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Despite remarkable advances in the assembly of highly structured coordination polymers and metal-organic frameworks, the rational design of such materials using more conformationally flexible organic ligands such as peptides remains challenging. In an effort to make the design of such materials fully programmable, we first developed a computational design method for generating metal-mediated 3D frameworks using rigid and symmetric peptide macrocycles with metal-coordinating sidechains. We solved the structures of six crystalline networks involving conformationally constrained 6 to 12 residue cyclic peptides with C2, C3, and S2 internal symmetry and three different types of metals (Zn

The Wairau Plain in Marlborough, New Zealand, host a shallow, highly conductive gravel aquifer which is mainly recharged by the braided Wairau River. The groundwater of the Wairau Aquifer is an important source of drinking water in the region and provides irrigation water for viticulture. Managing the groundwater is increasingly challenging because of a decline in levels and spring flows combined with a natural seasonality and an expected high vulnerability to climate change and overexploitation.A prerequisite for groundwater managment and limit-setting is the knowledge of the water supply (recharge) as well as the water discharge and takes from the aquifer. Both are spatialy and temporally highly variable and difficult to measure. In addition, the aquifer is influenced by ephemeral streams which could potentially lead to unknown groundwater sinks and sources and periodical shifts of boundary locations.In order to investigate these aspects and to estimate the water balance components and fluxes in the associated groundwater system, a coupled surface water – groundwater flow model (MODFLOW) has been set up. A variety of observations, ranging from groundwater heads to spring/river flows and exchange rates, were built into the model. Metered groundwater abstraction data was used to test and adapt a spatio-temporally distributed soil water balance model that is coupled to the MODFLOW model.The complex surface flow network of the Wairau Plain and strong contrasts of hydraulic conductivity (up to 4 orders of magnitude) between older hydrogeological units and more recent, interwoven fluvial sediments have been a major challenge in the model setup. An iterative procedure with step-wise increasing complexity of parameterization was adopted to derive a plausible model structure, that is commensurable with the various observation types. Model parameters were calibrated and (linear) uncertainty bounds estimated using the PEST software.The model performs well with respect to the plausibility of the groundwater flow field and the overall water balance. Groundwater heads, river-groundwater exchange flows and spring flows are generally well covered by the predictive uncertainty bounds during the evaluation period (data not utilized for calibration). The model provides insights into the relative contributions and the seasonality of the various water balance components of the Wairau Aquifer. It has been confirmed that the Wairau River is the main contributor to groundwater recharge, but also that recharge in a given year is matched by equal levels of discharge to low-land springs and off-shore. Although large river flood events during the wet period lead to interim excess groundwater storage, the recession to pre-flood groundwater levels is surprisingly fast (less than one year). On the other hand, unremarkable (high return period) flood events in the summer period, which keep river flows at elevated levels, have a noticeable effect on groundwater storage. This effect can last up until the following dry season.The model proved useful for assessing the status quo of the Wairau Aquifer groundwater resources. This is a prerequisite for the search and testing of alternative management options that are imminent due to the observed trends in groundwater levels.

This dataset contains the supplementary materialsfor "De novo design of small beta barrel proteins" Datasets. All dataset_SX.tar.gz files extract into a directory named data_archive. Dataset S1 (dataset_S1.tar.gz). Contains designs, input files (including blueprints, constraints, resfiles, and Rosetta xml scripts), commands, and selection scripts for Batch1-5 designs. data_archive/batch1 data_archive/batch2 data_archive/batch3 data_archive/batch4 data_archive/batch5 Dataset S2 (dataset_S2.tar.gz). Contains sequences, designs, input files (including blueprints, constraints, resfiles, and Rosetta xml scripts), commands, selection scripts, and TrRosetta and DeepAccNet (DAN) scores for chip library designs. data_archive/chip Dataset S3 (dataset_S3.tar.gz). Contains chip library protease stability assay data including sequence counts, protease EC50 and stability scores, selection results (experiments.csv), and experimental meta data. data_archive/protease_assay Dataset S4 (dataset_S4.tar.gz). Contains the LASSO regression model and feature data used for training from the chip library protease stability screen results and for predicting protease stability for the constrained hallucinated designs. data_archive/lasso_regression_model Dataset S5 (dataset_S5.tar.gz). Contains the mass spectrometry barcode library data (skyline.csv). data_archive/ms_barcodes Dataset S6 (dataset_S6.tar.gz). Contains common input files, the fragment database in HDF5 format used for structure profiles (PSSMs), command and inputs for Rosetta design filter metrics, and a script to extract DeepAccNet (DAN) scores. data_archive/common_inputs data_archive/databases/ss_grouped_vall_all.h5 data_archive/filter data_archive/deepaccnet Dataset S7 (dataset_S7.tar.gz). Contains native small beta barrel PDB sets and the clustering script used for selection. data_archive/natives Dataset S8 (dataset_S8.tar.gz). Contains a scaffold set of 12911 designed mini-barrels which have a high probability of folding based on AlphaFold2 metrics (pLDDT > 88 and model RMSD < 2.0). data_archive/scaffolds &nbsp

