cssi/SciSciGPT-SciSciNet huggingface dataset:
A real-time hourly ozone prediction system using deep convolutional neural network

This study uses a deep learning approach to forecast ozone concentrations over Seoul, South Korea for 2017. We use a deep convolutional neural network (CNN). We apply this method to predict the hourly ozone concentration on each day for the entire year using several predictors from the previous day, including the wind fields, temperature, relative humidity, pressure, and precipitation, along with in situ ozone and NO2 concentrations. We refer to a history of all observed parameters between 2014 and 2016 for training the predictive models. Model-measurement comparisons for the 25 monitoring sites for the year 2017 report average indices of agreement (IOA) of 0.84–0.89 and a Pearson correlation coefficient of 0.74–0.81, indicating reasonable performance for the CNN forecasting model. Although the CNN model successfully captures daily trends as well as yearly high and low variations of the ozone concentrations, it notably underpredicts high ozone peaks during the summer. The forecasting results are generally more accurate for the stations located in the southern regions of the Han River, the result of more stable topographical and meteorological conditions. Furthermore, through two separate daytime and nighttime forecasts, we find that the monthly IOA of the CNN model is 0.05–0.30 higher during the daytime, resulting from the unavailability of some of the input parameters during the nighttime. While the CNN model can predict the next 24 h of ozone concentrations within less than a minute, we identify several limitations of deep learning models for real-time air quality forecasting for further improvement.
Multi-view Supervision for Single-view Reconstruction via Differentiable Ray Consistency.

We study the notion of consistency between a 3D shape and a 2D observation and propose a differentiable formulation which allows computing gradients of the 3D shape given an observation from an arbitrary view. We do so by reformulating view consistency using a differentiable ray consistency (DRC) term. We show that this formulation can be incorporated in a learning framework to leverage different types of multi-view observations e.g. foreground masks, depth, color images, semantics etc. as supervision for learning single-view 3D prediction. We present empirical analysis of our technique in a controlled setting. We also show that this approach allows us to improve over existing techniques for single-view reconstruction of objects from the PASCAL VOC dataset.
Male circumcision in so many words.

INTEREST in male circumcision as an HIV prevention intervention is focused on the promise it holds to reduce the risk of HIV infection for men engaged in heterosexual vaginal intercourse. Following an international consultation on 6-8 March 2007 WHO and UNAIDS released "Conclusions and Recommendations" on the policy and programmatic implications of the existing data on male circumcision and HIV prevention. This is a welcome step in what will inevitably be a long process to ensure male circumcision is appropriately implemented as part of the response to HIV. Beyond simply the offer of the service if male circumcision is to be an effective strategy over the long term these conclusions and recommendations will need to be translated into guidelines and adapted and adopted at national and local level. Policies and programmes will need to be developed and appropriate monitoring and evaluation systems created. In doing so the devil as they say will be in the details. Some issues to be considered as this process moves forward are outlined below. (excerpt)
Chapter 5 – Implementation: Search Through Closing: Phases 3–10 of the Acquisition Process

This chapter starts with the presumption that a firm has developed a viable business plan that requires an acquisition to realize the firm’s strategic direction. Whereas Chapter 4 addressed the creation of business and acquisition plans (Phases 1 and 2), this chapter focuses on Phases 3–10 of the acquisition process, including search, screening, first contact, negotiation, integration planning, closing, integration implementation, and evaluation.
Why Grade Distribution Is Often Multi-modal: An Uncertainty-Based Explanation

There are many different independent factors that affect student grades. There are many physical situations like this, in which many different independent factors affect a phenomenon, and in most such situations, we encounter normal distribution – in full accordance with the Central Limit Theorem, which explains that in such situations, distribution should be close to normal. However, the grade distribution is definitely not normal – it is multi-modal. In this paper, we explain this strange phenomenon, and, moreover, we explain several observed features of this multi-modal distribution.
Floquet Chern insulators of light.

Achieving topologically-protected robust transport in optical systems has recently been of great interest. Most studied topological photonic structures can be understood by solving the eigenvalue problem of Maxwell’s equations for static linear systems. Here, we extend topological phases into dynamically driven systems and achieve a Floquet Chern insulator of light in nonlinear photonic crystals (PhCs). Specifically, we start by presenting the Floquet eigenvalue problem in driven two-dimensional PhCs. We then define topological invariant associated with Floquet bands, and show that topological band gaps with non-zero Chern number can be opened by breaking time-reversal symmetry through the driving field. Finally, we numerically demonstrate the existence of chiral edge states at the interfaces between a Floquet Chern insulator and normal insulators, where the transport is non-reciprocal and uni-directional. Our work paves the way to further exploring topological phases in driven optical systems and their optoelectronic applications. Topological photonic structures can be understood by solving the eigenvalue problem of Maxwell’s equations in the static case. Here, the authors study Floquet topological phases in nonlinear photonic crystals under external drive and show how non-reciprocal transport can be achieved in a Floquet Chern insulator.
Implementing best practices for the provision of long-acting reversible contraception: a survey of obstetrician-gynecologists.

Abstract Objective To examine obstetrician-gynecologists' practices regarding provision of long-acting reversible contraceptive (LARC) methods same-day, immediately postpartum, or to women under age 21. Study design Between August 2016 and March 2017, the American College of Obstetricians and Gynecologists (ACOG) sent 2500 of their members an electronic survey questionnaire regarding the provision of LARC methods. ACOG mailed nonresponders paper surveys. Results After exclusions, the final sample was 1280 respondents (52.2% response rate). Although 91% of obstetrician-gynecologists reported providing IUDs, only 29% (95% CI, 26–32%) offered same-day placement. Ninety-two percent (95% CI, 90–94%) offered IUDs to eligible patients under age 21. Nineteen percent (95% CI, 16.1–21.3%) offered immediate postpartum IUD placement and 21% (95% CI, 18–23%) offered immediate postpartum implant placement. Obstetrician-gynecologists practicing in states where Medicaid reimbursed for immediate postpartum LARC devices within the global fee for delivery (versus separate reimbursement) had lower odds of offering them. Conclusion While most ob-gyns are offering IUDs to women under age 21, many are still not offering them same-day. A minority of ob-gyns offer either IUDs or implants immediately postpartum, and there are important geographic and practice setting disparities in this practice. Implications Efforts to align LARC practices with published evidence and improve access to LARC methods for women desiring them will require a multipronged effort including continuing education of physicians, patient education and outreach, as well as advocacy to improve insurance coverage and reimbursement.
Loss of NF-κB p50 function synergistically augments microglial priming in the middle-aged brain

While NF-κB p50 function is impaired in central nervous system disease, aging in non-CNS tissues, and response to reactive oxygen species, the role of NF-κB p50 in aging-associated microglial pro-inflammatory priming is poorly understood. Male NF-κB p50+/+ and NF-κB p50−/− mice at three different ages (1.5–3.0 month old, 8.0–11.0 month old, and 16.0–18.0 month old) were treated with LPS (5 mg/kg, IP) to trigger peripheral inflammation, where circulating cytokines, neuroinflammation, microglia morphology, and NF-κB p50/p65 function in brain tissue were determined 3 h later. Peripheral LPS injection in 9-month-old C57BL/6 mice resulted in lower NF-κB p50 DNA binding of nuclear extracts from the whole brain, when compared to 3-week-old C57BL/6 mice, revealing differences in LPS-induced NF-κB p50 activity in the brain across the mouse lifespan. To examine the consequences of loss NF-κB p50 function with aging, NF-κB p50+/+ and NF-κB p50−/− mice of three different age groups (1.5–3.0 month old, 8.0–11.0 month old, and 16.0–18.0 month old) were injected with LPS (5 mg/kg, IP). NF-κB p50−/− mice showed markedly elevated circulating, midbrain, and microglial TNFα when compared to NF-κB p50+/+ mice at all ages. Notably, the 16.0–18.0-month-old (middle aged) NF-κB p50−/− mice exhibited synergistically augmented LPS-induced serum and midbrain TNFα when compared to the younger (1.5–3.0 month old, young adult) NF-κB p50−/− mice. The 16.0–18.0-month-old LPS-treated NF-κB p50−/− mice also had the highest midbrain IL-1β expression, largest number of microglia with changes in morphology, and greatest elevation of pro-inflammatory factors in isolated adult microglia. Interestingly, aging NF-κB p50−/− mice exhibited decreased brain NF-κB p65 expression and activity. These findings support that loss of NF-κB p50 function and aging in middle-aged mice may interact to excessively augment peripheral/microglial pro-inflammatory responses and point to a novel neuroinflammation signaling mechanism independent the NF-κB p50/p65 transcription factor in this process.
Synchronized Progress in Interconnection Networks (SPIN): A New Theory for Deadlock Freedom

Routing deadlocks, i.e., a cyclic dependence between buffered packets, are a fundamental network design challenge. Existing solutions require resource over provisioning. We propose a new theory for deadlock freedom, Synchronized Progress in Interconnection Networks (SPIN) that solves the problem through coordinated movement of deadlocked packets.
How Has Takeover Competition Changed Over Time

