cssi/SciSciGPT-SciSciNet huggingface dataset:
Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15

Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding.Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis.Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors (P = 2.6 × 10-8).Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping.Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR.
Homeostatic Feedback Modulates the Development of Two-State Patterned Activity in a Model Serotonin Motor Circuit in Caenorhabditis elegans.

Neuron activity accompanies synapse formation and maintenance, but how early circuit activity contributes to behavior development is not well understood. Here, we use the Caenorhabditis elegans egg-laying motor circuit as a model to understand how coordinated cell and circuit activity develops and drives a robust two-state behavior in adults. Using calcium imaging in behaving animals, we find the serotonergic hermaphrodite-specific neurons (HSNs) and vulval muscles show rhythmic calcium transients in L4 larvae before eggs are produced. HSN activity in L4 is tonic and lacks the alternating burst-firing/quiescent pattern seen in egg-laying adults. Vulval muscle activity in L4 is initially uncoordinated but becomes synchronous as the anterior and posterior muscle arms meet at HSN synaptic release sites. However, coordinated muscle activity does not require presynaptic HSN input. Using reversible silencing experiments, we show that neuronal and vulval muscle activity in L4 is not required for the onset of adult behavior. Instead, the accumulation of eggs in the adult uterus renders the muscles sensitive to HSN input. Sterilization or acute electrical silencing of the vulval muscles inhibits presynaptic HSN activity and reversal of muscle silencing triggers a homeostatic increase in HSN activity and egg release that maintains ∼12–15 eggs in the uterus. Feedback of egg accumulation depends upon the vulval muscle postsynaptic terminus, suggesting that a retrograde signal sustains HSN synaptic activity and egg release. Our results show that egg-laying behavior in C. elegans is driven by a homeostat that scales serotonin motor neuron activity in response to postsynaptic muscle feedback. SIGNIFICANCE STATEMENT The functional importance of early, spontaneous neuron activity in synapse and circuit development is not well understood. Here, we show in the nematode Caenorhabditis elegans that the serotonergic hermaphrodite-specific neurons (HSNs) and postsynaptic vulval muscles show activity during circuit development, well before the onset of adult behavior. Surprisingly, early activity is not required for circuit development or the onset of adult behavior and the circuit remains unable to drive egg laying until fertilized embryos are deposited into the uterus. Egg accumulation potentiates vulval muscle excitability, but ultimately acts to promote burst firing in the presynaptic HSNs which results in egg laying. Our results suggest that mechanosensory feedback acts at three distinct steps to initiate, sustain, and terminate C. elegans egg-laying circuit activity and behavior.
Identifying topological order through unsupervised machine learning

The Landau description of phase transitions relies on the identification of a local order parameter that indicates the onset of a symmetry-breaking phase. In contrast, topological phase transitions evade this paradigm and, as a result, are harder to identify. Recently, machine learning techniques have been shown to be capable of characterizing topological order in the presence of human supervision. Here, we propose an unsupervised approach based on diffusion maps that learns topological phase transitions from raw data without the need for manual feature engineering. Using bare spin configurations as input, the approach is shown to be capable of classifying samples of the two-dimensional XY model by winding number and capture the Berezinskii–Kosterlitz–Thouless transition. We also demonstrate the success of the approach on the Ising gauge theory, another paradigmatic model with topological order. In addition, a connection between the output of diffusion maps and the eigenstates of a quantum-well Hamiltonian is derived. Topological classification via diffusion maps can therefore enable fully unsupervised studies of exotic phases of matter. Machine learning techniques have latterly gained currency in condensed-matter physics, for example by identifying phase transitions. An unsupervised machine learning algorithm that identifies topological order is now demonstrated.
Cheap-stock tunneling around preemptive rights

Abstract Preemptive rights are thought to protect minority shareholders from cheap-stock tunneling by a controlling shareholder. We show that preemptive rights, while making cheap-stock tunneling more difficult, cannot prevent it when asymmetric information about the value of the offered shares makes it impossible for the minority to know whether these shares are cheap or overpriced. Our analysis can help explain why sophisticated investors in unlisted firms and regulators of listed firms do not rely entirely on preemptive rights to address cheap-stock tunneling, supplementing them with other restrictions on equity issues.
Salini ’s Nature: Arbitrators’ Duty of Jurisdictional Policing

