gebhart/patrepeval huggingface dataset:
Using Feature Construction to Improve the Performance of Neural Networks (1998)

Recent years have seen the growth in popularity of neural networks for business decision support because of their capabilities for modeling, estimating, and classifying. Compared to other AI methods for problem solving such as expert systems, neural network approaches are especially useful for their ability to learn adaptively from observations. However, neural network learning performed by algorithms such as back-propagation (BP) are known to be slow due to the size of the search space involved and also the iterative manner in which the algorithm works. In this paper, we show that the degree of difficulty in neural network learning is inherent in the given set of training examples. We propose a technique for measuring such learning difficulty, and then develop a feature construction methodology that helps transform the training data so that both the learning speed and classification accuracy of neural network algorithms are improved. We show the efficacy of the proposed method for financial risk classification, a domain characterized by frequent data noise, lack of functional structure, and high attribute interactions. Moreover, the empirical studies also provide insights into the structural characteristics of neural networks with respect to the input data used as well as possible mechanisms to improve the learning performance.
Automated Volumetric Analysis of Interface Fluid in Descemet Stripping Automated Endothelial Keratoplasty Using Intraoperative Optical Coherence Tomography (2014)

Quantitative analysis of iOCT volumetric scans shows the significant effect of controlled pressure elevation and corneal sweep on graft apposition in DSAEK. Computerized iOCT analysis yields objective measurements of interface fluid intraoperatively, which provides information on anatomic outcomes and could be used in future trials.
Laparoscopic excision of ovarian neoplasms subsequently found to be malignant (1992)

One hundred fifty-six members and candidate members of the Society of Gynecologic Oncologists responded to a survey concerning the "laparoscopic management of ovarian neoplasms subsequently found to be malignant." Twenty-nine responders (19%) reported a total of 42 cases of ovarian malignancy. The laparoscopic procedure was aborted or the cyst was aspirated in 38% of the cases, and partial or complete excisions were attempted in 33 and 29%, respectively. The characteristics of the masses were as follows: less than 8 cm 67%, cystic 62%, unilocular 48%, and unilateral 81%. All four "benign" characteristics were present in 31% of the cases found to be malignant, and three of four characteristics were present in 24%. Laparotomy was performed at the time of laparoscopy in 17% of cases, after laparoscopy in 71% with an average interval of 4.8 weeks, and not at all in 12%. Fifty-seven percent of the cases were invasive epithelial malignancies, whereas 29% were tumors of low malignant potential. At least 50% of the patients had stages II-IV. We conclude that attempted laparoscopic excisions of adnexal masses that are subsequently found to be malignant are not uncommon, and that the presence of so-called "benign" characteristics does not preclude malignancy. Attempts at partial or complete excision are common, as are delays in subsequent definitive surgery. The stage of disease is often advanced, and all histologic types of malignancy are encountered. We advocate careful evaluation of this practice, with development of strict guidelines to ensure optimal patient care.
Peak-to-average power reduction in space division multiplexing based OFDM systems through spatial shifting (2005)

A new method to reduce the peak-to-average power ratio (PAPR) in space division multiplexing systems applying orthogonal frequency division multiplexing is proposed. The method applies spatial shifting to partial transmit sequences to achieve a decreased PAPR on all transmit branches.
Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. (1992)

We have investigated the cell surface recognition mechanisms used by human monocyte-derived macrophages (MO ) in phago- cytosis of intact aging human neutrophils (PMNs) undergoing apoptosis. This study shows that the adhesive protein thrombo- spondin (TSP) was present in the interaction, both associated with the MO surface and in solution at a mean concentration of 0.59 ,g/ml. The interaction was inhibited by treatment of MO (but not aged PMN) with cycloheximide, but could be "res- cued" by replenishment with exogenous TSP. Under control conditions, MO recognition of aged PMNs was specifically po- tentiated by purified platelet TSP at 5 ,g/ml, present either in the interaction or if preincubated with either cell type, suggest- ing that TSP might act as a "molecular bridge" between the two cell types. In support, both aged PMN and MO were found to adhere to TSP, and phagocytosis of aged PMN was specifically inhibited by (a) excess soluble TSP; (b) antibodies to TSP that also inhibit TSP-mediated adhesion to aged PMN; and (c) down-regulation of M4 receptors for TSP by plating MO on TSP-coated surfaces. Furthermore, inhibition with mAbs / Arg-Gly-Asp-Ser peptide of the candidate MO receptors for TSP, CD36, and a,83 exerted synergistic effects on both MO recognition of aged PMN and MO adhesion to TSP, indicating that "two point" adhesion of TSP to these MO structures is involved in phagocytosis of aged PMN. Our findings indicate newly defined roles for TSP and CD36 in phagocytic clearance of senescent neutrophils, which may limit inflammatory tissue injury and promote resolution. ( J. Clin. Invest.
IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. (1988)

