Smooth and sharp creation of a pointlike source for a (3+1)-dimensional quantum field

We analyze the smooth and sharp creation of a pointlike source for a quantized massless scalar field in (3+1)-dimensional Minkowski spacetime, as a model for the breakdown of correlations that has been proposed to occur at the horizon of an evaporating black hole. The creation is implemented by a time-dependent self-adjointness parameter at the excised spatial origin. In a smooth creation, the renormalized energy density is well defined away from the source, but it is unbounded both above and below: the outgoing pulse contains an infinite negative energy, while a cloud of infinite positive energy lingers near the fully-formed source. In the sharp creation limit, diverges everywhere in the timelike future of the creation event, and so does the response of an Unruh-DeWitt detector that operates in the timelike future of the creation event. The source creation is significantly more singular than the corresponding process in 1 + 1 dimensions, analyzed previously, and it may be sufficiently singular to break quantum correlations as proposed in a black hole spacetime

New Insights into Bacterial Chemoreceptor Array Structure and Assembly from Electron Cryotomography

Bacterial chemoreceptors cluster in highly ordered, cooperative, extended arrays with a conserved architecture, but the principles that govern array assembly remain unclear. Here we show images of cellular arrays as well as selected chemoreceptor complexes reconstituted in vitro that reveal new principles of array structure and assembly. First, in every case, receptors clustered in a trimers-of-dimers configuration, suggesting this is a highly favored fundamental building block. Second, these trimers-of-receptor dimers exhibited great versatility in the kinds of contacts they formed with each other and with other components of the signaling pathway, although only one architectural type occurred in native arrays. Third, the membrane, while it likely accelerates the formation of arrays, was neither necessary nor sufficient for lattice formation. Molecular crowding substituted for the stabilizing effect of the membrane and allowed cytoplasmic receptor fragments to form sandwiched lattices that strongly resemble the cytoplasmic chemoreceptor arrays found in some bacterial species. Finally, the effective determinant of array structure seemed to be CheA and CheW, which formed a “superlattice” of alternating CheA-filled and CheA-empty rings that linked receptor trimers-of-dimer units into their native hexagonal lattice. While concomitant overexpression of receptors, CheA, and CheW yielded arrays with native spacing, the CheA occupancy was lower and less ordered, suggesting that temporal and spatial coordination of gene expression driven by a single transcription factor may be vital for full order, or that array overgrowth may trigger a disassembly process. The results described here provide new insights into the assembly intermediates and assembly mechanism of this massive macromolecular complex

Patterns of periodic holes created by increased cell motility

The reaction and diffusion of morphogens is a mechanism widely used to explain many spatial patterns in physics, chemistry and developmental biology. However, because experimental control is limited in most biological systems, it is often unclear what mechanisms account for the biological patterns that arise. Here, we study a biological model of cultured vascular mesenchymal cells (VMCs), which normally self-organize into aggregates that form into labyrinthine configurations. We use an experimental control and a mathematical model that includes reacting and diffusing morphogens and a third variable reflecting local cell density. With direct measurements showing that cell motility was increased ninefold and threefold by inhibiting either Rho kinase or non-muscle myosin-II, respectively, our experimental results and mathematical modelling demonstrate that increased motility alters the multicellular pattern of the VMC cultures, from labyrinthine to a pattern of periodic holes. These results suggest implications for the tissue engineering of functional replacements for trabecular or spongy tissue such as endocardium and bone

Clinical and Experimental Applications of NIR-LED Photobiomodulation

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as “photobiomodulation,” uses light in the far-red to near-infrared region of the spectrum (630–1000 nm) and modulates numerous cellular functions. Positive effects of NIR–light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction

Dust and gas in the magellanic clouds from the heritage herschel key project. II. Gas-to-dust ratio variations across interstellar medium phases

The spatial variations of the gas-to-dust ratio (GDR) provide constraints on the chemical evolution and lifecycle of dust in galaxies. We examine the relation between dust and gas at 10-50 pc resolution in the Large and Small Magellanic Clouds (LMC and SMC) based on Herschel far-infrared (FIR), HI 21 cm, CO, and Hiα observations. In the diffuse atomic interstellar medium (ISM), we derive the GDR as the slope of the dust-gas relation and find GDRs of 380-130+250 ± 3 in the LMC, and 1200-420+1600 ± 120 in the SMC, not including helium. The atomic-to-molecular transition is located at dust surface densities of 0.05 M⊙ pc-2 in the LMC and 0.03 M⊙ pc-2 in the SMC, corresponding to AV ∼ 0.4 and 0.2, respectively. We investigate the range of CO-to-H2 conversion factor to best account for all the molecular gas in the beam of the observations, and find upper limits on XCO to be 6 × 1020 cm-2 K-1 km-1 s in the LMC (Z = 0.5 Z⊙) at 15 pc resolution, and 4 × 1021 cm-2 K-1 km-1 s in the SMC (Z = 0.2 Z⊙) at 45 pc resolution. In the LMC, the slope of the dust-gas relation in the dense ISM is lower than in the diffuse ISM by a factor ∼2, even after accounting for the effects of CO-dark H2 in the translucent envelopes of molecular clouds. Coagulation of dust grains and the subsequent dust emissivity increase in molecular clouds, and/or accretion of gas-phase metals onto dust grains, and the subsequent dust abundance (dust-to-gas ratio) increase in molecular clouds could explain the observations. In the SMC, variations in the dust-gas slope caused by coagulation or accretion are degenerate with the effects of CO-dark H2. Within the expected 5-20 times Galactic XCO range, the dust-gas slope can be either constant or decrease by a factor of several across ISM phases. Further modeling and observations are required to break the degeneracy between dust grain coagulation, accretion, and CO-dark H2. Our analysis demonstrates that obtaining robust ISM masses remains a non-trivial endeavor even in the local Universe using state-of-the-art maps of thermal dust emissio

