cssi/SciSciGPT-SciSciNet huggingface dataset:
Nitric oxide-synthesizing perivascular nerves in the rat middle cerebral artery.

Although perivascular nerves containing nitric oxide synthase (NOS) have been anatomically described for rat cerebral arteries, a dilator function for these nerves has eluded investigators when using isolated vessels. Rat middle cerebral arteries (MCAs) were isolated, pressurized, and electrically stimulated. The resting diameter of the MCAs after pressurization was 233 +/- 4 microns (n = 17) in one study. The MCAs showed a frequency-dependent dilation when stimulated. Maximum dilation (25-30% increase in diameter) occurred at a frequency of 8-16 Hz. Removal of endothelium or glibenclamide (10(-5) M), a blocker of ATP-sensitive potassium channels, had no effect on the dilations. The dilations were completely blocked with NG-nitro-L-arginine methyl ester (L-NAME) (10(-5) M), a general NOS inhibitor, and cold storage (24 h). The inhibition by L-NAME could be reversed by the addition of 10(-8) M L-arginine, the active precursor of NOS. Furthermore, 7-nitroindazole (10(-4) M), an inhibitor specific for the ne...
Role of paraventricular nucleus in control of blood pressure and drinking in rats

The present investigation examined the abilities of angiotensin (ANG) II and III to produce increases in blood pressure and drinking when microinfused into the paraventricular nucleus (PVN) of the hypothalamus of the Sprague-Dawley rat. Dose-dependent elevations in systemic blood pressure and heart rate were measured to both ANG II and III in the anesthetized rat, with ANG II more potent than ANG III at the two highest doses examined. Pretreatment with the specific ANG receptor antagonist [Sar1,Thr8]ANG II (sarthran), blocked subsequent ANG II- and III-induced elevations in blood pressure, suggesting that these responses were dependent on the activation of ANG receptors. A similar analysis in awake rats yielded nearly equivalent results. A final experiment demonstrated that microinfusions of ANG II and III into the PVN produced drinking in a dose-dependent manner, with greater consumption to ANG II than ANG III. Again, sarthran was found to block the dipsogenic response. Histological examination revealed that the location of the injection site was linked to the character of the ANG-dependent response. These data suggest that the PVN may play a critical role in mediating central ANG effects on body water homeostasis and blood pressure regulation. Furthermore, it appears that subnuclei of the PVN may participate differentially in ANG-mediated actions.
Networks, Collective Action, and State Formation

The study of state formation often focuses on building state capacity. The formation and subsequent bolstering of state capacity, however, are distinctly different activities. While the study of state capacity building has provided considerable insight into the role of formal institutions in maintaining stable governance, the implicit assumption in this work is the existence of a state upon which to build capacity. The collective decision to formalize institutions into a state - a necessary prior condition for building state capacity - is rarely addressed. In the following paper the role of informal institutions; specifically, social networks as informal institutions, in the process of state germination is explored. Using Afghanistan as a framework for the discussion, the research presented below attempts to illustrate the importance of the initial structural conditions of these networks, and the actors therein, in this process. The paper begins with a brief description of the role of informal institution and social networks in Afghanistan. Next, a provision point public goods game is presented as a basic model of the collective action problem inherent in state formation. Then, a network variant of this game is presented, which is implemented as a computational model. In the final sections the results of simulations from the computational model are presented, with a discussion and conclusions.
Cognitive Behavioral Therapies

Cognitive behavioral therapy (CBT) has been demonstrated to be the most efficacious treatment for numerous problems when compared to other treatment modalities. The CBT paradigm has been successfully used to assist both children with internalizing and externalizing disorders, and also those without difficulties. However, the majority of studies examining the effectiveness of CBT have been conducted using predominantly White, middle-class samples. There has been a dearth of research regarding the efficacy of CBT in non-White populations, likely due to the lack of ethnic minority participants in psychological research. This is particularly true in regards to research on anxiety disorders among African American youth. It is important to examine specific factors effecting treatment and research participation among African Americans (i.e., the socio-historical context of the African American experience, cultural mistrust, limited access to resources, and limited culturally competent clinicians) and the cultural ingredients that facilitate successful outcomes. As such, the purpose of this chapter is to review the literature pertaining to CBT, address the findings related specifically to the treatment of African American youth, and to examine the gaps in the literature and need for further research in this population.
Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication

A key contributor to HIV-1 genetic variation is reverse transcriptase errors. Some mutations result because reverse transcriptase (RT) lacks 3' to 5' proofreading exonuclease and can extend mismatches. However, RT also excises terminal nucleotides to a limited extent, and this activity contributes to AZT resistance. Because HIV-1 mismatch resolution has been studied in vitro but only indirectly during replication, we developed a novel system to study mismatched base pair resolution during HIV-1 replication in cultured cells using vectors that force template switching at defined locations. These vectors generated mismatched reverse transcription intermediates, with proviral products diagnostic of mismatch resolution mechanisms. Outcomes for wild-type (WT) RT and an AZT-resistant (AZT(R)) RT containing a thymidine analog mutation set-D67N, K70R, D215F, and K219Q-were compared. AZT(R) RT did not excise terminal nucleotides more frequently than WT, and for the majority of tested mismatches, both WT and AZT(R) RTs extended mismatches in more than 90% of proviruses. However, striking enzyme-specific differences were observed for one mispair, with WT RT preferentially resolving dC-rC pairs either by excising the mismatched base or switching templates prematurely, while AZT(R) RT primarily misaligned the primer strand, causing deletions via dislocation mutagenesis. Overall, the results confirmed HIV-1 RT's high capacity for mismatch extension during virus replication and revealed dramatic differences in aberrant intermediate resolution repertoires between WT and AZT(R) RTs on one mismatched replication intermediate. Correlating mismatch extension frequencies observed here with reported viral mutation rates suggests a complex interplay of nucleotide discrimination and mismatch extension drives HIV-1 mutagenesis.
“Residue antigen” from a strain of Friedlander bacillus.

The work of Zinsser and Parker,1 Heidelberger and Avery2 and one of us (Mueller)3 has indicated that most bacteria produce carbohydrate gums possessing the property of reacting specifically with antibodies formed in response to injections of the original bacteria. It is, therefore, of interest to study a number of these gums, called by Zinsser “residue antigens,” from different bacterial sources. Only by such study can it be determined to what extent it will be necessary to alter the present conception of the chemical basis of immunological specificity.Since the Friedlander Bacillus grows readily and abundantly on simple media, and is known to produce considerable quantities of a complex carbohydrate presumably related to the capsular material,4∗ this organism was chosen as being particularly adapted to the work.An old stock strain has been used, the source of which is unknown. It may be mentioned here that among several strains examined, there are distinct serological differences, as might be expected fr...
PREVENTION OF SECONDARY DETERIORATION OF THE CHRONICALLY ILL PATIENT.

Physical and emotional deterioration secondary to chronic illness often is more damaging than the underlying disease. The adverse effects of prolonged partial or total immobilization have been demonstrated in numerous experimental studies which serve as warnings against prolonged bed rest.In many chronic diseases, therapeutic exercises are the cornerstone of effective management to prevent disuse atrophy and joint contractures. Precautions to guard against accidental injury and recognition of the adverse psychologic effects of being bedridden are other components of the concept of “secondary prevention.”
A Note on the Moser-Hald Variation of Newton's Method

Publisher Summary This chapter presents a note on the Moser–Hald variation of Newton's method. The classical Newton method for finding a zero of a function f : R n → R n is to iterate the equation x k+ 1 = x k – Df ( x k ) –1 f ( x k ), where Df ( x ) denotes the Jacobian matrix of f at the point x . If the initial condition x 0 is sufficiently close to a simple zero of f , then the method converges quadratically to the zero. The chapter also presents a view of the Moser–Hald scheme from a slightly different perspective and explains the computation of the inverse of a linear map.
Equivalent Survival Following Fludarabine/Melphalan Reduced Intensity Conditioning with or without Rabbit ATG As Part of GvHD Prophylaxis

Abstract 1959 Introduction: Reduced intensity conditioning (RIC) prior to allogeneic transplantation allows donor cell engraftment with the maintenance of a graft versus malignancy effect. A recent CIBMTR registry study suggested worse outcomes for patients receiving anti-thymocyte globulin (ATG) as part of the conditioning regimen. To further study the role of ATG when added to a fludarabine and melphalan RIC regimen in the unrelated donor (URD) setting, we have retrospectively studied 76 consecutive patients with advanced hematologic malignancies who underwent URD transplantation. Comparisons were made between cohorts that did or did not receive ATG (given primarily for HLA disparity) for pretransplant graft vs. host disease (GvHD) prophylaxis. Pateints and Methods: Seventy six patients with advanced hematologic malignancies (43% CIBMTR high-risk) received fludarabine and melphalan (FluMel) conditioning with or without pre-transplant rabbit ATG 6 mg/kg as part of GvHD prophylaxis. Twenty five patients who received ATG (24 of whom received grafts from donors mismatched at 1 or 2 HLA loci) were compared with 51 patients who did not receive ATG (45 of whom received grafts from HLA matched donors with six donors mismatched at a single locus). The majority of patients received post-transplant tacrolimus with either methotrexate (MTX) or mycophenolate mofetil for GvHD prophylaxis. With the exception of HLA disparity, pre-transplant patient characteristics were similar between groups (Figure 1). Results: With median follow up of 481 days and 376 days for the ATG and no ATG cohorts, respectively, K-M overall survival estimates were similar, with 2 year OS of 62 vs. 47 percent, respectively, for the ATG vs no ATG groups (p=.34). On multivariate analysis, the inclusion of MTX in GvHD prophylaxis was favorably associated with overall survival (p=.004), and was associated with a significant reduction in the incidence of severe (gr 3–4) acute GvHD (p=.03). There were no significant differences in pre-transplant creatinine, age, or comorbidity index scores between patients who did or did not receive MTX. Conclusions: Fludarabine and melphalan RIC, with or without pre-transplant ATG, produced similar outcomes following URD transplantation, despite the fact that patients receiving ATG in this series were more likely to have received a HLA mismatched graft. The inclusion of MTX for GVHD prophylaxis resulted in less severe acute GVHD and better survival when compared with tacrolimus/MMF. Disclosures: Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Kaufman:Merck: Research Funding; Keryx: Consultancy; Novartis: Consultancy; Onyx Pharmaceuticals: Consultancy; Millenium: Consultancy; Celgene: Research Funding. Lonial:Millennium Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Onyx: Consultancy; Merck: Consultancy. Sinha:Celgene: Research Funding.
“Guns Don’t Kill People … Selfies Do”: rethinking narcissism as exhibitionism in selfie-related deaths

