cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4129: Novel small molecule TLR7/8 agonists for enhancing NK cell-mediated ADCC

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is a key mechanism of action for some therapeutic antibodies. ADCC involves killing of an antibody‐coated target cell by an effector cell through the release of cytotoxic or cell death‐inducing molecules. ADCC is triggered through interaction of Fcγ receptors present on the effector cell surface with the Fc region of the target-bound antibody. Natural killer (NK) cells are one of the primary effector cells that mediate ADCC. There is significant interest in designing therapeutic agents that can enhance ADCC because this can result in improved clinical responses with approved antibodies. We have developed a suite of highly substituted imidazoquinolines, which activate TLR 7 and/or 8 and induce significantly higher levels of cytokines compared to the FDA-approved TLR7 agonist imiquimod. In the current study, we evaluated our series of TLR7-specific, 8-specific and 7/8 dual selective agonists for their ability to improve ADCC with Cetuximab. We investigated NK cell activation in the presence of these compounds, as well as NK cell mediated ADCC against an EGFR expressing lung cancer cell line, A549. In addition, we also measured cytokine induction in human peripheral blood mononuclear cells in response to these compounds. Our studies show dual TLR 7/8 and 8-specific agonists induce robust pro-inflammatory cytokine secretion and activate NK cells. however, mixed agonists also induce greater immunosuppressive cytokines compared to TLR8-specific agonists. Further, these agonists also significantly enhanced Cetuximab mediated ADCC in vitro. In vivo studies examining the anticancer efficacy of the combination of selected TLR7/8 agonists and Cetuximab are ongoing. Citation Format: Vidhi Khanna, Hyunjoon Kim, Wenqui Zhang, Peter Larson, David Ferguson, Jayanth Panyam. Novel small molecule TLR7/8 agonists for enhancing NK cell-mediated ADCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4129.
Diffuse optical tomography of the breast: a potential modifiable biomarker of breast cancer risk with neoadjuvant chemotherapy.

The purpose of this study is to evaluate whether a diffuse optical tomography breast imaging system (DOTBIS) can provide a comparable optical-based image index of mammographic breast density, an established biomarker of breast cancer risk. Oxyhemoglobin concentration (ctO2Hb) measured by DOTBIS was collected from 40 patients with stage II-III breast cancer. The tumor-free contralateral breast was used for this evaluation. We observed a moderate positive correlation between the patient’s mammogram density classification and ctO2Hb, rs = 0.486 (p = 0.001). In addition, significant reduction in ctO2Hb levels were noted during neoadjuvant chemotherapy treatment (p = 0.017). This observation indicates that ctO2Hb levels measured by DOTBIS could be a novel modifiable imaging biomarker of breast cancer risk and warrants further investigation.
Small Cell and Squamous Cell Carcinomas of the Head and Neck: Comparing Incidence and Survival Trends Based on Surveillance, Epidemiology, and End Results (SEER) Data

Background Small cell carcinomas of the head and neck (SmCCHNs) are rare neoplasms with an unfavorable prognosis. Population-based data describing survival and prognostic factors for SmCCHN are limited. Methods Data were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1973-2013. Patient and tumor-related characteristics for SmCCHN were compared with those for squamous cell carcinoma of the head and neck (SCCHN). Survival was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. Results The data set included 609 SmCCHN and 227,943 SCCHN cases. Both histological subtypes were more common in men than women and more common in white patients. SmCCHN was most likely to originate in the larynx, glottis and hypopharynx, or salivary glands and to present with more advanced stage and grade. SCCHN was most likely to originate in the oral cavity and was found infrequently in the salivary glands. Overall 5- and 10-year survival estimates were 27% and 18% for SmCCHN and 46% and 31% for SCCHN, respectively. In multivariable survival analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade, and receipt of radiation, the hazard ratio (HR) comparing SmCCHN with SCCHN was 1.53 with a 95% confidence interval (CI) from 1.39 to 1.68. Average 5-year survival varied widely between the histologic types when comparing tumor sites: 14.5% for SmCCHN versus 48.9% for SCCHN in the oropharynx. In propensity score matched analyses, the corresponding HR was 1.27 (95% CI, 1.15-1.40). Conclusion Compared with SCCHN, SmCCHN carries a worse survival and is more likely to present with more advanced stage. Implications for practice Small cell carcinoma of the head and neck (SmCCHN) is a rare subtype of head and neck cancer. In this Surveillance, Epidemiology, and End Results (SEER) data analysis, the characteristics and survival of SmCCHN are compared with those of the common squamous cell carcinoma of the head and neck. Results show that SmCCHN carries a worse prognosis and tends to present at a more advanced stage; SmCCHN also is ten times more likely to originate from the salivary glands. These findings may have implications for clinical practice, as location of the tumor may strongly associate with the pathologic diagnosis. If a SmCCHN is diagnosed, a disseminated disease is likely; hence vigilance in staging procedures is indicated.
Molecular Mechanism of the Association Between Atrial Fibrillation and Heart Failure Includes Energy Metabolic Dysregulation Due to Mitochondrial Dysfunction.

