cssi/SciSciGPT-SciSciNet huggingface dataset:
On the Optimality of Ergodic Trajectories for Information Gathering Tasks

Recently, ergodic control has been suggested as a means to guide mobile sensors for information gathering tasks. In ergodic control, a mobile sensor follows a trajectory that is ergodic with respect to some information density distribution. A trajectory is ergodic if time spent in a state space region is proportional to the information density of the region. Although ergodic control has shown promising experimental results, there is little understanding of why it works or when it is optimal. In this paper, we study a problem class under which optimal information gathering trajectories are ergodic. This class relies on a submodularity assumption for repeated measurements from the same state. It is assumed that information available in a region decays linearly with time spent there. This assumption informs selection of the horizon used in ergodic trajectory generation. We support our claims with a set of experiments that demonstrate the link between ergodicity, optimal information gathering, and submodularity.
Coulomb log for conductivity of dense plasmas

The Coulomb log (log Λ) approximation is widely used to approximate electron transport coefficients in dense plasmas. It is a classical approximation to the momentum transport cross section. The accuracy of this approximation for electrical conductivity in dense plasmas is assessed by comparing to fully quantum mechanical calculations for realistic scattering potentials. It is found that the classical approximation is accurate to ±10% when log Λ > 3, irrespective of the plasma species. The thermodynamic regime (density and temperature) for which log Λ > 3 corresponds to does, however, strongly depend on the material. For increasing Z, log Λ is greater than 3 for increasingly high temperatures and lower densities.
Tunable quantum Hall edge conduction in bilayer graphene through spin-orbit interaction

Bilayer graphene, in the presence of a one-sided spin-orbit interaction (SOI) induced by a suitably chosen substrate, is predicted to exhibit unconventional Quantum Hall states. The new states arise due to strong SOI-induced splittings of the eight zeroth Landau levels, which are strongly layer-polarized, residing fully or partially on one of the two graphene layers. In particular, an Ising SOI in the meV scale is sufficient to invert the Landau level order between the $n=0$ and $n=1$ orbital levels under moderately weak magnetic fields $B \lesssim 10$T. Furthermore, when the Ising field opposes the $B$ field, the order of the spin-polarized levels can also be inverted. We show that, under these conditions, three different compensated electron-hole phases, with equal concentrations of electrons and holes, can occur at $\nu = 0$ filling. The three phases have distinct edge conductivity values. One of the phases is especially interesting, since its edge conduction can be turned on and off by switching the sign of the interlayer bias.
PHASELESS SUBSPACE TRACKING

This work takes the first steps towards solving the "phaseless subspace tracking" (PST) problem. PST involves recovering a time sequence of signals (or images) from phaseless linear projections of each signal under the following structural assumption: the signal sequence is generated from a much lower dimensional subspace (than the signal dimension) and this subspace can change over time, albeit gradually. It can be simply understood as a dynamic (time-varying subspace) extension of the low-rank phase retrieval problem studied in recent work.
The business of educating the next generation of surgeons

Surgical education community needs to be informed about how education is funded and how it is threatened. In order to explore these issues the Association of Surgical Education convened a panel with significant experience in managing surgery departments to discuss the business of surgical education. They specifically addressed methods to recognize and reward faculty, educate residents on safety, quality and cost, and increase departmental revenue. This information is important in the current educational environment where there is an increased need for institutions to find alternate revenue streams to sustain graduate medical education. It is also important to find additional revenue streams to fund new residency slots to accommodate the greater number medical students who have been admitted to medical schools in response to meet the projected shortage of physicians.
Discovery of a periosteal stem cell mediating intramembranous bone formation

Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear1–5. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway4, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions. A periosteal stem cell specialized in intramembranous bone formation has been identified and was found to be essential for normal bone development and fracture healing.
Sublinear time low-rank approximation of distance matrices

Let Ƥ = {p1, p2, . . .pn} and Q = {q1, q2 . . . qm} be two point sets in an arbitrary metric space. Let A represent the m × n pairwise distance matrix with Ai.j = d(pi, qj). Such distance matrices are commonly computed in software packages and have applications to learning image manifolds, handwriting recognition, and multi-dimensional unfolding, among other things. In an attempt to reduce their description size, we study low rank approximation of such matrices. Our main result is to show that for any underlying distance metric d, it is possible to achieve an additive error low rank approximation in sublinear time. We note that it is provably impossible to achieve such a guarantee in sublinear time for arbitrary matrices A, and our proof exploits special properties of distance matrices. We develop a recursive algorithm based on additive projection-cost preserving sampling. We then show that in general, relative error approximation in sublinear time is impossible for distance matrices, even if one allows for bicriteria solutions. Additionally, we show that if Ƥ = Q and d is the squared Euclidean distance, which is not a metric but rather the square of a metric, then a relative error bicriteria solution can be found in sublinear time. Finally, we empirically compare our algorithm with the singular value decomposition (SVD) and input sparsity time algorithms. Our algorithm is several hundred times faster than the SVD, and about 8-20 times faster than input sparsity methods on real-world and and synthetic datasets of size 108. Accuracy-wise, our algorithm is only slightly worse than that of the SVD (optimal) and input-sparsity time algorithms.
Object-Centered Image Stitching

