cssi/SciSciGPT-SciSciNet huggingface dataset:
Leucine increases mitochondrial metabolism and lipid content without altering insulin signaling in myotubes.

Abstract Elevated circulating branched-chain amino acids (BCAA) such as leucine have been consistently correlated with increasing severity of insulin resistance across numerous populations. BCAA may promote insulin resistance through either mTOR-mediated suppression of insulin receptor substrate-1 or through the accumulation of toxic BCAA catabolites. Although the link between circulating BCAA and insulin resistance has been consistent, it has yet to be concluded if BCAA causally contribute to the development or worsening of insulin resistance. This work investigated the effect of leucine both with and without varying levels of insulin resistance on metabolism, metabolic gene expression, and insulin signaling. C2C12 myotubes were treated with and without varied concentrations of leucine up to 2 mM for 24 h both with and without varied levels of insulin resistance. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Mitochondrial metabolism was measured via O2 consumption. Leucine at 2 mM increased oxidative metabolism as well as gene expression of mitochondrial biogenesis, which was associated with increased cellular lipid content. Despite increased lipid content of leucine-treated cells, neither acute nor chronic leucine treatment at 2 mM affected insulin signaling in insulin sensitive, mildly insulin resistant, or severely insulin resistant cells. Similarly, leucine at lower concentrations (0.25 mM, 0.5 mM, and 1 mM) did not alter insulin signaling either, regardless of insulin resistance. Leucine appears to improve myotube oxidative metabolism and related metabolic gene expression. And despite increased lipid content of leucine-treated cells, leucine does not appear to alter insulin sensitivity either acutely or chronically, regardless of level of insulin resistance.
Pancreas donor selection

Abstract Pancreas transplantation is the only durable cure for insulin-dependent diabetes mellitus. While results have significantly improved, listing for and transplantation of pancreatic allografts appears to be decreasing. Data on pancreas outcomes suggest that even “nonideal” allografts can be safely used to expand the donor supply. The chapter reviews the outcomes with ideal and nonideal allografts such as those from donors who are older, had high body mass index, or donated after cardiac death. Pancreas outcome can be effectively and accurately predicted when using the Pancreas Donor Risk Index (P-DRI) which is based on preoperative variables including donor gender, age, race, BMI, height, cause of death, preservation time, DCD status, and serum creatinine. Although the P-DRI scoring system is highly reliable, the final assessment of the safety of transplant must be made by direct examination of the allograft after recovery by an experienced pancreas transplant surgeon.
Experiments in multiple-waveband passive polarimetric and active infrared imaging for material classification

Unique laboratory experiments are conducted using multiple waveband passive polarimetric and active infrared imaging systems to measure the optical signature of a diverse sample set in support of innovative research in material classification. The primary objective of this work is to explore the feasibility of utilizing multiple sensors of varying waveband or modality to enable or improve classification of common materials relevant in remote sensing applications. This objective includes current remote sensing technologies such as passive polarimetric imaging across multiple infrared wavebands, and light detection and ranging (LiDAR) active imaging. Therefore, to fully explore this objective, representative measurements of diverse materials are collected with three passive polarimeters and a LiDAR system. The measurements characterize material properties such as bidirectional reflectivity, directional emissivity, and surface roughness, which can be used for material classification. Typical passive polarimetric classification techniques assume the polarized signature is generated by reflection, and the imaging geometry is known. We propose to utilize both the polarized signature created by reflections as well as self-emission from the material. The reflectivity and imaging geometry estimations are assisted with the inclusion of LiDAR measurements. We present details of the experiment setup, sample set, analysis of imagery, and observations drawn from experimental results. The capability of classifying materials using passive polarimetric and active infrared imaging systems is investigated.
Synthesis and Characterization of a Tetradentate, N-Heterocyclic Carbene Copper(II) Complex and Its Use as a Chan–Evans–Lam Coupling Catalyst

Copper N-heterocyclic carbenes (NHCs) are an emerging area of focus for catalysis and other applications. Using a straightforward methodology, a new and highly modifiable tetradentate copper(II) NH...
Private Law, Public Law, and the Production of American Virtue

This Essay, contributed to a festschrift celebrating the scholarship of Marshall Shapo, suggests that the time has come to revitalize private law – tort law, in particular – as an engine of national virtue. The groundswell of activism in the summer of 2020 lends itself to particularizing this argument to the virtue of racial justice, but it is equally applicable to gender justice, economic justice, and innumerable other areas where social fracture burdens human flourishing. The piece summarizes the intellectual history that has led legal academics to treat public law as the only legal intervention applicable to social ills like racism. It then pivots to survey how disciplines outside law understand the component parts of racism and the most effective responses to them. Sociologists have observed that systemic drivers of racism which play out in public are made possible in large part by individual drivers of racism which play out in private; these include, “most insidiously” white denial and apathy about racial inequality. Political scientists have suggested that a powerful mechanism to address this private racism is the centering of Black people as narrators of their life experiences and the positioning of white people as attentive listeners to those stories. The piece goes on to suggest that tort litigation has a unique ability to facilitate this process, and thus may produce distinct shifts in private attitude that complement the systemic reforms at the heart of public law. Finally, in an act of legal archaeology, the piece shows these processes at work in the iconic battery case of Fisher v. Carrousel Motor Hotel, Inc. In conclusion, it suggests that Marshall Shapo’s entire body of work can be understood as a commitment to tort’s virtue-production capacity.
Original antigenic sin responses to heterologous Betacoronavirus spike proteins are observed in mice following intramuscular administration, but are not apparent in children following SARS-CoV-2 infection