This article examines the duty of jurisdictional policing that Salini v. Morocco inferred from the ICSID Convention. According to Salini , ICSID arbitrators must determine whether a dispute arises from an “investment” that satisfies an objective definition of that term, regardless of the subjective definition used by the parties to a case. Salini thus suggests that this duty cannot be waived or varied by the parties. Its proponents claim that Salini ’s duty serves ICSID ’s vital institutional interests. Moreover, ICSID can enforce Salini ’s duty. Taken together, these considerations signal that Salini ’s duty is owed not only to the parties to the case, but also to ICSID itself as an institution. As Salini migrates beyond ICSID to other investor-state tribunals, however, the nature of this duty may be revealed as not only institutional but systemic – a duty inherent in the investor-state arbitrators’ function that serves the interests of the investor-state dispute system.
Complexity and the Cathedral: making law and economics more Calabresian

This article argues that Calabresi and Melamed’s “Cathedral” framework of property rules, liability rules, and inalienability rules needs to be extended using the tools of complex systems theory in order to capture important institutional features of the law. As an applied field, law and economics looks to law in choosing the appropriate analytical tools from economics—something that Calabresi has identified (in strong form) as law and economics as opposed to economic analysis of law. Recognizing law as a complex system requires a rethinking of some Realist-inspired assumptions that underpin economically inspired analysis of law. These assumptions include a preference for narrow, concrete concepts and a skepticism about traditional doctrines and baselines—and ultimately Legal Realism’s extreme nominalism and the strong bundle of rights picture of property. The article shows how the Calabresi and Melamed (CM these include narrow entitlements to engage in specific activities, liability rules that allow an affected party to buy out an activity (Rule 4), opportunistic behavior by parties that destabilizes liability rules, and the role of equity as an institutional response. Extending the C&M framework to treat it as a system helps prevent the C&M framework from flattening the law out. If we supplement the C&M framework to take account of law as a system, we can bring it closer to Calabresian law and economics.
A double-edged sword: How and why resetting performance metrics affects motivation and performance

Abstract Inside and outside of workplaces, individuals’ performance on a metric (e.g., sales) is often decoupled from past performance (rather than being tracked as a continuation of past performance). How do people respond to such performance resets, a type of fresh start on performance records, particularly when resets are not anticipated? Three laboratory experiments and one field study analyzing 40 years of data from professional baseball players demonstrate their impact. Specifically, unanticipated resets increase self-efficacy and thus boost motivation and future performance when they follow weak performance. However, such resets decrease self-efficacy and thus harm motivation and future performance when they follow strong performance. By identifying the conditions that determine whether performance resets improve or harm motivation, and highlighting the role of self-efficacy, this paper provides novel insights into how different ways of tracking performance influence motivation, as well as how fresh starts change behavior.
Cardiovascular disease in Williams syndrome.

Purpose of reviewWilliams syndrome is a multisystem disorder seen with some regularity at most pediatric centers and usually fairly often at larger centers. Cardiovascular abnormalities, because of elastin deficiency, are the leading cause of morbidity and mortality in patients with Williams syndrom
Revisiting a synthetic intracellular regulatory network that exhibits oscillations

In 2000, Elowitz and Leibler introduced the repressilator-a synthetic gene circuit with three genes that cyclically repress transcription of the next gene-as well as a corresponding mathematical model. Experimental data and model simulations exhibited oscillations in the protein concentrations across generations. Muller et al. (J Math Biol 53(6):905-937, 2006) generalized the model to an arbitrary number of genes and analyzed the resulting dynamics. Their new model arose from five key assumptions, two of which are restrictive given current biological knowledge. Accordingly, we propose a new repressilator system that allows for general functions to model transcription, degradation, and translation. We prove that, with an odd number of genes, the new model has a unique steady state and the system converges to this steady state or to a periodic orbit. We also give a necessary and sufficient condition for stability of steady states when the number of genes is even and conjecture a condition for stability for an odd number. Finally, we derive a new rate function describing transcription that arises under more reasonable biological assumptions than the widely used single-step binding assumption. With this new transcription-rate function, we compare the model's amplitude and period with that of a model with the conventional transcription-rate function. Taken together, our results enhance our understanding of genetic regulation by repression.
Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database

Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates. We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan–Meier method. A total of 8554 patients fulfilled study criteria (n = 980/11.5% R vs. n = 7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p < 0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p < 0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p = 0.0004), had lower grade disease (p = 0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had ≥ 2 R vs. 79% had 1; 21% had ≥ 2 NR, p = 0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p = 0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p = 0.56) and readmissions (5.9%-R, 5.8%-NR, p = 0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p = 0.796). There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.
Sporidial Fusion and Infection of Maize Seedlings by the Smut Fungus Ustilago Maydis