Abstract We study a random sample of completed and withdrawn takeovers during the 1981 to 2014 time period to provide new evidence on the role of takeover impediments such as poison pills, staggered boards and state antitakeover devices. Do such impediments act in the interest of management by promoting entrenchment or do they act in shareholder interest by improving bargaining power during the takeover auction process? We first confirm the growing trend of takeover impediments over time in our sample. We then relate these trends to changes in the takeover auction process over time. Although we corroborate prior findings of a decline in hostile takeovers and publicly reported takeover auctions between the 1980s and later time periods, we find that takeover competition across the entire auction process between deal initiation and completion has not declined. In effect, takeover competition via auctions has gone underground. Moreover, takeover premiums have not declined over time. We interpret the results to be consistent with the shareholder interest/bargaining power hypothesis and inconsistent with the management interest/entrenchment hypothesis. Our analysis highlights the usefulness of research sources for SEC merger documents including microfiche, Lexis Nexis and Thomson One Financial that provide historical information on the takeover auction process prior to the EDGAR filings that started in the mid-1990s.
Computational Modeling of Anthocyanin Pathway Evolution: Biases, Hotspots, and Trade-offs.

The alteration of metabolic pathways is a common mechanism underlying the evolution of new phenotypes. Flower color is a striking example of the importance of metabolic evolution in a complex phenotype, wherein shifts in the activity of the underlying pathway lead to a wide range of pigments. Although experimental work has identified common classes of mutations responsible for transitions among colors, we lack a unifying model that relates pathway function and activity to the evolution of distinct pigment phenotypes. One challenge in creating such a model is the branching structure of pigment pathways, which may lead to evolutionary trade-offs due to competition for shared substrates. In order to predict the effects of shifts in enzyme function and activity on pigment production, we created a simple kinetic model of a major plant pigmentation pathway: the anthocyanin pathway. This model describes the production of the three classes of blue, purple, and red anthocyanin pigments, and accordingly, includes multiple branches and substrate competition. We first studied the general behavior of this model using a naive set of parameters. We then stochastically evolved the pathway toward a defined optimum and analyzed the patterns of fixed mutations. This approach allowed us to quantify the probability density of trajectories through pathway state space and identify the types and number of changes. Finally, we examined whether our simulated results qualitatively align with experimental observations, i.e., the predominance of mutations which change color by altering the function of branching genes in the pathway. These analyses provide a theoretical framework that can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.
Utilizing Deep Learning Towards Multi-modal Bio-sensing and Vision-based Affective Computing

In recent years, the use of bio-sensing signals such as electroencephalogram (EEG), electrocardiogram (ECG) etc. have garnered interest towards applications in affective computing. The parallel trend of deep learning has led to a huge leap in performance towards solving various vision-based research problems such as object detection. Yet, these advances in deep learning have not adequately translated into bio-sensing research. This work applies novel deep-learning-based methods to various bio-sensing and video data of four publicly available multi-modal emotion datasets. For each dataset, we first individually evaluate the emotion-classification performance obtained by each modality. We then evaluate the performance obtained by fusing the features from these modalities. We show that our algorithms outperform the results reported by other studies for emotion/valence/arousal/liking classification on DEAP and MAHNOB-HCI datasets and set up benchmarks for the newer AMIGOS and DREAMER datasets. We also evaluate the performance of our algorithms by combining the datasets and by using transfer learning to show that the proposed method overcomes the inconsistencies between the datasets. Hence, we do a thorough analysis on multi-modal affective data from more than 120 subjects and 2,800 trials. Finally, utilizing a convolution-deconvolution network, we propose a new technique towards identifying salient brain regions corresponding to various affective states.
Outcomes of laparoscopic and open CAPD catheter placement: A single-center experience.

Abstract Background Continuous Ambulatory Peritoneal Dialysis (CAPD) catheter placement is typically a straightforward surgical procedure performed on chronically ill patients with end-stage renal disease (ESRD). Post-operative outcomes and reoperative rates vary greatly in the medical literature. We report our experience using both minimally invasive and open techniques in placing CAPD catheters and offer our surgical outcomes. Methods This study is an IRB-approved, retrospective review (2005–2018) of all patients undergoing CAPD catheter placement at Mayo Clinic-Rochester. Analysis focused on specific patient outcomes, including early ( Results A total of 173 patients with ESRD (mean ASA score = 3.1) underwent laparoscopic (n = 22) and open (n = 151) CAPD catheter placement (mean follow-up = 309 days; range: 1–3497 days). The total index operation complication rate was 41%. The total index reoperation rate was 37% and was similar in open and laparoscopic approaches. CAPD catheters malfunctioned in 19 patients (11% of total) and each underwent reoperation. CAPD catheter infections occurred in 30 patients (17% of total), and 24 required reoperation; 6 patients were treated successfully with antibiotics. CAPD catheter migrations occurred in 21 patients (12% of total) and all underwent reoperation. Conclusion Although CAPD catheter placements in patients with ESRD are technically easy to accomplish, the long term outcomes suggest as many as one in three patients will struggle with catheter function or infection. This study has led to changes in our technical CAPD catheter placement procedures, as well as the post-operative patient care algorithm.
Chiral 2‐(ω‐Aminoalkyl)‐oxazolines by ring transformation of lactam derivatives

