cssi/SciSciGPT-SciSciNet huggingface dataset:
Intelligent Aggressiveness: Using Forecast Multipliers, Hybrid Forecasting, Fare Adjustment, and Unconstraining Methods to Increase Revenue*

Many studies have begun the exploration of airlines using intelligent aggressiveness (IA) in unidimensional directions (e.g., forecast multipliers alone). This article uses the sophisticated passenger origin–destination simulator (PODS) to examine the revenue impact of four different IA levers—forecast multipliers, unconstraining, hybrid forecasting (HF) and fare adjustment (FA). We also explore the impacts in two different origin–destination networks. Due to the competitive nature of PODS (two or four airlines competing) and its allowance for customer choice, we are able to assess all the implications, including the impact of spill, upgrades and recapture. We find that with a single IA lever, independent of the network and demand level, in a more-restricted fare environment, the optimal lever is almost always HF with moderate-to-aggressive estimates of willingness-to-pay, with revenue gains of 0.4–4.3% in a large global network, and gains of 1.7–4.2% in a domestic network, depending on demand level and optimization method used. We also test two additional, less-restricted fare environments and find that revenue improvements have a wider range (0.8–6.3%) with a single lever in the larger network. Finally, we explore the impacts of allowing the competitors to use basic IA and the airline of interest to use multiple IA levers.
Identification of an ATP-controlled allosteric switch that controls actin filament nucleation by Arp2/3 complex

Nucleation of branched actin filaments by Arp2/3 complex is tightly regulated to control actin assembly in cells. Arp2/3 complex activation involves conformational changes brought about by ATP, Nucleation Promoting Factor (NPF) proteins, actin filaments and NPF-recruited actin monomers. To understand how these factors promote activation, we must first understand how the complex is held inactive in their absence. Here we demonstrate that the Arp3 C-terminal tail is a structural switch that prevents Arp2/3 complex from adopting an active conformation. The interaction between the tail and a hydrophobic groove in Arp3 blocks movement of Arp2 and Arp3 into an activated filament-like (short pitch) conformation. Our data indicate ATP binding destabilizes this interaction via an allosteric link between the Arp3 nucleotide cleft and the hydrophobic groove, thereby promoting the short-pitch conformation. Our results help explain how Arp2/3 complex is locked in an inactive state without activators and how autoinhibition is relieved.
Trans-aortic Alfieri stitch at the time of septal myectomy for hypertrophic obstructive cardiomyopathy.

BACKGROUND Systolic anterior motion (SAM) of the mitral valve, left ventricular outflow tract (LVOT) obstruction, and mitral regurgitation (MR) are known adverse outcomes that can occur after septal myectomy for hypertrophic obstructive cardiomyopathy. The objective of this study was to describe outcomes of a surgical technique to prevent these complications. METHODS We have adopted a technique where we place an Alfieri stitch in the mitral valve through the aortotomy while performing septal myectomy. A retrospective review was performed and outcomes associated with this technique were noted. RESULTS Twenty-four patients underwent septal myectomy and mitral valve repair using this technique. Mean age was 57 ± 10 years. Twenty patients were in class III/IV heart failure, and all had documented SAM. Mean LVOT gradient improved from 78 ± 48 mmHg preoperatively to 19 ± 20 mmHg after myectomy (p < 0.001). No patients had postoperative SAM, and no patients required a second aortic crossclamping for mitral repair. Seventeen of 19 patients with ≥mild MR had improvement in MR. During follow-up, 16 patients had no/trivial MR, seven had mild MR, and one had moderate MR. The mean postoperative mitral gradient was 4.5 ± 3.0 mmHg. Thirteen patients had postoperative complications including one death in a patient who developed a ventricular septal defect. CONCLUSIONS Trans-aortic Alfieri stitch placement during septal myectomy is feasible in most cases as an additional tool to improve MR and minimize SAM. This technique may have a role in addressing mitral disease, such as a long anterior leaflet or fibrotic mitral valve, at the time of myectomy without the need for left atriotomy for mitral exposure.
PARKING FACILITY LAYOUT: LEVEL-OF-SERVICE APPROACH

The primary function of a parking facility is to serve its users in an efficient and convenient manner. The basic objective of this study is to establish a method of measuring parking efficiency of individual facilities, based on the level-of-service concept. It is felt that the approach in this study will standardize the facility service satisfaction to the parker and thus furnish general guidance for the preliminary design and evaluation of parking facilities. In approaching this objective the study identifies and evaluates a group of principal variables which exert significance on parking service provided by parking facilities. The variable investigation indicated that availability and flow/capacity ratio are the most prominent parameters, and therefore, are included in the derived method for designating the level of service of parking facilities. Finally, a feedback analysis is made to balance the design of parking layout considering both quantitative and qualitative factors. This study identifies a group of principal variables influencing the service level provided by a typical parking facility.
Spontaneous cracking of amorphous solid water films and the dependence on microporous structure

