Miracle-dz/UniFAR-FTUs huggingface dataset:
Postprandial and Fasting Hepatic Glucose Fluxes in Long-Standing Type 1 Diabetes

OBJECTIVE Intravenous insulin infusion partly improves liver glucose fluxes in type 1 diabetes (T1D). This study tests the hypothesis that continuous subcutaneous insulin infusion (CSII) normalizes hepatic glycogen metabolism. RESEARCH DESIGN AND METHODS T1D with poor glycemic control (T1Dp; HbA1c: 8.5 ± 0.4%), T1D with improved glycemic control on CSII (T1Di; 7.0 ± 0.3%), and healthy humans (control subjects [CON]; 5.2 ± 0.4%) were studied. Net hepatic glycogen synthesis and glycogenolysis were measured with in vivo 13C magnetic resonance spectroscopy. Endogenous glucose production (EGP) and gluconeogenesis (GNG) were assessed with [6,6-2H2]glucose, glycogen phosphorylase (GP) flux, and gluconeogenic fluxes with 2H2O/paracetamol. RESULTS When compared with CON, net glycogen synthesis was 70% lower in T1Dp (P = 0.038) but not different in T1Di. During fasting, T1Dp had 25 and 42% higher EGP than T1Di (P = 0.004) and CON (P < 0.001; T1Di vs. CON: P = NS). GNG was 74 and 67% higher in T1Dp than in T1Di (P = 0.002) and CON (P = 0.001). In T1Dp, GP flux (7.0 ± 1.6 μmol ⋅ kg−1 ⋅ min−1) was twofold higher than net glycogenolysis, but comparable in T1Di and CON (3.7 ± 0.8 and 4.9 ± 1.0 μmol ⋅ kg−1 ⋅ min−1). Thus T1Dp exhibited glycogen cycling (3.5 ± 2.0 μmol ⋅ kg−1 ⋅ min−1), which accounted for 47% of GP flux. CONCLUSIONS Poorly controlled T1D not only exhibits augmented fasting gluconeogenesis but also increased glycogen cycling. Intensified subcutaneous insulin treatment restores these abnormalities, indicating that hepatic glucose metabolism is not irreversibly altered even in long-standing T1D.
A New Rabbit-Skin Model to Evaluate Protective Efficacy of Tuberculosis Vaccines

Background: BCG protection is suboptimal and there is significant interest to develop new tuberculosis (TB) vaccines. However, there are significant limitations of the current vaccine evaluation systems in the mouse model. Here, we developed a BCG-challenge rabbit skin model as a new way to evaluate the protective efficacy of selected TB subunit vaccine candidates. Methods: Rabbits were immunized with subunit vaccines, including EAMM (ESAT6-Ag85B-MPT64<190−198>-Mtb8.4), MH (Mtb10.4-HspX), and LT70 (ESAT6-Ag85B-MPT64<190−198>-Mtb8.4-Rv2626c) three times subcutaneously every 3-weeks and challenged with the attenuated Mycobacterium bovis BCG intradermally 6-weeks after last immunization. The immune response induced by the vaccine candidates was measured, the histopathology induced by the BCG challenge was studied, and the number of bacilli in the liquefied caseum was determined. Results: The subunit vaccines generated high antigen-specific IgG antibodies and fastened the liquefaction and healing process, and significantly reduced the viable BCG load. The subunit vaccine LT70 and EAMM-MH reduced BCG bacterial load in comparison to proteins EAMM, MH, Rv2626c, and also BCG itself. The Koch phenomena induced by the LT70 and combination of EAMM-MH were the same as that produced by BCG itself and were more rapid than those induced by the other proteins and the saline controls. Conclusions: The subunit vaccines LT70 and the combination of EAMM-MH showed promising protective efficacy as expected in the rabbit skin model, which can serve as a visual and convenient new model for evaluating TB vaccines.
Learning Curve for Laparoscopic Major Hepatectomy: Use of the Cumulative Sum Method

