cssi/SciSciGPT-SciSciNet huggingface dataset:
Mathematical modeling of an immune checkpoint inhibitor and its synergy with an immunostimulant

Immune checkpoint inhibitors (ICIs) are a novel cancer therapy that may induce tumor regression across multiple types of cancer. There has recently been interest in combining the ICIs with other forms of treatments, as not all patients benefit from monotherapy. We propose a mathematical model consisting of ordinary differential equations to investigate the combination treatments of the ICI avelumab and the immunostimulant NHS-muIL12. We validated the model using the average tumor volume curves provided in Xu et al. (2017). We initially analyzed a simple generic model without the use of any drug, which provided us with mathematical conditions for local stability for both the tumorous and tumor-free equilibrium. This enabled us to adapt these conditions for special cases of the model. Additionally, we conducted systematic mathematical analysis for the case that both drugs are applied continuously. Numerical simulations suggest that the two drugs act synergistically, such that, compared to monotherapy, only about one-third the dose of both drugs is required in combination for tumor control.
Expression of R345W-Fibulin-3 Induces Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells.

Purpose To investigate the role of protein misfolding in retinal pigment epithelial (RPE) cell dysfunction, the effects of R345W-Fibulin-3 expression on RPE cell phenotype were studied. Methods Primary RPE cells were cultured to confluence on Transwells and infected with lentivirus constructs to express wild-type (WT)- or R345W-Fibulin-3. Barrier function was assessed by evaluating zonula occludens-1 (ZO-1) distribution and trans-epithelial electrical resistance (TER). Polarized secretion of vascular endothelial growth factor (VEGF), was measured by Enzyme-linked immunosorbent assay (ELISA). Differentiation status was assessed by qPCR of genes known to be preferentially expressed in terminally differentiated RPE cells, and conversion to an epithelial-mesenchymal transition (EMT) phenotype was assessed by a migration assay. Results Compared to RPE cells expressing WT-Fibulin-3, ZO-1 distribution was disrupted and TER values were significantly lower in RPE cells expressing R345W-Fibulin-3. In cells expressing mutant Fibulin-3, VEGF secretion was attenuated basally but not in the apical direction, whereas Fibulin-3 secretion was reduced in both the apical and basal directions. Retinal pigment epithelial signature genes were downregulated and multiple genes associated with EMT were upregulated in the mutant group. Migration assays revealed a faster recovery rate in ARPE-19 cells overexpressing R345W-Fibulin-3 compared to WT. Conclusions The results suggest that expression of R345W-Fibulin-3 promotes EMT in RPE cells.
Where’s Daddy? Challenges in the Measurement of Men’s Fertility

In this chapter, we dissect the observed differences in men’s and women’s fertility as represented in the 2014 Survey of Income and Program Participation’s (SIPP) Wave 1 data. We consider the differences between men’s, women’s, and children’s reports of fathers and fatherhood. We argue that these data offer evidence of a “missing man” problem, rather than misreporting of the part of SIPP respondents. We then use the triangulation of these data points to model the size, and some of the characteristics, of the missing men. This estimation technique should be applied to other data sources to further disentangle what or who may be missing from our current estimates of men’s fertility. Based on our derived estimates, we conclude by offering a re-estimation of key factors of men’s fertility in a sample that did not differentially omit not just fathers, but certain types of fathers. We offer this as evidence in support of more, and more in-depth, research into men’s fertility, and men’s survey non-response.
The German Welfare State as a Holding Environment for Refugees: A Case Study of Incorporation

Focusing on the psychological dimensions of the social incorporation of Syrian refugees into the German welfare state, this chapter examines the actual experience of one Syrian refugee. Through the sensual and bodily experience of encounters between strangers and citizens, it demonstrates how the welfare state creates a secure “holding environment” that facilitates the development of a capacity to care for oneself and for others. While refugee incorporation is always potentially threatening to the integrity of both the individual and social body, it can be evaluated positively with the emergence of elements of mutual belonging. It is likely to be perceived as a failure unless there is a mutual modification of the internal images refugees and residents of welfare states have of each other.
Determining the optimal expression method for dual-color imaging

Abstract Background Fluorescence imaging is a widely used technique that permits for cell-type-specific recording from hundreds of neurons simultaneously. Often, to obtain cell-type-specific recordings from more than one cell type, researchers add an additional fluorescent protein to mark a second neuronal subpopulation. Currently, however, no consensus exists on the best expression method for multiple fluorescent proteins. New Method We optimized the coexpression of two fluorescent proteins across multiple brain regions and mouse lines. Results The single-virus method, a viral injection in a double transgenic reporter mouse, results in limited fluorescent coexpression. In contrast the double-virus method, injecting a mixture of two viruses in a Cre driver mouse, results in up to 70 % coexpression of the fluorescent markers in vitro. Using the double-virus method allows for population activity recording and neuronal subpopulation determination. Comparison with Existing Method The standard for expressing two fluorescent proteins is to use a double transgenic reporter mouse with a single viral injection. Injecting two viruses into a Cre driver mouse resulted in significantly higher coexpression compared to the standard method. This result generalized to multiple brain regions and mouse lines in vitro, as well as in vivo. Conclusion Efficiently coexpressing multiple fluorescent proteins provides population activity while identifying a neuronal subpopulation of interest. The improved coexpression is applicable to a wide breadth of experiments, ranging from engram investigation to voltage imaging.
Linking mPFC circuit maturation to the developmental regulation of emotional memory and cognitive flexibility

