Miracle-dz/UniFAR-FTUs huggingface dataset:
The fifth immunoglobulin-like domain of the Kit receptor is required for proteolytic cleavage from the cell surface.

Stem cell factor (SCF) initiates its biological effects by binding to its receptor Kit. Cell surface Kit is proteolytically cleaved to generate soluble Kit. Structure-function analysis of the extracellular region of Kit has implicated the first three immunoglobulin-like domains in SCF binding, and the fourth immunoglobulin-like domain in receptor dimerization. However, the role of the fifth immunoglobulin-like domain is unknown. To test the hypothesis that the fifth immunoglobulin-like domain is important for proteolytic cleavage of Kit from the cell surface, we constructed a mutant form of Kit in which the first four immunoglobulin-like domains are linked to the transmembrane and cytoplasmic domains (designated Kit-Del5). Kit-wild type (Kit-WT) and Kit-Del5 were expressed in the murine mast cell line IC2. Flow cytometry demonstrated that both Kit-WT and Kit-Del5 are displayed on the IC2 cell surface, and immunoblotting confirmed the presence of Kit proteins of the expected molecular weights, 154 kDa and 134 kDa, respectively. Although IC2-Kit-WT cells proteolytically cleave cell surface Kit, generating a 98 kDa soluble form of Kit, IC2-Kit-Del5 cells do not. These findings demonstrate that the fifth immunoglobulin-like domain of Kit is required for proteolytic cleavage of Kit from the cell surface.
MicroRNA-155 in the Heart: The Right Time at the Right Place in the Right Cell.

Cardiovascular complications arising as a consequence of vascular disease are on the rise in the world, with an urgent need to develop therapies that can prevent the drivers of atherosclerosis and promote healing of infarcted tissue after an ischemic event. Rupture of culprit atherosclerotic lesions is the main driver of downstream myocardial infarction (MI), accounting for 7 million deaths annually and 23 million individuals living with heart failure worldwide.1 Accordingly, there has been a tremendous interest in using novel therapies to revascularize ischemic tissue and to repair damaged myocardium after MI.2 Although there is a clear clinical need to promote collateral vessel growth to facilitate healing and to preserve tissue integrity after an ischemic event, the mechanisms that govern the growth of collateral vessels remain largely unknown. In this issue of Circulation , Pankratz and colleagues3 use microRNAs (miRNAs) to study the different mechanisms that promote angiogenesis and arteriogenesis and find that microRNA-155 (miR-155) has dual and opposing roles in both processes. Article see p 1575 The authors first set out to discover the miRNA-based mechanisms that promote neovascularization. Using a model of femoral artery ligation, they found the expression of 30 miRNAs differentially regulated 7 days after ligation. On the basis of the substantial downregulation of miR-155 during this neovascularization period, they hypothesized that miR-155 antagonizes factors that regulate angiogenesis. Indeed, they followed up by showing that endothelial cells (ECs) devoid of miR-155 (from miR-155−/− mice) have an improved angiogenic capacity compared with wild-type ECs and concluded that miR-155 antagonizes angiogenesis. They demonstrated that miR-155 was able to inhibit angiogenesis through inhibition of AGTR1, a known miR-155 target gene that promotes angiogenesis and inhibits inflammation, in ECs.4 Using an in vivo Matrigel assay that assesses the sprouting of new capillaries into a basement membrane-like …
Heterogeneity in infection outcome: lessons from a bumblebee‐trypanosome system

Interactions between insect hosts and their parasites are significant because their parasites can also be parasites of humans and of species that we utilize. Host–parasite interactions are complex, even in insects, and there can be heterogeneous outcomes in infection success, load, virulence and transmission, with consequences for the evolution of hosts and their parasites, and also for epidemiology. A comprehension that the triad of host, parasite and environment interact to dictate infection outcome is key for anyone interested in host–parasite research. Studies in model systems used to good effect to characterize insect immunity and infection rarely scrutinize such heterogeneity. Evolutionary ecology studies addressing natural variation offer a window on the causes and consequences of such heterogeneity. A system at the forefront in this area is that of bumblebees and their trypanosome parasite Crithidia. Placing results and interpretations in a broader context we synthesize the plethora of work on bumblebee immunity and parasite interactions. We describe and discuss the sources of heterogeneity that should also be considered in human‐relevant insect–parasite systems, including genotypic variation in both parasites and hosts, the mediating role of the environment, and explore the emerging evidence for microbiota modulating defence against parasites.
Caiipa: automated large-scale mobile app testing through contextual fuzzing

