gebhart/patrepeval huggingface dataset:
Pharmacogenomics on Gastric Cancer (2004)

Gastric cancer is one of most common malignancies in the world. 5-fluoroyracil, CPT-11, TS-1, Paclitaxel and Docetaxel are used as chemotherapeutic agents for advanced gastric cancer, although endoscopic mucosal resection and surgical gastrectomy are potentially curative treatments. Most important problems associated chemotherapeutic agents are side effects and drug resistances. TSG101, implicated in membrane trafficking and transcriptional regulation, is upregulated in gastric cancer with multidrug resistant phenotype. Shen et al reported that transient transfection of TSG101 siRNA reduced the expression level of TSG101 protein as well as resistance to vincristine and adriamycin in gastric cancer cells. Bioinformatics, microarray analyses, SNP typing, and high-throughput functional analyses are applied for pharmacogenomics in the post-genome era. Therapeutics based on the genotyping of each patient is the future goal of personalized medicine (or tailor-made medicine) for gastric cancer.
Feed forward neural networks for the analysis of censored survival data: a partial logistic regression approach (1998)

Flexible modelling in survival analysis can be useful both for exploratory and predictive purposes. Feed forward neural networks were recently considered for flexible non-linear modelling of censored survival data through the generalization of both discrete and continuous time models. We show that by treating the time interval as an input variable in a standard feed forward network with logistic activation and entropy error function, it is possible to estimate smoothed discrete hazards as conditional probabilities of failure. We considered an easily implementable approach with a fast selection criteria of the best configurations. Examples on data sets from two clinical trials are provided. The proposed artificial neural network (ANN) approach can be applied for the estimation of the functional relationships between covariates and time in survival data to improve model predictivity in the presence of complex prognostic relationships.
Applications of Spectral Imaging: Detection and Analysis of Human Melanoma and Its Precursors (2001)

Light-based imaging has extensive applications for medicine and biology, and recent advances in optical imaging modalities, such as confocal and multi-photon scanning fluorescence microscopy, bioluminescence, optical coherence tomography, and spectral imaging, have opened new avenues for visualizing and recording over time dynamic changes in genetic, developmental, and disease mechanisms that cannot be captured by conventional light microscopy. In the present article, we focus on spectral imaging, and using human melanoma and its precursor lesions as an example, we describe the ability of spectral imaging to detect early-stage disease, capture gene expression profiles in tissue specimens, and visualize gene functions in tumors growing in living animals.
Interpolating Subdivision for meshes with arbitrary topology (1996)

Subdivision is a powerful paradigm for the generation of surfaces of arbitrary topology. Given an initial triangular mesh the goal is to produce a smooth and visually pleasing surface whose shape is controlled by the initial mesh. Of particular interest are interpolating schemes since they match the original data exactly, and play an important role in fast multiresolution and wavelet techniques. Dyn, Gregory, and Levin introduced the Butterfly scheme, which yields C1 surfaces in the topologically regular setting. Unfortunately it exhibits undesirable artifacts in the case of an irregular topology. We examine these failures and derive an improved scheme, which retains the simplicity of the Butterfly scheme, is interpolating, and results in smoother surfaces. 1
Naturally Occurring Adenines within mRNA Coding Sequences Affect Ribosome Binding and Expression in Escherichia coli (2006)

