Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane-protein traffic in pathogen-infected cells.

For more than two decades, the standard paradigm for discussing membrane traffic in pathogen-infected cells has centered around fusion of the microbe-containing vacuole with lysosomes, and upon vacuole acidification. Organisms have been placed in one of three relatively invariant categories: pathogens residing in vacuoles which fuse with lysosomes and acidify, those that readily disrupt the vacuolar membrane and subsequently replicate in the host cell cytosol, and microbes residing in vacuoles which neither fuse with lysosomes nor acidify. The nature of membrane traffic was thought to be dictated almost exclusively by the requirement of the pathogen to avoid killing by the low pH and the degradative enzymes present in lysosomes. It is increasingly clear that this paradigm is oversimplified (1, 2). It neither appropriately reflects the selectivity and plasticity of membrane traffic within cells, nor does it give adequate weight to membrane traffic events which may be largely of importance for nutrient acquisition or induction of gene expression by the intracellular organism. This perspective will describe membrane traffic in pathogen-infected cells in the context of more recent advances in the cell biology of vesicular traffic, and with the above considerations in mind.
The structure of cytoplasm in directly frozen cultured cells. II. Cytoplasmic domains associated with organelle movements

The relationship between organelle movement and cytoplasmic structure in cultured fibroblasts or epithelial cells was studied using video- enhanced differential interference contrast microscopy and electron microscopy of directly frozen whole mounts. Two functional cytoplasmic domains are characterized by these techniques. A central domain rich in microtubules is associated with directed as well as Brownian movements of organelles, while a surrounding domain rich in f-actin supports directed but often intermittent organelle movements more distally along small but distinct individual microtubule tracks. Differences in the organization of the cytoplasm near microtubules may explain why organelle movements are typically continuous in central regions but usually intermittent along the small tracks through the periphery. The central type of cytoplasm has a looser cytoskeletal meshwork than the peripheral cytoplasm which might, therefore, interfere less frequently with organelles moving along microtubules there.
N-Cadherin Expression and Epithelial-Mesenchymal Transition in Pancreatic Carcinoma

Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β, and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.
Congestion games with failures

We introduce a new class of games, congestion games with failures (CGFs), which extends the class of congestion games to allow for facility failures. In a basic CGF (BCGF) agents share a common set of facilities (service providers), where each service provider (SP) may fail with some known probability. For reliability reasons, an agent may choose a subset of the SPs in order to try and perform his task. The cost of an agent for utilizing any SP is a function of the total number of agents using this SP. A main feature of this setting is that the cost for an agent for successful completion of his task is the minimum of the costs of his successful attempts. We show that although BCGFs do not admit a potential function, and thus are not isomorphic to classic congestion games, they always possess a pure-strategy Nash equilibrium. We also show that the SPs' congestion experienced in different Nash equilibria is (almost) unique. For the subclass of symmetric BCGFs we give a characterization of best and worst Nash equilibria. We extend the basic model by making task submission costly and define a model for taxed CGFs (TCGFs). We prove the existence of a pure-strategy Nash equilibrium for quasi-symmetric TCGFs, and present an efficient algorithm for constructing such Nash equilibrium in symmetric TCGFs.
Changes in excitability of human motor axons underlying post‐ischaemic fasciculations: evidence for two stable states.

