cssi/SciSciGPT-SciSciNet huggingface dataset:
Wound location is independently associated with adverse outcomes following first-time revascularization for tissue loss.

Abstract Objective Few studies adequately evaluate the impact of wound location on patient outcomes after lower extremity revascularization. Consequently, we evaluated the relationship between lower extremity wound location and long-term outcomes. Methods We reviewed all patients at our institution undergoing any first-time open surgical bypass or percutaneous transluminal angioplasty with or without stenting for tissue loss between 2005 and 2014. We categorized wounds into three distinct groups: forefoot (ie, toes and metatarsal heads), midfoot (ie, dorsal, plantar, lateral, medial surfaces excluding toes, metatarsal heads, or heel), and heel. Limbs with multiple wounds were excluded from analyses. We compared rates of perioperative complications, wound healing, reintervention, limb salvage, amputation-free survival, and survival using χ2, Kaplan-Meier, and Cox regression analyses. Results Of 2869 infrainguinal revascularizations from 2005 to 2014, 1126 underwent a first-time revascularization for tissue loss, of which 253 patients had multiple wounds, 197 had wounds proximal to the ankle, 100 had unreliable wound information, and 576 (forefoot, n = 397; midfoot, n = 61; heel, n = 118) fit our criteria and had a single foot wound with reliable information regarding wound specifics. Patients with forefoot, midfoot, and heel wounds had similar rates of coronary artery disease, hypertension, diabetes, and smoking history (all P > .05). Conversely, there were significant differences in patient age (71 vs 69 vs 70 years), prevalence of gangrene (41% vs 5% vs 21%), and dialysis dependence (18% vs 17% vs 30%) (all P Conclusions Heel wounds confer considerably higher short- and long-term morbidity and mortality compared with midfoot or forefoot wounds in patients undergoing any first-time lower extremity revascularization.
Characteristics and Outcomes of Patients with Heart Failure Admitted with Covid-19 in a Cohort Study from Southeast Michigan

Introduction Cardiovascular comorbidities confer worse outcomes for patients with Coronavirus disease 2019 (COVID-19), but the impact of heart failure (HF) with preserved (HFpEF) and reduced (HFrEF) ejection fraction has not been well characterized. The aim herein is to examine outcomes in COVID-19 patients with and without HF. Methods Patients (n = 437) consecutively admitted with COVID-19 were categorized according to the presence vs. absence of HF and subcategorized according to HFpEF and HFrEF (EF Results The median cohort patient age was 68 (56-76) years, 43% (n = 189) were female, and 41% (n = 179) were Caucasian. HF was present in 29.7% (n = 130) of patients of which 43.8% (n = 57) had HFrEF and 56.2% (N = 73) had HFpEF. Patients with HF were more likely to be of older age and have more comorbidities. Overall inpatient mortality in the cohort was 12.3%. Compared to patients without HF (7.6%), patients with HFpEF (39.1%) and HFrEF (23.5%) had higher inpatient mortality (p 0.05) and there were no differences in inflammatory markers (ferritin, D-dimer, CRP, LDH). Independent predictors of inpatient mortality included: HFpEF (adjOR 2.55 (1.37-4.76)), age > 65 years (adjOR 3.00 (1.66-5.43), African American race (adjOR 1.82 (1.00-3.30)), Other race (adjOR 2.34 (1.02-5.37), p = 0.043), cerebrovascular disease (adjOR 3.07 (1.54-6.10), p = 0.001), and chronic hypoxic respiratory failure [adjOR 3.02 (1.19-7.62], p = 0.019)], whereas HFrEF was not (adjOR 1.58 (0.77-3.23). Discussion HF is prevalent in patients admitted with COVID-19. Patients with HFpEF had 2.6-fold higher mortality than those without HF and greater burdens of inpatient complications. Patients with HFpEF with COVID19 may warrant closer outpatient monitoring and a lower threshold for admission.
The Effect of Lunar-like Satellites on the Orbital Infrared Light Curves of Earth-analog Planets

We investigate the influence of lunar-like satellites on the infrared orbital light curves of Earth-analog extra-solar planets. Such light curves will be obtained by NASA's Terrestrial Planet Finder (TPF) and ESA's Darwin missions as a consequence of repeat observations to confirm the companion status of a putative planet. We use an energy balance model to calculate disk-averaged infrared (bolometric) fluxes from planet-satellite systems over a full orbital period (one year). The satellites are assumed to lack an atmosphere, have a low thermal inertia like that of the Moon and span a range of plausible radii. The planets are assumed to have thermal and orbital properties that mimic those of the Earth while their obliquities and orbital longitudes of inferior conjunction remain free parameters. Even if the gross thermal properties of the planet can be independently constrained (e.g. via spectroscopy or visible-wavelength detection of specular glint from a surface ocean) only the largest (approximately Mars-size) lunar-like satellites can be detected by light curve data from a TPF-like instrument (i.e. one that achieves a photometric signal-to-noise of 10-20 at infrared wavelengths). Non-detection of a lunar-like satellite can obfuscate the interpretation of a given system's infrared light curve so that it may resemble a single planet with high obliquity, different orbital longitude of vernal equinox relative to inferior conjunction and in some cases drastically different thermal characteristics. If the thermal properties of the planet are not independently established then the presence of a lunar-like satellite cannot be inferred from infrared data, thus demonstrating that photometric light curves alone can only be used for preliminary study of extra-solar Earth-like planets.
The Effect of Tax-Related Material Weakness in Internal Controls on the Market Valuation of Unrecognized Tax Benefits

