cssi/SciSciGPT-SciSciNet huggingface dataset:
Upregulation of Functional Kv11.1a Isoform Expression by Modified U1 Small Nuclear RNA

Abstract The KCNH2 or human ether-a go-go-related gene (hERG) encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier potassium current in the heart. The expression of Kv11.1 C-terminal isoforms is directed by the alternative splicing and polyadenylation of intron 9. Splicing of intron 9 leads to the formation of a functional, full-length Kv11.1a isoform and polyadenylation of intron 9 results in the production of a non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO plays an important role in regulating Kv11.1 channel function. In the heart, only one-third of KCNH2 pre-mRNA is processed to Kv11.1a due to the weak 5′ splice site of intron 9. We previously showed that the weak 5′ splice site is caused by sequence deviation from the consensus, and that mutations toward the consensus sequence increased the efficiency of intron 9 splicing. It is well established that 5′ splice sites are recognized by complementary base-paring with U1 small nuclear RNA (U1 snRNA). In this study, we modified the sequence of U1 snRNA to increase its complementarity to the 5′ splice site of KCNH2 intron 9 and observed a significant increase in the efficiency of intron 9 splicing. RNase protection assay and western blot analysis showed that modified U1 snRNA increased the expression of the functional Kv11.1a isoform and concomitantly decreased the expression of the non-functional Kv11.1a-USO isoform. In patch-clamp experiments, modified U1 snRNA significantly increased Kv11.1 current. Our findings suggest that relative expression of Kv11.1 C-terminal isoforms can be regulated by modified U1 snRNA.
Phosphotryptic peptide analysis of human progesterone receptor. New phosphorylated sites formed in nuclei after hormone treatment.

Abstract Human progesterone receptors (PR) exist as two independent naturally occurring steroid-binding forms of approximately 120 kDa (B-receptors) and 94 kDa (A-receptors). Both are phosphorylated in hormone-untreated T47Dco breast cancer cells. Hormone treatment leads to receptor transformation and an increased phosphorylation state: the 32P-labeling intensity is 3-5 times higher after progestin treatment and 8-10 times higher after RU 486 treatment. Only serine residues are phosphorylated. To determine whether there are unique phosphorylation sites in transformed nuclear PR, we analyzed the phosphopeptides of untransformed and transformed A- and B-receptors by tryptic cleavage and reverse-phase high pressure liquid chromatography. Untransformed A- and B-receptors share at least five common phosphopeptides, and a sixth is unique to B. Following transformation by either R5020 or RU 486, A-receptors generate at least six and B-receptors seven phosphopeptides. Compared with untransformed PR, there are at least two different phosphopeptides in transformed nuclear PR. Cyanogen bromide cleavage of transformed nuclear A-receptors, which lack the proximal 165 amino-terminal residues of the 933 amino acid B-receptors, produces two large fragments of approximately 43 and 19 kDa. These fragments contain all of the 32P label and comprise amino acids 165-595. Cleavage of transformed B-receptors also produces peptides of 43 and 19 kDa plus an additional 36-kDa fragment corresponding to residues 1-165. No 32P-labeled low molecular mass peptides are detected. Thus, all the hormone-dependent phosphoserine residues produced in nuclei are located in the first 595 amino acids of human PR, representing the amino terminus and 28 residues of the DNA-binding domain.
Effectiveness of workplace diabetes prevention programs: A systematic review of the evidence

Abstract Purpose The primary purpose is to review diabetes workplace interventions and the degree to which they improve diabetes-related outcomes in employees diagnosed with or at risk for T2DM. Methods Three electronic databases and ancestry searches were used to identify peer reviewed articles published in English from 2000 to June 2017. Results The number of participants represented by the 22 selected studies, excluding one large outlier, was 4243. On average, the samples were 57% female and ethnically diverse. Interventions—healthy eating behaviors, physical activity, and/or monitoring and self-managing diabetes and cardiovascular risk factors—were delivered in group sessions of fewer than 20 employees. Programs involved 1-h weekly sessions held during lunch hour or at other times during the workday for 12 to 24 weeks. Study outcomes, commonly measured at 6 and/or 12 months, were consistently positive. Conclusion The literature search uncovered beginning evidence that workplace interventions hold promise for preventing diabetes and/or its complications. More rigorous, creatively designed, workplace studies, are needed for employees at high-risk for developing diabetes. Practice implications Implications include the need for employer education about the benefits of employer support for such programs and attention to motivational strategies so employees will take full advantage of programs that are offered.
Topographical reconstructions from monocular optical colonoscopy images via deep learning

Colorectal cancer is a leading cause of cancer deaths worldwide, but mortality can be mitigated by the detection and removal of premalignant lesions. Unfortunately, conventional 2D optical colonoscopy does not capture topographical information of the surface of the mucosa and thus has a high lesion miss rate. In this short paper, we use a joint deep convolutional neural network-conditional random field (CRF) framework for depth estimation from monocular colonoscopy images. Unlike previous approaches, this method does not make any geometric assumptions. The estimated depth is used to reconstruct the topography of the surface of the colon. Using digitally generated synthetic endoscopy data and CT-Phantom data, with corresponding ground truth depths, we train the unary and pairwise potential functions of a conditional random filed in a joint network. Results show that this approach can estimate depths for test data with an 84% accuracy. We show that estimated depth maps can be used for reconstructing the topography of the mucosa from real colonoscopy images. This topographical information can be used for improving learning-based algorithms for detection, segmentation and identification of lesions.
Present, Past and Future Precipitation: Can We Trust the Models?