2-(ω-Aminoalkyl)-oxazolines 7 as starting materials for further asymmetric synthesis can be prepared in enantiomerically pure form by ring transformation of lactim ethers 1 or lactam acetals 2 with chiral 2-aminoalcohols 3. Hydroxyethyllactam imines 5, lactamimino-alkyloxazolines 8, or ω-aminoalkaneamides 9 can be formed as by-products by condensation without ring transformation, by further reaction with lactim ether 1, or by hydrolysis, respectively.
Asymmetric Heck cyclization route to indolizidine and azaazulene alkaloids: synthesis of (+)-5-epiindolizidine 167B and indolizidine 223AB

Abstract Asymmetric intramolecular Heck cyclization of endocyclic enamides occurs at room temperature to give indoloizidine and azaazulene ring systems in up to 86% enantiomeric excess. A synthesis of (+)-epiindolizidine 167B and formal synthesis of 5 E ,9 Z -indolizidine 223AB is described.
Hydrocarbon C-H bond activation by rhodium porphyrins

Rhodium porphyrins provide a variety of C-H bond reactions with both aromatic and aliphatic hydrocarbons that acquire unusual selectivity in part through the steric requirements of the porphyrin ligand. Rhodium(III) porphyrins selectively react with aromatic C-H bonds by electrophilic substitution with the virtual exclusion of aliphatic C-H bond activation. Rhodium(II) porphyrins react by a metal-centered radical pathway with alkyl aromatics and alkanes selectively at the alkyl C-H bond with total exclusion of aromatic C-H bond activation. Reactions of rhodium(II) metalloradicals with alkyl C-H bonds have large deuterium isotope effects, small activation enthalpies and large negative activation entropies consistent with a near linear symmetrical four-centered transition state (Rh˙⋯H⋯C⋯˙Rh). The nature of this transition state and the dimensions of rhodium porphyrins provide steric constraints that preclude aromatic C-H bond reactions and give high kinetic preference for methane activation as the smallest alkane substrate. Rhodium(II) tethered diporphyrin bimetalloradical complexes convert the C-H bond reactions to bimolecular processes with dramatically increased reaction rates and high selectivity for methane activation.
Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host.

ABSTRACT A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found that in vivoH. ducreyi transcripts were distinct from those in the inocula, as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were found to be involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggest that H. ducreyi exploits the metabolic niche created by the host immune response. IMPORTANCE Dual RNA sequencing (RNA-seq) offers the promise of determining an interactome at a transcriptional level between a bacterium and the host but has yet to be done on any bacterial infection in human tissue. We performed dual RNA-seq and metabolomics analyses on wounded and infected sites following experimental infection of the arm with H. ducreyi. Our results suggest that H. ducreyi survives in an abscess by utilizing l-ascorbate as an alternative carbon source, possibly taking advantage of host ascorbic acid recycling, and that H. ducreyi also adapts by upregulating genes involved in anaerobic metabolism and inorganic ion and nutrient transport. To our knowledge, this is the first description of an interaction network between a bacterium and the human host at a site of infection.
Diagnostic Algorithms to Study Post-Concussion Syndrome Using Electronic Health Records: Validating a Method to Capture an Important Patient Population

Post-concussion syndrome (PCS) is characterized by persistent cognitive, somatic, and emotional symptoms after a mild traumatic brain injury (mTBI). Genetic and other biological variables may contribute to PCS etiology, and the emergence of biobanks linked to electronic health records (EHRs) offers new opportunities for research on PCS. We sought to validate the EHR data of PCS patients by comparing two diagnostic algorithms deployed in the Vanderbilt University Medical Center de-identified database of 2.8 million patient EHRs. The algorithms identified individuals with PCS by: 1) natural language processing (NLP) of narrative text in the EHR combined with structured demographic, diagnostic, and encounter data; or 2) coded billing and procedure data. The predictive value of each algorithm was assessed, and cases and controls identified by each approach were compared on demographic and medical characteristics. The NLP algorithm identified 507 cases and 10,857 controls. The negative predictive value in controls was 78% and the positive predictive value (PPV) in cases was 82%. Conversely, the coded algorithm identified 1142 patients with two or more PCS billing codes and had a PPV of 76%. Comparisons of PCS controls to both case groups recovered known epidemiology of PCS: cases were more likely than controls to be female and to have pre-morbid diagnoses of anxiety, migraine, and post-traumatic stress disorder. In contrast, controls and cases were equally likely to have attention deficit hyperactive disorder and learning disabilities, in accordance with the findings of recent systematic reviews of PCS risk factors. We conclude that EHRs are a valuable research tool for PCS. Ascertainment based on coded data alone had a predictive value comparable to an NLP algorithm, recovered known PCS risk factors, and maximized the number of included patients.
Photochemistry of diethynyl sulfides: a cycloaromatization for the formation of five-membered rings.

