gebhart/patrepeval huggingface dataset:
CLEANUP: a fast computer program for removing redundancies from nucleotide sequence databases (1996)

A key concept in comparing sequence collections is the issue of redundancy. The production of sequence collections free from redundancy is undoubtedly very useful, both in performing statistical analyses and accelerating extensive database searching on nucleotide sequences. Indeed, publicly available databases contain multiple entries of identical or almost identical sequences. Performing statistical analysis on such biased data makes the risk of assigning high significance to non-significant patterns very high. In order to carry out unbiased statistical analysis as well as more efficient database searching it is thus necessary to analyse sequence data that have been purged of redundancy. Given that a unambiguous definition of redundancy is impracticable for biological sequence data, in the present program a quantitative description of redundancy will be used, based on the measure of sequence similarity. A sequence is considered redundant if it shows a degree of similarity and overlapping with a longer sequence in the database greater than a threshold fixed by the user. In this paper we present a new algorithm based on an "approximate string matching' procedure, which is able to determine the overall degree of similarity between each pair of sequences contained in a nucleotide sequence database and to generate automatically nucleotide sequence collections free from redundancies.
Phthalate Esters Enhance Quinolinate Production by Inhibiting -Amino- -Carboxymuconate- -Semialdehyde Decarboxylase (ACMSD), a Key Enzyme of the Tryptophan Pathway (2004)

Tryptophan is metabolized to alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) via 3-hydroxyanthranilate (3-HA). ACMS decarboxylase (ACMSD) directs ACMS to acetyl CoA; otherwise ACMS is non-enzymatically converted to quinolinate (QA), leading to the formation of NAD and its degradation products. Thus, ACMSD is a critical enzyme for tryptophan metabolism. Phthalate esters have been suspected of being environmental endocrine disrupters. Because of the structural similarity of phthalate esters with tryptophan metabolites, we examined the effects of phthalate esters on tryptophan metabolism. Phthalate esters containing diets were orally given to rats and the urinary excreted tryptophan metabolites were quantified. Of the phthalate esters with different side chains tested, di(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono(2-ethylhexyl)phthalate (MEHP), most strongly enhanced the production of QA and degradation products of nicotinamide, while 3-HA was unchanged. This pattern of metabolic change led us to assume that these esters lowered ACMSD protein or its activity. Although DEHP could not be tested because of its low solubility, MEHP reversibly inhibited ACMSD from rat liver and mouse kidney, and also the recombinant human enzyme. Correlation between inhibition of ACMSD by phthalate esters with different side chains and urinary excretion of QA supports the notion that phthalate esters perturb tryptophan metabolism by inhibiting ACMSD. Quinolinate is a potential endogenous toxin and has been implicated in the pathogenesis of various disorders. Although toxicity of phthalate esters through accumulation of QA remains to be investigated, they may be detrimental by acting as metabolic disrupters when intake of a tryptophan-rich diet and exposure to phthalate esters occur coincidentally.
Initial FGF23-Mediated Signaling Occurs in the Distal Convoluted Tubule (2009)

Fibroblast growth factor-23 (FGF23), a hormone central to phosphate and vitamin D metabolism, reduces renal absorption of phosphate by downregulating the sodium-phosphate cotransporter Npt2a. However, the mechanisms of FGF23 action in the kidney are unclear, as Npt2a localizes to the proximal tubule (PT) and the FGF23 coreceptor alpha-Klotho (KL) localizes to the distal convoluted tubule (DCT). Immunofluorescent analyses following FGF23 injection in mice showed robust staining for phospho-ERK1/2, a marker of FGF23 bioactivity, only within the DCT in a subset of KL-positive cells. This activity colocalized with the FGF23 receptor FGFR1 and was present in DCT cells that were adjacent to Npt2a-expressing PT segments. Although KL is expressed as both secreted and membrane-bound isoforms, only the membrane-bound isoform was capable of mediating FGF23 bioactivity. These findings provide novel insight into the mechanisms of hormone-regulated phosphate metabolism by identifying an intrarenal signaling axis for FGF23.
2,4-Diphenyl Furan Diamidines as Novel Anti-Pneumocystis carinii Pneumonia Agents (1999)