Proteins that switch between two structural states as a function of environmental stimuli are widespread in nature. These proteins structurally transduce biochemical information in a manner analogous to how transistors control information flow in computing devices. Engineering challenges ranging from biological computing devices to molecular motors require such two-state switches, but designing these is an unsolved problem as it requires sculpting an energy landscape with two low-energy but structurally distinct conformations that can be modulated by external inputs. Here we describe a general design approach for creating “hinge” proteins that populate one distinct state in the absence of ligand and a second designed state in the presence of ligand. X-ray crystallography, electron microscopy, and double electron-electron resonance spectroscopy demonstrate that despite the significant structural differences, the two states are designed with atomic level accuracy. The kinetics and thermodynamics of effector binding can be finely tuned by modulating the free energy differences between the two states; when this difference becomes sufficiently small, we obtain bistable proteins that populate both states in the absence of effector, but collapse to a single state upon effector addition. Like the transistor, these switches now enable the design of a wide array of molecular information processing systems.

Segments of proteins with β-strand propensity can self associate to form amyloid fibrils associated with many diseases. These regions often adopt alternative structures in their folded states, or are intrinsically disordered in solution, making it difficult to generate binders or inhibitors with existing strategies. Here we describe a general approach to bind such segments in β-strand and β-hairpin conformations usingde novodesigned scaffolds that contain deep peptide binding clefts flanked by β-strands that form hydrogen bonds to the peptide upon binding. The designs bind their cognate peptidesin vitrowith nanomolar affinities and in mammalian cells. The crystal structure of a designed protein-peptide complex is close to the design model, and NMR characterization reveals how the peptide binding cleft is protected in the apo state. We use the approach to design binders to segments of the amyloid forming proteins Transthyretin, Tau, Serum amyloid A1 and Aβ42. The Aβ binders block assembly of Aβ fibrils as effectively as the most potent of the clinically tested antibodies to date.

SummaryProtein crystallization plays a central role in structural biology1, with broad impact2in pharmaceutical formulation3, drug delivery4, biosensing5, and biocatalysis6,7. Despite this importance, the process of protein crystallization remains poorly understood and highly empirical8–10, with largely unpredictable crystal contacts, lattice packing arrangements, and space group preferences, and the programming of protein crystallization through precisely engineered sidechain-sidechain interactions across multiple protein-protein interfaces is an outstanding challenge. Here we develop a general computational approach to designing three-dimensional (3D) protein crystals with pre-specified lattice architectures at atomic accuracy that hierarchically constrains the overall degree of freedoms (DOFs) of the system. We use the approach to design three pairs of oligomers that can be individually purified, and upon mixing, spontaneously self-assemble into large 3D crystals (>100 μm). Small-angle X-ray scattering and X-ray crystallography show these crystals are nearly identical to the computational design models, with the design targetF4132 andI432 space groups and closely corresponding overall architectures and protein-protein interfaces. The crystal unit cell dimensions can be systematically redesigned while retaining space group symmetry and overall architecture, and the crystals are both extremely porous and highly stable, enabling the robust scaffolding of inorganic nanoparticle arrays. Our approach thus enables the computational design of protein crystals with high accuracy, and since both structure and assembly are encoded in the primary sequence, provides a powerful new platform for biological material engineering.