Abstract Background Atrial fibrillation (AF) and heart failure (HF) commonly coexist, yet the molecular mechanisms of this association have not been determined. We hypothesized that an energy deficit due to mitochondrial dysfunction plays a significant role in pathogenic link between AF and HF. Methods and Results Myocardial energy metabolism and mitochondria were examined in atrial tissue samples from patients and mice (cardiac specific LKB1 knockout) with HF and/or AF. There was significant atrial energy (ATP) deficit in patients with HF (11.5±1.3 nmoles/mg, n=10; versus without HF 17±3.8 nmoles/mg, n=5, p=0.032). AF was associated with further energy depletion (ATP 5.4±1.2 nmoles/mg, n=9) in HF (p=0.001) and metabolic stress (AMP/ATP 1.6±0.1 vs 0.7±0.2 in HF alone; p=0.043). The left atrium demonstrated lower ATP than the right (p=0.004). Mitochondrial dysfunction and remodeling caused ATP depletion with impaired oxidative phosphorylation complexes (succinate dehydrogenase and cytochrome c oxidase), increased reactive oxygen species, and mtDNA damage in mice and human atria with AF and HF. Conclusions Molecular mechanisms of the association between HF and AF include an energy deficit due to mitochondrial dysfunction in atrial myocardium. Mitochondrial functional and structural remodeling in human and mouse atria is associated with energy metabolic dysregulation and oxidative stress that promote AF in HF and vice versa.
Paper Trails: Fang Yongbin and the Material Culture of Calligraphy

Fang Yongbin’s (1542–1608) cache of paper-based ephemera—733 notes, invoices, and 190 name cards—now held in the Harvard-Yenching library, discloses the multidimensional expertise of the stationery dealer in late Ming China. This article explores how businessmen from Huizhou prefecture turned to the trade in writing materials to improvise with new forms of cultural entrepreneurship in the late sixteenth century. Introducing the diverse contents of the cache, I demonstrate how Fang’s involvement in the sale of desktop tools drew from, and creatively combined literary endeavors, shop-keeping, and artisanal labor. Unsettling discrete conceptions of “scholar,” “merchant,” and “craftsman,” Fang’s career reveals how stationery dealers vied to usurp custodianship over the material culture of calligraphy. The Harvard-Yenching cache registers the increasingly powerful influence exerted over the business of culture by those skilled in the making and marketing of writing materials: largely forgotten salesmen whose services made the art of writing possible in the first place.
TownSim: agent-based city evolution for naturalistic road network generation

We describe an agent-based city evolution algorithm creating road networks over time, and explore several approaches for analyzing the malleability of the algorithm to exposed parameters. In addition to qualitatively assessing the generated content, we look at the directionality, connectivity, and curvature of the generated road networks.
Breaking the boundaries of professional regulation: medical licensing, foreign influence, and the consolidation of homeopathy in Mexico

As doctors sought state support to regulate professional training and practice after Independence, Mexicans also developed different attitudes toward foreign ideas, influences, and professionals. Leveraging the allure of the foreign among Mexicans, homeopaths strategically used work, products, and organizations from abroad to establish their practices and fight changing professional policies in the country that threatened homeopathic institutions. Homeopaths inhabited the blurry and shifting boundary between professional and lay medical practice during the early Republican period, the Porfiriato, and the post-revolutionary era, and used the ambivalent feelings about medical licensing, and foreign influence in Mexican society to consolidate their position.
Asthma Across Childhood: Improving Adherence to Asthma Management from Early Childhood to Adolescence

Asthma affects nearly 6 million US children. Throughout childhood, children undergo a series of biological, developmental, and psychosocial changes. Thus, factors influencing a child's asthma management differ across 3 essential stages—early childhood (0-5 years), school-aged years (5-12 years), and adolescence (12-18 years)—and require varied intervention by parents, school personnel, clinicians, and the children themselves. Because asthma care in children is characterized by fluctuations in severity and coordination among many stakeholders, optimal asthma control is difficult to achieve in this young population. Challenges in childhood asthma management are reflected in the low rates of children's adherence to medication regimes. Although pharmacological and biological factors addressing age in physicians' treatment choices are well outlined, age-specific approaches to patient-provider communication and asthma-related interventions are also important in improving quality of life for patients with pediatric asthma.
Construction activity recognition with convolutional recurrent networks