Background: Laparoscopic liver resection (LLR) has now become a worldwide practice. However, the adoption of laparoscopic major hepatectomy (LMH) was slow. We report our center’s experience in laparoscopic major resections. Method: A total of 156 LLRs from 2002 to 2014 were studied. The clinical parameters of LMHs were compared with those of minor resections. The learning curve of LMHs was investigated using the cumulative sum (CUSUM) analysis of operative time. Subgroup analysis of right posterior sectionectomies against anterolateral hepatectomies was conducted. Results: Among the 156 LLRs, 49 (31%) were LMHs. CUSUM analysis showed that operative time improved after the 25th LMH. Beyond that proportion of pure laparoscopic LMHs increased (18/25 vs. 24/24, P=0.005); Pringle maneuver was not required (4/25 vs. 0/24, P=0.041). Blood loss (800 vs. 500 mL, P=0.034) and transfusion rate (13/25 to 3/24, P=0.003) improved in latter LMHs. Right posterior sectionectomies had significantly more blood loss than anterolateral LMHs (500 vs. 1500 mL, P=0.034). Conclusion: Laparoscopic major resection is safe and feasible; operative outcomes improved after overcoming the learning curve. Right posterior sectionectomy, however, should be further evaluated for its cost-effectiveness.
Large, rapidly evolving gene families are at the forefront of host–parasite interactions in Apicomplexa

SUMMARY The Apicomplexa is a phylum of parasitic protozoa, which includes the malaria parasite Plasmodium, amongst other species that can devastate human and animal health. The past decade has seen the release of genome sequences for many of the most important apicomplexan species, providing an excellent basis for improving our understanding of their biology. One of the key features of each genome is a unique set of large, variant gene families. Although closely related species share the same families, even different types of malaria parasite have distinct families. In some species they tend to be found at the ends of chromosomes, which may facilitate aspects of gene expression regulation and generation of sequence diversity. In others they are scattered apparently randomly across chromosomes. For some families there is evidence they are involved in antigenic variation, immune regulation and immune evasion. For others there are no known functions. Even where function is unknown these families are most often predicted to be exposed to the host, contain much sequence diversity and evolve rapidly. Based on these properties it is clear that they are at the forefront of host–parasite interactions. In this review I compare and contrast the genomic context, gene structure, gene expression, protein localization and function of these families across different species.
Detecting CD56+/NB84+/CD45- immunophenotype in the bone marrow of patients with metastatic neuroblastoma using flow cytometry.

BACKGROUND In order to identify neuroblastoma cells infiltrating the bone marrow, a triple-color flow-cytometric assay was developed combining CD56 and CD45 with the intracellular anti-NB84 specific antibody. MATERIALS AND METHODS The bilateral aspirates obtained from 27 consecutive children over the age of one year with stage 4 neuroblastoma were evaluated. RESULTS Neuroblastoma cells were detected in the bone marrow of 17/27 (63%) and 19/27 (70%) cases using cytomorphology and triple-color flow-cytometry, respectively. Using cytometry, the percentage of CD56+/NB84+/CD45-cells infiltrating the bone marrow ranged from 0.02% to 65%. Five out of eight patients without bone marrow involvement according to cytometry are in continuous complete remission, while only 3 out of 19 patients whose bone marrow gave positive results are still alive. CONCLUSION By combining CD45 and CD56 with the specific antibody, NB84, directed against neuroblastoma cells, we developed a rapid and reliable cytometric assay that can be associated with conventional cytomorphological bone marrow evaluation to detect infiltrating neuroblastoma cells, especially in cases of dubious positivity.
The OMP–lacZ Transgene Mimics the Unusual Expression Pattern of OR-Z6, a New Odorant Receptor Gene on Mouse Chromosome 6: Implication for Locus-Dependent Gene Expression

Reporter gene expression in the olfactory epithelium of H-lacZ6 transgenic mice mimics the cell-selective expression pattern known for some odorant receptor genes. The transgene construct in these mice consists of the lacZ coding region, driven by the proximal olfactory marker protein (OMP) gene promoter, and shows expression in a zonally confined subpopulation of olfactory neurons. To address mechanisms underlying the odorant receptor-like expression pattern of thelacZ construct, we analyzed the transgene-flanking region and identified OR-Z6, the first cloned odorant receptor gene that maps to mouse chromosome 6. OR-Z6bears the highest sequence similarity (85%) to a human odorant receptor gene at the syntenic location on human chromosome 7. We analyzed the expression pattern of OR-Z6 in olfactory tissues of H-lacZ6 mice and show that it bears strong similarities to that mapped for β-galactosidase. Expression of both genes in olfactory neurons is primarily restricted to the same medial subregion of the olfactory epithelium. Axons from both neuronal subpopulations project to the same ventromedial aspect of the anterior olfactory bulbs. Furthermore, colocalization analyses in H-lacZ6 mice demonstrate thatOR-Z6-reactive glomeruli receive axonal input fromlacZ-positive neurons as well. These results suggest that the expression of both genes is coordinated and that transgene expression in H-lacZ6 mice is regulated by locus-dependent mechanisms.
Developing Rice with High Yield under Phosphorus Deficiency: Pup1 Sequence to Application1[W][OA]

