cssi/SciSciGPT-SciSciNet huggingface dataset:
Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia.

Abstract The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.
Electroweakinos Hiding in Higgs Searches

Direct production of electroweakly charged states may not produce the high-energy jets or the significant missing energy required in many new physics searches at the LHC. However, because these states produce leptons, they are still potentially detectable over the sizeable standard model backgrounds. We show that current LHC Higgs searches, particularly in the $W{W}^{*}$ and $Z{Z}^{*}$ channels, are sensitive to new electroweak states, such as supersymmetric charginos or neutralinos. Indeed, the $1.7\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ Higgs searches can provide the strongest limits in certain regions of parameter space, extending the LEP bound up to $\ensuremath{\sim}200\text{ }\text{ }\mathrm{GeV}$ in some cases. Additionally, electroweakino production can form an interesting physics background for Higgs searches, especially at low luminosity and statistics. We show that dilepton searches with low missing energy requirements are complementary to existing searches in exploring regions of parameter space where new electroweak states are light or have compressed spectra.
Online knowledge-based support vector machines

Prior knowledge, in the form of simple advice rules, can greatly speed up convergence in learning algorithms. Online learning methods predict the label of the current point and then receive the correct label (and learn from that information). The goal of this work is to update the hypothesis taking into account not just the label feedback, but also the prior knowledge, in the form of soft polyhedral advice, so as to make increasingly accurate predictions on subsequent examples. Advice helps speed up and bias learning so that generalization can be obtained with less data. Our passive-aggressive approach updates the hypothesis using a hybrid loss that takes into account the margins of both the hypothesis and the advice on the current point. Encouraging computational results and loss bounds are provided.
The effects of salt concentration and pH upon water-binding, water-holding and protein extractability of turkey meat

Summary The effects of salt concentration and pH upon protein extractability and water-binding by homogenates of turkey breast, thigh and drumstick meat, and also the effect of salt concentration and centrifugal force upon water-binding of raw meat and water-holding of cooked meat from breast and thigh were studied. Concentrations of sodium chloride above 0.3 M caused swelling of meat homogenates. With the pH value adjusted to 6.0 and with sodium chloride concentrations greater than 0.6 M, breast meat was able to swell more than leg meat. Water-binding increased with increasing pH value. Breast meat homogenates had more extractable protein than leg meat homogenates and protein extraction was increased by increasing both salt concentration and pH. Cooked breast meat retained more water than leg meat with or without salt. At low concentrations of salt, cooked breast meat retained more water than raw meats, but this was reversed at higher salt concentrations.
Abstract 4024: Understanding the role of mitochondria in the progression from normal fibroblasts to DCIS associated fibroblasts

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background and Purpose: Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer which may progress to invasive breast cancer. Many studies have focused on the epithelial cell mechanisms of progression from normal breast tissue to DCIS. However, in this study we want to study mechanisms of progression in cancer associated fibroblasts from normal breast tissue to DCIS. Loss of caveolin 1 (CAV1) in fibroblasts is a marker of reduced mitochondrial membrane potential and is a prognostic biomarker in ductal carcinoma in situ. High mitochondrial membrane potential in epithelial cells is a crucial determinant of carcinogenesis. Methods: In the study we use MCF10DCIS as a model for DCIS. MCF10DCIS.com (MCF10DCIS) is a clonal breast cancer cell line. The MCF10A, non-tumorigenic epithelial cell line, and human immortalized but non-transformed dermal fibroblasts (BJ1) were used study the difference between non-tumorigenic epithelial cells and DCIS and interactions between these two epithelial cells and fibroblasts. In order to study the interaction between epithelial cells and fibroblasts, we set up a coculture model system comprised both epithelial cells and fibroblasts. Immunofluorescence staining and confocal microscopy were used here to visualize the specific protein expression in different cell types. Results: (1) MCF10DCIS cells in coculture with fibroblasts have increased mitotracker red staining while as fibroblasts have decreased mitotracker staining compared to homotypic culture. However, coculture of MCF10A cells with fibroblasts did not change the mitotracker staining in either MCF10A or fibroblasts. (2) Loss of stromal CAV1 protein expression is observed in fibroblasts when fibroblasts are cocultured with MCF10DCIS cells compared to homotypic culture. CAV1 protein expression is unchanged in coculture with MCF10A cells. Conclusion: Previous studies have demonstrated that loss of stromal CAV1 and changes in mitochondrial membrane potential are factors involved in the transition from DCIS to invasive breast cancer. In this study we show that loss of stromal CAV1 and increases in epithelial mitochondrial membrane potential may play a role in the progression to DCIS. Citation Format: Ying-Hui Ko, Zhao Lin, Ubaldo E. Martinez Outschoorn. Understanding the role of mitochondria in the progression from normal fibroblasts to DCIS associated fibroblasts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4024. doi:10.1158/1538-7445.AM2015-4024
Uses of Aerial Surveying in Highway Design and Location

