PIKK-ing a New Partner: A New Role for PKB in the DNA Damage Response

The protein kinase PKB/Akt has long been associated with regulating signaling pathways that promote cell survival and cell growth, for example, in response to growth factors. In contrast, the DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA damage and for cell survival after exposure to DNA-damaging agents, such as ionizing radiation. In a recent paper published in Molecular Cell, Hemmings and colleagues provide evidence that DNA-PK is required for the activation of PKB in response to exposure to ionizing radiation, suggesting that these two protein kinases may act together to promote survival after DNA damage

Supporting Career Development and Employment: Benefits Planning, Assistance and Outreach (BPA&O) and Protection and Advocacy for Beneficiaries of Social Security (PABSS)

This training curriculum is dedicated to increasing knowledge and understanding of the Social Security Administration\u27s disability and return to work programs and work incentive provisions as prescribed in the Social Security Act and Ticket to Work and Work Incentives Improvement Act of 1999 as well as other federal benefit programs. These informational resources were compiled and edited to provide continuing education and print materials for benefits specialists and protection and advocacy personnel on the interplay of these benefit programs and impact or employment

Advanced modulation technology development for earth station demodulator applications. Coded modulation system development

A jointly optimized coded modulation system is described which was designed, built, and tested by COMSAT Laboratories for NASA LeRC which provides a bandwidth efficiency of 2 bits/s/Hz at an information rate of 160 Mbit/s. A high speed rate 8/9 encoder with a Viterbi decoder and an Octal PSK modem are used to achieve this. The BER performance is approximately 1 dB from the theoretically calculated value for this system at a BER of 5 E-7 under nominal conditions. The system operates in burst mode for downlink applications and tests have demonstrated very little degradation in performance with frequency and level offset. Unique word miss rate measurements were conducted which demonstrate reliable acquisition at low values of Eb/No. Codec self tests have verified the performance of this subsystem in a stand alone mode. The codec is capable of operation at a 200 Mbit/s information rate as demonstrated using a codec test set which introduces noise digitally. The measured performance is within 0.2 dB of the computer simulated predictions. A gate array implementation of the most time critical element of the high speed Viterbi decoder was completed. This gate array add-compare-select chip significantly reduces the power consumption and improves the manufacturability of the decoder. This chip has general application in the implementation of high speed Viterbi decoders

LCF Life of NiCr-Y Coated Disk Alloys After Shot Peening, Oxidation and Hot Corrosion

In a prior companion study (Ref. 1), three different Ni-Cr coating compositions (29, 35.5, 45 wt% Cr) were applied at two thicknesses by Plasma Enhanced Magnetron Sputtering (PEMS) to two similar Ni-based disk alloys. One coating also received a thin ZrO2 overcoat. The low cycle fatigue (LCF) life of each coating was determined at 760 C and was less than that of the uncoated specimens. In this followon effort, shot peening was examined as a means to improve the as-deposited coating morphology as well as impart a residual compressive stress in the near-surface region. After evaluating the effect of the shot peening on the LCF life, the effectiveness of the shot-peened coating in protecting the disk alloy from oxidation and hot corrosion attack was evaluated. This evaluation was accomplished by exposing coated and shot-peened specimens to 500 h of oxidation followed by 50 h of hot corrosion, both at 760 C in air. These exposed specimens were then tested in fatigue and compared to similarly treated and exposed uncoated specimens. For all cases, shot peening improved the LCF life of the coated specimens. More specifically, the highest Cr coating showed the best LCF life of the coated specimens after shot peening, as well as after the environmental exposures. Characterization of the coatings after shot peening, oxidation, hot corrosion and LCF testing is presented and discussed

Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains

Abstract Background Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimates associations between maternal vitamins B12, B6 (pyridoxal phosphate [PLP] and 4-pyridoxic acid [PA]), and homocysteine (Hcy) concentrations, offspring weight (birth weight and 3-year weight gain), and DNA methylation at four differentially methylated regions (DMRs) known to be involved in fetal growth and development (H19, MEG3, SGCE/PEG10, and PLAGL1). Methods Study participants (n = 496) with biomarker and birth weight data were enrolled as part of the Newborn Epigenetics STudy. Weight gain data were available for 273 offspring. Among 484 mother-infant pairs, DNA methylation at regulatory sequences of genomically imprinted genes was measured in umbilical cord blood DNA using bisulfite pyrosequencing. We used generalized linear models to estimate associations. Results Multivariate adjusted regression models revealed an inverse association between maternal Hcy concentration and male birth weight (β = −210.40, standard error (SE) = 102.08, p = 0.04). The offspring of the mothers in the highest quartile of B12 experienced lower weight gain between birth and 3 years compared to the offspring of the mothers in the lowest (β = −2203.03, SE = 722.49, p = 0.003). Conversely, maternal PLP was associated with higher weight gain in males; higher maternal PLP concentrations were also associated with offspring DNA methylation levels at the MEG3 DMR (p < 0.01). Conclusions While maternal concentrations of B12, B6, and Hcy do not associate with birth weight overall, they may play an important role in 3-year weight gain. This is the first study to report an association between maternal PLP and methylation at the MEG3 DMR which may be an important epigenetic tag for maternal B vitamin adequacy

Trusted CI Experiences in Cybersecurity and Service to Open Science

This article describes experiences and lessons learned from the Trusted CI project, funded by the US National Science Foundation to serve the community as the NSF Cybersecurity Center of Excellence. Trusted CI is an effort to address cybersecurity for the open science community through a single organization that provides leadership, training, consulting, and knowledge to that community. The article describes the experiences and lessons learned of Trusted CI regarding both cybersecurity for open science and managing the process of providing centralized services to a broad and diverse community.Comment: 8 pages, PEARC '19: Practice and Experience in Advanced Research Computing, July 28-August 1, 2019, Chicago, IL, US

The Effectiveness of a NiCrY-Coating on a Powder Metallurgy Disk Superalloy

Protective ductile coatings could be necessary to mitigate oxidation and corrosion attack on superalloy disks in some turbine engine applications. However, the effects of coatings on fatigue life of the disk during service are an important concern. The objective of this study was to investigate how such a coating could perform after varied post-coating processing. Cylindrical gage fatigue specimens of powder metallurgy-processed disk superalloy LSHR were coated with a NiCrY coating, shot peened, preparation treated, exposed, and then subjected to fatigue at high temperature. The effects of varied shot peening, preparation treatment, and exposures on fatigue life with and without the coating were compared. Each of these variables and several of their interactions significantly influenced fatigue life

Maximizing the Benefit-Cost Ratio of Anthracyclines in Metastatic Breast Cancer: Case Report of a Patient with a Complete Response to High-Dose Doxorubicin

Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2– mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF)] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit