cssi/SciSciGPT-SciSciNet huggingface dataset:
Legal, ethical, and human rights considerations for physicians treating children with atypical or ambiguous genitalia

Some governments, human rights organizations, intersex organizations, and doctors have called for a moratorium on genital and gonadal surgeries for infants born with atypical or ambiguous genitalia. Moratorium supporters believe that the surgeries carry physical and emotional risks, the psychosocial benefits of these procedures have not been proven, and the surgeries violate the patients׳ fundamental human rights if they are performed before these patients can provide informed consent. Given these calls for a moratorium, treatment teams must determine how to treat their patients and how to counsel their patients׳ parents. This article examines the treatment teams׳ ethical and legal responsibilities and provides advice for treatment teams to follow that will protect their patients and their practices.
Towards Verifying Nonlinear Integer Arithmetic

We eliminate a key roadblock to efficient verification of nonlinear integer arithmetic using CDCL SAT solvers, by showing how to construct short resolution proofs for many properties of the most widely used multiplier circuits. Such short proofs were conjectured not to exist. More precisely, we give \(n^{O(1)}\) size regular resolution proofs for arbitrary degree 2 identities on array, diagonal, and Booth multipliers and \(n^{O(\log n)}\) size proofs for these identities on Wallace tree multipliers.
Gaugino-assisted anomaly mediation

We present a model of supersymmetry breaking mediated through a small extra dimension. Standard model matter multiplets and a supersymmetry-breaking (or ``hidden'') sector are confined to opposite four-dimensional boundaries while gauge multiplets live in the bulk. The hidden sector does not contain a singlet and the dominant contribution to gaugino masses is via anomaly-mediated supersymmetry breaking. Scalar masses get contributions from both anomaly mediation and a tiny hard breaking of supersymmetry by operators on the hidden-sector boundary. These operators contribute to scalar masses at one loop and in most of parameter space, their contribution dominates. Thus it is easy to make all squared scalar masses positive. As no additional fields or symmetries are required below the Planck scale, we consider this the simplest working model of anomaly mediation. The gaugino spectrum is left untouched and the phenomenology of the model is roughly similar to anomaly mediated supersymmetry breaking with a universal scalar mass added. We identify the main differences in the spectrum between this model and other approaches. We also discuss mechanisms for generating the μ term and constraints on additional bulk fields.
Organisational resilience: building business value in a changing world

As an indication of development, ecological, economic and social frame conditions change owing to local, national and global adjustments. More competition, open markets, changes in political frameworks, structural changes, etc., make up the challenges for economies as a whole, organisations and employees. On the whole, however, the discussion about challenges often forgets the consequences for 'organisational' resilience, i.e., an organisation's capacity to anticipate disturbance, adapt to events, and create lasting value and thrive in a changing world. The notion of a resilient organisation is an emerging concept to clarify and cope with the modern day pace of change. By linking resilience theory with the sustainable transition process of organisations, this contribution has attempted to explore opportunities for and barriers to the diffusion, institutionalisation and implementation of resilience concepts from a holistic perspective. Furthermore, this contribution works toward a unified theory of resilience to help embrace and manage organisational change effectively when considering the concept of a sustainable future. Recommendations are provided for continued research in the modelling of organisational resilience.
EMPA-REG OUTCOME: The Cardiologist's Point of View.

Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling. These concepts and hypotheses are discussed in this report.
The Triple Lattice PETs

Polytope exchange transformations (PETs) are higher dimensional generalizations of interval exchange transformations (IETs) which have been well-studied for more than 40 years. A general method of ...
Pharmacological Inhibition of the DNA Damage Checkpoint Prevents Radiation-Induced Oocyte Death.

Ovarian function is directly correlated with survival of the primordial follicle reserve. Women diagnosed with cancer have a primary imperative of treating the cancer, but since the resting oocytes are hypersensitive to the DNA-damaging modalities of certain chemo- and radiotherapeutic regimens, such patients face the collateral outcome of premature loss of fertility and ovarian endocrine function. Current options for fertility preservation primarily include the collection and cryopreservation of oocytes or in vitro-fertilized oocytes, but this necessitates a delay in cancer treatment and additional assisted reproductive technology procedures. Here, we evaluated the potential of pharmacological preservation of ovarian function by inhibiting a key element of the oocyte DNA damage checkpoint response, checkpoint kinase 2 (CHK2; CHEK2). Whereas nonlethal doses of ionizing radiation (IR) eradicate immature oocytes in wild-type mice, irradiated Chk2-/- mice retain their oocytes and, thus, fertility. Using an ovarian culture system, we show that transient administration of the CHK2 inhibitor 2-(4-(4-chlorophenoxy)phenyl)-1H-benzimidazole-5-carboxamide-hydrate ("CHK2iII") blocked activation of the CHK2 targets TRP53 and TRP63 in response to sterilizing doses of IR, and preserved oocyte viability. After transfer into sterilized host females, these ovaries proved functional and readily yielded normal offspring. These results provide experimental evidence that chemical inhibition of CHK2 is a potentially effective treatment for preserving the fertility and ovarian endocrine function of women exposed to DNA-damaging cancer therapies such as IR.
Inference of local regression in the presence of nuisance parameters

