Miracle-dz/UniFAR-FTUs huggingface dataset:
Inferring the functional effects of mutation through clusters of mutations in homologous proteins

Inferring functional consequences is a bottleneck in high‐throughput cancer mutation discovery and genetic association studies. Most polymorphisms and germline mutations are unlikely to have functionally significant consequences. Most cancer somatic mutations do not contribute to tumorigenesis and are not under selective pressure. Identifying and understanding functionally important mutations can clarify disease biology and lead to new therapeutic and diagnostic opportunities. We investigated the extent to which protein mutations with functional consequences are enriched in clusters at conserved positions across related proteins. We found that disease‐causing mutations form clusters more than random mutations or single nucleotide polymorphisms, confirming that mutation hotspots occur at the domain level. In addition to helping to identify functionally significant mutations, analysis of clustered mutations can indicate the mechanism and consequences for protein function. Our analysis focused on somatic cancer mutations suggests functional impact for many, including singleton mutations in FGFR1, FGFR3, GFI1B, PIK3CG, RALB, RAP2B, and STK11. This provides evidence and generates mechanistic hypotheses for the contribution of such mutations to cancer. The same approach can be applied to mutations suspected of involvement in other diseases. An interactive Web application for browsing mutation clusters is available at http://www.mcluster. org. Hum Mutat 30:1–9, 2010. © 2010 Wiley‐Liss, Inc.
E‐cadherin gene mutations in human intrahepatic cholangiocarcinoma

Deletions or mutations of the E‐cadherin gene may result in reduced cell adhesiveness. In particular, conservative point mutations within the N‐terminal calcium‐binding pocket (including exons 7, 8, and 9) are frequently detected in several cancers and are enough to abolish cell–cell adhesion. There have been no studies on E‐cadherin gene mutations in human intrahepatic cholangiocarcinoma (ICC). Human ICCs were therefore investigated for E‐cadherin gene mutations within exons 7, 8, and 9. In addition, the relationships were analysed between their mutations and the immunohistochemical expression of E‐cadherin, histological grade, and clinicopathological parameters. The E‐cadherin gene was analysed in 34 tumours by nested polymerase chain reaction/single‐strand conformation polymorphism (PCR/SSCP) followed by DNA sequencing. In four of the 34 cases (11.8%), tumour‐restricted mobility shifts were observed; two cases harboured a single shift, one case presented two different mobility shifts, and one case presented three different mobility shifts within exons 7 and 8, encoding extracellular domains of E‐cadherin. Polymorphism as previously reported was not identified and all seven new DNA alterations were not present in genomic DNA of non‐tumour origin. The E‐cadherin gene mutations correlated significantly with down‐regulated E‐cadherin protein expression and high ICC histological grade. These data suggest that E‐cadherin gene mutations in ICC are associated with reduced cell adhesiveness and high histological grade. Copyright © 2000 John Wiley & Sons, Ltd.
A platform for realistic online vehicular network management

This paper introduces a platform for realistic and computationally efficient online vehicular networks simulation. It permits decentralized traffic management applications simulation as nodes mobility is modifiable at runtime thanks to the integration of two state-of-the-art network and traffic simulators. The platform embeds a tool that generates vehicular traces based on traffic counting data and ensures performance through a geographical decomposition of the network. Evidence of its performance is given on a Luxembougian traffic management scenario, using real road network and traffic data.
Jets from massive unstable particles: Top-mass determination

