cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs.

Abstract Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification . Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.
Studies directed toward the synthesis of the scabrosins: validation of a tandem enyne metathesis approach

Abstract A synthetic approach to the scabrosin family of antibiotics using a ruthenium carbene-catalyzed tandem metathesis and a Pd(II)-catalyzed cyclization is described. The chiral propargyl amino acid is furnished through enantioselective phase-transfer propargylation. The synthesis of the cyclohexadiene ring system is achieved through ring synthesis using tandem enyne metathesis, previously developed in our lab. The complementary methods of methylene-free and 1,5-hexadiene-alkyne metatheses are compared. The indoline heterocycles are formed using a two-step chloroacetoxylation (Backvall reaction) with subsequent nucleophilic attack by an amide nucleophile. The indoline subunits were joined and cyclized to furnish the core diketopiperazine ring. The stereochemical assignment of intermediates is also discussed.
Synthesis, structure, and electrical resistivity of Cs3U18Se38

Abstract Cs 3 U 18 Se 38 was synthesized by the solid-state reactions of U, Se, CsCl or Cs 2 Se 3 , and P or As at 1273 K. This compound crystallizes in a new structure in the tetragonal space group D 18 4h - I 4/ mcm . The asymmetric unit contains U atoms in four different coordination environments. The overall three-dimensional network structure contains channels along the c axis, in which the Cs atoms lie. The formula Cs 3 U 18 Se 38 does not charge balance with the typical formal oxidation states of the elements. Electrical resistivity measurements conducted on a single crystal reveal a broad feature at 225 K, atypical semiconductor behavior below 57 K, and a calculated band gap of 0.0030(1) eV.
Structural and Energetic Properties of Closed Shell XFn (X = Cl, Br, and I; n = 1–7) and XOnFm (X = Cl, Br, and I; n = 1–3; m = 0–6) Molecules and Ions Leading to Stability Predictions for Yet Unknown Compounds

Atomization energies at 0 K and heats of formation at 0 and 298 K were predicted for the closed shell compounds XF, XF2–, XF2+, XF3, XF4–, XF4+, XF5, XF6–, XF6+ (X = Cl and Br) and XO+, XOF, XOF2–, XOF2+, XOF3, XOF4–, XOF4+, XOF5, XOF6–, XO2+, XO2F, XO2F2–, XO2F2+, XO2F3, XO2F4–, XO3+, XO3F, XO3F2– (X = Cl, Br, and I) using a composite electronic structure approach based on coupled cluster CCSD(T) calculations extrapolated to the complete basis set limit with additional corrections. The calculated heats of formation are in good agreement with the available experimental data. The calculated heats of formation were used to predict fluoride affinities, fluorine cation affinities, and F2 binding energies. On the basis of our results, BrOF5 and BrO2F3 are predicted to be stable against spontaneous loss of F2 and should be able to be synthesized, whereas BrF7, ClF7, BrOF6–, and ClOF6– are unstable by a very wide margin. The stability of ClOF5 is a borderline case. Although its F2 loss is predicted to be exother...
A Practical Synthesis of L-Azatyrosine.

Oncogenic Ras genes and the G-proteins which they encode are important targets for anticancer research. Ras proteins have been implicated to function as components of the cellular signal transduction pathways related to cell proliferation and differentiation. In their oncogenic form, the natural GTP-ase activity of Ras proteins is inhibited, leading to overstimulation of the signaling pathway for cell growth. The potential importance of oncogenic Ras genes and gene products as targets for cancer chemotherapy is underscored by the observation that up to 40% of human colon tumors and 95% of human pancreatic tumors have been found to contain oncogenic Ras genes.
The spermidine acetyltransferase SpeG regulates transcription of the small RNA rprA.

Spermidine N-acetyltransferase (SpeG) acetylates and thus neutralizes toxic polyamines. Studies indicate that SpeG plays an important role in virulence and pathogenicity of many bacteria, which have evolved SpeG-dependent strategies to control polyamine concentrations and survive in their hosts. In Escherichia coli, the two-component response regulator RcsB is reported to be subject to Ne-acetylation on several lysine residues, resulting in reduced DNA binding affinity and reduced transcription of the small RNA rprA; however, the physiological acetylation mechanism responsible for this behavior has not been fully determined. Here, we performed an acetyltransferase screen and found that SpeG inhibits rprA promoter activity in an acetylation-independent manner. Surface plasmon resonance analysis revealed that SpeG can physically interact with the DNA-binding carboxyl domain of RcsB. We hypothesize that SpeG interacts with the DNA-binding domain of RcsB and that this interaction might be responsible for SpeG-dependent inhibition of RcsB-dependent rprA transcription. This work provides a model for SpeG as a modulator of E. coli transcription through its ability to interact with the transcription factor RcsB. This is the first study to provide evidence that an enzyme involved in polyamine metabolism can influence the function of the global regulator RcsB, which integrates information concerning envelope stresses and central metabolic status to regulate diverse behaviors.
An efficient and general method for resolving cyclopropene carboxylic acids