Mating and infection structures of Ustilago maydis produced in culture and on maize plants were examined with light and electron microscopy. Fusion tubes formed between low numbers of compatible haploid sporidia incubated in water for 8-16 hours. Both nuclei from paired sporidia migrated into a rapidly elongating hypha that did not differentiate further in the absence of host cells. Sporidial fusion and hyphal emergence also occurred rapidly and consistently in leaf whorls of inoculated maize seedlings, and hyphae had entered maize leaves after 12 hours. Only young leaves in the inner part of the leaf whorl were infected. Hyphae did not grow through stomatal openings, but, instead, entered epidermal cells by penetrating the cuticle and then either growing directly through the underlying cell wall or first growing between epidermal cells before penetrating an anticlinal wall of one of the cells. Invaded
Spectrum-adapted Polynomial Approximation for Matrix Functions

We propose and investigate two new methods to approximate f(A)b for large, sparse, Hermitian matrices A. Computations of this form play an important role in numerous signal processing and machine learning tasks. The main idea behind both methods is to first estimate the spectral density of A, and then find polynomials of a fixed order that better approximate the function f on areas of the spectrum with a higher density of eigenvalues. Compared to state-of-the-art methods such as the Lanczos method and truncated Chebyshev expansion, the proposed methods tend to provide more accurate approximations of f(A)b at lower polynomial orders, and for matrices A with a large number of distinct interior eigenvalues and a small spectral width.
Multi-objective Bayesian materials discovery: Application on the discovery of precipitation strengthened NiTi shape memory alloys through micromechanical modeling

Abstract In this study, a framework for the multi-objective materials discovery based on Bayesian approaches is developed and demonstrated on the efficient discovery of precipitation-strengthened NiTi shape memory alloys with up to three desired properties. The framework is used to minimize the required computational experiments for the discovery of the targeted materials, performed by a thermodynamically-consistent micromechanical model that predicts the materials response based on its composition and microstructure. The developed scheme features a Bayesian optimal experimental design process that operates in a closed loop. During each iteration of the process, a Gaussian process regression model is constructed based on the available computational data and used to emulate the response of the material in the unexplored regions of the materials design space. The sequential exploration of the materials design space is carried out by using an optimal experiment selection policy based on the expected hyper-volume improvement acquisition function that accounts for the uncertainty on the predictions of the regression model. The results indicate the considerable efficiency of the proposed framework, in discovering the targeted materials, compared with the exhaustive model-driven exploration of the materials design space.
Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl^(Esr1)) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvl^(Esr1) neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvl^(Esr1) neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks.
Vesting Agent-Relative Permissions in a Proxy

We all have agent-relative permissions to give extra weight to our own well-being. If you and two strangers are drowning, and you can save either yourself or two strangers, you have an agent-relative permission to save yourself. But is it possible for you to ‘vest’ your agent-relative permissions in a third party – a ‘proxy’ – who can enact your agent-centered permissions on your behalf, thereby permitting her to do what would otherwise be impermissible? Some might think that the answer is ‘no’; it is definitive of agent-centered permissions that they apply only to the individuals ineliminably referenced in the content of that reason, which means that they lack reason-giving force for any ostensible proxy. The purpose of this paper is to (i) show that vesting agent-relative permissions is indeed possible, (ii) provide an account of how agent-relative permissions are vested by considering the structure of rights more generally, and (iii) show that we have a right to vest such permission in this way.
Attack at Fort Hood: Experiences and Suggestions for Security

In the past nine years, three lone wolf terrorists have targeted military bases or recruiting centers in the United States and research suggests attacks on the U.S. military are increasing globally...
Introduction to the finite-difference time-domain (FDTD) technique

Strengths & Weaknesses of FDTD • Strengths — Time Domain Solution Provides Wide Frequency Range With One Run — All Materials Possible — Animation Provides Insight — Well Suited to Inside / Outside Problems (Shielding) — Intuitive Technique • Weaknesses — All Space Must Be Gridded • Memory Limitations — Far-Field Usually Requires Post-Processing — Difficult To Analyze Long Wires
What Remains of Cross-Country Convergence?

