cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting IL-6 receptor reduces IgM levels and tumor growth in Waldenström macroglobulinemia.

The tumor microenvironment (TME) plays an important role in cancer cell biology and is implicated in resistance to therapy. In Waldenstrom macroglobulinemia (WM), a subtype of Non-Hodgkin lymphoma, the TME modulates WM biology by secreting cytokines that promote the malignant phenotype. In previous work, we have shown that TME-IL-6 promotes WM cell growth and IgM secretion in WM. Tocilizumab/Actemra is an anti-IL-6R antibody, which can competitively block IL-6 binding to the IL-6R. We investigated the efficacy of Tocilizumab in a preclinical mouse model of WM that considers the role of the TME in disease biology. Hairless SCID mice were subcutaneously implanted with BCWM.1 or RPCI-WM1 and bone marrow stromal cells. Groups of mice were treated with Tocilizumab or control antibody three times/week for 5 weeks and the effect on tumor burden and disease biology were evaluated. Although Tocilizumab had no effect on mice survival, there was a significant reduction in tumor growth rate in mice injected with RPCI-WM1 cells treated with Tocilizumab. In mice injected with BCWM.1 cells, there was a significant reduction in human IgM secretion in mice sera with Tocilizumab treatment. There was no significant change in mice weight suggesting Tocilizumab induced no toxicities to the mice. Taken together, our data found that administration of Tocilizumab to tumor bearing mice, results in a significant reduction in tumor volume and IgM secretion. Therefore, the evaluation of the role of Tocilizumab in WM patients may provide therapeutic efficacy by reducing IgM production and slowing the rate of tumor growth.
Titanium-catalyzed cascade carboalumination of 2-alkyl-substituted dienes and related trienes

Abstract The stereoselective “inter-intra” cascade carboalumination of dienes and trienes with Et2AlCl and Ti(OPr-i)4 provides a novel and stereoselective route to five- and six-membered rings including fused-, bridged-, and spiro-bicyclic structures with generation of quaternary carbon centers.
An improved synthesis of the octalactins

Abstract A new and efficient synthesis of the key C.1–C.9 intermediate 5 of the octalactins has been achieved starting from L-ascorbic acid.
Facile synthesis of lysophospholipids containing unsaturated fatty acid chains

Abstract The efficient synthesis of polyunsaturated phospholipids is challenging due to the sensitivity of the unsaturated moiety to the conditions employed in phosphate ester deprotection. We discuss here three independent methods that resolve this issue and enable the synthesis of a series of unsaturated lysophosphatidic acid mimics for the development of a more comprehensive understanding of the structure-activity relationship in this series.
Structural mechanism for Bruton’s tyrosine kinase activation at the cell membrane

Bruton's tyrosine kinase (Btk) is critical for B cell proliferation and activation, and the development of Btk inhibitors is a vigorously pursued strategy for the treatment of various B cell malignancies. A detailed mechanistic understanding of Btk activation has, however, been lacking. Here, inspired by a previous suggestion that Btk activation might depend on dimerization of its lipid-binding PH-TH module on the cell membrane, we performed long-timescale molecular dynamics simulations of membrane-bound PH-TH modules and observed that they dimerized into a single predominant conformation. We found that the phospholipid PIP3 stabilized the dimer allosterically by binding at multiple sites, and that the effects of PH-TH mutations on dimer stability were consistent with their known effects on Btk activity. Taken together, our simulation results strongly suggest that PIP3-mediated dimerization of Btk at the cell membrane is a critical step in Btk activation.
Reaction mechanisms on liquid and solid acid catalysts. Correlation with acidity

The probe bases used for measurement of strength of acid catalysts need to be structurally similar to the catalytic substrates. Traditional acidity measurements are inapplicable when the hydron transfer forms a tight ion pair, as on solid acids. Also, solid acids are much weaker than liquid acids of similar structure. Alkane activation by C–H and C–C cleavage, evidenced in strong superacids, does not occur in less strongly acidic media. The reactivity patterns and structure–reactivity relationships are the same for the cationoidic species (weakly coordinated carbocations) occurring in the less strong acids as for the full-fledged carbocations intervening in superacids. Even in trifluoromethanesulfonic acid, a weak superacid, the first step in alkane activation is an oxidation, forming unsaturated carbocations. On sulfated zirconia, the first step of alkane reactions is a one-electron oxidation. Mechanistic features incompatible with standard (or “traditional”) carbocationic processes, are observed in the reaction of 3-methylpentane on the zeolite HZSM-5.
Phosphine-catalyzed synthesis of β-lactones from ketenes and chiral β-oxyaldehydes

