gebhart/patrepeval huggingface dataset:
Gut microbes promote colonic serotonin production through an effect of short‐chain fatty acids on enterochromaffin cells (2014)

Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concentrations (GF, 17 ± 3 ng/mg; HM, 25 ± 2 ng/mg; and CR, 35 ± 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis.
Optimization of an integrated and automated macro inspection system for the utilization of wafer color variation detection in a photolithography cluster (2006)

The IBM 300 mm wafer manufacturing line provides a case study for the optimization of an automated macro defect inspection system to accurately flag global wafer color variation. The IBM inspection system was falsely flagging a large number of wafers primarily for global wafer color variation, leading to unacceptable amounts of production volume being placed on hold. A review of the macro inspection system identified several areas for improvement. An investigation into the installed hardware base found a panel behind the beam splitter was introducing noise through reflected light. This panel was replaced with a less reflective material. A review of the failed wafers found that maximum light levels were not achieved across all tools and an improved diffuser plate for the fiber optic output was designed to improve light transmittance. Global wafer color is determined by comparing the scanned wafer image to a "golden" data set, referred to as a "color baselist," which is composed of data from 30 wafers. A review of the recipe baselists revealed that some of the wafer samples did not accurately represent process conditions, and new wafer samples were collected. Finally, a tool-to-tool matching test revealed that the set of weightings given to each of the color parameters in the baselists was not optimized. After implementing the above changes, false global wafer color failures were virtually eliminated.
IEEE 802.11n MAC frame aggregation mechanisms for next-generation high-throughput WLANs (2008)

IEEE 802.11n is an ongoing next-generation wireless LAN standard that supports a very highspeed connection with more than 100 Mb/s data throughput measured at the medium access control layer. This article investigates the key MAC enhancements that help 802.11n achieve high throughput and high efficiency. A detailed description is given for various frame aggregation mechanisms proposed in the latest 802.11n draft standard. Our simulation results confirm that A-MSDU, A-MPDU, and a combination of these methods improve extensively the channel efficiency and data throughput. We analyze the performance of each frame aggregation scheme in distinct scenarios, and we conclude that overall, the two-level aggregation is the most efficacious.
Exploring Microfluidic Routes to Microgels of Biological Polymers (2007)

Abstract Polymer microgels in the size range from several micrometers to hundreds of micrometers are used in the pharmaceutical, cosmetics, nutrition, pesticide, and food industries, as well as in the encapsulation of cells. To date, a broad range of strategies for the generation of polymer microgels exist, however, these methods involve multistage processes, do not utilize biocompatible components or do not allow precise control of the dimensions and internal structure of the microgels. Recently, microfluidic strategies for the production of polymer particles have offered precise control over the shapes, morphologies, and size distributions of polymer colloids. This paper discusses the most recent results obtained by the authors in the area of the microfluidic production of biopolymer microgels. It provides a brief review of the microfluidic methods for the continuous synthesis and fabrication of microgels, sets the criteria for the successful microfluidic generation of biomicrogels, and describes two methods for the preparation of microgels by microfluidic means. The article concludes with a summary and an outlook. magnified image
Substructure similarity search in graph databases (2005)

Advanced database systems face a great challenge raised by the emergence of massive, complex structural data in bioinformatics, chem-informatics, and many other applications. The most fundamental support needed in these applications is the efficient search of complex structured data. Since exact matching is often too restrictive, similarity search of complex structures becomes a vital operation that must be supported efficiently.In this paper, we investigate the issues of substructure similarity search using indexed features in graph databases. By transforming the edge relaxation ratio of a query graph into the maximum allowed missing features, our structural filtering algorithm, called Grafil, can filter many graphs without performing pairwise similarity computations. It is further shown that using either too few or too many features can result in poor filtering performance. Thus the challenge is to design an effective feature set selection strategy for filtering. By examining the effect of different feature selection mechanisms, we develop a multi-filter composition strategy, where each filter uses a distinct and complementary subset of the features. We identify the criteria to form effective feature sets for filtering, and demonstrate that combining features with similar size and selectivity can improve the filtering and search performance significantly. Moreover, the concept presented in Grafil can be applied to searching approximate non-consecutive sequences, trees, and other complicated structures as well.
Penetration of Nonenveloped Viruses into the Cytoplasm (2007)

