gebhart/patrepeval huggingface dataset:
Crystal Structure of the Hypoxia-inducible Form of 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) (2005)

The hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) plays a crucial role in the progression of cancerous cells by enabling their glycolytic pathways even under severe hypoxic conditions. To understand its structural architecture and to provide a molecular scaffold for the design of new cancer therapeutics, the crystal structure of the human form was determined. The structure at 2.1 A resolution shows that the overall folding and functional dimerization are very similar to those of the liver (PFKFB1) and testis (PFKFB4) forms, as expected from sequence homology. However, in this structure, the N-terminal regulatory domain is revealed for the first time among the PFKFB isoforms. With a beta-hairpin structure, the N terminus interacts with the 2-Pase domain to secure binding of fructose-6-phosphate to the active pocket, slowing down the release of fructose-6-phosphate from the phosphoenzyme intermediate product complex. The C-terminal regulatory domain is mostly disordered, leaving the active pocket of the fructose-2,6-bisphosphatase domain wide open. The active pocket of the 6-phosphofructo-2-kinase domain has a more rigid conformation, allowing independent bindings of substrates, fructose-6-phosphate and ATP, with higher affinities than other isoforms. Intriguingly, the structure shows an EDTA molecule bound to the fructose-6-phosphate site of the 6-phosphofructo-2-kinase active pocket despite its unfavorable liganding concentration, suggesting a high affinity. EDTA is not removable from the site with fructose-6-P alone but is with both ATP and fructose-6-P or with fructose-2,6-bisphosphate. This finding suggests that a molecule in which EDTA is covalently linked to ADP is a good starting molecule for the development of new cancer-therapeutic molecules.
A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. (1989)

During the course of prenatal diagnosis for beta-thalassemia in Chinese patients, we encountered a mutation that was not detectable by oligonucleotides for the known Chinese mutations. Amplification of the beta-globin gene by the polymerase chain reaction and direct DNA sequencing revealed a previously undescribed -30 TATA box mutation which was carried by the father. Prenatal diagnosis was achieved, and the fetus did not inherit this beta-thalassemia allele.
Mechanics of fluids in porous media (1983)

Transport of quantities such as mass component of a phase and/or heat occurs in fields as diversified as petroleum reservoir engineering, groundwater hydraulics, soil mechanics, industrial filtration, water purification, wastewater treatment, soil drainage and irrigation, and geothermal energy production. In all these areas, scientists, engineers, and planners make use of mathematical models; these models describe the relevant transport processes that occur within controlled porous medium domains and enable forecasting of the future behavior of these domains in response to planned activities. The mathematical models, in turn, are based on the understanding of phenomena, often within the void space, and on theories that relate these phenomena to measurable quantities. Because of the pressing needs in areas of practical interest such as the development of groundwater energy storage and geothermal energy production, a vast amount of research in all these fields has contributed, especially in the last two decades, to our understanding and ability to describe transport phenomena in porous media. In recent years these research efforts have been significantly accelerated, attracting scientists from many disciplines. The practical needs of solving boundary value problems in heterogeneous domains, irregular boundaries, coupled phenomena and multiple dependent variables led to the development of a variety of powerful numerical techniques. The realization that fields are highly heterogeneous and that the degree of heterogeneity depends on the scale of the problem led to the introduction of stochastic concepts as an additional tool for the description of phenomena.
Purification and substrate specificity of endo-type inulinase from Penicillium purpurogenum. (1988)