Abstract Although heavy equipment is an indispensable resource in many construction projects, it is often underutilized. Inefficient usage patterns and frequent idling contribute to increased emissions and project costs. Efforts to improve usage patterns often begin with activity tracking. Recent research into automated activity tracking has leveraged sensing devices and Internet-of-Things (IoT) frameworks to power machine learning models that can predict the behaviors of monitored equipment. However, shallow machine learning models require complex manual feature engineering that could be further automated with more recent deep learning approaches. Deep learning approaches not only increase automation but also promise improved accuracies by avoiding biases introduced by manual feature design. This paper proposes a construction equipment activity recognition framework that uses deep learning architectures to predict the activities of heavy construction equipment monitored via accelerometers and applies this framework to a roller compactor and an excavator performing real work. The performance of a simple baseline convolutional neural network (CNN) is compared to a hybrid network that contains both convolutional and recurrent long short-term memory (LSTM) layers. The hybrid model outperforms the baseline model in all instances studied. In the task of classifying the activities of the roller compactor, the hybrid model achieves a validation accuracy of 77.1% when presented with six activities and a validation accuracy of 96.2% when distinguishing only direction. In the task of classifying seven activities of the excavator, the hybrid model achieves a validation accuracy of 77.6%, with some confusion between isolated activities and a Various category that includes elements of the isolated activities. With the Various category removed, the hybrid model achieves a validation accuracy of 90.7%. This study demonstrates that deep learning frameworks can model the activities of construction equipment with high accuracy. In particular, this work shows that convolutional and LSTM layers can each form effective parts of deep learning models that characterize equipment activities based on accelerometer data, and furthermore that these components can produce more effective models when combined. The findings of this study can be leveraged by researchers and industry professionals to develop reliable automated activity recognition systems for tracking and monitoring equipment performance and for measuring the productivity and the efficiency of the work performed.
Evidence of widespread topoclimatic limitation for lower treelines of the Intermountain West, United States

Many forests in dry mountain regions are characterized by a lower elevational treeline. Understanding the controls on the position of lower treeline is important for predicting future forest distributional shifts in response to global environmental change. Lower treelines currently at their climate limit are expected to be more sensitive to changing climate, whereas lower treelines constrained by non-climatic factors are less likely to respond directly to climate change but may be sensitive to other global change agents. In this study, we used existing vegetation classifications to map lower treelines for our 1.7 million km2 study region in the U. S. Intermountain West. We modeled topoclimatic drivers of lower treeline position for each of three dominant forest types to identify topoclimatically limited treelines. We then used spatial data of edaphic properties, recent fire, and land use to identify lower treelines potentially constrained above their ecophysiological limits by non-climatic processes. We found that the lower treeline ecotone of pinyon-juniper woodlands is largely limited by topoclimate and is likely to be sensitive to increasing temperatures and associated droughts, though these effects may be heterogeneously distributed across the landscape. In contrast, dry mixed-conifer lower treelines in the northern portion of the study area rarely reached their modeled topoclimatic limit, suggesting that non-climatic processes, including fire and land use, constrain the lower treeline above its ecophysiological limits in this forest type. Our results suggest that much of the lower treeline in the Intermountain West is currently climate limited and will thus be sensitive to ongoing climate changes. Lower treelines in other arid or semi-arid mountainous regions around the globe may also be strongly sensitive to climate, though treeline response to climate change will be mediated at the local scale by soil properties, biotic interactions, and natural or anthropogenic disturbances. Our regional study of lower treeline provides a framework for identifying the drivers of lower treeline formation and allows for more robust projections of future treeline dynamics, which are needed to anticipate shifting global distributions of the forest biome.
Real-world analysis of peptide receptor radionuclide therapy (PRRT) in the treatment of neuroendocrine tumors.

e16701Background: PRRT received FDA approval in 2018 for treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEPNETs) based on NETTER-1 trial data that include...
National Evaluation of Patient Preferences in Selecting Hospitals and Health Care Providers

BACKGROUND Patient utilization of public reporting has been suboptimal despite attempts to encourage use. Lack of utilization may be due to discordance between reported metrics and what patients want to know when making health care choices. OBJECTIVE The objective of this study was to identify measures of quality that individuals want to be presented in public reporting and explore factors associated with researching health care. RESEARCH DESIGN Patient interviews and focus groups were conducted to develop a survey exploring the relative importance of various health care measures. SUBJECTS Interviews and focus groups conducted at local outpatient clinics. A survey administered nationally on an anonymous digital platform. MEASURES Likert scale responses were compared using tests of central tendency. Rank-order responses were compared using analysis of variance testing. Associations with binary outcomes were analyzed using multivariable logistic regression. RESULTS Overall, 4672 responses were received (42.0% response rate). Census balancing yielded 2004 surveys for analysis. Measures identified as most important were hospital reputation (considered important by 61.9%), physician experience (51.5%), and primary care recommendations (43.2%). Unimportant factors included guideline adherence (17.6%) and hospital academic affiliation (13.3%, P<0.001 for all compared with most important factors). Morbidity and mortality outcome measures were not among the most important factors. Patients were unlikely to rank outcome measures as the most important factors in choosing health care providers, irrespective of age, sex, educational status, or income. CONCLUSIONS Patients valued hospital reputation, physician experience, and primary care recommendations while publicly reported metrics like patient outcomes were less important. Public quality reports contain information that patients perceive to be of relatively low value, which may contribute to low utilization.
A Pressure Sensing System with ±0.75 mmHg (3σ) Inaccuracy for Battery-Powered Low Power IoT Applications

