cssi/SciSciGPT-SciSciNet huggingface dataset:
Bound and continuum-embedded states of cyanopolyyne anions.

Cyanopolyyne anions were among the first anions discovered in the interstellar medium. The discovery has raised questions about the routes of formation of these anions in space. Some of the proposed mechanisms assumed that anionic excited electronic states, either metastable or weakly bound, play a key role in the formation process. The verification of this hypothesis requires detailed knowledge of the electronic states of the anions. Here we investigate the bound and continuum states of four cyanopolyyne anions, CN−, C3N−, C5N−, and C7N−, by means of ab initio calculations. We employ the equation-of-motion coupled-cluster method augmented with complex absorbing potential. We predict that already in CN−, the smallest anion in the family, there are several low-lying metastable states of both singlet and triplet spin symmetry. These states, identified as shape resonances, are located between 6.3–8.5 eV above the ground state of the anion (or 2.3–4.5 eV above the ground state of the parent radical) and have widths of a few tenths of eV up to 1 eV. We analyze the identified resonances in terms of leading molecular orbital contributions and Dyson orbitals. As the carbon chain length increases in the C2n+1N− series, these resonances gradually become stabilized and eventually turn into stable valence bound states. The trends in the energies of the transitions leading to both resonance and bound excited states can be rationalized by means of the Huckel model. Apart from valence excited states, some of the cyanopolyynes can also support dipole bound states and dipole stabilized resonances, owing to a large dipole moment of the parent radicals in the lowest 2Σ+ state.
Radical amino acid mutations persist longer in the absence of sex

Harmful mutations are ubiquitous and inevitable, and the rate at which these mutations are removed from populations is a critical determinant of evolutionary fate. Closely related sexual and asexual taxa provide a particularly powerful setting to study deleterious mutation elimination because sexual reproduction should facilitate mutational clearance by reducing selective interference between sites and by allowing the production of offspring with different mutational complements than their parents. Here, we compared the rate of removal of conservative (i.e., similar biochemical properties) and radical (i.e., distinct biochemical properties) nonsynonymous mutations from mitochondrial genomes of sexual versus asexual Potamopyrgus antipodarum, a New Zealand freshwater snail characterized by coexisting and ecologically similar sexual and asexual lineages. Our analyses revealed that radical nonsynonymous mutations are cleared at higher rates than conservative changes and that sexual lineages eliminate radical changes more rapidly than asexual counterparts. These results are consistent with reduced efficacy of purifying selection in asexual lineages allowing harmful mutations to remain polymorphic longer than in sexual lineages. Together, these data illuminate some of the population-level processes contributing to mitochondrial mutation accumulation and suggest that mutation accumulation could influence the outcome of competition between sexual and asexual lineages.
Recent Advances in Understanding Bisphosphonate Effects on Bone Mechanical Properties

Bisphosphonates have well-established effects on suppressing bone resorption and slowing bone loss, yet the effects on bone mechanical properties are less clear. We review recent data from pre-clinical and clinical experiments that assessed mechanical properties of bisphosphonate-treated specimens. Pre-clinical work has utilized new techniques to show reduced fatigue life and transfer of stress from the mineral to collagen. Several notable studies have examined mechanical properties of tissue from patients treated with bisphosphonates with mixed results. Pre-clinical data suggest effects on mechanics may be independent of remodeling suppression. The direct effect of bisphosphonates on bone mechanics remains unclear but recent work has set a solid foundation for the coming years.
Correlated Dynamics in Aqueous Proton Diffusion

The aqueous proton displays an anomalously large diffusion coefficient that is up to 7 times that of similarly sized cations. There is general consensus that the proton achieves its high diffusion through the Grotthuss mechanism, whereby protons hop from one molecule to the next. A main assumption concerning the extraction of the timescale of the Grotthuss mechanism from experimental results has been that, on average, there is an equal probability for the proton to hop to any of its neighboring water molecules. Herein, we present ab initio simulations that show this assumption is not generally valid. Specifically, we observe that there is an increased probability for the proton to revert back to its previous location. These correlations indicate that the interpretation of the experimental results need to be re-examined and suggest that the timescale of the Grotthuss mechanism is significantly shorter than was previously thought.
Evidence for ephemeral middle Eocene to early Oligocene Greenland glacial ice and pan-Arctic sea ice.