Abstract In this Letter we describe a catalytic procedure for the diastereoselective synthesis of β-lactones bearing up to three stereogenic centers, from disubstituted ketenes and chiral β-oxyaldehydes. Tri- n -butylphosphine was determined to be the best catalyst with yields of up to 95% and moderate to good diastereoselectivity (dr up to 4:1) obtained in the formation of highly substituted β-lactones.
An efficient palladium-catalyzed Negishi cross-coupling reaction with arylvinyl iodides: facile regioselective synthesis of E-stilbenes and their analogues

Abstract A general synthetic route for the Pd-catalyzed cross-coupling of an arylzinc reagent with arylvinyl iodides (Negishi cross-coupling) has been developed. The system permits efficient and selective preparation of E -stilbenes and their analogues. It also functions effectively at low levels of catalyst loading without the need for an additional ligand and tolerates a wide range of functional groups including heteroaromatic substrates. A systematic study of various parameters was performed and correlated with catalyst–substrate activity.
Generation of Functional Human Adipose Tissue in Mice from Primed Progenitor Cells

Adipose tissue (AT) is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes cell death, leading to inflammation, calcification, and requirement for fu...
Polarization-Based Illumination Detection for Coherent Augmented Reality Scene Rendering in Dynamic Environments

A virtual object that is integrated into the real world in a perceptually coherent manner using the physical illumination information in the current environment is still under development. Several researchers investigated the problem producing a high-quality result; however, pre-computation and offline availability of resources were the essential assumption upon which the system relied. In this paper, we propose a novel and robust approach to identifying the incident light in the scene using the polarization properties of the light wave and using this information to produce a visually coherent augmented reality within a dynamic environment. This approach is part of a complete system which has three simultaneous components that run in real-time: (i) the detection of the incident light angle, (ii) the estimation of the reflected light, and (iii) the creation of the shading properties which are required to provide any virtual object with the detected lighting, reflected shadows, and adequate materials. Finally, the system performance is analyzed where our approach has reduced the overall computational cost.
Direct preparation of benzylic manganese reagents from benzyl halides, sulfonates, and phosphates and their reactions: applications in organic synthesis

Abstract The use of highly active manganese (Mn)*, prepared by the Rieke method, was investigated for the direct preparation of benzylic manganese reagents. The oxidative addition of the highly active manganese to benzylic halides was easily completed under mild conditions. Moreover, benzylic manganese sulfonates and phosphates were prepared by direct oxidative addition of Mn* to the carbon–oxygen bonds of benzylic sulfonates and phosphates. The resulting benzylic manganese reagents were found to undergo cross-coupling reactions with a variety of electrophiles. Most of these reactions were carried out in the absence of any transition metal catalyst under mild conditions. In addition, the use of highly active manganese was also studied for preparation of homo-coupled products of functionalized benzyl halides without transition metal catalysts. These useful approaches provided not only a facile synthetic route to the preparation of resoricinolic lipids but a facile synthesis of functionalized 4-benzylpyridines by regioselective and chemo selective γ-addition of benzylic group to N -alkoxycarbonylpyridinum salts.
PABA Release from Chitosan-PCL with Induced Electric Current

Controlled drug delivery systems such as the stimulation-based biomaterial scaffolds for sequestration and release of drugs offer safety and regulated therapeutic approach. In this study, the drug: para-aminobenzoic acid (PABA) was absorbed into a crosslinked chitosan and poly(caprolactone) (PCL) hydrogel and its release kinetics quantified under different conditions. It was experimentally-observed that the higher the pH (or the more basic the pH), the slower the PABA saturation release trended over time. At the acidic environment of pH 4, PABA was released the fastest, and enhanced by the degradation of chitosan-PCL gel. When a constant electric current of 0.6 mA sa applied, PABA release was induced at pH 10. However, at pH 7, PABA was stably-bound to the chitosan-PCL matrix, with or without the external current. The selective sequestration of PABA at basic pH and its stimulated release via electric current application can be further explored for clinical translatability.
A PRACTICAL SYNTHESIS OF ANTIVIRAL CYCLOPROPANE NUCLEOSIDE A-5021

Abstract (1′ S ,2′ R )-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine (A-5021, 1 ) was synthesized from optically active cyclopropane lactone 2 by employing: (1) selective reduction of the ester; (2) alkylation of 2-amino-6-chloropurine; and (3) reductive opening of the lactone ring. This route eliminates the protection steps to give 1 in a good yield and is of practical value.
Syntheses of (E)- and (Z)-volkendousin

Abstract The first syntheses of the antitumor agents (E)-volkendousin (1) and acetonide 3 have been accomplished by efficient routes from readily available dehydroisoandrosterone (7) using allylic oxidation with SeO2 to introduce the 4/gb-hydroxy group and 16-ketone. This sequence should make these compounds readily available for further biological evaluation.
Benzothiazines in Organic Synthesis. The Preparation of Enantiomerically Pure 4-Substituted Quinolones

