gebhart/patrepeval huggingface dataset:
Influence of nucleic acid base aromaticity on substrate reactivity with enzymes acting on single-stranded DNA (1993)

Stacking between aromatic amino acids and nucleic acid bases may play an important role in the interaction of enzymes with nucleic acid substrates. In such circumstances, disruption of base aromaticity would be expected to decrease enzyme activity on the modified substrates. We have examined the requirement for DNA base aromaticity of five enzymes that act on single-stranded DNA, T4 polynucleotide kinase, nucleases P1 and S1, and snake venom and calf spleen phosphodiesterases, by comparing their kinetics of reaction with a series of dinucleoside monophosphates containing thymidine or a ring-saturated derivative. The modified substrates contained either cis-5R,6S-di-hydro-5,6-dihydroxythymidine (thymidine glycol) or a mixture of the 5R and 5S isomers of 5,6-dihydrothymidine. It was observed that for all the enzymes, except snake venom phosphodiesterase, the parent molecules were better substrates than the dihydrothymidine derivatives, while the thymidine glycol compounds were significantly poorer substrates. Snake venom phosphodiesterase acted on the unmodified and dihydrothymidine molecules at almost the same rate. These results imply that for all the remaining enzymes base aromaticity is a factor in enzyme-substrate interaction, but that additional factors must contribute to the poorer substrate capacity of the thymidine glycol compounds. The influence of the stereochemistry of the dihydrothymidine derivatives was also investigated. We observed that nuclease P1 and S1 hydrolysed the molecules containing 5R-dihydrothymidine approximately 50-times faster than those containing the S-isomer. The other enzymes displayed no measurable stereospecificity.
Myostatin: Biology and Clinical Relevance (2006)

Myostatin is a negative regulator of muscle mass. Important advances in our understanding of the complex biology of this factor have revealed the therapeutic potential of antagonizing the myostatin pathway. Here we present the rationale for evaluating anti-myostatin therapies in human muscle-wasting disorders.
Microsatellite instability in young patients with colorectal cancer (1998)

Genetic instability is closely correlated to the pathogenesis of hereditary non-polyposis colon cancer (HNPCC), which is clinically characterized by a family history and early onset. To investigate the role of genetic instability in young patients with colorectal cancer (CRC), 22 CRC patients, who were aged younger than 30 at the time of diagnosis, were studied. Patients with familial adenomatous polyposis were excluded. Among the 22 cases, seven were identified as microsatellite instability positive (MI+), and more than five microsatellite markers among the 15 tested markers showed an additional band pattern in the tumor tissue. None of the remaining 15 cases showed instability in any microsatellite marker. Two of seven MI+ cases were classic HNPCC. While all MI+ cases had one or no metastatic lymph node, 53.3% of MI- cases showed metastasis in two or more regional lymph nodes. Allelic deletion of the 17p12-13 chromosome around the p53 locus occurred in 16.7% of MI+ cases, and 80.0% of MI- cases showed loss of heterozygosity at that locus. hMSH2 Protein expression, assessed by immunohistochemistry, was absent in two cases, both of which were MI+. When we tested two to four sites of MI+ tumors, transforming growth factor beta receptor type II was mutated in a homogeneous pattern in five MI+ cases. In addition, frame-shift mutations of BAX, insulin-like growth factor II receptor, hMSH3 and hMSH6 were found in three cases, five cases, five cases and one case, respectively. In contrast to the consistent mutation of the transforming growth factor-beta receptor type II gene, mutations of other genes varied in different portions of the tumors.
Aspects of vision loss – visual functions and functional vision (2003)