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha helical coiled coils have such symmetric extendable architectures, but are limited by the relatively fixed geometry and flexibility of the helical protomers. Here, we describe a systematic approach to generating modular and rigid repeat protein oligomers with coincident C2to C8and superhelical symmetry axes that can be readily extended by repeat propagation. From these building blocks, we demonstrate that a wide range of unbounded fibers can be systematically designed by introducing hydrophilic surface patches that force staggering of the monomers; the geometry of such fibers can be precisely tuned by varying the number of repeat units in the monomer and the placement of the hydrophilic patches.

Context Although cancer and HIV/AIDS are common causes of death in Vietnam, limited data exist on their palliative care needs. As palliative care becomes part of Universal Health Coverage, evidence is needed to scale up appropriate care. Objectives To elicit from people with cancer or HIV/AIDS in Vietnam, and their caregivers, the specific multidimensional symptoms and concerns that cause serious health-related suffering. Methods Semistructured, qualitative, in-depth interviews were conducted with stage III or IV cancer patients, people with HIV/AIDS, and their caregivers at three cancer treatment centers and two HIV/AIDS treatment centers in northern, central, and southern Vietnam. Interviews were analyzed using thematic analysis. Results Sixty people were interviewed (21 cancer patients, 20 people with HIV/AIDS, 19 caregivers). Pain and other physical symptoms severely impacted their daily lives. Psychological distress—including sadness, depression, worry, and a feeling of having no future—was mentioned frequently, and it was exacerbated by disease progression and by social problems such as financial difficulties and, among people with HIV/AIDS, stigma. Caregivers also suffered physically and psychosocially. Spirituality emerged as a source of strength for patients. Findings highlighted patients' and family caregivers’ desire for more information about diagnosis, prognosis, and treatment, a shift toward individual decision-making. Conclusion The findings demonstrate common, multidimensional, and severe suffering among people living with cancer or HIV/AIDS and their caregivers in Vietnam. These qualitative data should guide development of optimum clinical assessment tools and palliative care services for these populations.

In pseudocyclic proteins such as TIM barrels, β barrels, and some helical transmembrane channels, a single subunit is repeated in a cyclic pattern, giving rise to a central cavity which can serve as a pocket for ligand binding or enzymatic activity. Inspired by these proteins, we devised a deep learning-based approach to broadly exploring the space of closed repeat proteins starting from only a specification of the repeat number and length. Biophysical data for 38 structurally diverse pseudocyclic designs produced in E. coli are consistent with the design models, and two crystal structures we were able to obtain are very close to the designed structures. Docking studies suggest the diversity of folds and central pockets provide effective starting points for designing small molecule binders or enzymes.

Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. Retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the novel nanoparticles we describe may be broadly useful in biotechnological applications.

Although research has identified effective evidence-based depression prevention interventions for diverse youth, little is known about how the intervention process unfolds with immigrant family youth. This study utilized a qualitative approach to explore cultural and clinical differences in the implementation of Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST) in two schools, one serving youth from primarily immigrant, Asian American families and the second, youth from mostly nonimmigrant, non-Hispanic White families. A total of 131 IPT–AST sessions were audio recorded, transcribed, and coded for presence and patterns of cultural and clinical constructs. Results revealed that sessions with immigrant family youth were more likely to contain discussions of interpersonal problems characterized by estrangement, goals of spending time together with important others, mentions of emotion suppression and academic achievement expectations, conversations about acculturation, differences in value orientation, and discomfort with implementing new intervention skills. Dialogue from interventionist and youth exchanges is presented to illustrate how these themes emerged and were addressed by interventionists in a culturally responsive manner. The study highlights how IPT–AST with immigrant family and Asian American youth may unfold differently compared to youth from nonimmigrant families. Implications of findings for providers are discussed.

Synthesis of 2-dodecanoyl furan is a crucial step in the formulation of oleo-furan sulfonates as bio-surfactants from biomass-derived furans and vegetable-oil-derived molecules. Herein, cross-ketonization of 2-furoic acid and lauric acid is proposed to produce the bio-surfactant precursor. Among the commonly reported metal oxide ketonization catalysts, the inexpensive and abundant iron oxides are demonstrated as effective and recyclable catalysts, enabling up to 77% selectivity to 2-dodecanoyl furan at 56% lauric acid conversion. Catalyst characterization by X-ray diffraction, H2 temperature-programmed reduction, and X-ray photoelectron spectroscopy indicates that Fe3O4 is the catalytically active and stable phase. 13C isotopic tracing experiments suggest that cross-ketonization on Fe3O4 proceeds via a β-keto acid intermediate.

