cssi/SciSciGPT-SciSciNet huggingface dataset:
Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in Mice

TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a crucial role in innate immunity. Enhanced TBK1 function is associated with autoimmune diseases and cancer, implicating the potential benefit of therapeutically targeting TBK1. In this article, we examined a recently identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found that Compound II is a potent and specific inhibitor of TBK1-mediated IFN response. Compound II inhibited polyinosinic-polycytidylic acid–induced immune activation in vitro and in vivo. Compound II treatment also ameliorated autoimmune disease phenotypes of Trex1−/− mice, increased mouse survival, and dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In addition, we found that TBK1 gene expression is elevated in systemic lupus erythematosus patient cells, and systemic lupus erythematosus cells with high IFN signature responded well to Compound II treatment. Together, our findings provided critical experimental evidence for inhibiting TBK1 with Compound II as an effective treatment for TREX1-associated autoimmune diseases and potentially other interferonopathies.
Aligned Natural Inflation in String Theory

The authors discuss type IIB string theory realizations of Kim-Nilles-Peloso (KNP) multiple axion inflation, which provides a super-Planckian effective axion decay constant, necessary for UV stable realistic slow roll inflation.
A Framework for Transformation

Transformation of supply chains can be driven by a company's internal problems or they can be externally driven. The type and extent of restructuring should be determined by the nature of these drivers. The relevant question to ask would be how one identifies the external/internal forces driving changes, and the mapping between the drivers and the supply chain capabilities.
Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol

Aims IDOL (inducible degrader of the low-density lipoprotein receptor, LDLR) is an E3 ubiquitin ligase that promotes the ubiquitination and degradation of the LDLR. IDOL is a potential therapeutic target for the development of a novel class of low-density lipoprotein cholesterol (LDL-C)-lowering therapies. In an attempt to develop a mouse model for testing IDOL inhibitors, we examined the effects of adeno-associated virus (AAV)-mediated stable expression of human IDOL in the livers of mice ‘humanized’ with regard to lipoprotein metabolism. Methods and results Using a liver-specific AAV serotype 8 (AAV8)-mediated delivery, AAV-hIDOL produced a dose-dependent increase in LDL-C levels and a decrease in liver LDLR protein. Furthermore, we expressed hIDOL in a ‘humanized’ mouse model of heterozygous familial hypercholesterolaemia (LDLR+/−/Apobec1−/−/hApoB-Tg, LAhB). In this model, total cholesterol (TC) and LDL-C levels were increased by ∼60% starting from 1 week and were sustainable for at least 3 weeks post-injection. Finally, we demonstrate that the effects caused by hIDOL expression are LDLR- dependent given the unchanged plasma lipids in LAhB mice lacking LDLR. Conclusion In conclusion, our study demonstrates a dose-dependent physiological effect of human IDOL on LDL metabolism in mice. This provides a potential model for preclinical testing of IDOL inhibitors for reduction of LDL-C levels.
Abstract: Revisiting the Model Size Effect in Structural Equation Modeling (SEM).

It is generally believed that fitting a large SEM model with moderate to small sample sizes results in a likelihood ratio statistic distribution with inflated Type I error rate, thus poorly approxi...
Hepatocellular injury in hepatitis B and C virus infections.

Most of the liver cell injury in hepatitis B and C infections is likely to be immune-media ted. Variation in the pathogenesis of these infections likely is contributed by a variety of host and virus factors. Host factors include the human leukocyte antigen (HLA) haplotype as well as the ability of the host to both recognize antigen on virus-infected cells and to receive the appropriate costimulatory signals in a timely fashion during infection. Virus factors include the genetic variation, direct cytopathic effects, and the alteration of infected hepatocytes to cytotoxic cytokines. The lack of suitable tissue culture systems and animal models limits the ability to understand the pathogenesis fully but provides challenges for their future development so that the basis for liver cell damage can be elucidated and approaches for therapeutic intervention can be achieved.
Prevention of neonatal anemia in the rat by the pituitary erythropoietic factor.

Of all the substances tested for the prevention of the neonatal anemia in the rat, only the pituitary preparations, erythropoietically active in the repair of post-hypophysectomy anemia, were able to prevent the development of neonatal anemia of the newborn rat.
One Middle School's Elimination of Homogeneous Grouping: A Qualitative Study

AbstractIn this study, the authors examine one middle school's elimination of tracking in math, English, and reading classes. In general, the study bridges the gap between research that clarifies the deleterious effects of tracking and other research that provides strategies for handling heterogeneity. Previously, the process of getting “untracked” has been unexplored. Specifically, two qualitative procedures, interviewing and participant observation, provided answers to the following questions: 1. What allowed a school to initiate a shift to heterogeneous grouping?2. What attitudes or beliefs did administrators and teachers share?3. What steps characterized the implementation process?4. What challenges did school personnel face in switching to heterogeneous grouping?5. What were the perceptions of students regarding heterogeneous grouping? The findings underscore the importance of a shared decision-making model, the possibility for a successful transition to heterogeneous grouping, and the shared beliefs...
Impact of Business Cultural Values on Web Homepage Design That May Hinder International Business

