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Frozen pears, obtained by repeated freezing and thawing under cold outdoor conditions in winter, are very popular in northeast China. The effects of three freeze-thaw cycles (FT1-FT3) on Nanguo pear flavor were studied under fast (-80°C) and slow (-20°C) freezing conditions. Significant differences were found in the flavor of Nanguo pear after subsequent freeze-thaw cycles. The total soluble solid (TSS) content of fresh pear was 14.17 g/100 g and increased significantly after the first freeze-thaw cycle to 17.57-18.17 g/100 g. Lower TSS content was found in pears after the repeated freeze-thawing process. Citric acid was determined as the main organic acid of Nanguo pear. Its content and the overall content of organic acids decreased successively after each freezing and thawing cycle. The electronic tongue analysis results showed that the sourness of fresh pears generally decreased after their repeated freezing and thawing, that the odor of Nanguo pear changed significantly after freeze-thaw cycles, and that nitrogen oxides and hydrocarbons were the most differentiating odor compounds. The content of ethyl caproate was the highest in the volatile compound profile of the Nanguo pear and ranged from 377.26 to 526.77 µg/kg. In short, after repeated freezing and thawing, the changes in the chemical composition impart the frozen pear a unique flavor. [ABSTRACT FROM AUTHOR]

Policymakers are increasingly interested in quantifying nonprofit hospitals' tax benefits to assess whether hospitals' nonprofit status is justified. Property taxes that nonprofits would otherwise pay are among the more difficult tax benefit to quantify. This paper aims to educate stakeholders on the issues with estimating nonprofit hospitals' property tax benefits. We focus on Indiana because of relative advantages in its property tax record system. We first use a statewide database that identifies tax-exempt hospital properties to estimate property tax savings for all nonprofit hospitals in the state. We then examine five counties to quantify property tax benefits for specific hospitals. Using statewide data, we estimate a total property tax savings of $75.3 million in 2020 for all nonprofit hospitals in Indiana. However, upon closer examination of the five selected counties, we find that the state's identification code for hospital properties fails to identify over 500 property accounts associated with the nonprofit hospitals. Allowing for these additional properties increases nonprofit hospitals' tax savings in these counties by about 71%. These results suggest that our statewide estimate most likely understates nonprofit hospitals' property tax benefits by a significant amount. If statewide estimates were comparably understated, property tax savings in 2020 for all nonprofit hospitals in Indiana would be closer to $128 million. We conclude with policy recommendations. [ABSTRACT FROM AUTHOR]

The article discusses findings that trustee compensation was negatively linked to U.S. nonprofit hospitals' charity care provision, and its possible effect on trustee selection and the fulfillment of their fiduciary duties in 2019. Topics covered include the possible deviation of trustees' activities from hospitals' stated charitable missions, and whether these reflect organizational attributes like hospital executives' priorities. Also noted are trustees' expected mitigation of this risk.

The different tax treatment of government, nonprofit, and for-profit hospitals implies different charity care obligations, with the greatest obligation for government hospitals and the least for for-profit hospitals. Prior research has not examined charity care provision among all three ownership types at the national level. Using 2018 Medicare Hospital Cost Reports, we compared charity care provision across 1,024 government, 2,709 nonprofit, and 930 for-profit hospitals. In aggregate, nonprofit hospitals spent $2.3 of every $100 in total expenses incurred on charity care, which was less than government ($4.1) or for-profit ($3.8) hospitals. No hospital ownership type outperformed the other two types with respect to charity care provision in a majority of hospital service areas containing all three types. Using different kinds of analyses, we also found wide variation in charity care provision within ownership types and a lack of a consistent pattern across ownership types. These results suggest that many government and nonprofit hospitals' charity care provision was not aligned with their charity care obligations arising from their favorable tax treatment. Policy makers may consider initiatives to enhance hospitals' charity care provision, particularly hospitals with government and nonprofit ownership. [ABSTRACT FROM AUTHOR]