The first five-membered ring cycloaromatization reaction has been demonstrated. Photoirradiation of bis(phenylethynyl) sulfide in hexanes/1,4-cyclohexadiene produces 3,4-diphenylthiophene through the presumed intermediacy of 2,5-didehydrothiophene. In addition, phenylacetylene is produced in this reaction consistent with competing direct carbon−sulfur cleavage. For reactions in ethanol or 2-propanol production of the thiophene is accompanied by the formation of phenylacetylene and a thionoester of the corresponding alcohol. Thiophene products also result from the irradiation of other diethynyl sulfides.
A convenient and high yield method to prepare 4-hydroxypyroglutamic acids

Abstract RuO 2 /NaIO 4 oxidation of N -Boc-4-silyloxy and 4-acetoxy proline methyl esters under ethyl acetate/water biphase condition gave N -Boc-4-silyloxy and 4-acetoxy pyroglutamic acid derivatives in high yields. Desilylation with TBAF afforded both cis- and trans - N -Boc-methyl-4-hydroxy pyroglutamates.
Complex interactions between local adaptation, phenotypic plasticity and sex affect vulnerability to warming in a widespread marine copepod

Predicting the response of populations to climate change requires an understanding of how various factors affect thermal performance. Genetic differentiation is well known to affect thermal performance, but the effects of sex and developmental phenotypic plasticity often go uncharacterized. We used common garden experiments to test for effects of local adaptation, developmental phenotypic plasticity and individual sex on thermal performance of the ubiquitous copepod, Acartia tonsa (Calanoida, Crustacea) from two populations strongly differing in thermal regimes (Florida and Connecticut, USA). Females had higher thermal tolerance than males in both populations, while the Florida population had higher thermal tolerance compared with the Connecticut population. An effect of developmental phenotypic plasticity on thermal tolerance was observed only in the Connecticut population. Our results show clearly that thermal performance is affected by complex interactions of the three tested variables. Ignoring sex-specific differences in thermal performance may result in a severe underestimation of population-level impacts of warming because of population decline due to sperm limitation. Furthermore, despite having a higher thermal tolerance, low-latitude populations may be more vulnerable to warming as they lack the ability to respond to increases in temperature through phenotypic plasticity.
Preparation of ketones via the palladium-catalyzed cross-coupling of acid chlorides with trialkylboranes

Abstract Trialkylboranes react with acid chlorides in the presence of palladium to generate alkyl and aryl ketones in good yields.
(Trialkylsilyl)vinylketenes: Synthesis and Application as Diene Components in Diels−Alder Cycloadditions

New strategies for the synthesis of (trialkylsilyl)vinylketenes (“TAS-vinylketenes”) are described based on the photochemical Wolff rearrangement of α‘-silyl-α‘-diazo-α,β-unsaturated ketones and the 4π electrocyclic ring opening of cyclobutenones. These remarkably robust vinylketenes undergo highly regioselective [4 + 2] cycloadditions with reactive olefinic and acetylenic dienophiles to produce highly substituted cyclohexenones and phenols in which the ketene carbonyl dominates in controlling the regiochemical course of the reaction. The stereochemical course of these cycloadditions follows the Alder endo rule, as illustrated in the reaction of nitropropene with TAS-vinylketene 22.
A directed amidohalogenation reaction an unusual reaction of azidoformates

Abstract The thermal intramolecular reaction of an azidoformate and an olefin does not provide the expected aziridine, but rather an amidohalide. This unusual product is formed via an intramolecular nitrene addition to the olefin to initially provide an aziridine. Under the reaction conditions HCl is generated from the solvent which protonates and opens the aziridine providing the observed product. This reaction proceeds with good stereoselectivity giving stereoisomeric ratios of 3:1 to 6.7:1.
CryoAPEX – an electron tomography tool for subcellular localization of membrane proteins

ABSTRACT We describe a method, termed cryoAPEX, which couples chemical fixation and high-pressure freezing of cells with peroxidase tagging (APEX) to allow precise localization of membrane proteins in the context of a well-preserved subcellular membrane architecture. Further, cryoAPEX is compatible with electron tomography. As an example, we apply cryoAPEX to obtain a high-resolution three-dimensional contextual map of the human FIC (filamentation induced by cAMP) protein, HYPE (also known as FICD). HYPE is a single-pass membrane protein that localizes to the endoplasmic reticulum (ER) lumen and regulates the unfolded protein response. Alternate cellular locations for HYPE have been suggested. CryoAPEX analysis shows that, under normal and/or resting conditions, HYPE localizes robustly within the subdomains of the ER and is not detected in the secretory pathway or other organelles. CryoAPEX is broadly applicable for assessing both lumenal and cytosol-facing membrane proteins.
Towards a Post-clustering Test for Differential Expression.

