cssi/SciSciGPT-SciSciNet huggingface dataset:
Moving free radical and redox biology ahead in the next decade(s)

The direct observation of free radicals in biological samples in 1954 provided support for what had been inferred for several decades, i.e. living, fully functioning organisms produce free radicals [1]. Following this, in conjunction with observations from radiation biology, Harman proposed the free radical theory of aging that is still being actively investigated [2]. The discovery of superoxide dismutase along with the realization that enzymes can make free radicals brought an entirely new view to the role of free radicals in biology [3]. Initially research focused on: the basic chemistry of the various free radicals and related oxidants; potential oxidative damage to cells and tissues; and the mechanisms and consequences that free radicals/oxidants could inflict in cells and tissues. However, this focus slowly changed as it was realized that superoxide and related oxidants in conjunction with superoxide dismutases are part of the basic biology of cells and tissues [4]. Because of the wide range of reactive species that could be generated in cells and tissues, the terms “reactive oxygen species (ROS)”, for the many oxidants, along with “oxidative stress”, to represent the consequence due to the damaging chemical reactions of these oxidants, were introduced in the 1980’s [5]; this vocabulary was a means to bring a more comprehensive and inclusive view to the field. However, these terms now appear to be a hindrance to the advancement of research in the field of free radical and redox biology because they provide very general information rather than the detailed information needed for deeper understanding. For more rapid advances in the field of free radical and redox biology I suggest that investigators consider three matters: vocabulary; the information actually provided by instrumentation and associated chemical tools used in free radical research; as well as quantitation.
Matrix Gla Protein Binds to Fibronectin and Enhances Cell Attachment and Spreading on Fibronectin

Background. Matrix Gla protein (MGP) is a vitamin K-dependent, extracellular matrix protein. MGP is a calcification inhibitor of arteries and cartilage. However MGP is synthesized in many tissues and is especially enriched in embryonic tissues and in cancer cells. The presence of MGP in those instances does not correlate well with the calcification inhibitory role. This study explores a potential mechanism for MGP to bind to matrix proteins and alter cell matrix interactions. Methods. To determine whether MGP influences cell behavior through interaction with fibronectin, we studied MGP binding to fibronectin, the effect of MGP on fibronectin mediated cell attachment and spreading and immunolocalized MGP and fibronectin. Results. First, MGP binds to fibronectin. The binding site for MGP is in a specific fibronectin fragment, called III1-C or anastellin. The binding site for fibronectin is in a MGP C-terminal peptide comprising amino acids 61–77. Second, MGP enhances cell attachment and cell spreading on fibronectin. MGP alone does not promote cell adhesion. Third, MGP is present in fibronectin-rich regions of tissue sections. Conclusions. MGP binds to fibronectin. The presence of MGP increased cell-fibronectin interactions.
Perpendicular transport in 1‐ and 2‐dimensional shock simulations

We consider the foundations of 1- and 2-dimensional shock simulations in which the physical quantities are independent of a coordinate which is not parallel to the magnetic field. We show analytically that in such simulations the ions are effectively tied to the convected magnetic lines of force because of the presence of an ignorable spatial coordinate. This conclusion has important consequences. In particular we conclude that the acceleration of energetic charged particles at quasi-perpendicular shocks cannot be properly studied in such simulations because the role of perpendicular diffusion cannot be properly evaluated.
A 3-D pyramid/prism approach to view knowledge requirements for the batch means method when taught in a language-focused, undergraduate simulation course

We develop a 3-D knowledge pyramid/prism model to structure the relationships of (i) lower-level learning, (ii) 'optional' knowledge bases, (iii) concurrent knowledge, and (ii) new knowledge; so one may view the learning needs of a higher-level learning objective. Our paradigm stems from Bloom's taxonomy of learning, but has the advantage of supporting 'just-in-time' and 'learn-by-doing' delivery, teaching and learning styles. We illustrate the paradigm through the BMMKP (the 3-D knowledge pyramid/prism model of the highest-level, batch-means-method learning objective for our language-focused, undergraduate course). The BMMKP reveals how highly dependent and fully integrated this learning is to calculus, probability, statistics, and queuing theory---regardless of the simulation modeling language chosen to teach in the course. The BMMKP is then used to develop a set of lower-level learning objectives for the undergraduate course. The 3-D pyramid/prism approach should lend itself well as a communication tool for visualizing other simulation learning objectives.
The promise and perils of Antarctic fishes: The remarkable life forms of the Southern Ocean have much to teach science about survival, but human activity is threatening their existence