This work presents an energy-efficient piezoresistive pressure sensing system for low-power IoT applications. The sensor adopts duty-cycling and sub-ranging to achieve high energy efficiency and accuracy. Fabricated in 180nm CMOS, the test chip with pressure transducer achieves state-of-art energy efficiency of 6.1 nJ•mmHg2 with ±0.75 mmHg 3σ inaccuracy. The sensor is integrated into a wireless sensor node to demonstrate its operation at a system level.
Privacy in Pandemic: Law, Technology, and Public Health in the COVID-19 Crisis

The COVID-19 pandemic has caused millions of deaths and disastrous consequences around the world, with lasting repercussions for every field of law, including privacy and technology. The unique characteristics of this pandemic have precipitated an increase in use of new technologies, including remote communications platforms, healthcare robots, and medical AI. Public and private actors are using new technologies, like heat sensing, and technologically-influenced programs, like contact tracing, alike in response, leading to a rise in government and corporate surveillance in sectors like healthcare, employment, education, and commerce. Advocates have raised the alarm for privacy and civil liberties violations, but the emergency nature of the pandemic has drowned out many concerns. This Article is the first comprehensive account of privacy impacts related to technology and public health responses to the COVID-19 crisis. Many have written on the general need for better health privacy protections, education privacy protections, consumer privacy protections, and protections against government and corporate surveillance. However, this Article is the first comprehensive article to examine these problems of privacy and technology specifically in light of the pandemic, arguing that the lens of the pandemic exposes the need for both widescale and small-scale reform of privacy law. This Article approaches these problems with a focus on technical realities and social salience, and with a critical awareness of digital and political inequities, crafting normative recommendations with these concepts in mind. Understanding privacy in this time of pandemic is critical for law and policymaking in the near future and for the long-term goals of creating a future society that protects both civil liberties and public health. It is also important to create a contemporary scholarly understanding of privacy in pandemic at this moment in time, as a matter of historical record. By examining privacy in pandemic, in the midst of pandemic, this Article seeks to create a holistic scholarly foundation for future work on privacy, technology, public health, and legal responses to global crises.
The October 1998 Crisis in Turkish-Syrian Relations: A Prospect Theory Approach

This paper attempts to answer the question of what made the Turkish threats in the 1998 October crisis with Syria different from all others made over the last two decades; and what were the main reasons for Hafez Assad’s capitulation vis-a-vis Turkish demands. Using the prospect theory, this paper argues that it was not the changing balance-of-power or the deterring effect of the Turkish-Israeli cooperation that brought about Turkish resolve and Syrian capitulation at the end of the crisis, but Hafez Assad’s domestic policy constraints and health problems.
The Third Pillar: Pico and Kabbalism

Kabbalism is the third pillar of Pico’s approach. In it he found the Christian message and classical philosophy, particularly the Platonic tradition, re-presented within the exceptionalism of a direct, secret revelation hidden for centuries and now available through Pico. He was the first Christian philosopher to utilize Kabbalism beginning ‘Christian Kabbalism.’ Recently the role of Kabbalism in his work, and his role in introducing it have been reevaluated. Kabbalism is now understood as a major component of his concordance but his work rests on the scholarship of others. This chapter explores the history of Jewish mysticism, the development of Kabbalah, key texts and then begins to explore Pico’s use of Kabbalism in his work. He has three pillars to his intellectual enterprise but believed that Kabbalism provided a deeper ‘first’ truth or foundation to the universe than Platonism and Aristotelianism.
Very long-chain acyl-CoA synthetase 3 mediates onco-sphingolipid metabolism in malignant glioma