Earth's modern climate is defined by the presence of ice at both poles, but that ice is now disappearing. Therefore understanding the origin and causes of polar ice stability is more critical than ever. Here we provide novel geochemical data that constrain past dynamics of glacial ice on Greenland and Arctic sea ice. Based on accurate source determinations of individual ice-rafted Fe-oxide grains, we find evidence for episodic glaciation of distinct source regions on Greenland as far-ranging as similar to 68 degrees N and similar to 80 degrees N synchronous with ice-rafting from circum-Arctic sources, beginning in the middle Eocene. Glacial intervals broadly coincide with reduced CO2, with a potential threshold for glacial ice stability near similar to 500 p.p.m.v. The middle Eocene represents the Cenozoic onset of a dynamic cryosphere, with ice in both hemispheres during transient glacials and substantial regional climate heterogeneity. A more stable cryosphere developed at the Eocene-Oligocene transition, and is now threatened by anthropogenic emissions.
GRAFENE: Graphlet-based alignment-free network approach integrates 3D structural and sequence (residue order) data to improve protein structural comparison

Initial protein structural comparisons were sequence-based. Since amino acids that are distant in the sequence can be close in the 3-dimensional (3D) structure, 3D contact approaches can complement sequence approaches. Traditional 3D contact approaches study 3D structures directly and are alignment-based. Instead, 3D structures can be modeled as protein structure networks (PSNs). Then, network approaches can compare proteins by comparing their PSNs. These can be alignment-based or alignment-free. We focus on the latter. Existing network alignment-free approaches have drawbacks: 1) They rely on naive measures of network topology. 2) They are not robust to PSN size. They cannot integrate 3) multiple PSN measures or 4) PSN data with sequence data, although this could improve comparison because the different data types capture complementary aspects of the protein structure. We address this by: 1) exploiting well-established graphlet measures via a new network alignment-free approach, 2) introducing normalized graphlet measures to remove the bias of PSN size, 3) allowing for integrating multiple PSN measures, and 4) using ordered graphlets to combine the complementary PSN data and sequence (specifically, residue order) data. We compare synthetic networks and real-world PSNs more accurately and faster than existing network (alignment-free and alignment-based), 3D contact, or sequence approaches.
Non-linear shift from grassland to shrubland in temperate barrier islands

Woody plant encroachment into grasslands is a major land cover change taking place in many regions of the world, including arctic, alpine and desert ecosystems. This change in plant dominance is also affecting coastal ecosystems, including barrier islands, which are known for being vulnerable to the effects of climate change. In the last century, the woody plant species Morella cerifera L. (Myricaceae), has encroached into grass covered swales in many of the barrier islands of Virginia along the Atlantic seaboard. The abrupt shift to shrub cover in these islands could result from positive feedbacks with the physical environment, though the underlying mechanisms remain poorly understood. We use a combination of experimental and modeling approaches to investigate the role of climate warming and the ability of M. cerifera to mitigate its microclimate thereby leading to the emergence of alternative stable states in barrier island vegetation. Nighttime air temperatures were significantly higher in myrtle shrublands than grasslands, particularly in the winter season. The difference in the mean of the 5% and 10% lowest minimum temperatures between shrubland and grassland calculated from two independent datasets ranged from 1.3 to 2.4°C. The model results clearly show that a small increase in near-surface temperature can induce a non-linear shift in ecosystem state from a stable state with no shrubs to an alternative stable state dominated by M. cerifera. This modeling framework improves our understanding and prediction of barrier island vegetation stability and resilience under climate change, and highlights the existence of important nonlinearities and hystereses that limit the reversibility of this ongoing shift in vegetation dominance.
Judicial appraisals of risk assessment in sentencing

The assessment of an offender's risk of recidivism is emerging as a key consideration in sentencing policy in many US jurisdictions. However, little information is available on how actual sentencing judges view this development. This study surveys the views of a population sample of judges in Virginia, the state that has gone further than any other in legislatively mandating risk assessment for certain drug and property offenders. Results indicate that a strong majority of judges endorse the principle that sentencing eligible offenders should include a consideration of recidivism risk. However, a strong majority also report the availability of alternatives to imprisonment in their jurisdictions to be inadequate at best. Finally, most judges oppose the adoption of a policy requiring them to provide a written reason for declining to impose alternative interventions on "low-risk" offenders.
Approximation by Combinations of ReLU and Squared ReLU Ridge Functions With $\ell^1$ and $\ell^0$ Controls

We establish $L^{\infty } $ and $L^{2} $ error bounds for functions of many variables that are approximated by linear combinations of rectified linear unit (ReLU) and squared ReLU ridge functions with $\ell ^{1} $ and $\ell ^{0} $ controls on their inner and outer parameters. With the squared ReLU ridge function, we show that the $L^{2} $ approximation error is inversely proportional to the inner layer $\ell ^{0} $ sparsity and it need only be sublinear in the outer layer $\ell ^{0} $ sparsity. Our constructions are obtained using a variant of the Maurey–Jones–Barron probabilistic method, which can be interpreted as either stratified sampling with proportionate allocation or two-stage cluster sampling. We also provide companion error lower bounds that reveal near optimality of our constructions. Despite the sparsity assumptions, we showcase the richness and flexibility of these ridge combinations by defining a large family of functions, in terms of certain spectral conditions, that are particularly well approximated by them.
Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