The financial viability of rural hospitals has been a matter of serious concern, with ongoing closures affecting rural residents' access to medical services. We examined the financial viability of 1,004 US rural hospitals that had consistent rural status in 2011-17. The median overall profit margin improved for nonprofit critical access hospitals (from 2.5 percent to 3.2 percent) but declined for other hospitals (from 3.0 percent to 2.6 percent for nonprofit non-critical access hospitals, from 3.2 percent to 0.4 percent for for-profit critical access hospitals, and from 5.7 percent to 1.6 percent for for-profit non-critical access hospitals). Occupancy rate and charge markup were positively associated with overall margins: In 2017 hospitals with low versus high occupancy rates had median overall profit margins of 0.1 percent versus 4.7 percent, and hospitals with low versus high charge markups had median overall margins of 1.8 percent versus 3.5 percent. Rural hospital financial viability deteriorated in states that did not expand eligibility for Medicaid and was lower in the South. Rural hospitals that closed during the study period had a median overall profit margin of -3.2 percent in their final year before closure. Policy makers should compare the incremental cost of providing essential services between hospitals and other settings to balance access and efficiency. [ABSTRACT FROM AUTHOR]

The article discusses 2012-16 data which shows that air ambulance service charges were 4.1-9.5 times higher than Medicare payments for the same services in 2016. Topics covered include the varying charges across the U.S., with the highest ones coming from the largest providers, and a market failure's possible causation of the charges, with patients lacking control over the air ambulance provider that transports them. Also noted is the need to regulate air ambulance billing practices.

Much research has focused on differences in hospital prices paid by private (commercial) versus public (Medicare and Medicaid) health insurers. Far less is known about price differences across commercial payers--health maintenance organizations (HMOs) or preferred provider organizations (PPOs) versus other payers, such as casualty (automobile), workers' compensation, and travel insurers. We found that other insurers had far less negotiating power with hospitals than commercial HMO/PPO insurers did. In the period 2010-16, the median price paid by HMO/PPO insurers for hospital services in Florida increased from 1.9 times to 2.5 times the Medicare price, respectively, while the median price paid by other insurers increased from 2.8 times to 3.8 times the Medicare price. Commercial HMO/PPO insurers' prices were similar across major hospital systems, regardless of ownership, while other insurers' prices differed substantially across systems. In 2016 the twenty hospitals with the highest prices (7.8-14.1 times the Medicare rate) for other insurers in Florida were all affiliated with the Hospital Corporation of America. These hospitals generated 24 percent of their commercial net revenue (median) from other payers, despite treating a relatively small proportion of patients covered by these payers. Protecting patients with other insurance from high hospital prices requires efforts by policy makers, hospitals, and insurers. [ABSTRACT FROM AUTHOR]

Many hospital executives and economists have suggested that since Medicare adopted a hospital prospective payment system in 1985, prices on the hospital chargemaster (an exhaustive list of the prices for all hospital procedures and supplies) have become irrelevant. However, using 2013 nationally representative hospital data from Medicare, we found that a one-unit increase in the charge-to-cost ratio (chargemaster price divided by Medicare-allowable cost) was associated with $64 higher patient care revenue per adjusted discharge. Furthermore, hospitals appeared to systematically adjust their charge-to-cost ratios: The average ratio ranged between 1.8 and 28.5 across patient care departments, and for-profit hospitals were associated with a 2.30 and a 2.07 higher charge-to-cost ratio than government and nonprofit hospitals, respectively. We also found correlation between the proportion of uninsured patients, a hospital's system affiliation, and its regional power with the charge-to-cost ratio. These findings suggest that hospitals still consider the chargemaster price to be an important way to enhance revenue. Policy makers might consider developing additional policy tools that improve markup transparency to protect patients from unexpectedly high charges for specific services. [ABSTRACT FROM AUTHOR]

