cssi/SciSciGPT-SciSciNet huggingface dataset:
Bilateral Spontaneous Otoacoustic Emissions Show Coupling between Active Oscillators in the Two Ears

Spontaneous otoacoustic emissions (SOAEs) are weak sounds that emanate from the ears of tetrapods in the absence of acoustic stimulation. These emissions are an epiphenomenon of the inner ear's active process, which enhances the auditory system's sensitivity to weak sounds, but their mechanism of production remains a matter of debate. We recorded SOAEs simultaneously from the two ears of the tokay gecko and found that binaural emissions could be strongly correlated: some emissions occurred at the same frequency in both ears and were highly synchronized. Suppression of the emissions in one ear often changed the amplitude or shifted the frequency of emissions in the other. Decreasing the frequency of emissions from one ear by lowering its temperature usually reduced the frequency of the contralateral emissions. To understand the relationship between binaural SOAEs, we developed a mathematical model of the eardrums as noisy nonlinear oscillators coupled by the air within an animal's mouth. By according with the model, the results indicate that some SOAEs are generated bilaterally through acoustic coupling across the oral cavity. The model predicts that sound localization through the acoustic coupling between ears is influenced by the active processes of both ears.
Long‐term community change through multiple rapid transitions in a desert rodent community

While studies increasingly document long-term change in community composition, whether long-term change occurs gradually or via rapid reorganization events remains unclear. We used Latent Dirichlet Allocation (LDA) and a change-point model to examine the long-term dynamics of a desert rodent community undergoing compositional change over a 38-yr span. Our approach detected three rapid reorganization events, where changes in the relative abundances of dominant and rare species occurred, and a separate period of increased variance in the structure of the community. These events coincided with time periods, possibly related to climate events, where the total abundance of rodents was extremely low. There are a variety of processes that could link low abundance events with a higher probability of rapid ecological transitions, including higher importance of stochastic processes (i.e., competitive interactions or priority effects) and the removal of structuring effects of competitive dominants or incumbent species. Continued study of the dynamics of community change will provide important information not only on the processes structuring communities, but will also provide guidance for forecasting how communities will undergo change in the future.
Synthesis of Phosphino Oxazoline Ligand Libraries from Amino Acid and Phosphino Carboxylate Building Blocks

A modular route to new phosphine−oxazoline ligands is reported. The ability of these ligands to asymmetrically catalyze the addition of dimethyl malonate to 1,3-diphenylprop-2-enyl acetate was inve...
Ligand-free CuI-catalyzed cyanation of aryl halides using K4[Fe(CN)6] as cyanide source and water as solvent

Abstract A methodology for the cyanation of aryl iodides is reported using copper iodide as the catalyst, K4[Fe(CN)6] as the cyanide source, and small quantities of water and tetraethylene glycol as the solvent. Reactions are complete within 30 min of microwave heating at 175 °C. A simple work-up procedure has also been devised.
Quantifying gravity wave forcing using scale invariance

Despite the increasing resolution, forcing on the mean circulation by resolved waves in general circulation models is not yet converging. Parameterization of the forcing remains a major source of model uncertainty. This study examines the scale invariance of zonal spectra of momentum flux and wave forcing, and shows that it can be used to quantify the forcing by unresolved waves with knowledge of the resolved ones in global models. The result reveals the leading order importance of the small-scale wave forcing, which is in general agreement with that required for obtaining the zonal mean wind climatology. It is also found that wave and mean flow interaction is important in maintaining the robust spectral structure. This method may provide a strategy to design physically consistent and scale-aware parameterization schemes for scale invariant quantities, when a model has sufficient resolution to partially resolve their spectra.
NMR silent, naturally-occurring quinones: A case of radicals

Abstract Kinobscurinone, a benzo[b]fluorenone quinone previously reported to be “NMR silent”, affording neither 1H- nor 13C NMR spectra under a variety of conditions, has now been shown to exist in part as a free radical under ambient conditions. The g value for kinobscurinone was found to be 2.0052; no hyperfine splitting was observed. ESR signals were similarly observed for three other substituted benzo[b]fluorene quinones.
Microwave-assisted benzyne-click chemistry: preparation of 1H-benzo[d][1,2,3]triazoles

Abstract The benzotriazoles were prepared by three-component and two-component microwave-assisted [3+2] cycloadditions of various azides to benzyne, 3-methoxybenzyne, and 4,5-difluorobenzyne. In the three-component reaction, the aryne is generated, in the presence of an azide prepared in situ, by the reaction of an o-(trimethylsilylaryl) triflate with either CsF or KF/18-Crown-6. However, in the two-component reactions, a freshly prepared azide is added to the reaction vessel prior to aryne generation. Good to excellent yields of benzotriazoles were obtained in 15–20 min when the microwave-assisted reactions were carried out at 125 °C. These reaction times are significantly faster than similar reactions carried out using conventional heating.
In vitro-transcribed guide RNAs trigger an innate immune response via the RIG-I pathway

