Correlates of Fatigue in Patients With Heart Failure

This study was conducted to determine the prevalence of fatigue and identify its demographic, clinical, and psychological correlates in 150 heart failure (HF) patients (73% men, 66% Caucasian, mean age 55 years, mean ejection fraction 26.7%±11%), from a single HF center, using the Profile of Mood States-Fatigue Subscale, the Minnesota Living With Heart Failure Questionnaire, and the Beck Depression Inventory. Sociodemographic and clinical data were obtained through self-report and chart abstraction. High levels of fatigue were reported in 50.4% of men and 51.2% of women. In a multivariate model, maximal workload, physical health, emotional health, and depression explained 51% of the variance in fatigue (P<.001). Fatigue in patients with HF is associated with both clinical and psychosocial variables, offering a number of targets for intervention. These findings suggest the need for multiple risk factor intervention strategies that improve physical and emotional health to decrease fatigue. Patients with depression warrant particular scrutiny

Mobile Loyalty Application Development Based on Android

The research objective is to develop an application that allows users to participate in a loyalty program and facilitate Smartphone enterprise (Merchant) in access, sale and observation of customer transactions through mobile applications. Design method used is object-based design that includes a UML of use case diagrams, use case narrative, class diagram, sequence diagrams and activity diagrams. Results achieved in the form of mobile applications that are able to facilitate customer in managing loyalty cards as well as to increase customer loyalty. This application features, such as add points, redeem, news, transaction history, and message that can facilitate customer in managing customer loyalty card. The conclusion of this design is that the application of E Points can enable customers to manage a loyalty card in Smartphone, add points, redeem rewards, obtain the latest promotional information through news features, and view transaction history

Immunization of Alpacas (\u3cem\u3eLama pacos\u3c/em\u3e) with Protein Antigens and Production of Antigen-Specific Single Domain Antibodies

In this manuscript, a method for the immunization of alpaca and the use of molecular biology methods to produce antigen-specific single domain antibodies is described and demonstrated. Camelids, such as alpacas and llamas, have become a valuable resource for biomedical research since they produce a novel type of heavy chain-only antibody which can be used to produce single domain antibodies. Because the immune system is highly flexible, single domain antibodies can be made to many different protein antigens, and even different conformations of the antigen, with a very high degree of specificity. These features, among others, make single domain antibodies an invaluable tool for biomedical research. A method for the production of single domain antibodies from alpacas is reported. A protocol for immunization, blood collection, and B-cell isolation is described. The B-cells are used for the construction of an immunized library, which is used in the selection of specific single domain antibodies via panning. Putative specific single domain antibodies obtained via panning are confirmed by pull-down, ELISA, or gel-shift assays. The resulting single domain antibodies can then be used either directly or as a part of an engineered reagent. The uses of single domain antibody and single domain antibody-based regents include structural, biochemical, cellular, in vivo, and therapeutic applications. Single domain antibodies can be produced in large quantities as recombinant proteins in prokaryotic expression systems, purified, and used directly or can be engineered to contain specific markers or tags that can be used as reporters in cellular studies or in diagnostics

The Notch intracellular domain represses CRE-dependent transcription

AbstractMembers of the cyclic-AMP response-element binding protein (CREB) transcription factor family regulate the expression of genes needed for long-term memory formation. Loss of Notch impairs long-term, but not short-term, memory in flies and mammals. We investigated if the Notch-1 (N1) exerts an effect on CREB-dependent gene transcription. We observed that N1 inhibits CREB mediated activation of cyclic-AMP response element (CRE) containing promoters in a γ-secretase-dependent manner. We went on to find that the γ-cleaved N1 intracellular domain (N1ICD) sequesters nuclear CREB1α, inhibits cAMP/PKA-mediated neurite outgrowth and represses the expression of specific CREB regulated genes associated with learning and memory in primary cortical neurons. Similar transcriptional effects were observed with the N2ICD, N3ICD and N4ICDs. Together, these observations indicate that the effects of Notch on learning and memory are, at least in part, via an effect on CREB-regulated gene expression

