gebhart/patrepeval huggingface dataset:
Development of Potent and Selective Inhibitors of Aldo–Keto Reductase 1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase) Based onN-Phenyl-Aminobenzoates and Their Structure–Activity Relationships (2012)

Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.
Biosynthesis of tritium, deuterium and carbon‐13 labeled cycloheximide (1980)

Abstract Tritium, deuterium, and carbon‐13 labeled cycloheximide were prepared through fermentation of Streptomyces griseus in the presence of S‐methyl labeled L‐methionine. Cycloheximide‐ 3 H of specific activity 4.96 mCi/mg (1.40 Ci/mmol) was obtained in 25% overall radiochemical yield. Nuclear magnetic resonance and mass spectral analyses of the deuterium and carbon‐13 labeled products showed that isotope incorporation occurred virtually exclusively in the two methyl groups in cycloheximide, with negligible (&lt;5%) incorporation in the rest of the molecule. Furthermore, deuterated species contained either three or six deuterium atoms, indicating that the methyl groups were transferred intact from L‐methionine. Also, the two methyl groups in cycloheximide were of equal isotope enrichment. The overall enrichment achieved in the methyl groups was 55% and 45%, respectively, in the deuterium and carbon‐13 labeled compounds.
High Frequencies of Fertilization and Haploid Seedling Production in Crosses Between Commercial Hexaploid Wheat Varieties and Maize (1991)

Abstract Nineteen commercial hexaploid wheat varieties were crossed with the maize F 1 hybrid ‘Seneca 60’. Fertilization frequencies ranged from 32.1 % to 47.5 % of pollinated florets (mean 39.5 %) in the 14 winter wheat varieties and from 40.7 % to 51.4 % (mean 47.8 %) in the five spring wheat varieties. In some cases only an endosperm was formed and the frequencies of embryo formation were therefore slightly lower, being 28.2 % to 45.9 % (mean 36.4 %) for winter wheats and 39.8 % to 48.6 % (mean 45.1 %) for spring wheats. Mean values were significantly higher in the spring wheats but no significant variation was found between varieties within the spring or winter categories. In the five spring wheats the mean yield of embryos, and hence the potential yield of haploid plants, was 3.4‐fold higher than with the tetraploid Hordeum bulbosum clone PB179. For the 14 winter wheats the figure was 10.9‐fold higher. These differences were highly significant (p &lt; 0.001) in all varieties. A single 2,4‐D treatment given to spikes one day after pollination with maize enabled embryos to be recovered from all 19 varieties. A total of 311 embryos were recovered from 950 florets (an average of 7.3 embryos per spike) of which 191 germinated, giving an average yield of one haploid plant for every 5.0 florets pollinated (4.4 haploid plants per spike).
EPIC: Ending Piracy of Integrated Circuits (2008)

As semiconductor manufacturing requires greater capital investments, the use of contract foundries has grown dramatically, increasing exposure to mask theft and unauthorized excess production. While only recently studied, IC piracy has now become a major challenge for the electronics and defense industries. We propose a novel comprehensive technique to end piracy of integrated circuits (EPIC). It requires that every chip be activated with an external key, which can only be generated by the holder of IP rights, and cannot be duplicated. EPIC is based on (i) automatically-generated chip IDs, (ii) a novel combinational locking algorithm, and (Hi) innovative use of public-key cryptography. Our evaluation suggests that the overhead of EPIC on circuit delay and power is negligible, and the standard flows for verification and test do not require change. In fact, major required components have already been integrated into several chips in production. We also use formal methods to evaluate combinational locking and computational attacks. A comprehensive protocol analysis concludes that EPIC is surprisingly resistant to various piracy attempts.
Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis (2015)

To establish the individualized treatment of patients with colorectal cancer, factors associated with chemotherapeutic effects should be identified. However, to the best of our knowledge, few studies are available on this topic, although it is known that the prognosis of patients and sensitivity to chemotherapy depend on the location of the tumor and that the tumor location is important for individualized treatment. In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Large-scale population analysis was performed to determine the association of gene expression with the clinicopathological features, in particular, the location of the colorectal cancer. From the results of our analysis of the mRNA expression of these 10 genes, we noted the strongest correlation between DPYD and TYMP, followed by TYMS and DHFR. The location of the colorectal cancer was classified into 4 regions (the right‑ and left-sided colon, rectosigmoid and rectum) and was compared with gene expression. A significant difference in all genes, apart from VEGF, was noted. Of the remaining 9 genes, the highest expression of TYMS and DPYD was observed in the right‑sided colon; the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was approximately equivalent in the right-sided colon and rectum, and higher than that in other locations. The data generated from this study may prove to be useful for the development of individualized chemotherapeutic treatments for patients with colorectal cancer, and will mean that the tumor location is taken into account.
Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy (2009)