Throughout our waking hours, we experience an ever-changing stream of input from our senses. The brain responds to this varying input by adjusting its own activity levels and even its own structure. It does this by changing the strength of the connections between neurons, or the properties of the neurons themselves. Known as plasticity, this process of continuous change enables the brain to develop, learn and to recover from injury. The visual systems of mammals are particularly well suited to studying how sensory experience alters the brain. Studies in animals show that lack of sensory input to one or both eyes during a critical period in development causes long-lasting changes in the brain’s visual circuits. Similarly, children with the condition amblyopia or ‘lazy eye’ – in which one eye has impaired vision and the brain ignores input from that eye – can end up with permanent deficits in their vision if the condition is not treated during childhood. Changes in sensory input are thought to trigger plasticity in the brain by altering the activity of specific genes. But exactly how this process works is unclear. Moore, Richards et al. now show that a gene called Rem2 has an important role in regulating visual plasticity. In the key experiments, young mice had their vision in one eye blocked for a few days. Analysis of their brains showed that mice that had been genetically modified to lack the Rem2 gene responded differently to this change in their environment (i.e. the loss of input to one eye) than their normal counterparts. Further experiments suggest that Rem2 regulates the excitability of individual neurons: that is, how much the neurons respond to any given input. In the absence of Rem2, neurons in visual areas of the brain become hyperactive. This prevents them from adjusting their activity levels in response to changes in sensory input, which in turn leads to impaired plasticity. Being able to harness the brain’s visual plasticity mechanisms on demand, for example by regulating Rem2 activity, could benefit individuals with disorders such as amblyopia. Rem2 is also active in many other parts of the brain besides those that support vision. This suggests that manipulating this gene could affect numerous forms of plasticity. However, various barriers must be overcome before we could use this approach to treat brain disorders. These include obtaining a more in depth understanding of the role of the Rem2 gene in the human brain.
Astrophysical tests of screened modified gravity

Screened modified gravity models evade solar system tests of relativistic gravitation but exhibit novel and interesting effects on scales between the solar system and the Hubble flow: astrophysical...
Revealing the effects of damping on the flow-induced vibration of flexible cylinders

Abstract This study reveals how damping shapes the global vortex-induced vibration (VIV) response of flexible cylinders. Global behavior may vary from full-length standing waves to traveling waves on infinite cylinders. Structural damping rules the standing wave case whereas radiation damping regulates VIV response on very long cylinders. A single scalar equation expresses the balance of power flowing through the structure. In that equation, A r m s , which is the root-mean-square response in the VIV excitation region, is shown to be an excellent indicator of global response because of its relation to power flow. Under steady-state conditions, the net power flow must be zero, which directly leads to three independent dimensionless damping parameters, namely α , β R , and c * . β R indicates when radiation damping is important, α reveals the relative importance of structural versus radiation damping, and c ∗ locates the global VIV behavior on the spectrum of lightly to strongly damped systems. Structural, hydrodynamic, and wave radiation damping are all taken into account. Plots of A r m s ∗ versus c ∗ show the global effects of damping on response. Uncontrolled factors often reveal themselves as graphical anomalies, leading to new insights on VIV. Data from experiments and numerical simulations are presented to support the conclusions.
Advancing Multi-Accented Lstm-CTC Speech Recognition Using a Domain Specific Student-Teacher Learning Paradigm

Non-native speech causes automatic speech recognition systems to degrade in performance. Past strategies to address this challenge have considered model adaptation, accent classification with a model selection, alternate pronunciation lexicon, etc. In this study, we consider a recurrent neural network (RNN) with connectionist temporal classification (CTC) cost function trained on multi-accent English data including US (Native), Indian and Hispanic accents. We exploit dark knowledge from a model trained with the multi-accent data to train student models under the guidance of both a teacher model and CTC cost of target transcription. We show that transferring knowledge from a single RNN-CTC trained model toward a student model, yields better performance than the stand-alone teacher model. Since the outputs of different trained CTC models are not necessarily aligned, it is not possible to simply use an ensemble of CTC teacher models. To address this problem, we train accent specific models under the guidance of a single multi-accent teacher, which results in having multiple aligned and trained CTC models. Furthermore, we train a student model under the supervision of the accent-specific teachers, resulting in an even further complementary model, which achieves +20.1% relative Character Error Rate (CER) reduction compared to the baseline trained without any teacher. Having this effective multi-accent model, we can achieve further improvement for each accent by adapting the model to each accent. Using the accent specific model’s outputs to regularize the adapting process (i.e., a knowledge distillation version of Kullback-Leibler (KL) divergence) results in even superior performance compared to the conventional approach using general teacher models.
Random Directed Graph Distributions in the Triad Census in Social Networks

