Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8

Degradation of nuclear proteins by the 26S proteasome is essential for cell viability. In yeast, the nuclear envelope protein Cut8 mediates nuclear proteasomal sequestration by an uncharacterized mechanism. Here we describe structures of Schizosaccharomyces pombe Cut8, which shows that it contains a unique, modular fold composed of an extended N-terminal, lysine-rich segment that when ubiquitinated binds the proteasome, a dimer domain followed by a six-helix bundle connected to a flexible C tail. The Cut8 six-helix bundle shows structural similarity to 14-3-3 phosphoprotein-binding domains, and binding assays show that this domain is necessary and sufficient for liposome and cholesterol binding. Moreover, specific mutations in the 14-3-3 regions corresponding to putative cholesterol recognition/interaction amino acid consensus motifs abrogate cholesterol binding. In vivo studies confirmed that the 14-3-3 region is necessary for Cut8 membrane localization and that dimerization is critical for its function. Thus, the data reveal the Cut8 organization at the nuclear envelope. Reconstruction of Cut8 evolution suggests that it was present in the last common ancestor of extant eukaryotes and accordingly that nuclear proteasomal sequestration is an ancestral eukaryotic feature. The importance of Cut8 for cell viability and its absence in humans suggests it as a possible target for the development of specific chemotherapeutics against invasive fungal infections.
Local barycentric coordinates

Barycentric coordinates yield a powerful and yet simple paradigm to interpolate data values on polyhedral domains. They represent interior points of the domain as an affine combination of a set of control points, defining an interpolation scheme for any function defined on a set of control points. Numerous barycentric coordinate schemes have been proposed satisfying a large variety of properties. However, they typically define interpolation as a combination of all control points. Thus a local change in the value at a single control point will create a global change by propagation into the whole domain. In this context, we present a family of local barycentric coordinates (LBC), which select for each interior point a small set of control points and satisfy common requirements on barycentric coordinates, such as linearity, non-negativity, and smoothness. LBC are achieved through a convex optimization based on total variation, and provide a compact representation that reduces memory footprint and allows for fast deformations. Our experiments show that LBC provide more local and finer control on shape deformation than previous approaches, and lead to more intuitive deformation results.
A psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R) cognitive distress, fatigue, hyperglycemia, and hypoglycemia subscales in patients with type 1 and type 2 diabetes

Objective: To explore the use of Diabetes Symptom Checklist-Revised (DSC-R) Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia subscales as measures of acute diabetes-associated symptoms in patients with both type 1 and 2 diabetes. Research design and methods: Our study was conducted in context of two international, multicenter, randomized clinical trials for inhaled insulin. Confirmatory factor analyses and assessments of reliability and construct validity were performed. Results: Study participants were 371 patients with type 2 (56% male; mean age, 57 years) and 481 with type 1 diabetes (57% male, mean age, 40 years). In both populations a four-factor model was the best fit. Cronbach’s α  0.79 and intraclass correlation coefficient  0.63; subscales correlated ( P  0.05) with measures of well-being and satisfaction (0.12  r  0.71). In patients with type 1 diabetes, three subscales correlated ( P  0.05) with A1C. Conclusions: The psychometric properties of the DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia suggest they may be utilized in clinical trials as reliable and valid measures of acute symptoms of diabetes.
ARY ulation of regional differences in ons by EGF family-matrix interac

The mammalian cerebral cortex is characterized by functionally and anatomically discrete areas that arise during development from forebrain progenitors. While the fate of the neuroepithelial cells that generate different cortical areas has been examined (Barbe and Levitt, 1991; Arimatsu et al., 1992; Cohen-Tannoudji et al., 1994), specific mechanisms that control their differentiation have not been identified. One hypothesis suggests that post-mitotic neurons migrate to form a relatively uniform cortical plate composed of neurons capable of expressing phenotypic traits of different neocortical areas (O’Leary, 1989; Schlagger and O’Leary, 1991; O’Leary et al., 1994). The formation of distinct cortical areas would occur through environmental cues in the cortical plate, with thalamic afferents playing a major role. An earlier model (Rakic, 1988) postulated that in addition to the late-acting influences by inputs to the cortex, differences among the progenitors of the neuroepithelium are established early. A primitive map, or ‘protomap,’ would subsequently be transmitted to the cortical plate as newly generated neurons move to their final position in the cerebral wall. Thus, a neuron’s final position in the cortex would relate to the point at which it exited the ventricular zone (Rakic, 1978), a hypothesis supported by the well-known association of most migrating neurons with radial glial fibers (Rakic, 1971, 1972; Levitt and Rakic, 1980; Misson et al., 1991). It is from this early, provisional regionalization of the cerebral wall, as well as through subsequent interactions of cortical cells with their environment, that discrete cortical areas would arise. There is also evidence, however, that some cells from the precursor pool can disperse to widely divergent cortical areas (Walsh and Cepko, 1992; Fishell et al., 1993; O’Rourke et al., 1992). Migration of this type suggests that daughter cells, arising from the same progenitor, can differentiate into neurons residing in different cortical areas. In cortex formed in such a Developm Printed in
AN ASP-BASED MODEL EMPLOYING A TABU SEARCH METHOD FOR MAKING e-LOGISTICS DECISIONS