Translation initiation requires the precise positioning of a ribosome at the start codon. The major signals of bacterial mRNA that direct the ribosome to a translational start site are the Shine-Dalgarno (SD) sequence within the untranslated leader and the start codon. Evidence for the presence of many non-SD-led genes in prokaryotes provides a motive for studying additional interactions between ribosomes and mRNA that contribute to translation initiation. A high incidence of adenines has been reported downstream of the start codon for many Escherichia coli genes, and addition of downstream adenine-rich sequences increases expression from several genes in E. coli. Here we describe site-directed mutagenesis of the E. coli aroL, pncB, and cysJ coding sequences that was used to assess the contribution of naturally occurring adenines to in vivo expression and in vitro ribosome binding from mRNAs with different SD-containing untranslated leaders. Base substitutions that decreased the downstream adenines by one or two nucleotides decreased expression significantly from aroL-, pncB-, and cysJ-lacZ fusions; mutations that increased downstream adenines by one or two nucleotides increased expression significantly from aroL- and cysJ-lacZ fusions. Using primer extension inhibition (toeprint) and filter binding assays to measure ribosome binding, the changes in in vivo expression correlated closely with changes in in vitro ribosome binding strength. Our data are consistent with a model in which downstream adenines influence expression through their effects on the mRNA-ribosome association rate and the amount of ternary complex formed. This work provides evidence that adenine-rich sequence motifs might serve as a general enhancer of E. coli translation.
THE LIN-12/Notch SIGNALING PATHWAY AND ITS REGULATION (1997)

Notch, LIN-12, and GLP-1 are receptors that mediate a broad range of cell interactions during Drosophila and nematode development. Signaling by these receptors relies on a conserved pathway with three core components: DSL ligand, LNG receptor, and a CSL effector that links the receptor to its transcriptional response. Although key functional regions have been identified in each class of proteins, the mechanism for signal transduction is not yet understood. Diverse regulatory mechanisms influence signaling by the LIN-12/Notch pathway. Inductive signaling relies on the synthesis of ligand and receptor in distinct but neighboring cells. By contrast, lateral signaling leads to the transformation of equivalent cells that express both ligand and receptor into nonequivalent cells that express either ligand or receptor. This transformation appears to rely on regulatory feedback loops within the LIN-12/Notch pathway. In addition, the pathway can be regulated by intrinsic factors that are asymmetrically segregated during cell division or by extrinsic cues via other signaling pathways. Specificity in the pathway does not appear to reside in the particular ligand or receptor used for a given cell-cell interaction. The existence of multiple ligands and receptors may have evolved from the stringent demands placed upon the regulation of genes encoding them.
One‐Dimensional SDS Gel Electrophoresis of Proteins (2006)

Electrophoresis is used to separate complex mixtures of proteins (e.g., from cells, subcellular fractions, column fractions, or immunoprecipitates), to investigate subunit compositions, and to verify homogeneity of protein samples. It can also serve to purify proteins for use in further applications. In polyacrylamide gel electrophoresis, proteins migrate in response to an electrical field through pores in a polyacrylamide gel matrix; pore size decreases with increasing acrylamide concentration. The combination of pore size and protein charge, size, and shape determines the migration rate of the protein. In this unit, the standard Laemmli method is described for discontinuous gel electrophoresis under denaturing conditions, that is, in the presence of sodium dodecyl sulfate (SDS). Both full-size and minigel formats are detailed. Several modifications are provided for specific applications. For separation of peptides and small proteins, the standard buffers are replaced with either a Tris-tricine buffer system or a modified Tris buffer in the absence of urea. Continuous SDS-PAGE is a simplified method in which the same buffer is used for both the gel and electrode solutions and the stacking gel is omitted. Other protocols cover the preparation and use of ultrathin gels and gradient gels, and the simultaneous preparation of multiple gels.
α-Turn Mimetics:  Short Peptide α-Helices Composed of Cyclic Metallopentapeptide Modules (2004)

