cssi/SciSciGPT-SciSciNet huggingface dataset:
Development and Evaluation of Talazoparib Nanoemulsion for Systemic Therapy of BRCA1-mutant Cancer.

Aim This is a debut study report on talazoparib (BMN-673)-loaded nanoemulsion (TZNE) for parenteral administration. Materials and methods TZNE (0.05% drug, 151.4±0.7 nm droplet size, polydispersity index of 0.120±0.010 and zeta potential of -33.30±1.22 mV) was designed, developed and characterized using in vitro studies. A cumulative in vitro release study was performed in physiological phosphate buffer solution at different pH (5.3, 6.5 and 7.4) using a dialysis method. Cytotoxicity and apoptosis assays were performed on MDA-MB-231, NCI/ADR-RES, 2008 C13, CP-70 and SKOV-3 cell lines using CellTiter® Blue. Quantitative and qualitative cell uptake was studied using fluorescent probe, coumarin-6 (C-6). Results The drug release form TZNE nanoemulsion was slow and sustained for 24 h. Cytotoxicity and apoptosis were found to be concentration-dependent. The half-maximal inhibitory concentration of TZNE was 0.4852 and 1.35, 11.757 and 0.4696, and 1.169 and 0.7235 μM in MDA-MB-231, SKOV-3 and NCI/ADR-RES cells with 48 and 72 h incubation, respectively. Cellular uptake studies using fluorescent probe, coumarin-6 C-6, showed higher cellular uptake of TNZE compared with free C6. Results suggest that nanoemulsion could provide a new platform for systemic delivery of talazoparib.
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases

A hallmark event in neurodegenerative diseases (NDs) is the misfolding, aggregation, and accumulation of proteins, leading to cellular dysfunction, loss of synaptic connections, and brain damage. Despite the involvement of distinct proteins in different NDs, the process of protein misfolding and aggregation is remarkably similar. A recent breakthrough in the field was the discovery that misfolded protein aggregates can self-propagate through seeding and spread the pathological abnormalities between cells and tissues in a manner akin to the behavior of infectious prions in prion diseases. This discovery has vast implications for understanding the mechanisms involved in the initiation and progression of NDs, as well as for the design of novel strategies for treatment and diagnosis. In this Review, we provide a critical discussion of the role of protein misfolding and aggregation in NDs. Commonalities and differences between distinct protein aggregates will be highlighted, in addition to evidence supporting the hypothesis that misfolded aggregates can be transmissible by the prion principle. We will also describe the molecular basis and implications for prion-like conformational strains, cross-interaction between different misfolded proteins in the brain, and how these concepts can be applied to the development of novel strategies for therapy and diagnosis.
Geometric-Feature-Based Spectral Graph Matching in Pharyngeal Surface Registration

Fusion between an endoscopic movie and a CT can aid specifying the tumor target volume for radiotherapy. That requires a deformable pharyngeal surface registration between a 3D endoscope reconstruction and a CT segmentation. In this paper, we propose to use local geometric features for deriving a set of initial correspondences between two surfaces, with which an association graph can be constructed for registration by spectral graph matching. We also define a new similarity measurement to provide a meaningful way for computing inter-surface affinities in the association graph. Our registration method can deal with large non-rigid anatomical deformation, as well as missing data and topology change. We tested the robustness of our method with synthetic deformations and showed registration results on real data.
Connected Vehicle Prognostics Framework for Dynamic Systems

Connected vehicle analytics has a promise to substantially advance vehicle prognostics and health management. However, the practical implementation of connected vehicle prognostics faces a number of challenges, such as the limitation of communication bandwidth resulting in potential loss of data that is critical for adequate prognostics models. The paper discusses a modelling framework for connected vehicle prognostics for dynamic systems that allows addressing connectivity limitations and memory constraints. The framework is based on a hybrid prognostics approach combining in-vehicle physics-based data aggregation model and cloud-based data-driven prognostics leveraging cross-vehicle and external data sources. The application of the framework is illustrated by models for brake pads wear and cabin air filter prognostics.
Pressure Redistribution Crib Mattress: A Quality Improvement Project.

Background Selective use of pressure-redistributing support surfaces is considered an essential component of a pressure injury prevention bundle. Critically ill children who are too big for an isolette but too little for a bed are usually placed in critical care cribs that have unique features such as moveable side rails and a built-in scale for weighing the patient, but they do not have a mattress designed to redistribute pressure. The primary aim of this quality improvement project was to evaluate a pressure redistribution mattress designed for use in critical care cribs. Cases We retrospectively reviewed 22 charts of critically ill pediatric patients who participated in a product trial completed over a 12-week period in a stand-alone children's hospital in the Western United States. We reviewed demographic data, skin assessments, Braden Q Scale score, and support surface use. Our review revealed no pressure injury occurrences over the 12-week data collection period. Conclusions Findings from this quality improvement project suggest that the pressure-redistributing mattress, when used as part of an intervention bundle, prevents pressure injuries in critically ill pediatric patients.
Association of periodontal disease with depression and adverse birth outcomes: Results from the Perinatal database; Finger Lakes region, New York State.