Image stitching is typically decomposed into three phases: registration, which aligns the source images with a common target image; seam finding, which determines for each target pixel the source image it should come from; and blending, which smooths transitions over the seams. As described in [1], the seam finding phase attempts to place seams between pixels where the transition between source images is not noticeable. Here, we observe that the most problematic failures of this approach occur when objects are cropped, omitted, or duplicated. We therefore take an object-centered approach to the problem, leveraging recent advances in object detection [2, 3, 4]. We penalize candidate solutions with this class of error by modifying the energy function used in the seam finding stage. This produces substantially more realistic stitching results on challenging imagery. In addition, these methods can be used to determine when there is non-recoverable occlusion in the input data, and also suggest a simple evaluation metric that can be used to evaluate the output of stitching algorithms.
Combinatorial Approach for Complex Disorder Prediction: Case Study of Neurodevelopmental Disorders.

Early prediction of complex disorders (e.g., autism and other neurodevelopmental disorders) is one of the fundamental goals of precision medicine and personalized genomics. An early prediction of complex disorders can improve the prognosis, increase the effectiveness of interventions and treatments, and enhance the life quality of affected patients. Considering the genetic heritability of neurodevelopmental disorders, we are proposing a novel framework for utilizing rare coding variation for early prediction of these disorders in subset of affected samples. We provide a combinatorial framework for addressing this problem, denoted as Odin ( O racle for DI sorder predictio N ), to make a prediction for a small yet significant subset of affected cases while having very low false positive rate prediction for unaffected samples. Odin also takes advantage of the available functional information (e.g., pairwise coexpression of genes during brain development) to increase the prediction power beyond genes with recurrent variants. Application of our method accurately recovers an additional 8% of autism cases without any severe variant in known recurrent mutated genes with a less than 1% false positive rate. Furthermore, Odin predicted a set of 391 genes that severe variants in these genes can cause autism or other developmental delay disorders. Approaches such as the one presented in this paper are needed to translate the biomedical discoveries into actionable items by clinicians. Odin is publicly available at https://github.com/HormozdiariLab/Odin
Pre-crowdsourcing: Predicting wireless propagation with phone-based channel quality measurements

Abstract Conducting in-field performance analysis for wireless carrier coverage and capacity is extremely costly in terms of equipment, manpower, and time. At the same time, there is a growing number of opportunities for crowdsourcing of network and sensor information via smart applications, firmware, and cellular standards. These facilities offer carriers feedback about user-perceived wireless channel quality. Crowdsourcing provides the ability to rapidly collect feedback with dense levels of penetration using client smartphones. However, mobile phones often fail to capture the fidelity and high sampling rates of more-advanced equipment (e.g., a channel scanner) used when drive testing for analysis of propagation characteristics. In this work, we quantify the impact of various effects induced by mobile phones when interpreting signal quality such as averaging over multiple samples, imprecise quantization, and non-uniform and/or less frequent channel sampling. To do so, we conduct extensive in-field experiments across heterogeneous devices and environments to empirically characterize the path loss via phone measurements on LTE networks. We find that mobile phones are comparable to advanced equipment in inferred radio propagation, within 0.1 of the calculated path loss exponent by the channel scanner across downtown, single-family, and multi-family residential areas. Lastly, we develop an intuition for the importance crowdsourcing-based propagation prediction by evaluating the effect on coverage estimation when deploying operational networks. For example, we find that even a prediction error of 0.4 for the path loss exponent would cause a 40% redundancy in the covered area or coverage holes for 25% of the targeted area based on whether the error was above or below the actual value, respectively.
Program Synthesis using Abstraction Refinement

We present a new approach to example-guided program synthesis based on counterexample-guided abstraction refinement. Our method uses the abstract semantics of the underlying DSL to find a program $P$ whose abstract behavior satisfies the examples. However, since program $P$ may be spurious with respect to the concrete semantics, our approach iteratively refines the abstraction until we either find a program that satisfies the examples or prove that no such DSL program exists. Because many programs have the same input-output behavior in terms of their abstract semantics, this synthesis methodology significantly reduces the search space compared to existing techniques that use purely concrete semantics.
Bonsai: Synthesis-Based Reasoning for Type Systems

We describe algorithms for symbolic reasoning about executable models of type systems, supporting three queries intended for designers of type systems. First, we check for type soundness bugs and synthesize a counterexample program if such a bug is found. Second, we compare two versions of a type system, synthesizing a program accepted by one but rejected by the other. Third, we minimize the size of synthesized counterexample programs.
Predicting combined effects of land use and climate change on river and stream salinity

Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I devel...
The Association between the Change in Directly Measured Cardiorespiratory Fitness across Time and Mortality Risk.