OBJECTIVES: Although negotiation of family relatedness and personal autonomy is a key developmental task of adolescence, what is most adaptive for adolescents may vary across cultures. The purpose of the present study was to examine whether relations between family obligation values and adolescent internalizing symptoms may vary as a function of the level of parental autonomy support perceived by the adolescent, and to assess the extent to which such associations vary by ethnic group. METHODS: The study included 614 adolescents (Mean age = 15.57 years, 50% male) from Vietnamese-American (55%) and European-American (45%) backgrounds. Adolescents reported their: (a) family obligation values to (a1) respect, (a2) provide current assistance, and (a3) provide future support to the family, (b) perceived maternal and paternal autonomy support, and (c) internalizing symptoms. RESULTS: Effects of family obligation values differed across the three subdomains as a function of maternal autonomy support and ethnic group. Family obligation values to respect the family (a1, above) were related to lower levels of internalizing symptoms for both Vietnamese- and European-American adolescents who received high levels of maternal autonomy support. Ethnic differences emerged such that only among Vietnamese-American adolescents, there was a negative relation between current assistance values (a2, above) and internalizing symptoms among adolescents with high maternal autonomy support. CONCLUSIONS: Overall, findings highlight the importance for parents to nurture adolescents’ family obligation values while also promoting their autonomy development.

PURPOSE: Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial. METHODS AND MATERIALS: A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial. ABM for individual patients was defined as the subvolume of pelvic bone greater than the individual mean standardized uptake value on registered (18)F-fluorodeoxyglucose PET/CT images. Atlas-based and custom ABM segmentations were compared using the Dice similarity coefficient and mean distance to agreement and used to generate ABM-sparing intensity modulated radiation therapy plans. Dose-volume metrics and normal tissue complication probabilities of the two approaches were compared using linear regression. RESULTS: Atlas-based ABM volumes (mean [standard deviation], 548.4 [88.3] cm(3)) were slightly larger than custom ABM volumes (535.1 [93.2] cm(3)), with a Dice similarity coefficient of 0.73. Total pelvic bone marrow V(20) and D(mean) were systematically higher and custom ABM V(10) was systematically lower with custom-based plans (slope: 1.021 [95% confidence interval (CI), 1.005-1.037], 1.014 [95% CI, 1.006-1.022], and 0.98 [95% CI, 0.97-0.99], respectively). We found no significant differences between atlas-based and custom-based plans in bowel, rectum, bladder, femoral heads, or target dose-volume metrics. CONCLUSIONS: Atlas-based ABM segmentation can reduce pelvic bone marrow dose while achieving comparable target and other normal tissue dosimetry. This approach may allow ABM sparing in settings where PET/CT is unavailable.

The growing interest in biomass as a renewable feedstock drives research toward innovative processes and performance-advantaged bioproducts. Homogeneous metal salt solutions are promising media owi...

Background/objective The growingly diverse aging population presents a challenge for the geriatric workforce, particularly its capacity to effectively respond to the sociocultural and linguistic needs of ethnic minority older adults. Informed by research on the importance of culturally-competent care in reducing racial and ethnic health disparities, this study sought to understand the meaning of healthy aging from the perspectives of Korean American, Vietnamese American, and Latino older adults. Methods Interviews were conducted with 30 participants recruited from community-based organizations in Southern California. Results Several dimensions emerged in the participants' understanding of healthy aging: (1) having good physical and mental health (2) optimism and acceptance; (3) social connectedness; (4) taking charge of one's health; and (5) independence and self-worth. Conclusions Results could inform the development of a culturally-responsive geriatric healthcare system that takes into account older adults' beliefs, preferences, and needs to promote successful aging.