Vapor-deposited, porous, amorphous, water-ice films, also called amorphous solid water (ASW), crack spontaneously during growth when the film thickness exceeds a critical value (Lc). We measured the Lc during growth of ASW films as a function of growth temperature (Tg = 10 K, 30 K, and 50 K) and deposition angle (θ = 0°, 45°, and 55°) using a quartz crystal microbalance, an optical interferometer, and an infrared spectrometer. The critical thickness, 1–5 μm under our experimental conditions, increases with Tg and θ, an indication of film porosity. We suggest that ASW films undergo tensile stress due to the mismatch between substrate adhesion and contracting forces derived from the incompletely coordinated molecules on the surfaces of the pores. We provide a model to explain the observed dependences of Lc on the Tg and θ in the context of Griffith theory and estimate the tensile strength of low-temperature ASW to be ∼25–40 MPa. Our model can be applied more generally to describe fracture of other solids with microporous structures, such as metallic or ceramic materials with voids.
Abstract 9478: GRK2-Mediated Phosphorylative Desensitization of AdipoR1 in the Failing Heart

Adiponectin (APN) is a novel adipokine whose cardioprotective actions in acute myocardial infarction (MI) are well-defined. However, the role of APN in chronic heart failure (HF) is controversial. Experimental studies demonstrate APN deficiency exacerbates HF progression. Paradoxically, clinical observations report APN increases in relation to worsening HF. Here, we determine whether APN receptors 1 and 2 (AdipoR1/AdipoR2, the 7-transmembrane domain-containing receptors mediating APN actions) are phosphorylatively modified post-MI, similar to G-protein coupled receptors (GPCR), impeding APN signaling. Receptor phosphorylation, kinase expression, and APN function were determined via in vivo, ex vivo, and in vitro models. Neither AdipoR1 nor AdipoR2 were phosphorylated in the normal heart. However, AdipoR1 was phosphorylated post-MI, peaking at 7 days, and remained significantly phosphorylated thereafter. The extent of post-MI AdipoR1 phosphorylation positively correlated with the expression level of GPCR kinease-2 (GRK2). Cardiac-specific GRK2 knockdown virtually abolished post-MI AdipoR1 phosphorylation, whereas virus-mediated GRK2 overexpression significantly phosphorylated AdipoR1 and blocked APN metabolic-regulatory/anti-inflammatory signaling. Ex vivo experiments demonstrated AMPK activation and anti-TNFα effect of APN were significantly inhibited in cardiomyocytes isolated from non-ischemic cardiac regions 7 days post-MI. In vivo experiments demonstrated that acute APN administration induced cardiac GLUT4 translocation, and eNOS phosphorylation was blunted 7 days post-MI. Continuous APN administration beginning 7 days post-MI failed to protect against adverse cardiac remodeling and HF progression in WT mice, which was restored by cardiac-specific GRK2 knockdown. These results demonstrate for the first time that the cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2-mediated AdipoR1 phosphorylative desensitization during post-MI HF development, suggesting that inhibiting GRK2-mediated AdipoR1 phosphorylation may be a novel therapeutic target, restoring APN signaling and mitigating post-MI remodeling and HF.
Trip Route Planning for Bicycle-Sharing Systems

Bicycle-sharing systems (BSSs) offering shared bike usages to the public are becoming more and more popular nowadays. In bicycle-sharing systems, people can borrow and return bikes at any bike stations in the service region, but the free-ride time is usually limited. Therefore, for long-distance bike trips, individuals need to pre-schedule the bike trip route in advance and change the bike within the free-ride time so no over-time fees will be charged. In this paper, we will study the trip route planning problem for individuals when using the bicycle-sharing systems. Given the trip origin and destination, we aim at identifying the optimal trip route from the origin to the destination through the bike stations. To address the problem, we conduct a thorough analysis about an existing BSS, Divvy, launched in Chicago. Based on the analysis results, a novel bike route planning framework "BSSs based Trip rOute Planning" (STOP) is proposed in this paper, which can identify the optimal trip route by mapping the problem into a minimum-cost network flow problem. Extensive experiments conducted on real-world bicycle-sharing system datasets demonstrate the effectiveness of STOP.
Atomic Resolution Study of the Interfacial Bonding at Si 3 N 4 /CeO 2-δ Grain Boundaries

This paper reviews minimal repair models where information is available about the condition of the system analyzed. In the traditional minimal repair model, the age of the system is not changed by the repair. When additional information is available, the concept of a minimal repair has to be generalized, and in this paper, we look closer at some of the suggestions that have been put forward. A point process framework can be used to describe the generalized minimal repair concepts. Several examples demonstrate the applications of the models for optimal replacement problems.
BOUNDARIES: BOURGEOIS BELGIUM AND “TENTACULAR” MODERNISM

The sweep, originality, and plenitude of Jerrold Seigel's work have transformed our field. His prolific and creative scholarship encompasses the history of ideas, the history of cultural forms, and the history of intellectuals, areas typically examined separately as coherent and discrete sections of intellectual history. I have been reading Seigel for many years now, assigned his texts in my classes, and watched students come alive as they encounter his Marx, his Bohemia, his Baudelaire, his Foucault, his Simmel. My own research and writing have been deeply influenced by key ideas generated in Seigel's body of work, testing and contesting, for example, his project of historicizing subjectivity and identity in modern Europe.
Sleep in ambulatory patients with stable cirrhosis of the liver.

