Miracle-dz/UniFAR-FTUs huggingface dataset:
A detailed analysis of treatment delay from the onset of symptoms in early rheumatoid arthritis patients

Objectives: A treatment delay of more than 12 weeks can negatively affect treatment response in rheumatoid arthritis (RA). Our aim was to quantify the different stages of delay before RA treatment in different rheumatology centres and to explore influencing factors. Method: A total of 156 disease-modifying anti-rheumatic drug (DMARD)-naive early RA patients were included from eight practices: one academic hospital, five general hospitals, and two private practices. Eight different types of delay were defined from symptom onset until treatment initiation. Information on the duration of each stage of delay was collected from the patient, their general practitioner (GP), and patient files at the rheumatology practice. Patient/GP demographics and disease activity/severity parameters were recorded. Results: The median total delay from symptom onset until treatment initiation was 23 weeks whereas patient-, GP- and rheumatologist-related median delay was 10, 4, and 7 weeks, respectively. Only 21.6% of the patients had a total delay of less than 12 weeks. The total median delay in private rheumatology practices was less than in academic and general hospitals (p < 0.001). Furthermore, RA patients treated within 12 weeks of symptom onset showed a higher level of disease activity. The duration of rheumatologist-related delay was inversely correlated with disease activity parameters. Patients with morning stiffness were treated, on average, 3 weeks sooner than those without morning stiffness (p < 0.006). Conclusions: In only one out of five early RA patients was treatment initiated within 12 weeks of symptom onset, as recommended. Patient-related delay contributed most to overall delay. Disease activity and type of rheumatology centre are pivotal determinants of delay.
Second-Order Perturbative Solution of Scattering From Two Rough Surfaces With Arbitrary Dielectric Profiles

Analytical expressions for the cross-polarization components of the normalized radar cross sections (NRCS) of three-dimensional stratified media with two rough surfaces are presented. In a recent paper, the zeroth- and the first-order scattering solutions of a two-rough-surface structure with arbitrary dielectric profiles were presented using the small perturbation approach based on the extended boundary conditions (EBC). In this study, the proposed method is extended to obtain the second-order solutions including cross-polarized fields. Unlike copolarizations, the main contribution of cross-polarizations is determined by the second-order solutions. A direct extension of the recently proposed formulation leads to difficult and lengthy manipulations; hence, first a compact recursive matrix formulation for the unknown surface fields of an arbitrary order is derived. Then, for the second-order fields, the matrix system is efficiently and straightforwardly solved. Finally, the cross-polarized scattered fields and the normalized radar cross sections are derived. The final solutions are given in simple, compact, and closed-form expressions that make the computations very easy. The derived expressions are validated against known solutions of special cases, available in the literature. The results are shown to be exactly consistent with existing ones, both analytically and numerically.
A Peer Dataset Comparison Outlier Detection Model Applied to Financial Surveillance

Outlier detection is a key element for intelligent financial surveillance system. The detection procedures generally fall into two categories: comparing every transaction against its account history and further more, comparing against a peer group to determine if the behavior is unusual. The later approach shows particular merits in efficiently extracting suspicious transaction and reducing false positive rate. Peer group analysis concept is largely dependent on a cross-datasets outlier detection model. In this paper, we propose a new cross outlier detection model based on distance definition incorporated with the financial transaction data features. An approximation algorithm accompanied with the model is provided to optimize the computation of the deviation from tested data point to the reference dataset. An experiment based on real bank data blended with synthetic outlier cases shows promising results of our model in reducing false positive rate while enhancing the discriminative rate remarkably
Topographer Reconstruction of the Nonrotation–Symmetric Anterior Corneal Surface Features