Scalable and comprehensive testing of mobile apps is extremely challenging. Every test input needs to be run with a variety of contexts, such as: device heterogeneity, wireless network speeds, locations, and unpredictable sensor inputs. The range of values for each context, e.g. location, can be very large. In this paper we present Caiipa, a cloud service for testing apps over an expanded mobile context space in a scalable way. It incorporates key techniques to make app testing more tractable, including a context test space prioritizer to quickly discover failure scenarios for each app. We have implemented Caiipa on a cluster of VMs and real devices that can each emulate various combinations of contexts for tablet and phone apps. We evaluate Caiipa by testing 265 commercially available mobile apps based on a comprehensive library of real-world conditions. Our results show that Caiipa leads to improvements of 11.1x and 8.4x in the number of crashes and performance bugs discovered compared to conventional UI-based automation (i.e., monkey-testing).
Adaptation for Device Independent Authoring

The impact of device independent authoring on software engineering manifests itself mainly at the middleware level. Until recently middleware platforms were targeted at vertical coverage of specific scenarios. Consumer devices with integrated Internet-access are becoming more popular and their diversity grows with their market penetration and with the extension of the mobile communication infrastructure. This requires software architectures that are capable of supporting horizontal coverage of a wide range of devices and scenarios. This paper presents the Multi User Interface, Single Application project. It provides a feasable approach for multiplatform support through the introduction of an adaptable and abstract interaction-oriented user interface language.
γ‐Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: potential role as an antiproliferative, pro‐apoptotic and chemosensitizing agent

Activation of signal transducer and activator of transcription 3 (STAT3) play a critical role in the survival, proliferation, angiogenesis and chemoresistance of tumour cells. Thus, agents that suppress STAT3 phosphorylation have potential as cancer therapies. In the present study, we investigated whether the apoptotic, antiproliferative and chemosensitizing effects of γ‐tocotrienol are associated with its ability to suppress STAT3 activation in hepatocellular carcinoma (HCC).
Repair of potentially lethal lesions in x-irradiated, density-inhibited Chinese hamster cells: metabolic effects and hypoxia.

Plateau phase Chinese hamster cells (HA-1), growing in monolayers, form a convenient system for studying the repair of potentially lethal damage. Cells are irradiated under conditions of density inhibition, and the interval between irradiation and explant (to assay survival) is varied. Repair is evidenced by higher survival of those cells maintained in plateau. This increase in survival can be expressed as a slope-modifying factor. The magnitude of the slope-modifying factor is determined by the cells' post-irradiation environment. Cells overlaid with Hanks' BSS in the interval between irradiation and explant showed a maximum slope-modifying factor (∼1.3), cells in serum free or "conditioned" medium a somewhat lower value, while minimum repair was seen if the cells were in fresh medium supplemented with fetal bovine serum. Hypoxia does not seem to affect the magnitude of repair of potential lethal damage if the comparison of survival increase is made at similar survival (rather than dose) levels. Cells in.
Non-Constituent Coordination: Theory and Practice

Despite the large amount of theoretical work done on non-constituent coordination during the last two decades, many computational systems still treat coordination using adapted parsing strategies, in a similar fashion to the SYSCONJ system developed for ATNs. This paper reviews the theoretical literature, and shows why many of the theoretical accounts actually have worse coverage than accounts based on processing. Finally, it shows how processing accounts can be described formally and declaratively in terms of Dynamic Grammars.
Activation of GPR 30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen 2 . Lewis rats

