cssi/SciSciGPT-SciSciNet huggingface dataset:
Rearrangements at the Heterodimer Interface are Integral to NMDA Receptor Activation

Upon binding the neurotransmitter glutamate and the obligatory co-agonist glycine, NMDA receptors activate by opening a membrane permeable pore or desensitize by switching into a high-affinity non-conducting conformation. Both activation and desensitization require that the agonist-binding clamshell within each subunit closes to engulf the agonists. It has been hypothesized that this movement strains the contacts between agonist-binding domains of GluN1 and GluN2 and rupture of this interface causes receptor desensitization by disengaging agonist-binding from pore-opening. To investigate the role of inter-subunit contacts in NMDA receptor gating, we cross-linked the dimer interface by introducing cysteine residues at positions predicted to interact across subunits: N521 and L777 of GluN1 and E516 and L780 of GluN2A, respectively. Steady-state single-channel recordings indicated that cross-linked receptors had drastically reduced open probabilities (∼200-fold, Po = 0.0032) due to ∼5-fold shorter openings and ∼100-fold longer closures (means, SEM): MOT = 1.8 ± 0.2 ms, MCT = 792 ± 213 ms (n = 6; 80,028 events). However, the mean duration of closed intervals associated with desensitization remained unaltered (wt, tauD=2700 ms; mut, tauD=3150). Reduction of the disulfide bonds (10 mM DTT) significantly potentiated single channel currents (means, SEM: Po = 0.14 ± 0.02) by restoring the mean duration of openings (11.7 ± 1.6 ms) and significantly shortening mean closed durations (90 ± 19 ms), but had no discernible effects on microscopic desensitization (n = 7; 262,396 events). Based on these data, we propose that flexibility in the heterodimer interface at the level of agonist-binding domains represents an integral part of NMDA receptor activation.
On the molecular basis of the thermal sensitivity of an Escherichia coli topA mutant.

Studies of two temperature-sensitiveEscherichia coli topA strains AS17 and BR83, both of which were supposed to carry a topA amber mutation and a temperature-sensitive supD43,74 amber-suppressor, led to conflicting results regarding the essentiality of DNA topoisomerase I in cells grown in media of low osmolarity. We have therefore reexamined the molecular basis of the temperature sensitivity of strain AS17. We find that the supD allele in this strain had lost its temperature sensitivity. The temperature sensitivity of the strain, in media of all osmolarity, results from the synthesis of a mutant DNA topoisomerase I that is itself temperature-sensitive. Nucleotide sequencing of the AS17 topA allele and studies of its expected cellular product show that the mutant enzyme is not as active as its wild-type parent even at 30 °C, a permissive temperature for the strain, and its activity relative to the wild-type enzyme is further reduced at 42 °C, a nonpermissive temperature. Our results thus implicate an indispensable role of DNA topoisomerase I in E. coli cells grown in media of any osmolarity.
Psychosocial Impact of Cancer in Low-Income Rural/Urban Women: Phase II

Data reported here are from phase one of a larger ongoing study of depression and cancer-related quality of life in low-income rural and urban Southern women who have been diagnosed with breast or cervical cancer. This phase of the pilot project examined the psychosocial impact of a new diagnosis of breast or cervical cancer and identified personal issues and concerns of those diagnosed. A telephone survey design was used to solicit information from 28 low-income rural and urban Southern women regarding diagnosis, treatment, side-effects, available support systems, coping techniques, barriers to treatment, and the significance of God or spirituality during the course of their illnesses. Content analysis indicated that many similarities exist in the experiences of rural and urban women regardless of race, socioeconomic status, or residence. However, many differences exist that negatively impact and contribute to health disparity and an unequal distribution of cancer burden.
Avian Host-Selection by Culex pipiens in Experimental Trials

Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42-6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22-2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission.
Transient Effects of Pulsed Nuclear Radiation on Electronic Parts and Materials

Nuclear radiation induced transient changes in the electrical characteristics of electronic parts and materials obtained in recent experiments at the GODIVA II pulse reactor are described and discussed. The electronic parts investigated and monitored during exposure include: coaxial cables; resistors of various types and manufacture, ranging in value from 100 ohm to 1 megohm; sensistors; capacitors, ceramic and tantalum; rectifiers, silicon and selenium; and magnetic cores, ferrite. Most of the parts during exposure show transient parameter changes which exceed the tolerance values and then recover generally to the nominal value within two to five msec. This behavior is of serious concern in data and information processing equipment and in high-frequency and high-accuracy instrumentation which are exposed to such a nuclear environment, yet which must maintain their operational tolerance even for short periods of time.
Finding solutions to NP problems: philosophical differences between quantum and evolutionary search algorithms