The medial prefrontal cortex (mPFC) and its abundant connections with other brain regions play key roles in memory, cognition, decision making, social behaviors, and mood. Dysfunction in mPFC is implicated in psychiatric disorders in which these behaviors go awry. The prolonged maturation of mPFC likely enables complex behaviors to emerge, but also increases their vulnerability to disruption. Many foundational studies have characterized either mPFC synaptic or behavioral development without establishing connections between them. Here, we review this rich body of literature, aligning major events in mPFC development with the maturation of complex behaviors. We focus on emotional memory and cognitive flexibility, and highlight new work linking mPFC circuit disruption to alterations of these behaviors in disease models. We advance new hypotheses about the causal connections between mPFC synaptic development and behavioral maturation and propose research strategies to establish an integrated understanding of neural architecture and behavioral repertoires.
Preventing overpacking of compressed moderately dense granular gases

Extending the direct simulation Monte Carlo (DSMC) method to moderately dense granular flows has demanded recovering collisional pressures. There have been several reported DSMC variants that successfully recover the non-ideal equation of state but have largely been validated for systems with a homogeneous solids fraction field. Initially homogeneous systems that develop strong density gradients, such as the case of granular clustering, are seldom investigated due to the numerical phenomenon of particle packing past physical limits, or overpacking. In the presence of external gradients or internal clustering mechanisms, particles will compact into small volumes. We believe overpacking is a product of the unconditional acceptance of particle positions, and a proposed direct solution is modulating the flow of particles via a random walk. Termed as Energy DSMC (EDSMC), we show that integration of a modified Metropolis algorithm prevents overpacking to the Enskog Simulation Monte Carlo a la Bird.
Antibody-drug conjugate efficacy in neuroblastoma - role of payload, resistance mechanisms, target density, and antibody internalization

Antibody-drug conjugates (ADCs) are a targeted cancer therapy that utilize the specificity of antibodies to deliver potent drugs selectively to tumors. Here we define the complex interaction among factors that dictate ADC efficacy in neuroblastoma by testing both a comprehensive panel of ADC payloads in a diverse set of neuroblastoma cell lines and utilizing the glypican 2 (GPC2)-targeting D3-GPC2-PBD ADC to study the role of target antigen density and antibody internalization in ADC efficacy in neuroblastoma. We first find that DNA binding drugs are significantly more cytotoxic to neuroblastomas than payloads that bind tubulin or inhibit DNA topoisomerase 1. We additionally show that neuroblastomas with high expression of the ABCB1 drug transporter or that harbor a TP53 mutation are significantly more resistant to tubulin and DNA/DNA topoisomerase 1 binding payloads, respectively. Next, we utilized the GPC2-specific D3-GPC2-IgG1 antibody to show that neuroblastomas internalize this antibody/GPC2 complex at significantly different rates and that these antibody internalization kinetics correlate significantly with GPC2 cell surface density. However, sensitivity to pyrrolobenzodiazepine (PBD) dimers primarily dictated sensitivity to the corresponding D3-GPC2-PBD ADC, overall having a larger influence on ADC sensitivity than GPC2 cell surface density or antibody internalization. Finally, we utilized GPC2 isogenic Kelly neuroblastoma cells with different levels of cell surface GPC2 expression to define the threshold of target density required for ADC efficacy. Taken together, DNA binding ADC payloads should be prioritized for development for neuroblastoma given their superior efficacy and considering that ADC payload sensitivity is a major determinant of ADC efficacy.
Nutrient Inputs Stimulate Mercury Methylation by Syntrophs in a Subarctic Peatland.