Some of uses of aerial photographs cited with special emphasis on their application in Kentucky Department of Highways projects.
ORCHESTRATING A NEAR-REAL-TIME IMAGING MISSION IN NATIONAL AIRSPACE USING A SOLAR-POWERED UAV

In September 2002, NASA’s solar-powered Pathfinder-Plus (PF+) UAV was used to collect digital imagery within the National Airspace System (NAS) over the 1400 ha Kauai Coffee Plantation on southern Kauai, HI. The U.S. Navy Pacific Missile Range Facility (PMRF), on westernmost Kauai, served as the range provider. The aircraft control station was established at PMRF, and a payload control station 25 km to the east at KCP. The transponder-equipped PF+ climbed to 21k ft within restricted PMRF airspace before entering the NAS above Kauai, where it was monitored by Honolulu Air Traffic Control. Pre-planned flight tracks were combined with spontaneous, controlled maneuvers to guide the UAV to cloud-free areas. PF+ loitered for four hours over KCP, continuously acquiring imagery with two solar-powered imaging systems. Image data were transmitted to the payload station tracking antenna at rates of 3-6 Mbit sec over a line-of-sight wireless local area network, and were available for ground station viewing, enhancement, and photo quality printing within five minutes after collection. Mission planning included development of an airspace management plan, an Application for Certificate of Authorization (COA), a Memorandum of Agreement with the FAA Honolulu Control Facility (HCF), and Notice to Airmen (NOTAM) data for issuance by the FAA Honolulu Automated Flight Service Station (AFSS).
Optimization when Cost of Optimization is Comparable to the Objective Function

Anirban Chaudhuri, Raphael T. Haftka University of Florida, Gainesville, Florida, 32601 Abstract This work deals with the time critical nature of simulation-based design of engineering systems where delays in launching the product could lead to decreased market value. This work looks at two scenarios: (a) fixed function evaluation budget, and (b) cost included as a significant part of the objective function. For the first case, the implications of switching from an adaptive sampling strategy in surrogate-based optimization to a pure exploitation of surrogate prediction was investigated for test functions with competitive and non-competitive local optima. For the second case, an optimization formulation was proposed to include the cost in the objective function. In this case the cost affected not only the sampling process but also the stopping criterion for the algorithm.
Two-Dimensional, Acene-Containing Conjugated Polymers That Show Ratiometric Fluorescent Response to Singlet Oxygen

This paper describes two-dimensional conjugated poly(phenylene–ethynylene)s (PPEs) linked to singlet oxygen-reactive diethynyltetracene units through phenylene–ethynylene (PE) bridges that are conjugated to the polymer backbones. Successive Sonogashira coupling reactions enabled the preparation of the tetracene-containing PE pendants, the linking of the pendants to the monomer unit, and the polymerization reactions. Small molecule models of the polymers showed ratiometric responses of fluorescence upon exposure to photogenerated singlet oxygen due to cycloaddition reactions increasing the excited state of individual chromophores. The fluorescent responses of the tetracene-linked PPEs, however, showed markedly different behavior: (i) an initial increase in fluorescence intensity and fluorescence lifetime of the side-chain tetracenes upon exposure to 1O2 indicated an analyte-induced slowing of self-quenching due to high local acene concentration, and (ii) ratiometric blue-shifted response did not occur unti...
Surface-wave studies of some South Carolina earthquakes

Long-period surface waves generated by three South Carolina earthquakes are used to infer focal mechanisms and seismic moments of the events. The 3 February 1972 Bowman, South Carolina, earthquake is found to be shallow and to require an almost strike-slip focal mechanism with pressure axes trending northeast-southwest. The 22 November 1974 Charleston, South Carolina, earthquake was smaller and was recorded by only three long-period WWSSN stations. For this earthquake, only an estimate of the seismic moment and focal depth were possible. The focal mechanism of the 2 August 1974 Clarkhill reservoir earthquake indicated motion on a northwest striking almost vertical dip-slip fault. In order to specify preferred motions on the nodal planes, full waveform modeling of the long-period traces at ATL was necessary. The results are not without ambiguity, but represent the best estimates of source parameters for these earthquakes.
The Impact of Stone Supply Stress on the Innovation of a Cultural Variant: The Relationship of Folsom and Midland