Abstract We consider inference based on local estimating equations in the presence of nuisance parameters. The framework is useful for a number of applications including those in economic policy evaluation based on discontinuities or kinks and in real-time financial risk management. We focus on the criterion-function-based (in particular, empirical likelihood-based) inference, and establish conditions under which the test statistic has a pivotal asymptotic distribution. In the key step of eliminating nuisance parameters in the (possibly non-smooth) criterion function, we consider two different approaches based on either concentration or Laplace-type plug-in estimation. The former is natural, and the latter does not require optimization and can be computationally attractive in applications. Our framework can easily incorporate bias correction induced by localization, and the inference is robust to the identification strength of the parameter of interest. The high-level assumptions are illustrated with several examples. We also conduct Monte Carlo simulations and provide an empirical application which assesses heterogeneous effects of academic probation in college and gender differences under the quantile regression discontinuity design.
Expected Power System Production Costs Using Large Deviation and Mixture of Normals Approximations

Abstract This paper proposes a possible enhancement to the computational performance of the large deviation method for determining expected system production costs. With the use of a mixed normal distribution to approximate the initial load duration curve, a faster algorithm which results in considerable amount of savings in computation time is developed. The proposed method is tested using a synthetic system with two different load duration curves and the results are compared to several other approximation methods. Depending on the accuracy with which a mixture of normals can be obtained to represent the load duration curve, the modified large deviation approximation method is comparable in speed and accuracy to the method of cumulants.
Prenatal Diagnosis Improves the Prognosis of Children With Obstructive Uropathies

Five neonates with gross obstructive uropathies diagnosed in utero were operated during the first few days of life. Follow-up studies of up to 2 years postoperatively showed normal development of all the children. Radiologic investigations showed no obstruction and normal growth of renal parenchyma in all but one case, thus differing markedly from infants with gross obstructive uropathies who were diagnosed and referred to us some months after birth. The importance of prenatal diagnosis and hence early post partum treatment of obstructive uropathies appears to us proven.
Nephrogenic Adenoma and Embryonic Kidney Tubules Share PNA Receptor Sites

Nephrogenic adenoma a rare bladder, ureter, or urethral lesion, is of disputed pathogenesis, metaplastic and congenital etiologies both being implicated in its development. Since light and electron microscopy have been unable to fully resolve the lesion's pathogenesis, the authors used biotinylated lectins as probes and avidin-biotin peroxidase complex (ABC) as a visualant to study cases of nephrogenic adenomas and compared their lectin binding patterns with those of normal transitional epithelium, human embryonic kidneys, and cases of cystitis cystica and glandularis and squamous metaplasia of the bladder in an effort to clarify this issue. Only the epithelial lining of the luminal surface and tubuli in nephrogenic adenoma and tubules in embryonic kidney exhibited free PNA receptor sites. The striking staining similarities between the epithelial components of nephrogenic adenomas and mesonephric and metanephric tubules complement previous findings concerning the origin of nephrogenic adenoma.
Use of the Candela Laser in the Ureter

SUMMARY The Candela pulsed dye laser is safe and effective. Complications are few and related more to the ureteroscopy than to the laser. Current results in the lower ureter utilizing primarily ultrasound as a method of power lithotripsy have been excellent, 1 and it is difficult to see how lasertripsy will improve on these. The importance of the laser is related to its small size and its flexibility. This will permit simpler access to the stone employing instruments such as small-caliber rigid ureteroscopes and small steerable flexible instruments. If these instruments can be passed without ureteral dilatation, access to the stone will be safer, and they may well extend the range of stones regularly susceptible to ureteroscopic removal.
Extracorporeal Shock Wave Lithotripsy: Interventional Radiologic Solutions to Associated Problems