Abstract A general method is described for the resolution of cycloprop-2-ene carboxylic acids via diastereomeric N -acyloxazolidines prepared from enantiomerically pure oxazolidinones. Although a number of oxazolidinones were shown to resolve cyclopropene carboxylic acids, the oxazolidinones of S -phenylalaninol, S -phenylglycine and (1 S ,2 R )- cis -1-amino-2-indanol are optimal in terms of resolving power and cost effectiveness. Separations were performed using simple flash chromatography, and because there is typically a large difference in R f values it is possible to separate gram quantities of pure diastereomers in a single chromatogram. The cycloprop-2-ene carboxylic acids that can be resolved include those that are substituted at the 1-position by H, Ph, α-naphthyl, CO 2 Me, CH 2 OMOM, and trans-styryl; alkene substituents include Me, n -alkyl, Ph and tethered alkynes. Remarkably, 2-methyl-3-propylcycloprop-2-ene carboxylic acid can also be resolved with ease. The relative configurations of four diastereomerically pure oxazolidines were determined by X-ray crystallography. Reduction of the N -acyloxazolidinones with LiBH 4 give enantiomerically pure derivatives of 3-hydroxymethylcyclopropene that react with either MeMgCl or vinylMgCl and catalytic CuI to give enantiomerically pure products of syn -addition.
Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide.

The type two intramolecular Diels−Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (±)-ledol and (±)-ledene and a formal synthesis of (±)-compressanolide.
Detecting presence of mutational signatures in cancer with confidence.

Motivation Cancers arise as the result of somatically acquired changes in the DNA of cancer cells. However, in addition to the mutations that confer a growth advantage, cancer genomes accumulate a large number of somatic mutations resulting from normal DNA damage and repair processes as well as carcinogenic exposures or cancer related aberrations of DNA maintenance machinery. These mutagenic processes often produce characteristic mutational patterns called mutational signatures. The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology. However, the results from different decomposition methods are not always consistent. Hence, one needs to be able to not only decompose a patient's mutational profile into signatures but also establish the accuracy of such decomposition. Results We proposed two complementary ways of measuring confidence and stability of decomposition results and applied them to analyze mutational signatures in breast cancer genomes. We identified both very stable and highly unstable signatures, as well as signatures that previously have not been associated with breast cancer. We also provided additional support for the novel signatures. Our results emphasize the importance of assessing the confidence and stability of inferred signature contributions. Availability and implementation All tools developed in this paper have been implemented in an R package, called SignatureEstimation, which is available from https://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/index.cgi\#signatureestimation. Supplementary information Supplementary data are available at Bioinformatics online.
Asymmetric enolate alkylation via templation with chiral synthetic receptors

Abstract C 3 -Symmetric chiral receptors have been developed for enantioselective alkylation of sodium enolates of active methylene compounds. It has been demonstrated that a 1:1 binding complex forms between these receptors and sodium enolates in THF- d 8 /CD 3 CN by 1 H NMR titration experiments. Moderate enantiomeric enrichment of the benzylation product of 2-acetylcyclohexanone has been demonstrated using this strategy. Templation of enolate alkylation by synthetic receptors represents a new approach to asymmetric induction.
Insertion of acetylenes into carbon-hydrogen bonds catalyzed by rhodium-trimethylphosphine complexes

Rhodium-trimethylphosphine species have been found to catalyze the insertion of alkyne triple bonds into phenyl-H and alkynyl-H bonds. Several observations are consistent with a thermal catalytic cycle involving a concerted addition to the triple bond
The Carcinogenome Project: In Vitro Gene Expression Profiling of Chemical Perturbations to Predict Long-Term Carcinogenicity

Background: Most chemicals in commerce have not been evaluated for their carcinogenic potential. The de facto gold-standard approach to carcinogen testing adopts the 2-y rodent bioassay, a time-con...
The synthesis of fluorinated α-pyrans via fluorinated vinylcopper reagents

