cssi/SciSciGPT-SciSciNet huggingface dataset:
Cross Subspace Alignment and the Asymptotic Capacity of $X$ -Secure $T$ -Private Information Retrieval

$X$ -secure and $T$ -private information retrieval (XSTPIR) is a form of private information retrieval where data security is guaranteed against collusion among up to $X$ servers and the user’s privacy is guaranteed against collusion among up to $T$ servers. The capacity of XSTPIR is characterized for an arbitrary number of servers $N$ and arbitrary security and privacy thresholds $X$ and $T$ , in the limit as the number of messages $K\rightarrow \infty $ . Capacity is also characterized for any number of messages if either $N=3, X=T=1$ or if $N\leq X+T$ . Insights are drawn from these results, about aligning versus decoding noise, dependence of PIR rate on field size, and robustness to symmetric security constraints. In particular, the idea of cross subspace alignment, i.e., introducing a subspace dependence between Reed–Solomon code parameters, emerges as the optimal way to align undesired terms while keeping desired terms resolvable.
New lower bounds for the number of pseudoline arrangements

Arrangements of lines and pseudolines are fundamental objects in discrete and computational geometry. They also appear in other areas of computer science, such as the study of sorting networks. Let $B_n$ be the number of nonisomorphic arrangements of $n$ pseudolines and let $b_n=\log_2{B_n}$. The problem of estimating $B_n$ was posed by Knuth in 1992. Knuth conjectured that $b_n \leq {n \choose 2} + o(n^2)$ and also derived the first upper and lower bounds: $b_n \leq 0.7924 (n^2 +n)$ and $b_n \geq n^2/6 -O(n)$. The upper bound underwent several improvements, $b_n \leq 0.6988\, n^2$ (Felsner, 1997), and $b_n \leq 0.6571\, n^2$ (Felsner and Valtr, 2011), for large $n$. Here we show that $b_n \geq cn^2 -O(n \log{n})$ for some constant $c>0.2083$. In particular, $b_n \geq 0.2083\, n^2$ for large $n$. This improves the previous best lower bound, $b_n \geq 0.1887\, n^2$, due to Felsner and Valtr (2011). Our arguments are elementary and geometric in nature. Further, our constructions are likely to spur new developments and improved lower bounds for related problems, such as in topological graph drawings.
Enhanced voltage generation through electrolyte flow on liquid-filled surfaces.

The generation of electrical voltage through the flow of an electrolyte over a charged surface may be used for energy transduction. Here, we show that enhanced electrical potential differences (i.e., streaming potential) may be obtained through the flow of salt water on liquid-filled surfaces that are infiltrated with a lower dielectric constant liquid, such as oil, to harness electrolyte slip and associated surface charge. A record-high figure of merit, in terms of the voltage generated per unit applied pressure, of 0.043 mV Pa-1 is obtained through the use of the liquid-filled surfaces. In comparison with air-filled surfaces, the figure of merit associated with the liquid-filled surface increases by a factor of 1.4. These results lay the basis for innovative surface charge engineering methodology for the study of electrokinetic phenomena at the microscale, with possible application in new electrical power sources.
Effective Cloud Detection and Segmentation Using a Gradient-Based Algorithm for Satellite Imagery: Application to Improve PERSIANN-CCS

AbstractThe effective identification of clouds and monitoring of their evolution are important toward more accurate quantitative precipitation estimation and forecast. In this study, a new gradient...
Assessment of Current Epidemiology and Risk Factors Surrounding Brachial Plexus Birth Palsy

Purpose Brachial plexus birth palsy (BPBP) is common; however, the current incidence is unknown and more than 50% of infants with BPBP have no known risk factors. The purpose of this study was to determine the current incidence of BPBP, assess known risk factors, and evaluate hypotonia as a new risk factor, as well as estimate the length of stay (LOS) and direct costs of children with an associated BPBP injury. Methods Data from the 1997 to 2012 Kids’ Inpatient Database data sets were evaluated to identify patients with a BPBP injury and various risk factors. Evaluation of LOS data and direct costs was also performed. Multivariable logistic regression analysis was utilized to assess the association of BPBP with its known and previously undescribed risk factors. Results The incidence of BPBP has steadily decreased from 1997 to 2012, with an incidence of 0.9 ± 0.01 per 1,000 live births recorded in 2012. Shoulder dystocia is the number 1 risk factor for the development of a BPBP injury. Hypotonia is a newly recognized risk factor for the development of BPBP. Fifty-five percent of infants with BPBP have no known perinatal risk factors. The initial hospital LOS is approximately 20% longer for children with a BPBP injury and the hospital stay direct costs are approximately 40% higher. Conclusions The incidence of BPBP is decreasing over time. Shoulder dystocia continues to be the most common risk factor for sustaining a BPBP injury. Children with a BPBP injury have longer LOSs and hospital direct costs compared with children without a BPBP injury. Type of study/level of evidence Prognostic II.
Criminal Quarantine and the Burden of Proof

In the recent literature a number of free will skeptics, skeptics who believe (as I do) that punishment is justified only if deserved, have argued for these two points: first, that the free will realist who would justify punishment has the burden of establishing to a high level of certainty - perhaps beyond a reasonable doubt, but certainly at least by clear and convincing evidence - that any person to be punished acted freely in breaking the law; and, second, that that level of evidence is simply not there. In this paper I make two parallel points against a quarantine theory of criminal justice. First, the free will skeptic who would justify universal criminal quarantine is also faced with a burden of proof, the burden to establish to a similarly high level that no human being ever acts freely. Second, there is not sufficient evidence for that conclusion either. I believe that the quandary that this creates for criminal justice can be resolved by distinguishing the methods associated with a particular approach from the approach itself: if our choice is between the methods of punishment and the methods of quarantine, the methods that constitute punishment are, I would argue, morally preferable to those that constitute quarantine.
Rejig: A Scalable Online Algorithm for Cache Server Configuration Changes

A cache server configuration describes an assignment of data fragments to cache manager instances (CMIs). A load balancer may change this assignment by migrating fragments from one CMI to another. Similarly, an auto-scaling component may change the assignment by either inserting or removing CMIs in response to load fluctuations. These changes may generate stale cache entries. Rejig is a scalable online algorithm that manages configuration changes while providing read-after-write consistency. It is novel for several reasons. First, it allows for a subset of its clients and CMIs to use different configurations. Second, its client components propagate configuration changes to one another on demand and by using CMIs. This enables Rejig to scale and support diverse application classes including trusted mobile clients accessing the caching layer. When clients have intermittent network connectivity, Rejig detects if their cached configurations may result in stale data and updates them to the latest with no performance impact on either the CMIs or other clients. Rejig’s overhead is in the form of 4 extra bytes of memory per cache entry and 4 extra bytes of the network bandwidth per request from a client to a CMI.
Distributed Wildfire Surveillance with Autonomous Aircraft Using Deep Reinforcement Learning

Teams of autonomous unmanned aircraft can be used to monitor wildfires, enabling firefighters to make informed decisions. However, controlling multiple autonomous fixed-wing aircraft to maximize fo...
Cicero: Multi-Turn, Contextual Argumentation for Accurate Crowdsourcing

Traditional approaches for ensuring high quality crowdwork have failed to achieve high-accuracy on difficult problems. Aggregating redundant answers often fails on the hardest problems when the majority is confused. Argumentation has been shown to be effective in mitigating these drawbacks. However, existing argumentation systems only support limited interactions and show workers general justifications, not context-specific arguments targeted to their reasoning. This paper presents Cicero, a new workflow that improves crowd accuracy on difficult tasks by engaging workers in multi-turn, contextual discussions through real-time, synchronous argumentation. Our experiments show that compared to previous argumentation systems which only improve the average individual worker accuracy by 6.8 percentage points on the Relation Extraction domain, our workflow achieves 16.7 percentage point improvement. Furthermore, previous argumentation approaches don't apply to tasks with many possible answers; in contrast, Cicero works well in these cases, raising accuracy from 66.7% to 98.8% on the Codenames domain.
History of Discrimination and Clustering

The history of discrimination and clustering is primarily defined by the development of two quantitative procedures, discriminant analysis, and cluster analysis. Although they have different goals, the procedures address complimentary problems in classification, and thus are frequently used together. Keywords: classification; discriminant analysis; cluster analysis; numerical taxonomy
Proceedings of the 2010 Workshop on Analysis and Programming Languages for Web Applications and Cloud Applications

It is our pleasure to welcome you to the 2010 Workshop on the Analysis and Programming Languages for Web Applications and Cloud Applications (APLWACA, pronounced "apple-whacka"). APLWACA is a new forum that aims to bring together programming language researchers working in the area of web and cloud applications. The deployment and use of web and cloud applications has increased dramatically in recent years; we felt that this important and growing area is under-examined by programming language researchers. This workshop seeks to publicize and popularize web and cloud application research in the programming language community. The focus of the workshop is primarily on reliability, security, and performance of web and cloud applications. The call for papers encouraged proposals of new, speculative ideas, evaluations of new or known techniques in practical settings;,and discussions of important existing and emerging problems. The call for papers attracted 9 submissions: 3 full-length papers, and 6 short papers. Each submission received at least three reviews. All reviews were made available to all program committee members, and the !nal decision on which papers to accept was made during an on-line program committee meeting. Two long papers and four short ones will appear in the proceedings and be presented at the Workshop.
Neural organization of speech production: A lesion-based study of error patterns in connected speech.

