Miracle-dz/UniFAR-FTUs huggingface dataset:
Simple Synthesis of Modafinil Derivatives and Their Anti-inflammatory Activity

Simple synthesis of modafinil derivatives and their biological activity are described. The key synthetic strategies involve substitution and coupling reactions. We determined the anti-inflammatory effects of modafinil derivatives in cultured BV2 cells by measuring the inhibition of nitrite production and expression of iNOS and COX-2 after LPS stimulation. It was found that for sulfide analogues introduction of aliphatic groups on the amide part (compounds 11a–d) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds 11e–k). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds 12a–d) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds 12e–k) in BV-2 microglia cells.
Retinal neurodegeneration: early pathology in diabetes

Normal vision depends on the normal function of retinal neurons, so vision loss in diabetes must ultimately be explained in terms of altered neuronal function. However, to date relatively little attention has been paid to the impact of diabetes on the neural retina. Instead, the focus of most research has been primarily on retinal vascular changes, with the assumption that they cause altered neuronal function and consequently vision loss. An increasing body of evidence suggests that alterations in neuronal function and viability may contribute to the pathogenic mechanisms of diabetic retinopathy beginning shortly after the onset of diabetes. This view arises from neurophysiological, psychometric, histopathological and biochemical observations in humans and experimental animals. The collective evidence from past and recent studies supports the hypothesis that neurodegeneration, together with functional changes in the vasculature, is an important component of diabetic retinopathy. The authors invite other investigators to include the neural retina as a component of their studies so that the pathogenesis of diabetic retinopathy can be understood more clearly.
characterization of axonal Disease in Patients with Multiple sclerosis Using high-gradient-Diffusion Mr imaging 1

244 radiology.rsna. org n Radiology: Volume 280: Number 1—July 2016 1 From the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129 (S.Y.H., A.N., T.W., L.L.W.); Department of Neurology, Massachusetts General Hospital, Boston, Mass (S.M.T., E.C.K.); and Richard M. Lucas Center for Imaging, Department of Radiology, Stanford University, Stanford, Calif (J.A.M.). Received July 17, 2015; revision requested August 25; revision received September 14; accepted October 1; final version accepted November 10. S.Y. H. supported by an RSNA Research Resident Grant. Address correspondence to S.Y. H. (e-mail: syhuang@nmr.mgh.harvard.edu).
Equivalence of the Fokker-Planck approach and the nonlinear sigma model for disordered wires in the unitary symmetry class.

The exact solution of the Dorokhov-Mello-Pereyra-Kumar-equation for quasi one-dimensional disordered conductors in the unitary symmetry class is employed to calculate all $m$-point correlation functions by a generalization of the method of orthogonal polynomials. We obtain closed expressions for the first two conductance moments which are valid for the whole range of length scales from the metallic regime ($L\ll Nl$) to the insulating regime ($L\gg Nl$) and for arbitrary channel number. In the limit $N\to\infty$ (with $L/(Nl)=const. $) our expressions agree exactly with those of the non-linear $\sigma$-model derived from microscopic Hamiltonians.
All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer.

BACKGROUND Presence of five or more circulating tumor cells (CTC) in patients with metastatic carcinomas is associated with poor survival. Although many objects positive for epithelial cell adhesion molecules and cytokeratin (EpCAM+CK+) are not counted as CTC, they may be an important predictor for survival. We evaluated the association between these objects and survival in patients with prostate cancer. PATIENTS AND METHODS Included in this follow-up study were 179 patients with castration-resistant prostate cancer. CellSearch was used to isolate EpCAM+ objects and to stain DNA, cytokeratin and CD45. All EpCAM+CK+ objects were subdivided into seven classes on the basis of predefined morphological appearance in 63 independent samples. Association of each class with survival was studied using Kaplan-Meier and Cox regression analyses. RESULTS Each EpCAM+CK+CD45- class showed a strong association with overall survival (P < 0.001). This included small tumor microparticles (S-TMP), which did not require a nucleus and thus are unable to metastasize. A higher number of objects in any class was associated with decreased survival. A good prediction model included large tumor cell fragments (L-TCF), age, hemoglobin and lactate dehydrogenase. Models with S-TMP or CTC instead of L-TCF performed similarly. CONCLUSION EpCAM+CK+CD45- that do not meet strict definitions for CTC are strong prognostic markers for survival.
Infinite-Resolution 3D Modeling from a Single Image for Free-Form Revolution Objects