Abstract Single-cell technologies have seen widespread adoption in recent years. The datasets generated by these technologies provide information on up to millions or more individual cells; however, the identities of the cells are often only determined computationally. Single-cell computational pipelines involve two critical steps: organizing the cells in a biologically meaningful way (clustering) and identifying the markers driving this organization (differential expression analysis). Because clustering algorithms force separation, performing differential expression analysis after clustering on the same dataset will generate artificially low p-values, potentially resulting in false discoveries. In this work, we introduce the truncated normal (TN) test, a test based on the truncated normal distribution that significantly corrects for this problem. We present a data-splitting-based framework that leverages the TN test to return reasonable p-values for arbitrary clustering schemes. We demonstrate the efficacy of our solution on simulated and real datasets, and we provide our code at https://github.com/jessemzhang/tn_test.
Epigenetic Changes Induced by Bacteroides fragilis Toxin.

Enterotoxigenic Bacteroides fragilis (ETBF) is a gram negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of Apc min/+ mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored. Here, the changes in gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) induced by treatment of HT29/C1 cells with BFT for 24 and 48 hours is examined. Our data show that several genes are differentially expressed after BFT treatment and these changes relate to the interaction between bacteria and CECs. Further, sites of increased chromatin accessibility are associated with the location of enhancers in CECs and binding sites of transcription factors in the AP-1/ATF family; they are also enriched for common differentially methylated regions (DMRs) in CRC. These data provide insight into the mechanisms by which BFT induces tumor formation and lay the groundwork for future in vivo studies to explore the impact of BFT on nuclear structure and function.
X-ray structural studies of several novel nitrocyclopropanes

The x-ray crystal structures forcis,cis- andtrans,trans- 2,3-dimethyl-1-nitrocyclopropanecarboxylic acid, 2,2,3,3-tetramethyl-1-nitrocyclopro-panecarbonitrile, 2,2,3,3-tetramethyl-1-nitrocyclo-propanecarboxamide, andtrans,trans,trans,trans-2,2′,3,3′-tetramethyl-1,1′-dinitrobicyclopropyl are reported. Contrary to expectations, π-accepting groups that are syn to dimethyl substituents prefer a conformation perpendicular to the three-membered ring when there is an sp2 electron-withdrawing substituent also bonded to the same carbon atom. Ab initio calculations are reported for model compounds and these results are compared with the experimentally determined ones.
Alkoxy-directed cyclopropanation of 1,1-disubstituted alkenes with esters: new approach to quaternary carbon centers

As a new approach to the stereocontrolled construction of quaternary centers, 1,2,2-trisubstituted cyclopropanols are prepared by the olefin exchange-mediated Kulinkovich cyclopropanation of esters with 1,1-disubstituted alkenes bearing homoallylic alcohols. Central to the successful cyclopropanation is the generation of a temporary alkoxy tether from a homoallylic alcohol.
A practical method for efficient and optimal production of Seleno‐methionine‐labeled recombinant protein complexes in the insect cells

The use of Seleno-methionine (SeMet) incorporated protein crystals for single or multi-wavelength anomalous diffraction (SAD or MAD) to facilitate phasing has become almost synonymous with modern X-ray crystallography. The anomalous signals from SeMets can be used for phasing as well as sequence markers for subsequent model building. The production of large quantities of SeMet incorporated recombinant proteins is relatively straightforward when expressed in Escherichia coli. In contrast, production of SeMet substituted recombinant proteins expressed in the insect cells is not as robust due to the toxicity of SeMet in eukaryotic systems. Previous protocols for SeMet-incorporation in the insect cells are laborious, and more suited for secreted proteins. In addition, these protocols have generally not addressed the SeMet toxicity issue, and typically result in low recovery of the labeled proteins. Here we report that SeMet toxicity can be circumvented by fully infecting insect cells with baculovirus. Quantitatively controlling infection levels using our Titer Estimation of Quality Control (TEQC) method allow for the incorporation of substantial amounts of SeMet, resulting in an efficient and optimal production of labeled recombinant protein complexes. With the method described here, we were able to consistently reach incorporation levels of about 75% and protein yield of 60-90% compared with native protein expression.
Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells

The neocortex comprises multiple information processing streams mediated by subsets of glutamatergic pyramidal cells (PCs) that receive diverse inputs and project to distinct targets. How GABAergic interneurons regulate the segregation and communication among intermingled PC subsets that contribute to separate brain networks remains unclear. Here we demonstrate that a subset of GABAergic chandelier cells (ChCs) in the prelimbic cortex, which innervate PCs at spike initiation site, selectively control PCs projecting to the basolateral amygdala (BLAPC) compared to those projecting to contralateral cortex (CCPC). These ChCs in turn receive preferential input from local and contralateral CCPCs as opposed to BLAPCs and BLA neurons (the prelimbic cortex-BLA network). Accordingly, optogenetic activation of ChCs rapidly suppresses BLAPCs and BLA activity in freely behaving mice. Thus, the exquisite connectivity of ChCs not only mediates directional inhibition between local PC ensembles but may also shape communication hierarchies between global networks.
Polioviruses that bind a chimeric Pvr–nectin-2 protein identify capsid residues involved in receptor interaction

Amino acid changes in the C'C"D region in poliovirus receptor domain 1 disrupt poliovirus binding. To examine further the role of the C'C"D region in poliovirus infection, we substituted this region of Pvr into the corresponding region of a murine homolog, nectin-2. The chimeric receptor, nectin-2Pvr(c'c"d), rendered transformed L cells susceptible to infection with poliovirus P1/Mahoney, but not with polioviruses P2/Lansing and P3/Leon, due to lack of binding. Twenty-four variants of P2/Lansing were selected that replicate in nectin-2Pvr(c'c"d) producing cell lines. Sequence analysis revealed 30 amino acid changes at 28 capsid residues. One change, K1103R, is found in nearly all isolates and is located at one end of the VP1 BC loop. Other alterations are located on the canyon surface, at the protomer interface, and along the perimeter of the canyon south wall. Unlike poliovirus-Pvr binding, the VP1 BC loop is required for infection of cells producing nectin-2Pvr(c'c"d).
Follow the protons: a low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases.

Seven proton transfers in five steps participate in a catalytic turnover of an aspartic protease. The Rosetta Stone for elucidating their role is a low-barrier hydrogen bond that holds the two aspartic carboxyls in a coplanar conformation. The proton of this bond shuttles between oxygens during chemical steps via hydrogen tunneling, unlike in previous proposals where it was transferred to substrate. After the release of products, both carboxyls are protonated and the bond is missing. Re-forming the bond is a significant step within a kinetic isomechanism. The bond also explainsat long lastthe extremely low pK in pH profiles.
FST and the triangle inequality for biallelic markers

The population differentiation statistic FST, introduced by Sewall Wright, is often treated as a pairwise distance measure between populations. As was known to Wright, however, FST is not a true metric because allele frequencies exist for which it does not satisfy the triangle inequality. We prove that a stronger result holds: for biallelic markers whose allele frequencies differ across three populations, FSTnever satisfies the triangle inequality. We study the deviation from the triangle inequality as a function of the allele frequencies of three populations, identifying the frequency vector at which the deviation is maximal. We also examine the implications of the failure of the triangle inequality for four-point conditions for placement of groups of four populations on evolutionary trees. Next, we study the extent to which FST fails to satisfy the triangle inequality in human genomic data, finding that some loci produce deviations near the maximum. We provide results describing the consequences of the theory for various types of data analysis, including multidimensional scaling and inference of neighbor-joining trees from pairwise FST matrices.
OptiClust, an Improved Method for Assigning Amplicon-Based Sequence Data to Operational Taxonomic Units.

ABSTRACT Assignment of 16S rRNA gene sequences to operational taxonomic units (OTUs) is a computational bottleneck in the process of analyzing microbial communities. Although this has been an active area of research, it has been difficult to overcome the time and memory demands while improving the quality of the OTU assignments. Here, we developed a new OTU assignment algorithm that iteratively reassigns sequences to new OTUs to optimize the Matthews correlation coefficient (MCC), a measure of the quality of OTU assignments. To assess the new algorithm, OptiClust, we compared it to 10 other algorithms using 16S rRNA gene sequences from two simulated and four natural communities. Using the OptiClust algorithm, the MCC values averaged 15.2 and 16.5% higher than the OTUs generated when we used the average neighbor and distance-based greedy clustering with VSEARCH, respectively. Furthermore, on average, OptiClust was 94.6 times faster than the average neighbor algorithm and just as fast as distance-based greedy clustering with VSEARCH. An empirical analysis of the efficiency of the algorithms showed that the time and memory required to perform the algorithm scaled quadratically with the number of unique sequences in the data set. The significant improvement in the quality of the OTU assignments over previously existing methods will significantly enhance downstream analysis by limiting the splitting of similar sequences into separate OTUs and merging of dissimilar sequences into the same OTU. The development of the OptiClust algorithm represents a significant advance that is likely to have numerous other applications. IMPORTANCE The analysis of microbial communities from diverse environments using 16S rRNA gene sequencing has expanded our knowledge of the biogeography of microorganisms. An important step in this analysis is the assignment of sequences into taxonomic groups based on their similarity to sequences in a database or based on their similarity to each other, irrespective of a database. In this study, we present a new algorithm for the latter approach. The algorithm, OptiClust, seeks to optimize a metric of assignment quality by shuffling sequences between taxonomic groups. We found that OptiClust produces more robust assignments and does so in a rapid and memory-efficient manner. This advance will allow for a more robust analysis of microbial communities and the factors that shape them. Podcast : A podcast concerning this article is available.
Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects.

