cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors

Angiogenesis is important in physiological and pathological conditions, as blood vessels provide nutrients and oxygen needed for tissue growth and survival. Therefore, targeting angiogenesis is a prominent strategy in both tissue engineering and cancer treatment. However, not all of the approaches to promote or inhibit angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation. However, pre-clinical and clinical evidence shows these therapies often have limited effects. To improve therapeutic strategies, including targeting FGF and VEGF in combination, we need a quantitative understanding of the how the promoters combine to stimulate angiogenesis. In this study, we trained and validated a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. This signaling is initiated by FGF binding to the FGF receptor 1 (FGFR1) and heparan sulfate glycosaminoglycans (HSGAGs) or VEGF binding to VEGF receptor 2 (VEGFR2) to promote downstream signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling and phosphorylation of extracellular regulated kinase (ERK), which promotes cell proliferation. We apply the model to predict the dynamics of phosphorylated ERK (pERK) in response to the stimulation by FGF and VEGF individually and in combination. The model predicts that FGF and VEGF have differential effects on pERK. Additionally, since VEGFR2 upregulation has been observed in pathological conditions, we apply the model to investigate the effects of VEGFR2 density and trafficking parameters. The model predictions show that these parameters significantly influence the response to VEGF stimulation. The model agrees with experimental data and is a framework to synthesize and quantitatively explain experimental studies. Ultimately, the model provides mechanistic insight into FGF and VEGF interactions needed to identify potential targets for pro- or anti-angiogenic therapies.
Resurfacing asteroids from thermally induced surface degradation

Abstract The spectral slopes of S and Q-type asteroids are altered by the weathering of their surfaces due to solar wind interactions and micrometeorite impacts, as well as any processes that work to remove that weathered material. These processes of space weathering and asteroid resurfacing compete with each other to determine the spectral slope of each asteroid, with space weathering raising the spectral slope and resurfacing lowering it. By considering the distribution of spectral slopes with respect to orbital location and size, we can determine which potential resurfacing processes are the most dominant. In this study, we show that the spectral slopes of S and Q-type Near-Earth Asteroids (NEAs) decrease with decreasing perihelion, but only for perihelia q ≲ 0.9 AU. We then use this distribution of spectral slopes vs. perihelion as a constraint for modeling two proposed resurfacing mechanisms. For both models, we numerically integrate the orbits of NEAs over their lifetimes and track their spectral slopes. First, we model the resurfacing of asteroids due to close encounters with the terrestrial planets and found that no combination of parameters could explain the spectral slope vs. perihelion trend at q ≲ 0.9 AU. We also model the resurfacing of asteroids due to thermally induced surface degradation, by assuming a power law relationship between the resurfacing timescale and the solar distance. For a space weathering timescale of an asteroid on a circular orbit at 1 AU of τ S W 0 ≲ 5 Myr, we find a range of resurfacing timescales and power law exponents that generate a spectral slope vs. perihelion distribution consistent with observations. We discuss that previous studies supporting the resurfacing of asteroids due to close encounters could be a result of confounding variables, as the correlation of Q-type asteroids' past orbits with the terrestrial planets are confounded by the higher fraction of Q-type asteroids at low perihelia, which could be created by another mechanism. We also discuss previous studies that qualitatively support the process of thermally induced surface degradation at low perihelia, and conclude that thermal processes are the most consistent explanation for resurfacing of asteroids with low perihelia q ≲ 0.9 AU.
Investing in Human Capital : What Can We Learn from the World Bank's Portfolio Data ?

This paper compiles project-level data from the World Bank's lending history to describe patterns and the composition of its portfolio. The paper focuses particularly on the effect of countries' transition from International Development Association to International Bank for Reconstruction and Development status, which marks the point when countries start borrowing at near market rates, on lending for human development sectors (education, health and social protection). Using country and year fixed effects, which account for unobservable country characteristics (for example, national priorities) and time effects (for example, market interest rates), the paper finds that human development lending decreases when countries graduate from the International Development Association. The average difference in the binary indicator of lending for any sector is 27 percent while it is 60 percent for human development sectors. The share of human development lending (lending by human development Global Practices over total lending) is also 6.9 percentage points (30 percent) lower. This decline in human development lending in International Bank for Reconstruction and Development countries is accompanied by a greater use of budget support. The results are robust to controlling for non-World Bank aid, as well as various alternative specifications and estimation samples.
The new convivencia

This essay offers an introduction to the recent and impassioned debates between two Spanish Arabists, Emilio Gonzalez Ferrin and Alejandro Garcia Sanjuan, about the Islamic conquest of the Iberian ...
Approximating the rectilinear crossing number

A straight-line drawing of a graph G is a mapping which assigns to each vertex a point in the plane and to each edge a straight-line segment connecting the corresponding two points. The rectilinear crossing number of a graph \(G, \text {cr}(G)\), is the minimum number of pairs of crossing edges in any straight-line drawing of G. Determining or estimating \(\overline{\mathrm{cr}}(G)\) appears to be a difficult problem, and deciding if \(\overline{\mathrm{cr}}(G)\le k\) is known to be NP-hard. In fact, the asymptotic behavior of \(\overline{\mathrm{cr}}(K_n)\) is still unknown.
Doping Dependence Of The Thermal Conductivity Of Hydride Vapor Phase Epitaxy Grown n -GaN/Sapphire (0001) Using A Scanning Thermal Microscope