Abstract While numerous studies have explored single-word naming, few have evaluated the behavioral and neural correlates of more naturalistic language, like connected speech, which we produce every day. Here, in a retrospective analysis of 120 participants at least six months following left hemisphere stroke, we evaluated the distribution of word errors (paraphasias) and associated brain damage during connected speech (picture description) and object naming. While paraphasias in connected speech and naming shared underlying neural substrates, analysis of the distribution of paraphasias suggested that lexical-semantic load is likely reduced during connected speech. Using voxelwise lesion-symptom mapping (VLSM), we demonstrated that verbal (real word: semantically related and unrelated) and sound (phonemic and neologistic) paraphasias during both connected speech and naming loaded onto the left hemisphere ventral and dorsal streams of language, respectively. Furthermore, for the first time using both connected speech and naming data, we localized semantically related paraphasias to more anterior left hemisphere temporal cortex and unrelated paraphasias to more posterior left temporal and temporoparietal cortex. The connected speech results, in particular, highlight a gradient of specificity as one translates visual recognition from left temporo-occipital cortex to posterior and subsequently anterior temporal cortex. The robustness of VLSM results for sound paraphasias derived during connected speech was notable, in that analyses performed on sound paraphasias from the connected speech task, and not the naming task, demonstrated significant results following removal of lesion volume variance and related apraxia of speech variance. Therefore, connected speech may be a particularly sensitive task on which to evaluate further lexical-phonological processing in the brain. The results presented here demonstrate the related, though different, distribution of paraphasias during connected speech, confirm that paraphasias arising in connected speech and single-word naming likely share neural origins, and endorse the need for continued evaluation of the neural substrates of connected speech processes.
Application of adaptive-network-based fuzzy inference systems to the parameter optimization of a biochemical rule-based model.

Abstract In this study, the binding of allergens to antibody-receptor complexes was investigated. This process is important in understanding the allergic response. A BioNetGen model that simulates this process, combined with a novel method for encoding steric effects via the optimization of the cutoff distance and the rule binding rate, was previously developed. These parameters were optimized by fitting the model output to the output of a 3D simulation that explicitly represents molecular geometry. In this work, the parameters for the BioNetGen model were optimized using an adaptive-network-based fuzzy inference system in order to predict the rule rate and cutoff distance given a residual-sum-of-squares value or a probability distribution. The fuzzy systems were constructed using fuzzy c-means clustering with existing data from BioNetGen model parameter scans used as the training data. Fuzzy systems with various input data and number of clusters were created and tested. Their performance was analyzed with regard to the effective optimization of the rule-based model. The study found that the fuzzy system that uses a residual-sum-of-squares value as the input value performs acceptably well. However, the performance of the fuzzy systems that use probabilities as their input values performed inconsistently in the tests and need further development. This methodology could potentially be modified for use in fitting other biological models.
Improved Generalizability Through Improved Recruitment: Lessons Learned From a Large-Scale Randomized Trial:

Randomized control trials (RCTs) have long been considered the “gold standard” for evaluating the impacts of interventions. However, in most education RCTs, the sample of schools included is recrui...
Interpolation-Prediction Networks for Irregularly Sampled Time Series

In this paper, we present a new deep learning architecture for addressing the problem of supervised learning with sparse and irregularly sampled multivariate time series. The architecture is based on the use of a semi-parametric interpolation network followed by the application of a prediction network. The interpolation network allows for information to be shared across multiple dimensions of a multivariate time series during the interpolation stage, while any standard deep learning model can be used for the prediction network. This work is motivated by the analysis of physiological time series data in electronic health records, which are sparse, irregularly sampled, and multivariate. We investigate the performance of this architecture on both classification and regression tasks, showing that our approach outperforms a range of baseline and recently proposed models.
Trade Intensity and Liquidity

This analysis investigates how liquidity is affected by periods of high trade intensity. Using an orderbook constructed directly from CME FIX/FAST messages and timestamped to the millisecond, we te...
Predictive value of genetic testing for inherited retinal diseases in patients with suspected atypical autoimmune retinopathy

