cssi/SciSciGPT-SciSciNet huggingface dataset:
Cysteine biosynthesis is a determinant of Brucella ovis stress survival and fitness in the intracellular niche

Brucella ovis is an ovine intracellular pathogen with tropism for the male genital tract. To establish and maintain infection, B. ovis must survive stressful conditions inside host cells, including low pH, nutrient limitation, and reactive oxygen species. These same conditions are often encountered in stationary phase cultures. Studies of stationary phase may thus inform understanding of Brucella infection biology, yet the genes that are important in Brucella stationary phase physiology remain poorly defined. We measured fitness of a barcoded pool of B. ovis Tn-himar mutants as a function of growth phase and identified cysE as a determinant of fitness in stationary phase. CysE catalyzes the first step in cysteine biosynthesis from serine. We provide genetic evidence that two related enzymes, CysK1 and CysK2, function redundantly to catalyze cysteine synthesis downstream of CysE. Deleting either cysE or both cysK1 and cysK2 leads to premature entry into stationary phase and reduced culture yield. These phenotypes are rescued by addition of cysteine or glutathione to the medium. We further show that deletion of cysE results in sensitivity to exogenous hydrogen peroxide. Finally, we demonstrate that B. ovis ΔcysE has no defect in host cell entry but is attenuated in macrophage-like cells and in ovine testis epithelial cells at one- and two-days post infection. Our study uncovered unexpected redundancy at the CysK step of cysteine biosynthesis in B. ovis, and demonstrated that cysteine anabolism is an important determinant of stationary phase entry in vitro and fitness in the intracellular niche.
National Trends in the Use of Neoadjuvant Therapy Before Cancer Surgery in the US From 2004 to 2016.

This cohort study uses information obtained from the US National Cancer Database to evaluate trends in the use of neoadjuvant therapy before tumor resection for various types of cancer from 2004 to 2016.
Effects of Self-focused Augmented Reality on Health Perceptions During the COVID-19 Pandemic: A Web-Based Between-Subject Experiment.

Background: Self-focused augmented reality (AR) technologies are growing in popularity and present an opportunity to address health communication and behavior change challenges. Objective: We aimed to examine the impact of self-focused AR and vicarious reinforcement on psychological predictors of behavior change during the COVID-19 pandemic. In addition, our study included measures of fear and message minimization to assess potential adverse reactions to the design interventions. Methods: A between-subjects web-based experiment was conducted to compare the health perceptions of participants in self-focused AR and vicarious reinforcement design conditions to those in a control condition. Participants were randomly assigned to the control group or to an intervention condition (ie, self-focused AR, reinforcement, self-focus AR × reinforcement, and avatar). Results: A total of 335 participants were included in the analysis. We found that participants who experienced self-focused AR and vicarious reinforcement scored higher in perceived threat severity (P=.03) and susceptibility (P=.01) when compared to the control. A significant indirect effect of self-focused AR and vicarious reinforcement on intention was found with perceived threat severity as a mediator (b=.06, 95% CI 0.02-0.12, SE .02). Self-focused AR and vicarious reinforcement did not result in higher levels of fear (P=.32) or message minimization (P=.42) when compared to the control. Conclusions: Augmenting one’s reflection with vicarious reinforcement may be an effective strategy for health communication designers. While our study’s results did not show adverse effects in regard to fear and message minimization, utilization of self-focused AR as a health communication strategy should be done with care due to the possible adverse effects of heightened levels of fear.
Discover Discriminatory Bias in High Accuracy Models Embedded in Machine Learning Algorithms

For all the excitement about Machine Learning Algorithms, there are serious impediments to its widespread adoption. Accuracy is not the only criteria in measuring the model performance, in real life, current model assessment techniques, like cross-validation or receiver operator characteristic (ROC) and lift curves, simply don’t tell us about all the nasty things that can happen such as Opaqueness, Social discrimination etc. within the models. And that’s why model debugging, the art and science of understanding and fixing problems in Machine Learning models, is so critical to the future of Machine Learning. Without being able to troubleshoot models when they under perform or misbehave, organizations simply won’t be able to adopt and deploy the algorithm for good and at scale. Inspired by this, we want to challenge the models that have very high accuracy, conduct model debugging and discrimination testing to discover the hidden inaccuracy. The results bring up the concern of how a seemingly reliable model can present bias that would be damaging if actually deployed in the future.
The global trade facilitation regulatory framework and the role of ICT