Purpose. The purpose of this study is to demonstrate the performance of a topographer (the VU topographer, prototype development, VU University Medical Center, Amsterdam, The Netherlands) that uses a color-coded stimulus pattern to reconstruct both the rotation–symmetric and nonrotation–symmetric shape features of the anterior corneal surface. Methods. Spherical surfaces, toric surfaces, the Rand surface (surface with peripheral corrugations), and sample eyes were measured. A ring topographer (Keratron, Optikon 2000, Rome, Italy) and the Haag-Streit ophthalmometer (Haag Streit, Bern, Switzerland) were used for comparison. Results. All three instruments produced similar values for the radii of curvature of spherical surfaces with a tolerance of 0.02 mm. The Keratron gave underestimated values for the astigmatic power of toric surfaces (>0.25 D for toric surfaces with astigmatism >9 D). Because it eliminates skew ray error, only the VU topographer was able to reconstruct the correct shape of the Rand surface in contrast with ring topographers. The effect of skew ray error was also observed in the surface reconstruction of a radially keratotomized (RK) eye. There was height difference of 2.75 ± 1.25 &mgr;m between the output of the VU topographer and the output of the Keratron. Conclusion. The VU topographer is just as accurate in reconstructing the rotation–symmetric features of the anterior corneal surface as the ring topographers but is superior in recovering the nonrotation–symmetric shape features.
LIBEFP: A new parallel implementation of the effective fragment potential method as a portable software library

A new high performance parallel implementation of the general Effective Fragment Potential (EFP) method in a form of a portable software library called libefp is presented. The libefp library was designed to provide developers of various quantum chemistry software packages with an easy way to add EFP functionality to the program of their choice. The general overview of the library is presented and various aspects of interfacing the library with third party quantum chemistry packages are considered. The reference implementation of common methods of computational chemistry such as geometry optimization and molecular dynamics on top of libefp is delivered in the form of efpmd program. Results of molecular dynamics simulation of liquid water using the developed software are described. © 2013 Wiley Periodicals, Inc.
CLONING, CHARACTERIZATION, AND EXPRESSION STUDIES IN ESCHERICHIA COLI OF GROWTH HORMONE cDNAs FROM INDIAN ZEBU CATTLE, REVERINE BUFFALO, AND BEETAL GOAT

ABSTRACT The growth hormone cDNAs from three different economically important animal species of indian origin viz., indian zebu cattle (Bos indicus), indian reverine buffalo (Bubalus bubalis), and beetal goat (Capra hircus) were isolated by the RT–PCR technique. The amplified product was then cloned into phagemid pBluescriptIIKS− and the nucleotide sequence of the entire 573 base coding region for each product was determined. The genetic sequences as well as the translated protein sequence of these ruminant species were compared to that of closely related species like taurine cattle (Bos taurus) and sheep (Ovis aries). A very high degree of nucleotide sequence homology, ranging between 97–98%, was observed. Subsequently, the buffalo and goat cDNAs were used for expression studies in Escherichia coli. Very low levels of expression resulted when the growth hormone cDNAs were directly placed under the strong E. coli (trc) or phage (T7) promoters with the approximate level being less than 0.1% and 1% of the intracellular E. coli proteins, respectively. The nearly 10-fold enhancement of the level of expression as observed was attributable to the nature of the untranslated leader sequence donated by the individual expression element. High level (about 20% of soluble E. coli protein) expression of buffalo/goat growth hormone was achieved as a fusion protein with glutathione-s-transferase (GST) in pGEX-KT. Further, although attempts at converting the GST-GH fusion protein system to a two-cistronic gene expression system were unsuccessful, the utilization of a short synthetic first cistron in the two-cistronic mode of expression resulted in high levels (approximately 30% of soluble protein cell fraction) of GH polypeptide with a native N-terminus in E. coli for all three cDNAs.
Multiple control elements mediate activation of the murine and human interleukin 12 p40 promoters: evidence of functional synergy between C/EBP and Rel proteins