Gliomas are the largest category of primary malignant brain tumors in adults, and glioblastomas account for nearly half of malignant gliomas. Glioblastomas are notoriously aggressive and drug-resistant, with a very poor 5 year survival rate of about 5%. New approaches to treatment are thus urgently needed. We previously identified an enzyme of fatty acid metabolism, very long-chain acyl-CoA synthetase 3 (ACSVL3), as a potential therapeutic target in glioblastoma. Using the glioblastoma cell line U87MG, we created a cell line with genomic deletion of ACSVL3 (U87-KO) and investigated potential mechanisms to explain how this enzyme supports the malignant properties of glioblastoma cells. Compared to U87MG cells, U87-KO cells grew slower and assumed a more normal morphology. They produced fewer, and far smaller, subcutaneous xenografts in nude mice. Acyl-CoA synthetases, including ACSVL3, convert fatty acids to their acyl-CoA derivatives, allowing participation in diverse downstream lipid pathways. We examined the effect of ACSVL3 depletion on several such pathways. Fatty acid degradation for energy production was not affected in U87-KO cells. Fatty acid synthesis, and incorporation of de novo synthesized fatty acids into membrane phospholipids needed for rapid tumor cell growth, was not significantly affected by lack of ACSVL3. In contrast, U87-KO cells exhibited evidence of altered sphingolipid metabolism. Levels of ceramides containing 18-22 carbon fatty acids were significantly lower in U87-KO cells. This paralleled the fatty acid substrate specificity profile of ACSVL3. The rate of incorporation of stearate, an 18-carbon saturated fatty acid, into ceramides was reduced in U87-KO cells, and proteomics revealed lower abundance of ceramide synthesis pathway enzymes. Sphingolipids, including gangliosides, are functional constituents of lipid rafts, membrane microdomains thought to be organizing centers for receptor-mediated signaling. Both raft morphology and ganglioside composition were altered by deficiency of ACSVL3. Finally, levels of sphingosine-1-phosphate, a sphingolipid signaling molecule, were reduced in U87-KO cells. We conclude that ACSVL3 supports the malignant behavior of U87MG cells, at least in part, by altering cellular sphingolipid metabolism.
Deep Learning to Enhance Transient Thermal Performance and Real-Time Control of an Energy Storage (TES) Platform

Phase Change Materials (PCMs) are used for thermal energy storage (TES) due to their high latent heat capacity. While inorganic PCMs have the ability to store large amounts of thermal energy (as they possess higher values of latent heat capacity) they need significant supercooling to initiate solidification - which compromises their operational reliability (compared to organic PCMs). ‘Cold Finger Technique’/ CFT (wherein a portion of the PCM is maintained in the solid-state as the un-melted PCM serves to initiate nucleation for subsequent solidification of the rest of the PCM) enables higher operational reliability at the expense of a marginal loss of storage capacity (from the portion of the PCM that remains un-melted). In order to apply CFT, one possible approach is to target a desired melt fraction in the early stages of operation for avoiding catastrophic failure (i.e., avoiding 100% melting). The objective is to reach as close to 100% melting as possible - without completely melting the whole mass of PCM - using a reliable and predictable method. Hence, at any instant, a reliable way is desired to predict the time remaining to reach a particular melt fraction of the PCM (during the melting cycle).In this study we determine the efficacy of employing Artificial Intelligence (AI) based techniques, especially Deep Learning, for predicting the time remaining to reach a target melt fraction at any instant during the melting cycle. The time history of the PCM melt fraction and temperature transients at multiple locations within the TES platform can thus be correlated by employing an Artificial Neural Network (ANN) to achieve this goal. The aim of this study is to develop and deploy ANN based prediction tools that can enable real-time predictions (e.g., when the melt cycle should be stopped and freezing cycle should be initiated) apriori based on instantaneous values of temperature measured during operation of a TES platform. The data for training and evaluating the efficacy of the ANN model predictions is obtained from PCM melting experiments performed in this study using PureTemp29. Initially a solid mass of PCM is melted (using a nichrome wire heater mounted at the bottom) in a graduated cylinder with three thermocouples recording the temperatures at distinct locations along the height of the cylinder. An automated digital data acquisition (DAQ) system is used to record the transient temperature profiles from these thermocouples. The height of the liquid meniscus (melted PCM) is recorded using a digital image acquisition apparatus (and also monitored periodically from the measuring cylinder containing the PCM) until the PCM is completely melted. The results show that the predictions of the ANN model are most accurate in the later stages of the melting cycle. The error decreases as the melt fraction approaches the target melt. For a target melt of 90%, the error in predictions in the last 1800 seconds of the melting cycle is in the range 150-350 seconds.
On the Complexity of Dynamic Submodular Maximization.

We study dynamic algorithms for the problem of maximizing a monotone submodular function over a stream of $n$ insertions and deletions. We show that any algorithm that maintains a $(0.5+\epsilon)$-approximate solution under a cardinality constraint, for any constant $\epsilon>0$, must have an amortized query complexity that is $\mathit{polynomial}$ in $n$. Moreover, a linear amortized query complexity is needed in order to maintain a $0.584$-approximate solution. This is in sharp contrast with recent dynamic algorithms of [LMNF+20, Mon20] that achieve $(0.5-\epsilon)$-approximation with a $\mathsf{poly}\log(n)$ amortized query complexity. On the positive side, when the stream is insertion-only, we present efficient algorithms for the problem under a cardinality constraint and under a matroid constraint with approximation guarantee $1-1/e-\epsilon$ and amortized query complexities $\smash{O(\log (k/\epsilon)/\epsilon^2)}$ and $\smash{k^{\tilde{O}(1/\epsilon^2)}\log n}$, respectively, where $k$ denotes the cardinality parameter or the rank of the matroid.
Characterization of the Interaction of a Protein Inhibitor with Adenosine 3',5'-Monophosphate-dependent Protein Kinases II. MECHANISM OF ACTION WITH THE HOLOENZYME

