Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Imaging of the Dynamics of Glucose Uptake in the Cytosol of COS-7 Cells by Fluorescent Nanosensors*

Glucose homeostasis is a function of glucose supply, transport across the plasma membrane, and metabolism. To monitor glucose dynamics in individual cells, a glucose nanosensor was developed by flanking the Escherichia coli periplasmic glucose/galactose-binding protein with two different green fluorescent protein variants. Upon binding of substrate the FLIPglu-170n sensor showed a concentration-dependent decrease in fluorescence resonance energy transfer between the attached chromophores with a binding affinity for glucose of 170 nm. Fluorescence resonance energy transfer measurements with different sugars indicated a broad selectivity for monosaccharides. An affinity mutant with a Kd of ∼600 μm was generated, which showed higher substrate specificity, and thus allowed specific monitoring of reversible glucose dynamics in COS-7 cells in the physiological range. At external glucose concentrations between 0.5 and 10 mm, reflecting typical blood levels, free cytosolic glucose concentrations remained at ∼50% of external levels. The removal of glucose lead to reduced glucose levels in the cell, demonstrating reversibility and visualizing homeostasis. Glucose levels dropped even in the presence of the transport inhibitor cytochalasin B, indicating rapid metabolism. Consistently, the addition of 2-deoxyglucose, which is not recognized by the sensor, affects glucose uptake and metabolism rates. Within the physiological range, glucose utilization, i.e. hexokinase activity, was not limiting. Furthermore, the results show that in COS-7 cells, cytosolic glucose concentrations can vary over at least two orders of magnitude. The glucose nanosensor provides a novel tool with numerous scientific, medical, and environmental applications.
Strong-field tests of relativistic gravity and binary pulsars.

Observations of pulsars in gravitationally bound binary systems provide a unique opportunity for testing the strong-field regime of relativistic gravity. We present a detailed account of the parametrized post-Keplerian'' (PPK) formalism, a general phenomenological framework designed to extract the maximum possible information from pulsar timing and pulse-structure data. The PPK approach allows dynamical information to be obtained from the data in a theory-independent way, and encoded in a certain number of fitted post-Keplerian parameters. We show that as many as 19 such parameters can be measured, under favorable conditions, giving access to 15 possible tests of relativistic gravity. We isolate and quantify the theoretical content of these tests by deriving, within the framework of generic boost-invariant theories, expressions linking the phenomenological parameters to the inertial masses of the pulsar and its companion, and to the polar angles of the spin axis of the pulsar. The prospects for extracting some of these tests from observations of known or yet-to-be-discovered binary pulsars is quantitatively assessed through numerical simulations. We show that the recently discovered binary pulsar PSR 1534+12 should, with presently available data, give access to two new strong-field tests of relativistic gravity, if the data are analyzed in the phenomenological waymore » emphasized in this paper. Moreover, in the long run, the first-disovered binary pulsar, PSR 1913+16, could give access to three strong-field tests, beyond the presently obtained {dot {omega}}{minus}{gamma}{minus}{ital {dot P}}{sub {ital b}} test. Finally, we show how, by combining the PPK approach with the predictions of a rather generic class of tensor biscalar theories, one can bring together tests based on observations of several different pulsars. « less
ALTRENOGEST AND PROGESTERONE THERAPY DURING PREGNANCY IN BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS) WITH PROGESTERONE INSUFFICIENCY