This paper uses instances of SAT, 3SAT and TSP to describe how evolutionary search (running on a classical computer) differs from quantum search (running on a quantum computer) for solving NP problems.
Direct amplification of single-stranded DNA for pyrosequencing using linear-after-the-exponential (LATE)–PCR

Pyrosequencing is a highly effective method for quantitatively genotyping short genetic sequences, but it currently is hampered by a labor-intensive sample preparation process designed to isolate single-stranded DNA from double-stranded products generated by conventional PCR. Here linear-after-the-exponential (LATE)–PCR is introduced as an efficient and potentially automatable method of directly amplifying single-stranded DNA for pyrosequencing, thereby eliminating the need for solid-phase sample preparation and reducing the risk of laboratory contamination. These improvements are illustrated for single-nucleotide polymorphism genotyping applications, including an integrated single-cell-through-sequencing assay to detect a mutation at the globin IVS 110 site that frequently is responsible for b-thalassemia.
Solvent effects on mutual diffusion in concentrated polystyrene solutions

In a previous paper, mutual diffusion coefficients for concentrated solutions of a monodisperse polystyrene in 14 solvents were reported. In this paper, these data are reinterpreted in terms of new thermodynamic data for these solvents. These new results permit evaluation of the activity derivative, ∂ In a1/∂ In v1, and therefore enable calculation of the diffusional friction coefficient from the mutual diffusion coefficient. The friction coefficient was found to be directly proportional to solvent viscosity to within the experimental errors involved in the combined transport and thermodynamic measurements. The molecular implications of this result are discussed.
Bit interleaved coded modulation using multiple turbo codes

Bandwidth efficient coding schemes employing bit interleaved coded modulation and low complexity multiple turbo codes are investigated. The BER performance of these designs is shown to be superior to bit interleaved coded modulation schemes using conventional turbo codes.
Identification of enterotoxigenic Escherichia coli by colony hybridization with nonradioactive digoxigenin-labeled DNA probes.

Abstract Enterotoxigenic Escherichia coli (ETEC) strains were readily identified in pure and mixed cultures with nonradioactive, digoxigenin-labeled DNA probes coding for heat-labile (LTI) and heat-stable (STaI, STaII, and STb) enterotoxins. Digoxigenin-labeled ETEC fragments were more sensitive than and exhibited less nonspecific background contamination than biotinylated ETEC probes.
Multiple-Baseline and Multiple-Probe Designs: Practical Alternatives for Special Education Assessment and Evaluation

At a time when the emphasis on accountability has never been greater, single-case designs can provide invaluable assistance to those caring for the developmentally disabled. While there are many types of single-case designs that can be used to collect accurate information regarding the quality of services, the present article is restricted to a consideration of multiple-baseline and multiple-probe designs. Although certain assessment and evaluation conditions might make different single-case designs more appropriate, the inherent flexibility of multiple-baseline and multiple-probe designs gives them greater potential for educational and treatment settings. Both designs are described, illustrated, and discussed. Practical and statistical criteria for assessing the significance of changes in behavior are presented.
Nutrition education delivered at the state fair: are your portions in proportion?

Overweight and obesity afflict an estimated 64% of adults in the United States’-an 8% increase in the past decade.’ Recent reports indicate no change in physical activity; people are just as inactive now as they were 10 years In contrast, caloric intake, the other side of the energy balance equation, has increased in the past 20 years. A 200 kcallday per capita increase occurred between 1977-1978 and 1994-19966*7; a 300 kcal/day per capita increase occurred between 1985 and 2000.8 The US food supply currently provides an additional 500 kcal/day per capita compared with the 1 9 7 0 ~ . ~ T h e abundant food supply makes food inexpensive, allowing retailers to entice consumers with larger portions at a lower price. Thus, portion sizes in the retail food industry have ball o ~ n e d , ~ ~ ’ ~ encouraging excessive caloric intake.”-’3 In addition, Americans are eating out more often, spending 47% of their food budget on meals outside the home in the 1990s versus 34% in the 197Os.l4 Americans are also experiencing portion distortion at home. One-third of 107 commonly consumed foods increased significantly in portion size in just 5 years; the majority were grains, cereals, and beverages.’5 Continuous exposure to larger portions, home and retail, not only encourages overeating but also leads to portion distortion. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Academic Statistics: Growth, Change, and Federal Support

Abstract Statistics is one of the few academic fields that continued to expand rapidly in the 1970's. We present data on growth in Ph.D. production, faculty size, and number of journals. Statistics is not a branch of mathematics but has both scientific and mathematical components. We examine federal support in light of the special characteristics of statistical research and the continuing growth of the field. Although the data are not completely adequate, it is clear that support of academic basic research in statistics does not reflect the increased prominence of statistics among the mathematical sciences. We make specific suggestions for fruitful use of increased resources for research.
Coral reef catastrophe.

