The protonation of methylamine base CH3NH2 by carbonic acid H2CO3 within a hydrogen (H)-bonded complex in aqueous solution was studied via Car–Parrinello dynamics in the preceding paper ...(Daschakraborty, S.; Kiefer, P. M.; Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. J. Phys. Chem. B 2016, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented, with specific emphasis on the water solvent’s role. The overall reaction is barrierless and very rapid, on an ∼100 fs time scale, with the proton transfer (PT) event itself being very sudden (<10 fs). This transfer is preceded by the acid–base H-bond’s compression, while the water solvent changes little until the actual PT occurrence; this results from the very strong driving force for the reaction, as indicated by the very favorable acid-protonated base ΔpK a difference. Further solvent rearrangement follows immediately the sudden PT’s production of an incipient contact ion pair, stabilizing it by establishment of equilibrium solvation. The solvent water’s short time scale ∼120 fs response to the incipient ion pair formation is primarily associated with librational modes and H-bond compression of water molecules around the carboxylate anion and the protonated base. This is consistent with this stabilization involving significant increase in H-bonding of hydration shell waters to the negatively charged carboxylate group oxygens’ (especially the former H2CO3 donor oxygen) and the nitrogen of the positively charged protonated base’s NH3 +.
Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was ...not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.
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► Increased FOXM1 leads to an expansion of mammary stem and progenitor pools ► Deletion of FoxM1 in virgin mice causes accumulation of the differentiated luminal cells ► FOXM1 acts as a transcriptional repressor of GATA-3 by promoting DNA methylation ► FOXM1 represses GATA-3 in an Rb-dependent manner
Poorly differentiated breast cancers carry a negative patient prognosis due to high rates of metastasis, relapse, and resistance to therapy. Expression of GATA-3, a regulator of mammary luminal differentiation, is extinguished in high-grade tumors. A strong reciprocal relationship exists between expression of the oncogenic transcription factor FoxM1 and the tumor suppressor GATA-3 in breast cancers. Raychaudhuri and colleagues identify FoxM1 as a regulator of mammary differentiation with significant implications for the development and progression of high-grade breast cancer.
CRESST is a direct dark matter search experiment, aiming for an observation of nuclear recoils induced by the interaction of dark matter particles with cryogenic scintillating calcium tungstate ...crystals. Instead of confining ourselves to standard spin-independent and spin-dependent searches, we re-analyze data from CRESST-II using a more general effective field theory (EFT) framework. On many of the EFT coupling constants, improved exclusion limits in the low-mass region (< 3–4 GeV/
c
2
) are presented.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in the reduced spectral resolution nominal observation mode. The data cover the period from ...January 2005 to April 2012 and the altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of modelled spectra to the measured limb spectral radiances. The spectral ν4-band at 816.5 ± 13 cm−1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The rate of linear growth in the lower latitudes lower stratosphere was about 6 to 7 pptv year−1 in the period 2005–2012. The profiles obtained were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and cryosampler balloon measurements. Between 13 and 22 km, average agreement within −3 to +5 pptv (MIPAS – ACE) with ACE-FTS v3.5 profiles is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15–50 pptv below 24 km and less than 10 pptv above 28 km. MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from the NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data. This is attributed to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10°-latitude/1-to-2-km-altitude bins. The relative linear variation was always positive, with relative increases of 40–70 % decade−1 in the tropics and global lower stratosphere, and up to 120 % decade−1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. Asian HCFC-22 emissions have become the major source of global upper tropospheric HCFC-22. In the upper troposphere, monsoon air, rich in HCFC-22, is instantaneously mixed into the tropics. In the middle stratosphere, between 20 and 30 km, the observed trend is inconsistent with the trend at the surface (corrected for the age of stratospheric air), hinting at circulation changes. There exists a stronger positive trend in HCFC-22 in the Southern Hemisphere and a more muted positive trend in the Northern Hemisphere, implying a potential change in the stratospheric circulation over the observation period.
The dynamic packaging of DNA into chromatin is a fundamental step in the control of diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote the formation ...of higher-order chromatin loops, the co-regulator machinery mediating loop assembly and disassembly is unknown. Using mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate that the Brg1 mutation abrogated a cell type-specific loop between the β-globin locus control region and the downstream βmajor promoter, despite trans-acting factor occupancy at both sites. By contrast, distinct loops were insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided additional evidence that BRG1 functions early in chromatin domain activation to mediate looping. Although the paradigm in which chromatin remodelers induce nucleosome structural transitions is well established, our results demonstrating an essential role of BRG1 in the genesis of specific chromatin loops expands the repertoire of their functions.