Multiple hypotheses have been proposed to explain the relationship between fully fluted Folsom points and unfluted Midland points. One hypothesis, proposed by Hofman (1992, “Recognition and interpretation of Folsom technological variability on the southern plains.” In Ice Age Hunters of the Rockies, edited by D. J. Stanford, and J. S. Day, 193–229. Boulder: University Press of Colorado), is that mobile Folsom bands shifted from making Folsom points, which often fatally broke during the production process, to less risky Midland points as stone supplies dwindled. In cultural evolutionary terms, this hypothesis proposes that an increase in local, site-scale functional controls, specifically stone supply stress, resulted in the modification of the existing Folsom point production recipe and led to the adoption of a new cultural variant, the Midland point. After testing archaeological implications of Hofman's hypothesis, I conclude that it is empirically supported and does explain the innovation of the Midland...
How do we use state of the art vestibular testing to diagnose and treat the dizzy patient? An overview of vestibular testing and balance system integration.

State of the art vestibular function testing is necessary to confirm patient complaints. It is only when these tests are used in conjunction with etiologic investigation that accurate and effective patient treatment can occur. This approach is not only realistic but cost effective when compared with months and years of symptomatic therapy.
Transforming mixed-signal circuits class through SoC FPAA IC, PCB, and toolset

We present a SoC large-scale Field Programmable Analog Array (FPAA) test system, enabled by configurable analog-digital ICs to create a simple interface for a wide range of experiments in classroom environments. This configurable system appears as a simple digital peripheral using a standard USB interface for communication and power. Combined with a high-level tool flow for on-chip application design, this FPAA device demonstrates a number of mixed-signal computations, classification, and signal processing and its impact on hands-on circuit instruction.
Incorporating Multicultural Counselling and Gender Issues into Rehabilitation Counsellor Education

In today’s rapidly changing society, counsellors need to have knowledge and skills to work effectively with a diverse consumer population. A review of rehabilitation counsellor education programs in the United States applying for CORE (Council on Rehabilitation Education) re-accreditation between 1991–1994 revealed that two-thirds of the programs had content deficits in multicultural and gender issues. Australia and other countries besides the United States have experienced increases in the number of cultural minorities entering the workforce. The role of women in the modern workforce also has undergone significant change. These issues need to be considered by rehabilitation counsellors in all countries. The importance of infusing these content areas in graduate training is addressed. The authors offer suggestions for infusion of cultural and gender issues into rehabilitation counselling curricula.
Bloomsbury and the Revolution in Aesthetics

Given the importance of the bonds of community and friendship it would have been strange if graduation from Cambridge had caused the Apostles to lose touch with each other. In fact, Moore’s ‘highest good’ proved strong enough to withstand the requirements of making a living. As is well known, most of the Apostles of Keynes’s generation settled in London in close proximity to each other, and from the original ‘at homes’ of some of them a new association eventually sprang up, looser than the Society, but one that, in time, would be a very important force in the cultural life of Britain. Perhaps because the influence of Bloomsbury — in view of some — was not totally wholesome, there has been an unnecessary effort, even on the part of some Bloomsberries, to deny its very existence. Thus Clive Bell asks, ‘Who are the members of Bloomsbury? For what do they stand?’ Both questions are easy to answer. The core of Bloomsbury comprised Roger Fry, the Stephen sisters — Vanessa and Virginia — their husbands, Clive Bell and Leonard Woolf, Duncan Grant, Lytton Strachey and Keynes. And they stood quite simply for changing the cultural values of the nation away from utilitarianism and towards Moorean ultimates. They were in the anti-Benthamite tradition of those writers who viewed themselves as having a mission to teach higher values to the masses, and especially to prevent their being swallowed up by the crassness of a commercial civilisation.
How accurately can students evaluate the quality of self-generated examples of declarative concepts? Not well, and feedback does not help

Abstract Students are commonly asked to learn declarative concepts in many courses. One strategy students report using involves generating concrete examples of abstract concepts. If students have difficulties evaluating the quality of their generated examples, then instructors will need to provide students with appropriate scaffolds or feedback to improve judgmentaccuracy. No prior research has investigated if students can accurately evaluate the quality of the examples they generate, which was the first aim of the current research. The second aim of this research was to investigate the extent to which providing feedback while students evaluate their generated examples can improve the accuracy of their example-quality judgments. In two experiments, students generated examples for declarative concepts from social psychology and then judged the quality of their examples. When making judgments, students received no feedback (in which they were only given the key term), full definition feedback (in which they were shown the definition of the declarative concept) or idea unit feedback (in which they first evaluated if they represented each idea unit of the definition within their example). Outcomes showed that students were overconfident when judging the quality of their examples, specifically for commission errors (i.e., examples that were entirely incorrect). Surprisingly, full definition and idea unit feedback did not help students improve the accuracy of their example-quality judgments. Thus, until scaffolds are discovered to reduce student overconfidence, instructors will need to assist in evaluating generated examples as students use this strategy to learn declarative concepts.
High-quality draft genome sequence of Thermocrinis jamiesonii GBS1T isolated from Great Boiling Spring, Nevada