Because of the globalized use of the Internet, companies of most countries rely heavily on websites for the sale of their products and services internationally. However, a company’s website, no matter how nicely designed in terms of graphics used and information provided, may still fail to achieve the expected result if it fails to consider the relevant business cultural values and conventions of the target country. This article, in light of American business values and Chinese business values and through case analyses, identifies the possible problems on those websites aiming at international business. Using specific company websites of both the United States and China and through comparison and contrast, the author analyzes problems in aspects of content, graphics, and layout in attempt to improve designers’ cultural awareness in these aspects and improve their skills for the localization of their international business websites.
Encapsulant thickness options as a factor to impact thermal performance of Chip-on-Board (COB) light emitting diodes

There is an important trend in light emitting diodes (LED) industry to produce continuously thinner package. Chip-on-Board (COB) packaged LED, as a promising thermal efficient package structure, has rarely been investigated for its thermal performance under smaller package thickness. In this work, encapsulant or overall package thickness as a factor to influence the junction temperature as well as the maximum phosphor temperature for COB LEDs is presented. Finite element method (FEM) is employed and validated by forward voltage method (FVM). As shown in the results, for single-chip COB LEDs with standard MESA structure and volume distributed phosphor, there is a lowest point in the maximum temperature while thinning encapsulant layer. But for multi-chip COB LEDs, the junction and phosphor temperature will be reduced with thinner encapsulant. In both cases, the largest deviation of the maximum temperature with different encapsulant thickness can be more than 10°C. Parametric studies of other critical factors such as different Die Attach Adhesive (DAA) materials and radius of encapsulant while thinning encapsulant thickness are also provided. There are two ways to enlarge the input power of COB LED: one is to raise the input power into each chip; the other is to increase the number of chips. It's interesting to find the different thermal behaviors for the two cases. Larger input power will cause a more stable maximum temperature for COB LEDs. While more chips leads to higher variation of the maximum temperature with respect to encapsulant thickness.
The Contribution of Trees

It is nearly impossible to do more than outline the ways in which forest trees and their products have been of use to man. Even though we are entering an age in which steel and plastics may seem to be outdating the use of wood, it is probable that new uses for wood and wood products are at least keeping pace with the loss of the old ones. Indeed, no material is more intimately connected with the growth and survival of our contemporary civilization than a wood product, paper. Yet as more people use (and waste) paper for more purposes every year, the outlook for the forests of the world is far from rosy. Even when the wood is not used for paper, the forests are disappearing, chiefly being cleared for agricultural purposes. Almost all of the tropical rain forests will probably disappear within the next century, yet it has been estimated that the economic possibilities of more than 90 per cent of the plant species in them remain unknown. Even where the forests are preserved, the most valuable timber trees have often been removed.
Free Speech, Private Space and the Constitution

Since the Supreme Court reinforced the state-action doctrine in the early Seventies and ruled that privately owned shopping malls could not qualify as a public forums under the First Amendment, efforts to protect free expression at privately-owned public gathering places have shifted to state courts. In 1980, the California Supreme Court became the first state high court to rule that under its own Constitution shopping malls were public forums. In 1995, the New Jersey Supreme Court was even more emphatic that under its Constitution human rights must prevail over property rights when the two came into conflict. The Court held that when suburban shopping malls replaced the old town squares as public gathering places, free speech had to move to the malls along with the populace. As the drive toward privatization of formerly public space accelerates, courts must now consider the constitutional obligation of private communities. Again, New Jersey courts are taking the lead. Stepping off from the Supreme Court's shopping mall opinion, the Appellate Division has ruled that residential condominiums cannot be turned into "political isolation booths." In a case involving a high-rise condominium, the court held that once the condo association opens a forum for some speech, it must allow access to opposing speech. Professor Askin traces the constitutional history of public forum doctrine under federal and state law -- including the specific incorporation by the New Jersey Supreme Court of the principle of Marsh v. Alabama (the company town case) under the state constitution. The article then explores the implications for the condominium explosion of the New Jersey Supreme Court's observation that: "We do not believe that those who adopted a constitutional provision granting free speech wanted it to diminish in importance as society changed, to be dependent on the unrelated accidents of economic transformation, or to be silenced because of a new way of doing business."
RGS2 modulates the activity and internalization of dopamine D2 receptors in neuroblastoma N2A cells.

