Distributions of surface water partial pressure of carbon dioxide (pCO2) were measured on nine cruises in the Delaware Estuary (USA). The Delaware River was highly supersaturated in pCO2 with respect ...to the atmosphere during all seasons, while the Delaware Bay was undersaturated in pCO2 during spring and late summer and moderately supersaturated during mid-summer, fall, and winter. While the smaller upper tidal river was a strong CO2 source (27.1 ± 6.4 mol-C m−2 yr−1), the much larger bay was a weak source (1.2 ± 1.4 mol-C m−2 yr−1), the latter of which had a much greater area than the former. In turn, the Delaware Estuary acted as a relatively weak CO2 source (2.4 ± 4.8 mol-C m−2 yr−1), which is in great contrast to many other estuarine systems. Seasonally, pCO2 changes were greatest at low salinities (0 ≤ S < 5), with pCO2 values in the summer nearly 3-fold greater than those observed in the spring and fall. Undersaturated pCO2 was observed over the widest salinity range (7.5 ≤ S < 30) during spring. Near to supersaturated pCO2 was generally observed in mid- to high-salinity waters (20 ≤ S < 30) except during spring and late summer. Strong seasonal trends in internal estuarine production and consumption of CO2 were observed throughout both the upper tidal river and lower bay. Positive correlations between river-borne and air–water CO2 fluxes in the upper estuary emphasize the significance of river-borne CO2 degassing to overall CO2 fluxes. While river-borne CO2 degassing heavily influenced CO2 dynamics in the upper tidal river, these forces were largely compensated for by internal biological processes within the extensive bay system of the lower estuary.
Intracranial aneurysms, a rare complication of radiation therapy, have been reported mainly in case reports or case series. We performed a multicenter, retrospective cohort study to investigate the ...characteristics of radiation-induced intracranial aneurysms.
Data on 2641 patients with intracranial aneurysms were retrospectively collected from 3 hospitals between January 2005 and June 2014. An additional 1519 patients were recruited from a single center between July 2014 and March 2020. Aneurysms in patients with a history of radiation therapy for at least 6 months were defined as radiation-related aneurysms. Patients' demographic profiles, clinical characteristics, and aneurysm parameters detected on CTA were compared between radiation-related and control groups.
Of the 4160 patients, the average age was 57.9 (SD, 13.5) years, 2406 (57.8%) were women, 477 (11.5%) had multiple aneurysms, 3009 (72.3%) had SAH, and 34 (0.8%) had radiation-related aneurysms. The male-to-female ratio in the radiation-related group was significantly higher than that in the control group (2.4:1 versus 0.72:1,
= .001). The mean age of the radiation-related group was significantly younger than in the control group (51.4 SD, 15.0 years versus 58.2 SD, 13.5 years,
= .003). More patients in the radiation-related group presented with SAH than in the control group (without age and sex matching, 88.2% versus 72.2%,
= .037; with age and sex matching, 88.2% versus 58.8%,
= .006). Of the 4813 intracranial aneurysms, only 43 (0.9%) aneurysms were categorized as in the radiation-related group, whereas 4770 (99.1%) aneurysms constituted the control group. Compared with the control group, there was a significantly higher proportion of sidewall aneurysms (46.5% versus 32.3%,
= .048) and a predilection for aneurysms involving the ICA and posterior circulation arteries (72.1% versus 52.2%,
= .046) in the radiation-related group.
Compared with the control group, radiation-related aneurysms are more prone to occur in men and young patients, with a higher percentage of sidewall aneurysms located in the ICA and posterior circulation arteries. Furthermore, SAH is highly prevalent in patients with radiation-induced aneurysms, indicating that dedicated screening for aneurysms after radiation therapy is necessary, but further studies are needed to determine when and how to screen.
Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor ...suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore demethylation. In addition, further methylome assessments revealed that breast cancer aggressiveness associated with Cav1 CGI shore methylation levels, with shore hypermethylation in minimally aggressive, luminal breast cancer cells and shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore methylation was also observed in human breast tumors, and overall survival rates of breast cancer patients lacking estrogen receptor α (ERα) negatively correlated with Cav1 expression. Based on this first study of Cav1 (a potential oncogene) CGI shore methylation, we suggest this phenomenon may represent a new prognostic marker for ERα-negative, basal-like breast cancer.
