cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterizing protein-DNA binding event subtypes in ChIP-exo data.

Motivation Regulatory proteins associate with the genome either by directly binding cognate DNA motifs or via protein-protein interactions with other regulators. Each recruitment mechanism may be associated with distinct motifs and may also result in distinct characteristic patterns in high-resolution protein-DNA binding assays. For example, the ChIP-exo protocol precisely characterizes protein-DNA crosslinking patterns by combining chromatin immunoprecipitation (ChIP) with 5' → 3' exonuclease digestion. Since different regulatory complexes will result in different protein-DNA crosslinking signatures, analysis of ChIP-exo tag enrichment patterns should enable detection of multiple protein-DNA binding modes for a given regulatory protein. However, current ChIP-exo analysis methods either treat all binding events as being of a uniform type or rely on motifs to cluster binding events into subtypes. Results To systematically detect multiple protein-DNA interaction modes in a single ChIP-exo experiment, we introduce the ChIP-exo mixture model (ChExMix). ChExMix probabilistically models the genomic locations and subtype memberships of binding events using both ChIP-exo tag distribution patterns and DNA motifs. We demonstrate that ChExMix achieves accurate detection and classification of binding event subtypes using in silico mixed ChIP-exo data. We further demonstrate the unique analysis abilities of ChExMix using a collection of ChIP-exo experiments that profile the binding of key transcription factors in MCF-7 cells. In these data, ChExMix identifies possible recruitment mechanisms of FoxA1 and ERα, thus demonstrating that ChExMix can effectively stratify ChIP-exo binding events into biologically meaningful subtypes. Availability and implementation ChExMix is available from https://github.com/seqcode/chexmix. Supplementary information Supplementary data are available at Bioinformatics online.
Forming appropriate peer groups for bank research: a cluster analysis of bank financial statements

Choosing appropriate peer groups for commercial banks is important to investors comparing bank performance, for regulators evaluating safety and soundness, for bank management looking at merger alternatives or relative performance, and for bank researchers testing hypotheses and making policy judgments about the banking system. We use commercial bank financial statements with common size variables as the inputs to a cluster analysis model to identify clusters or groups of banks with financial structures that are relatively homogeneous within groups and distinct across groups. Managerial strategies and idiosyncrasies, local and global economic conditions, and the regulatory environment shape bank financial statements, and financial statements should reflect the financial and operational differences across banks. Using year-end data from 2014, we cluster 6444 banks into several such groups. Our results show that bank clusters are formed largely around loan types, funding differences, and management’s strategic choices. We compare the ability of bank clusters and bank size to explain several widely used measures of bank performance and risk in additional years. These bank clusters are shown to have substantially greater explanatory power in regression models when compared to groupings based on bank size in several different years.
Segmentation of biological images containing multitarget labeling using the jelly filling framework

Biomedical imaging when combined with digital image analysis is capable of quantitative morphological and physiological characterizations of biological structures. Recent fluorescence microscopy techniques can collect hundreds of focal plane images from deeper tissue volumes, thus enabling characterization of three-dimensional (3-D) biological structures at subcellular resolution. Automatic analysis methods are required to obtain quantitative, objective, and reproducible measurements of biological quantities. However, these images typically contain many artifacts such as poor edge details, nonuniform brightness, and distortions that vary along different axes, all of which complicate the automatic image analysis. Another challenge is due to "multitarget labeling," in which a single probe labels multiple biological entities in acquired images. We present a "jelly filling" method for segmentation of 3-D biological images containing multitarget labeling. Intuitively, our iterative segmentation method is based on filling disjoint tubule regions of an image with a jelly-like fluid. This helps in the detection of components that are "floating" within a labeled jelly. Experimental results show that our proposed method is effective in segmenting important biological quantities.
An azeotropic drying‐free approach for copper‐mediated radiofluorination without addition of base

Copper-mediated radiofluorination provides a quick and versatile approach for 18 F-labeling of arenes and heteroarenes. However, this method is known to be base sensitive, which has been a barrier for preparative scale radiosynthesis. In this report, we provide an approach for copper-mediated radiofluorination without azeotropic drying or adding a base. [18 F]Fluoride trapped on a PS-HCO3 Sep-Pak was quantitatively eluted with a solution of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAP·OTf) in anhydrous N,N-dimethylformamide (DMF). The eluted solution was directly used for copper-mediated radiofluorination. Twelve boronic ester substrates were tested, yielding fluorinated products in 27% to 83% radiochemical yield based on HPLC analysis. This approach was successfully applied to the radiosynthesis of [18 F]flumazenil, a well-known positron emission tomography (PET) tracer for imaging central benzodiazepine receptors, with a radiochemical yield of 47%. This highly efficient protocol significantly augments the powerful copper-mediated radiofluorination approach.
Tumor establishment requires tumor autonomous and non autonomous decoupling of EGF signaling from apoptosis