In this article, a decision support system for solving the vehicle routing problem is presented. This system has been developed in a way that allows it to be used as a web-based application service provider. Therefore, it is feasible for any company to access it over the internet, in order to obtain the best fleet schedules (a set of least-cost routes) concerning its daily orders or supplies. The application consists of several web pages, written in plain Application Service Providers (ASP) and Hypertext Markup Language (HTML) code, containing the java applets and JavaScript functions that encapsulate the routing methods, and determine the routing plan.
Mammary serine protease inhibitor inhibits epithelial growth factor‐induced epithelial‐mesenchymal transition of esophageal carcinoma cells

By using proteomic technology, the authors previously observed the substantial down‐regulation of mammary serine protease inhibitor (maspin) in esophageal squamous cell carcinoma and metastases. In the current study, they examined the effects of maspin re‐expression in a maspin‐null esophageal cancer cell line EC109 and also investigated the underlying mechanism.
Design, Realization and Measurements of a Miniature Antenna for Implantable Wireless Communication Systems

The design procedure, realization and measurements of an implantable radiator for telemetry applications are presented. First, free space analysis allows the choice of the antenna typology with reduced computation time. Subsequently the antenna, inserted in a body phantom, is designed to take into account all the necessary electronic components, power supply and bio-compatible insulation so as to realize a complete implantable device. The conformal design has suitable dimensions for subcutaneous implantation (10 × 32.1 mm). The effect of different body phantoms is discussed. The radiator works in both the Medical Device Radiocommunication Service (MedRadio, 401-406 MHz) and the Industrial, Scientific and Medical (ISM, 2.4-2.5 GHz) bands. Simulated maximum gains attain -28.8 and - 18.5 dBi in the two desired frequency ranges, respectively, when the radiator is implanted subcutaneously in a homogenous cylindrical body phantom (80 × 110 mm) with muscle equivalent dielectric properties. Three antennas are realized and characterized in order to improve simulation calibration, electromagnetic performance, and to validate the repeatability of the manufacturing process. Measurements are also presented and a good correspondence with theoretical predictions is registered.
Shank3 Deficiency Induces NMDA Receptor Hypofunction via an Actin-Dependent Mechanism

Shank3, which encodes a scaffolding protein at glutamatergic synapses, is a genetic risk factor for autism. In this study, we examined the impact of Shank3 deficiency on the NMDA-type glutamate receptor, a key player in cognition and mental illnesses. We found that knockdown of Shank3 with a small interfering RNA (siRNA) caused a significant reduction of NMDAR-mediated ionic or synaptic current, as well as the surface expression of NR1 subunits, in rat cortical cultures. The effect of Shank3 siRNA on NMDAR currents was blocked by an actin stabilizer, and was occluded by an actin destabilizer, suggesting the involvement of actin cytoskeleton. Since actin dynamics is regulated by the GTPase Rac1 and downstream effector p21-activated kinase (PAK), we further examined Shank3 regulation of NMDARs when Rac1 or PAK was manipulated. We found that the reducing effect of Shank3 siRNA on NMDAR currents was mimicked and occluded by specific inhibitors for Rac1 or PAK, and was blocked by constitutively active Rac1 or PAK. Immunocytochemical data showed a strong reduction of F-actin clusters after Shank3 knockdown, which was occluded by a PAK inhibitor. Inhibiting cofilin, the primary downstream target of PAK and a major actin depolymerizing factor, prevented Shank3 siRNA from reducing NMDAR currents and F-actin clusters. Together, these results suggest that Shank3 deficiency induces NMDAR hypofunction by interfering with the Rac1/PAK/cofilin/actin signaling, leading to the loss of NMDAR membrane delivery or stability. It provides a potential mechanism for the role of Shank3 in cognitive deficit in autism.
Trace metal control of phytochelatin production in coastal waters

