cssi/SciSciGPT-SciSciNet huggingface dataset:
Biosimilars: Implications for health-system pharmacists

Purpose An update on scientific and regulatory challenges in the rapidly evolving field of biosimilar product development is presented. Summary The U.S. market for biosimilar products (i.e., highly similar “follow-on” versions of approved biological drugs) is expected to expand with establishment of an expedited-approval pathway for biosimilars similar to that implemented in European Union countries eight years ago. In 2012, the Food and Drug Administration (FDA) published draft guidance clarifying the requirements of the biosimilars approval pathway; although no biosimilar has yet been approved via that pathway, FDA is engaged in ongoing meetings with a number of potential applicants. Due to molecular differences between innovator products and biosimilar versions, biosimilars are highly sensitive to manufacturing changes that can potentially have important safety and efficacy implications. Establishing the interchangeability of biosimilar and innovator drugs may be difficult at first, and it is possible that some biosimilars might not carry all the same indications for which the reference drug is approved. Pharmaceutical cost savings attained through the use of biosimilars are expected to average 20–30%. With several top-selling biologicals likely to lose patent exclusivity by 2020, health systems should prepare for the availability of new biosimilars by addressing formulary management and therapeutic interchange issues, pharmacovigilance and patient safety concerns, and related financial and operational issues. Conclusion Over the coming years, biosimilars will present opportunities for health care organizations to manage the growth of pharmaceutical expenditures. Pharmacists can play a key role in preparing health systems for projected rapid expansion in the use of biosimilars and associated medication-use policy challenges.
Mass flux at ignition in reduced pressure environments

Ignition of solid combustible materials can occur at atmospheric pressures lower than standard either in high altitude environments or inside pressurized vehicles such as aircraft and spacecraft. NASA’s latest space exploration vehicles have a cabin atmosphere of reduced pressure and increased oxygen concentration. Recent piloted ignition experiments indicate that ignition times are reduced under these environmental conditions compared to normal atmospheric conditions, suggesting that the critical mass flux at ignition may also be reduced. Both effects may result in an increased fire risk of combustible solid materials in reduced pressure environments that warrant further investigation. As a result, a series of experiments are conducted to explicitly measure fuel mass flux at ignition and ignition delay time as a function of ambient pressure for the piloted ignition of PMMA under external radiant heating. Experimental findings reveal that ignition time and the fuel mass flux at ignition decrease when ambient pressure is lowered, proving with the latter what earlier authors had inferred. It is concluded that the reduced pressure environment results in smaller convective heat losses from the heated material to the surroundings, allowing for the material to heat more rapidly and pyrolyze faster. It is also proposed that a lower mass flux of volatiles is required to reach the lean flammability limit of the gases near the pilot at reduced pressures, due mainly to a reduced oxygen concentration, an enlarged boundary layer, and a thicker fuel species profile.
Facilitating Congestion Avoidance in Sensor Networks with a Mobile Sink

The imminent growth of user-centric, pervasive sensing environments promotes sink mobility in an increasing number of event-based, sensor network applications including rescue missions, intrusion detection and smart buildings. In these settings, one of the most critical challenges toward supporting quality of service, is effective distributed congestion avoidance. Congestion control techniques have been proposed in sensor networks mostly in the context of a static sink. In our work, we study the problem of congestion avoidance in the context of sensor networks with a mobile sink. Under sink mobility, various new challenges arise that need to be effectively addressed. Adaptation to sink mobility requires agile as well as effective load estimation techniques. In addition, unlike static networks, path reliability often fluctuates due to path reconfigurations. Thus, injecting traffic during transient periods of poor path quality might wastefully detain network resources. Our approach jointly considers the network load and path quality variations to facilitate intelligent, mobility-adaptive rate regulation at the sources. We implemented our techniques over a Mica2 testbed and through extensive experimental results, we demonstrate the working and benefits of our approach.
A Self-Questioning Strategy to Increase Young Writers' Revising Processes.

Researchers who study the writing process have found that beginning writers do little spontaneous revising of their own texts. This study explores the possibility that beginning writers do not revise because they do not read their own writing. The assumption behind the study is that explicit self-questioning strategies would engage young writers in reading their texts; thus they would become more active revisers. The experimental intervention is a question-prompt computer program (added to a word processing program) that guides the 11 to 16-year-old subjects to examine their own writing by asking themselves questions about their texts. This process was intended to engage the subjects in reading the text closely and revising more extensively. Analyses of the number and nature of revisions indicate that self-reflective question-prompts engage students in reading their texts and lead to significant changes in revising strategy.
A traceable calibration procedure for MEMS-based load cells

Characterizing the mechanical properties of materials and biological systems at the nanoscale requires accurate measurement of forces on the order of μN and less. Due to the scale of the measurements and size of the instrumentation, calibration of nanoscale devices presents a new challenge in metrology. In order to ensure accuracy of results, traceable calibrations must be performed on nanoscale instrumentation. Our group recently developed a novel MEMS-based high resolution load cell with force resolution on the order of μN. This paper reports on a simple method for traceably calibrating our device using dead weights that could be generalized to other MEMS-based load cells. In this article, fabrication of a MEMS load cell is detailed and we compare our calibrated force–displacement curves to a non-linear theoretical prediction, revealing errors as great as 29%.
Metastatic hepatocellular carcinoma presenting as a pancreatic mass by computed tomography scan and mimicking a primary neuroendocrine tumor: a potential pitfall in aspiration cytology.

Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting at late stage and portending a poor prognosis for the patient. The peripancreatic fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic primary pancreatic neoplasms, even in this location. It is crucial to be aware of this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and to develop a strategy to reach the correct diagnosis. We present an endoscopic ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a pancreatic mass radiologically that had neuroendocrine features on various cytological and histological preparations. The metastatic lesions were located surgically in the peripancreatic adipose tissue with involvement of one peripancreatic lymph node. This case illustrates the utility of FNA for diagnosing uncommon presentations of HCC and the importance of clinical history, cell block, and an immunocytochemical panel in determining the origin of the tumor. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc.
E-Resource Round Up

Welcome to another edition of E-Resource Round Up! This issue covers a wide range of e-resource topics, including:Reports from the 2020 Midwest Collaborative for Library Services E-Resources meetin...
Parent and family influences on young women's romantic and sexual decisions

Parents can play an important role in reducing their children's risk for teenage pregnancy and sexually transmitted infections, and in promoting sexual health during adolescence. The purpose of this study was to explore communication between parents, family members and young people and how it influences their romantic and sexual behaviours. Semi-structured interviews were conducted with 28 African American, American Indian, Euro-American and Latina women aged 19–29 years. Findings clustered into five themes. First, mothers were often the primary source of reproductive education. Second, fathers provided valuable guidance, although they were not the first source of information. Third, parental expectations influenced young people's sexual behaviours both positively and negatively. Fourth, aunts, uncles and grandparents were trusted sources of advice for personal discussions. Fifth, over one-third of participants perceived that there was no adult available to them during their teenage years for discussions ...
Trends in pubertal development in Europe

The secular changes in growth and maturation can be seen as indicators of socio-economic and health status. In most European countries the age of onset of puberty and of menarcheal age has been decreasing during the past few decades. The duration of puberty seems also to decrease, though few studies provide sufficient data to support this postulation. The four Dutch nationwide growth surveys are useful examples assessing the secular trend in pubertal development over the past 45 years. Genetic and environmental factors contribute to the secular changes. Environmental factors seem to be the most important. Recently, attention has been given to substances with oestrogen-like actions that are present in nutrients. The possible role of these substances in growth and maturation is discussed.
Exponential inequalities for self-normalized processes with applications

We prove the following exponential inequality for a pair of random variables $(A,B)$ with $B >0$ satisfying the canonical assumption , $E[\exp(\lambda A - \frac{\lambda^2}{2} B^2)]\leq 1$ for $\lambda \in R$, $$P\left( \frac{|A|}{\sqrt{ \frac{2q-1}{q} \left(B^2+ (E[|A|^p])^{2/p} \right) }} \geq x \right) \leq \left(\frac{q}{2q-1} \right)^{\frac{q}{2q-1}} x^{-\frac{q}{2q-1}} e^{-x^2/2} $$ for $x>0$, where $1/p+ 1/q =1$ and $p\geq1$. Applying this inequality, we obtain exponential bounds for the tail probabilities for self-normalized martingale difference sequences. We propose a method of hypothesis testing for the $L^p$-norm $(p \geq 1)$ of $A$ (in particular, martingales) and some stopping times. We apply this inequality to the stochastic TSP in $[0,1]^d$ ($d\geq 2$), connected to the CLT.
An empirical application of McPhee's formal theory of addiction.

(1971). An Empirical Application of McPhee's Formal Theory of Addiction. International Journal of the Addictions: Vol. 6, No. 1, pp. 19-28.
Gained in Translation: Protective Paradigms for the Poststenotic Kidney

