Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluorescence Resonance Energy Transfer (FRET) and Proximity Ligation Assays Reveal Functionally Relevant Homo- and Heteromeric Complexes among Hyaluronan Synthases HAS1, HAS2, and HAS3*

Background: Co-immunoprecipitation experiments suggest the existence of HAS2-HAS2 and HAS2-HAS3 enzyme complexes. Results: FRET and proximity ligation assays show homo- and heteromeric complexes among all HASs. Conclusion: Like Golgi glycosyltransferases, HASs form homo- and heteromeric complexes. Significance: Different HAS complexes may have specific effects on hyaluronan synthesis. In vertebrates, hyaluronan is produced in the plasma membrane from cytosolic UDP-sugar substrates by hyaluronan synthase 1–3 (HAS1–3) isoenzymes that transfer N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA) in alternative positions in the growing polysaccharide chain during its simultaneous extrusion into the extracellular space. It has been shown that HAS2 immunoprecipitates contain functional HAS2 homomers and also heteromers with HAS3 (Karousou, E., Kamiryo, M., Skandalis, S. S., Ruusala, A., Asteriou, T., Passi, A., Yamashita, H., Hellman, U., Heldin, C. H., and Heldin, P. (2010) The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J. Biol. Chem. 285, 23647–23654). Here we have systematically screened in live cells, potential interactions among the HAS isoenzymes using fluorescence resonance energy transfer (FRET) and flow cytometric quantification. We show that all HAS isoenzymes form homomeric and also heteromeric complexes with each other. The same complexes were detected both in Golgi apparatus and plasma membrane by using FRET microscopy and the acceptor photobleaching method. Proximity ligation assays with HAS antibodies confirmed the presence of HAS1-HAS2, HAS2-HAS2, and HAS2-HAS3 complexes between endogenously expressed HASs. C-terminal deletions revealed that the enzymes interact mainly via uncharacterized N-terminal 86-amino acid domain(s), but additional binding site(s) probably exist in their C-terminal parts. Of all the homomeric complexes HAS1 had the lowest and HAS3 the highest synthetic activity. Interestingly, HAS1 transfection reduced the synthesis of hyaluronan obtained by HAS2 and HAS3, suggesting functional cooperation between the isoenzymes. These data indicate a general tendency of HAS isoenzymes to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis.
Clustering observations using fuzzy similarities between ordered categorical data

In general, we use cluster analysis or factor analysis to cluster or position observations having multivariate continuous variables. Those methods are based on measurements or correlation coefficients between continuous variables. Therefore, there are many problems in applying those techniques to a dataset where ordered categorical data are collected. At first, we propose a fuzzy similarity between ordered categorical variables. Next, we propose techniques of clustering and positioning observations of statistical 2 or 3 dimensional dataset where ordered categorical data are collected. The effectiveness of the fuzzy similarity and our techniques is discussed through two examples of image datasets in marketing research.
Mitochondrial ribosome assembly in health and disease

The ribosome is a structurally and functionally conserved macromolecular machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which synthesize a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. High-resolution cryo-EM structures of the yeast, porcine and human mitoribosomal subunits and of the entire human mitoribosome have uncovered a wealth of new information to illustrate their evolutionary divergence from their bacterial ancestors and their adaptation to synthesis of highly hydrophobic membrane proteins. With such structural data becoming available, one of the most important remaining questions is that of the mitoribosome assembly pathway and factors involved. The regulation of mitoribosome biogenesis is paramount to mitochondrial respiration, and thus to cell viability, growth and differentiation. Moreover, mutations affecting the rRNA and protein components produce severe human mitochondrial disorders. Despite its biological and biomedical significance, knowledge on mitoribosome biogenesis and its deviations from the much-studied bacterial ribosome assembly processes is scarce, especially the order of rRNA processing and assembly events and the regulatory factors required to achieve fully functional particles. This article focuses on summarizing the current available information on mitoribosome assembly pathway, factors that form the mitoribosome assembly machinery, and the effect of defective mitoribosome assembly on human health.
Prognostic Significance of Ictal and Interictal Epileptiform Activity in Temporal Lobe Epilepsy