Although the precise mechanism by which nonenveloped viruses penetrate biological membranes is unclear, a more coherent understanding of this process is starting to emerge. To initiate membrane penetration, nonenveloped viruses engage host cell factors that impart conformational changes on the viral particles, resulting in the exposure of a hydrophobic moiety or the release of a lytic factor. The viruses' interactions with the limiting membrane subsequently compromise the bilayer integrity. This reaction presumably perforates the bilayer to enable the virus to cross the membrane and reach the cytosol. Valuable insights into this process can be gleaned from the membrane transport mechanisms of enveloped viruses and bacterial toxins. To identify systematically the cellular components that facilitate nonenveloped virus membrane penetration, sensitive assays that monitor the transport event directly must first be established. Moreover, higher-resolution structures of penetration intermediates, particularly those solved in complex with membranes, would provide important molecular details into this process.
Antibody engineering & therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA (2016)

The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries.
Class II box consensus sequences in the HLA-DR alpha gene: transcriptional function and interaction with nuclear proteins. (1989)

The promoter regions of class II major histocompatibility complex genes contain two highly conserved sequences, the X and Y boxes, which may be involved in the control of class II gene expression. In this study, we correlate in vivo functional assays for cis-acting regulatory elements in the HLA-DR alpha gene with in vitro binding assays for trans-acting regulatory proteins. Mutagenesis and transient transfection analyses indicated that both the X and Y boxes were important for HLA-DR alpha promoter function in a B lymphoblastoid cell line. Although specific nuclear protein interactions with the X consensus sequence were not apparent, the Y box, which contained an inverted CCAAT sequence, did bind specifically to at least one nuclear protein. This Y box-binding protein was present in nuclear extracts of all cell types examined, including human B and T cells and HeLa cells. The molecular mass of the protein, as determined by photoactivated protein-DNA cross-linking, was approximately 40 to 50 kilodaltons. Mutagenesis of the Y box that decreased protein binding also decreased promoter activity, implying that protein binding to this DNA sequence is important for DR alpha promoter function.
Acoustic characterisation of film splitting in a HSWO printing nip (2007)

An acoustic technique for investigation of ink film splitting was further developed and applied to monitor printing of light weight coated (LWC) papers on a heat-set web offset (HSWO) press. The ...
Critical binding and regulatory interactions between Ras and Raf occur through a small, stable N-terminal domain of Raf and specific Ras effector residues. (1994)

Genetic and biochemical evidence suggests that the Ras protooncogene product regulates the activation of the Raf kinase pathway, leading to the proposal that Raf is a direct mitogenic effector of activated Ras. Here we report the use of a novel competition assay to measure in vitro the relative affinity of the c-Raf-1 regulatory region for Ras-GTP, Ras-GDP, and 10 oncogenic and effector mutant Ras proteins. c-Raf-1 associates with normal Ras and the oncogenic V12 and L61 forms of Ras with equal affinity. The moderately transforming mutant Ras[E30K31] also bound to the c-Raf-1 regulatory region with normal affinity. Transformation-defective Ras effector mutants Ras[N33], Ras[S35], and Ras[N38] bound poorly. In contrast, the transformation defective Ras[G26I27] and Ras[E45] mutants bound to the c-Raf-1 regulatory region with nearly wild-type affinity. A stable, high-affinity Ras-binding region of c-Raf-1 was mapped to a 99-amino-acid subfragment of the first 257 residues. The smallest Ras-binding region identified consisted of N-terminal residues 51 to 131, although stable expression of the domain and high-affinity binding were improved by the presence of residues 132 to 149. Deletion of the Raf zinc finger region did not reduce Ras-binding affinity, while removal of the first 50 amino acids greatly increased affinity. Phosphorylation of Raf[1-149] by protein kinase A on serine 43 resulted in significant inhibiton of Ras binding. demonstrating that the mechanism of cyclic AMP downregulation results through structural changes occurring exclusively in this small Ras-binding domain.
Hormone-Dependent β-Casein mRNA Stabilization Requires Ongoing Protein Synthesis (1989)