ABSTRACTThis work explores how the Narcissus myth has been inaccurately adopted by media, specifically in the reporting of selfie-related deaths. Narcissus, a boy in love with his own image, loved himself so much he would not share his image with others. Considering sharing is an integral part of the selfie phenomenon, this work seeks to dismantle the narcissism misuse in media coverage of selfie-related deaths. Through critical textual analysis of six major newspapers, I argue that exhibitionism is a more accurate critique of the selfie. Furthermore, it is a critique that fits more in line with the digital age, as opposed to the analog nature of narcissism.
Friendship and the Solitude of Greatness: The Case of Charles de Gaulle

ABSTRACTThe French statesman Charles de Gaulle was, and remains, something of an enigma. A genuinely great man, at first glance, he seems to tower above mere humanity. In studying de Gaulle's biographies and writings, the statesman and military man eclipses the human being without leaving his human bearing wholly behind. De Gaulle himself emphasized the solitude and sadness that accompanied the burden of human greatness. Yet de Gaulle, the self-described “man of character,” “the born protector,” was also a loving husband, a not terribly demanding or severe father, a faithful Christian, and a French patriot. There were profound limits to his solitude and self-sufficiency. His austere magnanimity coincided with moderation, even benevolence. He loved his country, strove for greatness, and sacrificed something of his private happiness for the public good. He was a complex man and soul, and perhaps a conflicted one.
Common Factors Contributing to the Adjustment Process of Mothers of Children Diagnosed With Down Syndrome: A Qualitative Study

ABSTRACTGrounded theory analysis was used to identify common factors that contributed to the adjustment process of mothers following their child’s diagnosis of Down syndrome, and how they ultimately arrived at new perspectives of the diagnosis. Qualitative interviews were conducted and participant narratives were filled with references of: “shock and fear,” “not-knowing,” being negatively impacted by professionals, and encouragement they received from others. The final model included: initial reactions, barriers and buffers, and acquiring a new perspective. Mothers emphasized the benefits of raising a child with an extra chromosome and ultimately experiencing personal “growth” on this parenting journey. Implications for providers who interface with families living with children of Down syndrome were presented.
Microbiome and pancreatic cancer: A comprehensive topic review of literature.

Aim To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes. Methods A comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016. Results Diverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations. Conclusion Pilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival.
Long-term effects of bottom trawling on large sponges in the Gulf of Alaska

Abstract Manipulative studies that characterize short-term effects of bottom trawls on seafloor habitats are numerous, but studies that examine long-term effects are rare. The long-term (13 years) effects of a single bottom trawl on large (>20 cm) erect sponges were investigated by revisiting the site of prior experimental trawling studies. In prior studies, large sponges were assessed immediately after trawling and 1 yr post-trawling. Thirteen years post-trawling, the average density of large sponges was 31.7% lower (range 1.5–53.0%) and the incidence of sponge damage (torn, necrotic, missing tissue, prone) was 58.8% higher within strip transects in trawled versus untrawled reference areas. For all sponge species combined, the mean density of large sponges was 3.19 individuals 100 m−2 in trawled areas and 4.67 individuals 100 m−2 in reference areas. The most abundant sponge species in both trawled and reference areas was Rhabdocalyptus dawsoni. Mean density of this species differed greatly between trawled (1.57 individuals 100 m−2) and reference areas (2.91 individuals 100 m−2). Thirteen years after trawling, the mean percentage of damaged sponges on strip transects was 15.3% in trawled areas and 6.3% in reference areas. The rate of damage in trawled areas was less than that observed both immediately after trawling and 1 year later. The persistence of damage (lower sponge densities and higher rates of injury in trawled areas) and the potential resultant changes to benthic communities where deepwater habitat-forming biota, such as large erect sponges, are present provide rationale for cautious management of the long term effects of bottom trawling.
ARCHETYPE “HOME” IN THE PROSE OF RUSSIAN-LANGUAGE WRITERS OF KAZAKHSTAN: BILINGUISM AS A WAY OF REALISING PERSON’S “PLACE IN THE WORLD” (ON THE MATERIAL OF “TUYUK SU” BY G. BELGER)

