351 research outputs found
Studi Kasus Faktor Penyebab Kecelakaan Lalu Lintas Pada Tikungan Tajam
Hairpin curve is an accident prone location. The number of accidents on curve 1,5 to 4 times much more than on straight road. This study aimed to evaluate the geometric conditions on some curve that is reviewed by applicable geometric rules, to determine the characteristics of the accidents, to determine the relationship of modeling the causes of accidents, to determine the main factors causing traffic accidents, and provide troubleshooting recommendations. The analysis that is carried out are analysis of geometric condition evaluation, accident characteristics analysis, and cross tabulation analysis. Based on the evaluation of the geometric conditions, on all of the third curves there are not reach the technical standards because under minimum curve radius and the value of SMS of sample vehicle variety more than SS curve calculation speed limit nearly reach 50%. Based on the characteristics of accidents, on the third curves showed that the dominant factor causing accidents is human factor (70%). The results of study relationship between curve radius and degree of fatality indicate the value of R Square 0,859, meanwhile relationship between speed and degree of fatality indicate the value of R Square 0,91. The sum of the analysis showed the main factor causing traffic accidents is human factor specificly to the speed factor and then continued by curve radius factor. Several attempts types of treatment that can be applied is to install speed limit signs in some specific locations, make rumble strips before entering the hairpin curves
Behavioral, Cognitive, and Socioemotional Pathways from Early Childhood Adversity to BMI: Evidence from Two Prospective, Longitudinal Studies
Childhood adversity is associated with higher adult weight, but few investigations prospectively test mechanisms accounting for this association. Using two socioeconomically high-risk prospective longitudinal investigations, the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA; N = 267; 45.3% female) and the Fragile Families and Child Wellbeing Study (FFCWS; n = 2,587; 48.5% female), pathways between childhood adversity and later body mass index (BMI) were tested using impulsivity, emotion dysregulation, and overeating as mediators. Childhood adversity from 0 to 5 years included four types of adversities: greater unpredictability, threat/abuse, deprivation/neglect, and low socioeconomic status. Parents reported on child impulsivity, emotion dysregulation, and overeating. Height and weight were self-reported and measured at 32 and 37 years in MLSRA and at 15 years in FFCWS. FFCWS results indicated that threat, deprivation, and low socioeconomic status predicted greater impulsivity and emotion dysregulation at 5 years, which in turn predicted greater overeating at 9 years and higher BMI z-score at 15 years. Early unpredictability in FFCWS predicted higher BMI through greater impulsivity but not emotion dysregulation at age 5. MLSRA regression results replicated the threat/abuse → emotion dysregulation → overeating → higher BMI pathway. These findings suggest that different dimensions of early adversity may follow both similar and unique pathways to predict BMI
The temperature-dependence of host–guest binding thermodynamics: experimental and simulation studies
The Impact of SGLT2 Inhibitors, Compared with Insulin, on Diabetic Bone Disease in a Mouse Model of Type 1 Diabetes
Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of the renal sodium-dependent glucose co-transporter type 2 (SGLT2); 2) subcutaneous insulin, via minipump (INS, 0.125 units/day); 3) co-therapy (CANA + INS); or 4) no treatment (STZ, without therapy). These groups were also compared to non-diabetic control groups. Untreated diabetic mice experienced increased bone resorption and significant deficits in cortical and trabecular bone that contributed to structural weakness of the femur mid-shaft and the lumbar vertebra, as determined by three-point bending and compression tests, respectively. Treatment with either canagliflozin or insulin alone only partially rectified hyperglycemia and the diabetic bone phenotype. However, when used in combination, normalization of glycemic control was achieved, and a prevention of the DM-related deterioration in bone microarchitecture and bone strength occurred, due to additive effects of canagliflozin and insulin. Nevertheless, CANA-treated mice, whether diabetic or non-diabetic, demonstrated an increase in urinary calcium loss; FGF23 was also increased in CANA-treated DM mice. These findings could herald ongoing bone mineral losses following CANA exposure, suggesting that certain CANA-induced skeletal consequences might detract from therapeutic improvements in glycemic control, as they relate to diabetic bone disease
SGLT2 Inhibitor Therapy Improves Blood Glucose but Does Not Prevent Diabetic Bone Disease in Diabetic DBA/2J Male Mice
Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by ÎĽCT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p \u3c 0.0001, for all) while cortical porosity was increased (p \u3c 0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p \u3c 0.001 for all). Significant increases in PTH (p \u3c 0.0001), RatLAPs (p = 0.0002), and urine calcium concentration (p \u3c 0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with adverse effects on the trabecular compartment of bone
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Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors
The mammalian target of rapamycin (mTOR) regulates cell growth by integrating nutrient and growth factor signaling and is strongly implicated in cancer. But mTOR is not an oncogene, and which tumors will be resistant or sensitive to new ATP-competitive mTOR inhibitors now in clinical trials remains unknown. We screened a panel of over 600 human cancer cell lines to identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS and PIK3CA mutations were the most significant genetic markers for resistance and sensitivity to PP242, respectively; colon origin was the most significant marker for resistance based on tissue type. Among colon cancer cell lines, those with KRAS mutations were most resistant to PP242, while those without KRAS mutations most sensitive. Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR revealed that the degree of cellular growth inhibition induced by PP242 was correlated with inhibition of phosphorylation of the translational repressor 4E-BP1, but not ribosomal protein S6. In a tumor growth inhibition trial of PP242 in patient-derived colon cancer xenografts, resistance to PP242 induced inhibition of 4E-BP1 phosphorylation and xenograft growth was again observed in KRAS mutant tumors without PIK3CA co-mutation, compared to KRAS WT controls. We show that, in the absence of PIK3CA co-mutation, KRAS mutations are associated with resistance to PP242 and that this is specifically linked to changes in the level of phosphorylation of 4E-BP1
Orbit-Based Dynamical Models of the Sombrero Galaxy (NGC 4594)
We present axisymmetric, orbit-based models to study the central black hole,
stellar mass-to-light ratio, and dark matter halo of NGC 4594 (M104, the
Sombrero Galaxy). For stellar kinematics, we use published high-resolution
kinematics of the central region taken with the Hubble Space Telescope, newly
obtained Gemini long-slit spectra of the major axis, and integral field
kinematics from the SAURON instrument. At large radii, we use globular cluster
kinematics to trace the mass profile and apply extra leverage to recovering the
dark matter halo parameters. We find a black hole of mass M_{\bullet}=(6.6 +/-
0.4) x 10^8 M_{\odot}, and determine the stellar M/L_I=3.4 +/- 0.05
(uncertainties are the 68% confidence band marginalized over the other
parameters). Our best fit dark matter halo is a cored logarithmic model with
asymptotic circular speed V_c=376 +/- 12 km/s and core radius r_c= 4.7 +/- 0.6
kpc. The fraction of dark to total mass contained within the half-light radius
is 0.52. Taking the bulge and disk components into account in our calculation
of \sigma_e puts NGC 4594 squarely on the M-\sigma relation. We also determine
that NGC 4594 lies directly on the M-L relation.Comment: 13 pages, 10 figures, accepted for publication in Ap
Low temperature vibrational spectra, lattice dynamics, and phase transitions in some potassium hexahalometallates: K2[XY6] with X=Sn or Te and Y=Cl or Br
Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring
Background
Breastfeeding protects against illnesses and death in hazardous environments, an
effect partly mediated by improved immune function. One hypothesis suggests that
factors within milk supplement the inadequate immune response of the offspring,
but this has not been able to account for a series of observations showing that
factors within maternally derived milk may supplement the development of the
immune system through a direct effect on the primary lymphoid organs. In a
previous human study we reported evidence suggesting a link between IL-7 in
breast milk and the thymic output of infants. Here we report evidence in mice of
direct action of maternally-derived IL-7 on T cell development in the offspring.
Methods and Findings
 We have used recombinant IL-7 labelled with a fluorescent dye to trace the
movement in live mice of IL-7 from the stomach across the gut and into the
lymphoid tissues. To validate the functional ability of maternally derived IL-
7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets
of thymocytes and populations of peripheral T cells were significantly higher
than those found in knock-out mice receiving milk from IL-7 knock-out mothers.
Conclusions/Significance Our study provides direct evidence that interleukin 7,
a factor which is critical in the development of T lymphocytes, when maternally
derived can transfer across the intestine of the offspring, increase T cell
production in the thymus and support the survival of T cells in the peripheral
secondary lymphoid tissue
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