Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes

The bacterial pathogen Helicobacter pylori commonly colonizes the human gastric mucosa during early childhood and persists throughout life. The organism has evolved multiple mechanisms for evading clearance by the immune system and, despite inducing inflammation in the stomach, the majority of infections are asymptomatic. H. pylori is the leading cause of peptic ulcer disease and gastric cancer. However, disease outcomes are related to the pattern and severity of chronic inflammation in the gastric mucosa, which in turn is influenced by both bacterial and host factors. Despite over 2 decades of intensive research, there remains an incomplete understanding of the circumstances leading to disease development, due to the fascinating complexity of the host-pathogen interactions. There is accumulating data concerning the virulence factors associated with increased risk of disease, and the majority of these have pro-inflammatory activities. Despite this, only a small proportion of those infected with virulent strains develop disease. Several H. pylori virulence factors have multiple effects on different cell types, including the induction of pro- and anti-inflammatory, immune stimulatory, and immune modulatory responses. The expression of multiple virulence factors is also often linked, making it difficult to assess the meaning of their effects in isolation. Overall, H. pylori is thought to usually modulate inflammation and limit acute damage to the mucosa, enabling the bacteria to persist. If this delicate balance is disturbed, disease may then develop

Reconstruction of the Shapes of Gold Nanocrystals using Coherent X-ray Diffraction

Inverse problems arise frequently in physics: The magnitude of the Fourier transform of some function is measurable, but not its phase. The “phase problem” in crystallography arises because the number of discrete measurements (Bragg peak intensities) is only half the number of unknowns (electron density points in space). Sayre first proposed that oversampling of diffraction data should allow a solution, and this has recently been demonstrated. Here we report the successful phasing of an oversampled hard x-ray diffraction pattern measured from a single nanocrystal of gold

Information Security as Strategic (In)effectivity

Security of information flow is commonly understood as preventing any information leakage, regardless of how grave or harmless consequences the leakage can have. In this work, we suggest that information security is not a goal in itself, but rather a means of preventing potential attackers from compromising the correct behavior of the system. To formalize this, we first show how two information flows can be compared by looking at the adversary's ability to harm the system. Then, we propose that the information flow in a system is effectively information-secure if it does not allow for more harm than its idealized variant based on the classical notion of noninterference

Estimates of tropical bromoform emissions using an inversion method

Abstract. Bromine plays an important role in ozone chemistry in both the troposphere and stratosphere. When measured by mass, bromoform (CHBr3) is thought to be the largest organic source of bromine to the atmosphere. While seaweed and phytoplankton are known to be dominant sources, the size and the geographical distribution of CHBr3 emissions remains uncertain. Particularly little is known about emissions from the Maritime Continent, which have usually been assumed to be large, and which appear to be especially likely to reach the stratosphere. In this study we aim to reduce this uncertainty by combining the first multi-annual set of CHBr3 measurements from this region, and an inversion process, to investigate systematically the distribution and magnitude of CHBr3 emissions. The novelty of our approach lies in the application of the inversion method to CHBr3. We find that local measurements of a short-lived gas like CHBr3 can be used to constrain emissions from only a relatively small, sub-regional domain. We then obtain detailed estimates of CHBr3 emissions within this area, which appear to be relatively insensitive to the assumptions inherent in the inversion process. We extrapolate this information to produce estimated emissions for the entire tropics (defined as 20° S–20° N) of 225 Gg CHBr3 yr−1. The ocean in the area we base our extrapolations upon is typically somewhat shallower, and more biologically productive, than the tropical average. Despite this, our tropical estimate is lower than most other recent studies, and suggests that CHBr3 emissions in the coastline-rich Maritime Continent may not be stronger than emissions in other parts of the tropics. M. Ashfold thanks the Natural Environment Research Council (NERC) for a research studentship, and is grateful for support through the ERC ACCI project (project number 267760). N. Harris is supported by a NERC Advanced Research Fellowship. This work was supported through the EU SHIVA project, through the NERC OP3 project, and NERC grants NE/F020341/1 and NE/J006246/1. We also acknowledge the Department of Energy and Climate Change for their support in the development of InTEM (contract GA0201). For field site support we thank S.-M. Phang, A. A. Samah and M. S. M. Nadzir of Universiti Malaya, S. Ong and H. E. Ung of Global Satria, Maznorizan Mohamad, L. K. Peng and S. E. Yong of the Malaysian Meteorological Department, the Sabah Foundation, the Danum Valley Field Centre and the Royal Society. This paper constitutes publication no. 613 of the Royal Society South East Asia Rainforest Research Programme.This is the final published version. It first appeared at http://www.atmos-chem-phys.net/14/979/2014/acp-14-979-2014.html

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period

Background Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. Methods/design A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n = 116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n = 50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. Discussion The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Trial registration: Clinical Trials: NCT02591134; registered: 23.10.201

IPD—the Immuno Polymorphism Database

The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project

Exponentially Increasing Incidences of Cutaneous Malignant Melanoma in Europe Correlate with Low Personal Annual UV Doses and Suggests 2 Major Risk Factors

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

On the Hardness of SAT with Community Structure

Recent attempts to explain the effectiveness of Boolean satisfiability (SAT) solvers based on conflict-driven clause learning (CDCL) on large industrial benchmarks have focused on the concept of community structure. Specifically, industrial benchmarks have been empirically found to have good community structure, and experiments seem to show a correlation between such structure and the efficiency of CDCL. However, in this paper we establish hardness results suggesting that community structure is not sufficient to explain the success of CDCL in practice. First, we formally characterize a property shared by a wide class of metrics capturing community structure, including "modularity". Next, we show that the SAT instances with good community structure according to any metric with this property are still NP-hard. Finally, we study a class of random instances generated from the "pseudo-industrial" community attachment model of Gir\'aldez-Cru and Levy. We prove that, with high probability, instances from this model that have relatively few communities but are still highly modular require exponentially long resolution proofs and so are hard for CDCL. We also present experimental evidence that our result continues to hold for instances with many more communities. This indicates that actual industrial instances easily solved by CDCL may have some other relevant structure not captured by the community attachment model.Comment: 23 pages. Full version of a SAT 2016 pape

Synthesis of Subject-Specific Human Balance Responses using a Task-Level Neuromuscular Control Platform

Many activities of daily living require a high level of neuromuscular coordination and balance control to avoid falls. Complex musculoskeletal models paired with detailed neuromuscular simulations complement experimental studies and uncover principles of coordinated and uncoordinated movements. Here, we created a closed-loop forward dynamic simulation framework that utilizes a detailed musculoskeletal model (19 degrees of freedom, and 92 Muscles) to synthesize human balance responses after support-surface perturbation. In addition, surrogate response models of task-level experimental kinematics from two healthy subjects were provided as inputs to our closedloop simulations to inform the design of the task-level controller. The predicted muscle EMGs and the resulting synthesized subject joint angles showed good conformity with the average of experimental trials. The simulated whole-body center of mass displacements, generated from a single kinematics trial per perturbation direction, were on average, within 7 mm (anterior perturbations) and 13 mm (posterior perturbations) of experimental displacements. Our results confirmed how a complex subject-specific movement can be reconstructed by sequencing and prioritizing multiple task-level commands to achieve desired movements. By combining the multidisciplinary approaches of robotics and biomechanics, the platform demonstrated here offers great potential for studying human movement control and subject-specific outcome prediction