Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Analysis of Anti-Amoebae and Anti-Bacterial Activities of the Type VI Secretion System in Vibrio cholerae

A type VI secretion system (T6SS) was recently shown to be required for full virulence of Vibrio cholerae O37 serogroup strain V52. In this study, we systematically mutagenized each individual gene in T6SS locus and characterized their functions based on expression and secretion of the hemolysin co-regulated protein (Hcp), virulence towards amoebae of Dictyostelium discoideum and killing of Escherichia coli bacterial cells. We group the 17 proteins characterized in the T6SS locus into four categories: twelve (VipA, VipB, VCA0109–VCA0115, ClpV, VCA0119, and VasK) are essential for Hcp secretion and bacterial virulence, and thus likely function as structural components of the apparatus; two (VasH and VCA0122) are regulators that are required for T6SS gene expression and virulence; another two, VCA0121 and valine-glycine repeat protein G 3 (VgrG-3), are not essential for Hcp expression, secretion or bacterial virulence, and their functions are unknown; the last group is represented by VCA0118, which is not required for Hcp expression or secretion but still plays a role in both amoebae and bacterial killing and may therefore be an effector protein. We also showed that the clpV gene product is required for Dictyostelium virulence but is less important for killing E. coli. In addition, one vgrG gene (vgrG-2) outside of the T6SS gene cluster was required for bacterial killing but another (vgrG-1) was not. However, a bacterial killing defect was observed when vgrG-1 and vgrG-3 were both deleted. Several genes encoded in the same putative operon as vgrG-1 and vgrG-2 also contribute to virulence toward Dictyostelium but have a smaller effect on bacterial killing. Our results provide new insights into the functional requirements of V. cholerae's T6SS in the context of secretion as well as killing of bacterial and eukaryotic phagocytic cells.
Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet

Chronic over-nutrition is a major contributor to the spread of obesity and its related metabolic disorders. Development of therapeutics has been slow compared to the speedy increase in occurrence of these metabolic disorders. We have identified a natural compound, mangiferin (MGF) (a predominant component of the plants of Anemarrhena asphodeloides and Mangifera indica), that can protect against high fat diet (HFD) induced obesity, hyperglycemia, insulin resistance and hyperlipidemia in mice. However, the molecular mechanisms whereby MGF exerts these beneficial effects are unknown. To understand MGF mechanisms of action, we performed unbiased quantitative proteomic analysis of protein profiles in liver of mice fed with HFD utilizing 15N metabolically labeled liver proteins as internal standards. We found that out of 865 quantified proteins 87 of them were significantly differentially regulated by MGF. Among those 87 proteins, 50% of them are involved in two major processes, energy metabolism and biosynthesis of metabolites. Further classification indicated that MGF increased proteins important for mitochondrial biogenesis and oxidative activity including oxoglutarate dehydrogenase E1 (Dhtkd1) and cytochrome c oxidase subunit 6B1 (Cox6b1). Conversely, MGF reduced proteins critical for lipogenesis such as fatty acid stearoyl-CoA desaturase 1 (Scd1) and acetyl-CoA carboxylase 1 (Acac1). These mass spectrometry data were confirmed and validated by western blot assays. Together, data indicate that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis. This novel mode of dual pharmacodynamic actions enables MGF to enhance energy expenditure and inhibit lipogenesis, and thereby correct HFD induced liver steatosis and prevent adiposity. This provides a molecular basis supporting development of MGF or its metabolites into therapeutics to treat metabolic disorders.
Refractive shape from light field distortion

Acquiring transparent, refractive objects is challenging as these kinds of objects can only be observed by analyzing the distortion of reference background patterns. We present a new, single image approach to reconstructing thin transparent surfaces, such as thin solids or surfaces of fluids. Our method is based on observing the distortion of light field background illumination. Light field probes have the potential to encode up to four dimensions in varying colors and intensities: spatial and angular variation on the probe surface; commonly employed reference patterns are only two-dimensional by coding either position or angle on the probe. We show that the additional information can be used to reconstruct refractive surface normals and a sparse set of control points from a single photograph.
Inflation illusion and institutional ownership in REITs