Climate change dramatically impacts Arctic and subarctic regions, inducing shifts in wetland nutrient regimes as a consequence of thawing permafrost. Altered hydrological regimes may drive changes in the dynamics of microbial mercury (Hg) methylation and bioavailability. Important knowledge gaps remain on the contribution of specific microbial groups to methylmercury (MeHg) production in wetlands of various trophic status. Here, we measured aqueous chemistry, potential methylation rates (kmeth), volatile fatty acid (VFA) dynamics in peat-soil incubations, and genetic potential for Hg methylation across a groundwater-driven nutrient gradient in an interior Alaskan fen. We tested the hypotheses that (1) nutrient inputs will result in increased methylation potentials, and (2) syntrophic interactions contribute to methylation in subarctic wetlands. We observed that concentrations of nutrients, total Hg, and MeHg, abundance of hgcA genes, and rates of methylation in peat incubations (kmeth) were highest near the groundwater input and declined downgradient. hgcA sequences near the input were closely related to those from sulfate-reducing bacteria (SRB), methanogens, and syntrophs. Hg methylation in peat incubations collected near the input source (FPF2) were impacted by the addition of sulfate and some metabolic inhibitors while those down-gradient (FPF5) were not. Sulfate amendment to FPF2 incubations had higher kmeth relative to unamended controls despite no effect on kmeth from addition of the sulfate reduction inhibitor molybdate. The addition of the methanogenic inhibitor BES (25 mM) led to the accumulation of VFAs, but unlike molybdate, it did not affect Hg methylation rates. Rather, the concurrent additions of BES and molybdate significantly decreased kmeth, suggesting a role for interactions between SRB and methanogens in Hg methylation. The reduction in kmeth with combined addition of BES and molybdate, and accumulation of VFA in peat incubations containing BES, and a high abundance of syntroph-related hgcA sequences in peat metagenomes provide evidence for MeHg production by microorganisms growing in syntrophy. Collectively the results suggest that wetland nutrient regimes influence the activity of Hg methylating microorganisms and, consequently, Hg methylation rates. Our results provide key information about microbial Hg methylation and methylating communities under nutrient conditions that are expected to become more common as permafrost soils thaw.
The autonomy and focus of attention strategies under distraction: Frequency and sample entropy analyses in a dynamic balance task.

Abstract An external focus of attention has been shown to be effective in balance tasks. However, replication in applied settings is limited. The OPTIMAL theory proposes that a combination of autonomy and external focus increases focus to the task goal, and therefore more effective than external focus alone. However, research suggests that the combined effect is limited in discrete skills, and the increased focus effect is only reported by subjective assessment. The present study examined the effect of the combined strategy and its effect of “increased focus” compared to external focus and control groups under distraction. In experiment 1, participants (N = 60) practiced eight 35 s trials on a stabilometer followed by a 10 min-delayed retention test and an auditory distraction transfer test. The combined group chose a tape color to place on a stabilometer and was told to “keep the tapes parallel to the floor,” the external focus group was yoked with the combined group, and the control group was told to “do your best”. Performance was measured in Root Mean Square Error (RMSE). The increased focus effect was examined by both subjective (distraction score, a question about participants' perceptions) and objective (Mean Power Frequency, MPF, Sample entropy, SampEn) methods. Although participants improved significantly (p 0.05). An increased focus effect of the combined effect was not observed in any variables (p's > 0.05). In experiment 2, the practice duration was extended to replicate previous study designs (i.e., 90s trials; 2 days of practice; 24 h retention test; the number of participants). Consistent with experiment 1, group differences were not evident in RMSE, SampEn, and MPF (p's > 0.05). We suggest that autonomy may be required to be task-relevant, and simply telling to do best may be as useful as external focus or combined strategies in a continuous balance task. Further, the analysis showed that SampEn increased on Day 1 but decreased on Day 2, and MPF decreased within a session, but the average MPF increased by the day. Potential explanations and future directions when utilizing these metrics are discussed.
Three-Dimensional Printing in Neurosurgery Residency Training: A Systematic Review of the Literature

Background The use of three-dimensional (3D) printing in neurosurgery has become more prominent in recent years for surgical training, preoperative planning, and patient education. Several smaller studies are available using 3D printing; however, there is a lack of a concise review. This article provides a systematic review of 3D models in use by neurosurgical residents, with emphasis on training, learning, and simulation. Methods A structured literature search of PubMed and Embase was conducted using PRISMA guidelines to identify publications specific to 3D models trialed on neurosurgical residents. Criteria for eligibility included articles discussing only neurosurgery, 3D models in neurosurgery, and models specifically tested or trialed on residents. Results Overall, 40 articles were identified that met inclusion criteria. These studies encompassed different neurosurgical areas including aneurysm, spine, craniosynostosis, transsphenoidal, craniotomy, skull base, and tumor. Most articles were related to brain surgery. Of these studies, vascular surgery had the highest overall, with 13 of 40 articles, which include aneurysm clipping and other neurovascular surgeries. Twenty-two articles discussed cranial plus tumor surgeries, which included skull base, craniotomy, craniosynostosis, and transsphenoidal. Five studies were specific to spine surgery. Subjective outcome measures of neurosurgical residents were most commonly implemented, of which results were almost unanimously positive. Conclusions 3D printing technology is rapidly expanding in health care and neurosurgery in particular. The technology is quickly improving, and several studies have shown the effectiveness of 3D printing for neurosurgical residency education and training.
Conducting Ethical Research with Online Populations in the United States

