gebhart/patrepeval huggingface dataset:
Limitations of current medical therapies for the treatment of heart failure. (2003)

The medical treatment of heart failure has evolved over the past 40 years, from the primary use of diuretics and digitalis in the 1960s to the use of inotropic agents and vasodilators in the 1970s. More recently, the focus has been on the neurohormonal system, specifically the renin-angiotensin-aldosterone system and the sympathetic nervous system. Drugs that inhibit or block these systems (eg, angiotensin-converting enzyme inhibitors and beta-blocking drugs) are the primary agents recommended in recent heart failure guidelines. However, the actual percent reduction in mortality associated with the use of these agents has been relatively modest. This article will review the results and limitations of medical therapy for heart failure. Our understanding of the pathogenesis of heart failure may be incomplete, and alternative strategies, including mechanical devices, may play an increasing role in the treatment of heart failure in the future.
Prioritization of EGFR/IGF-IR/VEGFR2 combination targeted therapies utilizing cancer models. (2009)

Targeting VEGFR2 + EGFR was prioritized over other treatment strategies utilizing EGFR, IGF-IR and VEGFR2 antibodies. The criteria that proved to be valuable were a non-overlapping spectrum of anticancer activity and the prevention of resistance to another therapy in the combination.
Health‐related quality of life in narcolepsy (2001)

Narcolepsy is a chronic sleep disorder characterised by symptoms of excessive daytime sleepiness and cataplexy. The aim of this study was to describe the health-related quality of life of people with narcolepsy residing in the UK. The study comprised a postal survey of 500 members of the UK narcolepsy patient association, which included amongst other questions the UK Short Form 36 (SF-36), the Beck Depression Inventory (BDI), and the Ullanlinna Narcolepsy Scale (UNS). A total of 305 questionnaires were included in the final analysis. The results showed that the subjects had significantly lower median scores on all eight domains of the SF-36 than normative data, and scored particularly poorly for the domains of role physical, energy/vitality, and social functioning. The BDI indicated that 56.9% of subjects had some degree of depression. In addition, many individuals described limitations on their education, home, work and social life caused by their symptoms. There was little difference between the groups receiving different types of medication. This study is the largest of its type in the UK, although the limitations of using a sample from a patient association have been recognised. The results are consistent with studies of narcolepsy in other countries in demonstrating the extensive impact of this disorder on health-related quality of life.
Defining the sequence-recognition profile of DNA-binding molecules (2006)

Determining the sequence-recognition properties of DNA-binding proteins and small molecules remains a major challenge. To address this need, we have developed a high-throughput approach that provides a comprehensive profile of the binding properties of DNA-binding molecules. The approach is based on displaying every permutation of a duplex DNA sequence (up to 10 positional variants) on a microfabricated array. The entire sequence space is interrogated simultaneously, and the affinity of a DNA-binding molecule for every sequence is obtained in a rapid, unbiased, and unsupervised manner. Using this platform, we have determined the full molecular recognition profile of an engineered small molecule and a eukaryotic transcription factor. The approach also yielded unique insights into the altered sequence-recognition landscapes as a result of cooperative assembly of DNA-binding molecules in a ternary complex. Solution studies strongly corroborated the sequence preferences identified by the array analysis.
Hooked Trichomes: A Physical Plant Barrier to a Major Agricultural Pest (1976)

Hooked epidermal appendages (trichomes) on leaves of field bean cultivars effectively capture nymph and adult leafhoppers. Frequency of capture and capture mortality are highly correlated with trichome density. Hooked trichomes inserted at angles less than 30 degrees are ineffective in capture.
Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity. (1989)