BackgroundThe effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood. ObjectivesWe sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike protein on serologic responses to SARS-CoV-2 spike protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). MethodsGroups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 spike, and SARS-CoV-2 neutralization. Sera from children hospitalized with acute COVID-19, MIS-C or healthy controls (n=14 per group) were analyzed for these same antibodies. ResultsMice primed with SARS-CoV-2 spike and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P=0.012), these titers correlated positively with both SARS-CoV-2 binding (r=0.7577, P<0.001) and neutralizing (r=0.6201, P=0.001) antibodies. ConclusionsPrior murine exposure to HKU1 spike protein completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.
The Gender Credibility Gap: All-Male Boards and Substantive Gender Representation in Central Banking

Why do some countries appoint women to central bank boards and others not? Women held only 11% of seats on global central bank boards between 2000 and 2015, with much smaller representation in years prior and even lagging behind the meager 16 % world-wide average percent of women in national cabinets. We argue that the dearth of female central bankers stems from gender’s impact on central bankers’ ability to signal commitments to price stability. Governments that are concerned with inflation often seek central bankers that exude anti-inflationary bona fides. We argue that this trait is often heuristically informed by gender, such that women are especially under-represented where the need for individual bankers to project monetary conservatism is large. We hypothesize that the need is greatest and female central bankers scarcest in countries with histories of inflation, and with independent central banks and flexible exchange rates, both of which highlight central banker’s personal reputation for monetary stability. We test our theories using a new dataset on the gender composition of central bank boards in 114 countries for years 1998-2015 and find support for our theory. Notably, that support is strongest in the context of long-term trends rather than year-to-year changes. That is consistent with work on the long run political effects of memories of inflation and hyperinflation.
Calibration of a Rapid-Scan Polarizing Michelson Interferometer and InSb Detector

The application of FIR interferometry to plasma diagnosis requires an accurate relative calibration. Techniques are described whereby calibration using mercury arc lamps and other sources is performed. These calibrations reveal serious channelling problems in the detector and lamp. Modifications in these system elements have been performed to correct these problems.
Coded communities: organizing boundless diversity

Communication researchers have used speech codes theory to interpret local conduct. This qualitative meta-analysis draws upon twenty years of peer-reviewed journal articles and books (2000–2019) th...
You Can Count on Monsters: The First 100 Numbers and Their Characters

This book is a unique teaching tool that takes math lovers on a journey designed to motivate kids (and kids at heart) to learn the fun of factoring and prime numbers. This volume visually explores the concepts of factoring and the role of prime and composite numbers. The playful and colorful monsters are designed to give children (and even older audiences) an intuitive understanding of the building blocks of numbers and the basics of multiplication. The introduction and appendices can also help adult readers answer questions about factoring from their young audience. The artwork is crisp and creative and the colors are bright and engaging, making this volume a welcome deviation from standard math texts. Any person, regardless of age, can profit from reading this book. Readers will find themselves returning to its pages for a very long time, continually learning from and getting to know the monsters as their knowledge expands. You Can Count on Monsters is a magnificent addition for any math education program and is enthusiastically recommended to every teacher, parent and grandparent, student, child, or other individual interested in exploring the visually fascinating world of the numbers 1 through 100.
Engineering Risk Assessment of a dynamic space propulsion system benchmark problem

Abstract The Engineering Risk Assessment (ERA) team at NASA Ames Research Center develops dynamic models with linked physics-of-failure analyses to produce quantitative risk assessments of space exploration missions. This paper applies the ERA approach to the 2014 Probabilistic Safety Assessment and Management conference Space Propulsion System Benchmark Problem, which investigates dynamic system risk for a deep space ion propulsion system over three missions with time-varying thruster requirements and operations schedules. The dynamic missions are simulated using commercial software to generate integrated loss-of-mission (LOM) probability results via Monte Carlo sampling. The simulation model successfully captured all dynamics aspects of the benchmark missions, and convergence studies are presented to illustrate the sensitivity of integrated LOM results to the number of Monte Carlo trials. In addition, to evaluate the relative importance of dynamic modeling, the Ames Reliability Tool (ART) was used to build a series of quasi-dynamic, deterministic models that incorporated varying levels of the problem׳s dynamics. The ART model did a reasonable job of matching the simulation results for the simpler mission case, while auxiliary dynamic models were required to adequately capture risk-driver rankings for the more dynamic cases. This study highlights how state-of-the-art techniques can adapt to a range of dynamic problems.
Generalized hydrodynamics model for strongly coupled plasmas