3,4-Dihydroquinolin-2(1H)-ones have potential biological and pharmacological significance. Enantiomerically pure benzothiazines, readily available via an intramolecular addition of a sulfoximine-st...
A Unified Strategy for the Stereocontrolled Construction of Structurally Unusual Sesquiterpene Lactones. Asymmetric Synthesis of Vulgarolide and Deoxocrispolide

The bicyclic ketone (+)-17b reacts with vinylmagnesium bromide from its exo face, thus enabling exploitation of the anionic oxy-Cope rearrangement and direct alkylation of the enolate so formed with ethyl iodoacetate to provide 24 in an efficient, stereocontrolled manner. Tricyclic lactone 26b, readily produced from 24, proved to be a common precursor to both synthetic targets. The construction of vulgarolide (9) proceeded by transforming the SEM group in 26b into a mesylate for the purpose of conversion to epoxy acid 39 in advance of oxidative cleavage of the double bond. This transformation resulted in direct conversion to 9 and its epimer 42. Central to the companion synthesis of deoxocrispolide (4) was the ability of 37 to undergo the Michael addition of methoxide ion and of 54 to experience regiocontrolled dehydration to bridgehead olefin 55 in a protocol that involves the smooth translocation of bridgehead unsaturation with concomitant functionalization as an allylic alcohol.
Effective Conversion of Heteroaromatic Ketones into Primary Amines via Hydrogenation of Intermediate Ketoximes

A process to access heteroaromatic primary amines from the corresponding heteroaromatic ketones has been developed. A broad range of previously reported methods to convert ketones to primary amines was examined on heterocyclic ketones without success, including Leuckart–Wallach conditions, borane reductions, and transition-metal-catalyzed hydrogenations. Unique among the catalysts examined, Raney cobalt produced the desired primary heterocyclic amine. Raney cobalt hydrogenation of structurally varied heterocyclic ketoximes was demonstrated to form primary amines in good selectivity under mild conditions, and the products are easily isolated in high yield. Additionally, this is the first report of a systematic evaluation of the capabilities of Raney cobalt as an oxime hydrogenation catalyst.
Efficient access to 3-substituted-γ-hydroxylactams: the uncatalyzed addition of diorganozinc reagents to cyclic imides with heterocyclic substitution

Abstract A range of 3-substituted-γ-hydroxylactams have been prepared via the uncatalyzed addition of organozinc nucleophiles to cyclic imides. This reactivity is primarily limited to imides containing heterocyclic N-substitution, but proceeds efficiently with a variety of diorganozinc reagents, including those prepared and utilized without purification, as well as organozinc halides. It is hypothesized that the presence of a Lewis basic directing group is required for optimum reactivity.
Asymmetric Synthesis of Nucleosides via Molybdenum-Catalyzed Alkynol Cycloisomerization Coupled with Stereoselective Glycosylations of Deoxyfuranose Glycals and 3-Amidofuranose Glycals

Deoxygenated furanose glycals were efficiently prepared by molybdenum pentacarbonyl-catalyzed cycloisomerization of alkynyl alcohols, which were easily prepared in chiral nonracemic form by short s...
A novel mutual information estimator to measure spike train correlations in a model thalamocortical network.

In this study, a novel mutual information estimator was developed to analyze information flow in a model thalamocortical network. Our findings suggest that this estimator is a suitable tool for sig...
The kinases PIG-1 and PAR-1 act in redundant pathways to regulate asymmetric division in the EMS blastomere of C. elegans.

Abstract The PAR-1 kinase of C. elegans is localized to the posterior of the one-cell embryo and its mutations affect asymmetric spindle placement and partitioning of cytoplasmic components in the first cell cycle. However, par-1 mutations do not cause failure to restrict the anterior PAR polarity complex to the same extent as mutations in the posteriorly localized PAR-2 protein. Further, it has been difficult to examine the role of PAR-1 in subsequent divisions due to the early defects in par-1 mutant embryos. Here we show that the PIG-1 kinase acts redundantly with PAR-1 to restrict the anterior PAR-3 protein for normal polarity in the one-cell embryo. By using a temperature sensitive allele of par-1, which exhibits enhanced lethality when combined with a pig-1 mutation, we have further explored roles for these genes in subsequent divisions. We find that both PIG-1 and PAR-1 regulate spindle orientation in the EMS blastomere of the four-cell stage embryo to ensure that it undergoes an asymmetric division. In this cell, PIG-1 and PAR-1 act in parallel pathways for spindle positioning, PIG-1 in the MES-1/SRC-1 pathway and PAR-1 in the Wnt pathway.
A p-toluenesulfinic acid-catalyzed three-component Ugi-type reaction and its application for the synthesis of α-amino amides and amidines

