Miracle-dz/UniFAR-FTUs huggingface dataset:
GSK-3 Activity Is Critical for the Orientation of the Cortical Microtubules and the Dorsoventral Axis Determination in Zebrafish Embryos

The formation of dorsal-ventral (D–V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos.
Conservation of proteobacterial magnetosome genes and structures in an uncultivated member of the deep-branching Nitrospira phylum

Magnetotactic bacteria (MTB) are a phylogenetically diverse group which uses intracellular membrane-enclosed magnetite crystals called magnetosomes for navigation in their aquatic habitats. Although synthesis of these prokaryotic organelles is of broad interdisciplinary interest, its genetic analysis has been restricted to a few closely related members of the Proteobacteria, in which essential functions required for magnetosome formation are encoded within a large genomic magnetosome island. However, because of the lack of cultivated representatives from other phyla, it is unknown whether the evolutionary origin of magnetotaxis is monophyletic, and it has been questioned whether homologous mechanisms and structures are present in unrelated MTB. Here, we present the analysis of the uncultivated “Candidatus Magnetobacterium bavaricum” from the deep branching Nitrospira phylum by combining micromanipulation and whole genome amplification (WGA) with metagenomics. Target-specific sequences obtained by WGA of cells, which were magnetically collected and individually sorted from sediment samples, were used for PCR screening of metagenomic libraries. This led to the identification of a genomic cluster containing several putative magnetosome genes with homology to those in Proteobacteria. A variety of advanced electron microscopic imaging tools revealed a complex cell envelope and an intricate magnetosome architecture. The presence of magnetosome membranes as well as cytoskeletal magnetosome filaments suggests a similar mechanism of magnetosome formation in “Cand. M. bavaricum” as in Proteobacteria. Altogether, our findings suggest a monophyletic origin of magnetotaxis, and relevant genes were likely transferred horizontally between Proteobacteria and representatives of the Nitrospira phylum.
Poverty, Material Hardship and Depression.

OBJECTIVE Mental health disorders are of great social, economic, and policy concern. A higher incidence of major depressive disorder has been reported among those living in or near poverty. Our study examines the extent to which the relationship between income and depression is mediated by measures of material hardship. METHODS We use measures of depression at two points in time from the longitudinal Fragile Families Survey to better discern the causal direction of the relationship between income poverty, hardship, and depression. More specifically, we use conditional logistic fixed-effect models that control for time-invariant unmeasured heterogeneity in the sample. RESULTS We found a strong relationship between hardships and depression. The most prominent hardships were problems paying bills and phone turned off. We also found that hardship helped mediate much, though not all, of the link between poverty and depression in the conditional fixed effect logistic regression models. CONCLUSION Our policy simulations suggest that public health efforts to reduce depression may be enhanced from efforts that focus on specific forms of material hardship.
A human tumor necrosis factor p75 receptor agonist stimulates in vitro T cell proliferation but does not produce inflammation or shock in the baboon

Tumor necrosis factor (TNF) is a potentially useful adjunct to anticancer therapies. However, the clinical utility of TNF has been limited by generalized toxicity and hypotension. Recently, studies have begun to dissect the individual proinflammatory and immunologic responses that result from TNF binding to its two cellular receptors, p55 and p75, in an attempt to develop TNF receptor agonists with reduced systemic toxicity. To evaluate a p75 receptor selective TNF mutant (p75TNF), TNF and p75TNF were administered to healthy anesthetized baboons. Intravenous infusion of the p75TNF produced none of the hemodynamic changes seen after the infusion of TNF. Infusion of p75TNF also failed to induce the plasma appearance of interleukins 6 and 8. However, p75TNF enhanced in vitro baboon thymocyte proliferation to concanavalin A, and infusion of p75TNF resulted in increased soluble p55 and p75 receptor plasma concentrations. Local skin necrosis and tissue neutrophil infiltration were seen after subcutaneous injections of TNF and p55TNF. Subcutaneous injection of p75TNF did not result in skin necrosis but did result in a modest dermal infiltration of lymphocytes and macrophages. The findings suggest that p75TNF may stimulate T cell proliferation without the systemic and local toxicity seen with TNF.
Magnetic Resonance Elastography for Liver Fibrosis in Methotrexate Treatment.