To identify the characteristics of the most profitable US hospitals, we examined the profitability of acute care hospitals in fiscal year 2013, measured as net income from patient care services per adjusted discharge. Based on Medicare Cost Reports and Final Rule Data, the median hospital lost $82 for each such discharge. Forty-five percent of hospitals were profitable, with 2.5 percent earning more than $2,475 per adjusted discharge. The ten most profitable hospitals, seven of which were nonprofit, each earned more than $163 million in total profits from patient care services. Hospitals with for-profit status, higher markups, system affiliation, or regional power, as well as those located in states with price regulation, tended to be more profitable than other hospitals. Hospitals that treated a higher proportion of Medicare patients, had higher expenditures per adjusted discharge, were located in counties with a high proportion of uninsured patients, or were located in states with a dominant insurer or greater health maintenance organization (HMO) penetration had lower profitability than hospitals that did not have these characteristics. These findings can inform policy reforms, while providing a baseline against which to measure the impact of any subsequent reforms. [ABSTRACT FROM AUTHOR]

Using Medicare cost reports, we examined the fifty US hospitals with the highest charge-to-cost ratios in 2012. These hospitals have markups (ratios of charges over Medicare-allowable costs) approximately ten times their Medicare-allowable costs compared to a national average of 3.4 and a mode of 2.4. Analysis of the fifty hospitals showed that forty-nine are for profit (98 percent), forty-six are owned by for-profit hospital systems (92 percent), and twenty (40 percent) operate in Florida. One for-profit hospital system owns half of these fifty hospitals. While most public and private health insurers do not use hospital charges to set their payment rates, uninsured patients are commonly asked to pay the full charges, and out-of-network patients and casualty and workers' compensation insurers are often expected to pay a large portion of the full charges. Because it is difficult for patients to compare prices, market forces fail to constrain hospital charges. Federal and state governments may want to consider limitations on the charge-to-cost ratio, some form of all-payer rate setting, or mandated price disclosure to regulate hospital markups. [ABSTRACT FROM AUTHOR]

Background: HIV-infected long-term non-progressor (LTNP) subjects can prevent viral replication and may harbor useful information for the development of both antibody and active vaccination treatments. In this study we used LTNP sera to examine the epitopes presented to the gp160 protein, and from this procedure we hope to elucidate potential biomarkers pertaining to the level of resistance a patient may have in developing AIDS after infection with HIV. We used five clinical sera samples from LTNP patients to identify common epitopes by ELISA; peptides with high binding to sera were selected and analyzed for conservation among HIV clades. Antibodies were generated against one identified epitope using a chimeric peptide in BALB/c mice, and both the sera from these mice and LTNP sera were tested for viral inhibition capabilities. Results: A monoclonal antibody, CL3, against one identified epitope was used to compare these epitopes neutralizing capability. LTNP sera was also studied to determine chemokine/cytokine changes in these patients. The sera from LTNP patients 2, 3, 4, and 5 were identified as having the highest titers, and also significantly inhibited syncytia formation in vitro. Finally, the protein cytokine array demonstrated that I-309 and IGFBP-1 decreased in LTNPs, but levels of TIMP-1 and NAP-2 increased significantly. Conclusions: Our results indicate that the use of LTNP samples may be a useful for identifying further anti-viral epitopes, and may be a possible predictor for determining if patients show higher resistances of converting the HIV infection to AIDS. [ABSTRACT FROM AUTHOR]

Space charge distribution and breakdown strength were investigated in composites of low density polyethylene (LDPE) and various contents of montmorillonite (MMT). The disperse performance of MMT in LDPE was observed with scanning electron microscopy (SEM) and X-ray diffraction. For MMT concentration of 1 wt%, the better intercalation of LDPE into MMT interlayers and the tighter interface structure between polymer-filler were observed, relative to MMT concentration of 3 and 5 wt%. Space charge profiles were obtained using the pulsed electroacoustic (PEA) method. Less space charge accumulated in the LDPE/MMT with MMT content of 1 wt% than that in pure LDPE, and space charge in the central of LDPE/MMT was much more uniformly. On the other hand, when MMT concentration was up to 3 and 5wt%, large amounts of hetero charges were accumulated in the sample bulk. In MMT doped samples the dielectric strength increased up to a maximum at 1wt% loading, and then decreases at 3 and 5wt%. [ABSTRACT FROM AUTHOR]