This paper uses the concept of the triad census as, developed by Holland and Leinhardt, and describes several distributions on directed graphs. Methods are presented for calculating the mean and the covariance matrix of the triad census for the uniform distribution that conditions on the number of choices made by each individual in the social network. Several complex distributions on digraphs are approximated, and an application of these methods to a sociogram is given.
The patient said he would rather die: Should you let him?

It is a well-established canon of law in the United States that every person has the right to determine what happens to his own body, including refusal of life-sustaining treatment. Surgeons often find it difficult to accept prima facie a patient’s refusal of a life-saving operation that the surgeon knows can be done with a reasonable degree of success. Fortunately, we do not face that problem very often, but when we do, we frequently struggle with how to handle the situation, because usually no simple answers are evident. Just such a fictional case — a rupturing aortic aneurysm — was presented for debate at the 98th Annual Meeting of the American Association for Thoracic Surgery, pitting a professor of law with expertise in bioethics against a highly experienced cardiothoracic surgeon with a distinctly contrary view.
The probability distribution of word maps on finite groups

Abstract Word maps provide a wealth of information about finite groups. We examine the connection between the probability distribution induced by a word map and the underlying structure of a finite group. We show that a finite group is nilpotent if and only if every surjective word map has fibers of uniform size. Moreover, we show that probability distributions themselves are sufficient to identify nilpotent groups, and these same distributions can be used to determine abelian groups up to isomorphism. In addition we answer a question of Amit and Vishne.
Scalable Hash-Based Estimation of Divergence Measures.

We propose a scalable divergence estimation method based on hashing. Consider two continuous random variables $X$ and $Y$ whose densities have bounded support. We consider a particular locality sensitive random hashing, and consider the ratio of samples in each hash bin having non-zero numbers of Y samples. We prove that the weighted average of these ratios over all of the hash bins converges to f-divergences between the two samples sets. We show that the proposed estimator is optimal in terms of both MSE rate and computational complexity. We derive the MSE rates for two families of smooth functions; the Holder smoothness class and differentiable functions. In particular, it is proved that if the density functions have bounded derivatives up to the order $d/2$ , where $d$ is the dimension of samples, the optimal parametric MSE rate of $O(1/N)$ can be achieved. The computational complexity is shown to be $O(N)$ , which is optimal. To the best of our knowledge, this is the first empirical divergence estimator that has optimal computational complexity and achieves the optimal parametric MSE estimation rate.
On Finding Quantum Multi-collisions

A k-collision for a compressing hash function H is a set of k distinct inputs that all map to the same output. In this work, we show that for any constant k, \(\varTheta \left( N^{\frac{1}{2}(1-\frac{1}{2^k-1})}\right) \) quantum queries are both necessary and sufficient to achieve a k-collision with constant probability. This improves on both the best prior upper bound (Hosoyamada et al., ASIACRYPT 2017) and provides the first non-trivial lower bound, completely resolving the problem.
$L^{p}$ regularity of weighted Bergman projections

We investigate $L^p$ regularity of weighted Bergman projections on the unit disc and $L^p$ regularity of ordinary Bergman projections in higher dimensions.
Efficient surrogate modeling methods for large-scale Earth system models based on machine-learning techniques

Abstract. Improving predictive understanding of Earth system variability and change requires data–model integration. Efficient data–model integration for complex models requires surrogate modeling to reduce model evaluation time. However, building a surrogate of a large-scale Earth system model (ESM) with many output variables is computationally intensive because it involves a large number of expensive ESM simulations. In this effort, we propose an efficient surrogate method capable of using a few ESM runs to build an accurate and fast-to-evaluate surrogate system of model outputs over large spatial and temporal domains. We first use singular value decomposition to reduce the output dimensions and then use Bayesian optimization techniques to generate an accurate neural network surrogate model based on limited ESM simulation samples. Our machine-learning-based surrogate methods can build and evaluate a large surrogate system of many variables quickly. Thus, whenever the quantities of interest change, such as a different objective function, a new site, and a longer simulation time, we can simply extract the information of interest from the surrogate system without rebuilding new surrogates, which significantly reduces computational efforts. We apply the proposed method to a regional ecosystem model to approximate the relationship between eight model parameters and 42 660 carbon flux outputs. Results indicate that using only 20 model simulations, we can build an accurate surrogate system of the 42 660 variables, wherein the consistency between the surrogate prediction and actual model simulation is 0.93 and the mean squared error is 0.02. This highly accurate and fast-to-evaluate surrogate system will greatly enhance the computational efficiency of data–model integration to improve predictions and advance our understanding of the Earth system.
Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction.

