gebhart/patrepeval huggingface dataset:
Kinetic Characterization of Bifunctional Thymidylate Synthase-Dihydrofolate Reductase (TS-DHFR) from Cryptosporidium hominis (2004)

This study presents a kinetic characterization of the recently crystallized bifunctional thymidylate synthasedihydrofolate reductase (TS-DHFR) enzyme from the apicomplexa parasite, Cryptosporidium hominis. Our study focuses on determination of the C. hominis TS-DHFR kinetic mechanism, substrate channeling behavior, and domain-domain communication. Unexpectedly, the unique mechanistic features of C. hominis TS-DHFR involve the highly conserved TS domain. At 45 s(-) (1), C. hominis TS activity is 10-40-fold faster than other TS enzymes studied and a new kinetic mechanism was required to simulate C. hominis TS behavior. A large accumulation of dihydrofolate produced at TS and a lag in product formation at DHFR were observed. These observations make C. hominis TS-DHFR the first bifunctional TS-DHFR enzyme studied for which there is clear evidence against dihydrofolate substrate channeling. Furthermore, whereas with Leishmania major TS-DHFR there are multiple lines of evidence for domain-domain communication (ligand binding at one active site affecting activity of the other enzyme), no such effects were observed with C. hominis TS-DHFR.
U.S. drinking water challenges in the twenty-first century. (2002)

The access of almost all 270 million U.S. residents to reliable, safe drinking water distinguishes the United States in the twentieth century from that of the nineteenth century. The United States is a relatively water-abundant country with moderate population growth; nonetheless, current trends are sufficient to strain water resources over time, especially on a regional basis. We have examined the areas of public water infrastructure, global climate effects, waterborne disease (including emerging and resurging pathogens), land use, groundwater, surface water, and the U.S. regulatory history and its horizon. These issues are integrally interrelated and cross all levels of public and private jurisdictions. We conclude that U.S. public drinking water supplies will face challenges in these areas in the next century and that solutions to at least some of them will require institutional changes.
Regulation of Claudin-1 Expression Via Activation of Ron Tyrosine Kinase and Transforming Growth Factor-Beta Signaling Pathways in Ovarian Carcinoma (2010)

Epithelial ovarian carcinoma is the most common cause of death among gynecologic malignancies in the United States. In the U.S., more than 21,000 women will be diagnosed with ovarian cancer and about 15,000 women will die of the disease this year alone. Although migration and invasion play key roles in tumor progression, the specific molecular events leading to dissemination of ovarian tumor cells have not been well delineated. Tight junctions are an integral component of epithelial junction complexes, which play a vital role in maintaining epithelial integrity and cell polarity. Disruption of tight junctions is a hallmark of epithelial cancer development and malignant progression; specifically decreased claudin-1 expression has been associated with progression to tumor malignancy. Herein, we investigate the mechanism by which claudin-1 expression is regulated via activation of the TGFβ and RON tyrosine kinase receptor signaling pathways. We propose that claudin-1 expression is regulated by the activation of the TGFβ signaling pathway (dysregulated in ovarian carcinomas), particularly SnoN/SkiL, a key TGFβ co-repressor. In ovarian carcinoma cells, we observed that treatment with TGFβ and MSP1 led to a marked reduction in claudin-1 protein expression. Further, we not only noted that siRNA targeting RON led to upregulated claudin-1 mRNA and protein expression, but similar changes in mRNA and proteins of claudin-1 were observed with SnoN and β-catenin knockdown. Strikingly, with β-catenin knockdown, SnoN levels were notably decreased suggesting that β-catenin could potentially regulate SnoN expression. Collectively, our results demonstrate that claudin-1 expression is regulated by the transcriptional regulators β-catenin and SnoN. Since identification of novel biomarkers could be beneficial in diagnosis, prognosis and prediction of patient outcomes, these observations regarding the cellular events underlying regulation of claudin-1 expression are of translational potential.
Copilot: Design and Development (1998)