Concentrations of particulate phytochelatin, a metal-binding peptide produced by eukaryotic phytoplankton, ranged from 2 to 50 pmol (g Chl a)-’ in samples collected from small harbors in southeastern New England. Although there was no obvious relationship between phytochelatin and total Cu concentrations, phytochelatin varied systematically with free Cu concentrations [Cu*+]. Transects in which there was high [Cu*+] revealed high phytochelatin concentrations with a general decrease seaward. In those where [Cu*+] remained low and constant, phytochelatin levels also remained low and constant. Incubation experiments confirmed that Cu rather than Cd is likely responsible for the elevated concentrations of phytochelatin at our field sites, though Zn may also be important. Intracellular phytochelatin concentrations in laboratory cultures of Skeletonema costatum, a coastal diatom, increased with increasing concentrations of Cu and Zn in a metal-specific dose-response relationship. Additions of 12 nM Zn’ (inorganic Zn) to Cu-stressed cultures reduced phytochelatin production, suggesting that Zn competitively inhibits uptake of Cu. Antagonistic effects of metals in the field, as well as physiological differences between organisms growing in the field and in the laboratory, can probably explain why phytochelatin concentrations in S. costatum are higher than in particulate field samples at the same [Cu*+]. The concentrations of many trace metals in coastal waters are elevated as a result of anthropogenic inputs. Direct inputs of both domestic and industrial wastes, as well as more subtle inputs such as leaching from pressure-treated wood pilings and antifouling boat paints, are examples of how metals enter the water column. Laboratory studies have demonstrat-
Management of chronic pain in primary care

Purpose of reviewTo examine recent and current evidence available to guide the management of chronic pain in primary care. Recent findingsThe growing profile of chronic pain has facilitated some important consensus and guideline statements. Pharmacological management, based on available evidence and consensus, is essential in managing chronic pain in primary care, as part of a holistic approach, and with regular review. Studies of primary care management of chronic pain face considerable challenges, with assessment and interventions that are complex, and involving multidisciplinary approaches. Recent research evidence points to the effectiveness and feasibility of multidisciplinary interventions, with appropriate assessment and training. Specifically, a self-management programme, ‘collaborative care’, a cognitive-behavioural approach, and the Alexander technique show evidence of effectiveness in primary care, the latter two also proving cost-effective. SummaryMost chronic pain presents and is managed in primary care; yet, most evidence for its management is difficult to apply in the primary care setting. Despite growing evidence for the management of chronic pain generally, management in primary care must be largely guided by consensus, experience, and judicious extrapolation from research in other contexts or conditions. A need for increased and on-going education and resources is apparent, as is the need for more research based in primary care.
The Secrecy Capacity of the 2 × 2 MIMO Wiretap Channel

We consider the MIMO wiretap channel, that is a MIMO broadcast channel where the transmitter sends some confidential information to one user which is a legitimate receiver, while the other user is an eavesdropper. Perfect secrecy is achieved when the the transmitter and the legitimate receiver can communicate at some positive rate, while insuring that the eavesdropper gets zero bits of information. In this paper, we compute the secrecy capacity of a two antenna MIMO broadcast channel.
Hierarchical graph-based media content representation for real time search in large scale multimedia databases

This paper presents a system architecture and the appropriate algorithms for confidential searching of multimedia digital libraries. The proposed scheme uses Middleware service layer that allows pre-processing of raw content with technology owned by the Search Engine, without compromising the security of the original architecture in any way. The specific search algorithms described are a hierarchical graph structure algorithm for preprocessing, and a backtracking search algorithm that achieves good real-time performance (speed, and precision-recall values) under the given security constraints.
New generation sequencing in pathogen discovery and microbial surveillance

23rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Berlin, Germany, 27–30 April 2013 The annual congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) is recognized as the largest European congress for the presentation and discussion of the key priorities and more recent scientific developments in the fields of clinical microbiology and infection. This year, it attracted almost 10,000 participants from all over the world. Keynote lectures, symposia, meet-the-expert sessions, educational workshops, poster and oral sessions covered the diagnosis, treatment, epidemiology and prevention of infectious diseases, as well as related basic microbiology. Moreover, interactive sessions addressing specific subjects underlined the important educational aspect of the ECCMID’s congress. The scientific program, abstracts, oral presentations are available at their website 101. This meeting report is focused on one of the several challenging and one of the most transversal topics of the meeting: the application of the next-generation sequencing (NGS) to the microbial world.
Scheduling and thread management with RTEMS

The goal of a real-time operating system (RTOS) is to support real-time and embedded system (RT/ES) application development, which differ from general-purpose applications because of the size, weight, and power (SWaP) and timing constraints imposed by embedded applications. Useful RTOS features include real-time thread scheduling, thread communication, synchronization, interrupt handling, memory management, file systems, device drivers, networking, and debugging support. The Real-Time Executive for Multi-processor Systems (RTEMS) is a free and open-source RTOS that supports over a dozen processor architecture families and over 150 embedded system boards. RTEMS is designed to support embedded applications with stringent real-time requirements while being compatible with open standards such as POSIX. RTEMS includes optional services such as TCP/IP networking and file systems while still offering minimum executable sizes under 20 KB in useful configurations. One of the primary functions of an RTOS is to select threads that can obtain access to resources such as shared memory and processor time. RTEMS uses multiple algorithms to manage both waiting threads and those ready to execute. The thread execution schedulers include the traditional RTOS round robin and deterministic priority schedulers, rate monotonic, earliest deadline first (EDF), constant bandwidth server (CBS), and simple SMP scheduling algorithms. The RTEMS scheduling framework allows the application developer to select the thread scheduling algorithm that best meets the application's space and time requirements. ÂăWe will present how this framework can be used by researchers to integrate their own scheduling algorithm into RTEMS and test it using a scheduling simulator before deploying it on target hardware.
Numerical investigation of a new sheet metal shear cutting tool design to increase the part quality by superposed compression stress

Nowadays, a major criterion for the quality of shear cut workpieces is characterised by a smooth final cutting surface. Normally, this surface only can be manufactured by using fine cutting or trimming technology. Major disadvantage of these processes is the complex tooling design caused by a double-acting press and corresponding tool layout. Content of this numerical study is to investigate the impact of a new sheet metal cutting tool design to increase the clean-cut portion in conventional shear cutting of high strength steel (DP600). Using FEA-Software DEFORM 2D, the models of fine cutting, conventional cutting and cutting with new tool design were mapped by comparing cutting surface results and stress distribution in the shearing zone. The main criterion of the optimization of tool design focuses on an enlarged clean-cut area along the cutting surface compared to conventional shear cutting. This study is based on the design of experiments (DOE) using Latin-Hypercube-Variation of the factors cutting clearance, die radius, punch radius, punch velocity, part holder force and special geometry designs to identify and to optimise new tool geometry. New tool design shows a significant increase of clear-cut surface up to 73% compared to conventional cutting surfaces disclosing 35% when using tools according to standard design rules. Using this new punch design, it is possible to shear high strength steels revealing a noticeably performed shearing surface quality.
A Mobile Robot Path Planning Using Genetic Algorithm in Static Environment

In this study we present our initial idea for using genetic algorithms to help a controllable mobile robot to find an optimal path between a starting and ending point in a grid environment. The mobile robot has to find the optimal path which reduces the number of steps to be taken between the starting point and the target ending point. GAs can overcome many problems encountered by traditional search techniques such as the gradient based methods. The proposed controlling algorithm allows four-neighbor movements, so that path-planning can adapt with complicated search spaces with low complexities. The results are promising.
Scalable hardware memory disambiguation for high-ILP processors

Power is a major problem for scaling the hardware needed to support memory disambiguation in future out-of-order architectures. In current machines, the traditional detection of memory ordering violations requires frequent associative searches of state proportional to the instruction window size. A new class of solutions yields an order-of-magnitude reduction in the energy required to properly order loads and stores for windows of hundreds to thousands of in-flight instructions
Wireless sensing and identification of passive electromagnetic sensors based on millimetre-wave FMCW RADAR

The wireless measurement of various physical quantities from the analysis of the RADAR Cross Sections variability of passive electromagnetic sensors is presented. A millimetre-wave Frequency-Modulated Continuous-Wave RADAR is used for both remote sensing and wireless identification of sensors. Long reading ranges (up to some decameters) may be reached at the expense of poor measurement resolution (typically 10%).
Fast computation of 4-fingered force-closure grasps from surface points

This paper addresses the problem of computing frictional 4-fingered force-closure grasps of three-dimensional objects. The proposed approach searches for force-closure grasps from a collection of sampled points on the object's surface. Unlike most other works, the approach is not limited to the objects with a certain class of shapes. It can be applied to an object in any shape since only the object's surface points and corresponding surface normal at the points are needed. The efficiency of the approach arises from a heuristic for search space pruning which is based on ability to efficiently locate regions in three dimensional space where friction cones intersect and a randomized test for checking force-closure condition. The proposed approach is implemented and preliminary results are presented.
' s personal copy T-MAN : Gossip-based fast overlay topology construction q

Large-scale overlay networks have become crucial ingredients of fully-decentralized applications and peer-to-peer systems. Depending on the task at hand, overlay networks are organized into different topologies, such as rings, trees, semantic and geographic proximity networks. We argue that the central role overlay networks play in decentralized application development requires a more systematic study and effort towards understanding the possibilities and limits of overlay network construction in its generality. Our contribution in this paper is a gossip protocol called T-MAN that can build a wide range of overlay networks from scratch, relying only on minimal assumptions. The protocol is fast, robust, and very simple. It is also highly configurable as the desired topology itself is a parameter in the form of a ranking method that orders nodes according to preference for a base node to select them as neighbors. The paper presents extensive empirical analysis of the protocol along with theoretical analysis of certain aspects of its behavior. We also describe a practical application of T-MAN for building CHORD distributed hash table overlays efficiently from scratch. 2009 Elsevier B.V. All rights reserved.