cssi/SciSciGPT-SciSciNet huggingface dataset:
On Prediction Properties of Kriging: Uniform Error Bounds and Robustness

Kriging based on Gaussian random fields is widely used in reconstructing unknown functions. The kriging method has pointwise predictive distributions which are computationally simple. However, in m...
Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization

Double-strand breaks (DSBs) are among the most deleterious lesions DNA can endure. Yet, DSBs are programmed at the onset of meiosis, and are required to facilitate appropriate reduction of ploidy in daughter cells. Repair of these breaks is tightly controlled to favor homologous recombination (HR)—the only repair pathway that can form crossovers. However, little is known about how the activities of alternative repair pathways are regulated at these stages. We discovered an unexpected synthetic interaction between the DSB machinery and strand-exchange proteins. Depleting the Caenorhabditis elegans DSB-promoting factors HIM-5 and DSB-2 suppresses the formation of chromosome fusions that arise in the absence of RAD-51 or other strand-exchange mediators. Our investigations reveal that nonhomologous and theta-mediated end joining (c-NHEJ and TMEJ, respectively) and single strand annealing (SSA) function redundantly to repair DSBs when HR is compromised, and that HIM-5 influences the utilization of TMEJ and SSA.
Controller Synthesis for Discrete-Time Polynomial Systems via Occupation Measures

In this paper, we design nonlinear state feedback controllers for discrete-time polynomial dynamical systems via the occupation measure approach. We propose the discrete-time controlled Liouville equation, and use it to formulate the controller synthesis problem as an infinite-dimensional linear programming problem on measures, which is then relaxed as finite-dimensional semidefinite programming problems on moments of measures and their duals on sums-of-squares polynomials. Nonlinear controllers can be extracted from the solutions to the relaxed problems. The advantage of the occupation measure approach is that we solve convex problems instead of generally non-convex problems, and the computational complexity is polynomial in the state and input dimensions, and hence the approach is more scalable. In addition, we show that the approach can be applied to over-approximating the backward reachable set of discrete-time autonomous polynomial systems and the controllable set of discrete-time polynomial systems under known state feedback control laws. We illustrate our approach on several dynamical systems.
The dark side of institutional intermediaries: Junior stock exchanges and entrepreneurship

Research Summary: Our study shows how institutional intermediaries established to foster the creation of new firms might hinder new firm growth instead. We show that intermediaries can reduce new firm growth rates due to institutional conflict. To analyze this idea, we examine the setting of junior stock exchanges, which are commonly formed to facilitate entrepreneurial growth. The introduction of these exchanges focused investment into new technology firms, reduced investment in other sectors, and led to diminishing new firm growth. Our findings demonstrate how institutional conflict causes unintended effects and reveals the complexity of influencing entrepreneurship with institutional intermediaries. Managerial Summary: Investors and entrepreneurs face uncertainty when deciding what firms to start and fund. We show that an intermediation effort to make entry easier for entrepreneurs increases the uncertainty that entrepreneurs and investors face. For investors, the enthusiasm for technology firms engendered by the new exchange can motivate investment in marginal firms to maintain as desired deal flow. However, lower firm growth and less liquidity in the future is likely. For entrepreneurs, our results indicate that it is more challenging to manage technology firm growth as well as there is potential opportunity to investigate other industries. Finally, for policy‐makers and supporters of the new exchanges, our results imply that investment flows are altered as intended, but unless listing standards remain high, the virtuous cycle of investment upon which a healthy entrepreneurial climate rests may be disrupted, muting the intended effects of the new exchange.
Reveal the Supplier List? A Trade-off in Capacity vs. Responsibility

Problem definition: Under what conditions and how can a buying firm, by committing to publish a list of its suppliers and/or the identities and violations of terminated suppliers, increase its expe...
Prevalence and patterns of higher-order drug interactions in Escherichia coli .

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems.
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of "neutrophil-like" monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.
Automated Attack Discovery in TCP Congestion Control Using a Model-guided Approach.

In this work, we propose an automated method to find attacks against TCP congestion control implementations that combines the generality of implementation-agnostic fuzzing with the precision of runtime analysis. It uses a model-guided approach to generate abstract attack strategies by leveraging a state machine model of congestion control to find vulnerable state machine paths that an attacker could exploit to increase or decrease the throughput of a connection. These abstract strategies are then mapped to concrete attack strategies, which consist of sequences of actions such as injection or modification of acknowledgements. We design and implement a virtualized platform, TCPwn, that consists of a proxy-based attack injector to inject these concrete attack strategies. We evaluated 5 TCP implementations from 4 Linux distributions and Windows 8.1. Overall, we found 11 classes of attacks, of which 8 are new.
Transvision: exploring the state of the visual field in the age of extreme augmentation

