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Quantum computers promise to solve certain computational problems much faster than classical computers. However, current quantum processors are limited by their modest size and appreciable error rates. Recent efforts to demonstrate quantum speedups have therefore focused on problems that are both classically hard and naturally suited to current quantum hardware, such as sampling from complicated—although not explicitly useful—probability distributions1–3. Here we introduce and experimentally demonstrate a quantum algorithm that is similarly well suited to current hardware, but which samples from complicated distributions arising in several applications. The algorithm performs Markov chain Monte Carlo (MCMC), a prominent iterative technique4, to sample from the Boltzmann distribution of classical Ising models. Unlike most near-term quantum algorithms, ours provably converges to the correct distribution, despite being hard to simulate classically. But like most MCMC algorithms, its convergence rate is difficult to establish theoretically, so we instead analysed it through both experiments and simulations. In experiments, our quantum algorithm converged in fewer iterations than common classical MCMC alternatives, suggesting unusual robustness to noise. In simulations, we observed a polynomial speedup between cubic and quartic over such alternatives. This empirical speedup, should it persist to larger scales, could ease computational bottlenecks posed by this sampling problem in machine learning5, statistical physics6and optimization7. This algorithm therefore opens a new path for quantum computers to solve useful—not merely difficult—sampling problems.

The performance of computational methods for many-body physics and chemistry is strongly dependent on the choice of the basis used to formulate the problem. Hence, the search for similarity transformations that yield better bases is important for progress in the field. So far, tools from theoretical quantum information have not been thoroughly explored for this task. Here we take a step in this direction by presenting efficiently computable Clifford similarity transformations for the molecular electronic structure Hamiltonian, which expose bases with reduced entanglement in the corresponding molecular ground states. These transformations are constructed via block-diagonalization of a hierarchy of truncated molecular Hamiltonians, preserving the full spectrum of the original problem. We show that the bases introduced here allow for more efficient classical and quantum computations of ground-state properties. First, we find a systematic reduction of bipartite entanglement in molecular ground states as compared to standard problem representations. This entanglement reduction has implications in classical numerical methods, such as those based on the density matrix renormalization group. Then, we develop variational quantum algorithms that exploit the structure in the new bases, showing again improved results when the hierarchical Clifford transformations are used.

The mortality benefit of early recognition of infection with empiric initiation of antibiotics is well documented. (1) Pseudomonas aeruginosa has been a particularly problematic bacterial infection whose antibiotic resistance is [...]

This article states that in 2011, the America Invents Act altered the U.S. Patent and Trademark Office's policymaking authority, notably through the establishment of the Patent Trial and Appeal Board. It also highlights legal cases that have shaped the USPTO's policymaking landscape, such as Animal Legal Defense Fund v. Quigg and Cuozzo Speed Technologies, LLC v. Lee. It mentions that AIA expanded the USPTO's policymaking powers, granting it the ability to regulate post-grant proceedings.

A wave of global criticism confronted Brunei's full enforcement of the Syariah Penal Code (SPC) this year. United Nations High Commissioner for Human Rights, Michelle Bachelet, appealed to halt the [...]

Purpose: Intraoperative tranexamic acid (TXA) is used to reduce blood loss and the need for transfusions following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite evidence in literature and local practice protocols supporting TXA as a part of standard of care for joint arthroplasty, TXA administration is underutilized. We aimed to use group-facilitated audit and feedback as the foundation of a knowledge translation strategy to increase TXA use for THA and TKA procedures. Methods: Anesthesiologists consented to receive two data reports summarizing their individual rates of TXA use and postoperative blood transfusions compared with site peers. Variables collected included patient demographics, TXA usage, and the frequency and volume of red blood cell transfusions administered in the 72-hr postoperative period. The facilitated feedback session discussed report findings and focused on factors contributing to local practice patterns and opportunities for change. Results: Tranexamic acid use increased for THA procedures at the intervention site from 66.6 to 74.4% (absolute change, 7.9%; 95% confidence interval [CI], 2.4 to 13.3). Likewise, TXA use for TKA procedures increased from 62.4 to 82.3% (absolute change, 19.9%; 95% CI 15.0 to 25.0). Conclusions: Physicians and their teams were able to review their practice data on TXA utilization, reflect on differences compared with evidence-based guidelines, discuss findings with peers, and identify opportunities for improvement. The intervention increased the use of TXA for both TKA and THA and shifted the dosage to better align with evidence-based practice guidelines.