Abstract Background Questionnaires indicate that patients with liver disease have disturbed sleep. However, polysomnographic studies to quantify sleep architecture and sleep disorders in this population are lacking. The current study compared polysomnographic findings of two groups of patients with clinically stable but severe end-stage pathology of the liver and heart. Methods This was a prospective study of consecutive patients with end-stage liver disease or severe heart failure (HF). Measurements and results Patients underwent full-night, attended polysomnography along with a number of laboratory tests. Polysomnograms were scored blindly. Compared to HF patients, patients with cirrhosis suffered from severe periodic limb movements during sleep (PLMS), with an index of 39/hour associated with excessive arousals. In patients with cirrhosis, serum iron and ferritin levels were either at the upper normal limit or elevated. There were significant correlations between severity of PLMS versus blood levels of bilirubin (r = 0.73, p = 0.004) and ammonia (r = 0.74, p = 0.017). Conclusions This was the first polysomnographic study of patients with stable cirrhosis demonstrating severely disturbed sleep infrastructure and presence of excessive PLMS with arousals. The pathobiochemical mechanisms of these findings remain to be established. Independent of the mechanisms, these polysomnographic findings confirmed the subjective reports of poor sleep by patients with cirrhosis. Further, a subset of patients with cirrhosis acquired a syndrome similar to idiopathic Parkinson's disease, which per se was frequently associated with PLMS; the current results were consistent with this notion. Future studies are needed to determine if PLMS of cirrhosis is an early indication of incident Parkinsonian syndrome.
Treatment-associated TP53 DNA-binding domain missense mutations in the pathogenesis of secondary gliosarcoma.

// Margaret Pain 1, * , Huaien Wang 1, * , Eunjee Lee 2 , Maya Strahl 2 , Wissam Hamou 2 , Robert Sebra 2 , Jun Zhu 2 and Raymund L. Yong 1 1 Departments of Neurosurgery and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA 2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA * These authors have contributed equally to this work Correspondence to: Raymund L. Yong, email: raymund.yong@mountsinai.org Keywords: glioblastoma; gliosarcoma; TP53 mutation; temozolomide; mutagenesis Received: October 11, 2017 Accepted: December 11, 2017 Published: December 20, 2017 ABSTRACT Background: Gliosarcoma is a rare variant of glioblastoma (GBM) that exhibits frequent mutations in TP53 and can develop in a secondary fashion after chemoradiation of a primary GBM. Whether temozolomide (TMZ)-induced mutagenesis of the TP53 DNA-binding domain (DBD) can drive the pathogenesis of gliosarcoma is unclear. Methods: We identified a case of a primary GBM that rapidly progressed into secondary gliosarcoma shortly after chemoradiation was initiated. Bulk tumor was collected and gliomasphere cultures derived from both the pre- and post-treatment tumors. We performed targeted DNA sequencing and transcriptome analyses of the specimens to understand their phylogenetic relationship and identify differentially expressed gene pathways. Gliomaspheres from the primary GBM were treated with TMZ and then analyzed to compare patterns of mutagenesis in vivo and ex vivo . Results: The pre- and post-treatment tumors shared EGFR , CDKN2A , and PTEN mutations, but only the secondary gliosarcoma exhibited TP53 DBD missense mutations. Two mutations, R110C, and R175H, were identified, each in distinct clones. Both were base transitions characteristic of TMZ mutagenesis. Gene expression analysis identified increased JAK-STAT signaling in the gliosarcoma, together with reduced expression of microRNAs known to regulate epithelial-mesenchymal transition. Ex vivo treatment of the GBM spheres with TMZ generated numerous variants in cancer driver genes, including TP53 and CDH1 , which were mutated in the post-treatment tumor. Conclusions: TMZ-induced TP53 gain-of-function mutations can have a driving role in secondary gliosarcoma pathogenesis. Analysis of variants identified in ex vivo TMZ-treated gliomaspheres may have utility in predicting GBM evolutionary trajectories in vivo during standard chemoradiation.
Precise half-life measurement of the superallowed emitter 30 S

We have measured the half-life of $^{30}\mathrm{S}$, the parent of a superallowed ${0}^{+}\ensuremath{\rightarrow}{0}^{+}\phantom{\rule{0.28em}{0ex}}\ensuremath{\beta}$ transition, to a high precision using very pure sources and a $4\ensuremath{\pi}$ proportional gas counter to detect the decay positrons. Our result for the half-life is 1.179 92(34) s. As a by-product of this measurement, we determine the half-life of its daughter, $^{30}\mathrm{P}$, to be 2.501(2) min.
GaN-based vertical-cavity surface-emitting lasers with tunnel junction contacts grown by metal-organic chemical vapor deposition

We report the first demonstration of III–nitride vertical-cavity surface-emitting lasers (VCSELs) with tunnel junction (TJ) intracavity contacts grown completely by metal–organic chemical vapor deposition (MOCVD). For the TJs, n++-GaN was grown on in-situ activated p++-GaN after buffered HF surface treatment. The electrical properties and epitaxial morphologies of the TJs were first investigated on TJ LED test samples. A VCSEL with a TJ intracavity contact showed a lasing wavelength of 408 nm, a threshold current of ~15 mA (10 kA/cm2), a threshold voltage of 7.8 V, a maximum output power of 319 µW, and a differential efficiency of 0.28%.
Hormones in Antral Fluid and the Regulation of Ovarian Function

At a symposium on ovulation held under the auspices of the Society for the Study of Fertility in July 1976, Hans Lindner presented a paper entitled, “Intraovarian Factors in Ovulation: Determinants of Follicular Response to Gonadotropins.” In addition to a critical scholarly review, the paper contained a summary of contributions made by his associates in the Department of Hormone Research at the Weizmann Institute of Science. The paper reflected not only the breadth of Hans’, scholarship but the diversity of skills of the group of younger scientists whom he had attracted and motivated to work so productively on various aspects of hormonal regulation of ovulation and atresia in mammalian ovarian follicles.
Fundamentals of High Resolution Transmission Electron Microscopy

The recent emergence of high-resolution electron microscopes (HREMs) capable of resolving sub-2-Angstrom detail on a routine basis has led to an enormous increase in the range of materials which can be usefully studied. Not only is it possible to resolve individual atomic columns in low index zones of most common metals but observations of semiconductors, for example, are no longer restricted to the traditional [110] zone, thereby making it feasible at last to obtain two-dimensional information about surfaces, interfaces and other planar defects. There is a worldwide upsurge of interest in the capabilities of these machines and the so-called intermediate voltage (300–400kV) HREMs are selling rapidly despite their considerable expense. Novel applications in such diverse fields as solid state chemistry, mineralogy and materials science are appearing almost daily.
Cell–Extracellular Matrix Interactions in Repair and Regeneration

Abstract Cell–matrix interactions that occur during wound healing are extraordinarily complex, varying among cell types and changing over time owing to altered expression of matrix receptors and matrix molecules over time as healing proceeds. In this chapter, we summarize critical cell–matrix interactions associated with wound healing, discussing the matrix receptors involved in these interactions and major signaling pathways regulated by these interactions. We then compare cell–matrix interactions in normal adult scarring wound healing with fetal scarless healing. Finally, we discuss implications of cell–matrix interactions for regenerative medicine, focusing on the ways this information is used to promote regenerative wound healing.
Evaluation of Acellular Bilayer Silk Fibroin Grafts for Onlay Tracheoplasty in a Rat Defect Model.

ObjectiveTo assess the efficacy of acellular bilayer silk fibroin (BLSF) grafts to repair full-thickness tracheal defects and to compare the performance with conventional porcine small intestinal s...
Eco-utopia or eco-catastrophe? Imagining California as an ecological utopia

In this article, I explore four California-based eco-utopias: The Earth Abides (George Stewart, 1949), Ecotopia (Ernest Callenbach, 1975), Pacific Edge (Kim Stanley Robinson, 1990), and Snow Crash (Neal Stephenson, 1992). All four novels were written during, and deeply informed by, the Cold War (Although published in 1992, Snow Crash was clearly written toward the end of the Cold War and in the shadow of Soviet implosion), against a backdrop of imminent nuclear holocaust and a doubtful future. Since then, climate change has replaced the nuclear threat as a looming existential dilemma, on which a good deal of writing about the future is focused. Almost 70 years after the appearance of The Earth Abides, and 40 years after the publication of Ecotopia, eco-utopian imaginaries now seem both poignant yet more necessary than ever, given the tension between the anti-environmental proclivities of the Trump Administration, on the one hand, and the tendency of climate change to suck all of the air out of the room, on the other. And with drought, fire, flood, wind and climate change so much in the news, it is increasingly difficult to imagine eco-utopias of any sort; certainly they are not part of the contemporary zeitgeist—except in the minds of architects, bees and futurists, perhaps. But does this mean there is no point in thinking about them, or seeking insights that might make our future more sustainable? This article represents an attempt to revive eco-utopian visions and learn from them.
Increasing Numbers of Shoulder Corticosteroid Injections Within a Year Preoperatively May Be Associated With a Higher Rate of Subsequent Revision Rotator Cuff Surgery

Purpose To identify any dose-dependent association between the use of subacromial corticosteroid injections within a year before rotator cuff repair (RCR) and subsequent need for revision rotator cuff surgery. Methods Two large administrative databases were queried for patients undergoing arthroscopic RCR. A minimum of 1 year of preoperative database exposure and 2 years of postoperative database follow-up were required for inclusion. Patients were stratified into groups that received 0 (control), 1, 2, or 3 or more ipsilateral corticosteroid shoulder injections within the year prior to RCR. The outcome of interest was ipsilateral revision arthroscopic or open RCR or arthroscopic debridement for a diagnosis of rotator cuff tear within 2 years of the index surgery. Revision rates were compared between groups using a multivariate logistic regression analysis controlling for demographic and comorbidity confounders. Results A total of 110,567 patients from the Medicare database and 12,892 patients from the private insurance database were included. There was no association between a single injection within the year prior to RCR and revision surgery in either cohort. The use of 2 or more injections was associated with a significant increase in the risk of requiring revision surgery in both the Medicare (odds ratio [OR], 2.76-3.26; P Conclusions A single shoulder injection within a year prior to arthroscopic RCR was not associated with any increased risk of revision surgery; however, the administration of 2 or more injections was associated with a substantially increased risk of subsequent revision rotator cuff surgery (OR, 2.53-3.26). Although causality cannot be established on the basis of this database review, caution is recommended when considering more than 1 shoulder corticosteroid injection in patients with potentially repairable rotator cuff tears. Level of Evidence Level III, retrospective cohort study.
Indications for platelet transfusion in patients with thrombocytopenia.

Platelet transfusion has become a progressively more common and important therapeutic procedure in managing thrombocytopenic patients. Nevertheless, this therapy continues to evolve. Most platelet products are transfused into non-bleeding thrombocytopenic patients. The transfusion “trigger” or threshold for transfusion of these patients is now generally accepted to be 10,000/μL based on the results of a number of studies. However, it is important to emphasise that this “trigger” value generally applies to uncomplicated patients or those who are not febrile, have no infection, or are not being treated with a drug known to damage platelets. Importantly, even with a platelet “trigger” level established at 10,000/μL, platelet transfusion therapy must be individualised to the patient and the clinical situation. As noted above, fever and infection may be correlated with a greater risk of bleeding, but in addition, minor episodes of bleeding may also increase the subsequent risk of clinically significant bleeding; even haemoglobin concentration may play a role in determining bleeding risk. Finally, although prophylactic platelet transfusion is commonly used in the care of thrombocytopenic patients, therapeutic platelet transfusion may represent a reasonable option in managing the bleeding risk of some thrombocytopenic patients. Certainly in the studies by Wandt et al.26,27 and Stanworth et al.28 the use of therapeutic platelet transfusion resulted in an increased bleeding risk. However, in certain populations of patients, the bleeding seen in the therapeutic transfusion programme is generally mild (WHO bleeding category 2 or less). Nevertheless, the studies have repeatedly highlighted the importance of tailoring platelet transfusions to the clinical needs of each patient. While clinical guidelines for platelet transfusion therapy are reasonably well established, a review of the literature clearly indicates that platelet transfusions must be guided by the population of patients under consideration, the clinical conditions of the patients, and perhaps even the resources of the transfusing facility and its ability to respond rapidly to patients’ transfusion needs.
Granulomatous Appendicitis in the Pediatric Population

BackgroundThe clinical significance of a diagnosis of granulomatous appendicitis (GA) is not well established in the pediatric population.MethodsRetrospective review of the etiology and histopathol...
Reality-based algebras with a two-dimensional representation

Abstract It is shown that a two-dimensional irreducible representation of a reality-based algebra with a standard degree map is determined by the other irreducible representations of the algebra and the action of its given anti-automorphism on the distinguished basis. This generalizes known results for algebras of dimensions 5, 6, 7, and 8. Explicit conclusions equivalent to those for dimensions 5 and 6 are recovered here by specializing the procedure of proof of the main theorem.
Cofilin-induced structural changes in actin filaments stay local

Actin is a major cytoskeletal protein that plays crucial roles in a number of biological events involving force generation and shape changes. Actin monomers are polymerized into actin filaments, which serve as a core of the actin cytoskeleton together with many associated proteins. Although purified actin can be spontaneously polymerized under physiological conditions in test tubes, assembly and disassembly of actin are spatially and temporally controlled within cells. For example, concerted directional assembly of actin filaments can push membranes and organelles, whereas disassembly of actin filaments contributes to cytoskeletal remodeling and recycling of disassembled actin monomers for a new round of actin polymerization. Therefore, coordinated regulation of actin assembly and disassembly is often required to achieve normal cellular behaviors. Particularly, actin filament disassembly is a challenging task in the cytoplasm. Once actin is polymerized, slow spontaneous dissociation of actin subunits from filaments limits the rate of overall actin turnover. In addition, the cytoplasm generally contains high concentrations of actin monomers that can increase net actin assembly. One of the factors that promote actin filament disassembly is the actin depolymerizing factor (ADF)/cofilin family of proteins, which is expressed in various cell types across eukaryotes and involved in cellular processes that require dynamic rearrangement of the actin cytoskeleton, such as cell migration, cytokinesis, and morphogenesis (1, 2). ADF/cofilin (hereafter referred to as cofilin) promotes actin depolymerization and enhances actin turnover (3⇓–5). Cofilin binds to the side of actin filaments at a 1:1 (cofilin:actin subunit) molar ratio in a cooperative manner such that clusters of cofilin-decorated regions are generated. Then, filament severing occurs frequently at or near boundaries between cofilin-decorated and bare regions on the filament (6, 7). Therefore, cofilin severs actin filaments most efficiently when cofilin binds to filaments at low densities (8). However, the mechanism of … [↵][1]1Email: sono{at}emory.edu. [1]: #xref-corresp-1-1
An Overview of Timeline of Interventions in the Continuum of Cleft Lip and Palate Care

This article provides an overview of timeline of interventions and the critical role different providers have in the continuum of cleft lip and palate care. The earliest intervention is the presurgical infant orthopedic treatment, which is initiated in the first few weeks of life. This is followed by several interventions done in a phased manner. These include: lip repair, palate repair, velopharyngeal surgery, maxillary expansion, maxillary bone grafting, limited phase of orthodontic treatment, comprehensive phase of orthodontic treatment (with/without orthognathic surgery), and restorative dentistry.
Outcomes of Surgery for Coronal Instability