The adaptable nature of the Internet to accommodate new behavior lends itself to the need for ethical practices to be flexible. However, current ethical guidelines are not adaptable to an online context and online research has yet to identify principles that are agreed upon across disciplines. Additionally, the current guidelines are not able to address issues related to the use of online panels for Internet research. The increased use of online panels presents questions related not only to traditional concepts of ethics, but also to the exploitation of online work. Issues of appropriate online ethical research are not limited to how they can better serve research, however, as the creation of these guidelines requires the consideration of how too strict of guidelines may hinder future research. Currently, the conservative and cautious nature of the United States’ Institutional Review Board is already being questioned for overreaching in their consideration of what ethical research is. The chapter concludes with proposed steps for developing more viable ethical guidelines in online research.
Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer and Emerging Therapeutic Opportunities

The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have become the standard of care, in combination with anti-estrogen therapy, for patients with HR+/HER2- advanced breast cancer. Various preclinical and translational research efforts have begun to shed light on the genomic and molecular landscape of resistance to these agents. Drivers of resistance to CDK4/6i therapy can be broadly subdivided into alterations impacting cell cycle mediators and activation of oncogenic signal transduction pathways. The resistance drivers with the best translational evidence supporting their putative role have been identified via next-generation sequencing of resistant tumor biopsies in the clinic and validated in laboratory models of HR+ breast cancer. Despite the diverse landscape of resistance, several common, therapeutically actionable resistance nodes have been identified, including the mitotic spindle regulator Aurora Kinase A as well as the AKT and MAP kinase signaling pathways. Based upon these insights, precision-guided therapeutic strategies are under active clinical development. This review will highlight the emerging evidence, in the clinic and in the laboratory, implicating this diverse spectrum of molecular resistance drivers.
Stereotactic Radiation Therapy With Concurrent Immune Checkpoint Inhibitor Therapy in Patients With Relapsed or Refractory Central Nervous System Lymphoma.

Purpose/objective(s) Relapsed or refractory central nervous system lymphoma (CNSL) after high-dose methotrexate-based therapy is a challenging clinical entity with limited treatment options. Salvage systemic therapy and whole brain radiation therapy (WBRT) are commonly employed but are associated with significant toxicity and poor outcomes. Prior studies have shown that primary CNSLs frequently exhibit increased expression of PD-L1, and immune checkpoint inhibitor (ICI) therapy may be active in this setting. We assessed the safety and efficacy of concurrent ICI therapy and hypo-fractionated stereotactic radiation therapy (SRT) in patients with relapsed or refractory CNSL. Materials/methods We retrospectively analyzed the records of patients with relapsed or refractory CNSL treated with SRT + ICI at our institution from 2017 to 2020. ICI therapy included pembrolizumab 200 mg IV q3weeks or nivolumab 3 mg/mg IV q2weeks. Linac-based SRT was delivered in 5 daily fractions of 5 Gy. CTVs included all grossly enhancing disease on T1 weighted post-contrast MR scans, with 3 mm uniform PTV expansions. Patients were followed for symptomatic and radiographic response. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier analysis. Results Seven consecutive patients with relapsed or recurrent CNSL were analyzed: 6 with primary CNSL, 1 with secondary CNSL. Patients presented at a median age of 72.2 years (range: 40.9 - 89.9) after a median of 2 prior courses of systemic therapy. Five patients had a solitary intracranial lesion and 2 had multiple lesions. None had active extracranial disease. Median pre-SRT Karnofsky Performance Status (KPS) was 60 (range 50 - 90). All 7 patients completed SRT and received concurrent and adjuvant ICI therapy. Median follow-up after completion of SRT was 9.1 months. Acute toxicities of SRT and ICI therapy were minimal, including fatigue (3 patients), diarrhea (2), and adrenal insufficiency requiring oral steroids (1). Five patients (71.4%) achieved symptomatic improvement after SRT including 2 patients (28.5%) with a clinical complete response (CR). Median post-SRT KPS was 70 (range: 60 - 100). Six patients had follow-up imaging, and all had an objective response including 3 (50%) with a radiographic CR. The median time to best radiographic response was 2.0 months (range 0.3 - 3.7 months), and all treated lesions remained controlled on all subsequent imaging. Three patients (42.9%) experienced out-of-field intracranial recurrence. Median PFS was 7.7 months (95% CI: 4.0 - 11.4 months) and median OS was 12.6 months (95% CI: 7.5 - 12.7 months) post-SRT. Conclusion Among patients with relapsed or refractory CNSL, SRT + ICI appears to be well tolerated and offers excellent symptomatic and radiographic local control. Further studies are needed to identify appropriate candidates for salvage SRT + ICI, and to evaluate the clinical efficacy and neurocognitive impact of this approach.
Layout, Packaging, and Efficiency Implications of a 1.7 kV Hybrid Si/SiC Reverse Blocking Switch Module in Soft-Switching Current Source Converters