An inulinase was highly purified from the culture broth of Penicillium purpurogenum by chromatographies on DEAE-Sepharose CL-6B, Toyopearl HW-65, and Bio-Gel P-100. The enzyme was homogeneous by disc electrophoretic analysis. The molecular weight was 6.4 × 104 by SDS-disc electrophoresis and gel filtration on Bio-Gel P-150. The isoelectric point was pH 3.6 by isoelectric focusing. The enzyme hydrolyzed inulin rapidly, but did not affect sucrose. By paper chromatography analysis, the major products from inulin were tri-, tetra-, penta-, and hexasaccharides. The substrate specificity of the enzyme on hydrolyses of fructo-oligosaccharides[1F(1-β-D-fructofuranosyl)nsucrose (n = 1 to 6 and n (average of polymerization degree) = 8)] were examined. The Km values and relative maximum velocities for the hydrolyses of inulin and fructooligosaccharides (GFn, n = 2 to 7 and n = 9) were as follows: inulin, (DP = 35) 0.21 mM and 100; GF9, 0.24mM and 86.5; GF7, 0.33 mM and 132; GF6, 0.85 mM and 71.2; GF5, 3.8 HIM and 25.4; GF4, 2.8mM and 28.8; GF3, (nystose) 16mM and 0.8; GF2 (1-kestose), 8.4mM and 0.2. The molecular activities for the hydrolyses of fructo-oligosaccharides (GFn, n = 2 to 6) were increased depending on the degree of polymerization of fructosyl residues, and were nearly constant if the polymerization degree was over seven. These results strongly suggested that the endo-type inulinase from Penicillium purpurogenum had a subsite structure consisting of at least seven subsites.
Flow cytometric analysis of human bone marrow: I. Normal erythroid development (1987)

Abstract Flow cytometry was used to identify maturational differences of erythroid lineage cells in normal human bone marrow by combining physical characteristics, the expression of multiple cell surface antigens, and nucleic acid content. Normal low-density bone marrow cells could be divided into four populations, based on forward and right-angle light scattering. Erythroid cells, at different maturational stages, were found in three of these four marrow subpopulations. The sequentially correlated expression of three cell surface markers--HLe-1, transferrin receptor, and glycophorin--allowed us to study erythroid maturation from the colony forming cell to the mature erythrocyte. HLe-1 was expressed on the earliest identifiable erythroid cells and was progressively lost as the cells matured. Transferrin receptor began to be expressed at the BFU-E stage and disappeared at the late reticulocyte stage. Transferrin receptor expression preceded glycophorin expression, the latter beginning on morphologically recognizable erythroid precursors just after the CFU-E stage. In contrast to both HLe-1 and transferrin receptor, which were progressively lost during the maturational process, once glycophorin had been maximally expressed on the cell surface, it remained at constant quantities to the mature erythrocyte stage. Although developing nucleated erythroid cells at approximately the normoblast stage had light-scattering properties similar to those of lymphoid cells, these two cell types could be resolved by cell surface antigen expression. Normoblasts were glycophorin positive and HLe negative, whereas lymphoid cells expressed HLe and either Leu 4, Leu 11, or Leu 12. Decreases in cellular nucleic acid content, corresponding first to the extrusion of the nucleus and second to the loss of reticulum, characterized the later stages of erythroid development. These characteristics and instrumentation can be used to purify erythroid cells at various developmental stages.
Spring-Assisted Cranioplasty for the Correction of Nonsyndromic Scaphocephaly: A Quantitative Analysis of 100 Consecutive Cases (2017)

Therapeutic, IV.
Science: gene expression analysis (2002)

Every cell contains all the information necessary to grow, divide, and respond correctly to its environment. The DNA sequence that holds this information is already known for many organisms, and a canonical draft DNA sequence was known for humans by the end of 2000. With this sequence information, biology is poised to enter an era of massively accelerated data collection to elucidate the mechanisms of life and the ailments that result when these mechanisms fail. High-throughput gene expression detection and analysis depends on this genomic information and yields unprecedented amounts of data about the molecular mechanisms that regulate a cell's behavior. Thus, gene expression analysis exemplifies how knowledge discovery techniques are being applied to gene discovery in biology and pharmacological research. This case study will describe what gene expression is, ways in which this data is currently analyzed, and the challenges remaining for effectively deriving biological knowledge from large sets of gene expression data.
The multivariate L 1 -median and associated data depth (2000)