Patients presenting with coronal plane instability in association with varus or valgus deformity are a challenging population to treat. In most cases, isolated ligament repair or reconstruction is insufficient as soft tissues stretch with time. Therefore, osteotomy is typically required. There are data to support both a staged approach consisting of osteotomy followed by delayed ligamentous reconstruction as well as single-stage procedure. If a staged approach is chosen, subsequent ligament reconstruction may or may not be necessary depending on the patient’s symptoms following osteotomy. Patients with higher-energy injuries and those with multiple ligament injuries are more likely to require ligament reconstruction. Medial opening-wedge HTO is recommended for larger (>8 mm) corrections and corrections associated with posterior or posterolateral laxity and varus thrust.
Encouraging American Historically Black Colleges and Universities to Teach African Languages and Cultures

This chapter purports that Historically Black Colleges and Universities (HBCUs) have a vital role to play in a collective endeavor to reconnect America to Africa—the second-largest continent by area and population in the world (Worldatlas.com). The existing literature suggests that quite a few American HBCUs are already moving in that direction, but we need to do more, especially by engaging in sustainable cooperation with African nations through the learning and teaching of their languages and cultures. Additionally, this chapter makes suggestions and proposes a rationale based on historical facts in a worldwide geopolitical context, which, undeniably, repositions Africa, again, under the strategic radar of Europe and America, both of which are now in competition with Asia (mostly China and India).
3141 – LEUKEMIA-ASSOCIATED MUTATIONS IN DNMT3A MEDIATE SENSITIVITY TO REPLICATION STRESS INDUCED BY NUCLEOSIDE ANALOGS

Acute myeloid leukemia is characterized by recurrent somatic mutations in epigenetic modifier genes like DNA methyltransferase 3A (DNMT3A). Mutations in DNMT3A are commonly seen in older patients who are unfit for intensive chemotherapy and thus associated with unfavorable outcomes. Recent clinical trials have shown low-intensity regimens of nucleoside analogs (cytarabine and cladribine), to be effective in elderly AML patients, particularly those with DNMT3A mutations. Additionally, previous gene expression studies in DNMT3A cells uncovered signatures suggestive of replication stress and a resultant G2/M checkpoint adaptation. We hypothesized that this can be harnessed as a therapeutic vulnerability. We confirmed differential sensitivity to cytarabine in various model systems, with and without mutant DNMT3A, both in vitro and in vivo. We also observed that the cells with DNMT3A mutations accumulated more DNA damage, with the persistence of the intra S-phase checkpoint activation and elevated levels of activated p53. While DNMT3A-mutant cells remained proficient in engaging DNA double-strand break repair mechanisms, we observed impaired chromatin recruitment of proteins involved in nucleotide excision repair, after cytarabine treatment. Consistently, the DNMT3A-mutant cells displayed a higher rate of replication fork collapse after cytarabine wash-out. Despite persistent unrepaired DNA damage, the DNMT3A mutant cells were able to progress through mitosis, eventually leading to mitotic catastrophe. Consistent with these findings, transcriptomic analysis identified dysregulation of pathways related to cell cycle, DNA damage, and repair. Our studies aim to gain a better understanding of the role played by DNMT3A in modulating sensitivity to clinically relevant replication stalling drugs and thus making it a suitable approach to treat this poor prognosis subtype of AML.
Critical thinking in social contexts: A trajectory analysis of states’ K-5 social studies content standards

Abstract This study investigates the trajectories of intended critical thinking in a social context present in the K-5 social studies content standards of six states. It considers how the nature of context-based critical thinking present in the standards’ benchmarks is represented. The findings reveal a complex dynamic in K-5 social studies content standards, which fundamentally expect young learners to advance their critical thinking in social context. But the content standards promote inconsistent critical thinking in a social context across grade levels. The sophistication of context-based critical thinking decreases within the standards as students advance through the grades. As such, implications for elementary social studies education in terms of how standards reflect official stances from the state on the nature of social studies in elementary education are discussed.
MicroRNA-494 Regulates Endoplasmic Reticulum Stress in Endothelial Cells

Defects in stress responses are important contributors in many chronic conditions including cancer, cardiovascular disease, diabetes, and obesity-driven pathologies like non-alcoholic steatohepatitis (NASH). Specifically, endoplasmic reticulum (ER) stress is linked with these pathologies and control of ER stress can ameliorate tissue damage. MicroRNAs have a critical role in regulating diverse stress responses including ER stress. Here, we show that miR-494 plays a functional role during ER stress. Pharmacological ER stress inducers (tunicamycin (TCN) and thapsigargin) and hyperglycemia robustly increase the expression of miR-494 in vitro. ATF6 impacts the primary miR-494 levels whereas all three ER stress pathways are necessary for the increase in mature miR-494. Surprisingly, miR-494 pretreatment dampens the induction and magnitude of ER stress in response to TCN in endothelial cells and increases cell viability. Conversely, inhibition of miR-494 increases ER stress de novo and amplifies the effects of ER stress inducers. Using Mass Spectrometry (TMT-MS) we identified 23 proteins that are downregulated by both TCN and miR-494 in cultured human umbilical vein endothelial cells. Among these, we found 6 transcripts which harbor a putative miR-494 binding site. We validated the anti-apoptotic gene BIRC5 (survivin) and GINS4 as targets of miR-494 during ER stress. In summary, our data indicates that ER stress driven miR-494 may act in a feedback inhibitory loop to dampen downstream ER stress signaling.
Barking Dogs: Code Enforcement is All Bark and No Bite (Unless the Inspectors Have Assault Rifles)

