cssi/SciSciGPT-SciSciNet huggingface dataset:
The Implications of the Sequestosome 1 Mutation P392L in Patients with Paget's Disease in a United States Cohort.

Paget’s disease of bone (PDB) is associated with a germline mutation in Sequestosome1/p62 (SQSTM1) found in ≤16 % of sporadic cases worldwide, and in 19–46 % of those studied with familial PDB. The P392L is the most prevalent mutation identified to date. This mutation by itself does not confer PDB or define the phenotype of PDB in a given person. Environmental determinants remain elusive, although increasing age of the individual, other gene polymorphisms in the context of SQSTM1 mutations, and measles virus have been implicated. Measles exposure has been unexamined in this context. The goal of this study is to compare the background history and phenotype of patients with PDB carrying the SQSTM1 P392L mutation to those patients without. Focusing on age, ancestry, P329L mutation, family history, measles exposure, distribution of PDB, and age of onset, we examined outcomes at 10 years. We postulated that aging may play a role in defining phenotype, and that this may become more visible in a well-characterized cohort. This is an observational study focused on a cohort of patients with PDB drawn from the New England Registry in whom environmental and family history has been catalogued, linked to radiographic data. Of the 217 persons who were enrolled in the Registry, 42 (19 %) responded to a letter inviting them to participate in testing for the presence of the measles antibody, and in genetic testing for the P392L mutation. The mean age of the cohort in 2001 was 70 years (range 55–79); 27 were men (64 %). The measles antibody was found in all cases tested. Nine patients had the P392L mutation (21 %), 2 with familial PDB. In these persons, early diagnosis of disease and spinal stenosis marked the male phenotype only. European ancestry was noted in the minority of those with P392L mutation. Most deaths recorded occurred in the ninth decade of life or later. Spinal stenosis emerges as a prominent phenotype in SQSTM1 P392L-positive men with aging. In these 42 patients with PDB from the New England Registry, most do not carry the SQSTM1 P392L mutation, and many do not have European ancestry. Exposure to measles was confirmed in the majority.
Which Hedge Fund Managers Deliver in a Crisis? Assessing Performance When Returns are Skewed

: 92 percent of hedge funds in the TASS database exhibit significantly skewed returns. The alphas the managers of these funds earn are difficult to estimate accurately with OLS, especially in times of crisis. An alternative, the Residual Augmented Least Squares (RALS) estimator, is robust with respect to skewness. We demonstrate that the OLS performance assessment error relative to RALS depends systematically upon the sign of skewness in a fund’s returns and is economically significant. Furthermore, portfolios formed on RALS alphas persist more than those formed on OLS alphas and the performance persistence is concentrated in crisis periods.
A Two-Receptor Model for the Mechanism of Action of Prostaglandins in the Renal Collecting Tubule

Studies on the mechanism of action of steroid hormones have led to the concept that different steroids act through different receptors present in different target cells to elicit a common biochemical response, namely, regulation of transcription. One might presume that different prostaglandins also operate through different receptors to cause some common response. However, this response is still not defined. In this chapter we summarize our recent studies on the metabolism and function of prostaglandins by the renal collecting tubule (Garcia-Perez and Smith, 1983, 1984). Our major focus is to describe the development of a two-receptor model for the actions of prostaglandins in these cells.
Characterization of Turbine Vane Roughness Variations Using Self-Organizing Maps

Turbine vane roughness and blade roughness produce adverse effects including increased aerodynamic losses and increased heat transfer into the turbine components. Consequently, measuring levels of roughness and characterizing the roughness development as a function of operating time and conditions are critical to developing proper engine maintenance and replacement schedules. Because of real blade and vane three-dimensional geometries, historical roughness studies have employed two-dimensional traverses of surface elevation measurements performed at predetermined blade locations using stylus-based profilometry. While laser-based and white-light surface metrology has advanced considerably in the past decades, capturing the mean component geometry at the resolution required to characterize the roughness has proven to be difficult given the high surface curvature and typical surface reflectivities. Even on two-dimensional cascade vanes, local regions of high surface curvature result in situations where characterizing the nature of surface roughness is challenging. In this study, a single-vane cascade flow tunnel based on the VKI transonic vane shape was constructed to create deposition-like roughness. The roughness was generated using textured paint sprayed into the inlet plenum of the tunnel. The vane was then scanned using a NextEngine 3D Scanner HD laser scanning system. A combined self-organizing map and multi-dimensional statistics approach, which was developed by McClain and Kreeger (2013) for characterizing airframe ice roughness, is employed to represent the mean blade profile, to unwrap the surface topography, and to evaluate the roughness characteristics as a function of surface distance from the leading edge. The approach enables new insights into the variations of roughness parameters along the surface of engine components and test models. Finally, difficulties in extending the approach to real engine components with twist and other three-dimensional features are discussed.Copyright © 2015 by ASME
The Synthesis and Spectral Characteristics of Some Nitrosoanilines and Their Possible Mode of Action as Curing Agents for Various Types of Rubbers

Abstract Spectral characteristics of several known and new N-substituted-p-nitrosoanilines, e.g., Nitrol, of established utility in promoting the bonding between rubber and carbon black are described. A possible mode of action in their enhancement of the bonding process involving a classical free radical process is discussed.
Power spectrum, structure function, vertical wind shear, and turbulence in troposphere and stratosphere

It has been shown that a power law exists between vertical velocity differences\(\overline {\Delta v} \) measured over a layer thickness Δh, of the form\(\overline {\Delta v} = a_0 (\Delta h)a_1 \). This expression may be related directly to a structure function and to a power-spectrum function. Statistical derivations of the exponenta1 from detailedvertical wind profile measurements show resemblance with the spectral functions obtained for conditions of clear air turbulence.
“They will know our hearts”: Practicing the Art of Dissimulation on the Islamic Periphery

From the early sixteenth century, religious and legal authorities provided Spanish crypto-Muslims with guidelines for practicing taqiyya, the Islamic art of dissimulation. As theory collided with local realities, however, local actors innovated practice in the face of the continued divergence between an internal desire to practice Islam and external pressures to conform to Christianity. This article explores these tensions by analyzing the posthumous endowments of two wealthy Morisco brothers from the Castilian town of Deza who succeeded in convincing both Christian neighbors and the Inquisition of their sincere conversion to Christianity. The town’s Morisco community, however, viewed the brothers’ bequests as secret acts of Islamic charity. Such perceived efforts to enact taqiyya not only eroded Christian confidence that true converts could be discerned from false ones but also threatened to destabilize the Moriscos’ own religious identity and their relationship to both Christianity and Islam.
A high efficiency 20kWe microcogeneration unit based on a turbocharged automotive gas engine

Abstract The paper deals with the design and the overall performance of 20 kWe cogeneration plant, suitable for local energy conversion and based on a wide-spread automotive internal combustion engine. The manuscript starts by defining the state of art of commercial cogenerators of the same power, underlining that a higher electric efficiency, which leads to a lower heat to electricity ratio, can elevate the annual service factor and the economic effectiveness while reducing CO2 emission. Then is reported the concept which leaded to the specific choice of a small displacement, high boosted engine (in terms of brake mean effective pressure) made to obtain a significant improvement of the engine global efficiency especially at partial load (if compared to most of the best competitors) and consequently a higher electric efficiency. The unit has been derived from a turbocharged Diesel engine, then converted into a spark ignition methane/natural gas system and finally coupled with an asynchronous liquid cooled generator together with high efficiency heat exchangers and some unconventional heat recovery devices in order to maximize thermal efficiency. The whole system, after being placed into a sealed capsule expressly designed to reduce heat losses and noise emission, has been tested as an electricity/heat generation plant to know its running global behavior.
An Experimental Investigation of Lift Enhancement and Roll Control Using Plasma Actuators

This paper describes an experimental investigation into the use of near-trailing-edge mounted plasma actuators for lift enhancement and roll-control. Data are presented showing the effect that the actuators had on lift, pitch, and roll moment coefficients as a function of angle of attack, wind speed and actuator excitation power. The results indicate that the performance of the actuators is influenced by Reynolds number effects. In particular, the lift-enhancement effect of the actuators is shown to have a linear dependence on wind speed/Reynolds number at low wind speeds. The implications of these findings on the utility of plasma actuators as lift and roll-control devices are discussed.
Effect of acidic properties of mesoporous zeolites supporting pt nanoparticles on hydrogenative conversion of methylcyclopentane.

The effect of acidic properties of mesoporous zeolites on the control of product selectivity during the hydrogenative isomerization of methylcyclopentane has been investigated. A series of mesoporous zeolites with controlled acidic properties were prepared by postdealumination process with hydrochloric acid under hydrothermal conditions, and the resultant zeolites used for supporting colloidal Pt nanoparticles (NPs) with a mean size of 2.5 nm (±0.6 nm). As compared to the pure Pt NPs supported on catalytically inert mesoporous silica (MCF-17) as the reference catalyst that can produce isomers most selectively (∼80%), the Pt NPs supported on mesoporous zeolites produced C6-cyclic hydrocarbons (i.e., cyclohexane and benzene) most dominantly. The type and strength of the Bronsted (B) and Lewis (L) acid sites of those zeolites with a controlled Al amount are analyzed by using FT-IR after the adsorption of pyridine and NH3 temperature-programmed desorption measurements, and they are correlated with the selecti...
Recurring large deep earthquakes in Hindu Kush driven by a sinking slab

Hindu Kush subduction zone produces large intermediate-depth earthquakes within a small volume every 10–15 years. Here we study the last three M ≥ 7 events within the cluster and find complex and diverse rupture processes. However, their main subevents appear to recur on the same fault patch, dipping 70° to the south. This recurrence requires an average of 9.6 cm/yr slip rate on the patch, much higher than the ~1 cm/yr surface convergence rate measured geodetically. The high slip rate is likely caused by significant slab internal deformation, such as localized slab stretching/necking. We infer that the Hindu Kush subducted slab below 210 km is sinking through the mantle at a vertical rate of 10 cm/yr.
A Prevalence Analysis that Adjusts for Survival and Tumour Lethality

If animals with or without the tumour of interest die at a common rate, the tumour is typically referred to as non‐lethal and survival‐adjusted prevalence comparisons can be based on mortality and tumour response data alone. If these death rates differ, however, most analyses also require cause‐of‐death data or sacrifice data. This paper describes a regression analysis that adjusts for survival and allows different conditional death rates but does not require any data on cause of death and often is practical with few sacrifices. The interval analysis of Hoel and Walburg and the logistic regression analysis of Dinse and Lagakos, both of which are appropriate for non‐lethal tumours, are special cases of the analysis presented here. The methods proposed provide a framework for incorporating covariates, as well as for estimating the tumour's relative risk, and are illustrated with liver tumour data from the ED01 study.
A Storytelling Robot: Modeling and Evaluation of Human-like Gaze Behavior

Engaging storytelling is a necessary skill for humanoid robots if they are to be used in education and entertainment applications. Storytelling requires that the humanoid robot be aware of its audience and able to direct its gaze in a natural way. In this paper, we explore how human gaze can be modeled and implemented on a humanoid robot to create a natural, human-like behavior for storytelling. Our gaze model integrates data collected from a human storyteller and a discourse structure model developed by Cassell and her colleagues for human-like conversational agents (1994). We used this model to direct the gaze of a humanoid robot, Honda's ASIMO, as he recited a Japanese fairy tale using a pre-recorded human voice. We assessed the efficacy of this gaze algorithm by manipulating the frequency of ASIMO's gaze between two participants and used pre and post questionnaires to assess whether participants evaluated the robot more positively and did better on a recall task when ASIMO looked at them more. We found that participants performed significantly better in recalling ASIMO's story when the robot looked at them more. Our results also showed significant differences in how men and women evaluated ASIMO based on the frequency of gaze they received from the robot. Our study adds to the growing evidence that there are many commonalities between human-human communication and human-robot communication
Unintentional Epinephrine Auto-injector Injuries: A National Poison Center Observational Study.

Background: Epinephrine is the only first-line therapeutic agent used to treat life-threatening anaphylaxis. Epinephrine auto-injectors are commonly carried by patients at risk for anaphylaxis, and reported cases of unintentional auto-injector injury have increased over the last decade. Modifications of existing designs and release of a new style of auto-injector are intended to reduce epinephrine auto-injector misuse. Study Question: The aim of the study was to characterize reported cases of unintentional epinephrine auto-injector exposures from 2013 to 2014 and compare demographics, auto-injector model, and anatomical site of such exposures. Methods: The American Association of Poison Control Center's National Poison Data System was searched from January 1, 2013, to December 31, 2014, for cases of unintentional epinephrine auto-injector exposures. Anatomical site data were obtained from all cases reported to the Virginia Poison Center and participating regional poison center for Auvi-Q cases. Results: A total of 6806 cases of unintentional epinephrine auto-injector exposures were reported to US Poison Centers in 2013 and 2014. Of these cases, 3933 occurred with EpiPen, 2829 with EpiPen Jr, 44 with Auvi-Q, and no case reported of Adrenaclick. The most common site of unintentional injection for traditional epinephrine auto-injectors was the digit or thumb, with 58% of cases for EpiPen and 39% of cases with EpiPen Jr. With Auvi-Q, the most common site was the leg (78% of cases). Conclusions: The number of unintentional epinephrine auto-injector cases reported to American Poison Centers in 2013–2014 has increased compared with previous data. Most EpiPen exposures were in the digits, whereas Auvi-Q was most frequently in the leg. Because of the limitations of Poison Center data, more research is needed to identify incidence of unintentional exposures and the effectiveness of epinephrine auto-injector redesign.
Gamma tocotrienol and tocopherol-mediated cells death occurs through the production of 15-HETE in prostate cancer cells.

A106 Dietary vitamin E exists as either tocopherols or tocotrienols. Evidence indicates that vitamin Es other than α-tocopherol, may be potent cancer preventive agents. Growth arrest of the PC-3 prostate cancer cell lines was compared in the presence of dietary α-, γ-, and δ-vitamin E by the MTT assay. Physiological concentrations of γ-tocotrienol were tested for apoptotic potential using fluorescent microscopy. QPCR, Western blot, PPAR γ dominant negative and scintillation proximity assays were used to determine the effects of vitamin E on PPAR γ. The effect of vitamin E on 15-S-HETE was determined using ELISA. Tocotrienols induced more growth arrest than tocopherols. The gamma isoforms demonstrated selectivity for growth inhibition toward the cancer cells versus normal prostate epithelia. In PC-3 cells, cell death occurs with 1 µM at 24 hours and apoptosis occurs with 5 µM at 72 hours. PPAR γ was up regulated by dietary γ-vitamin Es. Dietary γ-vitamin E mediated growth arrest was demonstrated to be PPAR γ-dependent using a PPAR γ dominant negative vector. Neither γ-vitamin Es are direct PPAR γ ligands. Concentrations of 15-S-HETE in PC-3 cells were found to be up regulated by treatment with R-γ tocotrienol. These data support that tocotrienols could be more effective as prostate chemopreventive agents than tocopherols. As the γ-vitamin Es are not direct PPAR γ ligands, and 15-S-HETE is up regulated, our data suggest that R-γ-tocotrienol modulates arachidonic acid metabolism by up regulation of 15-S-HETE which induces the PPAR γ pathway, potentiating apoptosis.
Postoperative Complications of Total Joint Arthroplasty in Obese Patients Stratified by BMI.

Abstract Background High body mass index (BMI) is associated with significant complications in patients undergoing total joint arthroplasty. Many studies have evaluated this trend, but few have looked at the rates of complications based on BMI as a continuous variable. The purpose of this study was to stratify obese patients into 3 BMI categories and evaluate their rates of complications and gauge whether transitioning from higher to lower BMI category lowers complication. Methods Patients undergoing primary total joint arthroplasty were selected from the National Surgical Quality Improvement Program database from 2008-2015 and arranged into 3 groups based on BMI: O1 (BMI 30-34.9 kg/m2), O2 (BMI 35-39.9 kg/m2), and O3 (BMI >40 kg/m2). Thirty-day complications were recorded and evaluated utilizing univariate and multivariate analyses stratified by BMI. Results A total of 268,663 patients were identified. Patients with a BMI >30 kg/m2 had more infectious and medical complications compared with nonobese patients. Furthermore, there were increased complications as the BMI categories increased. Patients with a BMI >40 kg/m2 (O3) had longer operating times, length of stay, higher rates of readmissions, reoperations, deep venous thrombosis, renal insufficiency, superficial infections, deep infections, and wound dehiscence. These trends were present when comparing the O2 with O1 category as well. Conclusion We have demonstrated increased rates of medical and surgical complications in obese patients. Furthermore, we demonstrated a stepwise increase in complication rates when transitioning to higher BMI groups. Based on our data, we believe that preoperative counseling and interventions to decrease BMI should be explored before offering elective surgery to obese patients.
Self-Assessment of Teaching Skills Among Psychiatric Residents.

Psychiatry residency programs have increasingly emphasized the role of resident-as-teacher; however, little is known about resident self-perceptions of teaching skills. This study reports on psychiatry residents’ self-perceived skills in teaching medical students and compares cohort ratings with anonymous medical student evaluations of residents as teachers at our large academic residency program. In May–June 2016, 84 residents in our program were surveyed using an anonymous, web-based survey, and this data was then compared to 3 years of aggregate data from anonymous student evaluations of resident teaching at our institution. Forty-seven (47) residents responded to the survey (56% response rate). Residents reported self-perceived deficits in several specific teaching competencies. Medical students consistently rated residents higher with respect to teaching skills than residents rated themselves, and these data were highly statistically significant. This study underscores the benefits of resident self-assessment in comparison to medical student evaluations of residents as teachers and this information can be used to inform training programs’ resident-as-teacher curricula.
MPA Program Partnerships with Nonprofit Organizations: Benefits to MPA Programs, MPA Students and Graduates, Nonprofit Organizations, and Communities

Service to community is a long-standing tradition in American democracy and society. Nonprofit public service organizations are key actors in the provision of public goods and services, as well as ...
Peirce, Clifford, and Quantum Theory

Beginning in 1870 Charles Sanders Peirce published a series of papers on a “logic of relations,” which corresponded to a linear associative algebra. This algebra is related by a linear transformation to quaternions and thus to the C(3, 0) algebra of William Kingdon Clifford. This Clifford algebra contains the Pauli matrices and so constitutes an operator basis for the nonrelativistic quantum theory of spin one-half particles. A further unification is achieved by taking the wave functions themselves to be 2 × 2 matrices which are Peirce logical operators and also elements of the Clifford algebra. Thus we have discovered a direct path from the Peirce logic to quantum theory. A diagrammatic method follows from the Peirce/Clifford algebraic approach and is suitable for describing particle interactions.
A bibliometric analysis of dialogue and digital dialogic research: mapping the knowledge construction and invisible colleges in public relations research

ABSTRACTTaking a network perspective, this study uses a series of bibliometric analyses to systematically examine public relations scholarship on dialogue and digital dialogic communication. We exa...
Sonographic Estimated Fetal Weight and Cesarean Delivery among Nulliparous Women with Obesity.

Objective This study was aimed to examine the association between having an ultrasound estimate of fetal weight (US-EFW) and mode of delivery among obese women. Study Design A retrospective cohort study of nulliparous women with a body mass index of ≥ 35 kg/m2 who delivered term singleton gestations. We examined whether having had an US-EFW within 35 days of delivery, or an US-EFW ≥ 90th percentile for gestational age, was associated with intrapartum cesarean delivery. Results Of 2,826 women, 22.5% (n = 636) had an US-EFW within 35 days of delivery. Having an US-EFW was associated with increased frequency of cesarean (43.1% for those with an US-EFW versus 30.0% for those without, p Conclusion The presence of an US-EFW among nulliparous obese women was associated with undergoing intrapartum cesarean delivery.
Phase II trial of CPX-351 (cytarabine:daunorubicin) liposome injection in patients with acute myeloid leukemia >60 years of age who have not been treated with intensive chemotherapy.

7044Background: This study enrolled older patients without age limitation to intensive chemotherapy with CPX 351 allowing for prior treatment with low intensity regimens for MDS or AML. Methods: 30...
Patent-Eligible Processes: An Audience Perspective

Many of the problems with modern patent-eligibility analysis can be traced back to a fundamental philosophical divide between judges who treat eligibility as the primary tool for effectuating patent policy and those who take patent-eligibility as nothing more than a coarse filter to be invoked in rare cases. After several years in which the coarse filter approach seemed to have the upper hand, the eligibility-as-king approach now is firmly in ascendancy. This Article, resists that trend, exploring more centrist approaches to patent-eligibility, particularly in the context of process inventions. This Article first examines the practice of undertaking an eligibility analysis with no antecedent claim construction; then concludes that this practice is problematic, drawing on the authors’ prior work concerning the design of patent law rules in view of the audience for those rules. This Article also assesses the unfortunate renaissance of the “inventive concept” inquiry, arguing that the Court’s new embrace of that inquiry is a mistake that permits judges to privilege eligibility to the virtual exclusion of all other patentability doctrines.
Fearless steps, NASA’s first heroes: Conversational speech analysis of the Apollo-11 mission control personnel

Between 1963 and 1972, a massive team of dedicated scientists, engineers, and specialists at the NASA Mission Control Center (MCC) worked seamlessly together in a cohesive manner to successfully carry out multiple manned missions to the moon. All communications between personnel were carried out over multiple inter-connected audio channels and recorded on two 30-track analog tapes. Digitization of the entire Apollo-11 mission tapes made possible through the UTDallas-CRSS Fearless Steps (FS) initiative contains the recordings of all the crew members including the three astronauts. With over 600 speakers in constant communication ensuring the astronauts’ safety throughout the mission, the success of the Apollo missions can be attributed largely to the MCC crew members. The focus of this effort is thus, to analyze their high-level group dynamics and intricate communication characteristics and gain insight into the success parameters involved in such large-scale time-critical operations. The 100 hour FS Challenge corpus highlights multiple salient moments like Lift-Off and Lunar-Landing and poses its’ own challenges for core speech tasks. This effort aims at analyzing spontaneous multi-speaker conversations in recordings often degraded by various noise types. Analysis of speech characteristics under varying stress, overlap, and noise conditions are observed to develop novel speech-activity and speaker models. These domain-specific models are leveraged to develop state-of-the-art SLT systems.
Adolescent Sun Protection Behaviors and Beliefs

The incidence of melanoma and non-melanoma skin cancer has increased among children and adolescents. Studies in the pediatric population have shown low rates of sun protection with modest improvement over the past several decades. This descriptive study characterizes photo protection behaviors and knowledge, specifically among pediatric dermatology patients in order to identify gaps in knowledge and guide discussion for health providers. Adolescents ages 12 to 20 completed surveys, which evaluated use of sun protection, beliefs about tanning and skin cancer, and sources of information. Results demonstrated that only nine percent of participants reported daily, year-round use of sunscreen. The majority (71%) reported use only during the summer months or when spending prolonged periods of time outdoors. Rates of indoor tanning were lower than reported in the literature, with only one percent reporting indoor tanning use. The majority of patients reported family members were the primary source of sun protection education. The authors conclude that while adolescents receiving care in the pediatric dermatology setting demonstrate sufficient knowledge about skin cancer prevention, adherence remains low. This study identified family members as the primary source of sun protection knowledge. Dermatologists should consider increased parental education to improve adolescent patient behavior.
Deal–Grove-like thermal oxidation of Si (001) buried under a thin layer of SrTiO3

Dry oxidation of Si (001) beneath a thin epitaxial SrTiO3 layer has been studied using furnace annealing in flowing oxygen. A 10-nm layer of SrTiO3 is epitaxially grown on Si with no SiO2 interlayer. For such a structure, an annealing temperature of 800 °C was found to be the limiting temperature to prevent silicate formation and disruption of the interface structure. The effect of annealing time on the thickness of the SiO2 layer was investigated. In situ x-ray photoelectron spectroscopy and reflection-high-energy electron diffraction were used to ensure that the quality of SrTiO3 is unchanged after the annealing process. The experimental annealing data are compared with a theoretical oxygen diffusion model based on that of Deal, Grove, and Massoud. The model fits the experimental data well, indicating that oxygen diffusion through the SrTiO3 layer is not the limiting factor. One can therefore readily control the thickness of the SiO2 interlayer by simply controlling the annealing time in flowing oxygen.
An Efficient Utilization-Based Test for Scheduling Hard Real-Time Sporadic DAG Task Systems on Multiprocessors