Fluorinated vinylcopper reagents were prepared in situ via reaction of fluorinated vinylbromides or iodides with cadmium or zinc powder followed by metathesis with Cu(I)Br. Hexafluoro-2-butyne was then added to the solution of the F-vinylcopper reagent which resulted in a stereospecific syn addition of the F-vinylcopper reagent to the alkyne to provide in situ the corresponding dienylcopper reagent. Subsequent acylation of the dienylcopper reagent gave a dienylketone, which spontaneously cyclized to the 2H-pyran. This methodology provides a useful one flask route to fluorinated 2H-pyrans.
Syntheses, crystal structures, and metal ion complexation studies of novel diaza‐18‐crown‐6 ligands containing aromatic thiol‐derived side arms

The Mannich aminomethylation reaction of aromatic thiols has been used to produce diaza-18-crown-6 ligands containing thiol-derived side arms. Thiophenols were attached to the azacrown through N-CH2-S linkages even in the presence of hydroxy or acetamido groups. Heteroaromatic thiols containing N=C-SH (or NH-C=S) structural fragments were attached to diaza-18-crown-6 by N-CH2-N linkages with the thiol becoming a thione function. X-ray crystal structural analyses show the N-CH2-S and N-CH2-N linkages for some of the new macrocyclic compounds. Interactions of four of the new diaza-18-crown-6 ligands with Na+, K+, Ba2+, Ag+, Zn2+, Cd2+, Ni2+, and Cu2+ were evaluated by calorimetric titration at 25° in methanol. The results show that these ligands form stable complexes with many of the metal ions studied.
The versatility of α-chloropropargyl phenyl sulfide affords high stereo- and regioselectivities in indium-promoted coupling reactions under mild conditions

Coupling reactions between α-chloropropargyl phenyl sulfide (11) and a series of aldehydes under aqueous conditions are reported. Not only is good stereoselectivity observed between syn and anti isomeric products, but excellent regioselectivity is also witnessed. In reactions using indium metal as a promoter, the propargyl functionality (12) is retained, unlike the use of more traditional metals that result in formation of products containing a mixture of both propargyl (12) and allene (13) moieties. The reaction is postulated to proceed via either a chelated or nonchelated route, controlled by the presence or absence of indium (III) chloride, and may be used to create synthetically useful building blocks. The formation of epoxyalkyne (14) molecules, which are found in many natural products and have wide use as synthetic templates, is presented as one example.
Design and Implementation of an Efficient Synthetic Approach to Pyranosylated Indolocarbazoles: Total Synthesis of (+)-RK286c, (+)-MLR-52, (+)-Staurosporine, and (−)-TAN-1030a

A total synthesis of the natural products (+)-staurosporine (2), (+)-RK286c (3), (−)-TAN-1030a (4), and (+)-MLR-52 (5) has been achieved. The synthetic strategy involves the stereoselective ring expansion of a furanosylated indolocarbazole [(+)-8] to a pyranosylated congener [(+)-12] that serves as a common intermediate in the production of 2−5.
Ring-closing metathesis to a divergent endocyclic sulfonamide template

Abstract The efficient synthesis of a novel endocyclic sulfonamide template via a ring-closing metathesis methodology is reported. A solid-supported variant of the Grubbs catalyst is shown to be effective and the suitability of the template for both combinatorial derivatization and potential incorporation into peptidomimetics is demonstrated.
Historical contingency shapes adaptive radiation in Antarctic fishes

Adaptive radiation illustrates links between ecological opportunity, natural selection and the generation of biodiversity. Central to adaptive radiation is the association between a diversifying lineage and the evolution of phenotypic variation that facilitates the use of new environments or resources. However, is not clear whether adaptive evolution or historical contingency is more important for the origin of key phenotypic traits in adaptive radiation. Here we use targeted sequencing of >250,000 loci across 46 species to examine hypotheses concerning the origin and diversification of key traits in the adaptive radiation of Antarctic notothenioid fishes. Contrary to expectations of adaptive evolution, we show that notothenioids experienced a punctuated burst of genomic diversification and evolved key skeletal modifications before the onset of polar conditions in the Southern Ocean. We show that diversifying selection in pathways associated with human skeletal dysplasias facilitates ecologically important variation in buoyancy among Antarctic notothenioid species, and demonstrate the sufficiency of altered trip11, col1a2 and col1a1a function in zebrafish (Danio rerio) to phenocopy skeletal reduction in Antarctic notothenioids. Rather than adaptation being driven by the cooling of the Antarctic, our results highlight the role of historical contingency in shaping the adaptive radiation of notothenioids. Understanding the historical and environmental context for the origin of key traits in adaptive radiations extends beyond reconstructing events that result in evolutionary innovation, as it also provides a context in forecasting the effects of climate change on the stability and evolvability of natural populations. Phylogenetic comparative analysis of Antarctic notothenioid fishes reveals a burst of genomic diversification and evolution of key skeletal modifications before the onset of polar conditions in the Southern Ocean.
Synthesis and Structure of a 1-Germapropadiene

The reaction of t-BuLi with a fluoroalkynylgermane produces the title compound, 1. Single-crystal X-ray analysis shows the GeC bond length to be 1.783(2) A. The Ge atom is somewhat pyramidalized, and the GeCC bond angle (159.2°) reveals a bent structure at the central carbon atom.
Computational Comparison of SN2 Substitution Reactions of CHX•- and CH2X- with CH3X (X = Cl, Br). Do Open-Shell and Closed-Shell Anions React Differently?

The SN2 displacement reaction of the radical anions (CHCl•- and CHBr•-) and the closed-shell anions (CH2Cl- and CH2Br-) with CH3Cl and CH3Br were studied with density functional theory. It was determined that the anions CH2Cl- and CH2Br- were more reactive than the radical anions CHCl•- and CHBr•-, in agreement with experiment. The degree of charge transfer in the reactant complex is the best indicator of the reactivity trend. It was found that two reactions (CH2Cl- with CH3Cl and CH3Br) proceeded without an activation barrier at the B3LYP/6-31+G(d) level. The backside transition states (leading to inversion of configuration at the methyl group) were 20−30 kcal/mol lower in energy than the frontside transition states (leading to retention of configuration). Interestingly, it was found that the mechanism of backside and frontside attack by radical anions was different. In backside attack, the radical anion leads with the lone pair directed toward the methyl group to form an incipient two-center, two-electr...
Conversion of γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones

Abstract Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. This paper describes the development of a method for the direct conversion of unsubstituted and 4-substituted γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones and 2-phenyl-4,5-dihydro-2H-pyridazin-3-ones.
Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.
Genome-Scale Transcriptional Regulatory Network Models of Psychiatric and Neurodegenerative Disorders.

Summary Transcriptional regulatory changes in the developing and adult brain are prominent features of brain diseases, but the involvement of specific transcription factors (TFs) remains poorly understood. We integrated brain-specific DNase footprinting and TF-gene co-expression to reconstruct a transcriptional regulatory network (TRN) model for the human brain. We identified key regulator TFs whose predicted target genes were enriched for differentially expressed genes in the prefrontal cortex of individuals with psychiatric and neurodegenerative diseases. Many of these TFs were further implicated in the same diseases through disruption of their binding sites by disease-associated SNPs and associations of TF loci with disease risk. Using primary human neural stem cells, we validated network predictions that link the TF POU3F2 to schizophrenia and bipolar disorder via both cis- and trans-acting mechanisms. Our models of brain-specific TF binding sites and target genes provide a resource for network analysis of brain diseases.
Total Synthesis of (+)-Isolaurepinnacin. Use of Acetal-Alkene Cyclizations To Prepare Highly Functionalized Seven-Membered Cyclic Ethers

The first synthesis of the title compound is described. The synthesis features an acetal-vinylsilane cyclization to stereoselectively form the cis-2,7-disubstituted oxepene ring and introduce Δ4 unsaturation. Starting with (2R,3S)-2,3-epoxypentan-1-ol (16), mixed acetal 10 is formed in five steps and 72% overall yield. Treatment of 10 with excess BCl3 in CH2Cl2 at −78 → 0 °C promotes cyclization to afford Δ4-oxepene 39 in 90% yield after deprotection of the silyl ether. Elaboration of the (E)-enyne functionality of the six-carbon side chain completes the synthesis of (+)-isolaurepinnacin.
Catalytic enantioselective addition of arylboronic acids to N-boc imines generated in situ

The rhodium-catalyzed addition of arylboronic acids to N-Boc imines generated in situ from stable and easily prepared alpha-carbamoyl sulfones has been developed. High enantioselectivities are observed for additions of arylboronic acids with a variety of steric and electronic properties.
Studies on the Diels–Alder reaction of annulated furans: application to the synthesis of substituted phenanthrenes

Abstract In an attempt to utilize the synthetic power of the furan nucleus in the synthesis of complex natural products, we have developed an entry into annulated furan intermediates that involves an electrochemical annulation protocol. An approach to the eunicellin diterpenes based on this methodology required the use of an intermolecular Diels–Alder reaction on an annulated furan. Although well known for simple furans, there is a paucity of related examples on annulated furans. To examine the feasibility of such an approach to these diterpenes, we have studied this key cycloaddition reaction. Our studies indicate that the process can be hampered by a facile retro-Diels–Alder that is highly dependent on the dienophile employed.
On Matching and Thickness in Heterogeneous Dynamic Markets