Abstract Purpose The clinical features of autoimmune retinopathy (AIR) can resemble and be difficult to differentiate from inherited retinal degenerations (IRDs). Misdiagnosis of an IRD as AIR causes unnecessary treatment with immunosuppressive agents. The purpose of this study is to calculate the predictive value of genetic testing for IRDs in patients with suspected AIR and provide clinical examples where genetic testing has been useful. Methods We identified patients seen at MEEI between April 2013 and January 2017 for whom the differentiation of AIR vs. IRDs was difficult based on clinical assessment alone. All patients had some atypical features for AIR, but tested positive for anti-retinal antibodies. Within this group, we identified six patients who had genetic testing for IRDs with the Genetic Eye Disease panel for retinal genes (GEDi-R). We calculated the positive predictive value (PPV) and negative predictive value (NPV) of genetic testing in a population with approximately equal numbers of IRD and AIR patients. Results Six patients had clinical features that made distinguishing between IRDs and AIR on a clinical basis difficult and were sent for genetic testing: four women and two men with a mean age of 59.5 years. In two of these six patients, genetic diagnoses were made based upon the identification of known pathogenic variants in the common IRD genes USH2A and RHO. Two patients had variants of unknown significance within genes associated with IRDs, and the other two had no relevant genetic findings. Given the 60% sensitivity and 3% false positive rate for GEDi-R testing and assuming a 50% pre-test probability of having an IRD, the PPV for GEDi-R for detecting IRD is 95.2% and the NPV is 70.8%. Conclusions and Importance In patients for whom the differential diagnosis of AIR and IRDs is unclear based on clinical information, genetic testing can be a valuable tool when it identifies an IRD, sparing the patient unnecessary immunosuppressive treatment. However, the test has a low NPV so a negative genetic testing result does not confidently exclude IRD as the true diagnosis.
Agency Conflicts, Bank Capital Regulation, and Marking-to-Market

ABSTRACT We show how shareholder-debtholder agency conflicts interact with strategic reporting under asymmetric information to influence bank regulation. Relative to a benchmark unregulated economy...
Noninteractive Locally Private Learning of Linear Models via Polynomial Approximations.

Minimizing a convex risk function is the main step in many basic learning algorithms. We study protocols for convex optimization which provably leak very little about the individual data points that constitute the loss function. Specifically, we consider differentially private algorithms that operate in the local model, where each data record is stored on a separate user device and randomization is performed locally by those devices. We give new protocols for \emph{noninteractive} LDP convex optimization---i.e., protocols that require only a single randomized report from each user to an untrusted aggregator. We study our algorithms' performance with respect to expected loss---either over the data set at hand (empirical risk) or a larger population from which our data set is assumed to be drawn. Our error bounds depend on the form of individuals' contribution to the expected loss. For the case of \emph{generalized linear losses} (such as hinge and logistic losses), we give an LDP algorithm whose sample complexity is only linear in the dimensionality $p$ and quasipolynomial in other terms (the privacy parameters $\epsilon$ and $\delta$, and the desired excess risk $\alpha$). This is the first algorithm for nonsmooth losses with sub-exponential dependence on $p$. For the Euclidean median problem, where the loss is given by the Euclidean distance to a given data point, we give a protocol whose sample complexity grows quasipolynomially in $p$. This is the first protocol with sub-exponential dependence on $p$ for a loss that is not a generalized linear loss . Our result for the hinge loss is based on a technique, dubbed polynomial of inner product approximation, which may be applicable to other problems. Our results for generalized linear losses and the Euclidean median are based on new reductions to the case of hinge loss.
GreenLoading: Using the citizens band radio for energy-efficient offloading of shared interests

Abstract Cellular networks are susceptible to being severely capacity-constrained during peak traffic hours or at special events such as sports and concerts. Many other applications are emerging for LTE and 5G networks that inject machine-to-machine (M2M) communications for Internet of Things (IoT) devices that sense the environment and react to diurnal patterns observed. Both for users and devices, the high congestion levels frequently lead to numerous retransmissions and severe battery depletion. However, there are frequently social cues that could be gleaned from interactions from websites and social networks of shared interest to a particular region at a particular time. Cellular network operators have sought to address these high levels of fluctuations and traffic burstiness via the use of offloading to unlicensed bands, which may be instructed by these social cues. In this paper, we leverage shared interest information in a given area to conserve power via the use of offloading to the emerging Citizens Broadband Radio Service (CBRS). Our GreenLoading framework enables hierarchical data delivery to significantly reduce power consumption and user fairness variation and includes a Broker Priority Assignment (BPA) algorithm to select data brokers for users. With the use of in-field measurements and web-based Google data across four diverse U.S. cities, we show an order of magnitude power savings via GreenLoading over a 24-hour period, on average, and power savings up to 97% at peak traffic times. Finally, we consider the role that a relaxation of wait times can play in the power efficiency of a GreenLoading network.
Real-Time TDDFT Investigation of Optical Absorption in Gold Nanowires

Using a real-time TDDFT method, a set of linear gold nanowires Aum (m = 4, 6, 8, 10, 12) are investigated to understand the plasmon-like behavior that results from resonant excitation of a superpos...
Determining the Predictive Power of Vitamin D Levels in Iron Deficiency Anemia

Background:Iron deficiency anemia is one of the most common hypochromic microcytic anemias and nutritional disorders in today’s world. Vitamin D is an important steroid hormone for the metabolism of serum calcium and phosphorus and plays a major role in the function of various body systems. Evidence suggests that vitamin D deficiency is associated with iron deficiency anemia. We aimed to compare the serum level of vitamin D between children with iron deficiency anemia and healthy ones. Methods: This case-control study was conducted on 60 patients with iron deficiency anemia and 60 healthy ones who did not suffer from iron deficiency anemia. Patients participated in the study voluntarily. Vitamin D levels were measured using HPLC and ferritin by RIA method. To estimate the predictive value of vitamin D levels in iron deficiency anemia, ROC curve analysis was used. Results: In this study, 120 children aged 6-144 months with mean age of 30.2±31.4 months were analyzed; 49.2% of them were boys and 50.8% were girls. Vitamin D levels varied from 4.8 to 63.2 ng/ml with a mean of 23.87±12.57 ng/ml in all patients (19.25±9.15 ng/ml in the case group and 28.48±13.84 ng/ml in the control group (P<0.001). In other words, patients with a vitamin D level <23.6 ng/ml should be investigated for iron deficiency anemia, and sufficient vitamin D had a protective effect on iron deficiency anemia and each unit increase in vitamin D decreased the chance of iron deficiency anemia by 7.8%. Conclusion: The prevalence of simultaneous iron deficiency anemia and vitamin D deficiency is very high in children and there is a significant relationship between serum levels of 25(OH)D and hemoglobin.
High temperature behavior of alternant and nonalternant polycyclic aromatic hydrocarbons

Abstract Three different flash vacuum pyrolysis (FVP) set-ups were employed for the study of the thermal behavior of alternant and nonalternant polyclic aromatic hydrocarbons (PAH). The 1,2-switch of carbon atoms in the thermal automerizations of PAH, previously observed in benzene, pyrene and benz[ a ]anthracene, has been additionally observed for [1- 13 C]anthracene, [6- 13 C]benzo[ c ]phenanthrene and [1- 13 C]- and [4- 13 C]phenanthrenes at temperatures between 900 and 1100°C. Bay region PAH (chrysene, benz[ a ]anthracene, phenanthrene, picene, perylene, benzo[ ghi ]perylene, benzo[ e ]pyrene, and benz[ a,c ]-anthracene) were discovered to undergo an intriguing transformation when heated at 1100°C; the transformation is believed to be triggered by cyclodehydrogenation across the bay region. Thermal formation of five-membered rings was used to synthesize a series of new nonalternant hydrocarbons. When the thermal closure of a five-membered ring is energetically unfavorable, migration of an ethynyl group from one benzene ring to another along the edge of a PAH (e.g. anthracene) can take place.
A facile N-arylation of acetanilides with arynes

Abstract An efficient, mild and transition-metal-free method for the N -arylation of acetanilides, leading to a range of unsymmetrical diarylamine products is reported. Reactions of ortho -silylaryl triflates with acetanilides in the presence of tetrabutylammonium triphenyldifluorosilicate (TBAT) in toluene afforded the desired products in good to excellent yields. Regioselectivity was also observed when unsymmetrical aryne precursors were used.
Ruthenium-catalyzed tandem cross-metathesis/Wittig olefination: generation of conjugated dienoic esters from terminal olefins.

In the presence of ruthenium-based olefin metathesis catalysts and triphenylphosphine, α,β-unsaturated aldehydes can be olefinated with diazoacetates. This ruthenium-catalyzed transformation has been employed in tandem with olefin cross-metathesis to convert terminal olefins into 1,3-dienoic esters in a single operation.
Putting Mind Back into Nature: a Tribute to Henry P. Stapp

Henry P. Stapp has for 60 years been a leader—perhaps the leader—in exploring the role of mind/psyche/consciousness/experience in the ontology of quantum mechanics. Henry’s contention is that the very structure of quantum mechanics implies a central and irreducible role for mind: an experiential aspect of nature distinct from that of the physical matter and energy described by the dynamical equations of physics. The task then becomes to generate trans-disciplinary interest in exploring this thesis, and in particular to seek connections with neuroscience and with empirical psychology.
3,3-Dialkyl- and 3-Alkyl-3-Benzyl-Substituted 2-Pyrrolidinones: A New Class of Anticonvulsant Agents

A series of 3,3-dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones (lactams) have been prepared and evaluated for their anticonvulsant activities. In the pentylenetetrazole mouse seizure model, 3,3-diethyl lactam 7c and 3-benzyl-3-ethyl lactam 7j are the most effective anticonvulsants (ED50 = 46 and 42 mg/kg, respectively) and have protective index (PI = TD50/ED50) values of 5.65 and 3.00, respectively. These protective index values compare favorably to those of the clinically used antiepileptic drugs ethosuximide (ED50 = 161 mg/kg), phenobarbital (ED50 = 22 mg/kg), and valproic acid (ED50 = 133 mg/kg), which have PI values of 2.35, 4.00, and 2.12, respectively. The benzyl compounds [3-substituents are Bn, H (7h); Bn, Me (7i); and Bn, Et (7j)] are also very effective anticonvulsants against seizures induced by maximal electroshock (ED50 = 41, 55, and 74 mg/kg, respectively) and have PI values of 3.51, 3.04, and 1.70, respectively. The corresponding PI values for phenobarbital and valproic acid are...
Fractal Intersections and Products via Algorithmic Dimension.

Algorithmic fractal dimensions quantify the algorithmic information density of individual points and may be defined in terms of Kolmogorov complexity. This work uses these dimensions to bound the classical Hausdorff and packing dimensions of intersections and Cartesian products of fractals in Euclidean spaces. This approach shows that two prominent, fundamental results about the dimension of Borel or analytic sets also hold for arbitrary sets.
Rearrangement and double fluorination in the deiodinative fluorination of neopentyl iodide with xenon difluoride

Abstract Alkyl iodides give products from the neopentyl rearrangement on reaction with xenon difluoride. Neopentyl iodide performs a double rearrangement and yields a gem-difluoro product, 2,2-difluoro-3-methylbutane. Studies of the mechanism show that an alkene intermediate is involved in the double rearrangement process. Alkenes can be substituted as substrates in reaction with xenon difluoride–iodine to give gem-difluoro products. 13C Labeling verifies the skeletal rearrangement process.
From peptides to non-peptide peptidomimetics: design and synthesis of new piperidine inhibitors of aspartic peptidases.

The 3-alkoxy-4-arylpiperidine inhibitors of aspartic peptidases are shown to be a new type of non-peptide peptidomimetic inhibitor. These piperidines can be designed from peptide-derived inhibitors by use of a structure-generating program but only after the enzyme active site conformation has been modified in a mechanistically related fashion. New enantioselective syntheses of 3-alkoxy-4-arylpiperidine analogues are described.
Biomolecular Simulations under Realistic Macroscopic Salt Conditions

Biomolecular simulations are typically performed in an aqueous environment where the number of ions remains fixed for the duration of the simulation, generally with either a minimally neutralizing ion environment or a number of salt pairs intended to match the macroscopic salt concentration. In contrast, real biomolecules experience local ion environments where the salt concentration is dynamic and may differ from bulk. The degree of salt concentration variability and average deviation from the macroscopic concentration remains, as yet, unknown. Here, we describe the theory and implementation of a Monte Carlo osmostat that can be added to explicit solvent molecular dynamics or Monte Carlo simulations to sample from a semigrand canonical ensemble in which the number of salt pairs fluctuates dynamically during the simulation. The osmostat reproduces the correct equilibrium statistics for a simulation volume that can exchange ions with a large reservoir at a defined macroscopic salt concentration. To achieve...
Synthesis of “α-Homogalactostatin” and of its 1,N-anhydro derivative

Abstract α-Homogalactostatin 2 was prepared in 10 steps from 2,3,4,6-tetra-O-benzyl- d -galactose by way of a Wittig chain extension and a mercuricyclization. The synthesis of 2 was assisted by the unexpected participation of the nitrogen protecting group (benzyl carbamate) during iododemercuration. Intermediate 10 was converted in 2 steps into the 1,N-anhydro derivative of 2, compound 3, a potential inactivator of galactosidases.
Syntheses and reactions of optically active α-aminoallenylstannanes and α-aminopropargylboranes

An efficient synthesis of alpha-aminoallenylstannane from propargyloxazolidinone has been developed. It undergoes reaction with aldehydes to give homopropargylic alcohols with high syn selectivity. Epoxides undergo a similar reaction preceded by rearrangement to the aldehyde. These alcohols were used in the synthesis of beta-amino acids, azasugars, and deoxyammohexoses. Imines underwent reaction with this stannane to give 1,2-diamines. The related propargylborane reacts with aldehydes to produce allenyl carbinols. The Co-2(CO)(6) complexes of propargyloxazolidinones were developed as an alpha-aminopropargyl cation equivalent.
Synthesis of β-sulfanyl ketones via a tandem rearrangement-conjugate addition reaction catalyzed by a Re(V)-oxo complex

A method for synthesizing β-sulfanyl ketones via a tandem rearrangement and conjugate addition reaction has been developed. This methodology provides access to a range of β-sulfanyl ketones through the rearrangement of propargyl alcohols to the corresponding enones followed by the conjugate addition of unactivated thiols. The one-pot, tandem transformation is catalyzed by ReOCl3(OPPh3)(S(CH3)2) affording aryl and alkyl β-sulfanyl ketones in good to excellent yield.
Calcium Carbodiimide Compounds Revisited – Syntheses, Single Crystal Structure Determination and Vibrational Spectra of Ca11N6[CN2]2, Ca4N2[CN2] and Ca[CN2]

Single crystals of Ca11N6[CN2]2 (dark red needles, tetragonal, P42/mnm (no. 136), a = 1456.22(5), and c = 361.86(2) pm, Z = 2), Ca4N2[CN2] (transparent yellow needles, orthorhombic, Pnma (no. 62), a = 1146.51(11), b = 358.33(4), and c = 1385.77(13) pm, Z = 4) and Ca[CN2] (transparent, colorless, triangular plates, rhombohedral, R3m (no. 166), a = 369.00(3), and c = 1477.5(3) pm, Z = 3) were obtained by the reaction of Na2[CN2], CaCl2 and Ca3N2 (if demanded by stoichiometry) in arc-welded Ta ampoules at temperatures between 1200 – 1400 K. Their crystal structures were re-determined by means of single crystal X-ray structure analyses. Additionally, the Raman spectra were recorded on these same single crystals, whereas the IR spectra were obtained with the KBr pellet technique. The title compounds exhibit characteristic features for carbodiimide units with D∞h symmetry (d(C–N) = 121.7 – 123.8 pm and (N–C–N) = 180◦). The vibrational frequencies of these units are in the expected range (Ca11N6[CN2]2: νs = 1230, νs = 2008; δ = 673/645/624 cm−1; Ca4N2[CN2]: νs = 1230, νs = 1986; δ = 672/647 cm−1; Ca[CN2]: νs = 1274, νs = 2031, δ = 668 cm−1). The structural results are more precise than the previously reported data, and with the newly attained Raman spectrum of Ca11N6[CN2]2 we correct data reported earlier.
Custom synthesis of substituted butenolides, dihydropyranones, and α-E-alkylidenelactones via alkenylalumination

Abstract Alkenylalumination of aldehydes with [α-(ethoxycarbonyl)-β-(t-butyldimethylsilyloxyalkyl)alkenyl]diisobutylaluminum provides the corresponding α-Z-alkylidene-β′-hydroxy esters, which upon protection and treatment with trifluoroacetic acid lactonizes to furnish α-acetoxyalkyl butenolides (n = 1) and dihydropyranones (n = 2) in 40% overall yield. Conjugate addition to these lactenones and concurrent acetate elimination constitute a general and stereospecific synthesis of the corresponding α-E-alkylidene lactones.
Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing

Quantitative analysis of next-generation sequencing (NGS) data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are identified as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. Misidentification of these molecules as PCR duplicates can introduce unforeseen biases during analyses. Here, we developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed, single-index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters) enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of PCR duplicates results in improved accuracy of both allele frequency (AF) estimation in heterogeneous populations using DNA sequencing and gene expression quantification using RNA-Seq.
Measuring the reproducibility and quality of Hi-C data

Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established measures, such as the ratio of intra- to interchromosomal interactions, and novel ones, such as QuASAR-QC, to identify low-quality experiments. In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available at http://github.com/kundajelab/3DChromatin_ReplicateQC to facilitate adoption in the community.
A p‐benzyne to m‐benzyne conversion through a 1,2‐shift of a phenyl group. Completion of the benzyne cascade

Pyrolysis of 1,6-diphenylhexa-1,5-diyne-cis-3-ene at 800–1000°C leads to a mixture of 1- and 2-phenylbiphenylene, along with triphenylene. Formation of the two biphenylenes is taken as strong evidence of the rearrangement of a p-benzyne into a m-benzyne through a shift of one of the phenyl groups. Copyright © 2004 John Wiley & Sons, Ltd.
PHOTODISSOCIATION OF BRONO2 AND N2O5 : QUANTUM YIELDS FOR NO3 PRODUCTION AT 248, 308, AND 352.5 NM

Quantum yields for NO3 production in the photolysis of BrONO2 and N2O5 were measured at 248, 308, and 352.5 nm. The measured values for BrONO2 were found to be independent of pressure over the range 150−600 Torr and bath gas (N2 or O2) and are 0.28 ± 0.09, 1.01 ± 0.35, and 0.92 ± 0.43 at 248, 308, and 352.5 nm, respectively. Quantum yields of Br and BrO in the photolysis of BrONO2 were also estimated. The measured values for NO3 production in the photolysis of N2O5 were 0.64 ± 0.10, 0.96 ± 0.15, and 1.03 ± 0.15 at 248, 308, and 352.5 nm, respectively. Rate coefficients for the reactions Br + BrONO2 → Br2 + NO3 (18) and Cl + BrONO2 → ClBr + NO3 (19) were measured at 298 K to be k18 = (6.7 ± 0.7) × 10-11 cm3 molecule-1 s-1 and k19 = (1.27 ± 0.16) × 10-10 cm3 molecule-1 s-1. The NO3 product yields for reactions 18 and 19 were measured to be 0.88 ± 0.08 and 1.04 ± 0.24, respectively. The absorption cross sections for N2O5 between 208 and 398 nm are also reported. All quoted uncertainties are 2σ and include es...
Synthesis and in vitro antitumor activity of substituted anthracene-1,4-diones

Abstract Based on a rational approach, 6-substituted 1,4-anthracenediones were synthesized and found to exhibit potent cytotoxic activity against murine and human leukemic cells. The synthetic sequence includes a double Friedel–Crafts reaction, reductive quinone formation, and selective bromination of the alkyl side chain. A key intermediate, 6-bromomethyl-1,4-anthracenedione ( 10 ), was synthesized and converted to various active antitumor agents, including a water-soluble phosphate ester pro-drug. The interconversion reactions include displacement of the bromide with various nucleophiles and basic hydrolysis to the alcohol and subsequent oxidation to provide the aldehyde. Based on their ability to decrease L1210 and HL-60 tumor cell viability, 1,4-dihydroxyanthraquinones are inactive but 1,4-anthracenediones have interesting antitumor activity, which may be abolished by modification of the A-ring and improved by substitution of the C-ring. The cytostatic and cytotoxic activity of the representative compound 10 was verified at the National Cancer Institute in studies on the 60-human tumor cell line panel in the in vitro antitumor screening. A wide spectrum of tumor cells are sensitive to 10 inhibition, and concentrations required to inhibit tumor cell growth by 50% (GI 50 ) at 48 h are 10 may be different from those of daunomycin.
Schlafen 11 Restricts Flavivirus Replication.

ABSTRACT Schlafen 11 (Slfn11) is an interferon-stimulated gene that controls the synthesis of proteins by regulating tRNA abundance. Likely through this mechanism, Slfn11 has previously been shown to impair human immunodeficiency virus type 1 (HIV-1) infection and the expression of codon-biased open reading frames. Because replication of positive-sense single-stranded RNA [(+)ssRNA] viruses requires the immediate translation of the incoming viral genome, whereas negative-sense single-stranded RNA [(−)ssRNA] viruses carry at infection an RNA replicase that makes multiple translation-competent copies of the incoming viral genome, we reasoned that (+)ssRNA viruses will be more sensitive to the effect of Slfn11 on protein synthesis than (−)ssRNA viruses. To evaluate this hypothesis, we tested the effects of Slfn11 on the replication of a panel of ssRNA viruses in the human glioblastoma cell line A172, which naturally expresses Slfn11. Depletion of Slfn11 significantly increased the replication of (+)ssRNA viruses from the Flavivirus genus, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV), but had no significant effect on the replication of the (−)ssRNA viruses vesicular stomatitis virus (VSV) (Rhabdoviridae family) and Rift Valley fever virus (RVFV) (Phenuiviridae family). Quantification of the ratio of genome-containing viral particles to PFU indicated that Slfn11 impairs WNV infectivity. Intriguingly, Slfn11 prevented WNV-induced downregulation of a subset of tRNAs implicated in the translation of 11.8% of the viral polyprotein. Low-abundance tRNAs might promote optimal protein folding and enhance viral infectivity, as previously reported. In summary, this study demonstrates that Slfn11 restricts flavivirus replication by impairing viral infectivity. IMPORTANCE We provide evidence that the cellular protein Schlafen 11 (Slfn11) impairs replication of flaviviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV). However, replication of single-stranded negative RNA viruses was not affected. Specifically, Slfn11 decreases the infectivity of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrate that Slfn11 is not the limiting factor of this novel broad antiviral pathway.
Chlorofluorocarbene: first UV observation of a dihalocarbene in solution.

Chlorofluorocarbene (ClCF), generated by laser flash photolysis of chlorofluorodiazirine, absorbs at 368 nm in pentane. Absolute rate constants are reported for ClCF additions to several alkenes and pyridine. ClCF is less reactive toward alkenes than CCl2, and it does not react rapidly with oxygen. Pertinent computational studies are included.
Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.

Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .
Synthesis of 4-benzyl-3-phenylbutenolide natural products

Abstract The first total synthesis of eutypoid A and a new synthesis of racemic microperfuranone and gymnoascolide A have been achieved. The key steps in our synthetic strategy involve a Suzuki coupling reaction to install the C3 aryl ring and a Mannich-type reaction for the construction of the 4-benzylbutenolide core.
An Olefin Metathesis Route for the Preparation of (1→6)-Linked C-Disaccharide Glycals. A Convergent and Flexible Approach to C-Saccharide Synthesis

A convergent route to a variety of C-1-disaccharide glycals based on the olefin metathesis reaction of enol ethers and alkenes is described. The DCC-mediated coupling reaction of a variety of pentose enitols (1a-c) with a number of C-5- and C-6-monosaccharide carboxylic acids (2a-e) gave the corresponding esters 3a-l in good yield. Methylenation of these compounds was followed by ring-closing metathesis, mediated by the Schrock molybdenum catalyst 8 in warm toluene, to provide the target C-disaccharide glycals 5a-l. The formed enol ether double bond in 5a was then transformed, via standard manipulations, into a variety of C-disaccharide derivatives 21-25.