Stable recognition of the intron branchpoint (BP) by the U2 snRNP to form the pre-spliceosome is the first ATP-dependent step of splicing. Genetic and biochemical data from yeast indicate that Cus2 aids U2 snRNA folding into the stem IIa conformation prior to pre-spliceosome formation. Cus2 must then be removed by an ATP-dependent function of Prp5 before assembly can progress. However, the location from which Cus2 is displaced and the nature of its binding to the U2 snRNP are unknown. Here, we show that Cus2 contains a conserved UHM (U2AF homology motif) that binds Hsh155, the yeast homolog of human SF3b1, through a conserved ULM (U2AF ligand motif). Mutations in either motif block binding and allow pre-spliceosome formation without ATP. A 2.0 A resolution structure of the Hsh155 ULM in complex with the UHM of Tat-SF1, the human homolog of Cus2, and complementary binding assays show that the interaction is highly similar between yeast and humans. Furthermore, we show that Tat-SF1 can replace Cus2 function by enforcing ATP dependence of pre-spliceosome formation in yeast extracts. Cus2 is removed before pre-spliceosome formation, and both Cus2 and its Hsh155 ULM binding site are absent from available cryo-EM structure models. However, our data are consistent with the apparent location of the disordered Hsh155 ULM between the U2 stem-loop IIa and the HEAT repeats of Hsh155 that interact with Prp5. We propose a model in which Prp5 uses ATP to remove Cus2 from Hsh155 such that extended base-pairing between U2 snRNA and the intron BP can occur.
Analyzing the effects of a flipped classroom pedagogy on freshmen and sophomore STEM courses

This Research-to-Practice paper, a work-in-progress, describes work supported by the First in the World program at three different universities in California. A consortium of three California State Universities (CSUs)– San Jose State University, California State University- Los Angeles, and Cal Poly Pomona – have a four-year grant from the U.S Department of Education First-in-the-World (FITW) program. Surveys of students revealed that a major challenge to success is course bottlenecks – impasses where they cannot enroll in a course they need to make progress toward their degrees or when they cannot successfully complete a course and move forward. All three campuses have large numbers of high-need and underrepresented students (URM) and URM students are overrepresented among students who receive low grades in bottleneck courses. To address course bottlenecks, the flipped classroom approach has been implemented in seven gateway STEM courses collaboratively across the partner campuses. This paper targets faculty and administrators interested in promoting and implementing the flipped classroom pedagogy at their institutions. It provides a brief overview of the target courses and the impact of the curricular changes thus far. In addition, a description of the in-depth Calculus study of the flipped classroom approach across the three campuses is discussed.
Characteristics of Future Models of Integrated Outpatient Care.

Replacement of fee-for-service with capitation arrangements, forces physicians and institutions to minimize health care costs, while maintaining high-quality care. In this report we described how patients and their families (or caregivers) can work with members of the medical care team to achieve these twin goals of maintaining—and perhaps improving—high-quality care and minimizing costs. We described how increased self-management enables patients and their families/caregivers to provide electronic patient-reported outcomes (i.e., symptoms, events) (ePROs), as frequently as the patient or the medical care team consider appropriate. These capabilities also allow ongoing assessments of physiological measurements/phenomena (mHealth). Remote surveillance of these communications allows longer intervals between (fewer) patient visits to the medical-care team, when this is appropriate, or earlier interventions, when it is appropriate. Systems are now available that alert medical care providers to situations when interventions might be needed.
Analysis of Large Heterogeneous Repairable System Reliability Data With Static System Attributes and Dynamic Sensor Measurement in Big Data Environment

In the age of Big Data, one pressing challenge facing engineers is to perform reliability analysis for a large fleet of heterogeneous repairable systems with covariates. In addition to static covar...
Strain anisotropy and magnetic domain structures in multiferroic heterostructures: High-throughput finite-element and phase-field studies