Clustered, regularly interspaced, short palindromic repeat (CRISPR)–CRISPR-associated 9 (Cas9) genome editing is revolutionizing fundamental research and has great potential for the treatment of many diseases. While editing of immortalized cell lines has become relatively easy, editing of therapeutically relevant primary cells and tissues can remain challenging. One recent advancement is the delivery of a Cas9 protein and an in vitro–transcribed (IVT) guide RNA (gRNA) as a precomplexed ribonucleoprotein (RNP). This approach allows editing of primary cells such as T cells and hematopoietic stem cells, but the consequences beyond genome editing of introducing foreign Cas9 RNPs into mammalian cells are not fully understood. Here, we show that the IVT gRNAs commonly used by many laboratories for RNP editing trigger a potent innate immune response that is similar to canonical immune-stimulating ligands. IVT gRNAs are recognized in the cytosol through the retinoic acid–inducible gene I (RIG-I) pathway but not the melanoma differentiation–associated gene 5 (MDA5) pathway, thereby triggering a type I interferon response. Removal of the 5’-triphosphate from gRNAs ameliorates inflammatory signaling and prevents the loss of viability associated with genome editing in hematopoietic stem cells. The potential for Cas9 RNP editing to induce a potent antiviral response indicates that care must be taken when designing therapeutic strategies to edit primary cells.
Evolution of the Highly Repetitive PEVK Region of Titin Across Mammals

The protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin-named for its high proportion of Pro-Glu-Val-Lys amino acids-is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. The PEVK-C region can be further divided into a highly repetitive region (PEVK-CA) and one that is more variable (PEVK-CB). Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation.
Acetylation-Dependent Recruitment of the FACT Complex and Its Role in Regulating Pol II Occupancy Genome-Wide in Saccharomyces cerevisiae.

Histone chaperones, chromatin remodelers, and histone modifying complexes play a critical role in alleviating the nucleosomal barrier for DNA-dependent processes. Here, we have examined the role of two highly conserved yeast (Saccharomyces cerevisiae) histone chaperones, facilitates chromatin transcription (FACT) and Spt6, in regulating transcription. We show that the H3 tail contributes to the recruitment of FACT to coding sequences in a manner dependent on acetylation. We found that deleting a H3 histone acetyltransferase Gcn5 or mutating lysines on the H3 tail impairs FACT recruitment at ADH1 and ARG1 genes. However, deleting the H4 tail or mutating the H4 lysines failed to dampen FACT occupancy in coding regions. Additionally, we show that FACT depletion reduces RNA polymerase II (Pol II) occupancy genome-wide. Spt6 depletion leads to a reduction in Pol II occupancy toward the 3′-end, in a manner dependent on the gene length. Severe transcription and histone-eviction defects were also observed in a strain that was impaired for Spt6 recruitment (spt6Δ202) and depleted of FACT. Importantly, the severity of the defect strongly correlated with wild-type Pol II occupancies at these genes, indicating critical roles for Spt6 and Spt16 in promoting high-level transcription. Collectively, our results show that both FACT and Spt6 are important for transcription globally and may participate during different stages of transcription.
Metallopeptides for Asymmetric Dirhodium Catalysis

Natural peptide sequences ligate to dirhodium centers through two bridging aspartate side chains, creating a macromolecular ligand framework with helical structure. The generation of a small peptide library allowed optimization of peptide sequence and produced an efficient catalyst for enantioselective carbenoid insertion into Si−H bonds. Analysis of the library indicates that the i−1 and i+3 positions of nonapeptides have the most significant effect on enantioselectivity, though the structural basis for selectivity is different at each of the positions.
A mechanistic model for the selective oxidation of 1,4-diols to γ-lactols by o-iodoxybenzoic acid

Summary The selective oxidation of 1,4-diols to γ-lactols by o-iodoxybenzoic acid occurs by a rate-limiting carbonyl-forming elimination pathway in which the carbinol proton is abstracted internally via a six-atom cyclic arrangement, which explains the observed selectivity.
TEsmall Identifies Small RNAs Associated With Targeted Inhibitor Resistance in Melanoma

MicroRNAs (miRNAs) are small 21-22 nt RNAs that act to regulate the expression of mRNA target genes through direct binding to mRNA targets. While miRNAs typically dominate small RNA (sRNA) transcriptomes, many other classes are present including tRNAs, snoRNAs, snRNAs, Y-RNAs, piRNAs, and siRNAs. Interactions between processing machinery and targeting networks of these various sRNA classes remains unclear, largely because these sRNAs are typically analyzed separately. Here, we present TEsmall, a tool that allows for the simultaneous processing and analysis of sRNAs from each annotated class in a single integrated workflow. The pipeline begins with raw fastq reads and proceeds all the way to producing count tables formatted for differential expression analysis. Several interactive charts are also produced to look at overall distributions in length and annotation classes. We next applied the TEsmall pipeline to sRNA libraries generated from melanoma cells responding to targeted inhibitors of the MAPK pathway. Targeted oncogene inhibitors have emerged as way to tailor cancer therapies to the particular mutations present in a given tumor. While these targeted strategies are typically effective for short intervals, the emergence of resistance is extremely common, limiting the effectiveness of single-agent therapeutics and driving the need for a better understanding of resistance mechanisms. Using TEsmall, we identified several microRNAs and other sRNA classes that are enriched in inhibitor resistant melanoma cells in multiple melanoma cell lines and may be able to serve as markers of resistant populations more generally.
Alkynyliodonium salts in organic synthesis. Preparation of 2-substituted-3-p-toluenesulfonyldihydrofurans from 1-hydroxybut-3-ynyliodonium ethers via a formal stevens shift of a carbon group