INTRODUCTION Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). METHODS The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. RESULTS Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR= 1.18 per 1 kg/m2; 95% CI: 1.03, 1.36; p=0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p=0.51 and P=0.20, respectively). CONCLUSIONS MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment.
First Experience With Direct Factor Xa Inhibition in Patients With Stable Coronary Disease: A Pharmacokinetic and Pharmacodynamic Evaluation

Background—Thrombin generation is critical to the formation of an arterial thrombus after rupture of an atherosclerotic plaque. In patients with stable coronary disease receiving standard medical therapy, we evaluated the pharmacokinetics, pharmacodynamics, and safety profile of DX-9065a, a novel small-molecule anticoagulant that directly, selectively, and reversibly inhibits factor Xa. Methods and Results—In a double-blind trial, 73 patients (median age, 63 years; 29% women) were randomly assigned to receive a fixed-dose intravenous bolus, followed by a 72-hour infusion of placebo or 1 of 4 weight-adjusted regimens of DX-9065a. Plasma samples were collected during infusion and a 24-hour elimination period. Only minor bleeding occurred, predominantly ecchymoses at infusion sites, and its incidence did not differ significantly among the groups, including placebo. Median hemoglobin, platelet count, serum creatinine level, and liver function tests did not change significantly from baseline during infusion or elimination. Significant predictors of pharmacokinetic response included infusion dose and weight. At 60 hours into the DX-9065a infusion, plasma drug levels correlated strongly with anti–factor Xa activity (r =0.97), prothrombin time (r =0.77), and international normalized ratio (r =0.72) but less so with activated partial thromboplastin time (r =0.56; all P <0.001). Conclusions—This is the first study of a selective, reversible, and direct small-molecule factor Xa inhibitor in patients with stable coronary disease. These data lay the foundation for further investigation of factor Xa inhibitors in the treatment of patients with coronary atherothrombosis.
The β-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy*

Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau. The tauopathies are accompanied by abnormal changes in Tau protein, including pathological conformation, somatodendritic mislocalization, hyperphosphorylation, and aggregation, whose interdependence is not well understood. To address these issues we have created transgenic mouse lines in which different variants of full-length Tau are expressed in a regulatable fashion, allowing one to switch the expression on and off at defined time points. The Tau variants differ by small mutations in the hexapeptide motifs that control the ability of Tau to adopt a β-structure conformation and hence to aggregate. The “pro-aggregation” mutant ΔK280, derived from one of the mutations observed in frontotemporal dementias, aggregates avidly in vitro, whereas the “anti-aggregation” mutant ΔK280/PP cannot aggregate because of two β-breaking prolines. In the transgenic mice, the pro-aggregation Tau induces a pathological conformation and pre-tangle aggregation, even at low expression levels, the anti-aggregation mutant does not. This illustrates that abnormal aggregation is primarily controlled by the molecular structure of Tau in vitro and in the organism. Both variants of Tau become mislocalized and hyperphosphorylated independently of aggregation, suggesting that localization and phosphorylation are mainly a consequence of increased concentration. These pathological changes are reversible when the expression of Tau is switched off. The pro-aggregation Tau causes a strong reduction in spine synapses.
Trends in Cardiac Surgery-Associated Acute Renal Failure in the United States: A Disproportionate Increase after Heart Transplantation

Acute renal failure (ARF) is common after cardiac surgery and more frequent after complex cardiac surgery. While the incidence of ARF is increasing after coronary artery bypass graft (CABG) surgery, trends in other forms of cardiac surgery remain unclear. We investigated the trend of ARF in various cardiac procedures and compared patterns using CABG surgery as a reference group. The study population consisted of discharges from the Nationwide Inpatient Sample from 1988 to 2003, grouped according to surgery as: CABG, CABG with mitral valve, CABG with other valve, valve alone, and heart transplant. Standard diagnostic codes were used to identify ARF among discharges. Multivariable regression was used to determine trends in ARF among various procedures with CABG as a reference group. The incidence of ARF increased in all five groups (p < 0.001) over the 16-year period. The ARF incidence was highest in the heart transplant group (17%). Compared to the CABG population, patients following heart transplantation developed ARF at higher rates during the study period. In contrast, while ARF increased over time in other groups, the rates of rise were slower than in CABG patients. Among heart surgery procedures, ARF incidence is highest in heart transplantation. The incidence of ARF is also increasing at a faster rate in this group of patients in contrast to other procedure groups when compared to CABG surgery. The disproportionate increase in ARF burden after heart transplantation is a concern due to its strong association with chronic kidney disease and mortality.
Ontological access to images of fine art

