gebhart/patrepeval huggingface dataset:
Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains (2014)

PDE4 family cAMP phosphodiesterases play a pivotal role in determining compartmentalised cAMP signalling through targeted cAMP breakdown. Expressing the widely found PDE4D5 isoform, as both bait and prey in a yeast 2-hybrid system, we demonstrated interaction consistent with the notion that long PDE4 isoforms form dimers. Four potential dimerization sites were uncovered using a scanning peptide array approach, where a recombinant purified PDE4D5 fusion protein was used to probe a 25-mer library of overlapping peptides covering the entire PDE4D5 sequence. Key residues involved in PDE4D5 dimerization were defined using a site-directed mutagenesis programme directed by an alanine scanning peptide array approach. Critical residues stabilising PDE4D5 dimerization were defined within the regulatory UCR1 region found in long, but not short, PDE4 isoforms, namely the Arg(173), Asn(174) and Asn(175) (DD1) cluster. Disruption of the DD1 cluster was not sufficient, in itself, to destabilise PDE4D5 homodimers. Instead, disruption of an additional interface, located on the PDE4 catalytic unit, was also required to convert PDE4D5 into a monomeric form. This second dimerization site on the conserved PDE4 catalytic unit is dependent upon a critical ion pair interaction. This involves Asp(463) and Arg(499) in PDE4D5, which interact in a trans fashion involving the two PDE4D5 molecules participating in the homodimer. PDE4 long isoforms adopt a dimeric state in living cells that is underpinned by two key contributory interactions, one involving the UCR modules and one involving an interface on the core catalytic domain. We propose that short forms do not adopt a dimeric configuration because, in the absence of the UCR1 module, residual engagement of the remaining core catalytic domain interface provides insufficient free energy to drive dimerization. The functioning of PDE4 long and short forms is thus poised to be inherently distinct due to this difference in quaternary structure.
The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis (1997)

Passive immunization with the monoclonal antibody 61BG1.3 selectively prevents colonization by Porphyromonas gingivalis in humans (Booth V, Ashley FP, Lehner T. Infect Immun 1996; 64:422-7). The protective MoAb recognizes the beta component of the RI protease of P. gingivalis which is formed by proteolytic processing of a polyprotein precursor termed PrpR1. This subunit is both a haemagglutinin and an antigen which is recognized by sera from patients with periodontitis. In this study the relationship was investigated between a colonization epitope which is recognized by the MoAb 61BG1.3, a haemagglutinating and B cell epitope which are recognized by sera from patients with periodontitis. B cell epitopes were mapped by Western blotting with a series of truncated recombinant polypeptides spanning the adhesion domain within residues 784-1130 of PrpR1 and by ELISA using a panel of synthetic peptides spanning the same sequence. The epitope which is recognized by the protective MoAb was mapped within residues 907-931 of PrpR1, while serum responses of patients were directed predominantly to the adjacent carboxy-terminal sequence within residues 934-1042. The haemagglutinating epitope was mapped to residues 1073-1112. In view of our previous findings that the MoAb 61BG1.3 prevents colonization of P. gingivalis in vivo and inhibits haemagglutination, these two epitopes may be in proximity in the native protein. Active or passive immunization strategies which target the protective or haemagglutinating epitopes of the adhesion domain of PrpR1 may provide a means of preventing infection with P. gingivalis.
Atlas-based organ &#x00026; bone approximation for ex-vivo &#x03BC;MRI mouse data: A pilot study (2010)

In this paper we propose a novel semi-automated atlas-based approach for organ and bone approximation for micro-Magnetic Resonance Imaging (μMRI) data of mice. Based on a set of 18 manually indicated landmarks at specific joint & bone locations, individual atlas bones (pelvis, limb bones and sternum) are mapped to the target in a first step and a sparse set of corresponding landmarks on a skin surface representation is determined in a second step. Subsequently, this sparse set on the skin is used to derive a dense set of correspondences relying on matching spectra of local geodesic distances. Finally, determined by the skin correspondence, a Thin-Plate-Spline (TPS) approximation of major organs (heart, lungs, liver, spleen, stomach, kidneys) is performed. The method was tested using 3 µMRI mouse datasets and the MOBY atlas. The performance of the organ approximation algorithm was estimated using manual segmentations of 6 organs for each MRI dataset and calculating Dice indices of organ-volume overlap for each dataset and the atlas. The obtained results indicate excellent fitting of heart and kidneys and moderate fitting of spleen, lungs, liver and stomach. These initial results are satisfactory and comparable to other organ mapping studies using different approaches and μComputed Tomography (CT) mouse data.
CALL in Intensive Reading of College English (2005)