In this paper, translingualism is considered in the aspect of literary practice of polylingual writer G. Belger. On the material of the novel “Tuyuk su”, the polylinguistic language personality of the hero is reconstructed. In our point of view, it acts as an autobioreconstructive mask of the author himself. We come to the conclusion that as a result of interaction of several language systems within a single cognitive sphere, a more complex picture of the world is created. Both ethnic identity and the ways of person’s positioning in-the-world are determined by this fact.
How to Perform Superior Surgery on the Inferior Oblique and Avoid Inferior Surgery on the Superior Oblique

As stated in Chap. 8, “Vertical Deviations,” not all causes of overelevation in adduction are a result of inferior oblique muscle (IO) “overaction” (OA) . There are many causes of overelevation in adduction that are not caused by “OA” of the IO and will have an unsatisfactory response to surgical weakening of that muscle. These include pseudo-IO OA [1], anti-elevation syndrome (AES) [2], dissociated vertical divergence (DVD), Duane syndrome , pulley heterotopia [3, 4], inferior restrictions in the contralateral eye, and many cases with craniofacial syndromes.
Lands, realms, women and texts: Possession, entitlement and occupation

Words spread into diverse spaces. Such a word is ‘occupy’ along with its derivatives. It designates both possession and ownership, concepts explored in Shakespeare’s King John. Non-portable propert...
The Application of Deep Learning for the Classification of Internal Human Cardiac Anatomy

The applications of sensing and localization are becoming more sophisticated in many invasive and non-invasive surgical procedures and there is great interest to apply them to the human heart. Ideally, such tools could be indispensable for allowing physicians to spatially understand relative tissue morphologies and their associated electrical conduction. Yet today there remains a steep divide between the creation of spatial environment models and the contextual understandings of adjacent features. To begin to address this, we explore the problem of anatomical perception by applying deep learning to the identification of internal cardiac anatomy images.Copyright © 2018 by ASME
Combination Therapies: Short-Term Versus Long-Term Strategies

The previous chapters have shown that a combination of several drugs might be needed to overcome the problem of drug resistance in more advanced phases of the disease. At the same time, the basic kinetics of tumor cell decline indicates that treatment might have to be applied for a relatively long period of time. While the degree of side effects is relatively small with targeted drugs, the prolonged use of combination therapy could have a negative impact on the patients’ wellbeing. Using mathematical models, this chapter shows that the number of drugs used in combination can be reduced over time as the tumor cell population declines, without compromising the chances of treatment success. It is shown that the cancer size at which the number of drugs can be reduced does not correlate with the two phases of CML decline. Neither does it depend much on kinetic parameters of CML growth, except for the mutation rates. This is practical because even without any information on most parameters, and using only the data on the cancer size and the mutation rate, it is possible to predict at which stage of treatment the number of drugs can be reduced. Dependence of the treatment strategy on the activity spectra and potency of the drugs is discussed.
Aging-related increase in store-operated Ca2+ influx in human ventricular fibroblasts.

Human ventricular fibroblasts exhibit an age-related increase in store-operated Ca2+ influx induced by angiotensin II, an endogenous vasoactive hormone, or thapsigargin, an inhibitor of endoplasmic...
Correlates of War

The title of this article can be understood in three different ways. First, it is the name of a research project in quantitative history begun in 1964 at the University of Michigan, and still under way. Second, it means the extent to which a wide variety of factors rise and fall with fluctuations in the incidence of war: whether they correlate or covary with war, strongly or weakly, positively or negatively. And, third, it describes a research strategy by which we can make the transition from a stage in which the efforts to account for war were largely speculative and anecdotal to a stage in which well-articulated theoretical models can be subjected to the most rigorous scientific scrutinizing. Let me begin with a brief look at the intellectual history of the human effort to understand the ‘causes’ of war and thus to reduce its frequency or severity, or even perhaps to eliminate it entirely from the face of the earth.
The relations of regulation and emotionality to children's situational empathy-related responding.

The relations of dispositional regulation (attentional control, ego control), ego resiliency, and emotionality (general emotional intensity and negative emotionality) to situational measures of sympathy and personal distress were examined. Situational sympathy and personal distress were assessed with facial, self-reported, and heart rate reactions to an empathy-inducing film. Teachers and parents completed measures of children's dispositional regulation and emotionality. In general, children who evidenced sympathy (e.g., facial sadness, mean heart rate decline, and self-reported sympathy) were rated higher in regulation and resiliency, although findings sometimes were obtained for only one sex. Children who evidenced personal distress (e.g., facial distress), as well as facial sadness, were rated relatively high in emotionality. Gaze aversion from the film was correlated with regulation and boys' resiliency, and was negatively related to negative emotionality.
Distributed Microcomputers for the Automation of Electrical Power Distribution Systems