We have measured the doping concentration dependence of the room temperature thermal conductivity (κ) of two series of n-GaN/sapphire (0001) fabricated by hydride vapor phase epitaxy (HVPE). In both sets κ decreased linearly with log n, the variation being about a factor two decrease in κ for every decade increase in n. κ ≈ 1.95 W/cm-K was obtained for one of the most lightly doped samples (n = 6.9×1016 cm−3), higher than the previously reported κ ≈ 1.7-1.8 W/cm-K on lateral epitaxial overgrown material [V.A. Asnin et al, Appl. Phys. Lett. 75, 1240 (1999)] and κ ≈ 1.3 W/cm-K on a thick HVPE sample [E.K. Sichel and J.I. Pankove, J. Phys. Chem. Solids 38, 330 (1977)]. The decrease in the lattice component of κ due to increased phonon scattering from both the impurities and free electrons outweighs the increase in the electronic contribution to κ.
Does maturity matter? The case of treasury futures volume

We find that Treasury futures volume contains information about future economic and financial market conditions. Short‐ and long‐term volumes are economically different: A relatively higher volume in short‐term (long‐term) Treasury futures is counter‐cyclical (procyclical), preceding worse (better) economic and financial conditions. Further, we construct a single factor from futures volumes of different maturities that forecasts the performances of Treasury securities and the corporate debt and equity markets, as well as macroeconomic conditions. Our results are consistent with the notion that futures volumes from different market segments reflect differences in beliefs and contain different information about future financial and economic activity.
Mapping Missing Population in Rural India: A Deep Learning Approach with Satellite Imagery

Millions of people worldwide are absent from their country's census. Accurate, current, and granular population metrics are critical to improving government allocation of resources, to measuring disease control, to responding to natural disasters, and to studying any aspect of human life in these communities. Satellite imagery can provide sufficient information to build a population map without the cost and time of a government census. We present two Convolutional Neural Network (CNN) architectures which efficiently and effectively combine satellite imagery inputs from multiple sources to accurately predict the population density of a region. In this paper, we use satellite imagery from rural villages in India and population labels from the 2011 SECC census. Our best model achieves better performance than previous papers as well as LandScan, a community standard for global population distribution.
Synthesis of imidazo[4,5-c]pyridines with a trifluoromethyl group at C-4 and/or C-6

Thermal condensation of histamine with trifluoroacetaldehyde gives 4- (trifluoromethyl)spinacamine and subsequent dehydrogenation with sele- nium dioxide leads to 4-(trifluoromethyl)-1H-imidazo[4,5-c]pyridine (42%). Fluorination with sulfur tetrafluoride of L-spinacine, obtained from the condensation of L-histidine with formaldehyde, affords 6-(tri- fluoromethyl)spinacamine, which can be converted to 6-(trifluoromethyl) 1H-imidazo[4,5-c]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4-(trifluoromethyl)-L-spinacine gives 4,6- bis(trifluoromethyl)1H-imidazo[4,5-c]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sul- fur tetrafluoride
Application of Palladium(0)-Catalyzed Processes to the Synthesis of Oxazole-Containing Partial Ergot Alkaloids

Syntheses of the potent 5-HT1A agonists 2 and 3 were accomplished in several steps from the 6-iodo partial ergoline alkaloid 8. Disparate tactics available for construction of differentially substituted oxazoles led to the development of new and general methodology critical to the efficient preparations of 2 and 3. A novel palladium(0)- and copper(I)-cocatalyzed cyanation reaction provided efficient access to the nitrile 10, a key intermediate in the synthesis of 2. A palladium(0)-catalyzed cross-coupling reaction of 16 with oxazol-2-ylzinc chloride formed the potent 5-HT1A agonist 3.
Cu(I)-catalyzed highly exo-selective and enantioselective [3 + 2] cycloaddition of azomethine ylides with acrylates.

A novel Cu(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with acrylates has been developed. Up to 98/2 exo/endo selectivity and up to 98% enantiomeric excess have been achi...
Crystal growth, structure, and physical properties of Ln2PdGa12 (Ln = La, Pr, Nd, and Sm)

Abstract Single crystals of Ln2PdGa12 (Ln = La, Pr, Nd, Sm) were synthesized with a molten Ga flux. The intermetallic phases are isostructural to Sm2NiGa12 with cell dimensions of a ∼ 6.1 A and c ∼ 15.5 A. Pr2PdGa12, Nd2PdGa12, and Sm2PdGa12 order antiferromagnetically at 18, 7.5, and 7.5 K, respectively, and magnetic properties of single crystals oriented parallel and perpendicular to the magnetic field are presented. Fitting the low temperature heat capacity of Pr2PdGa12 gives a Sommerfeld coefficient (γ) of 250 mJ mol−1 K−2 and indicates the possibility of heavy fermion behavior.
Asymmetric synthesis of γ-lactones through reaction of sulfoxonium ylides, aldehydes, and ketenes

Abstract A method for the enantioselective synthesis of γ-lactones through the reaction of enantioenriched sulfoxonium ylides, aldehydes, and ketenes was developed. Enantioenriched (98% ee) aminosulfoxonium ylide was subjected to reaction with a variety of aldehydes (both aromatic and aliphatic) and disubstituted ketenes, leading to the formation of α,β-substituted γ-lactones in moderate to very good diastereoselectivity (dr up to 95:5) and with enantiomeric excesses of up to 79% ee. Best levels of enantioselectivity were observed in the reactions of enantioenriched aminosulfoxonium ylide with isobutyraldehyde and various alkylarylketenes.
Samarium-induced alkyl halide mediated reductive coupling of ketones

Abstract Reductive coupling of aromatic ketones was achieved by samarium metal in the presence of alkyl halides.
Rhodium-Catalyzed Asymmetric Amination of Allylic Trichloroacetimidates

A summary is presented of dynamic kinetic asymmetric transformations of racemic allylic trichloroacetimidates in the presence of chiral diene-ligated rhodium catalysts. The reaction is applicable to a wide variety of secondary and tertiary trichloroacetimidates containing aniline or benzylamine nucleophiles, affording nitrogen-containing tertiary and quaternary centers in good yields and with high levels of regio- and enantioselectivity. This catalytic method addresses many of the limitations previously associated with syntheses of these compounds.
Retinal ganglion cell axon sorting at the optic chiasm requires dystroglycan

Abstract In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo, but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Mis-sorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit.
Palladium-Catalyzed Stille Couplings with Fluorous Tin Reactants

A new class of “fluorous” aryl tin reactants was investigated for use in the Stille coupling. Fluorous compounds partition into a fluorocarbon (fluorous) phase in a fluorous/organic extraction. The...
Concise Bid Optimization Strategies with Multiple Budget Constraints

A major challenge faced by marketers attempting to optimize their advertising campaigns is to deal with budget constraints. The problem is even harder in the face of multidimensional budget constra...
Week-long imaging of cell divisions in the Arabidopsis root meristem

Characterizing the behaviors of dynamic systems requires capturing them with high temporal and spatial resolution. Owing to its transparency and genetic tractability, the Arabidopsis thaliana root lends itself well to live imaging when combined with cell and tissue-specific fluorescent reporters. We developed a novel 4D imaging method that utilizes simple confocal microscopy and readily available components to track cell divisions in the root stem cell niche and surrounding region for up to 1 week. Using this method, we performed a direct measurement of cell division intervals within and around the root stem cell niche. The results reveal a short, steep gradient of cell division rates in proximal stem cells, with progressively more rapid cell division rates from quiescent center (QC), to cells in direct contact with the QC (initials), to their immediate daughters, after which division rates appear to become more homogeneous. These results provide a baseline to study how perturbations in signaling could affect cell division patterns in the root meristem. This new setup further allows us to finely analyze meristematic cell division rates that lead to patterning.
Gas phase studies of silacyclobutanes: recent developments employing triple quadrupole detection

Abstract Four silacyclobutyl anions have been prepared and studied by gas phase ion-molecule chemistry using newly modified tandem flowing afterglow instrumentation. These silacyclobutyl anions, which include a pentacoordinate adduct of 1,1-dimethylsilacyclobutane and fluoride and an α-silylcarbanion, siloxide, and mercaptide corresponding to 1,1-dimethylsilacyclobutane, have been characterized by their chemical reactivity and collision-induced loss of ethylene under a variety of conditions. The CH, OH, and SH gas phase acidities of 1,1-dimethylsilacyclobutane. 1-hydroxy-1-methylsilacyclobutane, and 1-mercapto-1-methylsilacyclobutane have been measured and show no effect of the silacyclobutyl attachment. The full capabilities of the newly modified instrumentation include the mass selection of ions, their chemical characterization, collision-induced dissociation of both mass selected ions and those prepared by chemical reactions, and triple quadrupole detection.
H2CO AND N2H+ IN PROTOPLANETARY DISKS: EVIDENCE FOR A CO-ICE REGULATED CHEMISTRY

We present Submillimeter Array (SMA) observations of H2CO and N2H+ emission in the disks around the T Tauri star TW Hya and the Herbig Ae star HD 163296 at 2''-6'' resolution and discuss the distribution of these species with respect to CO freezeout. The H2CO and N2H+ emission toward HD 163296 does not peak at the continuum emission center that marks the stellar position but is instead significantly offset. Using a previously developed model for the physical structure of this disk, we show that the H2CO observations are reproduced if H2CO is present predominantly in the cold outer disk regions. A model where H2CO is present only beyond the CO snow line (estimated at a radius of 160 AU) matches the observations well. We also show that the average H2CO excitation temperature, calculated from two transitions of H2CO observed in these two disks and a larger sample of disks around T Tauri stars in the DISCS (the Disk Imaging Survey of Chemistry with SMA) program, is consistent with the CO freezeout temperature of ~20 K. In addition, we show that N2H+ and H2CO line fluxes in disks are strongly correlated, indicative of co-formation of these species across the sample. Taken together, these results imply that H2CO and N2H+ are generally present in disks only at low temperatures where CO depletes onto grains, consistent with fast destruction of N2H+ by gas-phase CO, and in situ formation of H2CO through hydrogenation of CO ice. In this scenario H2CO, CH3OH, and N2H+ emission in disks should appear as rings with the inner edge at the CO midplane snow line. This prediction can be tested directly using observations from ALMA with higher resolution and better sensitivity.
Novel efficient routes to heparin monosaccharides and disaccharides achieved via regio- and stereoselective glycosidation.