Abstract A mild, cost-effective, and simple three-component Ugi-type reaction using p-toluenesulfinic acid (pTSIA) as the acid catalyst has been developed to synthesize α-amino amides and α-amino amidines. Employing 1 equiv of amine used in the reaction generated α-amino amides exclusively, while 2 equiv of amines, especially with more nucleophilic aniline such as p-anisidine, yielded the α-amino amidines as the major product. This methodology would be suitable for the synthesis of natural or unnatural amino acids and drug-like amidine analogues.
Kepler-9: The first multi-transiting system and the first transit timing variations

Abstract Kepler-9, discovered by Holman et al. (2010), was the first system with multiple confirmed transiting planets and the first system to clearly show long-anticipated transit timing variations (TTVs). It was the first major novel exoplanet discovery of the Kepler Space Telescope mission. The Kepler pipeline identified two Saturn-radius candidates (called Kepler Objects of Interest or KOIs): KOI-377.01 with a 19-day period and KOI-377.02 with a 39-day period. Even with only 9 transits for KOI-377.01 and 6 of KOI-377.02, the transit times were completely inconsistent with a linear ephemeris and showed strongly anti-correlated variations in transit times. Holman et al. (2010) were able to readily show that these objects were planetary mass, confirming them as bona fide planets Kepler-9b and Kepler-9c. As a multi-transiting system exhibiting strong TTVs, the relative planetary properties (e.g., mass ratio, radius ratio) were strongly constrained, opening a new chapter in comparative planetology. KOI-377.03, a small planet with a 1.5-day period, was not initially discovered by the Kepler pipeline, but was identified during the analysis of the other planets and was later confirmed as Kepler-9d through the BLENDER technique by Torres et al. 2011. Holman et al. (2010) included significant dynamical analysis to characterize Kepler-9’s particular TTVs: planets near resonance show large amplitude anti-correlated TTVs with a period corresponding to the rotation of the line of conjunctions and an additional “chopping” signal due to the changing positions of the planets. We review the historical circumstances behind the discovery and characterization of these planets and the publication of Holman et al. (2010). We also review the updated properties of this system and propose ideas for future investigations.
Conservation and divergence of YODA MAPKKK function in regulation of grass epidermal patterning

All multicellular organisms must properly pattern cell types to generate functional tissues and organs. The organized and predictable cell lineages of the Brachypodium leaf enabled us to characterize the role of the MAPK kinase kinase gene BdYODA1 in regulating asymmetric cell divisions. We find that YODA genes promote normal stomatal spacing patterns in both Arabidopsis and Brachypodium, despite species-specific differences in those patterns. Using lineage tracing and cell fate markers, we show that, unexpectedly, patterning defects in bdyoda1 mutants do not arise from faulty physical asymmetry in cell divisions but rather from improper enforcement of alternative cellular fates after division. These cross-species comparisons allow us to refine our understanding of MAPK activities during plant asymmetric cell divisions.
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution

The success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time. By studying lung adenocarcinoma clinical specimens and preclinical models, our computational analyses revealed that the best anti-cancer strategies addressed existing resistant subpopulations as they emerged dynamically during treatment. In some cases, the best computed treatment strategy used unconventional therapy switching while the bulk tumor was responding, a prediction we confirmed in vitro. The new framework presented here could guide the principled implementation of dynamic molecular monitoring and treatment strategies to improve cancer control.
Biomedical text mining for research rigor and integrity: Tasks, challenges, directions

An estimated quarter of a trillion US dollars is invested in the biomedical research enterprise annually. There is growing alarm that a significant portion of this investment is wasted because of problems in reproducibility of research findings and in the rigor and integrity of research conduct and reporting. Recent years have seen a flurry of activities focusing on standardization and guideline development to enhance the reproducibility and rigor of biomedical research. Research activity is primarily communicated via textual artifacts, ranging from grant applications to journal publications. These artifacts can be both the source and the manifestation of practices leading to research waste. For example, an article may describe a poorly designed experiment, or the authors may reach conclusions not supported by the evidence presented. In this article, we pose the question of whether biomedical text mining techniques can assist the stakeholders in the biomedical research enterprise in doing their part toward enhancing research integrity and rigor. In particular, we identify four key areas in which text mining techniques can make a significant contribution: plagiarism/fraud detection, ensuring adherence to reporting guidelines, managing information overload and accurate citation/enhanced bibliometrics. We review the existing methods and tools for specific tasks, if they exist, or discuss relevant research that can provide guidance for future work. With the exponential increase in biomedical research output and the ability of text mining approaches to perform automatic tasks at large scale, we propose that such approaches can support tools that promote responsible research practices, providing significant benefits for the biomedical research enterprise.
PSF correction in soft X-ray tomography

In this article, we introduce a linear approximation of the forward model of soft X-ray tomography, such that the reconstruction is solvable by standard iterative schemes. This linear model takes into account the three-dimensional point spread function (PSF) of the optical system, which consequently enhances the reconstruction of data. The feasibility of the model is demonstrated on both simulated and experimental data, based on theoretically estimated and experimentally measured PSFs.
Selective ring opening cross metathesis of cyclooctadiene and trisubstituted cycloolefins.