The scheduling and schedulability analysis of real-time directed acyclic graph (DAG) task systems have received much recent attention. The DAG model can accurately represent intra-task parallelism and precedence constraints existing in many application domains. Existing techniques show that analyzing the DAG model is fundamentally more challenging compared to the ordinary sporadic task model, due to the complex intra-DAG precedence constraints which may cause rather pessimistic schedulability loss. However, such increased loss is counter-intuitive because the DAG structure shall better exploit the hardware parallelism provided by the multiprocessor platform. Our key observation is that the intra-DAG precedence constraints, if not carefully considered by the scheduling algorithm, may cause unpredictable execution behaviors of sub-tasks in a DAG and thus pessimistic analysis. In this paper, we present a set of novel scheduling and analysis techniques for better supporting hard real-time sporadic DAG tasks on multiprocessors, through smartly defining and analyzing the execution order of subtasks in each DAG. Combined with a new DAG-specific interval analysis framework, the proposed subtask ordering technique leads to a highly efficient utilization-based schedulability test. Importantly, the developed test becomes identical to the classical density test designed for the sporadic task model, if each DAG in the system has an out-degree of one (i.e., only containing a chain of subtasks). Experiments show the efficiency of the developed test, which improves schedulability upon existing utilization-based tests by over 60% on average and is often able to guarantee schedulability with little utilization loss.
Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

Secondary resistant mutations in cancer cells arise in response to certain small molecule inhibitors. These mutations inevitably cause recurrence and often progression to a more aggressive form. Resistant mutations may manifest in various forms. For example, some mutations decrease or abrogate the affinity of the drug for the protein. Others restore the function of the enzyme even in the presence of the inhibitor. In some cases, resistance is acquired through activation of a parallel pathway which bypasses the function of the drug targeted pathway. The Catalogue of Somatic Mutations in Cancer (COSMIC) produced a compendium of resistant mutations to small molecule inhibitors reported in the literature. Here, we build on these data and provide a comprehensive review of resistant mutations in cancers. We also discuss mechanistic parallels of resistance.
Resection of Periacetabular Lesions

Peri-acetabular pelvic resections are demanding operations with complex indications, anatomy, and postoperative rehabilitation. Sir Gordon Gordon-Taylor of Britain in 1935 called hindquarter amputations “one of the most colossal mutilations practiced on the human frame.” [1] It was attempted with and without success prior to the turn of the twentieth century with Girard of Berne documenting the first nonfatal pelvic resection for sarcoma in 1895 [2]. As the knowledge base of pelvic anatomy, oncology, and imaging technology grew, more attempts at hemipelvectomy were made, and various techniques were developed. The application of cross-sectional imaging as well as the rise of metallurgy and implant development in the 1970s expanded the indications of this operation.
Building an Infrastructure for Computer Science Education Research and Practice at Scale

The goal of this workshop is to bring together the existing community of researchers working on Infrastructure Design for Data-Intensive Research in Computer Science Education and a community of Learning at Scale researchers focused on Computer Science Education. While both communities share many similar goals and could greatly benefit from each other work, the interaction between the communities is small. We hope that the proposed workshop will be instrumental in bringing together like-minded researchers from different communities, establishing collaboration, and expanding the scope of infrastructure project to address critical scaling issues.
Evaluation of the prothrombin fragment 1.2 in patients with coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulable state. The D-dimer is frequently elevated in COVID-19, but other markers of coagulation activation, including the prothrombin fragment 1.2 (PF1.2) are poorly described. We studied hospitalized adults with COVID-19 and PF1.2 measurements performed at any time during hospitalization. We evaluated the relationship between PF1.2 and synchronously measured D-dimer. We utilized receiver operating characteristic (ROC) analysis to evaluate optimal thresholds for diagnosing thrombosis and multivariable logistic regression to evaluate association with thrombosis. A total of 115 patients were included [110 (95.7%) critically ill]. Both PF1.2 and D-dimer were moderately positively correlated (r = 0.542, P 523 pmol/L: 69.2% sensitivity, 67.7% specificity; >924 pmol/L: 37.9% sensitivity, 87.8% specificity). In multivariable analysis, a PF1.2 >500 pmol/L was significantly associated with VTE [adjusted odds ratio (OR) 4.26, 95% CI, 1.12-16.21, P = .034] and any thrombotic manifestation (adjusted OR 3.85, 95% CI, 1.39-10.65, P = .010); conversely, synchronously measured D-dimer was not significantly associated with thrombosis. 90.6% of patients with a non-elevated PF1.2 result did not develop VTE. So, PF1.2 may be a useful assay, and potentially more discriminant than D-dimer, in identifying thrombotic manifestations in hospitalized patients with COVID-19.
High-severity wildfire potential – associating meteorology, climate, resource demand and wildfire activity with preparedness levels