Constantly increasing global containerized trade leads to port congestion and delays in the movement of goods. In an era of global value chains (GVCs), trade facilitation is particularly important. Information and communication technology (ICT) applied in modern trade control and facilitation tools constitutes a remarkable enabler for the implementation of the World Trade Organization's Trade Facilitation Agreement articles. For instance a successful risk management policy being implemented with the support of a Customs Information System (CIS) that allows the storing and analysis of trade data at a declaration level. Similarly, exchange of data between trade stakeholders, including government inspection agencies and the private sector, cannot be achieved without fully automated Electronic Single Window (eSW) platforms. Today, the abundance of public and commercial datasets, combined with the availability of affordable technological solutions, places ICT in the center of this agenda and encourages governments to deploy hard and soft ICT infrastructure to digitalize the flow of international trade. However, such policies should not be designed in isolation and in the absence of supporting legal and regulatory framework to enable their proper operationalization.
Fluorine-18 Labeling of the MDM2 Inhibitor RG7388 for PET Imaging: Chemistry and Preliminary Evaluation

RG7388 (Idasanutlin) is a potent inhibitor of oncoprotein murine double minute 2 (MDM2). Herein we investigated the feasibility of developing 18F-labeled RG7388 as a radiotracer for imaging MDM2 expression in tumors with positron emission tomography (PET). Two fluorinated analogues of RG7388, 6 and 7, were synthesized by attaching a fluoronicotinyl moiety to RG7388 via a polyethylene glycol (PEG3) or a propyl linker. The inhibitory potency (IC50) of 6 and 7 against MDM2 was determined by a fluorescence polarization (FP)-based assay. Next, compound 6 was labeled with 18F using a trimethylammonium triflate precursor to obtain [18F]FN-PEG3-RG7388 ([18F]6), and its properties were evaluated in MDM2 expressing wild-type p53 tumor cell lines (SJSA-1 and HepG2) in vitro and in tumor xenografts in vivo. The FP assays revealed an IC50 against MDM2 of 119 nM and 160 nM for 6 and 7, respectively. 18F-labeling of 6 was achieved in 50.3 ± 7.5% radiochemical yield. [18F]6 exhibited a high uptake (∼70% of input dose) and specificity in SJSA-1 and HepG2 cell lines. Saturation binding assays revealed a binding affinity (Kd) of 128 nM for [18F]6 on SJSA-1 cells. In mice, [18F]6 showed fast clearance from blood with a maximum tumor uptake of 3.80 ± 0.85% injected dose per gram (ID/g) in HepG2 xenografts at 30 min postinjection (p.i.) and 1.32 ± 0.32% ID/g in SJSA-1 xenografts at 1 h p.i. Specificity of [18F]6 uptake in tumors was demonstrated by pretreatment of mice with SJSA-xenografts with a blocking dose of RG7388 (35 mg/kg body weight, i.p.). In vivo stability studies in mice using HPLC showed ∼60% and ∼30% intact [18F]6 remaining in plasma at 30 min and 1 h p.i., respectively, with the remaining activity attributed to polar peaks. Our results suggest that RG7388 is a promising molecular scaffold for 18F-labeled probe development for MDM2. Additional labeling strategies and functionalizing locations on RG7388 are under development to improve binding affinity and in vivo stability of the 18F-labeled compound to make it more amenable for PET imaging of MDM2 in vivo.
Preliminary Notes on Some Southwestern New Mexico Lithic Industries

During the months of January, February and March of 1967 Dr. Arthur J. Jelinek, then of the University of Michigan, directed an archaeological survey of the Mimbres River Valley and adjacent areas of Southwestern New Mexico. Archaeological materials were obtained from well over 200 sites and part of the analysis of these materials was carried out while we were in New Mexico. While Jelinek concentrated on field analysis of ceramics, I was able to work with the lithic materials from at least the first part of the survey. This paper is based on a preliminary analysis of 213 lots of chippage from 167 different sites. All told, we recorded, typed, counted and weighed over 27,500 fragments of chipped stone weighing well over 700 pounds. We were able to accomplish much of this work in New Mexico by spending approximately half of our time in the field and half in the laboratory. While final tool typing and description is far from complete we have so far recorded information on the numbers and weights of cobble tools; finished bifaces; rough bifaces; standardized scrapers including side scrapers, end scrapers and spokeshaves; cores including block, plano-convex and bi-convex cores; and flake groups including blocky flakes, flat flakes and flakes of bi-facial retouch. These flake and tool categories have all been discussed elsewhere (Fitting 1967; Fitting, DeVisscher and Wahla 1966; Fitting and Price 1968) and so we will not redefine them here. The final result of this study will be the articulation of tool and flake categories with the ceramic seriation and site typology for the entire survey area. It should then be possible to relate style change within individual tool categories to a time sequence. Within single time horizons site size and location could be correlated with specific tool types to suggest site function. By observing changes in site function and location over time, we will be able to deal with changing patterns of cultural adaptation as well as movements of people over time. Much of this projected correlation is dependent on the final analysis of the ceramics and site morphology and must be left for the future. It is possible to use what information is available to make some lower level inferences on areal and temporal differences with less reference to actual cultural adaptations.
Heritage or Hazard

On December 23, 1941, just 16 days after the Imperial Japanese navy’s bombing of Pearl Harbor in Hawaii and the entry of the United States into World War II, Union Oil Company’s tanker Montebello departed California’s Port San Luis, bound north for Vancouver with a cargo of crude oil. At dawn off Estero Bay, the ship was going about eight knots when lookout Dick Quincy saw a submarine surface (Quincy, personal communication, 2001). He gave the alarm. Everyone on the bridge saw the wake of a torpedo as it streaked toward them from the Imperial Japanese submarine I-21 (Browning, 1966). Montebello could not evade the onrushing torpedo, which slammed into the hull near the bow of the hapless vessel. Fortunately no one was on the foredeck at this early hour because of heavy seas.
Cephalochordate (amphioxus) embryos: procurement, culture, and basic methods.

