bluuebunny/crossref_metadata_2025 huggingface dataset:
Marie Cardona. An Ambivalent Nature‐Symbol in Albert Camus’s L’étranger
Authors: Scherr Arthur
Published: December 2010

Although a relatively minor character in Camus’s novel L’étranger, Marie Cardona, the protagonist Meursault’s lover, was the author’s favorite creation. She represents love of life and unabashed sexuality in the novel to a greater degree than any other character. Recently, feminist scholars have viewed her from complex, sometimes contradictory perspectives. They are unable to decide whether Camus designed her as an autonomous figure or a mere cardboard sexual plaything for the neurotic Meursault. Some critics link Camus’s alleged anti‐Arab racism to his supposed depiction of Marie as a helpless, passionless woman lacking an independent identity. This article depicts Marie as a “natural woman,” who ultimately appreciates Meursault’s blunt honesty, even when he says he does not love her. Contrary to most critics, Marie demonstrates an active sexuality rather than serving as Meursault’s sexual object. Indeed, the converse may be closer to the truth. After their initial encounter at the swimming pool, Meursault is often shy and passive and has to be coaxed into sexual behavior by the more aggressive Marie. After his mother’s death, Meursault seeks a close personal relationship with a woman, and hopes to find it with Marie. He rejects his brutish friend Raymond’s suggestion that they go to a brothel because he wants a more meaningful relationship. An essentially passive individual, Meursault requires the stimulation of a lustful, affectionate, life‐affirming young woman like Marie to awaken his sexuality. That Camus, an admirer of ancient Greco‐Roman myth, may have intended Marie to represent a Greek fertility goddess figure is suggested when she smites the asphodel flowers with her handbag on the way down to the beach where Meursault kills the Arab. The asphodel was the flower sacred to Persephone/Proserpine, wife of Hades/Pluto. Ironically, she was goddess of the Underworld and the dead and also daughter of Demeter/Ceres, goddess of fertility and the harvest. Since previous critics have linked the descent of Meursault and Marie to the beach from the bus‐stop to Dante’s descent from the “asphodel plateau” into Hell in the Divina commedia, this is a plausible interpretation of Marie’s subliminal identity. Marie embraces the sun and the sea and merges with them in a successfully consummated relationship. Unlike Meursault, for whom she may resemble his mother in her youth, she is at peace with herself and the world. For Camus, her dark, tanned skin symbolizes her identification with Nature and the body and rejection of thoughts of death. In her love of life and her play with the asphodels on the deathly plateau leading to the fatal beach, Marie reveals an essential innocence and ambivalence as a Persephone‐like, life/death Nature symbol, and a female, life‐assertive Antichrist.
The Politics of Improvement in Thomas Holcroft’s Anna St Ives
Authors: Jung Sandro
Published: December 2010

The article considers Thomas Holcroft’s Jacobin novel, Anna St Ives (1792), and, rather than focusing primarily on the oft‐explored narrative introducing Frank Henley and Anna St Ives as exponents of an enlightened philosophy of ‘mind’, concentrates on an alternative narrative of improvement. I shall focus on a discussion of the minor characters, Sir Arthur St Ives and Abimelech Henley, the baronet’s steward, and contextualise their landscaping activities as part of an improvement narrative that is informed by Enlightenment values of such landscape gardeners as William Shenstone and Thomas Whately. I shall also briefly relate the characters to an earlier comic tradition utilising the figure of the Quixote.
Telling Tales – Narrative Patterns in Rimbaud’s ‘Conte’, ‘Royauté’ and ‘Aube’. ‘Une belle gloire d’artiste et de conteur emportée!’
Authors: Macklin Gerry
Published: December 2010

In this paper I seek to examine three poems from Rimbaud’s Illuminations within the context of the poet’s well‐advertised predilection for the tale and fairy tale. Thus I seek to analyse ‘Conte’, ‘Aube’ and ‘Royauté’ as examples of how the poet begins from the notion of the fairy tale as a genre and proceeds to compose prose poems, which both imitate and deviate from the norms and protocols of this parent genre. Essentially, I offer close reading of each of the texts in order to illustrate key aspects of their structure and vocabulary and in the process I highlight what I consider to be essential elements of the Rimbaldian prose poem. I have referred from time to time to leading Rimbaldian scholars whose work has also looked at this or related areas of the poet’s writing.
MPEG‐hexPLA Micelles as Novel Carriers for Hypericin, a Fluorescent Marker for Use in Cancer Diagnostics
Authors: Mondon Karine , Zeisser‐Labouèbe Magali , Gurny Robert , Möller Michael
Published: December 2010