Atherosclerotic renovascular disease (ARVD) is more commonly identified than ever before, particularly among the elderly population. By some accounts, >10% of new patients entering dialysis programs in the United States have ARVD as a major contributor to their end-stage renal disease. ARVD is also associated with accelerated renal injury, hypertension, and cardiovascular complications. Renovascular hypertension (RVH) is an independent cardiovascular risk factor and induces greater decline in cardiac function and structure than essential hypertension.1 However, clinical trials show consistently that revascularization of the stenotic renal artery using percutaneous transluminal renal angioplasty (PTRA) results in limited and inconsistent recovery of renal function.2 The reasons for the failure of revascularization to resolve renal dysfunction are complex and may include procedural complications, as well as pre-existing parenchymal injury, including endothelial dysfunction, inflammation, fibrosis, and microvascular remodeling in the poststenotic kidney.3 Atherogenic comorbidities constitute important catalysts of renal damage in ARVD. In fact, atherosclerotic nephropathy can produce renal damage even with hemodynamically insignificant stenoses,4 suggesting a direct effect of atherosclerosis on the kidney. Furthermore, unlike patients with fibromuscular dysplasia, in patients with ARVD a decrease in stenotic-kidney perfusion does not correlate with the angiographic degree of stenosis,5 and cortical perfusion is reduced even with mild stenoses, underscoring the contribution of additional pathogenic factors to renal damage. Therefore, the quest for underlying mechanisms and promising interventions mandates development of experimental platforms that not only involve renal artery stenosis but also emulate the atherosclerotic milieu. Useful models of renal artery stenosis have been achieved in many laboratory animal species, including mice, rats, hamsters, rabbits, dogs, and monkeys, but usually without application of comorbidities.6 Our studies focused on developing a swine model with gradually developing renal artery stenosis secondary to unilateral renal arterial implantation of a local irritant coil. The advantages …
Gut, bugs, and brain: Role of commensal bacteria in the control of central nervous system disease

The mammalian gastrointestinal track harbors a highly heterogeneous population of microbial organisms that are essential for the complete development of the immune system. The gut microbes or "microbiota," coupled with host genetics, determine the development of both local microbial populations and the immune system to create a complex balance recently termed the "microbiome." Alterations of the gut microbiome may lead to dysregulation of immune responses both in the gut and in distal effector immune sites such as the central nervous system (CNS). Recent findings in experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis, suggest that altering certain bacterial populations present in the gut can lead to a proinflammatory condition that may result in the development of autoimmune diseases, in particular human multiple sclerosis. In contrast, other commensal bacteria and their antigenic products, when presented in the correct context, can protect against inflammation within the CNS.
2.2.1 Collaborative Systems Thinking Research: Exploring systems thinking within teams

This paper describes ongoing research that seeks to develop an empirical basis for collaborative systems thinking, defined as "an emergent behavior of teams resulting from the interactions of team members and utilizing a variety of thinking styles, design processes, tools, and communication media to consider system attributes, interrelationships, context and dynamics towards executing systems design". This type of thinking is critically important to addressing engineering systems challenges, and the research seeks to inform and enable effective systems engineering practice in contemporary engineering enterprises. Focusing on the aerospace domain, collaborative systems thinking is examined through the alignment of enterprise culture and standard technical processes. This paper draws on a variety of literature to compose a definition of collaborative systems thinking and propose a research agenda going forward.
Stabilization of millimeter-wave frequencies from passively mode-locked semiconductor lasers using an optoelectronic phase-locked loop

The use of an optoelectronic phase-locked loop to stabilize the pulsation frequency of a three-section, passively mode-locked quantum well laser diode at 41 GHz is discussed. It is shown that the free-running mode-locked signal, with a radio frequency (RF) linewidth of 770 kHz, can be stabilized to the linewidth of a reference RF oscillator ( >
Histological Analysis Reveals Larger Size at Maturity for Southern Flounder with Implications for Biological Reference Points

Abstract For fish stocks managed using biological reference points based upon spawning biomass, it is critical to have accurate maturity schedules. We investigated size- and age-dependent patterns in maturity for southern flounder Paralichthys lethostigma, a flatfish supporting valuable coastal fisheries in North Carolina and throughout its range. We evaluated both macroscopic and histological methods over two consecutive reproductive seasons. Histological analyses revealed that maturity occurred at larger sizes and older ages than previously estimated. Length at 50% maturity (L 50) was estimated at 408 mm total length (TL), which was more than 60 mm larger than currently assumed, and was relatively stable between study years. We found that only 44% of age-1 southern flounder were mature compared with an estimated 74% in an earlier study. We suspect that most of the differences in maturity timing of southern flounder between our findings and previous studies stem from macroscopic assignment error. During ...
A 4*4 active array using Gunn diodes

The authors present results from a new 16-element active array incorporating Gunn diodes (for 10 GHz oscillations). The Gunn diode heating problem previously encountered was overcome by using patch antennas in which the ground plane serves as a diode heat sink. An EIRP (equivalent isotropic radiated power) of 22 W was measured for this array. It is suggested that, by increasing the number of elements and using higher power diodes, EIRP of several hundred watts may be possible. >
Two Major Histocompatibility Complex Class I-Restricted Epitopes of the Borna Disease Virus p10 Protein Identified by Cytotoxic T Lymphocytes Induced by DNA-Based Immunization