Nowadays many universities in China are facing the same problems in College English teaching: large classes, students of different levels, limited periods, and lack of teachers, etc. CALL can help to solve these problems. This paper takes Northeastern University’s method to illustrate the ways CALL can be used in college intensive reading as well as its theoretical basis, procedures, its advantages and disadvantages, and finally offers some suggestions.
Inter-cell interference coordination by horizontal beamforming for small cells in 3D cell structure (2015)

3D cell structure, where small cells are three-dimensionally deployed on macro cells, is considered as one of the effective cell structures to accommodate data traffic growing rapidly in recent years. In this cell structure, inter-cell interference among small cells is one of the major issues. As a technique for mitigating inter-cell interference among small cells, we propose a network coordinated beamforming where small-cell base stations, applying horizontal beamforming, coordinate their beams by network coordination. We also clarify the throughput performance of the proposed method under a multi-cell environment considering a realistic cell structure using computer simulation.
Compressed Data Content Type for Cryptographic Message Syntax (CMS) (2002)

This document defines a format for using compressed data as a Cryptographic Message Syntax (CMS) content type.Compressing data before transmission provides a number of advantages, including the elimination of data redundancy which could help an attacker, speeding up processing by reducing the amount of data to be processed by later steps (such as signing or encryption), and reducing overall message size.Although there have been proposals for adding compression at other levels (for example at the MIME or SSL level), these don't address the problem of compression of CMS content unless the compression is supplied by an external means (for example by intermixing MIME and CMS).
Importance of the Carboxyl-terminal FTSL Motif of Membrane Cofactor Protein for Basolateral Sorting and Endocytosis (1999)

Membrane cofactor protein (MCP), a widely distributed complement regulatory protein, is expressed on the basolateral surface of polarized epithelial cells, and it is not endocytosed. The carboxyl-terminal tetrapeptide (FTSL) is required for polarized surface expression. The ability of this tetrapeptide to serve as an autonomous sorting signal has been analyzed by adding this sequence motif to the C terminus of an apical membrane protein, the influenza A virus hemagglutinin (HA). The recombinant protein HA-FTSL retained the apical localization of the parental HA protein. Substitution of the complete cytoplasmic tail of MCP for the cytoplasmic tail of HA resulted in the targeting of the chimeric protein (HA/MCP) to the basolateral surface suggesting that the carboxyl-terminal FTSL motif is a weak sorting signal that requires additional targeting information from the membrane-proximal part of the cytoplasmic tail of MCP for redirecting an apical protein to the basolateral membrane domain. In contrast to the native HA, the HA-FTSL protein was subject to endocytosis. The basolateral HA/MCP was also found to be internalized and thus differed from the basolateral MCP. This result suggests that the carboxyl-terminal FTSL motif serves as an internalization signal and that in native MCP sorting information outside the cytoplasmic tail counteracts this endocytosis signal. Substitution of a tyrosine for the phenylalanine dramatically increased the internalization with most of the HA-YTSL protein being present intracellularly. Our results are consistent with the view that the interplay of multiple sorting signals and the modification of a well known targeting signal (YTSL) by amino acid exchange (FTSL) determine the constitutive expression of MCP on the basolateral surface of polarized epithelial cells.
Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome (2016)

The function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients.
Inhibiting inflammatory cytokines. (1996)

Acute glomerulonephritis is a common cause of renal dysfunction and ultimately renal failure. The inflammation involved is a tightly regulated response with pro- and anti-inflammatory cytokines playing key roles. Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are the principal pro-inflammatory cytokines produced by intrinsic cells and infiltrating leukocytes. IL-1 and TNF can be directly antagonized using IL-1 receptor antagonist (IL-1ra) or binding proteins such as soluble receptors or antibodies. Alternatively, cytokines with anti-inflammatory properties can be used to decrease IL-1 and TNF synthesis, increase the production of their natural antagonists and deactivate inflammatory cells such as macrophages. This review will focus on these anti-inflammatory cytokines, principally IL-4, IL-6, IL-10 and IL-13, and highlight recent research of their activities in existing models of renal disease. The results of these experiments offer a promising new avenue of treatment.
20-fs pulse shaping with a 512-element phase only liquid crystal modulator (2000)

We report pulse shaping experiments in the 20-fs range using a 512-element phase-only liquid crystal modulator array. The results demonstrate the potential for significantly improved spectral resolution compared to 128-element liquid crystal modulators previously used for pulse shaping. Furthermore, we show that subtle nonlinear spatial dispersion has a profound effect on replica pulses arising due to the pixellated nature of the liquid crystal modulator and may dramatically reduce their (already low) peak intensity.
Aligning development tools with the way programmers think about code changes (2007)