Human perception has long been influenced by technological breakthroughs. An intimate mediation of technology lies in between our direct perceptions and the environment we perceive. Through three extreme ideal types of perceptual machines, this project defamiliarizes and questions the habitual ways in which we interpret, operate, and understand the visual world intervened by digital media. The three machines create: Hyper-sensitive vision - a speculation on social media's amplification effect and our filtered communication landscape. Hyper-focused vision - an analogue version of the searching behavior on the Internet. Hyper-commoditized vision - monetized vision that meditates on the omnipresent advertisement targeted all over our visual field. The site of intervention is the visual field in a technologically augmented society. All the three machines have both internal state and external signal. This duality allows them to be seen from outside and experienced from inside.
Cluster Randomized Trial of a School Intervention for Children with Autism Spectrum Disorder.

There are currently no empirically supported, comprehensive school-based interventions (CSBIs) for children with autism spectrum disorder (ASD) without concomitant intellectual and language disabil...
Curved space, curved time, and curved space-time in Schwarzschild geodetic geometry

We investigate geodesic orbits and manifolds for metrics associated with Schwarzschild geometry, considering space and time curvatures separately. For ‘a-temporal’ space, we solve a central geodesic orbit equation in terms of elliptic integrals. The intrinsic geometry of a two-sided equatorial plane corresponds to that of a full Flamm’s paraboloid. Two kinds of geodesics emerge. Both kinds may or may not encircle the hole region any number of times, crossing themselves correspondingly. Regular geodesics reach a periastron greater than the $$r_S$$ Schwarzschild radius, thus remaining confined to a half of Flamm’s paraboloid. Singular or s-geodesics tangentially reach the $$r_S$$ circle. These s-geodesics must then be regarded as funneling through the ‘belt’ of the full Flamm’s paraboloid. Infinitely many geodesics can possibly be drawn between any two points, but they must be of specific regular or singular types. A precise classification can be made in terms of impact parameters. Geodesic structure and completeness is conveyed by computer-generated figures depicting either Schwarzschild equatorial plane or Flamm’s paraboloid. For the ‘curved-time’ metric, devoid of any spatial curvature, geodesic orbits have the same apsides as in Schwarzschild space-time. We focus on null geodesics in particular. For the limit of light grazing the sun, asymptotic ‘spatial bending’ and ‘time bending’ become essentially equal, adding up to the total light deflection of 1.75 arc-seconds predicted by general relativity. However, for a much closer approach of the periastron to $$r_S$$ , ‘time bending’ largely exceeds ‘spatial bending’ of light, while their sum remains substantially below that of Schwarzschild space-time.
Auto-Tuning TensorFlow Threading Model for CPU Backend

TensorFlow**Other names and brands may be claimed as the property of others. is a popular deep learning framework used by data scientists to solve a wide-range of machine learning and deep learning problems such as image classification and speech recognition. It also operates at a large scale and in heterogeneous environments - it allows users to train neural network models or deploy them for inference using GPUs, CPUs, (Intel® Xeon® †Intel, the Intel logo and Xeon ® are trademarks of Intel Corporation or its subsidiaries in the U.S. and/or other countries. © Intel Corporation. CPUs) and deep learning specific custom-designed hardware such as TPUs. Even though TensorFlow supports a variety of optimized backends, realizing the best performance using a backend may require additional efforts. For instance, getting the best performance from a CPU backend requires careful tuning of its threading model. Unfortunately, the best tuning approach used today is manual, tedious, time-consuming, and, more importantly, may not guarantee the best performance. In this paper, we develop an automatic approach, called TensorTuner, to search for optimal parameter settings of TensorFlow's threading model for CPU backends. We evaluate TensorTuner on both Eigen and Intel's MKL CPU backends using a set of neural networks from TensorFlow's benchmarking suite. Our evaluation results demonstrate that the parameter settings found by TensorTuner produce 2% to 123% performance improvement for the Eigen CPU backend and 1.5% to 28% performance improvement for the MKL CPU backend over the performance obtained using their best-known parameter settings. This highlights the fact that the default parameter settings in Eigen CPU backend are not the ideal settings; and even for a carefully hand-tuned MKL backend, the settings are sub-optimal. Our evaluations also revealed that TensorTuner is efficient at finding the optimal settings - it is able to converge to the optimal settings quickly by pruning more than 90% of the parameter search space.
EMPIRICAL PERFORMANCE OF GARCH MODELS WITH HEAVY‐TAILED INNOVATIONS

We introduce a new type of heavy‐tailed distribution, the normal reciprocal inverse Gaussian distribution (NRIG), to the GARCH and Glosten‐Jagannathan‐Runkle (1993) GARCH models, and compare its empirical performance with two other popular types of heavy‐tailed distribution, the Student's t distribution and the normal inverse Gaussian distribution (NIG), using a variety of asset return series. Our results illustrate that there is no overwhelmingly dominant distribution in fitting the data under the GARCH framework, although the NRIG distribution performs slightly better than the other two types of distribution. For market indexes series, it is important to introduce both GJR‐terms and the NRIG distribution to improve the models’ performance, but it is ambiguous for individual stock prices series. Our results also show the GJR‐GARCH NRIG model has practical advantages in quantitative risk management. Finally, the convergence of numerical solutions in maximum‐likelihood estimation of GARCH and GJR‐GARCH models with the three types of heavy‐tailed distribution is investigated.
Access to Power

The traditional approaches to “access to justice” obscure the current distribution of economic, social, and political power, and how that distribution favors those who have power and burdens those ...
Outcomes of Umbilical Cord Blood Transplantation in Children with Batten Disease

Introduction Neuronal ceroid lipofuscinoses (NCL, Batten Disease) are a class of lysosomal storage diseases caused by mutations in ceroid lipofuscinoses (CLN) genes. Neurological deterioration is influenced by the CLN subtype, but death typically occurs in childhood. Symptoms include visual impairment, behavioral changes, loss of motor and/or cognitive skills, and seizures. Umbilical cord blood transplant (UCBT) is effective in treating many lysosomal storage disorders but there is very limited experience in BD. Methods We retrospectively studied 6 patients (pt) with BD receiving UCBT between the ages of 4 months and 8.6 years at our center. All received myeloablative conditioning with busulfan, cyclophosphamide and ATG. Cyclosporine and mycophenolate were given for prophylaxis of GVHD. Pts 5 and 6 were concomitantly enrolled on clinical trial (NCT02254863) and also received intra-thecal injection of DUOC-01 cells after hematologic engraftment. Selected patient and donor characteristics are shown in Table 1: Results Patients received UCB grafts matching at 4/6-6/6 loci with a median pre-cryo cell dose of 7.2 (range, 5.1-35.1) x107 cells/kg. All pts engrafted neutrophil and platelets in a median of 25 (range, 12-34) and 39 days (range, 32-105), respectively. Four patients developed Grade 2-4 acute GvHD and 2 developed extensive chronic GvHD. Pt 1, the only patient transplanted after severe neurologic decline with advanced disease, died from progressive BD and aseptic shock 12 months post-UCBT. All others are alive at a median of 3.8 years (range, 0.5-5.5). Pt 2 has normal motor function, is nonverbal and was diagnosed with autism 2 years post UCBT. Her brain MRI is normal to date. Pt 3 is blind, has had occasional seizures, requires educational support and has no MRI evidence of BD. Pts 4 and 5 have age appropriate neurocognition, no seizures, and receive only visual support in school. Both have normal MRIs. It is too early to assess neurologic outcomes in Pt 6 (7 months post-UCBT). Conclusion UCBT is feasible in children with BD. At a median follow up of 3.8 years (range, 0.5-5.5), 5/6 patients are alive and 4/5 are neuro-cognitively stable and one developed new onset seizures post-transplant. All 5 surviving pts have no MRI evidence of disease. With the inherent variability of the different forms of BD, additional pts and continued follow-up is needed to fully understand the effect of UCBT on the natural history of BD.
Stellar Energetic Particles in the Magnetically Turbulent Habitable Zones of TRAPPIST-1-like Planetary Systems

Planets in close proximity to their parent star, such as those in the habitable zones around M dwarfs, could be subject to particularly high doses of particle radiation. We have carried out test-particle simulations of ~GeV protons to investigate the propagation of energetic particles accelerated by flares or travelling shock waves within the stellar wind and magnetic field of a TRAPPIST-1-like system. Turbulence was simulated with small-scale magnetostatic perturbations with an isotropic power spectrum. We find that only a few percent of particles injected within half a stellar radius from the stellar surface escape, and that the escaping fraction increases strongly with increasing injection radius. Escaping particles are increasingly deflected and focused by the ambient spiralling magnetic field as the superimposed turbulence amplitude is increased. In our TRAPPIST-1-like simulations, regardless of the angular region of injection, particles are strongly focused onto two caps within the fast wind regions and centered on the equatorial planetary orbital plane. Based on a scaling relation between far-UV emission and energetic protons for solar flares applied to M dwarfs, the innermost putative habitable planet, TRAPPIST-1e, is bombarded by a proton flux up to 6 orders of magnitude larger than experienced by the present-day Earth. We note two mechanisms that could strongly limit EP fluxes from active stars: EPs from flares are contained by the stellar magnetic field; and potential CMEs that might generate EPs at larger distances also fail to escape.
Computer animation