This article introduces a minimal-cost fully automatic method to generate 3D object models with unlimited resolution from a single aligned image for arbitrary revolution objects. In this method, the scope is focused on objects with complex (non-lambertian) materials that have intricate free-form revolution surfaces. The method is solely based on a single 2D image extracting two cues: The object's external contour is robustly and precisely extracted by sub-pixel graph expansion followed by piecewise radial regression producing a continuous regularized function called ∞-resolution contour. The object's internal skeleton is efficiently approximated by pixel-wise MAT (medial-axis-transform). The MAT naturally exposes the object's rotational invariants. The integration of the ∞-resolution contour with the invariant rotation axis is done by a tensor product. When the resulting compact and implicit ∞-resolution 3D object model is tessellated at a given target resolution, the tensor product generates mesh vertices, normals and texture coordinates for realistic models. This method achieves unprecedented high quality 3D models with ultra-efficient serialization. These claims are supported by an extensive evaluation using data sets with ground-truth metrics for volume, area, file-size, and execution time.
Crime Scene Investigation with Bayesian Probabilistic Expert Systems

Criminal identification problems are examples of situations in which forensic approach the DNA profiles study is a common procedure. In order to deal with these problems it is needed an introduction to present and explain the various concepts involved, since distinct areas must be considered. Some problems are presented and the use of the ob- ject-oriented Bayesian networks, example of probabilistic expert systems, is shown.
Arrestin/Clathrin Interaction

Previously we demonstrated that nonvisual arrestins exhibit a high affinity interaction with clathrin, consistent with an adaptor function in the internalization of G protein-coupled receptors (Goodman, O. B., Jr., Krupnick, J. G., Santini, F., Gurevich, V. V., Penn, R. B., Gagnon, A. W., Keen, J. H., and Benovic, J. L. (1996) Nature 383, 447–450). In this report we show that a short sequence of highly conserved residues within the globular clathrin terminal domain is responsible for arrestin binding. Limited proteolysis of clathrin cages results in the release of terminal domains and concomitant abrogation of arrestin binding. The nonvisual arrestins, β-arrestin and arrestin3, but not visual arrestin, bind specifically to a glutathioneS-transferase-clathrin terminal domain fusion protein. Deletion analysis and alanine scanning mutagenesis localize the binding site to residues 89–100 of the clathrin heavy chain and indicate that residues 1–100 can function as an independent arrestin binding domain. Site-directed mutagenesis identifies an invariant glutamine (Glu-89) and two highly conserved lysines (Lys-96 and Lys-98) as residues critical for arrestin binding, complementing hydrophobic and acidic residues in arrestin3 which have been implicated in clathrin binding (Krupnick, J. G., Goodman, O. B., Jr., Keen, J. H., and Benovic, J. L. (1997) J. Biol. Chem. 272, 15011–15016). Despite exhibiting high affinity clathrin binding, arrestins do not induce coat assembly. The terminal domain is oriented toward the plasma membrane in coated pits, and its binding of both arrestins and AP-2 suggests that this domain is the anchor responsible for adaptor-receptor recruitment to the coated pit.
Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production

Retroviral vectors offer major advantages for gene transfer studies but have not been useful for producing proteins in large quantities. This deficiency has resulted in part from interference to superinfection, which limits the numbers of active proviruses in cells. Recently, we found that these vectors amplify when they are added as calcium phosphate precipitates to cocultures of cells that package retroviruses into ecotropic and amphotropic host range envelopes. Helper-free virions from either cell type can infect the other without interference, resulting in theoretically limitless back-and-forth (ping-pong) vector replication. In initial studies, however, amplifications of a vector that contained the human growth hormone gene ceased when the hormone produced was 0.3% or less of cellular protein synthesis. This limit was caused by two factors. First, recombinant shutoff viruses that are replication defective and encode envelope glycoproteins form at a low probability during any round of the vector replication cycle and these spread in cocultures, thereby establishing interference. Single cells in shutoff cocultures therefore synthesize both ecotropic and amphotropic envelope glycoproteins, and they release promiscuous (presumably hybrid) virions. The probability of forming shutoff viruses before the vector had amplified to a high multiplicity was reduced by using small cocultures. Second, cells with large numbers of proviruses are unhealthy and their proviral expression can be unstable. Stable expresser cell clones were obtained by selection. Thereby, cell lines were readily obtained that stably produce human growth hormone as 4 to 6% of the total protein synthesis. A ping-pong retroviral vector can be used for high-level protein production in vertebrate cells.
Improvement of Human Tracking in Stereoscopic Environment Using Subtraction Stereo with Shadow Detection