Abstract Dysregulated expression and function of dopamine D2 receptors (D2Rs) are implicated in drug addiction, Parkinson's disease and schizophrenia. In the current study, we examined whether D2Rs are modulated by regulator of G protein signaling 2 (RGS2), a member of the RGS family that regulates G protein signaling via acceleration of GTPase activity. Using neuroblastoma 2a (N2A) cells, we found that RGS2 was immunoprecipitated by aluminum fluoride-activated Gαi2 proteins. RGS2 siRNA knockdown enhanced membrane [35S] GTPγS binding to activated Gαi/o proteins, augmented inhibition of cAMP accumulation and increased ERK phosphorylation in the presence of a D2/D3R agonist quinpirole when compared to scrambled siRNA treatment. These data suggest that RGS2 is a negative modulator of D2R-mediated Gαi/o signaling. Moreover, RGS2 knockdown slightly increased constitutive D2R internalization and markedly abolished quinpirole-induced D2R internalization assessed by immunocytochemistry. RGS2 knockdown did not compromise agonist-induced β-arrestin membrane recruitment; however, it prevents β-arrestin dissociation from the membrane after prolonged quinpirole treatment during which time β-arrestin moved away from the membrane in control cells. Additionally, confocal microscopy analysis of β-arrestin post-endocytic fate revealed that quinpirole treatment caused β-arrestin to translocate to the early and the recycling endosome in a time-dependent manner in control cells whereas translocation of β-arrestin to these endosomes did not occur in RGS2 knockdown cells. The impaired β-arrestin translocation likely contributed to the abolishment of quinpirole-stimulated D2R internalization in RGS2 knockdown cells. Thus, RGS2 is integral for β-arrestin-mediated D2R internalization. The current study revealed a novel regulation of D2R signaling and internalization by RGS2 proteins.
Characterizing the Influence of Abstraction in Full-Scale Wind Turbine Nacelle Testing

In recent years, there has been a growing interest in full-scale wind turbine nacelle testing to complement individual component testing. As a result, several wind turbine nacelle test benches have been built to perform such testing with the intent of loading the integrated components as they are in the field. However, when mounted on a test bench the nacelle is not on the top of a tower and does not have blades attached to it--this is a form of abstraction. This paper aims to quantify the influence of such an abstraction on the dynamic response of the nacelle through a series of simulation case studies. The responses of several nacelle components are studied including the main bearing, main shaft, gearbox supports, generator, and yaw bearing interface. Results are presented to highlight the differences in the dynamic response of the nacelle caused by the abstraction. Additionally, the authors provide recommendations for mitigating the effects of the abstraction.
Potentiation of Melphalan-Induced Cytotoxicity through Targeting of the Base Excision Repair Pathway in Multiple Myeloma.

Abstract Melphalan (M) is an active agent against multiple myeloma (MM). One of the obstacles with M treatment is the patient's ability to tolerate side effects such as mucositis and pancytopenia. This is especially true for those patients >70 years of age. We hypothesize that potentiation of M-induced cytotoxicity is possible in MM with agents that target, and therefore further imbalance, multiple DNA repair pathways. A key protein in the Base Excision Repair (BER) pathway, Apurinic/apyrimidinic endonuclease/ redox factor (APE1/Ref-1 or APE1) plays a major role in the repair of damage caused by chemotherapeutic agents including M and Temozolomide (TMZ), interacts with a number of transcription factors (HIF1-a, p53, AP1, NFkB, etc) to regulate their function through oxidation/reduction (redox) signaling, and is overexpressed in refractory/relapsed MM cells. Furthermore, a reduction in APE1 protein sensitizes MM cells to melphalan indicating that inhibition of this protein may have therapeutic potential in MM. In order to decipher the importance of APE1's redox and repair functions in MM cells' response to DNA damage via melphalan and TMZ, we have available to us small molecule APE1 inhibitors that affect only the repair activity or only the redox activity of APE1. The mechanism of action of MLP is primarily via monoadduct leading to DNA interstrand cross-link (ICL) formation which is processed by the Nucleotide Excision Repair (NER) pathway. MLP also causes N7methyl-G and N3methyl-A adduct formation which are repaired by the BER pathway. For these studies, we treated RPMI 8226 cells with several chemotherapeutic agents: 1. M; 2. TMZ, which creates primarily N7methyl-G and N3methyl-A adducts; 3. Methoxyamine (MX), which has been shown to inhibit further processing by the BER pathway; and 4. a small molecule which blocks the redox function of APE1. Our purpose was to overwhelm the DNA repair pathways by causing the accumulation of DNA repair intermediates and inducing apoptosis. M-induced cytotoxicity is enhanced by TMZ (CI=0.08), MX (CI=0.89), and E3330 (CI=0.06), and this effect was synergistic as determined by CalcuSyn software which generates median effect and combinational index (CI) values, with CI
Social support buffers the effect of interpersonal life stress on suicidal ideation and self-injury during adolescence.