Abstract The titrations of the adenosine 3',5'-monophosphate-dependent protein kinase or the catalytic subunit derived therefrom by a heat-stable protein inhibitor are quantitatively identical. Evidence is presented that the inhibitor does not interact with adenosine 3',5'-monophosphate-dependent protein kinase in the absence of the cyclic nucleotide. There is no displacement of the regulatory subunit from the holoenzyme nor is there formation of a stable inhibitor-holoenzyme complex. The interaction of inhibitor and catalytic subunit is shown to be reversible by sucrose gradient ultracentrifugation and by dilution. The results demonstrate that the inhibitor interacts with adenosine 3',5'-monophosphate-dependent protein kinase only after cyclic nucleotide-promoted dissociation.
If you could be in charge: student ideas for promoting sustainability in housing

In the spring of 2010, 55 students at a major US university participated in a course entitled: Housing: Energy and the Environment. Over 20 different academic majors were represented in the class, including housing design, residential property management, various engineering specialties, environmental studies and architecture. The majority of the students in this class were knowledgeable about housing and planned careers in housing-, design-, management- or construction-related fields. For the final paper/exam in the class, the students were to design a programme that would ‘promote resource conservation and management, and environmental quality in the housing and building industry'. Examples included (but were not limited to) a government policy, certification programme, training programme or municipal code. A content analysis of the student exams was conducted to give insight into how the next generation of professionals and consumers might set priorities on sustainability and how they might consider implementing these priorities. Topics in the content analysis included programme content, type of programme, funding, target audience and technology. The most frequent programme topics were energy, resource and water conservation. The most common type of programme was training or education, and programmes were more likely to be targeted at building professionals, consumers or owners of buildings. The majority of the students did not address the issue of programme funding or assumed that the government would pay for their programmes. The programmes designed by the students suggest they believe in the importance of sustainable housing and expect to be involved in energy and environmentally friendly practices as professionals and consumers. Yet, these students also see the need for greater motivation, requirements and preparation to achieve energy independence and environmental sustainability.
McMillan-Rowell like oscillations in a superconductor-InAs/GaSb-superconductor junction

We have fabricated a superconductor (Ta)-InAs/GaSb bilayer-superconductor (Ta) junction device that has a long mean free path and can preserve the wavelike properties of particles (electrons and holes) inside the junction. Differential conductance measurements were carried out at low temperatures in this device, and McMillan-Rowell like oscillations (MROs) were observed. Surprisingly, a much larger Fermi velocity, compared to that from Shubnikov-de Haas oscillations, was obtained from the frequency of MROs. Possible mechanisms are discussed for this discrepancy.
A Review of “Disability Studies and the Hebrew Bible: Figuring Mephibosheth in the David Story”

Schipper tells us plainly what he has not done: he has not offered a biblical theology of disability, nor “presented the overarching biblical view on disability” (p. 129). And why? He answers, “the...
Cineradiographic Analysis of Vomiting in the Cat: I. Lower Esophagus, Stomach, and Small Intestine

Previous studies in our laboratories!' 2 have shown that the emetic apparatus in cats becomes functional between the 2nd and 10th postnatal days, as determined through tests with lanatoside C, total body x-irradi­ ation, tartar emetic, and copper sulfate. In the initial studies,! we observed that the sequence of events leading to the emetic reaction appeared much the same in the young and adult animals, except for the rela­ tively greater vigor of the response in adults. Slow motion cinematographic studies of the reaction 2 appeared to substantiate these early findings. The fact that we have ob­ served no notable differences in pattern in young and adult animals, and that very few of the young animals showed signs of vomit­ ing prior to the stage at which t he emetic mechanism became functional, however, does not preclude the possibility that certain of the "components" of the sequence of motor events leading to the emetic act not detectable by external observation may be­ come functional before others. In order to ascertain whether such activity does exist prior to its external manifestation, we have undertaken cineradiographic studies of the development of the emetic response in the cat. Although the primary aim of this over-all program is to study the development of the emetic reflex in early postnatal stages with the use of modern indirect cinefluorographic techniques, it has become clear in t he course of our preliminary studies that further
Statistical tests for a single change in mean against long-range dependence ∗†