The Soft-Switching Solid-State Transformer (S4T) is a flexible, multi-port, and isolated ZVS soft-switching power converter with emerging applications in multi-port data center power delivery, renewable energy integration in EV fast charging stations, and storage integration in next generation solar farms. As a current source converter, the S4T requires reverse blocking (RB) semiconductor devices with bidirectional voltage blocking capability and unidirectional current flow. While these switches had been implemented from the series connection of discrete devices in early S4T prototypes, larger scale projects require a more manufacturable, cost-effective, robust, and compact approach. This work presents the first device-level analysis of the soft-switching principles of the S4T in a commercial, high current 1.7 kV RB switch phase-leg module in which each switch position consists of the series connection of a Si IGBT and a SiC Schottky diode. The hybrid RB module was extensively tested in a soft-switching current source inverter bridge, replicating the unique ZVS soft-switching environment of the S4T, and enabling measurement of conduction loss, residual switching loss, and dI/dt and dV/dt stress. With Si IGBTs, residual switching loss from IGBT tail current and commutation loop parasitic inductance limited the achievable turn-off energy reduction under soft-switching. Nevertheless, the ZVS soft-switching environment of the S4T enabled a > 88.8% reduction in turn-on loss and a > 55.2% reduction in turn-off loss at 800 V and 90°c cold plate temperature.
Software design for distribution automation

This paper describes the design and implementation of standards based communications software for distribution automation. Design of a simple application to communicate with a program in control of sampling of an AC waveform and controlling a switch are detailed. The software developed provides one possible implementation of a standard communication method for communication between a central station and remote controllers. The software has been built using an EPRI Utility Communications Architecture (UCA) component called Manufacturing Messaging Service (MMS). >
Fostering Democratic Values in Inclusive Early Childhood Settings

What is democracy? In a democratic society people are given the power to make a variety of meaningful choices pertaining to their daily lives. The freedom to make these choices is what gives people a strong sense of empowerment. This freedom is extremely important in the role of education. John Dewey (1938), the noted scholar on education, described the vital importance of freedom in educational practices.
Probability of coverage, rate of rejection, and average location relative efficiency for trimmed and partial variance procedures

Recent concerns about the normality of the distribution of scores arose from a study that was done by Micceri (as cited in [20]). In addition, the simultaneous occurrence of variance heterogeneity and the treatment effect influenced the decision to execute this study [9]. Heterogeneity of score variances and distributional asymmetry influence one’s decision on the most appropriate procedure. Through a Monte Carlo simulation design, I assessed the probability of coverage, average location relative efficiency, and rate of rejection for the selected statistical procedures. When the purpose of the study is to estimate the populations’ mean difference, the partial variance procedure provides a better approximation of the confidence level and higher location relative efficiency than that observed for Yuen’s procedure.
Pair interactions in polyelectrolyte-nanoparticle systems: Influence of dielectric inhomogeneities and the partial dissociation of polymers and nanoparticles

We study the effective pair interactions between two charged spherical particles in polyelectrolyte solutions using polymer self-consistent field theory. In a recent study [V. Pryamitsyn and V. Ganesan, Macromolecules 47, 6095 (2015)], we considered a model in which the particles possess fixed charge density, the polymers contain a prespecified amount of dissociated charges and, the dielectric constant of the solution was assumed to be homogeneous in space and independent of the polymer concentration. In this article, we present results extending our earlier model to study situations in which either or both the particle and the polymers possess partially dissociable groups. Additionally, we also consider the case when the dielectric constant of the solution depends on the local concentration of the polymers and when the particle's dielectric constant is lower than that of the solvent. For each case, we quantify the polymer-mediated interactions between the particles as a function of the polymer concentrations and the degree of dissociation of the polymer and particles. Consistent with the results of our previous study, we observe that the polymer-mediated interparticle interactions consist of a short-range attraction and a long-range repulsion. The partial dissociablity of the polymer and particles was seen to have a strong influence on the strength of the repulsive portion of the interactions. Rendering the dielectric permittivity to be inhomogeneous has an even stronger effect on the repulsive interactions and results in changes to the qualitative nature of interactions in some parametric ranges.
Dose‐related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.
Effects of exposure to pesticides on carbaryl toxicity and cytochrome P450 activities in Aedes albopictus larvae (Diptera: Culicidae)

Abstract Cytochrome P450 monooxygenase (P450)-mediated metabolism is an important mechanism by which insects detoxify insecticides. In this report, a major contribution of P450s as a mechanism of insecticide detoxification was demonstrated by the effect of herbicides and fungicides and the synergist piperonyl butoxide on carbaryl toxicity and P450 activities in the mosquito Aedes albopictus. Mosquito larvae preexposed to technical and analytical grade pentachlorophenol (PCPT, PCPA) showed significant increases of survival from carbaryl toxicity. This phenomenon was reversed when piperonyl butoxide was also applied. Microsomes from PCPT- and PCPA-treated larvae showed higher levels of N-demethylation of p-chloro-N-methylaniline than those from control larvae. Microsomes from larvae treated with PCPT also yielded a very high level of O-demethylation of methoxyresorufin. However, peroxidation of tetramethylbenzidine was decreased in both treated groups. This suggests that PCP may induce certain P450 isozymes but suppress others. SDS-PAGE bands corresponding to the molecular weights of 61 and 63 kDa presented strong intensity in the treated microsomes; these may represent P450s induced by PCP. P450s in the mosquito larvae are active, inducible, and capable of detoxifying the insecticide carbaryl.
Moori: interactive audience participatory audio-visual performance