rIL-6/B cell stimulatory factor 2 was found to augment CTL generation from mature as well as immature human T cells stimulated with UV-treated allogeneic cells. rIL-6 also acted on peanut agglutinin-positive murine thymocytes and Lyt-2-positive splenic T cells to give rise to CTL. rIL-6 alone could not induce CTL generation, the presence of IL-2 during the early phase of culture period was found to be essential for the IL-6 activity in the induction of CTL. The effect of rIL-6 was not mediated by the induction of IL-2 inasmuch as rIL-6 did not augment IL-2 production in MLC and anti-IL-2 antibody could not neutralize IL-6 activity. rIL-6 augmented CTL generation even when added 72 h after the initiation of cultures. The enhancing activity of rIL-6 could be neutralized with anti-IL-6 antibodies even when added 72 h after the initiation of cultures. The present data indicate that IL-6 acts in the late phase of CTL generation.
A DNA‐Based Machine That Can Cyclically Bind and Release Thrombin (2004)

A DNA aptamer structure is the basis of a molecular machine that can be instructed to grab or release the human blood-clotting factor α-thrombin, depending on the operator DNA sequence addressing it. In the picture the aptamer structure, which assumes a conformation characterized by two stacked guanine quadruplex structures, is linked to thrombin (gray ellipse).
Genome-Wide Reprogramming in Hybrids of Somatic Cells and Embryonic Stem Cells (2007)

Recent experiments demonstrate that somatic nuclei can be reprogrammed to a pluripotent state when fused to ESCs. The resulting hybrids are pluripotent as judged by developmental assays, but detailed analyses of the underlying molecular-genetic control of reprogrammed transcription in such hybrids are required to better understand fusion-mediated reprogramming. We produced hybrids of mouse ESCs and fibroblasts that, although nearly tetraploid, exhibit characteristics of normal ESCs, including apparent immortality in culture, ESC-like colony morphology, and pluripotency. Comprehensive analysis of the mouse embryonic fibroblast/ESC hybrid transcriptome revealed global patterns of gene expression reminiscent of ESCs. However, combined analysis of variance and hierarchical clustering analyses revealed at least seven distinct classes of differentially regulated genes in comparisons of hybrids, ESCs, and somatic cells. The largest class includes somatic genes that are silenced in hybrids and ESCs, but a smaller class includes genes that are expressed at nearly equivalent levels in hybrids and ESCs that contain many genes implicated in pluripotency and chromatin function. Reprogrammed genes are distributed throughout the genome. Reprogramming events include both transcriptional silencing and activation of genes residing on chromosomes of somatic origin. Somatic/ESC hybrid cell lines resemble their pre-fusion ESC partners in terms of behavior in culture and pluripotency. However, they contain unique expression profiles that are similar but not identical to normal ESCs. ESC fusion-mediated reprogramming provides a tractable system for the investigation of mechanisms of reprogramming. Disclosure of potential conflicts of interest is found at the end of this article.
PKD2 , a Gene for Polycystic Kidney Disease That Encodes an Integral Membrane Protein (1996)