Borna disease virus (BDV) infection of Lewis rats is the most studied animal model of Borna disease, an often fatal encephalomyelitis. In this experimental model, BDV-specific CD8 + cytotoxic T lymphocytes (CTLs) play a prominent role in the immunopathogenesis of infection by the noncytolytic, persistent BDV. Of the six open reading frames of BDV, CTLs to BDV X (p10) and the l-polymerase have never been studied. In this study, we used plasmid immunization to investigate the CTL response to BDV X and N. Plasmid-based immunization was a potent CTL inducer in Lewis rats. Anti-X CTLs were primed by a single injection of the p10 cDNA. Two codominant p10 epitopes, M 1 SSDLRLTLL 10 and T 8 LLELVRRL 16 , associated with the RT1.A l major histocompatibility complex class I molecules of the Lewis rats, were identified. In addition, immunization with a BDV p40-expressing plasmid confirmed the previously reported RT1.A l -restricted A 230 SYAQMTTY 238 peptide as the CTL target for BDV N. In contrast to the CTL responses, plasmid vaccination was a poor inducer of an antibody response to p10. Three injections of a recombinant eukaryotic expression plasmid of BDV p10 were needed to generate a weak anti-p10 immunoglobulin M response. However, the antibody response could be optimized by a protein boost after priming with cDNA.
The Molecular Perspective: Epidermal Growth Factor

The Oncologist 2003;8:496-497 www.TheOncologist.com In the human body, cells must ask for permission to multiply. This is essential during the perfectly orchestrated growth that shapes an embryo, and is also essential in later life to restrict growth to the few places where it is needed, such as wounds that need to be healed. Normally, tissues communicate through a flurry of growth factors, passed from cell to cell to control growth levels and ensure that cells stay within the normal limits. Cancer cells, however, often acquire the ability to give themselves this permission, so they can grow without worrying about the consequences to their neighbors. Epidermal growth factor (EGF) and its receptor are one place where cancer cells short-circuit the normal controls. EGF is part of a complex network of growth factors and receptors that together help to modulate the growth of cells. EGF is released by cells, and then is picked up either by the cell itself, stimulating its own growth, or by neighboring cells, stimulating their ability to divide. Receptors on the surface of the cell bind to EGF and relay the signal inside. Fundamentals of Cancer Medicine The Oncologist
Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells

OR 97331-6512 Abstract Apolipoprotein E (apoE) is synthesized and se- creted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage choles- terol homeostasis by forming lipid complexes (nascent- HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endoge- nously produced apoE in mediating the recruitment of cel- lular cholesterol. THP-1 human monocytes were differenti- ated (300 n M phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol load- ing with acetylated LDL (50 m g protein/ml). ApoA-I (10 m g/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied by a signif- icant increase in the UC/PL mole ratio of nascent HDL (UC/PL 5 0.80 6 0.15) in the medium compared to com- plexes isolated from macrophages (UC/PL 5 0.59 6 0.08). Significantly more (70%) nascent-HDL were formed in incu- bations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4- fold increases were observed with macrophages and mac- rophage-foam cells, respectively, compared to incubations in the absence of apoA-I. Despite the increase in medium apoE accumulation, a majority (85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macro- phage-foam cells possessed apoA-I without apoE. ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL repre- sents a major metabolic pathway of cellular cholesterol re- cruitment compared to the endogenous production of apoE.— Bielicki, J. K., M. R. McCall, and T. M. Forte. Apoli- poprotein A-I promotes cholesterol release and apolipopro- tein E recruitment from THP-1 macrophage-like foam cells. J. Lipid Res. 1999. 40: 85-92.
Reformulating student contributions in tutorial dialogue

While some recent work in tutorial dialogue has touched upon tutor reformulations of student contributions, there has not yet been an attempt to characterize the intentions of reformulations in this educational context nor an attempt to determine which types of reformulation actually contribute to student learning. In this paper we take an initial look at tutor reformulations of student contributions in naturalistic tutorial dialogue in order to characterize the range of pedagogical intentions that may be associated with these reformulations. We further outline our plans for implementing reformulation in our tutorial dialogue system, Rimac, which engages high school physics students in post problem solving reflective discussions. By implementing reformulations in a tutorial dialogue system we can begin to test their impact on student learning in a more controlled way in addition to testing whether our approximation of reformulation is adequate.
Shifting the focus: Nonpathologizing approaches to healing from betrayal trauma through an emphasis on relational care