We examine the record of cross-country growth over the past 50 years and ask if developing countries have made progress on closing income gap between their per capita incomes and those in the advanced economies. We conclude that, as a group, they have not and then survey the literature on absolute convergence with particular emphasis on that from the last decade or so. That literature supports our conclusion of a lack of progress in closing the income gap between countries. We close with a brief examination of the recent literature on cross-individual distribution of income which finds that, despite the lack of progress on cross-country convergence, global inequality has tended to fall since 2000.
Subcell light current - voltage characterization of irradiated multijunction solar cell

The degradation of individual subcell J - V parameters, such as short circuit current, open circuit voltage, fill factor, and power of a GaInP/GaInAs/Ge triple junction solar cell by 1 MeV electrons were derived utilizing the spectral reciprocity relation between electroluminescence and external quantum efficiency. After exposure to a fluence of 1 × 1015 1 MeV electrons, it was observed that up to 67 % of the voltage loss is from the middle, GaInAs sub cell. Also, the dark saturation current of the Ge and GaInAs subcells increased but a simultaneous decrease in ideality factor caused a reduction of the open circuit voltage. The reduced ideality factor further indicates a change in the primary recombination mechanism.
Nearly flat Chern bands in moiré superlattices

The competition between the kinetic energy of electrons in a crystal and the inter-electron Coulomb repulsion underlies many fascinating phenomena in quantum materials. Superlattices formed from moir\'e patterns in graphene structures have emerged as tunable platforms for such physics. This paper shows that in many graphene moir\'e structures not only are the electronic bands narrow enough for Coulomb interaction to be important, but they are also topologically nontrivial. This setting of a strong correlated partially filled topological band promises to lead to many novel phenomena.
Landscape of gene transposition–duplication within the Brassicaceae family

We developed the CLfinder-OrthNet pipeline that detects co-linearity among multiple closely related genomes, finds orthologous gene groups, and encodes the evolutionary history of each orthologue group into a representative network (OrthNet). Using a search based on network topology, we identified 1,394 OrthNets that included gene transposition-duplication (tr-d) events, out of 17,432 identified in six Brassicaceae genomes. Occurrences of tr-d shared by subsets of Brassicaceae genomes mirrored the divergence times between the genomes and their repeat contents. The majority of tr-d events resulted in truncated open reading frames (ORFs) in the duplicated loci. However, the duplicates with complete ORFs were significantly more frequent than expected from random events. These were derived from older tr-d events and had a higher chance of being expressed. We also found an enrichment of tr-d events with complete loss of intergenic sequence conservation between the original and duplicated loci. Finally, we identified tr-d events uniquely found in two extremophytes among the six Brassicaceae genomes, including tr-d of SALT TOLERANCE 32 and ZINC TRANSPORTER 3 that relate to their adaptive evolution. CLfinder-OrthNet provides a flexible toolkit to compare gene order, visualize evolutionary paths among orthologues as networks, and identify gene loci that share an evolutionary history.
Effect of Postoperative Partial Bladder Filling after Minimally Invasive Hysterectomy on Postanesthesia Care Unit Discharge and Cost: a Single-Blinded, Randomized Controlled Trial.

Background Hysterectomy is one of the most common surgical procedures performed each year with substantial related health care costs. This trial studied the effect of postoperative bladder backfilling to submicturition level in the operating room and its effect on early postoperative patient care and related cost. Objective The objective of the study was to compare the effect of bladder backfilling on early postoperative patient care and related cost. Study Design This was a randomized, single-blinded, controlled trial conducted between April 2016 and February 2017 at a single urban university hospital providing tertiary care for minimally invasive gynecologic surgery. Ninety-one patients undergoing straight-stick laparoscopic and robot-assisted hysterectomy by minimally invasive gynecologic surgeons for benign indications were recruited. The bladder was partially backfilled with 150 mL of normal saline postoperatively in the intervention group and drained in the control group, as per standard of care. Main outcomes studied were time needed to void, time spent in the postanesthesia care unit, and postanesthesia care unit cost after minimally invasive hysterectomy. Our secondary outcomes were postoperative complications. Results Forty-six patients (50.5%) were randomized to the intervention group, and 45 patients (49.5%) to the control group. Baseline comparative analysis of demographics and preoperative patient-specific variables, surgical history, intraoperative characteristics, and administered medications found the 2 groups to be largely homogenous. After regression analyses for adjustment, we found a significant reduction in the time needed to void, time spent in the postanesthesia care unit, and postanesthesia care unit–associated cost in the intervention group. Patients voided 64.9 minutes earlier than the control group (P = .015) ans spent 64 fewer minutes in the postanesthesia care unit (P = .006), resulting in $401.5 (USD) saving per patient (P = .006). None of the patients encountered any postoperative complications. Conclusion Based on the findings of this randomized clinical trial, postoperative bladder backfilling to submicturition level shortens the time needed for patients to void in the postanesthesia care unit, resulting in shorter postanesthesia care unit stay and resultant cost savings. Conservatively projecting our findings on minimally invasive hysterectomy procedure is estimated to result in $69 million to $139 million (USD) per year in savings. Initiating similar investigations in other ambulatory surgical fields will likely result in a more substantial impact.
Nicastrin haploinsufficiency alters expression of type I interferon‐stimulated genes: the relationship to familial hidradenitis suppurativa