Tablets undergoing dissolution in the USP Dissolution Testing Apparatus II are often found at locations on the vessel bottom that are off-center with respect to the dissolution vessel and impeller. A previously validated CFD approach and a novel experimental method were used here to examine the effect of tablet location on strain rates and dissolution rates. Dissolution tests were conducted with non-disintegrating tablets (salicylic acid) and disintegrating tablets (Prednisone) immobilized at different locations along the vessel bottom. CFD was used to predict the velocity profiles and strain rates when the tablets were placed at such locations. A CFD-based model was derived to predict the mass transfer coefficient and dissolution curves, which were then compared to the experimental results. Both non-disintegrating and disintegrating off-center tablets experimentally produced higher dissolution rates than centered tablets. The CFD-predicted strain rate distribution along the bottom was highly not uniform and the predicted strain rates correlated well with the experimental mass transfer coefficients. The proposed CFD-based model predicts mass transfer rates that correlate well with the experimental ones. The exact tablet location has a significant impact on the dissolution profile. The proposed model can satisfactorily predict the mass transfer coefficients and dissolution profiles for non-disintegrating tablets. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1511–1531, 2009 [ABSTRACT FROM AUTHOR]

Abstract Purpose  The United States Pharmacopoeia (USP) imposes strict requirements on the geometry and operating conditions of the USP Dissolution Testing Apparatus II. A previously validated Computational Fluid Dynamics (CFD) approach was used here to study the hydrodynamics of USP Apparatus II when the impeller was placed at four different locations, all within the limits specified by USP. Method  CFD was used to predict the velocity profiles, energy dissipation rates, and strain rates when the impeller was placed in the reference location (centrally mounted, 25 mm off the vessel bottom), 2 mm off-center, 2 mm higher, and 2 mm lower than the reference location. Results  Small changes in impeller location, especially if associated with loss of symmetry, produced extensive changes in velocity profiles and shear rates. Centrally located impellers, irrespective of their off-bottom clearance, produced non-uniform but nearly symmetric strain rates. The off-center impeller produced a more uniform but slightly asymmetric strain rate distribution. Conclusions  The system hydrodynamics depends strongly on small differences in equipment configurations and operating conditions, which are likely to affect significantly the flow field and shear rate experienced by the oral dosage form being tested, and hence the solid–liquid mass transfer and dissolution rate. [ABSTRACT FROM AUTHOR]

Blend time, the time to achieve a predefined level of homogeneity of a tracer in a mixing vessel, is an important parameter to evaluate the mixing efficiency of mixing devices. In this work, the blend time required to homogenize the liquid content of a USP Dissolution Testing Apparatus II under a number of operating conditions was obtained using two different experimental methods (tracer detection via colorimetric and conductivity measurements), a computational approach (computational fluid dynamics (CFD)), and a semi-theoretical analysis of the phenomenon. Under the standard geometric and operating conditions in which the USP Apparatus II is typically used (N = 50 rpm) the experimental blend time to achieve a 92.74% uniformity level was found to be between 27.5 and 33.3 s, depending on the location of the injection point and monitoring point for the tracer. These values were in close agreement with those obtained from CFD simulations. Changing the impeller vertical position (±2 mm) had only a limited effect. The CFD predictions also indicated that blend time is inversely proportional to the agitation speed. This conclusion is in agreement with previous reports and equations for blend time in mixing vessels. The blend times obtained in this work appear to be some two orders of magnitude smaller than the time usually required for appreciable tablet dissolution during the typical dissolution test, implying that the liquid contents of the USP Apparatus II can be considered to be relatively well mixed during the typical dissolution test. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3072–3086, 2007 [ABSTRACT FROM AUTHOR]