A new methodology for the synthesis of heparin building blocks has been developed. We describe novel efficient routes to both l-iduronic acid and d-glucuronic acid acceptors. Glycosylation with thioglycosides donors gave corresponding disaccharides in a regio- and stereoselective fashion. An improved approach to synthesizing azido-glucose thioglycoside donor to render azido-sugar from mannose via nucleophilic substitution is described.
The vitamin D endocrine system and its therapeutic potential

Publisher Summary This chapter is devoted to describing the vitamin D endocrine system, how the active hormonal form of vitamin D works, and the potential for treatment of a variety of diseases, ranging from metabolic bone diseases to such diverse disorders as psoriasis and cancer. With the discovery of the activation of the vitamin D molecule has come the application of the metabolites of vitamin D and its analogues to human disease. The discovery of the vitamin D receptor in tissues has resulted in the discovery of new functions of vitamin D, as its involvement in the differentiation and development of the monocyte from the promyelocyte. A further detailed analysis of the role of 1,25-Dihydroxyvitamin D 3 in initiating transcription of target genes will yield new information that will be of value not only in understanding these complex systems but in providing guidance to maximize treatment of disease.
Quantitative Interactome Proteomics Reveals a Molecular Basis for ATF6-Dependent Regulation of a Destabilized Amyloidogenic Protein.

Summary Activation of the unfolded protein response (UPR)-associated transcription factor ATF6 has emerged as a promising strategy to reduce the secretion and subsequent toxic aggregation of destabilized, amyloidogenic proteins implicated in systemic amyloid diseases. However, the molecular mechanism by which ATF6 activation reduces the secretion of amyloidogenic proteins remains poorly defined. We employ a quantitative interactomics platform to define how ATF6 activation reduces secretion of a destabilized, amyloidogenic immunoglobulin light chain (LC) associated with light-chain amyloidosis (AL). Using this platform, we show that ATF6 activation increases the targeting of this destabilized LC to a subset of pro-folding ER proteostasis factors that retains the amyloidogenic LC within the ER, preventing its secretion. Our results define a molecular basis for the ATF6-dependent reduction in destabilized LC secretion and highlight the advantage for targeting this UPR-associated transcription factor to reduce secretion of destabilized, amyloidogenic proteins implicated in AL and related systemic amyloid diseases.
Dicationic dibenzofuran derivatives as anti-Pneumocystis carinii pneumonia agents: synthesis, DNA binding affinity, and anti-P. carinii activity in an immunosuppressed rat model

Abstract Previous work from our laboratory shows that compounds with two cations linked by a carbazole spacer were highly potent antiP. carinii agents. A prodrug approach designed to increase oral activity of the dicationic carbazoles by converting amidine groups to amidoxime groups was unsuccessful. The ring nitrogen was implicated as playing a role in the lack of activity of carbazole amidoximes. The current study was designed to determine if replacement of the carbazole ring nitrogen by isosteric oxygen to form dibenzofurans would improve effectiveness of amidoxime prodrugs. Eight dibenzofuran dicationic derivatives were synthesized and evaluated for anti-P. carinii activity in an immunosuppressed rat model. Since DNA binding has been hypothesized to play a key role in antimicrobial activity of dicationic compounds, the compounds were examined for their binding affinity to calf thymus DNA and a poly-dA•poly-dT oligomer. While several of the compounds were more potent anti-P. carinii agents than pentamidine, the corresponding amidoximes were significantly less effective than the amidoxime of pentamidine. No direct quantitative correlation was determined between DNA binding affinity and anti-P. carinii activity, but all active compounds were strong DNA binding agents.
On the marginal value of electricity storage

Abstract We investigate the problem of characterizing the economic value of energy storage capacity to a wind power producer (WPP) that sells its energy in a conventional two-settlement electricity market. The WPP can offer a forward contract to supply power in the day-ahead market, subject to financial penalties for imbalances between the contracted power and the power that is delivered in real-time. We consider the setting in which the WPP has access to a co-located energy storage system, and can thus reshape its wind power production subject to its storage capacity constraints. Modeling wind power as a random process, we show that the problem of determining optimal forward contract offerings—given recourse with storage—is convex. We further establish that the maximum expected profit is concave and non-decreasing in the energy storage capacity, which reveals that the greatest marginal benefit from energy storage is derived from initial investment in small storage capacity. We provide a characterization of the marginal value of small energy storage capacity to the WPP. The formulae we derive shed light on the relationship between the value of storage and certain statistical measures of variability in the underlying wind power process.
New Azacyclopropene Derivatives from Dysidea fragilis Collected in Pohnpei

The sponge Dysidea fragilis from Pohnpei contained four azacyclopropene derivatives, (4E)-S-dysidazirine [2], which is the optical enantiomer of the known compound dysidazirine [1], (4Z)-dysidazirine [3], (4E)-S-antazirine [4], and (4Z)-antazirine [5]. The structures of the new compounds were elucidated by interpretation of spectral data.
ERVcaller: identifying polymorphic endogenous retrovirus and other transposable element insertions using whole-genome sequencing data.

