gebhart/patrepeval huggingface dataset:
A simple method for site-directed mutagenesis using the polymerase chain reaction (1989)

We have developed a general and simple method for directing specific sequence changes in a plasmid using primed amplification by the polymerase chain reaction (PCR). The method is based on the amplification of the entire plasmid using primers that include the desired changes. The method is rapid, simple in its execution, and requires only minute amounts of plasmid template DNA. It is significant that there are no special requirements for appropriately placed restriction sites in the sequence to be manipulated. In our system the yield of transformants was high and the fraction of them harboring plasmids with only the desired change was consistently about 80%. The generality of the method should make it useful for the direct alteration of most cloned genes. The only limitation may be the total length of the plasmid to be manipulated. During the study we found that the Taq DNA polymerase used for PCR adds on a single extra base (usually an A) at the end of a large fraction of the newly synthesized chains. These had to be removed by the Klenow fragment of DNA polymerase to insure restoration of the gene sequence.
Comparison of symptomatic and asymptomatic atherosclerotic carotid plaques using parallel imaging and 3 T black-blood in vivo CMR (2013)

3 T bb-CMR is able to differentiate between symptomatic and asymptomatic carotid plaques, demonstrating the potential of bb-CMR to differentiate between stable and vulnerable lesions and ultimately to identify patients with low versus high risk for cardiovascular complications. Best predictors of the symptomatic side were a ruptured fibrous cap, AHA-LT 6, juxtaluminal hemorrhage/thrombus, and intraplaque hemorrhage.
Preparation of DNA-peptide conjugate using oxime resin. (1997)

In order to prepare oligonucleotide-peptide conjugate molecules bearing additional functions, such as cellular membrane permeability, nuclease resistance, which are indispensable to antisense and triplex oligonucleotides for their practical use in vivo, it is found that application of oxime resin (Kaiser resin) to automated DNA synthesis and succeeding cleavage of DNA fragment bound to oxime resin by various nucleophiles, such as amines, alkoxides and protected peptides, give DNA conjugate molecules conventionally in moderate to good yields.
An improved error estimation algorithm for stereophonic acoustic echo cancellation systems (2007)

The effect of graded hypoxia induced by hyperventilation on the activity of tyrosine hydroxylase was measured in vivo by microdialysis. Microdialysis probes were inserted into the striatum of newborn piglets and perfused with medium containing 3-hydroxybenzylhydrazine, an inhibitor of L-aromatic amino acid decarboxylase. The level of 3,4-dihydroxyphenylalanine (DOPA) measured in the effluent dialysate was then an index of tyrosine hydroxylase activity. The oxygen pressure in the veins and capillaries of the cortex was measured, through a cranial window placed over the parietal cortex, by the phosphorescence lifetime of palladium-meso-tetra(4-carboxyphenyl)porphine added to the blood. After baseline measurements, PaCO2 was decreased from 38 torr (control value) to 19, 13, and 11 torr resulting in decreases in the cortical oxygen pressure from 40 +/- 6 torr to 26 +/- 3, 23 +/- 4, and 20 +/- 4 torr, respectively. Decrease in the oxygen pressure to 26 +/- 3 torr caused a statistically significant increase of 25-30% in the level of DOPA in the effluent perfusate. During the next step of increase in ventilator rate, when oxygen decreased only slightly, the level of DOPA remained at the higher level. Ventilation rates that lowered the oxygen pressure to below 20 torr, however, caused a progressive decrease in the level of DOPA. During recovery, the level of DOPA steadily increased, attaining 160% of control value after 1.5 h. When the oxygen pressure was decreased to 16 +/- 2 torr by a single increase in ventilator rate, the DOPA level decreased in the effluent to 15-20% below control.(ABSTRACT TRUNCATED AT 250 WORDS)
Unsupervised Learning and Modeling of Knowledge and Intent for Spoken Dialogue Systems (2015)

