cssi/SciSciGPT-SciSciNet huggingface dataset:
CONSTITUTIONAL REVIEW AND TAX LAW: AN ANALYTICAL FRAMEWORK

This Article offers a more comprehensive and substantial approach to constitutional review of the general power to tax and the way tax laws should comply with constitutional rights and principles. The power of Congress to levy taxes is not confined to income taxes; it is broader and much more general. Article I, Section 8 of the Constitution describes the general power of Congress in terms of tax laws as follows: “The Congress shall have Power To lay and collect Taxes, Duties, Imposts and Excises, to pay the Debts and provide for the common Defense and general Welfare of the United States . . . .” This provision contains more than it seems at first glance. First, it says that only the legislature has the power to lay taxes. The legislature represents the people; hence, a tax should be levied only if there is a collective consent of the people, the taxpayers. Second, any tax should be enacted only for the provision of the “common defense and general welfare.” The Author's underlying assumption here is quite clear and straightforward: tax laws are not immune from judicial review and constitutional limitations restrict the power to impose taxes. Taxes should be scrutinized, via judicial review, like any other act of Congress. Any tax may be unconstitutional if it does not provide for the common defense and general welfare, or if it does not represent the collective consent. Furthermore, a tax should not violate any other constitutional rights or interests, e.g., property or equal protection rights.
Learning Grid Cells as Vector Representation of Self-Position Coupled with Matrix Representation of Self-Motion

This paper proposes a representational model for grid cells. In this model, the 2D self-position of the agent is represented by a high-dimensional vector, and the 2D self-motion or displacement of the agent is represented by a matrix that transforms the vector. Each component of the vector is a unit or a cell. The model consists of the following three sub-models. (1) Vector-matrix multiplication. The movement from the current position to the next position is modeled by matrix-vector multiplication, i.e., the vector of the next position is obtained by multiplying the matrix of the motion to the vector of the current position. (2) Magnified local isometry. The angle between two nearby vectors equals the Euclidean distance between the two corresponding positions multiplied by a magnifying factor. (3) Global adjacency kernel. The inner product between two vectors measures the adjacency between the two corresponding positions, which is defined by a kernel function of the Euclidean distance between the two positions. Our representational model has explicit algebra and geometry. It can learn hexagon patterns of grid cells, and it is capable of error correction, path integral and path planning.
Designing Robust N-of-1 Studies for Precision Medicine: Simulation Study and Design Recommendations.

: Recent advances in molecular biology, sensors, and digital medicine have led to an explosion of products and services for high-resolution monitoring of individual health. The N-of-1 study has emerged as an important methodological tool for harnessing these new data sources, enabling researchers to compare the effectiveness of health interventions at the level of a single individual. : N-of-1 studies are susceptible to several design flaws. We developed a model that generates realistic data for N-of-1 studies to enable researchers to optimize study designs in advance. : Our stochastic time-series model simulates an N-of-1 study, incorporating all study-relevant effects, such as carryover and wash-in effects, as well as various sources of noise. The model can be used to produce realistic simulated data for a near-infinite number of N-of-1 study designs, treatment profiles, and patient characteristics. : Using simulation, we demonstrate how the number of treatment blocks, ordering of treatments within blocks, duration of each treatment, and sampling frequency affect our ability to detect true differences in treatment efficacy. We provide a set of recommendations for study designs on the basis of treatment, outcomes, and instrument parameters, and make our simulation software publicly available for use by the precision medicine community. : Simulation can facilitate rapid optimization of N-of-1 study designs and increase the likelihood of study success while minimizing participant burden.
Benchmarking Approximate Inference Methods for Neural Structured Prediction

Exact structured inference with neural network scoring functions is computationally challenging but several methods have been proposed for approximating inference. One approach is to perform gradient descent with respect to the output structure directly (Belanger and McCallum, 2016). Another approach, proposed recently, is to train a neural network (an “inference network”) to perform inference (Tu and Gimpel, 2018). In this paper, we compare these two families of inference methods on three sequence labeling datasets. We choose sequence labeling because it permits us to use exact inference as a benchmark in terms of speed, accuracy, and search error. Across datasets, we demonstrate that inference networks achieve a better speed/accuracy/search error trade-off than gradient descent, while also being faster than exact inference at similar accuracy levels. We find further benefit by combining inference networks and gradient descent, using the former to provide a warm start for the latter.
Arriving at a decision: A semi-parametric approach to institutional birth choice in India

Abstract The Multinomial Logit (MNL) model is popular, but a semi-parametric specification of its link/utility function has seldom been used in empirical applications. This is primarily because of the resource intensive nature of semi-parametric estimation. In this paper we propose and implement a parallel computation algorithm to estimate the semi-parametric kernel MNL model. This algorithm reduces model estimation time by a factor of 2–10, depending on the size of the dataset and the available resources for computation. These computational gains make the estimation of this model feasible for large datasets. Additionally, using a Monte Carlo study we show that the kernel MNL outperforms the traditional linear MNL model in terms of fit and predicted choice probabilities. We demonstrate how kernel-based specification can unearth important heterogeneities in the effect of covariates through an empirical exercise. We use data from a nationally representative household survey (N = 157,804) to analyze the factors associated with institutional births (as opposed to home births) in India. Our revealed-preference results indicate that maternal education, household assets, distance to formal health facility, and birth order play an essential role in determining birth location choice. Although the directions of impact are similar across both the linear and the kernel MNL specifications, there are significant differences in the marginal effects of different factors across the two models. These differences, which arise due to the flexibility afforded by the semi-parametric specification, potentially bring additional nuance to policy discussions.
Social Accountability and Institutional Change: The Case of Citizen Oversight of Police

We examine the ability of social accountability to spur gradual institutional change at the municipal level, using the case of citizen oversight agencies (COAs) for police agencies. Using the gradual change framework (GCF) and social accountability framework to guide our empirical strategy, and data collected through an original survey of COAs, we test the impact of COAs on institutional outcomes in policing. We find, in accordance with the GCF, that the degree to which a COA reduces racial disparity in policing outcomes depends on its scope of authority, as well as the degree of discretion afforded by existing institutions to police officers. In general, the wider the scope of authority, and the broader the discretion afforded by existing institutions, the greater the likelihood of change in institutional outcomes.
Aging effects of motor prediction on protective balance and startle responses to sudden drop perturbations.

Abstract This pilot study investigated the effect of age on the ability of motor prediction during self-triggered drop perturbations (SLF) to modulate startle-like first trial response (FTR) magnitude during externally-triggered (EXT) drop perturbations. Ten healthy older (71.4 ± 1.44 years) and younger adults (26.2 ± 1.63 years) stood atop a moveable platform and received blocks of twelve consecutive EXT and SLF drop perturbations. Following the last SLF trial, participants received an additional EXT trial spaced 20 min apart to assess retention (EXT RTN) of any modulation effects. Electromyographic (EMG) activity was recorded bilaterally over the sternocleidomastoid (SCM), vastus lateralis (VL), biceps femoris (BF), medial gastrocnemius (MG), and tibialis anterior (TA). Whole-body kinematics and kinetic data were recorded. Stability in the antero-posterior direction was quantified using the margin of stability (MoS). Compared with EXT trials, both groups reduced SCM peak amplitude responses during SLF and EXT RTN trials. VL/BF and TA/MG coactivation were reduced during SLF FTR compared to EXT FTR (p
Cyclic Alkyne Approach to Heteroatom‐Containing Polycyclic Aromatic Hydrocarbon Scaffolds

We report a modular synthetic strategy for accessing heteroatom-containing polycyclic aromatic hydrocarbons (PAHs). Our approach relies on the controlled generation of transient heterocyclic alkynes and arynes. The strained intermediates undergo in situ trapping with readily accessible oxadiazinones. Four sequential pericyclic reactions occur, namely two Diels-Alder/retro-Diels-Alder sequences, which can be performed in a stepwise or one-pot fashion to assemble four new carbon-carbon (C-C) bonds. These studies underscore how the use of heterocyclic strained intermediates can be harnessed for the preparation of new organic materials.
The Role of Kinship and Siblings in Young Children’s Placement Preferences:

Although considerable attention has been directed toward the most appropriate placement for children following removal from home due to maltreatment, very little of this attention has focused on children's stated preferences, particularly when children are young. Specifically, children below 12 years of age are often presumed incompetent to form reasoned judgments about their best interests in placement. This assumption, however, has rarely been tested directly. We surveyed 100 4- to 11-year-olds removed from home because of maltreatment about their placement preferences. Children were less likely to indicate they wanted to return home if they were placed with siblings or with kin, consistent with statutory placement preferences. These results suggest that young children may express more mature preferences than recognized by the law, and that there may be value in asking even relatively young children about with whom they would like to live following their removal from home as a result of maltreatment.
Endurance training slows breast tumor growth in mice by suppressing Treg cells recruitment to tumors.

Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. Adult wild-type and athymic BALB/c female mice were endurance-trained for 8 weeks. Circulating leukocytes as well as muscle and liver mtDNA copy number were compared to aged-matched concurrent sedentary controls to establish systemic effects. 4 T1 murine mammary tumor cells were injected subcutaneously to the 4th mammary pad at the end of the training period. Tumor growth and survival rates were compared, together with antitumor immune response. Exercised wild-type had 17% slower growth rate, 24% longer survival, and 2-fold tumor-CD+ 8/FoxP3+ ratio than sedentary controls. Exercised athymic BALB/c females showed no difference in tumor growth or survival rates when compared to sedentary controls. Cytotoxic T cells are a significant factor in endurance exercise-induced suppression of tumor growth. Endurance exercise enhances antitumor immune efficacy by increasing intratumoral CD8+/FoxP3+ ratio.
Rapid synthesis of functionalized, alkoxy-substituted, allylstannanes from carbene complexes

Abstract Hydrostannation of readily available chromium and tungsten vinyl carbene complexes with tributyltin hydride provides a facile synthesis of highly substituted alkoxy-substituted allylstannanes. Preparation of acetal, keto, methoxy, and silyl substituted stannane reagents is demonstrated.
Synthesis of Pure Boron Single-Wall Nanotubes

We report here the first synthesis of pure boron single-wall nanotubes by reaction of BCl3 with H2 over an Mg−MCM-41 catalyst with parallel, uniform diameter (36 ± 1 A) cylindrical pores. The composition of the tubular structures observed in TEM was confirmed by electron energy loss spectroscopy, and the tubular geometry was confirmed by the presence of the characteristic spectral features in the Raman breathing mode region.
CCA based multi-view feature selection for multi-omics data integration

Recent technological advances in high-throughput omics technologies and their applications in genomic medicine have opened up outstanding opportunities for individualized medicine. However, several challenges arise in the integrative analysis of such data including heterogeneity and high dimensionality of the omics data. In this study, we present a novel multi-view feature selection algorithm based on the well- known canonical correlation analysis (CCA) statistical method for jointly selecting discriminative features from multi-omics data sources (multi-views). Our results demonstrate that models for predicting kidney renal clear cell carcinoma (KIRC) survival using our proposed method for jointly selecting discriminative features from copy number alteration (CNA), gene expression RNA-Seq, and reverse-phase protein arrays (RPPA) views outperform models trained using single-view data as well as three integrated models developed using data fusion approaches including CCA-based feature fusion.
Cyclocondensation of amidines with dimethyl acetylenedicarboxylate: A convenient entry into tetramic acids

Amidines undergo cyclocondensations with dimethyl acetylenedicarboxylate (DMAD) to give highly functionalized 5-dialkylamino-4-pyrrolin-3-ones. The products are crystalline, highly colored compounds that are uniquely functionalized and represent advanced intermediates in the construction of several other heterocyles, in particular the biologically active tetramic acids. The synthetic transformations of these compounds to tetramic acids are also described.
Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green

Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.
An information theoretic treatment of sequence-to-expression modeling

Studying a gene's regulatory mechanisms is a tedious process that involves identification of candidate regulators by transcription factor (TF) knockout or over-expression experiments, delineation of enhancers by reporter assays, and demonstration of direct TF influence by site mutagenesis, among other approaches. Such experiments are often chosen based on the biologist's intuition, from several testable hypotheses. We pursue the goal of making this process systematic by using ideas from information theory to reason about experiments in gene regulation, in the hope of ultimately enabling rigorous experiment design strategies. For this, we make use of a state-of-the-art mathematical model of gene expression, which provides a way to formalize our current knowledge of cis- as well as trans- regulatory mechanisms of a gene. Ambiguities in such knowledge can be expressed as uncertainties in the model, which we capture formally by building an ensemble of plausible models that fit the existing data and defining a probability distribution over the ensemble. We then characterize the impact of a new experiment on our understanding of the gene's regulation based on how the ensemble of plausible models and its probability distribution changes when challenged with results from that experiment. This allows us to assess the 'value' of the experiment retroactively as the reduction in entropy of the distribution (information gain) resulting from the experiment's results. We fully formalize this novel approach to reasoning about gene regulation experiments and use it to evaluate a variety of perturbation experiments on two developmental genes of D. melanogaster. We also provide objective and 'biologist-friendly' descriptions of the information gained from each such experiment. The rigorously defined information theoretic approaches presented here can be used in the future to formulate systematic strategies for experiment design pertaining to studies of gene regulatory mechanisms.
Human CODIS STR loci profiling from HTS data

Human DNA identification is currently performed by amplifying a small, defined set of short tandem repeat (STR) loci (e.g. CODIS) and analyzing the size of the alleles present at those loci by capillary electrophoresis. High-throughput DNA sequencing (HTS) could enable the simultaneous analysis of many additional STR and single nucleotide polymorphism (SNP) loci, improving accuracy and discrimination. However, it is necessary to demonstrate that HTS can generate accurate data on the CODIS loci to enable backwards compatibility with the FBI NDIS database. Sequencing can also detect novel polymorphisms within alleles that migrate with identical sizes by capillary electrophoresis, improving allele discrimination, and enhancing human identification analysis. All CODIS alleles from an individual can be amplified in a single, multiplex PCR reaction, and combined with additional barcoded samples prior to sequencing. A computational tool for allele identification from multiplexed sequence data has been developed. With longer-read-length platforms, 99.6% allele calling accuracy can be achieved. In the course of STR sequencing protocol development, 12 novel allele sequences have been identified for multiple loci. Sequencing STR loci combined with SNPs will enable new forensic applications.
Reflections on Future Directions in Organometallic Electrochemistry

Electrochemistry is employed both as an analytical instrumental technique and as a method of inducing changes in the structure and reactivity of organometallic complexes. It is the primary implemen...
Alkene Diamination Using Electron-Rich Amines: Hypervalent Iodine-Promoted Inter-/Intramolecular C–N Bond Formation

A combined inter-/intramolecular oxidative diamination of terminal alkenes is described that uses a hypervalent iodine oxidant and a nucleophilic amine to produce 3-aminoindolines at room temperature. This operationally straightforward and metal-free protocol is compatible with a broad range of functional groups. A mechanism involving the conversion of the amine to an electrophilic nitrogen source is advanced and used to identify a protocol effective with substoichiometric amounts of iodide and commercially available phenyl iodobenzene diacetate (PIDA) as the stoichiometric oxidant.
Studies on the synthesis of the indole alkaloids pauciflorine A and B

Abstract A double Bischler-Napieralski reaction of the 11-membered ring carbamate 15 gave the homoannular diene 17 in a single step.
Evolutionary Capacitance Emerges Spontaneously during Adaptation to Environmental Changes.

Summary All biological populations are to a greater or lesser degree evolvable, but the forces that shape evolvability, especially the evolution of evolvability as an adaptive response to pressure to evolve rapidly, are a source of controversy. One determinant of evolvability is the set of possible mutations available to a genotype, or “mutational neighborhood.” A benign (instead of deleterious) mutational neighborhood can enhance evolvability. Whether selection for evolvability itself can result in a more benign mutational neighborhood remains an open question. We document the evolution of increased evolvability in a fluctuating environment despite using a regime that precludes, by design, the adaptive evolution of evolvability. Instead, a benign mutational neighborhood arises as a byproduct of transiently elevated error rates via a mechanism that we call emergent evolutionary capacitance. This is evolutionary capacitance similar to that seen in a model system for capacitance, the yeast prion [PSI+], but without a capacitor.
Montmorillonite clay-catalyzed hetero-Diels–Alder reaction of 2,3-dimethyl-1,3-butadiene with benzaldehydes

Montmorillonite K10 clay was found to catalyze the hetero-Diels–Alder reaction of 2,3-dimethyl-1,3-butadiene with o-anisaldehyde and other benzaldehyde derivatives; a transition state involving chelation of the clay’s metal ions with the dienophile’s heteroatoms is proposed.
Controlling E. coli Gene Expression Noise

Intracellular protein copy numbers show significant cell-to-cell variability within an isogenic population due to the random nature of biological reactions. Here we show how the variability in copy number can be controlled by perturbing gene expression. Depending on the genetic network and host, different perturbations can be applied to control variability. To understand more fully how noise propagates and behaves in biochemical networks we developed stochastic control analysis (SCA) which is a sensitivity-based analysis framework for the study of noise control. Here we apply SCA to synthetic gene expression systems encoded on plasmids that are transformed into Escherichia coli. We show that (1) dual control of transcription and translation efficiencies provides the most efficient way of noise-versus-mean control. (2) The expressed proteins follow the gamma distribution function as found in chromosomal proteins. (3) One of the major sources of noise, leading to the cell-to-cell variability in protein copy numbers, is related to bursty translation. (4) By taking into account stochastic fluctuations in autofluorescence, the correct scaling relationship between the noise and mean levels of the protein copy numbers was recovered for the case of weak fluorescence signals.
Aza-analogues of cage compounds: Potential precursors to azacubanes and 1-azahomocubanes†

Exploration of the reactions of the 9-azahomocubane system led to derivatives of two small-ring systems containing aza-bridging atoms, 5-azatetracyclo[4.2.0.0 3,8 .0 4,7 ]octane and 9-azatetracyclo[4.3.0.0 2,5 .0 4,7 ]nonane. The structures were characterized by X-ray diffraction analyses. There are no prior X-ray structural reports on these systems
Chemistry of Borabenzene: Efficient and General Synthesis of New Neutral Borabenzene−Ligand Complexes

An array of neutral borabenzene−ligand complexes (ligand = pyridine, 2,6-lutidine, NEt3, PMe3, CN-t-Bu) have been synthesized in three straightforward steps from commercially available 1-(trimethylsilyl)-1,4-pentadiyne. An X-ray crystal structure of borabenzene−PMe3 is reported.
Synthesis of lariat ethers with pendent amine, amide, O-benzylhydroxamate, and urethane groups

Synthetic routes to twenty-six new crown ether compounds with pendent amine, amide, O-benzylhydrox-amate, and urethane groups are reported. The new lariat ether compounds are based on sym-dibenzo-16-crown-5, sym-dicyclohexano-16-crown-5, and 14-crown-4 scaffolds.
Hydrothermal Synthesis and Structural Characterization of Zeolite-like Structures Based on Gallium and Aluminum Germanates

While extensive commercial success has been achieved through the use of organic molecules in the synthesis of aluminosilicate zeolites, the synthesis of the germanium-based zeolite structures using organic structure-directing agents is a largely unexplored area. Here we report a novel class of germanate zeolite structures prepared with inorganic cations or organic amines as structure-directing agents. These new materials possess five 4-connected 3-dimensional topologies with large (12-ring), medium (10-ring), small (8-ring), or ultrasmall (6-ring) pores. They have a variety of chemical compositions such as various Ge to Ga (or Al) ratios and exhibit interesting structural features such as helical chains and odd-membered rings. UCSB-15GaGe and UCSB-15AlGe are the first germanate-based structures with 5-rings. UCSB-7 refers to a collection of isostructural, large-pore zeolite-like structures constructed by the cross-linking of helical ribbons. UCSB-3GaGe is the only known T3+/T4+ (T refers to tetrahedral at...
Whole-Genome Sequence Accuracy Is Improved by Replication in a Population of Mutagenized Sorghum

The accurate detection of induced mutations is critical for both forward and reverse genetics studies. Experimental chemical mutagenesis induces relatively few single base changes per individual. In a complex eukaryotic genome, false positive detection of mutations can occur at or above this mutagenesis rate. We demonstrate here, using a population of ethyl methanesulfonate (EMS)-treated Sorghum bicolor BTx623 individuals, that using replication to detect false positive-induced variants in next-generation sequencing (NGS) data permits higher throughput variant detection with greater accuracy. We used a lower sequence coverage depth (average of 7×) from 586 independently mutagenized individuals and detected 5,399,493 homozygous single nucleotide polymorphisms (SNPs). Of these, 76% originated from only 57,872 genomic positions prone to false positive variant calling. These positions are characterized by high copy number paralogs where the error-prone SNP positions are at copies containing a variant at the SNP position. The ability of short stretches of homology to generate these error-prone positions suggests that incompletely assembled or poorly mapped repeated sequences are one driver of these error-prone positions. Removal of these false positives left 1,275,872 homozygous and 477,531 heterozygous EMS-induced SNPs, which, congruent with the mutagenic mechanism of EMS, were >98% G:C to A:T transitions. Through this analysis, we generated a collection of sequence indexed mutants of sorghum. This collection contains 4035 high-impact homozygous mutations in 3637 genes and 56,514 homozygous missense mutations in 23,227 genes. Each line contains, on average, 2177 annotated homozygous SNPs per genome, including seven likely gene knockouts and 96 missense mutations. The number of mutations in a transcript was linearly correlated with the transcript length and also the G+C count, but not with the GC/AT ratio. Analysis of the detected mutagenized positions identified CG-rich patches, and flanking sequences strongly influenced EMS-induced mutation rates. This method for detecting false positive-induced mutations is generally applicable to any organism, is independent of the choice of in silico variant-calling algorithm, and is most valuable when the true mutation rate is likely to be low, such as in laboratory-induced mutations or somatic mutation detection in medicine.
Rapid solid-state metathesis routes to aluminum nitride.

Metathesis (exchange) reactions offer the possibility of controlling temperature through a judicious choice of precursors. Here, a reaction between AlCl3 and Ca3N2 is found to produce phase-pure aluminum nitride (AlN) in seconds. The CaCl2 byproduct salt, whose formation drives this highly exothermic reaction, is simply washed away after reaction completion. SEM images demonstrate that the AlN product is a micron-sized powder, while TEM shows well-formed crystallites. Thermodynamic calculations indicate that a reaction temperature of 2208 K could be reached under adiabatic conditions. Using an in situ thermocouple and a stainless steel reactor vessel to hold the precursors, a reaction temperature of 1673 K is measured 0.8 s after initiation. Switching to a thermally insulating ceramic vessel produces a maximum reaction temperature of 2010 K because of the more nearly adiabatic conditions. The high reaction temperature appears to be critical to forming phase-pure AlN. Experiments with Li3N, instead of Ca3N...
Synthesis of N4‐substituted[1,3,4]oxadiazinan‐2‐ones derived from norephedrine

[1,3,4]-Oxadiazinan-2-ones bearing substitution at the N4-position have been synthesized from norephedrine in good yield via N-alkylation, nitrosation, reduction and cyclization.
Synthesis of aryl ω‐(1‐methyl‐5‐imidazolyl and 1H‐5‐tetrazolyl)alkyl ketones

Successful syntheses of 2,4-dichlorophenyl 2-(1-methyl-5-imidazolyl)ethyl and 2,4-dichlorophenyl 3-(1-methyl-5-imidazolyl)propyl ketones are described. In addition, syntheses of 2,4-dichlorophenyl and 4-chlorophenyl 3-(1-methyl-1H-5-tetrazolyl)propyl ketones are reported.
Dose escalation for locally advanced pancreatic cancer: How high can we go?

Abstract Purpose There are limited treatment options for locally advanced, unresectable pancreatic cancer (LAPC) and no likelihood of cure without surgery. Radiation offers an option for local control, but radiation dose has previously been limited by nearby bowel toxicity. Advances in on-board imaging and treatment planning may allow for dose escalation not previously feasible and improve local control. In preparation for development of clinical trials of dose escalation in LAPC, we undertook a dosimetric study to determine the maximum possible dose escalation while maintaining known normal tissue constraints. Methods and Materials Twenty patients treated at our institution with either SBRT or dose-escalated hypofractionated IMRT (DE-IMRT) were re-planned using dose escalated SBRT to 70 Gy in 5 fractions to the GTV and 40 Gy in 5 fractions to the PTV. Standard accepted organ at risk (OAR) constraints were used for planning. Descriptive statistics were generated for homogeneity, conformality, OAR's and GTV/PTV. Results Mean iGTV coverage by 50 Gy was 91% (±0.07%), by 60 Gy was 61.3% (±0.08%) and by 70 Gy was 24.4% (±0.05%). Maximum PTV coverage by 70 Gy was 33%. Maximum PTV coverage by 60 Gy was 77.5%. The following organ at risk (OAR) constraints were achieved for 90% of generated plans: Duodenum V20 Conclusions Dose escalation to 60 Gy is dosimetrically feasible with adequate GTV coverage. The identified constraints for OAR's will be used in ongoing clinical trials.
The Power of Proofs-of-Possession: Securing Multiparty Signatures against Rogue-Key Attacks.

Multiparty signature protocols need protection against rogue-key attacks, made possible whenever an adversary can choose its public key(s) arbitrarily. For many schemes, provable security has only been established under the knowledge of secret key (KOSK) assumption where the adversary is required to reveal the secret keys it utilizes. In practice, certifying authorities rarely require the strong proofs of knowledge of secret keys required to substantiate the KOSK assumption. Instead, proofs of possession (POPs) are required and can be as simple as just a signature over the certificate request message. We propose a general registered key model, within which we can model both the KOSK assumption and in-use POP protocols. We show that simple POP protocols yield provable security of Boldyreva’s multisignature scheme [11], the LOSSW multisignature scheme [28], and a 2-user ring signature scheme due to Bender, Katz, and Morselli [10]. Our results are the first to provide formal evidence that POPs can stop rogue-key attacks.
Phosphotyrosyl mimetics in the development of signal transduction inhibitors.

Phosphotyrosyl (pTyr) residues play important roles in cellular signal transduction by facilitating recognition and binding necessary for critical protein−protein interactions, and for this reason pTyr motifs represent attractive starting points in the development of signaling antagonists. Although the pTyr phosphoryl moiety is central in these phenomena, its incorporation into signaling inhibitors is contraindicated due to enzymatic lability and limited bioavailabilty associated with phosphate esters. To address these limiations, an entire field of study has arisen devoted to the design and utilization of pTyr mimetics. This Account provides a perspective on the roles of pTyr residues in signal transduction and approaches to pTyr mimetic development.
2,3-Bis(phenylsulfonyl)-1,3-butadiene-mediated syntheses of piperidone derivatives

The key element for the synthesis of several alkaloid skeletons consists of a conjugate addition–dipolar cycloaddition of 2,3-bis(phenylsulfonyl)-1,3-butadiene with an appropriate oxime. The resulting cycloadducts are cleaved reductively to provide azapolycyclic scaffolds with strategically placed functionality for further manipulation to the target compounds.
Base-pair resolution detection of transcription factor binding site by deep deconvolutional network

Motivation Transcription factor (TF) binds to the promoter region of a gene to control gene expression. Identifying precise TF binding sites (TFBSs) is essential for understanding the detailed mechanisms of TF-mediated gene regulation. However, there is a shortage of computational approach that can deliver single base pair resolution prediction of TFBS. Results In this paper, we propose DeepSNR, a Deep Learning algorithm for predicting TF binding location at Single Nucleotide Resolution de novo from DNA sequence. DeepSNR adopts a novel deconvolutional network (deconvNet) model and is inspired by the similarity to image segmentation by deconvNet. The proposed deconvNet architecture is constructed on top of 'DeepBind' and we trained the entire model using TF-specific data from ChIP-exonuclease (ChIP-exo) experiments. DeepSNR has been shown to outperform motif search-based methods for several evaluation metrics. We have also demonstrated the usefulness of DeepSNR in the regulatory analysis of TFBS as well as in improving the TFBS prediction specificity using ChIP-seq data. Availability and implementation DeepSNR is available open source in the GitHub repository (https://github.com/sirajulsalekin/DeepSNR). Supplementary information Supplementary data are available at Bioinformatics online.
The new science of protein mimetics

New chemistries have been developed for de novo protein design. Protein mimetics of different structural and functional properties such as synthetic peptide ligases and Dn symmetrical helical bundles have been reported. The Template-Assembled Synthetic Protein (TASP) method (as well as the Molecular Kit approach) has also been utilized to prepare protein-like molecules. Here we report the synthesis of single chain, scaffold (TRIS)- and dendrimer-assembled collagen mimetics composed of the Gly-Nleu-Pro sequence where Nleu denotes N-isobutyl glycine. From the CD spectra and the thermal denaturation studies it can be seen that the collagen mimetics prepared form stable triple helices except the single chain structure. Furthermore, the 162-residue collagen mimetic dendrimer exhibits enhanced triple helical stability compared to the equivalent scaffold-terminated structure by an increase in the melting temperature in both H 2 O and 2:1 ethylene glycol/H 2 O (4 °C and 12 °C respectively). The concentration dependence for the melting transition of the collagen mimetic dendrimer was measured from which it was determined that the stabilization effect arises from the intramolecular clustering of the triple helical arrays about the core structure. This ensemble excludes solvent from the interior portion of the array which stabilizes the triple helix cluster.
High temperature limits on developmental canalization in the ascidian Ciona intestinalis.

Abstract The normal embryogenesis of marine animals is typically confined to a species-specific range of temperatures. Within that temperature range development results in a consistent, or canalized, phenotype, whereas above and below the range abnormal phenotypes are produced. This study reveals a high temperature threshold, occurring over a 1–2 °C range, for normal embryonic development in C. intestinalis. Above that threshold the prevalence of morphological abnormalities increases significantly, beginning with cleavage and gastrula stages, and becoming more pronounced as embryogenesis proceeds. However, even in highly morphologically abnormal temperature disrupted (TD) embryos, muscle, endoderm, notochord, epidermis, and sensory pigment cells are recognizable, as evidenced by histochemical markers or morphology. On the other hand, morphogenesis of the notochord and other structures is dependent on precise cell movement and shape changes after the gastrula stage, which are disrupted above the high temperature threshold. These findings suggest that morphogenetic processes may be more sensitive to high temperature than cell type specification events. They also point to avenues for investigation of the limiting factors to developmental canalization in marine invertebrates.
β-Scission of the N−O Bond in Alkyl Hydroxamate Radicals: A Fast Radical Trap

The rate of the β-scission of the N−O bond in the alkyl hydroxamate radical is faster than 2 × 108 s-1. This reaction may be useful as a radical trap.
Synthesis and Crystal Structure of Cubic Ca16Si17N34

Since the late 1960s, the exact structure of cubic calcium silicon nitride has been a source of debate. This paper offers evidence that the cubic phase CaSiN(2) described in the literature is actually Ca(16)Si(17)N(34). Presented here is a method for synthesizing single crystals of cubic-calcium silicon nitride from calcium nitride and elemental silicon under flowing nitrogen at 1500 °C. The colorless millimeter-sized crystals of Ca(16)Si(17)N(34) with a refractive index (n(25)) = 1.590 were found to be cubic (a = 14.8882 A) and belong to the space group F43m (216). The synthesis of bulk, powdered cubic-Ca(16)Si(17)N(34) from calcium cyanamide and silicon is also discussed. Ca(16)Si(17)N(34) is a relatively air-stable refractory ceramic. In contrast to the orthorhombic phase of CaSiN(2), in which Ca(2+) sits in octahedral sites, this cubic phase has Ca(2+) in cubic sites that makes it an interesting host for new phosphors and gives rise to unique crystal field splitting.
Highly Efficient, Facile, Room Temperature Intermolecular [5 + 2] Cycloadditions Catalyzed by Cationic Rhodium(I): One Step to Cycloheptenes and Their Libraries

A cationic rhodium(I) complex―[(C10H8)Rh(cod)]+ SbF6−―catalyzes the remarkably efficient intermolecular [5 + 2] cycloaddition of vinylcyclopropanes (VCPs) and various alkynes, providing cyclohepten...
Sequential application of stereoselective syn-oxidation methodologies to natural product synthesis: A potentially biomimetic approach to the C12–C21 bistetrahydrofuran region of monensin

Abstract The preparation of an all-Z-triene corresponding to an acyclic premonensin triene is described. In analogy to the Townsend syn-oxidative cyclization hypothesis for natural product biosynthesis, a sequence of regioselective and enantioselective syn-dihydroxylation of the triene, cis-selective syn-oxidative cyclization of the diol-diene, and trans-selective syn-oxidative cyclization of the remaining hydroxyalkene gives the correct stereochemical pattern corresponding to the C and D ring tetrahydrofurans of monensin.
Catalytic Asymmetric Staudinger Reactions to Form β-Lactams: An Unanticipated Dependence of Diastereoselectivity on the Choice of the Nitrogen Substituent

There are relatively few methods for the catalytic asymmetric synthesis of β-lactams, and those that have been reported are generally cis selective. This communication describes the first catalytic enantioselective Staudinger reactions that preferentially furnish trans β-lactams (trans = relationship of Ph to R1). The key to this method is the use of an N-triflyl protecting group for the imine. Along with serving as interesting targets in their own right, N-triflyl β-lactams readily react with nucleophiles to generate useful families of compounds, such as γ-amino alcohols and β-amino acids.
2π + 4π Cycloadditions of carbocation activated allenes

Abstract Boron trifluoride etherate opening of an allenic acetal produced an allene which was strongly activated by the α-carbocation to undergo 2π + 4β cycloaddition reactions.
Influence of polyamine architecture on the transport and topoisomerase II inhibitory properties of polyamine DNA-intercalator conjugates.

An efficient five-step synthetic method was developed to access a series of spermine derivatives containing appended acridine, anthracene, and 7-chloroquinoline motifs. The derivatives were composed of a spermine fragment covalently tethered at its N4 and N9 positions to an aromatic nucleus via an aliphatic chain (e.g., 8: acridine −[C4 aliphatic tether]−spermine−[C4 aliphatic tether]−acridine). The distance separating the spermine and aromatic nuclei was altered via different tethers composed of four or five methylene units. These bis ligands (8, 9, 12, and 13) were shown to inhibit human DNA topoisomerase II (topo II) activity at 5 μM. Enzymatic activity was assessed as the ability to unknot (decatenate) and cleave kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the acridine−spermine conjugates 8 and 9 to inhibit topo II activity as compared with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 5 μM). The parent polyamines, spermine (5 μM) and spermidine (10 μM...
Single-Cell Analysis Reveals Regional Reprogramming During Adaptation to Massive Small Bowel Resection in Mice

Background & Aims The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or “adapt”; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS. Methods Single-cell RNA sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH. Results Uniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factor Creb3l3 drive proximalization of cell identity in response to SBR. Conclusions Adaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes—conceivably by engaging the retinoid metabolism pathway—merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS.
1-(Azidomethyl)benzotriazole and -5-phenyl-1,2,3,4-tetrazole as 1, 3-dipolar cycloaddition components

1-(Azidomethyl)benzotriazole reacts with alkynes to give mixtures of isomeric 1,2,3-triazoles, whereas the interactions of 1-(azidomethyl)benzotriazole and -5-phenyl-1,2,3,4-tetrazole with alkenes proceed regioselectively to form 1,2,3-triazolines and/or aziridines and enamines in good yields. Diheterocyclosubstituted methanes thus obtained were investigated with respect to thermolysis, α-lithiation, and reactions with Grignard reagents.
Synthesis of 4-Cyano Pyrroles via Mild Knorr Reactions with β-Ketonitriles

Mild methods for conducting Knorr chemistry with β-ketonitriles were developed. This enabled the preparation of 4-cyano-penta-substituted pyrroles and gave access to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators for biological evaluation. In addition, a series of alkyl and aryl β-ketonitriles were employed in Knorr cyclizations to probe steric tolerance and the possibility of direct introduction of aromatic moieties via Knorr chemistry.
Efficiency versus convergence of Boolean kernels for on-line learning algorithms

The paper studies machine learning problems where each example is described using a set of Boolean features and where hypotheses are represented by linear threshold elements. One method of increasing the expressiveness of learned hypotheses in this context is to expand the feature set to include conjunctions of basic features. This can be done explicitly or where possible by using a kernel function. Focusing on the well known Perceptron and Winnow algorithms, the paper demonstrates a tradeoff between the computational efficiency with which the algorithm can be run over the expanded feature space and the generalization ability of the corresponding learning algorithm. We first describe several kernel functions which capture either limited forms of conjunctions or all conjunctions. We show that these kernels can be used to efficiently run the Perceptron algorithm over a feature space of exponentially many conjunctions; however we also show that using such kernels, the Perceptron algorithm can provably make an exponential number of mistakes even when learning simple functions. We then consider the question of whether kernel functions can analogously be used to run the multiplicative-update Winnow algorithm over an expanded feature space of exponentially many conjunctions. Known upper bounds imply that the Winnow algorithm can learn Disjunctive Normal Form (DNF) formulae with a polynomial mistake bound in this setting. However, we prove that it is computationally hard to simulate Winnow's behavior for learning DNF over such a feature set. This implies that the kernel functions which correspond to running Winnow for this problem are not efficiently computable, and that there is no general construction that can run Winnow with kernels.