Silicon Atomic Quantum Dots Enable Beyond-CMOS Electronics

We review our recent efforts in building atom-scale quantum-dot cellular automata circuits on a silicon surface. Our building block consists of silicon dangling bond on a H-Si(001) surface, which has been shown to act as a quantum dot. First the fabrication, experimental imaging, and charging character of the dangling bond are discussed. We then show how precise assemblies of such dots can be created to form artificial molecules. Such complex structures can be used as systems with custom optical properties, circuit elements for quantum-dot cellular automata, and quantum computing. Considerations on macro-to-atom connections are discussed.Comment: 28 pages, 19 figure

Interacting Supernovae: Types IIn and Ibn

Supernovae (SNe) that show evidence of strong shock interaction between their ejecta and pre-existing, slower circumstellar material (CSM) constitute an interesting, diverse, and still poorly understood category of explosive transients. The chief reason that they are extremely interesting is because they tell us that in a subset of stellar deaths, the progenitor star may become wildly unstable in the years, decades, or centuries before explosion. This is something that has not been included in standard stellar evolution models, but may significantly change the end product and yield of that evolution, and complicates our attempts to map SNe to their progenitors. Another reason they are interesting is because CSM interaction is an efficient engine for making bright transients, allowing super-luminous transients to arise from normal SN explosion energies, and allowing transients of normal SN luminosities to arise from sub-energetic explosions or low radioactivity yield. CSM interaction shrouds the fast ejecta in bright shock emission, obscuring our normal view of the underlying explosion, and the radiation hydrodynamics of the interaction is challenging to model. The CSM interaction may also be highly non-spherical, perhaps linked to binary interaction in the progenitor system. In some cases, these complications make it difficult to definitively tell the difference between a core-collapse or thermonuclear explosion, or to discern between a non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical parameters of individual events and connections to possible progenitor stars make this a rapidly evolving topic that continues to challenge paradigms of stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3 fig

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Effects of Temperature–Climate Patterns on the Production of Some Competitive Species on Grounds of Modelling

Climate change has serious effects on the setting up and the operation of natural ecosystems. Small increase in temperature could cause rise in the amount of some species or potential disappearance of others. During our researches, the dispersion of the species and biomass production of a theoretical ecosystem were examined on the effect of the temperature–climate change. The answers of the ecosystems which are given to the climate change could be described by means of global climate modelling and dynamic vegetation models. The examination of the operation of the ecosystems is only possible in huge centres on supercomputers because of the number and the complexity of the calculation. The number of the calculation could be decreased to the level of a PC by considering the temperature and the reproduction during modelling a theoretical ecosystem, and several important theoretical questions could be answered

Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.

Stressful life events produce a state of vulnerability to depression in some individuals. The mechanisms that contribute to vulnerability to depression remain poorly understood. A rat model of intense stress (social defeat (SD), first hit) produced vulnerability to depression in 40% of animals. Only vulnerable animals developed a depression-like phenotype after a second stressful hit (chronic mild stress). We found that this vulnerability to depression resulted from a persistent state of oxidative stress, which was reversed by treatment with antioxidants. This persistent state of oxidative stress was due to low brain-derived neurotrophic factor (BDNF) levels, which characterized the vulnerable animals. We found that BDNF constitutively controlled the nuclear translocation of the master redox-sensitive transcription factor Nrf2, which activates antioxidant defenses. Low BDNF levels in vulnerable animals prevented Nrf2 translocation and consequently prevented the activation of detoxifying/antioxidant enzymes, ultimately resulting in the generation of sustained oxidative stress. Activating Nrf2 translocation restored redox homeostasis and reversed vulnerability to depression. This mechanism was confirmed in Nrf2-null mice. The mice displayed high levels of oxidative stress and were inherently vulnerable to depression, but this phenotype was reversed by treatment with antioxidants. Our data reveal a novel role for BDNF in controlling redox homeostasis and provide a mechanistic explanation for post-stress vulnerability to depression while suggesting ways to reverse it. Because numerous enzymatic reactions produce reactive oxygen species that must then be cleared, the finding that BDNF controls endogenous redox homeostasis opens new avenues for investigation

Long-term patterns of body mass and stature evolution within the hominin lineage.

Body size is a central determinant of a species' biology and adaptive strategy, but the number of reliable estimates of hominin body mass and stature have been insufficient to determine long-term patterns and subtle interactions in these size components within our lineage. Here, we analyse 254 body mass and 204 stature estimates from a total of 311 hominin specimens dating from 4.4 Ma to the Holocene using multi-level chronological and taxonomic analytical categories. The results demonstrate complex temporal patterns of body size variation with phases of relative stasis intermitted by periods of rapid increases. The observed trajectories could result from punctuated increases at speciation events, but also differential proliferation of large-bodied taxa or the extinction of small-bodied populations. Combined taxonomic and temporal analyses show that in relation to australopithecines, early Homo is characterized by significantly larger average body mass and stature but retains considerable diversity, including small body sizes. Within later Homo, stature and body mass evolution follow different trajectories: average modern stature is maintained from ca 1.6 Ma, while consistently higher body masses are not established until the Middle Pleistocene at ca 0.5-0.4 Ma, likely caused by directional selection related to colonizing higher latitudes. Selection against small-bodied individuals (less than 40 kg; less than 140 cm) after 1.4 Ma is associated with a decrease in relative size variability in later Homo species compared with earlier Homo and australopithecines. The isolated small-bodied individuals of Homo naledi (ca 0.3 Ma) and Homo floresiensis (ca 100-60 ka) constitute important exceptions to these general patterns, adding further layers of complexity to the evolution of body size within the genus Homo. At the end of the Late Pleistocene and Holocene, body size in Homo sapiens declines on average, but also extends to lower limits not seen in comparable frequency since early Homo

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

Background In this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts) is considered as logistic only. Results We demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can lead to different evolutionary patterns for normal and tumor cells during a course of therapy. Conclusions These results have significance for understanding appropriate pharmacotherapy for elderly patients who are also undergoing chemotherapy

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)