Formate has great potential to function as a feedstock for biorefineries because it can be sustainably produced by a variety of processes that don't compete with agricultural production. However, ...naturally formatotrophic organisms are unsuitable for large-scale cultivation, difficult to engineer, or have inefficient native formate assimilation pathways. Thus, metabolic engineering needs to be developed for model industrial organisms to enable efficient formatotrophic growth. Here, we build a prototype synthetic formate utilizing bacterial microcompartment (sFUT) encapsulating the oxygen-sensitive glycyl radical enzyme pyruvate formate lyase and a phosphate acyltransferase to convert formate and acetyl-phosphate into the central biosynthetic intermediate pyruvate. This metabolic module offers a defined environment with a private cofactor coenzyme A that can cycle efficiently between the encapsulated enzymes. To facilitate initial design-build-test-refine cycles to construct an active metabolic core, we used a "wiffleball" architecture, defined as an icosahedral bacterial microcompartment (BMC) shell with unoccupied pentameric vertices to freely permit substrate and product exchange. The resulting sFUT prototype wiffleball is an active multi enzyme synthetic BMC functioning as platform technology.
Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent ...contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer.
Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas.
The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases.
This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.
Purpose
To determine the temporal evolution, clinical correlates, and prognostic significance of electroencephalographic (EEG) patterns in post-cardiac arrest comatose patients treated with ...hypothermia.
Methods
Prospective cohort study of consecutive post-anoxic patients receiving hypothermia and continuous EEG monitoring between May 2011 and June 2014 (
n
= 100). In addition to clinical variables, 5-min EEG clips at 6, 12, 24, 48, and 72 h after return of spontaneous circulation (ROSC) were reviewed. EEG background was classified according to the American Clinical Neurophysiological Society critical care EEG terminology. Clinical outcome at discharge was dichotomized as good Glasgow outcome scale (GOS) 4–5, low to moderate disability vs. poor (GOS 1–3, severe disability to death).
Results
Non-ventricular fibrillation/tachycardia arrest, longer time to ROSC, absence of brainstem reflexes, extensor or no motor response, lower pH, higher lactate, hypotension requiring >2 vasopressors, and absence of reactivity on EEG were all associated with poor outcome (all
p
values ≤0.01). Suppression-burst at any time indicated a poor prognosis, with a 0 % false positive rate (FPR) 95 % confidence interval (CI) 0–10 %. All patients (54/54) with suppression-burst or a low voltage (<20 µV) EEG at 24 h had a poor outcome, with an FPR of 0 % 95 % CI 0–8 %. Normal background voltage ≥20 µV without epileptiform discharges at any time interval carried a positive predictive value >70 % for good outcome.
Conclusions
Suppression-burst or a low voltage at 24 h after ROSC was not compatible with good outcome in this series. Normal background voltage without epileptiform discharges predicted a good outcome.
•Undocumented Latinos experience everyday discrimination that place them at higher risk for developing depressive symptoms.•Everyday discrimination against undocumented Latino immigrants likely ...increased during the 2015 Trump presidential campaign.•Everyday discrimination in the present study was associated with greater likelihood of being classified as higher risk for clinical depression.
Undocumented Latino immigrants in the United States face pervasive discrimination that increases their risk for experiencing depressive symptomatology. Although research has linked discrimination to depressive symptoms more broadly, we do not know whether everyday forms of discrimination are associated with elevated risk for clinical depression among this population. Using data collected from a community sample of undocumented Latino immigrants during the 2015 Trump campaign, we found that everyday discrimination was associated with significantly higher odds of being classified as higher risk for clinical depression. Findings indicate everyday discrimination as a risk factor for clinical depression among undocumented Latino immigrants.
IMPLICIT BIAS IN THE AGE OF TRUMP Lawrence, Charles R.
Harvard Law Review,
05/2020, Letnik:
133, Številka:
7
Book Review, Journal Article
Recenzirano
Book Review: 'Biased: Uncovering the hidden prejudice that shapes what we see, think, and do', By Jennifer L. Eberhardt. New York, N.Y.: Viking. 2019. Pp. 340. $28.00.
•A fully coupled THM model for simulating flow channeling in EGS heat production.•Aperture heterogeneity causes channelized flow and exacerbates flow channeling.•Longer aperture correlation length ...leads to worse and more variable performance.•Aperture standard deviation affects heat production when correlation length is long.
The evolution of flow pattern along a single fracture and its effects on heat production is a fundamental problem in the assessments of engineered geothermal systems (EGS). The channelized flow pattern associated with ubiquitous heterogeneity in fracture aperture distribution causes non-uniform temperature decrease in the rock body, which makes the flow increasingly concentrated into some preferential paths through the action of thermal stress. This mechanism may cause rapid heat production deterioration of EGS reservoirs. In this study, we investigated the effects of aperture heterogeneity on flow pattern evolution in a single fracture in a low-permeability crystalline formation. We developed a numerical model on the platform of GEOS to simulate the coupled thermo-hydro-mechanical processes in a penny-shaped fracture accessed via an injection well and a production well. We find that aperture heterogeneity generally exacerbates flow channeling and reservoir performance generally decreases with longer correlation length of aperture field. The expected production life is highly variable (5 years to beyond 30 years) when the aperture correlation length is longer than 1/5 of the well distance, whereas a heterogeneous fracture behaves similar to a homogeneous one when the correlation length is much shorter than the well distance. Besides, the mean production life decreases with greater aperture standard deviation only when the correlation length is relatively long. Although flow channeling is inevitable, initial aperture fields and well locations that enable tortuous preferential paths tend to deliver long heat production lives.
HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid ...kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.
Abstract
Radioactive gas signatures from underground nuclear explosions (UNEs) result from gas-migration processes occurring in the subsurface. The processes considered in this study either drive or ...retard upward migration of gases from the detonation cavity. The relative importance of these processes is evaluated by simulating subsurface transport in a dual-permeability medium for the multi-tracer Noble Gas Migration Experiment (NGME) originally intended to study some aspects of transport from a UNE. For this experiment, relevant driving processes include weak two-phase convection driven by the geothermal gradient, over pressuring of the detonation cavity, and barometric pumping while gas sorption, dissolution, radioactive decay, and usually diffusion represent retarding processes. From deterministic simulations we found that over-pressuring of the post-detonation chimney coupled with barometric pumping produced a synergistic effect amplifying the tracer-gas reaching the surface. Bounding simulations indicated that the sorption and dissolution of gases, tending to retard transport, were much smaller than anticipated by earlier laboratory studies. The NGME observations themselves show that differences in gas diffusivity have a larger effect on influencing upward transport than do the combined effects of tracer-gas sorption and dissolution, which is consistent with a Sobol’ sensitivity analysis. Both deterministic simulations and those considering parametric uncertainties of transport-related properties predict that the excess in concentration of SF
$$_6$$
6
compared to
$$^{127}$$
127
Xe as might be captured in small volumetric samples should be much smaller than the order-of-magnitude contrast found in the large-volume gas samples taken at the site. While extraction of large-volume subsurface gas samples is shown to be capable of distorting in situ gas compositions, the highly variable injection rate of SF
$$_6$$
6
into the detonation cavity relative to that of
$$^{127}$$
127
Xe at the start of the field experiment is the most likely explanation for the large difference in observed concentrations.
MicroRNA-21 (miR-21) is overexpressed in many human tumors and has been linked to various cellular processes altered in cancer. miR-21 is also up-regulated by a number of inflammatory agents, ...including IFN, which is of particular interest considering the close relationship between inflammation and cancer. Because miR-21 appears to be overexpressed in human melanoma, we examined the role of miR-21 in cancer development and metastasis in B16 mouse melanoma cells. We found that miR-21 is a member of an IFN-induced miRNA subset that requires STAT3 activation. To characterize the role of miR-21 in melanoma behavior, we transduced B16 cells with lentivirus encoding a miR-21 antagomir and isolated miR-21 knockdown B16 cells. miR-21 knockdown or IFN treatment alone inhibited B16 cell proliferation and migration in vitro, and in combination they had an enhanced effect. Moreover, miR-21 knockdown sensitized B16 cells to IFN-induced apoptosis. In B16 cells miR-21 targeted tumor suppressor (PTEN and PDCD4) and antiproliferative (BTG2) proteins. To characterize the role of miR-21 in vivo, empty vector- and antagomiR-21-transduced B16 melanoma cells were injected via tail vein into syngeneic C57BL/6 mice. Although empty vector-transduced B16 cells produced large lung metastases, miR-21 knockdown cells only formed small lung lesions. Importantly, miR-21 knockdown tumor-bearing mice exhibited prolonged survival compared with empty vector tumor-bearing mice. Thus, miR-21 regulates the metastatic behavior of B16 melanoma cells by promoting cell proliferation, survival, and migration/invasion as well as by suppressing IFN action, providing important new insights into the role of miR-21 in melanoma.
Background: miRNAs are involved in many critical biological processes.
Results: miR-21 induction is STAT3-dependent, and miR-21 knockdown inhibited melanoma cell proliferation and migration and enhanced apoptosis. Although B16 cells produced large lung metastases in mice, miR-21 knockdown cells only formed small lung lesions.
Conclusion: miR-21 regulates the metastatic behavior of melanoma.
Significance: miR-21 is identified as a potential drug target in melanoma.
ABSTRACT With a large, unique spectroscopic survey in the fields of 28 galaxy-scale strong gravitational lenses, we identify groups of galaxies in the 26 adequately sampled fields. Using a ...group-finding algorithm, we find 210 groups with at least 5 member galaxies; the median number of members is 8. Our sample spans redshifts of 0.04 ≤ zgrp ≤ 0.76 with a median of 0.31, including 174 groups with 0.1 < zgrp < 0.6. The groups have radial velocity dispersions of 60 ≤ grp ≤ 1200 km s−1 with a median of 350 km s−1. We also discover a supergroup in field B0712+472 at z = 0.29 that consists of three main groups. We recover groups similar to ∼85% of those previously reported in these fields within our redshift range of sensitivity and find 187 new groups with at least five members. The properties of our group catalog, specifically, (1) the distribution of grp, (2) the fraction of all sample galaxies that are group members, and (3) the fraction of groups with significant substructure, are consistent with those for other catalogs. The distribution of group virial masses agrees well with theoretical expectations. Of the lens galaxies, 12 of 26 (46%) (B1422+231, B1600+434, B2114+022, FBQS J0951+2635, HE0435-1223, HST J14113+5211, MG0751+2716, MGJ1654+1346, PG 1115+080, Q ER 0047-2808, RXJ1131-1231, and WFI J2033-4723) are members of groups with at least five galaxies, and one more (B0712+472) belongs to an additional, visually identified group candidate. There are groups not associated with the lens that still are likely to affect the lens model; in six of 25 (24%) fields (excluding the supergroup), there is at least one massive ( grp ≥ 500 km s−1) group or group candidate projected within 2′ of the lens.
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