Summary During organ turnover, robust mechanisms enforce a balanced equilibrium between cell division and death [1, 2]. Nascent tumors must destabilize these mechanisms to subvert cell equilibrium for cancerous growth [3–7]. The nature of these destabilizing events is central to understanding how new tumors become established and may suggest strategies for cancer prevention. One of the best characterized mechanisms for cell equilibrium is that of the adult Drosophila intestine. In this organ, division is coupled to death because Rhomboid, a protease that cleaves mitogenic EGFs for secretion, is induced in cells undergoing apoptotic elimination [8]. In Drosophila, as in mammals, intestinal stem cells give rise to adenomas following loss of adenomatous polyposis coli (APC) [9]. Examining Drosophila APC-/- tumorigenesis, we find that pre-tumor cells destabilize cell equilibrium by uncoupling rhomboid from apoptosis, which creates feed-forward amplification of EGF signaling for tumor establishment. Prior to tumor formation, APC-/- cells induce rhomboid in surrounding cells via activation of the stress signal JNK. During subsequent growth, APC-/- tumors induce rhomboid within the tumor itself via loss of E-cadherin and consequent activity of p120-catenin. Chronic induction of rhomboid in both tumor and surrounding cells leads to constitutive activation of EGFR and is essential for tumors to progress. Thus, incipient tumors combine non-autonomous and autonomous strategies to deregulate rhomboid and destabilize cell equilibrium. Since Rhomboid, EGFR, and E-cadherin are associated with colorectal cancer in humans [10–17], our findings may shed light on how human colorectal tumors progress.
BlAnC: Blockchain-based Anonymous and Decentralized Credit Networks

Distributed credit networks, such as Ripple~\citeripple and Stellar~\citestellar, are becoming popular as an alternative means for financial transactions. % However, the current designs do not preserve user privacy or are not truly decentralized. % In this paper, we explore the creation of a distributed credit network that preserves user and transaction privacy and unlinkability. We propose BlAnC, a novel, fully decentralized blockchain-based credit network where credit transfer between a sender-receiver pair happens on demand. In BlAnC, multiple concurrent transactions can occur seamlessly, and malicious network actors that do not follow the protocols and/or disrupt operations can be identified efficiently. % for potential debarring by the users from future transactions. % We perform security analysis of our proposed protocols in the universal composability framework to demonstrate its strength, and discuss how our network handles operational dynamics. % We also present preliminary experiments and scalability analyses.
K -Shell Core-Electron Excitations in Electronic Stopping of Protons in Water from First Principles

Understanding the role of core-electron excitation in liquid water under proton irradiation has become important due to the growing use of proton beams in radiation oncology. Using a first-principles, nonequilibrium simulation approach based on real-time, time-dependent density functional theory, we determine the electronic stopping power, the velocity-dependent energy transfer rate from irradiating ions to electrons. The electronic stopping power curve agrees quantitatively with experimental data over the velocity range available. At the same time, significant differences are observed between our first-principles result and commonly used perturbation theoretic models. Excitations of the water molecules' oxygen core electrons are a crucial factor in determining the electronic stopping power curve beyond its maximum. The core-electron contribution is responsible for as much as one third of the stopping power at the high proton velocity of 8.0 a.u. (1.6 MeV). $K$-shell core-electron excitations not only provide an additional channel for the energy transfer---they also significantly influence the valence electron excitations. In the excitation process, generated holes remain highly localized within a few angstroms around the irradiating proton path, whereas electrons are excited away from the path. In spite of their great contribution to the stopping power, $K$-shell electrons play a rather minor role in terms of the excitation density; only 1% of the hole population composes $K$-shell holes, even at the high proton velocity of 8.0 a.u. The excitation behavior revealed is distinctly different from that of photon-based ionizing radiation such as x or $\ensuremath{\gamma}$ rays.
Correlation Between Sheet Carrier Density-Mobility Product and Persistent Photoconductivity in AlGaN/GaN Modulation Doped Heterostructures

High quality Al0.25Ga0.75N/GaN modulation-doped heterojunction field-effect transistor (MOD-HFET) structures grown on sapphire substrates with high sheet carrier density and mobility products (nsμ > 1016/Vs at room temperature) have been grown by metal organic chemical vapor deposition (MOCVD). The optimized structures were achieved by varying structural parameters, including the AlGaN spacer layer thickness, the Si-doped AlGaN barrier layer thickness, the Si-doping concentration, and the growth pressure. In these structures, the persistent photoconductivity (PPC) effect associated with the two-dimensional electron gas (2DEG) system was invariantly observed. As a consequence, the characteristic parameters of the 2DEG were sensitive to light and the sensitivity was associated with permanent photoinduced increases in the 2DEG carrier mobility (μ) and sheet carrier density (ns). However, we observed that the magnitude of the PPC and hence the photoinduced instability associated with these heterostructures were a strong function of only one parameter, the product of ns and μ, which is the most important parameter for the HFET device design. For a fixed excitation photon dose, the ratio of the low temperature PPC to the dark conductivity level was observed to decrease from 200% to 3% as the nsμ (300 K) product was increased from 0.048 × 1016/Vs to 1.4 × 1016/Vs. Based on our studies, we suggest that the magnitude of the low temperature PPC can be used as a sensitive probe for monitoring the electronic quality of the AlGaN/GaN HFET structures.
Effect of Moisture on Dopant Segregation in Solid Hosts