The article" Catastrophes, phase shifts,and large-scale degradation of a Caribbean coral reef" by Terence P. Hughes (9 Sept., p.1547) relates the sad story of the decline of scleractinian coral populations in Jamaica over the past two decades. The article is a rare example of the long-term research needed to document trends on reefs; however, the monitoring program design appears to have excluded at least one potentially important causal factor, and the solution offered does not address sociopolitical reality. The data in the study by Hughes show a rapid decline of coral populations initiated by a 1980 hurricane. Coral cover declined further after the reduction of an herbivorous sea urchin, Diadema antillarum, resulting from disease, while the cover of fleshy macro-algae bloomed. Thus two natural events, hurricanes and disease, have decimated Jamaica's coral reefs. It is not clear what effect human activities have had on fleshy algae on these reefs and what, if anything, we can do to help the coral.
Detection of HC/O-18//plus/ in Sagittarius B2

Line emission at 85.1 GHz attributed to the J equals 1-0 rotational transition of the formyl ion HC(O-18)(plus) has been detected in Sgr B2 (OH). The double isotopic ratio (O-16/O-18)/(C-12/C-13) in the formyl ion in Sgr B2 is estimated to be in the range 5-10, hence within a factor 2 of the terrestrial value of 5.5. This determination implies that the C-13/C-12 ratio near the galactic center does not differ greatly from that in local molecular clouds.
Micromotion of cemented and uncemented femoral components

We evaluated the initial stability of cemented and uncemented femoral components within the femoral canals of cadaver femurs during simulated single limb stance and stair climbing. Both types were very stable in simulated single limb stance (maximum micromotion of 42 microns for cemented and 30 microns for uncemented components). However, in simulated stair climbing, the cemented components were much more stable than the uncemented components (76 microns as against 280 microns). There was also greater variation in the stability of uncemented components in simulated stair climbing, with two of the seven components moving 200 microns or more. Future implant designs should aim to improve the initial stability of cementless femoral components under torsional loads; this should improve the chances of bony ingrowth.
Age related changes in plasma cholesterol of the chicken.

SummaryThe average total plasma cholesterol level of hens from 8 to 57 months old was 197 mg% and did not vary with age. The cholesterol level of males remained relatively constant at 139 mg% between 8 and 25 months, but by 35-38 months it had risen significantly to 155 mg%. At 45 months of age. a small group of males had a level of 209 mg%.
Achievements and Prospects of Rice Breeding in Heilongjiang Province

Rice varieties breeding played a key role in rapid development of rice production in Heilongjiang province.The new varieties breeding and extension promote rapid development of the rice industry especially.Through detailing on characteristics of rice varieties and their application since the founding of new China,sixty years rice breeding achievements of Heilongjiang province was summarized.At the same time current rice breeding problems were pointed out and countermeasures were proposed.Finally,rice development of Heilongjiang province was prospected.
Applying of the Zero Line Current Transformer for Intelligent Electricity Meter

Intelligent electricity meter is a intelligent instrumentation whose core is the microprocessor application and network communication technology.Intelligent electricity meter is getting popularized and applied at home and abroad.Besides the basic function of the two-way measurement,intelligent electricity meter also has other various functions,for example,the points classification measurement,two-way communication,various control models,a variety of data transmission mode,electricity-theft preventing.This paper introduces the working principle of the intelligent electricity meter,expounds the application of zero line current transformer for intelligent electricity meter,analyses the actual connection mode of intelligent electricity meter installation and proposes the problems should be noticed when installing the intelligent electricity meter,and gives the relevant solutions.
Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP

ABSTRACT Murine polyomavirus has repeatedly provided insights into tumorigenesis, revealing key control mechanisms such as tyrosine phosphorylation and phosphoinositide 3-kinase (PI3K) signaling. We recently demonstrated that polyomavirus small T antigen (ST) binds YAP, a major effector of Hippo signaling, to regulate differentiation. Here we characterize YAP as a target of middle T antigen (MT) important for transformation. Through a surface including residues R103 and D182, wild-type MT binds to the YAP WW domains. Mutation of either R103 or D182 of MT abrogates YAP binding without affecting binding to other signaling molecules or the strength of PI3K or Ras signaling. Either genetic abrogation of YAP binding to MT or silencing of YAP via short hairpin RNA (shRNA) reduced MT transformation, suggesting that YAP makes a positive contribution to the transformed phenotype. MT targets YAP both by activating signaling pathways that affect it and by binding to it. MT signaling, whether from wild-type MT or the YAP-binding MT mutant, promoted YAP phosphorylation at S127 and S381/397 (YAP2/YAP1). Consistent with the known functions of these phosphorylated serines, MT signaling leads to the loss of YAP from the nucleus and degradation. Binding of YAP to MT brings it together with protein phosphatase 2A (PP2A), leading to the dephosphorylation of YAP in the MT complex. It also leads to the enrichment of YAP in membranes. Taken together, these results indicate that YAP promotes MT transformation via mechanisms that may depart from YAP9s canonical oncogenic transcriptional activation functions. IMPORTANCE The highly conserved Hippo/YAP pathway is important for tissue development and homeostasis. Increasingly, changes in this pathway are being associated with cancer. Middle T antigen (MT) is the primary polyomavirus oncogene responsible for tumor formation. In this study, we show that MT signaling promotes YAP phosphorylation, loss from the nucleus, and increased turnover. Notably, MT genetics demonstrate that YAP binding to MT is important for transformation. Because MT also binds PP2A, YAP bound to MT is dephosphorylated, stabilized, and localized to membranes. Taken together, these results indicate that YAP promotes MT transformation via mechanisms that depart from YAP9s canonical oncogenic transcriptional activation functions.
Animal models of human colorectal cancer: Current status, uses and limitations.

AIM: To make orthotopic colon cancer murine models a more clearly understood subject. The orthotopic tumor models have been found to be more relevant in replicating the human disease process as compared to heterotopic models, many techniques for making orthotopic colorectal murine models have been reported. METHODS: We evaluated the current literature for various reported orthotopic colon cancer models to understand their techniques, advantages and limitations. An extensive literature review was performed by searching the National Library of Medicine Database (PubMed) using MeSH terms animal model; colon cancer; orthotopic model; murine model. Twenty studies related to colon cancer orthotopic xenograft model were evaluated in detail and discussed here. RESULTS: The detailed analysis of all relevant reports on orthotopic model showed tumor take rate between 42%-100%. While models using the enema technique and minimally invasive technique have reported development of tumor from mucosa with tumor take rate between 87%-100% with metastasis in 76%-90%. CONCLUSION: Over the years, the increased understanding of the murine models of human colon cancer has resulted in the development of various models. Each reported model has some limitations. These latest models have opened up new doors for continuing cancer research for not only understanding the colon cancer pathogenesis but also aid in the development of newer chemotherapeutic drugs as they mimic the human disease closely.
Pathological Factors that Influence Prognosis in Stage a Prostatic Cancer: the Influence of Extent Versus Grade

To determine the pathologic factors useful in predicting prognosis in patients with stage A prostatic cancer we studied 117 patients followed for 2 to 15 years. Since no patient was treated until progression of disease occurred we were able to correlate pathologic findings with the natural history of the disease in an untreated population of patients. In 14 patients (12 per cent) extensive local (2) or metastatic (12) disease developed. Because 12 of the 14 patients had progression of the disease within 4 years we thought than an analysis of all patients followed for 4 years would be useful. Extent and grade of disease were the 2 factors that most accurately predicted progression. No patient with a low grade lesion (Hopkins grade 1 or Gleason total score 2 to 4) had progression and only 2 per cent of patients with less than 5 per cent cancer had progression. These patients were classified as stage A1 and 60 per cent of all patients were in this category. We believe that these patients require no further therapy. Of the patients with more than 5 per cent cancer 32 per cent had progression and 17 per cent of the patients with either Hopkins grade 2 to 3 disease or Gleason total score more than 4 had progression. These patients were classified as stage A2 and their optimal management remains to be determined.
Abstract LB-311: Elevated kynureninase protein expression is associated with KEAP1 mutant non-small cell lung cancer and is predictive of poor overall survival

