Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulations Provide Support for the Common Disease–Common Variant Hypothesis

The success of mapping genes involved in complex diseases, using association or linkage disequilibrium methods, depends heavily on the number and frequency of susceptibility alleles of these genes. These methods will be economically and statistically feasible if common diseases are usually influenced by one or a few susceptibility alleles at each locus (common disease–common variant, CDCV, hypothesis), but not so if there is a high degree of allelic heterogeneity. Here, we use forward-time population simulations to investigate the impact of various genetic and demographic factors on the allelic spectra of human diseases, on the basis of two models proposed by Reich and Lander and by Pritchard. Factors considered are more complex demographies, a finite-allele mutation model, population structure and migration, and interaction between disease susceptibility loci. The conclusion is that the CDCV hypothesis holds and that the phenomenon is caused by transient effects of demography (population expansion). As a result, we devise a multilocus generalization of the Reich and Lander model and demonstrate how interaction between loci with respect to their response to selection may lead to complex effects. We discuss the implications for mapping of complex diseases.
Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis

The Yersinia pestis V antigen is necessary for full induction of low-calcium response (LCR) stimulon virulence gene transcription, and it also is a secreted protein believed to have a direct antihost function. We made four nonpolar deletions in lcrV of Y. pestis to determine if secretion, regulation, and virulence functions could be localized within the V antigen (LcrV). Deletion of amino acids 25 to 40 caused secretion of LcrV to be decreased in efficiency; however, removal of residues 108 to 125 essentially abolished LcrV secretion. Neither mutation had a significant effect on LCR regulation. This showed that LcrV does not have to be secreted to have its regulatory effect and that the internal structure of V antigen is necessary for its secretion. Both mutants were avirulent in mice, showing that the regulatory effect of LcrV could be separated genetically from its virulence role and raising the possibility that residues 25 to 40 are essential for the virulence function. This study provides the best genetic evidence available that LcrV per se is necessary for the virulence of Y. pestis. The repressed LCR phenotype of a mutant lacking amino acids 188 to 207 of LcrV raised the possibility that the deleted region is necessary for regulation of LCR induction; however, this mutant LcrV was weakly expressed and may not have been present in sufficient amounts to have its regulatory effect. In double mutants containing this mutant lcrV and also lacking expression of known LCR negative regulators (LcrG, LcrE, and LcrH), full induction of the LCR occurred in the absence of functional LcrV, indicating that LcrV promotes induction not as an activator per se but rather by inhibiting negative regulators.
Affinity purification of PSD‐95‐containing postsynaptic complexes

A widely used method for the preparation of postsynaptic density (PSD) fractions consists of treatment of synaptosomal membranes with Triton X‐100 and further purification by density gradient centrifugation. In the present study, the purity of this preparation was assessed by electron microscopic analysis. Thin‐section and rotary shadow immuno‐electron microscopy of the Triton X‐100‐derived PSD fraction shows many PSD‐95‐positive structures that resemble in situ PSDs in shape and size. However, the fraction also includes contaminants such as CaMKII clusters, spectrin filaments and neurofilaments. We used magnetic beads coated with an antibody against PSD‐95 to further purify PSD‐95‐containing complexes from the Triton‐derived PSD fraction. Biochemical analysis of the affinity‐purified material shows a substantial reduction in the astrocytic marker glial fibrillary acidic protein and electron microscopic analysis shows mostly individual PSDs attached to magnetic beads. This preparation was used to assess the association of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)‐type glutamate receptors with the PSD‐95‐containing complex. AMPA receptors are demonstrated by immunoblotting to be present in the complex, although they do not co‐purify exclusively with PSD‐95, suggesting the existence of two pools of receptors, one associated with the PSD‐95 scaffold and the other not. Of the AMPA receptor‐anchoring proteins tested, SAP‐97 is present in the affinity‐purified preparation whereas GRIP is found only in trace amounts. These results imply that a subpopulation of AMPA receptors is anchored to the PSD‐95‐containing scaffold through interaction of GluR1 with SAP‐97.
Electric-Field-Induced Change of the Magnetoresistance in the Multiferroic Spin-Valve Based on ${\hbox {BiFeO}}_{3}$  Film