We study dynamic matching in an infinite-horizon stochastic market. Although all agents are potentially compatible with each other, some are hard to match and others are easy to match. Agents prefe...
VIEW-MOD: A Versatile Illumination Engine With a Modular Optical Design for Fluorescence Microscopy

We developed VIEW-MOD (Versatile Illumination Engine with a Modular Optical Design): a compact, multi-modality microscope, which accommodates multiple illumination schemes including variable angle total internal reflection, point scanning and vertical/horizontal light sheet. This system allows combining and flexibly switching between different illuminations and imaging modes by employing three electrically tunable lenses and two fast-steering mirrors. This versatile optics design provides control of 6 degrees of freedom of the illumination source (3 translation, 2 tilt, and beam shape) plus the axial position of the imaging plane. We also developed standalone software with an easy-to-use GUI to calibrate and control the microscope. We demonstrate the applications of this system and software in biosensor imaging, optogenetics and fast 3D volume imaging. This system is ready to fit into complex imaging circumstances requiring precise control of illumination and detection paths, and has a broad scope of usability for a myriad of biological applications.
Proving Unrealizability for Syntax-Guided Synthesis

We consider the problem of automatically establishing that a given syntax-guided-synthesis (SyGuS) problem is unrealizable (i.e., has no solution). Existing techniques have quite limited ability to establish unrealizability for general SyGuS instances in which the grammar describing the search space contains infinitely many programs. By encoding the synthesis problem’s grammar G as a nondeterministic program \(P_G\), we reduce the unrealizability problem to a reachability problem such that, if a standard program-analysis tool can establish that a certain assertion in \(P_G\) always holds, then the synthesis problem is unrealizable.
Bottom-quark forward–backward asymmetry, dark matter and the LHC

The LEP experiment at CERN provided accurate measurements of the Z neutral gauge boson properties. Although all measurements agree well with the SM predictions, the forward–backward asymmetry of th...
Caliber Corrected Markov Modeling (C2M2): Correcting Equilibrium Markov Models

Rate processes are often modeled using Markov State Models (MSMs). Suppose you know a prior MSM and then learn that your prediction of some particular observable rate is wrong. What is the best way to correct the whole MSM? For example, molecular dynamics simulations of protein folding may sample many microstates, possibly giving correct pathways through them while also giving the wrong overall folding rate when compared to experiment. Here, we describe Caliber Corrected Markov Modeling (C2M2), an approach based on the principle of maximum entropy for updating a Markov model by imposing state- and trajectory-based constraints. We show that such corrections are equivalent to asserting position-dependent diffusion coefficients in continuous-time continuous-space Markov processes modeled by a Smoluchowski equation. We derive the functional form of the diffusion coefficient explicitly in terms of the trajectory-based constraints. We illustrate with examples of 2D particle diffusion and an overdamped harmonic ...
The Expected Characteristic and Permanental Polynomials of the Random Gram Matrix

A $t \times n$ random matrix $A$ can be formed by sampling $n$ independent random column vectors, each containing $t$ components. The random Gram matrix of size $n$, $G_{n}=A^{T}A$, contains the dot products between all pairs of column vectors in the randomly generated matrix $A$, and has characteristic roots coinciding with the singular values of $A$. Furthermore, the sequences $\det{(G_{i})}$ and $\text{perm}(G_{i})$ (for $i = 0, 1, \dots, n$) are factors that comprise the expected coefficients of the characteristic and permanental polynomials of $G_{n}$. We prove theorems that relate the generating functions and recursions for the traces of matrix powers, expected characteristic coefficients, expected determinants $E(\det{(G_{n})})$, and expected permanents $E(\text{perm}(G_{n}))$ in terms of each other. Using the derived recursions, we exhibit the efficient computation of the expected determinant and expected permanent of a random Gram matrix $G_{n}$, formed according to any underlying distribution. These theoretical results may be used both to speed up numerical algorithms and to investigate the numerical properties of the expected characteristic and permanental coefficients of any matrix comprised of independently sampled columns.
Learning under $p$-Tampering Attacks.

Mahloujifar and Mahmoody (TCC'17) studied attacks against learning algorithms using a special case of Valiant's malicious noise, called $p$-tampering, in which the adversary could change training examples with independent probability $p$ but only using correct labels. They showed the power of such attacks by increasing the error probability in the so called `targeted' poisoning model in which the adversary's goal is to increase the loss of the generated hypothesis over a particular test example. At the heart of their attack was an efficient algorithm to bias the average output of any bounded real-valued function through $p$-tampering. In this work, we present new attacks for biasing the average output of bounded real-valued functions, improving upon the biasing attacks of MM16. Our improved biasing attacks, directly imply improved $p$-tampering attacks against learners in the targeted poisoning model. As a bonus, our attacks come with considerably simpler analysis compared to previous attacks. We also study the possibility of PAC learning under $p$-tampering attacks in the \emph{non-targeted} (aka indiscriminate) setting where the adversary's goal is to increase the risk of the generated hypothesis (for a random test example). We show that PAC learning is \emph{possible} under $p$-tampering poisoning attacks essentially whenever it is possible in the realizable setting without the attacks. We further show that PAC learning under `no-mistake' adversarial noise is \emph{not} possible, if the adversary could choose the (still limited to only $p$ fraction of) tampered examples that she substitutes with adversarially chosen ones. Our formal model for such `bounded-budget' tampering attackers is inspired by the notions of (strong) adaptive corruption in secure multi-party computation.
Deconvolutional paragraph representation learning

Learning latent representations from long text sequences is an important first step in many natural language processing applications. Recurrent Neural Networks (RNNs) have become a cornerstone for this challenging task. However, the quality of sentences during RNN-based decoding (reconstruction) decreases with the length of the text. We propose a sequence-to-sequence, purely convolutional and deconvolutional autoencoding framework that is free of the above issue, while also being computationally efficient. The proposed method is simple, easy to implement and can be leveraged as a building block for many applications. We show empirically that compared to RNNs, our framework is better at reconstructing and correcting long paragraphs. Quantitative evaluation on semi-supervised text classification and summarization tasks demonstrate the potential for better utilization of long unlabeled text data.
Black-Box Generation of Adversarial Text Sequences to Evade Deep Learning Classifiers

Although various techniques have been proposed to generate adversarial samples for white-box attacks on text, little attention has been paid to a black-box attack, which is a more realistic scenario. In this paper, we present a novel algorithm, DeepWordBug, to effectively generate small text perturbations in a black-box setting that forces a deep-learning classifier to misclassify a text input. We develop novel scoring strategies to find the most important words to modify such that the deep classifier makes a wrong prediction. Simple character-level transformations are applied to the highest-ranked words in order to minimize the edit distance of the perturbation. We evaluated DeepWordBug on two real-world text datasets: Enron spam emails and IMDB movie reviews. Our experimental results indicate that DeepWordBug can reduce the classification accuracy from 99% to 40% on Enron and from 87% to 26% on IMDB. Our results strongly demonstrate that the generated adversarial sequences from a deep-learning model can similarly evade other deep models.
Quantum fingerprints that keep secrets

We introduce a new type of cryptographic primitive that we call a hiding fingerprinting scheme. A (quantum) fingerprinting scheme maps a binary string of length n to d (qu)bits, typically d ≪ n, such that given any string y and a fingerprint of x, one can decide with high accuracy whether x = y. It can be seen that a classical fingerprint of x that guarantees error ≤ e necessarily reveals Ω(min {n, log(1/e)}) bits of information about x. We call a scheme hiding if it reveals o(min {n, log(1/e)}) bits; accordingly, no classical scheme is hiding. We construct quantum hiding fingerprinting schemes. Our schemes are computationally efficient and their hiding properties are shown to be optimal.
Resource-efficient common randomness and secret-key schemes

We study common randomness where two parties have access to i.i.d. samples from a known random source, and wish to generate a shared random key using limited (or no) communication with the largest possible probability of agreement. This problem is at the core of secret key generation in cryptography, with connections to communication under uncertainty and locality sensitive hashing. We take the approach of treating correlated sources as a critical resource, and ask whether common randomness can be generated resource-efficiently. We consider two notable sources in this setup arising from correlated bits and correlated Gaussians. We design the first explicit schemes that use only a polynomial number of samples (in the key length) so that the players can generate shared keys that agree with constant probability using optimal communication. The best previously known schemes were both non-constructive and used an exponential number of samples. In the amortized setting, we characterize the largest achievable ratio of key length to communication in terms of the external and internal information costs, two well-studied quantities in theoretical computer science. In the relaxed setting where the two parties merely wish to improve the correlation between the generated keys of length k, we show that there are no interactive protocols using o(k) bits of communication having agreement probability even as small as 2−o(k). For the related communication problem where the players wish to compute a joint function f of their inputs using i.i.d samples from a known source, we give a simultaneous message passing protocol using 2O(c) bits where c is the interactive randomized public-coin communication complexity of f. This matches the lower bound shown previously while the best previously known upper bound was doubly exponential in c. Our schemes reveal a new connection between common randomness and unbiased error-correcting codes, e.g., dual-BCH codes and their analogues in Euclidean space.
Stochastic Cubic Regularization for Fast Nonconvex Optimization

