Gutzwiller approximation for indistinguishable interacting Brownian particles on a lattice.

Nonequilibrium Brownian systems can be described using a creation and annihilation operator formalism for classical indistinguishable particles. This formalism has recently been used to derive a many-body master equation for Brownian particles on a lattice with interactions of arbitrary strength and range. One advantage of this formalism is the possibility of using solution methods for analogous many-body quantum systems. In this paper, we adapt the Gutzwiller approximation for the quantum Bose-Hubbard model to the many-body master equation for interacting Brownian particles in a lattice in the large-particle limit. Using the adapted Gutzwiller approximation, we numerically explore the complex behavior of nonequilibrium steady-state drift and number fluctuations throughout the full range of interaction strengths and densities for on-site and nearest-neighbor interactions.

Nonequilibrium master equation for interacting Brownian particles in a deep-well periodic potential.

Employing a creation and annihilation operator formulation, we derive an approximate many-body master equation describing discrete hopping from the more general continuous description of Brownian motion on a deep-well nonequilibrium periodic potential. The many-body master equation describes interactions of arbitrary strength and range arising from a "top-hat" two-body interaction potential. We show that this master equation reduces to the well-known asymmetric simple exclusion process and the zero range process in certain regimes. We also use the creation and annihilation operator formalism to derive results for the steady-state drift and the number fluctuations in special cases, including the unexplored limit of weak interparticle interactions.

Do school closures and school reopenings affect community transmission of COVID-19? A systematic review of observational studies.

OBJECTIVES: To systematically reivew the observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission. SETTING: Schools (including early years settings, primary schools and secondary schools). INTERVENTION: School closures and reopenings. OUTCOME MEASURE: Community transmission of SARS-CoV-2 (including any measure of community infections rate, hospital admissions or mortality attributed to COVID-19). METHODS: On 7 January 2021, we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index and Google, searching title and abstracts for terms related to SARS-CoV-2 AND terms related to schools or non-pharmaceutical interventions (NPIs). We used the Cochrane Risk of Bias In Non-randomised Studies of Interventions tool to evaluate bias. RESULTS: We identified 7474 articles, of which 40 were included, with data from 150 countries. Of these, 32 studies assessed school closures and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60% and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission. CONCLUSIONS: School closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures.

Inequalities in the uptake of, adherence to and effectiveness of behavioural weight management interventions: systematic review protocol.

INTRODUCTION: It has been suggested that interventions focusing on individual behaviour change, such as behavioural weight management interventions, may exacerbate health inequalities. These intervention-generated inequalities may occur at different stages, including intervention uptake, adherence and effectiveness. We will synthesise evidence on how different measures of inequality moderate the uptake, adherence and effectiveness of behavioural weight management interventions in adults. METHODS AND ANALYSIS: We will update a previous systematic literature review from the United States Preventive Services Taskforce to identify trials of behavioural weight management interventions in adults aged 18 years and over that were, or could feasibly be, conducted in or recruited from primary care. Medline, Cochrane database (CENTRAL) and PsycINFO will be searched. Only randomised controlled trials (RCTs) and cluster-RCTs will be included. Two investigators will independently screen articles for eligibility and conduct risk of bias assessment. We will curate publication families for eligible trials. The PROGRESS-Plus acronym (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) will be used to consider a comprehensive range of health inequalities. Data on trial uptake, intervention adherence, weight change and PROGRESS-Plus-related data will be extracted. Data will be synthesised narratively. We will present a Harvest plot for each PROGRESS-Plus criterion and whether each trial found a negative, positive or no health inequality gradient. We will also identify potential sources of unpublished original research data on these factors which can be synthesised through a future individual participant data meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are being collected. The completed systematic review will be disseminated in a peer-reviewed journal, at conferences, and contribute to the lead author's PhD thesis. Authors of trials included in the completed systematic review may be invited to collaborate on a future individual participant data meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42020173242.

Editorial Commentary: Release of the Medial Collateral During Arthroscopic Meniscectomy Should Be Encouraged, Not Feared!

In patients having arthroscopic medial meniscectomy, percutaneous pie crust or intra-articular release of the proximal medial collateral ligament is preferable to iatrogenic damage to the cartilage of the medial femoral condyle. In patients with tight medial compartments, release is recommended. Release of the medial collateral ligament during arthroscopic partial medial meniscectomy does not result in morbidity and should be encouraged, not feared.

A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis.

Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation of gene expression. Here we identify that the zygotene to pachytene transition is not only associated with the resumption of transcription but also a wave of programmed mRNA degradation that is essential for meiotic progression. We explored whether terminal uridydyl transferase 4- (TUT4-) or TUT7-mediated 3' mRNA uridylation contributes to this wave of mRNA degradation during pachynema. Indeed, both TUT4 and TUT7 are expressed throughout most of spermatogenesis, however, loss of either TUT4 or TUT7 does not have any major impact upon spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, while conditional gene targeting revealed an essential role for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of miRNA, piRNA and mRNA 3' uridylation. Although this reduction does not greatly alter miRNA or piRNA expression, TUT4/7-mediated uridylation is required for the clearance of many zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3' UTRs with length-adjusted enrichment for AU-rich elements. We also observed these features in TUT4/7-regulated maternal transcripts whose dosage was recently shown to be essential for sculpting a functional maternal transcriptome and meiosis. Therefore, mRNA 3' uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we have identified a novel requirement for 3' uridylation-programmed zygotene mRNA clearance in pachytene spermatocytes that is essential for male meiotic progression.

Clinical Inquiries: Can CBT effectively treat adult insomnia disorder?

Yes. Cognitive behavioral therapy (CBT) administered individually, in a group setting, or on the internet is effective for treating insomnia in adults compared with control (strength of recommendation [SOR]: A, meta-analyses). CBT is comparable to pharmacotherapy for improving measures of sleep (SOR: A, comparative meta-analysis). CBT produces sustainable improvements in subjective sleep quality for adults with comorbid insomnia (SOR: A, meta-analysis).

Reconstructing free-energy landscapes for nonequilibrium periodic potentials.

We present a method for reconstructing the free-energy landscape of overdamped Brownian motion on a tilted periodic potential. Our approach exploits the periodicity of the system by using the k-space form of the Smoluchowski equation and we employ an iterative approach to determine the nonequilibrium tilt. We reconstruct landscapes for a number of example potentials to show the applicability of the method to both deep and shallow wells and near-to- and far-from-equilibrium regimes. The method converges logarithmically with the number of Fourier terms in the potential.

A mild thermomechanical process for the enzymatic conversion of radiata pine into fermentable sugars and lignin.

BACKGROUND: Conversion of softwoods into sustainable fuels and chemicals is important for parts of the world where softwoods are the dominant forest species. While they have high theoretical sugar yields, softwoods are amongst the most recalcitrant feedstocks for enzymatic processes, typically requiring both more severe pretreatment conditions and higher enzyme doses than needed for other lignocellulosic feedstocks. Although a number of processes have been proposed for converting softwoods into sugars suitable for fuel and chemical production, there is still a need for a high-yielding, industrially scalable and cost-effective conversion route. RESULTS: We summarise work leading to the development of an efficient process for the enzymatic conversion of radiata pine (Pinus radiata) into wood sugars. The process involves initial pressurised steaming of wood chips under relatively mild conditions (173 °C for 3-72 min) without added acid catalyst. The steamed chips then pass through a compression screw to squeeze out a pressate rich in solubilised hemicelluloses. The pressed chips are disc-refined and wet ball-milled to produce a substrate which is rapidly saccharified using commercially available enzyme cocktails. Adding 0.1% polyethylene glycol during saccharification was found to be particularly effective with these substrates, reducing enzyme usage to acceptable levels, e.g. 5 FPU/g OD substrate. The pressate is separately hydrolysed using acid, providing additional hemicellulose-derived sugars, for an overall sugar yield of 535 kg/ODT chips (76% of theoretical). The total pretreatment energy input is comparable to other processes, with the additional energy for attrition being balanced by a lower thermal energy requirement. This pretreatment strategy produces substrates with low levels of fermentation inhibitors, so the glucose-rich mainline and pressate syrups can be fermented to ethanol without detoxification. The lignin from the process remains comparatively unmodified, as evident from the level of retained ß-ether interunit linkages, providing an opportunity for conversion into saleable co-products. CONCLUSIONS: This process is an efficient route for the enzymatic conversion of radiata pine, and potentially other softwoods, into a sugar syrup suitable for conversion into fuels and chemicals. Furthermore, the process uses standard equipment that is largely proven at commercial scale, de-risking process scale-up.

Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment.

Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the 'nexus' of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.

Energy transfer in a molecular motor in the Kramers regime.