This article focuses on several potential legal solutions to the problems created by blighted properties as a result of the foreclosure crisis. Specifically, this article discusses the current code enforcement models throughout the country and analyzes legal strategies to make them more effective. Also, this article discusses the handful of code enforcement departments that have gone to the opposite extreme and abused their power to maintain the safety and welfare of the community. Finally, the article addresses the success of several cities that are faced with severe blight, but turned to creative legal and administrative solutions to rehabilitate their neighborhoods. These solutions, I contend, should be extensively replicated throughout the country to achieve success in the fight against blight.
Pediatric moyamoya MRI score: an imaging-based scale to predict outcomes in surgically treated pediatric patients with moyamoya.

OBJECTIVE Moyamoya is a progressive arteriopathy that predisposes patients to stroke due to stenosis of the intracranial internal carotid arteries and their proximal branches. Despite the morbidity caused by this condition, the ability to accurately predict prognosis for individual patients remains challenging. The goal of this study was to develop a systematic scoring method based on parenchymal findings on preoperative brain MRI to predict long-term outcomes for surgically treated pediatric patients with moyamoya. METHODS A retrospective surgical cohort of pediatric patients (≤ 18 years of age at the time of the initial surgery) with moyamoya from a single center were studied. Radiological variables with existing correlations between outcomes in moyamoya or other vascular diseases were chosen to score preoperative MRI based on easily defined parenchymal findings that could be rapidly assessed and used to make a numeric score. Calculated scores were correlated with clinical outcome measures using the Pearson correlation coefficient and area under the receiver operating characteristic curve (AUROC). RESULTS A total of 35 children with moyamoya disease or moyamoya syndrome were included in the study, with a median follow-up time of 2.6 years from the time of surgery. The pediatric moyamoya MRI score (PMMS) consists of ischemic changes (0-2; 0 = none, 1 = focal, 2 = diffuse), encephalomalacia (0-2; 0 = none, 1 = focal, 2 = diffuse), and hemorrhage (0-1; 0 = not present, 1 = present). PMMSs were highly correlated with pediatric modified Rankin Scale scores at the last follow-up (r = 0.7, 95% CI 0.44-0.84; p < 0.001) as a six-point scale, and when dichotomized (AUROC = 0.85). CONCLUSIONS The PMMS was found to be a simple tool based on preoperative MRI data that could be quickly and easily calculated and correlated with disability. This scoring method may aid future development of predictive models of outcomes for children with moyamoya disease and moyamoya syndrome.
PTH 1-34 Replacement Therapy Has Minimal Effect on Quality of Life in Patients With Hypoparathyroidism.

In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and "brain fog." Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia; however, the effects of PTH treatment on QOL are unclear. Thirty-one patients with hypoparathyroidism were treated in an open-label study with full replacement subcutaneous PTH 1-34 twice daily for up to 5.3 years, with individualized fine-dosing titration. Prior to initiation of PTH 1-34, conventional therapy was optimized. The 36-Item Short Form (SF-36) Health Survey, Fatigue Symptom Inventory (FSI), and 6-minute walk test (6MWT) were assessed at PTH start (baseline), every 6 months on PTH, and after PTH discontinuation. The SF-36 assesses physical function (PF), physical role limitations (RP), bodily pain (BP), general health (GH), vitality (VT), emotional role limitations (RE), social function (SF), and mental health (MH). Compared to population norms, patients at baseline had lower scores in RP, GH, VT, and MH (p < 0.05), consistent with impaired QOL. With PTH therapy, only GH at 6 months and VT at 12 months improved (p < 0.05). At the last treatment time point, RP, VT, and SF improved compared to baseline (p < 0.05). However, follow-up scores were unchanged from baseline or last PTH treatment, except for SF, which had decreased at follow-up compared to on-PTH (p < 0.05). On the FSI, there were no changes in fatigue frequency; perceived interference was improved at 12 and 18 months and composite severity was improved only at 60 months (p < 0.05). The 6MWT measures did not change. In conclusion, hypoparathyroidism is associated with decreased QOL. Despite the bias in open-label studies to predict improvements in QOL, PTH therapy had limited and non-sustained effects on QOL, inconclusive changes in fatigue experience, and no change in the 6MWT. Although PTH 1-34 can adequately manage the hypocalcemia in hypoparathyroidism, its effects on QOL appear to be minimal. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.
GENE SEQUENCE DIVERSITY AND THE PHYLOGENETIC POSITION OF ALGAE ASSIGNED TO THE GENERA PHAEOPHILA AND OCHLOCHAETE (ULVOPHYCEAE, CHLOROPHYTA)1