We have isolated a 725-bp full-length cDNA clone for the human eosinophil cationic protein (ECP). ECP is a small, basic protein found in the matrix of the eosinophil's large specific granule that has cytotoxic, helminthotoxic, and ribonuclease activity, and is a member of the ribonuclease multigene family. The cDNA sequence shows 89% sequence identity with that reported for the related granule protein, eosinophil-derived neurotoxin (EDN). The open reading frame encodes a previously unidentified 27-amino acid leader sequence preceding a 133-residue mature ECP polypeptide with a molecular mass of 15.6 kD. The encoded amino acid sequence of ECP shows 66% identity to that of EDN and 31% identity to that of human pancreatic ribonuclease, including conservation of the essential structural cysteine and cataytic lysine and histidine residues. mRNA for ECP was detected in eosinophil-enriched peripheral granulocytes and in a subclone of the promyelocytic leukemia line, HL-60, induced toward eosinophilic differentiation with IL-5. No ECP mRNA was detected in uninduced HL-60 cells, or in HL-60 cells induced toward monocytic differentiation with vitamin D3 or toward neutrophilic differentiation with DMSO. In contrast, mRNA for EDN was detected in uninduced HL-60 cells and was upregulated in HL-60 cells induced with DMSO. Despite similarities in sequence and cellular localization, these results suggest that ECP and EDN are subject to different regulatory mechanisms.
Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens:  Synthesis, in Vitro Biological Activity, Pharmacokinetics, and Antitumor Activity in the LAPC4 Human Prostate Cancer Xenograft Model (2005)

New chemical entities, steroidal C-17 benzoazoles (5, 6, 9 and 10) and pyrazines (14 and 15) were rationally designed and synthesized. The key reaction for synthesis of the benzoazoles involved the nucleophilic vinylic "addition-elimination" substitution reaction of 3beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and benzoazole nucleophiles, while that for synthesis of pyrazines involved palladium-catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3beta-ol (13) with tributylstannyl diazines. Some of the compounds were shown to be potent inhibitors of human CYP17 enzyme as well as potent antagonist of both wild type and mutant androgen receptors (AR). The most potent CYP17 inhibitors were 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (5, code named VN/124-1), 3beta-hydroxy-17-(5(1)-pyrimidyl)androsta-5,16-diene (15) and 17-(1H-benzimidazole-1-yl)androsta-4,16-dien-3-one (6), with IC(50) values of 300, 500 and 915 nM, respectively. Compounds 5, 6, 14 and 15 were effective at preventing binding of (3)H-R1881 (methyltrienolone, a stable synthetic androgen) to both the mutant LNCaP AR and the wild-type AR, but with a 2.2- to 5-fold higher binding efficiency to the latter. Compounds 5 and 6 were also shown to be potent pure AR antagonists. The cell growth studies showed that 5 and 6 inhibit the growth of DHT-stimulated LNCaP and LAPC4 prostate cancer cells with IC(50) values in the low micromolar range (i.e., <10 microM). Their inhibitory potencies were comparable to that of casodex but remarkably superior to that of flutamide. The pharmacokinetics of compounds 5 and 6 in mice were investigated. Following s.c. administration of 50 mg/kg of 5 and 6, peak plasma levels of 16.82 and 5.15 ng/mL, respectively, occurred after 30 to 60 min, both compounds were cleared rapidly from plasma (terminal half-lives of 44.17 and 39.93 min, respectively), and neither was detectable at 8 h. Remarkably, compound 5 was rapidly converted into a metabolite tentatively identified as 17-(1H-benzimidazol-1-yl)androsta-3-one. When tested in vivo, 5 proved to be very effective at inhibiting the growth of androgen-dependent LAPC4 human prostate tumor xenograft, while 6 was ineffective. Compound 5 (50 mg/kg/twice daily) resulted in a 93.8% reduction (P = 0.00065) in the mean final tumor volume compared with controls, and it was also significantly more effective than castration. To our knowledge, this is the first example of an antihormonal agent (an inhibitor of androgen synthesis (CYP17 inhibitor)/antiandrogen) that is significantly more effective than castration in suppression of androgen-dependent prostate tumor growth. In view of these impressive anticancer properties, compound 5 is a strong candidate for development for the treatment of human prostate cancer.
Dual Conditional Cross-Entropy Filtering of Noisy Parallel Corpora (2018)

In this work we introduce dual conditional cross-entropy filtering for noisy parallel data. For each sentence pair of the noisy parallel corpus we compute cross-entropy scores according to two inverse translation models trained on clean data. We penalize divergent crossentropies and weigh the penalty by the crossentropy average of both models. Sorting or thresholding according to these scores results in better subsets of parallel data. We achieve higher BLEU scores with models trained on parallel data filtered only from Paracrawl than with models trained on clean WMT data. We further evaluate our method in the context of the WMT2018 shared task on parallel corpus filtering and achieve the overall highest ranking scores of the shared task, scoring top in three out of four subtasks.
Skin Manifestations of Food Allergy (2003)

The pediatrician is faced with evaluating a panoply of skin rashes, a subset of which may be induced by food allergy. Acute urticaria is a common manifestation of an allergic skin response to food, but food is rarely a cause of chronic urticaria. Approximately one third of infants/children with moderate to severe atopic dermatitis have food allergy. Although diagnosis of acute urticaria provoked by a food may be evident from a straightforward history and confirmed by diagnostic tests to detect food-specific IgE antibody, determination of the role of food allergy in patients with atopic dermatitis is more difficult and may require additional diagnostic maneuvers, including elimination diets and oral food challenges. The immunopathologic basis of food-allergic disorders that affect the skin and a rational approach to diagnosis and treatment are discussed. Additional disorders that are caused by or mimic ones caused by food allergy are reviewed.
Application of Penta-Di-Methyl-Amino-Tantalum to a Tantalum Source in Chemical Vapor Deposition of Tantalum Oxide Films (1991)

Penta-di-methyl-amino-tantalum (Ta[N(CH 3 ) 2 ] 5 ), a new source chemical of Ta in TaO chemical vapor deposition (CVD), has been studied. TG and DTA measurements show that Ta[N(CH 3 ) 2 ] 5 is chemically stable up to about 150°C and vaporizes at a temperature of 80°C. TaO films were deposited by LP-CVD at temperatures of 380∼520°C, by using the new chemical Ta[N(CH 3 ) 2 ] 5 and O 2 . The deposition rate of TaO with Ta[N(CH 3 ) 2 ] 5 is higher than that with Ta(OC 2 H 5 ) 5 , a conventional Ta source. The TaO CVD using Ta[N(CH 3 ) 2 ] 5 and O 2 yields a good step coverage. Although the as-deposited TaO films are oxygen poor in film composition, annealing in an oxidizing ambient improves the stoichiometry and reduces the leakage current.
Bridging the Gap between Preclinical and Clinical Microbicide Trials: Blind Evaluation of Candidate Gels in Murine Models of Efficacy and Safety (2011)

CS prevented genital herpes when present at the time of viral challenge, but increased the rate of infection when gel was applied daily for 7 days with a vaginal wash prior to viral inoculation. The findings presumably reflect altered epithelial architecture, which may have contributed to the trend towards increased HIV observed clinically.
Accumulation of lipid production in Chlorella minutissima by triacylglycerol biosynthesis-related genes cloned from Saccharomyces cerevisiae and Yarrowia lipolytica (2012)

Discovery of an alternative fuel is now an urgent matter because of the impending issue of oil depletion. Lipids synthesized in algal cells called triacylglycerols (TAGs) are thought to be of the most value as a potential biofuel source because they can use transesterification to manufacture biodiesel. Biodiesel is deemed as a good solution to overcoming the problem of oil depletion since it is capable of providing good performance similar to that of petroleum. Expression of several genomic sequences, including glycerol-3-phosphate dehydrogenase, glycerol-3-phosphate acyltransferase, lysophosphatidic acid acyltransferase, phosphatidic acid phosphatase, diacylglycerol acyltransferase, and phospholipid:diacylglycerol acyltransferase, can be useful for manipulating metabolic pathways for biofuel production. In this study, we found this approach indeed increased the storage lipid content of C. minutissima UTEX 2219 up to 2-fold over that of wild type. Thus, we conclude this approach can be used with the biodiesel production platform of C. minutissima UTEX 2219 for high lipid production that will, in turn, enhance productivity.
The effect of high and low frequency electroacupuncture in pain after lower abdominal surgery (2002)