Animated images are almost magical in their ability to capture our imagination. By telling a compelling story, astounding with special effects, or mesmerizing with abstract motion, animation can infuse a sequence of inert images with the illusion of motion and life. Creating this illusion, either by hand or with the assistance of computer software, is not easy. Each individual image, or frame, in the animated sequence must blend seamlessly with the other images to create smooth and continuous motion that flows through time.
Market Power and Income Taxation

Does significant market power or the presence of large rents affect optimal income taxation, calling for greater redistribution due to tainted gains? Or perhaps less because of an additional wedge that distorts labor effort? Do concerns about inequality have implications for antitrust, regulation, trade, and other policies that influence market power, which contributes to inequality? This article addresses these questions in a model with heterogeneous abilities and hence a concern for distribution, markups, multiple sectors, ownership that is a function of income, allowance for any share of profits to be recoveries of investments (including rent-seeking efforts), endogenous labor supply, and a nonlinear income tax. In this model, proportional markups with no profit dissipation have no effect on the economy, and a policy that reduces a nonproportional markup raises (lowers) welfare when it is higher (lower) than a weighted average of other markups. With proportional (partial or full) profit dissipation, proportional markups are equivalent to a downward shift of the distribution of abilities, and the welfare effect of correcting nonproportional markups associated with nonproportional profit dissipation now depends also on the degree of dissipation and how that is affected by the policy. In all cases, optimal policies maximize consumer plus producer surplus, without regard to a policy’s distributive effects on consumers and profits or how markups and income taxation distort labor effort.
Learning to Navigate Unseen Environments: Back Translation with Environmental Dropout

A grand goal in AI is to build a robot that can accurately navigate based on natural language instructions, which requires the agent to perceive the scene, understand and ground language, and act in the real-world environment. One key challenge here is to learn to navigate in new environments that are unseen during training. Most of the existing approaches perform dramatically worse in unseen environments as compared to seen ones. In this paper, we present a generalizable navigational agent. Our agent is trained in two stages. The first stage is training via mixed imitation and reinforcement learning, combining the benefits from both off-policy and on-policy optimization. The second stage is fine-tuning via newly-introduced ‘unseen’ triplets (environment, path, instruction). To generate these unseen triplets, we propose a simple but effective ‘environmental dropout’ method to mimic unseen environments, which overcomes the problem of limited seen environment variability. Next, we apply semi-supervised learning (via back-translation) on these dropout environments to generate new paths and instructions. Empirically, we show that our agent is substantially better at generalizability when fine-tuned with these triplets, outperforming the state-of-art approaches by a large margin on the private unseen test set of the Room-to-Room task, and achieving the top rank on the leaderboard.
English as a lingua franca in a multilingual India

In this opinion article, we highlight that the cultural policy of language in India has resulted in an impasse in regard to determining and deciding upon a national language policy. We then summarize how English use across India has been elevated to the status of a lingua franca (amidst the language policy impasse), making it an indispensable part of the system and the economy. In that context, this opinion article presents the various tenets of the language policy issue with recommendations for educators in India on how to utilize best practices from literacy, culture, and language education (LCLE) literature to improve and maintain the quality of education whilst operating within the confines of the language policy impasse.
Vitamin D3 constrains estrogen's effects and influences mammary epithelial organization in 3D cultures

Vitamin D3 (vitD3) and its active metabolite, calcitriol (1,25-(OH)2D3), affect multiple tissue types by interacting with the vitamin D receptor (VDR). Although vitD3 deficiency has been correlated with increased incidence of breast cancer and less favorable outcomes, randomized clinical trials have yet to provide conclusive evidence on the efficacy of vitD3 in preventing or treating breast cancer. Additionally, experimental studies are needed to assess the biological plausibility of these outcomes. The mammary gland of VDR KO mice shows a florid phenotype revealing alterations of developmental processes that are largely regulated by mammotropic hormones. However, most research conducted on vitD3’s effects used 2D cell cultures and supra-physiological doses of vitD3, conditions that spare the microenvironment in which morphogenesis takes place. We investigated the role of vitD3 in mammary epithelial morphogenesis using two 3D culture models. VitD3 interfered with estrogen’s actions on T47D human breast cancer cells in 3D differently at different doses, and recapitulated what is observed in vivo. Also, vitD3 can act autonomously and affected the organization of estrogen-insensitive MCF10A cells in 3D collagen matrix by influencing collagen fiber organization. Thus, vitD3 modulates mammary tissue organization independent of its effects on cell proliferation.
Carbocyclic 5′‐norcytidine (5′‐norcarbodine)