Among 1,500 patients treated with extracorporeal shock wave lithotripsy, 1,300 had calculi less than 2.5 cm in diameter and 200 had calculi of 2.5 cm or larger. Although most patients did well and required no further radiologic intervention, 178 interventional radiologic procedures were performed. Urinary tract obstruction often developed in patients with large stones when the collecting system filled with stone fragments (steinstrasse). Nephrostomy was performed in 5.3% of the total patient population and in 29% of the patients with stones measuring 2.5 cm or more. Only 1.8% of the patients with calculi smaller than 2.5 cm required radiologic intervention. When the obstructed collecting system could not be crossed with conventional angiographic techniques, the stone fragments were removed through a percutaneous nephrostomy tract either by flushing or by suctioning with a pulsating water jet.
Small Bowel Lymphoma Associated With AIDS

Patients with the Acquired Immunodeficiency Syndrome (AIDS) are known to be at increased risk for developing malignancy; however, The spectrum that these malignancies encompass has not been fully defined. An unusual case of a 32 year old homosexual male with AIDS who developed two spontaneous small bowel perforations is presented. The diagnosis of primary histiocytic lymphoma of the small intestine was established only after his second operation.
Nested interconnect macro electrical yield improvement for advanced triple patterning integration

For metal pitches below 50nm, triple patterning (LELELE) integration is utilized in most advanced technologies to build the Cu interconnect. This integration relies on etch to shrink to the target critical dimension. As a result of high iso-dense bias in conventional etch process, nested serpentine structures formed by different metal colors show massive shorts that limit defect density yield. In this paper, several approaches in improving the isodense bias, as well as improving the nested serpentine electrical yield will be discussed.
Genomic Signature of an Avian Lilliput Effect across the K-Pg Extinction

Survivorship following major mass extinctions may be associated with a decrease in body size—a phenomenon called the Lilliput Effect. Body size is a strong predictor of many life history traits (LHTs), and is known to influence demography and intrinsic biological processes. Pronounced changes in organismal size throughout Earth history are therefore likely to be associated with concomitant genome-wide changes in evolutionary rates. Here, we report pronounced heterogeneity in rates of molecular evolution (varying up to ~20-fold) across a large-scale avian phylogenomic dataset, and show that nucleotide substitution rates are strongly correlated with body size and metabolic rate. We also identify potential body size reductions associated with the Cretaceous-Paleogene (K-Pg) transition, consistent with a Lilliput Effect in the wake of that mass extinction event. We posit that selection for reduced body size across the K-Pg extinction horizon may have resulted in transient increases in substitution rate along the deepest branches of the extant avian tree of life. This ‘hidden’ rate acceleration may result in both strict and relaxed molecular clocks over-estimating the age of the avian crown group through the relationship between life history and demographic parameters that scale with molecular substitution rate. If reductions in body size (and/or selection for related demographic parameters like short generation times) are a common property of lineages surviving mass extinctions, this phenomenon may help resolve persistent divergence time debates across the tree of life. Furthermore, our results suggest that selection for certain life history traits may be associated with deterministic molecular evolutionary outcomes.
Supply chain disruption propagation: a systemic risk and normal accident theory perspective

When a disruption occurs in a firm, its effects are often felt throughout the supply chain. As supply chains expand globally and companies pursue velocity and efficiency, the probability of disruptions propagating throughout a chain grows. In this paper, we employ a qualitative, grounded theory case study approach to help understand what drives supply chain disruption propagation and to provide theoretical insights into this emerging area. For a more complete perspective, we study three interconnected tiers in seven unique supply chains. Each supply chain triad consists of (1) a focal firm (a manufacturer), (2) a supplier to the focal firm and (3) a customer of the focal firm allowing us to gain perspective from three levels in multiple supply chains. Three aggregate dimensions are defined which help explain the propagation of supply chain disruptions: the nature of the disruption, structure and dependence, and managerial decision-making. Within these dimensions, six themes are identified giving an increa...
TREM2 in Neurodegenerative Diseases.