The USP Apparatus II is the device commonly used to conduct dissolution testing in the pharmaceutical industry. Despite its widespread use, dissolution testing remains susceptible to significant error and test failures, and limited information is available on the hydrodynamics of this apparatus. In this work, laser-Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were used, respectively, to experimentally map and computationally predict the velocity distribution inside a standard USP Apparatus II under the typical operating conditions mandated by the dissolution test procedure. The flow in the apparatus is strongly dominated by the tangential component of the velocity. Secondary flows consist of an upper and lower recirculation loop in the vertical plane, above and below the impeller, respectively. A low recirculation zone was observed in the lower part of the hemispherical vessel bottom where the tablet dissolution process takes place. The radial and axial velocities in the region just below the impeller were found to be very small. This is the most critical region of the apparatus since the dissolving tablet will likely be at this location during the dissolution test. The velocities in this region change significantly over short distances along the vessel bottom. This implies that small variations in the location of the tablet on the vessel bottom caused by the randomness of the tablet descent through the liquid are likely to result in significantly different velocities and velocity gradients near the tablet. This is likely to introduce variability in the test. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2327–2349, 2007 [ABSTRACT FROM AUTHOR]

Continuous-variable quantum information, encoded into infinite-dimensional quantum systems, is a promising platform for the realization of many quantum information protocols, including quantum computation, quantum metrology, quantum cryptography, and quantum communication. To successfully demonstrate these protocols, an essential step is the certification of multimode continuous-variable quantum states and quantum devices. This problem is well studied under the assumption that multiple uses of the same device result in identical and independently distributed (i.i.d.) operations. However, in realistic scenarios, identical and independent state preparation and calls to the quantum devices cannot be generally guaranteed. Important instances include adversarial scenarios and instances of time-dependent and correlated noise. In this Letter, we propose the first set of reliable protocols for verifying multimode continuous-variable entangled states and devices in these non-i.i.d scenarios. Although not fully universal, these protocols are applicable to Gaussian quantum states, non-Gaussian hypergraph states, as well as amplification, attenuation, and purification of noisy coherent states. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Self-insured employers cover more people than Medicare, Medicaid, or direct purchasers of private insurance. This study examined the ability of self-insured employers to negotiate hospital prices and the relationship between hospital prices and employer market power in the United States. STUDY DESIGN: Repeated cross-section analysis of commercial claims. METHODS: We used the US Census Bureau County Business Patterns data to estimate employer market power at the metropolitan statistical area (MSA)--year level and used the Truven Health MarketScan commercial claims to estimate mean hospital prices and price ratios at the MSA-year level (2010-2016). We calculated descriptive statistics for employer market power, mean hospitalization prices, and a case mix--adjusted price ratio measure during the study period and analyzed the 10 most concentrated labor markets. We estimated MSA-year--level ordinary least squares regressions of hospitalization price and the price ratio measure on employer market power. RESULTS: Large self-insured employers had concentrated market power in very few MSAs in 2016. The mean value of our employer market power measure was 62 for 2016, compared with the mean value of 5410 for hospital market power in the United States. Regression analyses find a slight relationship: A 1-point increase in employer market power was associated with a $6.61 decrease in the hospitalization price (mean = $20,813), but this result becomes statistically insignificant once the models control for hospital wages. CONCLUSIONS: Employer market power is low in most MSAs. Self-insured employers may consider building purchase alliances with state and local government employee groups to enhance their market power and lower negotiated prices for hospital services. [ABSTRACT FROM AUTHOR]

Quantum benchmarks are routinely used to validate the experimental demonstration of quantum information protocols. Many relevant protocols, however, involve an infinite set of input states, of which only a finite subset can be used to test the quality of the implementation. This is a problem, because the benchmark for the finitely many states used in the test can be higher than the original benchmark calculated for infinitely many states. This situation arises in the teleportation and storage of coherent states, for which the benchmark of 50% fidelity is commonly used in experiments, although finite sets of coherent states normally lead to higher benchmarks. Here, we show that the average fidelity over all coherent states can be indirectly probed with a single setup, requiring only two-mode squeezing, a 50-50 beam splitter, and homodyne detection. Our setup enables a rigorous experimental validation of quantum teleportation, storage, amplification, attenuation, and purification of noisy coherent states. More generally, we prove that every quantum benchmark can be tested by preparing a single entangled state and measuring a single observable. [ABSTRACT FROM AUTHOR]