Abstract Background The relationship between cardiorespiratory fitness (CRF) and mortality risk has typically been assessed using a single measurement, though some evidence suggests the change in CRF over time influences risk. This evidence is predominantly based on studies using estimated CRF (CRFe). The strength of this relationship using change in directly measured CRF over time in apparently healthy men and women is not well understood. Purpose To examine the association of change in CRF over time, measured using cardiopulmonary exercise testing (CPX), with all-cause and disease-specific mortality and to compare baseline and subsequent CRF measurements as predictors of all-cause mortality. Methods Participants included 833 apparently healthy men and women (42.9 ± 10.8 years) who underwent two maximal CPXs, the second CPX being ≥1 year following the baseline assessment (mean 8.6 years, range 1.0 to 40.3 years). Participants were followed for up to 17.7 (SD 11.8) years for all-cause-, cardiovascular disease- (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (CPX1) peak oxygen consumption (VO2peak [mL·kg−1·min−1]) – visit 2 (CPX2) VO2peak, and mortality outcomes. A Wald-Chi square test of equality was used to compare the strength of CPX1 to CPX2 VO2peak in predicting mortality. Results During follow-up, 172 participants died. Overall, the change in CPX-CRF was inversely related to all-cause, CVD, and cancer mortality (p Conclusion The change in CRF over time was inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent test than CPX1 CRF. These findings emphasize the importance of adopting lifestyle behaviors that promote CRF, as well as support the need for routine assessment of CRF in clinical practice to better assess risk.
Different SUMO paralogues determine the fate of wild-type and mutant CFTRs: biogenesis versus degradation.

Degradation of the common CFTR mutant, F508del, by endoplasmic reticulum quality control can proceed via its conjugation to SUMO-2/3 and the SUMO-targeted ubiqutin ligase, RNF4. In contrast, the SU...
Ethanol activates immune response in lymphoblastoid cells.

Abstract The short-term effects of alcohol on gene expression in brain tissue cannot directly be studied in humans. Because neuroimmune signaling is altered by alcohol, immune cells are a logical, accessible choice to study and may provide biomarkers. RNAseq was used to study the effects of 48-h exposure to ethanol on lymphoblastoid cell lines (LCLs) from 20 alcoholic subjects and 20 control subjects. Ethanol exposure resulted in differential expression of 4456 of the 12,503 genes detectably expressed in the LCLs (FDR [false discovery rate] ≤ 0.05); 52% of these showed increased expression. Cells from alcoholic subjects and control subjects responded similarly. The genes whose expression changed fell into many pathways: NFκB, neuroinflammation, IL6, IL2, IL8, and dendritic cell maturation pathways were activated, consistent with increased signaling by NFκB, TNF, IL1, IL4, IL18, TLR4, and LPS. Signaling by Interferons A and B decreased, as did EIF2 signaling, phospholipase C signaling, and glycolysis. Baseline gene expression patterns were similar in LCLs from alcoholic subjects and control subjects. At relaxed stringency (p LCLs show many effects of ethanol exposure, some of which might provide biomarkers for alcohol use disorders. Identifying genes and pathways altered by ethanol can aid in interpreting which genes within loci identified by GWAS might play functional roles.
Intergenerational Mobility in Slums: Evidence from a Field Survey in Jakarta

Slums are central to the global debate on inequality, serving as entry points for people moving to cities in search of economic opportunity. Yet we know little about the extent of intergenerational...
Finding maximal 2-dimensional palindromes

Abstract This paper extends the problem of palindrome searching into a higher dimension, addressing two definitions of 2D palindromes. The first definition implies a square, while the second definition (also known as a centrosymmetric factor) can be any rectangular shape. We present a linear time algorithm for locating all maximal square 2D palindromes in a given 2D text. For the second definition of palindromes (rect2DP), we present two different algorithms. Given a text of size n × n , the first algorithm has time O ( n 3 ) , which is linear in the worst case output size. The second algorithm has time O ( n 2 log ⁡ n + o c c log ⁡ n ) , where occ is the number of maximal rect2DP in the output. This provides a tradeoff in terms of output size; if the output size is small, the second algorithm is preferable, while the first would be more efficient if the output size is Θ ( n 3 ) .
Engineering and Informatics Student Multidisciplinary Learning using 3D Visualization and 3D Display of Radio Frequency (RF) Concepts

This full paper addresses the Innovative Practice Category. We discuss our multidisciplinary approach to create a truly 3D representation and 3D display of RF signals in space through the development of two different training tools to enhance student understanding of Radio Communications. Both tools show the data on 3D autostereoscopic displays rather than rendered back to 2D displays. The first new tool is a series of 3D stereoscopic animations created by a multidisciplinary team of students from the Media Arts and Sciences (School of Informatics) and Electrical Engineering (School of Engineering) programs for use with an autostereoscopic display, where each animation focuses on a single topic within RF communication learning, using real-world examples. The second innovative tool models the Navy use-case of Electronic Warfare (EW) using examples with 3D antenna radiation patterns of signal propagation using U.S. Navy’s SIMDIS interactive 3D visualization environment. The developed scenarios are displayed on an autostereoscopic display, allowing students to manipulate RF signals in a 3D environment. Learning gains were assessed via a 2x2 crossover experimental design an engineering student group. Compared to the control group, students showed gains in understanding of the 3D shape of dipole antennas and understanding of the multiple RF antennas in a cell phone, and the connections between mobile phone antennas and cell towers. The results from these interventions collectively indicate that a truly 3D representation in space can be used to enhance students’ understanding of antennas and RF signals.
Luciferase-LOV BRET enables versatile and specific transcriptional readout of cellular protein-protein interactions

Technologies that convert transient protein-protein interactions (PPIs) into stable expression of a reporter gene are useful for genetic selections, high-throughput screening, and multiplexing with omics technologies. We previously reported SPARK (Kim et al., 2017), a transcription factor that is activated by the coincidence of blue light and a PPI. Here, we report an improved, second-generation SPARK2 that incorporates a luciferase moiety to control the light-sensitive LOV domain. SPARK2 can be temporally gated by either external light or addition of a small-molecule luciferin, which causes luciferase to open LOV via proximity-dependent BRET. Furthermore, the nested 'AND' gate design of SPARK2-in which both protease recruitment to the membrane-anchored transcription factor and LOV domain opening are regulated by the PPI of interest-yields a lower-background system and improved PPI specificity. We apply SPARK2 to high-throughput screening for GPCR agonists and for the detection of trans-cellular contacts, all with versatile transcriptional readout.
Depletion of Limiting rDNA Structural Complexes Triggers Chromosomal Instability and Replicative Aging of Saccharomyces cerevisiae

Sir2 is a highly conserved NAD+-dependent histone deacetylase that functions in heterochromatin formation and promotes replicative life span (RLS) in the budding yeast, Saccharomyces cerevisiae Within the yeast rDNA locus, Sir2 is required for efficient cohesin recruitment and maintaining the stability of the tandem array. In addition to the previously reported depletion of Sir2 in replicatively aged cells, we discovered that subunits of the Sir2-containing complexes silent information regulator (SIR) and regulator of nucleolar silencing and telophase (RENT) were depleted. Several other rDNA structural protein complexes also exhibited age-related depletion, most notably the cohesin complex. We hypothesized that mitotic chromosome instability (CIN) due to cohesin depletion could be a driver of replicative aging. Chromatin immunoprecipitation assays of the residual cohesin (Mcd1-Myc) in moderately aged cells showed strong depletion from the rDNA and initial redistribution to the point centromeres, which was then lost in older cells. Despite the shift in cohesin distribution, sister chromatid cohesion was partially attenuated in aged cells and the frequency of chromosome loss was increased. This age-induced CIN was exacerbated in strains lacking Sir2 and its paralog, Hst1, but suppressed in strains that stabilize the rDNA array due to deletion of FOB1 or through caloric restriction. Furthermore, ectopic expression of MCD1 from a doxycycline-inducible promoter was sufficient to suppress rDNA instability in aged cells and to extend RLS. Taken together, we conclude that age-induced depletion of cohesin and multiple other nucleolar chromatin factors destabilize the rDNA locus, which then results in general CIN and aneuploidy that shortens RLS.
Phonon-mediated quantum state transfer and remote qubit entanglement

Phonons, and in particular surface acoustic wave phonons, have been proposed as a means to coherently couple distant solid-state quantum systems. Individual phonons in a resonant structure can be controlled and detected by superconducting qubits, enabling the coherent generation and measurement of complex stationary phonon states. We report the deterministic emission and capture of itinerant surface acoustic wave phonons, enabling the quantum entanglement of two superconducting qubits. Using a 2-millimeter-long acoustic quantum communication channel, equivalent to a 500-nanosecond delay line, we demonstrate the emission and recapture of a phonon by one superconducting qubit, quantum state transfer between two superconducting qubits with a 67% efficiency, and, by partial transfer of a phonon, generation of an entangled Bell pair with a fidelity of 84%.
An unusual arteriovenous malformation involving the cervical vessels treated with endovascular repair.