ABSTRACTAs the diagnosis and treatment of mental disorders has become increasingly medicalized (Conrad & Slodden, 2013), consideration for the relational nature of trauma has been minimized in the healing process. As psychiatrist R. D. Laing (1971) outlined in his essays, the medical model is an approach to pathology that seeks to find medical treatments for symptoms and syndromes based on categorized diagnoses. We argue that such a model implicitly locates the pathology of trauma within the individual instead of within the person(s) who perpetrated the harm or the social and societal contexts in which it took place. In this article, we argue that this framework is pathologizing insofar as it both prioritizes symptom reduction as the goal of treatment and minimizes the significance of relational harm. After providing a brief overview of betrayal trauma (Freyd, 1996) and the importance of relational processes in healing, we describe standard treatments for betrayal trauma that are grounded in the medical m...
FT-IR Spectroscopy and Density Functional Theory Calculations of Carbon-13 Isotopologues of the Helical Peptide Z-AIB(6)-OTBU

Isotope-edited FT-IR spectroscopy is a combined synthetic and spectroscopic method used to characterize local (e.g., residue-level) vibrational environments of biomolecules. We have prepared the 31...
Carotid endarterectomy under local and/or regional anesthesia has less risk of myocardial infarction compared to general anesthesia: An analysis of national surgical quality improvement program database

Multiple studies have evaluated the effect of anesthesia type on carotid endarterectomy with inconsistent results. Our study compared 30-day postoperative myocardial infarction, stroke, and mortality between carotid endarterectomy under local or regional anesthesia and carotid endarterectomy under general anesthesia utilizing National Surgical Quality Improvement Program database. All patients listed in National Surgical Quality Improvement Program database that underwent carotid endarterectomy under general anesthesia and local or regional anesthesia from 2005 to 2011 were included with the exception of patients undergoing simultaneous carotid endarterectomy and coronary artery bypass grafting. The data revealed substantial differences between the two groups compared, and these were adjusted using multiple logistic regression. Postoperative myocardial infarction, stroke, and death at 30 days were compared between the two groups. A total of 42,265 carotid endarterectomy cases were included. A total of 37,502 (88.7%) were performed under general anesthesia and 4763 (11.3%) under local or regional anesthesia. Carotid endarterectomy under local or regional anesthesia had a significantly decreased risk of 30-day postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia (0.4% vs 0.86%, p = 0.012). No statistically significant differences were found in postoperative stroke or mortality. Carotid endarterectomy under local or regional anesthesia carries a decreased risk of postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia. Therefore, patients at risk of postoperative myocardial infarction undergoing carotid endarterectomy, consideration of local or regional anesthesia may reduce that risk.
Methods for Estimating Adult Densities of Liriomyza trifolii (Diptera: Agromyzidae) in Staked Tomato Fields

Linear regression equations for estimating densities of adult liriomyza trifolii (Burgess) in staked tomato fields were developed from data collected in fall 1986 and spring 1987 in Florida. Densities of adult flies were estimated separately for the fall and spring seasons as a function of the mean numbers of flies collected per day on yellow sticky cards. Predicted densities were compared with field estimates. In the fall, all predicted adult densities were within 95% CIs of field estimates. In the spring, 67% of the predicted densities fell within 95% CIs of field estimates. Predicted adult densities early in the season, when the leafminer population was below an action threshold, were the only predicted values not within the CLs of field estimates. Equations for estimating absolute density of adults should be of value for making leafminer pest control decisions.
Mycophenolate Mofetil and Mood Changes in Children with Skin Disorders

The Risk Evaluation and Mitigation Strategy program that the U.S. Food and Drug Administration has mandated has intensified the counseling associated with prescribing mycophenolate mofetil (MMF), because of its teratogenicity. In this brief report, two children are described who were prescribed MMF and within weeks developed psychiatric symptoms, with rapid resolution after discontinuation of the medication and no recurrence over 4 years of follow-up. Mood disorders are a rare but possible side effect that should be mentioned when discussing MMF with patients and families. Prompt discontinuation of the drug should lead to reversal of symptoms when the drug is implicated.
Subinguinal Microsurgical Varicocelectomy: A Technical Critique and Statistical Analysis of Semen and Pregnancy Data

AbstractA total of 606 modified subinguinal microscopic varicocelectomies was performed on 466 outpatients using local anesthesia and sedation. The patients selected for these procedures were infertile for at least 12 months and had at least 1 semen parameter below threshold level: less than 20 million per ml., less than 50% motility or less than 40% normal morphological forms. The lymphatics, spermatic artery and vas were preserved, whereas all refluxive veins were transected or obliterated. Postoperative complications were limited to transient epididymal discomfort in 5.5% of the patients, ecchymosis at the wound site in 3.4% and wound inflammation in 2.4%. There was only 1 permanent hydrocele. The palpable recurrence rate was 0.82% per procedure. The median values for each semen parameter were compared preoperatively and postoperatively by the Wilcoxon signed rank test. The differences in the median values were significant for all parameters. As an alternative statistical model, the average preoperativ...
Influenza A Virus Binding to Human Neutrophils and Cross-Linking Requirements for Activation