The selective ring opening cross metathesis of 1,5-cyclooctadiene and trisubstituted cycloolefins with acroyl species is described. The ring-opened products contain electronically differentiated olefins suitable for additional metathesis reactions. Trisubstituted cycloolefins open regioselectively, placing the acroyl cap on the less-substituted terminus.
DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification

Mutations in somatic cells generate a heterogeneous genomic population and may result in serious medical conditions. Although cancer is typically associated with somatic variations, advances in DNA sequencing indicate that cell-specific variants affect a number of phenotypes and pathologies. Here, we show that mutagenic damage accounts for the majority of the erroneous identification of variants with low to moderate (1 to 5%) frequency. More important, we found signatures of damage in most sequencing data sets in widely used resources, including the 1000 Genomes Project and The Cancer Genome Atlas, establishing damage as a pervasive cause of sequencing errors. The extent of this damage directly confounds the determination of somatic variants in these data sets.
Microwave-Assisted One-Pot Hydrostannylation/Stille Couplings

In a fraction of the time required by conventional methods, microwave-accelerated one-pot hydrostannylation/Stille coupling allows 1-alkynes to be efficiently transformed into 1,3-dienes or styrenes.
Role of membrane-tension gated Ca2+ flux in cell mechanosensation

Eukaryotic cells are sensitive to mechanical forces they experience from the environment. The process of mechanosensation is complex, and involves elements such as the cytoskeleton and active contraction from myosin motors. Ultimately, mechanosensation is connected to changes in gene expression in the cell, known as mechanotransduction. While the involvement of the cytoskeleton in mechanosensation is known, the processes upstream of cytoskeletal changes are unclear. In this paper, by using a microfluidic device that mechanically compresses live cells, we demonstrate that Ca2+ currents and membrane tension-sensitive ion channels directly signal to the Rho GTPase and myosin contraction. In response to membrane tension changes, cells actively regulate cortical myosin contraction to balance external forces. The process is captured by a mechanochemical model where membrane tension, myosin contraction and the osmotic pressure difference between the cytoplasm and extracellular environment are connected by mechanical force balance. Finally, to complete the picture of mechanotransduction, we find that the tension-sensitive transcription factor YAP family of proteins translocate from the nucleus to the cytoplasm in response to mechanical compression.
Enantioselective Allylations of Azlactones with Unsymmetrical Acyclic Allyl Esters

A catalytic asymmetric synthesis of quaternary amino acids has been developed. The method derives from the asymmetric allylic alkylation (AAA) reaction with chiral palladium catalysts derived from ...
Redox Fluctuations Control the Coupled Cycling of Iron and Carbon in Tropical Forest Soils

Oscillating redox conditions are a common feature of humid tropical forest soils, driven by an ample supply and dynamics of reductants, high moisture, microbial oxygen consumption, and finely textured clays that limit diffusion. However, the net result of variable soil redox regimes on iron (Fe) mineral dynamics and associated carbon (C) forms and fluxes is poorly understood in tropical soils. Using a 44-day redox incubation experiment with humid tropical forest soils from Puerto Rico, we examined patterns in Fe and C transformations under four redox regimes: static anoxic, "flux 4-day" (4d oxic, 4d anoxic), "flux 8-day" (8d oxic, 4d anoxic) and static oxic. Prolonged anoxia promoted reductive dissolution of Fe-oxides, and led to an increase in soluble Fe(II) and amorphous Fe oxide pools. Preferential dissolution of the less-crystalline Fe pool was evident immediately following a shift in bulk redox status (oxic to anoxic), and coincided with increased dissolved organic C, presumably due to acidification or direct release of organic matter (OM) from dissolving Fe(III) mineral phases. The average nominal oxidation state of water-soluble C was lowest under persistent anoxic conditions, suggesting that more reduced organic compounds were metabolically unavailable for microbial consumption under reducing conditions. Anoxic soil compounds had high H/C values (and were similar to lignin-like compounds) whereas oxic soil compounds had higher O/C values, akin to tannin- and cellulose-like components. Cumulative respiration derived from native soil organic C was highest in static oxic soils. These results show how Fe minerals and Fe-OM interactions in tropical soils are highly sensitive to variable redox effects. Shifting soil oxygen availability rapidly impacted exchanges between mineral-sorbed and aqueous C pools, increased the dissolved organic C pool under anoxic conditions implying that the periodicity of low-redox events may control the fate of C in wet tropical soils.
A Novel Application of Sodium Borohydride for the Regiospecific and Stereoselective Reduction of Conjugated Alkadiynes

Abstract Alkynes, when carrying an α-sulfonyl group, are shown to be stereoselectively reduced to z-alkenes using sodium borohydride under mildly basic conditions.
phylostratr: a framework for phylostratigraphy.