In the present study, we examined the effects of preoperative electroacupuncture (EA) at classical bilateral acupuncture points (Zusanli, also known as ST-36) on postoperative pain and opioid-related side effects. One hundred healthy consenting women undergoing lower abdominal surgery were randomly assigned to four treatment regimens: Group I (n=25), control; Group II (n=25), sham-EA (needle insertion without electrical stimulation); Group III (n=25), low-EA (2 Hz of electrical stimulation); and Group IV (n=25), high-EA (100 Hz of electrical stimulation). EA groups received needle insertion with or without electrical stimulation 20 min prior to anesthesia. All patients received patient-controlled analgesia (PCA) of morphine postoperation. Postoperative pain was evaluated by recording (1). the time of the first required analgesic, (2). the number of PCA demands, (3). the total amount of morphine required by PCA, and (4) patients' VAS pain score. We found that the time of first analgesic requested was 10, 18, 28, and 28 min in the control, sham-, low-, and high-EA groups, respectively. During the first 24h, the total amount of morphine required was decreased by 21, 43 and 61% in the sham-, low- and high-EA groups, respectively. The incidence of nausea and dizziness during the first 24h after surgery was significantly reduced in both the low-EA and high-EA groups compared with the control and sham-EA groups. We also found that sham-EA exerts a beneficial effect with respect to its pain relieving quality but not the side effect profiles. Our findings demonstrates that preoperative treatment with low-EA and high-EA can reduce postoperative analgesic requirements and associated side effects in patients undergoing lower abdominal surgery.
5,6-Diaryl-2,3-dihydroimidazo[2,1-b]thiazoles: a new class of immunoregulatory antiinflammatory agents (1985)

A series of substituted 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazoles were synthesized and evaluated in the rat adjuvant-induced arthritis and mouse oxazolone-induced contact sensitivity assays to determine the potential of these compounds for use as immunoregulatory antiinflammatory agents. This class of compounds was derived by combining salient structural features of the antiinflammatory agent flumizole and the immunoregulatory drug levamisole. Unlike the latter two, a number of compounds in the target series were found to possess the desired combination of activities. Exploration of structure-activity relationships in the adjuvant-induced arthritic rat assay revealed that optimal potency was exhibited by symmetrically substituted 5,6-diaryl compounds having one of the following alkyl heteroatom or halogen functions at the para position: methoxy, ethoxy, methylthio, N-ethyl-N-methylamino, fluoro, or chloro. Scrambling of these two substituent classes to yield the asymmetrically substituted 5,6-diaryl compounds resulted in potent activity only with the 5-alkyl heteroatom, 6-halo-substituted regioisomers. However in the oxazolone-induced contact sensitivity assay, no consistent relationship of variation in activity with structural change was apparent. The initial target compound 5,6-bis(4-methoxyphenyl)-2,3-dihydroimidazo[2,1-b]thiazole (1) was compared with its progenitors in additional models of inflammation and immunoregulation.
Peripheral MR angiography with variable velocity encoding. Work in progress. (1992)

An electrocardiographically triggered two-dimensional phase-contrast (PC) magnetic resonance angiographic pulse sequence was developed in which velocity encoding (VENC) was varied throughout an acquisition in response to changes in blood velocity during the cardiac cycle. This was done to better capture signal in the peripheral vasculature, where pulsatile flow degrades images. After reconstruction, a matched filter addition technique was applied to the cardiac phase images to obtain a single high-quality static image. Images were obtained of six healthy volunteers--with and without varying VENC--and contrast-to-noise ratio (C/N) calculations were performed for the added images. Varying VENC significantly improved vascular signal from small and large vessels (P less than .02), but it was most helpful for small vessels, for which the C/N increased by as much as 260% (average increase, 149%). These preliminary findings suggest that variable VENC can enhance the signal from the small and large peripheral blood vessels in cardiac-gated PC acquisitions.
Linear transmit processing in MIMO communications systems (2005)