ABSTRACT: This paper examines the effect of tax-related material weakness in internal controls (MWIC) over financial reporting investors' valuation of unrecognized tax benefits (UTBs). Firms are re...
Direct determination of absolute stereochemistry of α-methylselenocysteine using the Mosher method

Abstract Mosher amides of α-methylselenocysteine were synthesized to determine the absolute stereochemistry of the sterically hindered α-carbon utilizing 1H, 13C, 19F, and 77Se NMR spectroscopies. After analysis of these spectra using the established Mosher method, the stereochemistry of the α-carbon was determined to be (R), which was subsequently confirmed using x-ray crystallography.
Learning to be Creative: A Mutually Exciting Spatio-Temporal Point Process Model for Idea Generation in Open Innovation

This study investigates the creative idea generation process in an open innovation platform. Idea generation process is simultaneously influenced by multiple activities: knowledge acquisition from participants' interactions with each others' ideas, deliberate practice through persistent participation, and learning through failures. Due to the dynamic interplay across these activities, it is challenging to identify each activity's influence on creative ideation outcomes using reduced-form regression analysis. To overcome these challenges, we employ a comprehensive empirical framework, the mutually exciting spatio-temporal point process model with unobserved heterogeneity, which endogenizes the occurrences of these activities in continuous time and allows for user-dependent effects. By utilizing the activity stream data of 13,028 participants from 2010 to 2016 in an open innovation platform, we uncovered synergistic effects of these activities on creative outcomes. We find that knowledge acquired through interaction with others (i.e., stimulus ideas) plays a vital role in the creative ideation process, but their effect is more nuanced than what we have known so far. In contrast to the prior belief that distant analogies, stimulus ideas outside of a problem domain, spur creativity, we find that distant analogies lead to failures. Yet, we further find that such failures are indispensable to the creative ideation process because failures motivate idea generators (1) to acquire more knowledge by increasing their future interactions with other participants' ideas (learning from others), and (2) to persist in generating ideas that lead to improvements in their ability to apply the acquired knowledge and to identify innovation tasks that are relevant to their stock of acquired knowledge (learning by doing). Our results indicate that failures are a stronger driver of the learning activities than successes. Based on our findings, we offer insights on how to cultivate creativity in an open innovation setting.
Secrecy Inc.: How Governments Use Trade Secrets, Purported Competitive Harm and Third-Party Interventions to Privatize Public Records

As governments engage in public-private partnerships, they have devised ways to shield the public’s business from the traditional level scrutiny offered by citizens and journalists, watchdogs of the public trust. The authors propose rethinking public oversight of private vendors doing government business. First, the authors explore the historical and legal background of open records laws. This core purpose is undermined by overly broad interpretations of trade secrets and competitive harm exceptions, a trend exacerbated by the U.S. Supreme Court in a 2019 ruling. The authors demonstrate why public-private collusion to sabotage transparency demands a reinvigorated approach to the quasi-government body doctrine, which has been sharply limited for decades. The authors conclude with recommendations on reversing the trend.
The Stipulative Imagination of Thom Gunn

Thom Gunn is a British-American poet whose work has been praised and damned on both sides of the Atlantic. His first book of poems, Fighting Terms (1954), achieved considerable reputation in England, marking Gunn both as a member of "The Movement" then emerging in British letters and as an energetic young talent in his own right. English reviewers of Gunn's later volumes often decry what they consider a falling away from the wit, clarity, and prosodie control manifested in Fighting Terms.1 A number of American reviewers, on the other hand, have condescendingly dismissed Gunn as "a fashionable, rote versifier of some skill and intelligence"2 and his poems as manufactured, minor allegories.3 Surprisingly few critics have noted an obvious fact of Gunn's career: that he has been the most self-consciously existential poet of either Great Britain or America in recent years. Whether his existentialism is a dilettantish dallying or a deeply experienced world-view, it affects both the substance and the tech nique of his poetry. Critics and reviewers, for the most part, have failed to con front this poetry on its own terms, preferring their own criteria or prejudices. If only his versification were not so stiff and traditional, or his language so ab stract, American critics tell us, his poetry would measure up to his obvious in telligence. If only Gunn had maintained the technical brilliance of Fighting Terms, his early British admirers assert, his prosody would not have succumbed to creeping Americanism. Clearly Gunn cannot have the best of both worlds, British and American, when viewed from such perspectives. My central assumption here, in contrast, is a simple one: that a poet writes what he does not merely to be fashionable or to display his ingenuity, but to en act and enunciate his attitudes toward human experience. Gunn's attitudes, de rived from a consistently existential outlook, relate very closely to the kind of metaphor he develops in his poems: to the situations and persons he uses in these poems, and especially to the way he assigns value to or derives signifi cance from them. However much Gunn may have been captivated by literary
Observations on the Glass Phase Composition in Porcelains