Purpose: To identify signatures related to tryptophan metabolism independent of indoleamine 2,3-dioxygenase (IDO) that are predictive of tumor behavior. Introduction: Recent evidence has pointed to the importance of tryptophan catabolites on immune suppression and promotion of tumor growth. IDO1 is a rate-limiting enzyme in tryptophan catabolism currently targeted in clinical trials. Tryptophan catabolism can occur in IDO-negative tumors and resulting metabolites may have immunosuppressive and potential autocrine functions. Our late breaking finding is that we have uncovered signatures related to tryptophan metabolism independent of IDO that impact clinical outcome in NSCLC. Experimental Procedures: We initially carried out integrated genomic and proteomic profiling of 114 cancer cell lines. Small interfering RNA transfection experiments were used to evaluate the effect of KYNU knockdown on cell viability. TCGA data was analyzed to determine clinical relevance. Results: We identified kynureninase (KYNU), an enzyme involved in tryptophan metabolism that mediates formation of anthranilate and 3-hydroxyanthranilate, as uniquely overexpressed at the RNA and protein levels in NSCLC compared to other cancer types. These findings were not conserved for IDO or tryptophan 2,3-dioxygenase (TDO2), rate-limiting enzymes in tryptophan metabolism. Knockdown of KYNU reduced cell viability of NSCLC cell lines tested. Upregulation of KYNU was highly associated with KEAP1 mutational status and positively correlated with numerous Nrf-2 regulated-genes at both the protein and mRNA level. These findings were confirmed using TCGA data. KYNU mRNA levels predicted worse outcomes in stage II and III NSCLC adenocarcinoma and squamous cell carcinoma in TCGA cohorts independently of other covariates (P = : 0.008). Conclusion: We have uncovered a unique signature in NSCLC reflective of aberrant tryptophan metabolism mediated by elevated KYNU but not IDO/TDO2. KYNU expression is highly associated with KEAP1 mutational status. High KYNU mRNA levels was predictive of worse clinical outcomes in NSCLC. Citation Format: Johannes F. Fahrmann, Jennifer Dennison, Eunice Murage, Hong Wang, Edwin J. Ostrin, Ayumu Taguchi, Samir Hanash. Elevated kynureninase protein expression is associated with KEAP1 mutant non-small cell lung cancer and is predictive of poor overall survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-311.
Abstract 1913: Inhibition of S-Adenosylmethionine-dependent methyltransferase resists TGF-β1-induced EMT of pancreatic cancer via microRNA alterations

Identification of epigenetic reversal agents for use in combination chemotherapies for human pancreatic ductal adenocarcinomas remains an unmet clinical need. Pharmacological inhibitors of EZH2 are emerging as potential epigenetic reversal agents in various solid tumors and leukemia, however, the surprisingly small set of mRNA transcripts identified with EZH2 knockdown suggests novel mechanisms to govern their anti-tumorigenic effects. Here, we report 3-deazaneplanocin-A, an inhibitor of S-adenosyl-L-homocysteine hydrolase and EZH2 histone lysine-N-methyltransferase, to significantly reprogram the noncoding miRNA expression, including a subset of PDAC-downregulated miRNAs, to dampen TGF-β-induced EMT signals in pancreatic cancer. Particularly, we identify epigenetic silencing of miR-663a and -4787-5p in PDAC tissues and cell lines that are reactivated by 3-deazaneplanocin-A to directly target TGF-β1 for RNA interference. Lentiviral overexpression of miR-663a and -4787-5p partially phenocopied 3-deazaneplanocin-A9s EMT resisting effects in pancreatic cancer cells, whereas locked nucleic acid antimiR-663a and -4787-5p mitigated them. In vivo, 3-deazaneplanocin-A, miR-663a and -4787-5p significantly reduced tumor burden and metastasis in an orthotopic mouse pancreatic tumor model with miR-663a displaying more potency than miR-4787-5p in curtailing TGF-β1 signaling pathway. These findings reveal tumor miRNA reprogramming as a novel approach for controlling TGF-β-induced EMT in human PDAC and uncover a list of putative miRNA targets that may guide further selection and development of synthetic histone methylation reversal agents for clinical use. Citation Format: Rajgopal Govindarajan, Hardik Modi. Inhibition of S-Adenosylmethionine-dependent methyltransferase resists TGF-β1-induced EMT of pancreatic cancer via microRNA alterations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1913.
Advanced Model Order Reduction Techniques in VLSI Design: Passive hierarchical model order reduction

In this chapter, we focus on passive wideband modeling of RLCM circuits. We propose a new passive wideband reduction and realization framework for general passive high-order RLCM circuits. Our method starts with large RLCM circuits, which are extracted by existing geometry extraction tools like FastCap [83] and FastHenry [59] under some relaxation conditions of the full-wave Maxwell equations (like electro-quasi-static for FastCap or magneto-quasi-static for FastHenry) instead of measured or simulated data. It is our ultimate goal that we can obtain the compact models directly from complex interconnect geometry without measurement or full-wave simulations. The method presented in this chapter is called hierarchical model order reduction, HMOR , which is based on the general frequency-domain hierarchical model reduction algorithm [121, 122, 124] and an improved VPEC (vector potential equivalent circuit) [134] model for self and mutual inductance, which can be easily sparsified and is hierarchical-reduction friendly. The HMOR method achieves passive wideband modeling of RLC circuits via multi-point expension and the convex programming based passivity enforcement method. In this section, we will show that the frequency-domain hierarchical reduction is equivalent to implicit moment-matching around s = 0, and that the existing hierarchical reduction method by one-point expansion [121, 124] is numerically stable for general tree-structured circuits.
SAMER+: Balancing short term throughput and long term stability in cognitive radio mesh networks