Ovarian cancer is the most common gynecological cancer diagnosed in Western countries. Detection of micrometastases at an early stage of the disease could lead to a cure rate of 90% by limiting the spread of the disease outside the ovaries. In this article, hypericin (Hy), a hydrophobic photosensitizer used for the photodynamic diagnosis (PD) of ovarian cancer, was efficiently incorporated into a core of micelles made from methoxy‐poly(ethylene glycol) and hexyl‐substituted poly(lactides) copolymers. The fate of these micelles following intravenous injection was studied in vivo in two ovarian tumor‐bearing animal models. In the chick embryo chorioallantoic membrane model, 17 times more Hy accumulated in tumor nodules when Hy was delivered with micelles than when Hy was delivered as an ethanol solution. Studies of the biodistribution of Hy in Fisher rats revealed escape of these nanosized micelles (<32 nm) from the mononuclear phagocyte system. Hy‐loaded micelles showed maximal accumulation in tumors and demonstrated the best tumor/muscle contrast visible 3 h after injection in the rat model. The rapid and highly selective accumulation of Hy in tumors that we demonstrated in this study suggests that these micelle formulations could be used for the PD of ovarian cancer in the future.
Research Methodology: An Innovative Approach to a Venerable Course
Authors: Morrel‐Samuels Palmer , Zimmerman Marc
Published: December 2010

This paper outlines a number of innovations that we have recently implemented in the Research Methodology Course at the University of Michigan’s School of Public Health. Consistent with the goals of evidence‐based medicine, evidence‐based public health, intrinsic motivation, and phase 4 (T4) translational research, we have placed the emphasis on enhancing the students’ desire to learn—and more specifically on their desire to learn rigorous methods for conducting useful research that delivers practical benefits in a straightforward manner. A dozen innovations, along with some preliminary outcomes, are outlined in detail. Clin Trans Sci 2010; Volume 3: 309–311
Enhancing Participant Safety through Electronically Generated Medication Order Sets in a Clinical Research Environment: A Medical Informatics Initiative
Authors: Formea Christine M. , Picha Andrew F. , Griffin Monica G. , Schaller Jane A. , Lee Mary R.
Published: December 2010

While clinical medicine is often well supported by health system information technology infrastructure, clinical research may need to create strategies to use clinical‐medicine informational technology tools. The authors describe a medication‐safety initiative that was carried out in a National Institutes of Health Clinical and Translational Science Award (CTSA)‐sponsored clinical research environment. A web based, medical informatics application was designed and implemented that allowed research groups to build protocol specific, electronic medication templates that were subsequently used to create participant‐specific medication order sets for conductance of clinical research activities in the CTSA‐sponsored clinical research environment. The medical informatics initiative eliminated typewritten or handwritten medication orders, created research protocol‐specific templates meeting institutional order‐writing requirements, and formalized a rigorous review and approval process. Enhancing safety in medication ordering and prescribing practices in a clinical research environment provided the background for multidisciplinary cooperation in medical informatics. Clin Trans Sci 2010; Volume 3: 312–315
Pseudoxanthoma Elasticum: A Streamlined, Ethnicity‐based Mutation Detection Strategy
Authors: LaRusso Jennifer , Ringpfeil Franziska , Uitto Jouni
Published: December 2010