Abstract We present an unusual and complex arteriovenous malformation involving the vertebral artery, subclavian artery, and internal jugular vein in a 31-year-old man with no history of trauma or catheterization. The repair was done using endovascular techniques to minimize complications from nerve or vascular injury. The massively dilated jugular vein has remained diminished in size and the patient has remained asymptomatic at 8 months. We discuss the occurrence of this rare malformation as well as treatment options along with their risks and benefits.
Sorption and Transport of Vapors in ZIF-11: Adsorption, Diffusion, and Linker Flexibility

The adsorption and diffusion of alcohol and hydrocarbon vapors in zeolitic imidazolate frameworks (ZIF)-11 are reported as a function of loading at 308 K. The hydrophobicity of the benzimidazole li...
Zakat: Islam’s missed opportunity to limit predatory taxation

One of Islam’s five canonical pillars is a predictable, fixed, and mildly progressive tax system called zakat. It was meant to finance various causes typical of a pre-modern government. Implicit in the entire transfer system was personal property rights as well as constraints on government—two key elements of a liberal order. Those features could have provided the starting point for broadening political liberties under a state with explicitly restricted functions. Instead, just a few decades after the rise of Islam, zakat opened the door to arbitrary political rule and material insecurity. A major reason is that the Quran does not make explicit the underlying principles of governance. It simply outlines the specifics of zakat as they related to conditions in seventh-century Arabia.
Nanosecond mid-infrared pulse generation via modulated thermal emissivity

We demonstrate the generation of nanosecond mid-infrared pulses via fast modulation of thermal emissivity enabled by the absorption of visible pump pulses in unpatterned silicon and gallium arsenide. The free-carrier dynamics in these materials result in nanosecond-scale modulation of thermal emissivity, which leads to nanosecond pulsed thermal emission. To our knowledge, the nanosecond thermal-emissivity modulation in this work is three orders of magnitude faster than what has been previously demonstrated. We also indirectly observed subnanosecond thermal pulses from hot carriers in semiconductors. The experiments are well described by our multiphysics model. Our method of converting visible pulses into the mid infrared using modulated emissivity obeys different scaling laws and can have significant wavelength tunability compared to approaches based on conventional nonlinearities. American scientists have created ultrafast pulses of infrared radiation from the surface of two semiconducting materials for use in a range of new applications in optical communications, spectroscopy, and sensing. Fast pulses of light in the visible and near-infrared range have seen use in a variety of applications, including telecommunications and materials processing. However, generating pulses in the mid-infrared range has proved challenging as existing techniques require complex and expensive equipment that produce low-power pulses with limited tunability. Now, Yuzhe Xiao, Mikhail Kats, and colleagues from the University of Wisconsin–Madison and the Naval Research Laboratory in the United States have produced ultrafast mid-infrared light pulses that are highly tunable. By pumping the semiconductors silicon and gallium arsenide with visible light, the researchers were able to generate nanosecond pulsed thermal emission from their surfaces.
A novel and efficient synthesis of 2,5-substituted 1,2,4-triazol-3-ones

Abstract A novel procedure for preparing 1,2,4-triazol-3-ones is described. Various alkyl, aryl, and heterocyclic groups were introduced successfully at both the N2 and C5 positions. The triazolone ring was constructed through an intramolecular cyclization of a novel acyclic precursor, which in turn was synthesized by treating a mono protected hydrazine with an acyl isocyanate. Under conditions that remove the hydrazine protecting group, the intramolecular cyclization occurs rapidly, to deliver the 2,5-substituted 1,2,4-triazol-3-ones in excellent yields (79–99%) without column purification.
EXPERIMENTAL AND THEORETICAL INVESTIGATIONS OF RING-EXPANSION IN 1 -METHYLCYCLOPROPYLCARBENE

1-Methylcyclopropylcarbene, generated by photolysis of two isomeric hydrocarbon precursors, undergoes ring-expansion readily to give 1-methylcyclobutene. Experimentally, intramolecular carbon−hydrogen insertions are not observed. Trapping studies with TME demonstrates the formation of the expected cyclopropane adduct, and via a double-reciprocal analysis, the lifetime of 1-methylcyclopropylcarbene was determined to be 12 ns in 1,1,2-trichlorotrifluoroethane. Computational studies show that the barrier to ring-expansion is significantly smaller in 1-methylcyclopropylcarbene than in cyclopropylcarbene. The origin of the increased rate of ring-expansion is due to stabilization of the positive charge that occurs at the incipient tertiary carbon that is attached to the migrating carbon center.
DFT Study of Pericyclic Reaction Cascades in the Synthesis of Antibiotic TAN-1085

DFT calculations show that aromatic and bis-methoxy substituent effects in a synthetic precursor of TAN-1085 strongly favor a [1,7] sigmatropic hydrogen shift over the 6π electrocyclic pathway, rendering the latter unfavorable in synthesis.
Activation of Functional Arylzincs Prepared from Aryl Iodides and Highly Enantioselective Addition to Aldehydes

An easily available chiral ligand ( S)- 1 is found to activate the nucleophilic reaction of the arylzincs prepared in situ from the reaction of aryl iodides with Et(2)Zn. Both high yields and high enantioselectivity (up to >99% ee) for the reaction of these arylzincs with a variety of aldehydes are obtained. The mild reaction conditions and the good functional group tolerance make this catalytic asymmetric process synthetically useful.
Provable Security of S-BGP and other Path Vector Protocols: Model, Analysis and Extensions.

This paper provides the provable-security treatment of path vector routing protocols. We first design a security definition for routing path vector protocols by studying, generalizing, and formalizing numerous known threats. Our model incorporates three major security goals. It is quite strong, yet simple to use. We prove by reduction that S-BGP satisfies two out of the security model’s three goals, assuming the underlying signature scheme is secure. Under the same assumption, we next show how the protocol can be modified to meet all three security goals simultaneously. We also analyze SoBGP and show that it fails to meet two security goals. Finally, we study security of partial PKI deployment of path vector protocols when not all nodes have public keys. We investigate the possibilities of relaxing the PKI requirement and relying on non-cryptographic physical security of networks that use the protocol in order to achieve possibly weaker, but still well-defined, notions of security. We also present the necessary and sufficient conditions to achieve full security in the partial PKI deployment scenario. We believe our conclusions will prove useful for protocol developers, standards bodies and government agencies.
17O NMR spectroscopy: Intramolecular hydrogen bonding in hydroxypyridine carboxy esters

Natural abundance 17O nmr chemical shift data for 8 aryl esters and 10 pyridine carboxy esters, including 6 ortho-hydroxy esters, recorded in acetomitrile at 75° are reported. The carbonyl group 17O nmr chemical shift data for methyl 2-, 3- and 4-pyridinecarboxylate are correlated with σ+ constants. The hydrogen bonding component (ΔδHB) to the ester carbonyl 17O nmr chemical shift for the intramolecular hydrogen bonded ortho-hydroxy systems are 9.8 ppm, 13.6 ppm and 4.3 ppm for benzoates, 2-pyridinecarboxylates and 4-pyridinecarboxylates, respectively. The relationships of the ester ΔδHB values to other hydrogen bond acceptor ΔδHB values are discussed.
Dynamics of fast reactions in ionic liquids

Pulse radiolysis and laser flash photolysis are complementary tools for studying fast reactions in ionic liquids. Both techniques have been used to study solvation processes in quaternary ammonium ionic liquids, which extend into the nanosecond regime and influence the reactivity and energetics of radiolytically-generated excess electrons. The preparation and properties of ionic liquid families designed to further these studies is reported.
Two‐Step Novel Synthesis of 2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐4,7‐diphenyloxepine‐3‐carbonitrile and 5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐6‐phenyl‐2H‐pyran‐3‐carbonitrile

Abstract Starting from indan‐1,3‐dione, a novel two‐step synthesis of the oxepine derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction conditions is described.
Competitive free radical 4‐nitrophenylation of pyridine and thiophene

Competitive free radical 4-nitrophenylation of pyridine and thiophene shows a relative reactivity of thiophene:pyridine of 1.3:1 as based on product isolation. A three-center reaction is proposed to account for the predominance of alpha substitution in each system. Column chromatography and 1 H nmr are used for separation and identification of products
Membrane bending occurs at all stages of clathrin-coat assembly and defines endocytic dynamics.

Clathrin-mediated endocytosis (CME) internalizes plasma membrane by reshaping small regions of the cell surface into spherical vesicles. The key mechanistic question of how coat assembly produces membrane curvature has been studied with molecular and cellular structural biology approaches, without direct visualization of the process in living cells; resulting in two competing models for membrane bending. Here we use polarized total internal reflection fluorescence microscopy (pol-TIRF) combined with electron, atomic force, and super-resolution optical microscopy to measure membrane curvature during CME. Surprisingly, coat assembly accommodates membrane bending concurrent with or after the assembly of the clathrin lattice. Once curvature began, CME proceeded to scission with robust timing. Four color pol-TIRF showed that CALM accumulated at high levels during membrane bending, implicating its auxiliary role in curvature generation. We conclude that clathrin-coat assembly is versatile and that multiple membrane-bending trajectories likely reflect the energetics of coat assembly relative to competing forces. Two distinct and opposing models for clathrin-mediated endocytosis have been inferred from EM and structural biology data. Here the authors develop an optical method to directly visualize membrane-bending dynamics and show that coat assembly accommodates membrane bending during or after the assembly of the clathrin lattice, which is not predicted by either model.
1,3,5-Trisubstituted aryls as highly selective PPARδ agonists

Abstract A series of highly potent and selective PPARδ agonists is described using the known non-selective ligand GW2433 as a structural template. Compound 1 is bioavailable, potent (10 nM), and shows no cross-activity with other PPAR subtypes up to 10 μM, making it a useful tool in studying the biological effects of selective PPARδ activation.
The reaction of [60]fullerene with 2-diazo-4,5-dicyanoimidazole

Abstract The reaction of [60]fullerene with 2-diazo-4,5-dicyanoimidazole affords new compound 4 which contains an electron poor aromatic heterocycle attached to the fullerene sphere.
Development of New Bioreactor Systems and Their Applications in the Chiral Industry

The D-p-hydroxyphenylglycine (D-HPG) production process from DL-5-p-hydroxyphenylhydantoin by a combination of two immobilized enzymes, hydantoinase and N-carbamoyl-D-amino acid amidohydrolase (DCase), was established. A hydantoinase obtained from a thermophilic bacterium and a DCase from a mesophilic bacterium improved the thermostability by a protein engineering technique. The latter enzyme could be used over 700 times as a bioreactor. An enzymatic reduction system was developed to produce optically active alcohols from the corresponding carbonyl compounds. Effective production of ethyl (S) -4-chloro-3-hydroxybutyrate was achieved by the use of the recombinant Escherichia coli that was co-harbored in the genes of a carbonyl reductase (S1) from Candida magnoliae and glucose dehydrogenase from Bacillus megaterium, in high productivity (350 g/l, over 99% e.e.). Successful change in the cofactor dependency of S1, from NADPH to NADH, was accomplished highly efficiently by the use of in silico screening.
New palladium(II)-catalyzed asymmetric 1,2-dibromo synthesis.

The oxidation of olefins by chiral monometallic and bimetallic Pd(II)−Cu(II) catalysts in bromide-containing aqueous−THF reaction mixtures produced chiral 1,2-dibromides. With α-olefins, the ee's were about 95% while most of the internal alkenes gave somewhat lower enantioselectivities (∼80%).
Computer Simulations Predict High Structural Heterogeneity of Functional State of NMDA Receptors.

N-methyl-D-aspartate receptors (NMDARs)-i.e., transmembrane proteins expressed in neurons-play a central role in the molecular mechanisms of learning and memory formation. It is unclear how the known atomic structures of NMDARs determined by x-ray crystallography and electron cryomicroscopy (18 published Protein Data Bank entries) relate to the functional states of NMDARs inferred from electrophysiological recordings (multiple closed, open, preopen, etc. states). We address this problem by using molecular dynamics simulations at atomic resolution, a method successfully applied in the past to much smaller biomolecules. Our simulations predict that several conformations of NMDARs with experimentally determined geometries, including four "nonactive" electron cryomicroscopy structures, rapidly interconvert on submicrosecond timescales and therefore may correspond to the same functional state of the receptor (specifically, one of the closed states). This conclusion is not trivial because these conformational transitions involve changes in certain interatomic distances as large as tens of A. The simulations also predict differences in the conformational dynamics of the apo and holo (i.e., agonist and coagonist bound) forms of the receptor on the microsecond timescale. To our knowledge, five new conformations of NMDARs, with geometries joining various features from different known experimental structures, are also predicted by the model. The main limitation of this work stems from its limited sampling (30 μs of aggregate length of molecular dynamics trajectories). Though this level significantly exceeds the sampling in previous simulations of parts of NMDARs, it is still much lower than the sampling recently achieved for smaller biomolecules (up to a few milliseconds), thus precluding, in particular, the observation of transitions between different functional states of NMDARs. Despite this limitation, such computational predictions may guide further experimental studies on the structure, dynamics, and function of NMDARs, for example by suggesting optimal locations of spectroscopic probes. Overall, atomic resolution simulations provide, to our knowledge, a novel perspective on the structure and dynamics of NMDARs, complementing information obtained by experimental methods.
Templated Synthesis of Interlocked Molecules

Mechanically interlocked molecular compounds can be synthesized in high yields by using template-directed assistance to covalent synthesis. Catenanes and rotaxanes are two classes of mechanically interlocked molecules that have been prepared using a variety of methods such as “clipping”,“slipping”, and “threading-followed-by-stoppering”, under both kinetic and thermodynamic regimes. These different methods have utilized a range of templates such as transistion metals, p-donor/p-acceptors, and hydrogen-bonding motifs. Multivalency has emerged as another tool to aid and abet the supramolecularly assisted synthesis of mechanically interlocked molecules. Recent advances in our understanding of the nature of the mechanical bond has led to the construction of molecular machines with controllable motions that have, in one instance, been introduced into molecular electronic devices.
Total synthesis of novel 6-substituted lavendamycin antitumor agents

[structure: see text] Novel 6-substituted lavendamycins have been synthesized for the first time. The key step in these syntheses is a Pictet-Spengler condensation (Scheme 1). Efficient methods for the synthesis of each compound, including a novel reaction for the facile introduction of alkylamino groups at the C-6 position of the lavendamycin system, are discussed. Possible mechanisms for these reactions are also presented.
Synthesis and structural characterization of dense polycrystalline Mg9Sn5, a metastable Mg–Sn phase

Abstract We present a method for synthesizing bulk dense polycrystalline Mg 9 Sn 5 , a phase that is related to the familiar Mg 2 Sn phase but is metastable at ambient pressure and temperature. Our procedure requires significantly lower temperatures and pressures, which are in the 100 MPa range compared to the previously reported methods that required pressures in the GPa range. We used a combination of high energy ball milling and current activated pressure assisted densification (CAPAD) to synthesize and retain the high pressure phase in a bulk (low porosity) form. We show the effect of CAPAD processing temperature and pressure on the density and phase composition of the material. We also present the first neutron diffraction study to confirm phase identity and refine the structure of Mg 9 Sn 5 .
Synthesis and characterization of a new 5-thiol-protected deoxyuridine phosphoramidite for site-specific modification of DNA.