We theoretically show that the shot-noise-limited sensitivity of stimulated Raman scattering (SRS) microscopy, which enables high-contrast vibrational imaging, is similar to that of coherent anti-Stokes Raman scattering microscopy. We experimentally confirm that the sensitivity of our SRS microscope is lower than the shot-noise limit only by <15 dB, which indicates that the high-sensitivity of SRS microscopy is readily available.
Variable Resistance to Palivizumab in Cotton Rats by Respiratory Syncytial Virus Mutants (2004)

Both in vitro and in vivo, individual RSV PZ escape mutants varied in their susceptibility to PZ. Mutations associated with resistance to PZ did not always result in failure of PZ prophylaxis.
Fasting proinsulin concentrations predict the development of type 2 diabetes. (1999)

Fasting 32,33 split proinsulin independently predicts the development of diabetes. This prediction was better than that observed for either the insulin or intact proinsulin concentrations. The combination of family history, fasting glucose, and total proinsulin identified a subgroup of individuals at high risk of progression who might benefit from targeted interventions.
Fungal metabolites of sorbic acid (1990)

A number of fungal detoxification reactions of sorbic acid have been reviewed. These include decarboxylation to give trans-1,3-pentadiene, esterification to give ethyl sorbate, reduction to give 4-hexenol and 4-hexenoic acid. It was shown that seven Penicillium species could convert sorbic acid into 1,3-pentadiene whilst P. bilaii, P. fellutanum and P. glabrum did not. However, most Eurotium species were unable to bring about this conversion. Considerable differences in the resistance of two isolates of P. crustosum to sorbic acid were found. An isolate from coconut was more resistant than one isolated from hazelnuts. Both sorbic acid and caproic acid (hexanoic) brought about disorganization of the mitochondrial membranes in P. crustosum. It is suggested that these lipophilic acids inhibit growth by interfering with the electrochemical membrane potential across the mitochondrial membranes.
Further Study of Factors Affecting the Metabolic Clearance Rate of Testosterone in Man1 (1968)

A study of the effect of various factors on the metabolic clearance rate of testosterone (MCRT) is presented. Change from the supine to the erect position resulted in a sharp fall in the MCRT in one subject, with little or no significant change in 3 additional subjects. In one of the latter group, however, there subsequently occurred a significant increase in the MCRT upon changing from the erect to the supine position. Acute increases in the plasma concentration of testosterone in normal menstruating women and in a bilaterally adrenalectomized castrated woman were not associated with any appreciable change in the MCRT until a plasma level of testosterone exceeding 1.2 μg/100 ml was reached. In a normal and a hypogonadal male, an acute increase in the circulating level of testosterone produced a moderate increase in the MCRT. The increase, however, was considerably smaller than that found after chronic administration of the steroid. The decrease in the plasma concentration of testosterone following intramuscular injection of testosterone propionate was not accompanied by a proportionate fall in the MCRT. This suggests that, in addition to the possible role of testosterone binding, induction of testosterone catabolizing enzymes is involved in regulating the plasma clearance of the steroid. Sequential measurements of the MCRT in the same subjects (5 normal men and 1 normal woman) at various intervals were within 10% of the base line values. Moreover, the mean percentage change for the entire group was –1.6%. This demonstrates the temporal constancy of the clearance measurement. There was no significant difference in the MCRT measured in plasma and whole blood in male or female subjects. This suggests that the red blood cells did not take up any appreciable quantities of the labeled hormone during the period of the experiment. The measurement of the MCRT in an additional group of normal men and women again demonstrates the sex difference in the plasma clearance of the steroid, the values in men being approximately twice those found in women. The sex-related difference persisted when the MCRT was corrected for body surface area (m2). However, when the MCRT/m2 was divided by the log of the plasma production rate of testosterone, this difference disappeared. This suggests that the MCRT is a direct function of the production rate of the steroid. The basal plasma production rates of testosterone in these subjects were 5.78±1.42 (sd) mg/day in the men and 0.29±0.07 (sd) mg/day in the women. Combining these values with our previous reported data gives over-all means for 18 normal men and 14 normal women of 6.23 ± 1.73 (sd) and 0.32 ±0.10 (sd) mg/day, respectively.
Understanding the management of client perceived response time (2006)

