The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer.

Activating transcription factor 5 (ATF5) is a cellular prosurvival transcription factor within the basic leucine zipper (bZip) family that is involved in cellular differentiation and promotes cellular adaptation to stress. Recent studies have characterized the oncogenic role of ATF5 in the development of several different types of cancer, notably glioblastoma. Preclinical assessment of a systemically deliverable dominant-negative ATF5 (dnATF5) biologic has found that targeting ATF5 results in tumor regression and tumor growth inhibition of glioblastoma xenografts in mouse models. In this review, we comprehensively and critically detail the current scientific literature on ATF5 in the context of cellular differentiation, survival, and response to stressors in normal tissues. Furthermore, we will discuss how the prosurvival role of ATF5 aides in cancer development, followed by current advances in targeting ATF5 using dominant-negative biologics, and perspectives on future research

Total Joint Implant Alloy Oxide Layer Cell-Induced Damage

Cobalt-Chromium alloy is commonly used in total joint arthroplasty (TJA). Several studies have investigated evidence of inflammatory-cell-induced-corrosion (ICIC) causing pitting in TJA retrieved implants. Others have determined that placing orthopedic alloys into lower pH solutions will increase the rate of corrosion. We have determined that electrochemical potential and corrosion rates of human knee synovial fluid show a variation greater than an order of magnitude. This means there is going to be a significant variation between a patient’s local environment of the TJA implant and may affect how macrophages interact with alloy oxide layers. Knee disability can be quantified by using the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR). In order to determine predictive measures of patient outcomes, we plan to measure the electrochemical properties of patient implants and associate them with these KOOSJR scores. In addition, we plan to further investigate the effects and extent of macrophage-mediated damage to alloys when under inflammatory conditions. The current results are inconclusive, but suggest that there is a relationship between these parameters and patient outcomes and encourage further investigation of the mechanisms at play

The Impact on Maryland\u27s Budget of Allowing Same-Sex Couples to Marry

This analysis estimates the potential impact of extending marriage rights to same-sex couples on Maryland’s state budget. Drawing on data from the U.S. Census Bureau and Maryland statistical reports, we estimate that extending marriage rights to same-sex couples would result in a net gain of approximately $3.2 million each year. This net gain is attributable to savings in expenditures on meanstested public benefit programs and an increase in sales and lodging tax revenue from weddings and wedding-related tourism

Ideal Gas in a strong Gravitational field: Area dependence of Entropy

We study the thermodynamic parameters like entropy, energy etc. of a box of gas made up of indistinguishable particles when the box is kept in various static background spacetimes having a horizon. We compute the thermodynamic variables using both statistical mechanics as well as by solving the hydrodynamical equations for the system. When the box is far away from the horizon, the entropy of the gas depends on the volume of the box except for small corrections due to background geometry. As the box is moved closer to the horizon with one (leading) edge of the box at about Planck length (L_p) away from the horizon, the entropy shows an area dependence rather than a volume dependence. More precisely, it depends on a small volume A*L_p/2 of the box, upto an order O(L_p/K)^2 where A is the transverse area of the box and K is the (proper) longitudinal size of the box related to the distance between leading and trailing edge in the vertical direction (i.e in the direction of the gravitational field). Thus the contribution to the entropy comes from only a fraction O(L_p/K) of the matter degrees of freedom and the rest are suppressed when the box approaches the horizon. Near the horizon all the thermodynamical quantities behave as though the box of gas has a volume A*L_p/2 and is kept in a Minkowski spacetime. These effects are: (i) purely kinematic in their origin and are independent of the spacetime curvature (in the sense that Rindler approximation of the metric near the horizon can reproduce the results) and (ii) observer dependent. When the equilibrium temperature of the gas is taken to be equal to the the horizon temperature, we get the familiar A/L_p^2 dependence in the expression for entropy. All these results hold in a D+1 dimensional spherically symmetric spacetime.Comment: 19 pages, added some discussion, matches published versio

“If You Are Old Enough to Die for Your Country, You Should Be Able to Get a Pinch of Snuff”: Views of Tobacco 21 Among Appalachian Youth

Background: Multiple strategies have been utilized in attempts to decrease the prevalence of youth tobacco use. One strategy, raising the minimum legal sale age (MLSA) of tobacco products to 21, known as Tobacco 21, has recently gained popularity. Tobacco 21 legislation targets youth tobacco use by obstructing two main sources of youth tobacco products: stores and older friends. Although these sources are the most common for youth across the nation, regional differences have not been explored. Further, youth perspectives about raising the tobacco MLSA have not been considered. Youth may help identify potential challenges to implementing tobacco control measures, as well as suggest alternatives for intervention, thus helping to shape successful tobacco control policies. Study Aim: This study aimed to 1) examine youth perspectives on raising the tobacco minimum legal sale age to 21 and 2) identify common sources of tobacco products among middle and high school students living in rural, low-income Appalachian communities. Methods: A cross-sectional survey about perceptions and use of tobacco products was conducted with students in the Appalachian regions of Kentucky and North Carolina (N=426). Questions were asked concerning perspectives on the effect of Tobacco 21 implementation. Descriptive statistics characterized participants by Tobacco 21 perspectives. Participants were given the opportunity to further expand upon their opinions in an open-ended format. Results: The majority (58.7%) of participants responded that the same number of youth would use tobacco if the legal purchase age were raised, followed by responses that fewer would use (28.9%) and more would use (12.4%). Significant differences emerged based on tobacco use status (p\u3c.05), friends’ tobacco use (p\u3c.001), and whether participants identified family members as sources of youth tobacco products (p=.047). When given the opportunity to expand upon their views concerning the implementation of Tobacco 21 laws in their communities, many respondents cited poor enforcement of tobacco MLSAs at stores, continued access to tobacco products from family members and friends, and the overall abundance of tobacco in their communities as potential barriers to the successful implementation. Conclusion: Fewer than one-third of participants believed that Tobacco 21 legislation would succeed in reducing the prevalence of youth tobacco use. Perspectives on the effect of Tobacco 21 legislation were related to personal tobacco use, exposure to tobacco users, and beliefs that family members provide tobacco products to youth. Open-ended responses identify potential obstacles in implementing Tobacco 21 legislation in Appalachia. Future research should attempt to include youth perspectives when designing and implementing tobacco control policies and examine family members as sources of tobacco products for youth