[reaction: see text]p-Toluenesulfinate addition to 1-hydroxybut-3-ynyliodonium ethers triggers a sequence of reactions which ultimately delivers 2-substituted-3-p-toluenesulfonyldihydrofuran products along with 3-p-toluenesulfonyldihydrofuran as a major byproduct. A putative 1,2-alkyl shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the alkyl group.
The influence of everyday events on prospective timing "in the moment".

We conducted two experiments to investigate how the eventfulness of everyday experiences influences people’s prospective timing ability. Specifically, we investigated whether events contained within movies of everyday activities serve as markers of time, as predicted by Event Segmentation Theory, or whether events pull attention away from the primary timing task, as predicted by the Attentional Gate theory. In the two experiments reported here, we asked participants to reproduce a previously learned 30-s target duration while watching a movie that contained eventful and uneventful intervals. In Experiment 2, reproduction also occurred during “blank movies” while watching a fixation. In both experiments, participants made shorter and more variable reproductions while simultaneously watching eventful as compared to uneventful movie intervals. Moreover, in Experiment 2, the longest reproductions were produced when participants had to watch the blank movies, which contained no events. These results support Event Segmentation Theory and demonstrate that the elapsing events during prospective temporal reproduction appear to serve as markers of temporal duration rather than distracting from the timing task.
A modification-specific peptide-based immunization approach using CRM197 carrier protein: Development of a selective vaccine against pyroglutamate Aβ peptides.

Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer’s disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models, but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, showed an increased risk of encephalitis, most likely because of autoimmune proinflammatory T helper 1 (Th1) response against all forms of Aβ. Immunization against less abundant but potentially more pathologically relevant Aβ products, such as N-terminally truncated pyroglutamate-3 Aβ (AβpE3), could provide efficacy and improve tolerability in Aβ immunotherapy. Here, we describe a selective vaccine against AβpE3 that uses the diphtheria toxin mutant CRM197 as a carrier protein for epitope presentation. CRM197 is currently used in licensed vaccines and has demonstrated excellent immunogenicity and safety in humans. In mice, our AβpE3:CRM197 vaccine triggered the production of specific anti-AβpE3 antibodies that did not cross-react with Aβ1-42, non-cyclized AβE3 or N-terminally truncated pyroglutamate-11 Aβ (AβpE11). AβpE3:CRM197 antiserum strongly labeled AβpE3 in insoluble protein extracts and decorated cortical amyloid plaques in human AD brains. Anti-AβpE3 antibodies were almost exclusively of the IgG1 isotype, suggesting an antiinflammatory Th2 response bias to the AβpE3:CRM197 vaccine. To the best of our knowledge, this study shows for the first time that CRM197 has potential as a safe and suitable vaccine carrier for active and selective immunization against specific protein sequence modifications or conformations such as AβpE3.
Total Synthesis and Structural Revision of (+)-Amphidinolide W

An enantioselective first total syntheis of amphidinolide W (2) and a revision of its C6 absolute stereochemistry (1) are described. Amphidinolide W (1), a 12-membered macrolide isolated from Amphidinium sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent, and four of the five chiral centers were derived through asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W (1) has now been revised through our current synthesis.
Organocatalytic asymmetric conjugate addition of thioacetic acid to β-nitrostyrenes

A method for organocatalytic, enantioselective Michael addition reactions of thioacetic acid with a range of trans-β-nitrostyrenes has been developed. The processes, promoted by the chiral amine thiourea organocatalyst, take place in high yields with up to 70% ee.
Identifying G protein‐coupled receptor dimers from crystal packings

Dimers of G protein-coupled receptors (GPCRs) are believed to be important for signaling with their associated G proteins. Low-resolution electron microscopy has shown rhodopsin dimers in native retinal membranes, and CXCR4 dimers have been found in several different crystal structures. Evidence for dimers of other GPCRs is more indirect. An alternative to computational modeling studies is to search for parallel dimers in the packing environments of the reported crystal structures of GPCRs. Two major structural types of GPCR dimers exist (as predicted by others), but there is considerable structural variation within each cluster. The different structural variants described here might reflect different functional properties and should provide a range of model structures for computational and experimental examination.
A new route to 2-substituted Δ2-thiazolines: Stille cross-couplings of 2-bromo-Δ2-thiazolines