The millisecond-duration radio flashes known as fast radio bursts (FRBs) represent an enigmatic astrophysical phenomenon. Recently, the sub-arcsecond localization (∼100 mas precision) of FRB 121102 ...using the Very Large Array has led to its unambiguous association with persistent radio and optical counterparts, and to the identification of its host galaxy. However, an even more precise localization is needed in order to probe the direct physical relationship between the millisecond bursts themselves and the associated persistent emission. Here, we report very-long-baseline radio interferometric observations using the European VLBI Network and the 305 m Arecibo telescope, which simultaneously detect both the bursts and the persistent radio emission at milliarcsecond angular scales and show that they are co-located to within a projected linear separation of 40 pc ( 12 mas angular separation, at 95% confidence). We detect consistent angular broadening of the bursts and persistent radio source (∼2-4 mas at 1.7 GHz), which are both similar to the expected Milky Way scattering contribution. The persistent radio source has a projected size constrained to be 0.7 pc ( 0.2 mas angular extent at 5.0 GHz) and a lower limit for the brightness temperature of T b 5 × 10 7 K . Together, these observations provide strong evidence for a direct physical link between FRB 121102 and the compact persistent radio source. We argue that a burst source associated with a low-luminosity active galactic nucleus or a young neutron star energizing a supernova remnant are the two scenarios for FRB 121102 that best match the observed data.
Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB ...patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50~60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12–3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.
Multielement solid solution alloys are intrinsically disordered on the atomic scale, and many of their advanced properties originate from the local structural characteristics. The local structure of ...a NiCoCr solid solution alloy is measured with x-ray or neutron total scattering and extended x-ray absorption fine structure (EXAFS) techniques. The atomic pair distribution function analysis does not exhibit an observable structural distortion. However, an EXAFS analysis suggests that the Cr atoms are favorably bonded with Ni and Co in the solid solution alloys. This short-range order (SRO) may make an important contribution to the low values of the electrical and thermal conductivities of the Cr-alloyed solid solutions. In addition, an EXAFS analysis of Ni ion irradiated samples reveals that the degree of SRO in NiCoCr alloys is enhanced after irradiation.
Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains ...unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin® or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection.
Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most ocular pain arises from the ...cornea. However, the underlying mechanisms remain unknown. Using genetic axonal tracing approaches, we discover distinct sensory innervation patterns between the conjunctiva and cornea. Further genetic and functional analyses in rodent models show that a subset of conjunctival-selective sensory fibers marked by MrgprA3 expression, rather than corneal sensory fibers, mediates ocular itch. Importantly, the actions of both histamine and nonhistamine pruritogens converge onto this unique subset of conjunctiva sensory fibers and enable them to play a key role in mediating itch associated with allergic conjunctivitis. This is distinct from skin itch, in which discrete populations of sensory neurons cooperate to carry itch. Finally, we provide proof of concept that selective silencing of conjunctiva itch-sensing fibers by pruritogen-mediated entry of sodium channel blocker QX-314 is a feasible therapeutic strategy to treat ocular itch in mice. Itch-sensing fibers also innervate the human conjunctiva and allow pharmacological silencing using QX-314. Our results cast new light on the neural mechanisms of ocular itch and open a new avenue for developing therapeutic strategies.
Generation of CD8+ memory T cells requires metabolic reprogramming that is characterized by enhanced mitochondrial fatty-acid oxidation (FAO). However, where the fatty acids (FA) that fuel this ...process come from remains unclear. While CD8+ memory T cells engage FAO to a greater extent, we found that they acquired substantially fewer long-chain FA from their external environment than CD8+ effector T (Teff) cells. Rather than using extracellular FA directly, memory T cells used extracellular glucose to support FAO and oxidative phosphorylation (OXPHOS), suggesting that lipids must be synthesized to generate the substrates needed for FAO. We have demonstrated that memory T cells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and memory T cell development. Our observations link LAL to metabolic reprogramming in lymphocytes and show that cell intrinsic lipolysis is deterministic for memory T cell fate.
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•Unlike Teff cells, memory T cells do not acquire substantial amounts of long-chain FA•Glucose supports mitochondrial FAO and OXPHOS in memory T cells•Memory T cells use LAL-mediated cell-intrinsic lipolysis to mobilize FA for FAO•T cell-intrinsic lysosomal lipolysis is important for memory T cell development
CD8+ memory T cells engage fatty-acid oxidation (FAO); however, the source of fatty acids that fuel FAO is unclear. O’Sullivan et al. show that memory T cells rely on glucose, and cell-intrinsic lipolysis to mobilize substrates, for FAO.
Correlated electron materials can undergo a variety of phase transitions, including superconductivity, the metal-insulator transition and colossal magnetoresistance. Moreover, multiple physical ...phases or domains with dimensions of nanometres to micrometres can coexist in these materials at temperatures where a pure phase is expected. Making use of the properties of correlated electron materials in device applications will require the ability to control domain structures and phase transitions in these materials. Lattice strain has been shown to cause the coexistence of metallic and insulating phases in the Mott insulator VO(2). Here, we show that we can nucleate and manipulate ordered arrays of metallic and insulating domains along single-crystal beams of VO(2) by continuously tuning the strain over a wide range of values. The Mott transition between a low-temperature insulating phase and a high-temperature metallic phase usually occurs at 341 K in VO(2), but the active control of strain allows us to reduce this transition temperature to room temperature. In addition to device applications, the ability to control the phase structure of VO(2) with strain could lead to a deeper understanding of the correlated electron materials in general.
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