The composition of the glass phase in a fired porcelain sample can be calculated exactly by taking the difference of the bulk chemical analysis and the quantitative crystalline phase composition obtained from powder X-ray diffraction. Data indicates that all of the glass phase compositions are similar at any given heat treatment temperature. The ratio of alkali (R 2 O) to alumina (Al 2 O 3 ) is essentially constant over the firing temperature range of 1150-1400°C. It is therefore proposed that the glass phase composition of triaxial porcelains lies on the glass formation boundary within the R 2 O-Al 2 O 3 -SiO 2 system. This observation has important implications for fast-firing, pyroplastic deformation, and fired strength of porcelains, and can be used to explain many of the inconsistencies in the published literature.
A generative model for semantic role labeling

Determining the semantic role of sentence constituents is a key task in determining sentence meanings lying behind a veneer of variant syntactic expression. We present a model of natural language generation from semantics using the FrameNet semantic role and frame ontology. We train the model using the FrameNet corpus and apply it to the task of automatic semantic role and frame identification, producing results competitive with previous work (about 70% role labeling accuracy). Unlike previous models used for this task, our model does not assume that the frame of a sentence is known, and is able to identify null-instantiated roles, which commonly occur in our corpus and whose identification is crucial to natural language interpretation.
Impact of channel estimation error on multiuser detection via the replica method

For practical wireless DS-CDMA systems, channel estimation is imperfect due to noise and interference. The impact of channel estimation error on multiuser detection (MUD) is analyzed under the framework of the replica method. System performance is obtained in the large system limit for optimal MUD, linear MUD and turbo MUD, and is validated by the numerical results of finite systems.
Causal Models: How People Think About the World and Its Alternatives

1. Agency and the Role of Causation in Mental Life Part I. The Theory 2. The Information Is in the Invariants 3. What Is a Cause? 4. Causal Models 5. Observation Versus Action Part II. Evidence and Application 6. Reasoning About Causation 7. Decision Making via Causal Consequences 8. The Psychology of Judgment: Causality Is Pervasive 9. Causality and Conceptual Structure 10. Categorical Induction 11. Locating Causal Structure in Language 12. Causal Learning 13. Conclusion: Causation in the Mind Notes References Index
Adaptations mediated by Akt via ATP citrate lyase and glycogen synthase kinase-3 to enhance glycolysis in astrocytoma pseudopodia

Proc Amer Assoc Cancer Res, Volume 47, 2006 1816 Malignant astrocytomas are lethal brain tumors that resist all therapies. Astrocytoma cell lines (U87 and LN229) display robust migration despite inhibition of mitochondria respiration, such as encountered in hypoxia. Whereas acidosis regulates glycolysis in normal cells, especially when they are disconnected from the vasculature, activated Akt putatively promotes mechanisms in tumor cells to remove metabolic acids intracellularly. Previous studies investigated Akt mediated signaling that putatively promoted removal of lactic acid via gluconeogenesis and glycogenesis. Akt’s phosphorylation of glycogen synthase kinase-3 (GSK3) that led to removal of GSK3’s constitutive inhibition of glycogen synthase (GS) by phosphorylation was associated with only a slight plateau of extracellular levels of lactic acid released by actively migrating cells under hypoxic conditions. Glycolytic migration was sensitive to inhibition of gluconeogenesis and control of Akt by phosphatase and tensin homolog (PTEN) and inhibition of phosphatidylinositol-3 kinase (PI3K). Lactic acid levels from intact cells rose when PTEN was restored to mutated cells (Beckner et al., Lab Invest, (in press) online 9/19/05). Citric acid with 3 carboxyl groups constitutes another potential contribution to acidosis in hypoxia. As the first intermediate of the Kreb’s cycle, citric acid is released by inactive mitochondria to the cytosol. Akt phosphorylates ATP citrate lyase (ACL) (Berwick et al., J Biol Chem 277:33895-900, 2002). ACL metabolizes cytosolic citrate to products that can be incorporated into cell constituents ([Fig. 1][1]). ACL is the most abundant endogenous protein increased in U87 pseudopodia compared to whole cells, as identified in 1D gels. Increased pseudopodial ACL was confirmed on U87 and LN229 immunoblots. Radicicol, an inhibitor of ACL (Ki et al., J Biol Chem 15:39231-6, 2000), inhibited (p < 0.01) hepatocyte growth factor-stimulated U87 migration in dose curves (at least 68.5 μM). Both ACL and GS, as a result of Akt’s activity, potentially mediate avoidance of metabolic acidosis to permit glycolysis in hypoxic conditions such as invasion. Funding from the Nick Eric Wichman Foundation. ![Figure][2] [1]: #F1 [2]: pending:yes
Role of Cardiac MRI in the Assessment of Cardiomyopathy

Combining the diagnostic utilities of cardiac structures, myocardial perfusion, and various tissue characterizing pulse sequence methods in matching scan planes within a single imaging session, cardiac magnetic resonance imaging (CMR) provides a novel interrogation of myocardial physiology and abnormal anatomy from various forms of cardiomyopathy. Establishment of technical imaging standards and clinical adaptation in the past years has helped recognize the distinguishing features of different cardiomyopathies, with CMR currently assuming a pivotal role in the diagnosis of cases of new-onset cardiomyopathy in experienced centers. Quantitative measurements such as ventricular volumes, myocardial iron content, and extent of late gadolinium enhancement can effectively monitor disease status, guide medical therapy, and impact patient outcomes in specific clinical settings. This chapter will aim to summarize these current CMR applications with case examples.
trans-acting factors interact with a cyclic AMP response element to modulate expression of the human gonadotropin alpha gene.