Spoken dialogue systems (SDS) are rapidly appearing in various smart devices (smartphone, smart-TV, in-car navigating system, etc). The key role in a successful SDS is a spoken language understanding (SLU) component, which parses user utterances into semantic concepts in order to understand users' intentions. However, such semantic concepts and their structure are manually created by experts, and the annotation process results in extremely high cost and poor scalability in system development. Therefore, the dissertation focuses on improving SDS generalization and scalability by automatically inferring domain knowledge and learning structures from unlabeled conversations through a matrix factorization (MF) technique. With the automatically acquired semantic concepts and structures, we further investigate whether such information can be utilized to effectively understand user utterances and then show the feasibility of reducing human effort during SDS development.
Effect of length and location of heterologous sequences on RecA-mediated strand exchange. (1994)

We systematically investigated the effect of heterology on RecA-mediated strand exchange between double-stranded linear and single-stranded circular DNA. Strand exchange took place through heterologies of up to 150-200 base pairs when the insertion was at the proximal (initiating) end of the duplex DNA but was completely blocked by an insert of only 22 base pairs placed at the distal end of the duplex. In the case of medial heterology created by insertion either in the duplex or the single-stranded DNA, the ability of RecA to exchange strands decreased as the heterology was shifted toward the distal end of the duplex. These results suggest that two different strand exchange mechanisms operate in the proximal and distal portions of the duplex substrate.
Use of ursodeoxycholic acid in liver diseases (2001)

Ursodeoxycholic acid is currently the only established drug for the treatment of chronic cholestatic liver diseases. It has cytoprotective, anti-apoptotic, membrane stabilizing, anti-oxidative and immunomodulatory effects. Prolonged administration of ursodeoxycholic acid in patients with primary biliary cirrhosis (PBC) is associated with survival benefit and a delaying of liver transplantation. There is evidence that it might even prevent progression of the histologic stage of PBC. It also has a beneficial effect on primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, liver disease associated with cystic fibrosis, chronic graft versus host disease, total parenteral nutrition associated cholestasis and various pediatric cholestatic liver diseases. In the present review the current knowledge about the mechanisms of the action and role of ursodeoxycholic acid in the treatment of various liver diseases has been discussed.
Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias (2000)

The cortex of the brain is organized into clear horizontal layers, laminae, which subserve much of the connectional anatomy of the brain. We hypothesize that there is also a vertical anatomical organization that might subserve local interactions of neuronal functional units, in accord with longstanding electrophysiological observations. We develop and apply a general quantitative method, inspired by analogous methods in condensed matter physics, to examine the anatomical organization of the cortex in human brain. We find, in addition to obvious laminae, anatomical evidence for tightly packed microcolumnar ensembles containing approximately 11 neurons, with a periodicity of about 80 microm. We examine the structural integrity of this new architectural feature in two common dementing illnesses, Alzheimer disease and dementia with Lewy bodies. In Alzheimer disease, there is a dramatic, nearly complete loss of microcolumnar ensemble organization. The relative degree of loss of microcolumnar ensembles is directly proportional to the number of neurofibrillary tangles, but not related to the amount of amyloid-beta deposition. In dementia with Lewy bodies, a similar disruption of microcolumnar ensemble architecture occurs despite minimal neuronal loss. These observations show that quantitative analysis of complex cortical architecture can be applied to analyze the anatomical basis of brain disorders.
Accurate, scalable and informative design space exploration for large and sophisticated multi-core oriented architectures (2009)

As microprocessors become more complex, early design space exploration plays an essential role in reducing the time to market and post-silicon surprises. The trend toward multi-/many- core processors will result in sophisticated large-scale architecture substrates (e.g. non-uniformly accessed caches interconnected by network-on-chip) that exhibit increasingly complex and heterogeneous behavior. While conventional analytical modeling techniques can be used to efficiently explore the characteristics (e.g. IPC and power) of monolithic architecture design, existing methods lack the ability to accurately and informatively forecast the complex behavior of large and distributed architecture substrates across the design space. This limitation will only be exacerbated with the rapidly increased integration scale (e.g. number of cores per chip). In this paper, we propose novel, multi-scale 2D predictive models which can efficiently reason the characteristics of large and sophisticated multi-core oriented architectures during the design space exploration stage without using detailed cycle-level simulations. Our proposed techniques employ 2D wavelet multiresolution analysis and neural network regression modeling. We extensively evaluate the efficiency of our predictive models in forecasting the complex and heterogeneous characteristics of large and distributed shared cache interconnected by a network on chip in multi-core designs using both multi-programmed and multithreaded workloads. Experimental results show that the models achieve high accuracy while maintaining low complexity and computation overhead. Through case studies, we demonstrate that the proposed techniques can be used to informatively explore and accurately evaluate global, cooperative multi-core resource allocation and thermal-aware designs that cannot be achieved using conventional design exploration methods.
Prevalence of colorectal adenoma in an average-risk population aged 40–50 versus 50–60 years (2014)