Abstract 2-Substituted thiazolines are obtained by a Stille cross-coupling of 2-bromothiazolines and various tributylstannyl compounds.
Vasomotor Symptoms Monitoring with a Commercial Activity Tracking Watch

Personal fitness/health tracking devices that include electrodermal activity sensors enable tracking of vasomotor symptoms (hot flashes). Multiple conditions are associated with vasomotor symptoms. This article describes nighttime tracking of vasomotor symptoms for an individual over a two-year period. This volunteer was a participant in a longitudinal study on volunteers wearing physiological monitors. Personal tracking of vasomotor symptoms will provide new insights on the differences between conditions and impacts on individual’s health.
High Temporal-Resolution Dynamic PET Image Reconstruction Using a New Spatiotemporal Kernel Method

Current clinical dynamic PET has an effective temporal resolution of 5–10 seconds, which can be adequate for traditional compartmental modeling but is inadequate for exploiting the benefit of more advanced tracer kinetic modeling for characterization of diseases (e.g., cancer and heart disease). There is a need to improve dynamic PET to allow fine temporal sampling of 1–2 seconds. However, the reconstruction of these short-time frames from tomographic data is extremely challenging as the count level of each frame is very low and high noise presents in both spatial and temporal domains. Previously, the kernel framework has been developed and demonstrated as a statistically efficient approach to utilizing image prior for low-count PET image reconstruction. Nevertheless, the existing kernel methods mainly explore spatial correlations in the data and only have a limited ability in suppressing temporal noise. In this paper, we propose a new kernel method which extends the previous spatial kernel method to the general spatiotemporal domain. The new kernelized model encodes both spatial and temporal correlations obtained from image prior information and are incorporated into the PET forward projection model to improve themaximumlikelihood(ML) image reconstruction. Computer simulations and an application to real patient scan have shown that the proposed approach can achieve effective noise reduction in both spatial and temporal domains and outperform the spatial kernel method and conventional ML reconstruction method for improving the high temporal-resolution dynamic PET imaging.
A concise sequential photochemical-metathesis approach for the synthesis of (+)-castanospermine and possible uniflorine-A stereoisomers

Abstract A recently developed strategy for polyhydroxylated indolizidine ring construction has been applied to the synthesis of (+)-castanospermine and possible isomers of uniflorine-A. The routes to these targets rely on the use of the earlier discovered photocyclization reaction of pyridinium perchlorate in a concise route for preparation of a key N-allylacetamidocyclopentendiol intermediate. Ring rearrangement metathesis of this substance gives an allyl-tetrahydropyridine, which is then transformed to the targets by execution of regio- and stereo-controlled hydroxylation processes followed by indolizidine ring construction.
Kinetic Control of Proline Amide Rotamers: Total Synthesis of trans,trans- and cis,cis-Ceratospongamide

Ceratospongamide is a cyclic peptide natural product that is biosynthesized as a mixture of two proline rotamers. Remarkably, these rotamers do not detectably interconvert at temperatures up to 100...
The essential genome of the crenarchaeal model Sulfolobus islandicus

Sulfolobus islandicus is a model microorganism in the TACK superphylum of the Archaea, a key lineage in the evolutionary history of cells. Here we report a genome-wide identification of the repertoire of genes essential to S. islandicus growth in culture. We confirm previous targeted gene knockouts, uncover the non-essentiality of functions assumed to be essential to the Sulfolobus cell, including the proteinaceous S-layer, and highlight essential genes whose functions are yet to be determined. Phyletic distributions illustrate the potential transitions that may have occurred during the evolution of this archaeal microorganism, and highlight sets of genes that may have been associated with each transition. We use this comparative context as a lens to focus future research on archaea-specific uncharacterized essential genes that may provide valuable insights into the evolutionary history of cells. Sulfolobus islandicus is a model organism within the TACK superphylum of the Archaea. Here, the authors perform a genome-wide analysis of essential genes in this organism, show that the proteinaceous S-layer is not essential, and explore potential stages of evolution of the essential gene repertoire in Archaea.
Synthesis of naphthalene and indene precursors to naphthoic and indenoic acids

Abstract As part of ongoing research to investigate structural requirements for lactate dehydrogenase inhibition by highly substituted naphthoic and indenoic acids, certain naphthalene and indene precursors to those types of compounds are required. Described here are efficient preparations of 1-naphthoic acid precursors 6-benzyl-2,3-dimethoxy-1-propylnaphthalenes, including compounds with substituted benzyl groups and 7-benzyl-2,3-dimethoxy-1-propylnaphthalene. Also described are the syntheses of indenoic acid precursors 2-benzyl-5,6-dimethoxy-7-propyl-1 H -indenes, including compounds with substituted benzyl groups. These compounds were made from the key intermediates 6,7-dimethoxy-5-propyl-1-tetralone, 6,7-dimethoxy-8-propyl-1-tetralone, and 5,6-dimethoxy-4-propyl-1-indanone.
Synthesis, Structure, and Properties of a Three-Dimensional Open-Framework Niobium Fluorogermanate (NGH-5)