1. We have investigated the origin of post‐ischaemic ectopic discharges in human nerve by recording changes in electrical excitability following periods of ischaemia (15‐20 min) sufficient to induce spontaneous motor fasciculations. The ulnar nerve was stimulated beneath a pressure cuff on the upper arm, and compound motor action potentials recorded from abductor digiti minimi. 2. On releasing the cuff after 15 min of ischaemia, thresholds to short current pulses increased in two distinct phases: a slow phase followed by a rapid rise to a peak threshold. The rapid rise was too fast to track (i.e. 100% threshold increase in less than 4 s), and was sometimes followed after 30‐40 s by an equally rapid fall. Small polarizing currents affected the timing of the rapid threshold increase, as if it was occurring at a particular membrane potential. 3. By recording complete stimulus‐response curves every few seconds, we found that the rapid threshold changes were associated with a bimodal distribution of thresholds. Most fibres were found in either a high‐threshold or low‐threshold state, and these two states converged over a period of about 10 min. 4. Spontaneous motor fasciculations were only recorded after the rapid rise in threshold and when the fibres existed in two threshold states. The spontaneous activity was not responsible for inducing the two states, since they could also be recorded in its absence. 5. A computer model of a human motor axon node and internode was constructed, incorporating channel types demonstrated in other axons, and channel densities adjusted to match the responses of human axons to depolarizing and hyperpolarizing current pulses. An increase in extracellular potassium concentration produced a region of negative slope conductance in the current‐voltage relationship of the model, and the appearance of two stable states with enhanced activity of the electrogenic sodium pump. 6. Transitions between the two stable states of the model could account qualitatively for the rapid threshold changes recorded from post‐ischaemic axons. In the model, spontaneous action potentials occurred following some transitions from the high potential state to the low potential state. We suggest that post‐ischaemic motor fasciculations in man also involve transitions between two equilibrium states, occurring in axons with high extracellular potassium and high electrogenic pump activity.
Chemosensory Regulation of a HEAT-Repeat Protein Couples Aggregation and Sporulation in Myxococcus xanthus

ABSTRACT Chemosensory systems are complex, highly modified two-component systems (TCS) used by bacteria to control various biological functions ranging from motility to sporulation. Chemosensory systems and TCS both modulate phosphorelays comprised of histidine kinases and response regulators, some of which are single-domain response regulators (SD-RRs) such as CheY. In this study, we have identified and characterized the Che7 chemosensory system of Myxococcus xanthus, a common soil bacterium which displays multicellular development in response to stress. Both genetic and biochemical analyses indicate that the Che7 system regulates development via a direct interaction between the SD-RR CheY7 and a HEAT repeat domain-containing protein, Cpc7. Phosphorylation of the SD-RR affects the interaction with its target, and residues within the α4-β5-α5 fold of the REC domain govern this interaction. The identification of the Cpc7 interaction with CheY7 extends the diversity of known targets for SD-RRs in biological systems.
A Sensor-data Acquisition Grid Architecture

This paper presents SAGA, a functional software architecture for distributing sensor data. The recursive architecture is dynamically instantiated for collecting, composing and storing data at multiple locations. Objectives are to support devices that are intermittently connected over different access-technologies, to save energy by avoiding repetitive transmission from sensors, and to scale out data compositions for different application services. When the architecture is instantiated the entities form a directed graph across organizational boundaries between sensors and applications. Data may be retrieved from sensors on-demand or be disseminated in real-time, for composition and delivery to the applications. The architecture is based on current sensor network principles such as client-server, representational state transfer and web services. The architecture is presented together with identified key requirements and design choices, and it has been instantiated in a prototype implementation for a smart city application. Some key issues for further research are presented.
The Human Orphan Nuclear Receptor Tailless (TLX, NR2E1) Is Druggable

Nuclear receptors (NRs) are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1), a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP). Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal) assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.
Worldwide Evaluation of DNA Sequencing Approaches for Identification of Drug Resistance Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase

ABSTRACT A panel (ENVA-1) of well-defined blinded samples containing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase was analyzed by automated DNA sequencing in 23 laboratories worldwide. Drug resistance mutations at codons 41, 215, and 184 were present in the panel samples at different ratios to the wild type. The presence of mutant genotypes was determined qualitatively and quantitatively. All laboratories reported the presence of sequence heterogeneities at codons 41, 215, and 184 in one or more of the panel samples, though not all reported the correct codon genotypes. Two laboratories reported a mutant genotype in samples containing only the wild type, whereas two and three laboratories failed to detect the mutant genotypes at codons 41 and 215, respectively, in a completely mutant DNA population. Mutations present at relative concentrations of 25% of the total DNA population were successfully identified by 13 of 23, 10 of 23, and 16 of 23 labs for codons 41, 215, and 184Val, respectively. For more than 80% of those laboratories that qualitatively detected the presence of a mutation correctly, the estimated wild type/mutant ratio was less than 25% different from the input ratio in those samples containing 25 to 50% or 75% mutant input. This first multicenter study on the quality of DNA sequencing approaches for identifying HIV-1 drug resistance mutations revealed large interlaboratory differences in the quality of the results. The application of these procedures in their current state would in several cases lead to inaccurate or even incorrect diagnostic results. Therefore, proper quality control and standardization are urgently needed.
[Role of ERK/FoxO3a signal axis in inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation].