Motivation The goal of phylostratigraphy is to infer the evolutionary origin of each gene in an organism. This is done by searching for homologs within increasingly broad clades. The deepest clade that contains a homolog of the protein(s) encoded by a gene is that gene's phylostratum. Results We have created a general R-based framework, phylostratr, to estimate the phylostratum of every gene in a species. The program fully automates analysis: selecting species for balanced representation, retrieving sequences, building databases, inferring phylostrata and returning diagnostics. Key diagnostics include: detection of genes with inferred homologs in old clades, but not intermediate ones; proteome quality assessments; false-positive diagnostics, and checks for missing organellar genomes. phylostratr allows extensive customization and systematic comparisons of the influence of analysis parameters or genomes on phylostrata inference. A user may: modify the automatically generated clade tree or use their own tree; provide custom sequences in place of those automatically retrieved from UniProt; replace BLAST with an alternative algorithm; or tailor the method and sensitivity of the homology inference classifier. We show the utility of phylostratr through case studies in Arabidopsis thaliana and Saccharomyces cerevisiae. Availability and implementation Source code available at https://github.com/arendsee/phylostratr. Supplementary information Supplementary data are available at Bioinformatics online.
Targeted Memory Reactivation during Sleep Elicits Neural Signals Related to Learning Content

Retrieval of learning-related neural activity patterns is thought to drive memory stabilization. However, finding reliable, noninvasive, content-specific indicators of memory retrieval remains a central challenge. Here, we attempted to decode the content of retrieved memories in the EEG during sleep. During encoding, male and female human subjects learned to associate spatial locations of visual objects with left- or right-hand movements, and each object was accompanied by an inherently related sound. During subsequent slow-wave sleep within an afternoon nap, we presented half of the sound cues that were associated (during wake) with left- and right-hand movements before bringing subjects back for a final postnap test. We trained a classifier on sleep EEG data (focusing on lateralized EEG features that discriminated left- vs right-sided trials during wake) to predict learning content when we cued the memories during sleep. Discrimination performance was significantly above chance and predicted subsequent memory, supporting the idea that retrieval leads to memory stabilization. Moreover, these lateralized signals increased with postcue sleep spindle power, demonstrating that retrieval has a strong relationship with spindles. These results show that lateralized activity related to individual memories can be decoded from sleep EEG, providing an effective indicator of offline retrieval.SIGNIFICANCE STATEMENT Memories are thought to be retrieved during sleep, leading to their long-term stabilization. However, there has been relatively little work in humans linking neural measures of retrieval of individual memories during sleep to subsequent memory performance. This work leverages the prominent electrophysiological signal triggered by lateralized movements to robustly demonstrate the retrieval of specific cued memories during sleep. Moreover, these signals predict subsequent memory and are correlated with sleep spindles, neural oscillations that have previously been implicated in memory stabilization. Together, these findings link memory retrieval to stabilization and provide a powerful tool for investigating memory in a wide range of learning contexts and human populations.
Large-scale multiscale modeling of phase transformation in nanocrystalline materials: Atomistic and Phase-Field methods

In this research, atomistic molecular dynamics simulations are combined with mesoscopic phase-field computational methods in order to investigate phase-transformation in polycrystalline Aluminum microstructure. In fact, microstructural computational modeling of engineering materials could help to optimize their mechanical properties for industrial applications (e.g. directional solidification for turbine blades). As a result, a multiscale modeling approach is developed to find a relation between manufacturing variables (e.g. temperature) and microstructural properties of crystalline materials (e.g. grain size), which could be used to develop an advanced manufacturing process for sensitive applications. The results show that atomistic modeling of grain growth could be used as a first-principle approach in order to study phase transformation's kinetics, which could capture morphology of polycrystalline materials more accurately. On the other hand, phase-field mesoscopic approach needs less computational efforts, but still it relies on semi-empirical data to capture accurate phase transformation regimes, which makes this approach suitable for rapid examining of new manufacturing conditions as well as its effects on microstructural properties of polycrystalline materials.
Odyssey: a semi-automated pipeline for phasing, imputation, and analysis of genome-wide genetic data.