Summary: Long‐term electrocorticograms (ECoG), recorded by chronically implanted subdural electrodes during preoperative evaluation of 59 patients with temporal lobe epilepsy (TLE) were analyzed retrospectively to assess the prognostic relevance of distribution of interictal epileptiform potentials (IEP) and seizure origin (SO) and to investigate factors affecting their lateralization. Subsequent to preoperative evaluation, a standardized two thirds anterotemporal lobectomy including subtotal hippocampectomy had been performed in all patients. The following results were obtained: (a) Only patients with 100% lateralization of SO and IEP had excellent seizure outcome (= 89% seizure‐free); (b) patients with bitemporal SO were unlikely to benefit from surgical treatment (=12.5% seizure‐free); (c) 40–56% patients with unilateral temporal SO and bitemporal IEP, became seizure‐free irrespective of the degree of lateralization of IEP; and (d) multidimensional analysis of variance showed that lateralization of SO, presence of a magnetic resonance imaging (MRI)‐detectable lesion, presence of hippocampal sclerosis, presence of febrile seizures and seizures at age ≥6 years are the five most important variables indicating abolition of seizures. Combined analysis of ECoG‐recorded SO and IEP allows prediction of postoperative seizure control within close boundaries.
A solution NMR study of the binding kinetics and the internal dynamics of an HIV‐1 protease‐substrate complex

NMR studies of the binding of a substrate to an inactive HIV‐1 protease construct, containing an active site mutation PRD25N, are reported. Substrate titration measurements monitored by HSQC spectra and a 15N‐edited NOESY experiment show that the chromogenic substrate analog of the capsid/p2 cleavage site binds to PRD25N with an equilibrium dissociation constant, KD, of 0.27 ± 0.05 mM, and upper limits of the association and dissociation rate constants, 2×104 M−1s−1 and 10 s−1, respectively, at 20°C, pH 5.8. This association rate constant is not in the diffusion limit, suggesting that association is controlled by a rare event, such as opening of the protease flaps. Analysis of 15N relaxation experiments reveals a slight reduction of S2 values in the flap region, indicating a small increase in the amplitude of internal motion on the sub‐nsec timescale. In addition, several residues in the flap region are mobile on the conformational exchange timescale, msec–μsec. Flap dynamics of the protease‐substrate complex are compared with those of protease‐inhibitor complexes, and the implications of these results for substrate‐binding models are discussed.
Software Tools Assessment

t’s common knowledge that to stay competitive, your software organization must continuously improve product quality and customer satisfaction, as well as lower software development costs and shorten delivery time-all critical variables for software engineering practice. ’ You can pursue these challenges in many ways. One such way is to improve your development processes and organizational structures using frameworks such as the SEI’S Capability Maturity Model,’ Total Quality Management,3 the Quality Improvement Paradigm,4 or the Process Cycle.5 Another option is to adopt appropriate software tools. Tools have long been recognized as an effective way to improve software development variables such as productivity and product quality. However, to make effective use of specific tools you should first understand how a tool will affect these critical variables in your project.
Seafloor segmentation using combined texture features of sidescan sonar images

In this paper, an unsupervised seafloor segmentation method using combined texture features of sidescan sonar images is proposed. Two sets of features are considered in the proposed algorithm. One calculates the statistics from the gray-level co-occurrence matrix (GLCM), and the other obtains the statistics in the nonsubsampled contourlet transform domain (NSCT). The two sets of features are combined together to produce a multi-dimensional feature vector for each pixel. Principal component analysis (PCA) is used to reduce the dimensionality of each feature vector. The Silhouette index is adopted to automatically estimate the number of seafloor types in sonar images. The segmentation is achieved using k-means clustering based on the compact feature vectors. Experimental results show that the proposed method can improve the seafloor segmentation accuracy.
Seasonal Variation of Slipped Capital Femoral Epiphysis in the United States