Background Hidradenitis suppurativa (HS), also called acne inversa, is a chronic skin disease. The symptoms can be severe, and include intensely painful nodules and abscesses in apocrine-gland rich inverse skin, such as the buttocks, under the arms and in the groin. Autosomal dominant forms of HS exist, but are rare. Some of these kindred have heterozygous loss-of-function rare variants in the γ-secretase complex component nicastrin (NCSTN). Aim To investigate the effect of NCSTN haploinsufficiency on human keratinocytes and assess potential mechanisms for lesion development. Methods NCSTN was knocked down using a small hairpin RNA construct in both a keratinocyte cell line (HEK001) and an embryonic kidney cell line (HEK293), and differential gene expression was assessed using RNA microarray. Using the HEK293 line, a heterozygous deletion of NCSTN was created with CRISPR/Cas9 genome editing, and nuclear factor kappa B activity was assessed using a luciferase reporter. Results Compared with controls, the keratinocyte NCSTN knockdown cell line showed a significantly increased expression of genes related to the type I interferon response pathway. Both HEK001 and HEK293 knockdowns demonstrated evidence of altered growth. There was a small but significant increase in nuclear factor kappa B signalling in response to tumour necrosis factor treatment in HEK293 cells genome-edited for reduced NCSTN. Conclusions Our data suggest a role for increased keratinocyte inflammatory responsiveness in familial HS. Confirming this phenotype and characterizing additional effects in different cell types will require study beyond cell lines, such as in primary cells and tissues.
The Great Depression and the Great Recession: A View from Financial Markets

Abstract Similarities between the Great Depression and the Great Recession are documented with respect to the behavior of financial markets. A Great Depression regime is identified by using a Markov-switching VAR. The probability of this regime has remained close to zero for many decades, but spiked for a short period during the most recent financial crisis, the Great Recession. The Great Depression regime implies a collapse of the stock market, with small-growth stocks outperforming small-value stocks. A model with financial frictions and uncertainty about policy makers’ intervention suggests that policy intervention during the Great Recession might have avoided a second Great Depression. A multi-country analysis shows that the Great Depression and Great Recession were not like any other financial crises.
Comparison of multi-shot and single shot echo-planar diffusion tensor techniques for the optic pathway in patients with neurofibromatosis type 1

Diffusion tensor imaging (DTI) may be helpful in assessing optic pathway integrity as a marker for treatment in neurofibromatosis type 1 (NF1) patients with optic gliomas (OG). However, susceptibility artifacts are common in typical single-shot echo planar imaging (ssDTI). A readout-segmented multi-shot EPI technique (rsDTI) was utilized to minimize susceptibility distortions of the skull base and improve quantitative metrics. Healthy controls, children with NF1 without OG, and NF1 with OG ± visual symptoms were included. All subjects were scanned with both rsDTI and ssDTI sequences sequentially. Diffusion metrics and deterministic fiber tracking were calculated. Tract count, volume, and length were also compared by a two-factor mixed ANOVA. Five healthy controls, 7 NF1 children without OG, and 12 NF1 children with OG were imaged. Six OG patients had visual symptoms. Four subjects had no detectable optic pathway fibers on ssDTI due to susceptibility, for which rsDTI was able to delineate. Tract count (p < 0.001), tract volume (p < 0.001), and FA (P < 0.001) were significantly higher for rsDTI versus ssDTI for all subjects. MD (p < 0.001) and RD (p < 0.001) were significantly lower for rsDTI vs ssDTI. Finally, MD, AD, and RD had a significantly lower difference in NF1 children with visual symptoms compared to NF1 children without visual symptoms only on ssDTI scans. DTI with readout-segmented multi-shot EPI technique can better visualize the optic pathway and allow more confident measurements of anisotropy in NF1 patients. This is shown by a significant increase in FA, tract count, and volume with rsDTI versus ssDTI.
The Genetics and Genome-Wide Screening of Regrowth Loci, a Key Component of Perennialism in Zea diploperennis