Discovering the Pilot My first encounter with a Pilot was when I saw one on a coworker’s desk sometime in June 1996. He described it to me as “just like a Newton, only smaller.” He showed me the basics of the Graffiti writing style and handed me the Pilot and the Graffiti reference card. I was hooked. A few days later I purchased a Pilot 5000 from a local retailer and, being a software developer, I started looking for information on how to write my own programs for this little gem. I was encouraged by the amount of developer information on the Pilot web site, but I couldn’t find the Windows tools. All I found was the Metrowerks CodeWarrior for Pilot package, which only ran on the Macintosh. I didn’t have a Macintosh. So I bought the only thing that worked with Windows: The Conduit Software Development Kit for Windows. (I still haven’t tried to actually write a conduit.) Fortunately, there was at least one other developer out there who had a Pilot but no Macintosh. Darrin Massena (darrin@massena.com) had a Web site (www.massena.com/darrin/pilot/) and wrote a piece of software best described as a “discovery tool.” PilotHack is its name; it’s a monitor for computers where operating systems are optional. PilotHack shows you every single byte of the RAM and ROM in hex and ASCII. It still resides on my Pilot today. Darrin managed to put together some small Pilot applications using Microsoft’s Visual C++ 4.0 Cross-Development Edition for Macintosh. With a serious amount of tweaking, the compiler generated application images that the Pilot loaded. He also put together PILA, the PILot Assembler. PILA ran on Windows and created Pilot application images from 68000 assembly code. Finally, Darrin wrote the article “Writing Pilot Applications Under Windows,” which described what a state-of-the-art Windows SDK for Pilot would look like. This SDK included an editor, a compiler, an assembler, a resource editor, a linker, project management, a debugger, an emulator, samples, OS header files, documentation, on-line help, and a Windows-based IDE to integrate all the pieces together. Realizing that it was not possible for a single developer to do all this, he put out a call to other developers for support. When I read Darrin’s list, I couldn’t help but be drawn toward the emulator project. After all, I had some experience with emulators (I had written an Apple ][+ emulator in the past), I knew some 68000 assembly language, and the potential hack value if the project was successful was just too great to pass up.
Cooling and shielding systems for infrared detectors - requirements and limits (2005)

This paper presents three main cooling systems used for infrared detectors. At first thermoelectric devices are discussed. They allow cooling down the detector with low efficiency and not to the very low temperature. They do not generate any vibrations and therefore are suitable for thermal detectors, where the microphone effect can decrease their performance. Photon detectors need to be cooled down even to 77K or better. The only way to have such deep cooling is to use the cooler based on thermodynamic cycle such as Stirling one. With the high efficiency one can easily obtain cryogenic temperature for a detector. The electromagnetic noise and vibration generation are the main disadvantages of using such devices. Joule-Thomson effect during gas expansion is 3<sup>rd</sup>cooling system discussed in the paper. It is highly effective process, used for gas liquefaction too. The working gas is being removed during cooling into the atmosphere, so the need of continuous supplying with compressed one, what makes this system very difficult for remote applications. In the paper, simple calculations are presented to illustrate the advantages and disadvantages of the different cooling systems.
ASIC design considerations for power management in laptop computers (1991)

During battery operation, the laptop personal computer system power management is an extremely critical design criteria. A device that controls power at differing levels-in the keyboard, the display, as well as in the system's integrated circuits themselves-is described in this paper. Automatic system turn-on, wake up sequencing, low batter indication, system bus interfacing and other system considerations are also addressed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
On Distance Measurement Methods for Turbo Codes (2005)