The electric-field control of magnetization has many potential applications in magnetic memory storage, sensors, and spintronics. A new multiferroic spin-valve (SV) heterostructure was grown by combining a multiferroic BiFeO3 (BFO) and a Co90Fe10/Cu/Co90Fe10 spin valve on Pt/Ti/SiO2/Si substrate. Through the magnetoelectric coupling between a BFO layer and Co90Fe10 layer, the magnetoresistance of SV could be controlled by electric field applied on the BFO layer. The BFO film exhibits an obvious ferroelectric property with a remnant polarization of 17 μC/cm2 and a coercive field of 400 kV/cm. The exchange bias of 6 Oe and magnetoresistance (MR) of 1.04% were observed in the heterostructure at room temperature. Moreover, an electric-field-induced change of MR was demonstrated when we employed 0.5- and -0.5-V voltage between top and bottom electrode layer. Furthermore, the values of MR of the spin were changed into 0.71% and 0.95%, respectively. This realization of the electric-field-induced change of MR indicates the great potential applications in future functional devices.
Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways

Drosophila peripheral nerves, similar structurally to the peripheral nerves of mammals, comprise a layer of axons and inner glia, surrounded by an outer perineurial glial layer. Although it is well established that intercellular communication occurs among cells within peripheral nerves, the signaling pathways used and the effects of this signaling on nerve structure and function remain incompletely understood. Here we demonstrate with genetic methods that the Drosophila peripheral nerve is a favorable system for the study of intercellular signaling. We show that growth of the perineurial glia is controlled by interactions among five genes: ine, which encodes a putative neurotransmitter transporter; eag, which encodes a potassium channel; push, which encodes a large, Zn2+-finger-containing protein; amn, which encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide; and NF1, the Drosophila ortholog of the human gene responsible for type 1 neurofibromatosis. In other Drosophila systems, push and NF1 are required for signaling pathways mediated by Amn or the pituitary adenylate cyclase activator peptide. Our results support a model in which the Amn neuropeptide, acting through Push and NF1, inhibits perineurial glial growth, whereas the substrate neurotransmitter of Ine promotes perineurial glial growth. Defective intercellular signaling within peripheral nerves might underlie the formation of neurofibromas, the hallmark of neurofibromatosis.
1,3-Di-4-pyridylpropane–4,4′-oxydibenzoic acid (1/1)

The hydrothermal reaction of Cd(NO3)2·4H2O, 1,3-di-4-pyridylpropane (BPP) and 4,4′-oxydibenzoic acid (OBA) led to the formation of the title compound, C13H14N2·C14H10O5. The asymmetric unit consists of one molecule of OBA and one of BPP. In the OBA molecule, one COOH group is nearly planar with its attached benzene ring [dihedral angle = 0.9 (1)°], while the other COOH group is slightly twisted with a dihedral angle of 10.8 (3)°. The carboxyl groups form strong intermolecular O—H⋯N hydrogen bonds with N atoms of the pyridine rings in BPP, linking the molecules into zigzag chains.
Plant foods in the management of diabetes mellitus: Spices as beneficial antidiabetic food adjuncts

Diet has been recognized as a corner stone in the management of diabetes mellitus. Spices are the common dietary adjuncts that contribute to the taste and flavour of foods. Besides, spices are also known to exert several beneficial physiological effects including the antidiabetic influence. This review considers all the available information from animal experimentation as well as clinical trials where spices, their extracts or their active principles were examined for treatment of diabetes. Among the spices, fenugreek seeds (Trigonella foenumgraecum), garlic (Allium sativum), onion (Allium cepa), and turmeric (Curcuma longa) have been experimentally documented to possess antidiabetic potential. In a limited number of studies, cumin seeds (Cuminum cyminum), ginger (Zingiber officinale), mustard (Brassica nigra), curry leaves (Murraya koenigii) and coriander (Coriandrum sativum) have been reported to be hypoglycaemic.
Proteomic profile of carbonylated proteins in rat liver: Discovering possible mechanisms for tetracycline‐induced steatosis