Pseudoxanthoma elasticum (PXE), an autosomal recessive multisystem disorder, is caused by mutations in the ABCC6 gene, and approximately 300 distinct mutations representing >1,000 mutant alleles have been disclosed thus far. Few population‐based studies have reported mutational hotspots in some geographic areas. In this study, we attempted to correlate recurring mutations with the individuals’ ethnic origin. Specifically, we plotted our international database of 70 families from distinct or mixed ethnic backgrounds against their mutations. The frequent p.R1141X mutation was distributed widely across Europe, while deletion of exons 23–29 (del23–29) was encountered in Northern Europe and in Northern Mediterranean countries. p.R1138W may be a marker for French descent, evidenced by its presence also in French Canadians. The splice site transition mutation 3736–1G→A was seen in the neighboring countries Greece and Turkey, whereas 2542 delG occurs only in the Japanese. Two mutations seem to be present worldwide without evidence of a founder effect, p.Q378X and p.R1339C, suggesting the presence of mutational hotspots. Knowledge of this distribution will allow us to streamline mutation screening through a targeted, stepwise approach when the ethnicity of a patient is known. This will facilitate the identification of individuals at risk, improving their care to prevent ophthalmological and vascular disease. Clin Trans Sci 2010; Volume 3: 295–298
Exploring the Functional Advantages of Spatial and Visual Cognition From an Architectural Perspective
Authors: Lathrop Scott D. , Wintermute Samuel , Laird John E.
Published: December 2010

We present a general cognitive architecture that tightly integrates symbolic, spatial, and visual representations. A key means to achieving this integration is allowing cognition to move freely between these modes, using mental imagery. The specific components and their integration are motivated by results from psychology, as well as the need for developing a functional and efficient implementation. We discuss functional benefits that result from the combination of multiple content‐based representations and the specialized processing units associated with them. Instantiating this theory, we then discuss the architectural components and processes, and illustrate the resulting functional advantages in two spatially and visually rich domains. The theory is then compared to other prominent approaches in the area.
Knowledge Based Reverse Engineering—An Approach for Reverse Engineering of a Mechanical Part
Authors: Durupt A. , Remy S. , Ducellier G.
Published: December 2010

Reverse engineering (RE) is a domain of current interest where physical models are measured or digitized in order to obtain a virtual model. Currently, these virtual models are rebuilt using approaches that consider only a geometric point of view. These models are generally frozen (i.e., poorly parameterized and not easy to modify). These kinds of models are good for many applications but people need more for redesign operations. This paper proposes a knowledge-based approach for reverse engineering that enables a RE user to rebuild nonfrozen models that are close to an original CAD model.
Ultrafast Laser Induced Structural Modification of Fused Silica—Part I: Feature Formation Mechanisms
Authors: Vukelić Siniša , Kongsuwan Panjawat , Yao Y. Lawrence
Published: December 2010

Nonlinear absorption of femtosecond-laser pulses enables the induction of structural changes in the interior of bulk transparent materials without affecting their surface. This property can be exploited for transmission welding of transparent dielectrics, three dimensional optical data storages, and waveguides. In the present study, femtosecond-laser pulses were tightly focused within the interior of bulk fused silica specimen. Localized plasma was formed, initiating rearrangement of the network structure. Features were generated through employment of single pulses as well as pulse trains using various processing conditions. The change in material properties were studied through employment of differential interference contrast optical microscopy and atomic force microscopy. The morphology of the altered material as well as the nature of the physical mechanisms (thermal, explosive plasma expansion, or in-between) responsible for the alteration of material properties as a function of process parameters is discussed.
Adaptive Extrusion Force Control of Freeze-Form Extrusion Fabrication Processes
Authors: Zhao Xiyue , Landers Robert G. , Leu Ming C.
Published: December 2010

Freeze-form extrusion fabrication is an additive manufacturing process that extrudes high solids loading aqueous ceramic pastes in a layer-by-layer fashion below the paste freezing temperature for component fabrication. Due to effects, such as the air bubble release, agglomerate breakdown, and change in paste properties during extrusion as a result of liquid phase migration, the extrusion force is difficult to control. In this paper, an adaptive controller is proposed to regulate the extrusion force. Recursive least-squares is used to estimate the extrusion force model parameters during fabrication and a low-order control scheme capable of tracking general reference trajectories is designed and implemented to regulate the extrusion process. The controller is implemented for sinusoidal reference trajectories and the results demonstrate excellent tracking performance of the adaptive extrusion force controller. Several parts were fabricated with the adaptive extrusion force controller. These results illustrate the need for extrusion force control and that variable reference extrusion force profiles are required to fabricate complex features.
Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation
Authors: Song Jikui , Rechkoblit Olga , Bestor Timothy H. , Patel Dinshaw J.
Published: December 2010