Results of several current atmospheric general circulation models were compared. The models show poor skill in reproducing observed precipitation, and differ considerably in their precipitation forecasts for the doubled CO2 world. Driven by the approximately modified insolation impact, they are unable to simulate an onset of a glaciation. Improved representation of oceanic heat and mass transports is necessary for reliable prediction of future precipitation shifts.
On Numerical Solution of the Markov Renewal Equation: Tight Upper and Lower Kernel Bounds

We develop tight bounds and a fast parallel algorithm to compute the Markov renewal kernel. Knowledge of the kernel allows us to solve Markov renewal equations numerically to study non-steady state behavior in a finite state Markov renewal process. Computational error and numerical stability for computing the bounds in parallel are discussed using well-known results from numerical analysis. We use our algorithm and computed bounds to study the expected number of departures as a function of time for a two node overflow queueing network.
Protein C antigen deficiency and warfarin necrosis

Recent reports have suggested a correlation between congenital protein C deficiency and tissue necrosis complicating oral anticoagulants (warfarin necrosis). The authors studied blood samples of 13 patients, obtained two weeks to more than six months after warfarin necrosis. Protein C antigen levels were assayed by an enzyme-linked immunosorbent assay method (Diagnostica Stago, France). Factors II, VII, IX, and X were assayed by functional methods, and IX and X additionally by immunologic methods. The results show that 11 of 13 patients with a history of tissue necrosis had low protein C levels, ranging from 23 to 69%, with the normal range being 70-140%. These results confirm that low protein C antigen levels are implicated in the pathogenesis of warfarin necrosis.
Development of Phonological, Lexical, and Syntactic Abilities in Children With Cochlear Implants Across the Elementary Grades.

Purpose This study assessed phonological, lexical, and morphosyntactic abilities at 6th grade for a group of children previously tested at 2nd grade to address 4 questions: (a) Do children with coc...
CARE PATHWAY FOR PATIENTS WITH ACS UNDERGOING PCI: OPPORTUNITIES FOR IMPROVING VALUE

Acute coronary syndrome (ACS) admissions are common and costly, amounting to $7 billion annually in the United States. The association between comprehensive ACS care strategies and outcomes are lacking. We identified 434,172 low-risk ACS patients (STEMI 35%, UA/NSTEMI 65%) enrolled in the Premier
Prescribing Response Strategies to Manage Customer Opinions: A Stochastic Differential Equation Approach

Today, the reputation of a firm is profoundly influenced by user opinions expressed in online consumer reviews. Managing these opinions is, therefore, critical for the success of firms. We study th...
Statistical Considerations for Subscore Reporting in Multistage Testing

This study examines factors that influence the reliability of subscores and the accuracy of subscore estimates in multistage testing (MST). The factors considered in the study include the number of subtests, subtest length, correlations among subscores, item pool characteristics such as item pool size relative to the number of items required for an MST and statistical properties of items. Results indicated that the factors that most influenced subscore reliability and subscore estimates were subtest length, item pool size, and the degree of item discrimination.
My Sister, Our Stories: Exploring the Lived Experience of School Leavers through Narrative and Poetics.

The purpose of this study was to explore the educational experiences of two adult female siblings who are both school leavers. Through the use of thematic narrative analysis, sibling narratives and poetic re-presentations, their stories were developed. These stories represent the participants' experiences of prior schooling and their current commitments to education. While each story conveyed a profound similarity in terms of prior schooling, contrasting narratives were illustrated through description of transitional moments and sibling relationship. The analysis also explored the intersections of race, gender, and social class within educative moments of the life experiences of the participants. Keywords: Adult Basic Education, Narrative, Thematic
Concentrated Burdens: How Self-Interest and Partisanship Shape Opinion on Opioid Treatment Policy

When does self-interest influence public opinion on contentious public policies? The bulk of theory in political science suggests that self-interest is only a minor force in public opinion. Using nationally representative survey data, we show how financial and spatial self-interest and partisanship all shape public opinion on opioid treatment policy. We find that a majority of respondents support a redistributive funding model for treatment programs, while treatment funded by taxation based on a community’s overdose rate is less popular. Moreover, financial self-interest cross-pressures lower-income Republicans, closing the partisan gap in support by more than half. We also experimentally test how the spatial burden of siting treatment clinics alters policy preferences. People across the political spectrum are less supportive when construction of a clinic is proposed closer to their home. These results highlight how partisanship and self-interest interact in shaping preferences on public policy with concentrated burdens.
AccD: A Compiler-based Framework for Accelerating Distance-related Algorithms on CPU-FPGA Platforms.