TREM2 variants have been identified as risk factors for Alzheimer’s disease (AD) and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor exclusively expressed on immune cells, identification of these variants conclusively demonstrates that the immune response can play an active role in the pathogenesis of NDDs. These TREM2 variants also confer the highest risk for developing Alzheimer’s disease of any risk factor identified in nearly two decades, suggesting that understanding more about TREM2 function could provide key insights into NDD pathology and provide avenues for novel immune-related NDD biomarkers and therapeutics. The expression, signaling and function of TREM2 in NDDs have been extensively investigated in an effort to understand the role of immune function in disease pathogenesis and progression. We provide a comprehensive review of our current understanding of TREM2 biology, including new insights into the regulation of TREM2 expression, and TREM2 signaling and function across NDDs. While many open questions remain, the current body of literature provides clarity on several issues. While it is still often cited that TREM2 expression is decreased by pro-inflammatory stimuli, it is now clear that this is true in vitro, but inflammatory stimuli in vivo almost universally increase TREM2 expression. Likewise, while TREM2 function is classically described as promoting an anti-inflammatory phenotype, more than half of published studies demonstrate a pro-inflammatory role for TREM2, suggesting that its role in inflammation is much more complex. Finally, these components of TREM2 biology are applied to a discussion of how TREM2 impacts NDD pathologies and the latest assessment of how these findings might be applied to immune-directed clinical biomarkers and therapeutics.
Chemical Control of a CRISPR-Cas9 Acetyltransferase.

Lysine acetyltransferases (KATs) play a critical role in the regulation of transcription and other genomic functions. However, a persistent challenge is the development of assays capable of defining KAT activity directly in living cells. Toward this goal, here we report the application of a previously reported dCas9-p300 fusion as a transcriptional reporter of KAT activity. First, we benchmark the activity of dCas9-p300 relative to other dCas9-based transcriptional activators and demonstrate its compatibility with second generation short guide RNA architectures. Next, we repurpose this technology to rapidly identify small molecule inhibitors of acetylation-dependent gene expression. These studies validate a recently reported p300 inhibitor chemotype and reveal a role for p300s bromodomain in dCas9-p300-mediated transcriptional activation. Comparison with other CRISPR-Cas9 transcriptional activators highlights the inherent ligand tunable nature of dCas9-p300 fusions, suggesting new opportunities for orthog...
The effects of bank regulators and external auditors on loan loss provisions

Abstract I examine whether bank regulators and external auditors have conflicting effects on loan loss provision timeliness, an accounting choice associated with important economic consequences and a potential conflict between regulators and auditors. In the absence of the other group, auditors and strict regulators are each positively associated with timeliness. However, audits are negatively associated with timeliness when strict regulators are present, consistent with a conflict for which auditors are the dominating group as audited banks attain a similar level of timeliness regardless of the extent of regulatory scrutiny. Collectively, this suggests that regulators and auditors differentially influence loan loss provisions.
“Hi Mommy”: Parental Preferences of Greetings by Medical Staff:

The therapeutic alliance between pediatricians and parents begins at the initial encounter. The manner in which pediatricians greet family members influences this relationship. This study evaluated whether parents are addressed using generic titles and investigated perceptions of parents regarding how they are addressed by medical staff. Written surveys of 137 parents of pediatric inpatients collected opinions about greetings during medical encounters. Parents were asked if they have been addressed as Mom/Dad/Mommy/Daddy during past medical encounters and which generic titles they would prefer. Using a Likert-type scale, the parents' perceptions of various salutations were assessed and compared. In this sample, 86% of parents were previously called Mom/Dad/Mommy/Daddy. Parents preferred to be addressed as Mom or Dad over other generic titles. Many disliked being addressed as Mommy/Daddy, Ma'am/Sir, or without a name, suggesting that providers should avoid the use of these salutations.
Blind normalization of speech from different channels

We show how to construct a channel-independent representation of speech that has propagated through a noisy reverberant channel. This is done by blindly rescaling the cepstral time series by a nonlinear function, with the form of this scale function being determined by previously encountered cepstra from that channel. The rescaled form of the time series is an invariant property of it in the following sense: It is unaffected if the time series is transformed by any time-independent invertible distortion. Because a linear channel with stationary noise and impulse response transforms cepstra in this way, the new technique can be used to remove the channel dependence of a cepstral time series. In experiments, the method achieved greater channel-independence than cepstral mean normalization, and it was comparable to the combination of cepstral mean normalization and spectral subtraction, despite the fact that no measurements of channel noise or reverberations were required (unlike spectral subtraction).
Stepping on a rake: The fiscal theory of monetary policy

Abstract The fiscal theory of the price level can describe monetary policy. Governments can set interest rate targets and thereby affect inflation, with no change in fiscal surpluses. The same basic mechanism describes interest rate targets, forward guidance, open market operations, and quantitative easing. It does not require any monetary, pricing, or other frictions. In the presence of long-term debt, higher interest rates lead to temporarily lower inflation, a challenging sign. I derive and replicate the results of the Sims (2011) “stepping on a rake” model, which first produced this negative sign, and produces realistic impulse-response functions. I show that Sims’ result is robust to many model features, but essentially requires long-term debt.
Scaling ORAM for Secure Computation

We design and implement a Distributed Oblivious Random Access Memory (DORAM) data structure that is optimized for use in two-party secure computation protocols. We improve upon the access time of previous constructions by a factor of up to ten, their memory overhead by a factor of one hundred or more, and their initialization time by a factor of thousands. We are able to instantiate ORAMs that hold 234 bytes, and perform operations on them in seconds, which was not previously feasible with any implemented scheme. Unlike prior ORAM constructions based on hierarchical hashing, permutation, or trees, our Distributed ORAM is derived from the new Function Secret Sharing scheme introduced by Boyle, Gilboa and Ishai. This significantly reduces the amount of secure computation required to implement an ORAM access, albeit at the cost of O(n) efficient local memory operations. We implement our construction and find that, despite its poor O(n) asymptotic complexity, it still outperforms the fastest previously known constructions, Circuit ORAM and Square-root ORAM, for datasets that are 32 KiB or larger, and outperforms prior work on applications such as stable matching or binary search by factors of two to ten.
Banking competition, production externalities, and the effects of monetary policy

Since the global financial crisis, there has been a significant amount of concern about the presence of large-scale financial intermediaries which affects the competitive landscape of the banking sector in advanced economies. In light of this issue, this paper develops a framework to demonstrate how the degree of concentration impacts economic activity. As is standard in the growth literature, we incorporate production externalities from the aggregate capital stock which promote economic development. In this setting, we show that monetary policy may need to accommodate departures from perfect competition by setting a higher rate of money growth. In fact, in the presence of large capital externalities, neither low inflation nor perfect competition may be optimal. That is, in environments where capital accumulation would be expected to be inefficiently low, the optimal rate of money growth is higher than the Friedman rule in order to encourage investment—yet, the optimal competitive structure favors increased concentration to foster a large seigniorage tax base that also adds to the capital stock.
Cost recovery and financial viability of the power sector in developing countries : a literature review

The financial viability of the power sector is a prerequisite for attracting the investment needed to ensure reliable energy supply, meet universal access targets, and hasten the clean energy transition. Adequate pricing of electricity to allow for cost recovery is also important to minimize the power sector’s negative macroeconomic, fiscal, environmental, and social impacts. This paper takes stock of the empirical and conceptual literature on the financial viability and cost recovery of the power sector in developing countries. Time-series data across countries are relatively scarce, but comparing the findings from 21 studies suggests that under-recovery of costs remains pervasive despite decades of efforts by governments and development institutions. Large electricity subsidies continue to burden governments, especially in the Middle East, South Asia, Central Asia, and Sub-Saharan Africa. Reviews by the World Bank and International Monetary Fund on outcomes of their own engagement also conclude that progress on cost recovery in supported countries has been limited. Although the aggregated view obscures fluctuation within individual countries over time, the available evidence suggests that countries progressing toward cost recovery may find themselves backsliding within a few years. As for understanding the circumstances under which progress can be made, a handful of studies point toward a correlation between sector reforms and cost recovery, although few of the studies address obvious endogeneity problems. To provide more solid guidance for future efforts to improve cost recovery, more research is needed on: (i) the determinants and enabling conditions of progress on cost recovery; (ii) tariff reform sequencing; and (iii) institutional arrangements, policies, and regulations that enable countries to sustain cost recovery once it is reached.
Peridynamic Modeling of Damage in Laminated Composites Reinforced with Z-pins due to Low-velocity Impacts

In this study, a new approach for predicting damage and specific failure modes in laminated fiber reinforced composites is presented. The new method is based on the peridynamic theory and models individual plies, and represents fiber and matrix materials in each ply explicitly. These features enable analysis of laminates with arbitrary fiber orientation in a convenient manner. Additionally, a new failure mode identification algorithm has been developed and implemented. Instead of the conventional peridynamic damage parameter, the new algorithm works with individual broken bonds, which makes identification of different failure modes including matrix cracking, fiber breakage and delamination straight-forward and unambiguous. The new peridynamic approach is demonstrated by considering low velocity impact damage on composite laminates with and without translaminar reinforcements. The translaminar reinforcement technique considered in this study is z-pinning; two different geometric configurations of z-pins are explored. The impact testing and the post-impact non-destructive evaluations with ultrasonic c-scans are performed at the Air Force Research Laboratory to characterize of the delaminations. The impact tests on different samples are simulated using the current peridynamic approach. The predicted impact damages are compared against the experimental measurements. The new approach is shown to capture low velocity impact damage both quantitatively and qualitatively.
Sexual assault on college campuses: A 50-state survey of criminal sexual assault statutes and their relevance to campus sexual assault.