Abstract Electric power distribution systems provide the link between electric utilities and its customers. With the increased cost of energy, the potential installation of dispersed energy sources such as small hydro, cogeneration, wind and solar, improved control of distribution systems will be needed in the near future. In addition, the need to reduce peak power demand has stimulated the development of load management technology to control individual customer loads. This technology can potentially provide communication links to all points in distribution systems. With this communication technology, it is now possible to provide total real-time control capability of distribution systems to maintain the reliability of this essential customer link, with the increased complexity and the wide geographic coverage in distribution systems.
Stem Cells and Cell–Matrix Interactions in Lung

Stem cells have become the focus of many investigations owing to emerging data implicating their role in normal physiological processes and as potential targets for the development of therapeutic interventions. The factors that control the functions of stem cells related to migration, homing, and differentiation, among others, remain incompletely elucidated, but it is evident that, like other cells, stem cells express receptors that recognize signals from their immediate microenvironment. One such set of signals comes from the stroma, which contains several types of extracellular matrix components (e.g., fibronectin, collagens, proteoglycans). Stem cells express functional matrix-binding receptors of the integrin family and, therefore, the relative composition of the extracellular matrix is likely to be an important determinant of stem cell behavior. This is critical since the relative tissue composition of the extracellular matrix changes depending on developmental stage. Furthermore, inflammation during injury results in extracellular matrix remodeling and so does cancer formation. Thus, the alterations in matrix expression and turnover that occur during the lifetime of an animal are likely to contribute to the various signals that influence stem cell function. Although there are studies that support this idea, this field is not mature and, consequently, the exact role of cell–stroma interactions in stem cell biology remains undefined. This chapter summarizes the limited data available in this area with the hope of stimulating much needed research designed to elucidate how cell–stroma interactions affect stem cell functions in normal and disease states, and how these events can be manipulated pharmacologically to improve clinical outcomes.
Symposium in Honor of Irving I. Gottesman (December 29, 1930–June 29, 2016)

The June 2016 death of our esteemed colleague, Dr Irving I. Gottesman, was felt as an extreme loss at so many levels by colleagues, students, friends, and family across the globe. Irv's stellar contributions to the field of twin research will continue to be remembered and cited for many years to come. In commemoration of his life and work, I organized a symposium at the 16th meeting of the International Society for Twin Studies, held in Madrid, Spain, November 16-18, 2017. The panelists included mostly former students, as well as colleagues, who presented their scientific research and personal remarks reflecting Irv's profound influence in shaping their lives and careers. A chronology of Irv's academic positions and honors is included in the introduction to this special issue of Twin Research and Human Genetics, followed by brief sketches of the panel participants; their scholarly papers and personal reflections follow.
A phase I dose-finding study of metformin in combination with concurrent cisplatin and radiation in patients with locally advanced head and neck squamous cell carcinoma.

6074Background: Up to 60% of HNSCC present as locally advanced disease (LAHNSCC). Although prognosis has improved significantly, 3 year PFS and OS remain at 62%, and 73% respectively (RTOG 0522) de...
Tunable intrinsic strain in two-dimensional transition metal electrocatalysts

Tuning surface strain is a powerful strategy for tailoring the reactivity of metal catalysts. Traditionally, surface strain is imposed by external stress from a heterogeneous substrate, but the effect is often obscured by interfacial reconstructions and nanocatalyst geometries. Here, we report on a strategy to resolve these problems by exploiting intrinsic surface stresses in two-dimensional transition metal nanosheets. Density functional theory calculations indicate that attractive interactions between surface atoms lead to tensile surface stresses that exert a pressure on the order of 105 atmospheres on the surface atoms and impart up to 10% compressive strain, with the exact magnitude inversely proportional to the nanosheet thickness. Atomic-level control of thickness thus enables generation and fine-tuning of intrinsic strain to optimize catalytic reactivity, which was confirmed experimentally on Pd(110) nanosheets for the oxygen reduction and hydrogen evolution reactions, with activity enhancements that were more than an order of magnitude greater than those of their nanoparticle counterparts.
SYNTHESIS OF 5-(4-SUBSTITUTED BENZYL)-2,4-DIAMINOQUINAZOLINES AS INHIBITORS OF CANDIDA ALBICANS DIHYDROFOLATE REDUCTASE

Several 5-(4-substituted benzyl)-2,4-diaminoquinazolines were prepared as potentially selective inhibitors of Candida albicans dihydrofolate reductase. These compounds were synthesized by a novel route, which included as a key step the displacement of a fluoro group in 2,6-difluorobenzonitrile by the anions of ethyl or methyl 4-substituted phenylacetates. The resultant diarylacetates were saponified and decarboxylated to the 2-fluoro-6-(4-substituted phenyl)benzonitriles. Ring closure of these benzonitriles with guanidine carbonate gave the 5-(4-substituted benzyl)-2,4-diaminoquinazolines.
Influence of antibody immobilization strategy on carbon electrode immunoarrays