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The novel severe acute respiratory syndrome coronavirus-2 virus, which has led to the global coronavirus disease-2019 (COVID-19) pandemic is known to adversely affect the cardiovascular system through multiple mechanisms. In this international, multicenter study conducted by the World Alliance Societies of Echocardiography, we aim to determine the clinical and echocardiographic phenotype of acute cardiac disease in COVID-19 patients, to explore phenotypic differences in different geographic regions across the world, and to identify parameters associated with in-hospital mortality.

Underground flows of acidic fluids through fractured rock can create new porosity and increase accessibility to hazardous trace elements such as arsenic. In this study, we developed a custom microfluidic cell for an in operandosynchrotron experiment using X-ray attenuation. The experiment mimics reactive fracture flow by passing an acidic fluid over a surface of mineralogically heterogeneous rock from the Eagle Ford shale. Over 48 h, calcite was preferentially dissolved, forming an altered layer 200–500 μm thick with a porosity of 63–68% and surface area >10× higher than that in the unreacted shale as shown by xCT analyses. Calcite dissolution rate quantified from the attenuation data was 3 × 10–4mol/m2s and decreased to 3 × 10–5mol/m2s after 24 h because of increasing diffusion limitations. Erosion of the fracture surface increased access to iron-rich minerals, thereby increasing access to toxic metals such as arsenic. Quantification using XRF and XANES microspectroscopy indicated up to 0.5 wt % of As(-I) in arsenopyrite and 1.2 wt % of As(V) associated with ferrihydrite. This study provides valuable contributions for understanding and predicting fracture alteration and changes to the mobilization potential of hazardous metals and metalloids.

Pathologic inflammation in response to injury, infection, or oxidative stress is a proposed mechanism relating cognitive decline to dementia. The kynurenine pathway and thioredoxin-interacting protein (TXNIP) activity regulate inflammation and neurotoxicity in Alzheimer disease (AD). We examined cognitive deficits, kynurenine pathway mediators, TXNIP, and oxidative damage in the cerebrum and spleen, including inflammatory cytokine production by stimulated splenocytes, from female triple transgenic (3xTg-AD) mice in early and late stages of disease progression, and characterized tissue-specific epigenetic regulation of Txnipgene expression. We show that cognitive deficits in 7-month–old 3xTg-AD mice are associated with a stable increase in cerebrum and spleen tryptophan metabolites, with a concomitant increase in amyloid β 40 (Aβ40)/Aβ42and tau/hyperphosphorylated tau pathologies and a coordinated reduction in spleen proinflammatory cytokine production in 17-month–old mice. The enhanced cerebrum TXNIP expression is associated with increased histone acetylation, transcription factor [Aβ42or CCCTC-binding factor (CTCF)] binding, and Txnippromoter hypomethylation, whereas the attenuated spleen TXNIP expression is associated with increased histone methylation, reduced CTCF binding, and Txnippromoter hypermethylation. These results suggest a causal relationship among epigenomic state, TXNIP expression, cerebral-spleen tryptophan metabolism, inflammatory cytokine production, and cognitive decline; and they provide a potential mechanism for Txnipgene regulation in normal and pathologic conditions, suggesting TXNIP levels may be a useful predictive or diagnostic biomarker for Aβ40/Aβ42targeted AD therapies.

Using recent advances in X-ray microscopy, this study aimed to elucidate mechanisms of uptake, subcellular distribution, and translocation of functionalized CeO2MNM (manufactured nanomaterials), having different charges, by tomato plants (Solanum lycopersicumcv Micro-Tom). We found that plant growth and Ce concentration in tissues were functions of surface charge and exposure concentration with root to shoot translocation being much greater for negatively charged CeO2than positive or neutral CeO2. Mechanisms of entry into roots and translocation within plants were examined using X-ray nano- and microprobes. There were dramatic differences in the tissue and subcellular distributions of Ce in plant roots exposed to dextran-coated CeO2nanoparticles conjugated with positive, neutral and negative functional groups. Positively charged CeO2remained mainly bound to the epidermis of the root with little present in the apoplast or cytoplasm. Negatively charged CeO2was found in the cytoplasm throughout the root cross section, and negatively charged CeO2was found within the apoplast in the cortex and both the apoplast and the cytoplasm in the vasculature. Neutral CeO2likely entered through the gaps between epidermal cells being sloughed off during root growth and penetrated deeper into the interior of the roots (vasculature) viaa combination of apoplastic and symplastic transport. Evidence of symplastic Ce transport was observed with the neutrally and negatively charged particles. We observed evidence of endocytosis as the mechanism for entry into the symplast allowing for entry into the xylem. This study provides critical information on how particle surface chemistry influences the biodistribution and cellular localization of nanomaterials in plants and is to date the highest resolution X-ray imaging of nanomaterials in plant cells.

Root uptake and translocation of engineered nanoparticles (NPs) by plants are dependent on both plant species and NP physicochemical properties. To evaluate the influence of NP surface charge and differences in root structure and vasculature on cerium distribution and spatial distribution within plants, two monocotyledons (corn and rice) and two dicotyledons (tomato and lettuce) were exposed hydroponically to positively-charged, negatively-charged, and neutral ∼4 nm CeO2NPs. Leaves were analyzed using synchrotron-based X-ray fluorescence microscopy to provide lateral Ce spatial distribution. Surface charge mediated CeO2NP interactions with roots for all plant species. Positively charged CeO2NPs associated to the roots more than the negatively charged NPs due to electrostatic attraction/repulsion to the negatively charged root surfaces, with the highest association for the tomato, likely due to higher root surface area. The positive NPs remained primarily adhered to the roots untransformed, while the neutral and negative NPs were more efficiently translocated from the roots to shoots. This translocation efficiency was highest for the tomato and lettuce compared to corn and rice. Across all plant species, the positive and neutral treatments resulted in the formation of Ce clusters outside of the main vasculature in the mesophyll, while the negative treatment resulted in Ce primarily in the main vasculature of the leaves. Comparing leaf vasculature, Ce was able to move much further outside of the main vasculature in the dicot plants than monocot plants, likely due to the larger airspace volume in dicot leaves compared to monocot leaves. These results provide valuable insight into the influence of plant structure and NP properties on metal transport and distribution of NPs in plants.

Clinical PET/MR imaging is being implemented at institutions worldwide as part of the standard-of-care imaging for select oncology patients. This article focuses on oncologic applications of PET/MR imaging in cancers of the head and neck. Although current published literature is relatively sparse, the potential benefits of a hybrid modality of PET/MR imaging are discussed along with several possible areas of research. With the increasing number of PET/MR imaging scanners in clinical use and ongoing research, the role of PET/MR imaging in the management of head and neck cancer is likely to become more evident in the near future.

Metal contaminants in soils can persist for millennia, causing lasting negative impacts on local ecosystems. Long‐term contaminant bioavailability is related to soil pH and to the strength and stability of solid‐phase associations. We combined physical density separation with synchrotron‐based microspectroscopy to reduce solid‐phase complexity and to study Zn speciation in field‐contaminated soils. We also investigated Zn uptake in two Zn‐hyperaccumulating ecotypes of Noccaea caerulescens(Ganges and Prayon). Soils were either moderately contaminated (500–800 mg Zn kg−1via contaminated biosolids application) or grossly enriched (26,000 mg Zn kg−1via geogenic enrichment). Soils were separated using sodium polytungstate into three fractions: light fraction (LF) (<1.6 g cm−3), medium fraction (MF) (1.6–2.8 g cm−3), and heavy fraction (HF) (>2.8 g cm−3). Approximately 45% of the total Zn was associated with MF in biosolids‐contaminated soils. From these data, we infer redistribution to the MF after biosolids application because Zn in biosolids is principally associated with HF and LF. Our results suggest that increasing proportions of HF‐associated Zn in soils may be related to greater relative Zn removal by Zn hyperaccumulating plants. Using density fractions enabled assessment of Zn speciation on a microscale despite incomplete fractionation. Analyzing both density fractions and whole soils revealed certain phases (e.g., ZnS, Zn coprecipitated with Fe oxides) that were not obvious in all analyses, indicating multiple views of the same soils enable a more complete understanding of Zn speciation. Ice embedding is a preferable method to prepare thin sections for μXAS analysis.Soil phases essential for retaining Zn may be obscured in complex samples.Zn removal is soil dependent and does not match well with single parameters.Zn redistribution can occur over decades after contamination.Solid phase Zn redistribution can continually alter Zn bioavailability.