Beginning with the exact equations of the Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy, we obtain the density, momentum, and stress tensor-moment equations. We close the moment equations with two closures, one that guarantees an equilibrium state given by density-functional theory and another that includes collisions in the relaxation of the stress tensor. The introduction of a density functional-theory closure ensures self-consistency in the equation-of-state properties of the plasma (ideal and excess pressure, electric fields, and correlations). The resulting generalized hydrodynamics thus includes all impacts of Coulomb coupling, viscous damping, and the high-frequency (viscoelastic) response. We compare our results with those of several known models, including generalized hydrodynamic theory and models obtained using the Singwi-Tosi-Land-Sjolander approximation and the quasilocalized charge approximation. We find that the viscoelastic response, including both the high-frequency elastic generalization and viscous wave damping, is important for correctly describing ion-acoustic waves. We illustrate this result by considering three very different systems: ultracold plasmas, dusty plasmas, and dense plasmas. The new model is validated by comparing its results with those of the current autocorrelation function obtained from molecular-dynamics simulations of Yukawa plasmas, and the agreement is excellent. Generalizations of this model to mixtures and quantum systems should be straightforward.
Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia.

Background Sepsis remains a major cause of morbidity and mortality. A variety of strategies targeting modulation of the pro-inflammatory response associated with early sepsis have been reported without clinical success. GLP-1 enhances glucose-stimulated insulin secretion. In addition, it was shown to have anti-inflammatory effects. We hypothesized that treatment with exendin-4, a GLP-1 receptor agonist, would attenuate inflammation and improve glucose control in a lipopolysaccharide (LPS) rat model of inflammation. Methods Two-month-old male Wistar rats were randomly assigned to one of the following four groups: 1) treatment: intraperitoneal (IP) injection of LPS 10 mg/kg followed by exendin-4, 30 μg/kg, 10 minutes later; 2) control-1: IP injection of LPS 10 mg/kg, followed by normal saline (NS); 3) control-2: IP NS injection followed by exendin-4; 4) sham: IP injection of NS followed by another NS injection. Glucose concentration, total white blood count with absolute neutrophil count, and pro- and anti-inflammatory cytokine concentrations were measured at 0, 3, 6, and 10 hours following LPS injection. Results At 3 hours, rats injected with LPS developed neutropenia, elevated pro- and anti-inflammatory cytokines, and mild hypoglycemia. Treatment with exendin-4 significantly modulated neutropenia, and decreased pro-inflammatory cytokine concentrations (IL-1α, IL-1β, IL-6, TNFα, and IFNγ). However, exendin-4 had no effect on IL-10 concentrations. LPS injection led to mild hypoglycemia, that was not observed in rats treated with exendin-4. Sham animals exhibited no significant change from baseline in all parameters. Conclusion In this LPS model of acute early phase inflammation, treatment with exendin-4 decreased pro-inflammatory cytokine concentrations without changing IL-10 blood levels and improved neutropenia. Following LPS injection, rats developed a tendency toward hypoglycemia that improved with exendin-4. Overall our data suggest that exogenous exendin-4 mediates anti-inflammatory effects early in this rat model of endotoxin-induced inflammation.
Pelvi-ureteric junction obstruction by crossing renal vessels: clinical and imaging features.

OBJECTIVE To present the characteristic clinical and imaging findings of pelvi-ureteric junction (PUJ) obstruction caused by crossing renal vessels (CRV), as it presents particular features within the spectrum of congenital hydronephrosis. PATIENTS AND METHODS Between April 1982 and December 2000, 384 children underwent surgery for PUJ obstruction. In 71 (18.5%; mean age 8.5 years, range 2 months to 14 years; 49 aged> 5 years), the obstruction was caused by CRV. The data collected from the medical records of these patients were analysed for their clinical presentation and imaging findings, i.e. ultrasonography (US), intravenous urography (IVU) and diuretic renography. RESULTS The main presenting symptom was recurrent renal colic (pain, nausea, vomiting) in 59%, followed by urinary infection (UTI) in 20%, gross haematuria in 11% and an incidental diagnosis in 10%. By contrast, in the 313 children with intrinsic PUJ obstruction, renal colic was present in only 10.5%. Moreover, from 1991 to 2000, when the use of prenatal US became widespread, hydronephrosis was detected prenatally in 42 of 212 children (20%) with intrinsic PUJ obstruction, but in only two of 31 (6%) with obstruction by CRV. However, in 10 children with CRV operated on during this period, prenatal US had shown mild hydronephrosis ( 25 mm), and colour Doppler US of two patients directly showed the CRV. In all 71 children with CRV obstruction diuretic IVU and renography during the acute symptoms had an obstructive pattern, and in 24 renal colic was reproduced during the examination. The differential kidney function was < 40% in 11 children who presented with UTI; two required nephrectomy and in the remaining 69 an Anderson-Hynes pyeloplasty, after which none had an episode of renal colic or UTI during a mean (range) follow-up of 10.2 (2–20) years. CONCLUSIONS PUJ obstruction by CRV should be suspected in older children presenting with recurrent renal colic and hydronephrosis. Good kidney function is expected in most of these children, despite their age, because the vascular obstruction is intermittent. Mild prenatal hydronephrosis that could decrease postnatally does not exclude the possibility of vascular obstruction, which may later become symptomatic. Imaging (US, diuretic IVU and renography) during an episode of pain is essential and colour Doppler US could help to establish the diagnosis in these cases. Knowing that a child has a CRV is important for choosing an open surgical approach rather than endoscopic pyelotomy, to avoid potential complications
Experimental Study of the Pathogenicity of Aspergilli for Mice

The relative virulence was determined for 14 species of aspergilli, by inoculating normal mice intravenously with graded doses of spores. Eleven were found to possess some degree of virulence, whereas three others were avirulent. Members of the Aspergillus flavus group were the only species that consistently killed mice with doses as low as 104 viable spores. When the in vivo fate of spores was compared for a virulent and an avirulent strain of Aspergillus, spores of the latter were cleared rapidly from the liver and spleen but grew in the kidneys and brain, producing progressive disease. Mice which inhaled spores did not succumb, but macrophages washed from their lungs contained spores. A relationship of virulence to spore characteristics such as germination time, size, shape, and external markings could not be established. Virulence could not be related to aflatoxin production inasmuch as at least one virulent strain did not produce aflatoxin in vitro.
Society for the Psychology of Women

The Division of the Psychology of Women was formally established in 1973 as Division 35 of the American Psychological Association (APA). Its name was changed to the Society for the Psychology of Women in 1991, and today the division is known to its members both as Division 35 and SPW. The impetus for the founding of the division came from women's social and political activism in the late 1960s, especially from members of the Association for Women in Psychology (AWP), which was founded in 1969. AWP and SPW continue to work together today by cosponsoring a hospitality suite during APA conventions and a prize for student research on the psychology of women and gender. Keywords: femininity; gender roles; psychology of women; psychology organization
International market segmentation and Eurodebt issues

Implications of capital market segmentation for international capital structure (ICS)—capital structure consisting of equity issued in one country and debt issued in another—are examined. Necessary conditions for the emergence of ICS are analyzed under two options for debt issues (foreign debt and Eurodebt) and comparisons are made. It is shown that in cases where the project cannot support an ICS including foreign debt Eurobonds can be issued and would be profitable.
Cigarette Advertising Bans and Smoking: The Flawed Policy Connection

Bans on the advertising of tobacco products are often justified on the grounds that they will reduce smoking initiation by the young and tobacco consumption by adults. This premise can be seriously challenged on the basis of: (1) studies of juvenile smoking determinants; (2) the experience of countries with such an advertising ban; and (3) statistics on adult tobacco consumption in a variety of countries. As such, it provides no serious basis for public policy to curtail smoking through advertising bans.
Regulated nuclear import of Rel proteins in the Drosophila immune response

The Drosophila immune response uses many of the same components as the mammalian innate immune response, including signalling pathways that activate transcription factors of the Rel/NK-kappaB family. In response to infection, two Rel proteins, Dif and Dorsal, translocate from the cytoplasm to the nuclei of larval fat-body cells. The Toll signalling pathway, which controls dorsal-ventral patterning during Drosophila embryogenesis, regulates the nuclear import of Dorsal in the immune response, but here we show that the Toll pathway is not required for nuclear import of Dif. Cytoplasmic retention of both Dorsal and Dif depends on Cactus protein; nuclear import of Dorsal and Dif is accompanied by degradation of Cactus. Therefore the two signalling pathways that target Cactus for degradation must discriminate between Cactus-Dorsal and Cactus-Dif complexes. We identified new genes that are required for normal induction of transcription of an antibacterial peptide during the immune response. Mutations in three of these genes prevent nuclear import of Dif in response to infection, and define new components of signalling pathways involving Rel. Mutations in three other genes cause constitutive nuclear localization of Dif; these mutations may block Rel protein activity by a novel mechanism.
A Statistical Model for Eddy‐Current Signals from Steam Generator Tubes

We propose a model for characterizing amplitude and phase probability distributions of eddy‐current signals. The squared amplitudes and phases of the potential defect signals are modeled as independent, identically distributed (i.i.d.) random variables following gamma and von Mises distributions, respectively. We derive a maximum likelihood (ML) method for estimating the amplitude and phase distribution parameters from measurements corrupted by additive complex white Gaussian noise. Newton‐Raphson iteration is utilized to compute the ML estimates of the unknown parameters. The obtained estimates can be used for flaw detection as well as efficient feature extractors in a defect classification scheme. Finally, we apply the proposed method to analyze rotating‐probe eddy‐current data from tube inspection of a steam generator in a nuclear power plant.
Why Have Kiwis not Become Tigers? Reforms, Entrepreneurship and Economic Performance in New Zealand (book version)