Perennialism is common among the higher plants, yet little is known about its inheritance. Previous genetic studies of the perennialism in Zea have yielded contradictory results. In this study, we take a reductionist approach by specifically focusing on one trait: regrowth (the plant9s ability to restart a new life cycle after senescence on the same body). To address this, six hybrids were made by reciprocally crossing perennial Zea diploperennis Iltis, Doebley & R. Guzman with inbred lines B73 and Mo17 and Rhee Flint, a heirloom variety, of Z . mays L. ssp. mays . All the F 1 plants demonstrated several cycles of growth, flowering, senescence and regrowth into normal flowering plants, indicating a dominant effect of the Z. diploperennis alleles. The regrowability (i.e. the plants9 ability to regrow after senescence) was stably transmitted to progeny of the hybrids. Segregation ratios of regrowth in the F 2 generations are consistent with the trait controlled by two dominant, complementary loci, but do not exclude the influence of other modifiers or environment. Genome-wide screening with genotyping-by-sequencing technology indicated two major regrowth loci, regrowth 1 ( reg1 ) and regrowth 2 ( reg2 ), were on chromosomes 2 and 7, respectively. These findings lay the foundation for further exploration of the molecular mechanism of regrowth in Z. diploperennis . Importantly, our data indicate that there is no major barrier to transferring this trait into maize or other grass crops for perennial crop development with proper technology, which enhances sustainability of grain crop production in an environmentally friendly way.
Ab Initio Mismatched Interface Theory of Graphene on α -RuCl 3 : Doping and Magnetism

Recent developments in twisted and lattice-mismatched bilayers have revealed a rich phase space of van der Waals systems and generated excitement. Among these systems are heterobilayers, which can offer new opportunities to control van der Waals systems with strong in plane correlations such as spin-orbit-assisted Mott insulator α-RuCl_{3}. Nevertheless, a theoretical ab initio framework for mismatched heterobilayers without even approximate periodicity is sorely lacking. We propose a general strategy for calculating electronic properties of such systems, mismatched interface theory (MINT), and apply it to the graphene/α-RuCl_{3} (GR/α-RuCl_{3}) heterostructure. Using MINT, we predict uniform doping of 4.77% from graphene to α-RuCl_{3} and magnetic interactions in α-RuCl_{3} to shift the system toward the Kitaev point. Hence, we demonstrate that MINT can guide targeted materialization of desired model systems and discuss recent experiments on GR/α-RuCl_{3} heterostructures.
Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology.

The Clinical Laboratory Improvement Amendments of 1988 require that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SOD2, TLR4, and TPMT were validated in a Clinical Laboratory Improvement Amendments–accredited laboratory. Because no known reference materials were available, existing DNA samples were used for the analytical validation studies. Pharmacogenetic testing methods developed here were shown to be accurate and 100% analytically sensitive and specific. Other Clinical Laboratory Improvement Amendments–accredited laboratories interested in offering pharmacogenetic testing for these genetic variants, related to genotype-guided therapy for oncology, could use these publicly available samples as reference materials when developing and validating new genetic tests or refining current assays.
Falling Between the Cracks: Discrimination Laws and Older Women

Theories and evidence suggest that older women may experience unique discrimination for being both old and female in the workplace. To provide a remedy for this type of discrimination — known as intersectional discrimination — legal scholars argue that age and sex discrimination laws must be used jointly and acknowledge intersectional discrimination (age‐plus‐sex or sex‐plus‐age discrimination) as a separate cause of action. Nonetheless, in general, courts have declined to do so even though older women are protected under both age and sex discrimination laws. This raises a concern that age discrimination laws may be ineffective, or less effective in protecting older women. I test this implication by estimating the differential effect of age discrimination laws on labor market outcomes between older women and older men. My findings show that age discrimination laws did far less to improve labor market outcomes for older women than for older men. These results may explain the persistent findings of discrimination against older women in the existing literature and support the legal scholars' argument that older women's intersectional discrimination must be recognized as a separate cause of action.
Treating Opioid Use Disorders in Drug Court: Participants’ Views on Using Medication-Assisted Treatments (MATs) to Support Recovery:

Drug courts began in 1989 in Miami-Dade County, FL. Due to their success in treating substance use disorders and reducing criminal recidivism, they have expanded globally and are currently operatin...
Mallows ranking models: maximum likelihood estimate and regeneration