Genome imputation, admixture resolution and genome-wide association analyses are timely and computationally intensive processes with many composite and requisite steps. Analysis time increases further when building and installing the run programs required for these analyses. For scientists that may not be as versed in programing language, but want to perform these operations hands on, there is a lengthy learning curve to utilize the vast number of programs available for these analyses. In an effort to streamline the entire process with easy-to-use steps for scientists working with big data, the Odyssey pipeline was developed. Odyssey is a simplified, efficient, semi-automated genome-wide imputation and analysis pipeline, which prepares raw genetic data, performs pre-imputation quality control, phasing, imputation, post-imputation quality control, population stratification analysis, and genome-wide association with statistical data analysis, including result visualization. Odyssey is a pipeline that integrates programs such as PLINK, SHAPEIT, Eagle, IMPUTE, Minimac, and several R packages, to create a seamless, easy-to-use, and modular workflow controlled via a single user-friendly configuration file. Odyssey was built with compatibility in mind, and thus utilizes the Singularity container solution, which can be run on Linux, MacOS, and Windows platforms. It is also easily scalable from a simple desktop to a High-Performance System (HPS). Odyssey facilitates efficient and fast genome-wide association analysis automation and can go from raw genetic data to genome: phenome association visualization and analyses results in 3–8 h on average, depending on the input data, choice of programs within the pipeline and available computer resources. Odyssey was built to be flexible, portable, compatible, scalable, and easy to setup. Biologists less familiar with programing can now work hands on with their own big data using this easy-to-use pipeline.
Asymptotic behavior of positive harmonic functions in certain unbounded domains

We derive asymptotic estimates at infinity for positive harmonic functions in a large class of non-smooth unbounded domains. These include domains whose sections, after rescaling, resemble a Lipschitz cylinder or a Lipschitz cone, e.g., various paraboloids and horns.
High satellite repeat turnover in great apes studied with short- and long-read technologies

Satellite repeats are a structural component of centromeres and telomeres, and in some instances their divergence is known to drive speciation. Due to their highly repetitive nature, satellite sequences have been understudied and underrepresented in genome assemblies. To investigate their turnover in great apes, we studied satellite repeats of unit sizes up to 50 bp in human, chimpanzee, bonobo, gorilla, and Sumatran and Bornean orangutans, using unassembled short and long sequencing reads. The density of satellite repeats, as identified from accurate short reads (Illumina), varied greatly among great ape genomes. These were dominated by a handful of abundant repeated motifs, frequently shared among species, which formed two groups: (1) the (AATGG)n repeat (critical for heat shock response) and its derivatives; and (2) subtelomeric 32-mers involved in telomeric metabolism. Using the densities of abundant repeats, individuals could be classified into species. However clustering did not reproduce the accepted species phylogeny, suggesting rapid repeat evolution. Several abundant repeats were enriched in males vs. females; using Y chromosome assemblies or FIuorescent In Situ Hybridization, we validated their location on the Y. Finally, applying a novel computational tool, we identified many satellite repeats completely embedded within long Oxford Nanopore and Pacific Biosciences reads. Such repeats were up to 59 kb in length and consisted of perfect repeats interspersed with other similar sequences. Our results based on sequencing reads generated with three different technologies provide the first detailed characterization of great ape satellite repeats, and open new avenues for exploring their functions.
Contextual fear learning and memory differ between stress coping styles in zebrafish

Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual’s survival. As part of an animal’s stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day post-conditioning, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-conditioning. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses.
Investigation of the Effects of Copper Nanoparticles on Magnesium–Sulfur Battery Performance: How Practical Is Metallic Copper Addition?

Rechargeable magnesium sulfur (Mg/S) batteries suffer from fast capacity fading, because of the difficulty with reoxidation of MgS and the polysulfide shuttle. Other works have reported that use of...
The Power of Sum-of-Squares for Detecting Hidden Structures

We study planted problems&#x2014;finding hidden structures in random noisy inputs&#x2014;through the lens of the sum-of-squares semidefinite programming hierarchy (SoS). This family of powerful semidefinite programs has recently yielded many new algorithms for planted problems, often achieving the best known polynomial-time guarantees in terms of accuracy of recovered solutions and robustness to noise. One theme in recent work is the design of spectral algorithms which match the guarantees of SoS algorithms for planted problems. Classical spectral algorithms are often unable to accomplish this: the twist in these new spectral algorithms is the use of spectral structure of matrices whose entries are low-degree polynomials of the input variables.We prove that for a wide class of planted problems, including refuting random constraint satisfaction problems, tensor and sparse PCA, densest-ksubgraph, community detection in stochastic block models, planted clique, and others, eigenvalues of degree-d matrix polynomials are as powerful as SoS semidefinite programs of degree d. For such problems it is therefore always possible to match the guarantees of SoS without solving a large semidefinite program.Using related ideas on SoS algorithms and lowdegree matrix polynomials (and inspired by recent work on SoS and the planted clique problem [BHK+16]), we prove a new SoS lower bound for the tensor PCA problem.
Covering Arrays for Equivalence Classes of Words

Covering arrays for words of length $t$ over a $d$ letter alphabet are $k \times n$ arrays with entries from the alphabet so that for each choice of $t$ columns, each of the $d^t$ $t$-letter words appears at least once among the rows of the selected columns. We study two schemes in which all words are not considered to be different. In the first case words are equivalent if they induce the same partition of a $t$ element set. In the second case, words of the same weight are equivalent. In both cases we produce logarithmic upper bounds on the minimum size $k=k(n)$ of a covering array. Definitive results for $t=2,3,4$, as well as general results, are provided.
Lech's conjecture in dimension three