Circular RNAs (circRNAs) are a novel class of endogenous, non-coding RNAs that form covalently closed continuous loops and that are both highly conserved and abundant in the mammalian brain. A role for circRNAs in sponging microRNAs (miRNAs) has been proposed, but the circRNA-miRNA-mRNA interaction networks in human brain cells have not been defined. Therefore, we identified circRNAs in RNA sequencing data previously generated from astrocytes microdissected from the posterior cingulate (PC) of Alzheimer’s disease (AD) patients (N = 10) and healthy elderly controls (N = 10) using four circRNA prediction algorithms - CIRI, CIRCexplorer, find_circ and KNIFE. Overall, utilizing these four tools, we identified a union of 4438 unique circRNAs across all samples, of which 70.3% were derived from exonic regions. Notably, the widely reported CDR1as circRNA was detected in all samples across both groups by find_circ. Given the putative miRNA regulatory function of circRNAs, we identified potential miRNA targets of circRNAs, and further, delineated circRNA-miRNA-mRNA networks using in silico methods. Pathway analysis of the genes regulated by these miRNAs identified significantly enriched immune response pathways, which is consistent with the known function of astrocytes as immune sensors in the brain. In this study, we performed circRNA detection on cell-specific transcriptomic data and identified potential circRNA-miRNA-mRNA regulatory networks in PC astrocytes. Given the known function of astrocytes in cerebral innate immunity and our identification of significantly enriched immune response pathways, the circRNAs we identified may be associated with such key functions. While we did not detect recurrent differentially expressed circRNAs in the context of healthy controls or AD, we report for the first time circRNAs and their potential regulatory impact in a cell-specific and region-specific manner in aged subjects. These predicted regulatory network and pathway analyses may help provide new insights into transcriptional regulation in the brain.
High lumenal chloride in the lysosome is critical for lysosome function

Lysosomes are organelles responsible for the breakdown and recycling of cellular machinery. Dysfunctional lysosomes give rise to lysosomal storage disorders as well as common neurodegenerative diseases. Here, we use a DNA-based, fluorescent chloride reporter to measure lysosomal chloride in Caenorhabditis elegans as well as murine and human cell culture models of lysosomal diseases. We find that the lysosome is highly enriched in chloride, and that chloride reduction correlates directly with a loss in the degradative function of the lysosome. In nematodes and mammalian cell culture models of diverse lysosomal disorders, where previously only lysosomal pH dysregulation has been described, massive reduction of lumenal chloride is observed that is ~103 fold greater than the accompanying pH change. Reducing chloride within the lysosome impacts Ca2+ release from the lysosome and impedes the activity of specific lysosomal enzymes indicating a broader role for chloride in lysosomal function.
MOCVD of group III chalcogenides

A review is presented of recent advances in the metal organic chemical vapour deposition (MOCVD) of thin films of group III chalcogenides, including their application for the passivation of GaAs surfaces. The majority of studies involve the deposition of thermodynamic phases of composition ME and M2E3 (MGa, In; ES, Se, Te), however, MOCVD allows for the growth of either high-pressure (tetragonal InS) or non-thermodynamic phases (metastable cubic phases of GaS and InSe). Based on the results to date, a series of goals for molecular control over the structure of deposited films is discussed.
Raspberry Pi–powered imaging for plant phenotyping

Premise of the study Image-based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost-prohibitive. To make high-throughput phenotyping methods more accessible, low-cost microcomputers and cameras can be used to acquire plant image data. Methods and results We used low-cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi-controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (e.g., shape, area, height, color) en masse using open-source image processing software such as PlantCV. Conclusions This protocol describes three low-cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open-source image processing tools, these imaging platforms provide viable low-cost solutions for incorporating high-throughput phenomics into a wide range of research programs.