Health plans and risk-bearing provider organizations seek information sources to inform proactive interventions for patients at risk of adverse health events. Interventions should take into account the strong relationship between social context and health. This retrospective cohort study of a Medicare Advantage population examined whether a change in self-reported health-related quality of life (HRQOL) signals a subsequent change in healthcare needs.A retrospective longitudinal analysis of administrative claims data was conducted for participants in a Medicare Advantage plan with prescription drug coverage (MAPD) who responded to 2 administrations of the Centers for Disease Control and Prevention 4-item Healthy Days survey within 6-18 months during 2015-2018. Changes in HRQOL, as measured by the Healthy Days instrument, were compared with changes in utilization and costs, which were considered to be a reflection of change in healthcare needs.A total of 48,841 individuals met inclusion criteria. Declining HRQOL was followed by increases in utilization and costs. An adjusted analysis showed that every additional unhealthy day reported one year after baseline was accompanied by an $8 increase in monthly healthcare costs in the subsequent six months for the average patient.Declining HRQOL signaled subsequent increases in healthcare needs and utilization.Findings suggest that HRQOL assessments in general, and the Healthy Days instrument in particular, could serve as a leading indicator of the need for interventions designed to mitigate poor health outcomes and rising healthcare costs.III.

Family members provide the majority of caregiving to individuals living with Alzheimer’s disease (AD) and related dementias. Asian American families are disproportionately impacted by the burden of caregiving due to limited knowledge about the disease in this community. This study explored how Vietnamese American caregivers understand AD and provide care to family members with AD. Twenty caregivers who have provided care to a family member with AD participated in a semi-structured qualitative interview. Data were analyzed using thematic analysis. Several themes were identified in the caregivers’ understanding of AD: (a) “Now I know:” the disruptions, shocks and surprises leading up to the initial diagnosis; (b) The frustrations of managing family members’ cognitive impairments; (c) “Going with the flow:” challenges in managing personality and behavioral changes; (d) The exhaustion of around-the-clock caregiving; (e) “Taking it day by day” in the face of progressively worsening symptoms. Underlining the participants’ descriptions of AD was a shared understanding of the progressively worsening, complex and unpredictable nature of the disease that makes it challenging for family caregivers on a daily basis. Findings provide important implications for healthcare workers’ outreach to Vietnamese American families to ease the caregiving experience through culturally-responsive education, thereby enhancing the families’ ability to recognize the early symptoms and seek appropriate help.

We investigate the effects of heightened corporate social responsibility (CSR) risk, through environmental and social (E&S) incidents, on corporate financial policies. We test for this relation by investigating changes in corporate financial policies of unaffected but at-risk firms after an E&S incident. We find that firms draw down on cash holding, cut capital expenditure and borrow more debt. The changes in financial policies coincide with an increase in CSR investment, which in turn helps preventing future E&S incidents. The reaction is more pronounced in firms with weaker reputational capital and corporate governance due to their inability to absorb adverse CSR shocks. Overall, our analysis suggests that firms are responsive to heightened CSR risk.

While homogeneous metal halides have been shown to catalyze glucose to fructose isomerization, direct experimental evidence in support of the catalytically active species remains elusive. Here, we integrate direct speciation methods with kinetics to provide strong evidence for the active species of AlCl3 in glucose–fructose isomerization in water. We investigate the effect of Lewis (AlCl3) and Bronsted (HCl) acids on aluminum hydrolysis and glucose conversion. We demonstrate the interplay between the acids using the Optimum Logic Inc. speciation model (OLI software). We measure aqueous aluminum species and protons through in situ and ex situ 27Al quantitative nuclear magnetic resonance (qNMR) and pH measurements, respectively, and quantify aluminum nanoparticles through a combination of inductively coupled plasma-mass spectrometry (ICP-MS), dynamic light scattering (DLS), and ultrafiltration. Direct speciation measurements correlated with the glucose isomerization rate indicate that the hydrolyzed Al(III) complex [Al(H2O)4(OH)2]1+ is the active species in glucose isomerization.

Research with hard-to-reach, monolingual adults from ethnic minority communities can present a multitude of challenges throughout the research process. This presentation will highlight challenges and lessons learned from two pilot studies with Vietnamese-, Cambodian-, and Korean-American family caregivers aged 50 and older. The first study (n=9) implemented a one-on-one, telephone-based psychosocial intervention before the COVID-19 pandemic; the second is an ongoing study (n=12) consisting of a group-based intervention via Zoom. Throughout recruitment, the following challenges arose: addressing the lack of familiarity with research among caregivers, earning the trust of caregivers, and identifying creative ways to recruit caregivers to participate. During study implementation, common challenges included: caregivers’ unpredictable daily schedule that made it difficult to participate in the scheduled classes, caregivers feeling apprehensive about technology and Zoom, access to reliable internet, and facilitating participation and engaging the voices of caregivers over the phone or via Zoom. Strategies were identified to address these barriers: engaging the support and collaboration of trusted, bilingual and bicultural community-based providers, building culturally-responsive rapport with caregivers, and seeking continuous feedback from caregivers to improve the appeal of the project implementation. The COVID-19 pandemic added an additional layer of difficulty to the research, requiring creativity and flexibility in implementation that took into consideration caregivers’ heightened anxiety, distress, lack of participation due to around-the-clock care, and loss and grief. The challenges and lessons learned from these studies could guide the development of future research efforts and strategies to effectively engage older hard-to-reach, monolingual Asian American caregivers.

