cssi/SciSciGPT-SciSciNet huggingface dataset:
Co-responsibility for Individualists

Some argue that if an agent intentionally participates in collective wrongdoing, that agent bears responsibility for contributing actions performed by other members of the agent’s collective. Some of these intention-state theorists distribute co-responsibility to group members by appeal to participatory intentions alone, while others require participants to instantiate additional beliefs or perform additional actions. I argue that prominent intention-state theories of co-responsibility fail to provide a compelling rationale for why participation in collective wrongdoing merits responsibility not only for one’s own actions but the contributing actions of others as well. I propose that authorization agreements provide us with a suitable rationale. Authorization may be expressly given, as when one person signs a document authorizing another to advance her aims. Or, authorization may be tacitly or implicitly given by participating in and sufficiently contributing to a common plan. If a person authorizes an agent to act, it is right to blame the authorizer for what the agent does on the authorizer’s behalf. An authorization theory justifies the distribution of co-responsibility by appeal to the morally transformative power of agreement, thereby providing a compelling rationale for why a person may be to blame for contributing actions performed by other agents.
Hepatic oligometastases treated with stereotactic body radiation therapy: Updated 10-year analysis of the Indiana University experience.

3583 Background: Stereotactic body radiation therapy (SBRT) is a non-invasive, effective technique in the treatment of a limited number of liver metastases from solid tumors. We present the 10 year...
Detection and tracking of bubbles in two-phase air water flow for non-convergent sinusoidal channel

Bubble detection and tracking, which is essential for the enhancement of gas–liquid two-phase flow applications, is difficult due to optical noise surrounding bubble boundaries. Two-phase flow applications involving unconventional wavy channels further complicate these tasks by introducing non-linearity. In this work, the authors apply a path-based approach to transform a sinusoidal channel into a straightened horizontal channel for bubble detection and tracking. Segmented morphological operations are applied to the linear channel to identify each bubble as a single entity and to eliminate noise caused due to illumination conditions. The bubbles are detected through blob analysis and are associated across different frames based on motion, estimated by Kalman filter in both sinusoidal and path-based approach to the sinusoidal channel. The results show that the proposed path-based straightened channel gives more accurate results for the benchmark parameters of bubble count and bubble velocities than the sinusoidal channel with a percentage error reduction of 31.61% for bubble count and 27.36% for velocity.
Target-directed enediynes: designed estramycins.

The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen−enediyne conjugates were assembled, and affinity for human estr...
Mediators in Arbitration

This Chapter focuses on mediation in practice and describes mediation’s role in contemporary transnational dispute system design. It acknowledges the general trend towards settlement facilitation in international arbitration and focuses on mediators giving shape and structure to that facilitation. It examines the mediation process, its advantages, commonalities with and differences from arbitration and the growth of transnational mediation practice. Reflection on the relationship between mediation and justice, equity and fairness, summons up several models of mediator behavior that seek to achieve justice. Special attention is paid to contemporary convergences with arbitration and mediation and the controversial mixture of arbitration and mediation — mediation processes that include aspects of mediation within arbitration and arbitration within mediation. Finally, it offers some cautionary considerations on blending mediation and arbitration and proposes several questions for reflection about the way forward.
Inhibition of Carbonic Anhydrase-IX As a Novel Strategy to Overcome Hypoxia Mediated Drug Resistance in FLT3/ITD Mutated Acute Myeloid Leukemia

Abstract Background: FLT3/ITD mutated (FLT3/ITD+) acute myeloid leukemia (AML) is an aggressive form of blood cancer that carries a poor prognosis due to short remission durations and high relapse rates. Several studies suggest that this poor outcome is due to a small fraction of leukemic cells (LCs) that elude treatment and survive in hypoxic niches of the bone marrow (BM) where they lead to relapse. The identification of molecules capable to target LCs under hypoxic conditions is therefore of utmost importance on the way to find a cure for AML. Our study addresses the effects of pharmacological inhibition of carbonic anhydrase-IX (CA9), a transmembrane protein which functions to maintain a neutral intracellular pH - a key survival mechanism for tumor cells to escape cell death in the hypoxic environment - on AML cells. Targeting CA9 is of particular interest as its expression is confined to only a few normal tissues. CA9 inhibition may therefore show relatively few side effects compared to standard chemotherapies. Methods: Molm14 (M14), M13, OCI-AML3, THP-1 and primary cells (PC) from FLT3/ITD+ AML patients were incubated under normoxic (21% O2) and hypoxic (1% O2) conditions in the presence or absence of Quizartinib (Quiz), Cytarabine (Cy) or the CA9 inhibitors FC531 (FC) or SLC-0111 (SLC). After 48h proliferation and apoptosis assays were performed using MTT assays, annexin V/PI staining and FACS analysis. Cells were also assessed for CA9 and CA12 mRNA expression as well as intracellular pH levels via RT-PCR and fluorescent imaging, respectively. FLT3/ITD+ AML xenografts were generated by injecting M14 cells in the tail vein of NSG mice. Tissue samples were fixed in 10% NBF, embedded in paraffin and stained with HE n=3, p 10µM) compared to M14 and M13 cells. Interestingly, these cell lines displayed higher levels of CA12 mRNA (CA9/12 ratio=0.68 [OCI-AML3] and 0.54 [THP-1]) compared to the FC sensitive cell lines M14 and M13 (CA-9/12 ratio=2.5 and 4.6, respectively). Next, we assessed the effects Cy (1µM), Quiz (100nM) and FC (200µM) against FLT/ITD+ PCs. As expected, Cy and Quiz did not confer cytotoxic effects under 1% O2. Surprisingly, FC was only mildly effective against FLT/ITD+ PCs, which harbored low CA9/12 ratios ( Disclosures No relevant conflicts of interest to declare.
Safety of Intravenous Heparin for Cardiac Surgery in Patients With Alpha-Gal Syndrome.