Abstract: Progesterone production is essential for growth and development of the conceptus during pregnancy. Abnormal development of the corpus luteum (CL) after conception can result in early embryonic loss or fetal abortion. Routine monitoring of bottlenose dolphin (Tursiops truncatus) pregnancy after artificial insemination or natural conception with ultrasonography and serum progesterone determination has allowed for the establishment of expected fetal growth rates and hormone concentrations. Using these monitoring techniques, we revealed four pregnant dolphins (12–24 yr old) with abnormally low progesterone production indicative of luteal insufficiency. Once diagnosed, animals were placed on altrenogest (0.044–0.088 mg/kg once daily) alone or with oral progesterone (50–200 mg twice daily). Doses of hormone were increased or decreased in each animal based on how fetal skull biparietal and thoracic growth rates compared with published normal values. Hormones were withdrawn starting from day 358 of gestation in animals 1 and 2, with labor occurring 6 and 7 days after withdrawal and at 376 and 373 days of gestation, respectively. Both deliveries were dystocic, with each calf requiring manual extraction and fetotomy for calf 1. The fetuses in animals 3 and 4 died at 348 and 390 days of gestation, respectively. Induction of labor was attempted in both animals, after fetal death, by using a combination of rapid progesterone withdrawal and steroid and prostaglandin F2α administration. The calf of animal 4 had to be removed with manual cervical dilation and fetotomy. All adult females survived the procedures. These data provide the first in vivo evidence that the CL is the primary source of progesterone throughout pregnancy in the bottlenose dolphin. Until further characterization of hormones required during pregnancy and at parturition has been accomplished, the exogenous progestagen supplementation protocol described here cannot be recommended for treatment of progesterone insufficiency in bottlenose dolphins.
COMPARATIVE MORPHOMETRIC ADAPTATION OF THE HOUSEFLY AND THE FACE FLY IN THE UNITED STATES

While the primary aim of morphometric analysis of geographic variation is to elucidate adaptation, selection is generally implicated through correlations of morphometric and environmental trends (e.g., Atchley, 1971; Johnston and Selander, 1971; Power, 1969). Because phenotypic trends can be invariably associated with some combination of environmental variables, these results provide only limited evidence of environmental action (e.g., Bryant, 1974; Felsenstein, 1975). When direct genetic tests are infeasible, an alternative approach is to compare geographic trends in closely related species, since parallel geographic variation in areas of sympatry would provide stronger evidence for adaptation to environment. Multivariate patterns of covariation among characters are presumed evidence of genetically based developmental processes (e.g., Blackith, 1960; Atchley, 1971) and comparative morphometrics in particular could offer an assessment of the selective basis and probable generality of these patterns. The major difficulty, of course, is finding suitable sympatric species with similar morphologies. The housefly, Musca domestica L, and the face fly, M. autumnalis DeGeer, occupy sympatric distributions in the United States, with the distribution of the northern limited face fly contained within the broader limits of the widespread housefly. Even though the face fly only frequents areas with cattle, the distributions of the two species do overlap locally and they can be found within a short distance of each other and occasionally on the same
The Effects of Speech Sound Disorders on Literacy Outcomes of School-age Children

The importance of identifying the relationship and independent variables of speech sound disorders and their effect on literacy, could have clinical benefits and improving speech and language intervention. In recent studies, researchers have found that deficits in phonological processes could be an indicator for predicting reading outcomes for children with speech sound disorders. It has been theorized that children who exhibit articulatory errors are the result of the inadequacy of the speech perceptual acoustic characteristics of speech phoneme errors. Objective: The purpose of this study is to examine the impact, if any, speech sound disorders have on school-age children and literacy and to determine if a relationship exists between children identified with a speech sound disorder and literacy achievement. Methods: A causal- comparative model was employed to investigate what possible effects speech sound disorders of school-age children have on reading achievement, and how it compares to children who are speech and language impaired and the norm group of students. Subjects for the study were collected using a stratified random sampling process from a local school district. Students were randomly chosen from each grade level (Kindergarten through 3rd grade) and then randomly selected again from each subgroup studied: 1) students identified as speech and language impairment, articulation (SLI-A), 2) students identified as speech and language impairment, language and articulation (SLI-LA however, in comparisons using the overall scores there were not any significant differences noted. In comparisons made between the norm group and SLI L&A comorbid group, results indicated that there are significant differences found in all statistical analysis completed. In comparing the SLI-A group and the SLI L& A comorbid groups within each grade level, significant differences were found within all grade levels, including the overall score comparison.
Source areas, drainage density, and channel initiation