Publisher Summary The chapter concerns methods for obtaining, raising, and manipulating living embryos of B. floridae . It includes methods for expressing reporter constructs and for manipulating levels of gene expression. The invertebrate chordate amphioxus, also called the lancelet, is the closest living invertebrate relative of the vertebrates. It is only possible to obtain fertilizable gametes from amphioxus on the days when they normally spawn in the field. The fertilization of eggs involves adding several drops of concentrated sperm to several thousand eggs in a 5- to 9-cm petri dish. Embryos are easily raised in petri dishes. Antibiotics are not essential; however, a 1:1000 dilution of penicillin G/streptomycin sulfate (100 mg/mL each penicillin G, sodium salt (>1400 units/mg) and streptomycin sulfate) will help prevent bacterial growth. Starting at 30 to 36 h of development, the embryos must be fed. The larvae are ciliary filter feeders and must have food constantly available from about 34 h. The removal of the fertilization envelope is necessary for spotting dye on the surface of embryos or for blastomere manipulations. All the manipulations of fertilized eggs lacking the fertilization envelope should be completed before first cleavage. Unfertilized eggs can be readily microinjected. Embryos cannot be microinjected after the fertilization envelope has elevated as the embryos are not fastened within the fertilization envelope and rotate out from under the microelectrode.
Discretely Monitored Options

This article reviews pricing techniques for options with path-dependent payoffs and which are monitored over a discrete set of dates. Keywords: path-dependent options; barrier options; look-back options; average options; Asian options; first passage problems; recursive integration; continuous correction; discrete monitoring; Levy processes
Silencing Theodicy with Enthusiasm: Aesthetic Experience as a Response to the Problem of Evil in Shaftesbury, Annie Dillard, and the Book of Job

The problem of evil is not only a logical problem about God's goodness but also an existential problem about the sense of God's presence, which the Biblical book of Job conceives as a problem of aesthetic experience. Thus, just as theism can be grounded in religious experience, atheism can be grounded in experience of evil. This phenomenon is illustrated by two contrasting literary descriptions of aesthetic experience by Jean-Paul Sartre and Annie Dillard. I illuminate both of these literary texts with a discussion of the 18th Century philosopher Lord Shaftesbury's concept of ‘enthusiasm’.
Gigachips: deliver affordable digital multimedia for work and play via broadband network and set-top box

Semiconductor technologies are enabling the new capabilities and services that the information superhighway promises. The delivery of digital information into the home and office will change the concept of what one can do at the home and office. Digital connectivity, and access to information, will be within everyone's reach. A wide range of talents must be combined and new kind of tools must be developed to efficiently transmit images and information that in raw form contain gigabits per second of data, but must be delivered in megabits of bandwidth. To meet all of the design challenges for delivering digital information across the broadband network and into the home in the existing infrastructure is the key.
Macro-econometric analysis of the effects of domestic credit conditions and monetary innovations on agriculture by vector-autoregression methods: United Kingdom, Japan, Australia, and Nigeria

This paper uses a maximum likelihood estimation procedure to investigate the dynamic relationship between money and agriculture in Australia. Bivariate causality tests were conducted among the variables in a vector autoregressive system, yielding interesting results. Using quarterly time series data for the period third quarter, 1969 up and until second quarter, 1984, we confirm an earlier contention that money matters for the agricultural sector of Australia. Introduction In a recent study on Australia, Sanni and Calkins (1985) presented a vector autoregressive (VAR) model to study the importance of domestic credit conditions proxied by money supply (AMI and, alternatively, AM2) on agricultural aggregates such as agricultural trade balance (ATB) and relative agricultural prices (RAP)• We assumed that all che variables entering our VAR system have luentical lag lengths. Using n=4 quarters versus n=6 quarters, we further assumed that the shorter lagged model is a constrained version of the more generously lagged model. We then employ the asymptotic chi-square distribution of the log likelihood ratio to discriminate against the longer lagged model. Our major conclusion is that money supply is important for the agricultural sector of Australia. Conventional research on the determination of the best order of lags for the multivariate autoregressive model cast serious doubts on
Cybernetic theory does not explain family and couple process: Systems theory and dialectical metatheory