The draft genome of Thermocrinis jamiesonii GBS1T is 1,315,625 bp in 10 contigs and encodes 1,463 predicted genes. The presence of sox genes and various glycoside hydrolases and the absence of uptake NiFe hydrogenases (hyaB) are consistent with a requirement for thiosulfate and suggest the ability to use carbohydrate polymers.
P074 : IDENTIFICATION OF NOVEL HLA ALLELES IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS

Background Identification of novel HLA alleles is a common finding in the HLA lab. This finding is particularly challenging in hematopoietic cell transplant (HCT) patients since may prevent them from finding HLA matched donors. In addition, somatic mutations can occur in blast cells of patients with hematological malignancies and are attributed to a mechanism of immune evasion. Herein, we describe the approach used at the University of Chicago Transplant Immunology Laboratory for patients with hematological malignancies who were evaluated for HCT work-up. DNA from recipients who carried novel HLA alleles detected in peripheral blood (PBL) were confirmed in recipient’s germline DNA obtained from buccal cells. Methods DNA was isolated from peripheral blood cells and buccal cells of 5 patients by automated and manual methods. The novel HLA-A, B, C, and DQB1 genes were amplified by polymerase chain reaction (PCR) using locus specific primers. Exons 2 through 4 for HLA-A, B, C, and exons 2 and 3 for HLA-DQB1 were sequenced by Atria sequencing kits, and analyzed by Assign 3.6 SBT Software (Abbot Molecular, Des Plaines, IL). Results Novel alleles were confirmed in buccal cells of patients 1, 2, 3 and 4. Patient 5 only carried the new allele in the blast cells. Patient 1 had a matched related donor (MRD) that carried the same polymorphism at HLA-DQB1 locus. Patients 2 and 3 did not have MRD, and due to presence of novel allele in the HLA-B locus, an 8/8 matched unrelated donor (MUD) could not be found. For patient 4, the polymorphism was located outside of the hypervariable region and was classified as a group of alleles which have the same antigen binding domains (P group). Patient 4 was most likely to find an 8/8 MUD due to this classification. For patient 5 the new allele was only present on DNA from somatic cells, did not affect donor searches, and multiple MUD were available through the National Marrow Donor Registry (NMDP). Conclusions Identification of novel alleles is a common finding that can affect HCT donor searches. Confirmation of genomic versus somatic nature of the polymorphisms through typing related relatives and/or DNA from an alternative source such as buccal cells might be of help for donor selection.
Development and Testing of the MyHealthyPregnancy App: A Behavioral Decision Research-Based Tool for Assessing and Communicating Pregnancy Risk.

Background: Despite significant advances in medical interventions and health care delivery, preterm births in the United States are on the rise. Existing research has identified important, seemingly simple precautions that could significantly reduce preterm birth risk. However, it has proven difficult to communicate even these simple recommendations to women in need of them. Our objective was to draw on methods from behavioral decision research to develop a personalized smartphone app-based medical communication tool to assess and communicate pregnancy risks related to preterm birth. Objective: A longitudinal, prospective pilot study was designed to develop an engaging, usable smartphone app that communicates personalized pregnancy risk and gathers risk data, with the goal of decreasing preterm birth rates in a typically hard-to-engage patient population. Methods: We used semistructured interviews and user testing to develop a smartphone app based on an approach founded in behavioral decision research. For usability evaluation, 16 participants were recruited from the outpatient clinic at a major academic hospital specializing in high-risk pregnancies and provided a smartphone with the preloaded app and a digital weight scale. Through the app, participants were queried daily to assess behavioral risks, mood, and symptomology associated with preterm birth risk. Participants also completed monthly phone interviews to report technical problems and their views on the app’s usefulness. Results: App use was higher among participants at higher risk, as reflected in reporting poorer daily moods (Odds ratio, OR 1.20, 95% CI 0.99-1.47, P=.08), being more likely to smoke (OR 4.00, 95% CI 0.93-16.9, P=.06), being earlier in their pregnancy (OR 1.07, 95% CI 1.02-1.12, P=.005), and having a lower body mass index (OR 1.07, 95% CI 1.00-1.15, P=.05). Participant-reported intention to breastfeed increased from baseline to the end of the trial, t15=−2.76, P=.01. Participants’ attendance at prenatal appointments was 84% compared with the clinic norm of 50%, indicating a conservatively estimated cost savings of ~US $450/patient over 3 months. Conclusions: Our app is an engaging method for assessing and communicating risk during pregnancy in a typically hard-to-reach population, providing accessible and personalized distant obstetrical care, designed to target preterm birth risk, specifically. [JMIR Mhealth Uhealth 2017;5(4):e42]
“Pressing the Wrong Button”: Pynchon’s Postmodernism and the Threat of Nuclear War in The Crying of Lot 49

