Analysis of task assignment policies in scalable distributedweb-server systems

A distributed multiserver Web site can provide the scalability necessary to keep up with growing client demand at popular sites. Load balancing of these distributed Web-server systems, consisting of multiple, homogeneous Web servers for document retrieval and a Domain Name Server (DNS) for address resolution, opens interesting new problems. In this paper, we investigate the effects of using a more active DNS which, as an atypical centralized scheduler, applies some scheduling strategy in routing the requests to the most suitable Web server. Unlike traditional parallel/distributed systems in which a centralized scheduler has full control of the system, the DNS controls only a very small fraction of the requests reaching the multiserver Web site. This peculiarity, especially in the presence of highly skewed load, makes it very difficult to achieve acceptable load balancing and avoid overloading some Web servers. This paper adapts traditional scheduling algorithms to the DNS, proposes new policies, and examines their impact under different scenarios. Extensive simulation results show the advantage of strategies that make scheduling decisions on the basis of the domain that originates the client requests and limited server state information (e.g., whether a server is overloaded or not). An initially unexpected result is that using detailed server information, especially based on history, does not seem useful in predicting the future load and can often lead to degraded performance     

Breakdown of the adiabatic Born-Oppenheimer approximation in graphene

The adiabatic Born-Oppenheimer approximation (ABO) has been the standard ansatz to describe the interaction between electrons and nuclei since the early days of quantum mechanics. ABO assumes that the lighter electrons adjust adiabatically to the motion of the heavier nuclei, remaining at any time in their instantaneous ground state. ABO is well justified when the energy gap between ground and excited electronic states is larger than the energy scale of the nuclear motion. In metals, the gap is zero and phenomena beyond ABO (such as phonon-mediated superconductivity or phonon-induced renormalization of the electronic properties) occur. The use of ABO to describe lattice motion in metals is, therefore, questionable. In spite of this, ABO has proved effective for the accurate determination of chemical reactions, molecular dynamics and phonon frequencies in a wide range of metallic systems. Here, we show that ABO fails in graphene. Graphene, recently discovered in the free state, is a zero-bandgap semiconductor that becomes a metal if the Fermi energy is tuned applying a gate voltage, Vg. This induces a stiffening of the Raman G peak that cannot be described within ABO.     

The Small Molecule GAL-201 Efficiently Detoxifies Soluble Amyloid β Oligomers: New Approach towards Oral Disease-Modifying Treatment of Alzheimer’s Disease

Soluble amyloid β (Aβ) oligomers have been shown to be highly toxic to neurons and are considered to be a major cause of the neurodegeneration underlying Alzheimer’s disease (AD). That makes soluble Aβ oligomers a promising drug target. In addition to eliminating these toxic species from the patients’ brain with antibody-based drugs, a new class of drugs is emerging, namely Aβ aggregation inhibitors or modulators, which aim to stop the formation of toxic Aβ oligomers at the source. Here, pharmacological data of the novel Aβ aggregation modulator GAL-201 are presented. This small molecule (288.34 g/mol) exhibits high binding affinity to misfolded Aβ_1-42 monomers (K_D = 2.5 ± 0.6 nM). Pharmacokinetic studies in rats using brain microdialysis are supportive of its oral bioavailability. The Aβ oligomer detoxifying potential of GAL-201 has been demonstrated by means of single cell recordings in isolated hippocampal neurons (perforated patch experiments) as well as in vitro and in vivo extracellular monitoring of long-term potentiation (LTP, in rat transverse hippocampal slices), a cellular correlate for synaptic plasticity. Upon preincubation, GAL-201 efficiently prevented the detrimental effect on LTP mediated by Aβ_1-42 oligomers. Furthermore, the potential to completely reverse an already established neurotoxic process could also be demonstrated. Of particular note in this context is the self-propagating detoxification potential of GAL-201, leading to a neutralization of Aβ oligomer toxicity even if GAL-201 has been stepwise removed from the medium (serial dilution), likely due to prion-like conformational changes in Aβ_1-42 monomer aggregates (trigger effect). The authors conclude that the data presented strongly support the further development of GAL-201 as a novel, orally available AD treatment with potentially superior clinical profile.     

Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.     

Characterisation of Progressive Skeletal Muscle Fibrosis in the Mdx Mouse Model of Duchenne Muscular Dystrophy: An In Vivo and In Vitro Study

Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions.     

Zr‐Doped Indium Oxide (IZRO) Transparent Electrodes for Perovskite‐Based Tandem Solar Cells

Parasitic absorption in transparent electrodes is one of the main roadblocks to enabling power conversion efficiencies (PCEs) for perovskite‐based tandem solar cells beyond 30%. To reduce such losses and maximize light coupling, the broadband transparency of such electrodes should be improved, especially at the front of the device. Here, the excellent properties of Zr‐doped indium oxide (IZRO) transparent electrodes for such applications, with improved near‐infrared (NIR) response, compared to conventional tin‐doped indium oxide (ITO) electrodes, are shown. Optimized IZRO films feature a very high electron mobility (up to ≈77 cm² V^?1 s^?1), enabling highly infrared transparent films with a very low sheet resistance (≈18 Ω □^?1 for annealed 100 nm films). For devices, this translates in a parasitic absorption of only ≈5% for IZRO within the solar spectrum (250–2500 nm range), to be compared with ≈10% for commercial ITO. Fundamentally, it is found that the high conductivity of annealed IZRO films is directly linked to promoted crystallinity of the indium oxide (In₂O₃) films due to Zr‐doping. Overall, on a four‐terminal perovskite/silicon tandem device level, an absolute 3.5 mA cm^?2 short‐circuit current improvement in silicon bottom cells is obtained by replacing commercial ITO electrodes with IZRO, resulting in improving the PCE from 23.3% to 26.2%.     

Optimal design of Service Overlay Networks with economic and performance constraints

In the last years, Service Overlay Networks (SONs) have emerged as a promising means to address some of the issues (e.g. end‐to‐end QoS) affecting the current Internet and to favor the development and deployment of new value‐added Internet services. The deployment of an SON is a capital‐intensive investment, since bandwidth with certain QoS guarantees must be purchased from the individual network domains through bilateral Service Level Agreements. Thus, minimizing the economic cost of the logical end‐to‐end service delivery infrastructure is one of the key objectives for the SON provider. When a SON is aimed at end‐to‐end QoS provisioning, its topology must be designed so as to also satisfy the specific requirements of QoS‐sensitive applications. This paper deals with the problem of planning the SON topology in order to take into account both cost and QoS constraints. More specifically, the paper proposes a set of new algorithms for the design of an optimized SON topology, which minimizes the economic cost while simultaneously meeting bandwidth and delay constraints. A performance comparison among such algorithms is finally carried out. Copyright © 2009 John Wiley & Sons, Ltd.     

Manual Therapy Facilitates Homeostatic Adaptation to Bone Microstructural Declines Induced by a Rat Model of Repetitive Forceful Task

The effectiveness of manual therapy in reducing the catabolic effects of performing repetitive intensive force tasks on bones has not been reported. We examined if manual therapy could reduce radial bone microstructural declines in adult female Sprague–Dawley rats performing a 12-week high-repetition and high-force task, with or without simultaneous manual therapy to forelimbs. Additional rats were provided 6 weeks of rest after task cessation, with or without manual therapy. The control rats were untreated or received manual therapy for 12 weeks. The untreated TASK rats showed increased catabolic indices in the radius (decreased trabecular bone volume and numbers, increased osteoclasts in these trabeculae, and mid-diaphyseal cortical bone thinning) and increased serum CTX-1, TNF-α, and muscle macrophages. In contrast, the TASK rats receiving manual therapy showed increased radial bone anabolism (increased trabecular bone volume and osteoblast numbers, decreased osteoclast numbers, and increased mid-diaphyseal total area and periosteal perimeter) and increased serum TNF-α and muscle macrophages. Rest, with or without manual therapy, improved the trabecular thickness and mid-diaphyseal cortical bone attributes but not the mineral density. Thus, preventive manual therapy reduced the net radial bone catabolism by increasing osteogenesis, while rest, with or without manual therapy, was less effective.     

Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K⁺ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K⁺ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K⁺-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K⁺ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.     

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.