Transition metal-doped semiconductor materials are extensively employed for light harvesting and photocatalytic applications owing to their increased light absorption and charge mobility. In this work, spatial tailoring of the Ni dopant in TiO2 nanostructures is performed by varying the secondary processing parameters to engineer the resulting optoelectronic properties for select applications. Specifically, the aging of the dried Ti sol and the resulting Ni segregation are observed to be moisture-driven phenomena based on the infrared and time-resolved UV–vis spectroscopy measurements. While X-ray diffraction and scanning transmission electron microscopy coupled with electron energy-loss spectroscopy characterizations show a clear difference in the crystal structures between pristine TiO2 powders and phase-segregated NiO–TiO2, the thermogravimetric measurements reveal substitution of the ethoxy group by ambient moisture, resulting in the ejection of hydroxylated Ni clusters. Furthermore, the doped system ...
Predicting progression of in situ carcinoma in the era of precision genomics

Cancer control depends on early detection, a discipline formalized in the 1950s by widespread use of the Papanicolaou test for detecting pre-invasive squamous epithelial neoplasia of the uterine cervix (1-3). Studies growing out of that public health initiative have revealed a long latency between the earliest cellular abnormalities and invasive cancer. Pre-invasive or intraepithelial neoplasia arises in predisposed benign tissue, often influenced by metaplasia or inflammation (4,5). These precursor lesions can be reliably diagnosed by the microscopic appearance, but the biological behavior of these lesions is difficult to predict by histology alone. In situ carcinoma of the cervix or breast has only a 50% probability of eventually becoming invasive cancer (1-3).
Acceleration of the reduction of aldehydes and ketones using Mn(dpm)3 catalyst and phenylsilane in the presence of dioxygen

Abstract Saturated ketones and aldehydes are reduced to alcohols by phenylsilane and Mn(dpm)3(cat) in the presence of dioxygen.
A facile route to 2-substituted N-Boc pyrrolidines

Abstract Dipole stabilized carbanion 2 cyclizes to afford the key intermediate 2-benzotriazolyl-N-Boc-pyrrolidine 3, which undergoes nucleophilic displacement of the benzotriazolyl group to afford various 2-substituted-N-Boc-pyrrolidines in good yields.
Generation and Selection of a Panel of Pan-Filovirus Single-Chain Antibodies using Cell-Free Ribosome Display

Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there is lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known Ebolavirus and Marburgvirus species. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.
Potent and selective α1A adrenoceptor partial agonists—Novel imidazole frameworks

Abstract Novel imidazole frameworks have been identified as potent partial agonists of the α1A adrenergic receptor, with good selectivity over the α1B, α1D and α2A receptor sub-types. Nitrile 28 possessed attractive CNS drug-like properties with good membrane permeability and no P-pg mediated efflux. 28 also possessed excellent solubility, metabolic stability and wide ligand selectivity.
Oxidative cyclization of 1,4-dienes to yield 2,3,5-trisubstituted tetrahydrofuran-diols

Abstract KMnO4 and OsO4 catalyze the oxidative cyclization of 1,4-dienes to provide 2,3,5-trisubstituted tetrahydrofuran-diols in 30% yield. This reaction proceeds stereoselectively via a proposed [3+2] cycloaddition. Competing oxidative pathways are the major non-productive processes that reduce the yield of the reaction; however, four stereogenic centers are established in one-step.
Synthesis of Metastable Post-Transition-Metal Iron Antimony Skutterudites Using the Multilayer Precursor Method

Modulated elemental reactants were used to form amorphous ternary reaction intermediates of the desired compositions. The amorphous reaction intermediate for each system crystallizes exothermically below 200 °C forming kinetically stable “filled” skutterudites of general formula M1-xFe4Sb12 where M = Sn, Al, Ga, In, and Zn. These metastable compounds can only be prepared by controlling the reaction intermediates, avoiding the formation of more thermodynamically stable binary compounds. We propose that the desired compounds nucleate from the amorphous precursor because slow solid-state diffusion rates hinder disproportionation into the more stable mix of binary compounds and elements. If modulated elemental reactants are prepared with layer thicknesses above a critical value (∼40 A), the thermodynamically stable binary compound FeSb2 interfacially nucleates, preventing formation of the desired metastable ternary compounds. The use of low-angle X-ray diffraction and calorimetry provide the data necessary to...
What Constitutes a Constitutional Amendment Culture