This paper gives three related results: (i) a new, simple, fast, monotonically converging algorithm for deriving the L1-median of a data cloud in Rd, a problem that can be traced to Fermat and has fascinated applied mathematicians for over three centuries; (ii) a new general definition for depth functions, as functions of multivariate medians, so that different definitions of medians will, correspondingly, give rise to different dept functions; and (iii) a simple closed-form formula of the L1-depth function for a given data cloud in Rd.
Metal films on polymer substrates stretched beyond 50% (2007)

When a freestanding plastically deformable metal film is stretched, it ruptures by strain localization, and the elongation is less than a few percent. When the film is deposited on a polymer substrate, however, strain localization may be retarded by the substrate. This paper reports Cu films deposited on Kapton substrates and stretched up to the rupture of the substrates (at an elongation between 50% and 60%). When Cr adhesion layers are introduced between Cu and Kapton, few microcracks in Cu may be found, and the measured electrical resistance agrees with a theoretical prediction. Micrographs show that the strain localization and debonding coevolve.
IVF in Sri Lanka: A concise history of regulatory impasse (2016)

This article outlines the development of IVF in Sri Lanka from the first successful births in the late 1990s and over the subsequent 15 years. It is based on anthropological fieldwork carried out at various points during this period. The piece focuses on the challenges entailed in achieving regulation of the new reproductive technologies against a backdrop of: (i) a bitter civil war; (ii) a complex mosaic of different religious traditions (specifically, Buddhism, Catholicism, Hinduism and Islam); and (iii) a shift towards neo-liberal marketization, particularly in relation to specialist and hi-tech medical interventions. The article concludes that 'soft' regulation operates both to avoid conflict around highly contentious issues in debates about reproductive rights as well as to enable commercially driven developments in technologically specialised areas of medicine.
Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline (2014)

Abs capable of effectively neutralizing HIV-1 generally exhibit very high levels of somatic hypermutation, both in their CDR and framework-variable regions. In many cases, full reversion of the Ab-framework mutations back to germline results in substantial to complete loss of HIV-1-neutralizing activity. However, it has been unclear whether all or most of the observed framework mutations would be necessary or whether a small subset of these mutations might be sufficient for broad and potent neutralization. To address this issue and to explore the dependence of neutralization activity on the level of somatic hypermutation in the Ab framework, we applied a computationally guided framework-reversion procedure to two broadly neutralizing anti-HIV-1 Abs, VRC01 and 10E8, which target two different HIV-1 sites of vulnerability. Ab variants in which up to 78% (38 of 49 for VRC01) and 89% (31 of 35 for 10E8) of framework mutations were reverted to germline retained breadth and potency within 3-fold of the mature Abs when evaluated on a panel of 21 diverse viral strains. Further, a VRC01 variant with an ∼50% framework-reverted L chain showed a 2-fold improvement in potency over the mature Ab. Our results indicate that only a small number of Ab-framework mutations may be sufficient for high breadth and potency of HIV-1 neutralization by Abs VRC01 and 10E8. Partial framework revertants of HIV-1 broadly neutralizing Abs may present advantages over their highly mutated counterparts as Ab therapeutics and as targets for immunogen design.
Role of resveratrol in the management of insulin resistance and related conditions: Mechanism of action (2017)

Resveratrol (RES), a well-known antioxidant, is present in numerous plant species and, as a result, is easily obtained through dietary intake of plant-based foods and beverages. Several studies suggest that RES has anti-carcinogenic, anti-microbial, and anti-viral effects. It may also have beneficial metabolic properties that result in mitigation of insulin resistance (IR) and related metabolic abnormalities, including dyslipidemia, hyperglycemia, and hyperinsulinemia through regulation of gene expression or the activity of rate-limiting enzymes. A large body of evidence supports the beneficial effects of RES in the management and treatment of IR, type 2 diabetes, and related complications through a multitude of mechanisms. This review article focuses on the mechanisms of action of RES, the mechanisms leading to improved insulin sensitivity, and its clinical role in the management and treatment of type 2 diabetes.
Parti Nomenclature of amyloid fibril proteins: Report from the meeting of the International Nomenclature Committee on Amyloidosis, August 8-9,1998 (1999)