The major quantitative trait locus (QTL) Phosphorus uptake1 (Pup1) confers tolerance of phosphorus deficiency in soil and is currently one of the most promising QTLs for the development of tolerant rice (Oryza sativa) varieties. To facilitate targeted introgression of Pup1 into intolerant varieties, the gene models predicted in the Pup1 region in the donor variety Kasalath were used to develop gene-based molecular markers that are evenly distributed over the fine-mapped 278-kb QTL region. To validate the gene models and optimize the markers, gene expression analyses and partial allelic sequencing were conducted. The markers were tested in more than 80 diverse rice accessions revealing three main groups with different Pup1 allele constitution. Accessions with tolerant (group I) and intolerant (group III) Pup1 alleles were distinguished from genotypes with Kasalath alleles at some of the analyzed loci (partial Pup1; group II). A germplasm survey additionally confirmed earlier data showing that Pup1 is largely absent from irrigated rice varieties but conserved in varieties and breeding lines adapted to drought-prone environments. A core set of Pup1 markers has been defined, and sequence polymorphisms suitable for single-nucleotide polymorphism marker development for high-throughput genotyping were identified. Following a marker-assisted backcrossing approach, Pup1 was introgressed into two irrigated rice varieties and three Indonesian upland varieties. First phenotypic evaluations of the introgression lines suggest that Pup1 is effective in different genetic backgrounds and environments and that it has the potential to significantly enhance grain yield under field conditions.
Social Connection Through Joint Action and Interpersonal Coordination

The pull to coordinate with other individuals is fundamental, serving as the basis for our social connectedness to others. Discussed is a dynamical and ecological perspective to joint action, an approach that embeds the individual's mind in a body and the body in a niche, a physical and social environment. Research on uninstructed coordination of simple incidental rhythmic movement, along with research on goal-directed, embodied cooperation, is reviewed. Finally, recent research is discussed that extends the coordination and cooperation studies, examining how synchronizing with another, and how emergent social units of perceiving and acting are reflected in people's feelings of connection to others.
On the Design of IT Artifacts and the Emergence of Business Processes as Organizational Routines

Much of the BPM literature views business process design and implementation as a topdown process that is built on strategic alignment and managerial control. This view is inconsistent with the observation that information infrastructures, including a company’s business process infrastructure, are at drift, a term that refers to the lack of top-down management control. The paper contributes to resolving this inconsistency by developing a framework that conceptualizes business processes as emergent organizational routines that are represented, enabled, and constrained by IT artifacts. IT artifacts are developed in processes of functional-hierarchical decomposition and social design processes. Organizational routines have ostensive and performative aspects, forming a mutually constitutive duality. A literature review demonstrates that the propositions offered by the framework have been insufficiently considered in the BPM field. The paper concludes with an outlook to applying the framework to theorizing on the emergence of business processes on online social network sites.
Carotid Baroreflex Function in Young Men with Borderline Blood Pressure Elevation

Carotid baroreflex function was assessed in 10 normotensive young men and 20 age-matched subjects with borderline hypertension (successive blood pressures above and below 140/90 mm Hg) by measuring sinus node responses to brief neck suction. Subjects with borderline hypertension were divided into two equal groups according to their average systolic arterial pressures. Baroreflex responses were reset to function at higher pressure levels than normal in subjects with mild borderline hypertension, but reflex sensitivity was normal. Responses were also reset in subjects with more severe borderline hypertension, but reflex sensitivity was subnormal. The results suggest that a gradation of baroreflex responsiveness exists among patients classified as having borderline hypertension: Subnormal responsiveness was found in those subjects whose resting average systolic arterial pressure was 140 mm Hg
Phase 1 clinical study of pegylated liposomal doxorubicin (JNS002) in Japanese patients with solid tumors.