We construct jet observables for energetic top quarks that can be used to determine a short-distance top quark mass from reconstruction in e+e- collisions with accuracy better than LambdaQCD. Using a sequence of effective field theories we connect the production energy, mass, and top width scales, Q>>m>>Gamma, for the top jet cross section, and derive a QCD factorization theorem for the top invariant mass spectrum. Our analysis accounts for alphas corrections from the production and mass scales, corrections due to constraints in defining invariant masses, nonperturbative corrections from the cross talk between the jets, and alphas corrections to the Breit-Wigner line shape. This paper mainly focuses on deriving the factorization theorem for hemisphere invariant mass distributions and other event shapes in e+e- collisions applicable at a future linear collider. We show that the invariant mass distribution is not a simple Breit-Wigner function involving the top width. Even at leading order it is shifted and broadened by nonperturbative soft QCD effects. We predict that the invariant mass peak position increases linearly with Q/m due to these nonperturbative effects. They are encoded in terms of a universal soft function that also describes soft effects for massless dijet events. In a future paper we compute alphas corrections to the jet invariant mass spectrum, including a summation of large logarithms between the scales Q, m, and Gamma.
Incidental lung carcinoma detected at CT in patients selected for lung volume reduction surgery to treat severe pulmonary emphysema.

PURPOSE The authors present their experience with previously unsuspected carcinoma of the lung detected at preoperative computed tomography (CT) in patients with severe pulmonary emphysema who were scheduled to undergo lung volume reduction surgery. MATERIALS AND METHODS Preoperative chest CT was performed in 148 patients (84 men, 64 women; mean age, 65 years +/- 8 [standard deviation]) with advanced pulmonary emphysema before lung volume reduction surgery. At surgery, an attempt was made to excise any pulmonary nodule considered suspicious for carcinoma at CT. RESULTS Eighteen pulmonary nodules suspicious for lung cancer were found at CT in 17 (11%) of the 148 patients. Sixteen of these 148 nodules were resected at lung volume reduction surgery. Nine non-small cell carcinomas (adenocarcinoma, n = 4, including three with bronchioloalveolar differentiation; poorly differentiated, n = 3; squamous cell carcinoma, n = 2) were found in eight (5%) patients. Eight of the cancers were stage I, and one was unstaged surgically. Maximum diameters of the cancers ranged between 1.0 and 3.8 cm (median, 1.6 cm). The seven (5%) other resected nodules were all benign. CONCLUSION A 5% rate of stage I primary lung cancer in patients selected for lung volume reduction surgery suggests that performance of chest CT in candidates for lung volume reduction surgery is appropriate not only to identify patterns of pulmonary parenchymal destruction but also to search for stage I lung cancer.
Region & gateway mapping: acquiring structured and object-oriented representations of indoor environments

State-of-the-art robot mapping approaches are capable of acquiring impressively accurate 2D and 3D models of their environments. To the best of our knowledge, few of them represent structure or acquire models of task-relevant objects. In this work, a new approach to mapping of indoor environments is presented, in which the environment structure in terms of regions and gateways is automatically extracted, while the robot explores. Objects, both in 2D and 3D, are modeled explicitly in those maps and allow for robust localization. We refer to those maps as structured object-oriented environment representations or Region & Gateway Maps (RG Maps). The process of building such maps is called Region & Gateway Mapping (RG Mapping). RG Maps and RG Mapping make several contributions to the field of map building of indoor environments. First, RG Mapping automatically recovers the structure of large classes of indoor environments and represents them explicitly. Therefore, novel algorithms have been developed for the detection and recognition of gateways, i.e. transitions between regions. Second, it detects rectangular 2D/3D objects using laser range as well as image data that are used for gateway detection and localization. Third, the semantic description, i.e. annotation of regions and objects, is obtained from human-machine interaction in the context of task assignment. Fourth, a compact Region & Gateway Graph is easily extracted from RG Maps, and it is used for efficient path planning on the global scale. It allows reasoning about the feasibility of a given path and learning of the properties of path segments while the robot moves through the environment. Fifth, due to the clustering of metric data into regions, region-based localization and path planning only need to consider the respective region data. Thus, the complexity of the data association problem for localization and the search space for metric path planning is substantially reduced. The RG Mapping and Navigation System has been fully implemented as a distributed (module-based) system, and runs in real-time on a real robot. Due to its architecture, the system can be easily ported to different platforms, provided that similar sensor data is available. In order to support reliable exploration of and navigation within RG Maps, the presented system features a novel approach to collision avoidance and low-level control. The low-level control allows for very precise and fast pursuing of short trajectory segments, which can be changed at any time. The collision avoidance generates trajectory segments based on the interpretation of the current sensor data and short-distance targets from the path planning process. As a result, the navigation behaviour of the robot is reproducible and predictable, which is a very desirable feature for high-level planning.
Investigation of the impact of modified montmorillonite on the viscosity of the solutions of polyvinyl alcohol

