Creating a self-induced dark spontaneous-force optical trap for neutral atoms

This communication describes the observation of a new type of dark spontaneous-force optical trap (dark SPOT) obtained without the use of a mask blocking the central part of the repumper laser beam. We observe that loading a magneto-optical trap (MOT) from a continuous and intense flux of slowed atoms and by appropriately tuning the frequency of the repumper laser is possible to achieve basically the same effect of the dark SPOT, using a simpler apparatus. This work characterizes the new system through measurements of absorption and fluorescence imaging of the atomic cloud and presents a very simple model to explain the main features of our observations. We believe that this new approach may simplify the current experiments to produce quantum degenerated gases.Comment: 13 pages, 8 figures, Submitted to Optics Communications (30/10/2003), accepted for publication (Feb/2004

Reduced contextually induced muscle thermogenesis in rats with calorie restriction and lower aerobic fitness but not monogenic obesity

We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and weight loss, the current study investigated whether skeletal muscle thermogenesis was altered with negative energy balance, obesity propensity seen in association with low intrinsic aerobic fitness, and monogenic obesity. First, weight loss subsequent to three weeks of 50% calorie restriction suppressed the muscle thermogenic response to predator odor. Next, we compared rats bred based on artificial selection for intrinsic aerobic fitness—high- and low-capacity runners (HCR, LCR)—that display robust leanness and obesity propensity, respectively. Aerobically fit HCR showed enhanced predator odor-induced muscle thermogenesis relative to the less-fit LCR. This contrasted with the profound monogenic obesity displayed by rats homozygous for a loss of function mutation in Melanocortin 4 receptor (Mc4rK314X/K314X rats), which showed no discernable deficit in thermogenesis. Taken together, these data imply that body size or obesity per se are not associated with deficient muscle thermogenesis. Rather, the physiological phenotype associated with polygenic obesity propensity may encompass pleiotropic mechanisms in the thermogenic pathway. Adaptive thermogenesis associated with weight loss also likely alters muscle thermogenic mechanisms.</p

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

The role of emotion, values, and beliefs in the construction of innovative work realities

Traditional approaches to requirements elicitation stress systematic and rational analysis and representation of organizational context and system requirements. This paper argues that (1) for an organization, a software system implements a shared vision of a future work reality and that (2) understanding the emotions, feelings, values, beliefs, and interests that drive organizational human action is needed in order to invent the requirements of such a software system. This paper debunks some myths about how organizations transform themselves through the adoption of Information and Communication Technology; describes the concepts of emotion, feeling, value, and belief; and presents some constructionist guidelines for the process of eliciting requirements for a software system that helps an organization to fundamentally change its work patterns.(undefined

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients

Introduction: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care. Methods: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18– 85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥ 4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration. Results: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥ 40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05– 2.17]), female sex (adjOR=1.37 [1.02– 1.85]), frailty (adjOR=2.39 [1.29– 4.27]), visit to A&E (adjOR=4.28 [2.31– 7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77– 5.79]). Aches and pain (adjOR=1.70 [1.21– 2.39]), appetite loss (adjOR=3.15 [1.78– 5.92]), confusion and disorientation (adjOR=2.17 [1.57– 2.99]), diarrhea (adjOR=1.4 [1.03– 1.89]), and persistent dry cough (adjOR=2.77 [1.94– 3.98]) were symptom features statistically more common in long COVID. Conclusion: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients

What Drives Fitness Apps Usage? An Empirical Evaluation

Part 3: Creating Value through ApplicationsInternational audienceThe increased health problems associated with lack of physical activity is of great concern around the world. Mobile phone based fitness applications appear to be a cost effective promising solution for this problem. The aim of this study is to develop a research model that can broaden understanding of the factors that influence the user acceptance of mobile fitness apps. Drawing from Unified Theory of Acceptance and Use of Technology (UTAUT) and Elaboration Likelihood Model (ELM), we conceptualize the antecedents and moderating factors of fitness app use. We validate our model using field survey. Implications for research and practice are discussed

The LHCb VELO Upgrade module construction

The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 μm thick, n-on-p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire-bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 μm, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm2W-1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022