Dissociation of C-Reactive Protein Levels from Long-Chain Omega-3 Fatty Acid Status and Antidepressant Response in Adolescents with Major Depressive Disorder: An Open-Label Dose-Ranging Trial

Major depressive disorder (MDD) is associated with long-chain omega-3 (LCn-3) fatty acid deficits and indices of chronic sustained inflammation including elevated C-reactive protein (CRP) levels. The present study combined a case-control analysis and a prospective 10-week open-label fish oil (FO) supplementation trial to investigate the relationships among plasma phospholipid LCn-3 fatty acid levels, plasma CRP concentrations, and depressive symptoms in adolescent MDD patients. Compared with healthy controls (n=20), MDD patients (n=20) exhibited significantly lower EPA+DHA levels (-62%, p£0.0001) and a higher ratio of arachidonic acid (AA) to EPA+DHA (+78%, p=0.0002). CRP concentrations did not differ between controls and MDD patients (0.16 vs. 0.17 mg/dL, p=0.96), and were positively correlated with depression symptom severity scores in MDD patients (r = +0.55, p=0.01). CRP concentrations were positively correlated with BMI in MDD patients (r = +0.63, p=0.005) and controls (r = +0.69, p=0.002). Low-dose (2.4 g/d) and high-dose (15 g/d) FO supplementation significantly increased EPA+DHA levels in MDD patients, but did not significantly alter CRP concentrations. Baseline and baseline-endpoint change in CRP levels were not correlated with baseline-endpoint reductions in depression severity. Together, these data demonstrate that the lower plasma phospholipid LCn-3 fatty acid composition exhibited by adolescent MDD patients is not associated with higher CRP levels, and that increasing LCn-3 fatty acid status reduces depression symptom severity independent of changes in CRP concentrations. Collectively, these data suggest that CRP concentrations are dissociable from LCn-3 fatty acid status and antidepressant response in adolescent MDD patients

Modeling and characterization of InAs∕GaAs quantum dot lasers grown using metal organic chemical vapor deposition

We report on the lasing characteristics of three- and five-stack InAs∕GaAsquantum dot(QD) lasers grown by metal organic chemical vapor deposition. By increasing the number of stacked dot layers to 5, lasing was achieved from the ground state at 1135nm for device lengths as short as 1.5mm (no reflectivity coatings). The unamplified spontaneous emission and Z ratio as a function of injection current were also investigated. While the five-stack QD lasers behaved as expected with Z ratios of ≈2 prior to lasing, the three-stack QD lasers, which lased from the excited state, exhibited Z-ratio values as high as 4. A simple model was developed and indicated that high Z ratios can be generated by three nonradiative recombination pathways: (i) high monomolecular recombination within the wetting layer, (ii) Auger recombination involving carriers within the QDs (“unmixed” Auger), and (iii) Auger recombination involving both the QD and wetting layer states (“mixed” Auger), which dominate once the excited and wetting layer states become populated.We also acknowledge the financial support of the Australian Research Council

Nuclear Incompressibility in Asymmetric Systems at Finite Temperature and Entropy

The nuclear incompressibility $\kappa$ is investigated in asymmetric systems in a mean field model. The calculations are done at zero and finite temperatures and include surface, Coulomb and symmetry energy terms for several equations of state. Also considered is the behavior of the incompressibility at constant entropy $kappa_Q$ which is shown to have a very different behavior than the isothermal $kappa$. Namely, $kappa_Q$ decreases with increasing entropy while the isothermal $kappa$ increases with increasing $T$. A duality is found between the adiabatic $kappa_Q$ and the T=0 isothermal $kappa$. Analytic and also simple approximate expressions for $kappa$ are given.Comment: 11 page

Mirrors for slow neutrons from holographic nanoparticle-polymer free-standing film-gratings

We report on successful tests of holographically arranged grating-structures in nanoparticle-polymer composites in the form of 100 microns thin free-standing films, i.e. without sample containers or covers that could cause unwanted absorption/incoherent scattering of very-cold neutrons. Despite their large diameter of 2 cm, the flexible materials are of high optical quality and yield mirror-like reflectivity of about 90% for neutrons of 4.1 nm wavelength