Interleukin 12 (IL-12) is a heterodimeric cytokine whose activity is critical for T-helper 1 responses. The gene for the IL-12 p40 subunit is expressed in macrophages following induction by bacterial products, and its expression is augmented by gamma interferon. In this study, we performed a functional analysis of the murine and human p40 promoters in the murine macrophage cell line RAW 264.7. Transcription from the murine p40 promoter was strongly induced by lipopolysaccharide and heat-killed Listeria monocytogenes (HKLM), but promoter activity was not enhanced by gamma interferon. Multiple cis-acting elements involved in activated transcription were identified through an extensive mutant analysis. The most critical element, whose activity is conserved in mice and humans, is located between positions -96 and -88 relative to the murine transcription start site. This element exhibits functional synergy with a previously described NF-kappaB half-site which interacts with Rel proteins. DNase I footprinting and electrophoretic mobility shift assays demonstrated that C/EBP proteins interact with the critical element, but in nuclear extracts, cooperative binding of C/EBP and Rel proteins to their respective sites was not observed. Interestingly, promoter activity was induced by HKLM in the presence of cycloheximide, consistent with induction by posttranslational mechanisms. The results suggest that C/EBP and Rel proteins play important roles in the activation of IL-12 p40 transcription by bacteria. However, many complex interactions will need to be clarified to fully understand p40 regulation.
Technology Diffusion and Economic Growth: An Alternative Conceptual Model

Abstract Technological development goes beyond the acquisition of requisite skills through environmental exposure, education and training to the ability to engage in innovative tasks whose results include improved processes, systems, higher levels of performance, greater efficiency and new products. This article reports the results of a study centred on the links between technology diffusion and economic growth in order to present an alternative interpretation of their role. The methodology involved an initial review of growth accounting procedures, the use of secondary data on registration of patents, energy generation statistics, income per capita and GDP. Next, using internet search engines, technology transfer, adoption and innovation are unpacked in the context of contemporary models of innovation, diffusion and adoption. The resulting elements are reconfigured into linear information flows that mimic knowledge transfer between the phases of the system with specified outcomes. The findings indicate mixed outputs on the basis of which an alternative conceptual model is developed.
Exploring insights for virulent gene inhibition of multidrug resistant Salmonella typhi, Vibrio cholerae, and Staphylococcus areus by potential phytoligands via in silico screening

In our recent studies on prevalence of multidrug resistant pathogens in Byramangala reservoir, Karnataka, India, we identified Salmonella typhi, Staphylococcus aureus, and Vibrio cholerae which had acquired multiple drug resistance (MDR) and emerged as superbugs. Hence, there is a pressing demand to identify alternative therapeutic remedies. Our study focused on the screening of herbal leads by structure-based virtual screening. The virulent gene products of these pathogens towards Kanamycin(aph), Trimethoprim(dfrA1), Methicillin (mecI), and Vancomycin (vanH) were identified as the probable drug targets and their 3D structures were predicted by homology modeling. The predicted models showed good stereochemical validity. By extensive literature survey, we selected 58 phytoligands and their drug likeliness and pharmacokinetic properties were computationally predicted. The inhibitory properties of these ligands against drug targets were studied by molecular docking. Our studies revealed that Baicalein from S. baicalensis (baikal skullcap) and Luteolin from Taraxacum officinale (dandelion) were identified as potential inhibitors against aph of S. typhi. Resveratrol from Vitis vinifera (grape vine) and Wogonin from S. baicalensis were identified as potential inhibitors against dfrA1 of S. typhi. Herniarin from Herniaria glabra (rupture worts) and Pyrocide from Daucus carota (Carrot) were identified as the best leads against dfrA1 of V. cholerae. Taraxacin of T. officinale (weber) and Luteolin were identified as potential inhibitors against Mec1. Apigenin from Coffee arabica (coffee) and Luteolin were identified as the best leads against vanH of S. aureus. Our findings pave crucial insights for exploring alternative therapeutics against MDR pathogens.
ON/OFF STORAGE SYSTEMS WITH STATE-DEPENDENT INPUT, OUTPUT, AND SWITCHING RATES

