatively studied by using the triptycene derived molecular models. This model system allows a stacking arrangement of two arenes to assume a near-perfect face-to-face configuration in its ground state conformation. Comparing to our previous study of the parallel displaced configuration, repulsive interactions are predominant for most arenes currently studied. However, if one arene is strongly electron deficient (Ar2=pentafluorobenzoate), attractive interactions were observed regardless of the character of the other arene (Ar1). For stacking interactions between Me2NC6H4 and C6F5CO groups, a DeltaH of -1.84+/-0.2 kcal/mol and a DeltaS of -2.9+/-0.8 cal/(mol.K) were determined. The general trend in the attractive stacking interaction toward a pentafluorobenzoate is Me2NC6H4>Me3C6H2>Me2C6H3>MeC6H4>MeOC6H4>C6H5>O2NC6H4. The observed trend is consistent with a donor-acceptor relationship and the acceptor is a C6F5CO group.
Synthesis of Highly Functionalized Chiral Nitriles by Radical Fragmentation of β-Hydroxy Azides. Convenient Transformation of Aldononitriles into 1,4- and 1,5-Iminoalditols (2004)

The synthesis of highly functionalized nitriles by an alkoxyl radical fragmentation of cyclic beta-hydroxy azides is described. The alkoxyl radicals were generated by reaction of the alcohols with (diacetoxyiodo)benzene and iodine under mild conditions compatible with the presence of sensitive substituents and the protective groups most frequently used in carbohydrate chemistry. To explore the scope and limitations of this methodology, experiments were carried out using a variety of beta-hydroxy azides of the carbohydrate (1-6, 33, and 41), monoterpenoid (21 and 22), and steroid (23-25) families of natural products. Of special interest are the aldopentonitriles (15-18, 34, and 42) and aldotetrononitriles (19 and 20) synthesized from the corresponding 2-azido-2-deoxycarbohydrates. To demonstrate the versatility of these aldononitriles as chiral synthons, 1,4-imino-1-deoxysugar (37) and 1,5-imino-1-deoxysugar (43) analogues of the polyhydroxypyrrolidine and -piperidine types were prepared.
cDNA-AFLP Reveals a Striking Overlap in Race-Specific Resistance and Wound Response Gene Expression Profiles (2000)

The tomato Cf-9 gene confers resistance to races of the fungal pathogen Cladosporium fulvum expressing the Avr9 gene. cDNA amplified fragment length polymorphism analysis was used to display transcripts whose expression is rapidly altered during the Avr9- and Cf-9-mediated defense response in tobacco cell cultures. Diphenyleneiodonium was used to abolish the production of active oxygen species during gene induction. Of 30,000 fragments inspected, 290 showed altered abundance, of which 263 were induced independently of active oxygen species. cDNA clones were obtained for 13 ACRE (for Avr9/Cf-9 rapidly elicited) genes. ACRE gene induction occurred in the presence of cycloheximide. Avr9 induced ACRE gene expression in leaves. Surprisingly, ACRE genes were also rapidly but transiently induced in leaves in response to other stresses. The amino acid sequences of some ACRE proteins are homologous to sequences of known proteins such as ethylene response element binding protein transcription factors, the N resistance protein, a calcium binding protein, 13-lipoxygenase, and a RING-H2 zinc finger protein. Rapid induction of ACRE genes suggests that they play a pivotal role during plant defense responses.
The proximity and the directional theories of issue voting: Comparative results for the USA and Germany (1997)

Abstract In several recent studies George Rabinowitz and his co–authors challenge the ‘classical’ spatial model of issue voting, the proximity model, by introducing a directional model. In this article we examine whether different measurement of perceived issue positions of candidates or parties leads to diverging judgments about the predictive power of the directional model (which is claimed to be empirically superior), as compared to the proximity model, using data from the USA and Germany. The results demonstrate that the measurement preferred by Rabinowitz et al. tends to bias empirical findings in favour of directional theory. If we use a more plausible operational definition of issue positions of candidates and parties the directional model in both countries fails to turn out superior.
Risks of High-Dose Stimulants in the Treatment of Disorders of Excessive Somnolence: A Case-Control Study (2005)

This study demonstrated a significantly higher occurrence of psychosis, substance misuse, and psychiatric hospitalizations in patients using high-dose stimulants compared to those using standard doses. Tachyarrhythmias and anorexia or weight loss were also more common in this group as compared with controls. Clinicians should be very cautious in prescribing dosages that exceed maximum guidelines.
Chondroitinase-mediated Degradation of Rare 3-O-Sulfated Glucuronic Acid in Functional Oversulfated Chondroitin Sulfate K and E (2007)