Background The effect of life stress on suicidal symptoms during adolescence is well documented. Stressful life events can trigger suicidality, but most adolescents are resilient and it is unclear which factors protect against the deleterious impact of stress. Social support is thought to be one such factor. Therefore, we investigated the buffering effect of specific sources of social support (parental and peer) on life stress (interpersonal and non-interpersonal) in predicting suicidal symptoms during adolescence. In order to test the specificity of this stress buffering, we also examined it with regard to dysphoric mood. Method Data come from the Adolescent Development of Emotions and Personality Traits (ADEPT) Project, a cohort of 550 adolescent females aged 13.5–15.5 recruited from Long Island. Self-reported social support, suicidality, and dysphoria were assessed at baseline and suicidality and dysphoria were assessed again at 9-month follow-up. Life stress was assessed by interview at the follow-up. Results High levels of parental support protected adolescent girls from developing suicidal symptoms following a stressor. This effect was less pronounced for peer support. Also, social support did not buffer the pathogenic effects of non-interpersonal stress. Finally, social support did not buffer the effect of life stress on dysphoric symptoms. Conclusions Altogether, our results highlight a distinct developmental pathway for the development of suicidal symptoms involving parental support that differs from the development of dysphoria, and signifies the importance and specificity of social support in protecting against suicidality in adolescent girls.
When the relationships fail: A microperspective on consumer responses to service failure

This article investigated the consumer response mechanism in a service failure context. A service failure response model was introduced that incorporated emotive antecedents, a mediation process, a...
The Value of Heterogeneous Pleasures

Pleasure is one of the most obvious candidates for directly improving wellbeing. Hedonists claim it is the only feature that can intrinsically make life better for the one living it, and that all of wellbeing derives from the relative pleasantness and unpleasantness of conscious experience. But Hedonism is incompatible with the ‘heterogeneity’ of pleasure: it cannot allow that distinct pleasures can feel completely differently, if experiences count as pleasant due to how they feel. I argue that a pluralistic variant of Hedonism can match its theoretical attractions while also accommodating the heterogeneity of pleasure. This has interesting implications for both the philosophical debate over the nature of wellbeing and psychological theories of how to measure and aggregate positive affect. In particular, my argument implies that there is no single dimension of ‘valence’ or ‘intensity’ on which pleasantness can be measured.
Geometry and Complexity Theory

Two central problems in computer science are P vs NP and the complexity of matrix multiplication. The first is also a leading candidate for the greatest unsolved problem in mathematics. The second is of enormous practical and theoretical importance. Algebraic geometry and representation theory provide fertile ground for advancing work on these problems and others in complexity. This introduction to algebraic complexity theory for graduate students and researchers in computer science and mathematics features concrete examples that demonstrate the application of geometric techniques to real world problems. Written by a noted expert in the field, it offers numerous open questions to motivate future research. Complexity theory has rejuvenated classical geometric questions and brought different areas of mathematics together in new ways. This book will show the beautiful, interesting, and important questions that have arisen as a result.
Therapeutic Targeting of the Receptor Tyrosine Kinase Met

There are different options to inhibit Met activation and these are in part limited depending on the transforming phenotype. For example, inhibiting ligand/receptor interactions may be a useful approach when inhibiting a paracrine/autocrine mechanism but will show little effect on a gain-of-function mutation of Met. It still remains unknown as to how much Met inhibition is required to achieve clinically beneficial anti-tumor and anti-metastatic results. The answer may potentially be different depending upon whether the ‘tumorigenic culprit’ lies with Met expression or mutations of the RTK. It will be necessary to further study and optimize targeted approaches for clinical studies. Another intriguing area of research, with specific Met inhibitors available, would be to test the drug efficaciesagainst different mutant forms of the Met oncoprotein. It is possible that some mutations of Met may cause resistance, or conversely a greater susceptibility, to the inhibitors. Among various strategies to inhibit HGF/Met signaling, developing specific small molecule inhibitors against Met may have the greatest potential in molecularly targeted anti-cancer therapy. However, lessons learned from Gleevec (imatinib mesylate) treatment in chronic myelogenous leukemia demonstrate that drug resistance is a real issu therapeutically. It will therefore be necessary to furthercharacterize the signaling mechanisms behind Met-mediated proliferation and other biological effects to identify additional molecules for targeted therapies.
Metastatic hepatocellular carcinoma diagnosed by fine needle aspiration: A clinical and cytologic study

Background Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide. The clinical and cytological features of metastatic HCC have not been well established. Methods To determine the clinical and cytological features of metastatic HCC, we retrospectively searched for all HCC metastasis diagnosed by fine needle aspiration or core biopsy. Results We found 12 bone metastases, 11 intra-abdominal, 4 lung, 3 soft tissue, and 2 lymph node metastases from 32 patients. 7/12 bone metastases were vertebral body, 4 were pelvic bone, and 1 case was humerus. 10/32 cases showed concurrent metastasis at a different location. The average metastasis size was 40.9 mm. Tumor grades of HCC showed near equal distribution. The following cytological features are most frequently associated with metastatic HCC: single tumor cells (88.9%), cytoplasmic vacuolization (70.4%), trabecular pattern (70.4%), bare nuclei (66.7%), prominent nucleoli (66.7%), tumor giant cells (44.4%), and traversing capillaries (44.4%) and encased by endothelium (18.5%). Immunohistochemical stains of 12 cases showed the majority were positive for E-Cadherin, Carcinoembryonic Antigen, and HepPar1. Negativity for CK7 and CK20 is contributory to making the diagnosis. Conclusion The most frequent metastatic HCC diagnosed by FNA was from bone, especially the vertebral body. The frequent cytomorphology and immunophenotype seen in primary HCC are good diagnostic criteria for diagnosing metastatic HCC.
Expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD.