This paper proposes a stochastic variant of a classic algorithm---the cubic-regularized Newton method [Nesterov and Polyak]. The proposed algorithm efficiently escapes saddle points and finds approximate local minima for general smooth, nonconvex functions in only $\mathcal{\tilde{O}}(\epsilon^{-3.5})$ stochastic gradient and stochastic Hessian-vector product evaluations. The latter can be computed as efficiently as stochastic gradients. This improves upon the $\mathcal{\tilde{O}}(\epsilon^{-4})$ rate of stochastic gradient descent. Our rate matches the best-known result for finding local minima without requiring any delicate acceleration or variance-reduction techniques.
cmenet: a new method for bi-level variable selection of conditional main effects

This article introduces a novel method for selecting main effects and a set of reparameterized effects called conditional main effects (CMEs), which capture the conditional effect of a factor at a ...
Global existence for quasilinear wave equations close to Schwarzschild

AbstractIn this article, we study the quasilinear wave equation □g(u,t,x)u=0 where the metric g(u,t,x) is close (and asymptotically equal) to the Schwarzschild metric g(0,t,x). Under suitable assum...
The initial state and hard probes: a brief review

Abstract We provide a brief review of some of the recent developments in our understanding of the initial state in ultrarelativistic heavy-ion collisions.
Information Projection and Approximate Inference for Structured Sparse Variables

Approximate inference via information projection has been recently introduced as a general-purpose approach for efficient probabilistic inference given sparse variables. This manuscript goes beyond classical sparsity by proposing efficient algorithms for approximate inference via information projection that are applicable to any structure on the set of variables that admits enumeration using a \emph{matroid}. We show that the resulting information projection can be reduced to combinatorial submodular optimization subject to matroid constraints. Further, leveraging recent advances in submodular optimization, we provide an efficient greedy algorithm with strong optimization-theoretic guarantees. The class of probabilistic models that can be expressed in this way is quite broad and, as we show, includes group sparse regression, group sparse principal components analysis and sparse canonical correlation analysis, among others. Moreover, empirical results on simulated data and high dimensional neuroimaging data highlight the superior performance of the information projection approach as compared to established baselines for a range of probabilistic models.
KKM type theorems with boundary conditions

We consider generalizations of Gale’s colored KKM lemma and Shapley’s KKMS theorem. It is shown that spaces and covers can be much more general and the boundary KKM rules can be substituted by more weaker boundary assumptions.
Toward Domain-Invariant Speech Recognition via Large Scale Training

Current state-of-the-art automatic speech recognition systems are trained to work in specific ‘domains’, defined based on factors like application, sampling rate and codec. When such recognizers are used in conditions that do not match the training domain, performance significantly drops. This work explores the idea of building a single domain-invariant model for varied use-cases by combining large scale training data from multiple application domains. Our final system is trained using 162,000 hours of speech. Additionally, each utterance is artificially distorted during training to simulate effects like background noise, codec distortion, and sampling rates. Our results show that, even at such a scale, a model thus trained works almost as well as those fine-tuned to specific subsets: A single model can be robust to multiple application domains, and variations like codecs and noise. More importantly, such models generalize better to unseen conditions and allow for rapid adaptation – we show that by using as little as 10 hours of data from a new domain, an adapted domain-invariant model can match performance of a domain-specific model trained from scratch using 70 times as much data. We also highlight some of the limitations of such models and areas that need addressing in future work.
On Relaxing Determinism in Arithmetic Circuits

The past decade has seen a significant interest in learning tractable probabilistic representations. Arithmetic circuits (ACs) were among the first proposed tractable representations, with some subsequent representations being instances of ACs with weaker or stronger properties. In this paper, we provide a formal basis under which variants on ACs can be compared, and where the precise roles and semantics of their various properties can be made more transparent. This allows us to place some recent developments on ACs in a clearer perspective and to also derive new results for ACs. This includes an exponential separation between ACs with and without determinism; completeness and incompleteness results; and tractability results (or lack thereof) when computing most probable explanations (MPEs).
Pluri-canonical maps of varieties of maximal Albanese dimension in positive characteristic

Abstract We show that if X is a nonsingular projective variety of general type over an algebraically closed field k of positive characteristic and X has maximal Albanese dimension and the Albanese map is separable, then | 4 K X | induces a birational map.
Competition and complexity in amphiphilic polymer morphology