Software developers must modify their programs to keepup with changing requirements and designs. Often, aconceptually simple change can require numerous editsthat are similar but not identical, leading to errors andomissions. Researchers have designed programming environmentsto address this problem, but most of thesesystems are counter-intuitive and difficult to use.By applying a task-centered design process, we developeda visual tool that allows programmers to makecomplex code transformations in an intuitive manner.This approach uses a representation that aligns wellwith programmers' mental models of programming structures.The visual language combines textual and graphicalelements and is expressive enough to support a broadrange of code-changing tasks. To simplify learning thesystem, its user interface scaffolds construction and executionof transformations. An evaluation with Java programmerssuggests that the interface is intuitive, easyto learn, and effective on a representative editing task.
Stereospecific polymerizations (1960)

Abstract Recent results of investigations of stereospecific polymerizations are reported. Butadiene polymers very high in cis ‐1,4 content have been obtained through polymerization in the presence of soluble catalysts prepared from compounds of group VIII metals, cobalt in particular, and from dialkylaluminum monohalides. The polymers thus obtained have higher melting temperatures and better elastomeric properties than those of cis ‐1,4 polybutadienes of lower steric purity. Two types of butadiene polymers having 1,2 enchainment and isotactic or syndiotactic structure may be prepared in the presence of soluble catalytic systems prepared from trialkylaluminum and complexes of chromium or vanadium. A great number of nonhydrocarbon monomers have also been polymerized stereospecifically, in the presence of catalysts acting in homogeneous phase. Metallorganic compounds of magnesium act as stereospecific catalysts for the polymerization of 2‐vinylpyridine, with production of crystalline isotactic polymers. Crystalline isotactic polymers of acetaldehyde have been prepared by polymerization at low temperature with the use of metallorganic compounds such as alkylaluminum and alkylzinc as catalysts. Aldehydes higher than acetaldehyde have also been polymerized stereospecifically with catalysts that act usually with a cationic mechanism, such as aluminum bromide. The crystalline structure and the crystalline helical chain conformation of a great number of these polyaldehydes have been determined. A chemical mechanism for this polymerization, which makes clear the stereospecificity of the process even in the presence of soluble catalysts, has been proposed. Stereospecific catalysts have been prepared from compounds of amides with very electropositive metals. In the presence of TiCl 3 , these catalysts promote the stereospecific polymerization of propylene to isotactic polymer, whereas, as such, they furnish crystalline polymers of acrylates, methacrylates, and 2‐vinylpyridine. The nature of the terminal groups of the polymers establishes the fact that the polymerization occurs with an anionic mechanism. The mechanism of the stereospecific polymerization of α‐olefins is discussed, and further evidence is given confirming the previously hypothesized anionic coordinated mechanism. The factors determining stereospecificity are also discussed; it is concluded that when a group rich in electrons in addition to the polymerizable double bond is present in the monomer, stereospecific polymerization may take place in the presence of catalysts acting in homogeneous as well as heterogeneous phase. In these cases, stereospecificity must be ascribed to the coordination of the monomer to the catalyst, which results in a constant mode of presentation of the monomer to the growing chain, and to a constant type of opening, cis or trans , of the polymerizable double bond. For the polymerization of propenyl ethers to di‐isotactic polymers, we established that this opening is of the cis type.
Transistor NOR circuit design (1957)

THE transistor NOR circuit was introduced because of the desire to have a single logic element which would combine well in logic configurations with a minimum of concern for matching and element loading. A NOR element has a signal output only if there are no input signals, and consequently has no output if any input signal is present. Such a single logic element must have a considerable amount of flexibility to meet the various input and output loadings, operating temperatures, and power-supply variations which may be encountered. This paper considers the circuit design of the transistor NOR circuit.
The characterization of the human Siah‐1 promoter<sup>1</sup> (2002)

Siah-1, the human homologue of Drosophila seven in absentia, is related to apoptosis and tumor suppression. Although it was reported that the expression of Siah-1 is induced by p53 and p21/WAF1, little is known about the transcriptional regulation of the Siah-1 gene. To investigate the transcriptional regulation, we isolated and sequenced the genomic fragment of the Siah-1 promoter region. The Siah-1 promoter has no typical TATA box or CCAAT box. Transient transfection assays using reporter plasmids in which the promoter region of the Siah-1 gene was deleted or mutated showed that one Sp1 site was responsible for the basal promoter activity. In Northern blotting analysis, the expression of the Siah-1 gene was upregulated by p53, but activation of the reporter plasmid by the p53 co-transfection assay was not shown, suggesting that a p53 responsive element does not exist in the promoter region we examined in this study but might be present in another region.
Evaluation of wrist strap monitors from an MR head perspective (2002)