To promote consistency in terminology, this paper explores the distinction between Visual Functions, which describe how the eye functions, and Functional Vision, which describes how the person functions in vision-related activities. Adequate assessment of Functional Vision is essential to measure outcomes of vision rehabilitation. Consistent measurement will require the development of a unified set of criteria, better suited to use in rehabilitation than the current ‘participation’ categories in International Classification of Functioning (ICF). Whether vision tests are used to explore the underlying causes of eye disease or their functional consequences affects the ways in which they are administered and interpreted. This is explored in detail for letter-chart acuity (the most common visual function test) and reading (the most common functional vision test). At the group level a statistical relationship between visual functions and functional vision can be shown, but individual variations are too great to use this relationship for individual predictions. Definitions of Ranges of Vision Loss are discussed that fit the visual function aspect as well as the functional vision aspect. In this context, the proper use of the terms ‘blindness,’ and ‘low vision’ and the more inclusive term ‘vision loss’ is discussed. Labeling patients with residual vision as ‘blind’ may have adverse psychological consequences. For calculating a statistical estimate of functional vision, based on visual function measurements, the revised AMA Guides can be used. The AMA approach is useful for certain statistical and administrative applications, but should not be used to predict individual rehabilitative needs.
MHC class II binding of peptides derived from HLA-DR 1 (1992)

The aim of these studies was to determine whether auto- and alloreactivity can arise from T cell recognition of MHC-peptides in context of syngeneic MHC. Four synthetic peptides derived from the first domain of the HLA-DR beta 1 * 0101 chain were used in limiting dilution analysis to prime T cells from HLA-DR1- and HLA-DR1+ responders. The frequency of T cells responding to these four peptides was similar in individuals with or without HLA-DR1. In both cases, the peptide corresponding to the nonpolymorphic sequence 43-62, was less immunogenic than peptides corresponding to the three hypervariable regions 1-20, 21-42, and 66-90, eliciting a lower number of reactive T cells. Experiments using a T cell line with specific reactivity to peptide 21-42 showed, however, that this response can be efficiently blocked by adding to the culture a nonpolymorphic sequence peptide. This suggests that alloreactivity can be blocked by use of monomorphic (self) peptides. The binding of both "monomorphic" and "polymorphic" synthetic DR1 peptides to affinity purified HLA-DR 1 and DR 11 molecules was measured using radiolabeled peptides and high performance size exclusion chromatography. The data showed that the polymorphic as well as monomorphic synthetic DR1 peptides bound to both DR1 and DR11 molecules. Competitive inhibition studies indicated that the monomorphic 43-62 peptide can block the binding of the polymorphic peptides, consistent with the results obtained in T cell cultures. Taken together these data suggest that anti-MHC autoreactive T cells are present in the periphery and that both auto and alloreactivity can be elicited by MHC peptides binding to MHC class II molecules.
Ultrathin SnO2 Nanosheets: Oriented Attachment Mechanism, Nonstoichiometric Defects, and Enhanced Lithium-Ion Battery Performances (2012)

We successfully synthesized large-scale and highly pure ultrathin SnO2 nanosheets (NSs), with a minimum thickness in the regime of ca. 2.1 nm as determined by HRTEM and in good agreement with XRD refinements and AFM height profiles. Through TEM and HRTEM observations on time-dependent samples, we found that the asprepared SnO2 NSs were assembled by “oriented attachment” of preformed SnO2 nanoparticles (NPs). Systematic trials showed that well-defined ultrathin SnO2 NSs could only be obtained under appropriate reaction time, solvent, additive, precursor concentration, and cooling rate. A certain degree of nonstoichiometry appears inevitable in the well-defined SnO2 NSs sample. However, deviations from the optimal synthetic parameters give rise to severe nonstoichiometry in the products, resulting in the formation of Sn3O4 or SnO. This finding may open new accesses to the fundamental investigations of tin oxides as well as their intertransition processes. Finally, we investigated the lithium-ion storage of the SnO2 NSs as compared to SnO2 hollow spheres and NPs. The results showed superior performance of SnO2 NSs sample over its two counterparts. This greatly enhanced Li-ion storage capability of SnO2 NSs is probably resulting from the ultrathin thicknesses and the unique porous structures: the nanometer-sized networks provide negligible diffusion times of ions thus faster phase transitions, while the “breathable” interior porous structure can effectively buffer the drastic volume changes during lithiation and delithiation reactions.
Transient Epileptic Amnesia in Dementia: A Treatable Unrecognized Cause of Episodic Amnestic Wandering (2000)