BACKGROUND Pegylated liposomal doxorubicin (PLD, JNS002) is a formulation of doxorubicin encapsulated polyethylene-glycol coated liposomes with prolonged circulation time and unique toxicity profile. This phase 1 study was aimed at investigating the maximum tolerated dose (MTD), recommended dose, toxicity, pharmacokinetics, and antitumor activity in Japanese patients with solid tumors. METHODS Patients with solid tumors not amenable to standard forms of treatment were eligible. PLD was administered as an intravenous infusion every 4 weeks. Dose escalation of PLD was planned from 30 to 60 mg/m(2) in 10 mg/m(2) increments. The pharmacokinetics of total doxorubicin (encapsulated plus non-encapsulated) in plasma were examined for the first cycle of treatment. RESULTS Fifteen patients, aged 49-69 (median; 56) years with advanced solid tumors were enrolled. The major non-hematological toxicities were hand-foot syndrome (HFS), rash and stomatitis. Myelosuppression, especially leukopenia and neutropenia were major hematological toxicities. Although HFS was not severe, a delay of doses for subsequent cycles was required with multiple dosing. The peak plasma concentration and the area under the concentration time curve of PLD increased proportionally to the dose. Objective response was observed in one patient and the normalization of tumor marker values in another. These two patients had been diagnosed with ovarian cancer. CONCLUSION The recommended dose for phase 2 clinical studies of PLD in Japanese patients was 50 mg/m(2) every 4 weeks. The encouraging results prompted us to plan a subsequent clinical study of PLD against ovarian cancer.
The flux-weighted gravity-luminosity relationship of blue supergiant stars as a constraint for stellar evolution

(abridged) The flux-weighted gravity-luminosity relationship (FGLR) of blue supergiant stars (BSG) links their absolute magnitude to the spectroscopically determined flux-weighted gravity log g = Teff^4. BSG are the brightest stars in the universe at visual light and the application of the FGLR has become a powerful tool to determine extragalactic distances. Observationally, the FGLR is a tight relationship with only small scatter. It is, therefore, ideal to be used as a constraint for stellar evolution models. The goal of this work is to investigate whether stellar evolution can reproduce the observed FGLR and to develop an improved foundation of the FGLR as an extragalactic distance indicator. We use different grids of stellar models for initial masses between 9 and 40 Msun, for metallicities between Z = 0.002 and 0.014, with and without rotation, computed with various mass loss rates during the red supergiant phase. For each of these models we discuss the details of post-main sequence evolution and construct theoretical FGLRs by means of population synthesis models which we then compare with the observed FGLR. In general, the stellar evolution model FGLRs agree reasonably well with the observed one. There are, however, differences between the models, in particular with regard to the shape and width (scatter) in the flux-weighted gravity-luminosity plane. The best agreement is obtained with models which include the effects of rotation and assume that the large majority, if not all the observed BSG evolve towards the red supergiant phase and only a few are evolving back from this stage. The effects of metallicity on the shape and scatter of the FGLR are small. (.)
In vitro evaluation of the genotoxicity of acetamiprid in human peripheral blood lymphocytes

Acetamiprid, a neonicotinoid insecticide, is commonly used both in agriculture and domestic areas against a wide range of insects. The potential genotoxicity of a commercial formulation of acetamiprid (Mosetam 20 SP, containing 20% acetamiprid as the active ingredient) on human peripheral blood lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus tests. Cells were treated with 25, 30, 35, and 40 μg/ml of acetamiprid for 24 and 48 hr. Acetamiprid induced SCEs and CAs significantly at all concentrations and treatment times and micronucleus formation was significantly induced at 30, 35, and 40 μg/ml of acetamiprid as compared with both the control and solvent control. Acetamiprid decreased the proliferation index (PI) at the two highest concentrations (35 and 40 μg/ml) for the 24‐hr treatment period and only at the highest concentration (40 μg/ml) for the 48‐hr treatment period when compared with the control and solvent control. Peripheral lymphocytes exposed to all concentrations of acetamiprid showed significant decreases in mitotic index (MI) and nuclear division index (NDI) for both treatment periods when compared with both the control and solvent control. Furthermore, acetamiprid decreased the MI in both treatment periods, and the NDI only in the 24‐hr treatment period to the same extent as the positive control, mitomycin C (MMC). This study presents the first in vitro evidence for the genotoxicity of a commercial formulation of acetamiprid in human peripheral lymphocytes. Environ. Mol. Mutagen. , 2007. © 2007 Wiley‐Liss, Inc.
Analysis of cracks in solids