Dicationic 2,4-bis(4-amidinophenyl)furans 5-10 and 2, 4-bis(4-amidinophenyl)-3,5-dimethylfurans 14 and 15 have been synthesized. Thermal melting studies revealed high binding affinity of the compounds to poly(dA-dT) and to the duplex oligomer d(CGCGAATTCGCG)2. All of the new compounds were effective against Pneumocystis carinii pneumonia in the immunosuppressed rat model with up to 200-fold increase in activity compared to the control compound pentamidine. No toxicity was noted for 5, 7-10 at the dose of 10 micromol/kg/d; however, the isopropyl analogue 7 showed toxicity comparable to pentamidine at the dosage of 20 micromol/kg/d. Dimethylation of the parent compound on the furan ring resulted in reduced activity and increased toxicity.
Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice (2015)

Our findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.
A 6-Week Randomized, Placebo-Controlled Trial of CP-316,311 (a Selective CRH 1 Antagonist) in the Treatment of Major Depression (2008)

Although CP-316,311 was safe and well tolerated in this study population, it failed to demonstrate efficacy in the treatment of major depression.
Beclin 1 Gene Transfer Activates Autophagy and Ameliorates the Neurodegenerative Pathology in α-Synuclein Models of Parkinson's and Lewy Body Diseases (2009)

Accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of Parkinson's disease (PD) and Lewy body disease (LBD), a heterogeneous group of disorders with dementia and parkinsonism, where Alzheimer's disease and PD interact. Accumulation of alpha-syn in these patients might be associated with alterations in the autophagy pathway. Therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy for LBD/PD. Overexpression of alpha-syn from lentivirus transduction in a neuronal cell line resulted in lysosomal accumulation and alterations in autophagy. Coexpression of beclin 1 activated autophagy, reduced accumulation of alpha-syn, and ameliorated associated neuritic alterations. The effects of beclin 1 overexpression on LC3 and alpha-syn accumulation were partially blocked by 3-MA and completely blocked by bafilomycin A1. In contrast, rapamycin enhanced the effects of beclin 1. To evaluate the potential effects of activating autophagy in vivo, a lentivirus expressing beclin 1 was delivered to the brain of a alpha-syn transgenic mouse. Neuropathological analysis demonstrated that beclin 1 injections ameliorated the synaptic and dendritic pathology in the tg mice and reduced the accumulation of alpha-syn in the limbic system without any significant deleterious effects. This was accompanied by enhanced lysosomal activation and reduced alterations in the autophagy pathway. Thus, beclin 1 plays an important role in the intracellular degradation of alpha-syn either directly or indirectly through the autophagy pathway and may present a novel therapeutic target for LBD/PD.
Scaling to 50-nm C-axis aligned crystalline In-Ga-Zn oxide FET with surrounded channel structure and its application for less-than-5-nsec writing speed memory (2014)

We report novel FETs with a structure in which not only the top surface but also the side surfaces of island-shaped c-axis aligned crystalline indium-gallium-zinc oxide (CAAC-IGZO) serving as a channel are surrounded by a gate electrode, that is, surrounded channel CAAC-IGZO FETs. The FETs maintained their favorable subthreshold characteristics even if the channel length was scaled down to approximately 50 nm, i.e., normally-off, DIBL of 67 mV/V, SS of 92 mV/dec, and an off-state current lower than the measurement limit (0.1 pA) for a gate insulating film EOT of 11 nm. Moreover, we applied an FET with such a structure to a memory and discussed the writing time and the retention time, which were expected to be less than 5 ns and greater than 1,000 sec, respectively, for storage capacitance of 1 fF from circuit simulation.
Circular dichroism and conformational polymorphism of DNA (2009)

Here we review studies that provided important information about conformational properties of DNA using circular dichroic (CD) spectroscopy. The conformational properties include the B-family of structures, A-form, Z-form, guanine quadruplexes, cytosine quadruplexes, triplexes and other less characterized structures. CD spectroscopy is extremely sensitive and relatively inexpensive. This fast and simple method can be used at low- as well as high-DNA concentrations and with short- as well as long-DNA molecules. The samples can easily be titrated with various agents to cause conformational isomerizations of DNA. The course of detected CD spectral changes makes possible to distinguish between gradual changes within a single DNA conformation and cooperative isomerizations between discrete structural states. It enables measuring kinetics of the appearance of particular conformers and determination of their thermodynamic parameters. In careful hands, CD spectroscopy is a valuable tool for mapping conformational properties of particular DNA molecules. Due to its numerous advantages, CD spectroscopy significantly participated in all basic conformational findings on DNA.
The complete general secretory pathway in gram-negative bacteria. (1993)