A large number of routing protocols for Cognitive radio networks (CRNs) have been proposed recently, each based on different design goals, and evaluated in different scenarios, under different assumptions. In our previous work, we conducted the first extensive empirical performance study of routing protocols for CRNs-Coolest Path, SAMER, and CRP — under the same realistic set of assumptions. Our study revealed that SAMER significantly outperforms the other protocols under low primary user activity but its performance degrades under high PU activity. In this work, we introduce an enhanced version of SAMER (SAMER+) that performs consistently well in both low and high PU activity scenarios. The core of SAMER+ is a new path metric that balances short term throughput and long term path stability. We evaluate SAMER+ using extensive simulations and compare it against SAMER and Coolest Path. Our results show that SAMER+ significantly outperforms both protocols in a variety of scenarios.
Substrate affinity differentially influences protein kinase C regulation and inhibitor potency

The overlapping network of kinase-substrate interactions provides exquisite specificity in cell signaling pathways, but also presents challenges to our ability to understand the mechanistic basis of biological processes. Efforts to dissect kinase-substrate interactions have been particularly limited by their inherently transient nature. Here, we use a library of FRET sensors to monitor these transient complexes, specifically examining weak interactions between the catalytic domain of protein kinase Cα and 14 substrate peptides. Combining results from this assay platform with those from standard kinase activity assays yields four novel insights into the kinase-substrate interaction. First, preferential binding of non-phosphorylated versus phosphorylated substrates leads to enhanced kinase-specific activity. Second, kinase-specific activity is inversely correlated with substrate binding affinity. Third, high affinity substrates can suppress phosphorylation of their low affinity counterparts. Finally, the substrate-competitive inhibitor bisindolylmaleimide I displaces low affinity substrates more potently leading to substrate selective inhibition of kinase activity. Overall, our approach complements existing structural and biophysical approaches to provide generalizable insights into the regulation of kinase activity.
Accurate Medicine: Indirect Targeting of NPM1-Mutated AML

Summary: Acute myeloid leukemia (AML) is now recognized to be an imprecise term that refers to a range of myeloid malignancies that have different genetical etiologies, clinical characteristics, and therapeutic sensitivities. Targeting the MLL1 and DOT1L histone modification complexes, both alone and in combination, showed activity against AML driven by a mutant NPM1 protein in several preclinical models and may represent a new treatment direction for this devastating disease. Cancer Discov; 6(10); 1087–9. ©2016 AACR. See related article by Kuhn and colleagues p. 1166.
Tyrosine Kinase Inhibitors in Pulmonary Vascular Disease

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by proliferation of granulocytes, caused by a translocation that produces the Philadelphia chromosome resulting in constitutively active BCR-ABL tyrosine kinase. Imatinib and dasatinib are 2 BCR-ABL tyrosine kinase inhibitors (TKI) used in the treatment of CML. Since the introduction of dasatinib earlier this decade, more than 100 cases of dasatinib-induced pulmonary arterial hypertension PAH have been reported in Europe. When imatinib was introduced, no such increase in pulmonary vasculopathy was identified. In this perspective piece, the author discusses the work of Guignabert et al., recently published in the Journal of Clinical Investigation, which examined the mechanism through which dasatinib mediates its toxic pulmonary vascular effects.
Searching for Staircases: Strengthening the Connections Between the Emergency Department and the Intensive Care Unit.

On a fall day in Chicago, a middle-aged man stepped out of a northbound train, appeared to choke, and collapsed. Paramedics arrived within minutes and administered several rounds of defibrillation and intravenous epinephrine. The patient was rapidly transported to an academic medical center, resuscitated in the Emergency Department (ED), and was soon surrounded by a multidisciplinary team of doctors, nurses, and respiratory therapists in the Intensive Care Unit (ICU). This article is protected by copyright. All rights reserved.
Asymmetries in the Generation and Transmission of Wealth

This Article assigns a redistributive role to the legal rules of trusts and estates. Unlike business law, trusts and estates has lagged in articulating a comprehensive theory on inequality. Consequently, income inequality is compounded intergenerationally as wealth inequality, with dire consequences for economic productivity and social stability. To move the discourse on wealth inequality, this Article explores the divergent approaches toward inequality in business law and trusts and estates. Additionally, this Article recasts trusts and estates’ legal rules as wealth transfer mechanisms. Four categories of rules are implicated: (1) rules that interact with the tax system, (2) rules that govern relations between beneficiaries and creditors, (3) rules that govern relations between beneficiaries and trustees, and (4) rules that govern relations among beneficiaries. More broadly, this Article contributes to three lines of scholarly debates. The first revolves around the propriety of drawing analogies between trust law and the law of enterprise organization. The second is whether legal rules or the tax system better effectuates redistribution. The third is whether legal rules should reflect our notions of fairness or welfare.
New Models for Engagement: Independent Publishing After 1990