Expression of an expanded (G4C2)30+ repeat found in C9orf72 is the most prominent mutation in familial FTD and ALS. An unbiased RNAi-based, large-scale screen in (G4C2)49-expressing Drosophila identified the CDC73/PAF1 complex (PAF1C) as a novel suppressor of (G4C2)49-toxicity. Downregulation of PAF1C, an activator of elongating RNAPII, caused suppression by reducing (G4C2)49-RNA levels. Remarkably, only PAF1C components Paf1 and Leo1 were selective for transcription of a long repeat expansion; transcript levels produced from shorter and longer repeat-containing transgenes were similarly affected by other components and Spt4, a previously identified transcriptional regulator of G4C2-repeats. Congruent with our fly data, PAF1 and LEO1 were upregulated in the frontal cortex of C9+ FTD patients and their expression correlated to expression of repeat-containing C9orf72. Surprisingly, this affect was specific to C9+ FTD versus C9+ ALS. This is the first evidence that PAF1C is playing a role in C9orf72-associated FTD. Further, PAF1C may affect other repeat-associated diseases.
Mean scores for self-report surveys completed using paper-and-pencil and computers: A meta-analytic test of equivalence

Abstract The large body of literature on the comparability of mean scores for self-report survey responses gathered using paper-and-pencil and computer data collection methodologies has yielded inconclusive results. However, no comprehensive meta-analysis has been conducted in this field, and those that are available for specific measures have typically not differentiated between studies using between-groups and within-subjects designs. Also, few individual studies, and no meta-analyses, have used correct statistical procedures to determine the equivalence of the two methodologies. Consequently, we conducted two meta-analyses assessing quantitative equivalence (i.e., mean scores), with the first consisting of 144 independent effect sizes from studies with between-groups designs and the second including 70 independent effect sizes from studies using within-subjects designs. Both meta-analyses assessing mean scores indicated equivalence across conditions, with large heterogeneity of variance in the between-groups analysis. Presence of others in both the paper-and-pencil and computer conditions accounted for a significant portion of this variance. Heterogeneity of variance was small for the within-subjects design analysis. Overall, results indicated that the mean scores for self-report surveys using paper-and-pencil and the computer are comparable, although heterogeneity differs for the study designs. Equivalence testing was demonstrated to be the recommended statistical procedure for this type of research.
Everything is Foreseen, Yet Free will is Given (Mishna Avot 3:15).

Jan Theeuwes’ review of visual selection shines a useful spotlight on the role of selection history in determining subsequent deployments of attention. However, he blurs an important distinction between volition and top-down guidance of attention and he underplays the role of both of those factors in the control of attention.
Gabriel Marcel: Ethics within a Christian Existentialism

Gabriel Marcel, an only child, was born in Paris in 1889, and his mother died when he was only four. His father, a diplomat, later married Marcel’s aunt. By this time his father (a lapsed Catholic) was an agnostic, and his aunt was nominally a liberal Protestant. As a result, Marcel did not receive any religious upbringing. His lycee years in Paris were not enjoyable, except for his studies in philosophy and music, two subjects that were to become very important for him. He later enrolled in the Sorbonne, where he attended lectures by Henri Bergson. He earned a licence en philosophie in 1907. He married Jacqueline Boegner in 1918, and they later adopted a son. During this time Marcel fell into a period of agnosticism.
Mandibular growth following implant restoration: does Wolff's law apply to residual ridge resorption?

This study measured bone height under a fixed detachable cantilever restoration supported by five or six endosseous implants in 60 consecutively treated patients. Panoramic films were made at surgery and 1, 2, 3, and 4 years postrestoration. A computer-enhanced method was used to measure mandibular height 5, 10, 15, and 20 mm distal to the last implant, which was used as a length. standard to correct for variation in film magnification. Implant restoration resulted in a significant growth of the mandible (baseline: 7.25 +/- 0.25 mm, 4 years: 8.18 +/- 0.18 mm; P = .05). The growth in dimension appears to occur during the first year of function.
One-volt silicon photonic crystal nanocavity modulator with indium oxide gate.