To investigate biochemical mechanisms for the tetracycline‐induced steatosis in rats, targeted proteins of oxidative modification were profiled. The results showed that tetracycline induced lipid accumulation, oxidative stress, and cell viability decline in HepG2 cells only under the circumstances of palmitic acid overload. Tetracycline administration in rats led to significant decrement in blood lipids, while resulted in more than four times increment in intrahepatic triacylglycerol and typical microvesicular steatosis in the livers. The triacylglycerol levels were positively correlated with oxidative stress. Proteomic profiles of carbonylated proteins revealed 26 targeted proteins susceptible to oxidative modification and most of them located in mitochondria. Among them, the long‐chain specific acyl‐CoA dehydrogenase was one of the key enzymes regulating fatty acid β‐oxidation. Oxidative modification of the enzyme in the tetracycline group depressed its enzymatic activity. In conclusion, the increased influx of lipid into the livers is the first hit of tetracycline‐induced microvesicular steatosis. Oxidative stress is an essential part of the second hit, which may arise from the lipid overload and attack a series of functional proteins, aggravating the development of steatosis. The 26 targeted proteins revealed here provide a potential direct link between oxidative stress and tetracycline‐induced steatosis.
Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array

Epithelial ovarian cancer has the highest mortality rate among gynecological cancers. Altered glycosylation is associated with oncogenic transformation producing tumor‐associated carbohydrate antigens. We investigated the potential of natural occurring antiglycan antibodies in the diagnosis of ovarian cancer by using printed glycan array. Antiglycan antibodies bound to 203 chemically synthesized printed glycans were detected via biotin‐streptavidin fluorescence system in serum of women with normal operative findings (healthy controls; n = 24) and nonmucinous borderline or ovarian cancer of various FIGO stages (n = 33). Data were validated measuring blood group associated di‐, tri and tetrasaccharide antigens on known ABO blood groups. Antiglycan antibodies demonstrated high reproducibility (rc > 0.9). Cluster analysis identified repetitive patterns of specific core carbohydrate structures: 11 N‐linked glycans, 3 O‐linked glycans and 2 glycosphingolipids. Biomarker detection revealed 24 glycans including P1 (Galα1–4Galβ1–4GlcNAcβ; p < 0.001) significantly discriminating between (low‐) malignant tumors and healthy controls. Comparable sensitivity and specificity with tumor marker CA125 was achieved by a panel of multivariate selected and linear combined antiglycan antibody signals (79.2 and 84.8%, respectively). Our findings demonstrate the potential of glycan arrays in the development of a new generation of biomarkers for ovarian cancer.
The persistence of the association between adolescent cannabis use and common mental disorders into young adulthood.

AIMS Debate continues about whether the association between cannabis use in adolescence and common mental disorders is causal. Most reports have focused on associations in adolescence, with few studies extending into adulthood. We examine the association from adolescence until the age of 29 years in a representative prospective cohort of young Australians. DESIGN Nine-wave, 15-year representative longitudinal cohort study, with six waves of data collection in adolescence (mean age 14.9-17.4 years) and three in young adulthood (mean age 20.7, 24.1 and 29.1 years). PARTICIPANTS Participants were a cohort of 1943 recruited in secondary school and surveyed at each wave when possible from mid-teen age to their late 20s. SETTING Victoria, Australia. MEASUREMENTS Psychiatric morbidity was assessed with the Revised Clinical Interview Schedule (CIS-R) at each adolescent wave, and as Composite International Diagnostic Interview (CIDI)-defined ICD-10 major depressive episode and anxiety disorder at 29 years. Frequency of cannabis use was measured in the past 6 months in adolescence. Cannabis use frequency in the last year and DSM-IV cannabis dependence were assessed at 29 years. Cross-sectional and prospective associations of these outcomes with cannabis use and dependence were estimated as odds ratios (OR), using multivariable logistic regression models, with the outcomes of interest, major depressive episode (MDE) and anxiety disorder (AD) at 29 years. FINDINGS There were no consistent associations between adolescent cannabis use and depression at age 29 years. Daily cannabis use was associated with anxiety disorder at 29 years [adjusted OR 2.5, 95% confidence interval (CI):< 1.2-5.2], as was cannabis dependence (adjusted OR 2.2, 95% CI: 1.1-4.4). Among weekly+ adolescent cannabis users, those who continued to use cannabis use daily at 29 years remained at significantly increased odds of anxiety disorder (adjusted OR 3.2, 95% CI: 1.1-9.2). CONCLUSIONS Regular (particularly daily) adolescent cannabis use is associated consistently with anxiety, but not depressive disorder, in adolescence and late young adulthood, even among regular users who then cease using the drug. It is possible that early cannabis exposure causes enduring mental health risks in the general cannabis-using adolescent population.
Ohmic Heating: Concept and Applications—A Review