The low-temperature hydrothermal synthesis and crystal structure of a new open-framework niobium germanate phase is reported. (C6H18N2)·Ge2.2Nb0.8O6.8F1.2 (NGH-5) was synthesized from GeO2, Nb2O5, and HF (aq) by using 1,4-trans-diaminocyclohexane (1,4-DACH) as an organic structure directing agent. The structure of NGH-5 was determined ab initio by using powder X-ray diffraction techniques and consists of a negatively charged three-dimensional Nb/Ge/O/F framework containing three orthogonal channel systems. Two of the channels are delimited by 10-membered rings of NbO5F octahedra and GeO4 tetrahedra; the third is delimited by an 8-membered ring. Charge-balancing (C6H18N2)2+ cations are encapsulated within the framework and are located at the center of the 10-membered ring channels. The NGH-5 framework is characterized by a low framework density and is closely related to the recently reported zirconium germanate ASU-15.
Preparation of α,α‐difluoromethylene functionalized sulfones

Sulfination of bromodifluoroacetate or acetamide 1 with sodium dithionite gives the corresponding sulfinates 2a, and 2b, respectively, which upon cuprous bromidc catalyzed allylation afford the allylsulfonyl-difluoroacetate and acetamides. Phenyl- or alkylsulfonyldifluoroacetates and acetamides can be readily prepared from reaction of 1 with thiolates, followed by oxidation with hydrogen peroxide.
A nontransmetalation reaction pathway for anionic four-electron donor-based palladacycle-catalyzed addition reactions of arylborons with aldehydes

Abstract A nontransmetalation reaction pathway for anionic four-electron donor-based (Type I) palladacycle-catalyzed addition reactions of arylborons with aldehydes is described. This new reaction pathway offers new catalysis opportunities for Type I palladacycle-catalyzed addition reactions such as the exceptionally low catalyst loading catalysis, with the catalyst loading as low as 0.0005 mol %. This new pathway may be applicable for other transition metal-catalyzed addition reactions and might lead to the development of new reactions including sequential/tandem reactions.
Preparation of β‐hydroxysulfides from 1,2,3‐thiadiazoles. Comparison of the effect of phenylmagnesium bromide on α‐Thio‐ and α‐selenoketones

Base decomposition of 4-substituted-phenyl-1,2,3-thiadiazoles at 78° resulted in 2-(4-substituted-phenyl)-ethynylthiolate anions which were immediately reacted with α-bromoketones to give a series of α-(2-[4-substituted-phenyf]ethynyl) thioketones. Unlike the selenophilic reaction of the Grignard reagents with α-selenoketones, the carbonyl group was the site of nucleophilic attack and the reaction of the α-thioketones with phenylmagnesium bromide gave the corresponding β-hydroxysulfides. The difference in mode of action toward the Grignard reagents was attributed to the difference in the bond strengths between carbon and the heteroatoms.
Effect of Surface Hydrophilicity on the Interfacial Properties of a Model Octane–Water–Silica System

We use molecular simulation to study the impact of substrate hydrophilicity on the wetting properties of water at a hydroxylated β-cristobalite (111) surface in a mother n-octane liquid. We employ ...
Bicriteria Rectilinear Shortest Paths Among Rectilinear Obstacles in the Plane

Given a rectilinear domain $$\mathcal {P}$$ of h pairwise-disjoint rectilinear obstacles with a total of n vertices in the plane, we study the problem of computing bicriteria rectilinear shortest paths between two points s and t in $$\mathcal {P}$$ . Three types of bicriteria rectilinear paths are considered: minimum-link shortest paths, shortest minimum-link paths, and minimum-cost paths where the cost of a path is a non-decreasing function of both the number of edges and the length of the path. The one-point and two-point path queries are also considered. Algorithms for these problems have been given previously. Our contributions are threefold. First, we find a critical error in all previous algorithms. Second, we correct the error in a not-so-trivial way. Third, we further improve the algorithms so that they are even faster than the previous (incorrect) algorithms when h is relatively small. For example, for the minimum-link shortest paths, we obtain the following results. Our algorithm computes a minimum-link shortest $$s$$ - $$t$$ path in $$O(n+h\log ^{3/2} h)$$ time. For the one-point queries, we build a data structure of size $$O(n+ h\log h)$$ in $$O(n+h\log ^{3/2} h)$$ time for a source point s, such that given any query point t, a minimum-link shortest $$s$$ - $$t$$ path can be computed in $$O(\log n)$$ time. For the two-point queries, with $$O(n+h^2\log ^2 h)$$ time and space preprocessing, a minimum-link shortest $$s$$ - $$t$$ path can be computed in $$O(\log n+\log ^2 h)$$ time for any two query points s and t; alternatively, with $$O(n+h^2\cdot \log ^{2} h \cdot 4^{\sqrt{\log h}})$$ time and $$O(n+h^2\cdot \log h \cdot 4^{\sqrt{\log h}})$$ space preprocessing, we can answer each two-point query in $$O(\log n)$$ time. Note that $$h^2\cdot \log ^{2} h \cdot 4^{\sqrt{\log h}}=O(h^{2+\epsilon })$$ for any $$\epsilon >0$$ . These results are particularly interesting when h is relatively small. For example, if $$h=O(n^{1/2-\epsilon })$$ for any $$\epsilon >0$$ , then all above results match the best results for the problems in simple rectilinear polygons, which are optimal. The complexities for the other two types of paths are slightly worse, but still linearly depend on n (in addition to g(h) for some functions g(h) of h).
Integrating biomedical research and electronic health records to create knowledge-based biologically meaningful machine-readable embeddings