A theoretical study of primary kinetic isotope effects (KIEs) is presented for proton transfer (PT) reactions in a polar environment in the nonadiabatic, i.e., tunneling, regime. This treatment ...differs from traditional descriptions for PT most notably in the identification of a solvent coordinate as the reaction coordinate. The theory explicitly addresses KIE features that are extremely sensitive to the proton donor−proton acceptor mode dynamics. Besides KIE behaviors that are not consistent with nontunneling PT, individual KIE aspects in some cases, such as magnitude, temperature dependence, variation with reaction asymmetry, and Swain−Schaad behavior can yield results consistent with nontunneling PT. However, a combination of KIE aspectswith particular emphasis on KIE variation with reaction asymmetry or temperaturecan clearly identify tunneling in PT systems. In addition, PT via excited proton vibrational states is shown to significantly contribute to the reaction rate and KIEs, especially for extremely asymmetric reactions, where it can dominate.
In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven ...categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering).
Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.
The CRESST experiment (Cryogenic Rare Even Search with Superconducting Thermometers), located at Laboratori Nazionali del Gran Sasso in Italy, searches for dark matter particles via their elastic ...scattering off nuclei in a target material. The CRESST target consists of scintillating CaWO4 crystals, which are operated as cryogenic calorimeters at millikelvin temperatures. Each interaction in the CaWO4 target crystal produces a phonon signal and a light signal that is measured by a second cryogenic calorimeter. Since the CRESST-II result in 2015, the experiment is leading the field of direct dark matter search for dark matter masses below 1.7 GeV/c2, extending the reach of direct searches to the sub-GeV/c2 mass region. For CRESST-III, whose Phase 1 started in July 2016, detectors have been optimized to reach the performance required to further probe the low-mass region with unprecedented sensitivity. In this contribution the achievements of the CRESST-III detectors will be discussed together with preliminary results and perspectives of Phase 1.
The Advanced Regional Prediction System is utilized to examine the evolution of the nocturnal boundary layer observed within Arizona's Meteor Crater, a small enclosed basin, on quiescent nights ...during the 2006 Meteor Crater Experiment field campaign. Two aspects of the observed basin atmosphere are investigated: a quasi steady‐state three‐layer temperature structure, including an isothermal layer away from the basin floor, and the intrusion of a regional‐scale cold air drainage flow into the basin. In general, the two‐dimensional numerical simulations are able to reproduce the salient features of the nocturnal boundary layer inside Meteor Crater. A combination of increasingly cold air intruding into the basin and pooling near the basin floor and compensating adiabatic ascent yield an isothermal layer over a large depth of the basin atmosphere. A series of experiments are then conducted in order to examine the sensitivity of basin thermal structure to upstream terrain slope, basin width, and the presence of a rim surrounding the basin. In the case of a large basin of O(10 km) in diameter, the cold air intrusion process remains, but the larger basin volume yields greater dilution of the cold air intruding into the basin, and a weak inversion develops inside the basin away from the floor. In the case of a small basin with the same dimensions as Meteor Crater but with flat upstream terrain, the influence of the surrounding terrain on basin cooling is negligible. Last, the presence of a rim surrounding the basin is found to not be necessary for isothermal layer development.
Key Points
Isothermal layer requires balance of cold air intrusion and adiabatic cooling
A basin rim is not required for isothermal layer development
As basin width increases, cooling processes better resemble flat terrain process
Parad items used in Hindu practices and Ayurvedic medicines contain elemental mercury (Hg0) and have traditionally been used in prayer and to treat a variety of diseases including diabetes, heart ...conditions, and sexual dysfunction. These items are often referred to as amalgams of silver, and take the form of shivlings, statues of gods, necklaces, and other jewelry. Fourteen parad items were purchased from online vendors in India and the United States and analyzed. All items produced copious amounts of Hg0 vapor, with Hg0 concentrations exceeding 1,000,000 ng/m3 as measured using a Mercury Instruments Mercury Tracker 3000 IP atomic absorption spectrometer. Measured concentrations were highly variable, so a simple qualitative experiment employing a UV-C light source and a thin-layer chromatography plate impregnated with a fluorescent dye that glows green when irradiated at 254 nm allowed for the indirect visualization of the Hg0 being evolved. In addition, all items were screened using a hand-held X-ray fluorescence analyzer to estimate the concentration of Hg, Sn, Pb, As, and Cd on the surface of the item. Select samples were then digested in aqua regia and analyzed for Hg content using a direct mercury analyzer. All samples were found to exceed 20% by mass Hg. The digestates were analyzed using inductively-coupled plasma-optical emission spectrometry and were determined to be between 10-55% by mass Pb and contain up to 0.3% by mass As. While Article 4 of the Minamata Convention on Mercury specifically requires parties to stop importing, exporting, and manufacturing Hg-added products, products used in traditional and religious practices are excluded.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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