Metal chlorides are demonstrated to behave as bifunctional acid catalysts in organic media in the one-pot reductive etherification of 5-hydroxymethylfurfural (HMF) in 2-propanol toward production of biodiesel. Two competing reaction pathways, direct etherification to 5-(isopropoxymethyl)furfural and reductive etherification to 2,5-bis(alkoxymethyl)furan, are proposed with the selectivity depending on the metal ion. Furfural and furfuryl alcohol are used as model compounds to investigate each pathway individually. The roles of Lewis/Bronsted acidity of metal chlorides solution are elucidated by kinetic studies in conjunction with salt speciation using electrospray soft ionization mass spectrometer. Bronsted acidic species, generated from alcoholysis of the metal chlorides, are the predominant catalytically active species in etherification. On the other hand, partially hydrolyzed metal cations produced by alcoholysis/hydrolysis are responsible Lewis acid centers for furfural reduction to furfuryl alcohol. I...

Numerical weather prediction models tend to underestimate cloud presence and therefore often overestimate global horizontal irradiance (GHI). The assimilation of cloud water path (CWP) retrievals from geostationary satellites using an ensemble Kalman filter (EnKF) led to improved short-term GHI forecasts of the Weather Research and Forecasting (WRF) model in mid-latitudes in case studies. An evaluation of the method under tropical conditions and a quantification of this improvement for study periods of more than a few days is still missing. This paper focuses on the assimilation of CWP retrievals in three phases (ice, supercooled, and liquid) in a 6-hourly cycling procedure, and on the impact of this method on short-term forecasts of GHI for Reunion Island, a tropical island in the South-West Indian Ocean. The multi-layer gridded cloud properties of NASA Langley's Satellite ClOud and Radiation Property retrieval System (SatCORPS) are assimilated using the EnKF of the Data Assimilation Research Testbed (DART) manhattan release (revision 12002) and the advanced research WRF (ARW) v3.9.1.1. The ability of the method to improve cloud analyses and GHI forecasts is demonstrated and a comparison using independent radiosoundings shows a reduction of specific humidity bias in the WRF analyses, especially in the low and mid troposphere. Ground-based GHI observations at 12 sites on Reunion Island are used to quantify the impact of CWP DA. Over a total of 44 days during austral summer time, when averaged over all sites, CWP data assimilation has a positive impact on GHI forecasts for all lead times between 5 and 14 hours. Root Mean Squared Error and Mean Absolute Error are reduced by 4 % and 3 % respectively.

While the mechanisms of glucose transformation via heterogeneous metal-substituted BEA zeolites have recently been elucidated, understanding of the same chemistry in homogeneous metal salt catalysts in water is still limited. Here, we investigate the mechanisms of various Lewis acid metal(III) chlorides in glucose isomerization, epimerization, and other interconversions using nuclear magnetic resonance spectroscopy (13C NMR and 1H NMR). We show that the metal chlorides isomerize glucose to fructose via a C2–C1 intramolecular hydride transfer, despite their wide range of catalytic activity. Glucose epimerization to mannose proceeds via two parallel mechanisms, a reverse C2–C1 hydride transfer, and a C1–C2 intramolecular carbon shift (the Bilik reaction), with the hydride transfer being predominant. We hypothesize that the relative activity for the Bilik reaction correlates with the ionic radius of the catalyzing metal aqua cation, with an optimum at ∼1 A for lanthanide cations. In addition, we show that th...