The ever-increasing global network traffic requires a high level of seamless integration between optical interconnect systems and complementary metal–oxide–semiconductor (CMOS) circuits. Therefore, it brings stringent requirements for future electro-optic (E-O) modulators, which should be ultracompact, energy efficient, high bandwidth, and in the meanwhile, able to be directly driven by the state-of-the-art CMOS circuits. In this Letter, we report a low-voltage silicon photonic crystal nanocavity modulator using an optimized metal–oxide–semiconductor (MOS) capacitor consisting of an In2O3/HfO2/p-Si stacked nanostructure. The strong light–matter interaction from the accumulated free carriers with the nanocavity resonant mode results in holistic improvement in device performance, including a high tuning efficiency of 250 pm/V and an average modulation strength of 4 dB/V with a moderate Q factor of ∼3700 and insertion loss of ∼6 dB using an ultrashort electrode length of only 350 nm. With 1 V driving voltage over a capacitive loading of only 13 fF, the silicon photonic nanocavity modulator can achieve more than 3 dB extinction ratio with energy consumption of only 3 fJ/bit. Such a low-voltage, low-capacitance silicon nanocavity modulator provides the feasibility to be directly driven by a CMOS logic gate for single-chip integration.
GPU-accelerated algorithm for asteroid shape modeling

Abstract Modeling asteroid shapes from optical and radio telescope data is computationally expensive and current sequential-fit inversion algorithms are very slow, up until recently often taking days or weeks for larger models. The modeling process is comprised of many serialized independent calculations that can be parallelized with inexpensive and ubiquitous graphical processing unit (GPU) hardware. We have accelerated the SHAPE modeling algorithm (Hudson, 1994) with an Nvidia GPU and algorithm optimization while maintaining full backward compatibility, achieving speed boosts of 2.2x-19.3x over the established algorithm. The highest speed boosts achieved were for portions of the modeling process taking up a majority of processing time on the existing algorithm, moving the average speedup factor towards the upper end of the range. We use scale model asteroids to show that our method can model shapes that are both unique to the observed data and stable. High resolution complex vertex models benefit the most from the new algorithm because of its better scalability to problem size on GPU hardware. Specific algorithm changes include facet-parallel rendering, pixel-parallel delay-Doppler mapping, parallel reductions, and streamed frame operations.
Climate Justice, Climate Policy, and the Role of Political Philosophy

One of the key features of Gajevic Sayegh’s article is the ‘bottom-up’ methodological approach to thinking about climate justice that he adopts and recommends to philosophers who aim both to produc...
A RETROSPECTIVE SNAPSHOT OF AMERICAN ZEN IN 1973

In the early 1970s, Zen in the United States remained a fledgling new religious movement, characterised by small, informal meditation groups or living room sanghas, and only a handful of larger pra...
Using Evaluative Criteria to Review Youth Anxiety Measures, Part II: Parent-Report.

This Evidence Base Update of parent-report measures of youth anxiety symptoms is a companion piece to our update on youth self-report anxiety symptom measures (Etkin et al., 2021). We rate the psyc...
When language outgrows them: Comprehension of ambiguous sentences in children with normal hearing and children with hearing loss.

Abstract Background In spite of recent gains in language development made by children with hearing loss (HL) as a result of improved auditory prostheses and earlier starts to intervention, these children continue to struggle academically at higher grade levels. We hypothesize that one reason for these incongruent outcomes for language and academics may be that the language demands of school escalate as grade level increases, outstripping the language abilities of children with HL. We tested that hypothesis by examining a higher level skill that is essential for success with academic language, the ability to access multiple interpretations for a sentence. Method 122 children participated at the end of middle school: 56 with normal hearing (NH), 15 with moderate HL who used hearing aids (HAs), and 51 with severe-to-profound HL who used cochlear implants (CIs). Children's abilities to provide more than one interpretation for an ambiguous sentence were assessed. These sentences were ambiguous due either to words having multiple meanings or to syntactic structure that could evoke more than one interpretation. Potential predictors of those abilities were evaluated, including expressive vocabulary, comprehension of syntactic structures, grammaticality judgments, forward digit span, and several audiologic factors. Results Children with NH performed best, children with CIs performed poorest, and children with HAs performed intermediately to those groups. Children in all groups achieved higher scores on the multiple meanings than on the syntactic structure items. The variables that were associated with performance varied across groups. Audiologic factors did not explain any variability in performance on the ambiguous sentences task for children with HL. Conclusions The kind of linguistic flexibility needed to consider more than one interpretation for sentences lacking immediate, real-world context is essential to processing academic language. Children with HL – especially those with severe-to-profound HL who required CIs – showed deficits in this skill, which could contribute to their ongoing academic struggles. Continued language support is needed for these children to allow them to acquire the higher level language skills necessary for success through all of their years in school.
Superior Polyaniline Cathode Material with Enhanced Capacity for Ammonium Ion Storage

A paradigm shift in aqueous rechargeable batteries has seen the development of nonmetal ammonium ions (NH4+) as charge carriers. NH4+ ions have a molecular weight of 18 g mol–1 and hydrated ionic s...
Connecting the grain-shearing, creep, and squirt flow models for wave propagation in the seabed

The generalized creep and squirt flow models are shown to be stationary creep processes. A fractional exponent is used to develop a new generalized squirt flow model. The responses of the grain-shearing and generalized creep models are identical, although based on entirely different concepts: a single spring and time-varying damper versus a continuous distribution of parallel Maxwell elements. The random structure of marine sand is more consistent with the latter, implying absence of strain-hardening. The generalized squirt flow model has a high frequency cutoff suited to practical systems, limited by the speed with which underlying physical changes can occur.
The role of monoamine oxidase enzymes in the pathophysiology of neurological disorders.