Motivation Approximately 8% of the human genome is derived from endogenous retroviruses (ERVs). In recent years, an increasing number of human diseases have been found to be associated with ERVs. However, it remains challenging to accurately detect the full spectrum of polymorphic (unfixed) ERVs using whole-genome sequencing (WGS) data. Results We designed a new tool, ERVcaller, to detect and genotype transposable element (TE) insertions, including ERVs, in the human genome. We evaluated ERVcaller using both simulated and real benchmark WGS datasets. Compared to existing tools, ERVcaller consistently obtained both the highest sensitivity and precision for detecting simulated ERV and other TE insertions derived from real polymorphic TE sequences. For the WGS data from the 1000 Genomes Project, ERVcaller detected the largest number of TE insertions per sample based on consensus TE loci. By analyzing the experimentally verified TE insertions, ERVcaller had 94.0% TE detection sensitivity and 96.6% genotyping accuracy. Polymerase chain reaction and Sanger sequencing in a small sample set verified 86.7% of examined insertion statuses and 100% of examined genotypes. In conclusion, ERVcaller is capable of detecting and genotyping TE insertions using WGS data with both high sensitivity and precision. This tool can be applied broadly to other species. Availability and implementation http://www.uvm.edu/genomics/software/ERVcaller.html. Supplementary information Supplementary data are available at Bioinformatics online.
Structural similarities among oxygen-deficient perovskites

A general review and description is given of vacancy patterns in oxygen-deficient perovskites A[sub m]B[sub m]O[sub 3m[minus]x]. Thirteen compounds that contain unique oxygen vacancy patterns and that adopt structures related to cubic closet packing are examined in detail: m = 2, x = 1, Ca[sub 2]Mn[sub 2]O[sub 5], LaSrCuGaO[sub 5], La[sub 2]Ni[sub 2]O[sub 5], LaSrCuAlO[sub 5], YBaCuFeO[sub 5], Ca[sub 2]Co[sub 2]O[sub 5]; m = 3, x = 1, 2, or 3, LaBa[sub 2]Cu[sub 2]TaO[sub 8], LaSr[sub 2]Fe[sub 3]O[sub 8], YBa[sub 2]Cu[sub 3]O[sub 7], LnSr[sub 2]Cu[sub 2]GaO[sub 7], YBa[sub 2]Cu[sub 3]O[sub 6]; m = 4, x = 1, Ba[sub 2]La[sub 2]Cu[sub 2]Sn[sub 2]O[sub 11] and Ca[sub 4]Ti[sub 2]Fe[sub 2]O[sub 11]. The structural similarity among the compounds is stressed by the presentation and examination of AO[sub 3[minus]x] slices. The influence of the A and B cations on the manner in which successive AO[sub 3[minus]x] layers are stacked is presented and discussed. 73 refs., 17 figs.
Pd-catalyzed selective tandem arylation–alkylation of 1,1-dihalo-1-alkenes with aryl- and alkylzinc derivatives to produce α-alkyl-substituted styrene derivatives

Abstract Trans -selective monoarylation of 1,1-dibromo- and 1,1-dichloro-1-alkenes ( 1 ) can be achieved in >80% yields and in ≥98–99% stereoselectivity with arylzinc bromides in the presence of a catalytic amount of Cl 2 Pd(DPEphos) or Cl 2 Pd(dppb), the former permitting cleaner and higher yielding reactions. Although THF is a generally satisfactory solvent, ether and toluene are superior to THF in some cases. The second substitution of ( Z )-α-bromostyrenes ( 3 ) with alkylzincs in the presence of 2 mol% of Pd( t Bu 3 P) 2 proceeds to give the corresponding 2 in >90% yields and in ≥98–99% stereoselectivity. Although somewhat less satisfactory, the use of Cl 2 Pd(DPEphos) permits a one-pot tandem arylation–alkylation.
CRF1 Receptor‐Dependent Increases in Irritability‐Like Behavior During Abstinence from Chronic Intermittent Ethanol Vapor Exposure