The combination of subtraction stereo with shadow detection we propose improves people tracking in stereoscopic environments. Subtraction stereo is a stereo matching method which is fast and robust for the correspondence problem – one of the most serious issues in computer vision – restricting the search range of matching to foreground regions. Shadow detection gives adequate foreground regions of tracked people by removing cast shadows. This leads to accurate three-dimensional measurement of positions in stereoscopicenvironmenttracking. Byfocusing ondisparity images obtained by subtraction stereo, we can detect people easily based on standard labeling. Objects can also be measured directly in size by subtraction stereo without geometric information about environments for tracking. This is important for installing the tracking system easily. To track multiple passing people, we use the extended Kalman filter to address the occlusion problem usually encountered in crowded environments. The proposed method is verified by experiments using unknown stereoscopic environments.
Development of seminal vesicles and coagulating glands in neonatal mice. I. The morphogenetic effects of various hormonal conditions

Seminal vesicles (SV) and coagulating glands (CG) from neonatal mice 1‐ to 7‐days old were observed in whole mount preparations. Untreated, normal SV developed elaborate epithelial branches beginning on day 3 with secondary branches appearing on day 6. Castration (C), estradiol treatment (E), and castration combined with estradiol treatment (C + E) inhibited the morphogenesis of the epithelial branches. Untreated CG formed solid epithelial stalks that developed lateral epithelial buds on day 3 which attained a complex morphological pattern by day 7. Treatment groups (C, E, and C + E) displayed a pattern of retarded growth with few epithelial buds appearing even at day 7. The effects of castration on both SV and CG were reversed by the addition of testosterone. Short term in vitro culture of 1‐day‐old SV and CG glands in control medium or medium supplemented with estradiol did not exhibit visible growth. Culture of SV and CG glands with testosterone or a piece of testis showed pronounced development.
Protection from high-fat-diet-induced impaired glucose tolerance in female Sprague-Dawley rats

In this study, we examined the long-term influence of a high-fat (HF) diet compared with a standard chow (SC) diet on glucose metabolism in genetically normal Sprague-Dawley rats. As the diet was given for a period of 14 months it represents almost a life-long exposure of the rats to the diet. Results showed that (1) after exposure to 14 months of SC or HF feeding, the fasting glucose levels were below 5.1 mmol/l in both genders; (2) the 2 h plasma glucose concentration (2 h PG) of male rats after an intraperitoneal glucose tolerance test for the SC groups and for the HF groups was significantly higher than for females; (3) the liver triglycerides content was significantly enhanced by HF feeding as compared with SC-feeding, and histological staining showed that both genders of the HF group developed severe liver steatosis; (4) the fasting insulin concentration in blood of HF-fed males was significantly higher than that of females and homeostasis model assessment of insulin resistance was also significantly higher; (5) the insulin secretion capabilities in response to glucose stimulation were significantly higher in HF-fed female rats than that of males. Taken together, these data indicate that glucose intolerance produced by a HF diet in rats shows a gender difference, and females are protected against development of impaired glucose tolerance under HF condition.
On a Controlled Random Deployment WSN-Based Monitoring System Allowing Fault Detection and Replacement

This paper presents a sensor random deployment scheme to monitor 2-dimensional areas for constraining applications while providing a mathematical control of the coverage quality it allows. In addition, useful techniques to detect and repair sensor failures are also added to provide system robustness based on this scheme. In particular, mathematical formulas are developed to express the probability of complete coverage when the environment characteristics are varying, taking into account the deployment parameters. Moreover, a methodology is presented to adapt this scheme to the need of various WSN-based monitoring applications. A simulation is also performed to show the efficiency of the developed strategy, highlight some of its features, and assess its impact on the lifetime of the monitoring system it serves.
Evolutionary Network Design: Hybrid Genetic Algorithms Approach

In recent years we have evidenced an extensive effort in the development of computer communication networks, which have deeply integrated in human being's everyday life. One of the important aspects of the network design process is the topological design problem involved in establishing a communication network. However, with the increase of the problem scale, the conventional techniques are facing the challenge to effectively and efficiently solve those complicated network design problems. In this article, we give a brief survey on our recent research works of network design problems by using genetic algorithms (GAs), such as, multistage process planning problem, fixed charge transportation problem, minimum spanning tree problem, centralized network design, and local area network design, shortest path problem, minimum cost maximum flow problem, and optimal scheduling problems based on network topology. All these problems are illustrated from the point of genetic representation encoding skill and the genetic operators with hybrid strategies. Numerical experiments show the effectiveness and efficiency of such kind of GA-based approach.
Familial congenital diaphragmatic hernia: is an imprinting mechanism involved?