Chondroitin sulfate K (CS-K) from king crab cartilage rich in rare 3-O-sulfated glucuronic acid (GlcUA(3S)) displayed neuritogenic activity and affinity toward various growth factors like CS-E from squid cartilage. CS-K-mediated neuritogenesis of mouse hippocampal neurons in culture was abolished by digestion with chondroitinase (CSase) ABC, indicating the possible involvement of GlcUA(3S). However, identification of GlcUA(3S) in CS chains by conventional high performance liquid chromatography has been hampered by its CSase ABC-mediated degradation. To investigate the degradation process, an authentic CS-E tetrasaccharide, Delta4,5HexUA-GalNAc(4S)-GlcUA(3S)-GalNAc(4S), was digested with CSase ABC, and the end product was identified as GalNAc(4S) by electrospray ionization mass spectrometry (ESI-MS). Putative GalNAc(6S) and GalNAc(4S,6S), derived presumably from GlcUA(3S)-GalNAc(6S) and GlcUA(3S)-GalNAc(4S,6S), respectively, were also detected by ESI-MS in the CSase ABC digest of a CS-E oligosaccharide fraction resistant to CSases AC-I and AC-II. Intermediates during the CSase ABC-mediated degradation of Delta4,5HexUA(3S)-GalNAc(4S) to GalNAc(4S) were identified through ESI-MS of a partial CSase ABC digest of a CS-K tetrasaccharide, GlcUA(3S)-GalNAc(4S)-GlcUA(3S)-GalNAc(4S), and the conceivable mechanism behind the degradation of the GlcUA(3S) moiety was elucidated. Although a fucose branch was also identified in CS-K, defucosylated CS-K exhibited greater neuritogenic activity than the native CS-K, excluding the possibility of the involvement of fucose in the activity. Rather, (3S)-containing disaccharides are likely involved. These findings will enable us to detect GlcUA(3S)-containing disaccharides in CS chains to better understand CS-mediated biological processes.
Creatinine elevation in patients receiving amiodarone correlates with serum amiodarone concentration. (1993)

Serum creatinine and drug concentrations were measured at 0, 1, 2, 3, 6, 9 and 12 months in 30 consecutive patients started on amiodarone. In 28 of these patients with no obvious cause for altered renal function, mean serum creatinine increased to 11% above baseline (P < 0.005). Rising creatinine concentrations correlated with amiodarone concentrations (y = 93.9 + 8.6x, r = 0.51, P < 0.0001). When assessing elevation of serum creatinine in a patient receiving amiodarone, physicians should be aware that it may be related to this drug.
Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice. (1991)

Synthesis of erythropoietin, the primary humoral regulator of erythropoiesis, in liver and kidney is inducible by anemia or hypoxia. Analysis of human erythropoietin gene expression in transgenic mice revealed that sequences located 6-14 kilobases 5' to the gene direct expression to the kidney, whereas sequences within the immediate 3'-flanking region control hepatocyte-specific expression. Human erythropoietin transcription initiation sites were differentially utilized in liver and kidney. Inducible transgene expression was precisely targeted to peritubular interstitial cells in the renal cortex that synthesize endogenous mouse erythropoietin. These studies demonstrate that multiple erythropoietin gene regulatory elements control cell-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia.
Tanezumab, a recombinant humanized mAb against nerve growth factor for the treatment of acute and chronic pain. (2010)

Persistent pain represents a major health problem, and most current therapeutic approaches are associated with unwanted effects and unsatisfactory pain relief. Therefore, an urgent need exists to develop more effective drugs that are directed toward new molecular targets. Nerve growth factor (NGF) is involved in pain transduction mechanisms, playing a key role as a master switch in many chronic and inflammatory pain states; the NGF ligand and its receptor TrkA constitute well-validated targets for pain therapy. Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions. In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models. Phase I and II clinical trials in osteoarthritic pain and chronic lower back pain demonstrated good efficacy for the compound, as well as a good safety and tolerability profile. Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system.
Efficiently computing and representing aspect graphs of polyhedral objects (1991)

An efficient algorithm and a data structure for computing and representing the aspect graph of polyhedral objects under orthographic projection are presented. The aspect graph is an approach to representing 3-D objects by a set of 2-D views, for the purpose of object recognition. In this approach the viewpoint space is partitioned into regions such that in each region the qualitative structure of the line drawing does not change. The viewing data of an object is the partition of the viewpoint space together with a representative view in each region. The algorithm computes the viewing data for line drawings of polyhedral objects under orthographic projection.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Insulin and Insulin-like Growth Factor Receptors and Responses (1988)

Insulin is a member of a family of structurally related hormones with diverse physiological functions. The basic structure of these molecules is present even in hormones isolated from invertebrates (Thorpe and Duve 1988). In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. The physiological role of insulin is primarily to regulate rapid anabolic responses, such as glucose uptake into muscle and fat cells (Rosen 1987). IGF-I, on the other hand, appears to be primarily involved in regulating a long-term response, the growth of an organism (Rechler et al. 1987). The physiological role(s) of the third member of this family, IGF-II, is not known.