According to current guidelines, screening colonoscopy begins at 50 years for the average-risk population, although there are not enough data on the incidence of precancerous lesions of individuals in the preceding decades. To evaluate the prevalence of colorectal polyps including potentially premalignant lesions in asymptomatic, average-risk individuals aged 40-49 versus 50-59 years, we offered total colonoscopy screening to individuals without any lower gastrointestinal symptoms. The primary end point was the prevalence of colorectal adenoma in two age groups. Of a total of 737 studies, 333 participants were 40-49 years old and 407 participants were 50-59 years old. The overall prevalence of adenomas was 11.2 and 16.4% in the group of 40-49 and 50-59 year olds, respectively. Advanced adenoma was more common in 50-59 year olds (1.2 vs. 2.9%). Malignancy was not reported in these groups. Furthermore, 77.5 and 68.6% of adenomas were observed in the distal colon in the groups of 40-49 year olds and 50-59 year olds, whereas in the proximal colon, 22.2 and 57.1% of adenomas in the groups of 40-49 year olds and 50-59 year olds, respectively, were advanced adenomas. In our study, male sex showed an association with adenoma. However, importantly, there was no significant association between age and colorectal adenoma. Although the prevalence of colorectal adenoma was similar in the two age groups investigated, the rate of advanced adenoma was higher in the group of individuals who were 50-59 years old, suggesting that colorectal cancer screening could be recommended at an age younger than 50 years.
Mice with Disseminated Candidiasis Die of Progressive Sepsis (2005)

These findings indicate that the murine model of hematogenously disseminated candidiasis accurately recapitulates the progressive sepsis seen during severe clinical cases. The results underscore the validity of the model for study of the pathophysiological aspects of this disease, as well as for the evaluation of antifungal drug efficacy.
Treatment of locally advanced and metastatic pancreatic cancer (2008)

Despite recent advances in multi-modality and targeted antineoplastic therapy, efforts to improve clinical outcomes for patients with pancreatic adenocarcinoma remain challenging. The potential for cure is applicable only to patients whose tumors are initially resectable or those with borderline, potentially resectable locally advanced tumors. However, these patients constitute < 10% of all newly diagnosed patients with pancreatic cancer [1]. For most patients with pancreatic cancer, the goal of therapy is palliation, and the prognosis is very poor. Patients with locally advanced pancreatic cancer have a median life expectancy of 6–10 months, and patients with metastatic disease have an even shorter median survival of approximately 3–6 months [2]. Current standard and experimental therapeutic options for patients with locally advanced and metastatic pancreatic cancer are evolving and are discussed below.
Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and Inhibitors (1997)

(1997). Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and Inhibitors. Drug Metabolism Reviews: Vol. 29, No. 1-2, pp. 413-580.
Vascular Endothelial Growth Factor Release Following Electrical Stimulation in Human Subjects (2013)

<b>Significance:</b> Angiogenesis is an important phenomenon involved in the healing of chronic wounds, and it is mainly mediated by the release of vascular endothelial growth factor (VEGF) from endothelial cells. Electrical stimulation (ES) is a well-documented treatment used to assist the healing of chronic wounds. Due to the importance of VEGF in the healing process, and the need to know the mechanisms of action of ES involved in the process, this report aimed to determine by a literature review whether the VEGF release occurs following ES in human subjects. <b>Recent Advances:</b> The findings of this literature review suggest that ES releases VEGF, and this effect may be responsible for promoting angiogenesis after ES. <b>Critical Issues:</b> Despite the findings of this literature review on the release of VEGF by ES on wound healing are promising, a large number of studies are needed to confirm such effects. <b>Future Directions:</b> Further studies should be conducted to identify the best parameters and treatment schedule of ES to be used for the VEGF release.
Interactive Shape Interpolation through Controllable Dynamic Deformation (2010)