Statistical tests are introduced for distinguishing between short-range dependent time series with a single change in mean, and long-range dependent time series, with the former making the null hypothesis. The tests are based on estimation of the self-similarity parameter after removing the change in mean from the series. The focus is on the GPH (Geweke and Porter-Hudak, 1983) and local Whittle estimation methods in the spectral domain. Theoretical properties of the resulting estimators are established when testing for a single change in mean, and small sample properties of the tests are examined in simulations. The introduced tests improve on the BHKS (Berkes et al., 2006) test which is the only other available test for the considered problem. It is argued that the BHKS test has a low power against long-range dependence alternatives and that this happens because the BHKS test statistic involves estimation of the long-run variance. The BHKS test could be improved readily by considering its R/S-like regression version which estimates the self-similarity parameter and which does not involve the long-run variance. Yet better alternatives are to use more powerful estimation methods (such as GPH or local Whittle) and lead to the tests introduced here.
High-quality results of cytoreductive surgery and heated intraperitoneal chemotherapy perfusion for carcinomatosis at a low volume institution.

Background and Objectives Maximal cytoreductive surgery (CS) with heated intraperitoneal chemotherapy perfusion (HIPEC) for peritoneal carcinomatosis can improve oncologic outcomes, but is associated with significant morbidity. Whether low-volume experience with CS/HIPEC results in acceptable outcomes is unknown. Methods A retrospective review of all patients undergoing CS/HIPEC by a single surgeon. Experience was divided into first versus second 50 cases, and patient characteristics, operative details, and outcomes were compared. Results Ninety patients underwent 100 CS/HIPEC procedures (mean age 57 years, 68% female). ­Compared to the initial experience, the second 50 cases included more high grade tumors (68 vs. 52%) and greater disease burden (PCI 14.2 vs. 12.4). Operative times remained unchanged and mean blood loss decreased (978 vs. 684 ml). Hospital stay (mean 18.1 vs. 12.6 days), major complications (24 vs. 16%), and perioperative mortality (8 vs. 2%) declined. Overall median survival was 18 months and was longer with low grade tumors (26 vs. 16 months, P = 0.03). Conclusions Patients experienced reduced EBL, fewer major complications, and shorter hospital stay, despite having higher disease burden and higher grade tumors. This suggests that even low-volume experience with CS/HIPEC can lead to a trend in reduction of adverse perioperative events with acceptable oncologic outcomes. J. Surg. Oncol. 2015 111:219–224. © 2015 Wiley Periodicals, Inc.
Regional Enteritis Involving the Duodenum

Summary A case of regional enteritis with involvement of the duodenum is presented. Regional enteritis of the duodenum may cause upper intestinal obstruction. It should be kept in mind that surgical trauma to such an area may lead to abscess and fistula formation. Regional enteritis can involve the duodenum with or without gross involvement of other portions of the gastrointestinal tract, such as the ileum, jejunum, stomach and colon. Regional duodenitis is a serious condition with a guarded prognosis. Recurrent bouts of enteritis involving other portions of the small bowel are not uncommon.
Determinants of Cauchy-Riemann operators as τ-functions

The τ-functions introduced by Sato, Miwa, and Jimbo for the deformation theory associated with the Riemann-Hilbert problem on P1 is shown to be a determinant for a singular Cauchy-Riemann operator whose domain incorporates functions with prescribed branching behavior. The analysis relies heavily on previous work of Malgrange on monodromy preserving deformation theory.
Probabilistic methods for design assessment of reliability with inspection

Conventional gas turbine rotor life prediction methodologies are based on nominal conditions that do not adequately account for material and manufacturing anomalies that can degrade the structural integrity of high-energy rotors. To account for these anomalies, the Rotor Integrity Subcommittee of the Aerospace Industries Association recommended adoption of a probabilistic damage tolerance approach to supplement the current safe-life methodology. The recommendation led to the development of a computer program called DARWIN that computes the probability of fracture as a function of flight cycles, considering random defect occurrence and location, random inspection schedules, and several other random variables. The probabilistic fatigue analysis methodology developed for DARWIN to address hard alpha material anomalies is presented. The capability of this computer program is demonstrated using several realistic rotor models provided by aircraft engine manufacturers. It is shown that the life approximation function and importance sampling methods significantly reduce computation time (nearly two orders of magnitude) compared to the Monte Carlo method. In addition, an optimal zone sampling strategy is presented that can minimize the total number of samples required to achieve e a a desired sampling accuracy result for a given confidence interval. This probabilistic methodology can be used to focus design efforts on variables that have the most influence on risk reduction.
Solid‐State nuclear magnetic resonance investigation of solvent dependence of tyrosyl ring motion in an enzyme