A second gene for autosomal dominant polycystic kidney disease was identified by positional cloning. Nonsense mutations in this gene (PKD2) segregated with the disease in three PKD2 families. The predicted 968-amino acid sequence of the PKD2 gene product has six transmembrane spans with intracellular amino- and carboxyl-termini. The PKD2 protein has amino acid similarity with PKD1, the Caenorhabditis elegans homolog of PKD1, and the family of voltage-activated calcium (and sodium) channels, and it contains a potential calcium-binding domain.
Temperature tuning of two-dimensional photonic crystals in the presence of phonons and a plasma of electrons and holes (2005)

We have theoretically studied the electromagnetic transmittance in finite samples of InSb-based two-dimensional photonic crystals. The cases of both $E$ and $H$ polarization were considered. Due to the temperature dependence of the intrinsic carrier concentration in the semiconductor, our square arrays of parallel InSb cylinders in air---or vice versa, parallel hollow cylinders in InSb---give rise to tunable transmission spectra. As the temperature increases from $200\phantom{\rule{0.3em}{0ex}}\text{to}\phantom{\rule{0.3em}{0ex}}290\phantom{\rule{0.3em}{0ex}}\mathrm{K}$, we find that the midgap frequencies move up in frequency while the widths of the gaps diminish, in agreement with the bulk band structure [see Halevi and Ramos-Mendieta, Phys. Rev. Lett. 85, 1875 (2000)]. The wave transmittance was calculated taking into account the dispersion due to phonons, as well as free charge carriers; absorptive mechanisms due to phonons, holes and electrons were also considered. We find that absorption affects considerably the transmittance intensity. In order to achieve significant tuning of the transmission, appropriate structural parameters and spectral regions are proposed. For select values of the frequency, even switching is possible, namely, the transmittance is finite for some value of the temperature and vanishes (or is very small) for a different value. We also proved that, for the plasma model with a background dielectric constant (as appropriate for a polar semiconductor), the band structure is determined by a standard eigenvalue problem. Application to hollow cylinders, forming a hexagonal lattice in InSb background, demonstrates the existence of a complete photonic gap---for both $E$ and $H$ polarizations---in a wide range of temperatures.
An integrated map of structural variation in 2,504 human genomes (2015)

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
Mutational analysis of the GAL4-encoded transcriptional activator protein of Saccharomyces cerevisiae. (1988)

The GAL4 protein of Saccharomyces cerevisiae binds to DNA upstream of each of six genes and stimulates their transcription. To locate regions of the protein responsible for these processes, we identified and characterized 88 gal4 mutations selected in vivo to reduce the ability to GAL4 protein to activate transcription. These mutations alter two regions of GAL4 protein: the DNA binding domain, and the transcription activation domain. Some mutations in the DNA binding domain that abolish the ability of GAL4 protein to bind to DNA in vitro change amino acid residues proposed to form a zinc finger, confirming that this structure is indeed involved in DNA binding. Four different amino acid changes in the zinc finger appear to reduce (but not abolish) the affinity of GAL4 protein for zinc ions, thereby identifying some of the amino acids involved in forming the zinc-binding structure. Several other mutations that abolish the DNA binding activity of the protein alter the 20 amino acids adjacent to the zinc finger, suggesting that these residues are part of the DNA binding domain. Two amino acid changes in the region adjacent to the zinc finger also appear to affect the ability of GAL4 protein to bind zinc ions, suggesting that this region of the protein can influence the structure of the zinc binding domain. The transcription activation domain of GAL4 protein is remarkably resistant to single amino acid changes: only 4 of the 42 mutations that alter this region of the protein are of the missense type. This observation is consistent with other lines of evidence that GAL4 protein possesses multiple transcription activation domains with unusual sequence flexibility.
Structure of the gene for the neuronal intermediate filament protein alpha-internexin and functional analysis of its promoter. (1991)

We have isolated the gene encoding the neuronal intermediate filament protein alpha-internexin using low stringency hybridization conditions and an NF-M (neurofilament middle molecular weight subunit) cDNA probe. This gene consists of three exons and two introns. The sequence data and the exon-intron organization of the gene establish its classification as a type IV intermediate filament gene. Transient transfection experiments showed that up to 5 kilobases of the alpha-internexin promoter region transcribed equally well in both the alpha-internexin-expressing and -nonexpressing cell lines. The results also demonstrated that the region from -77 to +73 relative to the transcription start site was sufficient for accurate basal transcription, but inclusion of the -254 to -78 region was required for efficient transcription. Sequence analysis shows that the -254 to -78 region contains several potential positive regulatory elements.
State of the Human Proteome in 2013 as Viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology- and Disease-Driven Human Proteome Project (2013)