Seasonal variation in the onset of symptoms of slipped capital femoral epiphysis (SCFE) has been described. The author examined seasonal variation of hospital admissions for SCFE using a national database and compared seasonal variation between the northern and southern United States, between girls and boys, and between black and white children. Significant seasonal variation was found in the North in both boys and girls, but there was less seasonal variation among blacks than among whites. Some seasonal variation was present in the South, but it did not reach the level of statistical significance. Although the cause of seasonal variation in SCFE remains unknown, the effect differs by latitude and skin pigmentation, suggesting a possible link to impaired vitamin D synthesis.
On Increasing the Slow-Fading Channel Diversity Using Block-Coded MIMO-OFDM With Reconfigurable Antennas

In this paper, we propose a new block coding scheme to increase the diversity gain of multiple-input-multiple-output (MIMO) orthogonal frequency-division multiplexing (OFDM) systems over slow-fading wireless channels. We assume that the antenna elements at the transmitter are reconfigurable and capable of independently changing the physical characteristics of their radiation patterns. The composite right-left handed leaky-wave antenna is an example of reconfigurable antennas with such characteristics. We use this feature of the antennas and develop a block coding scheme that exploits, in addition to the spatial and frequency diversity, a new additional degree of diversity, which is called state diversity. We determine the maximum achievable diversity order of the proposed coding scheme in spatially correlated frequency-selective channels. To demonstrate the performance of the proposed block coding technique, we provide numerical results and compare them with those of the previously developed coding schemes for MIMO-OFDM systems. The results indicate that the proposed code achieves significantly higher diversity and coding gain, even in spatially correlated channels, compared with the existing counterparts.
An evaluation framework for improving knowledge-intensive business processes

In the move from the industrial to the knowledge economy, organisations have shifted the focus from the improvement of their production processes to the improvement of their collaborative processes in a bid to optimise the effectiveness of their human capital. Our goal is to provide stakeholders of knowledge-intensive business processes with information about the performance of their process that allows them to make practical improvements to the process to gain a competitive edge. In this paper, we present the framework that we have developed to evaluate the tender response process for its organisational knowledge creation capability. We report here on the progress of our research and our interim findings.
Expression of CD133 Cancer Stem Cell Marker in Melanoma: A Systematic Review and Meta-Analysis

Background CD133-positive melanoma cells are thought to be melanoma-initiating cells with cancer stem cell (CSC) characteristics. Some researchers have reported that CD133-negative subsets can also initiate tumors, so the clinical significance of a CD133-positive subpopulation of cells in melanoma remains controversial. This systematic review was designed to assess the value of CD133 as a CSC marker in melanomas. A meta-analysis was also performed to cumulatively analyze the data on CD133 expression levels in the selected studies. Materials and Method Eligible studies were identified via an electronic search through various databases including PubMed, MEDLINE, Ovid MEDLINE, and Web of Science (from May 2005 through September 2014) using the following keywords: “CD133 or prominin-1”, “cancer stem cells”, and “melanoma”. Only articles in which CD133 antigen was detected by immunohistochemistry (IHC) were included. A meta-analysis was performed to identify any association between CD133 expression and clinical outcomes. Results Two hundred and ninety-nine melanoma cases from 5 studies were evaluated for expression levels of CD133 using IHC. Large heterogeneity was observed among the results (p<0.001, I2 = 94%). Approximately 47.9% (95% CI 23.7%-72.1%) of the studied melanoma cases had high CD133 expression. The I2 value and Q-test p value for heterogeneity were 89.0% and <0.001, respectively, and the pooled estimate of CD133 expression was 61.7% (95% CI 25.1%-98.4%). Conclusions Our findings suggest that CD133 is not yet proven to be an appropriate biomarker in identifying CSCs of melanoma. Thus, detection of CD133 in combination with other putative CSC markers may be more valuable for clinical application.
Restriction and modification in Bacillus subtilis: inducibility of a DNA methylating activity in nonmodifying cells

The nonrestricting/nonmodifying strain Bacillus subtilis 222 (r-m-) can be induced to synthesize a DNA-modifying activity upon treatment with either mitomycin C (MC) or UV light. This is shown by the following facts. (i) Infection of MC-pretreated 222 cells with unmodified SPP1 phage yields about 3% modified phage that are resistant to restriction in B. subtilis R (r+m+). The induced modifying activity causes the production of a small fraction of fully modified phage in a minority class of MC-treated host cells. (ii) The MC-pretreated host cells contain a DNA cytosine methylating activity: both bacterial and phage DNAs have elevated levels of 5-methylcytosine. (iii) The MC-induced methylation of SPP1 DNA takes place at the recognition nucleotide sequences of restriction endonuclease R from B. subtilis R. (iv) Crude extracts of MC-pretreated 222 cells have enhanced DNA methyltransferase activities, with a substrate specificity similar to that found in modification enzymes present in (constitutively) modifying strains.
2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase in

2-aminothiazole (1) was discovered as a novel Src family kinase inhibitor template through screening of our internal compound collection. Optimization through successive structure-activity relationship iterations identified analogs 2 (Dasatinib, BMS-354825) and 12m as pan-Src inhibitors with nanomolar to subnanomolar potencies in biochemical and cellular assays. Molecular modeling was used to construct a putative binding model for Lck inhibition by this class of compounds. The framework of key hydrogen-bond interactions proposed by this model was in agreement with the subsequent, published crystal structure of 2 bound to structurally similar Abl kinase. The oral efficacy of this class of inhibitors was demonstrated with 12m in inhibiting the proinflammatory cytokine IL-2 ex vivo in mice (ED50 approximately 5 mg/kg) and in reducing TNF levels in an acute murine model of inflammation (90% inhibition in LPS-induced TNFalpha production when dosed orally at 60 mg/kg, 2 h prior to LPS administration). The oral efficacy of 12m was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally at 0.3 and 3 mg/kg twice daily. Dasatinib (2) is currently in clinical trials for the treatment of chronic myelogenous leukemia.
ACCELERATOR PHYSICS CHALLENGES OF X-RAY FEL SASE SOURCES*

A great deal of international interest has recently focused on the design and construction of free-electron lasers (FEL) operating in the x-ray region ({approx}1 {angstrom}). At present, a linac-based machine utilizing the principle of self-amplified spontaneous emission (SASE) appears to be the most promising approach. This new class of FEL achieves lasing in a single pass of a high brightness electron beam through a long undulator. The requirements on electron beam quality become more demanding as the FEL radiation wavelength decreases, with the 1-{angstrom} goal still 3-orders of magnitude below the shortest wavelength operational SASE FEL (TTF-FEL at DESY [1]). The subpicosecond bunch length drives damaging effects such as coherent synchrotron radiation, and undulator vacuum chamber wakefields. Unlike linear colliders, beam brightness needs to be maintained only over a small ''slice'' of the bunch length, so the concepts of bunch integrated emittance and energy spread are less relevant than their high-frequency (or ''time-sliced'') counterparts, also adding a challenge to phase space diagnostics. Some of the challenges associated with the generation, preservation, measurement, and stability of high brightness FEL electron beams are discussed here.
An improved particle swarm optimization algorithm for radial basis function neural network

An improved particle swarm optimization (IMPSO) which synthesizes the existing models of constriction factor approach (CFA PSO) is proposed. In the proposed method, an adaptive algorithm based on the search space adjustable is applied to solve the problem that conventional particle swarm optimization (PSO) algorithm easily falls into local optimal and occur premature convergence. Then, the IMPSO is used to optimize the parameters of RBF neural network. The new training algorithm is used to approximate polynomial function and predict chaotic time series, compared with PSO, and CFA PSO, the algorithm speed up the speed of convergence, and has much greater accuracy.
On the Liapunov stability of multi-finger grasps