In order to advance precision medicine, detailed clinical features ought to be described in a way that leverages current knowledge. Although data collected from biomedical research is expanding at an almost exponential rate, our ability to transform that information into patient care has not kept at pace. A major barrier preventing this transformation is that multi-dimensional data collection and analysis is usually carried out without much understanding of the underlying knowledge structure. Here, in an effort to bridge this gap, Electronic Health Records (EHRs) of individual patients are connected to a heterogeneous knowledge network called Scalable Precision Medicine Oriented Knowledge Engine (SPOKE). Then an unsupervised machine-learning algorithm creates Propagated SPOKE Entry Vectors (PSEVs) that encode the importance of each SPOKE node for any code in the EHRs. We argue that these results, alongside the natural integration of PSEVs into any EHR machine-learning platform, provide a key step toward precision medicine.
NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content

In mature neurons, postsynaptic N-methyl-D-aspartate receptors (NMDARs) are segregated into two populations, synaptic and extrasynaptic, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content. Here, we identify the phosphorylation of the PDZ-ligand of the GluN2B subunit of NMDARs (at S1480) as a critical determinant in dynamically controlling NMDAR synaptic content. We find that phosphorylation of GluN2B at S1480 maintains NMDARs at extrasynaptic membranes as part of a protein complex containing protein phosphatase 1 (PP1). Global activation of NMDARs leads to the activation of PP1, which mediates dephosphorylation of GluN2B at S1480 to promote an increase in synaptic NMDAR content. Thus, PP1-mediated dephosphorylation of the GluN2B PDZ-ligand modulates the synaptic expression of NMDARs in mature neurons in an activity-dependent manner, a process with profound consequences for synaptic and structural plasticity, metaplasticity, and synaptic neurotransmission.
Confidence sets for phylogenetic trees

Inferring evolutionary histories (phylogenetic trees) has important applications in biology, criminology, and public health. However, phylogenetic trees are complex mathematical objects that reside...
Formation control with triangulated Laman graphs

Formation control deals with the design of decentralized control laws that stabilize agents at prescribed distances from each other. We call any configuration a target configuration if it satisfies the inter-agent distance conditions. It is well known that when the distance conditions are defined via a rigid graph, there is a finite number of target configurations modulo rotations and translations. We can thus recast the objective of formation control as stabilizing one or many of the target configurations. A major issue is that such control laws will also have equilibria corresponding to configurations which do not meet the desired inter-agent distance conditions; we refer to these as undesired equilibria. The undesired equilibria become problematic if they are also stable. Designing decentralized control laws whose stable equilibria are all target configurations in the case of a general rigid graph is still an open problem. We provide here new approaches to this problem, and propose a partial solution by exhibiting a class of rigid graphs and control laws for which all stable equilibria are target configurations.
Forward sensitivity analysis for contracting stochastic systems

In this paper we investigate gradient estimation for a class of contracting stochastic systems on a continuous state space. We find conditions on the one-step transitions, namely differentiability and contraction in a Wasserstein distance, that guarantee differentiability of stationary costs. Then we show how to estimate the derivatives, deriving an estimator that can be seen as a generalization of the forward sensitivity analysis method used in deterministic systems. We apply the results to examples, including a neural network model.
Fundamental limits of universal variable-to-fixed length coding of parametric sources

Universal variable-to-fixed (V-F) length coding of d-dimensional exponential family of distributions is considered. An achievable scheme is proposed, which consists of a dictionary to parse the source output stream. The previously-introduced notion of quantized type is employed for the dictionary construction. The quantized type class of a sequence is based on partitioning the space of minimal sufficient statistics into cuboids. The proposed dictionary consists of sequences in the boundaries of transition from low to high quantized type class size. Asymptotics of the ∊-coding rate of the proposed coding scheme for large enough dictionaries is derived. In particular, we show that the third-order coding rate of the proposed scheme is H d/2 log log M/log M, where H is the entropy of the source and M is the dictionary size. We further provide a converse, showing that this rate is optimal up to the third-order term.
Wireless whispering-gallery-mode sensor for thermal sensing and aerial mapping.