Drawing on recent and excellent critical work uncovering Pynchon’s relation to the historical moment in which his novels were written, this article argues that Pynchon’s The Crying of Lot 49 is motivated by an uncertainty that can be traced to the potential deployment of the bomb. I begin by examining the characteristically postmodern features of Pynchon’s text—its investigation of the communicative properties of language and its fracturing of a cohesive narrative into contingency and chance—to uncover their political valences. I argue that the text pivots around a nuclear anxiety that becomes evident in Pynchon’s treatment of language as communication and that links current generations to future ones. The bomb threatens to undo narrative progression, connecting Pynchon’s famously bizarre narrative to the development of nuclear weaponry: from its inception, the bomb was designed to never realize its own use, ushering an era where narrative progression deteriorates into absurdity.
Forward: To Prevent and to Punish: An International Conference in Commemoration of the Sixtieth Anniversary of the Genocide Convention

Introduction to An International Conference in Commemoration of the Sixtieth Anniversary of the Genocide Convention.
SICS: Secure and dynamic middlebox outsourcing

Outsourcing middleboxes brings threats to the enterprise's private information including the trafflc and rules of middleboxes. We present a secure and dynamic middlebox outsourcing framework SICS, short for Secure In-Cloud Service. SICS encrypts each packet header and uses a label for in-cloud rule matching, which enables the cloud to perform its functionalities correctly with minimum header information leakage.
Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

Author(s): Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.; Vinson, David R. | Abstract: Introduction: Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. Methods: From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Results: Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III-V), comparable to the larger cohort (pg0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0-3.0) and four had a supratherapeutic INR (g3.0). Fifteen patients (42%) had at least one subtherapeutic INR (l2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. Conclusion: We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence.
Drift-Invariant Detection for Multilevel Phase-Change Memory

Next-generation memory (NGM) technologies present a major opportunity but also a significant challenge, due to their intricate reliability issues. In particular, multilevel-cell (MLC) storage is highly desirable for increasing storage capacity and lowering total cost-per-bit. In phase-change memory (PCM), MLC storage is hampered by sensitivity to temperature variations and resistance drift. A novel drift-invariant detection (DID) scheme that estimates variable read thresholds based on ordered statistics and clustering of the soft read-back signals from a small block of 32 cells has been developed and implemented in hardware to improve reliability and prolong data retention. A low-complexity implementation of the DID on a FPGA platform comprises 20'000 LUTs and 6'000 flip-flops and has a latency of 90ns. We present results from an extensive performance verification that ascertains highly reliable data retrieval up to 13 orders of magnitude in time after programming. Such elevated reliability is necessary for the most anticipated application of NGM, namely persistent far-memory, where the NGM is used as a large memory pool, possibly together with DRAM.
Anti-Patterns in Infrastructure as Code

In DevOps, infrastructure as code (IaC) scripts are used by practitioners to create and manage an automated deployment pipeline that enables IT organizations to release their software changes rapidly at scale. Low quality IaC scripts can have serious consequences, potentially leading to wide-spread system outages and service discrepancies. The goal of this research is to help practitioners increase the quality of infrastructure as code (IaC) scripts by identifying anti-patterns in IaC scripts and development of IaC scripts. Using open source repositories, we conduct three initial studies to (i) quantify the frequency and categorize the defects in IaC scripts; and (ii) identify operations that characterize defective IaC scripts. Based on our empirical analysis we observe (i) the dominant defect defect categories to be related to syntax and configuration assignments, and (ii) three operations that characterize defective IaC scripts. The above-mentioned findings motivate us to identify anti-patterns in IaC scripts and IaC development. To this end, we propose three studies that identify (i) process anti-patterns; and (ii) security-related anti-patterns in IaC.
LIBRA: Thermal and Process Variation Aware Reliability Management in Photonic Networks-on-Chip

Silicon nanophotonics technology is being considered for future networks-on-chip (NoCs) as it can enable high bandwidth density and lower latency with traversal of data at the speed of light. But, the operation of photonic NoCs (PNoCs) is very sensitive to on-chip temperature and process variations. These variations can create significant reliability issues for PNoCs. For example, a microring resonator (MR) may resonate at another wavelength instead of its designated wavelength due to thermal and/or process variations, which can lead to bandwidth wastage and data corruption in PNoCs. This paper proposes a novel run-time framework called LIBRA to overcome temperature- and process variation- induced reliability issues in PNoCs. The framework consists of (i) a device-level reactive MR assignment mechanism that dynamically assigns a group of MRs to reliably modulate/receive data in a waveguide based on the chip thermal and process variation characteristics; and (ii) a system-level proactive thread migration technique to avoid on-chip thermal threshold violations and reduce MR tuning/ trimming power by dynamically migrating threads between cores. Our simulation results indicate that LIBRA can reliably satisfy on-chip thermal thresholds and maintain high network bandwidth while reducing total power by up to 61.3 percent, and thermal tuning/trimming power by up to 76.2 percent over state-of-the-art thermal and process variation aware solutions.
Antigenic Variation of the VSP Genes of Giardia Lamblia

Giardia lamblia, a protozoan parasite inhabiting the small intestine, is a common infection worldwide that frequently results in chronic diarrhea, malabsorption and upper gastrointestinal symptoms. Giardia undergoes surface antigenic variation in humans and animal model infections, a phenomenon that may account for both chronicity of infections and the relatively broad mammalian host specificity with genotypically identical organisms found in humans, cats, beavers, and other mammals. The variant-specific surface proteins (VSPs) are an unusual family of related cysteine-rich proteins, from 50 kD to over 200 kD in size, that coat the surface of the trophozoite. Only one VSP of the estimated 150 or more vsp genes is expressed on an individual at any specific time. However, the repertoires of vsp genes may differ depending on the genetic group. VSPs switch spontaneously every 6–12 generations although some Giardia also switch during encystation/excystation. All VSPs have a high cysteine content of about 12 % cysteines that are mostly present as CXXC motifs as well as a highly conserved C-terminus, a surface Zn finger motif, a GGCY motif and other common features. The biological function(s) of VSPs are uncertain but they undergo both immune and biological selection. The molecular mechanism(s) involved in antigenic variation are unknown but because there is the absence of gene movement or gene mutations and only one of 4 practically identical alleles (Giardia are tetraploid) is expressed; epigenetic processes are likely involved. Further studies of the mechanism of antigenic variation and the biological role of the VSPs promise to contribute to our understanding of G. lamblia and its pathogenesis.
Fluorescent In Situ Hybridization

Fluorescence in situ hybridization (FISH) arose from a marriage of classical DNA hybridization in solution to modern molecular biologic techniques, most notably the use of restriction endonucleases and, later, the polymerase chain reaction (PCR). The former has made identification of both genes and relevant interspersed sequences possible, whereas without the latter, many widely used probes would not be available. FISH allows one to localize a specific DNA sequence to a specific chromosome, region of a chromosome, or cell type. Generally, the morphology of the chromosome, cell, or tissue of interest is preserved to permit unambiguous identification of the target (1–3). Consequently, the technique has been widely used in a variety of venues. Gene mapping (4), chromosome identification (5), demonstration of gene amplification in some solid tumors (6,7), identification of chimeric populations, minimal residual disease, and tumor cells admixed in normal tissue (8,9) are just a few examples. The advantages of modern FISH techniques include: 1. Simple, straightforward, standardized techniques 2. Wide assortment of probes available commercially 3. Double labeling and use of multiple probes on a single cell 4. Rapid turnaround times (anywhere from 4 h to a maximum of 48 h).
In Praise of Pedantic Eclecticism: Pitfalls and Opportunities in the Psychology of Judging

This Chapter was written for a collection of essays about the psychology of judging. The Chapter examines some methodological aspects related to experimentation of judging. In particular, it addresses the prevailing concern with external validity. Two central points will be made here. First, it is important to acknowledge that all types of validity are intricately intertwined. Attempting to fix one aspect of validity can be overwhelmed by greater compromises in other aspects. For example, a proposal by Fred Schauer to compare the performance of judges to lay people in complex judicial decision making tasks stands to suffer from low construct validity, thus leading to uninterpretable results. To maximize validity, one needs to be pedantic about the design of the entire study. At the same time, the concern with external validity should not be exaggerated. The discrepancy between the experimental environment and real world settings does not automatically bar all applications of findings from the former to the latter. It does, however, require a cautious application and oftentimes a lot of data. When experimental findings do meet the rigorous demands of external validity and context-attentiveness, they can be applied to real world domains, including specialized ones. This possibility opens up the field of judging to a range of methodological approaches and thus offers the benefit of insights originating from diverse scientific perspectives. To demonstrate the possibilities in this regard, the discussion will center on the application of a particular body of research - coherence based reasoning - to judging.
KEEPING QUALITY OF DAIRY PRODUCTS OBTAINED AT RETAIL OUTLETS