The New Zealand economy is noteworthy in policy circles for its turnaround during the 1980s and early 1990s. Starting from a state of semi-autarky in the early 1980s, the country now has a much more flexible and efficient economic structure. In the 15 years to 1999, successive governments reformed its institutional environment by injecting high doses of deregulation and opening the economy to the world. Following these changes, New Zealand climbed up various indexes of economic freedom: its score increased from 5.9 in 1985 to 8.2 in 2003 on the Fraser Institute measure (Gwartney and Lawson 2005). Strong employment growth from the early 1990s and productivity gains increased economic growth. Yet its average growth rate in the past decade does not compare with that of the Asian tigers, Singapore and Hong Kong, or that of Ireland, Estonia and Luxembourg, countries that share some of the highest ranks in the index. Recent performance and the modest growth prospects for the years ahead have fuelled the debate about the success of the New Zealand reforms. Some economists think that the less than stellar economic performance results from the failure to complete the reform process. Others believe that the current situation is the result of too much reform: New Zealand has been a 'laboratory' for free-market policies, and they went too far. Some maintain that it is now time to go back to more middle-of-the-road policies, taking into account not only economic efficiency but also income distribution, the environment and other issues said to have been left out in the reform process. In this view, better 'management' of the economy should help to improve growth prospects. The Labour-led government espoused this opinion when it was elected in 1999. Still others think that owing to New Zealand's cultural heritage, its inhabitants are relatively uninterested in high levels of economic growth. New Zealanders, it is said, do not need much money to be happy because they hold dear some egalitarian ideas that go back to the nineteenth century, reflected today in the romantic search for a peaceful and green New Zealand and perhaps also in the revival of Maori tikanga. The paper describes the context in which New Zealand's reforms took place and then considers the five main reforms that did most to improve economic performance. Finally it examines the reasons why New Zealand is not performing like an Asian tiger and discuss some policy implications.
Role of the bisphosphonate etidronate in the therapy of cancer-related hypercalcemia

Bisphosphonates (formerly diphosphonates), analogues of endogenous pyrophosphates, are potent inhibitors of osteoclastic bone resorption. While the exact mechanism of action remains poorly understood, etidronate, the only bisphosphonate currently available in the United States for the treatment of hypercalcemia, decreases the elevated serum calcium levels and alleviates the symptoms associated with hypercalcemia of malignancy. Both open and controlled clinical studies have demonstrated that this agent, administered at a dose of 7.5 mg/kg/d in 2-hour intravenous infusions over 3 to 7 days, promotes normocalcemia. In a randomized study, etidronate was shown to be superior to maximally approved doses of calcitonin. Moreover, when administered to patients without overt renal failure (serum creatinine less than 2.5 mg/dL), the drug is remarkably free of significant acute toxicity and side effects. Therefore, an important therapeutic aspect of this agent is that it permits concurrent antibiotic and chemotherapy administration. Judicious use of appropriate and specific pharmacologic intervention strategies in the patient with cancer-related hypercalcemia is expected to enhance quality of life, improve systemic cancer therapy tolerance, and reduce the morbidity of this serious neoplastic complication.
Bifunctional Antibodies: Preclinical and Clinical Applications

Treating malignancies with antibody-based immunotherapy has revolutionized the concept of targeted therapy. Rituximab and Trastuzumab, two monoclonal antibodies approved in the 1990s by the FDA, elucidated the potential of harnessing the immune system to eliminate transformed cells. As with any cancer therapy, a significant proportion of patients relapse, driving the development of nontraditional antibody-based therapies. Therefore, in an effort to enhance the ability of antibodies to retarget immune cells toward cancer cells, bispecific antibodies were born. Created through a variety of techniques they conform to an assortment of structures, recapitulating the basic structure of an antibody or deconvoluting the antigen-binding domains into unique designs. The European Union’s approval in 2009 of Catumaxomab, a bispecific antibody that links cells of the innate and adaptive immune system to EpCAM + cells for the treatment of malignant ascites, marks the first clinically approved dual-targeting antibody. Blinatumomab, a bispecific T-cell engager (BiTE), links T-cells directly to malignant cells, activating target-cell apoptosis through perforin-granzyme release. Early clinical results of Blinatumomab show a remarkable 80 % response rate in a heavily pretreated ALL patient subgroup. These enticing clinical results represent the forefront of the bispecific antibody field but evidence exists that point to the clinical success of numerous bispecific antibody formats. Although it is unknown which format will exhibit the highest clinical efficacy, it is clear that dual-targeting antibodies represent the future of immunotherapy for the treatment of cancer.
Determination of (C-12)/(C-13) in the interstellar medium toward Zeta Ophiuchi and Xi Persei

The Lick Observatory Reticon (LOR) data presented in Hawkins et al. (1985) are reanalyzed in order to determine the cause of the significant discrepancy in (C-12)/(C-13) isotope ratios determined on the basis of observations of this isotope in the interstellar medium toward Zeta Ophiuchi and Xi Persei. A new set of Lick Observatory observations toward Zeta Oph are obtained using a CCD detector. The KPNO coude feed echelle spectrograph and a CCD detector are used to carry out high-resolution, high SNR ratio observations toward Zeta Oph and Xi Per. The LOR results for Zeta Oph are uncertain, ranging to 40 to 60, owing to the error in continuum placement. The KPNO results toward Zeta Oph are (C-12)H/(C-13)H(+)(0, 0) = 63 +/- 8, (C-12)H(+)/(C-13)H(+)(1, 0) = 67 +/- 19, and (C-12)N/(C-13)N = 100 + 88/- 33. Toward Xi Per, the KPNO measurements yield (C-12)H(+)/(C-13)H(+) = 49 +/- 15 from the 4232-A band, and a lower limit of 45 from the 3957-A observations.
p63-specific activation of the BPAG-1e promoter

p63 , a member of the p53 superfamily, is an essential cell fate determinant for stratified epithelium. Deficiency of p63 leads to lack of differentiated epithelium from the skin and the presence of trace undifferentiated cells left in the dermis. We found that transcriptionally active isoforms of p63, TAp63β and TAp63γ, activated the skin-specific promoter of bullous pemphigoid antigen 1 (BPAG-1). The p63-response element was localized between bases -177 and -153 upstream of exon 1 in the BPAG-1e promoter, whereas regions surrounding the response element suppressed transcriptional responses to p53 and TAp73β, resulting in p63-specific activation of the promoter. This represents a novel molecular mechanism by which target gene induction by p63 is distinguished from induction by other p53 family members.
Radar-echo duration and height of a perseid meteor

Abstract Three-station radar observations of an unusual Perseid meteor echo have yielded a height-duration profile of the echo components, with an overall duration of 549 sec. The main part of the enduring echo, at a mean height of 91 km, drifted in an easterly direction at a rate of 119 m/sec. The meteoric velocity and deceleration are discussed briefly. Of special interest is the appearance of diffuse echo components which have been due either to direct reflections from meteoric ionization created over the height range 130–160 km, or to ground scatter via the main part of the meteoric ionization.
A urea adduct of bis­(hinokitiolato)­copper(II)

Bis(μ2-3-isopropyl-7-oxocyclo­hepta-1,3,5-trien-1-olato)bis[(3-isopropyl-7-oxocyclo­hepta-1,3,5-trien-1-olato)copper(II)]–urea–acetone (1/6/2), [Cu2(C10H11O2)4]·6CH4N2O·2C3H6O, where 3-isopropyl-7-oxocyclo­hepta-1,3,5-trien-1-olate is the systematic name for the hinokitiolate anion, contains three novel structural features. First, it contains a bis­(hino­kitiolato)copper(II) dimer, [Cu(hino)2]2, unlike any other, demonstrating that linkage isomerism is another avenue by which Cu(hino)2 can transmute from one form to another. Second, [Cu(hino)2]2 is hydrogen bonded to two urea mol­ecules, indicating that hydrogen bonding cannot yet be discounted from any proposed mechanism of action for the anti­microbial and anti­viral properties of bis­(hino­kitiolato)­copper(II). Finally, corrugated urea layers crosslinked by [Cu(hino)2]2 dimers are observed, suggesting that a new family of host–guest materials, i.e. metallo–urea clathrates, exists to challenge our understanding of crystal engineering and crystal growth and design. Selected details of the structure are that the [Cu(hino)2]2 dimers possess crystallographic inversion symmetry, the Cu atoms have square-pyramidal coordination geometries, the basal Cu—O bonds are in the range 1.916 (2)–1.931 (2) A, the apical Cu—O bond length is 2.582 (2) A, the hinokitiolate bite angles are in the range 83.41 (7)–83.96 (8)°, the urea–Cu(hino)2 inter­actions have an R22(8) motif, and the urea layers result from the close packing of R86(28) `butterflies' and R86(24) `strips of tape'.
Quantum dynamics in simple fluids

We use quantum-correction factors to calculate approximately the quantum velocity time-correlation function (TCF) of supercritical Lennard-Jones argon from the classical TCF. We find that for this quite classical system, several different quantum-correction schemes yield essentially identical results for the real and imaginary parts of the quantum TCF, and also agree well with the recent forward–backward semiclassical dynamics (FBSD) results of Wright and Makri [J. Chem. Phys. 119, 1634 (2003)]. We also consider a more quantum-mechanical fluid of lighter atoms (neon) at a lower temperature. In this case different quantum-correction schemes give different results. FBSD calculations show that the harmonic quantum correction factor works the best for this system.
Inhibition of metabolism-mediated cytotoxicity by 1,1-disubstituted hydrazines in mouse mastocytoma (line P815) cells.

Abstract Cyclophosphamide (CPA), a compound requiring metabolic activation to form toxic metabolites, has been used as a model compound to validate the use of a hepatocyte/mouse mastocytoma (line P815) cell culture system capable of measuring metabolism-mediated cytotoxicity in vitro . A number of hydrazines were tested in this system and were found to be relatively non-toxic. However, an attempt has been made to correlate complex formation between hydrazine metabolites and cytochrome P-450 in rat hepatocytes and the inhibition of the metabolism-mediated cytotoxicity of CPA. N -Aminopiperidine (NAP) was the most potent hydrazine tested in this system, since it significantly reduced the metabolism-mediated toxicity of CPA. The concentration dependency of this phenomenon permitted the calculation of the amount of NAP that reduced CPA cytotoxicity by 50%. This value (approximately 1 mM) correlated well with the apparent Michaelis constant (1.2 mM) for the formation of the inhibitory metabolite complex with cytochrome P-450 in microsomal suspensions. There was good correlation between the abilities of a number of 1,1-disubstituted hydrazines to reduce the metabolism-mediated toxicity of CPA and the extent to which they form the inhibitory metabolite complex in microsomes. 1,2-Dimethylhydrazine did not form an observable inhibitory complex in microsomal suspensions and only slightly reduced the metabolism-mediated toxicity of CPA in the mouse mastocytoma cell culture system. However, some other hydrazine derivatives were shown to alter significantly cytochrome P-450 function in isolated hepatocytes. This in vitro system may be of use in the evaluation of the biological effects of xenobiotics, particularly those requiring metabolic activation by cytochrome P-450.
Community learning component in first year seminar

This Work in Progress paper describes current efforts to engage Liberal Art College freshman to the Engineering discipline and its impact to the broader community, through a topic-based, writing-intensive seminar course. In this particular seminar developed by the author, we aim to discuss the role of engineers in tackling challenges in the Community around the Hartford area and beyond. While students enrolled in the seminar course in this paper are mainly “undecided” students, we believe by emphasizing technologies applied to the immediate community around our students and humanitarian applications, we can inspire students' interest in Engineering and show students how the skills they will be learning can have a positive impact on the quality of life for the surrounding community. The seminar was assessed by gathering student comments concerning each major course components.
National trauma databank analysis of mortality and limb loss in isolated lower extremity vascular trauma

Objectives Lower extremity injury is common in trauma patients; however, the influence of arterial injury on devastating patient and limb outcomes can be confounded by the presence and physiological derangement of concomitant head or thoracoabdominal injuries. We analyzed isolated lower extremity injuries with an arterial component. Our aim was to elucidate factors associated with mortality and limb loss in this selected population. Methods We reviewed trauma incidents from the National Trauma Data Bank (2002-2006) containing isolated lower extremity injury codes and a specified infrainguinal arterial injury. Demographics, injury patterns, clinical characteristics, and adverse outcomes (death, amputation) during initial hospitalization were collected. Multivariate logistic regression was used to identify risk factors for limb loss. Results There were 651 isolated infrainguinal arterial injuries. Death (18) and early limb loss (42) were studied by mechanism (penetrating, n=431; blunt, n=220). Half of the deaths involved injury to the common femoral artery (CFA), and over 80% had injury to the CFA or superficial femoral artery (SFA). Death was three times as frequent in the CFA/SFA than in the popliteal/tibial injuries ( P = .02). Penetrating injuries were present in almost 80% of deaths, and most of these were gunshot wounds. Patients who died had mean initial systolic blood pressure of 59.7 mm Hg, and almost 40% had no blood pressure on arrival. Mean initial Glasgow Coma Score was 4.5, and almost 80% arrived with a Glasgow Coma Score of 3 despite the absence of head injury. Twenty-seven above- and 15 below-the-knee amputations were performed. The popliteal artery was injured in half of the amputations, with injury isolated to the popliteal or tibial arteries in about three-quarters. Amputation was twice as frequent in popliteal/tibial than CFA/SFA injury ( P = .03) and twice as frequent in blunt than penetrating injury ( P = .05). Multiple arterial injuries (odds ratio, 5.2; 95% confidence interval, 1.7-15.6; P = .003), and fracture (odds ratio, 2.2; 95% confidence interval, 1.1-4.2; P = .02) independently predicted amputation, while the presence of nerve injury and soft tissue disruption did not. Conclusions Isolated lower extremity trauma with vascular injury has a nearly 10% rate of mortality or limb loss. Mortality is associated with penetrating mechanism and early shock, likely resulting from prehospital proximal arterial hemorrhage. In contrast, early limb loss is more common with blunt distal vascular injury, especially to the popliteal and tibial arteries. Neither nerve nor soft tissue injury predicted limb loss but may result in delayed amputations not captured in this acute outcomes dataset.
Mix and match: heterodimers and opioid tolerance.

Heterodimerization of G protein-coupled receptors has become increasingly recognized as a valuable mechanism to increase receptor diversity. Heterodimers have been observed in the opioid receptor family, but one of the most intriguing is that formed between μ-opioid and δ-opioid receptors. In this issue of Neuron , He et al. present evidence further implicating these heterodimers in morphine tolerance.
Young-adult children of alcoholic parents: protective effects of positive family functioning.

The occurrence of alcoholism is clustered within families, but the detrimental effect of a positive family history may vary with the degree of family impairment involved. In this study we assessed the effects of family history and family environment on alcohol misuse. From ongoing studies we recruited parents who had a child aged 18–30, 20 with a DSM-III-R alcohol dependence diagnosis, 20 without. The child then completed a multidimensional assessment. The young-adult participants included 20 men and 20 women (mean age=24.8). Differences by family history were restricted to substance abuse behaviors. While a high level of alcohol problems occurred in both groups, those with an alcohol-dependent parent were more likely to be heavy drinkers and showed more symptoms of alcohol dependence. Overall psychological adjustment did not differ between the groups, however. Alcohol misuse measures did correlate moderately with symptoms of poor emotional health. The most important correlates of alcohol misuse measures in this study were exposure to parental alcoholism, abusive punishment, and psychological symptoms, with some separation of effects in the two subgroups. Psychological symptoms had a stronger relationship with misuse in subjects with social-drinking parents, while abuse was more associated in the group with an alcohol-dependent parent. These results confirm the importance of environmental interactions with familial risk. A biological vulnerability from an alcohol-dependent parent was not sufficient or necessary for the participants in this study to develop alcohol dependence as a young adult, although there was an increased risk. There appear to be strong protective effects of positive family relationships on the potential negative effects of a family history of alcoholism.
Covering convex sets with non-overlapping polygons

Abstract We prove that given n⩾3 convex, compact, and pairwise disjoint sets in the plane, they may be covered with n non-overlapping convex polygons with a total of not more than 6n−9 sides, and with not more than 3n−6 distinct slopes. Furthermore, we construct sets that require 6n−9 sides and 3n−6 slopes for n⩾3. The upper bound on the number of slopes implies a new bound on a recently studied transversal problem.
From buds to follicles: matrix metalloproteinases in developmental tissue remodeling during feather morphogenesis

Organogenesis involves a series of dynamic morphogenesis and remodeling processes. Since feathers exhibit complex forms, we have been using the feather as a model to analyze how molecular pathways and cellular events are used. While several major molecular pathways have been studied, the roles of matrix degrading proteases and inhibitors in feather morphogenesis are unknown. Here we addressed this knowledge gap by studying the temporal and spatial expression of proteases and inhibitors in developing feathers using mammalian antibodies that cross react with chicken proteins. We also investigated the effect of protease inhibitors on feather development employing an in vitro feather bud culture system. The results show that antibodies specific for mammalian MMP2 and TIMP2 stained positive in both feather epithelium and mesenchyme. The staining co-localized in structures of E10-E13 developing feathers. Interestingly, MMP2 and TIMP2 exhibited a complementary staining pattern in developing E15 and E20 feathers and in maturing feather filaments. Although they exhibited a slight delay in feather bud development, similar patterns of MMP2 and TIMP2 staining were observed in in vitro culture explants. The broad spectrum pharmacological inhibitors AG3340 and BB103 (MMP inhibitors) but not Aprotinin (a plasmin inhibitor) showed a reversible effect on epithelium invagination and feather bud elongation. TIMP2, a physiological inhibitor to MMPs, exhibited a similar effect. Markers of feather morphogenesis showed that MMP activity was required for both epithelium invagination and mesenchymal cell proliferation. Inhibition of MMP activity led to an overall delay in the expression of molecules that regulate either early feather bud growth and/or differentiation and thereby produced abnormal buds with incomplete follicle formation. This work demonstrates that MMPs and their inhibitors are not only important in injury repair, but also in development tissue remodeling as demonstrated here for the formation of feather follicles.
A comprehensive systematic approach to identification of influenza A virus genotype using RT-PCR and RFLP

Amplification of influenza A virus gene segments by reverse transcription-polymerase chain reaction (RT-PCR) can be combined with enzymatic digestion to reveal unique restriction fragment length polymorphisms specific for H1N1 and H3N2 subtype viruses. We have used the method to provide a rapid, specific and reproducible identification of the genotype of high-growth influenza reassortants derived from A/Puerto Rico/8/34 (PR8). Digestion of the gene segments amplified from wild-type viruses, PR8 and reassortants at sites unique to either the wild-type strain or to PR8 provided positive, unambiguous identification of the origin of each of the internal genes, and distinguished the internal genes of both H1N1 and H3N2 strains from those of PR8. This method has also permitted us to quickly confirm that reassorting has occurred and to optimize the selection of reassortant clones with maximum number of PR8 internal genes. Since the method can detect 1-10% of a second strain in a mixed population, the method can also be used to detect samples containing more than one viral subtype and to assess the purity of influenza viruses used for manufacturing vaccines.