Background Alpha-gal syndrome is a tick-acquired disease caused by immunoglobulin E (IgE) to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), causing allergic reactions to meat and products sourced from nonprimate mammals. As heparin is porcine-derived, we hypothesized that patients with alpha-gal syndrome who received high-dose heparin for cardiac surgery would have increased risk of anaphylaxis. Methods All cardiac surgery patients at an academic medical center from 2007 to 2019 were cross-referenced with research and clinical databases for the alpha-gal IgE blood test. Clinical data were obtained through the institutional Society of Thoracic Surgeons Adult Cardiac Database and chart review. Patients were stratified by development of an allergic reaction for univariate statistical analysis. Results Of the 8819 patients, 17 (0.19%) had a positive alpha-gal test before cardiac surgery. Of these 17 patients, 4 (24%) had a severe allergic reaction. The median alpha-gal titer was significantly higher in patients with a reaction (75 [interquartile range, 61-96] IU/mL vs 8 [interquartile range, 3-18] IU/mL; P = .006). There were no differences in median heparin loading dose, total dose, or maximum activated clotting time (all P > .05). In a subgroup of 8 patients with recent alpha-gal IgE level, 4 (50%) developed an allergic reaction. Conclusions Although alpha-gal is rare in patients undergoing cardiac surgery, there is up to a 50% risk of serious allergic reaction to heparin for cardiopulmonary bypass. Higher preoperative alpha-gal titers may confer a higher risk of severe allergic reaction. For patients with a clinical suspicion of alpha-gal syndrome, we recommend prescreening with IgE levels and premedicating before receiving high doses of intravenous heparin.
Patient Preference in the Selection of Prosthetic Joint Stiffness

Clinical prescription and tuning of prosthetic legs relies heavily on a trial-and-error paradigm. Patient preference, a formalized representation of what patients want provides an efficient method for identifying appropriate prosthesis mechanics. Unfortunately, a lack of the scientific and technological tools necessary to formally measure and rigorously understand preference has led to limitations in ascertaining its role in the prescription process. In this study, our objective was to understand how preference changes with walking speed and how preference corresponds to clinical metrics of gait performance. We characterized preferred stiffness of the Variable Stiffness Prosthetic Ankle Foot (VSPA Foot) across speeds in persons with below knee amputation. We then assessed metabolic expenditure and performance in the ten-meter walk test at several stiffness values around the preferred stiffness. Preferred stiffness did not correlate with body mass, and was lower at the self-selected treadmill walking speed than at either the fast or slow speeds. There was a significant increase in self-selected overground speed in the ten meter walk test at stiffness values at or above the preferred stiffness. Changes to prosthetic ankle stiffness within +/-30% of the preferred stiffness did not significantly affect metabolic expenditure. These results indicate that preferred stiffness may be associated with significant changes in self-selected overground walking speed (p$\lt $0.001), and may not be driven by metabolic optimality (p$\gt $0.93). This outcome motivates future work to identify other potential drivers of preference, including biomechanical correlates of gait, and highlights the potential value of formally incorporating patient preference into the clinical prescription process.
Lagging strand encoding promotes adaptive evolution

Abstract Cells may be able to promote adaptive evolution in a gene-specific and temporally-controlled manner. Genes encoded on the lagging strand have a higher mutation rate and evolve faster than genes on the leading strand. This effect is likely driven by head-on replication-transcription conflicts, which occur when lagging strand genes are transcribed during DNA replication. We previously suggested that the ability to selectively increase mutagenesis in a subset of genes may provide an adaptive advantage for cells. However, it is also possible that this effect could be neutral or even highly deleterious. Distinguishing between these models is important because, if the adaptive model is correct, it would indicate that 1) head-on conflicts, which are generally deleterious, can also provide a benefit to cells, and 2) cells possess the remarkable ability to fine-tune adaptive evolution. Furthermore, investigating these models may address the long-standing debate regarding whether accelerated evolution through conflicts can be adaptive. To distinguish between the adaptive and neutral models, we conducted single nucleotide polymorphism (SNP) analyses on wild strains of bacteria, from divergent phyla. To test the adaptive hypothesis, we analyzed convergent mutation patterns. As a simple test of the neutral hypothesis, we performed in silico modeling. Our results show that convergent mutations are enriched in lagging strand genes and that these mutations are unlikely to have arisen by chance. Additionally, we observe that convergent mutation frequency has a stronger positive correlation with gene-length in lagging strand genes. This effect strongly suggests that head-on conflicts between the DNA replication and transcription machineries are a key mechanism driving the formation of convergent mutations. Together, our data indicate that head-on replication-transcription conflicts can promote adaptive evolution in a variety of bacterial species, and potentially other organisms.
Ultrafast terahertz Faraday rotation in graphene

Terahertz (THz) Faraday rotation measurements were performed to investigate carrier dynamics in p-type Chemical vapor deposition (CVD) graphene. We used static and time-resolved polarization-sensitive THz transmission measurements in a magnetic field to probe free carriers in GaAs, InP, and Graphene. Static measurements probe the equilibrium carrier density and momentum scattering rate. Time-resolved (optical pump/THz probe) measurements probe the change in these quantities following photoexcitation. In a typical CVD graphene sample, we found that 0.5 ps following photoexcitation with 1 × 1013 photons/cm2 pulses at 800 nm the effective hole scattering time decreased from 37 fs to 34.5 fs, while the carrier concentration increased from 2.0 × 1012 cm−2 to 2.04 × 1012 cm−2, leading to a transient decrease in the conductivity of the film.
Spectral properties of a non-compact operator in ecology.

Ecologists have recently used integral projection models (IPMs) to study fish and other animals which continue to grow throughout their lives. Such animals cannot shrink, since they have bony skeletons; a mathematical consequence of this is that the kernel of the integral projection operator T is unbounded, and the operator is not compact. To our knowledge, all theoretical work done on IPMs has assumed the operator is compact, and in particular has a bounded kernel. A priori, it is unclear whether these IPMs have an asymptotic growth rate $$\lambda $$ , or a stable-stage distribution $$\psi $$ . In the case of a compact operator, these quantities are its spectral radius and the associated eigenvector, respectively. Under biologically reasonable assumptions, we prove that the non-compact operators in these IPMs share some important traits with their compact counterparts: the operator T has a unique positive eigenvector $$\psi $$ corresponding to its spectral radius $$\lambda $$ , this $$\lambda $$ is strictly greater than the supremum of the modulus of all other spectral values, and for any nonnegative initial population $$\varphi _0$$ , there is a $$c>0$$ such that $$T^n\varphi _0/\lambda ^n \rightarrow c \cdot \psi $$ .
Insufficient sleep impairs T-cell response to SARS-CoV-2

Introduction: Considering the unrelenting nature of the COVID-19 global crisis, there is an urgent need to identify modifiable factors that modulate susceptibility and immune responses to SARS-CoV-2, which is also relevant for vaccine response. Insufficient sleep, a highly prevalent and frequently overlooked lifestyle pattern, impairs formation of immunological memory and T cell responses to viral infection, which may influence immune responses to SARS-CoV-2 infection. We hypothesized that objectively monitored, mild sleep restriction (SR) for 6 weeks reduces T cell cross-reactivity to SARS-CoV-2 compared with baseline in healthy individuals. Methods: Ten healthy participants (50% women;40% African-American, 30% White and 30% other), age 42±17 y;BMI 26.8±5.3 kg/m2) with normal habitual sleep duration (7-8 h/night confirmed by 2-week actigraphy screening) underwent 6 weeks of mild SR (1.5 h less than their habitual sleep [HS]) prior to the COVID-19 pandemic. Peripheral blood mononuclear cells (PBMC) were isolated using Ficoll-Paque density-gradient sedimentation from participants at baseline and after 6 weeks of SR. Mean (±SD) sleep duration was 7 h 33 min ± 49 min during HS vs. 6 h ± 38 min during SR (p<0.001). PBMC were cryopreserved in liquid nitrogen until stimulated with SARSCo-V-2 spike glycoprotein peptides (pool 1 = N-terminal and pooI 2 = C-Terminal) for 16 hours. Levels of SARSCoV-2 spike-specific CD4+ (OX40+CD137+) and CD8+ (CD69+CD137+) T cells were quantified by flow cytometry. Levels of cytokines released into supernatant after stimulation with spike peptide pools were quantified using human Th cytokine panel (12-plex) kit (Milipore Sigma). Results: Levels of SARS-CoV-2 spikespecific CD4+ T cells decreased after sleep restriction compared with baseline (pool 1: 0.12±0.02 vs. 0.30±0.08, p=0.04 and pool 2: 0.13±0.02 vs. 0.26±0.05, p=0.02). Similarly, SR reduced levels of SARS-CoV-2 spike-specific CD8+ T cells compared with baseline (pool 1: 0.08±0.01 vs. 0.17±0.04, p=0.07 and pool 2: 0.07±0.01 vs. 0.16±0.03, p=0.04). Levels of IL-13 and IL-22 decreased after SR compared with baseline (p=0.008 and 0.05, respectively). Conclusion: Insufficient sleep reduces T-cell cross-reactivity to SARS-CoV-2 in healthy individuals. Impaired T-cell immunity in insufficient sleep may have implications for COVID-19 susceptibility and immunity as well as vaccine response.
An Introduction to Life Cycle Assessment of Natural Gas-Fired Electricity

The electric sector is undergoing a transition to a more environmentally sustainable energy system, and electricity generated from natural gas has played a role to date as a lower carbon alternative to coal. While it combusts the cleanest burning fossil fuel, natural gas-fired power is not without environmental impacts. Life cycle assessment offers an internationally standardized methodology to quantify the environmental burdens from materials extraction to waste disposal. Environmental impacts of gas-fired power can thus be robustly examined using this approach. The primary goal of the book is to introduce the reader to the field of life cycle assessment with an unbiased, comprehensive examination of the state of knowledge of natural gas-fired electricity. Due to the irreducible variability of infrastructure types across an expansive network associated with this product system, the focus of the analyses laid out in this book is on the fuel cycle and electricity generation. Wider systems boundaries that include upstream material extraction and waste disposal are considered as applicable. This chapter introduces the premise of the book and lays out the subsequent chapters for the readers. Insights are developed on not only how to undertake a life cycle assessment of gas-fired power, but also how to assess uncertainty, emerging markets and their implications and the role of natural gas as a bridge fuel.
Biomaterial-Facilitated Immunotherapy for Established Oral Cancers