Abstract Why are some constitutions amended frequently and others hardly at all? An obvious candidate determinant is constitutional rigidity, i.e., the size and number of procedural barriers to amendment. Given some demand for amendment, greater rigidity implies a smaller supply. However, measures of rigidity often do not correlate significantly (or even with the predicted sign) with amendment rates. Ginsburg and Melton (2015) argue that amendment culture – “shared attitudes about the desirability of amendment” – is a more important determinant of amendment rates. We study up to 128 constitutional episodes from 54 countries and estimate relationships between amendment rates and Hofstede cultural indices. Cultures that are more individualistic and less prone to uncertainty avoidance are associated with higher amendment rates. When cultural dimensions are controlled for, the lagged amendment rate (Ginsburg and Melton’s proxy for culture) is not a robust correlate.
Multimodal representations of person identity individuated with fMRI

Recognizing the identity of a person is fundamental to guide social interactions. We can recognize the identity of a person looking at her face, but also listening to her voice. An important question concerns how visual and auditory information come together, enabling us to recognize identity independently of the modality of the stimulus. This study reports converging evidence across univariate contrasts and multivariate classification showing that the posterior superior temporal sulcus (pSTS), previously known to encode polymodal visual and auditory representations, encodes information about person identity with invariance within and across modality. In particular, pSTS shows selectivity for faces, selectivity for voices, classification of face identity across image transformations within the visual modality, and classification of person identity across modality.
Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center

Background Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. Procedure This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. Results There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1–2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). Conclusions The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials.
Rh3Ga5: a new intermetallic compound in the rhodium–gallium system and its crystal structure

Abstract A new binary compound in the rhodium–gallium system has been synthesized. Rh3Ga5 crystallizes in the triclinic space group P 1 with the unit cell parameters a=4.961(1) A, b=6.655(1) A, c=7.870(3) A, α=100.76(3)°, β=104.67(3)°, γ=101.50(3)°. Its crystal structure can be described in terms of strongly distorted close packed layers that are broken in some places by less dense packing. An alternative polyhedral description of the structure is also presented.
Novel microwave initiated solid-state metathesis synthesis and characterization of lanthanide phosphates and vanadates, LMO4 (L = Y, La and M = V, P)

Abstract A novel solid-state metathesis (SSM) approach represented by the reaction (LCl3 + Na3VO4 → LVO4 + NaCl) (L = Y, La) is proposed to synthesize technologically important rare-earth phosphates and vanadates. The SSM reaction, driven in the forward direction is facilitated by the formation of high lattice energy by-product like NaCl. The structural, thermal, optical, and chemical properties of synthesized powders are determined by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and diffused reflectance (DR) spectra in the UV–vis range. The direct band gap of the synthesized materials was found out to be ∼3.5 eV for LaVO4, YVO4, YPO4 and ∼2.6 eV for LaPO4.
Enantioselective hydroamination/cyclization of aminoalkenes by (bis)-C2 symmetric and (mono)-C2 symmetric anionic tetraamide complexes of La(III)

Abstract Enantioselective hydroamination/cyclizations of several monosubstituted and disubstituted aminoalkenes have been achieved, catalyzed by tetracoordinate anionic La(III) complexes.
REGIOSELECTIVE ALKYLATION OF N-(DIPHENYLMETHYLIDINE)-3-(AMINOMETHYL)PYRIDINE : A SIMPLE ROUTE TO MINOR TOBACCO ALKALOIDS AND RELATED COMPOUNDS

Abstract A simple synthetic route to minor tobacco alkaloids and related compounds is described involving regioselective alkylation of N-(diphenylmethylidine)-3-(aminomethyl)pyridine with a suitable dielectrophile.
Asymmetric synthesis of 4-[(t-butoxycarbonyl)amino]-pyrazolidin-3-one : precursor to bicyclic pyrazolidinone antibacterials

Abstract The preparation of chiral pyrazolidin-3-one 1 is described. The key step was cyclization via a Mitsunobu reaction using the trifluoroacetyl group to activate the terminal nitrogen.
Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis.

Systemic sclerosis with pulmonary arterial hypertension (SSc-PAH) is a debilitating and frequently lethal disease of unknown cause lacking effective treatment options. Lymphocyte anomalies and autoantibodies observed in systemic sclerosis have suggested an autoimmune character. We study the clonal structure of the B cell repertoire in SSc-PAH using immunoglobulin heavy chain (IGH) sequencing before and after B cell depletion. We found SSc-PAH to be associated with anomalies in B cell development, namely, altered VDJ rearrangement frequencies (reduced IGHV2-5 segment usage) and an increased somatic mutation–fixation probability in expanded B cell lineages. SSc-PAH was also characterized by anomalies in B cell homeostasis, namely, an expanded immunoglobulin D–positive (IgD+) proportion with reduced mutation loads and an expanded proportion of highly antibody-secreting cells. Disease signatures pertaining to IGHV2-5 segment usage, IgD proportions, and mutation loads were temporarily reversed after B cell depletion. Analyzing the time course of B cell depletion, we find that the kinetics of naive replenishment are predictable from baseline measurements alone, that release of plasma cells into the periphery can precede naive replenishment, and that modes of B cell receptor diversity are highly elastic. Our findings reveal humoral immune signatures of SSc-PAH and uncover determinism in the effects of B cell depletion on the antibody repertoire.
Anopheles mosquitoes may drive invasion and transmission of Mayaro virus across geographically diverse regions