Abstract The alpha subunit of the placental hormone chorionic gonadotropin is regulated by cyclic AMP (cAMP) at the transcriptional level. A cAMP-responsive fusion gene (alpha-CAT) containing 1.5 kilobases of the alpha gene 5'-flanking sequence linked to the chloramphenicol acetyltransferase (CAT) gene was used as a transcriptional reporter in competition assays in transfected JEG-3 choriocarcinoma cells. Expression of the alpha-CAT fusion gene increased linearly with increasing amounts of transfected plasmid and was maximal at the same amount of alpha-CAT DNA (2 micrograms) with or without cAMP treatment. Various amounts of different competitor DNA sequences were cotransfected with the alpha-CAT reporter plasmid to examine the interactions of intracellular trans-acting factors with the regulatory elements of the alpha gene promoter. An 800-base-pair fragment of alpha gene 5'-flanking sequence inhibited both basal and cAMP-stimulated transcription of the alpha-CAT reporter plasmid in a dose-dependent manner, indicative of interactions with one or more trans-acting factors that activate alpha gene expression. The alpha gene sequences that interact with intracellular regulatory factors were defined by using several discrete regions of the 5'-flanking sequence as competitors for alpha-CAT expression. A proximal promoter sequence (-99 to +44) containing the CCAAT box, TATA box, and transcriptional initiation site was a relatively ineffective competitor of alpha-CAT transcription. In contrast, an upstream sequence between -236 and -100 was an effective competitor for transcriptional activators of alpha-CAT expression. Competition for alpha-CAT expression by this regulatory sequence did not require cis interactions with downstream promoter elements and was equally effective with or without cAMP treatment. An 18-base-pair repeated sequence within this region of the alpha gene (-146 to -111) greatly enhanced both basal gene expression and cAMP responsivity and also competed for limiting cellular transcription factors. These findings suggest that JEG-3 cells contain trans-acting factors that interact with a cAMP response element to activate alpha gene transcription. The chorionic gonadotropin beta gene 5'-flanking sequence also competed for alpha-CAT expression, suggesting that a common trans-acting factor is shared by the regulatory sequences of the alpha and beta genes.
Physical Activity and Nutrition in Children and Youth: An Overview of Obesity Prevention☆☆☆

Abstract Obesity, especially among children, has become epidemic. Even with major advances in genetics, behavior is likely to continue to play a central role in the development of adiposity and obesity. Interventions to help children and adolescents change their dietary or physical activity behaviors may be justified on four grounds: (1) immediate social and health benefits may be obtained; (2) critical periods in childhood may require certain behaviors to lead to healthy outcomes in adulthood; (3) chronic diseases and their elevated risk factors detected in youth may track into the adult years; and (4) the behaviors established in childhood may track into the adult years. Immediate benefits for children (ground 1) and the high tracking of obesity from childhood to the adult years (relates especially to grounds 3 and 4) are the strongest reasons for helping children acquire and retain healthy habits. The nine other papers in this supplemental issue address measurement and intervention issues, with special emphasis on obesity prevention. Reviews of the measurement literature were conducted for diet, nutritional status, physical activity, physical fitness, process evaluation, and environmental factors. Reviews of the intervention literature were conducted for health care providers, schools, and larger community settings. Effective programs for children can and should be designed, implemented, and evaluated.
Dynamics and Structure of Interacting Nonpremixed Flames

Abstract Interaction between neighboring parallel and nearly parallel flames occurs more frequently as the turbulent length scales become smaller, and when a flame trapped in a large vortical structure spins further inside its core. In this paper, a model to simulate the interaction between neighboring, strained thin flames is proposed, and is used to investigate the mechanism and impact of the interaction for the case of a methane–air flame described by a four-step reduced kinetics mechanism. In the model, the interaction between neighboring strained flames is simplified by combining them into a single stagnation-point flow structure with one of the major reactants trapped in the vicinity of the stagnation plane. We find that in both cases of flames converging toward the oxidizer or the fuel, the interaction does not occur until the reaction zones overlap. The difference between the two cases is caused by the deep penetration of oxygen into the fuel side in the former case as opposed to the rapid decomposition of the fuel as soon as the temperature rise is sufficiently high in the latter case. In both configurations, during the interaction phase, the burning rate increases as the hydrogen radical concentration rises due to the overlap of the two reaction zones, leading to a sudden termination of combustion as the trapped reactant is depleted, followed by an overshoot in the peak temperature. Thus, the interaction between neighboring flames is governed by chemical rather than thermal exchange. The burning enhancement in the first case is connected with the abundance of H in the last stages of oxygen consumption, while in the second case, it is due more to the burning of CO. Results also show that the after-extinction evolution of CO is quite different in two the cases. In the case of flames interacting across the oxidizer, the after-extinction dynamics of CO is similar to that of other major species, while for flames converging toward the fuel, CO after reaching levels higher than encountered in isolated flames, is rapidly consumed.
African monsoons, an immediate climate response to orbital insolation