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis. [ABSTRACT FROM AUTHOR]

Increasing insurance deductibles have prompted some medical centers to initiate transparent pricing. However, the impact of price transparency (PT) on surgical volume, revenue, and patient satisfaction is unknown, along with the barriers to achieving PT. We identified ambulatory surgical centers in the Free Market Medical Association database that publicly list prices for surgical services online. Six of eight centers (75%) responded to our data collection inquiry. Among five centers that reported their patient volume and revenue after adopting PT, patient volume increased by a median of 50 per cent (range 10-200%) at one year. Four centers (80%) reported an increase in revenue by a median of 30 per cent (range 4-75%), whereas three centers (60%) experienced an increase in third-party administrator contracts with the average increase being seven new third-party administrator contracts (range = 2-12 contracts). Three centers (50%) reported a reduction in their administrative burden and five centers (83%) reported an increase in patient satisfaction and patient engagement after PT. The leading barrier reported to making prices transparent was discouragement from another practice, hospital, or insurance company. The findings of this preliminary study may help guide medical practices in designing and implementing PT strategies. [ABSTRACT FROM AUTHOR]

Hospitals must disclose their cash prices, commercial negotiated rates, and chargemaster prices for seventy common, shoppable services under the hospital price transparency rule. Examining prices reported by 2,379 hospitals as of September 9, 2022, we found that a given hospital's cash prices and commercial negotiated rates both tended to reflect a predetermined and consistent percentage discount from its chargemaster prices. On average, cash prices and commercial negotiated rates were 64 percent and 58 percent of the corresponding chargemaster prices for the same procedures at the same hospital and in the same service setting, respectively. Cash prices were lower than the median commercial negotiated rates in 47 percent of instances, and most likely so at hospitals with government or nonprofit ownership, located outside of metropolitan areas, or located in counties with relatively high uninsurance rates or low median household incomes. Hospitals with stronger market power were most likely to offer cash prices below their median negotiated rates, whereas hospitals in areas where insurers had stronger market power were less likely to do so. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Centrosomal protein FOR20 has been reported to be crucial for essential cellular processes, including ciliogenesis, cell migration, and cell cycle in vertebrates. However, the function of FOR20 during mammalian embryonic development remains unknown. To investigate the in vivo function of the For20 gene in mammals, we generated For20 homozygous knockout mice by gene targeting. Our data reveal that homozygous knockout of For20 results in significant embryonic growth arrest and lethality during gestation, while the heterozygotes show no obvious defects. The absence of For20 leads to impaired left‐right patterning of embryos and reduced cilia in the embryonic node. Deletion of For20 also disrupts angiogenesis in yolk sacs and embryos. These results highlight a critical role of For20 in early mammalian embryogenesis. [ABSTRACT FROM AUTHOR]

We report the design, synthesis, characterization and evaluation of a novel class of γ-AApeptide one-bead-one-compound (OBOC) library, from which a small γ-AApeptide was identified to effectively prevent and disassemble Aβ aggregation. [ABSTRACT FROM AUTHOR]