Background In humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests that measure withdrawal in animal models is that they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models. The corticotropin-releasing factor (CRF)-CRF1 receptor system has been suggested to be critical for the emergence of anxiety-like behavior in ethanol dependence, but the role of this system in irritability-like behavior has not been characterized. Methods The present study compared the effects of chronic intermittent ethanol (CIE) vapor exposure-induced ethanol dependence on irritability-like behavior in rats using the bottle-brush test during acute withdrawal and protracted abstinence. Rats were trained to self-administer ethanol in operant chambers and then either left in a nondependent state or made dependent via CIE. Naive, nondependent, and dependent rats were tested for irritability-like behavior in the bottle-brush test 8 hours and 2 weeks into abstinence from ethanol. Separate cohorts of dependent and nondependent rats were used to examine the effect of the specific CRF1 receptor antagonist R121919 on irritability-like behavior. Results Dependent rats exhibited escalated ethanol intake compared with their own pre-CIE baseline and nondependent rats. At both time points of abstinence, ethanol-dependent rats exhibited increased aggressive-like responses compared with naive and nondependent rats. R121919 reduced irritability-like behavior in both dependent and nondependent rats, but dependent rats were more sensitive to R121919. Conclusions Irritability-like behavior is a clinically relevant and reliable measure of negative emotional states that is partially mediated by activation of the CRF-CRF1 system and remains elevated during protracted abstinence in ethanol-dependent rats.
Novel cobalt-catalyzed carbonylation of 2-aryl-2-oxazolines.

Catalytic ring-expanding carbonylation of 2-aryl-2-oxazolines is reported as a novel method for the synthesis of 4,5-dihydro-1,3-oxazin-6-ones. Various observations suggest the involvement of cobalt radicals as the catalytically active species.
Ring Closing Metathesis Mediated Synthesis of 4a-Aryloxodecahydroisoquinolines, Intermediates in the Preparation of Novel Opiates

The concise syntheses of the 4a-aryldecahydroisoquinolines 1 and 2 through a uniform strategy starting from N-methyl-3-allyl-4-piperidinone are reported in this Letter. Key transformations include a ring closing metathesis reaction to prepare a trans-octahydroisoquinoline common intermediate and a regiocontrolled hydroboration−oxidation sequence.
An efficient method for the oxidation of sulfides to sulfones

Abstract Ruthenium trichloride - sodium periodate is a highly efficient and powerful system for the oxidation of unreactive sulfides to sulfones.
A convenient synthetic approach to 1,5-diiodonaphthalene derivatives

Abstract A convenient and efficient synthetic approach to the synthesis of 1,5-diiodonaphthalene derivatives is reported.
A NEW METHOD FOR THE SYNTHESIS OF 3β-HYDROXY-4α-BROMOCARANE AND OF cis-3-CARENE EPOXIDE

(1991). A NEW METHOD FOR THE SYNTHESIS OF 3β-HYDROXY-4α-BROMOCARANE AND OF cis-3-CARENE EPOXIDE. Organic Preparations and Procedures International: Vol. 23, No. 5, pp. 667-670.
Expeditious Routes to Polycyclic Molecular Frameworks via One-Pot, Two-Step Ugi Ring-Closing Sequences

A very general and robust multicomponent-reaction protocol involving an Ugi condensation between ethyl glyoxylate, isonitriles, N -Boc-α-amino acids, and mono - N -Boc-protected diamines followed by a series of acid-promoted cyclization steps in a one-pot fashion is reported. This process allows for the assembly of complex polycyclic structures by means of just two simple synthetic operations and a single chromatographic purification in high overall yields. Of note, the first scaffolds derived from a highly ­selective sequence of ring-closing events involving three internal amino nucleophiles is reported.
Anodic oxidations of electron-rich olefins: radical cation based approaches to the synthesis of bridged bicyclic ring skeletons

Abstract The use of intramolecular anodic olefin coupling reactions for building bicyclo[3.2.1]octane ring skeletons has been examined. While simple model systems using bis enol ether substrates readily led to the formation of bicyclic products, application of the reactions to total synthesis efforts were hindered by reactions forming dimethoxy acetal groups at both the terminating and initiating ends of the cyclization reactions. In an effort to solve this problem, ketene acetal based initiating groups have been studied. The use of a ketene dithioacetal group proved especially useful for this purpose.
A formal total synthesis of dictyostatin

Abstract A convergent formal synthesis of the antimitotic macrolide dictyostatin has been achieved. The C11–C26 fragment of dictyostatin was prepared via convergent assembly of the central deoxypropionate motif utilizing a site- and stereoselective titanium-mediated reductive cross-coupling and an asymmetric hydrogenation of the resulting stereodefined 1,3-diene.
Cyanide-bridged lanthanide(III)-transition metal extended arrays: interconversion of one-dimensional arrays from single-strand (type A) to double-strand (type B) structures. Complexes of a new type of single-strand array (type C).

A series of one-dimensional arrays of lanthanide−transition metal complexes has been prepared and characterized. These complexes, {(DMF)10Ln2[Ni(CN)4]3}∞, crystallize as linear single-strand arrays (structural type A) (Ln = Sm, 1a; Eu, 2a) or double-strand arrays (structural type B) (Ln = Sm, 1b; Eu, 2b) depending upon the conditions chosen, and they are interconvertible. The single-strand type A structure can be converted to the double-strand type B structure. When the 1b and 2b type B crystals are completely dissolved in DMF, their infrared spectra are identical to the infrared spectra of 1a and 2a type A crystals dissolved in DMF. These solutions produce type A crystals initially. It is believed that formation of the type A structure is kinetically favored while the type B structure is thermodynamically favored for lanthanide−nickel complexes 1 and 2. On the other hand the complex {(DMF)10Y2[Pd(CN)4]3}∞, 3, appears to crystallize only as the double-strand array (type B). The complexes {(DMF)12Ce2[Ni(CN...
Nearly mass degenerate Majorana neutrinos: Double beta decay and neutrino oscillations