The authors present two patients with dementia who displayed recurrent transient episodes of amnestic wandering and disorientation characterized by getting lost in familiar environments. At other times these patients did not wander or become disoriented. The inability to recall any information during these episodes, and the marked difference of the episodic amnesia exacerbations from the progressive amnesia characteristic of Alzheimer disease seen in these patients led to their evaluation. These clinical episodes and the bilateral interictal epileptiform electroencephalographic changes found in both patients led to the diagnosis of transient epileptic amnesia, a syndrome that can be diagnostically elusive. These transient amnestic wandering events subsided after treatment with antiepileptic drugs in both patients. The authors suggest that transient wandering of this type may be caused by ictal events or postictal confusional states. This report emphasizes the importance of recognizing transient epileptic amnesia as an easily treatable cause of episodic behavioral abnormalities responsive to antiepileptic therapy, especially in those patients who have a markedly inconsistent pattern of wandering, disorientation in familiar settings, and amnesia exacerbation manifested by no recall of the emotional stress of getting lost or of any information during these episodes. Recognition of this type of behavioral disruption and its proper treatment can lead to improved quality of life for these patients, maintain these patients in their homes and out of chronic care institutions longer, and facilitate the community's and caretaker's interactive roles with the patient.
Plasma Membranes Contain Half the Phospholipid and 90% of the Cholesterol and Sphingomyelin in Cultured Human Fibroblasts (1989)

The literature suggests that cholesterol and sphingomyelin might be essentially confined to plasma membranes in mammalian cells; however, this premise has thus far escaped a direct test. We explored the issue in three ways. First, we fractionated whole homogenates of cultured human fibroblasts by equilibrium sucrose density gradient centrifugation. We found that the profiles of cholesterol and sphingomyelin were indistinguishable from those of two plasma membrane markers, 5' nucleotidase and [3H]galactose, which was conjugated to the surface of intact cells from an exogenous donor by galactosyltransferase. Second, we determined the relative surface areas of intact cells from their uptake of 1-(4-trimethyl-amino)phenyl-6-phenylhexa-1,3,5-triene, a cationic fluorescent dye which partitions into but does not cross plasma membranes. Relative to human red cell ghosts, the apparent surface area of the fibroblasts was 17,500 microns2/cell while for canine hepatocytes, the value was 11,500 microns2/cell. The relative ratios of cell cholesterol to dye binding (hence, surface area) were quite similar in ghosts, fibroblasts, and liver cells; namely 1.0, 1.12, and 0.67, respectively. Finally, we found that the specific ratios of both cholesterol and sphingomyelin to 5' nucleotidase were only 10% less in gradient-purified plasma membranes than in whole homogenates. Similar results were obtained using an entirely different method of purification: two-phase aqueous partition. The cholesterol and sphingomyelin in fractions rich in other membranes was closely proportional to their 5' nucleotidase content, suggesting that the presence of these lipids reflected contamination by plasma membrane fragments. The 5' nucleotidase/phospholipid ratio in the purified plasma membrane fraction was roughly twice that in whole cells. We conclude that the compartment marked by 5' nucleotidase in cultured human fibroblasts contains approximately 90% of the two named lipids and half the cell phospholipid phosphorus.
Identification and restoration of spatially variant motion blurs in sequential images (1992)

Sequential imaging cameras are designed to record objects in motion. When the speed of the objects exceeds the temporal resolution of the shutter, the image is blurred. Because objects in a scene are often moving in different directions at different speeds, the degradation of a recorded image may be characterized by a space-variant point spread function (PSF). The sequential nature of such images can be used to determine the relative motion of various parts of the image. This information can be used to estimate the space-variant PSF. A modification of the Landweber iteration is developed to utilize the space-variant PSF to produce an estimate of the original image.
Dry Powder Nitroimidazopyran Antibiotic PA-824 Aerosol for Inhalation (2009)

We formulated PA-824, a nitroimidazopyran with promise for the treatment of tuberculosis, for efficient aerosol delivery to the lungs in a dry powder porous particle form. The objectives of this study were to prepare and characterize a particulate form of PA-824, assess the stability of this aerosol formulation under different environmental conditions, and determine the pharmacokinetic parameters for the powder after pulmonary administration. The drug was spray dried into porous particles containing a high drug load and possessing desirable aerosol properties for efficient deposition in the lungs. The physical, aerodynamic, and chemical properties of the dry powder were stable at room temperature for 6 months and under refrigerated conditions for at least 1 year. Pharmacokinetic parameters were determined in guinea pigs after the pulmonary administration of the PA-824 powder formulation at three doses (20, 40, and 60 mg/kg of body weight) and compared to those after the intravenous (20 mg/kg) and oral (40 mg/kg) delivery of the drug. Oral and inhaled delivery of PA-824 achieved equivalent systemic delivery at the same body dose within the first 12 h of dosing. However, animals dosed by the pulmonary route showed drug loads that remained locally in the lungs for 32 h postexposure, whereas those given the drug orally cleared the drug more rapidly. Therefore, we expect from these pharmacokinetic data that pulmonary delivery may achieve the same efficacy as oral delivery at the same body dose, with a potential improvement in efficacy related to pulmonary infection. This may translate into the ability to deliver lower body doses of this drug for the treatment of tuberculosis by aerosol.
Id Genes Are Direct Targets of Bone Morphogenetic Protein Induction in Embryonic Stem Cells (1999)

Bone morphogenetic proteins (BMPs) are morphogenetic signaling molecules essential for embryonic patterning. To obtain molecular insight into the influence of BMPs on morphogenesis, we searched for new genes directly activated by BMP signaling. In vitro cultured mouse embryonic stem (ES) cells were used, cultivated in chemically defined growth medium (CDM). CDM-cultured ES cells responded very selectively to stimulation by various mesoderm inducers (BMP2/4, activin A, and basic fibroblast growth factor). BMP2/4 rapidly induced transcript levels of the homeobox genes Msx-1 and Msx-2 and the proto-oncogene JunB, whereas c-jun transcripts displayed delayed albeit prolonged increase. Using differential display cDNA cloning, six direct BMP target genes were identified. These include Id3, which showed strong mRNA induction, and the moderately induced Cyr61, DEK, and eIF4AII genes, as well as a gene encoding a GC-binding protein. Besides Id3, also the Id1 and Id2 genes were activated by BMP4 in both ES cells and a range of different cell lines. Id genes encode negative regulators of basic helix-loop-helix transcription factors. In vivo we observed local ectopic expression of Id3 and Msx-2 mRNAs in Ft/+ embryos at overlapping regions of ectopic Bmp4 misexpression. We therefore propose that the Msx and Id genes are direct target genes of embryonic BMP4 signaling in vivo.
Fermentation of Plant Cell Wall Derived Polysaccharides and Their Corresponding Oligosaccharides by Intestinal Bacteria (2000)

New types of nondigestible oligosaccharides were produced from plant cell wall polysaccharides, and the fermentation of these oligosaccharides and their parental polysaccharides by relevant individual intestinal species of bacteria was studied. Oligosaccharides were produced from soy arabinogalactan, sugar beet arabinan, wheat flour arabinoxylan, polygalacturonan, and rhamnogalacturonan fraction from apple. All of the tested substrates were fermented to some extent by one or more of the individual species of bacteria tested. Bacteroides spp. are able to utilize plant cell wall derived oligosaccharides besides their reported activity toward plant polysaccharides. Bifidobacterium spp. are also able to utilize the rather complex plant cell wall derived oligosaccharides in addition to the bifidogenic fructooligosaccharides. Clostridium spp., Klebsiella spp., and Escherichia coli fermented some of the selected substrates in vitro. These studies do not allow prediction of the fermentation in vivo but give valuable information on the fermentative capability of the tested intestinal strains.
Production of knockout mice by DNA microinjection of various CRISPR/Cas9 vectors into freeze-thawed fertilized oocytes (2015)

Our report offers several choices of researcher-friendly consolidated procedures for making CRISPR/Cas9-mediated knockout mice, with sophisticated construction systems for various types of CRISPR vectors, convenient preparation of in vitro fertilized or mated freeze-thawed oocytes, and an efficient method of mutant screening.
Comparison of the aggregation properties, secondary structure and apoptotic effects of wild‐type, Flemish and Dutch N‐terminally truncated amyloid β peptides (2001)

The Dutch (E22Q) and Flemish (A21G) mutations in the betaAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three Abeta(12-42) variants [wild-type (WT), Dutch and Flemish] were tested. At a concentration of 5 microM the aggregation of these peptides followed the order: Abeta(1-42) WT > Abeta(12-42) WT > Abeta(12-42) Flemish > Abeta(12-42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their alpha-helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in beta-sheet and random coil content. Apoptosis was induced in neuronal cells by the Abeta(12-42) WT and Flemish peptides at concentrations as low as 1-5 microM, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase-3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N-truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length Abeta(1-42) peptide was weaker than that induced by its N-truncated variant. These data suggest that N-truncation enhanced the cytotoxic effects of Abeta WT and Flemish peptides, which may play a role in the accelerated progression of dementia.
A tutorial on particle filters for on-line nonlinear/non-Gaussian Bayesian tracking (2001)

Bayesian methods provide a rigorous general framework for dynamic state estimation problems. We describe the nonlinear/non-Gaussian tracking problem and its optimal Bayesian solution. Since the optimal solution is intractable, several different approximation strategies are then described. These approaches include the extended Kalman filter and particle filters. For a particular problem, if the assumptions of the Kalman filter hold, then no other algorithm can out-perform it. However, in a variety of real scenarios, the assumptions do not hold and approximate techniques must be employed. The extended Kalman filter approximates the models used for the dynamics and measurement process, in order to be able to approximate the probability density by a Gaussian. Particle filtering approximates the density directly as a finite number of samples. A number of different types of particle filter exist and some have been shown to outperform others when used for particular applications. However, when designing a particle filter for a particular application, it is the choice of importance density that is critical. These notes are of a tutorial nature and so, to facilitate easy implementation, &apos;pseudo-code&apos; for algorithms are included at relevant points. (15 pages)
Biodiesel for Diesel Engines (2008)

Biodiesel fuels are attracting increasing attention worldwide as a blending component or a direct replacement for diesel fuel in vehicle engines. The purpose of the transesterification process is to lower the viscosity of the oil. The most important variables affecting the methyl ester yield during the transesterification reaction are the molar ratio of alcohol to vegetable oil and the reaction temperature. Methanol is the commonly used alcohol in this process, due in part to its low cost. Methyl esters of vegetable oils have several outstanding advantages among other new-renewable and clean engine fuel alternatives. Biodiesel fuel is a renewable substitute fuel for petroleum diesel or petrodiesel fuel made from vegetable or animal fats. Biodiesel can be used in any mixture with petrodiesel as it has very similar characteristics but it has lower exhaust emissions. Biodiesel fuel has better properties than that of petrodiesel fuel such as renewable, biodegradable, non-toxic, and essentially free of sulfur and aromatics. Biodiesel has become more attractive recently because of its environmental benefits.
Matrix Factorization Techniques for Recommender Systems (2009)

As the Netflix Prize competition has demonstrated, matrix factorization models are superior to classic nearest neighbor techniques for producing product recommendations, allowing the incorporation of additional information such as implicit feedback, temporal effects, and confidence levels.