The phylogenetic position of microfilamentous marine green algae assigned to the species Phaeophila dendroides, Entocladia tenuis (Phaeophila tenuis, and Ochlochaete hystrix was examined through phylogenetic analyses of nuclear-encoded small subunit rDNA and chloroplast-encoded tufA gene sequences. These analyses placed the P. dendroides strains within the Ulvophyceae, at the base of a clade that contains representatives of the families Ulvaceae, Ulvellaceae, and the species Bolbocoleon piliferum, supporting an earlier hypothesis that P. dendroides constitutes a distinct lineage. Substantial divergence in both nuclear and plastid DNA sequences exists among strains of P. dendroides from different geographic localities, but these isolated strains are morphologically indistinguishable. The lineage may have an accelerated rate of gene sequence evolution relative to other microfilamentous marine green algae. Entocladia tenuis and O. hystrix are placed neither in the P. dendroides clade nor in the Ulvellaceae as previous taxonomic schemes predicted but instead form a new clade or clades at the base of the Ulvaceae. Ruthnielsenia gen. nov. is proposed to accommodate Kylin's species, which cannot be placed in Entocladia (=Acrochaete), Phaeophila, or Ochlochaete. Ruthnielsenia tenuis (Kylin) comb. nov., previously known only from Atlantic coasts, is reported for the first time from the Pacific coast of North America (San Juan Island, WA, USA). Isolates of R. tenuis from the Atlantic and Pacific coasts of North America have identical small subunit rDNA and tufA gene sequences.
Heterosexism and Homophobia

Acceptance of homosexuality is increasing in Western cultures, but homophobic negative, fearful, or hateful attitudes and behavior toward gays, lesbians, and bisexuals are still pervasive in those same cultures. Social science studies emphasize that homophobia is deeply rooted in cultural beliefs about gender and supported by heterosexist assumptions that only heterosexual relationships are natural and normal. Homophobia is institutionalized through the actions of law enforcement, the judiciary, politicians, and religious leaders, as well as through public support for continued homophobic discrimination. Challenges to homophobic social practices are rising, but action to insure the rights of all sexual minorities remains essential.
Toward the Dominance of Vision

Sensing the Past . Seeing, Hearing, Smelling, Tasting, and Touching in History. By Mark M. Smith . University of California Press, Berkeley, 2008. 190 pp. $55. ISBN 9780520254954. Paper, $19.95. ISBN 9780520254961. This short historical survey demonstrates how sensory perception is a cultural as well as physiological act.
Design and Development of a SIP-based Video Conferencing Application

Media communication using SIP is providing us with capabilities to architect applications over ubiquitous platforms including the Internet. Although there are certain attempts to make media-enabled applications, there exists a need to deploy security and directory features that constitute middleware services. The software application, described in the paper, is part of a research initiative in Internet2 community to deploy middleware services on video conferencing application. The paper describes the architecture of a Java-based SIP Client and the results of interoperability tests between four SIP user agents. Efforts are being made to enable the application with secured middleware features.
Levels of Generality in the Definition of Rights

This article focuses on one important aspect of the quest for constitutional meaning: how to determine whether a particular liberty - whether or not expressly enumerated in the Bill of Rights - is a "fundamental" right. Whether under the somewhat tarnished banner of substantive due process or under a different rubric, the designation of a right as fundamental requires that the state offer a compelling justification for limitations of that right. In addition, under the Equal Protection Clause of the Fourteenth Amendment, state-sanctioned inequalities that bear upon the exercise of a fundamental right will be upheld only if they serve a compelling governmental interest.' Because the "strict" scrutiny which applies to laws that affect fundamental rights in either of these two ways is usually "fatal," whether to designate a right as fundamental poses a central substantive question in modern constitutional law.
Analysis of Neural Cell Function in Gene Knockout Mice: Behavior

A powerful tool to investigative gene function is the ability to create mice with targeted gene mutations. Analysis of the resulting phenotype is sometimes difficult, however, because individual genes have more than one function, and observed effects on complex behaviors are often a result of abnormalities of any of a number of individual processes. One way to address this issue is by examining mice in a battery of behavioral tests to assess the specificity of any observed differences among genotypes. This chapter describes a test battery used to examine metabolic and behavioral phenotypes in mice with mutations in specific glycan-binding proteins and glycosyltransferases genes. Because the potential consequences of these genetic deletions are varied, a large number of assays across a variety of domains was included in the battery. The power and usefulness of this approach is in discovering areas for more detailed investigation.
Berber Culture on the World Stage: From Village to Video

Berber Culture on the World Stage: From Village to Video. Jane E. Goodman. Bloomington: Indiana University Press, 2005. 239 pp.
Disassembly of preformed amyloid beta fibrils by small organofluorine molecules.

A potential therapeutic approach for Alzheimer’s disease is to reduce the amount of toxic amyloid-beta oligomers and fibrillar amyloid plaques. In order to contribute to this approach the ability of small organofluorine compounds that were previously reported as successful inhibitors of fibrillogenesis to destabilize preformed fibrils of the amyloid-beta peptide was studied. These organofluorine molecules including chiral compounds were tested in vitro using standard methods based on Thioflavin-T (THT) fluorescence spectroscopy, atomic force microscopy (AFM) and Fourier-transform infrared spectroscopy (FTIR). It was observed that 5′-halogen substituted 3,3,3-trifluoromethyl-2-hydroxyl-(indol-3-yl)-propionic acid esters showed significant activity in the disassembly of the preformed fibrils. Since the same compounds were identified as strong fibrillogenesis inhibitors as well, this dual action makes them promising candidates for further drug development.