Tyrosyl ring motions in alpha-lytic protease were investigated by solid-state deuterium nuclear magnetic resonance (NMR) spectroscopy in lyophilized enzyme powder, in powder suspended in organic solvents, and in aqueous crystals. Ring flipping rates were determined by examining deuterium quadrupole echo line shapes. Of the four Tyr residues in the enzyme, one was flipping at the slow ( or =10(7) s(-1)) exchange limit of the line shape experiment in all the environments tested. Flipping rates of the remaining two Tyr residues depended markedly on the solvent, with the lowest flipping rates ( or =10(7) s(-1) in aqueous crystals. The deuterium spectrum of native alpha-lytic protease was compared with that of the enzyme whose active center was covalently modified with an inhibitor, which binds next to Tyr-123, constraining its ring. This experiment revealed that water addition to acetonitrile specifically increased the flipping rate of this active center residue. Librational motions ("wobbling"), estimated by their effect on spin-lattice relaxation times, were slowest in the anhydrous solvents, intermediate in the hydrated solvents, and fastest in the aqueous crystals. Thus, alpha-lytic protease is more rigid in organic solvents than in water, as judged by mobility of its tyrosyl residues. Water stripping by hydrophilic solvents did not increase enzyme rigidity, nor were there clear correlations between mobility and either enzymatic activity or solvent dielectric constant.
The size and position of heterologous insertions in a silent locus differentially affect pilin recombination in Neisseria gonorrhoeae.

Gonococcal pilus antigenic and phase variation result from unidirectional, RecA-dependent recombination of DNA sequences from a silent pilin copy (pilS ) into the expressed pilin gene (pilE ). To develop a quantitative assay for pilin gene recombination that is independent of phase variation, a promoterless cat gene was inserted into pilS, and recombination of ′cat into pilE was detected by selection of chloramphenicol-resistant (CmR) variants expressing ′cat from the pilin promoter. Although RecA-dependent CmR variants occurred, none were generated by the simple transfer of ′cat into pilE. Instead, each CmR variant contained a new pilin locus that was a hybrid of sequences from the pilE and the pilS1::′cat loci in addition to the two starting loci. Therefore, this system could not be used to quantify antigenic variation. However, combined studies of these hybrid loci and of recombination products generated during additional pilS mutational analyses demonstrated that both the size and position of an insertion in pilS differentially affect pilin recombination. Also, the hybrid loci appear to be intermediates of antigenic variation. This enabled the creation of molecular models for the recombination reactions that result in pilin antigenic variation.
HLA-B27 transgenic mice are susceptible to collagen-induced arthritis: type II collagen as a potential target in human disease.

Abstract HLA-B27 is highly linked with a group of human diseases called spondyloarthropathies (SpA). Many of these disorders begin after an infection with an enterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are not known. Proteins such as collagen and proteoglycans have been thought to be potent autoantigens in arthritidis including B27-associated human diseases. Type II collagen is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in patients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgenic animals. To determine whether CII may be a target antigen in the B27-linked diseases, B27 + mβ 2 m o/o (HLA-B27 transgenic mice lacking mouse β 2 m with and without human β 2 m) mice were immunized with type II collagen inside the barrier facility. Male HLA-B27 transgenic mice developed collagen-induced arthritis compared to transgene negative littermates or female counterparts. There was no difference in the incidence of arthritis in HLA-B27 transgenic mice with and without human β 2 m. Our data suggest that β 2 m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the development of arthritis. Our data also suggest that CII may be a potential target antigen in the cartilage during the disease process.
Everybody's Going: City Newspapers and the Early Mass Market for Movies:

The emergence of the mass market as a concept ordering distinctions in urban space is investigated through newspaper reporting and promotion of early movie‐going in Toronto, 1907–1916. The analysis...
Proctolin and excitation of the crayfish swimmeret system

The ventral nerve cord of crayfish contains axons of five pairs of excitatory interneurons, each of which can activate the swimmeret system. Perfusion of the ventral nerve cord with the neuropeptide proctolin also activates the swimmeret system. The experiments reported here were conducted to test the hypothesis that one or more of these excitatory interneurons uses proctolin as a transmitter. Each of the five excitatory axons was located and stimulated separately in an individual crayfish, and similar motor activity was elicited by stimulating each of them. Quantitative comparison of spontaneous swimmeret motor patterns with activity caused by stimulating one of these excitatory axons, EC, or by perfusing with proctolin solutions showed that the motor patterns produced under these three conditions were not significantly different (P > 0.05). By using a new, affinity-purified proctolin antiserum, we labeled axons in the connective tissue between the last thoracic and first abdominal ganglion and compared the positions of labeled axons with the previously described positions of the excitatory axons. About 0.3% of the axons in these connective tissues showed proctolin-like immunoreactivity, but heavily labeled pairs of axons did occur bilaterally in the regions of excitatory swimmeret axons. The projections of these labeled axons into the abdominal ganglia were traced in serial plastic sections. Labeled processes were abundant in the lateral neuropils, the loci of the swimmeret pattern-generating circuitry. From this evidence, we propose that three of these excitatory swimmeret interneurons use proctolin as a transmitter, but that a fourth does not. The evidence for the fifth axon is ambiguous.