The role of ongoing protein synthesis in mediating the posttranscriptional effects of hormones on casein gene expression in the COMMA D mouse mammary epithelial cell line was investigated using the protein synthesis inhibitors, cycloheximide and anisomycin. When COMMA D cells were pretreated with insulin and PRL for 24 h, the addition of glucocorticoids induced a greater than 20-fold increase in beta-casein mRNA accumulation with an apparent lag of greater than 8 h. Addition of cycloheximide and anisomycin not only prevented this increase, but unexpectedly, resulted in the rapid disappearance of preexisting beta-casein mRNA with a half-life of approximately 2 h. Under the same conditions, the levels of beta-actin and histone H4 mRNAs were increased markedly. In contrast, when cells were pretreated with all three lactogenic hormones for 48 h before the addition of either protein synthesis inhibitors or actinomycin D, the effects of these inhibitors on the levels of beta-casein mRNA were greatly diminished. This differential sensitivity of beta-casein mRNA to protein synthesis inhibitors was observed only in cells pretreated for greater than 24 h with all three hormones. Experiments performed in the absence of inhibitors indicated that beta-casein mRNA has a long half-life even after hormone withdrawal. These results suggest that hormone-dependent stabilization of cytoplasmic beta-casein mRNA requires ongoing protein synthesis. Cells cultured in the presence of all three lactogenic hormones slowly accumulate a labile protein(s), which exerts a selective effect on casein mRNA stability.
Fixed Abrasive Diamond Wire Saw Slicing of Single-Crystal Silicon Carbide Wafers (2004)

Abstract This article investigates the slicing of single-crystal silicon carbide (SiC) with a fixed abrasive diamond wire. A spool-to-spool rocking motion diamond wire saw machine using a 0.22 mm nominal diameter diamond wire with 20 µm average size diamond grit was used. The effect of wire downfeed speed on wafer surface roughness and subsurface damage was first investigated. The surface marks generated by loose diamond grit and stagnation of the wire during the change of the wire-cutting direction were studied. The use of scanning acoustic microscopy (SAcM) as a nondestructive evaluation method to identify the subsurface damage was explored. Effects of using a new diamond wire on cutting forces and surface roughness were also investigated. Scanning electron microscopy has been used to examine the machined surfaces and wire wear. This study demonstrated the feasibility of fixed abrasive diamond wire cutting of SiC wafers and the usage of a SAcM to examine the subsurface damage.
Transcutaneous spinal cord direct current stimulation inhibits the lower limb nociceptive flexion reflex in human beings (2010)

Aiming at developing a new, noninvasive approach to spinal cord neuromodulation, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in the central pain pathways in human beings. A double-blind crossover design was used to investigate the effects of anodal direct current (2mA, 15min) applied on the skin overlying the thoracic spinal cord on the lower-limb flexion reflex in a group of 11 healthy volunteers. To investigate whether transcutaneous spinal cord DC stimulation (tsDCS) acts indirectly on the nociceptive reflex by modulating excitability in mono-oligosynaptic segmental reflex pathways, we also evaluated the H-reflex size from soleus muscle after tibial nerve stimulation. In our healthy subjects, anodal thoracic tsDCS reduced the total lower-limb flexion reflex area by 40.25% immediately after stimulation (T0) and by 46.9% 30min after stimulation offset (T30). When we analyzed the 2 lower-limb flexion reflex components (RII tactile and RIII nociceptive) separately, we found that anodal tsDCS induced a significant reduction in RIII area with a slight but not significant effect on RII area. After anodal tsDCS, the RIII area decreased by 27% at T0 and by 28% at T30. Both sham and active tsDCS left all the tested H-reflex variables unchanged. None of our subjects reported adverse effects after active stimulation. These results suggest that tsDCS holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain. Thoracic transcutaneous direct current stimulation induces depression of nociceptive lower limb flexion reflex in human beings that persists after stimulation offset; this form of stimulation holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain.
Context dependent recurrent neural network language model (2012)