IMPORTANCE: Surgeons need to understand the expected outcomes for super obese patients undergoing tracheotomy to appropriately counsel patients and families about likely risks and benefits. OBJECTIVE: To determine the outcomes, complications, and mortality after tracheotomy in super obese patients (those with a body mass index [BMI] greater than 50). DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of billing records from a tertiary care academic medical center from November 1, 2010, through June 30, 2013, to identify patients undergoing tracheotomy. Medical records were reviewed to identify patients with a BMI (calculated as weight in kilograms divided by height in meters squared) greater than 50 and a control group with a BMI of 30 to 50. Patient characteristics, including BMI, age, race/ethnicity, primary diagnosis for hospitalization, medical comorbidities, and surgical technique, were measured. MAIN OUTCOMES AND MEASURES: The primary outcome measure was dependence on tracheostomy at discharge. Secondary outcomes included rates of ventilator dependence, mortality, postoperative complications, and discharge disposition. RESULTS: The super obese population included 31 patients and was predominantly African American (20 patients [65%]) and female (21 patients [68%]). Mean BMI of super obese patients was 64.0 (range, 50.2-95.5). The obese patient population was mainly African American (25 patients [74%]) and female (17 patients [50%]). Twenty-five of 31 super obese patients (81%) were discharged with a tracheotomy tube in place, compared with 16 of 34 obese patients (52%). Seven patients (23%) in the super obese group were ventilator dependent at discharge, compared with 4 patients (13%) in the obese group. Only 2 of the super obese patients (3%) were decannulated before discharge, compared with 15 (44%) in the obese group. In-hospital mortality was similar for the 2 groups (super obese, 4 patients [13%] and obese, 3 patients [9%]). The overall complication rate was 19% in the super obese group (6 patients) compared with 6% in the obese group (2 patients). Super obese patients were less likely to be discharged to a health care facility (17 patients [55%]) compared with patients in the obese group (22 patients [65%]). CONCLUSIONS AND RELEVANCE: Tracheotomy in super obese patients is a safe and effective strategy for airway management. Critically ill, super obese patients have a high likelihood of remaining dependent on a tracheotomy or ventilator at the time of discharge.

Transthoracic echocardiography is the leading cardiac imaging modality for patients admitted with COVID-19, a condition of high short-term mortality. The aim of this study was to test the hypothesis that artificial intelligence (AI)–based analysis of echocardiographic images could predict mortality more accurately than conventional analysis by a human expert.

I don't mean to put down all the chicks who want to skate out there, but seriously, you're fucking it all up. It's either you skate or you don't--just stop [...]

Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress–like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure.

Cathode solubility in batteries can lead to decreased and unpredictable long-term battery behavior due to transition metal deposition on the negative electrode such that it no longer supports high current. Analysis of negative electrodes from cells containing vanadium oxide or phosphorus oxide based cathode systems retrieved after long-term testing was conducted. This report demonstrates the use of synchrotron based X-ray microfluorescence (XRμF) to map negative battery electrodes in conjunction with microbeam X-ray absorption spectroscopy (μXAS) to determine the oxidation states of the metal centers resident in the solid electrolyte interphase (SEI) and at the electrode surface. Based on the empirical findings, a conceptual model for the location of metal ions in the SEI and their role in impacting lithium ion mobility at the electrode surfaces is proposed.

The article discusses a court case where the U.S. Supreme Court held that it is unconstitutional to execute the intellectually disabled and that Florida's bright-line IQ cutoff was unconstitutional. Florida courts found defendant Freddie Lee Hall fit to die despite his suffering from intellectual deficiencies throughout his life. The Court stated that persons faced with the most severe sanction should have a fair opportunity to show that the Constitutions prohibits their execution.

A number of synchrotron X-ray fluorescence microprobes (XFMs) around the world offer synchrotron X-ray microdiffraction (µXRD) to enhance mineral phase identification in geological and other environmental samples. Synchrotron µXRD can significantly enhance micro X-ray fluorescence and micro X-ray absorption fine structure measurements by providing direct structural information on the identity of minerals, their crystallinity, and potential impurities in crystal structures. The information is useful to understand the sequestration of metals in mineral deposits, mineral processing residues, soils, or sediments. Synchrotron µXRD was employed to characterize a surficial calcrete uranium (U) ore sample and to illustrate its usefulness in conjunction with U LIII µXANES analysis. µXRD and U LIII µXANES revealed that the mineral carnotite [K2(UO2)2(V2O8)·nH2O, n= 0, 1, 2, or 3] was not the sole U bearing mineral phase present and that surface complexes and or an amorphous precipitate were present as well. Unit-cell analysis from the µXRD patterns revealed that the interlayer spacing of carnotite was not uniform and that significant unit-cell volume expansions occurred likely because of variable cations (K+, Rb+, and Sr2+) and variably hydrated interlayer cations being present in the interlayer. Oriented specimen, single crystal effects, and the fixed orientation of the sample relative to the incident beam and the charge-coupled device camera limit the number of visible reflections and complicate mineral phase identification. With careful analysis of multiple structural analysis tools available at XFMs, however, a strong link between X-ray amorphous and X-ray crystalline materials in geologic and environmental samples can be established.

Functional magnetic resonance imaging (fMRI) is used clinically to map the visual cortex before brain surgery or other invasive treatments to achieve an optimal balance between therapeutic effect and the avoidance of postoperative vision deficits. Clinically optimized stimuli, behavioral task, analysis, and displays permit identification of cortical subregions supporting high-acuity central vision that is critical for reading and other essential visual functions. Emerging techniques such as resting-state fMRI may facilitate the use of fMRI–based vision mapping in a broader range of patients.

To determine the return to active duty rate of military service members undergoing lower extremity limb salvage while using a novel custom orthosis and specialized rehabilitation compared with those receiving a novel custom orthosis alone.

BACKGROUND: In Alzheimer's disease (AD), alterations in metal homeostasis, including the accumulation of metal ions in the plaques and an increase of iron in the cortex, have been well documented but the mechanisms involved are poorly understood.OBJECTIVE: In this study, we compared the metal content in the plaques and the iron speciation in the cortex of three mouse models, two of which show neurodegeneration (5xFAD and Tg-SwDI/NOS2−/−) (CVN) and one that shows very little neurodegeneration (PSAPP).METHODS: The Fe, Cu and Zn contents and speciation were determined using synchrotron X-ray fluorescence microscopy (XFM) and X-ray absorption spectroscopy (XAS), respectively.RESULTS: In the mouse models with reported significant neurodegeneration, we found that plaques contained ~25% more copper compared to the PSAPP mice. The iron content in the cortex increased at the late stage of the disease in all mouse models, but iron speciation remains unchanged.CONCLUSIONS: The elevation of copper in the plaques and iron in the cortex is associated with AD severity, suggesting that these redox-active metal ions may be inducing oxidative damage and directly influencing neurodegeneration.

Debate over agricultural methods and productivity during the Preclassic and Classic Maya period (1000 BCE to 900 CE) focuses on the agronomic utility of both upland and lowland soil resources of the karst topography characteristic of northern Guatemala and much of the Yucatan peninsula. In settings where direct evidence of agriculture is sparse, stable carbon (C) isotope evidence from soil organic matter (SOM) provides information on past vegetation changes related to ancient maize agriculture. Areas of ancient sustained maize cultivation can be identified in an ecosystem dominated by C3forest vegetation because of the unique C4photosynthetic pathway of maize. The decomposition of plant materials with divergent photosynthetic mechanisms (C3versus C4) results in SOM with correspondingly distinct stable C isotope ratios (δ13C). Such differences are preserved and detectable within the refractory humin fraction of the SOM. This study analyzes the physical and chemical soil properties including stable C isotopes of soils collected from upland and lowland locations near Tikal, Guatemala. Toeslope soils contained strong isotopic evidence of C4vegetation likely the result of ancient maize agriculture, while the evidence from shallow soils of the summit and backslopes was less conclusive. In both upland and lowland contexts, however, the stronger evidence of ancient vegetation shifts associated with maize agriculture was found in the deeper fine‐textured soils in the footslopes and toeslopes. Examination of soils on toeslopes revealed evidence of deposition from erosional processes upslope that may have been related to the spread of agriculture to less productive soils over time.

Many wounded warriors experienced high-energy lower-extremity trauma (HELET) that may be limb threatening. Volumetric muscle loss, posttraumatic osteoarthritis, nerve injuries, and pain may severely limit physical function. Several wounded warriors express a strong desire to return to their units and be deployed in their original military occupational specialty. We began the return-to-run (RTR) clinical pathway at our institution 2 years ago to facilitate high-performance goals such as these. It involves an energy storing ankle foot orthosis, the intrepid dynamic exoskeletal orthosis in combination with high-intensity, progression-oriented rehabilitation. We sought to determine the rate of deployment or predeployment training after participation in this noninvasive intervention.

Plasma-induced damage to low-k dielectric materials can be quantified by separation of the effects of charged-particle bombardment, photon bombardment, and gas-radical flux. For ion and photon bombardment, the spatial location and extent of the damage can be determined. Damage effects from radical flux will be shown to be small. Both SiCOH and photo-programmable low-k (PPLK) dielectrics will be discussed.

The ability to return to running and sports participation after lower extremity limb salvage has not been well documented previously. Although the ability to ambulate without pain or assistive devices is generally a criteria for a good limb salvage outcome, many patients at our institution have expressed a desire to return to a more athletic lifestyle to include running and sports participation. The purpose of this study was to investigate the types of athletic endeavors our high-energy lower extremity trauma patients were able to pursue after limb salvage.

In this article the authors discuss the provisions of the Foreign Corrupt Practices Act (FCPA) as enforced by the Department of Justice and the Securities and Exchange Commission in the U.S. They examine the prohibitions and coverage of the legislation against bribery practices. They enumerate instances where the government can prove an FCPA violation from companies and individuals. Furthermore, they also examine the internal controls of the legislation.

This study explored and characterized soil physical and chemical properties to determine how the ancient Maya of Chunchucmil, Yucatán, Mexico, fed themselves. Our objectives were to examine the soil resources and the areas of agricultural importance surrounding Chunchucmil and to search for evidence of agricultural intensification of soils by night soil and charcoal amendments. The C isotopic signature of ancient C4crops was not detected, suggesting that either maize (Zea maysL.) was not extensively produced or that the mix of native C3and C4plants in the savanna hid the signature. There were no soil chemical or biomarker evidences of ancient agricultural intensification, suggesting that ancient agriculture was mainly based on shifting cultivation and arboriculture at Chunchucmil. Concentrations of black carbon, Ca, P, K, Mg, and organic C within urban and rural settlements were enhanced, but probably by incidental human activities. We estimate that the land requirement to sustain the population of Chunchucmil at its height would have been greater than the available resources based on traditional agricultural methods. We cannot ignore the possibilities of intensification techniques, like intensive weeding, watering, and organic fertilizers that would have left no or only modestly elevated major elements. But it is probable that the ancient Maya of Chunchucmil traded marine and estuary products from the Gulf Coast and other high‐value trade items for imported agricultural products.

Manganese (Mn) exists as Mn(II), Mn(III), or Mn(IV) in soils, and the Mn oxidation state controls the roles of Mn in numerous environmental processes. However, the variations of Mn oxidation states with climate remain unknown. We determined the Mn oxidation states in highly weathered bulk volcanic soils (primary minerals free) across two rainfall gradients covering mean annual precipitation (MAP) of 0.25–5 m in the Hawaiian Islands. With increasing MAP, the soil redox conditions generally shifted from oxic to suboxic and to anoxic despite fluctuating at each site; concurrently, the proportions of Mn(IV) and Mn(II) decreased and increased, respectively. Mn(III) was low at both low and high MAP, but accumulated substantially, up to 80% of total Mn, in soils with prevalent suboxic conditions at intermediate MAP. Mn(III) was likely hosted in Mn(III,IV) and iron(III) oxides or complexed with organic matter, and its distribution among these hosts varied with soil redox potentials and soil pH. Soil redox conditions and rainfall-driven leaching jointly controlled exchangeable Mn(II) in soils, with its concentration peaking at intermediate MAP. The Mn redox chemistry was at disequilibrium, with the oxidation states correlating with long-term average soil redox potentials better than with soil pH. The soil redox conditions likely fluctuated between oxic and anoxic conditions more frequently at intermediate than at low and high MAP, creating biogeochemical hot spots where Mn, Fe, and other redox-sensitive elements may be actively cycled.

Abstract: Microarray studies yield data sets consisting of a large number of candidate predictors (genes) on a small number of observations (samples). When interest lies in predicting phenotypic class using gene expression data, often the goals are both to produce an accurate classifier and to uncover the predictive structure of the problem. Most machine learning methods, such as -nearest neighbors, support vector machines, and neural networks, are useful for classification. However, these methods provide no insight regarding the covariates that best contribute to the predictive structure. Other methods, such as linear discriminant analysis, require the predictor space be substantially reduced prior to deriving the classifier. A recently developed method, random forests (RF), does not require reduction of the predictor space prior to classification. Additionally, RF yield variable importance measures for each candidate predictor. This study examined the effectiveness of RF variable importance measures in identifying the true predictor among a large number of candidate predictors. An extensive simulation study was conducted using 20 levels of correlation among the predictor variables and 7 levels of association between the true predictor and the dichotomous response. We conclude that the RF methodology is attractive for use in classification problems when the goals of the study are to produce an accurate classifier and to provide insight regarding the discriminative ability of individual predictor variables. Such goals are common among microarray studies, and therefore application of the RF methodology for the purpose of obtaining variable importance measures is demonstrated on a microarray data set. [Copyright &y& Elsevier]

This paper reviews progress in phytoextraction of soil elements and illustrates the key role of hyperaccumulator plant species in useful phytoextraction technologies. Much research has focused on elements which are not practically phytoextracted (Pb); on addition of chelating agents which cause unacceptable contaminant leaching and are cost prohibitive; and on plant species which offer no useful phytoextraction capability (e.g., Brassica junceaCzern). Nickel phytoextraction by Alyssumhyperaccumulator species, which have been developed into a commercial phytomining technology, is discussed in more detail. Nickel is ultimately accumulated in vacuoles of leaf epidermal cells which prevents metal toxicity and provides defense against some insect predators and plant diseases. Constitutive up‐regulation of trans‐membrane element transporters appears to be the key process that allows these plants to achieve hyperaccumulation. Cadmium phytoextraction is needed for rice soils contaminated by mine wastes and smelter emissions with 100‐fold more soil Zn than Cd. Although many plant species can accumulate high levels of Cd in the absence of Zn, when Cd/Zn > 100, only Thlaspi caerulescensfrom southern France has demonstrated the ability to phytoextract useful amounts of Cd. Production of element‐enriched biomass with value as ore or fertilizer or improved food (Se) or feed supplement may offset costs of phytoextraction crop production. Transgenic phytoextraction plants have been achieved for Hg, but not for other elements. Although several researchers have been attempting to clone all genes required for effective hyperaccumulation of several elements, success appears years away; such demonstrations will be needed to prove we have identified all necessary processes in hyperaccumulation.

Abstract: The recent trend toward increasing packing density and the demand for improved reliability have dramatically challenged ultra large scale integrated circuit technologists to develop more robust fabrication processes. Finer feature sizes and the addition of layers of interconnect, combined with large mechanical stresses, have greatly exacerbated the insidious problem of stress-induced voiding—open circuits can appear in Al lines immediately after fabrication or after years of shelf storage. Finite element analysis shows that one of the prime candidates for controlling the root cause of the failure mechanism, stress-assisted grain-boundary diffusion, is carefully engineered Al grain size. This paper examines various parameters related to grain size that directly result in mechanically weak populations of interconnect elements. We highlight some critical factors that give rise to unique implementation issues, including the complex statistical nature of the susceptible sites and the evolution of the microstructure during device fabrication. The resulting experimental reliability enhancement can be startling—a new deposition process accounted for a 350% increase in lifetime in sub-micron wide lines.

A retrospective chart review of Medicare patients was conducted to investigate possible variables which might contribute to rehospitalization of the patient within 15 days of prior discharge. If variables could be identified it might be possible to prevent the readmission through proactive measures. The findings revealed that variables reoccurred as the charts were reviewed and out of those several were nutrition-related. Further studies must be conducted to determine if nutrition and appropriate nutrition care is included in discharge planning.

Data on 339 subjects who were over 51 years of age was analyzed and Pearson product variant correlation coefficients were estimated between the variables of nutrient intake, nutrition, knowledge, source of information and self perceived health status. Nutrient status was based on the consumption of eight nutrients (protein, calcium, iron, vitamin A, vitamin C, niacin, riboflavin and thiamin). A significant positive relationship was found between nutrition status and nutrition knowledge, but no significant relationships were found between self-perceived health status and nutrition status or between self- erceived health status and nutrition knowledge. A significant Diffrence was found between sources of nutrition knowledge physicians, dietitians, nurses, etc.) and nutrition status usin the chi-square statistic. There was no significant difference on a chi-suare test of sources of nutrition information and self-perceived health status or on self-perceived health status and nutrition status. A stepwise multivariate approach was used to estimate the amount of variance contributed by the independent variables of nutrition knowledge and sources of nutrition information on the dependent variable of nutrition status.

Subjective indicators of life quality are used frequently in the planning and decision making process. The limitations inherent in the use of subjective indicators often go unnoticed among those most likely to use such data in the context of planned change. We direct attention to a potential source of error in subjective evaluations of community services and facilities. Specifically, we utilize repeated measures to test for response bias that results from placing items in alternative sections of the same survey instrument. Evidence concerning the hypothesized presence of systematic bias was mixed. When overall service evaluation items were embedded within a section devoted exclusively to that service, considerable systematic bias was observed. The findings indicate that the choice of question format depends upon the ultimate use to which the data will be put.