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats
The Effects of Heme Pocket Hydrophobicity on the Ligand Binding Dynamics in Myoglobin as Studied with Leucine 29 Mutants*

To examine the effects of heme pocket hydrophobicity on the ligand binding in myoglobin, some artificial mutants of human myoglobin have been prepared, in which less hydrophobic amino acid residue (Ala, Gly, Ser) is located at the Leu29 (10th residue of the B helix) position. CO rebinding rates for the mutants were markedly decelerated, while the1H, and 15N NMR spectra of the mutants show that the structural changes around the heme iron for these mutants are rather small. The kinetic and structural properties of the mutants indicate that the ligand binding rate depends on the hydrophobicity inside the heme cavity for these mutants in addition to the volume of the side chain at the 29-position. On the basis of the IR stretching frequency of liganded CO, invasion of water molecules into the heme pocket in the mutants is suggested, which would be induced by the decrease in the hydrophobicity due to the amino acid substitution. A slight red shift of the position of the Soret peak for the serine mutant L29S also supports the reduced hydrophobicity inside the heme cavity. We can concluded that, together with the kinetic properties of the mutants, the hydrophobicity of the heme pocket is one of the key factors in regulating the ligand binding to the heme iron.
A reusable coverage-driven verification environment for Network-on-Chip communication in embedded system platforms

Functional verification plays an important role in the design flow of an Intellectual Property (IP) core and, in general, of an embedded system. The industrial trend of the last two decades has been to produce more and more complex embedded systems by integrating several IP cores on a single chip die; while this is easily possible thanks to the availability of ready-to-use off-the-shelf components, the functional verification of the whole system becomes a major concern. Hand-written HDL testbenches or formal approaches to verification are no more feasible methods to assess good quality verification in a reasonable amount of time. To meet the new requirements of complex systems design, EDA companies are developing verification tools that bring rapid development, reusability concepts and automation techniques also in the world of functional verification. This work faces the issue of providing an automated verification environment for a Network-on-Chip component that is part of a complex communication infrastructure within a multi-core embedded system. In this context, reusability is a key feature of the environment, because it allows the user to easily move from component verification to network verification. The verification tool used in this work is Specman elite by Cadence and the IP it is applied to is a Spidergon-STNoC (by STMicroelectronics) component. Verification environment design guidelines are provided together with a final coverage report summary.
Phase III Study Comparing Methotrexate and Tacrolimus ( Prograf , FK 506 ) With Methotrexate and Cyclosporine for Graft-Versus-Host Disease Prophylaxis After HLA-Identical Sibling Bone Marrow Transplantation

By Voravit Ratanatharathorn, Richard A. Nash, Donna Przepiorka, Steven M. Devine, Jared L. Klein, Daniel Weisdorf, Joseph W. Fay, Auayporn Nademanee, Joseph H. Antin, Neal P. Christiansen, Richard van der Jagt, Roger H. Herzig, Mark R. Litzow, Steven N. Wolff, Walter L. Longo, Finn B. Petersen, Chatchada Karanes, Belinda Avalos, Rainer Storb, Donald N. Buell, Rochelle M. Maher, William E. Fitzsimmons, and John R. Wingard
Determination of Pavement Rehabilitation Activities through a Permutation Algorithm

This paper presents a mathematical programming model for optimal pavement rehabilitation planning. The model maximized the rehabilitation area through a newly developed permutation algorithm, based on the procedures outlined in the harmony search (HS) algorithm. Additionally, the proposed algorithm was based on an optimal solution method for the problem of multilocation rehabilitation activities on pavement structure, using empirical deterioration and rehabilitation effectiveness models, according to a limited maintenance budget. Thus, nonlinear pavement performance and rehabilitation activity decision models were used to maximize the objective functions of the rehabilitation area within a limited budget, through the permutation algorithm. Our results showed that the heuristic permutation algorithm provided a good optimum in terms of maximizing the rehabilitation area, compared with a method of the worst-first maintenance currently used in Seoul.
Quantitation of small-animal (124)I activity distributions using a clinical PET/CT scanner.