Editor—Isolated congenital diaphragmatic hernia (ICDH) may be sporadic or familial. The mode of inheritance in familial cases (IFCDH) is a matter for debate and different patterns have been proposed. For example, multifactorial inheritance was suggested by Wolff1 and by Norio et al . 2 However, autosomal recessive inheritance has been suggested in clinical studies3-6 and also in animal studies.7 8 Also, there have been various families reported to date in which other patterns of inheritance are possible (table 1). View this table: Table 1 Published isolated familial congenital diaphragmatic hernia (IFCDH) cases If all the published pedigrees with familial CDH are analysed, autosomal dominant, autosomal recessive, and X linked inheritance patterns can be seen. We propose a hypothesis which unifies these various mechanisms, which is to consider imprinting as involved in the inheritance pattern of this condition. In 1994, two non-consanguineous girls with isolated CDH and balanced translocations involving 8q22.3 were reported by Temple et al . 14 …
Water quality impact of a dairy cow herd crossing a stream

Abstract The water quality impact of a herd of 246 dairy cows crossing a stream ford was documented. Two cow crossings produced plumes of turbid water associated with very high concentrations of faecal indicator bacteria (Escherichia coli) and high suspended solids (SS) and total nitrogen (TN). On the first crossing, towards the milking shed, the cows were tightly‐bunched and produced a sharp spike of contamination (E. coli peaking at 50 000 cfu/100 ml). After milking, the cows wandered back across the stream as individuals or small groups, and contaminants were less elevated, albeit for a longer period. Light attenuation, measured continuously by beam transmissometer, correlated closely with E. coli, SS, and TN, permitting the total yield of these contaminants to be estimated. Contaminant yields for the two crossings were very similar, suggesting that time taken and whether or not cows are herded may not greatly influence water quality impact. The cows defecated c. 50 times more per metre of stream crossing than elsewhere on the raceway. This study has shown that cattle accessing stream channels can cause appreciable direct water contamination, suggesting that excluding cattle from streams will have major water quality benefits.
A system identification method with roughly quantized data using semidefinite programming

This paper provides a semidefinite programming approach to an identification of linear systems with roughly quantized outputs. Measurement data sampled from low resolution sensors have large quantization errors, which deteriorate the identification accuracy. The identification problem is formulated into nonlinear and nonconvex programming, however, the proposed approach provides a new method to obtain an approximate optimal value via recursive semidefinite programming. Numerical examples demonstrate that we can estimate both plant parameters and true output and show the effectiveness of the proposed method.
Reconstitution of purified acetylcholine receptors with functional ion channels in planar lipid bilayers.

Acetylcholine receptor, solubilized and purified from Torpedo californica electric organ under conditions that preserve the activity of its ion channel, was reconstituted into vesicles of soybean lipid by the cholate-dialysis technique. The reconstituted vesicles were then spread into monolayers at an air-water interface and planar bilayers were subsequently formed by apposition of two monolayers. Addition of carbamoylcholine caused an increase in membrane conductance that was transient and relaxed spontaneously to the base level (i.e., became desensitized). The response to carbamoylcholine was dose dependent and competitively inhibited by curare. Fluctuations of membrane conductance corresponding to the opening and closing of receptor channels were observed. Fluctuation analysis indicated a single-channel conductance of 16 +/- 3 pS (in 0.1 M NaCl) with a mean channel open time estimated to be 35 +/- 5 ms. Thus, purified acetylcholine receptor reconstituted into lipid bilayers exhibited the pharmacological specificity, activation, and desensitization properties expected of this receptor in native membranes.
Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries.
High Level Expression and Dimer Characterization of the S100 EF-hand Proteins, Migration Inhibitory Factor-related Proteins 8 and 14*

The phenotypical and functional heterogeneity of different macrophage subpopulations are defined by discrete changes in the expression of two S100 calcium-binding proteins, migration inhibitory factor-related proteins (MRPs) 8 and 14. To further our understanding of MRP8 and MRP14 in the developmental stages of inflammatory responses, overexpression of the MRPs was obtained through a combination of a T7-based expression vector and the Escherichia coli BL21 (DE3) cell line. An efficient, two-step chromatographic protocol was then developed for rapid, facile purification. Extensive biophysical characterization and chemical cross-linking experiments show that MRP8 and MRP14 form oligomers with a strong preference to associate as a heterodimer. Heteronuclear NMR experiments indicate that a specific well packed dimer is formed only in equimolar mixtures of the two proteins. Our results suggest that there is a unique complementarity in the interface of the MRP8/MRP14 complex that cannot be fully reproduced in the MRP8 and MRP14 homodimers.