Abstract Understanding magnetic domain structures and their responses to electric fields in multiferroic heterostructures is critical to the design of electric-field-driven spintronic devices. High-throughput finite-element and phase-field simulations are performed to probe the piezoelectric strain anisotropy and its relaxation, magnetic domain structures and their responses to applied voltages as function of the in-plane dimensions and thickness of the magnetic Ni nanoislands grown on a Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 (PMN-PT) membrane. The piezoelectric strain anisotropy is found to increase with the in-plane aspect ratio, but it can be significantly relaxed, as large as >80%, in nanoislands of thickness larger than >15 nm. Magnetic domain diagrams are established to identify the domain structures for Ni nanoislands of different lengths of in-plane major and minor axis, as well as thickness. When a voltage is applied to the multiferroic heterostructure, the single-domain magnetic domain can be switched by the piezoelectric strain, whereas the vortex domain is not switched. However, for a multiferroic heterostructure with a thick nanoisland wherein most of the piezoelectric strain is relaxed, the single-domain magnetic domain shows a weak response to the voltage and cannot be switched. The effect of thickness variation in real magnets on the switching is also discussed. The present results are expected to provide guidance to the understanding and design of multiferroic nanostructures for achieving electric-field-modulated magnetic properties.
Perturbation of Hydrogen-Bonding Networks over Supported Lipid Bilayers by Poly(allylamine hydrochloride).

Water is vital to many biochemical processes and is necessary for driving fundamental interactions of cell membranes with their external environments, yet it is difficult to probe the membrane/water interface directly and without the use of external labels. Here, we employ vibrational sum frequency generation spectroscopy to understand the role of interfacial water molecules above bilayers formed from zwitterionic (phosphatidylcholine) and anionic (phosphatidylglycerol, PG, and phosphatidylserine, PS) lipids as they are exposed to the common polycation poly(allylamine hydrochloride) (PAH) in 100 mM NaCl. We show that as the concentration of PAH is increased, the interfacial water molecules are irreversibly displaced and find that it requires 10 times more PAH to displace interfacial water molecules from membranes formed from purely zwitterionic lipids when compared to membranes that contain the anionic PG and PS lipids. This outcome is likely due to the difference in (1) the energy with which water molecu...
An Empirical Investigation of the Relationship between Local Government Budgets, IT Expenditures, and Cyber Losses

Information technology (IT) is the key component of e-government infrastructures, but at the same time, it makes governments more exposed to the cyber risk. In this study, we take an empirical approach to investigate the cyber risk in the public sector. We describe the most common cyber threats facing local governments and build linear models to explain the relationships between cyber losses, local government budgets, and IT expenditures. We find that local governments are affected by cyber incidents more frequently, and disruption incidents that lead to the malfunction of e-government services are on the rise. In addition, the magnitude of cyber losses used to have a strong positive relationship with the affected governments’ budget size. However, in recent years, this relationship is weakening, and small local governments are more heavily impacted by cyber incidents than before. Our findings further suggest that investing in information technology is becoming more effective in terms of lowering the loss-to-budget ratio. However, this also means local governments with small budgets do not benefit from this change as much as the large ones do.
Collective Progress in the Light of Equity Under the Global Stocktake

Following the Paris Rulebook decisions adopted at COP 24/CMA 1.3 in December 2018, six articles were written on different aspects of the Rulebook for publication in a special issue of Climate Law, due out in April 2019. This is one of those articles. The Global Stocktake compels states periodically to focus on the Paris Agreement’s ultimate aims. Without it, each state’s attention would have been fixated on its own Nationally Determined Contribution and little else. The Paris Rulebook clarifies how the stocktaking mechanism is to function — in all but one respect: although the rules keep the emphasis squarely on “collective progress” as the proper object of the stocktake’s assessment, the text is ambiguous as to whether its implied opposite — individual state progress — is to be excluded from the assessment. The ambiguity rides mainly on the notion of “equity” — a term as dutifully inserted into key passages of the Rulebook as its explanation is studiously avoided. Whatever the negotiators may have intended in this respect, an objective construction of the Rulebook shows that an assessment of the individual progress of states is permitted to occupy a substantial part of the stocktaking process, except when it comes to formal reporting on the stocktake’s outputs. The non-exclusion of individual assessment from the dialogue that powers the stocktake means that, while the ideology of “national self-determination” may have succeeded in turning out an Article 15 Committee of unprecedented blandness, it has neglected to defend its flanks in the Global Stocktake, making for an unpredictable, yet potentially useful process.
Class groups of Kummer extensions via cup products in Galois cohomology

We use Galois cohomology to study the $p$-rank of the class group of $\mathbf{Q}(N^{1/p})$, where $N \equiv 1 \bmod{p}$ is prime. We prove a partial converse to a theorem of Calegari--Emerton, and provide a new explanation of the known counterexamples to the full converse of their result. In the case $p = 5$, we prove a complete characterization of the $5$-rank of the class group of $\mathbf{Q}(N^{1/5})$ in terms of whether or not $\prod_{k=1}^{(N-1)/2} k^{k}$ and $\frac{\sqrt{5} - 1}{2}$ are $5$th powers mod $N$.
Regioselective lactonization of naphthoquinones: synthesis and antitumoral activity of the WS-5995 antibiotics

Abstract An acid promoted quinolactonization of naphthoquinones has been developed, providing direct access to either ortho or para isomers as desired. Application of this methodology in syntheses of the antibiotics WS-5995A, WS-5995C and functional analogs is demonstrated. Preliminary antitumoral activity of the analogs is presented together with electrochemical analysis.
Development and Validation of a Phenotypic High-Content Imaging Assay for Assessing the Antiviral Activity of Small-Molecule Inhibitors Targeting Zika Virus.

Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barre syndrome. There are currently no drugs available to treat ZIKV infection, and accordingly, there is an unmet medical need for the discovery of new therapies. High-throughput drug screening efforts focusing on indirect readouts of cell viability are prone to a higher frequency of false positives in cases where the virus is viable in the cell but the cytopathic effect (CPE) is reduced or delayed. Here, we describe a fast and label-free phenotypic high-content imaging assay to detect cells affected by the virus-induced CPE using automated imaging and analysis. Protection from the CPE correlates with a decrease in viral antigen production, as observed by immunofluorescence. We trained our assay using a collection of nucleoside analogues with activity against ZIKV; the previously reported antiviral activities of 2'-C-methylribonucleosides and ribavirin against the Zika virus in Vero cells were confirmed using our developed method. To validate the ability of our assay to reveal new anti-ZIKV compounds, we profiled a novel library of 24 natural product derivatives and found compound 1 to be an inhibitor of the ZIKV-induced cytopathic effect; the activity of the compound was confirmed in human fetal neural stem cells (NSCs). The described technique can be easily leveraged as a primary screening assay for profiling of the activities of large compound libraries against ZIKV and can be expanded to other ZIKV strains and other cell lines displaying morphological changes upon ZIKV infection.
Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Learning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the Drosophila synthetic population resource (DSPR), a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and other traits. Fruit flies can be trained in a "heat box" to learn to remain on one side of a chamber (place learning) and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for ~49 000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA-Seq on pooled samples of seven high performing and seven low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.
Boron Trihalide Mediated Substitution of Hydroxyl Groups with Alkenyl, Alkynyl, and Allyl Moieties

The coupling of alcohols with alkenyl- and alkynylboron dihalides with high olefin stereoselectivity is described. The reaction provides a facile route to internal acetylenes. Notably, the allylation of propargylic alcohols mediated by boron trichloride proceeds smoothly at room temperature and gives excellent regioselectivity.
Perturbative N = 2 Supersymmetric Quantum Mechanics and L-Theory with Complex Coefficients

We construct L-theory with complex coefficients from the geometry of 1|2-dimensional perturbative mechanics. Methods of perturbative quantization lead to wrong-way maps that we identify with those coming from the MSO orientation of L-theory tensored with the complex numbers. In particular, the total volume of a space of 1|2-dimensional vacua reads off the signature of a 4k-dimensional oriented manifold.
Iridium-catalyzed selective N-allylation of hydrazines

Abstract A highly chemo- and regioselective iridium-catalyzed allylic amination is described. The reaction of various hydrazones and hydrazides with allylic carbonates proceeds at ambient temperature in the presence of an [Ir(COD)Cl]2/pyridine catalyst, ammonium iodide, and diethylzinc to afford the corresponding N-allylation products in high yields with excellent chemo- and regioselectivities. Only the more nucleophilic nitrogen of a given hydrazine derivative undergoes the C–N bond formation to yield a branched allylic isomer as the exclusive product.
A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration

Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of light-sensitive photoreceptors that impairs the vision of 9.1 million people in the US. An attractive treatment option is to use gene therapy to deliver broad-spectrum neuroprotective factors. However, this approach has had limited clinical translation because of the inability to control transgene expression. To address this problem, we generated an adeno-associated virus vector named RPF2 that was engineered to express domains of leukemia inhibitory factor fused to the destabilization domain of bacterial dihydrofolate reductase. Fusion proteins containing the destabilization domain are degraded in mammalian cells but can be stabilized with the binding of the drug trimethoprim. Our data show that expression levels of RPF2 are tightly regulated by the dose of trimethoprim and can be reversed by trimethoprim withdrawal. We further show that stabilized RPF2 can protect photoreceptors and prevent blindness in treated mice.
Tandem Intramolecular Silylformylation and Silicon-Assisted Cross-Coupling Reactions. Synthesis of Geometrically Defined α,β-Unsaturated Aldehydes