Although neutrophils are not viewed as a principal defense against influenza A virus (IAV) infection, their interactions are both complex and clinically relevant. Activation of the neutrophil is distinctive from that described for chemoattractants. To more fully characterize the pathway by which IAV stimulates the human neutrophil, we have examined its binding characteristics. First, inhibition studies with various sialic acid-containing and sialic-free sugars showed that IAV binds to sialic acid residues and activates receptors distinct from those used by Concanavalin-A (Con-A) and formyl-methionyl-leucyl-phenylalanine (FMLP) and that overlap those bound by wheat germ agglutinin (WGA). That viral hemagglutinin (HA) mediates viral binding and activation was shown by preincubating neutrophils with purified monovalent bromelain-released HA (BHA) and showing that IAV-induced membrane depolarization and hydrogen peroxide (H2O2) production were inhibited approximately 95%. However, binding inhibition required significantly higher concentrations of purified HA, suggesting that binding and cell activation have different interactive requirements. Desialation of the neutrophil surface membrane by neuraminidase treatment resulted in a 90.6% +/- 4.4% and 53.1% +/- 8.7% inhibition of IAV activation of neutrophils and viral binding, respectively. Resialation with ganglioside GT1b totally restored viral binding, but did not reverse the inhibition of activation. Thus, although HA was shown to mediate binding and neutrophil activation, viral binding per se was insufficient to stimulate the cell. Having demonstrated the functional role of HA, we sought to establish the mechanism of stimulation. HA in three different forms (BHA, HA-rosettes, and HA-liposomes) failed to activate the cell, although H2O2 production evoked by IAV stimulation was reduced in competitive inhibition studies with each preparation. Upon cross-linking with a monoclonal antibody to HA, activation comparable to that of intact virus was observed. The requirement for cross-linking of functional receptors, as opposed to activation through the neutrophil Fc receptor, was confirmed in experiments using staphylococcal A protein. These studies have shown the chemical specificity of IAV binding to the human neutrophil, the character of the receptor(s) stimulated to activate the IAV-evoked response, and the activation requirement for cross-linking those receptors responsible for stimulating functional responses.
‘Navigating sovereignty under a Cold War military industrial colonial complex: US military empire and Marshallese decolonization’

AbstractAs World War II unsettled the global balance of power ushering in a wave of decolonization, the postwar period also saw the expansion of US military imperialism into Micronesia. In this central Pacific region, a new colonial era began rooted in US strategic concerns and mandated under a 1947 United Nations Trusteeship Agreement. During the Cold War, the United States buttressed its nuclear arsenal by testing its deadliest weapons of mass destruction (nuclear and intercontinental ballistic missile) in the Marshall Islands, residing on the eastern edge of Micronesia. This weapons testing program would inform Marshallese struggles towards self-determination, ultimately shaping the contours of Marshallese sovereignty as the region achieved formal decolonization through a Compact of Free Association in 1986.
Academic Preparation and Confidence Level of Elementary-School Science Teachers

Professional societies and state departments of education have mandated guidelines for teaching elementary science. Although school districts and ultimately teachers are responsible for following s...
Timing and duration of nursing from birth affect neonatal porcine uterine matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1

Nursing for 2 d from birth supports neonatal porcine uterine and cervical development. However, it is not clear how timing or duration of lactocrine signaling from birth (postnatal day = PND 0) affects development of neonatal female reproductive tract tissues. Therefore, studies were conducted to determine effects of age at first nursing and duration of nursing from birth on specific elements of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) system in uterine and cervical tissues at PND 2. When nursing was initiated at 0 h or 30 min of age, targeted proteins, including proMMP9 and MMP9, were detected in uterine and cervical tissues on PND 2, as was uterine TIMP1. However, these proteins were undetectable when nursing was delayed for 12 h and when gilts were fed milk replacer for 48 h from birth. Increasing the duration of nursing from 30 min to 12 h from birth increased uterine (P < 0.05) and cervical (P < 0.001) MMP9 levels to those observed in gilts nursed for 48 h. Similarly, uterine TIMP1 levels increased with duration of nursing. Uterine MMP2 levels were detectable but unaffected by age at first nursing or duration of nursing from birth. Uterine MMP2 and MMP9 activities, monitored by zymography, reflected immunoblotting data. Results provide evidence for the utility of MMP9 and TIMP1 as markers of age- and lactocrine-sensitive porcine female reproductive tract development.
Repackaging photon energy using exciton fission and fusion in molecular crystals(Conference Presentation)