Comparative studies of pure polyvinyl alcohol solutions and compositions based on this alcohol were carried out. The results of research on viscometers of different types — capillary (VTL-2) and ball (Geppler viscometer). The influence of montmorillonite-polyvinylpyrrolidone mixture (MPM) on the dynamic and kinematic viscosity of polyvinyl alcohol solutions was established. It was established that the viscosity of the solution of the composition based on PVA and MPM is 1.3 times higher than the viscosity of the pure polyvinyl alcohol at a concentration of 0.01 g / ml.
Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis.

We investigated whether a relationship between risk of death and treatment effect could explain the disparate results between the preclinical and clinical sepsis trials of antiinflammatory agents over the last decade. A metaregression analysis of cited preclinical studies showed that the treatment effects of these agents were highly dependent on risk of death (p = 0.0001) and that animals were studied at significantly higher control mortality rates than humans (median [25th-75th quartile], 88% [79-96%] versus 39% [32-42%], p = 0.0001). An analysis of the clinical trials showed that antiinflammatory agents were also significantly more efficacious in septic patients with higher risk of death (p = 0.002) and were harmful in those with low risk. To test this relationship prospectively, we studied antiinflammatory agents in models employing differing doses of bacterial challenge to produce the full range of risk of death. We found that the efficacy of these agents, although very beneficial at high control mortality rates, was much reduced (p = 0.0001) and similar to those in human trials at moderate control mortality rates (i.e., 30 to 40%). The efficacy of antiinflammatory agents during sepsis is dependent on the risk of death, an observation that explains the apparent contradiction between preclinical and clinical trial results. Accounting for this relationship may be necessary for the safe and effective development of antiinflammatory therapies for sepsis.
Social Media based learning from a European perspective: A Framework for Social Innovation

This paper presents our experience in developing an online curriculum dedicated to promoting the use of social media in an educational context on a European scale. We describe ‘social media based learning’ as a new form of using old technology. Our focus is not based on the technology itself but rather the engagement with technology that positions this as a social innovation. The term “social innovation” describes new intentional social practices that are aiming at better satisfying or answering needs and problems. “An innovation is therefore social to the extent that it is socially accepted and diffused (.)” (Howaldt, J. & Schwarz, M. 2010, 26).
Early Detection of Pedicle Screw-Related Spinal Cord Injury By Continuous Intraoperative Neurophysiological Monitoring (IONM)

ABSTRACT. Pedicle screw placement has a high risk of damaging the motor and sensory pathways due to the close proximity to the spinal cord and nerve roots. Early detection and prevention of injury can be achieved by utilizing Somatosensory Evoked Potentials (SSEP) and Transcranial electrical Motor Evoked Potentials (TCeMEP) during a scoliosis surgery. A 19-year-old female presented for correction of scoliosis. After intubation, electrodes were placed for upper and lower SSEPs, EMGs and TCeMEPs. Total intravenous anesthesia was used. Baseline SSEP and TCeMEP responses were present in all limbs. Eight pedicle screws were placed. After placing the last screw, TCeMEP signals were lost bilaterally in lower extremities. Surgery was paused. After removing all the screws TCeMEP responses returned to baseline in left lower limb but remained absent in right lower limb. A wake-up test was performed which was positive in her right leg. Blood pressure was increased and bolus of steroids was given. There was no improvement in right lower limb TCeMEP responses. Surgeon was advised to stop the surgery and proceed for MRI and follow-up. SSEP signals remained stable in all four extremities. The surgical correction was cancelled. MRI revealed intramedullary spinal cord ischemic changes at Til. After extubation, patient was unable to move her right lower extremity with flaccid paralysis. She also complained about severe burning in her left lower extremity. The patient was taken for rehabilitation exercises. One week post-op, she was moving hip flexors and two weeks later had a full motor function, bilaterally. Real-time IONM was useful in early identification of spinal cord injury. Significant changes were seen in TCeMEP, without any change in SSEP. We highly recommend utilizing continuous TCeMEP and SSEP monitoring during pedicle screw placement for prevention of injury to the spinal cord. In this case, the patient would have been paralyzed post-operatively without the use of IONM.
The relation between dopamine oxidation currents in the nucleus accumbens and conditioned increases in motor activity in rats following repeated administration of d‐amphetamine or cocaine