As a promising solution to boost the performance of distance-related algorithms (e.g., K-means and KNN), FPGA-based acceleration attracts lots of attention, but also comes with numerous challenges. In this work, we propose AccD, a compiler-based framework for accelerating distance-related algorithms on CPU-FPGA platforms. Specifically, AccD provides a Domain-specific Language to unify distance-related algorithms effectively, and an optimizing compiler to reconcile the benefits from both the algorithmic optimization on the CPU and the hardware acceleration on the FPGA. The output of AccD is a high-performance and power-efficient design that can be easily synthesized and deployed on mainstream CPU-FPGA platforms. Intensive experiments show that AccD designs achieve 31.42x speedup and 99.63x better energy efficiency on average over standard CPU-based implementations.
Stress in international work: Stressors and coping strategies of RNGO international directors

This study examines how international directors in religiously-affiliated nongovernmental organizations (RNGOs) cope with workplace stress. Interviews were conducted with directors from eight RNGOs...
What Do, What Did, and What Should We Do About “A’s”?

Original article: Aguinis, H., Cummings, C., Ramani, R., and Cummings, T., “An A is an A:” The New Bottom Line for Valuing Academic Research, https://doi.org/10.5465/amp.2017.0193In responding to A...
Fabrication of pH-responsive monodisperse microcapsules using interfacial tension of immiscible phases

Monodisperse, stimuli-responsive microcapsules are required for applications involving precise delivery of chemical payloads but are difficult to fabricate with high throughput and control over capsule geometry and shell wall properties, especially in the presence of organic solvents. In this paper, we adapt a facile technique based on the interfacial tension of immiscible phases for the generation of monodisperse emulsion templates and microcapsules. In this technique, either one (single emulsion) or two (double emulsion) dispersed phases are simultaneously delivered while reciprocating across the interface of a stationary immiscible continuous phase. The interfacial tension of the continuous phase results in the separation of a monodisperse droplet in every cycle. Monodisperse single emulsion-templated microcapsules based on cyclic poly(phthalaldehyde) (cPPA) and polymethacrylate (Eudragit E100) shell walls are formed with hydrophobic cores. The acid-triggered release of Eudragit and cPPA microcapsules containing an oil core is demonstrated in an acidic media. Tunable, monodisperse double emulsion templates with an aqueous core are formed with sizes ranging from 295 μm to 1200 μm and reciprocation frequencies of 1 Hz to 7 Hz. The double emulsion templates are converted to monodisperse, responsive microcapsules with a hydrophilic core through photocuring or selective solvent evaporation to form the polymer shell wall. Microcapsules with a variety of polymeric shell walls based on photocurable polyisocyanurate, cPPA and polylactide are fabricated. The acid-triggered release of cPPA microcapsules containing an aqueous core with a slower degradation rate is also demonstrated. We achieve excellent control over the emulsion templates and microcapsules, with polydispersity less than 2% and the ability to predict the size reliably based on process parameters. The cost-effectiveness, ease of fabrication and potential for scale-up make this technique very promising for fabrication of a diverse range of stimuli-responsive microcapsules.
Influence of implant design and parasagittal acromial morphology on acromial and scapular spine strain after reverse total shoulder arthroplasty: a cadaveric and computer-based biomechanical analysis.

Background The purpose was to analyze the influence of deltoid lengthening due to different implant designs and anatomic variations of the acromion and scapular spine (SS) in the parasagittal plane on strain patterns after reverse shoulder arthroplasty (RSA). Methods Ten cadaveric shoulders with strain rosettes placed on the surface of the acromial body (Levy II) and SS (Levy III) were tested using a shoulder simulator. RSA using humeral onlay (+3, +5, +8, +10, +13 mm) and glenosphere lateralization (0, +6 mm) was performed. Arm lengthening and magnitude of strain on acromion/SS were measured. The length of deltoid was assessed using validated computer modeling. Anatomic variance of the SS angle and position of acromion in relation to the scapular plane was examined. For comparison of strain as a function of deltoid lengthening, 25 mm was used as a threshold value for comparison based on previous literature demonstrating a decrease in Constant score and active anterior elevation in patients with arm lengthening >25 mm. Results At maximal deltoid lengthening (30.8 mm), average strains were 1112 μe (acromion) and 1165 μe (SS) (P Conclusion Deltoid lengthening above 25 mm produced large strains on the acromion/SS. Anatomic variation may indicate that as the acromion is more posteriorly oriented, the SS takes more strain from the deltoid vs. the acromion. Our study's data may help surgeons identify a high-risk population for increased strain patterns after RSA.
Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers.

While pralatrexate (PDX) has been successfully developed for the treatment of T-cell lymphoma, the mechanistic basis for its T-cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired PDX resistance, we generated resistant cells lines over a broad concentration range. PDX-resistant cell lines H9-12 and H9-200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells. Expression analysis of the proteins known to be important determinants of antifolate pharmacology revealed increase expression of dihydrofolate reductase (DHFR) due to gene amplification, and reduced folate carrier1 downregulation, as the putative mechanisms of resistance in H9-12 and H9-200 cells. Cross resistance was only seen with methotrexate but not with romidepsin, azacitidine (AZA), decitabine, gemcitabine, doxorubicin, or bortezomib. Resistance to PDX was reversed by pretreatment with hypomethylating agents in a concentration-dependent fashion. Comparison of gene expression profiles of parental and resistant cell lines confirmed markedly different patterns of gene expression, and identified the dual specificity phosphatase four (DUSP4) as one of the molecular target of PDX activity. Reduced STAT5 phosphorylation following exposure to PDX was observed in the H9 but not in the H9-12 and H9-200 cells. These data suggest that combination with hypomethylating agents could be potent, and that DUSP4 and STAT5 could represent putative biomarkers of PDX activity.
Physical Indeterminacy in Digital Computation

[Church 1931] and [Turing 1936] developed equivalent models of computation based on the concept of an algorithm, which by definition is provided an input from which it is to compute a value without external interaction. After physical computers were constructed, they soon diverged from computing only algorithms meaning that the Church/Turing theory of computation no longer applied to computation in practice because computer systems are highly interactive as they compute, which inspired the development of the Actor Model in 1972 to characterize all digital computation. Indeterminate computation can be thousands of times faster than the parallel λ-calculus (cf. [Takahashi 1989]) or pure logic programs [Hewitt 1969]. This article presents metatheory for a universal theory of digital computation that is more general and powerful than Church/Turing computation [Church 1935, Turing 1936]. Meta[Actors] (meta theory of Actors) proves that theory Actors has the following properties: • The theory Actors is uniquely categorical, i.e., it characterizes Actors (including types) up to an unique isomorphism. • The theory Actors is model sound, i.e., every theorem of Actors of is true in the unique up to isomorphism model. • The unique up to isomorphism model has partial predicates and propositions because of indeterminacy. • Proof checking in the theory Actors is computationally decidable. • There are no “monsters” [Lakatos 1976] in models of the theory Actors such as the ones in 1st-order theories of computation in which there can be Zeno-like computations, which have an infinite number of computational steps between two steps. Consequently unlike 1st-order theories, the theory Actors is not subject to cyberattacks using “monsters” in models. • The theory Actors is algorithmically inexhaustible, i.e., it is impossible to computationally enumerate theorems of the theory thereby reinforcing the intuition behind [Franzen, 2004]. Contrary to [Church 1934], the conclusion in this article is to abandon the assumption that theorems of a theory must be computationally enumerable while retaining the requirement that proof checking must be computationally decidable. Thesis: Any digital system can be directly modeled and implemented using Actors.
Future climate response to Antarctic Ice Sheet melt caused by anthropogenic warming

Meltwater and ice discharge from a retreating Antarctic Ice Sheet could have important impacts on future global climate. Here, we report on multi-century (present–2250) climate simulations performed using a coupled numerical model integrated under future greenhouse-gas emission scenarios IPCC RCP4.5 and RCP8.5, with meltwater and ice discharge provided by a dynamic-thermodynamic ice sheet model. Accounting for Antarctic discharge raises subsurface ocean temperatures by >1°C at the ice margin relative to simulations ignoring discharge. In contrast, expanded sea ice and 2° to 10°C cooler surface air and surface ocean temperatures in the Southern Ocean delay the increase of projected global mean anthropogenic warming through 2250. In addition, the projected loss of Arctic winter sea ice and weakening of the Atlantic Meridional Overturning Circulation are delayed by several decades. Our results demonstrate a need to accurately account for meltwater input from ice sheets in order to make confident climate predictions.
Looking Past Orthotopic Liver Transplantation: A Review of Emerging Strategies for Managing Acute and Acute-on-Chronic Liver Failure

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are both characterized by an acute insult leading to dysfunction of the liver and often other organs. Acute liver failure is defined by coagulopathy (INR > 1.5) and hepatic encephalopathy in the context of a new hepatic insult within the past 26 weeks [1]. It is relatively rare, with approximately 2000 cases per year diagnosed in the United States [2]. ACLF refers to an acute decompensation of chronic liver disease, but lacks a single clear definition [1]; the definitions used the most in studies discussed herein are reviewed in Table 17.1. Orthotopic liver transplant (OLT) is a valuable therapy for both conditions, but as with chronic liver failure, the demand for organs exceeds the supply. In the absence of liver transplant, the mortality of ALF has been estimated at >80% in some studies [1]. While the inconsistent definition makes ACLF mortality difficult to determine, a review based on the Asian Pacific Association for the Study of the Liver (APASL) and the European Foundation for the Study of Chronic Liver Failure (EASL-CLIF) definitions found a 90-day transplant-free mortality of about 50% [5].
Depression and Nicotine Withdrawal Associations with Combustible and Electronic Cigarette Use.

Depression is a risk factor for nicotine use and withdrawal. Population level epidemiologic studies that include users of either combustible or electronic cigarette (NICUSER) could inform interventions to reduce nicotine dependence in vulnerable populations. The current study examined the relationship between depression diagnosis (DEPDX), NICUSER, and lifetime rates of DSM-V nicotine withdrawal (NW) symptoms in a nationally representative sample of US adults (N = 979), who answered related questions in surveys administered through GfK's KnowledgePanel. Over 42% of the sample reported lifetime ever combustible cigarette use, 15.6% electronic-cigarette use, and 45.9% either (NICUSER). Weighted logistic regression analyses (controlling for age and gender) found that DEPDX was associated with 2.3 times increased odds (ratio (OR); 95% Confidence Interval (CI): 1.5-3.5) of being a NICUSER. Regarding risks of NW symptoms among NICUSER, models that additionally controlled for frequency of nicotine use found that DEPDX was significantly associated with increased odds of concentration problems (OR = 2.4; 95% CI: 1.3-4.5) and depressed mood (OR = 2.2; 95% CI: 1.1-4.1) when quitting or cutting down on nicotine use. Results highlight the consistent comorbidity between depression, nicotine use, and symptomatic nicotine withdrawal in a population-based sample of combustible and electronic cigarette users.
A method for measuring fluid pressure and solid deformation profiles in uniaxial porous media flows

Flow through rigid, reactive, or deformable porous media has relevance to the dynamical behavior studied across a broad range of problems in science and engineering. Here, we describe an apparatus designed to simultaneously measure the pervadic pressure profile, fluid volume flux, and deformation in an evolving poroelastic medium. We demonstrate the apparatus in measurements of flow-induced compression of a soft latex foam. The approach can be used in both rigid and reactive porous media.
Information security and cyber threats and vulnerabilities

Abstract This chapter provides an overview of information security including key concepts, types of controls, access methods, and auditing concepts. The chapter also provides an overview of transportation-related cybersecurity systems and technologies used in martime transportation.
LGBT-Who? You’re Fired: Addressing Employment Discrimination Through Congressional Representation Rather than Judicial Appointment

Although today’s society is much more accepting, LGBT discrimination is still very real. Using the momentum from the landmark case Obergerfell, LGBT advocates have directed their attention to employment discrimination protections. These efforts have come in several forms, including legal action under Title VII of the Civil Rights Act. After some success, there is currently a circuit split on whether or not Title VII protection extends to sexual orientation and gender identity discrimination. Regardless of the recent progress from LGBT claimants, this Article contends that the judicial approach will be ineffective, given the recently confirmed Supreme Court Justice and other obstacles. Rather, this Article recommends congressional action and the enactment of the Equality Act as the solution for LGBT employment discrimination. Instead of solely relying on nine individuals that may not provide a clear solution, the Equality Act would provide an unambiguous, effective solution that serves as a direct representation of what the nation’s citizens need and want.
Treatment Outcomes of Head and Neck Cancer Patients in the Elderly Receiving Different Chemoradiation Combinations: A Single-Center Experience.

OBJECTIVES This study aimed to assess the effect of definitive or adjuvant concurrent chemoradiation (CRT) among elderly patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). MATERIALS AND METHODS We retrospectively analyzed 150 elderly LA HNSCC patients (age ≥70) at a single institution. Demographics, disease control outcomes, and toxicities with different chemotherapy regimens were reviewed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) estimates. RESULTS Median age at diagnosis was 74 years (range 70-88). Of the cohort, 98 (65.3%) patients received definitive and 52 (34.7%) received adjuvant CRT; 44 (29.3%) patients received weekly carboplatin and paclitaxel, 43 (28.7%) weekly cetuximab, 33 (22%) weekly carboplatin, and 30 (20%) weekly cisplatin. The OS at 2 years was 70% (95% confidence interval [CI]: 63-79%), and PFS at 2 years was 61% (95% CI: 53-70%). There was no significant difference in OS or PFS between definitive and adjuvant CRT (p = 0.867 and p = 0.475, respectively). Type of chemotherapy regimen (single-agent carboplatin vs. others) (95% CI: 1.1-3.9; p = 0.009) was a key prognostic factor in predicting OS in multivariable analysis. Concurrent use of cetuximab was associated with increased risk of PEG tube dependence at 6 months (p < 0.001). CONCLUSIONS Management of LA HNSCC in the elderly is a challenging scenario. Our study shows that CRT is a feasible treatment modality for elderly patients with LA HNSCC. We recommend CRT with weekly cisplatin or weekly carboplatin and paclitaxel. A chemotherapy regimen should be carefully selected in this difficult to treat population.
Interaction of Growth Hormone and Nutritional Intake in Facilitating Nitrogen Conservation and Promoting Lipolysis

Growth hormone (GH) has multiple actions on target tissues that are coordinated to promote somatic growth. To provide adequate substrate for growth, GH has significant effects on carbohydrate, lipid and protein metabolism. While the effects on lipid and carbohydrate metabolism are believed to be direct or to be mediated through increased insulin secretion, the effects on protein synthesis are indirect, being mediated through the synthesis and secretion of somatomedin-C/insulin-like growth factor I (SmC/IGF-I), a potent stimulator of protein synthesis. The metabolic processes that coordinate the direct effects of GH with its indirect growth-promoting actions are incompletely understood.
Concise Total Synthesis of (+)-Luteoalbusins A and B

The first total synthesis of (+)-luteoalbusins A and B is described. Highly regio- and diastereoselective chemical transformations in our syntheses include a Friedel-Crafts C3-indole addition to a cyclotryptophan-derived diketopiperazine, a late-stage diketopiperazine dihydroxylation, and a C11-sulfidation sequence, in addition to congener-specific polysulfane synthesis and cyclization to the corresponding epipolythiodiketopiperazine. We also report the cytoxicity of both alkaloids, and closely related derivatives, against A549, HeLa, HCT116, and MCF7 human cancer cell lines.
Eighth‐Grade School Form and Resilience in the Transition to High School: A Comparison of Middle Schools and K‐8 Schools

We examine a set of academic and social outcomes in 9th grade, comparing middle school attendees with those who attended K-8 schools. Previous research with these data has shown that there are few differences in 8th-grade outcomes by school type. Here we extend these findings to determine whether school form influences student outcomes in the first year of high school. The results reveal several domains in which attendance at a middle school results in worse outcomes (e.g., greater rates of course failure); however, we find that a large portion of the difference by type of a student's 8th-grade school is accounted for by differential rates of attendance at the district's magnet schools. That is, our results indicate that type of school attended during the middle grades is significantly and positively related to magnet school attendance and thereby on the academic outcomes in the 9th-grade year.
The vasopressin-sensitive adenylate cyclase of the rat renal medulla.

Abstract A partially purified plasma membrane fraction was prepared from the rat renal medulla by flotation in a discontinuous sucrose density gradient. The preparation was enriched in vasopressin-stimulated adenylate cyclase activity to a greater extent than either fluoride-stimulated or basal activity. The Km for vasopressin was 4 to 15 x 10-9 m in different preparations. The Km for ATP was 0.12 to 0.16 mm for basal, hormone-stimulated, and fluoride-stimulated activities. The different reaction rates under the three conditions were due to differences in the maximal velocity of the reaction. The concentration of Mg++ required for half-maximal enzyme activity was the same for basal, vasopressin-stimulated, and fluoride-stimulated activities. The activation energy of the reaction was 15 to 17 Cal per mole for all three conditions. The reversibility of hormone stimulation of adenylate cyclase was studied by measuring the rate of change of enzyme activity following dilution of the hormone. Decreasing the concentration of hormone led to an immediate drop in the rate of formation of adenosine cyclic 3':5'-monophosphate to that expected at the lower vasopressin concentration. This indicates that the hormone is in equilibrium with the receptors and that the binding of hormone is rapidly reversible.
Ionospheric response to sudden stratospheric warming events at low and high solar activity

The sensitivity of the ionospheric response to a sudden stratospheric warming (SSW) event has been examined under conditions of low and high solar activity through simulations using the whole atmosphere model (WAM) and the global ionosphere plasmasphere model (GIP). During non-SSW conditions, simulated daytime mean vertical drifts at the magnetic equator show similar solar activity dependence as an empirical model. Model results of ionospheric total electron content (TEC) and equatorial vertical drift for the January 2009 major SSW, which occurred at very low solar activity conditions, show reasonable agreement with observations. The simulations demonstrate that the E region dynamo is capable of creating the semidiurnal variation of vertical drift. WAM and GIP were also run at high solar activity conditions, using the same lower atmosphere conditions as present in the January 2009 SSW event. The simulations indicate that the amplitude and phase of migrating tides in the dynamo region during the event have similar magnitudes for both solar flux conditions. However, comparing the ionospheric responses to a major SSW under low and high solar activity periods, it was found that the changes in the ionospheric vertical drifts and relative changes in TEC decreased with increasing solar activity. The simulations indicate that the F region dynamo becomes more important throughout the daytime and contributes to the upward drift in the afternoon during the event when the solar activity is higher. Our test simulations also confirm that the increase of the ionospheric conductivity associated with increasing solar activity is responsible for the decrease of vertical drift changes during an SSW. In particular, first, the increase in F region conductivity allows the closure of E region currents through the F region, reducing the polarization electric field before noon. Second, the F region dynamo contributes an upward drift postnoon, maintaining upward drifts till after sunset. The direct changes of the thermospheric wind at higher solar activity due to increased dissipation of the tides from the lower atmosphere are relatively minor and do not contribute greatly to the changes of ionospheric responses in the low-latitude region.
Market-based risk allocation for multi-agent systems