The Internet of Things (IoT)1,2 employs a large number of spatially distributed wireless sensors to monitor physical environments, e.g., temperature, humidity, and air pressure, and has many applications, including environmental monitoring3, health care monitoring4, smart cities5, and precision agriculture. A wireless sensor can collect, analyze, and transmit measurements of its environment1,2. Currently, wireless sensors used in the IoT are predominately based on electronic devices that may suffer from electromagnetic interference in many circumstances. Being immune to the electromagnetic interference, optical sensors provide a significant advantage in harsh environments6. Furthermore, by introducing optical resonance to enhance light–matter interactions, optical sensors based on resonators exhibit small footprints, extreme sensitivity, and versatile functionalities7,8, which can significantly enhance the capability and flexibility of wireless sensors. Here we provide the first demonstration of a wireless photonic sensor node based on a whispering-gallery-mode (WGM) optical resonator, in which light propagates along the circular rim of such a structure like a sphere, a disk, or a toroid by continuous total internal reflection. The sensor node is controlled via a customized iOS app. Its performance was studied in two practical scenarios: (1) real-time measurement of the air temperature over 12 h and (2) aerial mapping of the temperature distribution using a sensor node mounted on an unmanned drone. Our work demonstrates the capability of WGM optical sensors in practical applications and may pave the way for the large-scale deployment of WGM sensors in the IoT.
Potential fitting biases resulting from grouping data into variable width bins

Abstract When reading peer-reviewed scientific literature describing any analysis of empirical data, it is natural and correct to proceed with the underlying assumption that experiments have made good faith efforts to ensure that their analyses yield unbiased results. However, particle physics experiments are expensive and time consuming to carry out, thus if an analysis has inherent bias (even if unintentional), much money and effort can be wasted trying to replicate or understand the results, particularly if the analysis is fundamental to our understanding of the universe. In this note we discuss the significant biases that can result from data binning schemes. As we will show, if data are binned such that they provide the best comparison to a particular (but incorrect) model, the resulting model parameter estimates when fitting to the binned data can be significantly biased, leading us to too often accept the model hypothesis when it is not in fact true. When using binned likelihood or least squares methods there is of course no a priori requirement that data bin sizes need to be constant, but we show that fitting to data grouped into variable width bins is particularly prone to produce biased results if the bin boundaries are chosen to optimize the comparison of the binned data to a wrong model. The degree of bias that can be achieved simply with variable binning can be surprisingly large. Fitting the data with an unbinned likelihood method, when possible to do so, is the best way for researchers to show that their analyses are not biased by binning effects. Failing that, equal bin widths should be employed as a cross-check of the fitting analysis whenever possible.
Funnel libraries for real-time robust feedback motion planning:

We consider the problem of generating motion plans for a robot that are guaranteed to succeed despite uncertainty in the environment, parametric model uncertainty, and disturbances. Furthermore, we...
Discriminative learning via semidefinite probabilistic models

Discriminative linear models are a popular tool in machine learning. These can be generally divided into two types: linear classifiers, such as support vector machines (SVMs), which are well studied and provide state-of-the-art results, and probabilistic models such as logistic regression. One shortcoming of SVMs is that their output (known as the "margin") is not calibrated, so that it is difficult to incorporate such models as components of larger systems. This problem is solved in the probabilistic approach. We combine these two approaches above by constructing a model which is both linear in the model parameters and probabilistic, thus allowing maximum margin training with calibrated outputs. Our model assumes that classes correspond to linear sub-spaces (rather than to half spaces), a view which is closely related to concepts in quantum detection theory. The corresponding optimization problems are semidefinite programs which can be solved efficiently. We illustrate the performance of our algorithm on real world datasets, and show that it outperforms second-order kernel methods.
Testing closeness with unequal sized samples

We consider the problem of testing whether two unequal-sized samples were drawn from identical distributions, versus distributions that differ significantly. Specifically, given a target error parameter e > 0, m1 independent draws from an unknown distribution p with discrete support, and m2 draws from an unknown distribution q of discrete support, we describe a test for distinguishing the case that p = q from the case that ‖p - q‖1 ≥ e. If p and q are supported on at most n elements, then our test is successful with high probability provided m1 ≥ n2/3/e4/3 and m2 = Ω (max{n/√m1 e2, √n/e2}). We show that this tradeoff is information theoretically optimal throughout this range in the dependencies on all parameters, n, m1, and e, to constant factors for worst-case distributions. As a consequence, we obtain an algorithm for estimating the mixing time of a Markov chain on n states up to a log n factor that uses O(n3/2τmix) queries to a "next node" oracle. The core of our testing algorithm is a relatively simple statistic that seems to perform well in practice, both on synthetic and on natural language data. We believe that this statistic might prove to be a useful primitive within larger machine learning and natural language processing systems.
Fekete polynomials and shapes of Julia sets