Introduction: Modelling of solids with cracks - Elements of convex analysis Approximation methods Problems with singular boundaries. Cracks in plates and shells: Viscoelastic contact problem for a plate A plate under creep conditions A plate with vertical and horizontal displacements Contact problem for a plate having a crack Cracks of minimal opening in plates Solving methods for plates with cracks Contact problem for a shell with a crack Signorini problem for cracks in shells Simplified nonpenetration conditions in contact problems Solving methods for the simplified models. Cracks in complicated plates: Plate with a crack under the creep condition Contact of two plates one of which has a crack Thermoelastic plates with cracks Cracks of minimal opening in thermoelastic plates Inclined cracks in plates Friction problem for plates with cracks. Variation of cracks in solids: Variation of a crack length A plate with a crack A crack moving to the external boundary A case of a shallow shell A crack near the boundary Asymptotics of the energy functional for the Poisson equation Asymptotics of the energy functional for the Lam? equations Three-dimensional case Extreme crack shapes in a shallow shell. Cracks in elastoplastic bodies: Elastoplastic problems for the Hencky model Elastoplastic problems for the Prandtl-Reuss model Elastoplastic problems for plates with cracks The Prandtl-Reuss elastoplastic plates Contact elastoplastic problem for the curvilinear Kirchhoff rod Contact elastoplastic problem for the curvilinear Timoshenko rod Viscoelastoplastic curvilinear Timoshenko rod Curvilinear rod under creep conditions Conclusion.
Aging Neuroscience Hypothesis and Theory Article Aging Induced Loss of Complexity and Dedifferentiation: Consequences for Coordination Dynamics within and between Brain, Muscular and Behavioral Levels

Growing evidence demonstrates that aging not only leads to structural and functional alterations of individual components of the neuro-musculo-skeletal system (NMSS) but also results in a systemic reorganization of interactions within and between the different levels and functional domains. Understanding the principles that drive the dynamics of these reorganizations is an important challenge for aging research. The present Hypothesis and Theory paper is a contribution in this direction. We propose that age-related declines in brain and behavior that have been characterized in the literature as dedifferentiation and the loss of complexity (LOC) are: (i) synonymous; and (ii) integrated. We argue that a causal link between the aforementioned phenomena exists, evident in the dynamic changes occurring in the aging NMSS. Through models and methods provided by a dynamical systems approach to coordination processes in complex living systems, we: (i) formalize operational hypotheses about the general principles of changes in cross-level and cross-domain interactions during aging; and (ii) develop a theory of the aging NMSS based on the combination of the frameworks of coordination dynamics (CD), dedifferentiation, and LOC. Finally, we provide operational predictions in the study of aging at neural, muscular, and behavioral levels, which lead to testable hypotheses and an experimental agenda to explore the link between CD, LOC and dedifferentiation within and between these different levels.
The emissivity of foam-covered water surface at L-band: theoretical modeling and experimental results from the FROG 2003 field experiment

Sea surface salinity can be measured by microwave radiometry at L-band (1400-1427 MHz). This frequency is a compromise between sensitivity to the salinity, small atmospheric perturbation, and reasonable pixel resolution. The description of the ocean emission depends on two main factors: (1) the sea water permittivity, which is a function of salinity, temperature, and frequency, and (2) the sea surface state, which depends on the wind-induced wave spectrum, swell, and rain-induced roughness spectrum, and by the foam coverage and its emissivity. This study presents a simplified two-layer emission model for foam-covered water and the results of a controlled experiment to measure the foam emissivity as a function of salinity, foam thickness, incidence angle, and polarization. Experimental results are presented, and then compared to the two-layer foam emission model with the measured foam parameters used as input model parameters. At 37 psu salt water the foam-induced emissivity increase is /spl sim/0.007 per millimeter of foam thickness (extrapolated to nadir), increasing with increasing incidence angles at vertical polarization, and decreasing with increasing incidence angles at horizontal polarization.