cssi/SciSciGPT-SciSciNet huggingface dataset:
Microsatellite Instability (MSI) as an Independent Predictor of Pathologic Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer Database (NCDB) Analysis.

OBJECTIVE The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. BACKGROUND We utilized the National Cancer Database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. METHODS We analyzed 5086 patients between 2010 and 2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional-hazard ratios were used for survival. RESULTS All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared with 73% without it (<0.001). CONCLUSION Microsatellite instability was independently associated with a reduction in pCR for locally advanced rectal cancer after neoadjuvant chemoradiation in this NCDB-based analysis.
Building Dynamic Knowledge Graphs from Text using Machine Reading Comprehension.

We propose a neural machine-reading model that constructs dynamic knowledge graphs from procedural text. It builds these graphs recurrently for each step of the described procedure, and uses them to track the evolving states of participant entities. We harness and extend a recently proposed machine reading comprehension (MRC) model to query for entity states, since these states are generally communicated in spans of text and MRC models perform well in extracting entity-centric spans. The explicit, structured, and evolving knowledge graph representations that our model constructs can be used in downstream question answering tasks to improve machine comprehension of text, as we demonstrate empirically. On two comprehension tasks from the recently proposed PROPARA dataset (Dalvi et al., 2018), our model achieves state-of-the-art results. We further show that our model is competitive on the RECIPES dataset (Kiddon et al., 2015), suggesting it may be generally applicable. We present some evidence that the model’s knowledge graphs help it to impose commonsense constraints on its predictions.
A 0.3PJ/Bit 112GB/S PAM4 1+0.5D TX-DFE Precoder and 8-Tap FFE in 14NM CMOS

We present a digital implementation of a TX precoder/ equalizer that, similar to a Tomlinson-Harashima Precoder (THP), provides a decision feedback equalizer (DFE) function on the transmitter side. The TX-DFE avoids error propagation together with the complexity and power overhead of an RX-DFE. The I-tap precoder is implemented using a table-based digital FFE, which also shapes the channel pulse to a 1 +0.5D response and cancels pre-cursor inter-symbol interference (lSI). The combined precoder/8-tap FFE was implemented in 14nm FinFet CMOS, and was measured to operate at 112Gb/s consuming 0.3pJ/bit energy.
The Non-hardness of Approximating Circuit Size

The Minimum Circuit Size Problem (\(\mathsf {MCSP}\)) has been the focus of intense study recently; \(\mathsf {MCSP}\) is hard for \(\mathsf {SZK}\) under rather powerful reductions [4], and is provably not hard under “local” reductions computable in \({\mathsf {TIME}}(n^{0.49})\) [22]. The question of whether \(\mathsf {MCSP}\) is \(\mathsf {NP}\)-hard (or indeed, hard even for small subclasses of \(\mathsf {P}\)) under some of the more familiar notions of reducibility (such as many-one or Turing reductions computable in polynomial time or in \(\mathsf {AC}^0\)) is closely related to many of the longstanding open questions in complexity theory [7, 8, 16, 17, 18, 20, 22].
The Silliness of Magical Realism

Relative plausibility, even after countless explanatory articles, remains an underdeveloped model bereft of underlying theory. Multivalent logic, a fully developed and accepted system of logic, com...
Terahertz hyperspectral imaging with dual chip-scale combs

Hyperspectral imaging is a spectroscopic imaging technique that allows for the creation of images with pixels containing information from multiple spectral bands. At terahertz wavelengths, it has emerged as a prominent tool for a number of applications, ranging from nonionizing cancer diagnosis and pharmaceutical characterization to nondestructive artifact testing. Contemporary terahertz imaging systems typically rely on nonlinear optical downconversion of a fiber-based near-infrared femtosecond laser, requiring complex optical systems. Here, we demonstrate hyperspectral imaging with chip-scale frequency combs based on terahertz quantum cascade lasers. The dual combs are free-running and emit coherent terahertz radiation that covers a bandwidth of 220 GHz at 3.4 THz with ∼10 μW per line. The combination of the fast acquisition rate of dual-comb spectroscopy with the monolithic design, scalability, and chip-scale size of the combs is highly appealing for future imaging applications in biomedicine and the pharmaceutical industry.
Transplantation of Human Skin Microbiota in Models of Atopic Dermatitis

Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus . Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes, and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate if parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative (CGN) bacteria collected from human skin. CGN bacteria were collected from healthy controls and patients with AD. Impacts on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN bacteria taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus . Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.
An Allosteric Interaction Network Promotes Conformation State-Dependent Eviction of the Nas6 Assembly Chaperone from Nascent 26S Proteasomes.