A recent series of highly publicized campus sexual assaults and the questionable responses by the academic institutions where they occurred has led some policymakers and academic administrators to call for legislative and institutional change. For such changes to be effective, academic administrators and legislators need solutions that effectively protect victims, punish perpetrators, and encourage institutional compliance with relevant legislation. Furthermore, there has been significant debate about how much the criminal justice system can and should be involved when sexual assaults occur on college campuses. To address these questions, there needs to be a more thorough understanding of existing state sexual assault laws and their capacity to handle sexual assaults that occur on college campuses. This project identified and systematically examined all U.S. state statutes relating to sexual assault to evaluate to what extent these laws are appropriate and accessible for victims of campus sexual assault. Results revealed that all 50 states have at least 1 criminal statute addressing sexual assault, with a total of 432 statutory subsections being identified for inclusion. Across statutes, key concepts relating to consent and incapacity were often ill defined or undefined, and many of the statutes appear to be poorly suited to handling campus sexual assaults. These findings have implications for the adjudication of campus sexual assaults, and such results can potentially be used to amend existing legislation and inform future legislation. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
The true meaning of diversity seen through the first principles of fundamental physics

The word Diversity in the dictionary implies variety in form. And the basic concept derived from these principles is that if one has multiple copies of the same system, presumably one would have a better chance of achieving the desired goals. The fundamental problem with this simplistic way of reasoning is that one needs to understand the physical environment where such an experiment needs to be carried out and how one should interpret the final result. The current state of the art applies some statistical framework to the physical scene to explain the added advantage of diversity. To appreciate the true physical significance of diversity we have to go back to the roots! We need to understand first what the statistical framework implies and secondly how it relates to the problem at hand. So we need to address the following questions: 1. Who first introduced the concept of ensemble averaging in physics and in what context? 2. What is the physical significance of ensemble averaging?
Heavily and Fully Modified RNAs Guide Efficient SpyCas9-mediated Genome Editing

RNA-based drugs depend on chemical modifications to increase potency and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. Here, we explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor. We identify several heavily modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2′-OH groups) that are functional in human cells. These designs will contribute to Cas9-based therapeutics since heavily modified RNAs tend to be more stable in vivo (thus increasing potency). We anticipate that our designs will improve the use of Cas9 via RNP and mRNA delivery for in vivo and ex vivo purposes.
Additional flap on plastic stents for improved antimigration effect in the treatment of post-cholecystectomy bile leak

Background and study aims In plastic stent insertion for treatment of post-cholecystectomy bile leak, stent migration may be more common due to the absence of a shelf to anchor the stent. We evaluated how adding a flap to straight plastic stents for this indication might influence the rate of stent migration when compared to use of conventional plastic stents. Patients and methods This is a retrospective study including patients referred for ERCP for treatment of post-cholecystectomy bile leak. Patients with a customized anti-migration flap stent had the additional flap created on the distal end of straight plastic stents, intended to aid in anchoring in the distal supra-sphincteric biliary duct. The primary endpoint is stent migration events. The secondary endpoint is bile leak resolution after first ERCP session. Results Thirty-two patients were treated with the experimental additional flap stents and 225 patients were treated with standard straight biliary stents. The total failure rate of bile leak resolution after a single endoscopic treatment for all treated was 10.5 % (27/257) and the total stent migration rate for all enrolled was 15.2 % (39/257). Stent migration rate was lower in the additional flap stent group than in the conventional group (3.1 % vs. 16.9 %, respectively, P = 0.04). Furthermore, significantly more patients had resolution of their bile leak after the first ERCP session in the group with the additional flap (100 % vs. 88 %, respectively, P = 0.03). Conclusion A plastic biliary stent with an extra flap may have improved performance with regard to stent migration and resolution of bile leak over standard plastic biliary stents.
gmxapi: a high-level interface for advanced control and extension of molecular dynamics simulations.

Summary Molecular dynamics simulations have found use in a wide variety of biomolecular applications, from protein folding kinetics to computational drug design to refinement of molecular structures. Two areas where users and developers frequently need to extend the built-in capabilities of most software packages are implementing custom interactions, for instance biases derived from experimental data, and running ensembles of simulations. We present a Python high-level interface for the popular simulation package GROMACS that i) allows custom potential functions without modifying the simulation package code, ii) maintains the optimized performance of GROMACS and iii) presents an abstract interface to building and executing computational graphs that allows transparent low-level optimization of data flow and task placement. Minimal dependencies make this integrated API for the GROMACS simulation engine simple, portable and maintainable. We demonstrate this API for experimentally-driven refinement of protein conformational ensembles. Availability and implementation LGPLv2.1 source and instructions are available at https://github.com/kassonlab/gmxapi. Supplementary information Supplementary data are available at Bioinformatics online.
Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit.