We present a theoretical treatment of energy transfer in a molecular motor described in terms of overdamped Brownian motion on a multidimensional tilted periodic potential. The tilt represents a thermodynamic force driving the system out of equilibrium and, for nonseparable potentials, energy transfer occurs between degrees of freedom. For deep potential wells, the continuous theory transforms to a discrete master equation that is tractable analytically. We use this master equation to derive formal expressions for the hopping rates, drift and diffusion, and the efficiency and rate of energy transfer in terms of the thermodynamic force. These results span both strong and weak coupling between degrees of freedom, describe the near and far from equilibrium regimes, and are consistent with generalized detailed balance and the Onsager relations. We thereby derive a number of diverse results for molecular motors within a single theoretical framework.

Tight-binding approach to overdamped Brownian motion on a multidimensional tilted periodic potential.

We present a theoretical treatment of overdamped Brownian motion on a multidimensional tilted periodic potential that is analogous to the tight-binding model of quantum mechanics. In our approach, we expand the continuous Smoluchowski equation in the localized Wannier states of the periodic potential to derive a discrete master equation. This master equation can be interpreted in terms of hopping within and between Bloch bands, and for weak tilting and long times we show that a single-band description is valid. In the limit of deep potential wells, we derive a simple functional dependence of the hopping rates and the lowest band eigenvalues on the tilt. We also derive formal expressions for the drift and diffusion in terms of the lowest band eigenvalues.

Optimizing the enzyme loading and incubation time in enzymatic hydrolysis of lignocellulosic substrates.

A mathematical model for costing enzymatic hydrolysis of lignocellulosics is presented. This model is based on three variable parameters describing substrate characteristics and three unit costs for substrate, enzymes and incubation. The model is used to minimize the cost of fermentable sugars, as intermediate products on the route to ethanol or other biorefinery products, by calculating optimized values of enzyme loading and incubation time. This approach allows comparisons between substrates, with processing conditions optimized independently for each substrate. Steam-exploded pine wood was hydrolyzed in order to test the theoretical relationship between sugar yield and processing conditions.

Thermodynamic analysis of a high-yield biochemical process for biofuel production.

This paper presents a thermodynamic analysis of a high-yield biochemical process for biofuel production from lignocelluosic biomass based on a previously proposed process. Unlike the standard biochemical process, which ferments sugar intermediates to ethanol, the process under consideration converts sugars to acetic acid which is esterified and hydrogenated to produce ethanol. This process has a significantly higher yield and produces no carbon dioxide. However, we find that the thermodynamic efficiency of the process is not increased in proportion to the yield gain. An additional survey of various biofuel production processes showed no direct correlation between yield and thermodynamic efficiency. This survey and the detailed thermodynamic analyses lead us to conclude that yield alone is an unreliable performance metric for biofuel technologies.

Transplacental transmission of Leishmania infantum as a means for continued disease incidence in North America.

BACKGROUND: Dogs are the predominant domestic reservoir for human L. infantum infection. Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with an annual quantitative PCR prevalence of greater than 20% within an at-risk Foxhound population. Although classically Leishmania is transmitted by infected sand flies and phlebotomine sand flies exist in the United States, means of ongoing L. infantum transmission in U.S. dogs is currently unknown. Possibilities include vertical (transplacental/transmammary) and horizontal/venereal transmission. Several reports have indicated that endemic ZVL may be transmitted vertically. AIMS: Our aims for this present study were to establish whether vertical/transplacental transmission was occurring in this population of Leishmania-infected US dogs and determine the effect that this means of transmission has on immune recognition of Leishmania. METHODOLOGY: A pregnant L. infantum-infected dam donated to Iowa State University gave birth in-house to 12 pups. Eight pups humanely euthanized at the time of birth and four pups and the dam humanely euthanized three months post-partum were studied via L. infantum-kinetoplast specific quantitative PCR (kqPCR), gross and histopathological assessment and CD4+ T cell proliferation assay. KEY RESULTS: This novel report describes disseminated L. infantum parasites as identified by kqPCR in 8 day old pups born to a naturally-infected, seropositive U.S. dog with no travel history. This is the first report of vertical transmission of L. infantum in naturally-infected dogs in North America, emphasizing that this novel means of transmission could possibly sustain infection within populations. MAJOR CONCLUSIONS: Evidence that vertical transmission of ZVL may be a driving force for ongoing disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL, as at present parasite elimination efforts in endemic areas are largely focused on vector-borne transmission between canines and people. Determining frequency of vertical transmission and incorporating canine sterilization with vector control may have a more significant impact on ZVL transmission to people in endemic areas than current control efforts.