A new nucleotide analogue was developed for site-specific incorporation of a reactive thiol group into DNA. This creates a unique site for the post-synthetic modification of that nucleotide with a variety of molecular tags, such as photo-cross-linkers and fluorescent or spin−label moieties. 5‘-O-(4,4‘-Dimethoxytrityl)-5-[S-(2,4-dinitrophenyl)thio]-2‘-deoxyuridine 3‘-O-(2-cyanoethyl N,N‘-diisopropylphosphoramidite) was synthesized and incorporated at internal positions in several oligonucleotides using automated DNA synthesis and standard phosphoramidite chemistry. The coupling yield of the analogue was comparable to the coupling yield for a standard phosphoramidite, and no significant differences were observed in the overall yields of the dinitrophenyl-labeled oligonucleotides compared to the corresponding unmodified oligonucleotides. Characterization of the dinitrophenyl-modified oligonucleotides included enzymatic degradation, HPLC chromatography, and gel electrophoresis. Deprotection of the mercaptan g...
Synthesis of vinyl glycosides and carbohydrate vinyl ethers from mixed acetals: a hetero-Diels–Alder approach to deoxygenated disaccharides

Abstract A new method for the synthesis of vinyl glycosides and carbohydrate vinyl ethers is described. Mixed acetal glycosides and other types of carbohydrate mixed acetals are treated with TMS-triflate and an amine base, conditions developed by Gassman for the synthesis of enol ethers from acetals. The elimination proceeds regioselectively in most cases but also gives silyl ethers as side products in others. The hetero-Diels–Alder reactions of carbohydrate 3- O - and 6- O -vinyl ethers with ethyl ( E )-ethoxymethylenepyruvate were carried out as part of a model study for the synthesis of deoxygenated disaccharides of antibiotics.
Imidazopyridinium and pyridopyrimidium bromides: Synthesis and hydrolysis

The reactions of symmetrical and unsymmetrical 2,2'-dipyridylamines with 1,2-dibromoethane and 1,3-dibromopropane give imidazopyridinium and pyridopyrimidium bromides, respectively. These acetone/CH 2 Cl 2 -insoluble, highly fluorescent quaternary ammonium salts undergo addition/ ring opening upon treatment with methanolic KOH to give pyridin-2-one derivatives. A sequential N,N-dialkylation/ ring-opening hydrolysis/N,N-dialkylation/ring-opening hydrolysis strategy was developed for the construction of unsymmetrical bis(pyridin-2-ones).
Inhibitory Units: An Organizing Nidus for Feature-Selective SubNetworks in Area V1.

Neuronal circuits often display small-world network architecture characterized by neuronal cliques of dense local connectivity communicating with each other through a limited number of cells that participate in multiple cliques. The principles by which such cliques organize to encode information remain poorly understood. Similarly tuned pyramidal cells that preferentially target each other may form multicellular encoding units performing distinct computational tasks. The existence of such units can reflect upon both spontaneous and stimulus-driven population events. We applied two-photon calcium imaging to study spontaneous population bursts in layer 2/3 of area V1 in male C57BL/6 mice. To identify potential small-world cliques, we searched for pyramidal cells whose calcium events had a consistent temporal relationship with the events of local inhibitory interneurons. This was guided by the intuition that groups of neurons whose synchronous firing represents a temporally coherent computational unit should be inhibited together. Pyramidal members of these interneuron-centered clusters on average displayed stronger functional connectivity between each other than with nonmember pyramidal neurons. The structure of the clusters evolved during postnatal development: cluster size and overlap between clusters decreased with developmental maturation. Pyramidal neurons in a cluster showed higher than chance tuning function similarity between each other and with the linked interneuron. Thus, spontaneous population events in V1 are shaped by small-world subnetworks of pyramidal neurons that share functional properties and work as a coherent unit with a local interneuron. These interneuron-pyramidal cell partnerships may represent a fundamental neocortical unit of computation at the population level. SIGNIFICANCE STATEMENT Neuronal circuit in layer 2/3 of mouse area V1 possesses small-world network architecture, where cliques of densely interconnected neurons (“small worlds”) communicate via restricted number of hub cells. We show that: (1) in mouse V1 individual small-world cliques preferably incorporate pyramidal neurons with similar visual feature tuning, and (2) ongoing population activity of such pyramidal neuron clique is temporally linked to the activity of the local interneuron sharing its feature tuning with the clique members. Functional grouping of similarly tuned interneurons and pyramidal cells into cliques may ensure that ensembles of functionally alike pyramidal cells recruited during perceptual tasks and spontaneous activity are also turned off together as a unit, with interneurons serving as organizers of linked pyramidal ensemble activity.