This paper deals with the stability of a rigid body under multiple contact forces. First, the problem is considered at the force planning level, and the stability of a force distribution is formulated. For this problem, the stiffness tensor is derived, and its basic properties are analyzed. Necessary and sufficient conditions for stability of a force distribution are established in an analytical form. These conditions, considered under unilateral frictional constraints, are studied on an illustrative example. Next, it is shown that stabilization of an unstable force distribution can be done by a simple control law. The stability conditions for this control law are formulated by transforming the stiffness tensor to the center of stiffness. Finally, conclusions on the contradiction between the Liapunov stability and the contact stability of the objects are drawn.
Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results.

OBJECTIVE Studies of outcome in patients with medullary thyroid carcinoma require long follow-ups to accrue enough cancer-specific events. Owing to time-dependent changes in diagnosis and therapy, long observation periods render studies susceptible to 'time bias' which can yield spurious results. This study was designed to investigate cancer-specific event rates after initial neck resection in contemporaneous patients recruited within less than a decade. DESIGN Institutional cohort study of 128 consecutive patients who underwent compartment-oriented neck surgery between 1994 and 2002 at a tertiary surgical center for hitherto untreated medullary thyroid carcinoma. METHODS The Kaplan-Meier method was used in conjunction with the log-rank test for analysis of time-dependent outcomes. RESULTS Follow-up was available for 120 patients (94%) including 63 rearranged during transfection (RET) carriers. There were six locoregional recurrences in the 110 patients with clear surgical margins at initial neck resection, and 12 cancer-specific deaths in the 120 patients with available follow-up. On Kaplan-Meier analysis, most clinicopathological variables were significantly associated with recurrence-free survival and cancer-specific survival. Within the median observation period of 64.5 months, patients with node-negative tumors did not develop locoregional recurrence or die from their malignancies. The low event rates precluded multivariate analyses with all clinicopathological variables. With our extensive surgical approach, median recurrence-free survival and cancer-specific survival at 5 years were 95.2 and 89.3% respectively. DISCUSSION Compared with literature data, our 5-year locoregional recurrence rate of 4.8% appeared very favorable, and our 5-year cancer-specific mortality rate of 10.7% was among the lowest ever reported. The growing proportion of localized medullary thyroid carcinomas among contemporaneous patients can be expected to ultimately lower the event rates, complicating future studies of outcome.
Crystal structure of hydrous wadsleyite with 2.8% H2O and compressibility to 60 GPa

Abstract Hydrous wadsleyite (β-Mg2SiO4) with 2.8 wt% water content has been synthesized at 15 GPa and 1250 °C in a multi-anvil press. The unit-cell parameters are: a = 5.6686(8), b = 11.569(1), c = 8.2449(9) Å, β = 90.14(1)°, and V = 540.7(1) Å3, and the space group is I2/m. The structure was refined in space groups Imma and I2/m. The room-pressure structure differs from that of anhydrous wadsleyite principally in the increased cation distances around O1, the non-silicate oxygen. The compression of a single crystal of this wadsleyite was measured up to 61.3(7) GPa at room temperature in a diamond anvil cell with neon as pressure medium by X-ray diffraction at Sector 13 at the Advanced Photon Source, Argonne National Laboratory. The experimental pressure range was far beyond the wadsleyite-ringwoodite phase-transition pressure at 525 km depth (17.5 GPa), while a third-order Birch-Murnaghan equation of state (EoS) [V0 = 542.7(8) Å3, KT0 = 137(5) GPa, K′ = 4.6(3)] still fits the data well. In comparison, the second-order fit gives V0 = 542.7(8) Å3, KT = 147(2) GPa. The relation between isothermal bulk modulus of hydrous wadsleyite KT0 and water content CH2O is: KT0 = 171(1)-12(1) CH2O (up to 2.8 wt% water). The axial-compressibility βc is larger than both βa and βb, consistent with previous studies and analogous to the largest coefficient of thermal expansion along the c-axis.