cssi/SciSciGPT-SciSciNet huggingface dataset:
AN ANALYSIS OF METHODS TO PREVENT PERITONEAL DIALYSIS CATHETER INFECTIONS

Correspondence to: B. Piraino, Renal Electrolyte Division, University of Pittsburgh School of Medicine, Suite 200, 3504 Fifth Avenue, Pittsburgh, Pennsylvania 15213 USA. piraino@pitt.edu Received 10 June 2008; accepted 8 July 2008. Historically, exit-site infections (ESIs) have been problematic for patients on peritoneal dialysis (PD). Continuous ambulatory peritoneal dialysis (CAPD) patients with a history of ESI were much more likely to also have a history of peritonitis than those patients without a history of ESIs (64% vs 45%, p < 0.05), as shown in an observational study from the early days of PD, 1979 – 1984 (1). In that study, 83% of the catheters removed were in the group of patients with a history of at least one ESI, compared to 17% in those without an ESI (p < 0.001). Only 10% of catheter loss was due to a mechanical problem, 25% due to peritonitis alone, and the rest due to ESI and tunnel infection with or without peritonitis. Peritonitis that is related temporally and by organism to ESI and tunnel infection is most often caused by Staphylococcus aureus and Pseudomonas aeruginosa (2).
Toxicity and bioconcentration potential of the agricultural pesticide endosulfan in phytoplankton and zooplankton.

Agricultural pesticide runoff in southeastern coastal regions of the United States is a critical issue. Bioconcentration of pesticides by phytoplankton and zooplankton at the base of the aquatic food web may increase the persistence of pesticides in aquatic ecosystems and cause effects at higher trophic levels. This study examined the toxicity of a widely used agricultural pesticide, endosulfan, to Pseudokirchneriella subcapitatum (freshwater green alga) and Daphnia magna (freshwater cladoceran). We then investigated the potential of both plankton species to sequester endosulfan from their surrounding media. We also assessed the degree to which endosulfan is accumulated by D. magna via food (endosulfan-contaminated P. subcapitatum). A 96-h growth rate EC50 of 427.80 μg/L endosulfan was determined for P. subcapitatum, whereas a 24-h immobilization EC50 of 366.33 μg/L endosulfan was determined for D. magna. The 5-h EC50s for filtration and ingestion in D. magna were 165.57 μg/L and 166.44 μg/L, respectively. An average bioconcentration factor (BCF) of 2,682 was determined for P. subcapitatum exposed to 100 μg/L endosulfan for 16 h. An average BCF of 3,278 was determined for D. magna in a 100 μg/L endosulfan water-only exposure. There was negligible uptake of endosulfan by D. magna feeding on contaminated algae in clean water (BCF ∼ 0). Different proportions of parent isomers (endosulfan I and II) and the primary degradation product (endosulfan sulfate) were detected among treatments. Endosulfan was rapidly accumulated and concentrated from water by P. subcapitatum and D. magna neonates. Endosulfan contained in phytoplankton, however, was not bioaccumulated by zooplankton. These findings may prove useful in assessing ecosystem risk, because uptake from the water column appears to be the dominant route for bioconcentration of endosulfan by zooplankton.
A frequency channelized adaptive wideband receiver for high-speed links

A new class of high-speed link receiver architecture that operates at a fraction of the on-chip clock frequency is proposed. Instead of time-interleaving multiple ADCs as is conventionally done, the received signal is channelized into multiple frequency subbands using a bank of mixers and lowpass filters. The proposed receiver architecture enjoys numerous implementation advantages. Based on the frequency channelized signals, an adaptive synchronization/detection scheme is described. An adaptive solution is necessary since the propagation channel and the analog analysis filters are generally not perfectly known and the symbol rate is incommensurate with the free running ADC sampling rate.
Cellular distribution of inorganic mercury and its relation to cytotoxicity in bovine kidney cell cultures

A bovine kidney cell culture system was used to assess what relationship mercuric chloride (HgCl 2 ) uptake and subcellular distribution had to cytotoxicity. Twenty‐four‐hour incubations with 0.05–50 μM HgCl 2 elicited a concentration‐related cytotoxicity. Cellular accumulation of 203 Hg was also concentration‐related, with 1.0 nmol/10 6 cells at the IC50. Measurement of Hg uptake over the 24‐h exposure period revealed a multiphasic process. Peak accumulation was attained by 1 h and was followed by extrusion and plateauing of intracellular Hg levels. Least‐squares regression analysis of the cytotoxicity and cellular uptake data indicated a potential relationship between the Hg uptake and cytotoxicity (r = 0.91). However, the subcellular distribution of Hg was not concentration‐related. Mitochondria and soluble protein fractions accounted for greater than 65% of the cell‐associated Hg at all concentrations. The remaining Hg was distributed between the microsomal (6–10%) and nuclear and cell debris (11–22%)...
Mechanical disturbances in superconducting magnets-a review

The author reviews the progress achieved since MT6 in the understanding of mechanical disturbances in high-performance superconducting magnets. Attention is given to the use of acoustic emission technology for monitoring superconducting magnets. Energy, motion, and modeling aspects are also considered. In addition, it is suggested that the most important innovation for the stabilization of adiabatic solenoidal magnets in the past 14 years is the 'floating-coil' technique. Future research needs are also discussed. >
KGF-1 plasmid delivered with electroporation accelerates wound closure in diabetic mice

Introduction: Correcting the wound healing deficit of diabetes is an unmet medical challenge. Diminished levels of important growth factors are found in wounds of diabetic individuals. Methods: We optimized in vivo electroporation (EP) parameters to six 100 microsecond pulses of 1750 volts/cm (ECM830, BTX Genetronics, San Diego CA). EP increased expression of Luciferase Plasmid DNA by 10 fold. We utilized electroporation to increase transfection efficiency of a DNA expression vector for Keratinocyte Growth Factor (KGF-1, Invitrogen Carlsbad CA) using the gWIZ vector controlled by the CMV promoter. We assessed closure of 5mm full thickness wounds on the backs of 60 BKS.Cg-m Leprdb/db diabetic mice by calculating wound areas (pixels) using image analysis software based on NIH image (Scion Image, Frederick, MD). Results: The wounds treated with 40ug KGF-1 and electroporated (KGF-1/EP) closed faster than the untreated wounds (open area 220+-74 versus 576+-90, p<0.05 at day 12). In a second experiment wounds with KGF-1/EP healed faster than with KGF-1 alone (open area 637+-154 versus 971+-215, p<0.05 at day 12). Histological assessment was done with a grading scale for quality of epithelialization (Grade 1 : incomplete epithelium with micro ulcers, Grade 2 : thin epithelium, unresolved inflammation, Grade 3 : intact, not reticulated epithelium, Grade 4 : reticulated mature epithelium). The KGF-1/EP group healed better than control (3.3+-0.4 versus 1.5+-0.1 p<0.05). Conclusions: We conclude that electroporation assisted delivery of KGF-1 expression vector can improve closure of wounds in a diabetic mouse model.
“It Was Like A Fever…” Narrative and Identity in Social Protest

Although the 1960 student sit-ins were not nearly as uncoordinated as contemporaneous and subsequent accounts suggested, their repeated characterization in participants' accounts as “spontaneous” merits explanation. Analysis of campus newspaper articles and letters to the editor, speeches, and organizational and personal correspondence shows the emergence of a coherent and compelling narrative of the sit-ins, in which spontaneity denoted not a lack of prior coordination but independence from adult leadership, urgency, local initiative, and action by moral imperative rather than bureaucratic planning. Narratives of the sit-ins, told by many tellers, in more and less public settings, and in which spontaneity was a central theme, helped to constitute “student activist” as a new collective identity and to make high risk activism attractive. It was the storied character of representations of the sit-ins that compelled participation. This case suggests the more general importance of narrative—as distinct from collective action “frames”—in accounting for mobilization that takes place before the consolidation of movement organizations.
Displacement Discontinuity Modeling of Cracks

The limitations inherent to the BIE formulation of fracture mechanics problems were outlined in Chapter 4. It was shown that the integral equations degenerate when two surfaces of the same region become arbitrarily close.
An automated decision-tree approach to predicting protein interaction hot spots

Protein–protein interactions can be altered by mutating one or more “hot spots,” the subset of residues that account for most of the interface's binding free energy. The identification of hot spots requires a significant experimental effort, highlighting the practical value of hot spot predictions. We present two knowledge-based models that improve the ability to predict hot spots: K-FADE uses shape specificity features calculated by the Fast Atomic Density Evaluation (FADE) program, and K-CON uses biochemical contact features. The combined K-FADE/CON (KFC) model displays better overall predictive accuracy than computational alanine scanning (Robetta–Ala). In addition, because these methods predict different subsets of known hot spots, a large and significant increase in accuracy is achieved by combining KFC and Robetta–Ala. The KFC analysis is applied to the calmodulin (CaM)/smooth muscle myosin light chain kinase (smMLCK) interface, and to the bone morphogenetic protein-2 (BMP-2)/BMP receptor-type I (BMPR-IA) interface. The results indicate a strong correlation between KFC hot spot predictions and mutations that significantly reduce the binding affinity of the interface. Proteins 2007. © 2007 Wiley-Liss, Inc.
Book Review of the Code and the City

This book is organized into three parts, each consisting of three chapters. The first part describes the historical context and framework within which urban norms and standards are embedded. Chapter 1 provides an overview of the earliest urban form standards, which were created based on the power of a sovereign authority, as illustrated in some ancient civilizations such as the Indus Valley, China, Greece, Rome, and Byzantium. Ben-Joseph asserts that Islamic cities, on the other hand, were formed with a lot of adaptation based on “the principles of use rather than specific architectural regulations” (p. 16). Ben-Joseph uses historical evidence to show that order can emerge not only from centralized decision-making, but also from autonomous interactions of individuals in a community.
Hoxb8 Is Required for Normal Grooming Behavior in Mice

Repertoires of grooming behaviors critical to survival are exhibited by most animal species, including humans. Genes that influence this complex behavior are unknown. We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions. Additionally, these mice excessively groom normal cagemates. We have been unable to detect any skin or PNS abnormalities in Hoxb8 mutants. These observations suggest that the excessive, pathological grooming exhibited by these mice results from CNS abnormalities. Consistent with this interpretation, we demonstrate Hoxb8 expression in regions of the adult mouse CNS previously implicated in the control of grooming. The aberrant behavior observed in Hoxb8 mutants is not unlike that of humans suffering from the OC-spectrum disorder, trichotillomania. Interestingly, Hoxb8 is expressed in regions of the CNS known as the "OCD-circuit."
Analogical Learning in Negotiation Teams : Comparing Cases Promotes Learning and Transfer

We used structure-mapping theory (Gentner, 1983) to study learning in negotiation teams. We instructed some teams to compare two training cases and identify a key negotiation principle; other teams were given the same two cases to study and analyze separately. Teams who compared the two cases during the training period were more likely to transfer a key value-added strategy to a novel face-to-face, two-party negotiation situation than were teams who analyzed the same two cases separately. In fact, analyzing cases separately was no better than no training at all. Teams of negotiators showed comparable levels of knowledge transfer to solo negotiators.
c-mos and cdc2 cooperate in the translational activation of fibroblast growth factor receptor-1 during Xenopus oocyte maturation.

During oocyte maturation in Xenopus, previously quiescent maternal mRNAs are translationally activated at specific times. We hypothesized that the translational recruitment of individual messages i...
A sampling theorem for MLS surfaces

Recently, point set surfaces have been the focus of a large number of research efforts. Several different methods have been proposed to define surfaces from points and have been used in a variety of applications. However, so far little is know about the mathematical properties of the resulting surface. A central assumption for most algorithms is that the surface construction is well defined within a neighborhood of the samples. However, it is not clear that given an irregular sampling of a surface this is the case. The fundamental problem is that point based methods often use a weighted least squares fit of a plane to approximate a surface normal. If this minimization problem is ill-defined so is the surface construction. In this paper, we provide a proof that given reasonable sampling conditions the normal approximations are well defined within a neighborhood of the samples. Similar to methods in surface reconstruction, our sampling conditions are based on the local feature size and thus allow the sampling density to vary according to geometric complexity.
Concurrent testing of VLSI circuits using conservative logic

A concurrent error detection and design for testability technique based on conservative logic is presented. The theoretical derivations and experimental results show that conservative logic provides inherent support for concurrent error detection, and the resulting circuits can be tested using only two test patterns, independent of the function performed by the circuit. The background definitions are presented, and the fundamental conservative logic theory is developed. Several example designs of adder and multiplier circuits are presented and analyzed to illustrate the developed theory. A possible implementation of a conservative logic gate is presented, and its use in a VLSI circuit is described. The resulting circuit has been fabricated using the MOSIS process. The primary disadvantage of the approach is shown to be the implementation technology. >
First trimester serum analytes, maternal characteristics and ultrasound markers to predict pregnancies at risk for preterm birth

Introduction Markers of placental dysfunction are used for risk prediction of adverse obstetric outcomes including preeclampsia and growth restriction. Although medically indicated preterm birth is often distinguished from spontaneous preterm birth, we hypothesize that similar placental dysfunction may underlay all preterm birth. We aimed to investigate whether first trimester placental protein 13 (PP-13), pregnancy associated plasma protein A (PAPP-A) and uterine artery pulsatility index, with maternal characteristics could be used to predict all preterm birth.
C-(4,5,6-Trimethoxyindan-1-yl)methanamine: A Mescaline Analogue Designed Using a Homology Model of the 5-HT2A Receptor.

A conformationally restricted analogue of mescaline, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed using a 5-HT2A receptor homology model. The compound possessed 3-fold higher affinity and potency than and efficacy equal to that of mescaline at the 5-HT2A receptor. The new analogue substituted fully for LSD in drug discrimination studies and was 5-fold more potent than mescaline. Resolution of this analogue into its enantiomers corroborated the docking experiments, showing the R-(+) isomer to have higher affinity and potency and to have efficacy similar to that of mescaline at the 5-HT2A receptor.
Targeting of the VHL-Hypoxia-Inducible Factor-Hypoxia-Induced Gene Pathway for Renal Cell Carcinoma Therapy

Treatment of advanced renal cancer has made little progress in the past 30 yr. Most clinical efforts have incorporated cytokine-based therapy. The presumption has been that the cytokines may trigger a host immune response against the renal cancer. Only IFN-alpha and high-dose IL-2 seemed to have positive effects on patient outcomes. IFN has prolonged the lives of patients by a few months, and high-dose IL-2 is capable of inducing very prolonged remissions (>5 yr) for a small number of patients. Nephrectomy in the presence of metastatic disease has been established as an effective procedure for select patients, providing palliation and prolonging survival. Finally, enthusiasm has focused on the use of nonmyeloablative allogeneic stem cell transplantation and donor leukocyte infusion for the induction of graft versus tumor effects. Early results are both provocative and promising. A number of agents that target the critical gene products downstream from pVHL and hypoxia-inducible factor-1, such as vascular endothelial growth factor, PDGF, EGF receptor, and TGF-alpha, have recently become available. The new agents are capable of inhibiting specific cellular targets, and the biologic characteristics of clear cell carcinoma of the kidney support their application. If the correct targets are carefully selected for inhibition in tumors in which the targets are present (clear cell histologic features and loss of VHL expression), then results should resemble those others have observed with targeted therapy, such as the use of STI-571 (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors or anti-HER2/neu (Herceptin; Genentech, South San Francisco, CA) for treatment of breast cancer.
A machine learning approach for classification of anatomical coverage in CT

Automatic classification of anatomical coverage of medical images is critical for big data mining and as a pre-processing step to automatically trigger specific computer aided diagnosis systems. The traditional way to identify scans through DICOM headers has various limitations due to manual entry of series descriptions and non-standardized naming conventions. In this study, we present a machine learning approach where multiple binary classifiers were used to classify different anatomical coverages of CT scans. A one-vs-rest strategy was applied. For a given training set, a template scan was selected from the positive samples and all other scans were registered to it. Each registered scan was then evenly split into k × k × k non-overlapping blocks and for each block the mean intensity was computed. This resulted in a 1 × k3 feature vector for each scan. The feature vectors were then used to train a SVM based classifier. In this feasibility study, four classifiers were built to identify anatomic coverages of brain, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans. Each classifier was trained and tested using a set of 300 scans from different subjects, composed of 150 positive samples and 150 negative samples. Area under the ROC curve (AUC) of the testing set was measured to evaluate the performance in a two-fold cross validation setting. Our results showed good classification performance with an average AUC of 0.96.
A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti‐virulence factor

The orphan response regulator PmrA is essential for the intramacrophage growth and survival of Francisella tularensis. PmrA was thought to promote intramacrophage growth by binding directly to promoters on the Francisella Pathogenicity Island (FPI) and positively regulating the expression of FPI genes, which encode a Type VI secretion system required for intramacrophage growth. Using both ChIP-Seq and RNA-Seq we identify those regions of the F. tularensis chromosome occupied by PmrA and those genes that are regulated by PmrA. We find that PmrA associates with 252 distinct regions of the F. tularensis chromosome, but exerts regulatory effects at only a few of these locations. Rather than by functioning directly as an activator of FPI gene expression we present evidence that PmrA promotes intramacrophage growth by repressing the expression of a single target gene we refer to as priM (PmrA-repressed inhibitor of intramacrophage growth). Our findings thus indicate that the role of PmrA in facilitating intracellular growth is to repress a previously unknown anti-virulence factor. PriM is the first bacterially encoded factor to be described that can interfere with the intramacrophage growth and survival of F. tularensis.
Exploring implicit human responses to robot mistakes in a learning from demonstration task

As robots enter human environments, they will be expected to accomplish a tremendous range of tasks. It is not feasible for robot designers to pre-program these behaviors or know them in advance, so one way to address this is through end-user programming, such as learning from demonstration (LfD). While significant work has been done on the mechanics of enabling robot learning from human teachers, one unexplored aspect is enabling mutual feedback between both the human teacher and robot during the learning process, i.e., implicit learning. In this paper, we explore one aspect of this mutual understanding, grounding sequences, where both a human and robot provide non-verbal feedback to signify their mutual understanding during interaction. We conducted a study where people taught an autonomous humanoid robot a dance, and performed gesture analysis to measure people's responses to the robot during correct and incorrect demonstrations.
Tracing our roots: years of turmoil (1962-1977).

OBJECTIVE To describe the activities of the American Society of Clinical Pathologists and the sequence of events leading to the establishment of the National Accrediting Agency for Clinical Laboratory Science and Medical Laboratory Personnel. DESIGN A survey of literature on the history of clinical laboratory science was conducted. References consulted various books and professional journals. CONCLUSIONS By virtue of its close association with ASCP, ASMT became drawn into a series of legal actions between 1962 and 1977. Although ASMT was eventually dropped from all law-suits, the association's leadership recognized the need for greater autonomy and independence from ASCP. Clinical laboratory science achieved several victories during this period with respect to certification and mandatory re-registration by the BOR. Responsibility for accreditation of educational programs was shifted from the BOS to NAACLS and the establishment of the National Certification Agency for Medical Laboratory Personnel signified ASMT's commitment to certification by the profession for the profession.
P084 Post transplant DSA in a cohort of kidney recipients 8 to 16 years after transplantation

Aim We previously published a study (1998–2008) of 624 patients showing the association of pre-transplant DSA with poor kidney allograft survival. The aim of the current study was to assess development of post-transplant DSA in patients with well-functioning grafts >8 years after transplantation in comparison to patients with failed grafts. Methods HLA typing (A, B, C, DR, DQ) of recipients and donors was performed by standard serologic and/or DNA (SSP or SSO) methods. Anti-HLA antibody specificity was determined by single antigen beads (Lifecodes) on a Luminex platform. Though donors were not typed for DPB1 or DPA1 the de novo development of antibodies to DP alleles was presumed to be donor specific. Results Of 624 patients that were originally enrolled 131 were available for evaluation. 67 recipients had functioning kidney allografts 8 to 18 years after transplantation with >10 years follow up in 50% of these patients. The remaining 64 patients had graft failure (return to dialysis) with a median survival of 7.5 years. Of these patients, 44 (68%) had evidence of post-transplant DSA to HLA class 1 and/or class 2 as detected 0.1 to 5 years prior to graft failure. Most DSA positive recipients had antibodies to both Class 1 and 2 (32, 50%), whereas only 3 patients had DSA to Class 1 and only 9 patients had DSA to Class 2. Of patients with functioning grafts only 32% had evidence of DSA. In a new cohort transplanted in 2012–2015, that received identical induction and maintenance immunosuppression as the earlier cohort, similar DSA results were observed. Approximately, 33% of recipients with functioning kidney allografts had evidence of DSA whereas 65% of patients with failed grafts had DSA. In many cases, in both cohorts, the detection of a relatively low level of DSA occurred without concomitant clinical signs of rejection (e.g., a rise in creatinine). Conclusion As demonstrated in many studies of shorter duration the development of DSA was associated in this 18 year study with kidney allograft failure long after antibody has been detected and in the absence of standard clinical markers of rejection. Patients that exhibit persistent levels of DSA without clinical signs of rejection may benefit from enhanced immunosuppressive therapy to prevent damage to the kidney tubules and glomeruli that eventually lead to graft failure.
STIRring the grid: engaging energy systems design and planning in the context of urban sociotechnical imaginaries

Since the first electrification systems were established in the United States between 1910 and 1930, energy systems governance at the municipal level has included competing visions for how engineering design and energy policy-making should foster particular social outcomes. Using Phoenix as a representative metropolitan area, and the cases of distributed generation and in-home power management devices as examples, this paper explores how the norms and values embedded in energy systems design and planning shape how residents experience change in the energy grid. Through these case studies, the authors argue that such “sociotechnical imaginaries” – collectively formed visions of social life related to science and technology development – are a crucial, yet overlooked, pathway for social science to engage in fostering socially reflexive mechanisms in energy development. To conclude, the authors outline a research program for applying the established methodology of socio-technical integration research (STIR) ...
Flow regime transition criteria for upward two-phase cross-flow in horizontal tube bundles

Abstract In comparison with great success in the two-phase flow research for internal flows, relatively limited two-phase researches have been performed for external flows such as two-phase cross-flow in horizontal tube bundles. The recent demand of compact and efficient design of shell-tube type heat exchangers requires comprehensive understanding of void fraction, heat transfer, pressure drop, flow-induced vibration and flow regime in the shell side. The flow regimes are strongly related to the two-phase external-flow structure and affect the heat transfer performance in the heat exchangers. To this end, extensive literature survey has been performed to understand the flow regime appearing in the upward two-phase cross-flow in horizontal tube bundles. This study has classified the flow regime into 5 distinct flow regimes such as bubbly, cap bubbly, churn, finely dispersed bubbly and annular flows. A new model of the flow regime transition criteria has been proposed based on the analysis on the underlying physics of the upward two-phase cross-flow behavior in horizontal tube bundles. The newly developed flow regime transition criteria have been compared with 12 flow regime maps measured in horizontal tube bundles with normal square pitch array, normal triangular pitch array and parallel triangular pitch array. The test conditions of the 12 flow regime maps include the pitch/diameter ratio ranging from 1.17 to 1.5 and the tube diameter ranging from 0.00979 m to 0.020 m. The fluid systems are air-water, boiling iso-butane, boiling propane, boiling n-pentane, boiling R134a and R235fa. A fairly good agreement with some discrepancy has been obtained between the newly developed transition criteria and the measured flow regime maps.
Brokers and investment advisors

OF DISSERTATION BROKERS AND INVESTMENT ADVISORS Brokers and investment advisors are a large and important part of the financial industry. Using a novel data set that includes the majority of the financial advisory industry, in this dissertation I document the size of the financial advisory industry and the prevalence of customer complaints in the industry, which I use as a proxy for misconduct. I then test for two potential drivers of advisors’ misconduct: professional standards in the form of fiduciary responsibilities and influence from social networks. I find that variation in fiduciary duties—specifically fiduciary versus suitability standards— does not appear to affect advisors’ propensity for misconduct. My results indicate that a more likely explanation for differences between brokers and investment advisors stems from their respective product lines and business models. I then show that advisors often influence each other’s propensity to engage in misconduct, and that endogenous selection mechanisms, correlated environments, and location cannot fully explain variation in misconduct across groups of co-workers.
Direct detection of phenylephrine 3-O-sulfate in LS180 human intestinal cells using a novel hydrophilic interaction liquid chromatography (HILIC) assay.

Abstract The efficacy of phenylephrine (PE) is controversial due to its extensive pre-systemic metabolism through sulfation to form phenylephrine-3- O -sulfate (PES). Hence quantitation of PES is important in order to study the metabolism of PE. There are no published methods available for direction detection of PES. We have developed and validated a hydrophilic interaction liquid chromatography (HILIC) method for the direct detection of PES and simultaneous detection of PE to study the enzyme kinetics and metabolism of PE to enable approaches to reduce the presystemic metabolism of PE. This is the first method which facilitates direct detection of PES and simultaneous detection of PE using a zwitterionic HILIC column with improved sensitivity in a single short run. The observed quantitative ranges of our method for PE and PES were 0.39–200 μM and 0.0625–32 μM (respectively) with a run time of 6.0 min. The method was applied to the determination of PE and PES in LS180 human intestinal cell line, recombinant enzymes and human intestinal cytosol (HIC).
Structural basis for catalysis at the membrane-water interface

The membrane-water interface forms a uniquely heterogeneous and geometrically constrained environment for enzymatic catalysis. Integral membrane enzymes sample three environments - the uniformly hydrophobic interior of the membrane, the aqueous extramembrane region, and the fuzzy, amphipathic interfacial region formed by the tightly packed headgroups of the components of the lipid bilayer. Depending on the nature of the substrates and the location of the site of chemical modification, catalysis may occur in each of these environments. The availability of structural information for alpha-helical enzyme families from each of these classes, as well as several beta-barrel enzymes from the bacterial outer membrane, has allowed us to review here the different ways in which each enzyme fold has adapted to the nature of the substrates, products, and the unique environment of the membrane. Our focus here is on enzymes that process lipidic substrates. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.
Abstract IA26: Vaccines: The igniters of antitumor immunity

Pancreatic cancer is one of a number of malignancies that typically lack tumor infiltrating effector lymphocytes and are considered “non-immunogenic” neoplasms. This situation has drastically slowed the development and application of immune-based therapies for these cancers. In this study, we tested the hypothesis that vaccine based immunotherapy can convert pancreatic cancer, a “non-immunogenic” tumor, into an “immunogenic” tumor with infiltrating effector lymphocytes. We recently completed a novel neo-adjuvant and adjuvant study designed to evaluate post-immunotherapy changes within the tumor microenvironment (TME) of primary pancreatic tumors following treatment with the GM-CSF-secreting pancreatic cancer vaccine, given either alone or with immune modulating doses of cyclophosphamide to deplete regulatory T cells. Pathological examination of tumor tissue resected just two weeks following vaccination identified the formation of novel immunotherapy-induced tertiary lymphoid aggregates, organized lymphoid structures that are not observed in tumors resected from unvaccinated patients. This study shows for the first time that treatment with a vaccine-based immunotherapy directly alters the pancreatic cancer TME, allowing infiltration of organized and functional immune structures that convert an immunologically quiescent tumor into an immunologically active tumor. This study also demonstrates that the formation of these immune regulatory structures within the TME is just the first step toward establishing optimal anticancer immune responses within the TME since these lymphoid aggregates can express both effector activating and effector down-regulatory immune signatures. These data support combination immunotherapies that include vaccines that induce T cells and facilitate T cell trafficking into the TME given together with agents that modulate vaccine induced regulatory signals. In addition, these data suggest a new model for developing more effective immunotherapy for traditionally “non-immunogenic” tumors like pancreatic cancer. Finally, the intratumoral signatures identified in this study provide potential targets for developing strategies for modulating the TME and promoting more robust antitumor immune responses in future studies. Citation Format: Lei Zheng. Vaccines: The igniters of antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA26.
Abstract 2181: Antibody-conjugated nanoparticles for targeting metastatic triple-negative breast cancer

Early detection and the availability of new treatments have improved the survival rates of patients presenting with local or regional breast cancer to as high as 99% and 85%, respectively. On the contrary, patients with metastatic disease have a dismal 5-year survival rate of 17%. Thus, there is an urgent need for treatment strategies directed towards metastasis. Our lab has developed antibodies (Clone 6 and AM6) capable of recognizing tumor cells that have undergone epithelial-to-mesenchymal transition (EMT), a key step in the generation of circulating tumor cells and metastasis. The goal of the current study was to determine whether we use these antibodies as targeting ligands for directing anticancer drug-loaded polymeric nanoparticles to metastatic triple negative breast cancer cells as a novel therapeutic option. Polymeric PLGA nanoparticles loaded with paclitaxel, a chemotherapeutic agent, were functionalized with the antibodies using thiol-maleimide chemistry. We optimized the conjugation reaction in order to achieve maximal cell uptake of nanoparticles without compromising antibody binding. In vitro studies were carried out in an MDA-MB-231 derivative cell line with enhanced lung metastatic potential as well as a melanoma metastatic cell line M12. Clone 6 nanoparticles and AM6 nanoparticles showed significant improvement in cellular uptake as well as retention. A competition experiment confirmed target-mediated uptake of nanoparticles. Cytotoxicity studies showed improved cell kill using Clone 6 nanoparticles and AM6 nanoparticles. Based on these promising in vitro results, we are currently carrying out in vivo studies in mice. The development of a targeted drug delivery system for the treatment of metastatic triple negative breast cancer can significantly enhance the survival rate for patients who often have a life-expectancy of less than one year. Citation Format: Vidhi Khanna, Stephen Kalscheuer, Ameya Kirtane, Jayanth Panyam. Antibody-conjugated nanoparticles for targeting metastatic triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2181. doi:10.1158/1538-7445.AM2017-2181
Sex disparities in access to caregiving in Parkinson disease

Objective To compare access to caregiving between men and women with Parkinson disease (PD). Methods This was a cross-sectional and longitudinal study among participants with PD enrolled in the National Parkinson Foundation Parkinson9s Outcomes Project from 2009 to 2014 at 21 international sites. The primary outcome measures were presence of a caregiver at the baseline visit, caregiver burden as measured by the Multidimensional Caregiver Strain Index (MCSI) at baseline, and time to first paid caregiver. Results A total of 7,209 participants (63% men, 37% women) with PD were evaluated. Men had a mean age of 66.0 (SD 9.8) years, and women had a mean age of 66.9 (SD 9.7) years. More men than women had a caregiver (88.4% vs 79.4%, p p Conclusions Informal caregiving resources are lower for women than men with PD, despite the finding that their caregivers report less strain than those of men. In addition, women are more likely to use formal, paid caregivers. Strategies to improve access to caregiving, particularly for women, are needed.
Electrospun Fibers for Controlled Release of Nanoparticle-Assisted Phage Therapy Treatment of Topical Wounds

Bacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.
Intelligent Compaction for Quality Control and Acceptance for Soil and Base Compaction through Statistical Analysis

This paper presents the results of the intelligent compaction data that were collected from various layers including subgrade soil, lime-treated subgrade, cement-treated base and flexible aggregate...
Leveraging the NSSP R Studio Server to Automate QA Monitoring and Reporting

Objective: The aim of this project was to develop a nimble system to both monitor and report on the quality of Kentucky emergency department syndromic surveillance (SyS) data at system-wide and facility levels. Introduction: In 2016, the CDC funded 12 states, under the Enhanced State Opioid Overdose Surveillance (ESOOS) program, to utilize SyS to increase timeliness of state data on drug overdose events. In order to operationalize the objectives of the grant, there was a need to assess and monitor the quality of Kentucky’s SyS data, with limited resources. We leveraged the NSSP’s R Studio Server to automate quality assurance (QA) monitoring and reporting to meet these objectives. Methods: Using the R Server, we pulled data from the process messages table, aggregating messages to single patient encounters. In addition to compiling the code on a powerful remote server, the server can access the process table messages relatively quickly. We developed an R Markdown report to produce a report that includes a variety of system- and facility-level metrics that highlight key indicators of system performance and data flows. By using R, we were able to create an auto-generating QA report that runs weekly and e-mails for analyst review. Quality metrics included: % completeness of chief complaint and discharge diagnosis codes (overall and by facility)[Fig 1 & Fig 2]; visit trend by day of visit (with interactive spark lines)[Fig 2]; maximum date of message created, date message arrived at NSSP server, date of visit, and total messages[Fig 3]; message arrived trend (interactive sparklines)[Fig 3]; volume and type of error messages failing to process[Fig 4]; message volume by ADT type[Fig 5]; and volume of patient class by type by day[not shown]. Our SyS analyst reviews the report and delivers it to stakeholders with general comments about ongoing and newly emerging data quality concerns. Results: The report has proven to be beneficial in ongoing QA monitoring. The report is shared weekly with key stakeholders at the Kentucky Department for Public Health, Kentucky Health Information Exchange, NSSP, and regional ESSENCE users. Findings are reviewed at monthly SyS stakeholder meetings. The report has identified numerous errors, dead feeds, and other systems changes in near real-time; leading to corrective action and general data quality enhancement. Weekly monitoring of QA has improved data feed stability and communication of identified issue with key stakeholders. Conclusions: The R Studio Server provides a nimble platform to develop, refine, and automate a QA reporting system that can lead to improved SyS data quality. In Kentucky, in addition to improving overall data quality, these weekly reports and subsequent communication have help built relationships among key stakeholders and elevated the importance of syndromic surveillance data locally. Continual monitoring of data is critical to ensure quality and therefor the validity of the data.
Activated Kupffer cells attenuate the liver response to the peroxisome proliferator perfluorooctanoic acid

It has been suggested that peroxisome proliferators stimulate Kupffer cells, an effect which may be involved in their mechanism of action. To evaluate this hypothesis, this study was designed to investigate the effect of stimulating Kupffer cells on basal as well as induced peroxisomal enzyme activity. Twenty four hours following treatment of male Sprague-Dawley rats with the peroxisome proliferating agent perfluorooctanoic acid (PFOA), in corn oil or with corn oil alone, hepatic peroxisomal beta-oxidation was 4.6 +/- 0.2 and 1.8 +/- 0.1 U/g liver, respectively. As expected, PFOA did not influence the catalase activity. Stimulating Kupffer cells in vivo by zymosan A (25 mg/kg, i.v.) prior to treatment with corn oil or PFOA diminished basal as well as PFOA-induced peroxisomal beta-oxidation by 20-35%. Activation of Kupffer cells by zymosan A also diminished catalase activity by over 60%. Furthermore, PFOA reduced blood colloidal carbon clearance by 35% within 2 h of its administration. The data suggest that activation of Kupffer cells exerts a negative effect on basal as well as PFOA-induced peroxisomal enzyme activities. Data also suggest that PFOA inhibits Kupffer cells. Activated Kupffer cells may indeed produce factors which interfere with normal hepatic peroxisomal functions and responses.
Involvement of multiple survival signal transduction pathways in the neuroprotective, neurorescue and APP processing activity of rasagiline and its propargyl moiety.

Our recent studies aimed to elucidate the molecular and biochemical mechanism of actions of the novel anti-Parkinson’s drug, rasagiline, an irreversible and selective monoamine oxidase (MAO)-B inhibitor and its propargyl moiety, propargylamine. In cell death models induced by serum withdrawal in rat PC12 cells and human SH-SY5Y neuroblastoma cells, both rasagiline and propargylamine exerted neuroprotective and neurorescue activities via multiple survival pathways, including: stimulation of protein kinase C (PKC) phosphorylation; up-regulation of protein and gene levels of PKCα, PKCɛ and the anti-apoptotic Bcl-2, Bcl-xL, and Bcl-w; and up-regulation of the neurotrophic factors, BDNF and GDNF mRNAs. Rasagiline and propargylamine inhibited the cleavage and subsequent activation of procaspase- 3 and poly ADP-ribose polymerase. Additionally, these compounds significantly down-regulated PKCγ mRNA and decreased the level of the pro-apoptotic proteins, Bax, Bad, Bim and H2A.X. Rasagiline and propargylamine both regulated amyloid precursor protein (APP) processing towards the nonamyloidogenic pathway. These structure-activity studies have provided evidence that propargylamine promoted neuronal survival via neuroprotective/neurorescue pathways similar to that of rasagiline. In addition, recent study demonstrated that chronic low doses of rasagiline administered to mice subsequently to 1 methyl–4 phenyl 1,2,3,6 tetrahydropyridine (MPTP), rescued dopaminergic neurons in the substantia nigra pars compacta via activation of the Ras-PI3K-Akt survival pathway, suggesting that rasagiline may possess a disease modifying activity.
Religion and Ethics

Religion has always been intertwined with ethics. Often it is the religion that provides the justification for ethical discourse and often shapes the conversation in significant ways. The basic ethical methodology within religious traditions is similar. Scripture, the community, and religious experience are often central. The basic similarities between different religious traditions are then outlined, followed by an examination of the differences. The article concludes by discussing the impact of religion on certain social and applied ethical issues, such as medical ethics and technology.
Perspektiven einer partizipativen lokalen Governance

Das Bild von den BurgerInnen, die vor Ort in den Kommunen selbst die Verantwortung fur die Zukunft der Dorfer und Stadte, in denen sie leben, ubernehmen, war die Vision der Demokratischen Partei im Wahlkampf 2009 (Shushō kantei 2009).
Determining the migration of nadic acid, terephthalic acid, isophthalic acid and two oligomers from polyester food cans into food in the U.S. market

Abstract Concentrations of three monomers used in the manufacture of polyester resins for food cans, isophthalic acid (IPA), terephthalic acid (TA) and nadic acid (NA), and two oligomers were determined in canned food samples. All canned foods were purchased in local supermarkets in the United States. Concentrations of IPA and TA were determined to be from below the limit of detection in tomato sauce to 69 μg/kg in coconut milk, while the highest concentration of NA was found in pumpkin at 21 μg/kg. Estimated concentrations of oligomers in the food samples ranged from non-detect to 595 μg/kg. The influence of the storage time, lot type, and retail outlet on the migration concentrations was also investigated.
Intraoperatively the Patient Is Found Incidentally to Have Colon or Small Bowel Inflammation

Unexpected findings are encountered during surgery. This chapter reviews how to address incidentally discovered bowel inflammation during the course of an abdominal operation.