Abstract The theoretical foundation of family and couples therapy has been general systems theory, most notably that of Bertalanffy. However, there is a serious flaw between how theorists have been explaining what therapists have been seeing. This is primarily due to the use of the closed system concepts of cybernetics to explain open systems. This article briefly presents Bertalanffy's distinction between open and closed systems, reviews how closed system concepts came to be applied to families and couples, discusses the dilemmas this has created, and argues that the dialectical metatheory of Weeks and of Bopp and Weeks allows a more uniform approach to therapy.
Technical Note on Issuance Mechanisms for Government Securities

In developing strategies towards covering the government's debt borrowing needs, a government debt manager, in addition to taking decisions on selecting debt instruments, has to develop appropriate mechanisms to sell these instruments to the market. This note intends to address a variety of issuance mechanisms for government securities. The note includes four sections. The note starts with a brief discussion of the three sound issuance principles. Section II analyzes a variety of major techniques for selling government securities. Section III discusses the most commonly used selling technique - auction - from both theoretical and empirical perspectives. Finally, section IV discusses the primary dealership.
Infinitesimal contraction of the Feigenbaum renormalization operator in the horizontal direction

In this short note, we give a sketch of a new proof of the exponential contraction of the Feigenbaum renormalization operator in the hybrid class of the Feigenbaum fixed point. The proof uses the non existence of invariant line fields in the Feigenbaum tower (C. McMullen), the topological convergence (D. Sullivan), and a new infinitesimal argument, different from previous methods by C. McMullen and M. Lyubich. The method is very general: for instance, it can be used in the classical renormalization operator and in the Fibonacci renormalization operator.
Bounds on the Compactness of Neutron Stars from Brightness Oscillations during X-Ray Bursts

The discovery of high-amplitude brightness oscillations at the spin frequency or its first overtone in six neutron stars in low-mass X-ray binaries during type I X-ray bursts provides a powerful new way to constrain the compactness of these stars and hence to constrain the equation of state of the dense matter in all neutron stars. Here we report general relativistic calculations of the maximum fractional rms amplitudes that can be observed during bursts, as a function of stellar compactness. We compute the dependence of the oscillation amplitude on the compactness of the star, on the angular dependence of the emission from the surface, on the rotational velocity at the stellar surface, and on whether there are one or two emitting spots. We show that color oscillations caused by the spectral variation with the angle of emission, the rotation of the star, and the limited bandwidth of the detector all tend to increase the observed amplitude of the oscillation. Nevertheless, if two spots are emitting, as appears to be the case in 4U 1636-536 and KS 1731-26, very restrictive bounds on the compactness of the star can be derived.
Chinese Outward Direct Investment Research: Theoretical Integration and Recommendations

This article reports a detailed analysis of 138 peer-reviewed articles in 41 journals published in the last 12 years (2001-2012) that focus on Chinese outward foreign direct investment from a theoretical advancement perspective. It assesses how the topic has been explored both conceptually and empirically and identifies the substantive contributions to the literature using a thematic analysis. The article argues that research on the international expansion of Chinese multinational corporations offers a unique opportunity to extend and develop extant theorizing in four primary research streams: the latecomer perspective; Chinese state and government influences; the dynamics of firms and institutions; and the liability of foreignness. Building on the results of this analysis, the article offers five recommendations as promising ways to open up theoretical inquiry: (1) cross-fertilization among the four research streams; (2) integration of resource- and institution-based theories with other theoretical lenses; (3) research on the process dimensions using a longitudinal approach; (4) adoption of multi-levels of analysis; and (5) consideration of the wider emerging market literature.
Implementation of an in-situ particle monitor system on an oxide plasma process system

The implementation of an in-situ particle monitor (ISPM) on a high volume manufacturing oxide plasma etcher is discussed. Plasma process generated particles have been traditionally monitored using the Particle per Wafer Pass (PWP) methodology, using test wafers and a particle inspection system. As equipment throughputs continue to increase, more PWP test wafer runs are needed to maintain a quick response to sudden high particle events. Increasing the number of test wafer runs not only increases test wafer cost, but also reduces equipment availability and increases cost of ownership. The ISPM allows real-time response to high particle events, better understanding of equipment and process particulate status, reduced defectivity, increased tool availability, and reduced cost of ownership. An oxide plasma etching system was used in this investigation to collect a large data base of ISPM data. Strong correlation was established between regular PWP and ISPM data during RF-plasma on events. The ISPM was also demonstrated to provide valuable insights into the particle deposition mechanism. The initial particle counts were found to stay constant over a long duration of the equipment run time. However, when the PWP count started to increase, the ISPM signal increased sharply. Moreover, the frequency of high particle counts was observed to increase as the equipment run time increased. Finally, a process comparison based on the ISPM is discussed. Based on the correlation to PWP methodology, the increased data collection capability and potential reduction in cost of ownership, the ISPM has been implemented in the manufacturing line.
The mechanism of ryanodine action in rabbit ventricular muscle evaluated with Ca-selective microelectrodes and rapid cooling contractures.