Recurrent neural network language models (RNNLMs) have recently demonstrated state-of-the-art performance across a variety of tasks. In this paper, we improve their performance by providing a contextual real-valued input vector in association with each word. This vector is used to convey contextual information about the sentence being modeled. By performing Latent Dirichlet Allocation using a block of preceding text, we achieve a topic-conditioned RNNLM. This approach has the key advantage of avoiding the data fragmentation associated with building multiple topic models on different data subsets. We report perplexity results on the Penn Treebank data, where we achieve a new state-of-the-art. We further apply the model to the Wall Street Journal speech recognition task, where we observe improvements in word-error-rate.
Evaluation of Fatty Acid Extraction Methods for Thraustochytrium sp. ONC-T18 (2007)

Various extraction methods were assessed in their capacity to extract fatty acids from a dried biomass of Thraustochytrium sp. ONC-T18. Direct saponification using KOH in ethanol or in hexane:ethanol was one of the most efficient techniques to extract lipids (697 mg g(-1)). The highest amount of fatty acids (714 mg g(-1)) was extracted using a miniaturized Bligh and Dyer extraction technique. The use of ultrasonics to break down cell walls while extracting with solvents (methanol:chloroform) also offered high extraction yields of fatty acids (609 mg g(-1)). Moreover, when the transesterification mixture used for a direct transesterification method was doubled, the extraction of fatty acids increased approximately 77% (from 392 to 696 mg g(-1)). This work showed that Thraustochytrium sp. ONC-T18 has the ability to produce over 700 mg g(-1) of lipids, including more than 165 mg g(-1) of docosahexaenoic acid, which makes this microorganism a potential candidate for the commercial production of polyunsaturated fatty acids. Finally, other lipids, such as myristic, palmitic, palmitoleic, and oleic acids, were also produced and recovered in significant amounts (54, 196, 123, and 81 mg g(-1)), respectively.
Maintenance of p53 alterations throughout breast cancer progression. (1991)

Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein. In this study different stages of breast cancer progression were examined, from in situ to metastatic disease, to determine at what stage mutational activation occurs and whether it is maintained during tumor progression. Two (13%) of 15 pure intraductal tumors expressed high levels of p53 in all malignant epithelial cells. Sequencing of p53 mRNA from one of these tumors demonstrated a nucleotide substitution altering the amino acid composition of the protein. Six (17%) of 35 specimens which contained both in situ and invasive disease expressed high levels of p53. All malignant epithelial cells in these 6 cases stained positively and in no specimen did one component express different levels of the protein than the other growth phase. Sequence analysis of a tissue with significant amounts of both in situ and invasive disease revealed only a single point mutation, without evidence of wild-type nucleotide at the site of substitution, suggesting that p53 mRNA from each component of the tumor contained the same nucleotide substitution. Eleven (50%) of 22 pairs of primary tumors and their lymph node metastases expressed elevated levels of p53, and in each case, expression levels were identical in the primary and secondary sites. Identical mutations were found in the p53 mRNA from two paired primary and metastatic sites. Therefore, mutation within a highly conserved region of the p53 gene leading to overexpression of the protein product can occur in the earliest recognized phase of breast cancer and this alteration is maintained during progression from intraductal to infiltrating carcinoma. Mutations are also conserved during the process of metastatic spread.
[Analysis of differentially expressed proteome in urine  from non-small cell lung cancer patients]. (2015)

LRG1 and CA1 are abundant in urine in patients with NSCLC, while VPS4B and YWHAZ are low-abundance proteins. They could be regarded as biomarkers for early screening, monitoring prognosis and evaluating therapy of patients with NSCLC because of differential expression. The sensitivity of the four biomarkers of NSCLC is relatively low when they are used to screen or diagnose independently, while significantly improvement if they were in combined pattern, which will be of excellent applications to clinical diagnosis and treatment.
MCL-1–dependent leukemia cells are more sensitive to chemotherapy than BCL-2–dependent counterparts (2009)

Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on Emu-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL-1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1-dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity.