Effect of Process Parameters and Build Orientation on Microstructure and Impact Energy of Electron Beam Powder Bed Fused Ti-6Al-4V.

To fully exploit the benefits of additive manufacturing (AM), an understanding of its processing, microstructural, and mechanical aspects, and their interdependent characteristics, is necessary. In certain instances, AM materials may be desired for applications where impact toughness is a key property, such as in gas turbine fan blades, where foreign or direct object damage may occur. In this research, the impact energy of a series of Ti-6Al-4V specimens produced via electron beam powder bed fusion (EBPBF) was established via Charpy impact testing.

The Influence of Process Parameters and Build Orientation on the Creep Behaviour of a Laser Powder Bed Fused Ni-based Superalloy for Aerospace Applications.

Additive Layer Manufacturing (ALM) is an innovative net shape manufacturing technology that offers the ability to produce highly intricate components not possible through traditional wrought and cast procedures. Consequently, the aerospace industry is becoming ever more attentive in exploiting such technology for the fabrication of nickel-based superalloys in an attempt to drive further advancements within the holistic gas turbine. Given this, the requirement for the mechanical characterisation of such material is rising in parallel, with limitations in the availability of material processed restricting conventional mechanical testing; particularly with the abundance of process parameters to evaluate.

Defective fasting-induced PKA activation impairs adipose tissue glycogen degradation in obese Zucker rats.

Background: Obesity is associated with development of insulin resistance in adipose tissue (AT). Human obesity has been associated with increased glycogen deposition in adipocytes. Adipocytes synthesise glycogen prior to the formation of lipids.

No evidence of direct association between GLUT4 and glycogen in human skeletal muscle.

Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%.

Mas Receptor Activation Slows Tumor Growth and Attenuates Muscle Wasting in Cancer.

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. Cachexia robs patients of their strength and capacity to perform daily tasks and live independently. Effective treatments are needed urgently.

Early Identification of Potential SSDI Entrants in California: The Predictive Value of State Disability Insurance and Workers' Compensation Claims.

Purpose Examine the potential for using information in short-term disability claims to identify workers at high risk of leaving the workforce and entering Social Security Disability Insurance (SSDI). Methods We analyze state-wide California data on claimants of State Disability Insurance (SDI) and Workers' Compensation (WC) and present statistics on: (1) characteristics (primary diagnosis, sex, age, geography, wage level) by claim duration (0-3, 4-6, 7-12, 12 + months); and (2) the ability of initial claim characteristics to predict duration of at least 12 months. All data are for claims with disability lasting more than 1 week.

Mail order pharmacy use and adherence to secondary prevention drugs among stroke patients.

Background And Purpose: Mail order pharmacies (MOP) are increasingly being used to deliver medications for chronic disease management. Their use is linked to similar or even greater medication adherence than local pharmacy (LP) use. We are unaware of any studies that have evaluated the association of mail order pharmacy use with drug adherence among stroke patients.

Predicting Receipt of Social Security Administration Disability Benefits Using Biomarkers and Other Physiological Measures: Evidence From the Health and Retirement Study.

Objectives: The objective of this study was to assess how well physiological measures, including biomarkers and genetic indicators, predict receipt of Social Security Administration (SSA) disability benefits among U.S. adults aged 51 to 65 years.

Unravelling the Carbohydrate-Binding Preferences of the Carbohydrate-Binding Modules of AMP-Activated Protein Kinase.

The β subunit of adenosine monophosphate (AMP)-activated protein kinase (AMPK), which exists as two isoforms (β1 and β2) in humans, has a carbohydrate-binding module (CBM) that interacts with glycogen. Although the β1- and β2-CBMs are structurally similar, with strictly conserved ligand-contact residues, they show different carbohydrate affinities. β2-CBM shows the strongest affinity for both branched and unbranched oligosaccharides and it has recently been shown that a Thr insertion into β2-CBM (Thr101) forms a pocket to accommodate branches.

Using the Health and Retirement Study for Disability Policy Research: A Review.

The Health and Retirement Study (HRS) is a preeminent data source for research related to the experiences of workers nearing retirement, including the large share of those workers who experience a health shock or disability onset after age 50. In this article, we highlight key information collected from HRS respondents that benefits disability policy research and the body of knowledge that has resulted from this information. Our main goal is to identify from this research experience potential improvements in data collection and documentation that would further strengthen the HRS as a data source for disability policy researchers.

Employment Support for the Transition to Retirement.

As workers near retirement, many experience a medical event that limits the ability to work. Public programs provide health insurance and income support for these individuals, but that support is often not adequate to protect against poverty following the onset of a new health condition. Moreover, these policies generally are not designed to encourage continuing work rather than premature retirement.

β-subunit myristoylation functions as an energy sensor by modulating the dynamics of AMP-activated Protein Kinase.

The heterotrimeric AMP-activated protein kinase (AMPK), consisting of α, β and γ subunits, is a stress-sensing enzyme that is activated by phosphorylation of its activation loop in response to increases in cellular AMP. N-terminal myristoylation of the β-subunit has been shown to suppress Thr172 phosphorylation, keeping AMPK in an inactive state. Here we use amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate the structural and dynamic properties of the mammalian myristoylated and non-myristoylated inactivated AMPK (D139A) in the presence and absence of nucleotides.

Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury.

Background: Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration.

When phosphorylated at Thr148, the β2-subunit of AMP-activated kinase does not associate with glycogen in skeletal muscle.

The 5'-AMP-activated protein kinase (AMPK), a heterotrimeric complex that functions as an intracellular fuel sensor that affects metabolism, is activated in skeletal muscle in response to exercise and utilization of stored energy. The diffusibility properties of α- and β-AMPK were examined in isolated skeletal muscle fiber segments dissected from rat fast-twitch extensor digitorum longus and oxidative soleus muscles from which the surface membranes were removed by mechanical dissection. After the muscle segments were washed for 1 and 10 min, ∼60% and 75%, respectively, of the total AMPK pools were found in the diffusible fraction.

Trends in disability and program participation among U.S. veterans.

Background: Disability is increasingly part of the lives of veterans and more research is needed to understand its impact on veterans' participation in disability benefit programs.

Objective/hypothesis: We examine how recent trends in receipt of service-connected disability compensation from the Department of Veterans Affairs (VA) compare to trends in self-reported disability and participation in Social Security Disability Insurance (DI) and Supplemental Security Income (SSI) among veterans.

Methods: We use 2002-2013 data from the Current Population Survey to describe trends in receipt of VA disability compensation and to compare between trends in self-reported disability and DI/SSI participation for veterans versus nonveterans.

Regulation of Starch Stores by a Ca(2+)-Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii.

Transmissible stages of Toxoplasma gondii store energy in the form of the carbohydrate amylopectin. Here, we show that the Ca(2+)-dependent protein kinase CDPK2 is a critical regulator of amylopectin metabolism. Increased synthesis and loss of degradation of amylopectin in CDPK2 deficient parasites results in the hyperaccumulation of this sugar polymer.

Molecular Insights into the Enigmatic Metabolic Regulator, SnRK1.

Sucrose non-fermenting-1 (SNF1)-related kinase 1 (SnRK1) lies at the heart of metabolic homeostasis in plants and is crucial for normal development and response to stress. Evolutionarily related to SNF1 in yeast and AMP-activated kinase (AMPK) in mammals, SnRK1 acts protectively to maintain homeostasis in the face of fluctuations in energy status. Despite a conserved function, the structure and regulation of the plant kinase differ considerably from its relatively well-understood opisthokont orthologues.

FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy.

Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated.

Predicting Disability among Community-Dwelling Medicare Beneficiaries Using Claims-Based Indicators.

Objectives: To assess the feasibility of using existing claims-based algorithms to identify community-dwelling Medicare beneficiaries with disability based solely on the conditions for which they are being treated, and improving on these algorithms by combining them in predictive models.

Data Source: Data on 12,415 community-dwelling fee-for-service Medicare beneficiaries who first responded to the Medicare Current Beneficiary Survey (MCBS) in 2003-2006.

Study Design: Logistic regression models in which six claims-based disability indicators are used to predict self-reported disability.

Rat skeletal muscle glycogen degradation pathways reveal differential association of glycogen-related proteins with glycogen granules.

Glycogenin, glycogen-debranching enzyme (GDE) and glycogen phosphorylase (GP) are important enzymes that contribute to glycogen particle metabolism. In Long-Evans Hooded rat whole muscle homogenates prepared from extensor digitorum longus (EDL, fast-twitch) and soleus (SOL, oxidative, predominantly slow twitch), it was necessary to include α-amylase, which releases glucosyl units from glycogen, to detect glycogenin but not GDE or GP. Up to ∼12 % of intramuscular glycogen pool was broken down using either in vitro electrical stimulation or leaving muscle at room temperature >3 h (delayed, post-mortem).

The recruitment of AMP-activated protein kinase to glycogen is regulated by autophosphorylation.

The mammalian AMP-activated protein kinase (AMPK) is an obligatory αβγ heterotrimeric complex carrying a carbohydrate-binding module (CBM) in the β-subunit (AMPKβ) capable of attaching AMPK to glycogen. Nonetheless, AMPK localizes at many different cellular compartments, implying the existence of mechanisms that prevent AMPK from glycogen binding. Cell-free carbohydrate binding assays revealed that AMPK autophosphorylation abolished its carbohydrate-binding capacity.

Determinants of oligosaccharide specificity of the carbohydrate-binding modules of AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that is important in regulating energy metabolism in all eukaryotes. The β-subunit exists in two isoforms (β1 and β2) and contains a carbohydrate-binding module (CBM) that interacts with glycogen. The two CBM isoforms (β1- and β2-CBM) are near identical in sequence and structure, yet show differences in carbohydrate-binding affinity.

SnRK1 from Arabidopsis thaliana is an atypical AMPK.

SNF1-related protein kinase 1 (SnRK1) is the plant orthologue of the evolutionarily-conserved SNF1/AMPK/SnRK1 protein kinase family that contributes to cellular energy homeostasis. Functional as heterotrimers, family members comprise a catalytic α subunit and non-catalytic β and γ subunits; multiple isoforms of each subunit type exist, giving rise to various isoenzymes. The Arabidopsis thaliana genome contains homologues of each subunit type, and, in addition, two atypical subunits, β(3) and βγ, with unique domain architecture, that are found only amongst plants, suggesting atypical heterotrimers.

Myocardial glycogen dynamics: new perspectives on disease mechanisms.

Cardiac glycogen regulation involves a complex interplay between multiple signalling pathways, allosteric activation of enzymes, and sequestration for autophagic degradation. Signalling pathways appear to converge on glycogen regulatory enzymes via insulin (glycogen synthase kinase 3β, protein phosphatase 1, allosteric action of glucose-6-phosphate), β-adrenergic (phosphorylase kinase protein phosphatase 1 inhibitor), and 5' adenosine monophosphate-activated protein kinase (allosteric action of glucose-6-phosphate, direct glycogen binding, insulin receptor). While cytosolic glycogen synthesis and breakdown are relatively well understood, recent findings relating to phagic glycogen degradation highlight a new area of investigation in the heart.

Molecular basis of impaired glycogen metabolism during ischemic stroke and hypoxia.

Background: Ischemic stroke is the combinatorial effect of many pathological processes including the loss of energy supplies, excessive intracellular calcium accumulation, oxidative stress, and inflammatory responses. The brain's ability to maintain energy demand through this process involves metabolism of glycogen, which is critical for release of stored glucose. However, regulation of glycogen metabolism in ischemic stroke remains unknown.