Abstract Monoamine oxidase enzymes are responsible for the degredation of serotonin, dopamine, and norepinephrine in the central neurvous system. Although it has been nearly 100 years since they were first described, we are still learning about their role in the healthy brain and how they are altered in various disease states. The present review provides a survey of our current understanding of monoamine oxidases, with a focus on their contributions to neuropsychiatric, neurodevelopmental, and neurodegenerative disease. Important species differences in monoamine oxidase function and development in the brain are highlighted. Sex-specific monoamine oxidase regulatory mechanisms and their implications for various neurological disorders are also discussed. While our understanding of these critical enzymes has expanded over the last century, gaps exist in our understanding of sex and species differences and the roles monoamine oxidases may play in conditions often comorbid with neurological disorders.
Diseases of the Fallopian Tube

The fallopian tube, a small organ named after the Italian anatomist Gabriele Falloppio, has recently risen to center stage in the field of gynecologic pathology. This chapter provides a good discussion of commonly encountered entities in daily practice, including non-neoplastic lesions, precancerous lesions, and fallopian tube neoplasms. A wide variety of benign lesions including those related to infertility and ectopic pregnancy are discussed. Of these, acute and chronic inflammation of the fallopian tube and related complications play a key role. Pseudocarcinomatous hyperplasia can particularly pose diagnostic difficulty. Pregnancy-related tubal manifestations including the likelihood of overdiagnosis of hydatidiform mole are briefly noted. The spectrum of entities that include p53 signature, secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinoma (STIC) are emphasized and widely discussed; these concepts are at the forefront of our understanding of the initiation and development of extrauterine serous carcinoma. As a common primary fallopian tube carcinoma, high-grade serous carcinoma and endometrioid carcinoma are also discussed. Miscellaneous tumors commonly encountered in the paratubal regions are discussed and include mesothelial tumors (adenomatoid tumor, well-differentiated papillary mesothelioma, and peritoneal malignant mesothelioma) and the female adnexal tumor of probable Wolffian origin (FATWO). The final sections cover metastatic carcinomas to the fallopian tube from gynecologic and nongynecologic origins.
Aero-structural design and optimization of 50 MW wind turbine with over 250-m blades:

The quest for reduced levelized cost of energy has driven significant growth in wind turbine size; however, larger rotors face significant technical and logistical challenges. The largest published...
Paying patients to use lower-priced providers.

OBJECTIVE Many employers have introduced rewards programs as a new benefit design in which employees are paid $25-$500 if they receive care from lower-priced providers. Our goal was to assess the impact of the rewards program on procedure prices and choice of provider and how these outcomes vary by length of exposure to the program and patient population. STUDY SETTING A total of 87 employers from across the nation with 563,000 employees and dependents who have introduced the rewards program in 2017 and 2018. STUDY DESIGN Difference-in-difference analysis comparing changes in average prices and market share of lower-priced providers among employers who introduced the reward program to those that did not. DATA COLLECTION METHODS We used claims data for 3.9 million enrollees of a large health plan. PRINCIPAL FINDINGS Introduction of the program was associated with a 1.3% reduction in prices during the first year and a 3.7% reduction in the second year of access. Use of the program and price reductions are concentrated among magnetic resonance imaging (MRI) services, for which 30% of patients engaged with the program, 5.6% of patients received an incentive payment in the first year, and 7.8% received an incentive payment in the second year. MRI prices were 3.7% and 6.5% lower in the first and second years, respectively. We did not observe differential impacts related to enrollment in a consumer-directed health plan or the degree of market-level price variation. We also did not observe a change in utilization. CONCLUSIONS The introduction of financial incentives to reward patients from receiving care from lower-priced providers is associated with modest price reductions, and savings are concentrated among MRI services.
Structured time-delay models for dynamical systems with connections to FrenetSerret frame

Time-delay embedding and dimensionality reduction are powerful techniques for discovering effective coordinate systems to represent the dynamics of physical systems. Recently, it has been shown tha...
Allograft-prosthetic composite reverse total shoulder arthroplasty for reconstruction of proximal humerus tumor resections.