A preparation of (1′R,2′S,3′R,4′S)-1-(2′,3′,4′-trihydroxycyclopent-1′-yl)-lH-cytosine (5′-norcarbodine, 3) has formally been achieved in 2 steps from (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate (4) and cytosine. The L-like enantiomer of 3 (that is, 6) is also reported using the enantiomer of 4 (that is, 7). In evalu ating 3 and 6 for antiviral potential against a number of viruses, compound 3 was found to have activity towards Epstein-Barr virus (EBV).
Tandem dienyne cross-metathesis/ring-closing metathesis

Abstract Tandem enyne cross-metathesis/ring-closing metathesis between terminal alkynes and 1,5-hexadiene has been demonstrated using the 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene-substituted ruthenium benzylidene complex. Synthesis of 2-substituted 1,3-cyclohexadienes using this one step tandem reaction is reported. In addition, metathesis products were subjected to [4+2] cycloaddition with N -methylmaleimide yielding the corresponding cycloadducts in one synthetic step.
Asymmetric Synthesis of the Chlorocyclopropane-Containing Callipeltoside A Side Chain

The callipeltoside A chlorocyclopropyl-containing dienyne side chain has been synthesized in nine steps and 33% overall yield from commercially available 1,2,5,6-O-dicyclohexylidene-d-mannitol. The key steps in the synthesis are a highly diastereoselective cyclopropanation of a vinyl chloride allylic ether and a Suzuki cross-coupling to complete the carbon framework.
Stereospecific and Regioselective Reactions of Silacyclopropanes with Carbonyl Compounds Catalyzed by Copper Salts: Evidence for a Transmetalation Mechanism

Silacyclopropanes reacted with carbonyl compounds under mild conditions (10 mol % metal salt, e22 °C) in a stereospecific and highly stereo-, regio-, and chemoselective fashion. In most cases, CuI or CuBr2 were the optimal catalysts although ZnBr2 worked comparably well in a few examples. Insertion occurred with retention of configuration and, in the case of enals and formamides, with high diastereoselectivity at the newly formed stereogenic centers. For unsymmetrical substrates, insertion occurred at the more substituted carbon-silicon bond with complete regioselectivity. Competition experiments demonstrated that formamides reacted faster than enals, which reacted faster than enoates; saturated aldehydes did not undergo insertion. With a cis-disubstituted silacyclopropane, products of silylene transfer were observed. The stereochemistry, regiochemistry, and chemoselectivity of carbonyl insertion as well as the silylene transfer processes can be explained by a mechanism involving transmetalation of silicon to copper.
Cyclopent[a]anthraquinones as DNA-Intercalating Agents with Covalent Bond Formation Potential: Synthesis and Biological Activity

A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels−Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure−activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl]cyclopent[a]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (ip, QD × 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.
Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells.

DNA contains all the information and instructions needed to build an organism and enables its cells to fulfil their role. There are many different cell types in animals, and each type only needs a small portion of the information found in the DNA to do its job. Hence, only the sections – also known as genes – specific to a particular role need to be active or ‘expressed’ in any given cell type. The sets of genes that are active in a cell determine what that cell can do and make it different from other cell types. Short regions that surround the genes act as ‘switches’ to control their activity. To study how these switches work, researchers have developed techniques that can measure when specific ones are on or off in different cell types. A technique called NOMe-seq can simultaneously identify active and inactive regions in the genome by measuring markers that are specific for active and inactive regions. However, this approach was created for large samples containing thousands of cells, so-called bulk samples. Since the pattern of gene expression can vary between individual cells even if they are of the same cell type, it is important to analyse each individual cell. Sebastian Pott has now adapted the NOMe-seq technique for use in single cells. The modified protocol was used to study human cells that have been well studied and can be grown in the laboratory. The results of this proof-of-principle study showed that the adapted version of the technique obtained similar results as when used on bulk samples. This demonstrates that the method can reliably measure active and inactive regions in single cells across the genome. The next step will be to use this tool to study how genes are affected in diseases like cancer, where gene expression can be variable between individual cells. For example, understanding the differences between individual cells within a cancer sample might help to understand why some cancers react to treatments better than others.
Macrolactonization of hydroxy acids using a polymer bound carbodiimide

Abstract An efficient macrolactonization procedure using a polymer bound carbodiimide is described. The procedure uses the polymer supported reagent as a replacement for dicyclohexylcarbodiimide and thus considerably simplifies the workup for such reactions. Partitioning between macrolactone and diolide is shown to depend upon the equivalents of reagent used in cases for which lactonization is difficult.
Synthesis of axinohydantoins

A short synthesis of the hydantoin-containing marine sponge metabolites axinohydantoins is described. A key feature of the synthesis is a putative biomimetic, intramolecular cyclization of α-functionalized imidazolone 5, which affords the tricyclic pyrroloazepinone framework comprising 6. In addition, the conversion of imidazolones to α,β-unsaturated hydantoins is outlined and represents a new approach to these heterocyclic systems.
La6Br10Fe: A La6Fe Octahedron with a Mixed M6X12/M6X8 Type Environment⊥