Ohmic heating, also known as Joule heating, electrical resistance heating, and direct electrical resistance heating, is a process of heating the food by passing electric current. In ohmic heating the energy is dissipated directly into the food. Electrical conductivity is a key parameter in the design of an effective ohmic heater. A large number of potential applications exist for ohmic heating, including blanching, evaporation, dehydration, fermentation, sterilization, pasteurization, and heating of foods. Beyond heating, applied electric field under ohmic heating causes electroporation of cell membranes, which increase extraction rates, and reduce gelatinization temperature and enthalpy. Ohmic heating results in faster heating of food along with maintenance of color and nutritional value of food. Water absorption index, water solubility index, thermal properties, and pasting properties are altered with the application of ohmic heating. Ohmic heating results in pre-gelatinized starches, which reduce energy requirement during processing. But its higher initial cost, lack of its applications in foods containing fats and oils, and less awareness limit its use.
Acute Rheumatic Fever Associated With Household Crowding in a Developed Country

Background: Acute rheumatic fever (ARF) and its sequelae, chronic rheumatic heart disease, remain important causes of morbidity and mortality worldwide, but there is little recent information about risk factors. The aim of this study was to examine the association between ARF and household crowding in New Zealand between 1996 and 2005. Methods: This ecologic study used hospitalization data and census data to calculate incidence rates by census area unit (CAU). Rates of ARF were examined in relation to individual factors (age, ethnicity) and area factors based on the CAU of home address (household crowding, New Zealand deprivation index, household income, and proportion of children aged 5–14 years). The multivariate relationship between ARF incidence and CAU-based variables was assessed using a zero-inflated negative binomial model. Results: This study included 1249 new cases of ARF between 1996 and 2005. At the univariate level, ARF rates were associated with household crowding across all age groups and ethnicities. ARF rates were significantly and positively related to household crowding after controlling for age, ethnicity, household income, and the density of children in the neighborhood. The incidence rate ratio was 1.065 (95% confidence interval, 1.052–1.079) for the total population. Conclusions: In New Zealand, ARF rates are associated with household crowding at the CAU level. This finding supports action to reduce household crowding to improve health and reduce health inequalities. Our conclusion could be further investigated using a case-control study.
Characterisation and image-based flight control of an autonomous free fall skydiving robot

The Freefall Camera (FFC) is a robot designed to film skydivers in free fall and is, to the author's knowledge, the first robot to control its position and terminal velocity relative to another falling object. The robot is equipped with a vision sensor to track objects of a chosen colour. The control surfaces for free fall motion are four vertical ailerons that control planar position and orientation and two retractable flaps that control terminal velocity. To develop a robust controller, equations of motion were created and validated experimentally for movement in the vertical and planar rotational directions. The static and dynamic response of the system were then tested in a vertical wind tunnel to validate the models and use them to design and tune a PID + Filter controller for the free fall flight of the robot. Planar rotation tests showed a decrease in steady state angular velocity and dynamic response gain compared to the model and a slight increase in dynamic response phase shift. This was attributed to the effect of the turbulent air near the shell of the robot. Vertical translation tests showed a decrease in maximum terminal velocity compared to the model, likely due to the effect of air viscosity at higher Reynolds numbers. The models were used to tune a PID + Filter controller to achieve stable target tracking in the rotational and vertical degrees of freedom using image based visual servoing. Controlled flight of the FFC was then tested in a vertical wind tunnel, where the robot was able to successfully track a coloured target within 15° of the centre of the field of view.
Median effective dose (ED₅₀) of paracetamol and morphine for postoperative pain: a study of interaction.