Alpha-Helices are key structural components of proteins and important recognition motifs in biology. Short peptides (<or=15 residues) corresponding to these helical sequences are rarely helical away from their stabilizing protein environments. New techniques for stabilizing short peptide helices could be valuable for studying protein folding, modeling proteins, creating artificial proteins, and may aid the design of inhibitors or mimics of protein function. This study reports the facile incorporation of 3- and 4-alpha turns in 10-15 residue peptides through formation in situ of multiple cyclic metallopeptide modules [Pd(en)(H*XXXH*)](2+). The nonhelical peptides Ac-H*ELTH*H*VTDH*-NH(2) (1), Ac-H*ELTH*AVTDYH*ELTH*-NH(2) (2), and Ac-H*AAAH*HELTH*H*VTDH*-NH(2) (3) (H is histidine-methylated at imidazole-N3) react in N,N-dimethylformamide (DMF) or water with 2, 2, and 3 molar equivalents, respectively, of [Pd(en)(NO(3))(2)] to form exclusively [Pd(2)(en)(2)(Ac-H*ELTH*H*VTDH*-NH(2))](4+) (4), [Pd(2)(en)(2)(Ac-H*ELTH*AVTDYH*ELTH*-NH(2))](4+) (5), and [Pd(3)(en)(3)(Ac-H*AAAH*HELTH*H*VTDH*-NH(2))](6+) (6), characterized by mass spectrometry, 1D and 2D (1)H- and 1D (15)N-NMR spectroscopy. Despite the presence of multiple histidines and other possible metal-binding residues in these peptides, 2D (1)H NMR spectra reveal that Pd(en)(2+) is remarkably specific in coordinating to imidazole-N1 of only (i, i + 4) pairs of histidines (i.e., only those separated by three amino acids), resulting in 4-6 made up of cyclic metallopentapeptide modules ([Pd(en)(H*XXXH*)](2+))(n), n = 2, 2, 3, respectively, each cycle being a 22-membered ring. We have previously shown that a single metallopentapeptide can nucleate alpha-helicity (Kelso et al., Angew. Chem., Int. Ed. 2003, 42, 421-424.). We now demonstrate its use as an alpha-turn-mimicking module for the facile conversion of unstructured short peptides into helices of macrocycles and provide 1D and 2D NMR spectroscopic data, structure calculations via XPLOR and NMR analysis of molecular flexibility in solution (NAMFIS), and CD spectra in support of the alpha-helical nature of these monomeric metallopeptides in solution.
Available and emerging treatments for Parkinson&rsquo;s disease: a review (2011)

Parkinson's disease is a commonly encountered neurodegenerative disorder primarily found in aged populations. A number of medications are available to control symptoms, although these are less effective in advanced disease. Deep brain stimulation provides a practicable alternative at this stage, although a minority of patients meet the strict criteria for surgery. Novel medications that provide enhanced symptomatic control remain in developmental demand. Both gene and cell-based therapies have shown promise in early clinical studies. A major unmet need is a treatment that slows or stops disease progression.
The COMBINE SAFTEE: a structured instrument for collecting adverse events adapted for clinical studies in the alcoholism field. (2005)

Due to its high standardization level, the COMBINE SAFTEE could be incorporated into other brief compliance enhancement strategies in clinical studies to assess the efficacy of putative therapeutic drugs.
Pulmonary nodules: effect of increased data sampling on detection with spiral CT and confidence in diagnosis. (1995)

Increased reconstruction frequency of spiral CT volume data sets improves detection of pulmonary nodules and enhances confidence in the diagnosis.
G-CSF Therapy of Ongoing Experimental Allergic Encephalomyelitis Via Chemokine- and Cytokine-Based Immune Deviation (2002)

Converging evidence that G-CSF, the hemopoietic growth factor of the myeloid lineage, also exerts anti-inflammatory and pro-Th2 effects, prompted us to evaluate its direct therapeutic potential in autoimmune diseases. Here we report a novel activity of G-CSF in experimental allergic encephalomyelitis, a murine model for multiple sclerosis, driven by Th1-oriented autoaggressive cells. A short 7-day treatment with G-CSF, initiated at the onset of clinical signs, provided durable protection from experimental autoimmune encephalomyelitis. G-CSF-treated mice displayed limited demyelination, reduced recruitment of T cells to the CNS, and very discrete autoimmune inflammation, as well as barely detectable CNS mRNA levels of cytokines and chemokines. In the periphery, G-CSF treatment triggered an imbalance in the production by macrophages as well as autoreactive splenocytes of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1, the prototypical pro-Th1 and pro-Th2 CC chemokines, respectively. This chemokine imbalance was associated with an immune deviation of the autoreactive response, with reduced IFN-gamma and increased IL-4 and TGF-beta1 levels. Moreover, G-CSF limited the production of TNF-alpha, a cytokine also associated with early CNS infiltration and neurological deficit. These findings support the potential application of G-CSF in the treatment of human autoimmune diseases such as multiple sclerosis, taking advantage of the wide clinical favorable experience with this molecule.
Altered CD4+/CD8+ T-Cell Ratios in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis (2006)