The Croll–Milankovitch astronomical theory of climate1–3 has received strong support from the evidence of a linear climatic forcing by obliquity and precession, although nonlinearity had to be assumed for eccentricity4,5. Moreover, interglacials have appeared to be controlled by the orbital insolation6 although a phase shift of 6,000–5,000 yr is seen between an astronomical climate index and terrestrial climate indicators, dominated by the northern ice-sheet dynamics. Climate proxy data of low latitudes are less directly dependent on the ice sheets. Here it is shown that during the past 464,000 yr, African monsoons signalled by the East Mediterranean sapropels were heaviest always and only when a northern summer monsoon index, computed from the orbital variation of insolation, reached maximum values. This occurred during all the interglacials, but also twice during glacial periods. Thus tropical aridity is not the single climatic pattern of glacial periods. An immediate terrestrial climate response to orbital variations of insolation is established.
ChoiceNet gaming: Changing the gaming experience with economics

When playing online games, the user experience is often dictated by the performance of the network. To deliver the best possible gaming experience, game developers often find themselves developing work-arounds that try to mask the lack of control they have over of the existing TCP/IP Internet. ChoiceNet, an emerging future Internet architecture, attempts to give applications enhanced control (choice) over the service they receive from the network. In particular, ChoiceNet supports an economic plane in which applications can purchase services from any provider. Because providers are compensated, they are motivated to offer a variety of innovative, excellent services, enabling applications to select the service best suited for its needs. Instead of coding work-arounds, game developers can obtain precisely the network service that is needed to optimize the game experience. In this paper, we describe the emerging ChoiceNet architecture and show how computer games can benefit from the alternatives enabled by ChoiceNet. To demonstrate the benefits of the ChoiceNet architecture, we implemented a first person shooter game that uses ChoiceNet to “purchase” and then send data over the purchased path resulting in substantially lower latency than the default path. We describe the ChoiceNet services used to implement the game, and we present performance results that show a significant reduction in latency. We also show how ChoiceNet can be used to purchase reliable (non-lossy) communication paths that improve the user's experience.
A unified view of virtualization

Virtualization technologies have been developed by a number of computer science and engineering disciplines, sometimes independently, often by different groups and at different times. Not surprisingly, these groups each view virtualization as a sub-discipline, so it is studied in a fragmented way. In the future, however, virtualization will become an essential part of all computer systems by providing smart interconnection mechanisms for the three major system components - application software, system software, and hardware. Consequently, the study of virtualization technologies will become a discipline in its own right and will stand on equal footing with the other major areas of computer systems design.
Equinovarus Deformity Correction With the Taylor Spatial Frame

The Ilizarov method has gained much popularity over the years in the treatment of fractures, limb-length discrepancy, nonunion, bone defects, deformity (malunion), soft-tissue contracture, and osteomyelitis. More recent developments have been made in designing a multiplane external fixator, the Taylor Spatial Frame (Smith & Nephew, Memphis, TN), to treat these complex deformities. This versatile device allows gradual deformity correction using a system of 6 articulated struts, tibial rings, a foot-plate, half-pins and wires. The use of this system requires an understanding of basic Ilizarov principles and technique. The Taylor Spatial Frame corrects both osseous and soft-tissue deformities. Treatment of equinovarus is well suited for gradual correction. At our institution, we routinely use circular external fixation for correction of complex forefoot, hindfoot, ankle, and tibia deformities. Judicious use of the Taylor Spatial Frame allows for correction of deformity and preservation of limb length. Our goal in the treatment of equinovarus deformities is to achieve a painless, plantigrade, and functional foot. In this article, we share our surgical approach in treating equinovarus deformity contractures with the Taylor Spatial Frame.
Efficient manufacturing of viral vectors for cancer therapies

HEK-293 cell lines have been widely used for over 35 years by the scientific community. Currently HEK-293 cells are the most efficient system for the improved production of ribosomal proteins and viral vectors by large-scale transfection of suspension-growing cells in serum-free medium. Also, it is the most established cell line for the production of adeno- and adeno-associated viruses, retro- and lentiviruses for gene therapy applications. Additionally HEK-293 cells sustain replication of many viruses that are evaluated as vaccines or viro-therapeutic agents. Consequently numerous viral vectors produced in HEK-293 cells have been approved for phase II and phase III clinical trials. In this presentation, major achievements in process developments completed at NRC to support the large scale manufacturing of viral vectors and vaccines using HEK-293 technology platform will be reviewed. In particular, we will discuss the development of REOLYSIN®, an oncolytic reovirus type 3 Dearing based therapeutic that is currently evaluated in phase III. The REOLYSIN® manufacturing process was scaled-up to a 100 L operation volume to support multicenter clinical evaluation. Advanced online monitoring tools allowed a very precise characterisation of viral infection and production kinetics to demonstrate process robustness, define critical process parameters and establish the process operating space according to the Quality-by-Design guidelines. Through different examples, the presentation will also discuss practises and experiences at NRC in supporting translational research and technology transfer.
Acellular Low-Potassium Dextran Preserves Pulmonary Function After 48 Hours of Ischemia

Abstract Background . We previously have shown that extracellular preservation solutions provide superior pulmonary protection after 18 hours of cold ischemia at 4°C in an isolated, whole-blood–perfused, rabbit lung model. We also reported that the addition of 20% whole blood to a low-potassium dextran solution (BLPD) conferred no discernible advantage over low-potassium dextran (LPD) alone in this same model. Our current study was aimed at documenting the importance of blood in buffering extracellular preservation solutions during 24 to 48 hours of hypothermic ischemia. Methods . We studied three groups of lungs using an isolated, whole-blood–perfused, ventilated, rabbit lung model. Lungs were flushed with Euro-Collins, LPD, or BLPD solution, and then were reperfused after 24, 36, or 48 hours of hypothermic storage at 4°C. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, tidal volume, and dynamic airway compliance were obtained. Fresh, non-recirculated venous blood was used to determine single-pass pulmonary venous-to-arterial O 2 gradients. Results . The 24-hour Euro-Collins group could not be completed because of immediate reperfusion failure. The 36-hour LPD group oxygenated significantly better than the 36-hour BLPD group (363.3 ± 65.1 versus 145.3 ± 40.3 mm Hg, respectively; p = 0.015). The 48-hour LPD group also experienced significant improvements in oxygenation when compared with the 48-hour BLPD group (pulmonary venous-arterial O 2 difference of 239.4 ± 48.4 versus 70.7 ± 19.5 mm Hg, respectively; p = 0.012). The 48-hour LPD group also displayed significant improvements in pulmonary artery pressure (34.72 ± 0.96 versus 55.52 ± 7.37 mm Hg, respectively; p = 0.031) and pulmonary vascular resistance (39,737 ± 1,291 versus 67,594 ± 9,467 dynes · s · cm −5 , respectively; p = 0.027) when compared with the 48-hour BLPD group. There were no significant differences between the three LPD groups. Conclusions . Extracellular solutions provide improved pulmonary preservation in an isolated rabbit lung model after 48 hours of cold ischemia. The addition of blood to extracellular preservation solutions diminishes pulmonary function when combined with ischemic periods of 36 to 48 hours.
Radiative heat transfer in coupled Mie and Rayleigh atmosphere

Expressions describing radiative heat transfer in a coupled Mie and Rayleigh scattering atmosphere have been obtained by employing the modified two-stream approximation. The effect of tropospheric aerosols on the albedo as well as on heating rates in the wavelength region from 0.3 to 2.0 microns is studied. The present study indicates that the distinction between cooling or warming of the earth-atmosphere system for a realistic aerosol model proposed by McClatchey will depend on the surface reflectivity being smaller or larger than approximately 0.37. The effect of aerosols on the heating rate close to the surface has the same order of magnitude as atmospheric water vapor.
Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow

Hematopoietic progenitor/stem cell homing to the bone marrow requires the concerted action of several adhesion molecules. Endothelial P- and E-selectins play an important role in this process, but their ligands on a large subset of neonate-derived human CD34+ cells are absent, leading to a reduced ability to interact with the bone marrow (BM) microvasculature. We report here that this deficiency results from reduced α1,3-fucosyltransferase (FucT) expression and activity in these CD34+ cells. Incubation of CD34+ cells with recombinant human FucTVI rapidly corrected the deficiency in nonbinding CD34+ cells and further increased the density of ligands for both P- and E-selectins on all cord blood–derived CD34+ cells. Intravital microscopy studies revealed that these FucTVI-treated CD34+ cells displayed a marked enhancement in their initial interactions with the BM microvasculature, but unexpectedly, homing into the BM was not improved by FucTVI treatment. These data indicate that, although exogenous FucT enzyme activity can rapidly modulate selectin binding avidity of cord blood CD34+ cells, further studies are needed to understand how to translate a positive effect on progenitor cell adhesion in bone marrow microvessels into one that significantly influences migration and lodgement into the parenchyma.
The INSIGHT and NORDIL trials: Are calcium antagonists equivalent to established drug therapies for cardiovascular protection?

Calcium channel blockers have come into worldwide use for treating hypertension and other circulatory disorders. In recent years, results of several observational studies have suggested that these drugs may not be as safe or effective as other available therapies, such as diuretics and & #x00DF; -blockers, in the prevention of cardiovascular events. The Nordic Diltiazem (NORDIL) and the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) studies were the first two randomized interventional trials in hypertensive patients that directly compared the effects of therapy based on calcium antagonists with those of diuretic and s -blocker-based treatment on major cardiovascular endpoints. Both studies found that the effectiveness of calcium antagonist therapy was similar to that of diuretic and s -blocker therapy for preventing the composite primary endpoint of fatal and nonfatal stroke, myocardial infarction, and other cardiovascular death. The two studies shared several nonsignificant trends for cause-specific events, including greater stroke prevention and lesser coronary event prevention in the calcium antagonist groups compared with the diuretic and s -blocker groups. There is not yet sufficient evidence to prove whether cause-specific differences exist. Results of the NORDIL and INSIGHT studies support incorporating calcium antagonist-based therapy as an additional safe and effective approach for preventing blood pressure-related illness and death.
PERSPECTIVES: Is Medicine Altruistic? A Query from the Medical School Admissions Office

Background: Applicants to medical school often state that they are motivated by a desire to help others. Admissions officers must evaluate these claims, but assessment of altruism is difficult and imprecise. Summary: A purely utilitarian moral philosophy denies the possibility of altruism. However, the Enlightenment philosopher Hume described a force, sympathy, that engages channels of communication between persons and rewards benevolence. Although there are many pretenders to altruism, the medical school interview provides an opportunity to create a channel of sympathy and to assess its authenticity. Conclusions: By probing for evidence of clinical sympathy, the medical school interviewer may be able to verify whether the applicant's claims of altruism are authentic. Claims of altruism that have not been borne out in action should be viewed with skepticism.
Calibration of a multisensor structured light range scanner

An optical noncontact 3-D range scanner based on projection of 2-D structured light patterns and multiplexed charge injection device (OlD) camera sensors is developed. The system acquires scan data in 0.75 s and allows 360-deg examination of the object. The resultant 3-D surface data is suitable for computer graphics display and manipulation, numerically controlled replication, and for further processing such as surface measurement extraction. The scanner uses a set of six stationary sensors placed around the object to be scanned. A sensor consists of a pattern projector and a solid state video camera. The projectors are sequenced by a module called the video acquisition and control unit (VAU). This complex system must be accurately calibrated for seamless merging of overlapped surfaces obtained from different cameras. The calibration considerations in such a system are discussed. The calibration is accomplished using statistical parameter estimation algorithms. Known reference objects are used in the calibration procedure.
Towards the interpretation of Uranus's eccentric magnetic field

Abstract Coriolis forces stimulate dynamo action in a rapidly-rotating fluid by promoting complexities in the pattern of fluid motions, notably departures from symmetry about the axis of rotation. This pattern and its time variations determine the instantaneous form and temporal behaviour of the magnetic field so produced. Instantaneous magnetic fields will usually exhibit in their broad-scale features approximate alignment with the rotation axis. This is borne out by observations of the magnetic fields of the Earth, Jupiter and Saturn, and it is likely on general grounds that Neptune will be found to have an aligned magnetic field. But, as is shown by laboratory and theoretical studies of thermal convection in rapidly-rotating fluids, for some ranges of rotation speed, rate of heating, etc. certain patterns can occur which in electrically-conducting fluids would produce magnetic fields exhibiting departures from alignment with the rotation axis, which instantaneously could be quite pronounced but would a...
Gas Diffusion and Solubility in Poly(organophosphazenes): Results of Molecular Simulation Studies

A combination of quantum chemistry, molecular dynamics, and Monte Carlo methods have been used to investigate gas diffusion and solubility in three isomeric poly[di(butoxyphosphazenes)] and in amorphous and crystalline states of poly[bis(2,2,2-trifluoroethoxyphosphazene)] (PTFEP). In this review of recently published studies reported from our laboratory, conclusions are reached in regards to the relationship between polymer structure and gas diffusion and sorption in poly(organophosphazenes). These conclusions also serve to validate our current understanding of the nature of gas transport in other polymers. Specifically, gas diffusivity has been shown to increase with increasing side-chain and main-chain mobility as determined from vectorial autocorrelation function analysis; however, high diffusivity is accompanied by a loss in diffusive selectivity resulting in decreasing permselectivity with increasing permeability. Simulation of crystalline supercells of PTFEP indicate that gas diffusion is unrestricted in the crystalline state as has been reported only for a few other polymers, principally poly(4-methyl-1-pentene). Gas solubility in poly(organophosphazenes) correlates well with gas condensability as measured by the Lennard–Jones potential well depth parameter, ɛ/k. Exceptions are cases where specific interactions can occur between gas molecules and the polymer chain such as is the case of CO2 and PTFEP. High-level ab initio calculations of the interaction of CO2 with low-molecular-weight fluoroalkanes indicate the presence of a weak quadrupole–dipole interaction. Association of CO2 with the trifluoromethyl groups of the trifluoroethoxy side chain of PTFEP has been confirmed by radial distribution function (RDF) analysis of MD trajectories. Comparison between solubility coefficients obtained from Grand Canonical Monte Carlo (GCMC) simulations of amorphous cells with experimental values of microcrystalline PTFEP indicates that gas solubility in polyphosphazenes such as PTFEP that exhibit a mesophase/crystalline state is greatly reduced.
American radium engenders telecurie therapy during World War I.