Members of the superfamily of solute carrier (SLC) transmembrane proteins transport diverse substrates across distinct cellular membranes. Three SLC protein families transport distinct neurotransmitters into synaptic vesicles to enable synaptic transmission in the nervous system. Among them is the SLC17A6/7/8 family of vesicular glutamate transporters, which endows specific neuronal cell types with the ability to use glutamate as a neurotransmitter. The genome of the nematode Caenorhabditis elegans encodes three SLC17A6/7/8 family members, one of which, eat-4/VGLUT, has been shown to be involved in glutamatergic neurotransmission. Here, we describe our analysis of the two remaining, previously uncharacterized SLC17A6/7/8 family members, vglu-2 and vglu-3. These two genes directly neighbor one another and are the result of a recent gene duplication event in C. elegans, but not in other Caenorhabditis species. Compared to EAT-4, the VGLU-2 and VGLU-3 protein sequences display a more distant similarity to canonical, vertebrate VGLUT proteins. We tagged both genomic loci with gfp and detected no expression of vglu-3 at any stage of development in any cell type of both C. elegans sexes. In contrast, vglu-2::gfp is dynamically expressed in a restricted set of distinct cell types. Within the nervous system, vglu-2::gfp is exclusively expressed in a single interneuron class, AIA, where it localizes to vesicular structures in the soma, but not along the axon, suggesting that VGLU-2 may not be involved in synaptic transport of glutamate. Nevertheless, vglu-2 mutants are partly defective in the function of the AIA neuron in olfactory behavior. Outside the nervous system, VGLU-2 is expressed in collagen secreting skin cells where VGLU-2 most prominently localizes to early endosomes, and to a lesser degree to apical clathrin-coated pits, the trans-Golgi network, and late endosomes. On early endosomes, VGLU-2 colocalizes most strongly with the recycling promoting factor SNX-1, a retromer component. Loss of vglu-2 affects the permeability of the collagen-containing cuticle of the worm, and based on the function of a vertebrate VGLUT1 protein in osteoclasts, we speculate that vglu-2 may have a role in collagen trafficking in the skin. We conclude that C. elegans SLC17A6/7/8 family members have diverse functions within and outside the nervous system. [ABSTRACT FROM AUTHOR]

Background: As the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand.Methods: This study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents' functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH.Results: Younger age (χ2 = 27.5, p < 0.05), male sex (χ2 = 11.5, p < 0.1), and living in the suburbs (χ2 = 55.1, p < 0.05) were associated with better SRH scores. Higher SRH scores were also linked with health behaviour of the respondents; namely, do not smoke (χ2 = 18.0, p < 0.1), do not drink (χ2 = 18.6, p < 0.1), or engage in regular outdoor activities (χ2 = 69.3, p < 0.05). The respondents with better social support report higher SRH scores than those without. Respondents' ability to hear (χ2 = 38.7, p < 0.05), speak (χ2 = 16.1, p < 0.05) and see (χ2 = 78.3, p < 0.05) impacted their SRH scores as well. Meanwhile, chronic illness except asthma was a major influence factor in low SRH score. Applying multiple regression models, a series of determinants were analysed to establish the extent to which they contribute to SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic and health risk behaviours, 2.4% from social support, 8.5% from mental health, 20% from physical conditions, and13% from chronic diseases.Conclusions: This is the first study that examines the determinants of SRH among Shanghai elders. Nearly 40% of our study's respondents reported their health status as "good". The main determinants of SRH among elders include living condition, health risk behaviour, social support, health status, and the economic status of the neighbourhood. [ABSTRACT FROM AUTHOR]

China has abundant reserves of magnesite, making it the world's leading source of this strategic mineral. Sparry magnesite is the main type of magnesite deposit, and is easy to exploit. It occurs mainly as the sedimentary-metamorphic type. Production is centred on eastern Liaoning Province, where a world-class large to super large magnesite ore processing and production facility has been developed. Hydrothermal metasomatic deposits, associated with ultramafic complexes and eluvial deposits produced by weathering, are two other important types found in China. The Western section of the Bangonghu-Nujiang metallogenic belt is an important target region for prospecting lake-sedimentary magnesite deposits. Based on a systematic analysis of material from 62 magnesite production areas, this study investigated the metallogeny of magnesite and delineated 13 magnesite metallogenic belts. Maps were produced showing metallogenic regularities in magnesite deposits, the metallogenic system of the magnesite deposits, and the distribution of the metallogenic belts of Chinese magnesite deposits. It provides a theoretical basis for forecasting the location of potential magnesite resources in China. Finally, it explores some key scientific issues, including the formation processes of ultra magnesite ore-concentrated areas, and their sources of magnesium. [ABSTRACT FROM AUTHOR]