Natalizumab treatment alters the CSF CD4(+)/CD8(+) ratio. Lower expression of unbound alpha4 integrin on CD4(+) T cells is one possible mechanism. These results may have implications for the observation that some natalizumab-treated patients with MS developed progressive multifocal leukoencephalopathy.
Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21. (1995)

Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity. The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type IIFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16INK4A) and CDKN2B (p15INK4B), and several CpG islands. In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2.5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3' untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8-kDa protein in the pet gene (coding for cytochrome bc1 complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequence of this gene suggest that it codes for the MTAP enzyme.
The state of family medicine. (2012)

This special report reviews the value of family medicine, the challenges it faces, and AAFP data on the nature of family medicine practice today.
Axonal injury in multiple sclerosis (2003)

Renewed interest in axonal destruction in MS

Multiple sclerosis (MS) is an inflammatory demyelinating disease, which implies that myelin sheaths are the primary target in the destructive process. However, this primary demyelinating process is inevitably associated with axonal injury and destruction, which is variable in its extent between different plaques of the same patients and even more variable between lesions of different patients. Axonal pathology has been noted in the earliest pathological descriptions of the disease and its cause and functional consequences have been discussed in detail in the early 20th century.1 However, when it became clear from experimental studies that an inflammatory demyelinating disease similar to MS can be induced by autoimmunity against myelin antigens, the interest in axonal injury vanished. It only reappeared when recent MRI investigations provided increasing evidence for axonal and neuronal loss in MS brains.1

Detailed quantitative studies on axonal injury and loss in MS appeared in the late 1990s. Using amyloid precursor protein (APP) as a marker for acute axonal injury Ferguson et al showed that massive axonal damage occurs during the stage of active demyelination in fresh lesions.2 Similar conclusions were reached by Trapp et al studying axonal transsections in MS lesions by confocal laser microscopy.3 In addition, these studies confirmed earlier observations that acute axonal injury correlated with the degree of macrophage infiltration in the lesions and that macrophages were closely attached to damaged axons.2–4 These basic observations were extended in several ways by Kornek et al .5 In this study the quantity of acute axonal injury was correlated with lesional stages, defined by the presence and antigenic composition of myelin debris in macrophages. These data suggested that massive acute axonal injury occurs during a small time window of about two weeks after onset of …
The Role of Inattention on Academics, Fluid Reasoning, and Visual–Spatial Functioning in Two Subtypes of ADHD (2012)

The purpose of this study was to determine whether subtype differences and the role of inattention in children with attention-deficit hyperactivity disorder-combined type (ADHD-C) and ADHD-predominately inattentive type (ADHD-PI) and controls on measures of achievement, problem solving, and visual-spatial abilities are present. A secondary purpose was to evaluate the relation between ADHD symptoms and performance on visual-spatial-motor tasks. Children with ADHD-C and ADHD-PI and controls, all aged 8 to 16 years old, were compared on tests of achievement, fluid reasoning, and visual-motor skills. Children with ADHD-C and ADHD-PI performed significantly poorer on the mathematics calculation, written expression, fluid reasoning, and visual-motor tests compared with the controls. Inattention, but not hyperactivity or impulsivity, was found to significantly predict performance on these measures. The role of inattention on these tasks is important for understanding why children with both subtypes of ADHD experience significant academic problems even when performing in the average range on achievement tests.
Characterization of Asphaltene Transport over Geologic Time Aids in Explaining the Distribution of Heavy Oils and Solid Hydrocarbons in Reservoirs (2014)