Cellular Ca uptake and efflux in rabbit ventricular muscle was measured using double-barreled Ca microelectrodes in the extracellular space. When repetitive stimulation was stopped there was a slow loss of cellular Ca. Upon resumption of stimulation Ca was taken up by the cells. These Ca movements are thought to represent the loss of Ca from the sarcoplasmic reticulum and the cell during rest and the refilling of the sarcoplasmic reticulum during stimulation. Ryanodine (100 nM) greatly enhanced both the efflux of Ca during rest and the uptake of Ca induced by stimulation. These results are consistent with the conclusions drawn below, but they are dependent upon the interpretation that these extracellular Ca depletions are indicative of sarcoplasmic reticulum Ca movements. To examine further this process, contractures induced by rapid cooling to 0 °C were used as an independent assay of sarcoplasmic reticulum Ca content. These rapid cooling contractures were smaller after longer rest intervals (declining w...
Oxygen Depletion in Cells Irradiated at Ultra-high Dose-rates and at Conventional Dose-rates

Irradiation at conventional dose-rates of an oxygen-equilibrated bacterial cell suspension in a sealed vessel produces breaking survival curves similar to those observed for cells irradiated as a t...
On reinsurance and investment for large insurance portfolios

Abstract We consider a problem of optimal reinsurance and investment for an insurance company whose surplus is governed by a linear diffusion. The company’s risk (and simultaneously its potential profit) is reduced through reinsurance, while in addition the company invests its surplus in a financial market. Our main goal is to find an optimal reinsurance–investment policy which minimizes the probability of ruin. More specifically, in this paper we consider the case of proportional reinsurance, and investment in a Black–Scholes market with one risk-free asset (bond, or bank account) and one risky asset (stock). We apply stochastic control theory to solve this problem. It transpires that the qualitative nature of the solution depends significantly on the interplay between the exogenous parameters and the constraints that we impose on the investment, such as the presence or absence of shortselling and/or borrowing. In each case we solve the corresponding Hamilton–Jacobi–Bellman equation and find a closed-form expression for the minimal ruin probability as well as the optimal reinsurance–investment policy.
85: Venous Thromboembolism as the Initial Presentation of Primary Renal Amyloidosis

VENOUS THROMBOEMBOLISM AS THE INITIAL PRESENTATION OF PRIMARY RENAL AMYLOIDOSIS Mythili Ghanta , Sriranga L Bonam , Rajan Kapoor, Anjali Acharya Jacobi Medical Center, Bronx, New York, US Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins. Primary or AL amyloid is due to deposition of protein derived from immunoglobulin light chain fragments. Hematologic manifestations associated with Amyloidosis, include anemia, thrombocytopenia and bleeding diathesis which may be seen in up to 44% of cases. Venous Thrombo Embolism (VTE) is a less well recognized complication. We report a 65 year old Hispanic female who presented with history of two episodes of idiopathic VTE and hypoalbuminemia. Her initial presentation was 2 years ago, with bilateral lower extremity (LE) swelling and pain which was due to deep venous thrombosis (DVT). Evaluation for a hypercoagulable state was negative. She was treated with Coumadin for 6 months. She presented again 6 months later, with right LE DVT and was restarted on Coumadin. At this time, she was noted to have a serum albumin of 2.5 gm/dl which was persistently low for 2 years duration and proteinuria of 5gm/day with a normal complete blood count, renal panel and echocardiogram. Serum protein electrophoresis showed a monoclonal spike in the alpha region. Renal biopsy revealed primary amyloidosis. Kappa: Lambda ratio was normal and urine light chain assay was negative. Bone marrow biopsy shows only 1% plasma cells. In a review of medical records of 2,132 patients with biopsy proven AL amyloidosis from Mayo clinic, they found that thromoembolic phenomena can antedate the diagnosis of amyloidosis. In a study published from Cleveland clinic the incidence of VTE in amyloidosis was up to 11% at 10 years, which was comparable to the incidence of VTE in multiple myeloma. Impairment of thrombin antithrombin pathway, in association with low antithrombin biological activity has been recognized to have possible pathogenic role in hypercoagulability of amyloidosis. This case illustrates that primary amyloidosis can be an underdiagnosed cause of VTE and Nephrotic syndrome should be considered in the differential diagnosis of unexplained VTE.
Alone in the Garden: How Gregor Mendel’s Inattention to Audience May Have Affected the Reception of His Theory of Inheritance in “Experiments in Plant Hybridization”:

From a rhetorical perspective, Mendel’s work and its reception elicit two important questions: (a) why were Mendel’s arguments so compelling to 20th century biologists? And (b) why where they so roundly ignored by his contemporaries? The focus of this article is to examine the latter question while commenting on the former by employing several tactics for rhetorical analysis including historical, textual, and audience analyses. These analyses suggest that Mendel’s argument resembles 20th century biological arguments in its use of mathematical principles and formulae to both inform the design of experiments and support the law-like regularity of conclusions. These procedures, however, were not regarded by his audience of hybridists, botanists, cytologists, and naturalists as sufficiently persuasive or necessarily even legitimate. I will argue that had he taken a more rhetorical tact and considered the position of his audience on the legitimacy of the scope of his conclusions, his methods for making argumen...
Selecting placement sites for student teachers and pre‐student teachers: Six considerations

Abstract The literature on field placement practices suggests that colleges and universities base placement decisions for both pre‐student teaching and student teaching on six distinctive considerations. This manuscript summarizes the six considerations that appear to be operating: (a) diversity, (b) collaboration, (c) cooperating teacher preparation, (d) challenging belief, (e) mentor matching, and (f) clustering. The manuscript also presents a study of current placement practices in the United States and Canada and discusses the implications of the six considerations for teacher education field placement practices.
Mitochondrial localization of oxidative enzymes: staining results with two tetrazolium salts.

A comparison is made of the staining results obtained with Nitro-BT and MTT-Co++ as acceptors when DPNH is the substrate in frozen sections of cold formol-calcium-fixed rat kidney (normal and following ligation of the blood vessels) and human liver containing lipofuscin granules. The kidney results are evaluated in terms of mitochondrial morphology seen after classical mitochondrial stains and in electron micrographs. It is concluded that, except for formazan deposition on lipid-aqueous interfaces, Nitro-BT staining indicates the intracellular localization of oxidative enzymes, at least at the level of light microscopy. In contrast, the use of MTT-Co++ is not reliable for such intracellular localizations. The deposition of the formazan of MTT-Co++ is determined in large part by physicochemical factors other than enzyme localization. Despite marked abnormalities of the mitochondria in cells of the ligated kidney, MTT-Co++ formazan is generally deposited in the same dotlike fashion as in cells of normal kidney.
A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery.

Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair. We performed a prospective adaptive dose-finding trial of prophylactic DARB ( www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100β, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100β, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34). There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.
Characteristics of μ and δ opioid binding sites in striatal slices of morphine-tolerant and -dependent mice

Previously, we demonstrated the enhanced affinity of opioid receptors for naloxone in striatal slices from morphine-dependent mice. In our present study, binding characteristics of the mu opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) and dihydromorphine, the delta opioid receptor agonist, [D-Ala2, D-Leu5]enkephalin (DADLE), and the opioid antagonist, naloxone, were examined in striatal slices from morphine-tolerant and -dependent mice. Striatal slices from mice that were implanted with a morphine pellet for 3,7 and 21 days displayed significant decreases in Kd values (5.1, 4.6 and 5.5 nM, respectively) of [3H]DAMGO when compared to those in slices from control animals that were not implanted or implanted with placebo pellets (9.6 and 9.3 nM, respectively). Also, a significant increase in the binding affinity of naloxone, but not that of dihydromorphine, was observed in striatal slices of mice that were implanted with a morphine pellet for 3 days. Significant increases in the Bmax of delta binding sites in striatal slices of mice that were implanted with a morphine pellet for 3, 7 and 21 days (20.7, 18.1 and 17.7 pmol/mg tissue, respectively) were observed when compared to that in slices from control mice that were implanted with placebo pellets (11.4 pmol/mg tissue). The enhancement in the binding affinity of DAMGO and naloxone and the increased density of DADLE binding sites paralleled the development of morphine tolerance and dependence and [D-Pen2,D-Pen5]enkephalin cross-tolerance in whole animals. An antinociceptive potentiation between morphine and DAMGO was observed in morphine-tolerant and -dependent mice whereas in naive animals the effects of the two drugs were additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Tagging Technique for the Simultaneous Measurements of Flow Velocity and Temperature Fields

We report recent improvements to the Molecular Tagging Velocimetry and Thermometry (MTV&T) technique for the simultaneous measurements of velocity and temperature fields in fluid flows. Instead of using tiny particles, specially-designed phosphorescent molecules, which can be turned into long-lasting glowing molecules upon excitation by photons of appropriate wavelength, are used as tracers for both velocity and temperature measurements. A pulsed laser is used to "tag" the tracer molecules in the regions of interest, and the movements of the tagged molecules are imaged at two successive times within the photoluminescence lifetime of the tracer molecules. The measured Lagrangian displacement of the tagged molecules between the two image acquisitions provides the estimate of the fluid velocity vector. The simultaneous temperature measurement is achieved by taking advantage of the temperature dependence of phosphorescence lifetime, which is estimated from the intensity ratio of the tagged molecules in the two images. The implementation and application of the MTV&T technique are demonstrated by conducting simultaneous velocity and temperature measurements in the wake region of a heated circular cylinder and a transient electroosmotic flow (EOF) inside a microchannel.
Cancer Cells Resistant to Therapy Promote Cell Surface Relocalization of GRP78 Which Complexes with PI3K and Enhances PI(3,4,5)P3 Production