This paper is concerned with various Mallows ranking models. We study the statistical properties of the MLE of Mallows' $\phi$ model. We also make connections of various Mallows ranking models, encompassing recent progress in mathematics. Motivated by the infinite top-$t$ ranking model, we propose an algorithm to select the model size $t$ automatically. The key idea relies on the renewal property of such an infinite random permutation. Our algorithm shows good performance on several data sets.
KPynq: A Work-Efficient Triangle-Inequality Based K-Means on FPGA

K-means is a popular but computation-intensive algorithm for unsupervised learning. To address this issue, we present KPynq, a work-efficient triangle-inequality based K-means on FPGA for handling large-size, high-dimension datasets. KPynq leverages an algorithm-level optimization to balance the performance and computation irregularity, and a hardware architecture design to fully exploit the pipeline and parallel processing capability of various FPGAs. In the experiment, KPynq consistently outperforms the CPU-based standard K-means in terms of its speedup (up to 4.2x) and significant energy efficiency (up to 218x).
Crystal Structure of Human Nocturnin Catalytic Domain

Nocturnin (NOCT) helps the circadian clock to adjust metabolism according to day and night activity. NOCT is upregulated in early evening and it has been proposed that NOCT serves as a deadenylase for metabolic enzyme mRNAs. We present a 2.7-A crystal structure of the catalytic domain of human NOCT. Our structure shows that NOCT has a close overall similarity to CCR4 deadenylase family members, PDE12 and CNOT6L, and to a DNA repair enzyme TDP2. All the key catalytic residues present in PDE12, CNOT6L and TDP2 are conserved in NOCT and have the same conformations. However, we observe substantial differences in the surface properties of NOCT, an unexpectedly narrow active site pocket, and conserved structural elements in the vicinity of the catalytic center, which are unique to NOCT and absent in the deadenylases PDE12/CNOT6L. Moreover, we show that in contrast to human PDE12 and CNOT6L, NOCT is completely inactive against poly-A RNA. Our work thus reveals the structure of an intriguing circadian protein and suggests that NOCT has considerable differences from the related deadenylases, which may point to a unique cellular function of this enzyme.
Stereoselective Synthesis of Carbobicyclics via Organoyttrium-Catalyzed Sequential Cyclization/Silylation Reactions

The sequential cyclization/silylation of 1,5-dienes and 1,6-dienes was effected under mild reaction conditions using catalytic quantities of Cp2*YMe·THF. The process provides carbobicyclics in high yields and with excellent selectivities. The active catalyst is postulated to be Cp2*YH·THF, which is generated in situ. A variety of alkenyl-substituted cyclopentane and cyclohexane substrates were examined. The high diastereoselectivities apparently originate from a preference for a chairlike transition structure that minimizes unfavorable steric interactions between the bulky Cp* ligands of the catalyst and the preexisting ring of the substrate. Acyclic triene precursors, 4-ethenyl-substituted 1,5-heptadienes and 5-ethenyl-substituted 1,8-nonadienes were also examined. These triene substrates, when exposed to the cyclization/silylation protocol, provide the strained trans-bicyclo[3.3.0]octanes and trans-decalin systems in high yield with excellent diastereoselectivity. The high selectivity is again attribute...
Dibromoborane-dimethyl sulfide : A new, mild, chemoselective reagent for the rapid deoxygenation of sulfoxides to sulfides

Dibromoborane-dimethyl sulfide chemoselectively deoxygenates aliphatic and aromatic sulfoxides to the corresponding sulfides in excellent chemical yields in CH2Cl2 solvent in 15 minutes at both 0°C...
Investigating the probability of establishment of Zika virus and detection through mosquito surveillance under different temperature conditions

Because of the increasing threat that Zika virus (ZIKV) poses to more sub-tropical area due to increased global travel, there is a need for better understanding of the effect(s) of temperature on the establishment potential of ZIKV within these subtropical, temperate, and/or seasonal Ae. aegypti populations. The first step to determining risk establishment of ZIKV in these regions is to assess ZIKV's ability to infect mosquitoes at less tropical temperatures, and thus be detected through common surveillance programs. To that end, the effect of two rearing temperatures (RT) and extrinsic incubation temperatures (EIT) on infection and dissemination rates was evaluated, as well as the interactions of such. Total, there were four combinations (RT24-EIT24, RT24-EIT28, RT28-EIT24, RT28-EIT28). Further, a stochastic SEIR framework was adapted to determine whether observed data could lead to differential success of establishment of ZIKV in naive mosquito populations. There was no consistent pattern in significant differences found across treatments for either infection or dissemination rates (p>0.05), where only a significant difference was found in infection rates between RT24-EIT24 (44%) and RT28-EIT24 (82.6%). Across all temperature conditions, the model predicted between a 76.4% and 95.4% chance of successful establishment of ZIKV in naive mosquito populations under model assumptions. We further show that excluding the maximum observed infection and dissemination rates likely overestimates the probability of local establishment of ZIKV. These results indicate that 1) there is no straightforward relationship between RT, EIT, and infection/dissemination rates, 2) in more temperate climates, ZIKV may still have the ability to establish in populations of Aedes aegypti, 3) despite an overall lack of significant differences in infection/dissemination rates, temperature may still alter the kinetics of ZIKV within the mosquito enough to affect the likelihood of infection establishment and detection within the context of mosquito surveillance programs, and 4) both the temporal and magnitude qualities of vector competence are necessary for parameterization of within-mosquito virus kinetics.
Formation and evolution of cosmic D strings