Summary A study was made of the bacteriological and keeping quality of low-fat milk, skimmilk, and chocolate flavored milk obtained at retail outlets. Approximately 62% of the low-fat milk samples, 81% of the skimmilk samples, and 93% of the chocolate flavored milk did not have a satisfactory flavor score (36.0 or higher) after storage at 40 ± 2 F for 14 days. The samples ranged in age from 0 to 15 days at time of purchase, the average age being 4.3 days (low-fat milk), 5.3 days (skimmilk), and 5.9 days (chocolate flavored milk). The average days kept at 40 ± 2 F after purchase was 9.5 days (low-fat milk), 7.4 days (skimmilk), and 5.9 days (chocolate flavored milk). Highly significant correlations were observed between: purchase age and initial flavor; days kept and SPC on purchase day, and days kept and SPC after 7 days' storage. The quality of products of an individual brand tended to be similar; whereas, significant quality differences were observed between brands.
Hypothesis‐driven investigations of diverse pharmacological targets in two mouse models of autism

Autism spectrum disorder is a neurodevelopmental syndrome diagnosed primarily by persistent deficits in social interactions and communication, unusual sensory reactivity, motor stereotypies, repetitive behaviors, and restricted interests. No FDA-approved medical treatments exist for the diagnostic symptoms of autism. Here we interrogate multiple pharmacological targets in two distinct mouse models that incorporate well-replicated autism-relevant behavioral phenotypes. Compounds that modify inhibitory or excitatory neurotransmission were selected to address hypotheses based on previously published biological abnormalities in each model. Shank3B is a genetic model of a mutation found in autism and Phelan-McDermid syndrome, in which deficits in excitatory neurotransmission and synaptic plasticity have been reported. BTBR is an inbred strain model of forms of idiopathic autism in which reduced inhibitory neurotransmission and excessive mTOR signaling have been reported. The GABA-A receptor agonist gaboxadol significantly reduced repetitive self-grooming in three independent cohorts of BTBR. The TrkB receptor agonist 7,8-DHF improved spatial learning in Shank3B mice, and reversed aspects of social deficits in BTBR. CX546, a positive allosteric modulator of the glutamatergic AMPA receptor, and d-cycloserine, a partial agonist of the glycine site on the glutamatergic NMDA receptor, did not rescue aberrant behaviors in Shank3B mice. The mTOR inhibitor rapamycin did not ameliorate social deficits or repetitive behavior in BTBR mice. Comparison of positive and negative pharmacological outcomes, on multiple phenotypes, evaluated for replicability across independent cohorts, enhances the translational value of mouse models of autism for therapeutic discovery. GABA agonists present opportunities for personalized interventions to treat components of autism spectrum disorder. Autism Res 2019, 12: 401-421 © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Many of the risk genes for autism impair synapses, the connections between nerve cells in the brain. A drug that reverses the synaptic effects of a mutation could offer a precision therapy. Combining pharmacological and behavioral therapies could reduce symptoms and improve the quality of life for people with autism. Here we report reductions in repetitive behavior by a GABA-A receptor agonist, gaboxadol, and improvements in social and cognitive behaviors by a TrkB receptor agonist, in mouse models of autism.
8 – Technology, Science and the Arts

“When nations grow old the Arts grow cold, And Commerce settles on every tree.” WILLIAM BLAKE (1757–1827)
Associations of Sleep Duration With Cardiometabolic Outcomes in American Indians and Alaska Natives and Other Race/Ethnicities: Results From the BRFSS

Abstract Objectives This study assessed the associations between short and long sleep duration and prevalence of cardiometabolic outcomes in American Indians and Alaska Natives (AI/ANs) and compared these associations to those evident among other race/ethnicities. Methods We analyzed data from the 2013-2014 Behavioral Risk Factor Surveillance System. In total, 14,536 AI/ANs, 729,962 non-Hispanic whites, 71,765 blacks, and 59,472 Hispanics were included. Logistic regressions were conducted to compute unadjusted and adjusted odds ratios (OR) for the associations of interest. Results Among AI/ANs, 38.6% reported sleeping Conclusions Future studies are warranted to examine race/ethnic variability in the association between sleep duration and cardiometabolic outcomes.
Putting the Human in the Time Series Analytics Loop

Time series are one of the most common data types in nature. Given this fact, there are dozens of query-by-sketching/ query-by-example/ query-algebra systems proposed to allow users to search large time series collections. However, none of these systems have seen widespread adoption. We argue that there are two reasons why this is so. The first reason is that these systems are often complex and unintuitive, requiring the user to understand complex syntax/interfaces to construct high-quality queries. The second reason is less well appreciated. The expressiveness of most query-by-content systems is surprisingly limited. There are well defined, simple queries that cannot be answered by any current query-by-content system, even if it uses a state-of-the-art distance measure such as Dynamic Time Warping. In this work, we propose a natural language search mechanism for searching time series. We show that our system is expressive, intuitive, and requires little space and time overhead. Because our system is text-based, it can leverage decades of research text retrieval, including ideas such as relevance feedback. Moreover, we show that our system subsumes both motif/discord discovery and most existing query-by-content systems in the literature. We demonstrate the utility of our system with case studies in domains as diverse as animal motion studies, medicine and industry.
Effects of marked hypertriglyceridemia and lipid clearance techniques on canine biochemistry testing.