We examine and compare the different types of linear transmit processing for multiple input, multiple output systems, where we assume that the receive filter is independent of the transmit filter contrary to the joint optimization of transmit and receive filters. We can identify three filter types similar to receive processing: the transmit matched filter, the transmit zero-forcing filter, and the transmit Wiener filter. We show that the transmit filters are based on similar optimizations as the respective receive filters with an additional constraint for the transmit power. Moreover, the transmit Wiener filter has similar convergence properties as the receive Wiener filter, i.e., it converges to the matched filter and the zero-forcing filter for low and high signal-to-noise ratio, respectively. We give closed-form solutions for all transmit filters and present the fundamental result that their mean-square errors are equal to the errors of the respective receive filters, if the information symbols and the additive noise are uncorrelated. However, our simulations reveal that the bit-error ratio results of the transmit filters differ from the results for the respective receive filters.
ANTIGENIC STUDIES OF CANDIDA (1961)

Hasenclever, H. F. (U. S. Public Health Service, Bethesda, Md.), William O. Mitchell, and Joseph Loewe. Antigenic studies of Candida. II. Antigenic relation of Candida albicans group A and group B to Candida stellatoidea and Candida tropicalis. J. Bacteriol. 82:574-577. 1961.-Previous work in our laboratory has shown the presence of two antigenic groups within the species Candida albicans. These groups have been designated as groups A and B. Subsequent studies have been conducted to show the antigenic relationship of these groups with Candida stellatoidea and Candida tropicalis. Antisera to two strains each of C. albicans group A, C. albicans group B, C. stellatoidea, and C. tropicalis were used in this investigation. Individual suspensions from each of nine strains of C. stellatoidea and from ten strains each of the other groups and species were used to test the agglutinative properties of unadsorbed and adsorbed antisera. Separate samples of antisera to each immunizing strain were reciprocally cross adsorbed with the other immunizing strains and tested for agglutination. The results indicated that C. albicans group A and C. tropicalis were antigenically identical and C. albicans group B and C. stellatoidea were antigenically indistinguishable.
Strictly non-blocking N×N thermo-capillarity optical matrix switch using silica-based waveguide (2002)

We propose a silica-based strictly non-blocking N/spl times/N thermo-capiliarity optical matrix switch. The feasibility of 2-dimensional batch oil injection and multilayered wiring were confirmed by type 16/spl times/16 optical matrix switch.
A Neoplastic Gene Fusion Mimics Trans-Splicing of RNAs in Normal Human Cells (2008)

Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5' exons of the JAZF1 gene on chromosome 7p15 to 3' exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti-apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans-splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gene products normally generated by trans-splicing of RNAs in developing tissues.
Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo (2016)

Twenty-nine novel indole-chalcone derivatives were synthesized and evaluated for antiproliferative activity. Among them, 14k exhibited most potent activity, with IC50 values of 3-9 nM against six cancer cells, which displayed a 3.8-8.7-fold increase in activity when compare with compound 2. Further investigation revealed 14k was a novel tubulin polymerization inhibitor binding to the colchicine site. Its low cytotoxicity toward normal human cells and nearly equally potent activity against drug-resistant cells revealed the possibility for cancer therapy. Cellular mechanism studies elucidated 14k arrests cell cycle at G2/M phase and induces apoptosis along with the decrease of mitochondrial membrane potential. Furthermore, good metabolic stability of 14k was observed in mouse liver microsomes. Importantly, 14k and its phosphate salt 14k-P inhibited tumor growth in xenograft models in vivo without apparent toxicity, which was better than the reference compound CA-4P and 2. In summary, 14k deserves consideration for cancer therapy.