The title compound was synthesized from La, LaBr3, and Fe under Ar atmosphere at 800 degrees C. It crystallizes in space group P4(1) (No. 76) with lattice constants a = 8.255(1) A and c = 30.033(6) A. The structure features an isolated Fe-centered La 6 octahedron with all corners, 9 of its 12 edges, and 3 of its 8 triangular faces coordinated, bridged, or capped by Br atoms. The La6Fe octahedron is significantly distorted, and the La coordination by Br atoms deviates from the common close-packing arrangements found in other reduced rare earth metal halides. Band structure, bonding, and physical properties of the compound have been investigated.
Large scale synthesis of 4‐ethylpyrimidine

The reaction of methyl propionyl acetate with formamidine acetate in the presence of sodium methoxide produces 6-ethyl-4(3H)-pyrimidinone (1) in 67% isolated yield. Reaction with phosphorus oxychloride and subsequent catalytic hydrogenolysis affords 4-ethylpyrimidine (3) in 41% overall yield.
QUARK MIXING MATRIX STUDIES AND LEPTON FLAVOR VIOLATION SEARCHES USING RARE DECAYS OF KAONS

I review recent results from experiments on rare decays of kaons, concentrating on searches for lepton flavor violation (LFV) and on measurements of quark mixing (CKM) matrix elements. The LFV results are the culmination of 15 years of experimentation at Brookhaven National Laboratory and are unlikely to be improved upon soon. The CKM studies derive from measurements of decay rates of charged and neutral kaons into lepton anti-lepton pairs, both with and without a charged or neutral pion. I discuss recent results and prospects for improved measurements that could provide an unambiguous test of the Standard Model explanation for CP violation. This paper is the written version of a talk presented at the Lepton-Photon Conference in August 1999.
Select β-Lactam Combinations Exhibit Synergy against Mycobacterium abscessus In Vitro

Mycobacterium abscessus is a nontuberculous mycobacterium that causes invasive pulmonary infections in patients with structural lung disease. M. abscessus is intrinsically resistant to several classes of antibiotics, and an increasing number of strains isolated from patients exhibit resistance to most antibiotics considered for treatment of infections by this mycobacterium. Therefore, there is an unmet need for new regimens with improved efficacy to treat this disease. Synthesis of the essential cell wall peptidoglycan in M. abscessus is achieved via two enzyme classes, l,d- and d,d-transpeptidases, with each class preferentially inhibited by different subclasses of β-lactam antibiotics. We hypothesized that a combination of two β-lactams that comprehensively inhibit the two enzyme classes will exhibit synergy in killing M. abscessus Paired combinations of antibiotics tested for in vitro synergy against M. abscessus included dual β-lactams, a β-lactam and a β-lactamase inhibitor, and a β-lactam and a rifamycin. Of the initial 206 combinations screened, 24 pairs exhibited synergy. A total of 13/24 pairs were combinations of two β-lactams, and 12/24 pairs brought the MICs of both drugs to within the therapeutic range. Additionally, synergistic drug pairs significantly reduced the frequency of selection of spontaneous resistant mutants. These novel combinations of currently available antibiotics may offer viable immediate treatment options against highly-resistant M. abscessus infections.
Convenient and Improved Halogenation of 3,5-Diarylisoxazoles Using N-Halosuccinimides

The convenient C-4 halogenation of 3,5-diarylisoxazoles using N-halosuccinimides (NBS, NCS, or NIS) in acetic acid is described. A strong acid catalyst was required for efficient halogenation of some isoxazoles depending on the substituent on the 5-phenyl ring. Finally, the 4-iodoisoxazoles were found to undergo a novel proto-deiodination upon heating in the presence of H 2 SO 4 .
TRANSFORMING A NONSELECTIVE CARBENE REARRANGEMENT INTO A HIGHLY SELECTIVE PROCESS BY USING CRYSTALLINE MEDIA

Of all the methods that may be applied to the study and understanding of carbene reactivity,1 crystal chemistry may offer the most insight into structural questions.2 By superimposing high environmental barriers over the relatively flat energy surfaces observed in fluid media, one may gain insight into the dynamics of these highly reactive species.3 One may expect that crystalline environments can preorganize carbene structures to favor some reaction pathways while blocking them from others.4 In this communication we report evidence supporting this hypothesis in the case of 1,2-diaryl-1-alkylidenes capable of undergoing intramolecular 1,2-H shifts and 1,2-Ph migrations. Experimental results with 1-(4′-biphenyl)-2-pheny-l-diazopropane (1) suggest that carbene 2 can be generated in the solid state by UV irradiation. As indicated in Scheme 1, the crystalline medium is capable of controlling the reaction to high yields and unprecedented selectivity. Formation of the main product may be explained in terms of overlap of the migrating hydrogen with the carbene empty p-orbital as applied to the conformation deduced from the crystal structure of the diazo precursor.
Neurodynamics and connectivity during facial fear perception: The role of threat exposure and signal congruity

