We searched for long-duration microlensing events originating from intermediate-mass black holes (BH) in the halo of the Milky Way, using archival data from the EROS-2 and MACHO photometric surveys ...towards the Large Magellanic Cloud (LMC). We combined data from these two surveys to create a common database of light curves for 14.1 million objects in the LMC, covering a total duration of 10.6 years, with flux series measured in four wide passbands. We carried out a microlensing search on these light curves, complemented by the light curves of 22.7 million objects, observed only by EROS-2 or only by MACHO, over about 7 years, with flux series measured in only two passbands. A likelihood analysis, taking into account the LMC self-lensing and Milky Way disk contributions, allows us to conclude that compact objects with masses in the range 10 − 100
M
⊙
cannot make up more than ∼15% of a standard halo total mass (at a 95% confidence level). Our analysis sensitivity weakens for heavier objects, although we still rule out the possibility of ∼50% of the halo being made of ∼1000
M
⊙
BHs. Combined with previous EROS results, an upper limit of ∼15% of the total halo mass can be obtained for the contribution of compact halo objects in the mass range 10
−6
− 10
2
M
⊙
.
Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to ...fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of "emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage.
Aims. The EROS-2 project was designed to test the hypothesis that massive compact halo objects (the so-called "machos") could be a major component of the dark matter halo of the Milky Way galaxy. To ...this end, EROS- 2 monitored over 6.7 years 33\times10 similar to stars in the Magellanic clouds for microlensing events caused by such objects. Methods. In this work, we use only a subsample of 7\times10 similar to bright stars spread over 84\,\rm deg arrow up of the LMC and 9\,\rm deg arrow up of the SMC. The strategy of using only bright stars helps to discriminate against background events due to variable stars and allows a simple determination of the effects of source confusion (blending). The use of a large solid angle makes the survey relatively insensitive to effects that could make the optical depth strongly direction dependent. Results. Using this sample of bright stars, only one candidate event was found, whereas similar to 39 events would have been expected if the Halo were entirely populated by objects of mass M\sim0.4 similar to M_{\odot}. Combined with the results of EROS-1, this implies that the optical depth toward the Large Magellanic Cloud ( LMC) due to such lenses is \tau<0.36\times10 (95% CL), corresponding to a fraction of the halo mass of less than 8%. This optical depth is considerably less than that measured by the MACHO collaboration in the central region of the LMC. More generally, machos in the mass range 0.6\times10 contains as a subset _\odot<M<15 similar to M_{\odot} are ruled out as the primary occupants of the Milky Way Halo.
Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move ...bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD-mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity.
ABSTRACT
The International Pulsar Timing Array 2nd data release is the combination of data sets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave ...signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95 per cent upper limits on their amplitude h95. The most sensitive frequency is 10 nHz with h95 = 9.1 × 10−15. We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit.
Physicochemical processes, such as the Lo-cat and Amine-Claus process, are commonly used to remove hydrogen sulfide from hydrocarbon gas streams such as landfill gas, natural gas, and synthesis gas. ...Biodesulfurization offers environmental advantages, but still requires optimization and more insight in the reaction pathways and kinetics. We carried out experiments with gas lift bioreactors inoculated with haloalkaliphilic sulfide-oxidizing bacteria. At oxygen-limiting levels, that is, below an O2/H2S mole ratio of 1, sulfide was oxidized to elemental sulfur and sulfate. We propose that the bacteria reduce NAD+ without direct transfer of electrons to oxygen and that this is most likely the main route for oxidizing sulfide to elemental sulfur which is subsequently oxidized to sulfate in oxygen-limited bioreactors. We call this pathway the limited oxygen route (LOR). Biomass growth under these conditions is significantly lower than at higher oxygen levels. These findings emphasize the importance of accurate process control. This work also identifies a need for studies exploring similar pathways in other sulfide oxidizers such as Thiobacillus bacteria.
Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed ...this molecular strategy to render cytotoxic T cells specific for fungi. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (designated “D-CAR”) upon binding with carbohydrate in the cell wall of Aspergillus germlings. T cells genetically modified with the Sleeping Beauty system to express D-CAR stably were propagated selectively on artificial activating and propagating cells using an approach similar to that approved by the Food and Drug Administration for manufacturing CD19-specific CAR ⁺ T cells for clinical trials. The D-CAR ⁺ T cells exhibited specificity for β-glucan which led to damage and inhibition of hyphal growth of Aspergillus in vitro and in vivo. Treatment of D-CAR ⁺ T cells with steroids did not compromise antifungal activity significantly. These data support the targeting of carbohydrate antigens by CAR ⁺ T cells and provide a clinically appealing strategy to enhance immunity for opportunistic fungal infections using T-cell gene therapy.
Abstract
Background
Surgeons urgently need guidance on how to deliver surgical services safely and effectively during the COVID-19 pandemic. The aim was to identify the key domains that should be ...considered when developing pandemic preparedness plans for surgical services.