The palladium- and copper-catalyzed cross-coupling reactions of cyclic silyl ethers with aryl iodides are reported. Silyl ethers 3 were readily prepared by intramolecular silylformylation of homopropargyl silyl ethers 2 under a carbon monoxide atmosphere. The reaction of cyclic silyl ethers 3 with various aryl iodides 7 in the presence of [(allyl)PdCl]2, CuI, a hydrosilane, and KF·2H2O in DMF at room temperature provided the α,β-unsaturated aldehyde coupling products 8 in high yields. The need for copper in this process suggested that transmetalation from silicon to copper is an important step in the mechanism. Although siloxane 3 and the product 8 are not stable under basic conditions, KF·2H2O provided the appropriate balance of reactivity toward silicon and reduced basicity. The addition of a hydrosilane to [(allyl)PdCl]2 was needed to reduce the palladium(II) to the active palladium(0) form.
Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats.

Abstract The dynorphin/kappa opioid receptor (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adult rodents, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U-62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U-62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U-62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U-62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.
Unusual formation of sterically hindered primary amines in a series of pyrrolo- and pyrido[1,2-a]indoles

2,3-Dihydro-2,2,9-trimethyl-1 H -pyrrolo[1,2- a ]indol-1-amine and its 1-(1-pyrrolidinyl) analog have been synthesized from the corresponding 1-ol via mesylation in pyridine followed by treatment with pyrrolidine. Mechanisms of the former, unexpected amination are briefly discussed. Evidence is presented that the pyridine ring serves as a masked amino group. The phenomenon is partly attributed to steric congestion. Similar preparation of 2-bromo-6,7,8,9-tetrahydro-8,8,10-trimethylpyridol[1,2- a ]indol-9-amine supports this notion.
1-[2-(Trimethylsilyl)ethoxy]ethyl (SEE): A novel hybrid hydroxy-protecting group between 1-(ethoxy)ethyl (EE) and 2-(trimethylsilyl)ethoxymethyl (SEM)

Abstract The highly versatile 1-[(2-trimethylsilyl)ethoxy]ethyl (SEE) group, readily obtainable from an alcohol and 2-(trimethylsilyl)ethyl vinyl ether in the presence of a catalytic amount of PPTS, has been developed for the protection of hydroxyl groups. Its deprotection can be achieved under virtually neutral conditions with the use of a fluoride ion source, thus allowing for effective protection of hydroxyl groups of compounds that contain acid- and/or base-sensitive functional groups.
Drosophila embryonic type II neuroblasts: origin, temporal patterning, and contribution to the adult central complex

Drosophila neuroblasts are an excellent model for investigating how neuronal diversity is generated. Most brain neuroblasts generate a series of ganglion mother cells (GMCs) that each make two neurons (type I lineage), but 16 brain neuroblasts generate a series of intermediate neural progenitors (INPs) that each produce 4-6 GMCs and 8-12 neurons (type II lineage). Thus, type II lineages are similar to primate cortical lineages, and may serve as models for understanding cortical expansion. Yet the origin of type II neuroblasts remains mysterious: do they form in the embryo or larva? If they form in the embryo, do their progeny populate the adult central complex, as do the larval type II neuroblast progeny? Here, we present molecular and clonal data showing that all type II neuroblasts form in the embryo, produce INPs and express known temporal transcription factors. Embryonic type II neuroblasts and INPs undergo quiescence, and produce embryonic-born progeny that contribute to the adult central complex. Our results provide a foundation for investigating the development of the central complex, and tools for characterizing early-born neurons in central complex function.
Linking nutrient stoichiometry to Zika virus transmission in a mosquito

Food quality and quantity serve as the basis for cycling of key chemical elements in trophic interactions; yet the role of nutrient stoichiometry in shaping host–pathogen interactions is under appreciated. Most of the emergent mosquito-borne viruses affecting human health are transmitted by mosquitoes that inhabit container systems during their immature stages, where allochthonous input of detritus serves as the basal nutrients. Quantity and type of detritus (animal and plant) were manipulated in microcosms containing newly hatched Aedes aegypti mosquito larvae. Adult mosquitoes derived from these microcosms were allowed to ingest Zika virus-infected blood and then tested for disseminated infection, transmission, and total nutrients (percent carbon, percent nitrogen, ratio of carbon to nitrogen). Treatments lacking high-quality animal (insect) detritus significantly delayed development. Survivorship to adulthood was closely associated with the amount of insect detritus present. Insect detritus was positively correlated with percent nitrogen, which affected Zika virus infection. Disseminated infection and transmission decreased with increasing insect detritus and percent nitrogen. We provide the first definitive evidence linking nutrient stoichiometry to arbovirus infection and transmission in a mosquito using a model system of invasive Ae. aegypti and emergent Zika virus.