The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics data sets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively - for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ∼14,000 Swiss-Prot entries, an increase over 2012 of ∼7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and is a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue.
tRNA properties help shape codon pair preferences in open reading frames (2006)

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three distinct and marked effects were revealed once codon and dipeptide biases had been subtracted. First, in the majority of genomes, codon pair preference is primarily determined by a tetranucleotide combination of the third nucleotide of the P-site codon, and all 3 nt of the A-site codon. Second, pairs of rare codons are generally under-used in eukaryotes, but over-used in prokaryotes. Third, the analysis revealed a highly significant effect of tRNA-mediated selection on codon pairing in unicellular eukaryotes, Bacillus subtilis, and the gamma proteobacteria. This was evident because in these organisms, synonymous codons decoded in the A-site by the same tRNA exhibit significantly similar P-site pairing preferences. Codon pair preference is thus influenced by the identity of A-site tRNAs, in combination with the P-site codon third nucleotide. Multivariate analysis identified conserved nucleotide positions within A-site tRNA sequences that modulate codon pair preferences. Structural features that regulate tRNA geometry within the ribosome may govern genomic codon pair patterns, driving enhanced translational fidelity and/or rate.
Metabolic reduction of naltrexone. I. Synthesis, separation and characterization of naloxone and naltrexone reduction products and qualitative assay of urine and bile following administration of naltrexone, alpha-naltrexol, or beta-naltrexol. (1975)

Reduction of naltrexone and naloxone with sodium borohydride gave a mixture (85:15) of the 6alpha- and 6beta-hydroxy epimers, alpha- and beta-naltrexol and alpha- and beta-naloxol, respectively. Each pair of epimers was separated by preparative thin-layer chromatography and the physical and spectral properties of each compound were determined. Previous assignments for the configuration of the epimers were verified. A semi-quantitative electron capture gas-liquid chromatographic method was devised for distinguishing either alpha- or beta-naltrexol in the presence of the other and in the presence of large amounts (at least 10-fold greater) of naltrexone. The method was used to determine the approximate weight ratio of beta-naltrexol to naltrexone present in enzymatically hydrolyzed urine samples. It was found that substantially greater quantities of beta-naltrexol and/or its conjugates were excreted in the urine of man, monkey, guinea pig and rabbit after administration of naltrexone, whereas very small quantities were excreted by the mouse, rat and dog. In contrast, just trace amounts of the 6alpha-hydroxy epimer, alpha-naltrexol, were detected in the urine of only 2 of the 7 species that had received naltrexone, i.e., monkey and guinea pig. After administration of 3H-15,16-naltrexone, 1 mg/kg, i.v. to the guinea pig, 25% of the radioactivity found following thin-layer chromatography of the extract of acid-hydrolyzed urine corresponded to beta-naltrexol. In gall bladder bile from the guinea pig, only conjugates of naltrexone and beta-naltrexol were found 2 hours after administration of naltrexone. Following administration of beta-naltrexol, 1 mg/kg, i.v. to guinea pigs only beta-naltrexol and/or its conjugates were detected in urine or bile. However, urine collected after administration of alpha-naltrexol, 1 mg/kg, i.v. to guinea pigs contained alpha-naltrexol and its conjugates, as well as a yet unidentified metabolite.
Are Persistently Symptomatic Vertebral Compression Fractures Associated With Abnormal Inflammatory Profiles? A Prospective Study (2010)

Diagnostic level of evidence II.
Preliminary efficacy of fluticasone delivered by a novel device in recalcitrant chronic rhinosinusitis (2010)

The OptiNose breath-actuated bi-directional delivery device administering fluticasone propionate (400 µg b.i.d.) is an effective and well tolerated treatment for recalcitrant CRS.
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution (2017)

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. VIDEO ABSTRACT.