Preterm and low birth weight infants are at greater risk for mortality and a variety of health and developmental problems. Data from the Finger Lakes Perinatal Data System database on 316,956 deliveries occurring between 2004–2014 and pregnancy outcomes were analyzed to assess the association of periodontal (gum) disease with depression, other maternal factors and adverse birth outcomes. Adjusted effects of periodontal disease and depression on adverse birth outcomes were estimated using multiple logistic regression models and path analysis. Having preterm delivery was associated significantly with depression (OR = 1.177; 95% CI: [1.146, 1.208]), having adequate health care (OR = 1.638; 95% CI: [1.589, 1.689]), smoking during pregnancy (OR = 1.259; 95% CI: [1.220, 1.300]), and being less educated (OR = 1.214; 95% CI: [1.174, 1.256]). Having low birth weight was significantly associated with depression (OR = 1.206; 95% CI: [1.170, 1.208]), smoking during pregnancy (OR = 1.855; 95% CI: [1.793, 1.919]), and being less educated (OR = 1.322; 95% CI: [1.275, 1.370]). Periodontal disease was significantly associated with alcohol use during pregnancy (OR = 1.314; 95% CI: [1.227, 1.407]) and white race (OR = 1.192; 95% CI: [1.167, 1.217]). Depression was significantly associated with periodontal disease (OR = 1.762; 95% CI: [1.727, 1.797]) and alcohol use during pregnancy (OR = 1.470; 95% CI: [1.377, 1.570]). We concluded that a positive association existed between depression during pregnancy and adverse birth outcomes, and that depression served as a mediator in the association of periodontal disease with adverse birth outcomes.
Clinical evaluation of a 31-year-old woman with crural monomelic amyotrophy

This report describes the clinical presentation of a female patient diagnosed with crural MMA. Careful clinical correlation is necessary to distinguish crural MMA from other motor neuron diseases. When crural MMA is diagnosed, treatment options aim to alleviate symptoms.
Enhancing the Educational Value and Faculty Attendance of a Morbidity and Mortality Conference.

Objective There exists significant variation in the approach to and execution of morbidity and mortality conference (M&MC). Faculty attendance remains a working challenge. We sought to change our department's M&MC and hypothesized improved educational value and attendance. Design Complications were submitted in Clavien-Dindo format. A designated M&MC moderator facilitated discussion. A teaching point (TP) was assigned to each complication intended to be the focus of discussion. Presentations followed a structured 6-slide PowerPoint template. A web-based tool using Google Forms was developed and distributed as an “App” for tracking of attendance. An anonymous online survey was distributed to participants to elucidate perception of M&MC following the intervention. Setting Academic medical center. Participants Postgraduate year-1 to 5 surgery residents and faculty at West Virginia University, Morgantown. Results Forty-eight of sixty-three surveys were returned (response rate 76%). Twenty-five faculty (70%) and 23 residents (82%) responded. A predetermined TP was viewed as the most favorable change made by both faculty and residents. 65% of faculty and residents acknowledged improved educational value, 58% found a single moderator to help streamline Morbidity and Mortality (M&M) presentations and 71% felt that a standard PowerPoint template improved quality of presentations. Both residents (96%) and faculty (68%) believed a predetermined TP improved the educational value of the conference and medical knowledge during preparation. More residents (43%) than faculty (16%) believed that changes to the department's M&MC format allowed better identification of quality improvement issues. Furthermore, the majority of residents (83%) believed that changes to the department's M&M format allowed better identification of system factors compared to faculty (32%), p = 0.003. Faculty participation increased from 60% to 80% after changes (p = 0.03). Conclusions The educational value of M&MC and attendance can be improved with simple changes, but faculty and residents may have different expectations and perceptions.
A Strategic Approach to a Total Laparoscopic Hysterectomy for an Advanced Cesarean Section Scar Ectopic Pregnancy with Cystotomy Repair.

Study Objective Present an interesting case of an advanced cesarean scar ectopic pregnancy that failed medical management and underwent treatment with a total laparoscopic hysterectomy. Design Video Case Report. Setting Tertiary Referral Hospital at a community-based OB/GYN residency program. Patients or Participants 37-year-old G3P3013 at 9 weeks gestation with a cesarean scar ectopic pregnancy. Interventions This video will present an interesting case of a 37yo G5P3013 that presented with a 9-week cesarean scar ectopic pregnancy. Initial treatment was with injection of KCL into the fetal heart and methotrexate into the gestational sac at 10 weeks gestation. The patient presented 5 weeks after initial treatment with persistent pain and vaginal bleeding. The patient was the thoroughly counseled on her treatment options. She had no desire for future pregnancy and the plan was made for total laparoscopic hysterectomy with bilateral salpingectomy. This video presentation shows how as strategic anatomic approach using isolation of the blood supply and utilizing avascular spaces can allow this case to be completed in a minimally invasive fashion. This case will also present the steps to repairing an incidental cystotomy that was encountered in the dissection Measurements and Main Results N/A Conclusion Advanced cesarean scar ectopic pregnancy can be treated in a minimally invasive fashion with total laparoscopic hysterectomy when future fertility is not desired.
A review on dry reforming of methane over perovskite derived catalysts

Abstract Dry reforming of methane (DRM) is widely studied as one of the potential routes for syngas production from two greenhouse gases (CH4 & CO2) and can reduce the net emission of these gases if the energy used for it is derived from non-hydrocarbon source. Many conventional metal/support catalyst systems, though are highly active, deactivate within few hours due to surface coke deposition or sintering of the active metal clusters. In order to overcome these challenges and withstand the extreme operating temperatures of DRM, active metals can be incorporated into crystalline oxides like perovskites, pyrochlores, hydrotalcites and hexaaluminates. These metal-containing oxides, once the active metal is reduced, produce a highly dispersed active catalyst. This review emphasizes the application of perovskite-derived catalysts in dry reforming of methane. Perovskites are crystalline oxides with general formula of ABO3, where A is generally a rare earth, alkaline earth or alkali metal cation while B is a transition metal cation. The exsolution process involved in the reduction of perovskite catalysts produces smaller size metal particles which in turn dictate the superior catalytic performance of these materials. Preparation methods, “A” and/or “B” site partial substitutions and additional use of high surface area supports (like mesoporous silicates and basic oxides) for dispersing perovskite catalysts, greatly influence the physicochemical and catalytic behavior of these perovskite derived catalysts. “A” site substitutions generally enhance the oxygen mobility in the perovskite structure by generating oxygen vacancies which suppress the carbon deposition, while bimetallic synergistic effects are produced by addition of a second metal at the “B” site which tend to increase the activity and stability of these catalysts. This review also includes a detailed discussion on the mechanism of DRM in perovskite derived catalysts.
TST’s Jubilee Year—A Celebration of Its Doctoral Alumni

The following is a collection of reflections by doctoral alumni that contribute to the celebration of the fiftieth anniversary of the Toronto School of Theology (TST). These reflections indicate ho...
Peptide Hormone Insulin Regulates Function, Expression, and SUMOylation of Organic Anion Transporter 3

Organic anion transporter 3 (OAT3) plays an important role in the disposition of various anionic drugs which impacts the pharmacokinetics and pharmacodynamics of the therapeutics, thus influencing the pharmacological effects and toxicity of the drugs. In this study, we investigated the effect of insulin on the regulation of OAT3 function, expression, and SUMOylation. We demonstrated that insulin induced an increase in OAT3 transport activity through a dose- and time-dependent manner in COS-7 cells. The insulin-induced elevation in OAT3 function was blocked by PKA inhibitor H89, which correlated well with OAT3 protein expression. Moreover, both PKA activator Bt2-cAMP-induced increase and insulin-induced increase in OAT3 function were blocked by PKB inhibitor AKTi1/2. To further investigate the involvement of SUMOylation, we treated OAT3-expressing cells with insulin in presence or absence of H89 or AKTi1/2 followed by examining OAT3 SUMOylation. We showed that insulin enhanced OAT3 SUMOylation, and such enhancement was abrogated by H89 and AKTi1/2. Lastly, insulin increased OAT3 function and SUMOylation in rat kidney slice. In conclusion, our investigations demonstrated that insulin regulated OAT3 function, expression, and SUMOylation through PKA/PKB signaling pathway. Graphical abstract.
Survivorship Care Plan Preferences and Utilization Among Asian American Breast Cancer Survivors.

Problem identification The survivorship care plan (SCP) is an individualized document with cancer diagnosis, treatment, surveillance, and health promotion recommendations. This integrative review synthesizes the extant literature to understand preferences and utilization of SCPs among Asian American survivors. Literature search The CINAHL®, Embase®, PsycINFO®, and PubMed® databases were searched for articles about Asian American women with breast or cervical cancer and SCPs. Data evaluation Two independent reviewers evaluated 481 titles and abstracts according to inclusion and exclusion criteria. Of those 481 titles and abstracts, 14 articles were selected for inclusion. Synthesis There was little evidence surrounding utilization of SCPs. Articles identified addressed only survivors of breast cancer, predominately of Southeast Asian descent. Asian American women with breast cancer reported preferences surrounding their survivorship needs. Barriers to delivery of the SCP were related to socioeconomic factors. Implications for research There is a paucity of information guiding evidence-based delivery of SCPs in the vastly heterogenous population of Asian American survivors. More work is needed to provide high-quality care to these survivors.
Cargo port choice equilibrium: A multi-perspective look at shippers’ port choice

Abstract Traditionally, cargo port choice has been investigated from the perspective of port users. More recently, studies on cargo port choice from the perspective of the port service providers have appeared. Irrespective of the perspective taken, the common element in these studies is that they focus on one perspective at a time. In this paper, it is postulated that cargo port choice should really be examined from both perspectives, simultaneously, as cargo port choice is made by both users and providers of cargo port services. The port users we will focus on in this paper are the shippers. To model this simultaneous choice, a new modeling framework is proposed, i.e. cargo port choice equilibrium. This new framework enables policy makers and other maritime industry stakeholders to evaluate the network-wide impact (i.e. across all cargo ports) of a range of policy measures while considering the choices by both shippers and port service providers. One key consequence of our equilibrium model is that prior findings in the port choice literature might no longer be valid without further qualifications. Overall, this paper generalizes, unifies and extends a segment of the port choice literature.
Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 2: Model for the Drug-combination Nanoparticles.

Abstract We previously developed a mechanism-based pharmacokinetic (MBPK) model to characterize the PK of a lymphocyte-targeted, long-acting 3 HIV drug-combination nanoparticle (DcNP) formulation of lopinavir, ritonavir, and tenofovir. MBPK describes time-courses of plasma drug concentration and has provided an initial hypothesis for the lymphatic PK of DcNP. Because anatomical and physiological interpretation of MBPK is limited, in this Part 2, we report the development of a Physiologically Based Pharmacokinetic (PBPK) model for a detailed evaluation of the lymphatic and tissue PK of drugs associated with DcNP. The DcNP model is linked to the PBPK model presented earlier in Part 1 to account for the disposition of released free drugs. A key feature of the DcNP model is the uptake of the injected dose from the subcutaneous site to the adjacent lymphoid depot, routing through the nodes within and throughout the lymphatic network, and its subsequent passage into the blood circulation. Furthermore, the model accounts for DcNP transport to the lymph by lymphatic recirculation and mononuclear cell migration. The present PBPK model can be extended to other nano-drug combinations that target or transit through the lymphatic system. The PBPK model may allow scaling and prediction of DcNP PK in humans.
Innate Immunity and Cancer Pathophysiology.

Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by the innate immune system. Cellular and molecular mediators of inflammation modulate tumor growth directly and by influencing the adaptive immune response. Depending on the balance of immune cell types and signals within the tumor microenvironment, inflammation can support or restrain the tumor. Adding to the complexity, research from the past two decades has revealed that innate immune cells are highly heterogeneous and plastic, with variable phenotypes depending on tumor type, stage, and treatment. The field is now on the cusp of being able to harness this wealth of data to (a) classify tumors on the basis of their immune makeup, with implications for prognosis, treatment choice, and clinical outcome, and (b) design therapeutic strategies that activate antitumor immune responses by targeting innate immune cells. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Dose response of red imported fire ant colonies to Solenopsis invicta virus 3

Baiting tests were conducted to evaluate the effect of increasing Solenopsis invicta virus 3 (SINV-3) dose on fire ant colonies. Actively growing early-stage fire ant (Solenopsis invicta Buren) laboratory colonies were pulse-exposed for 24 hours to six concentrations of SINV-3 (101, 103, 105, 107, 109 genome equivalents/μl) in 1 ml of a 10 % sucrose bait and monitored regularly for two months. SINV-3 concentration had a significant effect on colony health. Brood rating (proportion of brood to worker ants) began to depart from the control group at 19 days for the 109 concentration and 26 days for the 107 concentration. At 60 days, brood rating was significantly lower among colonies treated with 109, 107, and 105 SINV-3 concentrations. The intermediate concentration, 105, appeared to cause a chronic, low-level infection with one colony (n = 9) supporting virus replication. Newly synthesized virus was not detected in any fire ant colonies treated at the 101 concentration, indicating that active infections failed to be established at this level of exposure. The highest bait concentration chosen, 109, appeared most effective from a control aspect; mean colony brood rating at this concentration (1.1 ± 0.9 at the 60 day time point) indicated poor colony health with minimal brood production. No clear relationship was observed between the quantity of plus genome strand detected and brood rating. Conversely, there was a strong relationship between the presence of the replicative genome strand and declining brood rating, which may serve as a predictor of disease severity. Recommendations for field treatment levels to control fire ants with SINV-3 are discussed.
The strategic use and misuse of interorganizational information systems: the case of EDI

The author considers the problem of managing IIS (interorganizational information system) technologies within trading networks off firms. Research on adopters of electronic data interchange (EDI) systems suggests that strategic advantages can be obtained from EDI in terms of supply and distribution channel control. However, potential advantages are largely unrealized for three reasons: loose-coupling with network partners obstructs necessary coordination; centralized control of EDI in inappropriate functional areas aggravates these coordination problems; and the failure to strategically integrate EDI within the firm limits its potential impact. >
How Do Strategic Factor Markets Respond to Rivalry in the Product Market

This paper explores the interplay between product market, strategic factor market, and resource development. More competition in the product market makes resource buyers bid higher for resources, as the value of trying to preempt the resources is higher. Holding other initial conditions constant, resources are developed more in industries with factor markets than in industries without. When buyers of resources cannot integrate more than one resource, developers choose to develop either at a low or high level, generating a type of heterogeneity that would not arise otherwise. Changes in the intensity of competition in the product market can have the opposite effect on resource development efforts depending on the presence or absence of factor markets
Caring in Confucian Philosophy

This article examines the intersections of Confucian philosophy and feminist ethics of care. It explains the origins and contribution of care ethics to modern ethical discourse and the controversy that surrounds this ethical theory. The article discusses the emergence of comparative research on the compatibility (or incompatibility) of Confucian ren and feminist care. It first explores the question whether it is philosophically feasible to disassociate Confucian ren from its historical context by deploying it for contemporary feminist debates, especially considering that, strictly speaking, no direct counterpart in the original Confucian texts is an exact match to the words ‘care’ or ‘caring’. Following this exploration, the article investigates what ren is and whether Confucian ren is feminist care, what the ‘No Exit’ Objection and the ‘Domesticity’ Objection are, and how ren or caring in Confucian philosophy can answer these objections. The article concludes with an affirmation of the social transformative power of ren and its feminist potential.
Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change

Non-coding RNAs (ncRNAs) have a multitude of roles in the cell, many of which remain to be discovered. However, it is difficult to detect novel ncRNAs in biochemical screens. To advance biological knowledge, computational methods that can accurately detect ncRNAs in sequenced genomes are therefore desirable. The increasing number of genomic sequences provides a rich dataset for computational comparative sequence analysis and detection of novel ncRNAs. Here, Dynalign, a program for predicting secondary structures common to two RNA sequences on the basis of minimizing folding free energy change, is utilized as a computational ncRNA detection tool. The Dynalign-computed optimal total free energy change, which scores the structural alignment and the free energy change of folding into a common structure for two RNA sequences, is shown to be an effective measure for distinguishing ncRNA from randomized sequences. To make the classification as a ncRNA, the total free energy change of an input sequence pair can either be compared with the total free energy changes of a set of control sequence pairs, or be used in combination with sequence length and nucleotide frequencies as input to a classification support vector machine. The latter method is much faster, but slightly less sensitive at a given specificity. Additionally, the classification support vector machine method is shown to be sensitive and specific on genomic ncRNA screens of two different Escherichia coli and Salmonella typhi genome alignments, in which many ncRNAs are known. The Dynalign computational experiments are also compared with two other ncRNA detection programs, RNAz and QRNA. The Dynalign-based support vector machine method is more sensitive for known ncRNAs in the test genomic screens than RNAz and QRNA. Additionally, both Dynalign-based methods are more sensitive than RNAz and QRNA at low sequence pair identities. Dynalign can be used as a comparable or more accurate tool than RNAz or QRNA in genomic screens, especially for low-identity regions. Dynalign provides a method for discovering ncRNAs in sequenced genomes that other methods may not identify. Significant improvements in Dynalign runtime have also been achieved.
A COLD-SENSITIVE ZYGOTIC LETHAL CAUSING HIGH FREQUENCIES OF NONDISJUNCTION DURING MEIOSIS I IN DROSOPHILA MELANOGASTER FEMALES

ABSTRACT The X -linked, cold-sensitive zygotic lethal, l(1)TW-6 cs , both in homozygous and heterozygous females, induces nondisjunction of all four chromosomes at Meiosis I at both 25° and 17°. Nondisjunction frequencies approaching 0.5 for the X and fourth chromosomes have been observed at 16°–18°. The disjunction of the X chromosomes in males is not affected. The mutant causes mitotic irregularities in zygotes at both 25° and 17°. Mortality of all zygotes produced by the crosses 6 cs /6 cs × 6 cs /B s Y and FM7/6 cs × 6 cs /B s Y is respectively 86% and 67–74% at 25° and 99.8–99.9% and 94% at 17°. The mortality of 6 cs hemizygotes derived from females carrying no doses of 6 cs ( C(1)DX,y f/y × 6 cs /B s Y ) is 45–55% at 25° and 98% at 17°. The length of the temperature-sensitive period for 6 cs homo- and hemizygotes is affected by the maternal dosage of 6 cs ; the shortest TSP is for zero and the longest is for two maternal doses. Mortality takes place primarily during embryogenesis with some larval and little pupal mortality. Analysis of sectioned embryos indicates that the large array of different patterns of damage observed could have arisen from abnormal cleavage divisions and the incomplete population of the blastoderm with nuclei.
Gap anisotropy and universal pairing scale in a spin-fluctuation model of cuprate superconductors

We consider the evolution of ${d}_{{x}^{2}\ensuremath{-}{y}^{2}}$ pairing, mediated by nearly critical spin fluctuations, with the coupling strength. We show that the onset temperature for pairing, ${T}^{\ensuremath{\ast}}$, smoothly evolves between weak and strong couplings passing through a broad maximum at intermediate coupling. At strong coupling, ${T}^{\ensuremath{\ast}}$ is of order of the magnetic exchange energy $J$. We argue that for all couplings, pairing is confined to the vicinity of the Fermi surface. We also find that thermal spin fluctuations only modestly reduce ${T}^{\ensuremath{\ast}}$, even at criticality, but they substantially smooth the gap anisotropy. The latter evolves with coupling being the largest at weak coupling.
Ethics in Clinical Trials Progress ni Acute Stroke Research

We are delighted to respond to Dr Slyter’s1 commentary on acute stroke research. At the outset, we would like to state that stroke research is critically important for improving the health of the public, that many important clinical questions cannot be answered without clinical trials, and that the NINDS and stroke investigators are committed to protecting those who choose to participate in clinical research. Dr Slyter voices specific concerns about early phase 1 studies that offer no therapeutic benefit to the patient. He is also concerned about how to treat patients assigned to the control group in a randomized trial when there is widespread controversy about standard care, which may be as much a medical issue as an ethical one. Dr Slyter questions the management of blood pressure in the NINDS rt-PA Stroke Trial. In fact, management of blood pressure in the trial was designed with careful consideration of the patients in both the placebo and active treatment arms of the trial. The reader may wish to read the references concerning the treatment of …
New Measures of Sperm Motion I. Adaptive Smoothing and Harmonic Analysis

Several kinematic measures from computer-aided sperm analysis (CASA) instruments depend critically upon the computation of the spatially averaged path of a sperm's curvilinear swimming trajectory. Presently available instruments compute the average path by smoothing the curvilinear trajectory using a fixed-length running average. We demonstrate that this method significantly distorts the spatially averaged path for irregularly swimming sperm, both within and between trajectories, resulting in inaccurate calculations for the velocity of the average path (VAP), amplitude of lateral head displacement (ALH), beat-cross frequency (BCF), wobble of the curvilinear trajectory (WOB), and straightness of the curvilinear trajectory (STR). The authors introduce an alternative approach, based on engineering signal processing techniques, where the width of the running average is adapted to the changing wavelengths of the major spatial oscillations of each curvilinear trajectory. How this adaptive method results in less distortion of the average path and produces more accurate characterizations of the above measures is shown. This method is implemented in a computer program developed by the authors, called PathTool. It is also demonstrated that the simple methods used to characterize the frequency and amplitude of the major oscillation in a sperm's curvilinear trajectory (ie, BCF and ALH) are only accurate for the most periodic, progressive, and symmetrical trajectories. Three new measures are introduced, based on mathematical harmonic analysis, that are more robust alternatives to the present methods. These new methods and measures are initially evaluated using prototypical sperm trajectories from human semen. Results suggest that adaptive smoothing and harmonic analysis produce more accurate estimates of the frequency and magnitude of oscillations in sperm trajectories than the method based on fixed-length smoothing, BCF, and ALH.
Problems in Impurity Analysis of an Insulating Powder Sample by SIMS.

This paper describes the source of variation in the SIMS determination of impurities in an insulating powder sample mixed together with graphite powders for electrical conductivity. The predominant factors were the local charge buildup on the sample surface and the local distribution of impurities originally present in the graphite powders. The local charge buildup due to the inhomogeneity of the tablet sample resulted in obvious changes of the secondary ion energy distributions. The local distribution of impurities in the graphite powders caused the occasionally anomalous high values in the determination.
A Rapid Assessment of Instructional Strategies to Teach Auditory-Visual Conditional Discriminations to Children with Autism.

Abstract The purpose of the present investigation was to evaluate a rapid assessment procedure to identify effective instructional strategies to teach auditory-visual conditional discriminations to children diagnosed with autism. We replicated and extended previous rapid skills assessments ( Lerman, Vorndran, Addison, & Kuhn, 2004 ) by evaluating the effects of reinforcement and prompting on the acquisition of auditory-visual conditional discriminations. The results showed that our assessment procedure identified at least one effective instructional strategy for each participant. In addition, our experimental design allowed us to identify the most efficient instructional strategy for all three participants.
Protein conformational changes involved in the cytochrome bc1 complex catalytic cycle

Early structures of the cytochrome bc1 complex revealed heterogeneity in the position of the soluble portion of the Rieske iron sulfur protein subunit, implicating a movement of this domain during function. Subsequent biochemical and biophysical works have firmly established that the motion of this subunit acts in the capacity of a conformationally assisted electron transfer step during the already complicated catalytic mechanism described within the modified version of Peter Mitchells Q cycle. How the movement of this subunit is initiated or how the frequency of its motion is controlled as a function of other steps during the catalysis remain topics of debate within the active research communities. This review addresses the historical aspects of the discovery and description of this movement, while attempting to provide a context for the involvement of conformational motion in the catalysis and efficiency of the enzyme. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.
Optimization of the local inhibition of intestinal adenosine deaminase (ADA) by erythro-9-(2-hydroxy-3-nonyl)adenine : Enhanced oral delivery of an ADA-activated prodrug for anti-HIV therapy

Abstract □ Previous in situ perfusion studies in rat ileal segments have demonstrated that high concentrations (> 40 μg/mL) of erythro - 9-(2-hydroxy-3-nonyl)adenine (EHNA), a semitight binding inhibitor of adenosine deaminase (ADA), are effective in completely inhibiting the intestinal metabolism of 6-chloro-2′,3′-dideoxypurine (6-Cl-ddP), an ADA activated prodrug of the anti-HIV agent 2′,3′-dideoxyinosine (ddI) designed for improved targeting to the central nervous system. However, the intestinal absorption of EHNA results in complete inhibition of the ADA activity in the mesenteric blood draining the isolated intestinal segment being perfused and may lead to complete inhibition of ADA present in the systemic circulation and other sites, an unacceptable outcome since bioconversion in the target tissue is required for prodrug efficacy. This study examines the feasibility of locally inhibiting ADA present in the intestinal wall using EHNA to increase the intestinal absorption of 6-Cl-ddP. Transport experiments conducted in isolated ileal segments from mesenteric cannulated rats using perfusate containing prodrug and various concentrations of EHNA demonstrated that a 0.1 μg/mL logarithmic mean lumenal concentration of EHNA was effective in increasing the intestinal bioavailability of Cl-ddP to > 90%. Intestinal uptake parameters for EHNA and pharmacokinetic parameters generated in vivo in chronically cath-eterized rats given intravenous infusions ranging from 12.5 to 310 μg/kg/min were used to demonstrate that 90% with minimal (
ACOUSTIC WAVE ANALYSIS FOR FOOD CRISPNESS EVALUATION

Sound signals for five snack food products at two moisture levels were recorded digitally and product crispness was evaluated by a trained sensory panel. Sound signal features were extracted by analyzing signal-value and power-value dependencies. Principal component regression and neural network techniques were used to determine the usefulness of the sound signal features as predictors of sensory crispness. In a validation test, a trained neural network model predicted sensory crispness from sound signal features to an R 2 -value of 0.89. The results show the effectiveness of the techniques employed to extract and use sound signal features for crispness evaluation.
Inheritance of burrow building in Peromyscus.

Burrow construction abilities of laboratory-reared oldfield mice (Peromyscus polionotus), deermice (P. maniculatus), and their F1 hybrids were compared using a spacious earth-filled test chamber. Mated paris with nursing litters were individually introduced into the chamber for 4 days in each test. Oldfield mice bred in metal or plastic cages for 20 or more generations constructed elaborate burrows, with entrance and escape tunnels, tunnel plugs, next chambers, and nests, essentially like those of wild mice of this species. Prairie deermice maintained for 25 or more generations in captivity constructed shallow or superficial burrows characteristic of deermice in nature. F1 hybrids made burrows like those of oldfield mice, complete in all particulars. First-generation backcross animals tested for burrow building exhibited a spectrum of performances. Species difference in burrow construction is principally genetic in origin, and during 20–25 generations in captivity no substantial loss of this ability occurred. F1 hybrid data indicate that the more complex burrow building exhibits genetic dominance, and backcross results show that at least two and probably more gene loci strongly influence the trait.
Engaging patients in the prevention of health care-associated infections: a survey of patients' awareness, knowledge, and perceptions regarding the risks and consequences of infection with methicillin-resistant Staphylococcus aureus and Clostridium difficile.

Background and objective Methicillin-resistant Staphylococcus aureus (MRSA) infections and Clostridium difficile infections (CDI) are major health care-associated infections (HAIs). Little is known about patients' knowledge of these HAIs. Therefore, we surveyed patients to determine awareness, knowledge, and perceptions of MRSA infections and CDI. Design An interviewer-administered questionnaire. Setting A tertiary care academic medical center. Participants Adult patients who met at least one of the following criteria: at risk of CDI or MRSA infection, current CDI or colonization or current MRSA infection or colonization, or history of CDI or MRSA infection. Methods Two unique surveys were developed and administered to 100 patients in 2011. Results Overall, 76% of patients surveyed were aware of MRSA, whereas 44% were aware of C difficile . The strongest predictor of patients' awareness of these infections was having a history of HAI. Patients with a history of HAI were significantly more likely to have heard of both MRSA (odds ratio, 13.29; 95% confidence interval, 2.84-62.14; P = .001) and C difficile (odds ratio, 9.78; 95% confidence interval, 2.66-35.95; P = .001), than those patients without a history of HAI. There was also a significant positive association between having a history of HAI and greater knowledge of the risk factors, health consequences, and prevention techniques relative to CDI and MRSA infections. Conclusions There are additional opportunities to engage patients about the risks and consequences of MRSA and CDIs, particularly those without a history of HAI.
Assessing volumetric strains and mass balance relationships resulting from biotite-controlled weathering: Implications for the isovolumetric weathering of the Boulder Creek Granodiorite, Boulder County, Colorado, USA