An analysis of channel head locations provides insight into controls on drainage density, the response of landscapes to climatic change, and the delineation of source areas for channel network simulations. Channel heads and colluvial deposits were mapped in a roughly 2 km2 area near San Francisco, California, and, although channel heads are located within colluvial deposits in hollows, many such deposits do not support channel heads. Channel heads were classified as either gradual or abrupt. For either type of channel head, the channel reach immediately downslope may be contiguous with the channel network or may consist of a series of short discontinuous channel segments. The local valley slope at the channel head is inversely related to both source area and source-basin length as well as to the contributing area per unit contour length at the channel head. In contrast, valley slope does not vary with drainage area upslope of channel heads. Field observations and a similarity between predicted and observed area-slope relations suggest that the location of channel heads on steep slopes may be controlled by subsurface flow-induced instability of the colluvial fill. Preliminary field observations also suggest that abrupt channel heads on gentle slopes are controlled by seepage erosion, whereas gradual channel head locations appear to be governed by saturation overland flow. Consideration of the geometric relationship between source areas and the first-order drainages that contain them results in an inverse relation between mean source-basin length and drainage density.
Influences on willingness to use vaginal or oral HIV PrEP during pregnancy and breastfeeding in Africa: the multisite MAMMA study

Women in sub‐Saharan Africa spend a substantial portion of their reproductive lives pregnant and/or breastfeeding (P/BF), yet they have limited options to prevent HIV during these maternal stages. In preparation for phase 3b prevention trials in P/BF women, we explored attitudes about using a vaginal ring or oral pills for pre‐exposure prophylaxis (PrEP), perceptions of HIV risk during P/BF and key influences on future PrEP use.
Cognitive Vulnerability to Unipolar and Bipolar Mood Disorders

In this article, we review findings on the role of negative cognitive styles and information processing biases as cognitive vulnerabilities to unipolar and bipolar mood disorders. We first briefly describe the cognitive theories of unipolar depression and the logic of their extension to bipolar disorders, as well as methodological issues involved in conducting vulnerability research, particularly with bipolar samples. We then review the evidence for negative cognitive styles, information processing, and rumination, alone and in combination with life events, as vulnerabilities to unipolar depression and bipolar disorder, as well as the developmental antecedents of cognitive vulnerability to both forms of mood disorder. In our review, we give particular attention to the findings from the Temple-Wisconsin Cognitive Vulnerability to Depression Project and the Wisconsin-Temple Longitudinal Investigation of Bipolar Spectrum Project. Our review suggests that similar cognitive vulnerabilities may increase individ.
Repression of Inflammasome by Francisella tularensis during Early Stages of Infection*

Background: The mechanism of repression of inflammasome caused by Francisella tularensis is not known. Results: F. tularensis represses AIM2 and NLRP3 inflammasomes in a FTL_0325-dependent fashion. Conclusion: Repression of inflammasome by F. tularensis results in fulminate infection. Significance: This study advances the understanding of mechanisms of immune suppression caused by F. tularensis. Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect.
Maintenance of growth rate at low temperature in rice and wheat cultivars with a high degree of respiratory homeostasis is associated with a high efficiency of respiratory ATP production.

Some plants have the ability to maintain similar respiratory rates (measured at the growth temperature) when grown at different temperatures. This phenomenon is referred to as respiratory homeostasis. Using wheat and rice cultivars with different degrees of respiratory homeostasis (H), we previously demonstrated that high-H cultivars maintained shoot and root growth at low temperature [Kurimoto et al. (2004) Plant Cell Environ. , 27: 853]. Here, we assess the relationship between respiratory homeostasis and the efficiency of respiratory ATP production, by measuring the levels of alternative oxidase (AOX) and uncoupling protein (UCP), which have the potential to decrease respiratory ATP production per unit of oxygen consumed. We also measured SHAM- and CN-resistant respiration of intact roots, and the capacity of the cytochrome pathway (CP) and AOX in isolated mitochondria. Irrespective of H, SHAM-resistant respiration of intact roots and CP capacity of isolated root mitochondria were larger when plants were grown at low temperature, and the maximal activity and relative amounts of cytochrome c oxidase showed a similar trend. In contrast, CN-resistant respiration of intact roots and relative amounts of AOX protein in mitochondria isolated from those roots, were lower in high-H plants grown at low temperature. In the roots of low-H cultivars, relative amounts of AOX protein were higher at low growth temperature. Relative amounts of UCP protein showed similar trends to AOX. We conclude that maintenance of growth rate in high-H plants grown at low temperature is associated with both respiratory homeostasis and a high efficiency of respiratory ATP production.
Confidence Intervals for Rank Statistics: Somers’ D and Extensions