In this paper, we introduce an interactive approach to generate physically based shape interpolation between poses. We extend linear modal analysis to offer an efficient and robust numerical technique to generate physically-plausible dynamics even for very large deformation. Our method also provides a rich set of intuitive editing tools with real-time feedback, including control over vibration frequencies, amplitudes, and damping of the resulting interpolation sequence. We demonstrate the versatility of our approach through a series of complex dynamic shape interpolations.
MBD3 and HDAC1, Two Components of the NuRD Complex, Are Localized at Aurora-A-positive Centrosomes in M Phase (2002)

MBD3, a component of the histone deacetylase NuRD complex, contains the methyl-CpG-binding domain (MBD), yet does not possess appreciable mCpG-specific binding activity. The functional significance of MBD3 in the NuRD complex remains enigmatic, partly because of the limited availability of biochemical approaches, such as immunoprecipitation, to analyze MBD3. In this study, we stably expressed the FLAG-tagged version of MBD3 in HeLa cells. We found that MBD3-FLAG was incorporated into the NuRD complex, and the MBD3-FLAG-containing NuRD complex was efficiently immunoprecipitated by anti-FLAG antibodies. By exploiting this system, we found that MBD3 is phosphorylated in vivo in the late G(2) and early M phases. Moreover, we found that Aurora-A, a serine/threonine kinase active specifically in the late G(2) and early M phases, phosphorylates MBD3 in vitro, physically associates with MBD3 in vivo, and co-localizes with MBD3 at the centrosomes in the early M phase. Interestingly, HDAC1 is distributed at the centrosomes in a manner similar to MBD3. These results suggest the highly dynamic nature of the temporal and spatial distributions, as well as the biochemical modification, of the NuRD complex in M phase, probably through an interaction with kinases, including Aurora-A. These observations will contribute significantly to the elucidation of the yet-uncharacterized cell cycle-controlled functions of the NuRD complex.
Compass-Based Automatic Picture Taking Using SenseCam (2008)

The substance-use, positive health practices, diet and eating habits, driving behaviours and preventive health care practices of 113 nurses living in the southeast of England were assessed by means of a postal questionnaire. Females were generally more compliant than males with most of the behaviours assessed. Females reported taking greater risks with driving behaviours by an occasional tendency to "drink and drive". Many males reported both a lack of knowledge of how to self-examine their testicles for signs of cancer and little compliance with this behaviour. This sample reported more smoking and alcohol use than previously reported samples of American nurses and U.K. norms. The nurses in this sample were more likely to avoid foods high in cholesterol, add fibre to their diet and be more vigilant in their driving behaviour than American nurses and British non-nurses.
Diverse Small Molecule Inhibitors of Human Apurinic/Apyrimidinic Endonuclease APE1 Identified from a Screen of a Large Public Collection (2012)

The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment.
Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin (1996)

<h3>Objective.</h3> —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. <h3>Design.</h3> —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. <h3>Setting.</h3> —Seven dermatology clinics in the eastern United States. <h3>Patients.</h3> —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. <h3>Interventions.</h3> —Oral administration of 200 μg of selenium per day or placebo. <h3>Main Outcome Measures.</h3> —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. <h3>Results.</h3> —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. <h3>Conclusions.</h3> —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.
The use of 33P-labeled oligonucleotides for in situ hybridization of vertebrate embryo frozen sections. (1993)

In situ hybridization was performed on frozen sections of whole E16 rat embryos or whole E7 chick embryos using oligonucleotide probes tagged with a 33P-poly A tail. We used two antisense oligonucleotide probes: a 57-mer rat agrin oligo and a 60-mer chicken B-cadherin oligo. After exposure to Hyperfilm beta max for three days, mRNA was detected in distinct organs and tissues of the embryo. After dipping the slides in liquid emulsion and exposing them for two weeks, the grains could be localized to a specific cellular layer, for example, the ganglion layer of the retina or the luminal epithelium of the gizzard. It is concluded that 33P autoradiography is excellent for defining gross areas or cellular layers of mRNA in a vertebrate embryo with a resolution of about 20 microns.