Abstract Asphaltenes are a very important component of reservoir fluids. They have a huge impact on crude oil viscosity and are a Flow Assurance concern. They can undergo a phase transition, giving rise to tar mats that seal aquifers precluding aquifer sweep. Local tar deposits can act as a drilling hazard. Upstructure tar (or bitumen) deposition can occur which can flow with produced light hydrocarbons greatly reducing the productivity index. In EOR, miscible gas injection can also give rise to asphaltene deposition. Characterizing these disparate observations is now performed within a simple overarching framework. Here, we combine asphaltene nanoscience, thermodynamics, and fluid mechanics to model asphaltene-rich fluid flow and asphaltene deposition that occur in reservoirs in geologic (or even production) time. This analysis successfully accounts for extensive measurements in several reservoirs in different stages of similar processes. Reservoir black oils with a late, light hydrocarbon charge experience asphaltene instability. This instability does not necessarily cause precipitation; instead, weak instability can cause a change in the nanocolloidal character of asphaltenes without precipitation. Consequently, this less stable asphaltene remains in the crude oil and is thus mobile. This process can result in fluid density inversions and gravity currents that pump asphaltene ‘clusters’ in oil over reservoir length scales relatively quickly in geologic time. These asphaltene clusters then establish very large asphaltene and viscosity gradients at the base of the reservoir. If the light hydrocarbon instability event continues, a regional tar mat can form. In contrast, if the light hydrocarbon charge is sufficiently rapid, the displacement of the contact between the original and new reservoir fluids overtakes and precipitates asphaltenes locally producing deposition upstructure often near the crest of the field. In this paper, several reservoirs are examined. Two reservoirs have massive, current gas charge and have bitumen deposition upstructure. Another reservoir is shown to be midway through a slower gas charge, with the asphaltene instability causing migration of asphaltenes from the top to the base of the oil column in the form of clusters creating large asphaltene gravity gradients. Another reservoir is shown to have this process completed yielding a 50 meter column of heavy oil at the base of the oil column underlain by a 10 meter regional tar mat. This integrated analysis enables a much simpler understanding of many production issues associated with asphaltenes and provides a way forward for treating disparate asphaltene problems within a single framework.
Energy control for long lifetime photovoltaic ac module inverter (2006)

Photovoltaic power generation is spreading all around the globe with increasing support from the public and governments. Among the obstacles yet to overcome are higher cell efficiency, lower cost, and longer lifetime. The latter is the focus of the research presented here as it provides an alternative photovoltaic ac module inverter with long lifetime. Four commercial inverters analyzed in our laboratory contained electrolytic capacitors whose lifetimes are limited to 12000 hours. In the proposed solution these components are obviated by using an energy control scheme that stores all the energy fluctuation in the dc-link polypropylene capacitor. The energy control strategy has been applied in a prototype power conditioning unit that comprises a phase-shift full-bridge dc-ac-dc converter connected in series with a current source inverter. The grid current magnitude is controlled using a proportional derivative compensator that maintains the average value of the dc-link capacitor at a voltage level of 475V, while allowing oscillations with a peak value of 125V. Simultaneously, a pulse-width-modulation integrated circuit controller maintains a steady dc voltage at the photovoltaic panel's terminals, hence enhancing the performance of the maximum power point tracking algorithm. The sinusoidal shape of the current injection is attained using current-mode-control. It is shown that the converter operates at high efficiency and that the energy fluctuation is absorbed at the dc-link capacitor. In addition, it is shown that the perturb and observe maximum power point tracking algorithm performs well over a day of variable irradiance conditions.