Host-defensepeptides (HDPs) such as magainin 2 have emerged aspotential therapeutic agents combating antibiotic resistance. Inspiredby their structures and mechanism of action, herein we report thefirst example of antimicrobial helical sulfono-γ-AApeptide foldamers.The lead molecule displays broad-spectrum and potent antimicrobialactivity against multi-drug-resistant Gram-positive and Gram-negativebacterial pathogens. Time-kill studies and fluorescence microscopysuggest that sulfono-γ-AApeptides eradicate bacteria by takinga mode of action analogous to that of HDPs. Clear structure–functionrelationships exist in the studied sequences. Longer sequences, presumablyadopting more-defined helical structures, are more potent than shorterones. Interestingly, the sequence with less helical propensity insolution could be more selective than the stronger helix-forming sequences.Moreover, this class of antimicrobial agents are resistant to proteolyticdegradation. These results may lead to the development of a new classof antimicrobial foldamers combating emerging antibiotic-resistantpathogens. [ABSTRACT FROM AUTHOR]

China has widely distributed silver deposits, and is rich in silver resources. Although silver deposits are mainly associated with Pb-Zn deposits, a number of independent silver deposits have also been discovered in recent years. Silver deposits include different types, such as submarine volcanism and continental volcanism related type, intrusion related type, and sedimentary related type. This study summarized the metallogenic regularity of China's silver deposits systematically based mainly on the data from 490 silver deposits. It is shown that submarine volcanic sedimentary type, continental volcanic or sub-volcanic type, skarn type, hydrothermal type (including vein type and stratabound type), sedimentary metamorphic type, sedimentary type and regolith type should be regarded as the most important prediction types of silver deposit. A total of 32 silver mineralization belts and 111 silver concentration areas have been delineated. The map of 'Spatial distribution of silver mineralization belts in China' and other series of maps finished in this study may provide a theoretical basis for the evaluation and prognosis of silver resources potential in China. [ABSTRACT FROM AUTHOR]

DNA methylation is an important epigenetic mark in many eukaryotic organisms. De novo DNA methylation in plants can be achieved by the RNA-directed DNA methylation (RdDM) pathway, where the plant-specific DNA-dependent RNA polymerase IV (Pol IV) transcribes target sequences to initiate 24-nt siRNA production and action. The putative DNA binding protein DTF1/SHH1 of Arabidopsis has been shown to associate with Pol IV and is required for 24-nt siRNA accumulation and transcriptional silencing at several RdDM target loci. However, the extent and mechanism of DTF1 function in RdDM is unclear. We show here that DTF1 is necessary for the accumulation of the majority of Pol IV-dependent 24-nt siRNAs. It is also required for a large proportion of Pol IV-dependent de novo DNA methylation. Interestingly, there is a group of RdDM target loci where 24-nt siRNA accumulation but not DNA methylation is dependent on DTF1. DTF1 interacts directly with the chromatin remodeling protein CLASSY 1 (CLSY1), and both DTF1 and CLSY1 are associated in vivo with Pol IV but not Pol V, which functions downstream in the RdDM effector complex. DTF1 and DTF2 (a DTF1-like protein) contain a SAWADEE domain, which was found to bind specifically to histone H3 containing H3K9 methylation. Taken together, our results show that DTF1 is a core component of the RdDM pathway, and suggest that DTF1 interacts with CLSY1 to assist in the recruitment of Pol IV to RdDM target loci where H3K9 methylation may be an important feature. Our results also suggest the involvement of DTF1 in an important negative feedback mechanism for DNA methylation at some RdDM target loci. [ABSTRACT FROM AUTHOR]

Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the intermediate zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin-mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription. [ABSTRACT FROM AUTHOR]

A response by the authors to a letter to the editor about their study on factors associated with the profitability of hospitals, not hospital systems is presented.