We report here the influence of antibody immobilization strategy for protein immunosensors on screen printed carbon electrode arrays in terms of antibody binding activity, analytical sensitivity, limit of detection, and stability. Horseradish peroxidase (HRP) was the model analyte with anti-HRP immobilized on the sensors, and HRP activity was used for detection. Covalently immobilized anti-HRP antibodies on electrodes coated with chitosan, electrochemically reduced graphene oxide (rGO), and dense gold nanoparticle (AuNP) films had only 20-30% of the total immobilized antibodies active for binding. Active antibodies increased to 60% with passively adsorbed antibodies on bare electrodes, to 85% with oriented antibodies using protein A covalently immobilized on AuNP-coated carbon electrode, and to 98% when attached to protein A passively adsorbed onto bare electrodes. Passively adsorbed antibodies on bare electrodes lost activity in 1-2 days, but antibodies immobilized using other strategies remained relatively stable after 5 days. Covalent immobilization gave limits of detection (LOD) of 40 fg mL-1, while passively adsorbed antibodies or protein A on carbon electrodes had LODs 4-8 fg mL-1, but were unstable. Sensitivity was highest for antibodies covalently attached to AuNP electrodes (2.40 nA per log pg per mL) that also had highest antibody coverage, and decreased slightly when protein A on AuNP was used to orient antibodies. Passively adsorbed antibodies and oriented antibodies on protein A gave slightly lower sensitivities. Immobilization strategy or antibody orientation did not have a significant effect on LOD, but dynamic range increased as the number of active antibodies on sensor surfaces increased.
Three-dimensional Nanoantenna Inverse-design

Realizing a diverse set of high-performance nanoantennas for phase-gradient applications can be extremely challenging without the aid of formal inverse-design techniques. To this end, an inverse-design procedure based on the Multi-Objective Lazy Ant Colony Optimization (MOLACO) algorithm is proposed for the synthesis of three-dimensional nanoantenna geometries that achieve high transmission performance and a wide range of phase options. A unit cell geometry suitable for a Membrane Projection Lithography fabrication technique is presented and explored by MOLACO in order to discover a set of highly transmissive nanoantennas that achieve a full 2π phase range. Finally, future research directions and applications are briefly discussed.
Foundational ways of thinking for understanding the idea of logarithm

Abstract This study explored two undergraduate precalculus students’ understandings of the idea of logarithm as they completed conceptually oriented exploratory lessons on exponential and logarithmic functions. The students participated in consecutive, individual teaching experiments that focused on Sparky – an animated mystical saguaro that doubled in height every week. The exponential lesson focused on developing students’ conceptions of growth factors and tupling (e.g., doubling) periods as a foundational understanding for conceptualizing logarithms and logarithmic properties meaningfully. This paper characterizes conceptions that are productive for students to acquire in introductory lessons on exponential and logarithmic growth, and discusses two understandings that were revealed to be foundational for students’ development of productive meanings for exponents, logarithms and logarithmic properties.
Abstract P030: Dct (pro)renin Receptor Via Its Soluble Product Inhibits Ncc Activity During Regulation Of Blood Pressure And Potassium Homeostasis In Mice

Sodium-chloride cotransporter (NCC), uniquely located at the distal convoluted tubule (DCT), is the target of thiazide diuretics and critically involved in renal handling of both Na+ and K+. Howeve...
Climate change: how debates over standards shape the biophysical, social, political and economic climate.

In their understandable zeal to ward off the ‘nay-sayers’, for whom climate change is merely an illusion, rural sociologists have defended the modern constitution that separates the natural from the social. Yet, standards must be developed to identify the phenomena of concern to both climate scientists and the public. Standards must be identified to stabilize the phenomena of interest, making them into something that can be acted on. In addition, standards must point the way forward and measure progress toward the amelioration of the problem(s). In short, standards simultaneously perform, measure, and point toward the transformation of ‘the climate.’ Yet, even as standards are necessary, they may actually lead us astray. Drawing on Foucault and recent work in Science Studies, I argue that grappling with climate change will require changing the political and even epistemological climate, re-enacting the sciences as well as agriculture and food.
Mining tasks and task characteristics from electronic health record audit logs with unsupervised machine learning.

Objective The characteristics of clinician activities while interacting with electronic health record (EHR) systems can influence the time spent in EHRs and workload. This study aims to characterize EHR activities as tasks and define novel, data-driven metrics. Materials and methods We leveraged unsupervised learning approaches to learn tasks from sequences of events in EHR audit logs. We developed metrics characterizing the prevalence of unique events and event repetition and applied them to categorize tasks into 4 complexity profiles. Between these profiles, Mann-Whitney U tests were applied to measure the differences in performance time, event type, and clinician prevalence, or the number of unique clinicians who were observed performing these tasks. In addition, we apply process mining frameworks paired with clinical annotations to support the validity of a sample of our identified tasks. We apply our approaches to learn tasks performed by nurses in the Vanderbilt University Medical Center neonatal intensive care unit. Results We examined EHR audit logs generated by 33 neonatal intensive care unit nurses resulting in 57 234 sessions and 81 tasks. Our results indicated significant differences in performance time for each observed task complexity profile. There were no significant differences in clinician prevalence or in the frequency of viewing and modifying event types between tasks of different complexities. We presented a sample of expert-reviewed, annotated task workflows supporting the interpretation of their clinical meaningfulness. Conclusions The use of the audit log provides an opportunity to assist hospitals in further investigating clinician activities to optimize EHR workflows.
Gain without inversion and enhancement of refractive index via intervalley quantum coherence transfer in hybrid WS 2 -metallic nanoantenna systems