Warm and Dense Molecular Gas in the N159 Region: 12CO J=4-3 and 13CO J=3-2 Observations with NANTEN2 and ASTE

New 12CO J=4-3 and 13CO J=3-2 observations of the N159 region in the Large Magellanic Cloud have been made. The 12CO J=4-3 distribution is separated into three clumps. These new measurements toward the three clumps are used in coupled calculations of molecular rotational excitation and line radiation transfer, along with other transitions of the 12CO as well as the isotope transitions of 13CO. The temperatures and densities are determined to be ~70-80K and ~3x10^3 cm-3 in N159W and N159E and ~30K and ~1.6x10^3 cm-3 in N159S. These results are compared with the star formation activity. The N159E clump is associated with embedded cluster(s) as observed at 24 micron and the derived high temperature is explained as due to the heating by these sources. The N159E clump is likely responsible for a dark lane in a large HII region by the dust extinction. The N159W clump is associated with embedded clusters mainly toward the eastern edge of the clump only. These clusters show offsets of 20"-40" from the 12CO J=4-3 peak and are probably responsible for heating indicated by the derived high temperature. The N159W clump exhibits no sign of star formation toward the 12CO J=4-3 peak position and its western region. We suggest that the N159W peak represents a pre-star-cluster core of ~105M_sol which deserves further detailed studies. Note that recent star formation took place between N159W and N159E as indicated by several star clusters and HII regions, while the natal molecular gas toward the stars have already been dissipated by the ionization and stellar winds of the OB stars. The N159S clump shows little sign of star formation as is consistent with the lower temperature and somewhat lower density. The N159S clump is also a candidate for future star formation

Impact of the COVID-19 pandemic on women’s contraceptive use: a mixed-methods study in South Africa and Zambia

Background: The COVID-19 pandemic affected global access to health services, including contraception. We sought to explore effects of the pandemic on family planning (FP) service provision and use in South Africa and Zambia, including on implant and intrauterine device (IUD) users' desire and ability to obtain removal. Methods: Between August 2020 and April 2021, we conducted surveys with 537 women participating in an ongoing longitudinal contraceptive continuation study. We also carried out in-depth interviews with 39 of the survey participants and 36 key informants involved in FP provision. We conducted descriptive analysis of survey responses and thematic analysis of interviews. Results: Contraceptive use changed minimally in this sample with the emergence of COVID-19. Fewer than half of women (n=220) reported attempting to access FP since the start of the pandemic, the vast majority of whom were using short-acting methods. Among those who sought services, 95% obtained their preferred method. The proportion of women not using a method before and after pandemic start did not change in Zambia (31%); in South Africa, the proportion increased from 8% to 10%. Less than 7% of implant or IUD users in either country reported wanting removal. Among those who sought removal (n=22), 91% (n=10) in Zambia and 55% (n=6) in South Africa successfully obtained removal. In qualitative interviews, women with challenges accessing FP services mentioned long queues, deprioritization of contraceptive services, lack of transportation, stock-outs, and fear of contracting COVID-19 at a facility. Key informants reported stock-outs, especially of injectables, and staff shortages as barriers. Conclusions: We did not find a substantial impact of COVID-19 on contraceptive access among this sample; however, providers and others involved in service provision identified risks to continuity of care. As the COVID-19 pandemic wanes, it continues to be important to monitor people's ability to access their preferred contraceptive methods

Intermediate Vancomycin Susceptibility in a Community-associated MRSA Clone

We describe a case of treatment failure caused by a strain of USA300 community-associated methicillin-resistant Staphylococcus aureus (MRSA) with intermediate susceptibility to vancomycin and reduced susceptibility to daptomycin. The strain was isolated from the bone of a 56-year-old man with lumbar osteomyelitis after a 6-week treatment course of vancomycin for catheter-associated septic thrombophlebitis

Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer

PurposeAmplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that BET bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven NSCLC with BET inhibition.Experimental DesignWe performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cells lines harboring KRAS and/or LKB1 mutations. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. Effects of bromodomain inhibition on transcriptional pathways were explored and validated by expression analysis.ResultsWhile JQ1 is broadly active in NSCLC cells, activity of JQ1 in mutant KRAS NSCLC is abrogated by concurrent alteration or genetic knock-down of LKB1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1.ConclusionBromodomain inhibition comprises a promising therapeutic strategy for KRAS mutant NSCLC with wild-type LKB1, via inhibition of MYC function. Clinical studies of BET bromodomain inhibitors in aggressive NSCLC will be actively pursued