cssi/SciSciGPT-SciSciNet huggingface dataset:
Probing Biochemical Mechanisms of Action of Muscarinic M3 Receptor Antagonists with Label-Free Whole Cell Assays

Binding kinetics of drugs is increasingly recognized to be important for their in vivo efficacy and safety profiles. However, little is known about the effect of drug binding kinetics on receptor signaling in native cells. Here we used label-free whole cell dynamic mass redistribution (DMR) assays under persistent and duration-controlled stimulation conditions to investigate the influence of the binding kinetics of four antagonists on the signaling of endogenous muscarinic M3 receptor in native HT-29 cells. Results showed that DMR assays under different conditions differentiated the biochemical mechanisms of action of distinct M3 antagonists. When co-stimulated with acetylcholine, tiotropium, a relatively slow binding antagonist, was found to selectively block the late signaling of the receptor, suggesting that acetylcholine attains its binding equilibrium faster than tiotropium does, thereby still being able to initiate its rapid response until the antagonist draws up and fully blocks the signaling. Furthermore, DMR assays under microfluidics allowed estimation of the residence times of these antagonists acting at the receptor in native cells, which were found to be the determining factor for the blockage efficiency of M3 receptor signaling under duration-controlled conditions. This study demonstrates that DMR assays can be used to elucidate the functional consequence of kinetics-driven antagonist occupancy in native cells.
Deficient Methods or Different Data? Another Interpretation of Divergent Findings on Fundamentalism and Political Sexism: Response to Powell and Steelman

I welcome Powell and Steelman's interest in our (Peek and Brown) recent piece about sex prejudice among white Protestants, because I share their hope of stimulating "continued research on this important topic."1 The divergence between their findings and ours could be an intriguing starting point for subsequent research. However, I also have an additional hope: that this research will not be misled by Powell and Steelman's explanation that the divergence stems from our inadequate methods. In this short reply I examine, first, the allegation of deficient methods, then the effect of using different data sets, and finally the implications of these divergent findings for future research.
To observe the curative effect of He Ne laser irradiation in the treatment of infantile hepatitis syndrome in children

Objective:To observe the curative effect of He Ne laser in the treatment of infantile hepatitis syndrome in children. Methods: 160 cases of infant hepatitis syndrome were randomly divided into control group and treatment group with 80 cases in each group, the control group given hepatoprotective Tuihuang drug therapy; the treatment group in the control group based on the use of He Ne laser irradiation(He-Ne) of liver in children of Yu Xue. Recovery of the signs and symptoms of the two groups were observed after treatment, and the results were analyzed statistically. Results:significant efficiency in treatment group and control group were 87.5%, 65%. There was significant difference in the liver function index in comparison to other patients of the two groups(P 0.05). Conclusion:He Ne laser in the treatment of infantile hepatitis syndrome in children with good effect, the effective rate is high, it is worth promoting in clinical.
Manufacturing resource selection technology based on rapid extended manufacturing environment

Rapid Extended Manufacturing(REM) was proposed based on IT technology and network technology aiming to deal with armament rapid batch variable production.The difference between REM and networked manufacturing was also discussed.Manufacturing resource selection assessment index was classified as time index,cost index,history index,general index,resource status index and manufacturing capability index,comprehensive manufacturing resource assessment system was hence established.Lastly,manufacturing resource selection strategy and implementation algorithm were put forward by using both Analytic Hierarchy Process(AHP) and grey relation theory.Moreover,manufacturing resource selection process based on multi-hierarchy grey relation theory was studied by manufacturing of a key complicated part in airplane.
The impact of mammographic screening on the surgical management of breast cancer.

Background and Objectives Mammographic screening has been shown to result in downward stage migration, reflected by smaller tumor sizes and less extensive nodal involvement. National guidelines restrict screening recommendations in women age 40–49. The purpose of this study is to evaluate the specific impact of mammographic screening patterns on the surgical management of breast cancer in women aged 40–49. Methods The study is a population-based retrospective review of the Vermont Breast Cancer Surveillance System of women aged 40–49 with a diagnosis of breast cancer. Tumor stage and related characteristics at the time of diagnosis, as well as the type of surgical intervention performed were recorded for women presenting with screen-detected versus non-screen-detected breast cancer. Results Screen-detected breast cancers in women aged 40–49 were associated with a greater incidence of DCIS, smaller invasive tumor size, fewer cases of positive nodes, and higher rates of breast conservation compared to non-screened women presenting with symptomatic disease. Conclusions Mammographic screening is associated with less aggressive surgical treatment of breast cancer including higher rates of breast conservation. The observed changes in surgical management should factor into individual decision-making regarding screening mammography. J. Surg. Oncol. 2016;113:496–500. © 2016 Wiley Periodicals, Inc.
Surgical Management of Priapism in Children with Sickle Cell Anemia

AbstractPriapism has been reported to occur in 2 to 5 per cent of patients with sickle cell disease. Recently, creation of a percutaneous fistula between the glans penis and the corpora cavernosa has been applied widely in the management of patients with priapism, except in those cases of sickle cell anemia. Reported failures of such shunting procedures in the sickle cell patient has perhaps unduly denied surgical benefits to that population. We have managed successfully 5 such children with sickle cell anemia and priapism without complications by creation of a fistula between the glans penis and the corpora cavernosa. Our treatment plan is presented, which includes early shunting should initial nonoperative treatment fail.
An indexing vocabulary for case-based explanation

The success of case-based reasoning depends on effective retrieval of relevant prior cases. If retrieval is expensive, or if the cases retrieved are inappropriate, retrieval and adaptation costs will nullify many of the advantages of reasoning from prior experience. We propose an indexing vocabulary to facilitate retrieval of explanations in a casebased explanation system. The explanations we consider are explanations of anomalies (conflicts between new situations and prior expectations or beliefs). Our vocabulary groups anomalies according to the type of information used to generate the expectations or beliefs that failed, and according to how the expectations failed. We argue that by using this vocabulary to characterize anomalies, and retrieving explanations that were built to account for similarly-characterized past anomalies, a case-based explanation system can restrict retrieval to explanations likely to be relevant. In addition, the vocabulary can be used to organize general explanation strategies that suggest paths for explanation in novel situations.
Total Laryngopharyngoesophagectomy and Tracheal Resection With Free Tissue-Reinforced Gastric Pull-Up

Total laryngopharyngoesophagectomy with tracheal resection is an uncommon procedure. The resectability of a hypopharyngeal and cervical esophageal tumor typically depends on the ability to obtain clean surgical margins. The extent of the resection requires careful surgical planning and execution. Concomitant tracheal resection and manubriectomy due to tracheal invasion increases the complexity of these already challenging conditions. Although gastric pull-up procedures have been used to successfully reconstruct laryngopharyngoesophageal defects after tumor resection, a free tissue augmented reconstructive approach should be considered in more aggressive tumors with invasion of surrounding structures. Herein, we describe the use of combining gastric pull-up with anterolateral thigh free tissue transfer for optimal repair after radical tumor resection.
von Willebrand Factor-ADAMTS13 Interactions

Abstract SCI-18 ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) is a plasma metalloenzyme that cleaves von Willebrand factor (vWF), thereby limiting excessive platelet adhesion and aggregation and attenuating the rate of thrombus formation at the site of injury. Severe deficiency of plasma ADAMTS13 activity results in thrombotic thrombocytopenic purpura (TTP), a potentially fatal syndrome, while mild to moderate deficiency of plasma ADAMTS13 activity is associated with an increased risk for myocardial infarction and stroke. Adamts13 null mice in the ApoE null background exhibit a dramatically increased systemic inflammation and early atherosclerosis. Thus, ADAMTS13 plays a crucial role in pathogenesis of arterial thrombotic disorders such as TTP and chronic inflammatory diseases such as atherosclerosis. vWF is the only known substrate for ADAMTS13 to date. Structure-function analysis demonstrates that the N-terminal portion of ADAMTS13 (MDTCS) is sufficient for proteolytic cleavage of vWF, while the C-terminal portion of ADAMTS13 (T2–8 and CUB) inhibits shear-dependent platelet aggregation via free thiols (-SH). The proteolytic cleavage of vWF by ADAMTS13 is dramatically accelerated by binding of Factor VIII (FVIII) and/or platelets under shear stress. A B-domainless FVIII (FVIII-SQ) or a light chain of FVIII (FVIII-LC) appears to be sufficient for the enhanced proteolysis of vWF by ADAMTS13 in vitro and in vivo using a murine model. In contrast, a heavy chain of FVIII (FVIII-HC) or a light chain lacking an acidic region (a3) (FVIII-LC#x2610;¢a3) exhibits no rate enhancing effect under the same conditions. These results suggest that the light chain, particularly the acidic (a3) region that contains a high-affinity vWF binding site is required for the cofactor activity in accelerating vWF proteolysis. Consistent with this hypothesis, mutations in the D9D3 domain of vWF naturally occurring in patients with type 2N von Willebrand disease that reduces FVIII binding also impair the FVIII-dependent proteolysis by ADAMTS13 under fluid shear stress. To develop novel therapeutics, we have constructed, expressed, and screened for a panel of ADAMTS13 variants with a modification of the exosites (motif A and motif B) in the spacer domain. We identified several ADAMTS13 variants that have enhanced specific activity and are also resistant to inhibition by autoantibodies against ADAMTS13 in patients with acquired idiopathic TTP. These gain-of-function and autoantibody-resistant ADAMTS13 variants may be further developed as potential therapeutics for acquired TTP with inhibitors. Disclosures: No relevant conflicts of interest to declare.
Mechanical and Electromechanical Characterization of One-Dimensional Piezoelectric Nanomaterials

In this chapter nanoscale characterization techniques for piezoelectric materials are discussed, with a focus on nanomechanical and electromechanical methods for one-dimensional nanomaterials. One-dimensional nanostructures have been the focus of recent nanoscale research due to their potential application in future nanoelectronics and nanodevices. However, their small size and special geometry impose a challenge especially from experimental point of view and renders their characterization nontrivial. In this chapter, the common methods of nanomechanical and electromechanical characterization of these nanostructures are discussed, with an emphasis on piezoelectric one-dimensional materials. Advantages and limitations of each method are discussed and the relevant literature is presented.
Efficient Inhibition of Notch3 and Notch4 Family Members In Vivo by a Dominant Negative Mutant of Mastermind.

The four mammalian Notch receptors play multiple roles in the hematolymphoid system. Notch1 is critical for the generation of hematopoietic stem cells (HSCs) during embryonic development and for commitment to the T cell lineage, while Notch2 regulates marginal zone B cell development. In addition, important roles for Notch are starting to be identified in peripheral T cells, in which all four Notch family members are upregulated upon T cell activation. Canonical Notch signaling involves proteolytic cleavage of Notch receptors and translocation of intracellular Notch (ICN) to the nucleus where it interacts with the transcription factor CSL/RBP-J and recruits Mastermind-like proteins (MAMLs) for transcriptional activation. By inhibiting Notch1 and Notch2-dependent developmental decisions with a dominant negative mutant of MAML1 (DNMAML1), we have previously demonstrated that MAMLs critically regulate Notch signaling in vivo (Maillard et al., Blood 2004). However, it is unclear if Notch3 and Notch4 are equally dependent on the activity of MAMLs in vivo, and if DNMAML1 can thus be used as a true pan-Notch inhibitor. To address this question, we used a modified fetal thymic organ culture (FTOC) system and Notch-mediated T lineage commitment as a readout for Notch function. Fetal liver cells (FLCs) were transduced with retroviruses expressing ICN1, ICN3 or ICN4 and a retrovirus expressing DNMAML1. Irradiated fetal thymic lobes were reconstituted with transduced FLCs and cultured in the presence of gamma secretase inhibitors to inhibit the activation of endogenous Notch receptors. In this manner the effect of a specific ICN could be evaluated in the absence of endogenous Notch signals. Gamma secretase inhibitors resulted in a profound block in T cell development and in the generation of intrathymic B cells, consistent with Notch1 inhibition. ICN1, ICN3 and ICN4 were all able to rescue commitment to the T cell lineage and to block B cell development, indicating that each ICN can deliver appropriate signals for T lineage commitment in the absence of endogenous Notch1 signaling. In cells doubly transduced with specific ICNs and DNMAML1, the rescuing effect of ICN1, ICN3 or ICN4 was blocked, leading to the generation of B cells. In this competitive situation, DNMAML1 only partially inhibited ICN1, the most potent of all four Notch family members, but it was able to completely inhibit ICN3 and ICN4. We conclude that DNMAML1 can efficiently inhibit Notch3 and Notch4 in vivo. The results validate the use of DNMAML1 as a bona fide pan-Notch inhibitor in multiple settings, including studying the role of Notch in HSCs and peripheral T cells.
“Hot rocks that shoot ghost bullets”: Native American perceptions of a nuclear waste facility

ABSTRACTEnvironmental justice concerns are raised when environmental risks and hazards are inequitably distributed across society. Native American populations have long been at the center of environmental justice disputes, however relatively little quantitative research has examined how Native Americans view the risks related to the siting of a potentially hazardous facility. Combining 35 statewide surveys collected from 1990 to 2001, the following study explores the risk perceptions of Native American populations in New Mexico regarding the storage of nuclear waste. We find that Native Americans tend to have higher perceptions of risk regarding the Waste Isolation Pilot Plant (WIPP) facility than white respondents. We also explore variation within self-identified Native American respondents and find that older males tended to perceive less risk associated with WIPP and Native American respondents in counties with Navajo reservations tended to perceive more risk. These findings help in understanding how N...
Towards a Classification of Hilbert Modular Threefolds

We begin with the classical (full) modular group and variety of which Hilbert modular groups and varieties are generalizations.
High-Gain Millimeter and Submillimeter Free Electron Lasers

The relativistic electron beams produced by pulse-line accelerators (induction Linacs1, IRED accelerators2, and radial line accelerators3) can have suffiicent intensity to shift the laser interaction to the regime where collective electron oscillations participate in the wave amplification process. Free electron lasers with collective interactions can have sufficient gain so that practical amplifiers can be developed in addition to oscillators. Also there is potential for high efficiency in converting electron kinetic energy to photon energy. The electron energy characteristic of pulse-line accelerators (roughly 1–10 MeV) is relatively modest and lasers employing these acclerators are expected to operate in the wavelength range extending from millimeters to the near infrared. Electron beam pulse duration 10 ns – 10 μs is much longer than with r.f. accelerators, so that linewidth of the radiation may be compatible with good coherence even with operation in the millimeter wave regime.
The Geographic Distribution of Globin Gene Variation

With relatively few exeeptions, the globin gene mutations that are tabulated in the Appendix occur only rarely, with a majority of these mutations having been found in only one or a very limited number of individuals or families. Some of the other globin gene mutations have been shown to occur with relatively high frequency, but only in individuals within highly isolated populations. On the other hand, the group that includes Hb S, Hb C, Hb E, and the thalassemias includes enormous numbers of people and extends over a very wide geographical area. (For a more detailed account see Bowman, 1983, and Winter, 1985).
Equilibrium Effects of Health Care Price Information

Do information frictions in health care markets lead to higher prices and price dispersion? Focusing on medical imaging procedures, this paper examines the equilibrium effect of a unique statewide ...
Presentation and Survival of Gastric Cancer Patients at an Urban Academic Safety-Net Hospital.

Gastric cancer is decreasing nationally but remains pervasive globally. We evaluated our experience with gastric cancer at a safety-net hospital with a substantial immigrant population. Demographics, pathology, and treatment were analyzed for gastric adenocarcinoma at our institution (2004–2017). Chi-square analyses were performed for dependence of staging on demographics. Survival was evaluated with Kaplan-Meier and Cox regression analyses. We identified 249 patients (median age 65 years). Patients were predominantly born outside the USA or Canada (74.3%), non-white (70.7%), and federally insured (71.4%), and presented with late-stage disease (52.2%). Hispanic ethnicity, Central American birthplace, Medicaid insurance, and zip code poverty > 20% were associated with late-stage presentation (all p < 0.05). Univariate analyses showed decreased survival for patients with late-stage disease, highest zip code poverty, and age ≥ 65 (all p < 0.05). On multivariate analysis, survival was negatively associated with late-stage presentation (HR 4.45, p < 0.001), age ≥ 65 (1.80, p = 0.018), and H. pylori infection (2.02, p = 0.036). Hispanic ethnicity, Central American birthplace, Medicaid insurance, and increased neighborhood poverty were associated with late-stage presentation of gastric cancer with poor outcomes. Further study of these populations may lead to screening protocols in order to increase earlier detection and improve survival.
Mammogram Diagnostics Using Robust Wavelet-Based Estimator of Hurst Exponent

Breast cancer is one of the leading causes of death in women. Mammography is an effective method for early detection of breast cancer. Like other medical images, mammograms demonstrate a certain degree of self-similarity over a range of scales, which can be used in classifying individuals as cancerous or non-cancerous. In this paper, we study the robust estimation of Hurst exponent (self-similarity measure) in two-dimensional images based on non-decimated wavelet transforms (NDWT). The robustness is achieved by applying a general trimean estimator on non-decimated wavelet detail coefficients of the transformed data, and the general trimean estimator is derived as a weighted average of the distribution’s median and quantiles, combining the median’s emphasis on central values with the quantiles’ attention to the extremes. The properties of the proposed estimators are studied both theoretically and numerically. Compared with other standard wavelet-based methods (Veitch and Abry (VA) method, Soltani, Simard, and Boichu (SSB) method, median based estimators MEDL and MEDLA, and Theil-type (TT) weighted regression method), our methods reduce the variance of the estimators and increase the prediction precision in most cases. We apply proposed methods to digitized mammogram images, estimate Hurst exponent, and then use it as a discriminatory descriptor to classify mammograms to benign and malignant. Our methods yield the highest classification accuracy around 65%.
Equitable Gateways: Toward Expanded Federal Habeas Corpus Review of State Court Criminal Convictions

State prisoners who file federal habeas corpus petitions face a maze of procedural and substantive restrictions that effectively prevent almost all prisoners from obtaining meaningful review of their convictions. But it is a mistake to think that habeas litigation is just a Kafkaesque nightmare with no constructive potential. Federal courts do sometimes cut through the doctrinal morass to consider state prisoners’ claims, relying on what this Essay terms equitable gateways to federal habeas relief. Litigants and courts generally underestimate the potential these gateways offer, with the result that habeas litigation does not focus on them as often as it should. Here I consider one important category of equitable gateways animated by a concern about ensuring that federal claims get fair consideration in the courts. When a federal court believes that a state prisoner has not yet had a full and fair opportunity to present her federal claims and have them fairly considered, it is more likely to bypass procedural and substantive restrictions on review. But state prisoners often fail to highlight certain kinds of fair consideration failures, thus depriving themselves of potential access to the equitable gateways. This Essay suggests that this blind spot is partly due to the history of fair consideration principles: for decades, the idea of a fair consideration gateway was a central feature of proposals for further restricting the scope of federal habeas review. In current circumstances, however, fair consideration is a rubric for expanded habeas review, and habeas litigants should take note.
Teacher Job Satisfaction in a Quality School: Implications for Educational Leaders:

This article examines the relationship between the existing research and theoretical writings dealing with general job satisfaction, teacher job satisfaction, and William Glasser's concept of the q...
Development of Tetrahydroindazole‐Based Potent and Selective Sigma‐2 Receptor Ligands

The sigma-2 receptor has been shown to play important roles in a number of important diseases, including central nervous system (CNS) disorders and cancer. However, mechanisms by which sigma-2 contributes to these diseases remain unclear. The development of new sigma-2 ligands that can be used to probe the function of this protein and potentially as drug discovery leads is therefore of great importance. Herein we report the development of a series of tetrahydroindazole compounds that are highly potent and selective for sigma-2. Structure-activity relationship data were used to generate a pharmacophore model that summarizes the common features present in the potent ligands. Assays for solubility and microsomal stability showed that several members of this compound series possess promising characteristics for further development of useful chemical probes or drug discovery leads.
Representations of anorexia in an EAP classroom: critically engaging with the body and its discourses

Aside from mentioning possible issues of hidden identities and curriculum development relating to anorexia, little research has been done exploring how discourses of eating disorders and images of ...
Comparison of invasive and non-invasive blood pressure measurements in anesthetized female Dorset cross-bred lambs (Ovis aries).

Abstract The purpose of this study was to determine the level of agreement between invasive and noninvasive blood pressure measurements in anesthetized, non-surgically manipulated Dorset cross-bred lambs. Twelve healthy female Dorset cross-bred lambs, weighing 37.3 ± 7.4 kg (mean ± SD) underwent isoflurane anesthesia for simultaneous measurement of systolic arterial pressure (SAP), mean arterial pressure (MAP) and diastolic arterial pressure (DAP) from an invasive blood pressure source and a noninvasive oscillometric source (O-NIBP). The femoral artery was catheterized for invasive blood pressure measurements, while noninvasive blood pressure was measured from a cuff placed on the antebrachium. The Bland-Altman method was used to calculate agreement between SAP, MAP and DAP measurements. The bias ± SD between SAP, MAP and DAP measurements was 3.6 ± 12.0, 4.9 ± 9.1 mmHg and 4.1 ± 8.0, respectively. The 95% limits of agreement for SAP, MAP and DAP were − 19.9 to 27.1, −13.0 to 22.8 mmHg, and − 11.7 to 19.9, respectively. Overall, agreement was poor between femoral IBP and O-NIBP monitoring techniques in anesthetized Dorset cross-bred lambs, with O-NIBP underestimating the femoral IBP. Arterial blood pressure should be most accurately measured using an invasive blood pressure monitoring technique in lambs undergoing isoflurane anesthesia.
Similar rates of residual disease in patients with DCIS within 2 mm of lumpectomy margin regardless of the presence of invasive carcinoma.

The 2014 Society of Surgical Oncology/American Society for Radiation Oncology (SSO/ASTRO) breast-conserving surgery (BCS) margin guidelines for invasive cancer recommended “no ink on tumor” as an adequate margin width. However, 2016 SSO/ASTRO margin guidelines for pure DCIS recommended a 2 mm margin. Thus, management of a margin with DCIS > 0 mm but < 2 mm differs based on presence or absence of invasive carcinoma. We compared rates of residual disease in patients with pure DCIS to patients with invasive cancer with DCIS. BCS with complete shaved cavity margins (SCM) for invasive carcinoma or pure DCIS from 2004 to 2006 at our institution was reviewed. Margin width was measured on the main specimen and the presence of carcinoma in the SCM was used as a surrogate for residual disease in the cavity. Rates of residual disease were determined for varying margin widths of invasive carcinoma and DCIS. Of 329 BCS patients, 123 (37%) patients had pure DCIS and 206 (63%) had invasive cancer with DCIS. In the pure DCIS cohort, 61 patients had DCIS between 0 and 2 mm from the inked margin; 32 (52%) of which had residual disease in the SCM. In the invasive cancer plus DCIS cohort, 92 had DCIS between 0 and 2 mm from the inked margin; 39 (42%) of which had residual disease in the SCM (p = 0.221). Rates of residual disease are similar in patients treated with lumpectomy for pure DCIS and those with invasive carcinoma with DCIS when DCIS is found between 0 and 2 mm from the inked margin.
Experimental Nanovaccine Offers Protection Against Repeat Exposures to Trypanosoma cruzi Through Activation of Polyfunctional T Cell Response

A parasitic protozoan Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease. Previously, we have identified T. cruzi antigens TcG2 and TcG4 as potential vaccine candidates, cloned in eukaryotic expression vector pCDNA3.1 (referred as p2/4) and tested their ability to elicit protection from T. cruzi infection. In the present study, we subcloned the two antigens in a nanoplasmid that is optimized for delivery, antigen expression, and regulatory compliance standards, and evaluated the nanovaccine (referred as nano2/4) for prophylactic protection against repeat T. cruzi infections. For this, C57BL/6 mice were immunized with two doses of p2/4 or nano2/4 at 21 days interval, challenged with T. cruzi 21 days after 2nd immunization, and euthanized at 10- and 21-days post-infection (pi) corresponding to parasite dissemination and replication phase, respectively. Some mice were re-challenged 21 days pi and monitored at 7 days after re-infection. Without the help of a vaccine, T. cruzi elicited delayed and sub-par T cell activation and low levels of effector molecules that failed to control tissue dissemination and replication of the parasite and provided no protection against repeat challenge infection. The nano2/4 was most effective in eliciting an early activation and production of IFN-γ by CD4+T effector/effector memory (TEM) cells and cytolytic perforin (PFN) and granzyme B (GZB) molecules by CD4+ and CD8+ TEM subsets at 10 days pi that was followed by robust expansion of CD4+ and CD8+ TEM and TCM cells with further increase in IFN-γ production at 21 days pi. Consequently, nano2/4-immunized mice exhibited potent control of parasite dissemination at 10 days pi, and tissue parasite burden and tissue inflammatory infiltrate and necrosis were barely detectable at 21 days pi. Furthermore, nano2/4-immunized mice responded to re-challenge infection with high levels of effector molecules production by CD4+ and CD8+ TEM subpopulations that offered even better control of tissue parasite burden than was observed after 1st infection. In comparison, non-vaccinated/infected mice exhibited clinical features of sickness and 59% mortality within 7 days after re-infection. In conclusion, we show that delivery of TcG2 and TcG4 in nanoplasmid offers excellent, protective T cell immunity against repeat T. cruzi infections.
Communication, Agency, and the Relational Self in ASD and the Letters of Paul

The experience and reflections of people on the autism spectrum act as a “context of discovery” about human communication and agency, in conversation with a robust theological account drawn from Pa...
Performance of Waterproofing Membranes to Protect Concrete Bridge Decks

The installation of waterproofing membranes on concrete bridge decks is a commonly used strategy to prevent water on the roadway surface from penetrating into the deck and to reduce the load and fr...
Outcomes of Lung Transplantation From Hepatitis C Viremic Donors.

Abstract Background Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has encouraged lung transplantation with HCV positive donors. Early trials have been promising; however, nationwide data have not been previously examined. Methods The United Network for Organ Sharing registry was queried for adult patients receiving lung transplants from 2016 to 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) determined HCV status. Propensity matching was performed for comparison of outcomes.. Results Hepatitis C virus NAT-positive lungs were transplanted in 189 patients, compared with 9511 recipients of NAT-negative lungs. The HCV NAT-positive donors were younger (mean 33 vs 35 years, P = .017) with higher rates of Pa o 2/Fi o 2 greater than 300 (83.6% vs 76.5%, P = .029). Recipients of NAT-positive lungs had lower lung allocation scores (mean 39.3 vs 42.4, P = .009). Distance traveled was significantly further for HCV viremic donor lungs (mean 416 vs 206 miles, P .999), or reintubation (P = .304). At mean follow-up of 395 days, 63 recipients of NAT-positive lungs (40%) seroconverted, 14 with viremia. One-year mortality rates among seroconverted patients was 6% and did not differ significantly from 14% in nonseroconverted patients or 13.2% in recipients of HCV-negative lungs. Conclusions Short-term outcomes of lung transplantation from HCV viremic donors are promising, with no difference in early complications or survival. The effects of seroconversion and long-term outcomes including chronic rejection and infection need to be further explored.
Compliance Measurements of the Upper Airway in Pediatric Down Syndrome Sleep Apnea Patients

Compliance of soft tissue and muscle supporting the upper airway are two of several factors contributing to pharyngeal airway collapse. We present a novel, minimally invasive method of estimating regional variations in pharyngeal elasticity. Magnetic resonance images for pediatric sleep apnea patients with Down syndrome [9.5 ± 4.3 years (mean age ± standard deviation)] were analyzed to segment airways corresponding to baseline (no mask pressure) and two positive pressures. A three dimensional map was created to evaluate axial and circumferential variation in radial displacements of the airway, dilated by the positive pressures. The displacements were then normalized with respect to the appropriate transmural pressure and radius of an equivalent circle to obtain a measure of airway compliance. The resulting elasticity maps indicated the least and most compliant regions of the pharynx. Airway stiffness of the most compliant region [403 ± 204 (mean ± standard deviation) Pa] decreased with severity of obstructive sleep apnea. The non-linear response of the airway wall to continuous positive airway pressure was patient specific and varied between anatomical locations. We identified two distinct elasticity phenotypes. Patient phenotyping based on airway elasticity can potentially assist clinical practitioners in decision making on the treatments needed to improve airway patency.
TU-E-BRB-00: Deformable Image Registration: Is It Right for Your Clinic

Deformable image registration (DIR) is developing rapidly and is poised to substantially improve dose fusion accuracy for adaptive and retreatment planning and motion management and PET fusion to enhance contour delineation for treatment planning. However, DIR dose warping accuracy is difficult to quantify, in general, and particularly difficult to do so on a patient-specific basis. As clinical DIR options become more widely available, there is an increased need to understand the implications of incorporating DIR into clinical workflow. Several groups have assessed DIR accuracy in clinically relevant scenarios, but no comprehensive review material is yet available. This session will also discuss aspects of the AAPM Task Group 132 on the Use of Image Registration and Data Fusion Algorithms and Techniques in Radiotherapy Treatment Planning official report, which provides recommendations for DIR clinical use. We will summarize and compare various commercial DIR software options, outline successful clinical techniques, show specific examples with discussion of appropriate and inappropriate applications of DIR, discuss the clinical implications of DIR, provide an overview of current DIR error analysis research, review QA options and research phantom development and present TG-132 recommendations. Learning Objectives: 1. Compare/contrast commercial DIR software and QA options 2. Overview clinical DIR workflow for retreatment 3. To understand uncertainties introduced by DIR 4. Review TG-132 proposed recommendations
Cosmic-Ray Acceleration in UHE and VHE Gamma-Ray Sources

VHE (1012 eV) and UHE (1015 eV) gamma-ray emission has been reported (1) from the x-ray source Cygnus X-3, as well as from several known x-ray binaries, including Her X-1, LMC X-4, Cen X-3 and 4U 0115 + 63. These observations, if subsequently found to be statistically significant, imply the acceleration of high energy cosmic rays in these sources. In this paper, we discuss briefly some of the models so far proposed for cosmic ray acceleration in these sources.
Spectral Signatures of KiloHertz Quasi-Periodic Oscillations from Accreting Neutron Stars

Correlations discovered between millisecond timing properties and spectral properties in neutron star x-ray binaries are described and then interpreted in relation to accretion flows in the systems. Use of joint timing and spectral observations to test for the existence of the marginally stable orbit, a key prediction of strong field general relativity, is described and observations of the neutron star x-ray binary 4U1820-303 which suggest that the signature of the marginally stable orbit has been detected are presented.
Environmental Fate Modelling Of Contaminants In Constructed Wetlands

Background: Water management is a key focus area globally, and especially for the state of Qatar given its extremely arid environment. As such, research to develop technologies to enhance beneficial re-use of treated industrial waste water is recognized as a key challenge in this region. As a part of the Water Re-Use Research Program at ExxonMobil Research Qatar, a model was developed in collaboration with Simon Fraser University (Canada) for predicting the environmental fate of contaminants in constructed wetlands. Objective: This work will aid in design and monitoring of engineered wetlands to support water reuse applications. Methods: This model provides a method to estimate the extent to which contaminants of various kinds can be expected to be removed from wetlands through a combination of transformation and transport processes under various environmental conditions and wetland characteristics. The model was constructed to represent steady-state conditions and is based on conservation of mass principles. The model was developed for the use of Type I and Type II chemicals. Type I chemicals include organic substances and Type II chemicals include trace metals and inorganic substances .The model combines calculations for (i) environmental distribution of contaminants in aquatic systems; (ii) uptake, translocation and biotransformation of contaminants in vegetation; (iii) bioaccumulation in aquatic biota of wetlands; and (iv) toxicity in aquatic biota. Model inputs include wetland characteristics (e.g. compartment volumes, dimensions, organic carbon content, biotic growth rates); environmental conditions (e.g. Inflow& temperature); contaminant properties (e.g. molecular weight, degradation half-lives). The model outputs include predicted concentrations in various wetland compartments and mass balance inventory characterizing mass distribution and various loss processes. Results: Application of the model was tested for pyrene, arsenic and a naphthenic acid. The results show distinct differences in the predicted ability of wetlands to remove these contaminants from waste water. Conclusion: The evaluative model presented in this study provides useful insights that can guide further studies for designing and monitoring the effectiveness of engineered wetlands for wastewater reclamation purposes.
Processing of Nociceptive Mechanical and Thermal Information in Central Amygdala Neurons With Knee-Joint Input

Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the c...
Taxonomy, Role, and Significance of Microorganisms in Foods

Because human food sources are of plant and animal origin, it is important to understand the biological principles of the microbial flora associated with plants and animals in their natural habitats and respective roles. Although it sometimes appears that microorganisms are trying to ruin our food sources by infecting and destroying plants and animals, including humans, this is by no means their primary role in nature. In our present view of life on this planet, the primary function of microorganisms in nature is self-perpetuation.
Modular platform for low-light microscopy

Cell imaging using low-light techniques such as bioluminescence, radioluminescence, and low-excitation fluorescence has received increased attention, particularly due to broad commercialization of highly sensitive detectors. However, the dim signals are still regarded as difficult to image using conventional microscopes, where the only low-light microscope in the market is primarily optimized for bioluminescence imaging. Here, we developed a novel modular microscope that is cost-effective and suitable for imaging different low-light luminescence modes. Results show that this microscope system features excellent aberration correction capabilities and enhanced image resolution, where bioluminescence, radioluminescence and epifluorescence images were captured and compared with the commercial bioluminescence microscope.
Evaluation of small molecule SecA inhibitors against methicillin-resistant Staphylococcus aureus

Due to the emergence and rapid spread of drug resistance in bacteria, there is an urgent need for the development of novel antimicrobials. SecA, a key component of the general bacterial secretion system required for viability and virulence, is an attractive antimicrobial target. Earlier we reported that systematical dissection of a SecA inhibitor, Rose Bengal (RB), led to the development of novel small molecule SecA inhibitors active against Escherichia coli and Bacillus subtilis. In this study, two potent RB analogs were further evaluated for activities against methicillin-resistant Staphylococcus aureus (MRSA) strains and for their mechanism of actions. These analogs showed inhibition on the ATPase activities of S. aureus SecA1 (SaSecA1) and SecA2 (SaSecA2), and inhibition of SaSecA1-dependent protein-conducting channel. Moreover, these inhibitors reduce the secretion of three toxins from S. aureus and exert potent bacteriostatic effects against three MRSA strains. Our best inhibitor SCA-50 showed potent concentration-dependent bactericidal activity against MRSA Mu50 strain and very importantly, 2-60 fold more potent inhibitory effect on MRSA Mu50 than all the commonly used antibiotics including vancomycin, which is considered the last resort option in treating MRSA-related infections. Protein pull down experiments further confirmed SaSecA1 as a target. Deletion or overexpression of NorA and MepA efflux pumps had minimal effect on the antimicrobial activities against S. aureus, indicating that the effects of SecA inhibitors were not affected by the presence of these efflux pumps. Our studies show that these small molecule analogs target SecA functions, have potent antimicrobial activities, reduce the secretion of toxins, and have the ability to overcome the effect efflux pumps, which are responsible for multi-drug resistance. Thus, targeting SecA is an attractive antimicrobial strategy against MRSA.
Modulation of Renin‐Angiotensin System May Slow Conversion from Mild Cognitive Impairment to Alzheimer's Disease

Antihypertensives that modulate the renin-angiotensin system (RAS) on AD conversion in those with MCI has not been explored. Evidence suggests that blood-brain-barrier (BBB) permeability is necessary for these effects. We assessed the impact of RAS modulation on conversion to AD and cognitive decline in those with MCI, and the impact of BBB permeability and race on these associations. We analyzed data from the National Alzheimer’s Coordinating Center from the NIA-funded Alzheimer’s Disease Centers. We included individuals receiving antihypertensives with MCI at baseline and who had cognitive assessments on at least 2 follow-up visits. Outcomes included conversion to AD and cognitive and functional decline. Of 784 participants (M=75 years, 48% men), 488 were receiving RAS medications. RAS users were less likely to convert to AD (33% vs 40%; p=0.04) and demonstrated slower decline on the Clinical Dementia Rating sum-of-boxes (CDR-SOB, p<0.01) and Digit Span Forward (p=0.02) than non-RAS users. BBB-crossing RAS medications were associated with slower cognitive decline on the CDR-SOB, (p<0.01), the Mini Mental Status Examination, (p<0.01) and the Boston Naming test (p<0.01). RAS medications were somewhat associated with cognitive benefits in African Americans, more so than Caucasians. (MMSE (p=0.05) category fluency (p=0.04) and Digit Span Backwards, p=0.03)). RAS-modulating medications were associated with less conversion to AD. BBB permeability may produce additional cognitive benefit, and African Americans may benefit moreso from RAS-modulation than Caucasians. Results highlight the need for trials investigating RAS modulation during prodromal disease stages.
Error compensated oversampled sigma-delta A/D conversion technique

An oversampled multi bit sigma-delta modulator based on error compensation techniques for the D/A converter in the feedback loop is proposed. The circuit utilizes an accurate voltage reference generator to improve the linearity of the D/A converter. Low over-sampling ratios make it feasible for large signal bandwidths to be achieved in this converter. >
Rural native veterans in the Veterans Health Administration: characteristics and service utilization patterns.

Purpose The Department of Veterans Affairs (VA) and the Indian Health Service (IHS) signed a Memo of Understanding in 2010 to strengthen their partnership in improving health care services for Native veterans, who are disproportionately rural. This paper describes the demographic and service use profile of rural Native veterans who access VA health care. Methods Data were abstracted from the 2008 Veteran Health Administration (VHA) medical dataset, and the characteristics of rural Native veterans were compared to rural non-Native veterans. Findings Rural Native veterans were more rural (41% vs 35%) and more highly rural (8% vs 2%) compared to non-Native veterans. Rural Native veterans were younger, more likely to be female, and earned about the same median income compared to rural non-Native veterans. Although rural Native veterans had fewer diagnoses on average, they were more likely to have served in combat areas and to have higher levels of service-connected disability compared to other rural veterans. Conclusions Demographic and service-related characteristics of rural Native veterans who accessed VA care differ from those of rural non-Native veterans. Identifying specific health care and service use characteristics will assist in the development of appropriate policy and programs to serve rural Native veterans.
Evidence-based management of common chronic lower extremity ulcers

Chronic lower extremity ulcers are a significant burden on patients and health care systems worldwide. Although relatively common, these wounds can be difficult to treat and present a challenge to physicians. Treatment has often been based on anecdotal accounts; however, there is a growing emphasis on using evidence-based conclusions to guide clinical decisions. In this review article, the standard of care and adjuvant therapies of venous leg ulcers and diabetic foot ulcers are presented from an evidence-based perspective.
Strut Interference Effects on Pitot Tube Velocity Measurements

The possible impact of the presence of the strut portion of a Pitot tube on the efficacy of the tube as a velocity-measuring device has been evaluated by numerical simulation. At sufficiently low Reynolds numbers, there is a possibility that the precursive effects of the strut could alter the flow field adjacent to the static taps on the body of the Pitot tube and might even affect the impact pressure measured at the nose. The simulations were performed in dimensionless form with the Reynolds number being the only prescribed parameter, but the dimensions were taken from a short-shanked Pitot tube. Over the Reynolds number range from 1500 to 4000, a slight effect of the strut was identified. However, the variation due to the presence of the shank of the velocity measured by the Pitot tube operating in that range of Reynolds numbers was only 1.5%.Copyright © 2007 by ASME