Moori is a hybrid form of an audience participatory dynamic narrative and an audio-visual performance system. By incorporating a smart phone's dynamic interface and SMS, users share their thoughts to proposed questions by a performer. Through text inputs, buttons, and multi-touch pads, user-data is processed to generate algorithmic audio and visuals. The result is a collaboration between performer and audience members, a real-time audio-visual composition and a dramatic narrative. As authors, viewers transform the content in a collective narrative space.
Repeated Testing: An Overview and Analysis

Physicians often obtain the same test over and over again. This article first considers screening tests, such as mammographic screening for breast cancer, and describes several proposals for finding the interval that best balances cost, harms, and benefits. The same principles apply to monitoring a patient for recurrence of a disease, such as bladder cancer. The article closes with a theoretical consideration of the circumstances for repeating a test once to check a surprising value.
Effects of micropost spacing and stiffness on cell motility

Microfabrication processes enable the biophysical control of cellular environments at the micro- and nanoscale. The mechanical properties of arrayed microposts have been demonstrated to influence diverse cellular functions including cell motility, yet the cellular response to changes in micropost spacing remains unclear. In this work, a microfabricated post array with variable spacing and stiffness was constructed to investigate the effects of these biophysical factors on cell motility. Over a length of 675 mm, the spacing between arrayed microposts decreased from 6t o 2mm in a single direction, corresponding to an average spacing decrease of 40 nm from post-to-post. Simultaneously, the radii of 7 mmhigh microposts were decreased from 2 to 1 mm, resulting in a decrease in micropost stiffness from � 50 to 5 nN/mm, respectively. Over the course of 18 h studies, bovine aortic endothelial cells (BAECs) seeded on the microfabricated post array migrated for an average of 9.6+ 7.3 mm in the direction of decreasing interpost spacing, opposite the direction of durotaxis. By the end of the studies, 61% of seeded BAECs exhibited displacement in the direction of decreasing interpost spacing. The experimental results suggest that the spacing between microposts can be a determinant factor of cell migration direction in the design of micro- and nanotopographic cellular platforms.
Ergonomic deficits in robotic gynecologic oncology surgery: a need for intervention

Abstract Study Objective To evaluate surgeon strain using validated ergonomic assessment tools. Design Observational study (Canadian Task Force classification III). Setting Academic medical center. Participants Robotic surgeons performing gynecologic oncology surgical procedures. Interventions Videotape footage of surgeons performing robotic gynecologic oncology procedures was obtained. A human factors engineer experienced with health care ergonomics analyzed the video recordings and performed ergonomic evaluations of the surgeons. Measurements and Main Results An initial evaluation was conducted using the Rapid Upper Limb Assessment (RULA) survey, an ergonomic assessment and prioritization method for determining posture, force, and frequency concerns with focus on the upper limbs. A more detailed analysis followed using the Strain Index (SI) method, which uses multiplicative interactions to identify jobs that are potentially hazardous. Seventeen hours of video recordings were analyzed, and descriptive data based on RULA/SI analysis were collected. Ergonomic evaluation of surgeon activity resulted in a mean RULA score of 6.46 (maximum possible RULA score, 7), indicating a need for further investigation. The mean SI grand score was 24.34. SI scores >10 suggest a potential for hazard to the operator. Thus, the current use of the surgical robot is potentially dangerous with regards to ergonomic positioning and should be modified. Conclusion At a high-volume robotics center, there are ergonomics deficits that are hazardous to gynecologic surgeons and suggest the need for modification and intervention. A training strategy must be developed to address these ergonomic issues and knowledge deficiencies.
Varve studies at Hector Lake, Alberta, Canada, and the relationship between glacial activity and sedimentation

Glacial lake sedimentary records from Hector Lake in Banff National Park, Alberta, are examined with the aim of clarifying the relationship between glacial activity and outwash sedimentation. Rhythmic couplets in lake bottom sediments provide a method for accurate documentation and dating of recent sedimentation chronology, as analysis of 137Cs content indicates that the couplets are of annual periodicity (i.e., varves). A comparison of sedimentation rate records with recent regional glacial history indicates that high sedimentation rates of one to a few decades duration occur either during and immediately following periods of moraine deposition (ie, maximum ice stands) or during periods of rapid ice recession. Comparison of sedimentary records with somewhat longer term glacial and vegetation records indicates that sedimentation rate variations of several centuries duration closely parallel changes in upvalley ice extent. Over this time scale, high sedimentation rates occur during periods of relatively increased ice extent, low rates during periods of reduced ice extent. Within this general pattern, however, sedimentation rates may remain very high for nearly a century following maximum ice stands, due to the exposure of unstable glaciogenic deposits to fluvial reworking during ice recession.
Specular reflection on the Moon

Abstract An investigation of specular reflection of sunlight on the Moon has revealed that relatively poor quality reflectors with areas of less than one square meter produce sufficient enhanced illumination to be detected in large telescopes on the Earth. Consequently, small orientable reflectors on lunar satellites and landers would permit optical tracking of their trajectories, such reflectors would also provide a feasible means of communicating information to the Earth, and small natural reflectors on the surface may account for some bright flashes which have been sighted on the Moon.
Propagation of infectious bovine rhinotracheitis (bovine herpes-1) virus in murine primary cell cultures.