New digital communication applications, such as multimedia, require very powerful error correcting codes that deliver low error rates while operating at low to moderate signal-tonoise ratios (SNRs). Turbo codes have reasonable complexity and can achieve very low error rates if a proper interleaver design is in place. The use of well-designed interleavers result in very low error rates, especially for medium to long interleavers where turbo codes offer the greatest potential for achieving high minimum distance (dmin) values. The reliable determination of a code’s error performance at very low error rates using simulations may take months or may not be practical at all. However, the knowledge of dmin and its multiplicities can be used to estimate the error rates at high SNR. This thesis is concerned with efficient and accurate distance measurement methods for turbo codes. Since high values of dmin can be caused by high input weight values, say up to 20 or higher, if a brute force algorithm is used the accurate determination of dmin requires that all possible input sequences of input weight up to 20 be tested. Testing all possible input sequences becomes impractical as the size of the interleaver and the value of input weight increase. Thus, the accurate determination of the distance spectrum, or at least dmin and its multiplicities, is a significant problem, especially for interleavers that yield high dmin. Based on Garello’s true distance measurement method, this thesis presents an efficient and accurate distance measurement method for singleand double-binary turbo codes that uses proper trellis termination such as dual-termination or tail-biting. This method is applied to determine the distance spectra for the digital video broadcasting with return channel via satellite (DVB-RCS) standard double-binary turbo codes. It is also used to design new interleavers for DVB-RCS that yield a significant improvement in error performance compared to those in the standard. This method fits particularly well with tail-biting turbo codes that use structured interleavers. This is because the distance properties repeat and this method can use this knowledge to reduce the search space. The reduction in search space results in significant reduction in complexity (i.e., execution time), which allows the determination of high dmin values in reasonable time. This efficiency is demonstrated for both singleand doublebinary turbo codes, using structured interleavers that have high dmin values for various code rates. This method reduces the execution times by a factor of 40 to 400.
Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension. (1990)

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.
BREVE COMPARACIÓN ENTRE EL RÉGIMEN NORMATIVO DE COLABORACIÓN DEL ESTADO PERUANO CON LA IGLESIA CATÓLICA Y EL APLICABLE AL RESTO DE CONFESIONES RELIGIOSAS (2019)

This paper makes a brief comparative analysis between the Agreement signed between the Holy See and the Republic of Peru in 1980, which shows the legal framework for the cooperation provided to the Catholic Church; and the Religious Freedom Act and its current regulations, which regulate certain collaborative aspects concerning the other religious confessions in the country.
DNA Solution of Hard Computational Problems (1995)

DNA experiments are proposed to solve the famous "SAT" problem of computer science. This is a special case of a more general method that can solve NP-complete problems. The advantage of these results is the huge parallelism inherent in DNA-based computing. It has the potential to yield vast speedups over conventional electronic-based computers for such search problems.
Chlorsulfuron Modifies Biosynthesis of Acyl Acid Substituents of Sucrose Esters Secreted by Tobacco Trichomes (1990)

Sucrose esters and duvatrienediol diterpenes are principal constituents formed in and secreted outside head cells of trichomes occurring on surfaces of Nicotiana tabacum. Using trichome-bearing epidermal peels prepared from midveins of N. tabacum cv T.I. 1068 leaves, we found that chlorsulfuron reduced and modified radiolabeling of sucrose ester acyl acids derived from branched-chain amino acid metabolism. The herbicide did not effect formation and exudation of diterpenes which are products of isoprenoid metabolism. Treatment with 1.0 micromolar chlorsulfuron affected 8.5- and 6.3-fold reductions in radiolabeling of methylvaleryl and methylbutyryl groups of sucrose esters, respectively, and concomitant increases of 9- and 9.8-fold in radiolabeling of straight chain valeryl and butyryl groups, respectively. These results and others indicate that inhibition of acetolactate synthase causes an accumulation of 2-oxo-butyric acid that is utilized by enzymes common to Leu biosynthesis to form 2-oxo-valeric acid. Coenzyme A (CoA) activation of this keto acid gives rise to butyryl CoA, which is utilized to form butyryl containing sucrose esters. Alternatively, reutilization of 2-oxo-valeric acid by the same enzymes followed by CoA activation leads to valeryl containing sucrose esters. We propose that in trichome secretory cells synthase, isomerase and dehydrogenase enzymes which catalyze Leu synthesis/degredation in most tissues, convert iso-branched, anteiso-branched and straight-chain keto acids in the formation of sucrose ester acyl groups.
Change in MicroRNAs Associated with Neuronal Adaptive Responses in the Nucleus Accumbens under Neuropathic Pain (2011)