National and regional preparedness level (PL) designations support decisions about wildfire risk management. Such decisions occur across the fire season and influence pre-positioning of resources in areas of greatest fire potential, recall of personnel from off-duty status, requests for back-up resources from other areas, responses to requests to share resources with other regions during fire events, and decisions about fuel treatment and risk reduction, such as prescribed burning. In this paper, we assess the association between PLs assigned at national and regional (Northwest) scales and a set of predictors including meteorological and climate variables, wildfire activity and the mobilisation and allocation levels of fire suppression resources. To better understand the implicit weighting applied to these factors in setting PLs, we discern the qualitative and quantitative factors associated with PL designations by statistical analysis of the historical record of PLs across a range of conditions. Our analysis constitutes an important step towards efforts to forecast PLs and to support the future projection and anticipation of firefighting resource demand, thereby aiding wildfire risk management, planning and preparedness.
Loss of ACK1 Upregulates EGFR and Mediates Resistance to BRAF Inhibition.

Targeted BRAF(V600E) suppression by selective BRAF inhibitors (BRAFis; e.g., vemurafenib and dabrafenib) has led to a sea change in the treatment of metastatic melanoma. Despite frequent upfront responses, acquired resistance has compromised long-term applicability. Among the various mechanisms of resistance, activation of multiple receptor tyrosine kinases is a known critical factor that contributes to vemurafenib resistance⁠. EGFR activation has been recurrently identified in a set of vemurafenib-resistant melanomas, but little is known about how EGFR, or possibly other receptor tyrosine kinases, becomes activated. Here, we report that ACK1, a protein kinase that modulates EGFR turnover, is downregulated in vemurafenib-resistant melanoma cells. We also found that ACK1 depletion with short hairpin RNA decreased EGFR degradation when activated by epidermal growth factor, increased EGFR protein expression, and conferred resistance to BRAFis both in vitro and in vivo. Vemurafenib resistance mediated by ACK1 inhibition can be reversed by the EGFR inhibitor gefitinib. Our data indicate that ACK1 loss may be a post-transcriptional mechanism that increases EGFR signaling and contributes to drug resistance.
A 'Plausible' Showing after Bell Atlantic Corp. v. Twombly

The United States Supreme Court's decision in Bell Atlantic Corp. v. Twombly is creating quite a stir. Suddenly gone is the famous loosey-goosey rule of Conley v. Gibson "that a complaint should not be dismissed for failure to state a claim unless it appears beyond doubt that the plaintiff can prove no set of facts in support of his claim which would entitle him to relief." Now a complaint must provide "enough facts to state a claim to relief that is plausible on its face." Decided in 2007, Bell Atlantic was cited in over 6,000 cases in just its first year. Already being described as a landmark decision, Bell Atlantic nonetheless has lawyers and judges scratching their heads over the precise pleading standard to apply in its wake. As the Second Circuit (mildly) put it, "Considerable uncertainty concerning the standard for assessing the adequacy of pleadings has recently been created by the Supreme Court's decision in Bell Atlantic Corp. v. Twombly." Just what is a plausible "showing that the pleader is entitled to relief" under Rule 8(a)(2)? I believe an answer lies in the 27-year-old decision of the Former Fifth Circuit in In re Plywood Antitrust Litigation. Plywood Antitrust requires, at a minimum, that "a complaint . . . contain either direct or inferential allegations respecting all the material elements necessary to sustain a recovery under some viable legal theory." Already used in more than half the circuits, this standard paraphrases advice found in Professors Wright and Miller's venerable Federal Practice and Procedure for nearly forty years. Properly applied, this "all . . . material elements" standard satisfies Bell Atlantic's "plausibility" requirement in all respects. The Plywood Antitrust pleading standard works well after Bell Atlantic, first, because the Supreme Court referred to the standard, albeit parenthetically, with approval in Bell Atlantic. Second, the standard does much to harmonize the Federal Rules' goal of dispensing with pleading technicalities while still requiring enough general factual information about a pleader's claim to make the notice in "notice pleading" meaningful. Finally, and perhaps most importantly, it gives lawyers, litigants, and courts a standard they can actually use when drafting or assessing the sufficiency of pleadings.
Evolution and Revolution as Organizations Grow

Examines the impact that a firm's history has on the future of the firm. Firms pass through a series of developmental phases as they grow. Each of these phases begins with a period of calm ("evolution") and ends with a management crisis ("revolution"). By considering the history of the firm, i.e. the previous phases, the management of a growing firm can anticipate the next crisis and better prepare to deal with it. Five dimensions are identified as key to the development of this model. They are the age of the organization, the size of the organization, stages of evolution, stages of revolution, and growth rate of the industry. Based on these dimensions, the five phases of development for growing firms are identified. Each of these five phases starts with growth. The management styles which highlight these stages are creativity, direction, delegation, coordination, and collaboration, respectively. The crises that end each phase are leadership, autonomy, control, and red tape, respectively. Based on these phases, several recommendations are made for managers including understanding where the firm is in the developmental sequence and recognizing the limited range of solutions. (SRD)
Rare coding variants in five DNA damage repair genes associate with timing of natural menopause