We consider a storage model that can be on or off. When on, the content increases at some state-dependent rate and the system can switch to the off state at a state-dependent rate as well. When off, the content decreases at some state-dependent rate (unless it is at zero) and the system can switch to the on position at a state-dependent rate. This process is a special case of a piecewise deterministic Markov process. We identify the stationary distribution and conditions for its existence and uniqueness.
Maternal antioxidant concentrations after uncomplicated pregnancies

Background: To analyse the post-partum concentrations of intra- and extra-cellular blood antioxidants in women with uncomplicated pregnancies. Methods: Whole blood and plasma thiols, plasma vitamin E and C, serum cholesterol and triglyceride, ferric reducing ability of plasma (FRAP) concentrations were compared between women delivered by caesarean section (n=17) or spontaneous delivery (n=10). A repeated mixed model was used for statistical analysis. Results: The majority of whole blood thiols increased significantly in both groups the first days post-partum. However, within the caesarean group free cysteine, oxidised cysteine, homocysteine and glutathione and plasma cysteine and homocysteine levels dropped significantly after 24 h, while FRAP levels peaked significantly in this group. Plasma vitamin E levels decreased significantly in both groups within 24 to 48 h after delivery. Independent of the way of delivery whole blood and plasma thiols were significantly increased and vitamin E levels were significantly decreased 3 months post-partum while plasma vitamin C levels and FRAP were unchanged compared to ante-partum levels. Discussion: Decreased plasma vitamin E levels shortly post-partum are associated with decreased lipid peroxidation. The 24 h post-partum drop of some plasma and whole blood thiols in the caesarean group may be due to prolonged fasting.
Parathyroid Hormone-related Peptide (hPTHrP) and Parathyroid Hormone-related Peptide Receptor Type 1 (PTHR1) Expression in Human Thymus

Parathyroid hormone-related peptide (hPTHrP) is expressed in human tissues and regulates cellular proliferation, differentiation, and apoptosis by an autocrine/paracrine loop. In rodent thymus, both parathormone and parathyroid hormone-related peptide (PTHrP) are expressed by thymic epithelial cells (TECs). The present study demonstrated by RT-PCR and immunohistochemistry that hPTHrP and parathyroid hormone-related peptide receptor type 1 (PTHR1) were expressed in human thymus at both RNA and protein levels. hPTHrP was expressed mainly in the thymic medulla by epithelial (cytokeratin-positive), mature dendritic (CD40+/86+) and plasmacytoid interleukin (IL)-3Rα+ cells. This protein was also present in some cells forming Hassall's bodies and a few subcapsular and cortical TECs. PTHR1 was expressed by scattered subcapsular and cortical TECs and by rare TECs in the medulla. Thymocytes did not express either hPTHrP or PTHR1. Primary cultures of human TECs revealed the presence of both hPTHrP and PTHR1 mRNAs, confirming the capacity of TECs to synthesize both peptides. Moreover, synthetic (1–39) hPTHrP peptide administered on cultured TECs induced the expression of IL-6 mRNA, suggesting that hPTHrP can regulate thymic functions by inducing in TECs the expression of IL-6, which is involved in the development and maturation of thymocytes.
DeepRT: deep learning for peptide retention time prediction in proteomics

Accurate predictions of peptide retention times (RT) in liquid chromatography have many applications in mass spectrometry-based proteomics. Herein, we present DeepRT, a deep learning based software for peptide retention time prediction. DeepRT automatically learns features directly from the peptide sequences using the deep convolutional Neural Network (CNN) and Recurrent Neural Network (RNN) model, which eliminates the need to use hand-crafted features or rules. After the feature learning, principal component analysis (PCA) was used for dimensionality reduction, then three conventional machine learning methods were utilized to perform modeling. Two published datasets were used to evaluate the performance of DeepRT and we demonstrate that DeepRT greatly outperforms previous state-of-the-art approaches ELUDE and GPTime.
Monoclonal antibodies to murine CD40 define two distinct functional epitopes