The unifying feature of all proteins that are transported out of the cytoplasm of gram-negative bacteria by the general secretory pathway (GSP) is the presence of a long stretch of predominantly hydrophobic amino acids, the signal sequence. The interaction between signal sequence-bearing proteins and the cytoplasmic membrane may be a spontaneous event driven by the electrochemical energy potential across the cytoplasmic membrane, leading to membrane integration. The translocation of large, hydrophilic polypeptide segments to the periplasmic side of this membrane almost always requires at least six different proteins encoded by the sec genes and is dependent on both ATP hydrolysis and the electrochemical energy potential. Signal peptidases process precursors with a single, amino-terminal signal sequence, allowing them to be released into the periplasm, where they may remain or whence they may be inserted into the outer membrane. Selected proteins may also be transported across this membrane for assembly into cell surface appendages or for release into the extracellular medium. Many bacteria secrete a variety of structurally different proteins by a common pathway, referred to here as the main terminal branch of the GSP. This recently discovered branch pathway comprises at least 14 gene products. Other, simpler terminal branches of the GSP are also used by gram-negative bacteria to secrete a more limited range of extracellular proteins.
Recombinant production and purification of novel antisense antimicrobial peptide inEscherichia coli (1998)

A fusion protein was genetically engineered that contains an antimicrobial peptide, designated P2, at its carboxy terminus and bovine prochymosin at its amino terminus. Bovine prochymosin was chosen as the fusion partner because of its complete insolubility in Escherichia coli, a property utilized to protect the cells from the toxic effects of the antimicrobial peptide. This fusion protein was purified by centrifugation as an insoluble inclusion body. A methionine linker between prochymosin and the P2 peptide enabled P2 to be released by digestion with cyanogen bromide. Cation exchange HPLC followed by reversed-phase HPLC were used to purify the P2 peptide. The recombinant P2 peptide's molecular mass was confirmed by mass spectrometry to within 0.1% of the theoretical value (2480.9 Da), and the antimicrobial activity of the purified recombinant P2 against E. coli D31 was determined to be identical to that of the chemically synthesized peptide (minimal inhibitory concentration of 5 mg/mL). Although the yield of the fusion protein after expression by the cells was high (16% of the total cell protein), the percentage recovery of the P2 peptide in the inclusion bodies was relatively low, which appears to be due to losses in the cyanogen bromide digestion step.
Dispenser Printed Microscale Thermoelectric Generators for Powering Wireless Sensor Networks (2009)

Wireless sensor networks (WSN) are a promising technology for ubiquitous, active monitoring in residential, industrial and medical applications. These nodes combine a radio transceiver, microcontroller and sensors into a low power package. A current bottleneck for widespread adoption of WSN’s is the power supplies. While the power demands can be somewhat alleviated through novel electronics, any primary battery will have a finite lifetime. Energy harvesting, from ambient vibration, light, and heat sources, offers an opportunity to significantly extend the lifetime of the nodes and possibly provide perpetual power. Thermal energy is an ideal source for WSNs due to the availability of low-grade ambient waste heat sources. Thermoelectric devices convert temperature gradients into DC electric power in compact form factors. Efficient device designs require hundreds of high-aspect ratio semi-conductor microelements fabricated electrically in series and thermally in parallel. This design requirement presents problems for standard microfabrication techniques due to thickness limitations of standard semiconductor processes. We present a new method of contact dispenser printing, specifically developed to additively create microscale generators. Initial materials performance results show promising results and are further detailed in this work.
Dimensions of the human eye relevant to radiation protection (dosimetry) (1975)

An attempt has been made to clarify the two most important issues relevant to personal eye dosimetry. This involves the identification of the cells which are most at risk from radiation and the specification of their position in the eye. A survey of the radiobiological literature concerning animals and humans shows that the epithelial cells in the equatorial region of the lens are those which are involved in radiation cataract induction. The depth of these cells has been evaluated in the human eye by means of geometrical construction. The relevant dimensions have been determined from a survey of published anatomical data and supplemented by new data obtained by slit-image photography. In a normal adult population (20-65 years) the minimum depth of the incriminated cells is 2.3 plus or minus 0.4 mm; the upper and lower values are associated with young and old subjects respectively. Approximate calculations for isotropic 90Sr/90Y and 106Rh beta-radiation fields indicate that a planar dosemeter, which integrates the tissue dose between depths of 2.5-3.5 mm, should give a reasonable measure of the mean equatorial dose for the variety of eye and irradiation geometries likely to be met during a life-time exposure. The long established, but tentative, value of 3 mm for the effective depth of the lens is thus confirmed.
Textured thin-film Si solar selective absorbers using reactive ion etching (1980)