This paper attempts to uncover institutional rationality (or irrationality) in the US public REITs market by exploring portfolio implications of the Modiglian and Cohn (1979) inflation-illusion hypothesis. Modigliani and Cohn (1979) hypothesize that stock market investors may suffer from inflation illusion by mistakenly using nominal interest rates to discount real earnings. As a result, stocks will generally be undervalued in times of high inflation and thus are poor hedges against inflation. Consequently, bad hedges are underpriced in times of high inflation and overpriced when inflation is low. Rational investors, facing a market of inflation-illusioned investors, would then liquidate their positions in good hedges and tilt their portfolios toward bad hedges when inflation is high and away from the bad hedges from inflation is low. I test the above rational portfolio-tilting hypothesis using data on institutional ownership in the public REITs market. Specifically, I use cross-sectional data on institutional ownership and use the Fama-Schwert (1977) methodology to identify whether or not a particular REIT stock is a good inflation hedge. I then examine whether institutional investors' preferences change with the level of expected and unexpected inflation. I find that institutions do in fact tilt their portfolios away from REITs that are superior inflation hedges and tilt toward REITs that are bad hedges in periods of high expected inflation , holding constant other reasons that may influence institutional ownership (e.g. size, liquidity, and momentum). Furthermore, these assets are less likely to be mispriced because institutional ownership decreases with the amount of mispricing in these securities.
Analysis of FoxP3+ T-Regulatory Cells and CD8+T-Cells in Ovarian Carcinoma: Location and Tumor Infiltration Patterns Are Key Prognostic Markers

Purpose Tumor infiltrating CD4+CD25+FoxP3+ regulatory immune cells (Treg) have been associated with impaired anti- tumor immune response and unfavorable prognosis for patients affected by ovarian carcinoma, whereas CD8+ T-cells have been found to positively influence survival rates in a large panel of solid tumors. Recently, density, location and tumor infiltration patterns of the respective immune cell subtypes have been identified as key prognostic factors for different types of tumors. Patients and Methods We stained 210 human ovarian carcinoma samples immunhistochemically for FoxP3 and CD8 to identify the impact different immune cell patterns have on generally accepted prognostic variables as well as on overall survival. Results We found that FoxP3+ cells located within lymphoid aggregates surrounding the tumor were strongly associated with reduced survival time (P = 0.007). Central accumulation of CD8+ effector cells within the tumor bed shows a positive effect on survival (P = 0,001). Conclusion The distribution pattern of immune cells within the tumor environment strongly influences prognosis and overall survival time of patients with ovarian carcinoma.
A RE-EXAMINATION OF THE “ VARIANCE BOUNDS ” METHODOLOGY ; A GENERAL EQUILIBRIUM SURPRISE

Tests of “variance bounds” have usually been derived in the context of a model with a single representative firm. In the equilibrium framework of this paper we show that when the economy has multiple firms, the results of the classic variance bounds literature do not have any theoretical validity. The price volatility of a firm does not depend on the volatility of the firm’s dividends. As a consequence the “perfect foresight” price paths traditionally calculated in this literature do not contain correct information about the price volatility of the firm.
Keyword Optimization in Search-Based Advertising Markets

Search-based advertising is a multi-billion industry which is part of the growing electronic commerce market. In this work, we study the search-based advertising market from the advertiser’s point of view. There are three natural participants in the search-based advertising: the advertisers, promoting their products to consumers based on their search queries, the users, which are searching for content, and the search providers, who match the advertisers and users by placing ads in search result pages. It is customary today for the advertisers to pay only for ad clicks. This guides both the advertisers’ and the search providers’ strategy. The advertisers’ strategy, which is the focus of this work, requires them to select keywords, bids and a budget constraint imposed on their advertising spending. We abstract an optimization problem in which the advertisers set a daily budget and select a set of keywords on which they bid. We assume that the cost and benefit of keywords is fixed and known, sidestepping this important strategic issue and focusing on the keyword optimization problem. The advertisers’ goal is to optimize the utility subject to its budget constraint. Clearly the advertisers would like to buy the most profitable keywords, subject to the budget constraint. The problem is that there is uncertainty regarding the type and number of queries in a day, and the advertisers have to fix a single policy for the online day. If too few keywords are selected, the advertisers remain with unused budget. If too many keywords are selected, at the time keywords associated with ’good’ ads appear, the daily budget may have already been exhausted. We study the advertisers’ keyword optimization problem in three different settings: in an offline problem setting in which all problem parameters are known beforehand, in a stochastic model in which the advertiser knows only some of the parameters of the stochastic model, and in an adversarial model which makes no statistical assumptions about the generation of the query sequences. For each of these models we provide lower and upper bounds to the performance of learning algorithms while using the notion of regret minimization [1]. We support our theoretical results with extensive simulations in a simulated environment while comparing our algorithm’s performance against the performance of algorithms suggested in [3].
Switching Serial-Number Coding Scheme and Its Application in FFS Scheduling Problem with Inter-stage Constraints