We conduct a combined experimental and computational study to reveal the kinetics of tandem glucose isomerization and fructose dehydration to 5-hydroxymethylfurfural (HMF) over a bifunctional zeolite H-BEA-25 in water. The model accounts for multicomponent adsorption, homogeneous Bronsted acid catalyzed chemistry of fructose, intrinsic heterogeneous Lewis acid catalyzed isomerization, Bronsted acid catalyzed fructose dehydration, HMF rehydration, and humin formation chemistry. The octahedrally coordinated extra-framework Al sites catalyze glucose to fructose isomerization effectively. The activation energy for the isomerization in H-BEA-25 is between those reported for Ti-BEA and Sn-BEA. We reveal that tandem reactions exhibit multiple kinetic regimes. When a bifunctional catalyst with a fixed total number of acid sites is used (e.g., aluminosilicate zeolites), the HMF formation rate exhibits a volcano type curve vs. the Lewis to Bronsted acid site ratio. On the other hand, when the two types of sites are varied independently (e.g., in Sn-BEA and HCl), the HMF formation rate increases and then approaches a plateau with increasing Bronsted acid site density. These appear to be generic features of tandem reactions catalyzed by multiple or multifunctional catalysts. We show that materials with stronger sugar adsorption would produce HMF in significantly higher yields and higher rate than H-BEA. When HMF degradation reactions are suppressed, a ratio of Lewis to Bronsted acid sites of ∼0.3 maximizes the HMF rate produced from glucose and the HMF yield (which is predicted to be ∼60% at 130 °C). These predictions provide a framework for understanding and improving tandem reactions catalyzed by heterogeneous catalysts.

Background Labor and birth companionship is a key aspect of respectful maternity care. Lack of companionship deters women from accessing facility-based delivery care, though formal and informal policies against companionship are common in sub-Saharan African countries. Aim To identify client and provider factors associated with labor and birth companionship Design Cross-sectional evaluation among delivery clients and providers in 61 health facilities in Kigoma Region, Tanzania, April–July 2016. Methods Multilevel, mixed effects logistic regression analyses were conducted on linked data from providers (n = 249) and delivery clients (n = 935). Outcome variables were Companion in labor and Companion at the time of birth. Findings Less than half of women reported having a labor companion (44.7%) and 12% reported having a birth companion. Among providers, 26.1% and 10.0% reported allowing a labor and birth companion, respectively. Clients had significantly greater odds of having a labor companion if their provider reported the following traits: working more than 55 hours/week (aOR 2.46, 95% CI 1.23–4.97), feeling very satisfied with their job (aOR 3.66, 95% CI 1.36–9.85), and allowing women to have a labor companion (aOR 3.73, 95% CI 1.58–8.81). Clients had significantly lower odds of having a labor companion if their provider reported having an on-site supervisor (aOR 0.48, 95% CI 0.24–0.95). Clients had significantly greater odds of having a birth companion if they self-reported labor complications (aOR 2.82, 95% CI 1.02–7.81) and had a labor companion (aOR 44.74, 95% CI 11.99–166.91). Clients had significantly greater odds of having a birth companion if their provider attended more than 10 deliveries in the last month (aOR 3.43, 95% CI 1.08–10.96) compared to fewer deliveries. Conclusions and implications for practice These results suggest that health providers are the gatekeepers of companionship, and the work environment influences providers’ allowance of companionship. Facilities where providers experience staff shortages and high workload may be particularly responsive to programmatic interventions that aim to increase staff acceptance of birth companionship.

While homogeneous metal halides have been shown to catalyze glucose to fructose isomerization, direct experimental evidence in support of the catalytically active species remains elusive. Here, we integrate direct speciation methods with kinetics to provide strong evidence for the active species of AlCl

Background: SMYD2 is a methyltransferase whose role in cancer is poorly understood and is lacking cell-active chemical tools. Results: We describe LLY-507, a small molecule inhibitor of SMYD2. Conclusion: LLY-507 is potent, selective, cell-active, and binds SMYD2 in a high resolution co-crystal. Significance: LLY-507 is a first-in-class cell-potent chemical probe that will be valuable in dissecting SMYD2 biology., SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. However, the mechanism(s) by which SMYD2 promotes oncogenesis is not understood. A small molecule probe for SMYD2 would allow for the pharmacological dissection of this biology. In this report, we disclose LLY-507, a cell-active, potent small molecule inhibitor of SMYD2. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. A 1.63-Å resolution crystal structure of SMYD2 in complex with LLY-507 shows the inhibitor binding in the substrate peptide binding pocket. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys370 at submicromolar concentrations. We used LLY-507 to further test other potential roles of SMYD2. Mass spectrometry-based proteomics showed that cellular global histone methylation levels were not significantly affected by SMYD2 inhibition with LLY-507, and subcellular fractionation studies indicate that SMYD2 is primarily cytoplasmic, suggesting that SMYD2 targets a very small subset of histones at specific chromatin loci and/or non-histone substrates. Breast and liver cancers were identified through in silico data mining as tumor types that display amplification and/or overexpression of SMYD2. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. These findings suggest that LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes.