The ability to downconvert (1 photon to 2 photons) and upconvert (2 photons to 1 photon) energy can boost solar energy conversion efficiencies by 30% or more. Downconversion can be accomplished through exciton fission, in which an initially created high energy singlet exciton spontaneously splits into a pair of lower energy triplet excitons. In organic semiconductors like tetracene and rubrene, the Frenkel character of the excitons leads to energetically separate singlet and triplet bands, providing an ideal set of energy levels for both processes to take place. In this talk, our efforts to understand the basic photophysics of singlet fission using time-resolved transient absorption, photoluminescence and magnetic field effects will be described. The role of molecular packing in controlling the fission rate will be emphasized. Upconversion occurs via the reverse process, where a pair of triplet excitons fuse into a high-energy singlet state. While most approaches to upconversion require a sensitizer to populate the dark triplet states, an alternate approach is to take advantage of low-energy intermolecular states in organic crystals to sensitize triplet states. We show that this process can be surprisingly efficient in certain molecular crystals, even in the absence of sensitizers. The exciton interactions responsible for this process are investigated using steady-state and time-resolved spectroscopy.
Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main and Multivessel Coronary Artery Disease: Do We Have the Evidence?

Approximately 60 randomized controlled trials performed over the last 3 decades have failed to demonstrate statistically significant differences in death or myocardial infarction (MI) between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), apart from a few notable exceptions in which CABG was superior to PCI. The benefits for CABG have been reported in patients with diabetes mellitus with multivessel disease and in patients with and without diabetes mellitus with 3-vessel disease and intermediate or high SYNTAX trial (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) scores (≥23). 1 In theory, although PCI is limited to treatment of culprit lesions, by bypassing the length of the epicardial vessel, CABG may address both today’s and tomorrow’s culprits by bypassing vulnerable plaques responsible for future adverse events.2 This mechanism may underlie the effectiveness of CABG in patients with extensive coronary disease. However, most completed trials in multivessel disease may have limited relevance to contemporary practice because of technological and pharmacological advances that have changed the practice of PCI, including the introduction of safer and more effective drug-eluting stents; more judicious use of PCI, based on fractional flow reserve measurements; PCI optimization with intravascular ultrasound and optimal coherence tomography; and improved antithrombotic and antiplatelet agents. In addition, the use of risk stratification and assessment tools, such as the baseline and residual SYNTAX scores, which assess the potential extent of revascularization, may be helpful in identifying patients who may have …
The economic burden of neonatal abstinence syndrome in the United States

Background and aims While hospital charges related to neonatal abstinence syndrome (NAS) have increased recently, there are no data available regarding costs. Therefore, we sought to describe the NAS population and compare with the non-NAS population, determine the incidence of NAS in the United States and estimate the total annual costs and hospital days of NAS admissions, and estimate the incremental costs and length of stay of an NAS admission compared with a non-NAS admission. Design Retrospective, observational study. Data were obtained from the Kids' Inpatient Database (2003–12). Survey-weighting was used to obtain national counts of NAS births. The incremental burden of costs and length of stay were estimated for NAS admissions and compared to non-NAS admissions. Setting United States hospitals from states participating in the Kids' Inpatient Database (KID), a nationally representative sample of all-payer in-patient pediatric discharges. Participants Infants with a diagnosis of NAS (27 943) were identified from the KID using ICD-9-CM codes and compared with non-NAS infants (3 783 629). Measurements Primary outcome measures were provider costs and length of stay for NAS and non-NAS admissions. Costs were calculated using cost-to-charge ratios and were adjusted for inflation to 2014 US dollars. Findings Between 2003 and 2012, NAS admissions increased more than fourfold, resulting in a surge in annual costs from US$61 million and 67 869 hospital days in 2003 to nearly US$316 million and 291 168 hospital days in 2012. For an infant affected by NAS, the hospital stay was nearly 3.5 times as long (16.57 hospital days compared with 4.98 for a non-NAS patient, P < 0.001) and the costs more than three times greater (US$16 893 compared to US$5610 for a non-affected infant, P < 0.001). Conclusion The incidence of neonatal abstinence syndrome is increasing in the United States, and carries an enormous burden in terms of hospital days and costs. The number of US hospital admissions involving neonatal abstinence syndrome increased more than fourfold between the years 2003 and 2012. In 2012, neonatal abstinence syndrome cost nearly $316 million in the United States.
Twelve Problems with Substantive Due Process

