cssi/SciSciGPT-SciSciNet huggingface dataset:
Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning

Currently, there is neither effective antiviral drugs nor vaccine for coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to its high conservativeness and low similarity with human genes, SARS-CoV-2 main protease (Mpro) is one of the most favorable drug targets. However, the current understanding of the molecular mechanism of Mpro inhibition is limited by the lack of reliable binding affinity ranking and prediction of existing structures of Mpro-inhibitor complexes. This work integrates mathematics (i.e., algebraic topology) and deep learning (MathDL) to provide a reliable ranking of the binding affinities of 137 SARS-CoV-2 Mpro inhibitor structures. We reveal that Gly143 residue in Mpro is the most attractive site to form hydrogen bonds, followed by Glu166, Cys145, and His163. We also identify 71 targeted covalent bonding inhibitors. MathDL was validated on the PDBbind v2016 core set benchmark and a carefully curated SARS-CoV-2 inhibitor dataset to ensure the reliability of the present binding affinity prediction. The present binding affinity ranking, interaction analysis, and fragment decomposition offer a foundation for future drug discovery efforts.
Health knowledge of young adults from two socioeconomic levels.

Abstract The purpose and experimental design of this investigation were directed to the question: Do students who attend a high school from an attendance district designated as a high socioeconomic area respond the same to a standardized health knowledge test as students who attend a high school from an attendance district designated as a low socioeconomic area? The 1969 edition of the Kilander Health Knowledge test was used as the criterion measurement instrument and was administered to all of the 9th and 12th grade students attending two high schools. The criterion measure was the total correct response on the criterion instrument. A triple classification 2 × 2 × 2 ANOVA design was used to test the hypothesis that no significant difference would exist in the effects to be considered. A significant difference between criterion groups was obtained for effect A (socioeconomic level), effect B (grade level), and effect C (sex), in addition to a significant A × B interaction effect. These results suggested t...
Health Care Provider Barriers to Patient Referral to Palliative Care.

Objective:The purpose of this study was to explore healthcare provider-perceived challenges to HBPC patient referral and elicited providers’ feedback for overcoming these challenges.Methods:We cond...
Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a prospective single-center experience with mid-term follow-up (with video).

Background and Aims Gastroparesis (GP) is a multifactorial disease associated with a large burden on the health care systems. Pyloric-directed therapies including gastric peroral endoscopic myotomy (G-POEM) can be effective in improving patient quality of life and symptom severity. We report on the safety and efficacy of G-POEM and its impact on the quality of life of patients managed at a large referral center. Methods Consecutive patients with confirmed GP referred for G-POEM due to failure of medical therapy were included. All patients were assessed at baseline and then at 1, 3, 6, and 12 and 24 months after G-POEM using validated symptom and quality of life instruments, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and 36-Item Short Form Survey (SF-36). Patients were evaluated before and 6 months after the procedure with EGD, 4-hour scintigraphy, and pyloric EndoFLIP. Technical success was defined as the ability to perform full-thickness pyloromyotomy. Clinical response was defined as an improvement of ≥1 point on GCSI. Results Fifty-two patients (median age, 48 years; range, 25-80 years, 88% female) underwent G-POEM between February 2018 and September 2020 for the following phenotypes: vomiting-predominant (n=30), dyspepsia-predominant (n=16), and regurgitation-predominant (n=6) GP. The technical success rate was 100%. Adverse events were noted in 3 of 52 patients (5.77%), and were all managed successfully endoscopically. Clinical response was achieved in 68%, 58%, and 48% of patients at 1-month, 6-month, and 12-month follow-up (P Conclusions G-POEM appears to be a safe and feasible treatment alternative for refractory GP with significant short-term and mid-term improvements in overall symptoms, quality of life scores, and health care utilization.
The Negative Permanence of Plastic

The development and installation of susta13inable energy systems create jobs, regional development, and long term economic growth. The challenges presented by sustainable urban development are critical. Back in 2010, 82% of Americans lived in cities; by 2050 it will be 90 %. Cities are responsible for around two-thirds of the energy used, 60% of all water consumed, and 70% of all greenhouse gases produced worldwide. Sustainable cities are looking at ways to become more environmentally friendly, increase the quality of life for their residents, and cut costs at the same time.
The future of the shell: Unix and beyond

The Unix shell is fifty years old, and it continues to be the primary way to configure, deploy, and manage systems of all kinds. What do the next fifty years hold? What is the command-line interface of the 21st century? This 90-minute panel brings together researchers and engineers from disparate communities (systems, languages, security) to think about the shell's strengths and weaknesses, challenges and opportunities around the shell, and the shell's future.
Receipt of evidence-based alcohol-related care in a national sample of transgender patients with unhealthy alcohol use: Overall and relative to non-transgender patients.

Abstract Background/objective Evidence-based alcohol-related care–brief intervention for all patients with unhealthy alcohol use and specialty addictions treatment and/or pharmacotherapy for patients with alcohol use disorder (AUD)–should be routinely offered. Transgender persons may be particularly in need of alcohol-related care, given common experiences of social and economic hardship that may compound the adverse effects of unhealthy alcohol use. We examined receipt of alcohol-related care among transgender patients compared to non-transgender patients in a large national sample of Veterans Health Administration (VA) outpatients with unhealthy alcohol use. Methods We extracted electronic health record data for patients from all VA facilities who had an outpatient visit 10/1/09–7/31/17 and a documented positive screen for unhealthy alcohol use (AUDIT-C ≥ 5). We identified transgender patients with a validated approach using transgender-related diagnostic codes. We fit modified Poisson models, adjusted for demographics and comorbidities, to estimate the average predicted prevalence of brief intervention (documented 0–14 days following most recent positive screening), specialty addictions treatment for AUD (documented 0–365 days following screening), and filled prescriptions for medications to treat AUD (documented 0–365 days following screening) for transgender patients, and compared to that of non-transgender patients. Results Among transgender Veterans with unhealthy alcohol use (N = 1392), the adjusted prevalence of receiving brief intervention was 75.4% (95% CI 72.2–78.5), specialty addictions treatment for AUD was 15.7% (95% CI 13.7–17.7), and any AUD pharmacotherapy was 19.0% (95% CI 17.1–20.8). Receipt of brief intervention did not differ for transgender relative to non-transgender patients (Prevalence Ratio [PR] 1.01, 95% CI 0.98–1.04, p = 0.574). However, transgender patients were more likely to receive specialty addictions treatment (PR 1.24, 95% CI 1.12–1.37, p Conclusions Findings suggest the majority of transgender VHA patients with unhealthy alcohol use receive brief intervention, though a quarter still do not. Nonetheless, rates of specialty addictions treatment and pharmacotherapy are low overall, although transgender patients may be receiving this care at greater rates than non-transgender patients. Further research is needed to investigate these findings and to increase receipt of evidence-based care overall.
The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy) are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.
Improved Recombination Lower Bounds for Haplotype Data

Recombination is an important evolutionary mechanism responsible for the genetic diversity in humans and other organisms. Recently, there has been extensive research on understanding the fine scale variation in recombination rates across the human genome using DNA polymorphism data. A combinatorial approach toward this is to estimate the minimum number of recombination events in any history of the sample. Recently, Myers and Griffiths [1] proposed two measures, R h and R s , that give lower bounds on the minimum number of recombination events. In this paper, we provide new and improved methods (both in terms of running time and ability to detect past recombination events) for computing recombination lower bounds. Our principal results include: We show that computing the lower bound R h is NP-hard and adapt the greedy algorithm for the set cover problem [2] to obtain a polynomial time algorithm for computing a diversity based bound R g . This algorithm is several orders of magnitude faster than the Recmin program [1] and the bound R g matches the bound R h almost always. We also show that computing the lower bound is also NP-hard using a reduction from MAX-2SAT. We give a O(m 2 n ) time algorithm for computing R s for a dataset with n haplotypes and m SNP’s. We propose a new bound R I which extends the history based bound R s using the notion of intermediate haplotypes. This bound detects more recombination events than both R h and R s bounds on many real datasets. We extend our algorithms for computing R g and R s to obtain lower bounds for haplotypes with missing data. These methods can detect more recombination events for the LPL dataset [3] than previous bounds and provide stronger evidence for the presence of a recombination hotspot. We apply our lower bounds to a real dataset [4] and demonstrate that these can provide a good indication for the presence and the location of recombination hotspots.
The ‘pains’ of electronic monitoring: a slap on the wrist or just as bad as prison?

The purpose of this research is to examine whether inmates that have served electronic monitoring (EM) find it more punitive than offenders that have not served electronic monitoring. We asked a sample of 1194 inmates currently incarcerated in a Midwestern state to estimate exchange rates of electronic monitoring over prison by rating how many months of EM they would serve to avoid 12 months in prison. The results indicate that inmates view EM as less punitive than prison and that monitored offenders find EM more punitive than unmonitored offenders. Additionally, black inmates were more likely to have served EM than white inmates and older inmates find EM more punitive than younger inmates. Previously monitored offenders report that they will be less likely to rely on family and friends upon release from prison. These results suggest that EM is perceived as a punitive sanction by those that have experienced it. Furthermore, racial differences uncovered here may help explain why minorities view alternative...
Recent Developments in Light Scattering Experiments on Laboratory Plasmas

In the past, light scattering techniques were mainly aimed at measuring plasma parameters such as the electron density and the temperatures of electrons and ions. These efforts were most successful and, thus, have demonstrated that such techniques represent a superior tool of plasma diagnostics also for laboratory plasmas A review of this earlier development of the field can be found for example in the articles by Kunze1 and by Evans and Katzenstein2. With the further refinement of the employed techniques a wider range of plasmas as well as the finer details of spectra became accessible. As a result deviations from the light scattering spectra calculated under the assumption of Maxwellian velocity distributions for electrons and ions became apparent. In addition, the measurement of magnetic fields by light scattering was shown to be feasible as was the detection of enhanced plasma waves in turbulent plasmas. These more recent developments in the field of light scattering by plasmas form the subject of this article which is not claimed to be fully comprehensive but is intended to demonstrate these developments by typical cases.
Snort - Lightweight Intrusion Detection for Networks

Network intrusion detection systems (NIDS) are an important part of any network security architecture. They provide a layer of defense which monitors network traffic for predefined suspicious activity or patterns, and alert system administrators when potential hostile traffic is detected. Commercial NIDS have many differences, but Information Systems departments must face the commonalities that they share such as significant system footprint, complex deployment and high monetary cost. Snort was designed to address these issues.
Time dependent voltage in CuInSe/sub 2/ and CdTe solar cells

The open circuit voltage of CuInSe/sub 2/ and CdTe solar cells continues to increase during the time range of 10/sup -3/ to 10/sup 4/ s after the cell is illuminated or otherwise placed in forward bias. The effect is qualitatively similar in all samples measured to date, however, the magnitude of the voltage shift varies from 3 to 40 mV. The shift increases with increasing light intensity. The voltage shift depends on the voltage history of the sample and not the illumination history. Application of an appropriate pre-measurement bias in the dark can significantly reduce the voltage shift. When the cell remains in the dark with a constant forward current, a nearly identical voltage shift is seen. The time required for the cell to relax back to the dark zero-bias steady-state condition is similar to the time the cell has been in forward bias. A likely cause for the shift is electron-trapping centers near the diode junction which change occupation with changes in voltage. The voltage shift has important consequences for pulse-simulator measurements, which, because of the shift, tend to underestimate the steady-state voltage. >
Fuzzy set methods for uncertainty representation in risky financial decisions

The problem of selecting an investment option in the face of uncertainty with respect to the payoff is considered. Methods for the representation of uncertainty based on the theory of fuzzy sets and the Dempster-Shafer belief structure are described. Approaches for comparing alternatives under various kinds of uncertainty are discussed.
Adverse Childhood Experiences (ACEs), Service Use, and Service Helpfulness Among People Experiencing Homelessness

This study examines categories of adverse childhood experiences (ACEs) and service use backgrounds among a convenience sample of people experiencing homelessness (N = 224), using logistic regression analysis (n = 174) and descriptive and comparative analyses. Eighty-seven percent reported at least 1 of 10 ACEs prior to age 18. Over half (53.2%) reported 4 or more ACEs. Approximately half reported parental loss, emotional neglect, living with a substance abuser, and emotional abuse. ACEs were significantly correlated with one another. Among those who used prior services, ACEs predicted interpersonal prevention, clinical, and criminal justice services for emotional or substance abuse problems. Most indicated services were helpful. This study provides data for policy and program leaders to ensure at-risk families and communities have access to responsive services.
An Acetylacetonate-Based Semiconductor−Sensitizer Linkage

Coordination compounds of the general type Ru(dmb)2(LL)(PF6)2, where dmb is 4,4‘-(CH3)2-2,2‘-bipyridine and LL is 4-(CH3)-4‘-(COOH)-2,2‘-bipyridine, or 4-(CH3)-4‘-((CH2)3COOH)-2,2‘-bipyridine, or 4-(CH3)-4‘-((CH2)3COCH2COOC2H5)-2,2‘-bipyridine were prepared for the attachment to semiconductor metal oxide surfaces. The optical and redox properties of these compounds in dichloromethane solution are reported. Binding to porous nanostructured TiO2 films was analyzed with the Langmuir adsorption isotherm model. Photoelectrochemical measurements of the modified TiO2 electrodes in regenerative solar cells are reported. The results indicate that intimate electronic coupling between the surface link and the chromophoric ligand is not a strict requirement in the design of sensitizers for photovoltaic applications. Interfacial kinetics for recombination of the electron in the solid with the oxidized form of the sensitizer were quantitated by excited state absorption spectroscopy.
Isolation of a C (Ibc) protein from group B Streptococcus which elicits mouse protective antibody.

Abstract The C (lbc) proteins of group B Streptococcus (GBS) have been shown to induce mouse protective antibodies when present as immunogens on whole organisms. However, characterization of specific proteins responsible for inducing protection has not been reported. We have grown type lc GBS in a dialysate of Todd Hewitt broth and analyzed the proteins extruded into the broth. Multiple proteins of varying size were visualized by SDS-PAGE. Ultrafiltration was used to separate the GBS components by molecular weight (MW) into 2 pools, those below 30000 MW but above 10000 MW (P10) and those above 30000 MW (P30). The P10 contained 4 major proteins, including a 14000 MW protein. Balb-c mice were immunized with the P10 fraction and the antisera used in mouse protection studies. This immune sera protected 100% of mice against challenge with type lb GBS and protection was not altered by prior absorption of the sera with type la or lb capsular polysaccharide. The P10 was fractionated by column chromatography and eluted proteins examined by SDS-PAGE and Western blot with the mouse protective antisera elicited to the P10. There was one major immunologically reactive protein at 14000 MW which eluted in a partially purified form from the column. The 14000 MW protein was reisolated from preparative SDS-PAGE gels and used to elicit antiserum in a rabbit. In mouse protection studies this rabbit antiserum protected mice against subsequent challenge with type lb GBS (89% protection). Surface antigens were extracted from 125 I-labelled type Ic GBS and immunoprecipitated with antiserum to the 14000 MW protein. The 14000 MW protein and multiple higher molecular weight proteins were immunologically cross-reactive suggesting the presence of shared epitopes. Thus the 14000 MW protein from type lc GBS that is antigenic and elicits mouse protective antibodies against the heterologous type lb GBS fulfills the criteria for a C protein of GBS.
Contribution of the B16 and B26 tyrosine residues to the biological activity of insulin

We report the synthesis and biological evaluation of five insulin analogues in which one or both of the B-chain tyrosine residues have been substituted. [B16 Phe]insulin and [B16 Trp]insulin display a very modest reduction in potency (c. 65%) relative to porcine insulin; [B26 Phe]insulin is less active (30-50%), and the doubly substituted [B16 Phe, B26 Phe]insulin displays still lower potency (c. 35%). The further substitution of Asp for B10 His in [B16 Phe, B26 Phe]insulin raises its activity to approximately twofold greater than natural insulin, an increase of approximately fivefold over the parent compound. We conclude that the bulk and/or aromaticity of the amino acid residue at position B16, but not its hydrogen-bonding capacity, contributes to the biological activity of the hormone. We further conclude that hydrogen-bonding capacity or special side-chain packing characteristics are required at the B26 position for insulin to display high biological activity.
Simple Physical Principles and Vertebrate Aquatic Locomotion

SYNOPSIS. Swimming is a common and important component of vertebrate behavior. Therefore the study of swimming form and function is essential to understanding vertebrate biology. An interactive process between biologists and hydrodynamicists has proven extremely successful in providing such understanding. This process starts with a definition of forces that may act on an animal; viscous and pressure drag, acceleration reaction, lift and body inertia, and ground reaction. Dominant force components are selected on the basis of ground contact, Reynolds number, reduced frequency, and shape. Conservation of momentum requires forces and their moments be in balance leading to models describing swimming motions and associated forces. These provide the bridge between the hydrodynamics studies and biological applications. Numerical solutions to models estimate thrust and drag, and rates of working, which are several times greater than expected for manmade non-flexing bodies. These solutions are used in prediction of optimal two-phase swimming behaviors, alternating high resistance swimming with low resistance behavior such as gliding. Qualitative predictions from models define optimal forms for various behaviors and habitats. Optimal forms tend to be mutually exclusive, providing benchmarks for analyses relating form and function in an ecological context. Life history patterns are also affected by locomotor capabilities of various morphologies. Scale effects limit the distribution of propulsors. Numerical solutions to models are probably only good within an order of magnitude because of the assumptions in their formulation, but rankings of mechanisms or organisms are adequate for comparative study. Predictions must be tempered by consideration of non-locomotor function, developmental limitations of structural options, and non-equilibrium community structures.
Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production.

The cell surface/endosomal Toll-like Receptors (TLRs) are instrumental in initiating immune responses to both bacteria and viruses. With the exception of TLR2, all TLRs and cytosolic RIG-I-like receptors (RLRs) with known virus-derived ligands induce type I interferons (IFNs) in macrophages or dendritic cells. Herein, we report that prior ligation of TLR2, an event previously shown to induce “homo” or “hetero” tolerance, strongly “primes” macrophages for increased Type I IFN production in response to subsequent TLR/RLR signaling. This occurs by increasing activation of the transcription factor, IFN Regulatory Factor-3 (IRF-3) that, in turn, leads to enhanced induction of IFN-β, while expression of other pro-inflammatory genes are suppressed (tolerized). In vitro or in vivo “priming” of murine macrophages with TLR2 ligands increase virus-mediated IFN induction and resistance to infection. This priming effect of TLR2 is mediated by the selective upregulation of the K63 ubiquitin ligase, TRAF3. Thus, we provide a mechanistic explanation for the observed antiviral actions of MyD88-dependent TLR2 and further define the role of TRAF3 in viral innate immunity.
Metabolism of Separated Leaf Cells: II. Uptake and Incorporation of Protein and Ribonucleic Acid Precursors by Tobacco Cells.

Enzymatically separated tobacco leaf cells took up amino acids, uracil, and uridine from the incubation medium and incorporated them into proteins and RNA, respectively, at a linear rate for approximately 30 hours. Both uptake and incorporation were light-dependent, although cells prepared from preilluminated plants or preillumination of cells allowed some uptake and incorporation to occur in the dark. The light was necessary to satisfy a photosynthetic requirement, but could be replaced in part by ATP in the medium.Several lines of evidence support the conclusion that the rate of uptake of amino acids, uracil, and uridine was dependent upon the subsequent incorporation of these compounds into macromolecules.
Statistical analysis of commuters' route, mode, and departure time flexibility

This paper studies the effects of traffic information on Seattle-area commuters. Models of commuters' route-change frequency, the duration of traffic delay needed to induce a route change, and the influence of pre-trip traffic information on departure-time choice, mode choice, and route choice are estimated. Two modeling techniques are used in these estimations: an ordered logit probability approach and a Weibull duration model with a heterogeneity correction term. The findings of these model estimations provide important insights into how traveler information systems should be designed, implemented, and marketed.
Analysis of mid-tropospheric space shuttle exhausted aluminum oxide particles

Aluminum oxide particles from the exhaust of the Space Shuttle were collected immediately after the launch of the SEPEX mission and during the descent over the altitude interval of 7.6-4.6 km. The SEM examination revealed that the particles were spherical and ranged in diameter from about 0.1 micron to 10 microns. Results from the energy dispersive analysis (by an X-ray method) and of the particle chemistry (by electron spectroscopy) confirmed that the particles were predominantly composed of aluminum and oxygen. The particle size distribution of the Al2O3 was bimodal, with one observed peak centered near 2.0 microns; the other distribution mode centered at a diameter of less than 0.3 micron, but could not be accurately located. A mass median diameter was slightly less than 2 microns. Evaluation of ice nucleation activity revealed only a small fraction (about 1 ppm) of active ice nuclei among the Al2O3 particulates.
On the mechanism of photoinduced nucleation in a diffusion cloud chamber

Photoinduced nucleation of NO2 in supersaturated nonane has been studied in a diffusion cloud chamber. The photonucleation spectrum is found to correlate with the yield spectrum for the production of reactive radical species (O + NO) and not with the absorption spectrum of the nucleation inducing agent. A mechanism is proposed in which hydrogen abstraction by O from the nonane produces radicals which then react with each other or with NO2 to produce species of low volatility that lead to nucleation. Studies of photoinduced nucleation by several alkyl iodides (known to produce radicals upon UV absorption) further support the proposed radical mechanism for photoinduced nucleation.
Abstract 3: HER2 gene-amplified human breast cancer cells harboring a gatekeeper T768M mutation in HER2 overexpress EGFR ligands and are sensitive to dual therapeutic blockade of EGFR and HER2

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Intrinsic or acquired mutations in receptor tyrosine kinases (RTKs) can confer resistance to RTK-targeted therapies. A previous study reported that a ‘gatekeeper’ T768M mutation in HER2 confers resistance to the tyrosine kinase inhibitor (TKI) lapatinib. We generated BT474 cells stably expressing either T768M HER2 or GFP. Treatment with lapatinib disrupted HER3-p85 complex and blocked phosphorylation of HER2, HER3, AKT and Erk1/2 in BT474-GFP but not in BT474-T768M cells. BT474-T768M cells were also resistant to other anti-HER2 therapies such as trastuzumab. BT474-T768M cells were sensitive to the PI3K inhibitor BKM120 but not the MEK inhibitor CI1040, suggesting they still depend on the PI3K pathway for survival. Treatment with the irreversible HER2/EGFR inhibitor BIBW2992 (afatinib) eliminated P-HER2 and inhibited growth of cells expressing the mutant, suggesting they still depend on the ErbB receptor network to activate PI3K. Indeed, like in BT474-GFP (control) cells, BIBW2992 disrupted the association of p85 (PI3K) with HER3 and blocked phosphorylation of AKT. A co-culture experiment with varying proportions of BT474-GFP and BT474-T768M cells revealed that lapatinib-resistant acini emerge when as low as 5% of the population has T768M HER2. Moreover, we found that only 3.2% of the HER2 alleles had the T768M mutation in the BT474-T768M cells. This result suggests that allelic dilution will render it difficult to identify this drug resistant mutation with conventional sequencing techniques (i.e., Sanger) in patients with HER2 gene-amplified breast cancer. Next, we stably expressed either wild-type or T768M HER2 in MCF10A cells. Both WT and T768M HER2 resulted in increased phosphorylation of HER3 and AKT. MCF10A-HER2 but not MCF10A-T768M cells were sensitive to growth inhibition by lapatinib. Lapatinib blocked HER2, HER3 and tyrosine phoshorylation in MCF10A-HER2 but not in MCF10A-T768M cells. Quantitative PCR indicated that the BT474-T768M cells produce more EGFR ligands (EGF, TGFα, amphiregulin and HB-EGF) compared to BT474-GFP cells. Treatment with cetuximab, an EGFR antibody that blocks ligand binding, restored sensitivity of BT474-T768M cells to trastuzumab. Further, the BT474-T768M cells were sensitive to a combination of trastuzumab and lapatinib both in vitro and in vivo. Hence, dual blockade of HER2 and EGFR might be effective at trumping the development of HER2-overexpressing cancers bearing a gatekeeper mutation in T768M. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3. doi:1538-7445.AM2012-3
SU‐E‐J‐95: Increasing Soft Tissue Contrast by Combining New CT Technologies and Imaging Dose for Radiation Treatment Planning and Delivery Guidance

Purpose: CT dose is normally minimized based on ALARA principle. For radiation therapy (RT), a slightly increased CT dose in exchange for improved soft‐tissue contrast may be justified. In this work, we investigate the impact of CT imaging dose and other acquisition and reconstruction parameters on CT quality for RT planning and delivery guidance. Methods: CT data of various phantoms were acquired using a CT‐on‐rails (Somaton Definition AS Open, Siemens) with a series of acquisition parameters, such as tube voltage and current, rotation time, pitch, imaging dose control methods, and reconstruction algorithms, and were analyzed based on contrast‐to‐noise ratio (CNR) and dose‐weighted CNR (CNRD) to identify image quality enhancement protocols (IQEP). The IQEPs were then used to acquire CT during daily IGRT for selected patients with head and neck, prostate, and pancreas cancers. The impact of the improved CT images on RT was assessed with (1) accuracy and reproducibility of auto‐segmentation using ABAS (Elekta) and (2) intra‐and inter‐variability of manual contouring of the relevant organs by 10 observers. Results: As expected, the CNR generally increases with mAs from phantom CT data, while CNRD experiences a slow increase with mAs or reaches a plateau and then drops above certain mAs depending phantom size and relative electron density or contrast level. There is complicated interplay between kVp and mAs, particularly with regards to perception. Visual inspection of the patient CTs obtained with IQEPs showed clearer organ boundaries as compared to those from the standard CT protocols. This improvement was supported by the reduced intra‐and inter‐variability of manual contouring. The CT doses with IQEPs were 2–3 times higher than those from the standard protocols. Conclusion: CT quality can be improved by optimizing parameters in CT protocols for modern scanners, leading to improved accuracy of organ delineation for RT planning and delivery.
Simulation optimization: a survey of simulation optimization techniques and procedures

Discrete-event simulation optimization is a problem of significant interest to practitioners interested in extracting useful information about an actual (or yet to be designed) system that can be modeled using discrete-event simulation. This paper presents a brief survey of the literature on discrete-event simulation optimization over the past decade (1988 to the present). Swisher et al. (2000) provides a more comprehensive review of this topic while Jacobson and Schruben (1989) covers the literature preceding 1988. Optimization of both discrete and continuous input parameters are examined herein. The continuous input parameter case is separated into gradient and non-gradient based optimization procedures. The discrete input parameter case differentiates techniques appropriate for small and for large numbers of feasible input parameter values.
Replica studies of habit-modified ammonium dihydrogen phosphate and ammonium dihydrogen arsenate crystals

Abstract Carbon replicas of fracture surfaces of ammonium dihydrogen phosphate and ammonium dihydrogen arsenate crystals grown from solutions containing chromic, ferric, or stannic ions reveal certain growth features not found in the pure crystals. In some areas a water-insoluble residue is found at the surface. It is believed that this residue is a metal phosphate or arsenate formed during growth of the crystal or occluded from suspension in the solution. At high concentrations of foreign ions in solution a microstructure has been found, consisting of units tapered in a direction parallel to the z -axis of the crystal. Insoluble residues as amorphous films or discrete particles are found concentrated about these units. Similar tapered units visible to the eye are formed at the intersection of the prism and pyramid faces when growth is forced on seed crystals at concentrations of foreign ions sufficiently high to inhibit growth. Other surface features found repeatedly include layer growth, dendrites, and polygonal boundaries outlined by small particles.
Ray casting and the enclosing-net algorithm for extracting shapes from volume data

One of the most useful applications of virtual reality is to let doctors view the inside of the human body non-invasively and in real time. In this paper, we first survey the area of virtual reality and volume-visualization techniques. We discuss our ray casting implementation for viewing the medical data which is available as a set of slices from NMR and CT scans. Next we present a new method, the enclosing-net algorithm, for extracting iso-surfaces from volume data. A simple implementation of our technique is described. Since the topology of the extracted surface is well defined and non-ambiguous, the enclosing-net algorithm eliminates a major problem of surface extraction techniques. In addition, the number of polygons representing the surface can be controlled to obtain a finer shape. Therefore real-time interaction is feasible on both low-end and high-end graphics machines, making the enclosing-net algorithm suitable for virtual reality experiments.
Self-Contained Thermoelectric Generator for Cell Phones

Results of research and development of a 1 W thermoelectric generator for cell phones are presented. A physical model of the generator with catalytic combustion of gas fuel is proposed. A computer simulation method is used to determine the optimal parameters of the thermopile, catalytic heat source, and microgenerator heat rejection system whereby the efficiency of gas combustion heat conversion into electrical energy is a factor of two higher compared with existing analogs. The generator design is described, and results of experimental research on its parameters and the charging rate of cell phone batteries with capacity of 900 mA h to 1600 mA h are given. In the self-contained operating mode of various low-power devices, the elaborated thermoelectric generator with a catalytic heat source is an alternative to traditional sources of chemical energy.
The spatiotemporal dynamics of insular ant metapopulations

The ant species inhabiting 129 small Bahamian cays were surveyed annually over a 5-yr period. Stepwise multiple linear regression analyses revealed that plant species number was the best single predictor of ant species richness. Vegetated area or cay elevation (depending on the analysis) were second selected variables. Variation in the selected pre- dictor variables explained 56.8-71.7% of the variation in ant species number. An "all- subsets" regression approach yielded similar results. Stepwise multiple logistic regression analyses revealed that the probability of occurrence of Dorymyrmex pyramicus was posi- tively related to vegetated area and elevation, whereas that of Pheidole punctatissima was positively related to plant species number and distance. Species turnover was documented on 42% of the cays inhabited by ants over the course of the study. Mean annual relative turnover was low and variable, ranging from 0.83 to 22.37%/yr when calculated on a per- species basis, and from 2.13 to 5.70%/yr when calculated on a per-island basis. Sampling error was quantified, and pseudoturnover was found to inflate observed turnover for only one species (P. punctatissima). A comparison of immigration and extinction rates indicated the existence of a dynamic equilibrium between these two processes. The probabilities of immigration and extinction (pooled over all species) were both positively related to veg- etation height. Observed turnover rates for ants were lower than those reported from other, more limited studies of insular ants and from studies of insular arthropods in general, and were more similar to documented vertebrate turnover rates. Incidence functions revealed that the three most common species, Brachymyrmex cf. obscurior, D. pyramicus, and P. punctatissima, displayed different patterns of distribution in relation to insular ant species richness.
Comparative longitudinal study on microcomputer availability and usage in accounting curriculums

Abstract This paper presents comparative survey data on personal computer (microcomputer) availability and usage in the accounting curriculum. A first study, made in 1983, comprised 418 schools with accounting programs listed in Hasselback's 1983 Accounting Faculty Directory . At that time, the 79 usable (a 19% response rate) to the study implied that accounting programs were lagging in the integration of microcomputer applications into accounting curriculums. A second follow-up study in 1985 encompassed 500 schools listed in Hasselback's 1984 Accounting Faculty Directory . The 123 fully usable surveys answered (a 25% response rate) suggested that increasing use of microcomputers by business and CPA firms had provided an impetus for accounting departments to integrate greater micro applications into their courses. The most recent investigation in 1988 included 462 schools listed in Hasselback's 1987 Accounting Faculty Directory . One hundred eighteen usable replies were returned, representing a 26% response rate. The remainder of this study examines and discusses the current and projected availability and use of microcomputers in accounting curriculums as indicated by the latest survey results. Comparative data from the two aforementioned surveys will be incorporated where the presentation of such facts seems to be appropriate.
Ecdysone agonist halofenozide affects corpora allata and reproductive physiology of the Formosan subterranean termite, Coptotermes formosanus.

Following a short swarming flight, winged adults of the Formosan subterranean termite, Coptotermes formosanus lose their wings and form tandem pairs. These dealates or primary reproductives then form incipient colonies. Topical application of 5 μg of the non-steroidal ecdysone agonist RH-0345 (halofenozide) in 0.1 μl DMSO to the primary reproductives during the 2000 season resulted in significant reduction in the number of eggs laid. There was however complete recovery of the treated females. Apparently the non-treated partner removed the treatment chemical while grooming indicating oral activity. In 2001 both topical application as well as feeding methods were tried. Significant effects were observed only in the topical treatment group, perhaps because of inconsistency in feeding. In this group, total progeny, the number of ovarioles in ovaries and the size of the female’s corpora allata (CA) were all significantly reduced. Ultrastructure of the CA of treated females showed extensive vacuolation near the surface of the gland. The experiment was repeated in 2002 using both topical application and an improved oral feeding method. Whereas there was apparent recovery in the topically treated group after 90 days, the oral treatment was more persistent in its effect perhaps due to a higher amount of halofenozide consumed during feeding.
Washington State reorganization: more of the story

The creation of a new Department of Health in Washington State in 1989 provided an opportunity for analysis of the many forces beyond the pressure of interest groups leading to such a change. Interviews with key actors from executive and legislative branches of state government, local government, and interested health organizations were conducted to uncover the full scope considered for the new department, and the interactions that led to the final, narrower entity. A process model based on these findings is presented as a useful tool for those seeking to improve public health at the state level through changes in the organizational units responsible for health activities.
Modulation of hypoglycemia-induced increases in plasma epinephrine by estrogen in the female rat.

Clinical studies have demonstrated that estrogen replacement therapy suppresses stress-induced increases in plasma catecholamines. The present study determined whether normal circulating levels of estrogen can modulate hypoglycemia-induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin-induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14-day ovariectomized (OVEX) rats compared to that in sham-operated controls. In 17β-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was reduced significantly when compared to that in vehicle-replaced OVEX rats. OVEX and E2 replacement had no effect on tyrosine hydroxylase or phenylethanolamine N-methyltransferase mRNA levels in the adrenal medulla. In isolated adrenal medullary chromaffin cells, agonist-induced increases in intracellular Ca2+ were unaffected by 48-hr exposure to 10 nM E2. In contrast, acute (3-min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced Ca2+ transients. In addition, in OVEX rats, a constant infusion of E2 significantly reduced the insulin-induced increase in plasma EPI concentration compared to that in vehicle-infused controls. These data demonstrate that physiologic levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect seems independent of steroid influence on adrenal medullary secretion or biosynthesis. In contrast, acute exposure to high levels of E2 can also suppress hypoglycemia-induced increases in plasma epinephrine, due at least in part to inhibition of stimulus-secretion coupling. © 2004 Wiley-Liss, Inc.
Raman spectroscopic and electrochemical characterization of myoglobin thin film: implication of the role of histidine 64 for fast heterogeneous electron transfer.

Myoglobin (Mb) thin films formed on various substrates have been characterized by using Raman spectroscopy, reflectance absorbance FT-IR, UV−vis absorption spectroscopy, and electrochemical methods. Raman spectra were obtained upon excitation within the Soret band as well as α−β bands. The spin state marker bands observed from the Mb film in the 1550−1630 cm-1 region (excitation at 514.5 nm) are ∼20 cm-1 higher than those of aqueous metMb having the high spin state. The 1210 cm-1 band (methine bridge C−H vibration) also shifts to 1240 cm-1 upon the formation of the film. These results indicate that the heme iron of myoglobin in the film is the ferric low-spin state, and the iron atom is pulled to the heme plane. A comparison of the Raman spectra of the Mb film with that of an Mb-imidazole derivative leads to the conclusion that the distal histidine is responsible for the change in the spectral characteristics. The escape of water from the sixth position upon the formation of the Mb film may result in a co...
Spinal Posture Affects Whiplash Biomechanics

The present study implemented the MADYMO 50th percentile male head-neck model to investigate effects of initial spinal posture on cervical spine kinematics in whiplash. The model was altered to three initial postures: lordosis, straight, kyphosis. The three models were exercised under 2.6 m/sec rear impact pulses. Segmental kinematics and ligament strains were investigated during cervical S-curvature and throughout the whiplash event. Anterior longitudinal ligament strains during S-curvature varied from 20 to 47% of maximum strains. Facet joint strains during S-curvature were 42 to 100% of maximum strains. This finding indicates that facet joint ligaments are more susceptible to whiplash injury during S-curvature, while anterior longitudinal ligament injury likely occurs during the extension phase. Kyphosis and straight postures increased anterior longitudinal ligament strains in the upper cervical spine from the lordosis posture. Lower cervical facet joint and anterior longitudinal ligament strains were greater in the lordosis posture. This study shows that spinal posture may affect injury mechanisms and render a specific population more susceptible to whiplash injury.Copyright © 2003 by ASME