Abstract The strong functionalized Cahn–Hilliard equation models self assembly of amphiphilic polymers in solvent. It supports codimension one and two structures that each admit two classes of bifurcations: pearling, a short-wavelength in-plane modulation of interfacial width, and meandering, a long-wavelength instability that induces a transition to curve-lengthening flow. These two potential instabilities afford distinctive routes to changes in codimension and creation of non-codimensional defects such as end caps and Y -junctions. Prior work has characterized the onset of pearling, showing that it couples strongly to the spatially constant, temporally dynamic, bulk value of the chemical potential. We present a multiscale analysis of the competitive evolution of codimension one and two structures of amphiphilic polymers within the H − 1 gradient flow of the strong Functionalized Cahn–Hilliard equation. Specifically we show that structures of each codimension transition from a curve lengthening to a curve shortening flow as the chemical potential falls through a corresponding critical value. The differences in these critical values quantify the competition between the morphologies of differing codimension for the amphiphilic polymer mass. We present a bifurcation diagram for the morphological competition and compare our results quantitatively to simulations of the full system and qualitatively to simulations of self-consistent mean field models and laboratory experiments. In particular we propose that the experimentally observed onset of morphological complexity arises from a transient passage through pearling instability while the associated flow is in the curve lengthening regime.
On Counting Perfect Matchings in General Graphs

Counting perfect matchings has played a central role in the theory of counting problems. The permanent, corresponding to bipartite graphs, was shown to be #P-complete to compute exactly by Valiant (1979), and a fully polynomial randomized approximation scheme (FPRAS) was presented by Jerrum, Sinclair, and Vigoda (2004) using a Markov chain Monte Carlo (MCMC) approach. However, it has remained an open question whether there exists an FPRAS for counting perfect matchings in general graphs. In fact, it was unresolved whether the same Markov chain defined by JSV is rapidly mixing in general. In this paper, we show that it is not. We prove torpid mixing for any weighting scheme on hole patterns in the JSV chain. As a first step toward overcoming this obstacle, we introduce a new algorithm for counting matchings based on the Gallai−Edmonds decomposition of a graph, and give an FPRAS for counting matchings in graphs that are sufficiently close to bipartite. In particular, we obtain a fixed-parameter tractable algorithm for counting matchings in general graphs, parameterized by the greatest “order” of a factor-critical subgraph.
Constraints for proton structure fluctuations from exclusive scattering

Abstract We constrain the average density profile of the proton and the amount of event-by-event fluctuations by simultaneously calculating the coherent and incoherent exclusive diffractive vector meson production cross section in deep inelastic scattering. Working within the Color Glass Condensate picture, we find that the gluonic density of the proton must have large geometric fluctuations in order to describe the experimentally measured large incoherent cross section.
The Price of Anarchy in Transportation Networks: Data-Driven Evaluation and Reduction Strategies

Among the many functions a smart city must support, transportation dominates in terms of resource consumption, strain on the environment, and frustration of its citizens. We study transportation networks under two different routing policies, the commonly assumed selfish user-centric routing policy and a socially optimal system-centric one. We consider a performance metric of efficiency–the Price of Anarchy (PoA)–defined as the ratio of the total travel latency cost under selfish routing over the corresponding quantity under socially optimal routing. We develop a data-driven approach to estimate the PoA, which we subsequently use to conduct a case study using extensive actual traffic data from the Eastern Massachusetts road network. To estimate the PoA, our approach learns from data a complete model of the transportation network, including origin-destination demand and user preferences. We leverage this model to propose possible strategies to reduce the PoA and increase efficiency.
An asymptotic formula for the zeros of the deformed exponential function

Abstract We study the asymptotic representation for the zeros of the deformed exponential function ∑ n = 0 ∞ 1 n ! q n ( n − 1 ) / 2 x n , q ∈ ( 0 , 1 ) . Indeed, we obtain an asymptotic formula for these zeros: x n = − n q 1 − n ( 1 + g ( q ) n − 2 + o ( n − 2 ) ) , n ≥ 1 , where g ( q ) = ∑ k = 1 ∞ σ ( k ) q k is the generating function of the sum-of-divisors function σ ( k ) . This improves earlier results by Langley [3] and Liu [4] . The proof of this formula is reduced to estimating the sum of an alternating series, where the Jacobi's triple product identity plays a key role.
Khovanov homology, open books, and tight contact structures

Abstract We define the reduced Khovanov homology of an open book ( S , ϕ ) , and identify a distinguished “contact element” in this group which may be used to establish the tightness or non-fillability of contact structures compatible with ( S , ϕ ) . Our construction generalizes the relationship between the reduced Khovanov homology of a link and the Heegaard Floer homology of its branched double cover. As an application, we give combinatorial proofs of tightness for several contact structures which are not Stein-fillable. Lastly, we investigate a comultiplication structure on the reduced Khovanov homology of an open book which parallels the comultiplication on Heegaard Floer homology defined in Baldwin (2008) [4] .