Flexible flow shop (FFS) has multiple machines in each stage, and usually not all the machines of a stage, but a subset of them can be assigned to a job because of various constraints. Recent studies have considered the inner-stage constraints, and this paper addresses the inter-stage constraints between two successive working centers. Traditional genetic algorithm (GA) is not applicable because its chromosome becomes too long when the problem size increases. This paper proposes serial-number coding scheme (SCS) firstly, which can shorten chromosome length substantially. Then switching SCS (SSCS) is developed further to reduce hamming distance between neighboring solutions. SSCS based genetic algorithm (SSGA) shows better computability and performance than traditional genetic algorithm.
La communication engageante : une solution pour favoriser les comportements pro-environnementaux

Malgre des sondages dʼopinion affirmant que les attitudes a lʼegard de lʼenvironnement et de la protection de la planete sont fortement positives, les comportements ne semblent pas toujours suivre tout a fait cette voie. Comment amener les gens a adopter des comportements responsables et favorables a lʼenvironnement ? Lʼengagement, et plus particulierement la communication engageante, comptent parmi les modeles les plus efficaces de la psychologie sociale dans ce domaine. En effet, on se rend compte que meme si les campagnes de sensibilisation sont necessaires, elles ne sont pas suffisantes lorsque lʼon observe que les gens sont favorables a la preservation de la planete mais que les comportements ne changent pas suffisamment. Lʼengagement, defini comme le lien entre un individu et ses actes, est un courant theorique qui met lʼaccent sur nos comportements. En effet, ce sont nos actions qui nous engagent et non pas nos attitudes, nos opinions ou nos idees. Pour etre efficace, il faut donc agir sur les actions des personnes directement et non plus seulement sur leurs attitudes pour modifier les habitudes. Les campagnes de sensibilisation seraient ainsi plus efficaces si elles sʼappuyaient davantage sur des « comportements preparatoires engageants ». De tels actes permettent en effet de rendre plus resistantes les attitudes qui y sont liees et augmentent la probabilite que de nouveaux comportements, allant dans le meme sens que le premier, se mettent en place par la suite. De nombreuses etudes confirment lʼefficacite de ce courant de recherche dans les differents champs lies au domaine de lʼenvironnement : la sensibilisation en general, lʼeconomie dʼenergie ou le tri des dechets.
Two-photon fluorescent holographic rewritable micropatterning.

Monomeric amorphous systems involving an upper azo-based layer and a lower fluorophore layer have been carefully designed to enable holographic formation of micrometric emissive photopatterns through reversible photoinduced mass migration of azoderivatives. The fluorescent patterns evidenced by NIR biphotonic excitation match the micrometric surface relief. After successful erasure by using a circularly polarized visible light, new patterns can be written again.
Nonnative SOD1 trimer is toxic to motor neurons in a model of amyotrophic lateral sclerosis

Significance Protein aggregation is a hallmark of neurodegenerative disease and is hypothesized to cause neuron death. Despite extensive study of disease-associated aggregating proteins, mechanisms of neuron death remain a mystery, and no cures or effective treatments yet exist. Here, we demonstrate the toxicity of a small aggregate of the Cu,Zn superoxide dismutase (SOD1) protein, associated with amyotrophic lateral sclerosis (ALS). We present an experimentally verified structural model of this toxic species and show that SOD1 mutants designed to promote formation of this aggregate increase cell death, providing a direct link between aggregate presence and neuron death. Knowledge of toxic species and the ability to manipulate their formation provides a valuable direction for pursuit of therapeutic strategies in ALS. Since the linking of mutations in the Cu,Zn superoxide dismutase gene (sod1) to amyotrophic lateral sclerosis (ALS) in 1993, researchers have sought the connection between SOD1 and motor neuron death. Disease-linked mutations tend to destabilize the native dimeric structure of SOD1, and plaques containing misfolded and aggregated SOD1 have been found in the motor neurons of patients with ALS. Despite advances in understanding of ALS disease progression and SOD1 folding and stability, cytotoxic species and mechanisms remain unknown, greatly impeding the search for and design of therapeutic interventions. Here, we definitively link cytotoxicity associated with SOD1 aggregation in ALS to a nonnative trimeric SOD1 species. We develop methodology for the incorporation of low-resolution experimental data into simulations toward the structural modeling of metastable, multidomain aggregation intermediates. We apply this methodology to derive the structure of a SOD1 trimer, which we validate in vitro and in hybridized motor neurons. We show that SOD1 mutants designed to promote trimerization increase cell death. Further, we demonstrate that the cytotoxicity of the designed mutants correlates with trimer stability, providing a direct link between the presence of misfolded oligomers and neuron death. Identification of cytotoxic species is the first and critical step in elucidating the molecular etiology of ALS, and the ability to manipulate formation of these species will provide an avenue for the development of future therapeutic strategies.
Alterations to cell metabolism in connective tissues of the knee after ovariohysterectomy in a rabbit model: are there implications for the postmenopausal athlete?