UNLABELLED Time-dependent PET imaging can be an important tool in the assessment of radiotracer performance in murine models. We have performed a quantitative analysis of PET images of (124)I, acquired on a clinical PET system using a small-animal phantom. We then compared the recovered activity concentrations with the known activity concentration in the phantom spheres. The recovery coefficients found from the phantom data were applied to in vivo (124)I anti-HER2/neu C6.5 diabody PET data and compared with necropsy biodistribution data from the same tumor-bearing immunodeficient mouse. METHODS The small-animal phantom consisted of a 4 x 8 cm water-filled acrylic cylinder with hollow spheres filled with water ranging in volume from 0.0625 to 1.0 mL and activity concentration of 27 +/- 2 kBq/mL. The background activity concentrations varied from 0 to 0.05 to 0.10 of the spheres. Data were acquired at 0, 5, and 10 cm from the scanner longitudinal axis. Recovery coefficients were theoretically calculated for spheres of different volume, background-to-target concentrations, and distance from the scanner's longitudinal axis. The theoretic recovery coefficients were applied to the maximum sphere activity concentration measured from the PET images, thus obtaining a recovered activity concentration to be compared with the known activity concentration of the spheres. RESULTS The mean recovered activity concentration for the phantom spheres was 25 +/- 2 kBq/mL. The (124)I diabody PET image of a mouse with a tumor xenograft was then analyzed using the techniques described. The tumor percentage injected dose per gram estimated from the murine PET image (4.8 +/- 0.4) compared well with those obtained from necropsy studies (5.1). CONCLUSION This study indicates the feasibility of performing quantitative imaging on murine (124)I antibody fragment PET images using a large-bore clinical scanner, which enables high-throughput studies to evaluate the performance of PET tracers in a timely and cost-effective manner by imaging multiple animals simultaneously. Tracers deemed promising by this screening method can then be further evaluated using traditional necropsy studies. Our group is currently conducting time-dependent (124)I diabody PET and necropsy comparative studies with larger numbers of mice.
A suf operon requirement for Fe–S cluster assembly during iron starvation in Escherichia coli

The suf and isc operons of Escherichia coli have been implicated in Fe–S cluster assembly. However, it has been unclear why E. coli has two systems for Fe–S cluster biosynthesis. We have examined the regulatory characteristics and mutant phenotypes of both operons to discern if the two operons have redundant functions or if their cellular roles are divergent. Both operons are similarly induced by hydrogen peroxide and the iron chelator 2,2′‐dipyridyl, although by different mechanisms. Regulation of the isc operon is mediated by IscR, whereas the suf operon requires OxyR and IHF for the response to oxidative stress and Fur for induction by iron starvation. Simultaneous deletion of iscS and most suf genes is synthetically lethal. However, although the suf and isc operons have overlapping functions, they act as distinct complexes because the SufS desulphurase alone cannot substitute for the IscS enzyme. In addition, suf deletion mutants are more sensitive to iron starvation than isc mutants, and the activity of the Fe–S enzyme gluconate dehydratase is diminished in the suf mutant during iron starvation. These findings are consistent with the model that the isc operon encodes the housekeeping Fe–S cluster assembly system in E. coli, whereas the suf operon is specifically adapted to synthesize Fe–S clusters when iron or sulphur metabolism is disrupted by iron starvation or oxidative stress.
Convergence theorem for a general class of power-control algorithms

We consider the convergence issues of distributed power-control algorithms for mobile cellular systems. A convergence theorem for power-control algorithms of canonical type is proved. Our result generalizes Yates' framework and provides a new outlook on the problem. The general applicability of the theorem is demonstrated by showing that many well-known distributed algorithms are canonical. Furthermore, by devising some new discrete algorithms, we exemplify how the theorem can be used to aid new design.
Development of a first person shooter game controller