Thermodynamic analysis of lignocellulosic biofuel production via a biochemical process: guiding technology selection and research focus.

The aim of this paper is to present an exergy analysis of bioethanol production process from lignocellulosic feedstock via a biochemical process to asses the overall thermodynamic efficiency and identify the main loss processes. The thermodynamic efficiency of the biochemical process was found to be 35% and the major inefficiencies of this process were identified as: the combustion of lignin for process heat and power production and the simultaneous scarification and co-fermentation process accounting for 67% and 27% of the lost exergy, respectively. These results were also compared with a previous analysis of a thermochemical process for producing biofuel. Despite fundamental differences, the biochemical and thermochemical processes considered here had similar levels of thermodynamic efficiency. Process heat and power production was the major contributor to exergy loss in both of the processes. Unlike the thermochemical process, the overall efficiency of the biochemical process largely depends on how the lignin is utilized.

Efficiency improvements by geothermal heat integration in a lignocellulosic biorefinery.

In an integrated geothermal biorefinery, low-grade geothermal heat is used as process heat to allow the co-products of biofuel production to become available for higher-value uses. In this paper we consider integrating geothermal heat into a biochemical lignocellulosic biorefinery so that the lignin-enriched residue can be used either as a feedstock for chemicals and materials or for on-site electricity generation. Depending on the relative economic value of these two uses, we can maximize revenue of a biorefinery by judicious distribution of the lignin-enriched residue between these two options. We quantify the performance improvement from integrating geothermal energy for an optimized system. We then use a thermodynamic argument to show that integrating geothermal heat into a biorefinery represents an improvement in overall resource utilization efficiency in all cases considered. Finally, possible future technologies for electricity generation are considered which could improve this efficiency further.

Scaling laws and technology development strategies for biorefineries and bioenergy plants.

The economies of scale of larger biorefineries or bioenergy plants compete with the diseconomies of scale of transporting geographically distributed biomass to a central location. This results in an optimum plant size that depends on the scaling parameters of the two contributions. This is a fundamental aspect of biorefineries and bioenergy plants and has important consequences for technology development as "bigger is better" is not necessarily true. In this paper we explore the consequences of these scaling effects via a simplified model of biomass transportation and plant costs. Analysis of this model suggests that there is a need for much more sophisticated technology development strategies to exploit the consequences of these scaling effects. We suggest three potential strategies in terms of the scaling parameters of the system.

Clinical grade production and characterization of a fusion protein comprised of the chemokine CCL2-ligand genetically fused to a mutated and truncated form of the Shiga A1 subunit.

First generation chemokine ligand-Shiga A1 (SA1) fusion proteins (leukocyte population modulators, LPMs) were previously only obtained in small quantities due to the ribosomal inactivating protein properties of the SA1 moiety which inhibits protein synthesis in host cells. We therefore employed 4-aminopyrazolo[3,4-d]-pyrimidine, an inhibitor of Shiga A1, to allow the growth of these cells prior to induction and during the expression phase post-induction with IPTG. Scale-up allowed the production of gram quantities of clinical grade material of the lead candidate, OPL-CCL2-LPM. A manufacturing cell bank was established and used to produce OPL-CCL2-LPM in a fed-batch fermentation process. Induction of the expression of OPL-CCL2-LPM led to the production of 22.47 mg/L per OD(600) unit. The LPM was purified from inclusion bodies using solubilization, renaturation, refolding and chromatography steps. The identity and purity of the OPL-CCL2-LPM was determined using several analytical techniques. The product retained the ability of the SA1 moiety to inhibit protein synthesis as measured in a rabbit reticulocyte lysate cell-free protein synthesis assay and was cytotoxic to target cells. Binding studies established that the protein exerts its effects via CCR2, the cognate receptor for CCL2. Clinical trials in inflammatory nephropathies are planned.

Millimeter- and submillimeter-wave characterization of various fabrics.

Transmission measurements of 14 fabrics are presented in the millimeter-wave and submillimeter-wave electromagnetic regions from 130 GHz to 1.2 THz. Three independent sources and experimental set-ups were used to obtain accurate results over a wide spectral range. Reflectivity, a useful parameter for imaging applications, was also measured for a subset of samples in the submillimeter-wave regime along with polarization sensitivity of the transmitted beam and transmission through doubled layers. All of the measurements were performed in free space. Details of these experimental set-ups along with their respective challenges are presented.