Two rat IgG2a antibodies which define distinct epitopes on murine CD40 have been generated. These antibodies specifically bind recombinant murine CD40 expressed on L cells, and the soluble extracellular domain of murine CD40 coated onto microtiter plates. Both antibodies bind B220+ but not B220 murine spleen cells, and immunoprecipitate a 45‐kDa protein from the surface of purified murine splenic B cells. These antibodies exhibit separate functional properties, consistent with the notion that they define two distinct CD40 epitopes. One of the monoclonal antibodies (designated 1C10) directly induces a specific proliferative response from mature murine B cells, up‐regulates several B cell surface antigens, and rescues immature B lymphoma cells from anti‐IgM‐induced growth arrest. The other monoclonal antibody (designated 4F11) exhibits none of these properties, but is capable of synergizing with suboptimal amounts of either anti‐IgM antibodies or the 1C10 agonistic anti‐CD40 antibody to produce an optimal proliferative response of purified small dense B cells. Furthermore, 4F11 antibody synergizes with suboptimal amounts of 1C10 antibody to rescue B lymphoma cells from anti‐IgM‐induced growth arrest. The 1C10 and 4F11 antibodies were unable to cross‐block each other's binding to recombinant CD40 expressed in L cells, providing strong support for the notion that the antibodies recognize distinct epitopes on CD40. The potential implications of two functionally distinct CD40 epitopes are discussed.
Control of M. tuberculosis ESAT-6 Secretion and Specific T Cell Recognition by PhoP

Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobacterium bovis BCG (BCG) and Mycobacterium tuberculosis H37Ra (H37Ra), which both lost their virulence during in vitro serial passage. Whereas the attenuation of BCG is due mainly to loss of the ESAT-6 secretion system, ESX-1, the reason why H37Ra is attenuated remained unknown. However, here we show that a point mutation (S219L) in the predicted DNA binding region of the regulator PhoP is involved in the attenuation of H37Ra via a mechanism that impacts on the secretion of the major T cell antigen ESAT-6. Only H37Ra “knock-ins” that carried an integrated cosmid with the wild-type phoP gene from M. tuberculosis H37Rv showed changes in colony morphology, increased virulence, ESAT-6 secretion, and induction of specific T cell responses, whereas other H37Ra constructs did not. This finding established a link between the PhoP regulator and ESAT-6 secretion that opens exciting new perspectives for elucidating virulence regulation in M. tuberculosis.
Knowledge-Based Regional Economic Development: A Synthetic Review of Knowledge Spillovers, Entrepreneurship, and Entrepreneurial Ecosystems

The geographical nature of knowledge spillovers and entrepreneurship has been well documented in the literature. In most regional or urban studies, these two topics are separately discussed. This research reviews literature at the intersection of knowledge spillovers, entrepreneurship, and regional economic development. The key argument is that entrepreneurship can serve as a mechanism for transmitting knowledge spillovers and accordingly contribute to regional innovation, cluster formation, and economic development. However, the effectiveness of this mechanism depends on various factors in the regional entrepreneurial ecosystem, notably including knowledge bases, absorptive capacity, competition, networks of people, diversity, and culture.
A Measurement of NAT & Firewall Characteristics in Peer to Peer Systems

NATs and ﬁrewalls break the original model of IP end-to-end connectivity across the Internet, since their presence creates a new Internet architecture made of many private networks. This architecture, designed upon the client/server model, introduces complications in communication between hosts and has performance impacts, especially for P2P protocols, since hosts outside a private network are not able to initiate a connection to hosts inside that private network. In this paper we present a study of the current distribution and characteristics of the NATs and ﬁrewalls existing in the Internet, with respect to UDP communication. We believe that our study provides valuable insights for the development of P2P systems that intend to address the NAT/ﬁrewall issue effectively.