Model-Independent Comparison of Direct vs. Indirect Detection of Supersymmetric Dark Matter

We compare the rate for elastic scattering of neutralinos from various nuclei with the flux of upward muons induced by energetic neutrinos from neutralino annihilation in the Sun and Earth. We consider both scalar and axial-vector interactions of neutralinos with nuclei. We find that the event rate in a kg of germanium is roughly equivalent to that in a $10^5$- to $10^7$-m$^2$ muon detector for a neutralino with primarily scalar coupling to nuclei. For an axially coupled neutralino, the event rate in a 50-gram hydrogen detector is roughly the same as that in a 10- to 500-m$^2$ muon detector. Expected experimental backgrounds favor forthcoming elastic-scattering detectors for scalar couplings while the neutrino detectors have the advantage for axial-vector couplings.Comment: 10 pages, self-unpacking uuencoded PostScript fil

Plasmas and Controlled Nuclear Fusion

Contains reports on five research projects.U. S. Atomic Energy Commission (Contract AT(30-1)-3980

Physics and Astrophysics of Strange Quark Matter

3-flavor quark matter (strange quark matter; SQM) can be stable or metastable for a wide range of strong interaction parameters. If so, SQM can play an important role in cosmology, neutron stars, cosmic ray physics, and relativistic heavy-ion collisions. As an example of the intimate connections between astrophysics and heavy-ion collision physics, this Chapter gives an overview of the physical properties of SQM in bulk and of small-baryon number strangelets; discusses the possible formation, destruction, and implications of lumps of SQM (quark nuggets) in the early Universe; and describes the structure and signature of strange stars, as well as formation and detection of strangelets in cosmic rays. It is concluded, that astrophysical and laboratory searches are complementary in many respects, and that both should be pursued to test the intriguing possibility of a strange ground state for hadronic matter, and (more generally) to improve our knowledge of the strong interactions.Comment: 45 pages incl. figures. To appear in "Hadrons in Dense Matter and Hadrosynthesis", Lecture Notes in Physics, Springer Verlag (ed. J.Cleymans

Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement

BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging. METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung. FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar. CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level

Structural Insight into the Rotational Switching Mechanism of the Bacterial Flagellar Motor

Structural analysis of a clockwise-biased rotation mutant of the bacterial flagellar rotor protein FliG provides a new model for the arrangement of FliG subunits in the motor, and novel insights into rotation switching

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial

Background Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer, Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. Methods The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1–5 for combination with GC at conventional doses (cisplatin 70 mg/m2, IV infusion, day 8; gemcitabine 1000 mg/m2, IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. Discussion SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC

Methicillin-Susceptible ST398 Staphylococcus aureus Responsible for Bloodstream Infections: An Emerging Human-Adapted Subclone?

In the course of an annual 3-month bloodstream infections (BSI) survey conducted during a four-year period in 31 healthcare institutions located in three noncontiguous French regions, we report 18 ST398 Staphylococcus aureus BSI. ST398 BSI incidence showed a seven-fold increase during the study period (0.002 per 1,000 patient days in 2007 vs. 0.014 in 2010). ST398 BSI isolates differed from the pig-borne multiresistant clone: 17/18 BSI isolates were methicillin susceptible and none was of t011, t034 or t108 pig-borne spa-types. ST398 BSI isolates had homogenous resistance patterns (15/18 with only Eryr) and prophagic content (all harboured the hlb-converting Sau3int phage). The clustering of BSI and pig-borne isolates by spa-typing and MLVA, the occurrence of Sau3int phage in BSI isolates and the lack of this phage in pig-borne isolates suggest that the emergence of BSI isolates could have arisen from horizontal transfer, at least of the Sau3int phage, in genetically diverse MSSA ST398 isolates. The acquisition of the phage likely plays a role in the increasing ability of the lysogenic ST398 isolates to colonize human. The mode of acquisition of the non pig-borne ST398 isolates by our 18 patients remains unclear. ST398 BSI were diagnosed in patients lacking livestock exposure and were significantly associated with digestive portals of entry (3/18 [16.7%] for ST398 vs. 19/767 [2.5%] for non ST398 BSI; p = .012). This raises the question of possible foodborne human infections. We suggest the need for active surveillance to study and control the spread of this human-adapted subclone increasingly isolated in the hospital setting

The increasing importance of satellite observations to assess the ocean carbon sink and ocean acidification

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordData availability Data will be made available on request.The strong control that the emissions of carbon dioxide (CO2) have over Earth's climate identifies the need for accurate quantification of the emitted CO2 and its redistribution within the Earth system. The ocean annually absorbs more than a quarter of all CO2 emissions and this absorption is fundamentally altering the ocean chemistry. The ocean thus provides a fundamental component and powerful constraint within global carbon assessments used to guide policy action for reducing emissions. These carbon assessments rely heavily on satellite observations, but their inclusion is often invisible or opaque to policy. One reason is that satellite observations are rarely used exclusively, but often in conjunction with other types of observations, thereby complementing and expanding their usability yet losing their visibility. This exploitation of satellite observations led by the satellite and ocean carbon scientific communities is based on exciting developments in satellite science that have broadened the suite of environmental data that can now reliably be observed from space. However, the full potential of satellite observations to expand the scientific knowledge on critical processes such as the atmosphere-ocean exchange of CO2 and ocean acidification, including its impact on ocean health, remains largely unexplored. There is clear potential to begin using these observation-based approaches for directly guiding ocean management and conservation decisions, in particular in regions where in situ data collection is more difficult, and interest in them is growing within the environmental policy communities. We review these developments, identify new opportunities and scientific priorities, and identify that the formation of an international advisory group could accelerate policy relevant advancements within both the ocean carbon and satellite communities. Some barriers to understanding exist but these should not stop the exploitation and the full visibility of satellite observations to policy makers and users, so these observations can fulfil their full potential and recognition for supporting society.European Space Agenc

The Evolution of Host Specialization in the Vertebrate Gut Symbiont Lactobacillus reuteri

Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In order to differentiate true host-specific genome content from strain-level differences, comparative genome hybridizations were performed to query 57 L. reuteri strains originating from six different vertebrate hosts in combination with genome sequence comparisons of nine strains encompassing five phylogenetic lineages of the species. This approach revealed that rodent strains, although showing a high degree of genomic plasticity, possessed a specific genome inventory that was rare or absent in strains from other vertebrate hosts. The distinct genome content of L. reuteri lineages reflected the niche characteristics in the gastrointestinal tracts of their respective hosts, and inactivation of seven out of eight representative rodent-specific genes in L. reuteri 100-23 resulted in impaired ecological performance in the gut of mice. The comparative genomic analyses suggested fundamentally different trends of genome evolution in rodent and human L. reuteri populations, with the former possessing a large and adaptable pan-genome while the latter being subjected to a process of reductive evolution. In conclusion, this study provided experimental evidence and a molecular basis for the evolution of host specificity in a vertebrate gut symbiont, and it identified genomic events that have shaped this process