Fearful faces convey threat cues whose meaning is contextualized by eye gaze: While averted gaze is congruent with facial fear (both signal avoidance), direct gaze (an approach signal) is incongruent with it. We have previously shown using fMRI that the amygdala is engaged more strongly by fear with averted gaze during brief exposures. However, the amygdala also responds more to fear with direct gaze during longer exposures. Here we examined previously unexplored brain oscillatory responses to characterize the neurodynamics and connectivity during brief (~250 ms) and longer (~883 ms) exposures of fearful faces with direct or averted eye gaze. We performed two experiments: one replicating the exposure time by gaze direction interaction in fMRI (N = 23), and another where we confirmed greater early phase locking to averted-gaze fear (congruent threat signal) with MEG (N = 60) in a network of face processing regions, regardless of exposure duration. Phase locking to direct-gaze fear (incongruent threat signal) then increased significantly for brief exposures at ~350 ms, and at ~700 ms for longer exposures. Our results characterize the stages of congruent and incongruent facial threat signal processing and show that stimulus exposure strongly affects the onset and duration of these stages.
Microwave-Assisted Single-Step Functionalization and in Situ Derivatization of Carbon Nanotubes with Gold Nanoparticles

Microwaves are used to functionalize and derivatize multiwalled carbon nanotubes with gold nanoparticles formed by metal ion reduction, all in a single processing step. This strategy provides a rapid and cost-efficient method to attach nanoparticles onto nanotubes for a wide variety of applications.
In Vivo Characterization and Quantification of Neurofibrillary Tau PET Radioligand 18F-MK-6240 in Humans from Alzheimer Disease Dementia to Young Controls

Tau PET imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer disease (AD). This work investigates in vivo kinetics, quantification strategies, and imaging characteristics of a novel tau PET radioligand 18F-MK-6240 in humans. Methods: Fifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted MRI as well as 11C-PiB and 18F-MK-6240 PET imaging. PET data were coregistered to the MRI, and time–activity curves were extracted from regions of interest to assess 18F-MK-6240 kinetics. The pons and inferior cerebellum were investigated as potential reference regions. Reference tissue methods (Logan graphical analysis [LGA] and multilinear reference tissue method [MRTM2]) were investigated for quantification of 18F-MK-6240 distribution volume ratios (DVRs) in a subset of 19 participants. Stability of DVR methods was evaluated using truncated scan durations. SUV ratio (SUVR) estimates were compared with DVR estimates to determine the optimal timing window for SUVR analysis. Parametric SUVR images were used to identify regions of potential off-target binding and to compare binding patterns with neurofibrillary tau staging established in neuropathology literature. Results: SUVs in the pons and the inferior cerebellum indicated consistent clearance across all 51 subjects. LGA and MRTM2 DVR estimates were similar, with LGA slightly underestimating DVR compared with MRTM2. DVR estimates remained stable when truncating the scan duration to 60 min. SUVR determined 70–90 min after injection of 18F-MK-6240 indicated linearity near unity when compared with DVR estimates and minimized potential spill-in from uptake outside the brain. 18F-MK-6240 binding patterns in target regions were consistent with neuropathological neurofibrillary tau staging. Off-target binding regions included the ethmoid sinus, clivus, meninges, substantia nigra, but not the basal ganglia or choroid plexus. Conclusion:18F-MK-6240 is a promising PET radioligand for in vivo imaging of neurofibrillary tau aggregates in AD with minimal off-target binding in the human brain.
The remarkable ability of B3LYP/3-21G(*) calculations to describe geometry, spectral and electrochemical properties of molecular and supramolecular porphyrin–fullerene conjugates

Abstract In recent years, application of calculated density functional theory Kohn–Sham (DFT-KS) orbitals and eigenvalues have gained increased popularity due to their ability to display and predict physico-chemical properties of large systems. Our interest in this area has been to employ the exchange-correlation hybrid functional B3LYP with a small 3-21G (*) basis to determine the geometry of large donor–acceptor assemblies followed by comparison of the computed KS orbital energies with measured electrochemical and spectral properties. The surprisingly localized orbitals allow prediction of the site of electron transfer during electrochemical oxidation and reduction of covalently bonded or self assembled porphyrin–fullerene donor–acceptor systems. The highest occupied orbitals (HOMOs) track oxidation potentials while the lowest unoccupied orbitals (LUMOs) track the reduction potentials of these compounds. Such studies are important to determine the position of energy levels of these donor–acceptor systems for understanding the pathways of photo initiated electron or energy transfer processes. The geometry and association energy of supramolecular assemblies (including loosely bound complexes self-assembled by H-bonding, electrostatics, or by π–π porphyrin–fullerene interactions) are also well represented, but the association energy must be scaled to agree with experimental values. The unusual success of the B3LYP/3-21G (*) method may be attributable, in part, to fortuitous shadowing of the interaction energy by significant basis set superposition effects. Results of several molecular and supramolecular systems at this computational level, comprised of porphyrin–fullerene donor–acceptor entities, developed in our laboratory, are reviewed. To cite this article: M.E. Zandler, F. D'Souza, C. R. Chimie 9 (2006) .
Electrophilic Fluorination-Nucleophilic Addition Reaction Mediated by Selectfluor: Mechanistic Studies and New Applications.

The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
Stereoselective total syntheses and reassignment of stereochemistry of the freshwater cyanobacterial hepatotoxins cylindrospermopsin and 7-epicylindrospermopsin.

A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from co...
Redox potential as a master variable controlling pathways of metal reduction by Geobacter sulfurreducens.

Geobacter sulfurreducens uses at least two different pathways to transport electrons out of the inner membrane quinone pool before reducing acceptors beyond the outer membrane. When growing on electrodes poised at oxidizing potentials, the CbcL-dependent pathway operates at or below redox potentials of –0.10 V vs the standard hydrogen electrode, whereas the ImcH-dependent pathway operates only above this value. Here, we provide evidence that G. sulfurreducens also requires different electron transfer proteins for reduction of a wide range of Fe(III)- and Mn(IV)-(oxyhydr)oxides, and must transition from a high- to low-potential pathway during reduction of commonly studied soluble and insoluble metal electron acceptors. Freshly precipitated Fe(III)-(oxyhydr)oxides could not be reduced by mutants lacking the high-potential pathway. Aging these minerals by autoclaving did not change their powder X-ray diffraction pattern, but restored reduction by mutants lacking the high-potential pathway. Mutants lacking the low-potential, CbcL-dependent pathway had higher growth yields with both soluble and insoluble Fe(III). Together, these data suggest that the ImcH-dependent pathway exists to harvest additional energy when conditions permit, and CbcL switches on to allow respiration closer to thermodynamic equilibrium conditions. With evidence of multiple pathways within a single organism, the study of extracellular respiration should consider not only the crystal structure or solubility of a mineral electron acceptor, but rather the redox potential, as this variable determines the energetic reward affecting reduction rates, extents, and final microbial growth yields in the environment.
Reactions of Dichloroperfluorocycloalkenes with Tetraazamacrocyclic Amines

1,2-Dichlorotetrafluorocyclobutene (A) and 1,2-dichlorohexafluorocylopentene-1 (B) were reacted with triazamacrocyclic amines (1,4,8-triazacycloundecane (1) and 1,5,9-triazacyclo-dodecane (2)) at 80 °C in the presence of stoichiometric amounts of triethylamine in benzene. Cycloalkene A formed a 2:1 product 3 with 1 and a 3:1 product 4 with 2. Cycloalkene B formed only 2:1 products 5 and 6 with 1 and 2, respectively. The crystal structures of 3 and 4 were determined by single-crystal X-ray diffraction.
Methylsulfenylation of thioacetals as a method for synthesizing 2-thio-substituted furans.

The dimethyl(methylthio)sulfonium tetrafluoroborate induced cyclization of various bis(methylsulfanyl) carbonyl compounds is described. The reaction proceeds by methylthiolation of the thioacetal g...
Preparation of 5-(cyclohexylmethyl)barbituric acid derivatives by acid-catalyzed reductive cyclohexylmethylation of barbituric acids with p-hydroxy or p-methoxybenzaldehydes

Abstract A very inexpensive, simple, and high yield procedure for the preparation of valuable pharmaceutical intermediates, 5-cyclohexylmethylbarbiturates, was developed starting from either p -hydroxy or p -methoxybenzaldehyde and barbituric acid. Although the reaction sequence involves several steps, such as selecting a suitable catalyst (5% PdC in 2% percent molar ratio) and solvent (methanol–hydrochloric acid 1:1) the preparation can be carried out in only one practical step (one-pot preparation).
Short, stereoselective synthesis of C-glycosyl asparagines via an olefin cross-metathesis

The Grubbs second generation ruthenium catalyst was employed for the cross metathesis between α- and β-C-allyl glycosides and suitably protected l-vinyl glycines to furnish olefinic products in 57–94% yields. Hydrogenation afforded the C-glycosyl asparagines in high yield.