Somers’ D is an asymmetric measure of association between two variables, which plays a central role as a parameter behind rank or nonparametric statistical methods. Given predictor variable X and outcome variable Y, we may estimate D YX as a measure of the effect of X on Y, or we may estimate DXY as a performance indicator of X as a predictor of Y. The somersd package allows the estimation of Somers’ D and Kendall's τ A with confidence limits as well as p-values. The Stata 9 version of somersd can estimate extended versions of Somers’ D not previously available, including the Gini index, the parameter tested by the sign test, and extensions to left- or right-censored data. It can also estimate stratified versions of Somers’ D, restricted to pairs in the same stratum. Therefore, it is possible to define strata by grouping values of a confounder, or of a propensity score based on multiple confounders, and to estimate versions of Somers’ D that measure the association between the outcome and the predictor, adjusted for the confounders. The Stata 9 version of somersd uses the Mata language for improved computational efficiency with large datasets.
Stress Analysis of Cushion form Bearings for Total Hip Replacements

Cushion form bearings comprise a thin layer of low elastic modulus material on the articulating surface of the bearing, which can deform to help preserve a film of lubricant between the bearing surfaces and therefore reduce friction and wear. The long-term function of this type of bearing is dependent on the strength and durability of this compliant layer. Finite difference and finite element methods have been used to analyse the stress distribution in the compliant layer of cushion form bearing for artificial hip joints under physiological loading conditions. A good agreement between finite difference and finite element methods was found. Under normal loading, the highest value of the maximum shear stress was found to be at the interface between the compliant layer and the more rigid substrate close to the edge of the contact. The values of maximum shear stress in the centre of the contact close to the articulating surface were lower than in the equivalent Hertzian contact. A friction force acting at the surface had little effect on the stress distribution for coefficients of friction less than 0.05. However, for higher values of friction coefficient (larger than 0.2), corresponding to inadequate lubrication, the maximum shear stress increased by a factor of four and was found to be located at the surface. The analysis predicts that the mode of failure will be at the interface with the substrate under fluid film or mixed lubrication conditions and at the articulating surface when the bearing runs dry with higher levels of friction. Both failure modes have been observed experimentally under the conditions specified.
GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

The role of GABAergic neurons in activating female sexual behavior and possible mechanisms for GABAergic effects on behavior were examined in female rats. First, effects of the ovarian hormones estrogen and progesterone (P), at doses which promote lordosis, on levels and turnover/activity of GABA, were examined in brain areas which regulate lordosis. Utilizing AOAA, an inhibitor of GABA degradation, the accumulation rate of GABA (turnover/activity) was assessed in ovariectomized (Ovx), Ovx + estrogen and Ovx + estrogen + P-treated rats. Estradiol increased GABA accumulation rates in the arcuate-median eminence and in the area dorsal to and surrounding the VMN (VMN-S). P administration following estrogen priming enhanced GABA turnover in the medial preoptic area (mPOA) and further increased turnover in the VMN-S while GABA turnover decreased in the dorsomedial nucleus. No effects of hormones were noted in the VMN itself or in the dorsal midbrain central gray. Reverse dialysis of the GABAA antagonist bicuculline into the basomedial hypothalamus was associated with a time-dependent inhibition of lordosis and a 300% increase in 5-HT release in the basomedial hypothalamus as measured by in vivo dialysis. These results provide additional evidence that GABAergic neurons mediate the physiological regulation of female sexual behavior and suggest that such mediation may involve an interaction with 5-HT containing neurons.
On the double critical-state model for type-II superconductivity in 3D

In this paper we mathematically analyse an evolution variational inequality which formulates the double critical-state model for type-II superconductivity in 3D space and propose a finite element method to discretize the formulation. The double critical-state model originally proposed by Clem and Perez-Gonzalez is formulated as a model in 3D space which characterises the nonlinear relation between the electric field, the electric current, the perpendicular component of the electric current to the magnetic flux, and the parallel component of the current to the magnetic flux in bulk type-II superconductor. The existence of a solution to the variational inequality formulation is proved and the representation theorem of subdifferential for a class of energy functionals including our energy is established. The variational inequality formulation is discretized in time by a semi-implicit scheme and in space by the edge finite element of lowest order on a tetrahedral mesh. The fully discrete formulation is an unconstrained optimisation problem. The subsequence convergence property of the fully discrete solution is proved. Some numerical results computed under a rotating applied magnetic field are presented.