Abstract Let ( R , m ) → ( S , n ) be a flat local extension of local rings. Lech conjectured around 1960 that there should be a general inequality e ( R ) ≤ e ( S ) on the Hilbert–Samuel multiplicities [24] . This conjecture is known when the base ring R has dimension less than or equal to two [24] , and remains open in higher dimensions. In this paper, we prove Lech's conjecture in dimension three when R has equal characteristic. In higher dimension, our method yields substantial partial estimate: e ( R ) ≤ ( d ! / 2 d ) ⋅ e ( S ) where d = dim ⁡ R ≥ 4 , in equal characteristic.
Energy Harvesting Networks With Energy Cooperation: Procrastinating Policies

This paper considers multiterminal networks with energy harvesting transmitter nodes that are also capable of wirelessly transferring energy to or receiving energy from other nodes in the network. In particular, the jointly optimal transmit power and energy transfer policies that maximize sum-throughput for the two-way, two-hop, and multiple access channels are identified. It is shown for nodes with infinite-sized batteries that delaying energy transfers until energy is needed immediately at the receiving node is sum-throughput optimal. Focusing on such procrastinating policies without loss of optimality, the stated joint optimization problem can be decomposed into energy transfer and consumed energy allocation problems which are solved in tandem. This decomposition is shown to hold for the finite-sized battery case as well, using partially procrastinating policies that avoid battery overflows. It is observed that for the two-hop channel, the proposed algorithm has a two fluid water-filling interpretation, and for the multiple access channel, it reduces to a single transmitter problem with aggregate energy arrivals. Numerical results demonstrate the throughput improvement with bi-directional energy cooperation over no cooperation and uni-directional cooperation.
Global solution curves for several classes of singular periodic problems

Abstract Using continuation methods and bifurcation theory, we study the exact multiplicity of periodic solutions, and the global solution structure, for three classes of periodically forced equations with singularities, including the equations arising in micro-electro-mechanical systems (MEMS), the ones in condensed matter physics, as well as A.C. Lazer and S. Solimini’s (Lazer and Solimini, 1987) problem.
The Effect of Network Width on the Performance of Large-batch Training

Distributed implementations of mini-batch stochastic gradient descent (SGD) suffer from communication overheads, attributed to the high frequency of gradient updates inherent in small-batch training. Training with large batches can reduce these overheads; however it besets the convergence of the algorithm and the generalization performance. In this work, we take a first step towards analyzing how the structure (width and depth) of a neural network affects the performance of large-batch training. We present new theoretical results which suggest that--for a fixed number of parameters--wider networks are more amenable to fast large-batch training compared to deeper ones. We provide extensive experiments on residual and fully-connected neural networks which suggest that wider networks can be trained using larger batches without incurring a convergence slow-down, unlike their deeper variants.
Generalized differentiation of piecewise linear functions in second-order variational analysis

Abstract The paper is devoted to a comprehensive second-order study of a remarkable class of convex extended-real-valued functions that is highly important in many aspects of nonlinear and variational analysis, specifically those related to optimization and stability. This class consists of lower semicontinuous functions with possibly infinite values on finite-dimensional spaces, which are labeled as “piecewise linear” ones and can be equivalently described via the convexity of their epigraphs. In this paper we calculate the second-order subdifferentials (generalized Hessians) of arbitrary convex piecewise linear functions, together with the corresponding geometric objects, entirely in terms of their initial data. The obtained formulas allow us, in particular, to justify a new exact (equality-type) second-order sum rule for such functions in the general nonsmooth setting.
Kron Reduction of Graphs With Applications to Electrical Networks

Consider a weighted undirected graph and its corresponding Laplacian matrix, possibly augmented with additional diagonal elements corresponding to self-loops. The Kron reduction of this graph is again a graph whose Laplacian matrix is obtained by the Schur complement of the original Laplacian matrix with respect to a specified subset of nodes. The Kron reduction process is ubiquitous in classic circuit theory and in related disciplines such as electrical impedance tomography, smart grid monitoring, transient stability assessment, and analysis of power electronics. Kron reduction is also relevant in other physical domains, in computational applications, and in the reduction of Markov chains. Related concepts have also been studied as purely theoretic problems in the literature on linear algebra. In this paper we analyze the Kron reduction process from the viewpoint of algebraic graph theory. Specifically, we provide a comprehensive and detailed graph-theoretic analysis of Kron reduction encompassing topological, algebraic, spectral, resistive, and sensitivity analyses. Throughout our theoretic elaborations we especially emphasize the practical applicability of our results to various problem setups arising in engineering, computation, and linear algebra. Our analysis of Kron reduction leads to novel insights both on the mathematical and the physical side.