A Dyson Sphere around a black hole

The search for extraterrestrial intelligence (SETI) has been conducted for nearly 60 years. A Dyson Sphere, a spherical structure that surrounds a star and transports its radiative energy outward as an energy source for an advanced civilisation, is one of the main targets of SETI. In this study, we discuss whether building a Dyson Sphere around a black hole is effective. We consider six energy sources: (i) the cosmic microwave background, (ii) the Hawking radiation, (iii) an accretion disk, (iv) Bondi accretion, (v) a corona, and (vi) relativistic jets. To develop future civilisations (for example, a Type II civilisation), $4\times10^{26}\,{\rm W}$($1\,{\rm L_{\odot}}$) is expected to be needed. Among (iii) to (vi), the largest luminosity can be collected from an accretion disk, reaching $10^{5}\,{\rm L_{\odot}}$, enough to maintain a Type II civilisation. Moreover, if a Dyson Sphere collects not only the electromagnetic radiation but also other types of energy (e.g., kinetic energy) from the jets, the total collected energy would be approximately 5 times larger. Considering the emission from a Dyson Sphere, our results show that the Dyson Sphere around a stellar-mass black hole in the Milky Way ($10\,\rm kpc$ away from us) is detectable in the ultraviolet$(\rm 10-400\,{\rm nm)}$, optical$(\rm 400-760\,{\rm nm)}$, near-infrared($\rm 760\,{\rm nm}-5\,{\rm \mu m}$), and mid-infrared($\rm 5-40\,{\rm \mu m}$) wavelengths via the waste heat radiation using current telescopes such as Galaxy Evolution Explorer Ultraviolet Sky Surveys. Performing model fitting to observed spectral energy distributions and measuring the variability of radial velocity may help us to identify these possible artificial structures.Comment: This paper has been accepted for publication in MNRA

Alpha-Synuclein Modulates the Physical Properties of DNA

Published by Wiley-VCH Verlag GmbH &amp; Co. KGaA. Fundamental research on Parkinson\u27s disease (PD) most often focuses on the ability of α-synuclein (aS) to form oligomers and amyloids, and how such species promote brain cell death. However, there are indications that aS also plays a gene-regulatory role in the cell nucleus. Here, the interaction between monomeric aS and DNA in vitro has been investigated with single-molecule techniques. Using a nanofluidic channel system, it was discovered that aS binds to DNA and by studying the DNA–protein complexes at different confinements we determined that aS binding increases the persistence length of DNA from 70 to 90 nm at high coverage. By atomic force microscopy it was revealed that at low protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein. As DNA-aS interactions may play roles in PD, it is of importance to characterize biophysical properties of such complexes in detail

Extinction-free Census of AGNs in the AKARI/IRC North Ecliptic Pole Field from 23-band Infrared Photometry from Space Telescopes

In order to understand the interaction between the central black hole and the whole galaxy or their co-evolution history along with cosmic time, a complete census of active galactic nuclei (AGN) is crucial. However, AGNs are often missed in optical, UV and soft X-ray observations since they could be obscured by gas and dust. A mid-infrared (mid-IR) survey supported by multiwavelength data is one of the best ways to find obscured AGN activities because it suffers less from extinction. Previous large IR photometric surveys, e.g., WISE and Spitzer, have gaps between the mid-IR filters. Therefore, star forming galaxy (SFG)-AGN diagnostics in the mid-IR were limited. The AKARI satellite has a unique continuous 9-band filter coverage in the near to mid-IR wavelengths. In this work, we take advantage of the state-of-the-art spectral energy distribution (SED) modelling software, CIGALE, to find AGNs in mid-IR. We found 126 AGNs in the NEP-Wide field with this method. We also investigate the energy released from the AGN as a fraction of the total IR luminosity of a galaxy. We found that the AGN contribution is larger at higher redshifts for a given IR luminosity. With the upcoming deep IR surveys, e.g., JWST, we expect to find more AGNs with our method

An informatics consult approach for generating clinical evidence for treatment decisions.

BACKGROUND: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. METHODS: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. RESULTS: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results. CONCLUSION: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service

Purkinje cell input to cerebellar nuclei in tottering: Ultrastructure and physiology

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei