cssi/SciSciGPT-SciSciNet huggingface dataset:
Interconnection of high speed token ring LANs: a switch-connection approach

The use of a switch for the interconnection of two high-speed token-ring LANs to avoid congestion at the bridge caused by the large bridge processing time is proposed. A simple network access method is described, and the delay performance of the switch-connected system is analyzed and compared with that of the bridge-connected system. For high-speed token-ring LANs, the comparison shows that the bridge will be a bottleneck unless its processing time is significantly reduced. The proposed interconnection using the switch eliminates the bottleneck problem and, depending on the bridge processing time, it can attain better delay performance than the bridge-connected system over a wide range of system parameters. >
Vascular matrix and vein graft failure. Is the message in the medium

The pioneering work of Favaloro1 established the era of surgical revascularization for the treatment of ischemic heart disease. The benefits of this procedure were recognized early, and the use of the saphenous vein as a bypass conduit rapidly gained widespread acceptance as an effective treatment for angina. However, surgical revascularization has significant shortcomings, principal among which is the high rate of accelerated atherosclerosis that develops in vein grafts: at 10 years after surgery, 40% of grafts are occluded and only 50% are free of significant disease.2 Vein graft failure is a consequence of three related processes. Early after implantation, thrombosis plays a critical role, both by predisposing to acute occlusion and by serving as a stimulus for neointima formation and, ultimately, graft atherosclerosis. Within 6 weeks after implantation, virtually all arterialized vein grafts develop intimal hyperplasia, which, although it only modestly compromises the lumen of the graft, renders the graft susceptible to atherosclerosis.3 The cellular events that account for this intimal response include migration and proliferation of vascular smooth muscle cells, perhaps derived from adventitial fibroblasts (myofibroblasts),4 followed by extracellular matrix synthesis and deposition. This latter process ultimately leads to progressive intimal fibrosis with relatively reduced intimal cellularity.5 Vein grafts are susceptible to intimal hyperplasia and atherosclerosis for two main reasons. First, explanted vein grafts are prone to vessel wall ischemia owing to a loss of functional vasa vasorum; regrowth of these nutrient vessels appears as early as 5 days after graft placement, but a rich network sufficient to provide blood flow to the thickened neointima takes up to 6 months to develop.6 Second, an arterialized vein graft is subject to an acute, marked increase in wall stress. These two processes, ischemia and wall stress, induce endothelial dysfunction or loss, which reduces the availability …
Increasing Aspiring Principals' Readiness to Serve: Knowledge and Skill Application Laboratories.

Most leadership programs emphasize knowledge over skills, being skillful over how to be skillful, knowledge about skills over skill application, and ad hoc and hard-to-assess field activities over focused and observable skill practice. “Knowledge and skill application laboratories” provide opportunities to experiment with — and receive criteria-based feedback from multiple observers on — new ways of thinking and behaving. They challenge students to integrate course-specific content with universally applicable skills: diagnosis, goal setting, communication, teamwork, and conflict management. We describe the purpose, history, and objectives of this kind of laboratory, sample lab activities, design considerations, and what we learned.
Microemulsion; Surfactant Vesicle and Polymerized Surfactant Vesicle Entrapped Colloidal Catalysts and Semiconductors: Preparation, Characterization, and Utilization

Noble metal catalysts have been extensively utilized in many important industrial processes for some time. Typically, they are deposited on solid surfaces in reactors. Physical chemical characterizations of catalytic surfaces have only recently become available.1 In general, catalytic activity is related to surface area. Smaller particles have larger surface areas and are, therefore, better catalysts than larger particles.
Experimental Approaches and Future Applications of Robotic Surgery in the Head and Neck

Robotic surgery in the head and neck has developed rapidly in the past 10 years, particularly after the Da Vinci robot by Intuitive Surgical received FDA approval in 2009 for applications in the head and neck. Currently, applications have been primarily focused on transoral robotic surgery (TORS) and minimally invasive thyroid surgery. However, the three-dimensional view provided by the robotic camera, the advanced wrist rotation and flexibility, and ability to approach areas that previously required large open incisions have created a paradigm shift setting the stage for exploration into innovative approaches in the head and neck. From congential cysts to salivary gland tumors to neck dissection, more minimally invasive techniques are being continually studied, developed, and published.
Novel Mechanism of Inhibition by the P2 Receptor Antagonist PPADS of ATP-Activated Current in Dorsal Root Ganglion Neurons

The antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) has been proposed to selectively antagonize the actions of ATP at P2X receptors. Whole cell patch-clamp recording techni...
Case Report: The Successful Therapy with Streptokinase-Streptodornase of Ankle Ulcers Associated with Mediterranean Anemia

1. A successful method of treatment of chronic leg ulcers associated with Mediterranean anemia, employing streptokinase-streptodornase in carboxymethylcellulose jelly, is presented.
Gender Barriers of Women Striving for a Corporate Officer Position: A Literature Review

Literature examined from the past 30 years discovered that even though gender issues have received a great deal of attention, little research has been conducted on gender barriers and disparities in the corporate suite (Agars, 2004). Through examination of this literature, it became evident that women and men are not equally represented, and Agars (2004) wondered whether gender discrimination is a primary cause. Women have made tremendous breakthroughs within middle management but a lack of progress has been seen in obtaining corporate officer positions. The purpose of this paper is to provide an extensive literature review regarding the gender barriers that are applied to females who strive for a corporate officer position.
A Programmer-Centric Approach to Program Verification in ATS

Formal specification is widely employed in the construction of high-quality software. However, there is often a huge gap between formal specification and actual implementation. While there is already a vast body of work on software testing and verification, the task to ensure that an implementation indeed meets its specification is still undeniably of great difficulty. ATS is a programming language equipped with a highly expressive type system that allows the programmer to specify and implement and then verify within the language itself that an implementation meets its specification. In this paper, we present largely through examples a programmer-centric style of program verification that puts emphasis on requesting the programmer to explain in a literate fashion why his or her code works. This is a solid step in the pursuit of software construction that is verifiably correct according to specification.
Ultraviolet Point Radiation in the Production of Arrythmias in the Heart of the Chick Embryo.

By means of apparatus previously described,1 a point source of radiation could be directed on the desired spot on the developing embryonic heart and its effect on the rhythm noted. Studies were made on embryos varying in age from 2 to 20 days, and the following results obtained: Short exposures of the sinus region of the heart produced an increase in rate of beat within 30 seconds after the exposure was begun. A long-continued exposure slowed the rate. Exposure on the ventral aspect of either auricle (at a point of visible condensation of tissue) also produced a marked increase. Exposure of the ventricle did not change the rate of beat except when the point of the quartz rod was placed on the interventricular septum at the base of the auricles. A slight increase was then obtained in hearts whose rate had already been slowed.Also, in young hearts (2 to 6 days old), it was possible to obtain complete reversal of the direction of beat by a preliminary slowing brought about by lowering the temperature, and th...
Against evidence-based oppression: Marginalized youth and the politics of risk-based assessment and intervention:

Actuarial risk/needs assessments exert a formidable influence over the policy and practice of youth offender intervention. Risk-prediction instruments and the programming they inspire are thought not only to link scholarship to practice, but are deemed evidence-based. However, risk-based assessments and programs display a number of troubling characteristics: they reduce the lived experience of racialized inequality into an elevated risk score; they prioritize a very limited set of hyper-individualistic interventions, at the expense of others; and they privilege narrow individual-level outcomes as proof of overall success. As currently practiced, actuarial youth justice replicates earlier interventions that ask young people to navigate structural causes of crime at the individual level, while laundering various racialized inequalities at the root of violence and criminalization. This iteration of actuarial youth justice is not inevitable, and we discuss alternatives to actuarial youth justice as currently ...
Problem and Countermeasure Analysis of IT Professional Teachers' Performance Evaluation in Vocational College

Currently,teachers' performance evaluation is one of the key issues in the training of IT professionals in vocational colleges.This paper carries out an in-depth analysis on the current problems and reasons of IT teacher evaluation,and brings forward the countermeasures of establishing a "Dual Evaluation System" of the "Trinity" by combining the actual demand of current IT professionals training in vocational colleges.
[Current status of hepatitis B immunization and strengthened immune memory among first-year middle school students in Tianjin].

Objective To investigate the immunization status of hepatitis B vaccine who were inoculated at birth.HBV infections and the vaccine booster effect in the first-year middle school students (12-14 years old).Methods A cluster,stratified simplified random sampling method was administrated.The sample size was at least 218.which was calculated by Epi Info 3.3.2 software at 53% the minimum acceptable anti-HBs positive rate and 95%confidence level.A total of 250 and 236 students participated in the infection status and booster immunization effects investigation.The HBsAg.anti-HBs and anti-HBc IgG were detected by Enzyme-linked immunosorbent assay (ELISA).HBV DNA was detected by fluorescence quantitative PCR,and the diagnostic test kit were produced respectively by ABBOTT,Diasofin and Beijing Wantai Biological Pharmacy Enterprise Co.Results For the immunization status before booster:the positive rate of anti-HBs was 62.80%(157/250),the GMT was 73.79 IU/L;the currently HBV infection rate(HBsAg and anti-HBc positive) was 2.80%(7/250).After injection,the anti-HBs positive rate was 94.92%(224/236).Compared with the before booster results,the significant difference was observed(χ2=73.92,P=0.00).The GMT was 521.15 IU/L,comparing with the before booster results,there was significant difference(t=15.98,P=0.00).The anti-HBs conversion rate(from negative to positive)was 91.86%(79/86) after immune-enhancement;of which,11 students got the second dose of booster vaccine who are no-responders after first injection.in addition 8 students got the anti-HBs.Conclusion It is an effective method to put the first-year middle school students into the immune-enhancement program,so as to improve the immunization memory effect and avoid the loss of protective antibodies. Key words: Hepatitis B vaccines; Immunity,active; Immunization,secondary; Dose-response relationship,immunologic
Gene Inactivation in Coxiella burnetii

Coxiella burnetii, the agent of human Q fever, is a zoonotic bacterial pathogen with a worldwide distribution. Owing to an historic lack of methods for genetic manipulation, virulence factors deployed by this bacterium for disease pathogenesis are poorly understood. However, the recent advance of host cell-free (axenic) growth of C. burnetii has coincided with development of several new genetic technologies including site-specific and random transposon systems, shuttle vectors, and an inducible gene expression system. We have recently added two methods for targeted gene inactivation to the expanding C. burnetii genetics toolbox. Here, we describe a "loop in/loop out" gene inactivation system for C. burnetii. This procedure allows for generation of site-directed mutants in approximately 10 weeks and has been used by our laboratory to generate more than 50 individual C. burnetii mutants. The collection of C. burnetii genetic tools now allows for conventional mutation and complementation strategies to define virulence factors.
Abstract 4658: Resveratrol aspirinate derivatives as novel chemopreventive agents for colon cancer

In more than a century of use, the benefits of aspirin have been exploited in different therapeutic areas, from inflammation to cardiovascular diseases and cancer prevention. However, the major limitation to the use of aspirin is its side effect to cause ulceration and bleeding in the gastrointestinal tract. The present study found that resveratrol, a natural chemopreventive agent from grapes and berries, and its methylated derivatives can react with acetylsalicyloyl chloride to form resveratrol aspirinate (RAS) and related derivatives. Among all the synthesized derivatives, we found that RAS is the most active component and have much stronger growth inhibitory effect on human colon cancer cells (HCT-116 and HT-29) than resveratrol and aspirin along, as well as the combination of resveratrol and aspirin. In addition, we found that RAS can be hydrolyzed to regenerate resveratrol and aspirin in mice and in human colon cancer cells. Therefore they serve as prodrugs of aspirin and resveratrol and its derivatives. Compared to simply combining aspirin and resveratrol, RAS has not only greater growth inhibitory effects on human colon cancer cells, but also can prevent the damage of gastric epithelial cells caused by direct contact between aspirin and gastric mucosa. Further mechanistic studies found that RAS inhibited cell growth through regulating cell cycle arrest via down-regulation of cyclins D1 and E, and inducing cancer cell apoptosis via mitochondrial pathway. In addition, two stable RAS analogues, for the first time, were successfully synthesized to demonstrate the importance of the scaffold composed of resveratrol and aspirin in the anti-cancer activity of RAS. Our results demonstrated for the first time that resveratrol based aspirin derivatives represent a brand-new, safer and improved alternative to aspirin in anti-cancer and anti-inflammatory therapies. Note: This abstract was not presented at the meeting. Citation Format: Shengmin Sang, Yingdong Zhu, Junsheng Fu, Kelly Shurlknight. Resveratrol aspirinate derivatives as novel chemopreventive agents for colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4658. doi:10.1158/1538-7445.AM2015-4658
A particular kind of ‘action-reaction’: Questions answering questions (in Spanish and Romanian dialogues)

In this article, I discuss a particular (and little studied) action-reaction exchange in Spanish and Romanian, consisting of a dyadic exchange where an exploratory speech act (i.e., a question) is followed by a sequence-dependent reactive speech act, which repeats parts or all of the trigger’s structure in an interrogative form. Rather than being a canonical echo question, the reactive speech act under discussion represents what I call an Interrogative Echo Response (IER), by virtue of the fact that it provides an answer of opposite polarity to that of the initiative move put forward by the questioner (or Interrogative Echo Reply, when the response may or must be explicitly provided after the sequence-dependent interrogative utterance). In both languages, these IERs (and IERps) have a distinct syntactic structure, and the discourse function they fulfill is that of rhetorically challenging the validity of the initial move and providing (or implying) a response of opposite polarity with regard to the triggering question.
Hospice/Palliative Care: Concepts of Disease and Dying

Population across the globe is not only aging but also becoming ethnically diverse. This is critically important in providing patient–centered end of life (EOL) care. This recognized diversity in the lived experience of ethnic older adults requires that the patient be individually assessed for their language of preference, need for interpreter use, health beliefs, cultural values, knowledge of disease process and hospice care during clinical encounter. Literature about ethnic older adults EOL is limited because it is based on observational research of low quality, on data extrapolated from younger generation and each ethnic group is heterogeneous in itself. Healthcare disparities in EOL exist for various reasons (i.e. geography, supply, and EOL conversation) but race and ethnicity reporting differ among research studies and very seldom ethnicity solely explain EOL care disparity. The following chapter intends to describe the delivery of EOL care, cultural background influences in death and disease concepts, EOL preferences and hospice use among ethnically diverse elders. A list of suggestions is provided to enhance EOL care by improving research, education, policy and communication with ethnic older adults with advance illness and their family caregivers.
Artifacts and Allegiances: How Museums Put the Nation and the World on Display (Levitt)

This work is a book review considering the title Artifacts and Allegiances: How Museums Put the Nation and the World on Display by Peggy Levitt.
Alemtuzumab (Campath 1-H) Exposure Correlates with Risk of Chronic Graft vs Host Disease and CMV Viremia after Allogeneic Transplantation.

Conditioning regimens using in vivo alemtuzumab (Campath-1H, humanized anti-CD52) are characterized by low rates of acute and chronic GVHD, but may also result in delayed immune reconstitution. Optimization of such regimens will depend on an understanding of the relation between alemtuzumab exposure, immune reconstitution and GVHD. We have conducted a prospective study of fludarabine 30 mg/m2/d x 5 days, melphalan 140 mg/m2 x 1 day and alemtuzumab 20 mg/d x 5 days as conditioning for related and unrelated allografts. Using an enzyme-linked immunosorbent assay (ELISA), we determined serum free and total Campath levels in 46 patients with hematologic malignancies (45) or sickle cell disease (1) on day 0, day 7, day 14, day 28, day 50, day 75, day 100, day 150 and at one year after transplant (HSCT). 26 (57%) had a matched sibling donor, 16 (35%) a matched unrelated donor (MUD) and 4 (9%) a mismatched related or unrelated donor. 44 pts engrafted and are included in the analysis. Median follow up for survivors was 2.8 years. Grade II–IV aGVHD occurred in 8 pts after a median of 42 days (range 22 to 60). Eight pts developed cGVHD after a median of 107 days (range 89–140). 15/41 (37%) at risk pts developed CMV reactivation. The half-life of free alemtuzumab (fA) was 26 days after HSCT with wide interpatient variation in fA pharmacokinetics (e.g. Coefficient of variation was 138% on day 0). On day 0, 1 patient had an undetectable level of fA. By day 28, 50, and 100, there were 6 (14.6%), 12 (35.3%), and 13 (52%) pts with undetectable fA, respectively. Figure 1 shows the fitted means and 95% confidence intervals of fA over time. Using log-rank and Cox proportional hazard models, there was no association between fA on day 0, day 28, or the last available fA, and development of acute GVHD. However, pts with higher average free and total Campath levels in the first month had a lower risk of developing cGVHD (p=0.02). The median fA concentration in the first month for pts with cGVHD was 0.32 (inter-quarter range IQR: 0.22–0.41), as compared with 0.97 (IQR: 0.23–3.31) in those without cGVHD. No significant association between absolute lymphocyte count and fA concentration was found after adjusting for time (p=0.28). Finally, among pts at risk, a higher fA concentration on day 0 (p=0.002), and in the first month (p=0.003) was significantly associated with CMV viremia. In summary, the estimated half-life of serum fA is 26 days after HSCT, but with considerable interpatient variability. Higher concentrations of fA were associated with a decreased incidence of cGVHD, but an increased risk of CMV reactivation. In contrast to a previous preliminary analysis, no association existed between fA and lymphocyte reconstitution. Variation in alemtuzumab pharmacokinetics may predict important clinical outcomes, such as cGVHD and CMV reactivation. Future studies are warranted to determine an optimal alemtuzumab exposure that hastens immune reconstitution while minimizing chronic GVHD.
Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and after anti‑tumor necrosis factor therapy: A comparison of anti‑nuclear antibody positive and negative subsets

Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.
Eight-page eroticism: sexual violence and the construction of normative masculinity in Tijuana Bibles

ABSTRACTIn the pre-Playboy era, erotica was not hidden under mattresses or under false floorboards; rather it was hidden in pockets, constantly available for perusal and arousal. Measuring 2.5 inches by 4 inches, the average wallet size of the era, Tijuana Bibles were eight-page pornographic comic books sold from approximately 1930 to 1960 behind counters, in back rooms and behind closed doors. Inspired by the growing comic book industry, the ‘bibles’ fulfilled growing demand for affordable and discreet erotica in the era of rapidly changing gender relations. The depictions of intercourse and, frequently, sexual violence in these comics were specifically designed to reflect the desired self-image of the typically male reader, while the portable nature of the books encouraged a dominant sharing and swapping culture within homosocial communities. This paper explores how Tijuana Bibles worked to promulgate and reinforce the glorification of sexual violence as a measure of sexual performance within said homos...
The Gut, Its Microbiome, and Hypertension

Evidence is rapidly accumulating implicating gut dysbiosis in hypertension (HTN). However, we are far from understanding whether this is a cause or consequence of HTN, and how to best translate this fundamental knowledge to advance the management of HTN. This review aims to summarize recent advances in the field, illustrate the connections between the gut and hypertension, and establish that the gut microbiota (GM)-gut interaction is centrally positioned for consideration as an innovative approach for HTN therapeutics. Animal models of HTN have shown that gut pathology occurs in HTN, and provides some clues to mechanisms linking the dysbiosis, gut pathology, and HTN. Circumstantial evidence links gut dysbiosis and HTN. Gut pathology, apparent in animal HTN models, has not been fully investigated in hypertensive patients. Objective evidence and an understanding of mechanisms could have a major impact for new antihypertensive therapies and/or improved applications of current ones.
The Bougie and First-Pass Success in the Emergency Department.

Study objective The bougie may improve first-pass intubation success in operating room patients. We seek to determine whether bougie use is associated with emergency department (ED) first-pass intubation success. Methods We studied consecutive adult ED intubations at an urban, academic medical center during 2013. Intubation events were identified by motion-activated video recording. We determined the association between bougie use and first-pass intubation success, adjusting for neuromuscular blockade, video laryngoscopy, abnormal airway anatomy, and whether the patient was placed in the sniffing position or the head was lifted off the bed during intubation. Results Intubation with a Macintosh blade was attempted in 543 cases; a bougie was used on the majority of initial attempts (80%; n=435). First-pass success was greater with than without bougie use (95% versus 86%; absolute difference 9% [95% confidence interval {CI} 2% to 16%]). The median first-attempt duration was higher with than without bougie (40 versus 27 seconds; difference 14 seconds [95% CI 11 to 16 seconds]). Bougie use was independently associated with greater first-pass success (adjusted odds ratio 2.83 [95% CI 1.35 to 5.92]). Conclusion Bougie was associated with increased first-pass intubation success. Bougie use may be helpful in ED intubation.
Moire Method — Its Potential Application to NDT

The moire method has been used to measure the in-plane and out-of-plane displacements. This method can be used under either static or dynamic conditions. The basic geometric principles of moire fringe formation and the essential experimental techniques are briefly reviewed. The potential application of the moire method to NDT is evaluated.
Behaving Oneself: The Place of Manners in Contemporary American Culture

(1987). Behaving Oneself: The Place of Manners in Contemporary American Culture. Annals of the International Communication Association: Vol. 10, Communication Yearbook 10, pp. 773-787.
Teaching Statistics with Data of Historic Significance: Galileo's Gravity and Motion Experiments

This article demonstrates the use of two datasets as an aid in teaching polynomial and nonlinear regression. The data were gathered by Galileo during his studies of falling bodies and projectiles. ...
Wind, Water, Earth, and Fire–A Return to an Aristotelian Environment*

The meteorological situation of coastal regions is strongly influenced by the shoreline and by topographic relief. In this instance, we have learned how to take water and land influences into accou...
Higher order ignorance inside the margins

According to the KK-principle, knowledge iterates freely. It has been argued, notably in Greco (J Philos 111:169–197, 2014a), that accounts of knowledge which involve essential appeal to normality are particularly conducive to defence of the KK-principle. The present article evaluates the prospects for employing normality in this role. First, it is argued that the defence of the KK-principle depends upon an implausible assumption about the logical principles governing iterated normality claims. Once this assumption is dropped, counter-instances to the principle can be expected to arise. Second, it is argued that even if the assumption is maintained, there are other logical properties of normality which can be expected to lead to failures of KK. Such failures are noteworthy, since they do not depend on either a margins-for-error principle or safety condition of the kinds Williamson (Mind 101:217–242, 1992; Knowledge and its limits, OUP, Oxford, 2000) appeals to in motivating rejection KK. “Introduction: KK and Being in a Position to Know” Section formulates two versions of the KK-Principle; “Inexact Knowledge and Margins for Error” Section presents a version of Williamson’s margins-for-error argument against it; “Knowledge and Normality” and “Iterated Normality” Sections discuss the defence of the KK-Principle due to Greco (J Philos 111:169–197, 2014a) and show that it is dependent upon the implausible assumption that the logic of normality ascriptions is at least as strong as K4; finally, “Knowledge in Abnormal Conditions” and “Higher-Order Ignorance Inside the Margins” Sections argue that a weakened version of Greco’s constraint on knowledge is plausible and demonstrate that this weakened constraint will, given uncontentious assumptions, systematically generate counter-instances to the KK-principle of a novel kind.
Abstract 18210: Acetylated Proline-Glycine-Proline Couples Extracellular Matrix Fragmentation to Increased Vascular Endothelin-1 Production in Heart Transplant Patients

Introduction: The endothelium is a critical regulator of vascular function, and alterations in the production of nitric oxide (NO) and endothelin-1 (ET1) are known to correlate with cardiovascular disease. Acetylated Proline-Glycine-Proline (AcPGP), a pro-inflammatory matrix-derived cytokine (matrikine), has recently been demonstrated to couple extracellular matrix (ECM) fragmentation to increased endothelial permeability. However, the impact of ECM damage and fragmentation in regulating endothelial function remains unknown. Herein, we report AcPGP to be a potent stimulator of ET1 both in vitro and in a cohort of heart transplant (HTx) patients. Methods: Coronary serum from HTx patients was collected during angiographic screening for transplant vasculopathy (N=7). Serum AcPGP was measured by mass spectroscopy. In vitro experiments employed human aortic endothelial cells cultured in a microfluidic cell culture model with both laminar and disturbed flow. Cells were treated with either AcPGP or control peptide Proline-Glycine-Glycine (PGG) for 48hours (250μg/mL). Static endothelial cell culture experiments were also conducted. An ET1 ELISA kit (R&D Systems) was used to measure ET1 concentrations. NO concentrations were measured by a chemiluminescence assay. Protein expression of Endothelin Converting Enzyme 1 (ECE1) was determined by western blot analysis. Results: Compared to PGG, AcPGP in the endothelial flow model induced a 2.7 fold increase in ET1 production (14.7 ± 2.8 versus 40 ± 8.5 pg/mL, P ). AcPGP in static endothelial cell culture also increased ET1 production in a dose-dependent manner within 24hours (0.1 – 1.0mg/mL, P ). No differences in endothelial cell NO production or ECE1 expression were observed. Clinically, ET1 linearly correlated with serum AcPGP concentrations from coronary samples (R 2 = 0.8, P = 0.01). Conclusions: The results identify AcPGP as a novel matrikine capable of increasing vascular ET1, and highlight its potential role as a paracrine regulator of vascular function and inflammation. Importantly, these results are the first to link ECM fragmentation with an established mediator of cardiovascular disease in HTx patients.
Creating porcine biomedical models through recombineering: Conference Reviews

Recent advances in genomics provide genetic information from humans and other mammals (mouse, rat, dog and primates) traditionally used as models as well as new candidates (pigs and cattle). In addition, linked enabling technologies, such as transgenesis and animal cloning, provide innovative ways to design and perform experiments to dissect complex biological systems. Exploitation of genomic information overcomes the traditional need to choose naturally occurring models. Thus, investigators can utilize emerging genomic knowledge and tools to create relevant animal models. This approach is referred to as reverse genetics. In contrast to ‘forward genetics’, in which gene(s) responsible for a particular phenotype are identified by positional cloning (phenotype to genotype), the ‘reverse genetics’ approach determines the function of a gene and predicts the phenotype of a cell, tissue, or organism (genotype to phenotype). The convergence of classical and reverse genetics, along with genomics, provides a working definition of a ‘genetic model’ organism (3). The recent construction of phenotypic maps defining quantitative trait loci (QTL) in various domesticated species provides insights into how allelic variations contribute to phenotypic diversity. Targeted chromosomal regions are characterized by the construction of bacterial artificial chromosome (BAC) contigs to isolate and characterize genes contributing towards phenotypic variation. Recombineering provides a powerful methodology to harvest genetic information responsible for phenotype. Linking recombineering with gene-targeted homologous recombination, coupled with nuclear transfer (NT) technology can provide ‘clones’ of genetically modified animals. Copyright © 2004 John Wiley & Sons, Ltd.
Governing Electromagnetics: Maxwell’s Equations

Some fundamental definitions and observations in conjunction with electromagnetic phenomena are:
Measurement Error in Determination of Band Size for Highly Polymorphic Single-Locus DNA Markers

When assessing single-locus DNA information in reference to forensic and parentage problems, most proposed statistical methods (Baird et al, 1986; Gjertson et al, 1988; Morris et al, to be published; and Berry, submitted for publication) incorporate continuous measurement errors (e) into their calculations. Errors arise while distinguishing length of enzyme-cleaved fragments from mobility in gel electrophoresis. Statistically, actual true gene size plus measurement error constitutes the underlying model for an observed allele (sometimes on the log scale) where errors are usually assumed to be distributed normally with mean zero and variance α2.
Photoreceptor Degeneration: Molecular Mechanisms of Photoreceptor Degeneration

Rod and cone photoreceptors initiate the visual process by capturing photons and transducing the information into chemical and electrical signals. These functionally specialized neurons have high metabolic activity and oxygen consumption, making them vulnerable to genetic insults and changes in microenvironment. Inherited retinal degenerative diseases are clinically and genetically heterogeneous, with more than 200 genes identified so far. In a majority of retinal degenerations, the genetic defects affect diverse functions in photoreceptors, such as phototransduction, gene regulation, splicing, or intracellular transport. To develop efficient therapies, it is critical to elucidate how genetic defects affect cellular functions and activate death pathways. Caspase-dependent and -independent apoptosis appear to be the major route for photoreceptor cell death in retinal diseases, although the importance of necrosis and autophagy has been demonstrated. Distinct molecules associated with oxidative or endoplasmic reticulum stress can activate these interconnected cell death pathways. Notably, in most inherited diseases, the first signs of photoreceptor dysfunction or loss are observed years after birth and late in life, indicating adaptive mechanisms that protect the cells and suggesting their breakdown may lead to cell death. Mitochondria are predicted to play a critical role in integrating cellular homeostasis to stress and initiation of death pathways. Investigations of adaptive behavior and pre-death molecules that modulate the response to genetic factors should provide attractive targets for the development of better therapeutic approaches.
Can Reducing Faults Prevent Vulnerabilities

Most security vulnerabilities result from ordinary coding errors. What does this mean for the prospects of more secure software?
Fault Detectability Conditions for Linear Deterministic Heat Equations

With the rise of distributed and connected modern engineering systems, the need for safe and reliable distributed parameter systems is becoming increasingly prominent. However, fault detection of partial differential equation systems remains relatively unexplored compared to its ordinary differential equation counterpart. In this letter, we attempt to advance such research by addressing the fault detectability problem for linear deterministic heat equations with additive faults. Fault detectability examines whether a fault is detectable given a system model and measured outputs. Essentially, similar to controllability and observability, fault detectability is an intrinsic property of the system and has to be verified before designing diagnostic algorithms. In this context, we derive fault detectability conditions for heat equations by utilizing the singular values of fault-to-output transfer function. We illustrate the proposed detectability conditions on battery thermal fault diagnosis case study.
Open Source Platforms and Frameworks for Artificial Intelligence and Machine Learning

In recent years Artificial Intelligence (AI) and Machine Learning (ML) have emerged from academic labs and become prominent drivers of innovation in the high-tech industry. The number of jobs in this area has rapidly increased along with research output from industry and the commercialization of that research. It is widely accepted that the changes resulting from these advances will shape society. Diversity in these fields must be increased not only to get people from underrepresented populations into these lucrative jobs but also to have a positive impact by expecting that a more diverse workforce will ensure the fairness of data-driven decisions made by AI and ML algorithms, an issue that has come under scrutiny. The work described here is a result of ongoing efforts to modernize AI and ML courses, and to make its techniques an integral part of the software engineering capstone course at our educational institutions. We report on how the courses and the practice of software engineering have adopted cloud based platforms where we gain the benefit of creating virtual machines and containers for necessary software stacks, the pedagogical benefits of using open-source software that enable blending of markup text, code and output from code within the same document. Information about the choice of software libraries to help students produce code and perform experiments on data at an early stage is an important topic that is included in the discussion. We list of examples of where we have leveraged existing student interest in application of AI and ML, to motivate the work on projects. The defense and intelligence community of the US government are invested in a diverse talent pool in this area. Efforts in specialized certification, and faculty-student visits to government labs are described in this work.
Unusual Manifestations of Paget’s Disease of Bone

A 72-year-old healthy Caucasian man presented to his primary care physician with deafness in his right ear. Appropriate referral leading to audiometry revealed sensorineural deafness, and he was provided with a hearing aid without much avail. He had no history of prior ear problems. He did complain of the occasional band-like headache that was not of an acute onset, severe, site-specific, or migraine-like. There was no associated nausea, vomiting, eye disease, or vertigo. The physician attributed the headaches to “stress” and prescribed paracetamol, which did provide the patient with some relief. Several months later, he developed a painful left hip after slipping in the shower, after which he could not bear weight due to intense pain. He was admitted to the emergency room, where on questioning, he recollected having occasional pain in his arms and legs that often “felt warm.” On examination, there was some superficial bruising, and his left leg was externally rotated with painful movements. Vitals remained normal while in the emergency room. X-ray revealed a subtrochanteric fracture. There was some sclerosis around the area of fracture, but the x-ray was generally of a poor quality. Even after 4 months, the fracture was found not to unite. He then went in for an elective hip replacement, and while in the hospital developed pneumococcal pneumonia and remained bedridden for almost 2 weeks.
Pathogen Dynamics in an Invasive Frog Compared to Native Species

Emerging infectious diseases threaten the survival of wildlife populations and species around the world. In particular, amphibians are experiencing population declines and species extinctions primarily in response to two pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and the iridovirus Ranavirus (Rv). Here, we use field surveys and quantitative (q)PCR to compare infection intensity and prevalence of Bd and Rv across species and seasons on Jekyll Island, a barrier island off the coast of Georgia, USA. We collected oral and skin swabs for 1 year from four anuran species and three families, including two native hylids (Hyla cinerea and Hyla squirella), a native ranid (Rana sphenocephala), and the invasive rain frog Eleutherodactylus planirostris. Bd infection dynamics did not vary significantly over sampling months, but Rv prevalence and intensity were significantly higher in fall 2014 compared to spring 2015. Additionally, Rv prevalence and intensity were significantly higher in E. planirostris than in the other three species. Our study highlights the potential role of invasive amphibians as drivers of disease dynamics and demonstrates the importance of pathogen surveillance across multiple time periods and species to accurately capture the infectious disease landscape.
Medical Device Recalls in Orthopedics: Recent Trends and Areas for Improvement

Abstract Background Medical device recalls have the potential to affect patient outcomes in orthopedic surgery. We assessed high-risk orthopedic medical device recalls in the recent past. Methods The publicly available Food and Drug Administration medical device recall database was mined for information on class 1 and class 2 recalls of orthopedic implants or medical devices related to orthopedic surgery from January 1, 2015 to December 31, 2019. Recall details, including reason for recall, class of recall, and the recalling company, were recorded. The data were quantified and analyzed in Excel. Results The results of this study showed that orthopedic device recalls constitute a significant percentage of total medical device recalls, ranging from 11.8% to 21.5%. In the last 5 years, 2018 was the busiest year for all medical and orthopedic device recalls. Packaging errors were the most common reasons for orthopedic device recalls, followed by design flaws and manufacturing issues. Marketing and software issues were uncommon reasons for orthopedic device recalls. Zimmer Biomet, Johnson & Johnson (parent company of DePuy Synthes), and Stryker had the highest number of orthopedic device recalls over the last 5 years and also constitute the top 3 orthopedic companies with the largest market share of orthopedic implants. Conclusion Orthopedic device recalls remain a significant concern and constitute, on average, 16.6% of all class II medical device recalls from 2015 to 2019. Manufacturing companies can reduce the number of orthopedic device recalls by improving their device design, manufacturing, and packaging stages of the production cycle. Level of Evidence III.
Robotic assisted minimally invasive thymectomy with simultaneous bilateral thoracoscopy and contralateral phrenic nerve visualization.

Background: Thoracoscopic approaches to thymectomy and anterior mediastinal mass resection has become increasingly common due to the potential for decreased blood loss and hospital length of stay. However, contralateral mediastinal and phrenic nerve visualization if often difficult from these unilateral approaches, which may affect the ability to achieve a full phrenic to phrenic dissection Herein, we present our early experience of robotic assisted minimally invasive thymectomy (RAMIT) with simultaneous bilateral thoracoscopy and contralateral phrenic nerve visualization. Methods: This was a retrospective review of all sequential patients undergoing RAMIT with simultaneous bilateral thoracoscopy from January 2015 to May 2016. This study was approved by our Institutional Review Board (PRO15080367). Individual patient consent was waived. Results: Twenty-six patients [median age 58 (range, 29–76) years] were included in this study. Sixteen operations were performed for anterior mediastinal mass, 7 for non-thymomatous myasthenia gravis, and 3 for concurrent myasthenia gravis and thymoma. Median blood loss and hospital stay were 25 mL (range, 3–150 mL) and 3 days (range, 2–8 days), respectively. Twenty-one (80.8%) patients experienced an uncomplicated hospital course. The highest graded complication by Clavien Dindo Classification was a grade III due to pleural effusion requiring drainage via pleural catheter. One patient experienced asymptomatic hemidiaphram palsy postoperatively. There were no 90-day postoperative deaths. Conclusions: RAMIT with simultaneous bilateral thoracoscopy is a feasible approach that may allow for enhanced visualization and more complete thymic resection compared to existing unilateral minimally invasive operations. Comparative studies and long-term follow up are needed to adequately assess the potential benefits of RAMIT.
A multidisciplinary approach to reducing ventilator-associated events in a busy urban hospital

Acute care hospitals are requested to perform ongoing surveillance of all patients undergoing mechanical ventilation for ventilator-associated events (VAEs), a serious and often devastating complication of the life-saving modality. Poor performance metrics in VAE rates were recognized at a tertiary care hospital in Hartford, Connecticut and as a result, a multidisciplinary team was developed in 2015 to analyze hospital and system data. The program utilized a multifaceted approach to reliably identify and subsequently prevent VAEs.