Beneath the surface of the Southern Ocean, in the deep waters of the continental shelf and continental slope of Antarctica, a magnificent fauna consisting of over 320 known species of fish thrives in the cold and dark. These fish are uniquely adapted to the extreme environment in which they live. Over the course of millennia, they have evolved a remarkable range of physiological and biochemical features, the most visually stunning of which is that some lack haemoglobin (Fig 1). Yet, these species are under threat from global climate change and fishing, and the secrets they might unlock for science could be lost in the next decades if action is not taken. Figure 1. The blackfin icefish Chaneocephalus aceratus . Photo credit: Steve Untracht. A human can survive in freezing water for around 15 min before their organs begin to shut down. The fauna of the Southern Ocean spend their entire lives at these extreme temperatures. The fish species present are dominated by members of the Notothenioidei, which comprises 50% and 90% of the Antarctic finfish diversity and biomass, respectively [1,2,3]. The notothenioids are a suborder of perch‐like fishes that are mainly benthic and highly endemic to the Antarctic region. They are divided into eight families that have radiated from an ancestral stock during the last 20 million years to fill a variety of niches. These families include the Nototheniidae—the most diverse and specious family of the notothenioids—the Bathydraconidae—the dragonfishes, so‐named because of their especially long and narrow body forms—and the Channichthyidae—the icefishes, known for their colourless blood. > …the Antarctic and its spectacular fauna are suffering a fate similar to others on the planet—their survival is threatened by anthropogenic activities The composition of today's Antarctic fish fauna has been strongly influenced by the distinctive oceanographic features of …
SLC19A3 encodes a second thiamine transporter ThTr2

Abstract Recently, a new family of facilitative carriers has been cloned consisting of the reduced folate (SLC19A1) and the thiamine (SLC19A2) transporters. Despite a high level of sequence identity and similarity there is essentially no functional overlap between these carriers. The former transports folates and the latter thiamine. In this paper we describe the function of SLC19A3, another member of this transporter family most recently cloned, after transient transfection of the cDNA into HeLa cells. Uptake of [ 3 H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control. Similarly, in the transfectants thiamine transport increased with an increase in pH with peak activity at pH ∼7.5. While [ 3 H]thiamine uptake was markedly inhibited by nonlabeled thiamine it was not inhibited by several organic cations in 100-fold excess. Hence this carrier has a high degree of specificity for vitamin B 1 . The data indicate that SLC19A3 has the characteristics of SLC19A2 (ThTr1) and represents a second thiamine transporter (ThTr2) in this family of facilitative carriers.
Modularized analog to digital converter development

Modularized A/D (analog-to-digital) device and system development which can be easily implemented is presented. Design schemes based on a 4-b minimal A/D converter which is expandable to 8, 12, 16, or 32 b on a modular basis is presented. In addition, this modular expansion can be used to realized any size A/D converter module. Such an adaptable system can be very efficient and cost effective, and can be customized for maximum utilization in a given application. In addition to system-level expansion schemes of the A/D converter system, actual logic and digital circuit realizations for a 4-b A/D converter module are presented. >
Posttraumatic Stress Disorder, Pulp Fiction, and the Press

Recent professional publications show that the diagnosis of posttraumatic stress disorder (PTSD) may be subject to abuse in forensic settings. Now, pulp fiction portrayals of PTSD and reports in the press also reflect how this relatively new diagnostic category can be abused. This trivialization of PTSD has implications for real survivors of truly traumatic events.
Assessing the sensitivity of transportation assets to extreme weather events and climate change

Transportation officials are increasingly faced with challenging decisions about how to design, plan, and manage infrastructure to confront changes in climate and extreme weather events. An understanding of which impacts affect infrastructure and at what point damage begins to occur is a critical step toward assessing overall vulnerability and risk. However, few resources exist to help managers and designers identify key thresholds and indicators of sensitivity to weather and climate impacts. This paper introduces a sensitivity matrix, a tool developed for the U.S. Department of Transportation's Gulf Coast Study, Phase 2, adaptation pilot project in Mobile, Alabama. This matrix is an important step toward a more comprehensive understanding of relationships between climate and transportation. Transportation planners can use this matrix to screen for assets that are particularly sensitive and, therefore, potentially vulnerable to climate change. Where possible, the matrix includes key thresholds at which da...
Common Spatio-Temporal Patterns for the P300 Speller

A brain-computer interface (BCI) is a device that provides an alternate non-muscular communication/control channel for individuals with severe neuromuscular disabilities. The P300 event-related potential has been demonstrated to be a reliable signal for controlling a BCI. The ultimate goal is to continue io improve the classification speed and accuracy of a P300-based BCI. The method of common spatial patterns (CSP) has proven success with sensorimotor rhythm-based BCIs and, with some modifications, can also be used to accurately classify the P300. The present method, common spatio-temporal patterns (CSTP), extends CSP by incorporating time-delay embedding to extract the prominent spatio-temporal patterns corresponding to each class. The results indicate that CSTP is capable of identifying a decomposition subspace that accurately classifies the P300. In addition, this subspace can be visualized to provide useful insight regarding the discriminable spatio-temporal characteristics of the P300
Decision Strategies in Health Care Choices for Self and Others: Older but not Younger Adults Make Adjustments for the Age of the Decision Target

Participants (N = 142 younger and older adults) made health care choices for themselves, a social partner of similar age, or a social partner substantially younger or older than themselves. Using computer-based decision scenarios, participants reviewed positive, negative, or neutral choice criteria before choosing. Older adults who chose for themselves reviewed a greater proportion of positive choice criteria, recalled their choices more positively, and showed more positive emotional responses than did younger adults. Comparable results were found when participants chose for another person of similar age. Older adults who were asked to choose for a young person, however, showed a reduced focus on positive information; in addition, their emotional experience during the review process was less positive. Younger adults' performance was not influenced by the decision target.
Supraventricular Tachycardia and the Struggle to be Believed

Background: Little research exists examining patient experiences of life with supraventricular tachycardia (SVT). Realistic expectations of symptoms, patient management strategies, and treatment op...
Borrelia burgdorferi BbHtrA degrades host ECM proteins and stimulates release of inflammatory cytokines in vitro.

Summary The Lyme disease spirochaete, Borrelia burgdorferi, causes damage to diverse host tissues and induces inflammation but the mechanisms of injury are poorly understood. We recently reported that a surface-exposed B. burgdorferi protease, which is expressed during human disease and is conserved within the major Lyme disease spirochaete species, degrades the extracellular matrix proteoglycan, aggrecan. Here we demonstrate that BbHtrA also degrades fibronectin and numerous proteoglycans found in skin, joints and neural tissues. BbHtrA degradation of fibronectin released known pro-inflammatory fibronectin fragments FnIII13–14 and Fnf-29, which may amplify the inflammatory processes triggered by the presence of the bacteria. When this hypothesis was tested directly by exposing chondrocytes to BbHtrA in vitro, inflammatory cytokines (sICAM-1 and IL-6) and chemokines (CXCL1, CCL1, CCL2 and CCL5) that are hallmarks of Lyme disease were induced. These results provide the first evidence that, by utilizing BbHtrA, B. burgdorferi may actively participate in its dissemination and in the tissue damage and inflammation observed in Lyme disease.
Rapid Differentiation of Monocytes into Type I IFN-Producing Myeloid Dendritic Cells as an Antiviral Strategy against Influenza Virus Infection

Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the virus-induced mDCs failed to upregulate DC maturation markers and were unable to induce allogeneic lymphoproliferation. Virus-induced mDCs secreted little, if any, proinflammatory cytokines; however, they secreted a substantial amount of chemoattractants for monocytes (MCP-1 and IP-10). Interestingly, the differentiated mDCs secreted type I IFN and upregulated the expression of IFN-stimulated genes (tetherin, IFITM3, and viperin), as well as cytosolic viral RNA sensors (RIG-I and MDA5). Additionally, culture supernatants from virus-induced mDCs suppressed the replication of virus in vitro. Furthermore, depletion of monocytes in a mouse model of influenza infection caused significant reduction of lung mDC numbers, as well as type I IFN production in the lung. Consequently, increased lung virus titer and higher mortality were observed. Taken together, our results demonstrate that the host responds to influenza virus infection by initiating rapid differentiation of circulating monocytes into IFN-producing mDCs, which contribute to innate antiviral immune responses.
Liver X Receptor Agonist Modulation of Cholesterol Efflux in Mice With Intestine-Specific Deletion of Microsomal Triglyceride Transfer Protein

Objective— Previous work demonstrated that intestinal cholesterol absorption and regulated expression of intestinal Niemann-Pick C1-like 1 and ATP-binding cassette protein A1 are required for liver X receptor (LXR) agonist–mediated increases in high-density lipoprotein biogenesis. We re-examined those conclusions in mice with intestine-specific deletion of the microsomal triglyceride transfer protein ( MTTP-IKO ), where chylomicron formation is eliminated. Methods and Results— MTTP-IKO mice demonstrated sustained ≈90% reduction in cholesterol absorption and >80% reduction in Niemann-Pick C1-like 1 expression, yet LXR agonist treatment increased serum high-density lipoprotein and upregulated intestinal ATP-binding cassette protein A1 expression. Hepatic lipogenesis and triglyceride content increased with LXR agonist treatment in both genotypes. Biliary cholesterol secretion was increased in MTTP-IKO mice without further increase upon LXR agonist administration. LXR agonist treatment caused a paradoxical increase in cholesterol absorption in MTTP-IKO mice and decreased fecal neutral sterol excretion, but to levels that still exceeded fecal neutral sterol excretion in LXR agonist–treated control mice. Finally, MTTP-IKO mice demonstrated indistinguishable patterns of increased cholesterol turnover and efflux after intravenous radiolabeled cholesterol administration, with or without LXR agonist treatment. Conclusion— Both intestinal and hepatic cholesterol efflux pathways are basally upregulated in MTTP-IKO mice. Moreover, LXR-dependent pathways modulate intestinal cholesterol absorption, transport, efflux, and high-density lipoprotein production independent of chylomicron assembly and secretion.
Civil Appellate Advocacy

Perhaps one of the few real-life practical skills taught in law school is appellate advocacy. However, as most lawyers are aware, the opportunities to utilize and hone these law school-taught skills are infrequent because relatively few cases are appealed. Accordingly, it is the purpose of this Practice Tips to review briefly those skills learned long ago in the moot courtroom and to update them with some practical approaches.
Enzyme histochemistry on bone marrow biopsies: reactions useful in the differential diagnosis of leukemia and lymphoma applied to 2-micron plastic sections.

Attempts to encourage widespread use of plastic embedding to improve morphological detail in human bone marrow biopsy specimens have failed because the procedures were too time-consuming and laborious to replace the simpler and more expeditious procedures for paraffin embedding. We have systematically investigated a variety of fixation and embedding procedures and arrived at a method that allows a plastic section to be produced as rapidly as a routine paraffin section. This method permits the use of histochemical procedures that are rapidly becoming mandatory in hematologic diagnosis. Because of the scarcity of normal human marrow samples, rat bone marrow was used. We established the method’s applicability to human marrow by using it extensively with human buffy coat cells and in preliminary trials with human marrow samples. Biopsy specimens were fixed in a mixture of paraformaldehyde, glutaraldehyde, and acrolein, and embedded in a mixture of glycol and methyl methacrylate. Sections 2 microns thick were cut; incubated for chloroacetate esterase, α-Naphthol butyrate esterase, acid phosphatase (with and without tartrate), or alkaline phosphatase; and examined by light microscopy. Specimens could be prepared for examination within 48 hours. Tissues fixed with this basic fixation procedure can subsequently be used for electron microscopic study if desired. This approach, which provides histochemical markers of various hematopoietic cell lines in intact tissues and excellent ultrastructural preservation, promises to be useful in the diagnosis of neoplasms and inflammatory lesions, particularly when applied to bone marrow, spleen, and lymph nodes.
Searching for Leadership at the Edge of Potential

In consideration of the leadership of human potential, the current article examined the notion of individuals serving in leader roles who hold a potentiating consciousness. It is really a matter of attitude. An attitude that embraces a eudaimonistic philosophy that will lead to the actualization of the very best in ourselves and others. Holding a potentiating consciousness is to live, learn, and lead on purpose.
‘A Bird is Known by its Feathers’—On the Importance and Complexities of Definitions in Legislation

AbstractThis article deals with legislative definitions. It discusses the purpose and characteristics of legislative definitions which act, inter alia, as a mechanism for creating legal certainty with regard to ambiguous terms, and to prevent cumbrous draftsmanship of legislation. The importance of legislative definitions is that from them, usually, the incidence of law is inferred. Legislative definitions not only determine the legal meaning of a term, rather they coercively determine the sole way by which a term should be used in certain factual circumstances. By that, the law becomes the main source through which language is used as a mechanism for social control. In other words, legislative definitions, contrary to dictionaries' definitions, are authoritative. The article continues to elaborate on the relationship between definitions and the principles of the rule of law and separation of powers, and between definitions and statutory interpretation. Finally, the article focuses on several difficulties...
Nuclear hormone receptors involved in neoplasia: erb A exhibits a novel DNA sequence specificity determined by amino acids outside of the zinc-finger domain.

Abstract The erb A oncogene is a dominant negative allele of a thyroid hormone receptor gene and acts in the cancer cell by encoding a transcriptional repressor. We demonstrate here that the DNA sequence recognition properties of the oncogenic form of the erb A protein are significantly altered from those of the normal thyroid hormone receptors and more closely resemble those of the retinoic acid receptors; this alteration appears to play an important role in defining the targets of erb A action in neoplasia. Unexpectedly, the novel DNA recognition properties of erb A are encoded by an N-terminal region not previously implicated as playing this function in current models of receptor-DNA interaction. Two N-terminal erb A amino acids in particular, histidine 12 and cysteine 32, contribute to this phenomenon, acting in conjunction with amino acids in the zinc finger domain. The effects of the N-terminal domain can be observed at the level of both DNA binding and transcriptional modulation. Our results indicate that unanticipated determinants within the nuclear hormone receptors participate in DNA sequence recognition and may contribute to the differential target gene specificity displayed by different receptor forms.
Liturgy and Ethics in Ancient Syriac Christianity: Two Paradigms

Early Syriac Christianity presents two notable paradigms for understanding liturgy as a means for the ethical formation of the congregation. Ephrem the Syrian (d. 373) in his hymns for the Nativity vigil, and Jacob of Sarug (d. 521) in his verse homilies, each addressed their congregations in ways that utilized ritual participation in the liturgy for ethical and moral cultivation. Ephrem sought to instill his congregation with a biblical and theological understanding of the Nativity that would yield ethical enactment in the world. Jacob worked to use the experience of liturgical participation to mold the Christian’s moral disposition. For both, God’s salvation enabled the healing of the human condition in its various dimensions: physical, social, ecclesial. Liturgy as disciplined ritual activity provided the tools by which their congregations could learn, experience, and enact that healing.
Adrenal function during long-term anesthesia in man.

SummaryPlasma 11-OHCS were measured in 12 subjects during 7 hr of general anesthesia with endotracheal nitrous oxide (N2O) and halothane, and halothane alone. The 5 subjects who received the N2O-halothane anesthesia showed an early rise in plasma 11-OHCS, which corresponded to the duration of the excitation phase. After the short rise, the plasma 11-OHCS fell to hypoadrenal levels. The subjects who received halothane only (rapid induction of anesthesia) showed no rise in plasma 11-OHCS, but the 11-OHCS fell to hypoadrenal levels after induction. After 2 to 4.5 hr of general anesthesia, the plasma 11-OHCS rose spontaneously and remained elevated until the end of anesthesia. The sudden rise was not due to changes in feedback threshold and did not correlate with changes in concentration of the anesthetic. The urinary catecholamine secretion was not significantly altered during the anesthesia compared to a control period.
Percutaneous transluminal angioplasty: review of iliac and femoral dilatations at the Cleveland Clinic.

Thirty-five iliac and 25 femoropopliteal percutaneous transluminal angioplasties (PTA) were performed at the Cleveland Clinic between February 1979 and April 1983. Patients were considered for PTA if they had disabling claudication, ischemic rest pain, ischemic ulceration or gangrene, or an arterial stenosis or occlusion that met the necessary radiographic criteria. Overall, 87% of the PTAs were an early success, and 63% remained successful at an average follow-up of eight months. The success rate for iliac PTA was 89%, with a late success rate of 74% if both the femoral and profunda femoris arteries were patent. These success rates decreased to 50% early and 25% late if only one femoral artery was patent. The femoropopliteal PTA group had an incidence of 80% early success and 56% late success. If three tibial outflow vessels were patent, the late success rate was 75%. When one or two of the tibial vessels were patent, the late success rates were 45% and 63%, respectively. The follow-up period in both groups was 9 to 11 months. The success rate for PTA is generally lower than that for surgical revascularization in patients with similar clinical symptoms and arterial pathology. However, PTA poses several advantages over surgical revascularization and should be considered, especially in the poor-risk patient.
Magnesium Pemoline: Effects on brightness discrimination using positive reward

A drug group was stomach loaded with 20 mg/kg Magnesium Pemoline in tragacanth, and a control group was loaded with the vessel substance only. Performances in a Y maze brightness-discrimination task with sucrose reinforcement were compared: The drug group performed significantly better in running speed, latency, trials and reinforcements to criterion, and percentage of correct choices. These results indicate that Magnesium Pemoline enhances learning by ad lib rats of a brightness discrimination Y maze with positive reinforcement.
Research Progress and Development of Agricultural Informatization Technology

This paper summarizes the research achievement around the key techniques and application of agricultural informatization of our academy in recent ten years.The main content included crop model and cultivational simulation,optimization and decision-making system,development of agricultural management information system,application of agriculture remote sensing monitoring,theory of field informatization and agricultural informatization.The key research in near and middle term which developed the study on precision agriculture suitable for management on small scale in Henan was proposed.
Contents and Distributions of Cadmium and Lead in Rice From Main Rice Cultivation Areas in China

A total of 120 samples of rough rice were collected from 6 main rice cultivation areas in China for analysis of content and distribution of Cd and Pb in the grains using atomic absorption spectrometry.Results show that the average Cd content in rough rice,milled rice,rice bran and rice bran oil was(0.116±0.057),(0.089±0.413),(0.149±0.069),and(0.111±0.043) mg·kg-1,respectively,and that the six main rice cultivation areas followed a descending order of Central China,South China,North China,Northwest China,Northeast China,and Southwest China in Cd content in rough rice and its processed products.The results also show that the average Pb content in rough rice,milled rice,rice bran and rice bran oil was(0.232±0.105),(0.125±0.061),(0.301±0.142),and(0.089±0.024) mg·kg-1,respectively,and that the six areas followed an descending order of Central China,South China,Northwest China,North China,Northeast China,and Southwest China in Pb content in rough rice and its processed products.In terms of average Cd content,rice bran came first and was then followed by rough rice,rice bran oil and milled rice in sequence,while in terms of Pb content,rice bran was still the first and was then followed by rough rice,milled rice and rice bran oil.The processing of rough rice into milled rice removed(9.40±1.46)% Cd and(36.03±1.15)% Pb,and the processing of rice bran into rice bran oil left(62.43±2.00)% Cd and(31.24±0.63)% Pb in the latter.
Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain.

Stewart, R. R., T. Zigova, and M. B. Luskin. Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain. J. Neurophysiol. 81: 95–102, 1999. T...
Optical Cryoimaging Reveals a Heterogeneous Distribution of Mitochondrial Redox State in ex vivo Guinea Pig Hearts and Its Alteration During Ischemia and Reperfusion

Oxidation of substrates to generate ATP in mitochondria is mediated by redox reactions of NADH and FADH2. Cardiac ischemia and reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation. We hypothesize that IR alters the metabolic heterogeneity of mitochondrial redox state of the heart that is only evident in the 3-D optical cryoimaging of the perfused heart before, during, and after IR. The study involved four groups of hearts: time control (TC: heart perfusion without IR), global ischemia (Isch), global ischemia followed by reperfusion (IR) and TC with PCP (a mitochondrial uncoupler) perfusion. Mitochondrial NADH and FAD autofluorescence signals were recorded spectrofluorometrically online in guinea pig ex vivo -perfused hearts in the Langendorff mode. At the end of each specified protocol, hearts were rapidly removed and snap frozen in liquid N2 for later 3-D optical cryoimaging of the mitochondrial NADH, FAD, and NADH/FAD redox ratio (RR). The TC hearts revealed a heterogeneous spatial distribution of NADH, FAD, and RR. Ischemia and IR altered the spatial distribution and caused an overall increase and decrease in the RR by 55% and 64%, respectively. Uncoupling with PCP resulted in the lowest level of the RR (73% oxidation) compared with TC. The 3-D optical cryoimaging of the heart provides novel insights into the heterogeneous distribution of mitochondrial NADH, FAD, RR, and metabolism from the base to the apex during ischemia and IR. This 3-D information of the mitochondrial redox state in the normal and ischemic heart was not apparent in the dynamic spectrofluorometric data.
Sudden-Onset, Discrete, Painful Lesions in a 39-Year-Old Man

A 39-year-old man sought evaluation of newly erupted skin lesions on his arms. Ten days earlier he had fallen on his forearms, but no bruises appeared at that time.
Non-Amalgamation and Conjugation for ℓ-Metabelian Lattice-Ordered Groups

In this simple paper (which is an off-shoot of far more difficult work attempted with J. S. Wilson) we consider amalgamation and conjugation questions for l-metabelian lattice-ordered groups. The first section gives a trivial example to show that one of the few positive amalgamation results cannot be generalised; the second begins a study of conjugation in subclasses of lattice-ordered groups (as opposed to the class of all lattice-ordered groups).
What Is Brand Hate

In this chapter, I define the concept of brand hate in light of the general psychology of hate as discussed in the previous chapter. Consumer perception of brand injustice and unfairness are discussed as the starting point of brand hate. The components of brand hate are conceptualized as “cold”, “cool”, and “hot” brand hate in light of consumer psychology and behavior literature. Types of consumer brand hate and potential hate interactions among various consumer behaviors are discussed. The conceptual link between brand hate and anti-branding is developed. Furthermore, I introduced various forms of brand hate emotions from various social context such as “brand bullying”. This chapter provides a broader conceptual context about the newly introduced brand hate concept, its components, and degree of brand hate (or defined as “severity of brand hate”).
Therapeutic targets in homocystinuria due to cystathionine β-synthase deficiency: new European guidelines

It is just over 50 years since classical homocystinuria was first described independently in 1962 by Carson and Neill in Northern Ireland and Gerritsen and colleagues in Madison, Wisconsin [1,2]. I...
Local radiative cooling of edge plasmas by intense neutral gas puffing

It is proposed that the overheating of tokamak limiters can be controlled by introducing a strong local source of neutral H/sub 2/ directly at that limiter to convert the incident particle energy into isotropic radiation. The neutral influx rate required to substantially reduce the heat flux to the limiter is calculated as a function of the incident plasma parameters using a simplified one-dimensional fluid model. Application of this scheme to large tokamaks is discussed.
Atrial Fibrillation and Other Supraventricular Tachycardias

Management of atrial fibrillation and other supraventricular tachycardias, whether as the primary admitting diagnosis or a secondary diagnosis such as in decompensated heart failure, is challenging and time consuming. A primary strategy of rhythm or rate control may be adopted and tailored to the individual clinical circumstances. Reduction of cardioembolic risk in atrial fibrillation is a central goal in the management of this disease, even after sinus rhythm has resumed.
Time-varying human ankle impedance in the sagittal and frontal planes during stance phase of walking

This paper, for the first time, describes the estimation of the time-varying impedance of the human ankle in the sagittal (SP) and frontal (FP) planes during the stance phase of walking. The result of this work is aimed to provide design parameters for the development of 2-DOF powered ankle-foot prostheses capable of mimicking the time-varying impedance of the human ankle. Sixteen axes of rotations combining different amounts of SP and FP rotations were studied. For each axis, positive and negative rotations were considered separately. Four unimpaired male subjects walked on an instrumented vibrating platform that applied combined torque perturbations in the SP and FP simultaneously, while the ankle angles and torques were recorded. Based on the recorded data, the ankle impedance was estimated with a time resolution of 20 ms from 7% to 93% of the stance length (SL). The ankle stiffness and damping showed great variability through the SL and across axes of rotation. The maximum stiffness was 4.7±0.5 Nm/rad/kg at 0.21 s of the SL when the ankle rotated at an axis 22.5° from the SP combining Dorsiflexion (D) and Inversion (I). The minimum stiffness was 1.4±0.6 Nm/rad/kg at 0.05 s of the SL at an axis 45° from the SP combining D and Eversion (E). The maximum damping was 0.09±0.02 Nms/rad/kg at 0.21 s of the SL combining D and I at an axis 25° from the SP. The minimum was 0.02±0.01 Nms/rad/kg at 0.05 s of the SL combining P and I at an axis 45° from the SP.
Generalized robust counterparts for constraints with bounded and unbounded uncertain parameters

Abstract Robust optimization has emerged as a powerful and efficient methodology for incorporating uncertain parameters into optimization models. In robust optimization, robust counterparts for uncertain constraints are created by imposing a known set of uncertain parameter realizations onto the new robust constraint. For constraints with all bounded parameters, the interval + ellipsoidal and interval + polyhedral uncertainty sets are well-established in robust optimization literature, while box, ellipsoidal, or polyhedral sets may be used for unbounded parameters. However, there has yet to be any counterparts proposed for constraints that simultaneously contain both bounded and unbounded parameters. This is crucial, as using the traditional box, ellipsoidal, or polyhedral sets with bounded parameters may impose impossible parameter realizations outside of their bounds, unnecessarily increasing the conservatism of results. In this work, robust counterparts for uncertain constraints with both bounded and unbounded uncertain parameters are derived: the generalized interval + box, generalized interval + ellipsoidal, and generalized interval + polyhedral counterparts. These counterparts reduce to the traditional box, ellipsoidal, and polyhedral counterparts if all parameters are unbounded, and reduce to the traditional interval + ellipsoidal and interval + polyhedral counterparts if all parameters are bounded. It is proven that established a priori probabilistic bounds remain valid for these counterparts. The importance of these developments is demonstrated with computational examples, showing the reduction of conservatism that is gained by appropriately limiting the possible realizations of the bounded parameters. The developments increase the scope and applicability of robust optimization as a tool for optimization under uncertainty.
Abstract WP401: Influence of Hospital-Level Practices on Readmission after Ischemic Stroke

Introduction: The Center for Medicare and Medicaid Services intends to publicly report hospital-level readmission rates after ischemic stroke to enable comparisons of hospital quality. The influence of hospitals and hospital-level practices on readmission rates is unknown. Methods: Adult subjects were entered into this cohort study when hospitalized for ischemic stroke (principal ICD-9-CM 433.x1, 434.x1, 436) in 6 states from 2003-2009 from the State Inpatient Databases. The primary outcome was any non-procedural readmission within 30 days. 26 hospital level practices of interest (utilization of diagnostic testing, procedures, ICU, tPA, and therapeutic modalities) were identified using a combination of ICD-9 procedure codes, diagnosis-related groups (DRGs) and Health Cost and Utilization Project utilization flags. Multilevel logistic regression was used to estimate the association between mean hospital-level practices and readmission after accounting for demographics, vascular risk factors, comorbidities, socioeconomic status and whether a practice was implemented in an individual patient. Results: Hospitals accounted for 3.7% of the variance in the probability of readmission, intraclass correlation coefficient 0.037 (95% CI 0.031-0.043). Only three practices were associated with readmission: higher use of occupational therapy and acceptance of transfers were associated with lower readmission rates, while higher use of hospice was associated with higher readmission rates. (Table) Conclusions: Hospitals are responsible for a small proportion of readmission variance. These findings suggest ways that readmission rates may be reduced and illustrate potential susceptibility of a publicly-reported readmission measure to manipulation.
Identification of Human Lung Epithelial Metabolic Responses to Acute Benzo(a)pyrene Exposure

Polycyclic aromatic hydrocarbons (PAH) are a family of compounds commonly produced in the burning of wood, fuels, or grilled meats. Several PAH members, such as benzo(a)pyrene (BaP) have been classified as carcinogenic; however, other risk factors include both asthma and inflammation. The concentration of BaP in plasma has been found to be in nanomolar to micromolar range based on exposure. Previous studies by our laboratory found alterations to the following metabolic pathways in the sera of individuals with elevated benzo(a)pyrene: linoleate, drug, among others. The purpose of this study was to evaluate the effects of the PAH’s, benzo(a)pyrene (BaP) on metabolism and cellular function in A549 lung epithelial cells. The A549 cells were grown until 90% confluency in complete culture media (10% FBS) and then incubated in low serum media (0.5% FBS) overnight before treatment with vehicle or 3 µM BaP for 24h. Treatment at these concentrations were calculated to be approximately 3 times higher than the highest concentration observed in human plasma. The cells were then lysed in 150 μL extraction buffer including 14 internal standards and extracted samples were analyzed by a Q-Exactive mass spectrometer by following the workflow for high-resolution metabolomics as previously reported. The results show that of 8532 m/z features that were detected, 621 metabolic features were significantly different (p ≤ 0.05) after BaP treatment compared to control. Using pathway enrichment analyses, 22 metabolic pathways were significantly affected by BaP, including amino acid, urea cycle, and fatty acid metabolisms, several of which were observed in the human sera samples. Subsequent time course studies (0-24h) were performed using the median physiological concentration of BaP (14.2 nM) detected from the human study were performed as described above. Significant alterations to amino acid metabolism, such as changes to tyrosine, glutamine and methionine were found using high resolution metabolomics analysis. Taken together, these results suggest a novel mechanism of acute BaP exposure to A549 cells by eliciting metabolic perturbations on critical metabolic pathways for proper lung physiology and function.
Doxycycline treatment efficacy in dogs with naturally occurring Anaplasma phagocytophilum infection.