Summary In the small intestine, type 2 responses are regulated by a signaling circuit that involves tuft cells and group 2 innate lymphoid cells (ILC2s). Here, we identified the microbial metabolite succinate as an activating ligand for small intestinal (SI) tuft cells. Sequencing analyses of tuft cells isolated from the small intestine, gall bladder, colon, thymus, and trachea revealed that expression of tuft cell chemosensory receptors is tissue specific. SI tuft cells expressed the succinate receptor (SUCNR1), and providing succinate in drinking water was sufficient to induce a multifaceted type 2 immune response via the tuft-ILC2 circuit. The helminth Nippostrongylus brasiliensis and a tritrichomonad protist both secreted succinate as a metabolite. In vivo sensing of the tritrichomonad required SUCNR1, whereas N. brasiliensis was SUCNR1 independent. These findings define a paradigm wherein tuft cells monitor microbial metabolites to initiate type 2 immunity and suggest the existence of other sensing pathways triggering the response to helminths.
A cell separation checkpoint that enforces the proper order of late cytokinetic events.

Eukaryotic cell division requires dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is selectively degraded in its primary septum immediately after its completion by secreted enzymes. We find this secretion event is linked to septum completion and forestalled when the process is slowed. Delay of septum degradation requires Fir1, an intrinsically disordered protein localized to the cytokinesis site that is degraded upon septum completion but stabilized when septation is aberrant. Fir1 protects cytokinesis in part by inhibiting a separation-specific exocytosis function of the NDR/LATS kinase Cbk1, a key component of “hippo” signaling that induces mother–daughter separation. We term this system enforcement of cytokinesis order, a checkpoint ensuring proper temporal sequence of mechanistically incompatible processes of cytokinesis.
Sample Selection Approaches to Estimating and Allocating House Transaction Funding Price Differentials

This study examines house transaction price differentials observed among funding type combinations; accounting for potential sample selection and spatial biases yields a better approximation of price differentials between group combinations. Consistent with expectations we detect, and correct for, selectivity and spatial biases. Transactions with conventional financing have superior characteristics compared to all-cash funded transactions, and Federal Housing Administration (FHA) and Veterans Affairs (VA) funded houses have inferior characteristics relative to all-cash characteristics. Price counterfactuals for (1) all-cash financed property, (2) conventional, (3) FHA, and (4) VA property transactions reveal, consistent with expectations, unexplained coefficient pricing premiums, i.e., a financing premium. However, total all-cash explained housing/neighborhood characteristics, are superior relative to FHA and VA financed properties. Results reinforce the notion that credit matters in the provision of financial services with regard to housing prices, while Blinder-Oaxaca price differential decompositions provide additional insights.
Scenario-based case study analysis of asteroid mitigation in the short response time regime

Asteroid impact on Earth is a rare but inevitable occurrence, with potentially cataclysmic consequences. If a pending impact is discovered, mitigation options include civil-defense preparations as well as missions to deflect the asteroid and/or robustly disrupt and disperse it to an extent that only a negligible fraction remains on a threatening path (National Research Council's “Defending the Planet,” 2010). If discovered with sufficient warning time, a kinetic impactor (KI) can deflect smaller objects, but response delays can rule out the option. If a body is too large to deflect by kinetic impact, or the time for response is insufficient, deflection or disruption can be achieved with a nuclear device. The use of nuclear ablation is considered within the context of current capabilities, requiring no need for nuclear testing. Existing, well-understood devices are sufficient for the largest known Potentially Hazardous Objects (PHOs). The National Aeronautics and Space Administration/Goddard Space Flight Center and the Department of Energy/National Nuclear Security Administration are collaborating to determine the critical characterization issues that define the boundaries for the asteroid-deflection options.
The radius of analyticity for solutions to a problem in epitaxial growth on the torus