Chronoamperometric recording techniques were used to monitor extracellular dopamine efflux in the nucleus accumbens associated with unconditioned and conditioned increases in motor activity in rats, following the intravenous administration of either d‐amphetamine (0.63 mg/kg) or cocaine (3 mg/kg), or the presentation of a conditioned stimulus paired repeatedly with one of these psychostimulants. Each drug was administered daily for 7 days, either in the home cage or an environment in which a compound stimulus (light offset, odour) was presented. Rats in control groups received saline instead of drug in the distinctive test environment. On day 7 of training, significant increases in unconditioned motor activity were observed in the 30 min session following infusions of either d‐amphetamine or cocaine. Associated dopamine oxidation currents in the nucleus accumbens increased immediately following administration of either drug and remained significantly elevated above baseline during the entire 30 min recording period. On the test day, presentation of the conditioned stimulus with vehicle infusions, in the distinct environment, was accompanied by an increase in dopamine oxidation currents and a conditioned increase in motor activity, only in the groups in which these stimuli had been paired with d‐amphetamine or cocaine. Neither the magnitude or duration of the conditioned motor activity matched the corresponding change in extracellular dopamine efflux in the nucleus accumbens. Accordingly, it is argued that the increase in dopamine concentration serves as a neurochemical correlate of the unconditioned and conditioned stimuli. The change in motor activity constitutes the unconditioned and conditioned responses that are subserved by the neural systems activated by the initial rise in extracellullar dopamine.
Immortalized Human HaCaT Keratinocytes Mitochondrial Apoptosis Pathway by Sanguinarine in Activation of Prodeath Bcl-2 Family Proteins and Updated Version

Sanguinarine, derived from the root of Sanguinaria canadensis and other poppy fumaria species, possesses strong antimicrobial, anti-inflammatory, and antioxidant properties. We earlier showed that sanguinarine kills human epidermoid carcinoma A431 cells via an induction of apoptosis [N. Ahmad et al., Clin. Cancer Res., 6: 1524–1528, 2000]. In this study, using immortalized human keratinocytes (HaCaT cells), we provide information about mechanism of the antiproliferative effect of sanguinarine. Sanguinarine [0.1 (M-2 (M)] treatment to HaCaT cells was found to inhibit in a dose-dependent manner the cell proliferation and induce apoptosis, as measured by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA, respectively. Sanguinarine treatment also resulted in a significant cleavage of poly(ADP-ribose) polymerase in HaCaT cells. Because mitochondrial pathway is critical for the regulation of apoptosis, we studied the involvement and regulation of mitochondrial events in sanguinarine-mediated apoptosis of HaCaT cells. As shown by the immunoblot analysis, our data clearly demonstrated that sanguinarine treatment to HaCaT cells resulted in a dose-dependent (a) increase in the level of Bax with a concomitant decrease in Bcl-2 levels and (b) increase in Bax/Bcl-2 ratio. Sanguinarine also resulted in significant increases in the proapoptotic members of Bcl-2 family proteins, i.e., Bak and Bid. This was accompanied by increase in (a) protein expression of cytochrome c and apoptotic protease-activating factor-1 and (b) activity and protein expression of caspase-3, caspase-7, caspase-8, and caspase-9. Taken together, our data showed the involvement of mitochondrial pathway and Bcl-2 family proteins during sanguinarine-mediated apoptosis of immortalized keratinocytes. We suggest that sanguinarine could be developed as a drug for the management of hyperproliferative skin disorders, including skin cancer.
Energy-Efficient Task Scheduling and Synchronization for Multicore Real-Time Systems