Objectives To evaluate doxycycline treatment efficacy and post-treatment pathogen persistence in dogs naturally infected with Anaplasma phagocytophilum in endemic regions of the USA. Materials and methods Symptomatic dogs in four US states (MN, WI, CT and CA) were evaluated before treatment with doxycycline and approximately 30 and 60 days post-treatment. Clinicopathological parameters, co-exposures and A. phagocytophilum DNA in whole blood and lymph node samples were compared between A. phagocytophilum infected and uninfected dogs. Results In total, 42 dogs fulfilled the inclusion criteria, with 16 dogs (38%) blood PCR-positive and 26 dogs (62%) blood PCR-negative for A. phagocytophilum. At initial evaluation, the proportion of clinicopathological abnormalities was similar between A. phagocytophilum infected and uninfected dogs, although thrombocytopenia and lymphopenia were statistically more prevalent among A. phagocytophilum infected dogs. Treatment with doxycycline resulted in resolution of all clinical abnormalities in infected dogs; four dogs had persistent haematological abnormalities, including mild leukopenia, eosinopenia and lymphopenia. All 16 infected dogs became blood PCR-negative approximately 30 and 60 days after treatment onset. Additionally, 13/13 (100%) lymph node specimens tested post-treatment were PCR-negative. Select clinicopathological abnormalities persisted in uninfected dogs after treatment. Clinical significance The results of this study support the efficacy of doxycycline therapy for clinical treatment of dogs naturally infected with A. phagocytophilum in the USA. This study did not find clinical, haematological or microbiological indicators that supported the persistence of A. phagocytophilum infection in naturally infected dogs following treatment with doxycycline for 28 days.
Cognitive and gait decrements among non-demented older adults with Type 2 diabetes or hypertension: a systematic review.

Objective: Older adults with Type 2 diabetes (DM2) and hypertension (HTN) often experience cognitive weaknesses. Growing evidence suggests that such weaknesses place patients at risk for gait distu...
Synthesis, Characterization, and Function of an RNA-Based Transfection Reagent

A synthetic 8-mer, amphipathic, trans-acting poly-2'-O-methyluridylic thiophosphate triester RNA element (2'-OMeUtaPS) can be prepared using solid-phase synthesis protocols. 2'-OMeUtaPS efficiently mediates the delivery of uncharged polyA-tailed phosphorodiamidate morpholino (PMO) sequences in HeLa pLuc 705 cells, as evidenced by flow cytometry measurements. In this cell line, 2'-OMeUtaPS-mediated transfection of an antisense polyA-tailed PMO sequence induces alternative splicing of an aberrant luciferase pre-mRNA splice site, leading to restoration of functional luciferase, as quantitatively measured using a typical luciferase assay. 2'-OMeUtaPS is also potent at delivering an uncharged antisense polyA-tailed PMO sequence in muscle cells of the mdx mouse model of muscular dystrophy; targeting the polyA-tailed PMO sequence against a splice site of the pre-mRNA encoding mutated dystrophin triggers an alternate splicing event that results in excision of the mutated exon (exon 23) from the pre-mRNA and production of functional dystrophin, as demonstrated by agarose gel electrophoresis. © 2018 by John Wiley & Sons, Inc.
Advection, Diffusion, and Drift Migrations of Larval Fish

The advection-diffusion equation provides a conceptual framework for the study of oceanic drift migrations, i.e. the equation’s parameters can be used to quantify and aid interpretation of drift of eggs and larval fishes. But first, relevant oceanic currents must be better characterized, and the capabilities of larvae to modify drift—through buoyancy, swimming, and orientation—need further study. Diffusion of larvae in the sea is not understood, and for the study of larval fish advection and diffusion it might be best to study special situations, e.g. discrete larval patch formation and dispersal.
Politics, Education, and Language Policy: The Case of Japanese Language Schools in Hawaii

(1978). Politics, Education, and Language Policy: The Case of Japanese Language Schools in Hawaii. Amerasia Journal: Vol. 5, No. 1, pp. 39-56.
Thiasyrbactins Induce Cell Death via Proteasome Inhibition in Multiple Myeloma Cells.

Author(s): Pierce, Marquicia R; Bakas, Nicole A; Pirrung, Michael C; Bachmann, Andre S | Abstract: Background/aimProteasome inhibition is a validated therapeutic strategy for the treatment of refractory and relapsed multiple myeloma (MM) and mantle cell lymphoma. We previously showed that thiasyrbactins (NAM compounds) are inhibitors with an affinity for the trypsin-like (T-L, β2) site of the constitutive proteasome, and more profoundly for the T-L site of the immunoproteasome.Materials and methodsIn this study, the biological activity of three NAM compounds was evaluated using four MM cell lines (ARD, U266, MM1R, and MM1S). We assessed the effect of (NAM-93, NAM-95, and NAM-105 on cell viability, as well as cell-based proteasomal activities, and determined the EC50 and Ki50 values, respectively.ResultsMM cells were most sensitive to NAM-93 with EC50 values l0.75 μM after 48 h of treatment. NAM-105 had a similar profile in most of the MM cells with EC50 values ranging between 0.42 and 3.02 μM. The level of inhibition of the proteasome T-L sub-catalytic activity in actively-growing MM cells was similar for NAM-93 and NAM-105. However, in each cell line, NAM-93 was more effective than NAM-105 at inhibiting overall trypsin-like sub-catalytic activity while NAM-105 was typically more effective at inhibiting overall chymotrypsin-like (CT-L, β5) sub-catalytic activity.ConclusionThese results show for the first time the proteasome-targeted biological activity of thiasyrbactins in MM tumor cells.
Effects of Abdominal Aortic Aneurysm Size on Mid- and Long-term Mortality After Endovascular Aneurysm Repair:

Purpose: To investigate the effect of abdominal aortic aneurysm (AAA) size on mid- and long-term survival after endovascular aneurysm repair (EVAR). Materials and Methods: Retrospective data were c...