I present twelve quick problems for the idea that “without due process of law” in the Fifth or Fourteenth Amendments can be tolerably paraphrased as “unreasonably”: (1) Textually, Magna Charta and its progeny treat “due process of law” as a restriction on methods of proving accusations. (2) These statutes’ contexts make clear that they limit royal power rather than giving the king a massive power (and duty) to review earlier statutes for reasonableness. (3) The most promising purported early instance of reasonableness review, Dr. Bonham’s Case, makes no mention of Magna Charta or its progeny. (4) Blackstone says that, while regrettable, prospectively-adopted and lawfully-imposed disproportionate sentences are consistent with Magna Charta and its progeny. (5) “Process” in the Sixth Amendment refers to factfinding writs. (6) No purported instances of antebellum substantive due process adopt a reasonableness reading. (7) Republicans simultaneously condemned slavery as immoral but held that slaves could be “lawfully claimed” and fugitives “lawfully reclaimed.” (8) Responding to Dred Scott, Lincoln explained the Fifth Amendment as a requirement of prospectivity and lawfulness, not an absolute protection for liberty or property. (9) Republicans held that “duly convicted” in the Thirteenth Amendment required conviction by due process of law, but allowed disproportionate, unreasonable sentences. (10) “Law” in the Privileges or Immunities Clause can be unreasonable or unjust. (11) Reverdy Johnson embraced due process while opposing the Civil Rights Act of 1866 and condemning the Privileges or Immunities Clause as vague and open-ended. (12) The history of citizens-only privileges makes the Privileges or Immunities Clause the only plausible source for a constitutional ban on unreasonable discrimination.
Spectral clustering based on learning similarity matrix.

Motivation Single-cell RNA-sequencing (scRNA-seq) technology can generate genome-wide expression data at the single-cell levels. One important objective in scRNA-seq analysis is to cluster cells where each cluster consists of cells belonging to the same cell type based on gene expression patterns. Results We introduce a novel spectral clustering framework that imposes sparse structures on a target matrix. Specifically, we utilize multiple doubly stochastic similarity matrices to learn a similarity matrix, motivated by the observation that each similarity matrix can be a different informative representation of the data. We impose a sparse structure on the target matrix followed by shrinking pairwise differences of the rows in the target matrix, motivated by the fact that the target matrix should have these structures in the ideal case. We solve the proposed non-convex problem iteratively using the ADMM algorithm and show the convergence of the algorithm. We evaluate the performance of the proposed clustering method on various simulated as well as real scRNA-seq data, and show that it can identify clusters accurately and robustly. Availability and implementation The algorithm is implemented in MATLAB. The source code can be downloaded at https://github.com/ishspsy/project/tree/master/MPSSC. Supplementary information Supplementary data are available at Bioinformatics online.
Electronic Properties of Amorphous Semiconductors

Representing systems of higher complexity, amorphous semiconductors require for their characterization a larger number of parameters than their crystalline counterparts. Furthermore, the theoretical difficulty of calculating the distribution of electronic states and their transport properties in disordered structures and the resulting need for simplifying approximations provide the theoretical expressions with considerable flexibility. At the same time amorphous semiconductors yield experimental data which are typically less structured and hence less rich in information than the equivalent data obtained with crystalline semiconductors. As a consequence, research on amorphous semiconductors is ironically often hampered by ‘good agreement with theory’. Many experiments fail to distinguish between mechanisms of quite different physical origin. This makes the problem of extracting a coherent picture from the experiments particularly difficult.
Contrasting variation within and covariation between gender-related traits in autogamous versus outcrossing species: Alternative evolutionary predictions

We present several predictions concerning the expression of genetic variation in, and covariation among, gender-related traits in perfect-flowered plant taxa with different breeding systems. We start with the inference that the pollen:ovule (P/O) ratio in obligately autogamous species (in which the ovules in a flower are fertilized only by the pollen it produces) should be under much stronger stabilizing selection than in outcrossing taxa. Consequently, we predict that obligately autogamous taxa should exhibit lower genetic coefficients of variation in the P/O ratio. Nevertheless, genetic variation in both pollen and ovule production per flower might persist within autogamous as well as outcrossing populations. In autogamous taxa, genotypes with relatively few pollen grains and ovules per flower (but producing relatively high numbers of flowers) and genotypes with comparatively high numbers of gametes per flower (but producing relatively few flowers) could co-exist if lifetime flower production is selectively neutral. In contrast, in outcrossers, the maintenance of genetic variation in ovule and pollen production per flower might result predominantly from their ability to maintain variation in phenotypic and functional gender. Given genetic variation in primary sexual traits, we predict that the genetic correlation between investment in male and female gametes per flower should qualitatively differ between selfers and outcrossers. We predict a positive genetic correlation between pollen and ovule production per flower in obligately autogamous taxa, primarily because strong stabilizing selection on the P/O ratio should select against the gender specialists that would be necessary to effect a negative genetic correlation between mean pollen and ovule production per flower. Moreover, the fact that autogamous individuals are 50% female and 50% male means that gender-biased phenotypes cannot be functionally gender-biased, preventing selection from favouring phenotypic extremes. In contrast, in outcrossing taxa, in which functionally male- and female-biased genotypes may co-exist, the maintenance of contrasting genders could contribute to the expression of negative genetic correlations between pollen and ovule production per flower. We discuss these and a number of corollary predictions, and we provide a preliminary empirical test of the first prediction.