Understanding and managing the response time of web services is of key importance as dependence on the World Wide Web continues to grow. We present Remote Latency-based Management (RLM), a novel server-side approach for managing pageview response times as perceived by remote clients, in real-time. RLM passively monitors server-side network traffic, accurately tracks the progress of page downloads and their response times in real-time, and dynamically adapts connection setup behavior and web page content as needed to meet response time goals. To manage client perceived pageview response times, RLM builds a novel event node model to guide the use of several techniques for manipulating the packet traffic in and out of a web server complex, including fast SYN and SYN/ACK retransmission, and embedded object removal and rewrite. RLM operates as a stand-alone appliance that simply sits in front of a web server complex, without any changes to existing web clients, servers, or applications. We have implemented RLM on an inexpensive, commodity, Linux-based PC and present experimental results that demonstrate its effectiveness in managing client perceived pageview response times on transactional e-commerce web workloads.
Caste in Africa? (1977)

Opening Paragraph Eminent Indologists have stated that it is inappropriate to use the word ‘caste’ in non-Hindu contexts. Despite such warnings numerous Africanists have used the term, with varying degrees of imprecision. In this paper I first outline different emphases which have appeared in the literature concerning caste in India; then discuss several examples of hierarchical systems in Africa which have been described as ‘caste’. Finally, I focus upon my own fieldwork data concerning the Dime of South-West Ethiopia, amongst whom there operates a system which can, I believe, be unequivocally labelled caste.
The lipids of an auxutrophic avirulent mutant ofCoccidioides immitis (1973)

Cells of a mouse-virulent Coccidioides immitis wild type, strain RS, and a mouse-avirulent induced mutant strain of RS, strain 95, were analyzed to characterize and compare the lipid content of mycelium and arthrospores. The arthrospores of strain RS contained 18% more total lipid, 15% more free lipid and 39% more bound lipid than arthrospores of strain 95 and the free lipid fraction contained 30% C-18:1 in contrast to the arthrospores of strain 95 which contained 79% C-18:1. The only significant variation between the lipids of the mycelial growth exhibited by strains RS and 95 was 33% more anteiso C-21 in some fractions of the free lipid of strain 95. The mycelium of the wild type organism, strain RS, contained 11·6% free lipid and 0·86% bound lipid. Phosphatidyl choline 21%, phosphatidyl ethanolamine 17%, sterol 26% and cariolipin 13% together constituted 95% of the total mycelial strain RS free lipid phospholipid fraction. The major mycelial fatty acids were C-16, 26·2%; C-18, 12·2%; C-18:1, 31·7% and C-18:2, 6·1%. These 4 fatty acids accounted for 76·2% of the free lipid present in strain RS cells. Bound lipids presented essentially the same total lipid, lipid class, phospholipid and fatty acid profile as the free lipids.
Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human monoclonal antibody SC-1: first clinical and histopathological results. (1998)

In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In seven cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in five patients a significant regression of tumor mass could be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients.
Stimulation of P-Glycoprotein ATPase by Analogues of Tetramethylrosamine:  Coupling of Drug Binding at the “R” Site to the ATP Hydrolysis Transition State (2006)