Virus synthesis in BALB/C mouse lung and kidney primary cultures infected with infectious bovine rhinotracheitis (IBR) virus started between 6 and 8 hours after virus inoculation and reached a maximum titer of 5.5 log10 plaque forming units (PFU) at 48 hours postinfection (PI). Cytopathic effect (CPE) in cell cultures occurred at 8–10 hours and over 90% of the cells had CPE by 48 to 72 hours PI. The bulk of the newly replicated virus (60–80%) was cell-associated as determined by plaque assay of extracellular and intracellular virus. Pulse-chase experiments demonstrated incorporation of radioactive precursors into viral DNA and protein macromolecules. Viral DNA synthesis was initiated between 2 and 4 hours PI and was maximum at 4 to 6 hours. Viral proteins were detected at 4 hours and peaked between 6 and 8 hours PI. Enzyme-linked immunosorbant assay (ELISA) confirmed synthesis of specific viral proteins, which gradually increased during the virus growth cycle. Abstract in French is given at the end of the article.
Truth and consequences in sex and marital therapy: The revelation of secrets in the therapeutic setting

Abstract This paper describes the development by the author and his colleagues of a policy of full revelation of secrets between spouses as a prerequisite to offering sex and marital therapy. This stand is controversial, for it directly contradicts the advice and practice of many sex and marital therapists. The exploration of this therapeutic position by therapists who are firmly convinced of the need for sexual and emotional commitment, but who will not themselves betray confidences, has offered crucial new opportunities to couples. For example, many couples have been able to confront the self-serving aspects of the wish to “protect” the other partner from knowledge that would in reality subject both partners to risk and a sense of vulnerability. Remarkably, there has not been one casualty in the series of more than 30 cases. Marital and sexual case illustrations, alternate methods of handling such secrets, and a discussion of the course of subsequent treatment are considered.
Decrease or increase in cardiac muscarinic cholinergic receptor number in rats treated with methacholine or atropine

The effects of chronic treatment of the rat with methacholine and atropine on the cardiac muscarinic cholinergic receptors were investigated. [3H]Quinuclidinyl benzilate ([3H]QNB) was used to directly estimate the number and affinity of the receptors in the heart ventricular membrane. Methacholine treatment decreased, in a dose-related and time-dependent manner, the specific binding of [3H]QNB by 34% as compared to the control. Atropine treatment, on the other hand, resulted in a dose-related increase (28 to 66%) in the number of the receptors. The equilibrium dissociation constant (KD) of the receptors for the ligand was the same (about 200 pM) for the control and the methacholine treated groups of rats, whereas a dose-related increase (39 to 105%) in the KD was noted for the atropine treated rats. Similarly, the concentration of acetylcholine causing a 50 percent inhibition (IC50) of the [3H]QNB binding was unaltered for the methacholine treated rats (4 μM), but it was increased 43% for the atropine treated rats.
Clinical applications of pulmonary delivery of antibiotics

The treatment of infection typically involves administration of antibiotics by a systemic route, such as intravenous or oral. However, pulmonary infections can also be approached by inhalation of antibiotics as the infection is more directly accessible via the airways, making inhalation delivery essentially topical administration. This approach offers deposition of high antimicrobial concentrations directly at the site of infection but with a potentially reduced systemic exposure. This review covers the evidence for aerosolized antibiotics for the treatment of a number of conditions such as cystic fibrosis (CF), where it has become the standard of care for chronic infection, as well as non-CF bronchiectasis, non-tuberculous mycobacteria, and ventilator-associated infection where such therapy does not have an approved indication but has been used with increasing frequency.
Effect of Electron Irradiation on Carrier Mobilities in Inversion Layers of Insulated Gate Field Effect Transistors

The effect of 1. 5 MeV and 20 keV electrons on the mobility was determined for a number of different types of n- and p-channel insulated gate field effect transistors with thermally grown oxide and deposited nitride passivation. An expression has been derived for the variation of the effective mobility with gate voltage as the result of surface scattering, which is in good agreement with values obtained from the channel conductance at 100 mV source to drain voltage. It is shown that the observed decrease in effective mobility after irradiation may be explained in terms of increased lattice scattering and Coulomb scattering by charged surface traps while the diffuse surface scattering remains unchanged. The channel conductance and transconductance of the devices were also measured in the saturation region.
Deviation from Stoichiometry in Cr2O3 at High Oxygen Partial Pressures