Traditionally, GRP78 has been regarded as an endoplasmic reticulum (ER) lumenal protein due to its carboxyl KDEL retention motif. Recently, a subfraction of GRP78 is found to localize to the surface of specific cell types, serving as co-receptors and regulating signaling. However, the physiological relevance of cell surface GRP78 (sGRP78) expression in cancer and its functional interactions at the cell surface are just emerging. In this report, we combined biochemical, imaging and mutational approaches to address these issues. For detection of sGRP78, we utilized a mouse monoclonal antibody highly potent and specific for GRP78 or epitope-tagged GRP78, coupled with imaging and biochemical techniques that allowed detection of sGRP78 but not intracellular GRP78. Our studies revealed that breast and prostate cancer cells resistant to hormonal therapy actively promote GRP78 to the cell surface, which can be further elevated by a variety of ER stress-inducing conditions. We showed that sGRP78 forms complex with PI3K, and overexpression of sGRP78 promotes PIP3 formation, indicative of PI3K activation. We further discovered that an insertion mutant of GRP78 at its N-terminus domain, while retaining stable expression and the ability to translocate to the cell surface as the wild-type protein, exhibited reduced complex formation with p85 and production of PIP3. Thus, our studies provide a mechanistic explanation for the regulation of the PI3K/AKT signaling by sGRP78. Our findings suggest that targeting sGRP78 may suppress therapeutic resistance in cancer cells and offer a novel strategy to suppress PI3K activity.
Demonstration of Energy-Coded Compton Scatter Tomography with Fan Beams for One-Sided Inspection

Abstract An instrument is demonstrated whereby radiographic images of a sample's electron density are compiled from the information encoded in the energy spectra of gamma rays backscattered from one side of the sample. It is assumed that access is restricted to only one surface of the object under inspection. Use of energy coding allows imaging in a fan beam rather than independent interrogation of individual volume elements. The Multiplexed Compton Scatter Tomograph instrument consists of an array of high-energy-resolution detectors and fan beam collimators. Instrument signals are converted to electron density images using a penalized weighted least squares image reconstruction algorithm coupled with a deterministic system model that includes effects of Doppler broadening. The proof-of-principle instrument is demonstrated on aluminum samples. In an 8 mm thick sample with a 4 mm void in its center, contrast recovery of 90% is achieved. In a 10 mm thick sample with a 3 mm void at the back about 85% of the contrast is recovered.
Natural accommodation in the growing chicken

Abstract A new technique, Infrared Photoretinoscopy, has been employed for recording natural accommodation in the chicken. The illumination of the pupil by the fundus reflection of infrared light provided by high output light emitting diodes (I.R. LED's) was monitored on a video screen. The defocus of the eye could be calculated by evaluating the fraction of the pupil which was illuminated. It was found that: (a) in the chick the full range of accommodation (about 17D) is present in the first day after hatching, (b) accommodation acts completely independently in both eyes, (c) the “near pupillary response” is weaker in younger chicks, (d) the pupil constriction in response to light starts at higher luminance in the younger chicks (e) the developmental decrease of the f/number is not sufficient to explain the change of the pupil reaction to light. Problems resulting from the use of drugs in order to measure the refractive state using normal retinoscopy are discussed.
Passivity-based controller design for stablization of underwater gliders

The problem of stabilizing steady gliding is very critical for an underwater glider, which is subject to many non-negligible disturbances from the aquatic environment. Traditional control methods like PID control, LQR control or torque control, can not provide simultaneously easy controller implementation and fast convergence speed for stabilization. In paper we propose a new nonlinear, passivity-based controller for the stablization problem. The controller is designed based on an approximation of a reduced model that is obtained through singular perturbation analysis, and consequently, it does not require full state feedback and is thus easy to implement. The local stability of the closed-loop full system is established through linearization. Simulation results are provided to demonstrate that the proposed controller achieves rapid convergence in stabilization.
Mechanics of Saw-Tooth Chip Formation in Metal Cutting

The saw-tooth chip was the last of the major types to be identified. This occurred in 1954 during machining studies of titanium alloys which were then being considered for aerospace applications because of their large strength-to-weight ratio and corrosion resistance. This is a type of chip that forms when very hard brittle materials are machined at high speeds and feeds. Since this is an area of machining which will be of increasing interest in the future, particularly in hard turning, it is important that the mechanism and mechanics of this type of chip formation be better understood. At present, there are two theories concerning the basic origin of saw-tooth chips. The first to appear assumed they are of thermal origin while the second assumes they arise due to the periodic development of cracks in the original surface of the work. The thesis presented here is that the root cause for saw-tooth chip formations is cyclic cracking. This is followed by a discussion of extensive experimental data that supports this point of view.
GAL4 system in Drosophila: a fly geneticist's Swiss army knife.