Abstract The age of menopause is associated with fertility and disease risk, and its genetic control is of great interest. We used whole-exome sequences from 119,992 women in the UK Biobank to test for associations between rare damaging variants and age at natural menopause. Rare damaging variants in three genes significantly associated with menopause: CHEK2 (p = 6.2 × 10−51) and DCLRE1A (p = 1.2 × 10−12) with later menopause and TOP3A (p = 8.8 × 10−8) with earlier menopause. Two additional genes were suggestive: RAD54L (p = 2.3 × 10−6) with later menopause and HROB (p = 2.7 × 10−6) with earlier menopause. In a follow-up analysis of repeated questionnaires in women who were initially pre-menopausal, CHEK2, TOP3A, and RAD54L genotype associated with subsequent menopause. Consistent with previous GWAS, all five genes are involved in the DNA-damage repair pathway. Phenome-wide scans across 363,977 men and women revealed that in addition to known associations with cancers and blood cell counts, rare variants in CHEK2 also associated with increased risk of uterine fibroids, polycystic ovary syndrome, and prostate hypertrophy; these associations are not shared with higher-penetrance breast cancer genes. Causal mediation analysis suggests that approximately 8% of the breast cancer risk conferred by CHEK2 pathogenic variants after menopause is mediated through delayed menopause.
Direct Eigenstructure Assignment for Model Updating

A direct updating approach for stiffness and damping matrices based on eigenstructure assignment is presented. The approach (which preserves symmetry, connectivity, and constraints imposed by stati...
To read or to rotate? comparing the effects of technical reading training and spatial skills training on novice programming ability

Understanding how to best support and train novice programmers is a critical component of producing better and more diverse software engineers. In this paper, we present the results of a controlled 11-week longitudinal study with 57 CS1 students comparing two skill-based interventions to improve programming performance. The first intervention involves spatial training, an established baseline known to be helpful in engineering contexts. The second intervention is a novel CS-focused technical reading training. In our reading training, we teach strategies for summarizing scientific papers and understanding scientific charts and figures; most of the covered readings were CS1-accessible portions of computer science research papers. For the spatial training, we use a standardized training curriculum previously found to improve programming skills by focusing on spatial ability (i.e., the ability to mentally manipulate objects). We first replicate findings that both reading ability and spatial ability correlate with programming success. Significantly, however, we find that those in our reading training exhibit larger programming ability gains than those in the standard spatial training (p = 0.02, f2=0.10). We also find that reading trained participants perform particularly well on programming problems that require tracing through code (p = 0.03, f2=0.10). Our results suggest that technical reading training could be beneficial for novice programmers. Finally, we discuss the implications of our results for future CS1 interventions, the possibility for non-programming based training to positively impact developers, and future directions for software engineering education research.
Mechanism for the activation of the anaplastic lymphoma kinase receptor.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that regulates important functions in the central nervous system1,2. The ALK gene is a hotspot for chromosomal translocation events that result in several fusion proteins that cause a variety of human malignancies3. Somatic and germline gain-of-function mutations in ALK were identified in paediatric neuroblastoma4–7. ALK is composed of an extracellular region (ECR), a single transmembrane helix and an intracellular tyrosine kinase domain8,9. ALK is activated by the binding of ALKAL1 and ALKAL2 ligands10–14 to its ECR, but the lack of structural information for the ALK-ECR or for ALKAL ligands has limited our understanding of ALK activation. Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. Our data reveal a mechanism of RTK activation that allows dimerization by either dimeric (ALKAL2) or monomeric (ALKAL1) ligands. This mechanism is underpinned by an unusual architecture of the receptor–ligand complex. The ALK-ECR undergoes a pronounced ligand-induced rearrangement and adopts an orientation parallel to the membrane surface. This orientation is further stabilized by an interaction between the ligand and the membrane. Our findings highlight the diversity in RTK oligomerization and activation mechanisms. Cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography are used to provide structural and mechanistic details of the activation of anaplastic lymphoma kinase by the ligands ALKAL1 and ALKAL2.
Some Aspects of the Arithmetic Theory of Polynomials

This is an expository paper based on our memos of two lectures, one at the A.M.S. annual meeting at Cincinnati in January of 1982 with Professor Mostow presiding and another at the conference at Yale in honor of his 60th birthday. We have emphasized the universality or the uniformity of results and problems for all local fields; and consequently we have included certain material which is usually considered as analysis rather than arithmetic. On the other hand, as the title suggests, we have covered only certain parts of the arithmetic theory of polynomials. For instance the arithmetic theory of polynomials over a finite field is almost entirely left out. Also we have not given enough explanation to the recent results of Barlet [3] and Heath-Brown [11], which were mentioned at the time of the conference respectively by Professors Deligne and Tamagawa. Nevertheless it is our hope that this paper will give a fair and useful survey of certain parts of the arithmetic theory of polynomials appropriate for the Festschrift.