Nomenclature of amyloid fibril proteins. Report from the meeting of the international nomenclature committee on amyloidosis, August 8-9, 1998. Part 1.
Deep Sampling Networks (2017)

Deep convolutional neural networks achieve excellent image up-sampling performance. However, CNN-based methods tend to restore high-resolution results highly depending on traditional interpolations (e.g. bicubic). In this paper, we present a deep sampling network (DSN) for down-sampling and up-sampling without any cheap interpolation. First, the down-sampling subnetwork is trained without supervision, thereby preserving more information and producing better visual effects in the low-resolution image. Second, the up-sampling subnetwork learns a sub-pixel residual with dense connections to accelerate convergence and improve performance. DSN's down-sampling subnetwork can be used to generate photo-realistic low-resolution images and replace traditional down-sampling method in image processing. With the powerful down-sampling process, the co-training DSN set a new state-of-the-art performance for image super-resolution. Moreover, DSN is compatible with existing image codecs to improve image compression.
Ipilimumab (yervoy) prolongs survival in advanced melanoma: serious side effects and a hefty price tag may limit its use. (2012)

Ipilimumab (Yervoy) for metastatic melanoma
Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype (2005)

Autosomal dominant cerebellar ataxias (ADCAs) are genetically classified into spinocerebellar ataxias (SCAs). We describe 14 patients of a Dutch pedigree displaying a distinct SCA-phenotype (SCA27) associated with a F145S mutation in the fibroblast growth factor 14 (FGF14) gene on chromosome 13q34. The patients showed a childhood-onset postural tremor and a slowly progressive ataxia evolving from young adulthood. Dyskinesia was often present, suggesting basal ganglia involvement, which was supported by functional imaging in 1 patient. Magnetic resonance imaging (MRI) of the brain showed only moderate cerebellar atrophy in the 2 eldest patients. Neuropsychological testing indicated low IQ and deficits in memory and executive functioning. Behavioral problems were also observed. Further investigations will have to determine the role of FGF14 in the pathogenesis of neurodegeneration and the frequency of this FGF14 mutation in SCA. (c) 2005 Movement Disorder Society.
Nanocluster model of photothermal assay: application for high-sensitive monitoring of nicotine-induced changes in metabolism, apoptosis, and necrosis at a cellular level (2005)

This study evaluates the capability of a photothermal (PT) assay to monitor the impact of nicotine on pancreatic cancer cells (AR42J). The specific PT response is closely proportional to nicotine concentrations at concentration range 1 nM to 100 microM, while at high concentrations of nicotine ranging from 1 mM to 50 mM, PT response shows dramatic decrease. According to the theoretical model, the mechanism of the PT assay is associated with metabolic and apoptotic-related shrinking of local cellular absorbing nanoscale zones caused by increased local absorption at low nicotine doses, while high doses of nicotine lead to apoptotic release of absorbing component (cytochrome c) into the intracellular space, and necrotic swelling of organelles, thereby causing a decrease in local absorption. This model is verified with conventional imaging and with Annexin-V Propidium iodide kits. The PT assay, in addition to its high sensitivity (3 orders of magnitude better than conventional assay), shows the potential to distinguish between various functional states of cells that are associated with changes in metabolism, early and late stages of apoptosis, and necrosis. Comparison of PT responses of pancreatic tumor cells AR42J with isolated primary pancreatic acinar cells and HepG2 cells shows a universal nature of PT assay.
Prospective Risk of Pancreatic Cancer in Familial Pancreatic Cancer Kindreds (2004)

Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk of pancreatic cancer in individuals with a family history of pancreatic cancer. Standardized incidence ratios were calculated by comparing the number of incident pancreatic cancers observed with those expected using Surveillance, Epidemiology and End Results (SEER) rates. Familial pancreatic cancer (FPC) kindreds were defined as kindreds having at least one pair of first-degree relatives with pancreatic cancer, and sporadic pancreatic cancer (SPC) kindreds as families without such an affected pair. Nineteen incident pancreatic cancers developed among 5,179 individuals from 838 kindreds (at baseline, 370 FPC kindreds and 468 SPC kindreds). Of these 5,179 individuals, 3,957 had at least one first-degree relative with pancreatic cancer and contributed 10,538 person-years of follow-up. In this group, the observed-to-expected rate of pancreatic cancer was significantly elevated in members of FPC kindreds [9.0; 95% confidence interval (CI), 4.5-16.1], but not in the SPC kindreds (1.8; 95% CI., 0.22-6.4). This risk in FPC kindreds was elevated in individuals with three (32.0; 95% CI, 10.2-74.7), two (6.4; CI, 1.8-16.4), or one (4.6; CI, 0.5-16.4) first-degree relative(s) with pancreatic cancer. Risk was not increased among 369 spouses and other genetically unrelated relatives. Risk was higher in smokers than in nonsmokers. Individuals with a strong family history of pancreatic cancer have a significantly increased risk of developing pancreatic cancer.
Results of Aggressive Resection of Lung Metastases from Colorectal Carcinoma Detected by Intensive Follow-Up (2002)

Intensive follow-up for lung metastases after resection of colorectal cancer and aggressive resection improved postoperative survival rate. Patients with well-differentiated adenocarcinoma of primary tumor, a solitary metastatic nodule, and disease-free interval of at least two years after initial surgery are likely to be long-term survivors.
Convolutional deep belief networks for scalable unsupervised learning of hierarchical representations (2009)

There has been much interest in unsupervised learning of hierarchical generative models such as deep belief networks. Scaling such models to full-sized, high-dimensional images remains a difficult problem. To address this problem, we present the convolutional deep belief network, a hierarchical generative model which scales to realistic image sizes. This model is translation-invariant and supports efficient bottom-up and top-down probabilistic inference. Key to our approach is probabilistic max-pooling, a novel technique which shrinks the representations of higher layers in a probabilistically sound way. Our experiments show that the algorithm learns useful high-level visual features, such as object parts, from unlabeled images of objects and natural scenes. We demonstrate excellent performance on several visual recognition tasks and show that our model can perform hierarchical (bottom-up and top-down) inference over full-sized images.
Analysis and Design of Class E Isolated DC/DC Converter Using Class E Low PWM (2001)

A class E isolated dc/dc converter for regulating the output voltage at a fixed switching frequency is presented, analyzed and experimentally verified. It consists of class E series-resonant inverter, high-frequency transformer and class E low pulse width modulation (PWM) synchronous rectifier. By controlling the conduction time of controlled switch in rectifier, high-frequency ac current is rectified and the output voltage can be controlled at the same time. The zero voltage switching (ZVS) condition of all switches can be maintained from full-loaded to open-loaded. The theoretical predictions were in good agreement with the experi- mental measurements and the maximum efficiency measured at switching frequency 1 MHz was 91.2%.
On-Body Sensing Solutions for Automatic Dietary Monitoring (2009)

In this paper, various on-body sensors can gather vital information about an individual's food intake. Such data can both help weight-loss professionals personalize programs for clients and inform nutrition research on eating behaviors.
Iodinane- and Metal-Free Synthesis of N-Cyano Sulfilimines:  Novel and Easy Access of NH-Sulfoximines (2007)

The synthesis of N-cyanosulfilimines can readily be achieved by reaction of the corresponding sulfides with cyanogen amine in the presence of a base and NBS or I2 as halogenating agents. Oxidation followed by C-N bond cleavage affords synthetically useful NH-free sulfoximines.