We prove that a nonempty, proper subset $S$ of the complex plane can be approximated in a strong sense by polynomial filled Julia sets if and only if $S$ is bounded and $\hat{\mathbb{C}} \setminus \textrm{int}(S)$ is connected. The proof that such a set is approximable by filled Julia sets is constructive and relies on Fekete polynomials. Illustrative examples are presented. We also prove an estimate for the rate of approximation in terms of geometric and potential theoretic quantities.
Follow the Compressed Leader: Faster Online Learning of Eigenvectors and Faster MMWU

The online problem of computing the top eigenvector is fundamental to machine learning. The famous matrix-multiplicative-weight-update (MMWU) framework solves this online problem and gives optimal regret. However, since MMWU runs very slow due to the computation of matrix exponentials, researchers proposed the follow-the-perturbed-leader (FTPL) framework which is faster, but a factor √d worse than the optimal regret for dimension-d matrices. We propose a follow-the-compressed-leader framework which, not only matches the optimal regret of MMWU (up to polylog factors), but runs no slower than FTPL. Our main idea is to “compress” the MMWU strategy to dimension 3 in the adversarial setting, or dimension 1 in the stochastic setting. This resolves an open question regarding how to obtain both (nearly) optimal and efficient algorithms for the online eigenvector problem.
Spin Tunneling in Conducting Oxides

Different tunneling mechanisms in conventional and half-metallic ferromagnetic tunnel junctions are analyzed within the same general method. Direct tunneling is compared with impurity-assisted, surface state assisted, and inelastic contributions to a tunneling magnetoresistance (TMR). Theoretically calculated direct tunneling in iron group systems leads to about a 30% change in resistance, which is close to experimentally observed values. It is shown that the larger observed values of the TMR might be a result of tunneling involving surface polarized states. We find that tunneling via resonant defect states in the barrier radically decreases the TMR (down to 4% with Fe-based electrodes), and a resonant tunnel diode structure would give a TMR of about 8%. With regards to inelastic tunneling, magnons and phonons exhibit opposite effects: one-magnon emission generally results in spin mixing and, consequently, reduces the TMR, whereas phonons are shown to enhance the TMR. The inclusion of both magnons and phonons reasonably explains an unusual bias dependence of the TMR. The model presented here is applied qualitatively to half-metallics with 100% spin polarization, where one-magnon processes are suppressed and the change in resistance in the absence of spin-mixing on impurities may be arbitrarily large. Even in the case of imperfect magnetic configurations, the resistance change can be a few 1000 percent. Examples of half-metallic systems are CrO2/TiO2 and CrO2/RuO2, and an account of their peculiar band structures is presented. The implications and relation of these systems to CMR materials, which are nearly half-metallic, are discussed.
Discrete Maximum Principle and a Delaunay-Type Mesh Condition for Linear Finite Element Approximations of Two-Dimensional Anisotropic Diffusion Problems

A Delaunay-type mesh condition is developed for a linear finite element approximation of two-dimensional anisotropic diffusion problems to satisfy a discrete maximum principle. The condition is weaker than the existing anisotropic non-obtuse angle condition and reduces to the well known Delaunay condition for the special case with the identity diffusion matrix. Numerical results are presented to verify the theoretical findings.
Bandwidth Partitioning and Downlink Analysis in Millimeter Wave Integrated Access and Backhaul for 5G

With the increasing network densification, it has become exceedingly difficult to provide traditional fiber backhaul access to each cell site, which is especially true for small cell base stations (SBSs). The increasing maturity of millimeter wave (mm-wave) communication has opened up the possibility of providing high-speed wireless backhaul to such cell sites. Since mm-wave is also suitable for access links, the third generation partnership project (3GPP) is envisioning an integrated access and backhaul (IAB) architecture for the fifth generation (5G) cellular networks in which the same infrastructure and spectral resources will be used for both access and backhaul. In this paper, we develop an analytical framework for IAB-enabled cellular network using which its downlink rate coverage probability is accurately characterized. Using this framework, we study the performance of three backhaul bandwidth (BW) partition strategies: 1) equal partition: when all SBSs obtain equal share of the backhaul BW; 2) instantaneous load-based partition: when the backhaul BW share of an SBS is proportional to its instantaneous load; and 3) average load-based partition: when the backhaul BW share of an SBS is proportional to its average load. Our analysis shows that depending on the choice of the partition strategy, there exists an optimal split of access and backhaul BW for which the rate coverage is maximized. Further, there exists a critical volume of cell-load (total number of users) beyond which the gains provided by the IAB-enabled network disappear and its performance converges to that of the traditional macro-only network with no SBSs.
Neural Ideals in SageMath

A major area in neuroscience research is the study of how the brain processes spatial information. Neurons in the brain represent external stimuli via neural codes. These codes often arise from stereotyped stimulus-response maps, associating to each neuron a convex receptive field. An important problem consists in determining what stimulus space features can be extracted directly from a neural code. The neural ideal is an algebraic object that encodes the full combinatorial data of a neural code. This ideal can be expressed in a canonical form that directly translates to a minimal description of the receptive field structure intrinsic to the code. Here, we describe a SageMath package that contains several algorithms related to the canonical form of a neural ideal.