We study the formation of D and F cosmic strings in D-brane annihilation after brane inflation. We show that D string formation by quantum de Sitter fluctuations is severely suppressed, due to suppression of RR field fluctuations in compact dimensions. We discuss the resonant mechanism of production of D and F strings, which are formed as magnetic and electric flux tubes of the two orthogonal gauge fields living on the world-volume of the unstable brane. We outline the subsequent cosmological evolution of the D−F string network. We also compare the nature of these strings with the ordinary cosmic strings and point out some differences and similarities.
New design concepts for constraining glycosylated amino acids

Abstract In an effort to probe the mechanism by which glycosyltransferases recognize glycoproteins and assemble the core structures of O-linked oligosaccharides, two constrained glycopeptides based on the α- N -acetylgalactosaminyl serine substructure were chosen for synthesis. These compounds representing one of the two possible gauche conformations of the d -serine and l -serine configurations of the parent substructure were successfully prepared in reasonable overall yield through a convergent strategy.
Phylogeny, ancestors, and anagenesis in the hominin fossil record

Probabilistic approaches to phylogenetic inference have recently gained traction in paleontological studies. Because they directly model processes of evolutionary change, probabilistic methods facilitate a deeper assessment of variability in evolutionary patterns by weighing evidence for competing models. Although phylogenetic methods used in paleontological studies have generally assumed that evolution proceeds by splitting cladogenesis, extensions to previous models help explore the potential for morphological and temporal data to provide differential support for contrasting modes of evolutionary divergence. Recent methodological developments have integrated ancestral relationships into probabilistic phylogenetic methods. These new approaches rely on parameter-rich models and sophisticated inferential methods, potentially obscuring the respective contributions of data and models. In this study, we describe a simple likelihoodist approach that combines probabilistic models of morphological evolution and fossil preservation to reconstruct both cladogenetic and anagenetic relationships. By applying this approach to a data set of fossil hominins, we demonstrate the capability of existing models to unveil evidence for anagenesis presented by morphological and temporal data. This evidence was previously recognized by qualitative assessments, but largely ignored by quantitative phylogenetic analyses. For example, we find support for directly ancestral relationships in multiple lineages: Sahelanthropus is ancestral to later hominins; Australopithecus anamensis is ancestral to Australopithecus afarensis; Australopithecus garhi is ancestral to Homo; Homo antecessor is ancestral to Homo heidelbergensis, which in turn is ancestral to both Homo sapiens and Homo neanderthalensis. By accommodating direct ancestry in phylogenetics, quantitative results align more closely with previous qualitative expectations.
The ring opening of cyclopropylidene to allene: key features of the accurate reaction surface

The global potential energy surface, determined in the first paper [1] for the groundstate ring opening of cyclopropylidene to allene, is complemented by accurate calculations of its key regions. The basis set is extended and polarization functions are included. The full configuration space of four electrons in four reactive orbitals is enlarged to the full configuration space of eight electrons in eight active orbitals by including correlations in the unbroken, but stretched CC sigma bonds. The effect of further single and double excitations is examined. The geometries and relative energies of the critical regions are found to change only little except for the ring-opening energy barrier which is lowered to about 7 kcal/mol, in good agreement with the experimental estimate of about 6 kcal/mol. Furthermore, the bifurcation is shown to occurafter the transition state, in the neighborhood of a conical intersection on the steepest descent path from the ring-opening transition state to the allene isomerization transition state. The steepest descent paths and the conical intersection are documented in detail. The cogwheel-like free internal rotation of the two methyl groups is confirmed by the accurate calculations. A similar richness of features is believed to exist on many potential energy surfaces governing chemical reactions.