The Togavirus (Alphavirus) Mayaro virus (MAYV) was initially described in 1954 from Mayaro County (Trinidad) and has been responsible for outbreaks in South America and the Caribbean. Imported MAYV cases are on the rise, leading to invasion concerns similar to Chikungunya and Zika viruses. Little is known about the range of mosquito species that are competent MAYV vectors. We tested vector competence of 2 MAYV genotypes in laboratory strains of six mosquito species (Aedes aegypti, Anopheles freeborni, An. gambiae, An. quadrimaculatus, An. stephensi, Culex quinquefasciatus). Ae. aegypti and Cx. quinquefasciatus were poor MAYV vectors, and had either poor or null infection and transmission rates at the tested viral challenge titers. In contrast, all Anopheles species were able to transmit MAYV, and 3 of the 4 species transmitted both genotypes. The Anopheles species tested are divergent and native to widely separated geographic regions (Africa, Asia, North America), suggesting that Anopheles may be important in the invasion and spread of MAYV across diverse regions of the world.
Efficient Synergistic Single-Cell Genome Assembly

As the vast majority of all microbes are unculturable, single-cell sequencing has become a significant method to gain insight into microbial physiology. Single-cell sequencing methods, currently powered by multiple displacement genome amplification (MDA), have passed important milestones such as finishing and closing the genome of a prokaryote. However, the quality and reliability of genome assemblies from single cells are still unsatisfactory due to uneven coverage depth and the absence of scattered chunks of the genome in the final collection of reads caused by MDA bias. In this work, our new algorithm Hybrid De novo Assembler (HyDA) demonstrates the power of co-assembly of multiple single-cell genomic data sets through significant improvement of the assembly quality in terms of predicted functional elements and length statistics. Co-assemblies contain significantly more base pairs and protein coding genes, cover more subsystems, and consist of longer contigs compared to individual assemblies by the same algorithm as well as state-of-the-art single-cell assemblers SPAdes and IDBA-UD. Hybrid \emph{De novo} Assembler (HyDA) is also able to avoid chimeric assemblies by detecting and separating shared and exclusive pieces of sequence for input data sets. By replacing one deep single-cell sequencing experiment with a few single-cell sequencing experiments of lower depth, the co-assembly method can hedge against the risk of failure and loss of the sample, without significantly increasing sequencing cost. Application of the single-cell co-assembler HyDA to the study of three uncultured members of an alkane-degrading methanogenic community validated the usefulness of the co-assembly concept. HyDA is open source and publicly available at http://chitsazlab.org/software.html and the raw reads are available at http://chitsazlab.org/research.html.
Memory deficits in males and females long after subchronic immune challenge

Abstract Memory impairments and cognitive decline persist long after recovery from major illness or injury, and correlate with increased risk of later dementia. Here we developed a subchronic peripheral immune challenge model to examine delayed and persistent memory impairments in females and in males. We show that intermittent injections of either lipopolysaccharides or Poly I:C cause memory decline in both sexes that are evident eight weeks after the immune challenge. Importantly, we observed sex-specific patterns of deficits. Females showed impairments in object recognition one week after challenge that persisted for at least eight weeks. In contrast, males had intact memory one week after the immune challenge but exhibited broad impairments in memory tasks including object recognition, and both context and tone fear conditioning several months later. The differential patterns of memory deficits in males and in females were observed without sustained microglial activation or changes in blood-brain barrier permeability. Together, these data suggest that transient neuroimmune activity results in differential vulnerabilities of females and males to memory decline after immune challenge. This model will be an important tool for determining the mechanisms in both sexes that contribute to memory impairments that develop over the weeks and months after recovery from illness. Future studies using this model will provide new insights into the role of chronic inflammation in the pathogenesis of long-lasting memory decline and dementias.
Further Pseudopericyclic Reactions: An ab Initio Study of the Conformations and Reactions of 5-Oxo-2,4-pentadienal and Related Molecules