DOPAMINE (DA) is released in the medial preoptic area (MPOA) of male rats during copulation. DA agonists infused into the MPOA facilitate, and antagonists impair, copulatory behavior. Local administration of the nitric oxide (NO) precursor L-arginine also increases DA release in the MPOA. The present experiment used microdialysis to test whether NO promotes DA release during copulation. Males received either an NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME, 400μM), or its inactive isomer D-NAME (400μM) into the MPOA via a microdialysis probe for 3 h prior to the introduction of a female. Following D-NAME administration, DA increased during copulation, while L-NAME prevented this increase. NO may therefore promote DA release in the MPOA of male rats, thereby facilitating copulation.

Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that catalyzes the post-translational symmetric dimethylation of protein substrates. PRMT5 plays a critical role in regulating biological processes including transcription, cell cycle progression, RNA splicing, and DNA repair. As such, dysregulation of PRMT5 activity is implicated in the development and progression of multiple cancers and is a target of growing clinical interest. Described herein are the structure-based drug designs, robust synthetic efforts, and lead optimization strategies toward the identification of two novel 5,5-fused bicyclic nucleoside-derived classes of potent and efficacious PRMT5 inhibitors. Utilization of compound docking and strain energy calculations inspired novel designs, and the development of flexible synthetic approaches enabled access to complex chemotypes with five contiguous stereocenters. Additional efforts in balancing bioavailability, solubility, potency, and CYP3A4 inhibition led to the identification of diverse lead compounds with favorable profiles, promising in vivoactivity, and low human dose projections.

In the context of a PRMT5 inhibitor program, we describe our efforts to develop a flexible and robust strategy to access tetrahydrofuro[3,4-b]furan nucleoside analogues. Ultimately, it was found that a Wolfe type carboetherification from an alkenol derived from d-glucofuranose diacetonide was capable of furnishing the B-ring and installing the desired heteroaryl group in a single step. Using this approach, key intermediate 1.3-Awas delivered on a gram scale in a 62% yield and 9.1:1 dr in favor of the desired S-isomer. After deprotection of 1.3-A, a late-stage glycosylation was performed under Mitsunobu conditions to install the pyrrolopyrimidine base. This provided serviceable yields of nucleoside analogues in the range of 31–48% yield. Compound 1.1-Cwas profiled in biochemical and cellular assays and was demonstrated to be a potent and cellularly active PRMT5 inhibitor, with a PRMT5-MEP50 biochemical IC50of 0.8 nM, a MCF-7 target engagement EC50of 3 nM, and a Z138 cell proliferation EC50of 15 nM. This work sets the stage for the development of new inhibitors of PRMT5 and novel nucleoside chemical matter for alternate drug discovery programs.

Bacteriologic diagnosis of typhoid fever and related infections has centered about the utilization of biochemical differences between the pathogenic organisms concerned and the non-pathogenic forms associated with them. The usual initial procedure in the examination of a suspected typhoid stool is seeding upon some lactose plating medium to eliminate all but the non-fermenting organisms present. The principal reasons to explain the failure to isolate the typhoid bacillus are: scarcity of B. typhosusin the stool, or the overwhelming antagonistic action of the associated bacteria. Glycerin, bile, and selectively bacteriostatic substances such as brilliant-green have been incorporated into the stool fluid or into the media. The object is either to forestall the destruction of whatever typhoid bacilli may be present or to hinder the growth of the non-pathogenic organisms of the mixture without inhibiting B. typhosus.Given a mixture in which the desired bacteria were present in very small numbers, it would seem, a priori, that instead of inhibitive methods, enrichment would be the procedure of choice. Based upon the conception that, under similar conditions, B. typhosusand the Salmonella organisms are more actively motile than B. coli, the principal interfering organism, we have experimented with methods of selective enrichment.1Our first attempts with liquid media were only partially successful. Difficulties with diffusion and convection currents during incubation were such as to make the results very irregular. The next trials were with semi-fluid agar in test-tubes; the inoculum was introduced into the bottom of the column of soft agar by a capillary pipette. Disruption of the agar by the pipette allowed rapid ascent of all the organisms in the test mixtures or in feces. Our best results have been with small U-tubes containing ordinary beef infusion to which 0.2% agar has heen added.

Blocking oxygen-sensing prolyl hydroxylases in the rodent CNS enhances functional recovery after brain hemorrhage.