Abstract An important process often cited in the development of saprock and saprolite is the isovolumetric weathering of granitic bedrock. Evidence for isovolumetric weathering includes the observation that the texture of the granitic protolith often remains recognizable in its weathered products. In contrast to the above often cited view, we present results from a study of two sites located on the 1.65 Ga Boulder Creek Granodiorite near Boulder, Colorado, USA, in which weakly chemically altered saprock derived from tonalitic and granodioritic–tonalitic bedrock records volumetric strains on the order of 7.6%–8.5% and 7.9%–8.2% respectively. We show that dilation is likely due to the alteration of biotite to vermiculite during the early stages of weathering, and is associated with an expansion normal to the {001} cleavage of ~ 40%. Theoretical calculations of volumetric strains based on the modal biotite present in the protolith support such an interpretation.
Functionalized hierarchically structured mesoporous silica by sol electrophoresis and self-assembly

Dye-functionalized mesoporous silica has gained considerable attention for use in optical applications. Much interest into the tunable functionality of these small-scale optical materials has been the focus for possible use in lasers, light filters, sensors, solar cells, and photocatalysis. Extensive exploration into functionalizing mesoporous silica has been made using sol-gel methods for incorporating polymeric dyes within the pore channels of the silica network to modify optical properties. However, research so far has been focused on functionalization of mesoporous silica powders or films on dense substrates, limiting applications in practice because of the difficult accessibility of mesopores. In this paper, we studied the development of hierarchically-structured mesoporous silica with chromophore dye molecules covalently linked within the channel walls of pores for the selective adsorption and detection of specific ions and chemical compounds. Hierarchically-structured, unidirectionally-aligned mesoporous silica was synthesized within the pores of polycarbonate membranes by surfactant-assisted sol electrophoretic deposition. After the removal of surfactants from the mesopores, the inner surface of the mesopores was functionalized with silane-containing chromophore molecules through self-assembly. Full coverage of these dye molecules on the surface of the mesopores was anticipated due to the fact that these reactant chromophore molecules, in solution, migrate through the pores. The organic chromophore dye molecules, assembled onto the surface of the mesopores, would have the amino groups exposed to the surface. These groups would have the capability to selectively interact with ions or chemical compounds in solution, for instance lead ions in water. Hence, the absorption spectrum of the chromophore dye molecules attached to the mesopores of silica was altered after exposure to lead ions in solution. In addition, the ion concentration in solution also differed. Such functionalized, hierarchically-structured mesoporous silica would have applications such as membranes for removal of, and sensors for, detecting trace amounts of ions and chemical compounds in water and air.
A comment on the Nielsen-Ninomiya theorem☆

An example of a local lattice hamiltonian in three space dimensions whose continuum limit spectrum consists of a single free Weyl particle and a set of non-propagating modes is presented. Our model satisfies all the hypotheses of the Nielsen-Ninomiya theorem. However, when locally coupled to a background abelian gauge field, it fails to exhibit the spectrum and anomalies expected for a charged Weyl field.
A Clinically Aggressive, Polymorphic, Polyclonal Posttransplantation Lymphoproliferative Disorder

Posttransplantation lymphoproliferative disorders (PTLD) have been divided, based on morphology, into polymorphic and monomorphic types, since findings in the literature reveal that polymorphic PTLD more likely responds to reduced immunosuppression. We report a clinically aggressive, polymorphic (and polyclonal) PTLD despite reduced immunosuppression and discuss possible therapeutic options. In addition, our case suggests that cytogenetic studies may be useful in determining prognosis when DNA molecular techniques do not detect monoclonality.
Chronic urticaria and systemic diseases.

As is evident from the foregoing discussion in this article, there is increasing evidence that a particular type of autoimmune reaction, directed against the Fc-epsilon RI, and less commonly against IgE, might be pathogenic in many cases of apparent CIU. The stimulus for this autoimmune response is currently unknown. Most of the evidence for an association of CU with certain systemic diseases is circumstantial, based on epidemiologic findings of an associated prevalence and possibly on the results of therapy directed at the systemic condition. If such associations truly occur, the underlying pathogenic mechanisms are obscure. Hopefully, further investigation will elucidate these relationships and possibly aid in the understanding of the pathogenesis of CIU itself.
Resolving structural isomers of monosaccharide methyl glycosides using drift tube and traveling wave ion mobility mass spectrometry.

Monosaccharide structural isomers including sixteen methyl-d-glycopyranosides and four methyl-N-acetylhexosamines were subjected to ion mobility measurements by electrospray ion mobility mass spectrometry. Two ion mobility-MS systems were employed: atmospheric pressure drift tube ion mobility time-of-flight mass spectrometry and a Synapt G2 HDMS system which incorporates a low pressure traveling wave ion mobility separator. All the compounds were investigated as [M + Na]+ ions in the positive mode. A majority of the monosaccharide structural isomers exhibited different mobility drift times in either system, depending on differences in their anomeric and stereochemical configurations. In general, drift time patterns (relative drift times of isomers) matched between the two instruments. Higher resolving power was observed using the atmospheric pressure drift tube. Collision cross section values of monosaccharide structural isomers were directly calculated from the atmospheric pressure ion mobility experimen...