The last decade has seen an enormous expansion in the genetic toolbox of model organisms. This has been particularly apparent in the fruitfly, Drosophila melanogaster, in which the development of these tools and their ongoing extension, along with the completion of the genome sequence has allowed for the analysis of most any process. One particularly elegant example of tool development was the creation of the GAL4/UAS system for targeted gene expression in Drosophila. In addition to helping make Drosophila one of the most genetically tractable metazoans, this system has also helped Drosophila attract attention from the biotechnology industry as a viable means to investigate the function of genes implicated in a wide variety of medically and economically important processes. In this article, we review the GAL4/UAS system in Drosophila and the numerous extensions that have morphed it into a veritable Swiss army knife for the analysis of gene function.
The glycosaminoglycans of estrogen-induced medullary bone in Japanese quail

Abstract Glycosaminoglycans were isolated from the femurs of estrogen-treated male Japanese quail. During the 72 h after the injection of estrogen the incorporation of a 1-h pulse of H235SO4 into keratan sulfate increased more than 100-fold in a pattern corresponding to the production of the induced medullary bone. The rate of incorporation into chondroitin 4-sulfate, the only other glycosaminoglycan detected, remained constant throughout the same time period. The rate of incorporation of the 1-h pulse of sulfate into chondroitin 4-sulfate and keratan sulfate was the same at 48 h of estrogen treatment. When birds (48 h estrogen) were allowed to live 6 h after the injection of the isotope, chondroitin 4-sulfate accumulated 5-fold over that found for similar animals labeled for only 1 h. Keratan sulfate, into which the isotope was incorporated at the same rate as the chondroitin sulfate in this experiment, did not accumulate much more in 6 h of labeling than in 1 h of labeling. This suggests that the keratan sulfate turns over more rapidly than the chondroitin 4-sulfate in this tissue. Autoradiography showed that the chondroitin 4-sulfate was associated mainly with the marrow cells near the cortical bone and the keratan sulfate with the newly synthesized medullary bone. These results suggest that keratan sulfate is a specific marker for this secondary bone matrix.
Systems Engineering Perspectives on Technology Readiness Assessments in Software-Intensive System Development

Technology readiness assessments as formal technologymaturity validation tools play an important role in system development and acquisition. Because of the particular diversity of technologies in software-intensive systems, such assessments pose a special challenge. This paper’s objective is to show how technology readiness assessments control the technology transition process from research to productization and to demonstrate that effective execution of this transition requires sophisticated systems engineering perspectives. To achieve this objective, a rigorous attempt was made to seek out and clarify the ambiguous elements of the process and to provide tangible guidance on the topic. Examples from the emerging technology-rich domains of unmanned aerial vehicles are used to facilitate a deeper understanding of the concepts introduced.
Structure of mesophase pitch fibers

Abstract The as-spun structure of mesophase pitch-based carbon fibers has been characterized by darkfield electron microscopy of microtomed fiber sections. Three levels of organization have been observed. At the molecular range, the pitch molecules are stacked together creating small coherent domains. At the intermediate range, microdomains are observed, consisting of molecular assemblies with long range orientational order. They are several μm long in the fiber direction, but their lateral extension is limited by wedge disclinations to a few hundred nm or less. Finally, the role of fluctuations of the microdomain density in controlling the degree of very long range statistical orientation over the fiber crosssection is described. The variety of observed textures encompasses the many types eventually observed in the carbonized fibers. The effect of pitch type on the microtexture and texture is demonstrated.
Neurobiology of empathy and callousness: Implications for the development of antisocial behavior

Information on the neurobiology of empathy and callousness provides clinicians with an opportunity to develop sophisticated understanding of mechanisms underpinning antisocial behavior and its counterpart, moral decision-making. This article provides an integrated in-depth review of hormones (e.g. peripheral steroid hormones such as cortisol) and brain structures (e.g. insula, anterior cingulate cortex, and amygdala) implicated in empathy, callousness, and psychopathic-like behavior. The overarching goal of this article is to relate these hormones and brain structures to moral decision-making. This review will begin in the brain, but will then integrate information about biological functioning in the body, specifically stress-reactivity. Our aim is to integrate understanding of neural processes with hormones such as cortisol, both of which have demonstrated relationships to empathy, psychopathy, and antisocial behavior. The review proposes that neurobiological impairments in individuals who display little empathy are not necessarily due to a reduced ability to understand the emotions of others. Instead, evidence suggests that individuals who show little arousal to the distress of others likewise show decreased physiological arousal to their own distress; one manifestation of reduced stress reactivity may be a dysfunction in empathy, which supports psychopathic-like constructs (e.g. callousness). This integration will assist in the development of objective methodologies that can inform and monitor treatment interventions focused on decreasing antisocial behavior. Copyright © 2009 John Wiley & Sons, Ltd.