Information retrieval in a knowledge rich domain poses challenges that are different from other domains. The domain of fine arts and cultural heritage is an exemplar of such a domain. The many facets of, and complex interrelations between, works of fine art are not easily addressed by conventional keyword-based approaches or even by structured cataloguing systems. Information retrieval challenges in this domain include: the conversion of existing legacy data into knowledge representations that emulate the semantics of the domain's relationships; and easy access to a robust knowledge representation for users unfamiliar with query languages. Our research addresses aspects of both challenges as they are connected and may benefit from being addressed in conjunction. Based on a study on user preferences in art image search and a review of existing structured resources for cataloguing art and heritage information, we have developed two prototypes: Ontology Populator and Artfinder. The first prototype, Ontology Populator, is used to automatically enrich data akin to legacy data kept by heritage institutions and transform it into a knowledge base. The second prototype is a graphical query builder, Artfinder, which interacts with the knowledge base. The Artfinder interface, is constructed dynamically from the structure of the underlying knowledge. A task-based evaluation of Artfinder was carried out with 10 expert and 10 layperson evaluators. Participants reviewed the interface favourably and the evaluation also revealed potential for improvement. Artfinder and its “query logic,” perhaps is a semantically richer mode of accessing knowledge repositories, allowing for logically more complex queries than are currently supported outside the realm of dedicated query languages. We believe that domain experts and perhaps informed laypersons will benefit from this retrieval approach.
Addition of amino acid moieties to lapatinib increases the anti‐cancer effect via amino acid transporters

Anti‐cancer agents delivered to cancer cells often show multi‐drug resistance (MDR) due to expulsion of the agents. One way to address this problem is to increase the accumulation of anti‐cancer agents in cells via amino acid transporters. Thus, val‐lapatinib and tyr‐lapatinib were newly synthesized by adding valine and tyrosine moieties, respectively, to the parent anti‐cancer agent lapatinib without stability issues in rat plasma. Val‐lapatinib and tyr‐lapatinib showed enhanced anti‐cancer effects versus the parent lapatinib in various cancer cell lines, including human breast cancer cells (MDA‐MB‐231, MCF7) and lung cancer cells (A549), but not in non‐cancerous MDCK‐II cells. A glutamine uptake study revealed that both val‐lapatinib and tyr‐lapatinib, but not the parent lapatinib, inhibited glutamine transport in MDA‐MB‐231 and MCF7 cells, suggesting the involvement of amino acid transporters. In conclusion, val‐lapatinib and tyr‐lapatinib have enhanced anti‐cancer effects, likely due to an increased uptake of the agents into cancer cells via amino acid transporters. The present data suggest that amino acid transporters may be an effective drug delivery target to increase the uptake of anti‐cancer agents, leading to one method of overcoming MDR in cancer cells. Copyright © 2013 John Wiley & Sons, Ltd.
Fusion to a pull‐down domain: a novel approach of producing Trigonopsis variabilisD‐amino acid oxidase as insoluble enzyme aggregates

Insoluble protein particles showing high specific enzyme activity are potentially useful biocatalysts. The commercialized crosslinked enzyme crystals and aggregates have the disadvantage that their preparation requires isolation of the protein before the critical precipitation step. We introduce a novel concept of controlled precipitation in vivo in which the target enzyme is fused to the cellulose‐binding domain (CBD) of Clostridium cellulovorans, and expression in Escherichia coli is performed under conditions that induce selective pull down of the folded chimeric protein via intermolecular self‐aggregation of the CBD. The case of D‐amino acid oxidase from Trigonopsis variabilis shows that upon fusion of the CBD to its N‐terminus, the otherwise mainly soluble recombinant enzyme was quantitatively precipitated in protein particles, which displayed 40% of the specific activity of the highly purified oxidase. By contrast, inclusion bodies derived from an enzyme chimera, which harbored a C‐terminal peptide tag, showed only little oxidase activity (≤ 10%). The aggregated CBD retained the ability to bind microcrystalline cellulose and flocculated polysaccharide particles upon attachment to them. The cellulose‐bound oxidase was stabilized about 36 times against inactivation of the soluble enzyme during conversion of D‐methionine and bubble aeration. Biotechnol. Bioeng. 2007;97: 454–461. © 2006 Wiley Periodicals, Inc.
Is Hand-Held Dynamometry Useful for the Measurement of Quadriceps Strength in Older People? A Comparison with the Gold Standard Biodex Dynamometry