Summary The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Chaperone eviction upon completion of proteasome assembly is necessary for normal proteasome function, but how they are released remains unresolved. Here, we demonstrate that the Nas6 assembly chaperone, homolog of the human oncogene gankyrin, is evicted from nascent proteasomes during completion of assembly via a conformation-specific allosteric interaction of the Rpn5 subunit with the proteasomal ATPase ring. Subsequent ATP binding by the ATPase subunit Rpt3 promotes conformational remodeling of the ATPase ring that evicts Nas6 from the nascent proteasome. Our study demonstrates how assembly-coupled allosteric signals promote chaperone eviction and provides a framework for understanding the eviction of other chaperones from this biomedically important molecular machine.
Measurement of internal dark current in a 17 GHz, high gradient accelerator structure

We report the measurement of the internal dark current in a 17 GHz, high gradient accelerator cavity and its comparison with theory. The cavities were fabricated from copper and had a sidewall that was either uncoated or coated with diamondlike carbon or TiN. The dark current was monitored by a downstream detector and by detectors behind two small slits made in the cavity sidewall. With an increasing gradient, the downstream current increased monotonically, as expected for field emission. The variation of the internal, side dark current was not monotonic but showed the onset of peaks at gradients near 45 and $65\text{ }\text{ }\mathrm{MV}/\mathrm{m}$. These were identified as the $N=2$ and $N=1$ single point multipactor resonances. The total internal dark current was estimated at $\ensuremath{\sim}15--30\text{ }\text{ }\mathrm{A}$. The magnitude of the internal dark current and its dependence on the gradient were in good agreement with simulations using the cst code as well as an in-house code. Processing to a higher gradient, $\ensuremath{\sim}90\text{ }\text{ }\mathrm{MV}/\mathrm{m}$, eliminated the $N=2$ mode, but the $N=1$ mode persisted. The coated sidewall cavities showed the same multipactor resonances as the uncoated structure. However, at the highest gradient achieved in testing, the coated structures showed a modest reduction in the internal dark current.
Disk Paxos

We present an algorithm, called Disk Paxos, for implementing a reliable distributed system with a network of processors and disks. Like the original Paxos algorithm, Disk Paxos maintains consistency in the presence of arbitrary non-Byzantine faults. Progress can be guaranteed as long as a majority of the disks are available, even if all processors but one have failed.
The Nucleic Acid Database

The Nucleic Acid Database was established in 1991 as a resource to assemble and distribute structural information about nucleic acids. Over the years, the NDB has developed generalized software for processing, archiving, querying and distributing structural data for nucleic acid-containing structures. The architecture and capabilities of the Nucleic Acid Database, as well as some of the research enabled by this resource, are presented in this article.
Scanning Electrochemical Microscopy

In this article, we introduce the principle of scanning electrochemical microscopy (SECM) and its applications as a powerful electrochemical method for material characterization. The principle of SECM is based on the use of a micrometer- or nanometer-sized ultramicroelectrode as the scanning chemical probe of electrons, ions, and molecules that are transferred across the interface between a target solid material and an electrolyte solution as well as air/liquid and liquid/liquid interfaces and membranes. In comparison to traditional electrochemical methods, SECM is much higher in spatial resolution and mass transport to find its advantages in the chemical imaging of a heterogeneously reactive material surface and the quantitative study of interfacial reaction dynamics. The unique capability of imaging an interfacial reactivity renders SECM complementary to other scanning probe microscopy techniques and also combinable with them to yield multidimensional images of the material surface. In this article, various operation modes of SECM are introduced and followed by examples of practical measurements based on imaging, approach curve, voltammetry, and amperometry. Present limits of the technique in both theory and experiment are briefly discussed. In addition, numerical and analytical approaches to data analysis as well as experimental protocols for tip fabrication and characterization are described. Keywords: scanning electrochemical microscopy (SECM); ultramicroelectrode (UME); chemical imaging; interface; heterogeneous electron transfer; electrode material; nanomaterial
Distribution-Free Methods for Longitudinal Data†

Many of the available methods for analyzing repeated measurements require distributional assumptions on either the joint distribution of a subject's repeated measurements or on the marginal distributions at each occasion. Although such methods are often adequate and appropriate, nonparametric approaches to the analysis of repeated measurements may also be indicated in certain situations. One approach is to use nonparametric summary statistics in order to reduce the vector of responses from each subject to a single measurement. Multivariate nonparametric approaches include generalizations of univariate distribution-free methods such as the Wilcoxon–Mann–Whitney and Kruskal–Wallis tests, randomization model methods based on the use of Cochran–-Mantel–Haenszel statistics, asymptotically distribution-free analogs of parametric procedures for normally distributed outcomes, distribution-free methods for incomplete repeated measurements based on U statistics, the rank transform method, and nonparametric regression methods such as kernel estimation, weighted local least squares estimation, and smoothing splines. Keywords: repeated measurements; nonparametric methods; randomization tests; Cochran–Mantel–Haenszel statistics; rank transformation
Privacy-Preserving Average Consensus via State Decomposition

Average consensus underpins key functionalities of distributed systems ranging from distributed information fusion, decision-making, distributed optimization, to load balancing and decentralized control. Existing distributed average consensus algorithms require each node to exchange and disclose state information to its neighbors, which is undesirable in cases where the state is private or contains sensitive information. In this paper, we propose a novel approach that avoids disclosing individual state information in average consensus by letting each node decompose its state into 2 substates. For each node, one of the two substates involves in computation and internode interactions as if it were the original state, while the other substate interacts only with the first substate of the same node, being completely invisible to other nodes. The initial values of the two substates are chosen randomly but with their mean fixed to the initial value of the original state, which is key to guarantee convergence to the desired consensus value. In direct contrast to differential-privacy based privacy-preserving average-consensus approaches, which enable privacy by compromising accuracy in the consensus value, the proposed approach can guarantee convergence to the exact desired value without any error. Not only is the proposed approach able to prevent the disclosure of a node's initial state to honest-but-curious neighbors, it can also provide protection against inference by external eavesdroppers able to wiretap communication links. Numerical simulations demonstrate the effectiveness of the approach and its advantages over state-of-the-art counterparts.
Towards Emergent Design: Analysis, Fitness and Heterogeneity of Agent Based Models Using Geometry of Behavioral Spaces Framework.

Detection and analysis of collective behavior in natural and artificial systems is a difficult task which is commonly delegated to a human observer. We present a statistical framework to automatically detect emergent, collective behavior of agents in agent based simulations which exhibit swarming and flocking behavior. Our tunable, transitional-, rotational-, and scale- invariant framework geometry of behavioral spaces identifies common behaviors among agents and translates these behaviors into a systems behavioral primitives, along with the agent transitions from one behavioral primitive to another. Finally, we use complex network analysis to detect collectives of agents that gravitate into a common cluster of behavioral primitives as the systems emergent behavior condenses or decays. We apply complex network theory to the analysis of collective behavior dynamics in the simulations of flocking and swarming to validate our analysis. Our framework does not use the knowledge of the parameter space that drive the models, and only relies on the temporal agent trajectories of exhibited behavior. The utility of detecting emergence from exhibited behavior makes this technique suitable as a fitness function for stochastic search algorithms, analyzing evolutionary dynamics of systems with collective behaviors, detecting structures in artificial chemistry experiments, or analyzing physical system such as bacterial formations.
Ribbon n-knots with isomorphic quandles

Let K,K′ be ribbon knottings of n-spheres or tori in Sn+2, n ≥ 2. We show that if the knot quandles of these knots are isomorphic, then the ribbon knottings are stably equivalent, in the sense of N...
Oral contraceptives provide protection against anterior cruciate ligament tears: a national database study of 165,748 female patients

ABSTRACTObjective: Anterior cruciate ligament (ACL) tears are more prevalent in females than males. One of the factors responsible for this may be the variation in levels of estrogen and progestero...
High-Nicotine Electronic Cigarette Products: Toxicity of JUUL Fluids and Aerosols Correlates Strongly with Nicotine and Some Flavor Chemical Concentrations.

Whereas JUUL electronic cigarettes (ECs) have captured the majority of the EC market, with a large fraction of their sales going to adolescents, little is known about their cytotoxicity and potential effects on health. The purpose of this study was to determine flavor chemical and nicotine concentrations in the eight currently marketed prefilled JUUL EC cartridges ("pods") and to evaluate the cytotoxicity of the different variants (e.g., "Cool Mint" and "Creme Brulee") using in vitro assays. Nicotine and flavor chemicals were analyzed using gas chromatography-mass spectrometry in pod fluid before and after vaping and in the corresponding aerosols. 59 flavor chemicals were identified in JUUL pod fluids, and 3 were >1 mg/mL. Duplicate pods were similar in flavor chemical composition and concentration. Nicotine concentrations (average 60.9 mg/mL) were significantly higher than those of any EC products we have previously analyzed. The transfer efficiency of individual flavor chemicals that were >1 mg/mL and nicotine from the pod fluid into aerosols was generally 35-80%. All pod fluids were cytotoxic at a 1:10 dilution (10%) in the MTT and neutral red uptake assays when tested with BEAS-2B lung epithelial cells. Most aerosols were cytotoxic in these assays at concentrations between 0.2 and 1.8%. The cytotoxicity of collected aerosol materials was highly correlated with nicotine and ethyl maltol concentrations and moderately to weakly correlated with total flavor chemical concentration and menthol concentration. Our study demonstrates that (1) some JUUL flavor pods have sufficiently high concentrations of flavor chemicals that may make them attractive to youth and (2) the concentrations of nicotine and some flavor chemicals (e.g., ethyl maltol) are high enough to be cytotoxic in acute in vitro assays, emphasizing the need to determine if JUUL products will lead to adverse health effects with chronic use.
Distributed Mechanism Design for Network Resource Allocation Problems

In the standard mechanism design framework, agents’ messages are gathered at a central point and allocation/tax functions are calculated in a centralized manner, i.e., as functions of all network agents’ messages. This requirement may cause communication and computation overhead and necessitates the design of mechanisms that alleviate this bottleneck. We consider a scenario where message transmission can only be performed locally so that the mechanism allocation/tax functions can be calculated in a decentralized manner. Each agent transmits messages to her local neighborhood, as defined by a given message-exchange network, and her allocation/tax functions are only functions of the available neighborhood messages. This scenario gives rise to a novel research problem that we call “distributed mechanism design.”In this paper, we propose two distributed mechanisms for network utility maximization problems that involve private and public goods with competition and cooperation between agents. As a concrete example, we use the problems of rate allocation in networks with either unicast or multirate multicast transmission protocols. The proposed mechanism for each of the protocols fully implements the optimal allocation in Nash equilibria, and its message space dimensionality scales linearly with respect to the number of agents in the network.
CO2 absorption rate and capacity of semi-aqueous piperazine for CO2 capture

Abstract Aqueous piperazine (PZ) is a representative second-generation solvent for flue gas amine scrubbing; however, the solid precipitation of aqueous PZ at lean loading needs to be addressed. Semi-aqueous piperazine composed of PZ, water, and a physical solvent (sulfolane or imidazole) has been characterized in a wetted wall column. No precipitation was observed in 5 m PZ in SUF/water or IMI/water in the loading range of 0.15–0.45 mol CO2/mole alkalinity at 20–60 °C. The average viscosity at 40 °C in this range is about 25 cP in 5 m PZ in 1SUF/1water, 9.5 cP in 5 m PZ in 1SUF/3water, and 15 cP in 5 m PZ in 1IMI/1water, greater than 4 cp in 5 m aqueous PZ. Adding SUF or IMI into aqueous PZ increases absorption rate (kg’) at lean and median loading but decreases kg’ at rich loading. kg’ in semi-aqueous PZ increases as temperature decreases from 60 to 20 °C. At 40 °C, kg’avg in 5 m semi-aqueous PZ is 15–35% greater for the operating range of 0.1–5 kPa P*CO2, and 20–50% greater for 0.1–1.5 kPa P*CO2 (natural gas conditions). CO2 cyclic capacity slightly increased after adding SUF or IMI.
Reducing the Search Space for Hyperparameter Optimization Using Group Sparsity

We propose a new algorithm for hyperparameter selection in machine learning algorithms. The algorithm is a novel modification of Harmonica, a spectral hyperparameter selection approach using sparse recovery methods. In particular, we show that a special encoding of hyperparameter space enables a natural group-sparse recovery formulation, which when coupled with HyperBand (a multi-armed bandit strategy) leads to improvement over existing hyperparameter optimization methods such as Successive Halving and Random Search. Experimental results on image datasets such as CIFAR-10 confirm the benefits of our approach.
Random Sampling for Distributed Coded Matrix Multiplication

Matrix multiplication is a fundamental building block for large scale computations arising in various applications, including machine learning. There has been significant recent interest in using coding to speed up distributed matrix multiplication, that are robust to stragglers (i.e., machines that may perform slower computations). In many scenarios, instead of exact computation, approximate matrix multiplication, i.e., allowing for a tolerable error is also sufficient. Such approximate schemes make use of randomization techniques to speed up the computation process. In this paper, we initiate the study of approximate coded matrix multiplication, and investigate the joint synergies offered by randomization and coding. Specifi-cally, we propose two coded randomized sampling schemes that use (a) codes to achieve a desired recovery threshold and (b) random sampling to obtain approximation of the matrix multiplication. Tradeoffs between the recovery threshold and approximation error obtained through random sampling are investigated for a class of coded matrix multiplication schemes.
Gibrat’s law for CO2 emissions

Abstract In this study, we analyze the statistical properties of the growth process of national CO2 emissions for over 200 countries and territories for the period 1995–2010. The results from empirical analysis establish that Gibrat’s law of proportionate effect holds for CO 2 emissions, indicating that national CO 2 emissions grow proportionately over time. Gibrat’s law is also confirmed for CO 2 emission per capita, while weak evidence is found for CO 2 emission per dollar of GDP.
Minimal but meaningful: Probing the limits of randomly assigned social identities.

Abstract The current studies (total N = 151) experimentally manipulated meaningfulness in novel social groups and measured any resulting ingroup biases. Study 1 showed that even when groups were arbitrary and presumptively meaningless, 5- to 8-year-old children developed equally strong ingroup biases as children in more meaningful groups. Study 2 explored the lengths required to effectively reduce ingroup biases by stressing the arbitrariness of the grouping dimension. Even in this case, ingroup bias persisted in resource allocation behavior, although it was attenuated on preference and similarity measures. These results suggest that one needs to go to great lengths to counteract children’s tendency to imbue newly encountered social groups with rich affiliative meaning.
Does automated driving affect time-to-collision judgments?

Abstract We compared time-to-collision (TTC) judgments between automated and manual driving to determine whether automation affected only responses (i.e., braking) or also affected visual perception (i.e., TTC estimation). Automation presumably frees cognitive resources because drivers do not have to control the vehicle. Those resources may be reallocated to processing visual information (e.g., optic flow) relevant for judgments of TTC. With a driving simulator, participants completed drives using manual or automated driving and responded to a rapidly decelerating vehicle using either the brake pedal or a button on the steering wheel (TTC judgment). They also completed a cognitive secondary task during half of the drives. Results suggest that automation can affect perceptual judgments (e.g., TTC estimation) in addition to driving responses (e.g., braking). TTC judgments were more accurate, and brake reaction times were faster, during automated driving than manual driving. This occurred even while performing a cognitively demanding secondary task, suggesting that participants used resources freed by automation to process visual information relevant to TTC judgments rather than complete non-driving tasks. TTC judgments were more accurate during automated driving than manual driving, presumably because automation freed up cognitive resources, allowing participants to assign those resources to processing of visual information (e.g., optic flow) relevant to judgments about collisions. To realize the safety benefit suggested by the results, automated systems should be designed so that cognitive resources freed by automation are assigned to information relevant to the driving task and not to non-driving tasks.
The stereochemistry of the Grignard — Ortho ester reaction revisited: Regioselective endocyclic cleavage in the reaction of Grignard reagents with cis-2-methoxy-4-methyl-1,3-dioxane

The reaction of cis-2-methoxy-4-methyl-1,3-dioxane (4) with Grignard reagents proceeds in a totally regioselective manner via rupture of the less congested C(2)O(1) bond remote from the 4-methyl substituent. The analogous r-2-methoxy-cis-4,cis-6-dimethyl-1,3-dioxane (2) is totally inert to the action of Grignard reagents.
Population structure, genetic connectivity, and adaptation in the Olympia oyster ( Ostrea lurida ) along the west coast of North America.

Effective management of threatened and exploited species requires an understanding of both the genetic connectivity among populations and local adaptation. The Olympia oyster (Ostrea lurida), patchily distributed from Baja California to the central coast of Canada, has a long history of population declines due to anthropogenic stressors. For such coastal marine species, population structure could follow a continuous isolation-by-distance model, contain regional blocks of genetic similarity separated by barriers to gene flow, or be consistent with a null model of no population structure. To distinguish between these hypotheses in O. lurida, 13,424 single nucleotide polymorphisms (SNPs) were used to characterize rangewide population structure, genetic connectivity, and adaptive divergence. Samples were collected across the species range on the west coast of North America, from southern California to Vancouver Island. A conservative approach for detecting putative loci under selection identified 235 SNPs across 129 GBS loci, which were functionally annotated and analyzed separately from the remaining neutral loci. While strong population structure was observed on a regional scale in both neutral and outlier markers, neutral markers had greater power to detect fine-scale structure. Geographic regions of reduced gene flow aligned with known marine biogeographic barriers, such as Cape Mendocino, Monterey Bay, and the currents around Cape Flattery. The outlier loci identified as under putative selection included genes involved in developmental regulation, sensory information processing, energy metabolism, immune response, and muscle contraction. These loci are excellent candidates for future research and may provide targets for genetic monitoring programs. Beyond specific applications for restoration and management of the Olympia oyster, this study lends to the growing body of evidence for both population structure and adaptive differentiation across a range of marine species exhibiting the potential for panmixia. Computational notebooks are available to facilitate reproducibility and future open-sourced research on the population structure of O. lurida.
A new reaction of aryl aldehydes with aryl acetylenes in the presence of boron trihalides.

The reactions of aryl aldehydes with 2 equiv of arylacetylenes in the presence of boron trichloride yield (E,Z)-1,3,5-triaryl-1,5-dichloro-1,4-pentadienes. Reactions carried out in the presence of ...
Hydroxynorleucine as a glycosyl acceptor is an efficient means for introducing amino acid functionality into complex carbohydrates

Abstract A new approach to the synthesis of biologically relevant glycosyl amino acids using a non-natural amino acid as the glycosyl acceptor is described. The procedure involves a glycosylation reaction of a suitable carbohydrate donor with Fmoc- l -hydroxynorleucine benzyl ester. This reaction results in the direct incorporation of the amino acid moiety. The acceptor can be used for the preparation of α- or β- O -linked glycosides depending upon the nature of the glycosyl donor. This method has been applied in the synthesis of six different tumor-associated carbohydrate antigens.
Criteria of Primality

In this article we present four necessary and sufficient conditions for a natural number to be prime.
Microwave assisted synthesis of triazolobenzoxazepine and triazolobenzoxazocine heterocycles

Abstract Intramolecular click chemistry was utilized to effect synthesis of the benzofused, triazole ring systems. The trimethylsilyl group was found to impede the reaction progress, and therefore, conditions employing in situ removal of the TMS group coupled with microwave irradiation give the penultimate targets with good conversion.
Preparation of highly substituted 4-aminopyridones via the reaction of 2-methylene dihydrobenzimidazole with vinyl isocyanates.