It has been proposed that all pseudopericyclic reactions are allowed, regardless of the number of electrons involved. 5-Oxo-2,4-pentadienal (1) is a vinylog of formylketene, and thus its reactions provide a test of this proposal. Ab initio (MP4(full, SDQ)/D95**//MP2/6-31G* + ZPE) calculations were carried out on all the conformations and several reactions of 1, as well as related systems. One of the eight possible conformations of 1 (zZz1) does not exist, but closes without a barrier, via a pseudopericyclic pathway to pyran-2-one (3). IR spectra of 1 in Ar matrices are consistent with three conformations (zZe1, eZz1, and eZe1). Calculated rotational barriers from zZe1 and eZz1 to 3 are consistent with observed kinetics for the of decay of 1. The structures of s-Z- and s-E-3-hydroxy-1,2-propadien-1-one (18 and 19) and the vinylogous cumulene 16 are predicted to have strongly bent geometries. The barrier to internal proton transfer from 16 is only 0.8 kcal/mol, while the barrier from 18 is 23.7 kcal/mol. Ba...
Convenient One-Pot Methodology for the Primary Aminomethylation of Electron Rich Heterocycles

Abstract Primary aminomethyl groups were introduced into the 2-position of electron rich heterocycles in moderate to good yields by a one-pot sequence involving lithiation, transmetalation into an organozinc reagent and treatment with 1-(triphenylphosphoroylideneaminomethyl) benzotriazole (betmip).
Synthesis of C-aryl glycosides related to the chrysomycins

Abstract A synthesis of chrysomycin substructure 44 is described in which a Ramberg-Backlund reaction plays a key role. Electrochemical oxidation of 44 provided 45 , and unsuccessful attempts to convert 45 to chrysomycin B ( 2 ) are presented.
Copper-Catalyzed Hydrofunctionalization of Alkynes

We have developed a general approach to the catalytic hydrofunctionalization of alkynes, involving hydrocupration and electrophilic functionalization of the resulting alkenylcopper intermediate. Using this approach with different electrophiles we have developed three transformations: semireduction, hydrobromination, and hydroalkylation of alkynes. In the context of a brief history of copper hydride complexes in organic chemistry, in this account we describe the key developments that inspired and enabled our research. We also describe the reaction development, the scope, and the mechanism of these transformations. In the process, we highlight some of the challenges inherent to our approach and summarize new insights that allowed us to successfully address them. 1 Introduction 2 Semireduction 3 Hydrobromination 4 Hydroalkylation 5 Conclusions
Alkylation of aromatic aldehydes with boron halide derivatives

Aryl aldehydes react with alkylboron chloride derivatives in the presence of base to generate the corresponding arylalkylmethanols in good yields. A variety of alkylboron chlorides can be utilized in the new alkylation reaction.
Copper-catalyzed allylic hydroxyamination and amination of alkenes with Boc-hydroxylamine

Abstract Olefins react regioselectively with Boc-NHOH in the presence of Cu(I,II) salts to produce allyl-N(OH)(Boc) derivatives, apparently via the intermediacy of Boc-N O; yields and rates are dramatically improved by the addition of H2O2. The corresponding allylamine derivatives, allyl-NH(Boc), are formed selectively from Boc-NHOH/olefin with CuBr/P(OEt)3.
Population regulation in microbial consortia using dual feedback control

An ongoing area of study in synthetic biology has been the design and construction of synthetic circuits that maintain homeostasis at the population level. Here, we are interested in designing a synthetic control circuit that regulates the total cell population and the relative ratio between cell strains in a culture that contains two different cell strains. We have developed a dual feedback control strategy that uses two separate control loops to achieve the two control objectives respectively. We have implemented the strategy in a population regulation circuit where both the total population size and relative cell strain ratio can be set by reference signals. The circuit shows robustness and adaptation to perturbations in cell growth rate and changes in cell numbers. The control architecture is general and could apply to any organism for which synthetic biology tools for quorum sensing, comparison between outputs, and growth control are available.
The Kondo Resonance in Electron Spectroscopy

The Kondo resonance is the spectral manifestation of the Kondo properties of the impurity Anderson model, and also plays a central role in the dynamical mean-field theory (DMFT) for correlated electron lattice systems. This article presents an overview of electron spectroscopy studies of the resonance for the 4f electrons of cerium compounds, and for the 3d electrons of V2O3, including beginning efforts at using angle resolved photoemission to determine the k-dependence of the resonance. The overview includes the comparison and analysis of spectroscopy data with theoretical spectra as calculated for the impurity model and as obtained by DMFT, and the Kondo volume collapse calculation of the cerium – phase transition boundary, with its spectroscopic underpinnings.
β-Amino alcohols derived from (1R,2S)-norephedrine and (1S,2S)-pseudonorephedrine as catalysts in the asymmetric addition of diethylzinc to aldehydes

Abstract A family of N -alkylnorephedrine and N -alkylpseudonorephedrine derived ligands were prepared and applied in the asymmetric alkylation of benzaldehyde using diethylzinc. The absolute configuration of the addition product was directed primarily by the benzylic position of the Ephedra alkaloid, while the magnitude of the enantiomeric ratio was heavily influenced by the nitrogen substituent. However, sterically demanding substituents at the nitrogen position caused the enantioselectivity to be the same for the two diastereomeric systems. Among the ligands that were prepared, it was determined that the N -cyclooctylpseudonorephedrine derivative 7b yielded the highest enantiomeric ratios (87.5:12.5 to 91.0:9.0) when applied in the catalytic asymmetric addition of diethylzinc to aldehydes.
RNA polymerases IV and V influence the 3' boundaries of Polymerase II transcription units in Arabidopsis.

Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in plants as specialized forms of Pol II. Their functions are best understood in the context of RNA-directed DNA methylation...
Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance.

Drug naive animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase is required to terminate Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/β neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.
Synthesis of 4-aryl-2,3-dihydropyrroles via Rh-catalyzed intramolecular hydroamino-methylation reaction

The rhodium-catalyzed intramolecular hydroaminomethylation reaction, generating 4-aryl-2,3-dihydropyrroles, has been developed. Triphenylphosphine has been proved to be the excellent ligand to prepare the dihydropyrrole derivatives in up to 99% yield. This procedure provides an efficient and simple alternative route to synthesize 4-aryl-2,3-dihydropyrrole derivatives only in one step.
Exchange-Coupled Soft Magnetic FeNi−SiO2 Nanocomposite

We report a method to make exchange-coupled soft magnetic FeNi−SiO2 nanocomposite material composed of FeNi nanoparticles coated with a thin SiO2 layer. Permeability is independent of frequency up to at least 100 MHz, with value as high as 16 in samples with density merely 93% of the ideal density. The quality factors are higher than conventional high-frequency CoNi ferrites after 10 MHz and decrease in a much slower fashion with increasing frequency. We ascribe these experimental observations to the exchange coupling among the magnetic particles.
Ab initio thermochemistry for unsaturated C2 hydrocarbons

The first systematic study of the sequential bond dissociation energies for ethylene and acetylene, using generalized valence bond (GVB) theory and the correlation-consistent configuration interaction (CCCI) method is presented. The ab initio GVB/CCCI sequential C-H bond strengths in ethylene and acetylene are: D{sub 0}(H{sub 2}CCH-H) = 109.5 (110.9 {plus minus} 2) kcal/mol, D{sub 0}(H{sub 2}CC-H) = 70.8 (74.4 {plus minus} 3) kcal/mol, D{sub 0}(HCCH-H) = 37.1 (40.0 {plus minus} 3) kcal/mol, D{sub 0}(CCH-H) = 86.3 (91.3 {plus minus} 5) kcal/mol, D{sub 0}(HCC-H) = 129.7 (131.1 {plus minus} 2) kcal/mol, and D{sub 0}(CC-H) = 95.6 (102.5 {plus minus} 3) kcal/mol. The values in parentheses represent best estimates for the actual band strengths, taking into account known systematic and random errors. New predictions for C{double bond}C double bond strengths are D{sub 0}(H{sub 2}C{double bond}CH) = 162.5 (168.2 {plus minus} 6) kcal/mol and D{sub 0}(H{sub 2}C{double bond}C) = 149.5 (155.5 {plus minus} 5) kcal/mol, while predictions for C{triple bond}C triple bond strengths are: D{sub 0}(HC{triple bond}C) = 160.4 (168.9 {plus minus} 13) kcal/mol and D{sub 0}(C{triple bond}C) = 134.7 (129.2 {plus minus} 15) kcal/mol.
Image Classification and Retrieval with Random Depthwise Signed Convolutional Neural Networks

We propose a random convolutional neural network to generate a feature space in which we study image classification and retrieval performance. Put briefly we apply random convolutional blocks followed by global average pooling to generate a new feature, and we repeat this k times to produce a k-dimensional feature space. This can be interpreted as partitioning the space of image patches with random hyperplanes which we formalize as a random depthwise convolutional neural network. In the network’s final layer we perform image classification and retrieval with the linear support vector machine and k-nearest neighbor classifiers and study other empirical properties. We show that the ratio of image pixel distribution similarity across classes to within classes is higher in our network’s final layer compared to the input space. When we apply the linear support vector machine for image classification we see that the accuracy is higher than if we were to train just the final layer of VGG16, ResNet18, and DenseNet40 with random weights. In the same setting we compare it to a recent unsupervised feature learning method and find our accuracy to be comparable on CIFAR10 but higher on CIFAR100 and STL10. We see that the accuracy is not far behind that of trained networks, particularly in the top-k setting. For example the top-2 accuracy of our network is near 90% on both CIFAR10 and a 10-class mini ImageNet, and 85% on STL10. We find that k-nearest neighbor gives a comparable precision on the Corel Princeton Image Similarity Benchmark than if we were to use the final layer of trained networks. As with other networks we find that our network fails to a black box attack even though we lack a gradient and use the sign activation. We highlight sensitivity of our network to background as a potential pitfall and an advantage. Overall our work pushes the boundary of what can be achieved with random weights.
Atom-Economical Synthesis of Functionalized Cycloalkanes via Catalytic Redox Cycloisomerization of Propargyl Alcohols