The deviation from stoichiometry, δ, in Cr2−δO3 was measured by a tensivolumetric method in the high pO2 range of ≊104 to 104 Pa at 1100°C. The value of δ, or chromium vacancy concentration, was≊9×10−5 mol/mol Cr2O3 in air for Cr2O3 with 99.999% purity. The chemical diffusion coefficient, DT, determined from equilibration data was ≊4.6× cm2·s−1 at 1100°C for pO2= 2.2 ×101 Pa. The self-diffusion coefficient of Cr ions was calculated from and δ and found to be≊1.6×10-17 cm2-s−1, in good agreement with recently measured values.
Distribution of P32 in tissues of normal animals.

SummaryThe distribution and the specific activity of P32 in the various organs of normal animals was studied at 1, 2, and 12 hours after intraperitoneal administration of the isotope. The P32 was rapidly taken up by the serum and distributed in the various organs. It appears that the distribution of P32 was not directly related to the amount of phosphorus present in the tissue but depended on the permeability of the cells to the phosphate ion.
A review of similarity between seed bank and standing vegetation across ecosystems

The relationship between above and belowground species composition has been researched in forests, grasslands, and wetlands to understand what mechanisms control community composition. I thoroughly reviewed 108 articles published between 1945 and 2006 that summarized and provided specific values on similarities between above and belowground communities to identify common trends among ecosystems. Using Sorenson's index of similarity, I found that standing vegetation and its associated seed bank was the least similar in forest ecosystems, most similar in grasslands, and of intermediate similarity in wetlands. I also discovered that species richness was not related to seed bank - vegetation similarity in any of the three ecosystems. Disturbances were a common mechanism driving community composition in all ecosystems, where similarity decreased with time since disturbance in forest and wetland ecosystems and increased with time since disturbance in grasslands. Knowing the relationships between seed bank and standing vegetation may help conservationists to manage against exotic species, plan for community responses to disturbances, restore diversity, and better understand the resilience of an ecosystem.
Osmotic regulation of evaporative water loss and body temperature by intracranial receptors in the heat-stressed cat

The effect on body temperature (Tb) regulation of alterations in the osmotic milieu of the intracranial compartment has been examined by intracerebroventricular (ICV) infusion of water (0.034 ml·min−1) in heat-stressed hydrated and dehydrated cats. At an ambient temperature (Ta) of 38°C, before ICV water infusion, mean Tb (measured in the hypothalamus) of normally hydrated cats was 38.8±0.1°C and mean evaporative water loss (EWL) was 1.32±0.18 W ·kg−1. ICV water infusion was without significant effect (P>0.05,t-test) on either of these values in normally hydrated animals. In dehydrated animals at Ta 38°C, Tb and EWL were both significantly altered (P<0.001) from the normally hydrated state and were measured at 39.9±0.2°C and 0.84±0.09 W·kg−1 respectively. Infusion of water into dehydrated animals significantly altered pre-infusion levels of Tb and EWL so that Tb fell to 39.4±0.2°C (P<0.001) and EWL rose to 1.46±0.09 W·kg−1 (P<0.001) No effect of ICV water infusion on mean plasma vasopressin levels (pAVP) was observed in normally hydrated animals (preinfusion pAVP = 1.3±0.2 μU·ml−1, post-infusion pAVP = 1.3±0.3 μU·ml−1,P<0.05). However, a significant reduction in pAVP occurred subsequent to infusion in dehydrated animals (pre-infusion pAVP = 16.6±1.85 μU ·ml−1, post-infusion pAVP = 10.7±2.3 μU·ml−1,P<0.05). The results suggest that intracranial sensory elements capable of responding to the concentration of water, or solutes in water, may be involved in the suppression of EWL in dehydrated, heat-stressed animals.
Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies.

Monoclonal antibodies (mAbs) are now commonly used therapeutic agents in cancer patients. Since US Food and Drug Administration approval of cetuximab for head and neck squamous cell carcinoma, it has been used increasingly in this disease. Several other mAbs also are in development or in clinical trials. Recently, evidence has accumulated that mAbs induce activation of cellular immunity, including natural killer and T cells and that this may contribute to clinical response. mAbs have been shown to mediate antibody-dependent cellular cytotoxicity, complement-dependent lysis, and activation of tumor antigen-specific T cells. Various patient and tumor factors, such as polymorphisms in Fcγ receptors expressed by immune cells, activity of T-regulatory cells, and tumor escape through downregulation of antigen-processing machinery in tumor cells, are likely to modulate the immune activation mediated by therapeutic mAbs. Understanding the interplay of these factors is likely to improve the selection of the most appropriate candidates for mAb-based immunotherapy, prediction of clinical response, and our understanding of mechanisms of tumor escape from therapeutic mAbs.