Following the playground murder of 13-year-old Ahmed Iqbal Ullah by a fellow student in 1986, many British people criticized the intense national focus on issues of race, and particularly Anti-Racism, as detrimental to racial harmony. This chapter looks at the way that two different publishers concerned with Black British and BAME child readers dealt with the backlash against Anti-Racism: Verna Wilkins, who in starting up Tamarind Press aimed to produce books about “ordinary” British characters who “happened” to be Black; and Jackie Ould, who through her work with the Ahmed Iqbal Ullah Trust encouraged multi-racial groups of children to become involved in book production—and Black history at the same time.
Exploiting heterogeneity for tail latency and energy efficiency

Interactive service providers have strict requirements on high-percentile (tail) latency to meet user expectations. If providers meet tail latency targets with less energy, they increase profits, because energy is a significant operating expense. Unfortunately, optimizing tail latency and energy are typically conflicting goals. Our work resolves this conflict by exploiting servers with per-core Dynamic Voltage and Frequency Scaling (DVFS) and Asymmetric Multicore Processors (AMPs). We introduce the Adaptive Slow-to- Fast scheduling framework, which matches the heterogeneity of the workload–a mix of short and long requests–to the heterogeneity of the hardware– cores running at different speeds. The scheduler prioritizes long requests to faster cores by exploiting the insight that long requests reveal themselves. We use control theory to design threshold-based scheduling policies that use individual request progress, load, competition, and latency targets to optimize performance and energy. We configure our framework to optimize Energy Efficiency for a given Tail Latency (EETL) for both DVFS and AMP. In this framework, each request self-schedules, starting on a slow core and then migrating itself to faster cores. At high load, when a desired AMP core speed s is not available for a request but a faster core is, the longest request on an s core type migrates early to make room for the other request. Compared to per-core DVFS systems, EETL for AMPs delivers the same tail latency, reduces energy by 18% to 50%, and improves capacity (throughput) by 32% to 82%. We demonstrate that our framework effectively exploits dynamic DVFS and static AMP heterogeneity to reduce provisioing and operational costs for interactive services. CCS CONCEPTS • Computer systems organization $\rightarrow$ Heterogeneous (hybrid) systems; • Software and its engineering $\rightarrow$ Scheduling;
Mourning and Melancholia: Conflicting Approaches to Reviving Gilmore Girls One Season at a Time:

In 2016, the canceled CW television series Gilmore Girls was revived on Netflix as four 90-minute “mini-movies” called Gilmore Girls: A Year in the Life. Factors contributing to the original series ending, including creator conflicts about its final year, have led to continued series devotion and, consequently, Netflix’s revival that aimed to court the show’s built-in audience as well as a new generation of viewers. To revive a show that caters to established fans and also appeals to potential new fans requires a blend of self-referentiality and narrative continuation. I argue that while established fans were catered to through A Year in the Life’s reinstatement of original creator Amy Sherman-Palladino’s intended series ending, Netflix simultaneously catered to new viewers through streaming features like archive-access and by co-opting the very ending that established fans desired.
Modeling Three-Dimensional Passive STAP With Heterogeneous Clutter and Pulse Diversity Waveform Effects

As passive radar becomes more popular, modeling its behavior and physics becomes more critical. Particular to space-time adaptive processing (STAP) for ground moving target indication, the way in which clutter is modeled will directly impact performance expectations and results. Furthermore, modeling Doppler modulation from uncooperative waveforms can also impact performance assessments. This paper introduces a three-dimensional model that incorporates a novel method for modeling clutter and waveform impacts in passive STAP.
Shanghai Disneyland: Authentically Disney and Distinctly Chinese