Assuming equal tree-level Majorana masses for the standard-model neutrinos, either from the canonical seesaw mechanism or from a heavy scalar triplet, I discuss how their radiative splitting may be relevant to neutrinoless double-beta decay and neutrino oscillations.
Tuning-Free, Low Memory Robust Estimator to Mitigate GPS Spoofing Attacks

The operation of critical infrastructures, such as the electrical power grid, cellphone towers, and financial institutions relies on precise timing provided by stationary global positioning system (GPS) receivers. These GPS devices are vulnerable to a type of spoofing called time synchronization attack (TSA), whose objective is to maliciously alter the timing provided by the GPS receiver. The objective of this letter is to design a tuning-free, low memory robust estimator to mitigate such spoofing attacks. The contribution is that the proposed method dispenses with several limitations found in the existing state-of-the-art methods in the literature that require parameter tuning, availability of the statistical distributions of noise, real-time optimization, or heavy computations. Specifically, we: 1) utilize an observer design for linear systems under unknown inputs; 2) adjust it to include a state-correction algorithm; 3) design a realistic experimental setup with real GPS data and sensible spoofing attacks; and 4) showcase how the proposed tuning-free, low memory robust estimator can combat TSAs. Numerical tests with real GPS data demonstrate that accurate time can be provided to the user under various attack conditions.
Syntheses and Structures of New Phases AeMxIn4-x (Ae = Sr, Ba; M = Mg, Zn): Size Effects and Site Preferences in BaAl4-Type Structures

The title phases were synthesized via high-temperature solid-state methods and structurally characterized by single-crystal X-ray diffraction. The phase widths of both SrMgxIn4-x (0.85 ≤ x ≤ 1.53) and BaMgxIn4-x (0 ≤ x ≤ 1.79) are consistent with size matches between Ae and the encapsulating M−In cages. All compounds crystallize in body-centered tetragonal BaAl4-type structure (I4/mmm, Z = 2) except that SrMgxIn4-x, 0.85 ≤ x ≤ 1.24, occurs in the lower-symmetry space group (I4m2, Z = 2) and the atoms are all ordered at the composition SrMgIn3. The substitution of the effectively smaller Mg or Zn atoms into the indium sublattice of the monoclinic SrIn4 (C2/m) dramatically changes the structure into the tetragonal BaAl4-type structure. Compared with the Mg compounds in which all Mg occupy the basal 4d crystallographic site, Zn occupies the other 4e (apical) site in both BaZn0.79(2)In3.21 and SrZn1.00(4)In3.00. These differences are related to the interplay of size and electronic factors. The latter may be ...
Large Scale Synthesis of A Derivative of An α-Galactosyl Trisaccharide Epitope Involved in the Hyperacute Rejection of Xenotransplantation

ABSTRACT A derivative of an α-galactosyl trisaccharide xenoactive antigen, (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-(1→3)-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranosyl azide (5), was synthesized on a large scale (50 gram). The synthesis involved a high yielding and highly stereoselective (α/β>20:1) glycosylation reaction utilizing a thiogalactoside as the donor and a selectively protected lactose azide as the acceptor. This derivative serves as a versatile intermediate that can be transformed into a variety of α-Gal containing glycoconjugates highly desired in xenotransplantation research and pharmaceutical development.
Microextrusion printing cell-laden networks of type I collagen with patterned fiber alignment and geometry

Type I collagen self-assembles into three-dimensional (3D) fibrous networks. These dynamic viscoelastic materials can be remodeled in response to mechanical and chemical signals to form anisotropic networks, the structure of which influences tissue development, homeostasis, and disease progression. Conventional approaches for fabricating anisotropic networks of type I collagen are often limited to unidirectional fiber alignment over small areas. Here, we describe a new approach for engineering cell-laden networks of aligned type I collagen fibers using 3D microextrusion printing of a collagen-Matrigel ink. We demonstrate hierarchical control of 3D-printed collagen with the ability to spatially pattern collagen fiber alignment and geometry. Our data suggest that collagen alignment results from a combination of molecular crowding in the ink and shear and extensional flows present during 3D printing. We demonstrate that human breast cancer cells cultured on 3D-printed collagen constructs orient along the direction of collagen fiber alignment. We also demonstrate the ability to simultaneously bioprint epithelial cell clusters and control the alignment and geometry of collagen fibers surrounding cells in the bioink. The resulting cell-laden constructs consist of epithelial cell clusters fully embedded in aligned networks of collagen fibers. Such 3D-printed constructs can be used for studies of developmental biology, tissue engineering, and regenerative medicine.
Adding concurrency to smart contracts