We evaluated a peptide-based immunotherapy termed SynerGel: an injectable, biomaterial-based platform for intratumoral drug delivery. A drug-mimicking peptide hydrogel named L-NIL-MDP was loaded with an antitumor cyclic dinucleotide (CDN) immunotherapy agonist. The biomaterial combines inducible nitric oxide synthase (iNOS) inhibition with controlled delivery of CDNs, demonstrating between 4- and 20-fold slower drug release than commercially available hydrogels. SynerGel allowed for immune-mediated elimination of established treatment-resistant oral tumors in a murine model, with a median survival of 67.5 days compared with 44 days in no-treatment control. This report details findings for a promising therapy showing improved efficacy over previous hydrogel systems.
Duodenal Mucosal Barrier in Functional Dyspepsia.

BACKGROUND & AIMS In addition to gastric sensorimotor dysfunctions, functional dyspepsia (FD) is also variably associated with duodenal micro-inflammation and epithelial barrier dysfunction, the pathogenesis and clinical significance of which are unknown. Our hypothesis was that miRNAs and/or inflammation degrade epithelial barrier proteins, resulting in increased duodenal mucosal permeability in FD. METHODS We compared the duodenal mucosal gene expression and miRNAs, in vivo permeability (lactulose-mannitol excretion between 0 and 60 and 60 and 120 minutes after saccharide ingestion), ex vivo assessments (transmucosal resistance, fluorescein isothiocyanate [FITC]-dextran flux, and basal ion transport), and duodenal histology (light and electron microscopy) in 40 patients with FD and 24 controls. RESULTS Compared with controls, the mRNA expression of several barrier proteins (zonula occludens-1, occludin, claudin-12, and E-cadherin) was modestly reduced (ie, a fold change of 0.8-0.85) in FD with increased expression of several miRNAs (eg, miR-142-3p and miR-144-3-p), which suppress these genes. The urinary lactulose excretion and the lactulose:mannitol ratio between 60 and 120 minutes were greater in FD than in controls (P < .05). The FITC-dextran flux, which reflects paracellular permeability, was inversely correlated (r = -0.32, P = .03) with transmucosal resistance and directly correlated (r = 0.4, P = .02) with lactulose:mannitol ratio. Other parameters (mucosal eosinophils, intraepithelial lymphocytes, and mast cells, transmucosal resistance, FITC-dextran flux, average intercellular distance, and proportion of dilated junctions) were not significantly different between groups. CONCLUSIONS In FD, there is a modest reduction in the expression of several duodenal epithelial barrier proteins, which may be secondary to up-regulation of regulatory miRNAs, and increased small intestinal permeability measured in vivo.
Kinetics of phosphate incorporation into adenosine triphosphate and guanosine triphosphate in bacteria.

Escherichia coli cells were labeled with 33PO4 for several generations and then 32PO4 was added, samples were taken at various times, and adenosine triphosphate (ATP) and guanosine triphosphate (GTP) were purified from an acid extract. The ratio of 32P/33P in each of the six phosphate species was determined and compared to the ratio expected at isotopic steady state. The rate constants of the simplest network of pools which could explain the data, and were consistent with metabolic pathways, were then calculated. In the range of times studied (30 to 3,000 s at 21.5 C) the following generalizations can be made. (i) The γ-phosphate at ATP requires 2,200 s to achieve 50% of its final specific activity and behaves as if it were exchanging with another species 4.4 times as large, with this other species turning over in 540 s. (ii) The β-phosphate of ATP and the γ-phosphate of GTP are in equilibrium with the γ-phosphate of ATP. (iii) The specific activity of the γ-phosphate of GTP lags 66 s behind the γ-phosphate of ATP. (iv) The α-phosphates of ATP and GTP have equal specific activities which lag far behind the other four phosphates. A single precursor pool with a turnover time of 416s fits the data best, although a fair fit can be obtained assuming several sequential precursor pools with much shorter turnover times. These findings are consistent with known biosynthetic pathways and the probable flows through them, including the relationship of nucleotide biosynthesis to ribonucleic acid synthesis and turnover.
Solvability and Approximate Solutions for the Robust Stabilization with Nominal and Robust Sensitivity Constraints

Multiplicative plant perturbations with H?-norm bounds are considered. The results of [9] are applied to the problem of robust stabilization with nominal sensitivity being less than some prespecified value and the robust performance (sensitivity) problem with a guaranteed stability robustness margin. A necessary and sufficient condition for the solvability of the first problem and a sufficient condition for the second problem are derived. Synthesis algorithms are given to construct real rational proper compensators satisfying our multiple design specifications.
Optimal per-pixel estimation for scalable video coding

We address the problem of real-time mode decisions for enhancement layer coding in the context of fine granularity scalable coding. While traditional mode selection strategies take into account the potential future drift stemming from coding the current frame with a particular enhancement layer coding mode, they usually fail to acknowledge the effect of past drift from previous partially reconstructed enhancement references. We introduce an optimal per-pixel drift estimation algorithm that calculates the effect of bandwidth variations and outages on the enhancement reference. Experimental results show the algorithm's advantages.
Outcomes Assessment for Point-of-Care Testing

“Outcomes Assessment” has become one of the enduring buzzwords of the decade. But it often seems to be like the weather: Everyone talks about it, but relatively few do anything about it. As clinical laboratory scientists, we have repeatedly challenged ourselves to demonstrate that laboratory results affect patient outcome. Yet very few well-done studies have been published. (How many times have you heard and read the results of those few studies by now?) One difficulty is the universal use of laboratory testing. Would it be acceptable to deny laboratory testing to a control group? The field of point-of-care testing (POCT) offers a major opportunity, because there are many tests not yet in widespread use. This allows ethical comparisons to be designed. (Imagine presenting to the Human Investigation Committee a study of the benefit of digoxin monitoring using a control group in which no digoxin measurements were allowed. Would they approve it? Such a study was done when digoxin assays were just being introduced and convincingly demonstrated a 50% reduction in clinical digitalis toxicity in monitored patients (1).) Another barrier is the tendency to focus on medical outcomes: decreased mortality or morbidity, shorter length of stay, decreased readmission rate, improved quality of life, etc. Medical interventions may directly alter medical outcomes, but laboratory tests do not. The effect of a test result is always filtered through the change in medical management it engenders. The ability to link the test result to the outcome requires a good correlation between the result and the therapeutic intervention. The size and duration of studies needed to establish the effectiveness of medical interventions are well known. How much larger and longer must a study be to average out the additional variation in the test itself and in the linkage between result and intervention? (Despite such …
Galileo’s Epistemology as the Basis for a Theory of the Growth of Knowledge

Thus far our investigations have helped us to reconstruct several of Galileo’s methodological rules. They are listed below in abbreviated form.
Macroengineering: An Environmental Restoration Management Process

Macroengineering: An Environmental Restoration Management Process provides a comprehensive understanding of all the technical, cost, and regulatory issues that an environmental project manager would potentially face on a large scale environmental restoration project. The author addresses unique technical issues encountered during DOD and DOE environmental cleanup efforts, such as radionuclide contamination, unexploded ordinance, heavy metals, and other common contaminants. Referencing the most recent regulations and practices in environmental cleanup projects, the book also includes useful charts and tables and serves both as a classroom text and a professional reference.
Lack of effect of thyroid hormone on late fetal rat brain development.

Studies were undertaken to test whether alterations in fetal brain thyroid hormone levels during the final week of gestation can prematurely induce gene expression in brain or affect cerebellar morphogenesis. Pregnant dams were treated either by administration of 0.025% methimazole (MMI) in the drinking water from day 14 post conception (PC14) or administration of 2.5 mg T4/100 g BW on PC15. On PC21, treatment with MMI resulted in a 53% fall in fetal brain T3 levels and excess T4 resulted in a 2- to 3-fold increase to concentrations observed in adult brains. Neither excess nor reduced levels of T3 caused alterations in the expression of the myelin basic protein, Pcp-2 or calmodulin kinase IV genes. Cerebella of control brains showed early evidence of foliation and the presence of a several cell thick Purkinje cell layer and an external granule layer. No treatment induced effects were evident. Thus, at the late fetal stage in the rat, the developing brain appears to be unresponsive to thyroid hormone despi...
Use of Low-Pass Noise in Word-Recognition Testing

This study attempted to determine whether word-recognition scores obtained in noise were more sensitive to the presence of a hearing loss than recognition scores obtained in quiet. Subjects with no...
More Than the Sum of Parts: The Grammar of Queen Anne Houses:

Shape grammars are specified that generate houses in the Queen Anne style which dominated domestic architecture in the United States of America in the 1880s; examples are used which are typical for Pittsburgh's historic Shadyside district. Separate grammars are given for the generation of plans and for the articulation of plans in three dimensions. Both grammars emphasize aspects of geometry and overall design and explain how individual parts and features are related to each other.
Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry.

Abstract The substitution of glycine for valine at amino acid 448 in the C4 domain of SIVmac239 envelope glycoprotein gp120 resulted in little or no viral infectivity for CEMX174 cells and rhesus monkey peripheral blood mononuclear cells. The block to viral replication was located at an early stage including virus entry into cells since the mutant virus was severely impaired in its ability to form newly synthesized viral DNA during the initial 14 hr after exposure to cells. Envelope glycoprotein with the 448V → G mutation bound to soluble CD4 in a manner similar to wild type in an in vitro assay and was also translated, processed, and cleaved in a manner similar to wild-type envelope protein. When CEMx174 cells were transfected with 448V → G mutant proviral DNA and held for longer than 40 days, a variant appeared in one culture that was able to replicate with near wild-type kinetics. Sequencing of viral DNA from cultures infected with this variant revealed that the original 448V → G mutation was retained in eight of eight clones analyzed but that six of eight clones analyzed had an additional mutation of V → I at amino acid 322 of gp120. Amino acid 322 in SIVmac gp120 is located in a region which corresponds to V3 of HIV. Analysis of site-specific mutants demonstrated that the mutation of V → I at position 322 can indeed compensate for the 448V → G mutation, resulting in efficient virus entry and replication by the double mutant. These results identify single amino acids in gp120 that are critical for early events in SIVmac replication and suggest that the "V3" and C4 domains of SIVmac gp120 cooperate to effect virus entry.
Numerical simulation and validation of distributed impact events

Abstract An underwater explosion (UNDEX) validation methodology was presented in O’Daniel et al. (2002, Int. J. Impact. Eng. 27, 919), describing a process where precision impact tests were used to generate a response equivalent to the underwater structural response of a flat panel subjected to a blast wave. A critical part of the methodology was to validate the code LS-DYNA3D (LSTC 936 (1995)) for the explicit finite element analyses of the short duration elastic responses of aluminum and composite panels subjected to low velocity, line and distributed impact loadings. A line impact was used as a base to perform preliminary tests of the precision impact test system, and the distributed impact configuration was necessary to generate a response similar to an underwater blast wave loading. Once validated for that range of structural response under impact loading conditions, LS-DYNA3D could then be used to predict impact tests to find responses that were equivalent to the UNDEX response of the target. This paper presents a detailed description of the precision impact events, and a comprehensive coverage of the validation of LS-DYNA3D for those impact events. O’Daniel et al. [1] provides an explanation of the equivalence between impact and UNDEX, as well as the overall methodology. A precision impact test machine was designed and fabricated, and low velocity impact tests were conducted to experimentally determine the panel responses for each impact configuration. Overall, the numerical predictions correlated well with the experimental results. However, better correlation may be achievable if more complex hyperelastic material models are used for the rubber materials in the composite and the impactor, a more detailed representation of the test frame-distributed impactor interface is included, and a static preload is numerically included in the panel-to-support interface. Details of the panel configurations, general impact solution methods, numerical simulations, precision impact equipment and impact tests, and comparisons between simulation and test results are presented.
Status of Coccobius nr. Fulvus (Hymenoptera: Aphelinidae), a Parasitoid of Euonymus Scale (Hemiptera: Diaspididae), 12–16 Years After Its Release in Massachusetts

From 1990 to 1995, a classical biocontrol pro gram was conducted in New England against an Asian scale, Unaspis euonymi (Comstock) (Hemi ptera: Diaspididae), which attacks landscape Eu onymus plants. Many Euonymus species are of Asian origin (Flint 1983) and widely planted as ornamentals (Gill et al. 1982). Collection of eu onymus scale natural enemies for release in the USA began in Korea (Drea & Hendrickson 1988; Hendrickson et al. 1991), but from 1990-1995 our laboratory collected additional species near Beijing, China (Van Driesche et al. 1998a), includ ing 2 predators (Chilocorus kuwanae Silvestri and Cybocephalus nr. nipponicus Endrody Younga) and 3 parasitoids (Coccobius nr. fulvus (Compere et Annecke), Encarsia nr. diaspidicola (Silvestri) and Aphytis sp.). Impacts of the 2 pred ators have been documented (Van Driesche et al. 1998b; Van Driesche & Nunn 2003). In 1991-1994, 3,862 adult C. nr. fulvus were re leased at 11 sites; 12,966 adults, nr. diaspidicola at 27 sites; and 801 adult Aphytis sp. at 5 sites in New England (mostly Massachusetts) (Van Drie sche et al. 1998a). By 1994, apparent establish ment (recovery in 1 subsequent year following re lease) had occurred for C. nr. fulvus and E. nr. di aspidicola. No next-year recoveries were made for Aphytis sp., the species released last and in small est numbers. No evidence of spread of any parasi toid was observed. In addition, a pre-existing cos mopolitan polyphagous aphelinid, Encarsia cit rina (Crawford), was observed in samples from Massachusetts. In 1991, it was detected at 44% of 79 sites in southern New England. In 1994, para sitism of dissected adult female euonymus scales by E. citrina, pooled by generation across 18 loca tions in Massachusetts, averaged 13.4% (n 2,174 scales) for the overwintered spring adults, 33.6% (n = 1,271 scales) for the summer generation, and 31.2% (n = 933 scales) for the fall generation. Our objectives here were (1) to sample for ex otic parasitoids of euonymus scale in western Massachusetts in 2006 and 2007 at their original release sites, (2) to sample non-release locations to detect parasitoid spread, and (3) to assess ef fects of exotic parasitoids on the pre-existing par asitoid E. citrina.
Efficient Couplers and Splitters from Dielectric Waveguides to Plasmonic Waveguides

We introduce a novel design and analysis of an ultra-compact coupler and a 1×2 splitter from silicon waveguides into plasmonic waveguides with high coupling efficiency and flexible splitting ratios.
Probing the Coenzyme and Substrate Binding Events of CDP-d-glucose 4,6-Dehydratase: Mechanistic Implications†

NAD+-dependent nucleotidyl diphosphohexose 4,6-dehydratases which transform nucleotidyl diphosphohexoses into the corresponding 4-keto-6-deoxy sugar derivatives are essential to the formation of all 6-deoxyhexoses. Studies of the CDP-d-glucose 4,6-dehydratase (Eod) from Yersinia had shown that this dimeric protein binds only 1 equiv of NAD+/mol of enzyme and, unlike other enzymes of the same class, displays a unique NAD+ requirement for full catalytic activity. Analysis of the primary sequence revealed an extended ADP-binding fold (GHTGFKG) which deviates from the common Rossmann consensus (GXGXXG) and thus may have contributed to Eod's limited NAD+ affinity. In particular, the presence of His17 in the β-turn region and that of Lys21 in a position typically occupied by a small hydrophobic residue may impose electronic or steric perturbations to this essential binding motif. To better understand the correlation between the binding properties and primary sequence, mutants (H17G and K21I) were constructed to...
An Optically Efficient Method for observing Single Plant Cells from Shake Cultures during Growth and Division

THE ease with which the individual cells of callus cultures of tissues of higher plants separate from each other has led to several successful methods of growing them singly. Muir, Hildebrandt and Riker1 grew a single crown-gall callus cell on a piece of filter paper over a large callus of the same strain. Torrey2 placed many separate cells around a nurse callus; some of the former divided once or more during the subsequent two weeks. Bergmann3 made a considerable advance by utilizing a plating method for individual cells of tobacco and of bean. Of the numerous separate cells in a thin plate of agar medium, individuals were followed by time-lapse photography during their division. Optical quality of the pictures was poor due to the necessity of observation through the bottom of a Petri dish and a layer of agar. A perusal of these methods or an attempt to duplicate them makes the investigator conscious of their deficiencies; there is no possibility of observing the single cell in the first and growth is recognized only when it has formed a callus that is visible to the unaided eye, the second has most of the disadvantages of the hanging-drop, and the third suffers from poor optical quality.
The Internet and World Wide Web as a Resource for Mental Health Occupational Therapists

SUMMARY The Information Superhighway, the buzzword referring to the Internet and World Wide Web system, is a new resource for occupational therapy. Therapists are discovering how the Internet and World Wide Web can allow them to access the information that they need for research, treatment planning, education, communication, and leisure pursuits. This article describes how the Internet and World Wide Web work, defines terms and tools common to these new technologies, and gives some specific locations that an occupational therapist may find useful. References are shared that relate to general mental health resources and occupational therapy in mental health resources.
Risk of new-onset urinary incontinence after forceps and vacuum delivery in primiparous women.

Abstract Objective: We sought to determine the incidence of new-onset urinary incontinence after forceps and vacuum delivery compared with spontaneous vaginal delivery. Study Design: We performed a prospective study in primiparous women delivered by forceps (n = 90), vacuum (n = 75), or spontaneous vaginal delivery (n = 150). Follow-up for urinary incontinence was at 2 weeks, 3 months, and 1 year after delivery. Results: The incidence of urinary incontinence was similar in the 3 groups at 2 weeks after delivery. The proportion of women developing new-onset urinary incontinence decreased significantly over time in the spontaneous vaginal ( P =.003) and vacuum delivery groups ( P =.009) but not in the forceps group ( P =.2). No relationship of urinary incontinence with vaginal lacerations, epidural anesthesia, length of second stage of labor, or infant birth weight was seen. Conclusions: In primiparous women, urinary incontinence after forceps delivery is more likely to persist compared with spontaneous vaginal or vacuum delivery. (Am J Obstet Gynecol 2001;185:1318-24.)
Absolute rate constants for some reactions of the triethylamine-boryl radical and the borane radical anion

Laser flash photolysis (LFP) of di-tert-butyl peroxide or dicumyl peroxide at ambient temperatures in the presence of Et3N→BH3 or BH4− generated the title radicals which were found to have broad, featureless absorptions in the visible region. Rate constants for H-atom abstraction from Et3N→BH3 by cumyloxyl radicals show a small solvent dependence, e.g. 12 × 107 and 2.2 × 107 dm3 mol−1 s−1 in isooctane and acetonitrile, respectively. Rate constants for halogen atom abstraction by Et3N→BH2˙ and BH3˙− from a number of chlorides and bromides were determined by LFP and by competitive kinetics, e.g., for Et3N→BH2˙ + CCl4/PhCH2Cl/CH3(CH2)2Cl, k = 4.4 × 109/1.1 × 107/5.1 × 105 dm3 mol−1 s−1 and for BH3˙− + CCl4/PhCH2Cl, k = 2.0 × 109/3.0 × 107 dm3 mol−1 s−1. Rates of addition of Et3N→BH2˙ to 1- and 1,1-substituted olefins increase dramatically as the electron affinity of the olefin increases, confirming the nucleophilic character of amine-boryl radicals. A comparison of the present results with literature data for the addition of olefins of four nucleophilic carbon-centered radicals proves that Et3N→BH2˙ is by far the most nucleophilic radical for which kinetic data are available. A few rate constants for abstraction of hydrogen from electron-deficient carbon by Et3N→BH2˙ are also reported.
No Computer Program Required : Even Pencil-and-Paper Argument Mapping Improves Critical-Thinking Skills

Argument mapping software abounds, 1 and one of the reasons is that using the software has been shown to teach/promote/improve critical thinking skills. These positive results are very encouraging, but they also raise the question of whether the computer tutorial environment is producing these results, or whether learning argument mapping, even with just paper and pencil, is sufficient. Based on the results of two empirical studies, I argue that the basic skill of being able to represent an argument diagrammatically plays an important role in the improvement of critical thinking skills. While these studies do not offer a direct comparison between the two methods, it is important for anyone wishing to employ argument mapping in the classroom to know that significant results can be obtained even with the most rudimentary of tools.
Single-Molecule Magnets: Novel Mn8 and Mn9 Carboxylate Clusters Containing an Unusual Pentadentate Ligand Derived from Pyridine-2,6-dimethanol

The reactions of the Mn(III)(3) and Mn(II)Mn(III)(2) complexes [Mn(3)O(O(2)CEt)(6)(py)(3)][ClO(4)] and [Mn(3)O(O(2)CEt)(6)(py)(3)] with pyridine-2,6-dimethanol (pdmH(2)) afford the mixed-valence Mn(II)(6)Mn(III)(2) octanuclear complex [Mn(8)O(2)(py)(4)(O(2)CEt)(8)(L)(2)][ClO(4)](2) (1) and the Mn(II)(7)Mn(III)(2) enneanuclear complex [Mn(9)(O(2)CEt)(12)(pdm)(pdmH)(2)(L)(2)] (2), respectively. Both compounds contain a novel pentadentate ligand, the dianion of (6-hydroxymethylpyridin-2-yl)-(6-hydroxymethylpyridin-2-ylmethoxy)methanol (LH(2)), which is the hemiacetal formed in situ from the Mn-assisted oxidation of pdmH(2). Complex 1 crystallizes in the monoclinic space group P2(1)/n with the following cell parameters at -160 degrees C: a = 16.6942(5) A, b = 13.8473(4) A, c = 20.0766(6) A, beta = 99.880(1) degrees, V = 4572.27 A(3), and Z = 2, R (R(w)) = 4.78 (5.25). Complex 2.0.2MeCN crystallizes in the triclinic space group Ponemacr; with the following cell parameters at -157 degrees C: a = 12.1312(4) A, b = 18.8481(6) A, c = 23.2600(7) A, alpha = 78.6887(8) degrees, beta = 77.9596(8) degrees, gamma = 82.3176(8) degrees, V = 5076.45 A(3), and Z = 2, R (R(w)) = 4.12 (4.03). Both complexes are new structural types comprising distorted-cubane units linked together, albeit in two very different ways. In addition, complex 2 features three distinct binding modes for the chelating ligands derived from deprotonated pdmH(2). Complexes 1 and 2 were characterized by variable-temperature ac and dc magnetic susceptibility measurements and found to possess spin ground states of 0 and 11/2, respectively. Least-squares fitting of the reduced magnetization data gave S = 11/2, g = 2.0, and D = -0.11 cm(-1) for complex 2, where D is the axial zero-field splitting parameter. Direct current magnetization versus field studies on 2 at <1 K show hysteresis behavior at <0.3 K, establishing 2 as a new single-molecule magnet. Magnetization decay measurements gave an effective barrier to magnetization relaxation of U(eff) = 3.1 cm(-1) = 4.5 K.
Full efficacy with no CNS side-effects: unachievable panacea or reality? DMPK considerations in design of drugs with limited brain penetration.

Optimising drug properties can be an important strategy to limit penetration into the CNS and offers advantages in reducing the risk of undesirable neurological effectsWhen considering the design of these drugs it is important to consider the relative influx and efflux rates at the relevant biological membranesThe highest degree of restriction at the brain is probably achievable by utilising active transport to exclude compounds from the brainAffinity for the efflux transporters Pgp and BCRP has been achieved in two in-house chemistry programmes by increasing polar surface area, which resulted in highly orally bioavailable low CNS penetrant compounds in preclinical species
Wind power planning: assessing long-term costs and benefits

Abstract In the following paper, a new and straightforward technique for estimating the social benefit of large-scale wind power production is presented. The social benefit is based upon wind power's energy and capacity services and the avoidance of environmental damages. The approach uses probabilistic load duration curves to account for the stochastic interaction between wind power availability, electricity demand, and conventional generator dispatch. The model is applied to potential offshore wind power development to the south of Long Island, NY. If natural gas combined cycle and integrated gasifier combined cycle (IGCC) are the alternative generation sources, wind power exhibits a negative social benefit due to its high capacity cost and the relatively low emissions of these advanced fossil-fuel technologies. Environmental benefits increase significantly if charges for CO2 emissions are included. Results also reveal a diminishing social benefit as wind power penetration increases. The dependence of wind power benefits on CO2 charges, and capital costs for wind turbines and IGCC plant is also discussed. The methodology is intended for use by energy planners in assessing the social benefit of future investments in wind power.
Determination of young's modulus of elastomers by use of a thermomechanical analyzer

This work used a conventional thermomechanical analyzer (TMA) to measure the depth of indentation at room temperature of elastomers and Finkin's equation to calculate Young's moduli of elastomers, which have been measured by Drutowski, from the radius of contact of an indentor on thin sheets of sample. Data obtained from the TMA are compared with those measured by radius of contact and Hertz contact theory and are found in good agreement. Measurements of Young's modulus as a function of temperature at different heating rates by TMA were made for an acrylic elastomer. The results are compared with theory and the deviations from theory are discussed.
Accuracy assessment of GPS satellite orbits

GPS orbit accuracy is examined using several evaluation procedures. The existence is shown of unmodeled effects which correlate with the eclipsing of the sun. The ability to obtain geodetic results that show an accuracy of 1-2 parts in 10 to the 8th or better has not diminished.