OBJECTIVE To investigate whether the ERK/FoxO3a signal axis could induce the inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation. METHOD The MTT method was adopted to observe the effect of different concentrations of VB-1 on human hepatoma carcinoma cell line HepG2 and immortalized human embryo liver cell line L-02. The cell growth was assessed by the clone formation assay. The protein phosphorylation levels of ERK1/2 and FoxO3a were measured by the western blot. RESULT VB-1 inhibited the viability of HepG2 cell line in a concentration-dependent manner, with a weak effect on L-02 cell line. VB-1 could effectively inhibit the anchorage-dependent growth of HepG2 cells, and reduce the expression levels of pERK1/2 and pFoxO3a in a concentration-dependent manner. MEK1/2 inhibitor PD98059 could enhance VB-1' s effect in inhibiting HepG2 cell proliferation and ERK1/2, FoxO3a phosphorylation. CONCLUSION VB-1 inhibits the proliferative activity of hepatoma carcinoma cell line HepG2 by blocking the ERK/FoxO3a signal axis.
Isotuberculosinol: the unusual case of an immunomodulatory diterpenoid from Mycobacterium tuberculosis.

Despite having served as a primary source for pharmaceutical agents, the physiological role played by natural products in their bacterial hosts is typically unknown. In addition, while terpenoids comprise the largest class of known natural products, it is unusual for these to be produced by bacteria. Accordingly, the recent findings demonstrating that Mycobacterium tuberculosis (Mtb) produces a diterpenoid, isotuberculosinol, is unusual in and of itself, and the accumulating evidence that this functions in the infection process of this pernicious human pathogen indicates a physiological role with medical relevance, all of which is reviewed here. Also presented is conservation of the biosynthetic capacity for isotuberculosinol production, which suggests that this is particularly important in Mtb, leading to speculation that this natural product may contribute to the highly infectious nature of Mtb in humans.
A Methodological Approach to Assessing the Health Impact of Environmental Chemical Mixtures: PCBs and Hypertension in the National Health and Nutrition Examination Survey

We describe an approach to examine the association between exposure to chemical mixtures and a health outcome, using as our case study polychlorinated biphenyls (PCBs) and hypertension. The association between serum PCB and hypertension among participants in the 1999–2004 National Health and Nutrition Examination Survey was examined. First, unconditional multivariate logistic regression was used to estimate odds ratios and associated 95% confidence intervals. Next, correlation and multicollinearity among PCB congeners was evaluated, and clustering analyses performed to determine groups of related congeners. Finally, a weighted sum was constructed to represent the relative importance of each congener in relation to hypertension risk. PCB serum concentrations varied by demographic characteristics, and were on average higher among those with hypertension. Logistic regression results showed mixed findings by congener and class. Further analyses identified groupings of correlated PCBs. Using a weighted sum approach to equalize different ranges and potencies, PCBs 66, 101, 118, 128 and 187 were significantly associated with increased risk of hypertension. Epidemiologic data were used to demonstrate an approach to evaluating the association between a complex environmental exposure and health outcome. The complexity of analyzing a large number of related exposures, where each may have different potency and range, are addressed in the context of the association between hypertension risk and exposure to PCBs.
Feature fusion based multilingual fingerspelling recognition

In this paper, we present a fingerspelling recognition module that has been designed to function in a smart system that is intended to act as a communication medium between people with hearing and visual disabilities. The method described is a computer vision based, close to real-time, automatic skin color based model hand gesture recognition module. We analyze and compare the recognition performance of appearance based hand descriptors on a self collected dataset. The dataset contains isolated videos of 88 different signs of the Czech, Turkish and Russian Sign Alphabets from 5 different signers with a total training and test length of 4 hours. On our test sets, we have achieved signer dependent and signer independent fingerspelling recognition rates of %82 and %42, respectively.
Variability among the Most Rapidly Evolving Plastid Genomic Regions is Lineage-Specific: Implications of Pairwise Genome Comparisons in Pyrus (Rosaceae) and Other Angiosperms for Marker Choice