User interfaces play an important role in gaming, their evolution have provided engaging forms of interaction and immersion. Early controllers used digital triggers and have been innovating along with computer graphics. Analogue joysticks became used to provide more accurate movements. Motion-based controllers have caught the attention of developers, researchers, users and enthusiasts as the player engages in movements that may help address a concern related to the lack of physical activity and sedentary caused while videogaming. In this paper we present the development of a realistic shooting game controller for first person shooting games using inertial sensors with haptic and sound feedback for as an alternative gamepad.
The decycling number of graphs

For a graph G and S ⊂ V (G), if G − S is acyclic, then S is said to be a decycling set of G. The size of a smallest decycling set of G is called the decycling number of G. The purpose of this paper is to provide a review of recent results and open problems on this parameter. Results to be reviewed include recent work on decycling numbers of cubes, grids and snakes and bounds on the decycling number of cubic graphs, and expected bounds on the decycling numbers of random regular graphs. A structural description of graphs with a fixed decycling number based on connectivity is also presented.
Visual short-term memory of stimulus velocity in patients with unilateral posterior brain damage

Neurophysiological studies indicate the existence of an area in the extrastriate monkey cortex specialized for the processing of stimulus motion. The present investigation was conducted to determine whether a homologous area exits in the human cortex that underlies the processing and short-term storage of velocity information. Contrast detection and velocity discrimination thresholds were measured in a group of 23 patients with unilateral focal damage to either the lateral occipital, temporal, or posterior parietal cortex. Their results were compared to those of 23 age-matched control subjects. Detection and discrimination thresholds were determined for spatially truncated sinewave gratings presented 4 degrees eccentric of fixation randomly in either the left and right visual fields. Contrast detection thresholds were measured in a spatial two-alternative forced-choice paradigm for three different drift rates (1, 2, and 4 Hz) for leftward and rightward drift directions. Simultaneous velocity discrimination thresholds were determined for reference and test gratings presented 4 degrees left and right of fixation. Sequential velocity discrimination thresholds were measured using a delay, with a interstimulus interval (ISIs) of 1, 3, and 10 sec. In a subset of five patients with superior temporal lobe damage, spatial frequency discrimination thresholds for stationary gratings were also determined. The results indicate the following: (1) contrast detection thresholds for drifting gratings did not significantly differ between the patient and control groups; (2) velocity discrimination thresholds were significantly elevated in the patients; (3) velocity discrimination thresholds significantly increased with increasing ISI in the patients; (4) velocity discrimination thresholds were elevated most when the patients had a lesion in the superior temporal cortex; (5) in the subgroup of five patients with superior temporal lobe damage, spatial frequency discrimination thresholds were not significantly elevated. The results suggest that there is a visual area in the human posterior temporal cortex that is involved in the processing and short-term storage of the velocity of moving visual stimuli.
Using Phylogeny to Improve Genome-Wide Distant Homology Recognition

The gap between the number of known protein sequences and structures continues to widen, particularly as a result of sequencing projects for entire genomes. Recently there have been many attempts to generate structural assignments to all genes on sets of completed genomes using fold-recognition methods. We developed a method that detects false positives made by these genome-wide structural assignment experiments by identifying isolated occurrences. The method was tested using two sets of assignments, generated by SUPERFAMILY and PSI-BLAST, on 150 completed genomes. A phylogeny of these genomes was built and a parsimony algorithm was used to identify isolated occurrences by detecting occurrences that cause a gain at leaf level. Isolated occurrences tend to have high e-values, and in both sets of assignments, a sudden increase in isolated occurrences is observed for e-values >10−8 for SUPERFAMILY and >10−4 for PSI-BLAST. Conditions to predict false positives are based on these results. Independent tests confirm that the predicted false positives are indeed more likely to be incorrectly assigned. Evaluation of the predicted false positives also showed that the accuracy of profile-based fold-recognition methods might depend on secondary structure content and sequence length. We show that false positives generated by fold-recognition methods can be identified by considering structural occurrence patterns on completed genomes; occurrences that are isolated within the phylogeny tend to be less reliable. The method provides a new independent way to examine the quality of fold assignments and may be used to improve the output of any genome-wide fold assignment method.