The multidrug resistance efflux pump P-glycoprotein (Pgp) couples drug export to ATP binding and hydrolysis. Details regarding drug trajectory, as well as the molecular basis for coupling, remain unknown. Nearly all drugs exported by Pgp have been assayed for competitive behavior with rhodamine123 transport at a canonical "R" drug binding site. Tetramethylrosamine (TMR) displays a relatively high affinity for Pgp when compared to other rhodamines. Here, we present the construction and characterization of a library of compounds based upon the TMR scaffold and use this set to assess the determinants of drug binding to the "R" site of Pgp. This set contained modifications in (1) the number, location, and conformational mobility of hydrogen-bond acceptors; (2) the heteroatom in the xanthylium core; and (3) the size of the substituent in the 9-position of the xanthylium core. Relative specificity for coupling to the distal ATP catalytic site was assessed by ATPase stimulation. We found marked ( approximately 1000-fold) variation in the ATPase specificity constant within the library of TMR analogues. Using established methods involving ADP-Vi trapping by wild-type Pgp and ATP binding by catalytic carboxylate mutant Pgp, these effects can be extended to ATP hydrolysis transition-state stabilization and ATP occlusion at a single site. These data support the idea that drugs trigger the engagement of ATP catalytic site residues necessary for hydrolysis. Further, the nature of the drug binding site and coupling mechanism may be dissected by variation of a drug-like scaffold. These studies may facilitate development of novel competitive inhibitors at the "R" drug site.
Construction of a recombinant adenovirus for efficient delivery of the I-Scel yeast endonuclease to human cells and its application in the in vivo cleavage of chromosomes to expose new potential telomeres (1999)

We have constructed a replication-defective adenovirus vector encoding the yeast I-SceI endonuclease under the control of the murine cytomegalovirus immediate-early gene promoter (AdMSceI) for efficient delivery of this enzyme to mammalian cells. We present evidence of AdMSceI-mediated I-SceI protein expression and cleavage activity in replicationpermissive 293 cells, and of cleavage of chromosomes in vivo in both 293 cells and in non-permissive human cells. We have exploited this system for the generation of chromosomes capped by artificial telomeric sequences in cells with integrated plasmids containing telomeric DNA arrays adjacent to an I-SceI recognition site. The properties of the AdMSceI virus described here make it a useful tool for studying biological processes involving induction of DNA breaks, recombination and gene targeting in cells grown in culture and in vivo.
Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors (2004)

A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (MMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.
Small-size, polarisation-independent phased-arraydemultiplexers on InP (1995)

Polarisation independent 1 × 4 and 1 × 16 phased-array wavelength demultiplexers are demonstrated using 1.1 µm quaternary ridge waveguides. The 1 × 16 device exhibits an average crosstalk of 14 dB for 2 nm channel spacing and 1.6 × 1.7 mm2 device size (with output guides), which is the smallest size reported to date. Moreover, zero birefringence is obtained at ~1.53 µm.
Buscando Identidad a través de Medios Masivos (2014)

During the latter half of the twentieth century, many Latin American authors experimented with innovative techniques and creative narrative methods that challenged the reader and attempted to comment on the current events of the time. This “New Literature” had several unifying characteristics, one of which is the use of mass media to comment on the theme of identity. Using several books from this Latin American post-Boom movement, this paper aims to show the use of communication tools – movies, biographies, radio, and photographs – to illustrate the struggle and search for characters’ real identities as a major recurrent theme. In all of the mentioned works, characters’ identities are revealed and affected by these forms of communication, and while these mass media are presented as objective and representative of the truth, they are ultimately shown to be prone to exploitation and made subjective.
Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis (2017)

Combination therapies that depend on checkpoint inhibitor antibodies (Abs) such as for PD-1 or its ligand (PD-L1) together with immune stimulatory agonist Abs like anti-OX40 are being tested in the clinic to achieve improved antitumor effects. Here, we studied the potential therapeutic and immune effects of one such combination: Ab to PD-1 with agonist Ab to OX40/vaccine. We tested the antitumor effects of different treatment sequencing of this combination. We report that simultaneous addition of anti-PD-1 to anti-OX40 negated the antitumor effects of OX40 Ab. Antigen-specific CD8<sup>+</sup> T-cell infiltration into the tumor was diminished, the resultant antitumor response weakened, and survival reduced. Although we observed an increase in IFNγ-producing E7-specifc CD8<sup>+</sup> T cells in the spleens of mice treated with the combination of PD-1 blockade with anti-OX40/vaccine, these cells underwent apoptosis both in the periphery and the tumor. These results indicate that anti-PD-1 added at the initiation of therapy exhibits a detrimental effect on the positive outcome of anti-OX40 agonist Ab. These findings have important implications on the design of combination immunotherapy for cancer, demonstrating the need to test treatment combination and sequencing before moving to the clinic. <i>Cancer Immunol Res; 5(9); 755-66. ©2017 AACR</i>.