Plastid genomes exhibit different levels of variability in their sequences, depending on the respective kinds of genomic regions. Genes are usually more conserved while noncoding introns and spacers evolve at a faster pace. While a set of about thirty maximum variable noncoding genomic regions has been suggested to provide universally promising phylogenetic markers throughout angiosperms, applications often require several regions to be sequenced for many individuals. Our project aims to illuminate evolutionary relationships and species-limits in the genus Pyrus (Rosaceae)—a typical case with very low genetic distances between taxa. In this study, we have sequenced the plastid genome of Pyrus spinosa and aligned it to the already available P. pyrifolia sequence. The overall p-distance of the two Pyrus genomes was 0.00145. The intergenic spacers between ndhC–trnV, trnR–atpA, ndhF–rpl32, psbM–trnD, and trnQ–rps16 were the most variable regions, also comprising the highest total numbers of substitutions, indels and inversions (potentially informative characters). Our comparative analysis of further plastid genome pairs with similar low p-distances from Oenothera (representing another rosid), Olea (asterids) and Cymbidium (monocots) showed in each case a different ranking of genomic regions in terms of variability and potentially informative characters. Only two intergenic spacers (ndhF–rpl32 and trnK–rps16) were consistently found among the 30 top-ranked regions. We have mapped the occurrence of substitutions and microstructural mutations in the four genome pairs. High AT content in specific sequence elements seems to foster frequent mutations. We conclude that the variability among the fastest evolving plastid genomic regions is lineage-specific and thus cannot be precisely predicted across angiosperms. The often lineage-specific occurrence of stem-loop elements in the sequences of introns and spacers also governs lineage-specific mutations. Sequencing whole plastid genomes to find markers for evolutionary analyses is therefore particularly useful when overall genetic distances are low.
A Novel 5.8GHz Circularly Polarized Rectenna for Microwave Power Transmission

This paper reports a novel circularly polarized rectenna designed and measured at 5.8 GHz for application involving microwave power transmission (WPT). A truncated corner square patch microstrip antenna used for the rectenna was developed. The axial ratio achieved was 0.3 dB at 5.82 GHz. A silicon Schottky barrier diode is employed as the rectifying device. Measured conversion efficiency results of the rectenna proved that the rectenna is suitable for component of the WPT system.
Degradation Study of Single and Double-Heterojunction InAlN/GaN HEMTs by Two-Dimensional Simulation

We study the concept of double-heterostructure quantum well (DHQW) InAlN/GaN/AlGaN high electron mobility transistor (HEMT) for higher device robustness and less degradation. Physics-based device simulation proves that the back barrier blocks the carrier injection into the device buffer. However, the energy of the injected electrons in the buffer is higher for any quantum well design in InAlN /GaN than in AlGaN/GaN HEMTs. This energy may be sufficient for releasing hydrogen from GaN point defects.
Design and development part 2 of Dexto:Eka: - The humanoid robot

Through this paper, we elucidate the second phase of the design and development of the tele-operated humanoid robot Dexto:Eka:. Phase one comprised of the development of a 6 DoF left anthropomorphic arm and left exo-frame. Here, we illustrate the development of the right arm, right exo-frame, torso, backbone, human machine interface and omni-directional locomotion system. Dexto:Eka: will be able to communicate with a remote user through Wi-Fi. An exo-frame capacitates it to emulate human arms and its locomotion is controlled by joystick. A Graphical User Interface monitors and helps in controlling the system.
Uncertainty and a 7-Valued Logic

Uncertainty is a research topic which has not only been well known to the AI community but also, more recently, in the programming languages community at some extent. This paper joins the well known uncertainty model of MYCIN, extended, with a seven-valued deductive logic introduced here, working towards the unification of two different forms of representation, and of reasons, as humans always do. This seven-valued logic is introduced by myself as a novelty, here in the present paper, after having proposed a similar but simplified five-valued logic and a system, but this seven-valued logic is fully compatible with the same uncertainty model.