Triglyceride concentrations in dogs with hyperlipidemic disorders can exceed concentrations used by assay manufacturers for interference testing. High-speed centrifugation or the polar solvent LipoClear reduce triglyceride concentrations, but efficacy requires evaluation in veterinary species. We determined the effect of marked hypertriglyceridemia on canine biochemistry testing; assessed the ability of high-speed centrifugation or LipoClear to correct lipemic interferences; and determined if LipoClear introduces inaccuracy into biochemistry assays. Fifteen pooled canine serum samples were aliquoted and spiked with equal volumes of water or Intralipid [triglyceride concentration 33.9 mmol/L (3,000 mg/dL)]. Intralipid aliquots underwent lipid removal by high-speed centrifugation or LipoClear treatment, and a water-spiked aliquot underwent LipoClear treatment. Biochemistry panels were performed using a Vitros 4600 chemistry analyzer. Results were compared by paired t-test or Wilcoxon test. Total observed errors were considered clinically acceptable if below veterinary allowable total error (TEa) guidelines. Statistically significant (p ≤ 0.05) interferences were introduced by Intralipid for 15 of 15 analytes. Median observed error exceeded TEa for potassium and enzymatic carbon dioxide, neither of which were identified by the manufacturer as susceptible to lipemic interference. After centrifugation, median observed error exceeded TEa for potassium and chloride. LipoClear treatment resulted in median errors that exceeded TEa for total protein, chloride, and phosphorus. Given that severe lipemia can occur in dogs with primary or secondary hyperlipidemia, veterinary laboratories should perform their own interference testing at triglyceride concentrations relevant to their patient population and provide this information to clinicians to ensure optimal case management.
Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis

Abstract Chemerin (RARRES2) is an endogenous leukocyte chemoattractant known to recruit innate immune cells through its chemotactic receptor, CMKLR1. RARRES2 is often downregulated in prostate cancer and across multiple tumor types compared to normal tissue. Additionally, a methylome-wide analysis identified RARRES2 as one of the most hypermethylated genes in sarcoma. Recent studies have shown that augmenting chemerin in the tumor microenvironment significantly suppresses tumor growth, at least in part by recruitment of immune effector cells. However, as tumor cells have been shown to express functional chemokine receptors that can impact their phenotype, we hypothesized that chemerin might have additional, tumor-intrinsic effects. Here, we show for the first time that human cancer cells exposed to exogenous chemerin significantly upregulate PTEN expression and activity. Additionally, chemerin-induced PTEN expression correlated with a concomitant reduction in PD-L1 mRNA and protein expression. Chemerin treatment of tumor cells led to significantly reduced tumor cell migration/invasion, as well as significantly increased cytotoxicity by T cells. siRNA knockdown of tumor expressed CMKLR1 abrogated chemerin-induced modulation of PTEN and PD-L1 expression and activity, supporting the presence of a CMKLR1/PTEN/PD-L1 signaling cascade. We then compared chemerin treatment to PD-L1 inhibition by siRNA knockdown or the antagonistic antibody atezolizumab in T cell cytotoxicity assays and surprisingly found chemerin treatment was as effective as both PD-L1 knockdown and atezolizumab treatment in mediating tumor lysis. Collectively, our data show a novel link between chemerin, PTEN and PD-L1 in human tumor lines, with functional consequences that may have a role in improving T cell-mediated immunotherapies.
Electro-actuated valves and self-vented channels enable programmable flow control and monitoring in capillary-driven microfluidics

Microfluidics are essential for many lab-on-a-chip applications, but it is still challenging to implement a portable and programmable device that can perform an assay protocol autonomously when used by a person with minimal training. Here, we present a versatile concept toward this goal by realizing programmable liquid circuits where liquids in capillary-driven microfluidic channels can be controlled and monitored from a smartphone to perform various advanced tasks of liquid manipulation. We achieve this by combining electro-actuated valves (e-gates) with passive capillary valves and self-vented channels. We demonstrate the concept by implementing a 5-mm-diameter microfluidic clock, a chip to control four liquids using 100 e-gates with electronic feedback, and designs to deliver and merge multiple liquids sequentially or in parallel in any order and combination. This concept is scalable, compatible with high-throughput manufacturing, and can be adopted in many microfluidics-based assays that would benefit from precise and easy handling of liquids.