A certain model for epitaxial film growth has recently attracted attention, with the existence of small global solutions having being proved in both the case of the n-dimensional torus and free space. We address a regularity question for these solutions, showing that in the case of the torus, the solutions become analytic at any positive time, with the radius of analyticity growing linearly for all time. As other authors have, we take the Laplacian of the initial data to be in the Wiener algebra, and we find an explicit smallness condition on the size of the data. Our particular condition on the torus is that the Laplacian of the initial data should have norm less than 1/4 in the Wiener algebra.
Multi-Criteria Evolution of Neural Network Topologies: Balancing Experience and Performance in Autonomous Systems

Majority of Artificial Neural Network (ANN) implementations in autonomous systems use a fixed/user-prescribed network topology, leading to sub-optimal performance and low portability. The existing neuro-evolution of augmenting topology or NEAT paradigm offers a powerful alternative by allowing the network topology and the connection weights to be simultaneously optimized through an evolutionary process. However, most NEAT implementations allow the consideration of only a single objective. There also persists the question of how to tractably introduce topological diversification that mitigates overfitting to training scenarios. To address these gaps, this paper develops a multi-objective neuro-evolution algorithm. While adopting the basic elements of NEAT, important modifications are made to the selection, speciation, and mutation processes. With the backdrop of small-robot path-planning applications, an experience-gain criterion is derived to encapsulate the amount of diverse local environment encountered by the system. This criterion facilitates the evolution of genes that support exploration, thereby seeking to generalize from a smaller set of mission scenarios than possible with performance maximization alone. The effectiveness of the single-objective (optimizing performance) and the multi-objective (optimizing performance and experience-gain) neuro-evolution approaches are evaluated on two different small-robot cases, with ANNs obtained by the multi-objective optimization observed to provide superior performance in unseen scenarios.
Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes.

A slight increase in melanoma risk was observed among sodium-glucose co-transporter-2 (SGLT-2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta-analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT-2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80-5.89; I2 , 0%). Similar results were observed in the subgroup analyses according to the type of SGLT-2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non-melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47-1.07; I2 , 0%), while a significantly decreased risk was observed among trials with duration <52 weeks (Peto OR, 0.12; 95% CI, 0.02-0.59; I2 , 0%). No evidence of publication bias was detected in the analyses. Current evidence from RCTs did not support a significantly increased risk of skin cancer associated with SGLT-2 inhibitors.
TeraSim: An ns-3 extension to simulate Terahertz-band communication networks

Abstract In the quest of higher wireless data-rates, Terahertz (THz)-band (0.1-10 THz) communication is envisioned as a key wireless technology of the next decade. In parallel to the development of THz transceivers and antennas, simulation tools are needed to expedite the development of communication and networking protocols tailored to this novel networking paradigm, at a fraction of the cost. The few simulation platforms developed to date for THz communication networks do not capture the peculiarities of the THz channel or the capabilities of THz devices. In this paper, TeraSim, i.e., an open source network simulation platform for THz communication networks is presented. TeraSim is built as an extension for ns-3, which is one of the most widely used teaching and education network simulation software. The simulator has been developed considering two major types of application scenarios, namely, nanoscale communication networks (average transmission range usually below one meter) and macroscale communication networks (distances larger than one meter). The simulator consists of a common channel module, separate physical and link layers for each scenario, and two assisting modules, namely, THz antenna module and energy harvesting module, originally designed for the macroscale and nanoscale scenario, respectively. The structure, relations and content of each module are presented in detail. Extensive simulation and test results are provided to validate the functionalities of the implemented modules. TeraSim is expected to enable the networking community to test THz networking protocols without having to delve into the channel and physical layers.
Revenue Guarantee Equivalence

We revisit the revenue comparison of standard auction formats, including first-price, second-price, and English auctions. We rank auctions according to their revenue guarantees, i.e., the greatest lower bound of revenue across all informational environments, where we hold fixed the distribution of bidders' values. We conclude that if we restrict attention to the symmetric affiliated models of Milgrom and Weber (1982) and monotonic pure-strategy equilibria, first-price, second-price, and English auctions are revenue guarantee equivalent: they have the same revenue guarantee, which is equal to that of the first-price auction as characterized by Bergemann, Brooks, and Morris (2017). If we consider all equilibria or if we allow more general models of information, then first-price auctions have a greater revenue guarantee than all other auctions considered.
Social Foundations of Thought and Action: A Social Cognitive Theory

1. Models of Human Nature and Casualty. 2. Observational Learning. 3. Enactive Learning. 4. Social Diffusion and Innovation. 5. Predictive Knowledge and Forethought. 6. Incentive Motivators. 7. Vicarious Motivators. 8. Self-Regulatory Mechanisms. 9. Self-Efficacy. 10. Cognitive Regulators. References. Index.