Background Proximal humerus reconstructions after resection of tumors are challenging. Early success of the reverse shoulder arthroplasty for reconstructions has recently been reported. The reverse allograft-prosthetic composite offers the advantage of improved glenohumeral stability compared with hemiarthroplasty for proximal humeral reconstructions as it uses the deltoid for stability. Methods This article describes the technique for treating proximal humeral tumors, including preoperative planning, biopsy principles, resection pearls, soft tissue tensioning, and specifics about reconstruction using the reverse allograft-prosthetic composite. Two cases are presented along with the functional outcomes with use of this technique. Biomechanical considerations during reconstruction are reviewed, including techniques to improve the deltoid compression force. Results Reported instability rates are less with reverse shoulder arthroplasty reconstruction as opposed to hemiarthroplasty or total shoulder arthroplasty reconstructions of tumor resections. Reported functional outcomes are promising for the reverse allograft-prosthetic composite reconstructions, although complications are reported. Conclusion Reverse allograft-prosthetic composites are a promising option for proximal humeral reconstructions, although nonunion of the allograft–host bone junction continues to be a challenge for this technique.
A computational approach for the identification of site-specific protein glycosylations through ion-trap mass spectrometry

Glycosylation is one of the most common post-translational modifications (PTMs) of proteins, the characterization of which is commonly achieved utilizing mass spectrometry (MS). However, its applicability is currently limited by the lack of computational tools capable of autmoated interpretation of high throughput MS experiments which would allow the characterization of glycosylation sites and their microheterogeneities. We present here a computational approach which overcomes this problem and allows the identification and assignment of the microheterogeneities of glycosylation sites of glycoproteins from liquid chromatography ion-trap-based mass spectrometry (LC/MS) data. This method was implemented in a software tool and tested on several model glycoproteins. The results demonstrate the potential of our computational approach in automating the high throughput identification of glycoproteins.
Pathogenic Mechanisms of HIV Disease: The Role of Viral Replication and Immune Activation

HIV replication and the immune response to the virus lead to a state of generalized immune activation, which drives the pathogenesis of HIV disease. HIV-induced immune activation results in increased T-cell turnover (production and destruction), increased death of T cells, a decline in the size of the CD4+ T-cell pool, and a state of activation-induced immunodeficiency. In many HIVinfected individuals, these phenomena can be reversed or mitigated with effective antiretroviral therapy (ART), which blunts HIV replication and can reduce plasma levels of viremia to undetectable levels. Recent data from our laboratory have demonstrated fundamental differences between viremic and aviremic individuals with regard to the physiologic state of the resting CD4+ T-cell reservoir of HIV and the phenotype and function of T cells, B cells and natural killer (NK) cells. In terms of the CD4+ T-cell reservoir, resting cells in viremic versus aviremic individuals differentially express certain genes associated with HIV replication and are continually poised to express virus as a result of continual activation related to viremia; thus, true latency likely does not exist in these patients. We had previously reported that much greater stability exists in aviremic individuals, suggesting the presence of a truly latent reservoir of virus in this population. However, recent data indicate that the normal physiologic process of low-level immune activation in aviremic individuals sustained the low level turnover and propagation of the latent HIV reservoir. Previously, we have demonstrated that HIV-mediated hyperactivation induces the terminal differentiation of B cells. More recently, we have determined that certain B-cell genes are upregulated in HIVviremic individuals as compared with HIV-aviremic individuals. Many of these genes are associated with terminal B-cell differentiation and death by apoptosis. Recent data indicate that there is a balance between expression of survival and apoptotic genes in HIV-infected individuals that is impacted by the presence and level of viremia. In viremic individuals we also have characterized a population of aberrantly activated CD56NK cells that manifest lower-than-normal expression of Natural Cytotoxicity Receptors and a normal or increased expression of inhibitory NK receptors. This dichotomy is reflected in decreased cytotoxic function and decreased secretion of TNF-alpha and interferon-gamma. In addition, NK cells from viremic individuals express Fas on their surfaces at significantly increased levels, and are more susceptible to apoptosis upon exposure to sFASL. Furthermore, viremia impacts the NK cell-dendritic cell interactions that are critical to normal immune responsiveness. Taken together, our data indicate that HIV pathogenesis involves both direct and indirect effects of HIV and a relentless cycle of aberrant immune activation that drives the disease process in HIV-infected individuals. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005
Intimacy across Borders: Race, Religion, and Migration in the U.S. Midwest

Review of: "Intimacy across Borders: Race, Religion, and Migration in the U.S. Midwest," by Jane Juffer.
The Hollowness of the Harm Principle

Among the various instruments in the toolbox of liberalism, the so-called "harm principle," presented as the central thesis of John Stuart Mill's classic "On Liberty," has been one of the most popular. The harm principle has been widely embraced and invoked in both academic and popular debate about a variety of issues ranging from obscenity to drug regulation to abortion to same-sex marriage, and its influence is discernible in legal arguments and judicial opinions as well. Despite the principle's apparent irresistibility, this essay argues that the principle is hollow. It is an empty vessel, alluring but without any inherent legal or political content, into which advocates can pour whatever substantive views and values they happen to favor. Perhaps the major problem that results is that advocates are tempted to advance their values and views not on their substantive merits, but rather by promoting the vessel, or the packaging. And like the harm principle itself, that temptation has proven irresistible - not merely to the office party debater or the talk show host, but to sophisticated philosophers as well, notably including the principle's most articulate proponents: J. S. Mill and Joel Feinberg. All in all, the harm principle serves to confuse and distract, and to permit advocates to gain illicit rhetorical advantage without earning their way. Our public deliberations would accordingly be enhanced if the harm principle were retired from duty.