BACKGROUND Paracetamol is widely used to treat postoperative pain and is well known for its morphine-sparing effect. Therefore, the effect of morphine-paracetamol combination can be synergistic, additive, or infra-additive. The primary aim of our study is to define the median effective analgesic doses (ED₅₀s) of paracetamol, morphine, and the combination of both. Also, the nature of the interaction for postoperative pain after moderately painful surgery using an up-and-down method and isobolographic analysis was determined. METHODS Ninety patients, undergoing moderately painful surgery, were included in one of the three groups. Determination of the median ED₅₀s was performed by the Dixon and Mood up-and-down method. Initial doses were 1.5 g and 5 mg, with dose adjustment intervals of 0.5 g and 1 mg, in the paracetamol and morphine groups, respectively. The initial doses of paracetamol and morphine were 1.5 g and 3 mg, in the paracetamol-morphine combination group with dose adjustment intervals of 0.25 g for paracetamol and 0.5 mg for morphine. Analgesic efficacy was defined as a reduction to or <3 on a 0-10 numeric rating scale, 45 min after the beginning of drug administration. Isobolographic analysis was used to define the nature of their interaction. RESULTS The median ED₅₀s of paracetamol and morphine were 2.1 g and 5 mg, respectively. The median ED₅₀ of the combination was 1.3 g for paracetamol and 2.7 mg for morphine. CONCLUSIONS Our study showed that the combination of the paracetamol and morphine produces an additive analgesic effect. Clinical trial registration NCT01366313.
Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles*

Hepatitis C virus (HCV) is an enveloped, positive strand RNA virus of about 9.6 kb. Like all enveloped viruses, the HCV membrane fuses with the host cell membrane during the entry process and thereby releases the genome into the cytoplasm, initiating the viral replication cycle. To investigate the features of HCV membrane fusion, we developed an in vitro fusion assay using cell culture-produced HCV and fluorescently labeled liposomes. With this model we could show that HCV-mediated fusion can be triggered in a receptor-independent but pH-dependent manner and that fusion of the HCV particles with liposomes is dependent on the viral dose and on the lipid composition of the target membranes. In addition CBH-5, an HCV E2-specific antibody, inhibited fusion in a dose-dependent manner. Interestingly, point mutations in E2, known to abrogate HCV glycoprotein-mediated fusion in a cell-based assay, altered or even abolished fusion in the liposome-based assay. When assaying the fusion properties of HCV particles with different buoyant density, we noted higher fusogenicity of particles with lower density. This could be attributable to inherently different properties of low density particles, to association of these particles with factors stimulating fusion, or to co-floatation of factors enhancing fusion activity in trans. Taken together, these data show the important role of lipids of both the viral and target membranes in HCV-mediated fusion, point to a crucial role played by the E2 glycoprotein in the process of HCV fusion, and reveal an important behavior of HCV of different densities with regard to fusion.
Hyperspectral imaging techniques for the characterization of Haematococcus pluvialis (Chlorophyceae)

A hyperspectral imaging camera was combined with a bright‐field microscope to investigate the intracellular distribution of pigments in cells of the green microalga Haematococcus pluvialis, a synonym for H. lacustris (Chlorophyceae). We applied multivariate curve resolution to the hyperspectral image data to estimate the pigment contents in culture and revealed that the predicted values were consistent with actual measurements obtained from extracted pigments. Because it was possible to estimate pigment contents in every pixel, the intracellular distribution of the pigments was investigated during various life‐cycle stages. Astaxanthin was localized specifically at the eyespot of zoospores in early culture stages. Then, it became widely distributed in cells, but subsequently localized differently than the chl. Integrated with our recently developed image‐processing program “HaematoCalMorph,” the hyperspectral imaging system was useful for monitoring intracellular distributions of pigments during culture as well as for studying cellular responses under various conditions.