Background Participation in regular exercise and athletic activities across the lifespan is encouraged to maintain the cardiovascular and musculoskeletal systems and general wellbeing. Before the menopause there is an increased risk of anterior cruciate ligament (ACL) injuries in female athletes, whereas there is an increased risk of joint diseases such as knee osteoarthritis after the menopause. Although there are few data regarding alterations in individual connective tissues of the knee in humans either before, during or after the menopause, it is possible to assess changes in experimental models following surgical menopause. Objective To assess changes in cell metabolism in the medial collateral ligament, ACL, patellar tendon, lateral and medial menisci, tibial plateau and femoral condyle articular cartilage and the synovium after surgical menopause in an experimental model system. Methods Panels of rabbits were subjected to ovariohysterectomy or sham operations, and RNA from each tissue was assessed for collagen, proteoglycan, proteinase, growth factor, sex hormone receptor and inflammatory mediator messenger RNA levels by reverse transcribed PCR. Results Unique alterations in cell metabolism were detected 2 months after surgical menopause and the pattern of significant changes was tissue specific (number of mRNA species altered, extent of changes, elevation/depression of changes). Conclusions Changes in cell metabolism may alter the set point for the tissues of the knee and subsequently the functioning of the knee after the menopause. Such changes may contribute to an increased risk of injury and/or degenerative conditions. Further studies in pre and postmenopausal women athletes may also shed light on whether the present findings can be extrapolated to human populations.
Being "BYTES-oriented" in HPC leads to an open big data/AI ecosystem and further advances into the post-moore era

With rapid rise and increase of Big Data and AI as a new breed of high-performance workloads on supercomputers, we need to accommodate them at scale, traditional simulation-based HPC and BD/AI will converge. Our TSUBAME3 supercomputer at Tokyo Institute of Technology became online in Aug. 2017, and became the greenest supercomputer in the world on the Green 500 ranking at 14.11 GFlops/W; the other aspect of TSUBAME3, is to embody various Data or “BYTES-oriented” features to allow for HPC to BD/AI convergence at scale, including significant scalable horizontal bandwidth as well as support for deep memory hierarchy and capacity, along with high flops in low precision arithmetic for deep learning. Furthermore, TSUBAM3's technologies will be commoditized to construct one of the world's largest BD/AI focused and “open-source” cloud infrastructure called ABCI (AI-Based Bridging Cloud Infrastructure), hosted by AIST-AIRC (AI Research Center), the largest public funded AI research center in Japan. The performance of the machine is slated to be several hundred AI-Petaflops for machine learning; the true nature of the machine however, is its BYTES-oriented, optimization acceleration in the memory hiearchy, I/O, the interconnect etc, for high-performance BD/AI. ABCI will be online Spring 2018 and its archiecture, software, as well as the datacenter infrastructure design itself will be made open to drive rapid adoptions and improvements by the community, unlike the concealed cloud infrastructures of today. Finally, transcending from FLOPS-centric mindset to being BYTES-oriented will be one of the key solutions to the upcoming “end-of-Moore's law” in the mind 2020s, upon which FLOPS increase will cease and BYTES-oriented advances will be the new source of performance increases over time in general for any computing.
1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.
Deer Mothers Are Sensitive to Infant Distress Vocalizations of Diverse Mammalian Species

Acoustic structure, behavioral context, and caregiver responses to infant distress vocalizations (cries) are similar across mammals, including humans. Are these similarities enough for animals to respond to distress vocalizations of taxonomically and ecologically distant species? We show that mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) mothers approach a speaker playing distress vocalizations of infant marmots (Marmota flaviventris), seals (Neophoca cinerea and Arctocephalus tropicalis), domestic cats (Felis catus), bats (Lasionycteris noctivagans), humans (Homo sapiens), and other mammals if the fundamental frequency (F0) falls or is manipulated to fall within the frequency range in which deer respond to young of their own species. They did not approach to predator sounds or to control sounds having the same F0 but a different structure. Our results suggest that acoustic traits of infant distress vocalizations that are essential for a response by caregivers, and a caregiver’s sensitivity to these acoustic traits, may be shared across diverse mammals.