Magnetoresistive (MR) heads are very sensitive devices that can be damaged by applying a current that exceeds the normal bias current of the head, which is typically around 10 mA for anisotropic magnetoresistive (AMR) devices. Contact with the head from a charged object can cause damaging current transients. Depending on the magnitude of the charge, these currents can reach peak values of hundreds of milliamps during this very fast discharge. All monitors tested resulted in a voltage on the operator under worst case conditions. This worst case voltage was AC for capacitive monitors and DC or pulsed DC for resistive and charge detecting monitors. Under best case conditions, there was at least one monitor in each category that exhibited near zero voltage on the operator. If the operator is holding a pair of metal tweezers and makes contact with an MR head, the voltage on the operator will cause current transients that are potentially harmful to the head. By considering the advances in MR technology in recent years, the data in this paper aims to assist the end user in selecting the most suitable wrist strap monitoring technology.
Flexible reflecting membranes micromachined in silicon (1994)

Flexible reflecting membranes with an electrostatically controlled surface shape have been fabricated in a silicon wafer by means of bulk micromachining. A typical membrane has a square aperture with a side length of 10 mm. The membrane is formed by a 500 nm thick tensile stressed silicon nitride diaphragm coated with a 200 nm thick reflecting aluminium layer to form a flexible mirror. The mirror has an initially plane surface with a mean square deviation out of plane approximately lambda /10 for lambda =633 nm. The high initial optical quality and the possibility of electrostatic control of the reflecting surface make the mirror useful for various on-chip electro-optical applications.
Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease (2017)

The heterogeneity of Alzheimer's disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners. A classifier for identifying rapid decliners in one study showed high sensitivity and specificity in the second study. Characterizing subgroups of at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic insights and facilitate clinical trials of drugs to delay the onset of AD.
Nucleotide sequence analysis of c‐<i>raf</i>‐1 cDNA and promoter from a radiation‐resistant human squamous carcinoma cell line: Deletion within exon 17 (1993)

The c-raf-1 proto-oncogene is the cellular homologue of v-raf, the oncogene of the acutely transforming retrovirus 3611-MSV. The product of c-raf-1 (raf-1) is a 74-kDa cytoplasmic serine/threonine protein kinase. We previously reported that antisense human c-raf-1 cDNA transfection results in reduction of the endogenous c-raf-1 transcript, decreased tumor growth rate, and enhanced radiation sensitivity of SQ-20B tumor cells established from a radiation-resistant laryngeal squamous cell carcinoma. In the study reported here, we used cDNA-linked polymerase chain reaction amplification and nucleotide sequencing to examine the structure of the 3233-bp SQ-20B c-raf-1 cDNA. The 812-bp c-raf-1 promoter region was analyzed by genomic DNA amplification followed by cloning and sequencing. Sequence comparison with a previously published c-raf-1 sequence indicated no structural changes within the coding region of SQ-20B c-raf-1. However, a 4-bp deletion was observed in the 3' untranslated region within exon 17. This deletion was also present in a c-raf-1 cDNA clone isolated from a SQ-20B cDNA library. While the possibility of a 3' transcriptional control mechanism cannot be ruled out, it appears that the raf-1 protein kinase may regulate the development of radioresistant malignancies via interaction with other molecules in the damage and repair-related signal transduction pathways.
Identification of Colitis and Cancer in Colon Biopsies by Fourier Transform Infrared Spectroscopy and Chemometrics (2012)

Cancer is a disease that does great harms to the health of human beings. FT-IR spectroscopy could identify variability at the molecular level in biological specimens. It is a rapid and noninvasive method, which could be used intraoperatively to modify surgical procedures. The aim of this paper is to identify and separate cancer from colitis in endoscopic colon biopsies through the use of FT-IR spectroscopy. A total of 88 endoscopic colon samples, including 41 cases of colitis and 47 cases of colon cancer, were obtained. Specimens were placed on an ATR accessory linked to FT-IR spectrometer with a MCT detector for greater stability and sensitivity. Later, specimens were sent for the histological examination as the reference in the spectral analysis. 41 colitis and 47 cancer specimens were compared. Spectra preprocessed with smoothing and normalization were used for discrimination analysis. PCA was processed to simplify the spectrum data set. Naive Bayes classifier model was constructed for diagnostic classification. Leave-one-out cross-validation method was utilized to assess the discrimination results. The sensitivity of FT-IR detection for cancer achieves 97.6%. The results showed that colon cancer could be distinguished from colitis with high accuracy using FT-IR spectroscopy and chemometrics.