The rapid construction of highly substituted 4-aminopyridones was achieved employing an efficient cyclization between various vinyl isocyanates and 2-methylene dihydrobenzimidazole.
Edge-masked CT image reconstruction from limited data

This paper presents a preliminary investigation of an iterative inversion algorithm for computed tomography image reconstruction that early results show performs well in terms of accuracy and speed using limited data. The computational method combines an image domain technique and statistical reconstruction by using an initial filtered back projection reconstruction to create a binary edge mask, which is then used in a weighted e2-regularized reconstruction. Both theoretical and empirical results are offered to support the algorithm. While in this paper a simple forward model is used and physical edges are used as the sparse feature, the proposed method is flexible and can accommodate any forward model and sparsifying transform.
Reducing resistance allele formation in CRISPR gene drive

CRISPR homing gene drives can convert heterozygous cells with one copy of the drive allele into homozygotes, thereby enabling super-Mendelian inheritance. Such a mechanism could be used, for example, to rapidly disseminate a genetic payload in a population, promising effective strategies for the control of vector-borne diseases. However, all CRISPR homing gene drives studied in insects thus far have produced significant quantities of resistance alleles that would limit their spread. In this study, we provide an experimental demonstration that multiplexing of guide RNAs can both significantly increase the drive conversion efficiency and reduce germline resistance rates of a CRISPR homing gene drive in Drosophila melanogaster We further show that an autosomal drive can achieve drive conversion in the male germline, with no subsequent formation of resistance alleles in embryos through paternal carryover of Cas9. Finally, we find that the nanos promoter significantly lowers somatic Cas9 expression compared with the vasa promoter, suggesting that nanos provides a superior choice in drive strategies where gene disruption in somatic cells could have fitness costs. Comparison of drive parameters among the different constructs developed in this study and a previous study suggests that, while drive conversion and germline resistance rates are similar between different genomic targets, embryo resistance rates can vary significantly. Taken together, our results mark an important step toward developing effective gene drives capable of functioning in natural populations and provide several possible avenues for further control of resistance rates.
acI Actinobacteria Assemble a Functional Actinorhodopsin with Natively Synthesized Retinal

Freshwater lakes harbor complex microbial communities, but these ecosystems are often dominated by acI Actinobacteria Members of this cosmopolitan lineage are proposed to bolster heterotrophic growth using phototrophy because their genomes encode actino-opsins (actR). This model has been difficult to validate experimentally because acI Actinobacteria are not consistently culturable. Based primarily on genomes from single cells and metagenomes, we provide a detailed biosynthetic route for members of acI clades A and B to synthesize retinal and its carotenoid precursors. Consequently, acI cells should be able to natively assemble light-driven actinorhodopsins (holo-ActR) to pump protons, unlike many bacteria that encode opsins but may need to exogenously obtain retinal because they lack retinal machinery. Moreover, we show that all acI clades contain genes for a secondary branch of the carotenoid pathway, implying synthesis of a complex carotenoid. Transcription analysis of acI Actinobacteria in a eutrophic lake shows that all retinal and carotenoid pathway operons are transcribed and that actR is among the most highly transcribed of all acI genes. Furthermore, heterologous expression of acI retinal pathway genes showed that lycopene, retinal, and ActR can be made using the genes encoded in these organisms. Model cells producing ActR and the key acI retinal-producing β-carotene oxygenase formed holo-ActR and acidified solution during illumination. Taken together, our results prove that acI Actinobacteria containing both ActR and acI retinal production machinery have the capacity to natively synthesize a green light-dependent outward proton-pumping rhodopsin.IMPORTANCE Microbes play critical roles in determining the quality of freshwater ecosystems, which are vital to human civilization. Because acI Actinobacteria are ubiquitous and abundant in freshwater lakes, clarifying their ecophysiology is a major step in determining the contributions that they make to nitrogen and carbon cycling. Without accurate knowledge of these cycles, freshwater systems cannot be incorporated into climate change models, ecosystem imbalances cannot be predicted, and policy for service disruption cannot be planned. Our work fills major gaps in microbial light utilization, secondary metabolite production, and energy cycling in freshwater habitats.
Ring Group Signatures.

In many applications of group signatures, not only a signer’s identity but also which group the signer belongs to is sensitive information regarding signer privacy. In this paper, we study these applications and combine a group signature with a ring signature to create a ring group signature, which specifies a set of possible groups without revealing which member of which group produced the signature. The main contributions of this paper are a formal definition of a ring group signature scheme and its security model, a generic construction and a concrete example of such a scheme. Both the construction and concrete scheme are provably secure if the underlying group signature and ring signature schemes are secure.
Stereoselectivities of Diels-Alder cycloadditions of tricyclic dienes to MTAD, PTAD, and N-methylmaleimide

Abstract Diels-Alder cycloadditions of 1,2,3,4,9,9-hexachloro-1α,4α,4aα,8aβ-tetrahydro-1,4-methanonaphthalene (5) and 1,2,3,4,9,9-hexachloro-1α,4α,6,7-tetrahydro-1,4-methanonaphthalene (6) to 4-methyl- and 4-phenyl-1,2,4-triazoline-3,5-dione [MTAD and PTAD, respectively] and to N-methylmaleimide (NMM) have been studied. The structures of several of the resulting cycloadducts were determined unequivocally by X-ray crystallographic methods.
Representation of Real-World Event Schemas during Narrative Perception

Understanding movies and stories requires maintaining a high-level situation model that abstracts away from perceptual details to describe the location, characters, actions, and causal relationships of the currently unfolding event. These models are built not only from information present in the current narrative, but also from prior knowledge about schematic event scripts, which describe typical event sequences encountered throughout a lifetime. We analyzed fMRI data from 44 human subjects (male and female) presented with 16 three-minute stories, consisting of four schematic events drawn from two different scripts (eating at a restaurant or going through the airport). Aside from this shared script structure, the stories varied widely in terms of their characters and storylines, and were presented in two highly dissimilar formats (audiovisual clips or spoken narration). One group was presented with the stories in an intact temporal sequence, while a separate control group was presented with the same events in scrambled order. Regions including the posterior medial cortex, medial prefrontal cortex (mPFC), and superior frontal gyrus exhibited schematic event patterns that generalized across stories, subjects, and modalities. Patterns in mPFC were also sensitive to overall script structure, with temporally scrambled events evoking weaker schematic representations. Using a Hidden Markov Model, patterns in these regions predicted the script (restaurant vs airport) of unlabeled data with high accuracy and were used to temporally align multiple stories with a shared script. These results extend work on the perception of controlled, artificial schemas in human and animal experiments to naturalistic perception of complex narratives. SIGNIFICANCE STATEMENT In almost all situations we encounter in our daily lives, we are able to draw on our schematic knowledge about what typically happens in the world to better perceive and mentally represent our ongoing experiences. In contrast to previous studies that investigated schematic cognition using simple, artificial associations, we measured brain activity from subjects watching movies and listening to stories depicting restaurant or airport experiences. Our results reveal a network of brain regions that is sensitive to the shared temporal structure of these naturalistic situations. These regions abstract away from the particular details of each story, activating a representation of the general type of situation being perceived.
Stochastic neural field model of stimulus-dependent variability in cortical neurons

We use stochastic neural field theory to analyze the stimulus-dependent tuning of neural variability in ring attractor networks. We apply perturbation methods to show how the neural field equations can be reduced to a pair of stochastic nonlinear phase equations describing the stochastic wandering of spontaneously formed tuning curves or bump solutions. These equations are analyzed using a modified version of the bivariate von Mises distribution, which is well-known in the theory of circular statistics. We first consider a single ring network and derive a simple mathematical expression that accounts for the experimentally observed bimodal (or M-shaped) tuning of neural variability. We then explore the effects of inter-network coupling on stimulus-dependent variability in a pair of ring networks. These could represent populations of cells in two different layers of a cortical hypercolumn linked via vertical synaptic connections, or two different cortical hypercolumns linked by horizontal patchy connections within the same layer. We find that neural variability can be suppressed or facilitated, depending on whether the inter-network coupling is excitatory or inhibitory, and on the relative strengths and biases of the external stimuli to the two networks. These results are consistent with the general observation that increasing the mean firing rate via external stimuli or modulating drives tends to reduce neural variability.
A Modified Clemmensen Reduction Procedure for Conversion of Aryl Ketones into Aryl Alkenes

Abstract Aryl alkenes can be prepared from aryl ketones through reduction by refluxing with amalgamated zinc in a mixture of formic acid and ethanol.
Preparation of α-C-Glycosides from Glycals

A novel approach to simple C-glycosides is reported. Reductive ring opening of 1,2-anhydro sugars with titanocene(III) chloride produces an anomeric radical that can be trapped with a variety of agents. The reaction stereospecifically affords α-glycosides and produces a free C-2 hydroxyl group allowing for further elaboration.
Synthesis and Characterization of Ternary SnxGe1–xSe Nanocrystals

The nanocrystals of title are synthesized by quick injection of tBu2Se2 and hexamethyldisilazane at 95 °C into a dodecylamine solution containing varying ratios of SnI4 and GeI4 (225 °C, 4.75 h).
Design and synthesis of a series of chlorinated 3-deazaadenine analogues.

Abstract A series of chlorinated adenine analogues were designed with sights set on the development of potential antitumor agents. During the synthetic efforts, two unexpected compounds were identified. Their synthesis, along with synthesis of the chlorinated targets is presented herein.
Discovering New Oxides

The formation of many oxides with unpredictable structures can be attributed to a balance between stable and unstable compositions. A surprising number of the members of the Ln4Cu3MoO12 and Ln‘2Ln‘ ‘2Cu3MoO12 (Ln = La−Nd, Sm−Lu) families form, all crystallizing in a hexagonal structure similar to that of YMnO3. Some do not form because either the average lanthanide size is too small (rLn 14 pm). Furthermore, even if Ln‘4Cu3MoO12 and Ln‘ ‘4Cu3MoO12 form single phases, attempts to synthesize the corresponding solution phase, Ln‘2Ln‘ ‘2Cu3MoO12, may result in a mixture of simpler metal oxides. The explanation illuminates the importance of unstable “umbrella” stoichiometries for the formation of unconventional structures in multication systems.
Diels-Alder reactions of N-acyl-2-alkyl(aryl)-5-vinyl-2,3-dihydro-4-pyridones.

Readily available N-acyl-5-vinyl-2,3-dihydro-4-pyridones undergo Diels−Alder cyclization with various dienophiles to afford novel octahydroquinolines containing synthetically useful functionality. With dihydropyridone 5 and cis-disubstituted dienophiles, the resulting cycloadducts were obtained as single diastereomers in good to excellent yield. The corresponding reaction of 5 with methyl acrylate, acrylonitrile, and phenyl vinyl sulfone showed modest preference for the endo adducts. The effect of the dihydropyridone C-2 and C-4 substituents on the degree of diastereofacial control was examined. By using this methodology, the core decahydroquinoline skeleton of gephyrotoxin was prepared in a stereocontrolled fashion. Interesting reactivity was observed with certain dienophiles leading to ring-opening of the initially formed cycloadducts. This tandem reaction provides a route to uniquely substituted β-aminoketones, alcohols, and unnatural amino acids.
Synthetic Studies on the Kinamycin Family of Antibiotics: Synthesis of 2-(Diazobenzyl)-p-naphthoquinone, 1,7-Dideoxy-3-demethylprekinamycin, and 1-Deoxy-3-demethylprekinamycin.

2-(Diazobenzyl)-p-naphthoquinone was synthesized from 2-benzyl-1,4-dimethoxynaphthalene by cerric ammonium nitrate oxidation to 2-benzyl-p-naphthoquinone followed by diazo transfer with tosyl azide. 1,7-Dideoxy-3-demethylprekinamycin was prepared from 1,4-dimethoxynaphthalene by bromination, lithiation, and condensation with acetanthranil to give 2-(2‘-N-acetaminobenzoyl)-1,4-dimethoxynaphthalene, which, following deacylation, was subjected to Pschorr cyclization to give 1,3,7-trihydro-O,O-dimethylkinafluorenone. This was then demethylated, subjected to hydrazinolysis, and then oxidized with Fetizon's reagent to complete the synthesis. 1-Deoxy-3-demethylprekinamycin was synthesized from 3-bromo-1,5-dimethoxy-4-naphthol by an identical route.
Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain

Bruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved, in-silico structural modeling of the kinase's solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK's kinase domain. Our conformational landscape links the active state to several inactive states, connected via a structurally diverse intermediate. Our calculations predict a kinome-wide conformational plasticity, and indicate the presence of several new potentially druggable BTK states. We further find that the population of these states and the kinetics of their inter-conversion are modulated by protonation of an aspartate residue, establishing the power of MD & MSMs in predicting effects of chemical perturbations.
Price Isn’t Everything: Behavioral Response around Changes in Sin Taxes

Taxes change behavior. But how does this change arise? In traditional economic models, change is achieved through the price channel: assuming all else is held constant, taxes increase prices and thus decrease demand. However, the assumption that all else is held constant may be violated in the course of a legal change, in part because the process by which laws are changed often involves the provision of information, attempts at persuasion, and the deployment of alternative dissuasive tools. We examine violations of this assumption in a particular policy domain: discouraging smoking with cigarette taxes. We document a marked increase in related media coverage, lobbying efforts, place-based smoking restrictions, and anti-smoking appropriations in the time period surrounding a tax law change. The intensity of these factors is directly associated with decreases in cigarette consumption in a manner that could be confused with price effects. Our results suggest that price effects may have a surprisingly small role in the behavioral response that occurs around tax law changes.