A kinetic model for the tandem conversion of glucose to 5-hydroxymethylfurfural (HMF) through fructose in aqueous CrCl3–HCl solution was developed by analyzing experimental data. We show that the coupling of Lewis and Bronsted acids in a single pot overcomes equilibrium limitations of the glucose–fructose isomerization leading to high glucose conversions and identify conditions that maximize HMF yield. Adjusting the HCl/CrCl3 concentration has a more pronounced effect on HMF yield at constant glucose conversion than that of temperature or CrCl3 concentration. This is attributed to the interactions between HCl and CrCl3 speciation in solution that leads to HMF yield being maximized at moderate HCl concentrations for each CrCl3 concentration. This volcano-like behavior is accompanied with a change in the rate-limiting step from fructose dehydration to glucose isomerization as the concentration of the Bronsted acid increases. The maximum HMF yield in a single aqueous phase is only modest and appears independent of catalysts’ concentrations as long as they are appropriately balanced. However, it can be further maximized in a biphasic system. Our findings are consistent with recent studies in other tandem reactions catalyzed by different catalysts.

Posttranslational modifications of histone tails are a key contributor to epigenetic regulation. Histone H3 Arg26 and Lys27 are both modified by multiple enzymes, and their modifications have profound effects on gene expression. Citrullination of H3R26 by PAD2 and methylation of H3K27 by PRC2 have opposing downstream impacts on gene regulation; H3R26 citrullination activates gene expression, and H3K27 methylation represses gene expression. Both of these modifications are drivers of a variety of cancers, and their writer enzymes, PAD2 and EZH2, are the targets of drug therapies. After biochemical and cell-based analysis of these modifications, a negative crosstalk interaction is observed. Methylation of H3K27 slows citrullination of H3R26 30-fold, whereas citrullination of H3R26 slows methylation 30,000-fold. Examination of the mechanism of this crosstalk interaction uncovered a change in structure of the histone tail upon citrullination which prevents methylation by the PRC2 complex. This mechanism of crosstalk is reiterated in cell lines using knockdowns and inhibitors of both enzymes. Based our data, we propose a model in which, after H3 Cit26 formation, H3K27 demethylases are recruited to the chromatin to activate transcription. In total, our studies support the existence of crosstalk between citrullination of H3R26 and methylation of H3K27.

With technological advancement of thermocatalytic processes for valorizing renewable biomass carbon, development of effective separation technologies for selective recovery of bioproducts from complex reaction media and their purification becomes essential. The high thermal sensitivity of biomass intermediates and their low volatility and high reactivity, along with the use of dilute solutions, make the bioproducts separations energy intensive and expensive. Novel separation techniques, including solvent extraction in biphasic systems and reactive adsorption using zeolite and carbon sorbents, membranes, and chromatography, have been developed. In parallel with experimental efforts, multiscale simulations have been reported for predicting solvent selection and adsorption separation. We discuss various separations that are potentially valuable to future biorefineries and the factors controlling separation performance. Particular emphasis is given to current gaps and opportunities for future development.

© Meharry Medical College. Purpose. This study examines the use of complementary and alternative medicine (CAM) by ethnicity/race among patients with type 2 diabetes. Subjects and methods. Four hundred and ten (410) patients with type 2 diabetes recruited from an academic-medical center completed a survey assessing CAM use, diabetes status, and sociodemographic characteristics. Results. Several significant ethnic/racial differences were observed in CAM use (both in the types of providers seen as well as in the herbs and dietary supplements used). Although White patients reported using CAM in addition to their diabetes medication (mean [SD] 4.9 [0.4] on a scale from 1=never to 5=always) more frequently than Mexican American patients (3.1 [1.6], p