Methods
A scoping search was conducted to identify published articles relating to management of surgical patients during pandemics. Key informant interviews were conducted with surgeons and anaesthetists with direct experience of working during infectious disease outbreaks, in order to identify key challenges and solutions to delivering effective surgical services during the COVID-19 pandemic.
Results
Thirteen articles were identified from the scoping search, and surgeons and anaesthetists representing 11 territories were interviewed. To mount an effective response to COVID-19, a pandemic response plan for surgical services should be developed in advance. Key domains that should be included are: provision of staff training (such as patient transfers, donning and doffing personal protection equipment, recognizing and managing COVID-19 infection); support for the overall hospital response to COVID-19 (reduction in non-urgent activities such as clinics, endoscopy, non-urgent elective surgery); establishment of a team-based approach for running emergency services; and recognition and management of COVID-19 infection in patients treated as an emergency and those who have had surgery. A backlog of procedures after the end of the COVID-19 pandemic is inevitable, and hospitals should plan how to address this effectively to ensure that patients having elective treatment have the best possible outcomes.
Conclusion
Hospitals should prepare detailed context-specific pandemic preparedness plans addressing the identified domains. Specific guidance should be updated continuously to reflect emerging evidence during the COVID-19 pandemic.
Graphical Abstract
During pandemics, surgical services need to balance supporting the whole hospital response and minimizing the risk of nosocomial spread of COVID-19 against continuing care for acute surgical conditions and managing urgent elective surgery. This article identifies the key considerations that should be included in pandemic plans for surgical services.
Graphical Abstract
Best available advice
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•Absorption of H2S from sour gas in the biodesulfurization process appears not to be purely physico-chemical.•Sulfide oxidizing bacteria are also active in the anaerobic absorber of ...the biodesulfurization process.•Sulfide oxidizing bacteria enhance the absorption of H2S from sour gas.•H2S absorption in the biodesulfurization process is dependent on temperature and biomass concentration.
We studied a biotechnological desulfurization process for removal of toxic hydrogen sulfide (H2S) from sour gas. The process consists of two steps: i) Selective absorption of H2S into a (bi)carbonate solution in the absorber column and ii) conversion of sulfide to sulfur by sulfide oxidizing bacteria (SOB) in the aerated bioreactor. In previous studies, several physico-chemical factors were assessed to explain the observed enhancement of H2S absorption in the absorber, but a full explanation was not provided. We investigated the relation between the metabolic activity of SOB and the enhancement factor. Two continuous experiments on pilot-scale were performed to determine H2S absorption efficiencies at different temperatures and biomass concentrations. The absorption efficiency improved at increasing temperatures, i.e. H2S concentration in the treated gas decreased from 715 ± 265 ppmv at 25.4 °C to 69 ± 25 ppmv at 39.4 °C. The opposite trend is expected when H2S absorption is solely determined by physico-chemical factors. Furthermore, increasing biomass concentrations to the absorber also resulted in decreased H2S concentrations in the treated gas, from approximately 6000 ppmv without biomass to 1664 ± 126 ppmv at 44 mg N/L. From our studies it can be concluded that SOB activity enhances H2S absorption and leads to increased H2S removal efficiencies in biotechnological gas desulfurization.
Elucidating the microstructure of supramolecular copolymers remains challenging, despite the progress in the field of supramolecular polymers. In this work, we present a detailed approach to ...investigate supramolecular copolymerizations under thermodynamic control. Our approach provides insight into the interactions of different types of monomers and hereby allows elucidating the microstructure of copolymers. We select two monomers that undergo cooperative supramolecular polymerization by way of threefold intermolecular hydrogen bonding in a helical manner, namely, benzene-1,3,5-tricarboxamide (BTA) and benzene-1,3,5-tris(carbothioamide) (thioBTA). Two enantiomeric forms and an achiral analogue of BTA and thioBTA are synthesized and their homo- and copolymerizations are studied using light scattering techniques, infrared, ultraviolet, and circular dichroism spectroscopy. After quantifying the thermodynamic parameters describing the homopolymerizations, we outline a method to follow the self-assembly of thioBTA derivatives in the copolymerization with BTA, which involves monitoring a characteristic spectroscopic signature as a function of temperature and relative concentration. Using modified types of sergeants-and-soldiers and majority-rules experiments, we obtain insights into the degree of aggregation and the net helicity. In addition, we apply a theoretical model of supramolecular copolymerization to substantiate the experimental results. We find that the model describes the two-component system well and allows deriving the hetero-interaction energies. The interactions between the same kinds of monomers (BTA–BTA and thioBTA–thioBTA) are slightly more favorable than those between different monomers (BTA–thioBTA), corresponding to a nearly random copolymerization. Finally, to study the interactions of the monomers at the molecular level, we perform density functional theory-based computations. The results corroborate that the two-component system exhibits a random distribution of the two monomer units along the copolymer chain.
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