In the recent years, many energy-efficient realtime task scheduling algorithms have been proposed for multicore platforms. Most of them focus on independent tasks, however, relatively little work has been done in the presence of task synchronization. In this paper, we are interested in scheduling of real-time tasks which may make requests for accessing shared resources at the run time. A similarity-based task-to-core partitioning algorithm is proposed to allocate the tasks which may access a similar set of shared resources to the same core so that a large number of blockings can be avoided. Furthermore, we also propose speed assignment methods to assign proper processor speeds for tasks' executions with full-chip and per-core DVFS techniques so that the overall energy consumption can be reduced. The schedulability analysis of our proposed approach is provided in this paper. The capabilities of our proposed approach were evaluated by a series of experiments for which we have some encouraging results.
A Process Model of Complementarity and Substitution of Contractual and Relational Governance in IS Outsourcing

This paper develops a process model of how and why complementarity and substitution form over time between contractual and relational governance in the context of information systems outsourcing. Our analysis identifies four distinct process patterns that explain this formation as the outcome of interaction processes between key elements of both contractual and relational governance. These patterns unveil the dynamic nature of complementarity and substitution. In particular, we show that the relationship between contractual and relational governance oscillates between complementarity and substitution. Those oscillations are triggered mainly by three types of contextual events (goal fuzziness, goal conflict, and goal misalignment). Surprisingly, substitution of informal control did not occur as an immediate reaction to external events but emerged as a consequence of preceding complementarity. Thus, our study challenges the prevailing view of an either/or dichotomy of complementarity and substitution by showing that they are causally connected over time.
[Histological studies on the roots of eighteen species of sect. microdiscus of the genus Adenophora].

The Chinese materia medica "Nanshasheng" (Radix Adenophorae) specified in Chinese Pharmacopoeia (1995) is the dried root of Adenophora tetraphylla (Thunb.) Fisch. or A. stricta Miq. (Fam. Campanulaceae). Results of an investigation on the botanical origin of the drug showed that the roots of 30 species (subspecies, varieties) of the genus Adenophora are also used in certain districts in China. Thus, it is necessary to study and compare the histological characters of these roots. In this paper, the root structure of 18 species from Sect. Microdiscus are reported, viz. Adenophora brevidiscifera Hong, A. coelestis Diels, A. stricta Miq. , A. stricta Miq. var. qinglongshanica P. F. Tu et G. J. Xu, A. stricta Miq. var. nanjingensis P. F. Tu et G. J. Xu, A. stricta Miq. subsp. henanica P. F. Tu et G. J. Xu, A. stricta Miq. subsp. sessilifolia Hong, A. longipedicellata Hong, A. gmelinii (Spreng.) Fisch. , A. polyantha Nakai, A. micrantha Hong, A. stenophylla Hemsl. , A. potaninii Korsh. , A. bockiana Diels, A. wawreana Zahlbr. , A. tricuspidata (Fisch. ex Roem. et Schult.) A. DC. , A. pereskiifolia (Fisch. ex Roem. et Schult.) G. Don and A. divaricata Franch. et Sav. According to the presence, arrangement and thickening of cell walls of sclerified cork cell (SCC) in cork tissue and the rate of secondary and anomalous structures, the histological structures of Adenophora roots are classified into types A, B and C. In type A, SCC are arranged in ring shape. Type A can be further classified into subtypes A1 and A2. Only the outer and anticlinal walls of SCC are thickened in subtype A1, and all cell walls of SCC are thickened in subtype A2. In type B, SCC are arranged scatteredly, not in ring shape. In type C, there is no SCC. Type C can be classified into subtypes C1, C2 and C3. In type C1, the secondary structure occupies more than 50% of the root diameter. In type C2, the anomalous structure is more than 50% of the root diameter, and the anomalous vascular bundles are in band form. The anomalous structure occupies more than 50% of the root diameter in subtype C3, and the anomalous vascular bundles are branched.