Excellent service operations understand the unique challenges of managing services and experiences. The Walt Disney Company's value proposition, or purpose, is to create a magical experience for customers. To deliver on that, service and employee systems must be designed in a manner that work together. After years of planning, construction, employee training, and marketing outreach to its largely Chinese guests, Shanghai Disneyland (SDL) finally opened its doors on June 16, 2016. Certain classic Disney elements had been customized for China, and others reflected the traditional Disney brand. The Walt Disney Company had done its homework—but the "unknowns" needed to be identified and remedied. Had the Walt Disney Company tailored its service offerings appropriately to the target market, and what adjustments, if any, were needed? This material lends itself well to exploring a storied service company on numerous dimensions—operational performance and strategy, service trade-offs, attribute maps, and many general management issues across functions, especially whether the company has been able to understand Chinese cultural differences in such a way that profitability will occur faster than in its other non-U.S. locations. Instructors may choose to use the case as a capstone to "The Walt Disney Company: Mickey Mouse Visits Shanghai" (UVA-OM-1545), which is set on the verge of SDL's opening. Excerpt UVA-OM-1568 Oct. 11, 2017 Shanghai Disneyland: Authentically Disney and Distinctly Chinese After years of planning, construction, employee training, and marketing outreach to its largely Chinese guests, Shanghai Disneyland (SDL) finally opened its doors on June 16, 2016. During a six-week preopening trial period, one million visitors rushed to enter the largest Walt Disney Company (DIS) global theme park. A staggering 70 million people in China tuned in to view the grand-opening ceremony live on TV or via digital streaming. Through the first seven months, close to six million people purchased tickets to SDL. While SDL was off to a promising start, DIS had learned from its previous global ventures that continuous improvement and flexibility to cater to local tastes were imperative to sustain and maximize success. Certain classic Disney elements had been customized for China, and others reflected the traditional DIS brand. Disney had done its homework—but it was the “unknowns” that needed to be identified and remedied. Had DIS tailored its service offerings appropriately to the target market, and what adjustments, if any, were needed? Authentically Disney and Distinctly Chinese? Seven months into operations at SDL, the question top of mind for many was: How had the property performed? The answers to that question depended upon who was asked and in what forum (public or private). According to SDL management, they struck a winning balance in the goal DIS Chairman and CEO Robert A. Iger had to make SDL “authentically Disney and distinctly Chinese.” . . .
CALCULATIONS OF THE SUPERCONDUCTING AND TRANSPORT PROPERTIES OF A15 STRUCTURE COMPOUNDS

Publisher Summary In this chapter, electronic band structure calculations are done for a series of ten different A15 structure compounds. The results obtained are used to study the superconducting properties of structure compounds along with a discussion of the thermal anomalies present in some of them. The electronic band-structure calculations are used as a basis for the studies presented in the chapter. The electronic band-structure calculations are performed using the self-consistent augmented-plane-wave method (APW). Those calculations include non-spin-dependent relativistic corrections, “warped muffin-tin” corrections to the usual APW approach, and make use of the local density approximation to the exchange-correlation potential. The density-of-states (N(E)) calculations are performed using a new Fourier series interpolation procedure with the final integrations being done using the tetrahedral method. Fermi velocities and other related transport quantities are performed by using appropriate modifications of the density-of-states techniques. The resistivity saturation is observed in A15 materials, in terms of the mean free path for electron–phonon scattering becoming comparable to the lattice spacing at approximately room temperature or above.
The Kallikrein—Kinin System in Asthma and Acute Respiratory Distress Syndrome

Publisher Summary The chapter reviews evidence for the involvement of kinins in asthma and the acute respiratory distress syndrome (ARDS). There is evidence that the kallikrein (KLK)–kinin system is important in chronic asthma as well as other manifestations of airway inflammation, including allergic and viral rhinitis. For many years, there have been indications that this cascade is important in the pathophysiology of acute lung injury, ARDS, and multiple-organ failure, associated with conditions such as sepsis, pancreatitis, primary pneumonia, or multiple traumas. It is unlikely that the clinical manifestations of severe and often life-threatening conditions—such as chronic asthma and acute lung injury—are due to a single mediator. There is little doubt that the KLK–kinin system is activated in these disorders and that local levels of kinins are markedly elevated in the inflammatory milieu. Thus, bradykinin (BK) and related kinins may have important roles in initiating and maintaining the pathophysiological changes that occur in the lungs. BK has deleterious, proinflammatory effects on many cell types that are mediated directly on those cells as well as by the myriad of other potentially injurious substances whose release this peptide can stimulate. Experiments in animal models of asthma and ARDS, particularly those demonstrating beneficial effects of selective kinin receptor antagonists, provide convincing testimony for a pivotal role of kinins in airway pathophysiology. Only after conducting clinical trials, utilizing kinin receptor antagonists, the roles of these endogenous peptides in human disease will become apparent.
Modification of Benthem Solution for Mode I Fracture of Cylinder with Spiral Crack Subjected to Torsion

In this paper, a Benthem asymptotic solution is adapted and modified for a linear elastic fracture mechanics of a V-notch spiral crack. A spiral crack on a cylindrical sample is implemented to quantify the mode I fracture toughness of materials subjected to pure quasi-static torsion. The torque corresponding to fracture initiation is measured experimentally and used with a modifying Benthem solution to quantify the fracture parameter. A geometric factor for a cylinder specimen with a spiral crack on the surface is developed by finite element simulation. The proposed solution, along with stress intensity factor data of different materials, is presented here as a benchmark work. The results show that the proposed formula of the stress intensity factor for spiral crack cylinder specimen is in agreement with the other conventional methods, with an average error of less than 5%. The stress distribution and details of the experimental and numerical analysis are discussed.