From 1899 to 1912 there was a European monopoly controlling the sale of radium for cancer therapy. This trust was finally broken, albeit only temporarily, in 1912/13 by American entrepreneurs J. Flannery, H. Kelly, and J. Douglas. Joe Flannery was a former mortician turned mining magnate. Dr. Howard Kelly was the renowned gynecological surgeon at Johns Hopkins Hospital and Medical School who defied tradition by maintaining his own private hospital. Professor James Douglas was the Arizona copper king who helped support Memorial Hospital in New York City as America's first cancer hospital. During 1913-1916 surgeons Howard Kelly (Baltimore) and H. H. Janeway (Memorial Hospital) began using radium and radon for the treatment of deep seated cancers. Their technique required placement of the sources several centimeters away from the skin surface. As this new concept, telecurie therapy, resulted in a significant decrease in dose rate, it was necessary for both surgeons to have several grams of radium, costing $180000/gram, in their possession. Fortunately, Kelly and Janeway were the sole beneficiaries of a radium mining company, the National Radium Institute, from 1913 to 1916. With this unique American source of radium and with Europe otherwise preoccupied, these two American surgeons pioneered megavoltage telecurie therapy, using the 1.2 MeV gamma rays of "mass radium."
Delayed Abscission and Shorter Internodes Correlate with a Reduction in the Ethylene Receptor LeETR1 Transcript in Transgenic Tomato

Stable transformation of tomato (Lycopersicon esculentum cv Ailsa Craig) plants with a construct containing the antisense sequence for the receiver domain and 3'-untranslated portion of the tomato ethylene receptor (LeETR1) under the control of an enhanced cauliflower mosaic virus 35S promoter resulted in some expected and unexpected phenotypes. In addition to reduced LeETR1 transcript levels, the two most consistently observed phenotypes in the transgenic lines were delayed abscission and reduced plant size. Fruit coloration and softening were essentially unaffected, and all the seedlings from first generation seed displayed a normal triple response to ethylene. Two independent lines with a single copy of the transgene and reduced LeETR1 transcript accumulation were selected for detailed phenotypic analysis of second generation (R1) plants. Delayed abscission, shorter internode length, and reduced auxin movement all correlated with the presence of the transgene and the degree of reduced LeETR1 transcript accumulation. No significant differences were noted for fruit coloration or fruit softening on R1 plants and all seedlings from R1 and R2 seed displayed a normal triple response. LeETR2 transcript accumulation was only slightly reduced in the R1 plants compared with azygous plants, and LeETR3 (NR) transcript levels appeared to be unaffected by the transgene. We propose that ethylene signal transduction occurs through parallel paths that partially intersect to regulate shared ethylene responses.
RNA polymerases and transcriptional activity of the fat body during the final larval instar of the tobacco hornworm Manduca sexta

The activities of RNA polymerases I and II in the fat body of the tobacco hornworm larva increased during feeding and then declined during wandering in the fifth instar (Sridhara and Gilbert, Dev Biol 45:7–21 [1975]). RNA polymerase II activity was much higher than that of RNA polymerase I. To determine how the differences in the activities of the two enzymes and their developmental changes correlate with changes in RNA and protein, the contents of these macromolecules were determined during the same period. RNA and protein increased by about 8 to 10-fold during the feeding period. Activities of RNA polymerases I and II in nuclei, as well as those present in “free” (not transcribing) and “engaged” (transcribing) pools, were measured. Incorporation of labeled uridine into RNA by fat body cells in vitro was correlated to nuclear enzyme activities. The amounts of RNA polymerases I, II, and III were determined by the application of an ELISA with subunit-specific monoclonal antibodies. Results showed that even though the in vitro activity of RNA polymerase II and its amounts are higher than those of RNA polymerase I and III, rRNA and tRNA syntheses predominated over mRNA synthesis in vivo. The activities and amounts of RNA polymerase II in the “free” pool were higher than those for RNA polymerase I. The “free” pools of the two enzymes increased as the larva progressed through the fifth instar. There appears to be little correlation between RNA polymerase activities and RNA synthesis during wandering, as RNA synthesis by the tissue and nuclear RNA polymerase activities declined faster than the amounts of the enzymes. The amount of RNA remained fairly steady during the same period. 20-hydroxyecdysone did not affect either the RNA polymerase activities or RNA synthesis of the fat body cultured in vitro. © 1995 Wiley-Liss, Inc.
Studies on the Rate and Control of Antibody Oxidation by Periodate

Abstract The oxidation of antibody carbohydrate residues by periodate is a common approach for the site-specific immobilization or modification of antibodies for use in various bioanalytical methods. This study examined the time dependence of this oxidation process under a variety of pH, temperature, and concentration conditions. Polyclonal rabbit immunoglobulin G (IgG) was used as the model system for these studies. Flow-injection analysis and a hydrazide label (Lucifer yellow CH) were used to monitor the progress of the oxidation reaction. It was found that the number of oxidized sites that were available for labeling could be varied between one and eight groups per antibody by adjusting the time, pH, periodate concentration, or reaction temperature. In each case, most of these groups were produced during the first 30-60 min of the reaction. A comparison was made between these results and those of previous studies that have examined the effects of periodate treatment on amino acid residues and antibody activity. From this work, general guidelines were developed for the control and optimization of antibody oxidation for use with assays that require either high or low levels of antibody modification.