Modern cryptocurrency systems, such as the Ethereum project, permit complex financial transactions through scripts called smart contracts. These smart contracts are executed many, many times, always without real concurrency. First, all smart contracts are serially executed by miners before appending them to the blockchain. Later, those contracts are serially re-executed by validators to verify that the smart contracts were executed correctly by miners. Serial execution limits system throughput and fails to exploit today’s concurrent multicore and cluster architectures. Nevertheless, serial execution appears to be required: contracts share state, and contract programming languages have a serial semantics. This paper presents a novel way to permit miners and validators to execute smart contracts in parallel, based on techniques adapted from software transactional memory. Miners execute smart contracts speculatively in parallel, allowing non-conflicting contracts to proceed concurrently, and “discovering” a serializable concurrent schedule for a block’s transactions, This schedule is captured and encoded as a deterministic fork-join program used by validators to re-execute the miner’s parallel schedule deterministically but concurrently. We have proved that the validator’s execution is equivalent to miner’s execution. Smart contract benchmarks run on a JVM with ScalaSTM show that a speedup of 1.39$$\times $$ can be obtained for miners and 1.59$$\times $$ for validators with just three concurrent threads.
In situ catalyst exsolution on perovskite oxides for the production of CO and synthesis gas in ceramic membrane reactors

This work demonstrates and assesses the concept of in situ catalyst exsolution in ceramic membrane reactors for the co-production of carbon monoxide (CO) and syngas through carbon dioxide (CO2) splitting and methane (CH4) partial oxidation, respectively. We use dense pellets of La0.85Ca0.10Fe0.95Ni0.05O3−δ (LCFN) as a model membrane reactor system. By combining in situ reaction rate measurements under finite oxygen (O2) flux and ex situ material characterization, we show that exsolution of nickel (Ni0) metal nanoparticles takes place in situ on both sides of the LCFN membrane under sufficiently reducing conditions controlled by the presence of CH4. To understand the impact of temperature and inlet fuel concentration on the nucleation, performance and long-term stability of the catalytic particles, exsolution of Ni0 from LCFN was investigated at 900 °C, 950 °C and 1000 °C and with different concentrations of CH4. Nickel particles with sizes ranging between 100 nm and 300 nm formed on LCFN pellets at 950 °C and 1000 °C using CH4 as the in situ reducing agent at a threshold inlet CH4 mole fraction of 16% and 4%, respectively. Nickel exsolution was not observed at 900 °C. No pre-reduction of the sample in a hydrogen (H2) environment was required. As a result, significant performance increase was obtained. Exsolution on LCFN samples at different temperatures results in almost identical performance when compared under similar conditions. Reaction rates obtained after nickel exsolution were stable over long durations, suggesting that the grown particles are resistant to agglomeration in the hydrocarbon environment. Results shown in this work demonstrate that in situ, on demand catalyst exsolution by using the feedstock fuel can be an effective way of improving the surface kinetics of perovskite oxides for ceramic membranes.
Width and finite extinction time of Ricci flow

This is an expository article with complete proofs intended for a general nonspecialist audience. The results are two-fold. First, we discuss a geometric invariant, that we call the width, of a manifold and show how it can be realized as the sum of areas of minimal 2–spheres. For instance, when M is a homotopy 3–sphere, the width is loosely speaking the area of the smallest 2–sphere needed to ‘pull over’ M. Second, we use this to conclude that Hamilton’s Ricci flow becomes extinct in finite time on any homotopy 3–sphere.
Essential manifolds with extra structures

Abstract We consider classes of algebraic manifolds A , of symplectic manifolds S , of symplectic manifolds with the hard Lefschetz property HS and the class of cohomologically symplectic manifolds CS . For every class of manifolds C we denote by EC ( π , n ) a subclass of n-dimensional rationally essential manifolds with fundamental group π. In this paper we prove that for all the above classes with symplectically aspherical form the condition EC ( π , 2 n ) ≠ ∅ implies that EC ( π , 2 n − 2 ) ≠ ∅ for every n > 2 . Also we prove that all the inclusions EA ⊂ EHS ⊂ ES ⊂ ECS are proper.
Number theory problems from the harmonic analysis of a fractal

Abstract We study some number theory problems related to the harmonic analysis (Fourier bases) of the Cantor set introduced by Jorgensen and Pedersen in [JP98] .
CancerLinker: Explorations of Cancer Study Network

Interactive visualization tools are highly desirable to biologist and cancer researchers to explore the complex structures, detect patterns and find out the relationships among bio-molecules responsible for a cancer type. A pathway contains various bio-molecules in different layers of the cell which are responsible for specific cancer type. Researchers are highly interested in understanding the relationships among the proteins of different pathways and furthermore want to know how those proteins are interacting in different pathways for various cancer types. Biologists find it useful to merge the data of different cancer studies in a single network and see the relationships among the different proteins which can help them to detect the common proteins in cancer studies and hence reveal the pattern of interaction of those proteins. We introduce CancerLinker, a visual analytic system that helps researchers to explore cancer study interaction network. We merge twenty-six cancer studies to explore pathway data and bio-molecules relationships that can provide the answers to some significant questions which are helpful in cancer research. CancerLinkeralso helps biologists explore the critical mutated proteins in multiple cancer studies. A bubble graph is constructed to visualize common protein based on its frequency and biological assemblies. Parallel coordinates highlight patterns of patient profiles (obtained from cBioportal by WebAPI services) on different attributes for a specified cancer study.