Neuropathic pain is the most difficult type of pain to control, and patients lose their motivation for the purposive pursuit with a decrease in their quality of life. Using a functional magnetic resonance imaging analysis, we demonstrated that blood oxygenation level-dependent signal intensity was increased in the ipsilateral nucleus accumbens (N.Acc.) following peripheral nerve injury. microRNAs are small, noncoding RNA molecules that direct the post-transcriptional suppression of gene expression, and play an important role in regulating synaptic plasticity. In this study, we found that sciatic nerve ligation induced a drastic decrease in the expression of miR200b and miR429 in N.Acc. neurons. The expression of DNA methyltransferase 3a (DNMT3a), which is the one of the predicted targets of miR200b/429, was significantly increased in the limbic forebrain including N.Acc. at 7 d after sciatic nerve ligation. Double-immunolabeling with antibodies specific to DNMT3a and NR1 showed that DNMT3a-immunoreactivity in the N.Acc. was located in NR1-labeled neurons, indicating that increased DNMT3a proteins were dominantly expressed in postsynaptic neurons in the N.Acc. area under a neuropathic pain-like state. The results of these analyses provide new insight into an epigenetic modification that is accompanied by a dramatic decrease in miR200b and miR429 along with the dysfunction of "mesolimbic motivation/valuation circuitry" under a neuropathic pain-like state. These phenomena may result in an increase in DNMT3a in neurons of the N.Acc. under neuropathic pain, which leads to the long-term transcription-silencing of several genes.
Effectiveness of Coadministration of Varenicline, Bupropion, and Serotonin Reuptake Inhibitors in a Smoking Cessation Program in the Real-Life Setting (2012)

Our results suggest that adjuvant treatment to varenicline therapy may be associated with improved success in smoking cessation, especially in patients with nicotine withdrawal symptoms. These results should be tested in randomized controlled trials.
FAMILY, WORK SITUATIONS FACED AND WORK LIFE BALANCE OF WOMEN WORKING IN TERTIARY EDUCATIONAL INSTITUTIONS (2015)

This paper aims to study the problems faced by working women in the academic field specially in tertiary education both at home and in their work place. It also studies about their work-life balance. Discussions were held and Questionnaire was used to study about the problems faced by women. Responses were collected from 60 women, analysed and the current situation is depicted. Women face problems at home (doing daily duties, helping children, treatment at home equal to spouse, independence in spending money, etc.) and work place (based on gender on appointment, pay, promotion, leave availing, etc.). They also have problems in balancing work and family life. Organization pays less attention in providing programs and policies in favour of women to help them balance their work and family life. The results of this study can help in developing a considerate working atmosphere for women in work place. This would assist the organizations in finding out solutions for retaining women workforce. Further society has to be educated on the situation of women, which would help them understand and empathize.
Multistability and Delayed Recurrent Loops (1996)

Multistable dynamical systems have important applications as pattern recognition and memory storage devices. Conditions under which time-delayed recurrent loops of spiking neurons exhibit multistability are presented. Our results are illustrated on both a simple integrate-and-fire neuron and a Hodgkin-Huxley-type neuron, whose recurrent inputs are delayed versions of their output spike trains. Two kinds of multistability with respect to initial spiking functions are found, depending on whether the neuron is excitable or repetitively firing in the absence of feedback.
THE MOLECULAR WEIGHT OF AMYLOPECTIN<sup>1</sup> (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE MOLECULAR WEIGHT OF AMYLOPECTIN1B. H. Zimm and Carl D. ThurmondCite this: J. Am. Chem. Soc. 1952, 74, 4, 1111–1112Publication Date (Print):February 1, 1952Publication History Published online1 May 2002Published inissue 1 February 1952https://pubs.acs.org/doi/10.1021/ja01124a541https://doi.org/10.1021/ja01124a541research-articleACS PublicationsRequest reuse permissionsArticle Views42Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Therapeutic Hemoglobin Levels after Gene Transfer in β-Thalassemia Mice and in Hematopoietic Cells of β-Thalassemia and Sickle Cells Disease Patients (2012)

Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S).Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials, before patients undergo myeloablation and bone marrow transplant.
Epigenetic Regulation of Hepatic Endoplasmic Reticulum Stress Pathways in the Ethanol-Fed Cystathionine Beta Synthase–Deficient Mouse (2009)

The pathogenesis of alcoholic steatohepatitis is mediated in part through the effects of altered methionine metabolism on epigenetic regulation of pathways of endoplasmic reticulum stress relating to apoptosis and lipogenesis.