We theoretically study formation of gain without inversion and resonant enhancement of refractive index with suppressed absorption in a system consisting of a monolayer of transition metal dichalcogenide (${\mathrm{WS}}_{2}$) and a metallic nanoantenna. We show that these processes happen when the hybrid system interacts with a right-circularly polarized laser beam, allowing quantum coherence transfer to happen from the K to ${\mathrm{K}}^{\ensuremath{'}}$ valley. Our results show that the quantum coherence transfer can convert the ${\mathrm{K}}^{\ensuremath{'}}$ valley into a conjugated system wherein the real and imaginary parts of its polarization become similar to the imaginary and real parts of the K valley polarization, respectively. This allows the maximum refractive index in the ${\mathrm{K}}^{\ensuremath{'}}$ valley to occur as the absorption becomes zero. We characterize the conjugated valley system by inspecting the evolution of its Bloch vector as the incident laser frequency varies. The theoretical approach includes density matrix formalism while considering a pure dephasing rate that represents the fast decay of exciton valley polarization in transition metal dichalcogenide monolayers.
Multiple roles for actin in secretory and endocytic pathways

Actin filaments play multiple roles in the secretory pathway and in endosome dynamics in mammals, including maintenance of Golgi structure, release of membrane cargo from the trans-Golgi network (TGN), endocytosis, and endosomal sorting dynamics. In addition, TGN carrier transport and endocytosis both occur by multiple mechanisms in mammals. Actin likely plays a role in at least four mammalian endocytic pathways, five pathways for membrane release from the TGN, and three processes involving endosomes. Also, the mammalian Golgi structure is highly dynamic, and actin is likely important for these dynamics. One challenge for many of these processes is the need to deal with other membrane-associated structures, such as the cortical actin network at the plasma membrane or the matrix that surrounds the Golgi. Arp2/3 complex is a major actin assembly factor in most of the processes mentioned, but roles for formins and tandem WH2-motif-containing assembly factors are being elucidated and are anticipated to grow with further study. The specific role for actin has not been defined for most of these processes, but is likely to involve the generation of force for membrane dynamics, either by actin polymerization itself or by myosin motor activity. Defining these processes mechanistically is necessary for understanding membrane dynamics in general, as well as pathways that utilize these processes, such as autophagy.
A Case Report of Brown Recluse Spider Bite.

Brown recluse spider is a spider of the genus Loxosceles and also known as violin spider or fiddle-back spider. Brown recluse spider is characterized by having six eyes, with a pair in front, a pair on both sides, and a gap between the pairs. The other spiders have eight eyes in two rows of four. Brown recluse spider bites are challenging to verify but may be clinically diagnosed with consideration of geographic location, seasonality, and clinical characteristics. We present a case that involves a brown recluse spider bite in a 59-year-old female with malnutrition and polysubstance use who developed systemic symptoms and a dermonecrotic wound. Local wound care and intravenous (IV) antibiotics lead to clinical improvement by hospital day three, at which time the patient left against medical advice. The case highlights the challenges of diagnosing a brown recluse spider bites, particularly in a patient with multiple risk factors for necrotizing soft tissue infection. Furthermore, the present case represents one of the few case reports of a brown recluse spider bite in Michigan.
Characterization of a Putative Fanconi Anemia D2 Protein Histone-Binding Domain and Chromodomain

Fanconi anemia (FA) is a genetic disease characterized by congenital defects, bone marrow failure and heightened cancer susceptibility. FA is caused by biallelic mutations in 16 genes. The FA prote...
The oxidative cleavage of folates. A critical study.

Abstract Alkaline permanganate oxidation has been used to determine the chain length of naturally occurring pteroylpolyglutamates on the assumption that all forms of folates cleave at the C9N10 bond to produce the corresponding p-aminobenzoyl-polyglutamates. The chain length of the latter could be determined by cochromatography with synthetic markers. The products of alkalinc (ammonium bicarbonate buffer, pH 9.0) permanganate oxidation of a number of reduced and oxidized, one-carbon-substituted and unsubstituted folic acid derivatives have been identified, and their yields and stability to the oxidative treatment have been determined. Unsubstituted, oxidized and reduced folic acid and N5-formyl-tetrahydrofolic acid are cleaved at the C9N10 bond to produce p-aminobenzoylglutamic acid. N5, N10-methenyl-tetrahydrofolic acid, N5,N10-methylene-tetrahydrofolic acid, and N10-formyl-tetrahydrofolic acid are not cleaved but are oxidized to N10-formyl-folic acid which is completely stable to the oxidative treatment employed. N5-methyl-tetrahydrofolic acid is not cleaved either but is oxidized to N5-methyl-dihydrofolic acid which upon continued oxidation decomposes slowly to unidentified products. The γ-glutamyl peptide linkage is completely stable to oxidation. Using p-amino-[3,5-3H]benzoylglutamic acid, it is also shown that this product, previously thought to be stable to the oxidative treatment is decomposed by it. The significance of these findings in terms of the errors that may have been introduced in prior estimations of the chain length and pool sizes of the naturally occurring pteroylpolyglutamates is discussed. The possibility of developing a method for the chain length determination of noncleavable pools of one-carbon-substituted folates using [2-14C]folic acid to label the folates in vivo is presented.
Equivalent Frame Analysis for Lateral Loads

The equivalent frame method for analyzing reinforced concrete buildings described in the ACI Building Code Requirements (ACI 318-77) is suitable for analyzing single stories for gravity loading only. A new procedure that permits using the equivalent frame concepts for the analysis of multistory buildings for both lateral and gravity loads is described. Limited verification studies show the method predicts lateral deflections that generally agree with measured deflections. Comparisons of the new analytical procedure with conventional plane frame analyses made using effective slab widths are given. Problems and limitations in applying the method in plane frame and space frame analyses are reviewed.
Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart

While the circulating renin-angiotensin system (RAS) plays an important role in short-term maintenance of cardiovascular homeostasis, recent studies point to a role in long-term cardiovascular regulation for endogenous RAS in target tissues. This article focuses on the multiple effects of tissue angiotensin enzyme (ACE) and angiotensin II (Ang II), its active peptide product. Ang II has been shown to be a potent growth factor in vascular smooth muscle cells. Depending on the local conditions, the vascular response may be either hypertrophy or hyperplasia. The molecular mechanisms involved in the interactions of Ang II with endothelium- and smooth muscle-derived cell products may play important roles in the modulation of vascular structure in hypertension and vascular injury. Evidence also points to a role for Ang II in the development of left ventricular hypertrophy in hypertension. In addition, cardiac RAS may contribute to the pathophysiology of heart failure. Experimental and clinical studies with ACE inhibitors point to a role for tissue ACE activity in the development of atherosclerosis, as well as cardiac hypertrophy and remodeling.
An Integrated Hybrid Nanophotonics Platform

Based on a hybrid-plasmon platform, we report first demonstrations of low-loss, deep-sub-λ waveguiding, plasmon semiconductor Nanolaser and strong emitter-to-waveguide coupling towards compact photonic integrated circuits and quantum optics devices.
Advances in disk technology: performance issues

Although the computer industry has made regular, significant advances in magnetic recording technology for hard disk drives, some advances-such as those in head design, media, and channel technology-are primarily concerned with increasing disk density and do not necessarily improve total performance. The author asks how, for example, does disk density affect data transfer rate? How do multiple platters affect head seek time? And how does partitioning large capacity drives affect performance for each partition? The answers to these questions-and others like them-largely depend on particular configurations and user workload.
Infrared Characteristics of Ocean Water (1.5 –15 μ)

Equations and tabulated values of the index of refraction and the extinction coefficient are presented which can be used to calculate the reflectance of ocean water in the 1.5–15-μ range. Using double beam spectrophotometers, the reflectance of artificial ocean water with respect to the reflectance of distilled water was measured and compared with the calculated values for incidence angles of 60° and 70°. The agreement between the calculated and measured values was found to be well within the limits of experimental accuracy.
Tryptophan-14 is the preferred site of DBNBS spin trapping in the self-peroxidation reaction of sperm whale metmyoglobin with a single equivalent of hydrogen peroxide.

The 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS)-metmyoglobin adduct formed following the horse metmyoglobin-H 2 O 2 reaction has been assigned to both a tyrosyl and a tryptophanyl residue radical. At low H 2 O 2 , hyperfine coupling to a 1 3 C atom in sperm whale metmyoglobin labeled at the tryptophan residues with 1 3 C allowed the unequivocal assignment of the primary adduct to a tryptophanyl radical. Trapping at Trp-14 of sperm whale myoglobin was indicated by greatly decreased electron paramagnetic resonance (EPR) spectral intensity of the DBNBS adducts of the Trp-14-Phe recombinant proteins. Complex EPR spectra with partially resolved hyperfine splittings from several atoms were obtained by pronase treatment of the DBNBS/ .W14F metmyoglobin adducts. The EPR spectra of authentic DBNBS/Tyr adducts were incubation time-dependent; the late time spectra resembled the spectra of pronase-treated DBNBS/W14F sperm whale myoglobin adducts, suggesting formation of an unstable tyrosyl radical adduct in the latter proteins. When the H 2 O 2 :metmyoglobin ratio was increased to 5:1, the EPR spectrum after pronase treatment supported trapping of a tyrosyl radical, although similar decreases in tryptophan content were detected at H 2 O 2 :metmyoglobin ratios of 1:1 and 5:1.