This paper proposes Market-based Iterative Risk Allocation (MIRA), a new market-based decentralized optimization algorithm for multi-agent systems under stochastic uncertainty, with a focus on problems with continuous action and state space. In large coordination problems, from power grid management to multi-vehicle missions, multiple agents act collectively in order to maximize the performance of the system, while satisfying mission constraints. These optimal action plans are particularly susceptible to risk when uncertainty is introduced. We present a decentralized optimization algorithm that minimizes the system cost while ensuring that the probability of violating mission constraints is below a user-specifie upper bound.We build upon the paradigm of risk allocation [3], in which the planner optimizes not only the sequence of actions, but also its allocation of risk among state constraints. We extend the concept of risk allocation to multi-agent systems by highlighting risk as a resource that is traded in a computational market. The equilibrium price of risk that balances the supply and demand is found by an iterative price adjustment process called t tonnement (also known as Walrasian auction). Our work is distinct from the classical tâtonnement approach in that we use Brent's method to provide fast guaranteed convergence to the equilibrium price. The simulation results demonstrate the efficien y and optimality of the proposed decentralized optimization algorithm.
Molecular structure and evolution of double-minute chromosomes in methotrexate-resistant cultured mouse cells

To determine whether microscopically visible double-minute chromosomes (DMs) are derived from submicroscopic precursors, we monitored the amplification of the dihydrofolate reductase (DHFR) gene in 10 independent isolates of methotrexate (MTX)-resistant mouse cells. At every other doubling in MTX concentration, the cells were examined both microscopically, to detect the presence of microscopically visible DMs, and by pulsed-field gel electrophoresis and hybridization to a DHFR-specific probe, to detect submicroscopic DMs. One of the cloned MTX-resistant isolates was examined in detail and was shown to originally contain amplified DHFR genes on circular DMs measuring 1 and 3 Mb in size; additionally, metaphase chromosome preparations from this cloned isolate were examined and were shown to contain microscopically visible DMs too large to enter a pulsed-field gel. During stepwise selection for increasing levels of MTX, the smaller DMs (not microscopically visible) were shown to be preferentially amplified, whereas the larger (microscopically visible) ones decreased in relative numbers. Rare-cutting NotI digestion patterns of total genomic DNA that includes the DMs containing the DHFR gene suggest that the DMs increase in copy number without any further significant rearrangements. We saw no evidence from any of the 10 isolates to suggest that microscopically visible DMs are formed from smaller submicroscopic precursors.
Reliability and Validity of Diagnostic Modalities for Temporomandibular Disorders

Temporomandibular disorders (TMD) encompass a group of musculoskeletal conditions that involve the temporomandibular joint (TMJ) or joints, the masticatory musculature, or both. These conditions are typically characterized by pain in the pre-auricular area that is usually aggravated by chewing or other jaw function and is often accompanied, either singly or in combination, by limitation of jaw movement, joint sounds, palpable muscle tenderness, or joint soreness. As with most other musculoskeletal conditions, the diagnostic "gold standard" for TMD is based upon an evaluation of the patient's history and clinical examination, supplemented, when appropriate, by TM joint imaging. It is against this "gold standard" that the reliability and validity of diagnostic modalities must be compared. With regard to electronic devices, several reviews of the scientific literature have concluded that the diagnostic reliability, validity, sensitivity, and specificity of such devices in the diagnosis of TMD have not been e...
Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen.

Purpose We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Design Cross-sectional, single-center, observational study. Participants One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Methods Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. Main Outcome Measures The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10 −3 cd/m 2 (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. Results A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age ( r = 0.34; P = 0.0002), decreasing BCVA ( r = −0.54; P P = 0.03), and decreasing subfoveal choroidal thickness ( r = −0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group ( P Conclusions Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD ( R 2 = 0.56), with the presence of RPD conferring the largest parameter estimate.
Design of Online Professional Development in Science Content and Pedagogy: A Pilot Study in Florida

The Exploring Florida Science project goals were: (1) increasing content knowledge of secondary science teachers, specifically in topics that are important to the future of the state, and (2) providing secondary science students with digital media for use in project-based learning. A team of instructional designers, educators, scientists, web designers and teacher educators designed an online professional development environment. Needs analysis included identification of the high incidence topics on the state science achievement test and topics of socio-scientific importance in the state. Development followed tenets of design-based research, and was guided by E-Learning for Educators standards and evaluated for content, pedagogy and usability using rubrics based on established guidelines. This paper details design, development, and evaluation frameworks, and summarizes pilot testing outcomes.
Characterization of the kinetic and mechanistic differences between free-surface and bulk grain growth in WC-Co materials

The rate of grain growth at different high temperatures in the bulk and at the free surface of a WC-Co substrate was measured. The microstructure, phase evolution, and elemental composition at the free surface were characterized at various stages of the grain-growth process and compared to equivalent characteristics of the bulk. A dramatic difference in the rate of grain growth between the free surface and the bulk of the material was observed. Grains in the free surface grew at a much faster rate than those in the bulk. Since this fast rate of growth was found to coincide with the vaporization of the binder phase from the free surface, it is suggested that this increase in the rate of growth is related to a change in the growth mechanism from an interfacial reaction limited growth in the bulk to a surface diffusion rate limited growth at the free surface. The contact points between grains provide bridges for atomic transport from high free-energy regions (small grains) to low free-energy regions (large grains); hence, the contiguity of the material has a strong influence on the rate of growth.
Validation of two fluoro-analogues of N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)benzylamine as serotonin transporter imaging agents using microPET.

Abstract Introduction Carbon-11 (C-11) N,N -dimethyl-2-(2′-amino-4′-hydroxymethyl-phenylthio)benzylamine ([ 11 C]HOMADAM) has been reported as highly specific and selective positron emission tomography (PET) radiotracer showing fast kinetics for the human brain serotonin transporter (SERT). In our continued effort to develop appropriate PET SERT radioligand that can be labeled with either C-11 or fluorine-18 (F-18), two new C-11 labeled analogues of HOMADAM, [ 11 C]- N,N -dimethyl-2-(2′-amino-5′-fluoro-4′-hydroxymethyl-phenylthio)benzylamine ([ 11 C]-( 2 )) and [ 11 C]- N,N -dimethyl-2-(2′-amino-4-fluoro-4′-hydroxymethyl-phenylthio)benzylamine ([ 11 C]-( 3 )) have been synthesized and evaluated along the previously reported [ 11 C]- N,N -dimethyl-2-(2′-amino-5-fluoro-4′-hydroxymethyl-phenylthio)benzylamine ([ 11 C]-( 1 )). Methods The in vitro competitive binding assays were performed in cells transfected with human SERT (hSERT), human dopamine transporter (hDAT), and human norepinephrine transporter (hNET). [ 11 C]-( 2 ) and [ 11 C]-( 3 ) were prepared by methylation of their monomethylbenzylamine precursors 13 and 22 with cyclotron produced [ 11 C]iodomethane ([ 11 C]CH 3 I), respectively. Uptake and kinetics of [ 11 C]-( 2 ) and [ 11 C]-( 3 ) in the brain regions of interest were determined in anesthetized rhesus monkeys using Concorde microPET P4. Results 2 and 3 displayed moderate and high affinity for the SERT with Kis (SERT) = 5.45 and 1.10 nM (vs [ 3 H]citalopram), respectively. After High Performance Liquid Chromatography (HPLC) purification, [ 11 C]-( 2 ) and [ 11 C]-( 3 ) were obtained in 23 and 9% radiochemical yield (RCY) and log P s 7.4 of 1.77 and 1.91, respectively. The microPET images of [ 11 C]-( 2 ) and [ 11 C]-( 3 ) showed clear localization in the monkey brain regions rich in SERT with midbrain to cerebellum ratios of 1.75 and 3.86 at 85 min post injection, respectively, comparing to 3.40 for [ 11 C]-( 1 ), at the same time. [ 11 C]-( 3 ) was selected for further examination and showed to be specific to the SERT as displacement with citalopram (a potent SERT ligand) reduced radioactivity in SERT rich regions, such as midbrain, to the cerebellum level. Conclusions Compound 2 , the 5′-fluoro-analogue of HOMADAM, had the lowest brain uptake and target to non-target ratios. Compound 3 , the 4-fluoro-analogue of HOMADAM, had good brain uptake and higher midbrain and thalamus to cerebellum ratios than compound 1 , the 5-fluoro-analogue of HOMADAM. Although 1 and 3 presented better imaging properties than 2 , none of the three candidates was suitable to surpass the binding or distributional qualities of the parent HOMADAM. Alternative fluoro-analogues of HOMADAM will soon be characterized, in future work, as SERT radioimaging agents.
Comparative efficacy of methyl bromide against codling moth (Lepidoptera : Tortricidae) larvae in 'Bing' and 'Rainier' cherries and confirmation of efficacy of a quarantine treatment for 'Rainier' cherries

Susceptibility of third-instar codling moth, Cydia pomonella (L.), to methyl bromide at 6 or 12°C was not significantly affected by the host cultivar of sweet cherry. The 95% CL for the LC50 and LC90s for larvae in ‘Bing’ and ‘Rainier’ cherries overlapped in fumigation tests at either temperature. Sorption of methyl bromide by both cultivars in comparative efficacy studies was substantial (averaging 51.0 and 55.5% for ‘Bing’ and ‘Rainier’ cherries, respectively) for both fumigation temperatures. None of the estimated 10,839 third-instar codling moth treated in ‘Rainier’ cherries in a confirmation test survived fumigation with methyl bromide at 64 g/m3 for 2 h at 6°C. These results showed that methyl bromide fumigation schedules previously approved against codling moth larvae in ‘Bing’ and other sweet cherry cultivars are equally effective against codling moth larvae in ‘Rainier’ cherries.