Background: The lower limb muscle strength is an important determinant of physical function in older people. However, measurement in clinical and epidemiological settings has been limited because of the requirement for large-scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD) has been developed to measure the quadriceps strength in a supine position. Objective: The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold standard Biodex dynamometer. Methods: The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women, aged 61–81 years, on their non-dominant leg. The agreement between the peak torques obtained by Biodex and HHD was analyzed. Results: The mean peak Biodex and HHD results were 83.4 ± (SD) 28.0 Nm and 68.9 ± 19.6 Nm, respectively. The HHD undermeasured the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to the Biodex, and this effect was most marked in the strongest participants. Nevertheless, there was a good correlation between the measures (r = 0.91, p < 0.0001). Classification of individuals into tertiles of muscle strength showed good agreement between the two methods (Kappa = 0.69, p < 0.0001). Conclusions: Our findings suggest that the HHD using a supine positioning offers a feasible, inexpensive, and portable test of quadriceps muscle strength for use in healthy older people. It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people, but is a useful tool for ranking muscle strength of older people in epidemiological studies. It may also be of value for quick and objective assessment of physical function in the clinical setting.
Comparison of Possible Multispectral Classification Schemes for Tree Crowns Individually Delineatedon High Spatial Resolution MEIS Images

RESUMELors de l'analyse par ordinateur d'images aeriennes multispectrales de haute definition ayant pour but l'inventaire forestier, il pourrait etre plus pratique d'utiliser les cimes d'arbre comme objets de notre analyse plutot que les peuplements forestiers ou les simples pixels. En partant de cette proposition, il devient important d'etre capable de definir spectralement ces cimes le plus succinctement possible. Cet article propose, decrit et compare sept manieres differentes de definir spectralement des cimes d'arbre provenant d'images aeriennes de haute resolution spatiale dans le but d'identifier leurs especes forestieres.Parmis les sept types de signatures spectrales testes, cinq menerent a des exactitudes de classification du meme ordre (72 ± 3%) en differentiant cinq especes de coniferes. Une amelioration de l'exactitude de classification (jusqu'a 76 %) fut rendu possible pour certainnes signatures en utilisant une procedure d'analyse canonique avant la classification. Les signatures basees sur .
Development of a reaction drive for a propulsion mechanism

A micro robot that can be swallowed with sensors to inspect the intestine without the need to cut open a patient must have a propulsion mechanism to direct it to the areas of interest. The use of a propulsion mechanism external to the pill could endanger the patient, what is proposed here is a method of propelling a micro (capsule) robot with an internal mechanism based on the inertia of a swinging mass. The dynamics and control issues of a pendulum-driven cart-pole system are similar to those of a capsule robot. Therefore, this paper reports an experimental study of a pendulum-driven cart-pole system. The experimental results demonstrate the proposed system.
REFRACTION-DIFFRACTION OF IRREGULAR WAVES OVER A MOUND

The transformation of monochromatic and directionally-spread irregular waves passing over a submerged elliptical mound was studied in a controlled laboratory experiment. A directional spectral wave generation was used to generate waves with equal peak frequencies and spectral energy, along with monochromatic waves of equivalent significant height and period. Spectra with both narrow and broad frequency and directional spreads were generated. Results indicate that monochromatic waves provide a poor approximation of irregular wave conditions if there is directional spread or high wave steepness.
Influence of solar variability on gravity wave structure and dissipation in the thermosphere from tropospheric convection

[1] We investigate the role convection plays in the thermosphere using deep convection and ray trace models with a general dissipative anelastic GW dispersion relation. In the absence of dissipation, a GW's vertical wavelength λz increases by , or greater if its intrinsic frequency ωIr is close to the smaller thermospheric buoyancy frequency N = N0. Here, and 0 are the asymptotic temperatures in the thermosphere and lower atmosphere, respectively, and N0 is the buoyancy frequency in the lower atmosphere. In the presence of dissipation, λz also increases in the thermosphere by a factor of ∼2–3 when ωIr > 0.2N0 and λz > 25 km during active solar conditions. GW dissipation altitudes and maximum vertical wavelengths, which increase as increases, are displayed for small-scale and midscale GWs. GWs excited from deep convection encounter horizontal shears, which impose anisotropy on the spectrum. Along with dissipative filtering, momentum flux divergence and body forces result. The thermospheric body forces resulting from our convection model achieve maximum accelerations at z 180–200 km, extend down to z 130 km, last for the duration of deep convection, are ∼600 km × 600 km × 40–80 km in the x, y, and z directions, and are very strong with accelerations ≃0.5–0.75 m s−2 and ≃0.25–0.4 m s−2 during extreme solar minimum ( = 600 K) and active solar conditions ( = 2000 K), respectively. During extreme solar minimum, there is negligible forcing above z ≃ 230 km, whereas the forcing extends up to z ≃ 360 km during active solar conditions. These horizontal, thermospheric body forces may be a new source of large-scale, long-period secondary GWs and induced TIDs (traveling ionospheric disturbances) at high altitudes in the thermposphere.