Solar selective surface photothermal absorbers consisting of thin-film Si with a submicron surface texture have been produced by reactive ion etching an evaporated Si film on a Mo layer. Such surfaces formed on 316 stainless steel and other substrates have solar absorptivities of 0.9 and calculated thermal emissivities of ∼0.2 at 200 °C. These selective surfaces are stable in air to 500 °C.
BREAST CANCER AND BREASTFEEDING: RESULTS FROM AN AUSTRALIAN CASE-CONTROL STUDY (1989)

A case-control study of breast cancer, diet, and lactational history was carried out in Brisbane, Australia, between 1981 and 1985. Cases were recruited from both the private and the public health care sectors. The breastfeeding histories of 459 cases and 1,091 controls selected from the electoral roll were analyzed. An odds ratio of 0.85 (95% confidence interval 0.55-1.30) for any lactation versus no lactation was observed, with no suggestion of a monotonic trend with increasing duration. This estimate was only slightly altered by multiple logistic regression analysis. A statistically significant nonlinear association was noted for breastfeeding of the first liveborn child (chi 2 = 14.8, df = 6; p less than 0.05), with a slightly elevated odds ratio for lactations of less than one month, a lowered odds ratio for lactations of one month to three months, and a weakly elevated odds ratio in women breastfeeding for more than nine months. Results for premenopausal women were very similar to those for postmenopausal women. Taken together with other recent studies, these results suggest that lactation may play a modest direct or indirect part in reducing the risk of breast cancer.
Tagging a Downy Mildew Resistance Gene in Cucumber Using RAPD Markers (1996)

Downy mildew in cucumber (C ucumis sativus L.) is a disease caused by Psuedoperonospora cubensis (Berk. and Curt.). Genetic resistance is used to control this disease. However, selection for resistance to downy mildew requires considerable effort. Molecular markers that are closely linked to a gene for downy mildew resistance may be useful for increasing selection efficiency. RAPD (randomly amplified polymorphic DNA) markers are molecular markers that have several advantages including economy, abundance and high rate polymorphism. Two populations, WI 1983 × Straight 8 and ZuDM1 × Straight 8, were used to identify RAPD markers linked to a downy mildew resistance gene. The WI 1983 × Straight 8 population contained 63 F 3 families and the ZuDM1 × Straight 8 population contained 90. These F 3 families were evaluated for disease reactions in four locations—Wisconsin, South Carolina, Spain, and The Netherlands. Four replications were conducted in Wisconsin and two in the remaining locations. The ranking of susceptible and resistant families was consistent over the locations. Spearman rank coefficients between locations ranged from 0.65 to 0.84. DNA samples from individual F 2 plants in each population were combined into two bulks, one resistant and one susceptible, based on the family performance. Then, PCR analysis was performed. Over 100 polymorphic primers were screened using this bulked segregant analysis to find the resistance gene to RAPD genetic linkage.
Vaginoplasty Using Amniotic Membranes in Cases of Vaginal Agenesis or after Vaginectomy (1992)

Various treatments have been proposed for vaginal agenesis. The authors describe successful procedures using amniotic membranes as a graft on vaginoplasties. The amnion was not stripped from the chorion. The results showed the vagina to be well formed and of normal depth and caliber.
Mutational Analyses of Multiple Oncogenic Pathways in Intraductal Papillary Mucinous Neoplasms of the Pancreas (2008)

The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.
The Pharmacologic Treatment of Anxiety Disorders (2010)

Anxiety disorders, as a group, are among the most common mental health conditions and frequently cause significant functional impairment. Both psychotherapeutic and pharmacologic techniques are recognized to be effective management strategies. This review provides a discussion of the major classes of psychotropic medications investigated in clinical trials of the following anxiety disorders: panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Findings suggest that both selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are useful first-line agents for most of the anxiety disorders, particularly given the frequent comorbidity with mood disorders. Highly serotonergic agents are preferred for obsessive-compulsive disorder. Other antidepressants, such as tricyclic antidepressants or monoamine oxidase inhibitors, are generally reserved as second- and third-line strategies due to tolerability issues. Evidence for other agents, including anticonvulsants and atypical antipsychotics, suggests that they may have an adjunctive role to antidepressants in cases of treatment resistance, while azapirones have been used effectively for generalized anxiety disorder, and a substantial body of evidence supports benzodiazepine use in panic disorder and generalized anxiety disorder. Despite notable advances, many patients with anxiety disorders fail to adequately respond to existing pharmacologic treatments. Increased research attention should be focused on systematizing pharmacologic and combined pharmacologic-psychosocial strategies to address treatment resistance and developing novel treatments for anxiety disorders.