An atom-economical procedure for the direct synthesis of cycloalkanes from propargyl alcohols is reported. This high-yielding one-pot process involves a sequence consisting of a Ru-catalyzed redox isomerization of ynols into enones or an enal followed by an intramolecular Michael addition of a variety of carbon nucleophiles. Furthermore, an asymmetric variant of this protocol realized by the aid of a chiral nonracemic diamine catalyst, which provides the cyclization products in up to 97% ee, is presented.
Formation of reactive o-quinone methides from the reaction of trimethylsilyl(methyl)-substituted 1,4-benzoquinones with nucleophiles

o-Quinone methides are formed from the reaction of nucleophiles with trimethylsilyl(methyl)-1,4-benzoquinones. These reactive intermediates are trapped by excess nucleophile to form substituted quinones following oxidation. In addition, varying amounts of a symmetrical dimer and a xanthen derivative were observed. The influence of different nucleophiles and ring substituents on the rate of reaction have been studied, and are consistent with rate-limiting formation of a vinylogous enolate initiated by attack of the nucleophile on the silyl group.
Loss of cytoplasmic incompatibility and minimal fecundity effects explain relatively low Wolbachia frequencies in Drosophila mauritiana.

Maternally transmitted Wolbachia bacteria infect about half of all insect species. Many Wolbachia cause cytoplasmic incompatibility (CI) and reduced egg hatch when uninfected females mate with infected males. Although CI produces a frequency-dependent fitness advantage that leads to high equilibrium Wolbachia frequencies, it does not aid Wolbachia spread from low frequencies. Indeed, the fitness advantages that produce initial Wolbachia spread and maintain non-CI Wolbachia remain elusive. wMau Wolbachia infecting Drosophila mauritiana do not cause CI, despite being very similar to CI-causing wNo from Drosophila simulans (0.068% sequence divergence over 682,494 bp), suggesting recent CI loss. Using draft wMau genomes, we identify a deletion in a CI-associated gene, consistent with theory predicting that selection within host lineages does not act to increase or maintain CI. In the laboratory, wMau shows near-perfect maternal transmission; but we find no significant effect on host fecundity, in contrast to published data. Intermediate wMau frequencies on the island of Mauritius are consistent with a balance between unidentified small, positive fitness effects and imperfect maternal transmission. Our phylogenomic analyses suggest that group-B Wolbachia, including wMau and wPip, diverged from group-A Wolbachia, such as wMel and wRi, 6-46 million years ago, more recently than previously estimated.
Novel Synthetic Routes to 8-Vinyl Chlorophyll Derivatives

New methodology was developed toward the synthesis of 8-de-ethyl-8-vinylchlorophyll-a 1. Such 8-de-ethyl-8-vinyl derivatives of the green plant pigment chlorophyll-a 2 have been proposed to be inte...
Hydraulic conductance and the maintenance of water balance in flowers

Flowers face desiccating conditions, yet little is known about their ability to transport water. We quantified variability in floral hydraulic conductance (Kflower ) for 20 species from 10 families and related it to traits hypothesized to be associated with liquid and vapour phase water transport. Basal angiosperm flowers had trait values associated with higher water and carbon costs than monocot and eudicot flowers. Kflower was coordinated with water supply (vein length per area, VLA) and loss (minimum epidermal conductance, gmin ) traits among the magnoliids, but was insensitive to variation in these traits among the monocots and eudicots. Phylogenetic independent contrast (PIC) correlations revealed that few traits had undergone coordinated evolution. However, VLA and the desiccation time (Tdes ), the quotient of water content and gmin , had significant trait and PIC correlations. The near absence of stomata from monocot and eudicot flowers may have been critical in minimizing water loss rates among these clades. Early divergent, basal angiosperm flowers maintain higher Kflower because of traits associated with high rates water loss and water supply, while monocot and eudicot flowers employ a more conservative strategy of limiting water loss and may rely on stored water to maintain turgor and delay desiccation.
4-Dihydroxyborylphenyl Analogues of 1-Aminocyclobutanecarboxylic Acids: Potential Boron Neutron Capture Therapy Agents

A series of 4-dihydroxyborylphenyl analogues of an unnatural α-amino acid, 1-aminocyclobutanecarboxylic acid (ACBC), was synthesized. Varying numbers of methylene units were introduced between the 4-boronophenyl and ACBC moieties in order to introduce different degrees of lipophilicity into the molecules. The key step in the syntheses was the preparation of the precursor p-boronophenyl-substituted cyclobutanones which were subsequently converted to the desired amino acids via the Bucherer−Strecker reaction.