The eukaryote maintenance DNA methyltransferase discriminates against de novo CpG methylation sites.
Passive Origins of Stomatal Control in Vascular Plants
Authors: Brodribb Tim J. , McAdam Scott A. M.
Published: December 2010

The transition from passive to active metabolic control of stomata and plant water balance occurred about 360 million years ago.
Time-Resolved Holography with Photoelectrons
Authors: Huismans Y. , Rouzée A. , Gijsbertsen A. , Jungmann J. H. , Smolkowska A. S. , Logman P. S. W. M. , Lépine F. , Cauchy C. , Zamith S. , Marchenko T. , Bakker J. M. , Berden G. , Redlich B. , van der Meer A. F. G. , Muller H. G. , Vermin W. , Schafer K. J. , Spanner M. , Ivanov M. Yu. , Smirnova O. , Bauer D. , Popruzhenko S. V. , Vrakking M. J. J.
Published: December 2010

The intefererence pattern produced by photoelectrons provides holographic snapshots of the photoionization process.
Quantitative Analysis of Culture Using Millions of Digitized Books
Authors: Michel Jean-Baptiste , Shen Yuan Kui , Aiden Aviva Presser , Veres Adrian , Gray Matthew K. ,   The Google Books Team, Pickett Joseph P. , Hoiberg Dale , Clancy Dan , Norvig Peter , Orwant Jon , Pinker Steven , Nowak Martin A. , Aiden Erez Lieberman
Published: December 2010

Linguistic and cultural changes are revealed through the analyses of words appearing in books.
Saharan dust and daily mortality in Emilia-Romagna (Italy)
Authors: Zauli Sajani Stefano , Miglio Rossella , Bonasoni Paolo , Cristofanelli Paolo , Marinoni Angela , Sartini Claudio , Goldoni Carlo Alberto , De Girolamo Gianfranco , Lauriola Paolo
Published: December 2010

Objective

To investigate the association between Saharan dust outbreaks and natural, cardiovascular and respiratory mortality.

Methods

A case–crossover design was adopted to assess the effects of Saharan dust days (SDD) on mortality in the Emilia-Romagna region of Italy. The population under study consisted of residents in the six main towns of the central-western part of the region who died between August 2002 and December 2006. The association of Saharan dust outbreaks and PM10concentration with mortality was estimated using conditional logistic regression, adjusted for apparent temperature, holidays, summer population decrease, flu epidemic weeks and heat wave days. The role of the interaction term between PM10and SDD was analysed to test for effect modification induced by SDD on the PM10-mortality concentration–response function. Separate estimates were undertaken for hot and cold seasons.

Results

We found some evidence of increased respiratory mortality for people aged 75 or older on SDD. Respiratory mortality increased by 22.0% (95% CI 4.0% to 43.1%) on the SDD in the whole year model and by 33.9% (8.4% to 65.4%) in the hot season model. Effects substantially attenuated for natural and cardiovascular mortality with ORs of 1.042 (95% CI 0.992 to 1.095) and 1.043 (95% CI 0.969 to 1.122), respectively.

Conclusions

Our findings suggest an association between respiratory mortality in the elderly and Saharan dust outbreaks. We found no evidence of an effect modification of dust events on the concentration–response relationship between PM10and daily deaths. Further work should be carried out to clarify the mechanism of action.
Detection of Coxiella burnetii in placenta and abortion samples from British ruminants using real‐time PCR
Authors: Jones R. M. , Twomey D. F. , Hannon S. , Errington J. , Pritchard G. C. , Sawyer J.
Published: December 2010

A real‐time PCR was developed to detect Coxiella burnetii (the cause of Q fever) in ruminant placentas and aborted fetuses. Primer and probe sets previously developed for human tissue studies were used to target the insertion sequence IS1111 gene for C burnetii. The assay was highly sensitive, with a limit of detection of 10 copies of template, theoretically equating to a single bacterium, and did not cross‐react with a panel of other bacteria. To determine sensitivity on field samples submitted for the diagnosis of abortion, results using the IS1111 PCR assay were compared with a com 1 PCR assay. When applied to ruminant abortion material, including placental cotyledons and fetal samples, the IS1111 and com 1 assays yielded positive results in 23 (25 per cent) of 93 and 19 (20 per cent) of 93 samples, respectively. One infected goat herd was monitored for 31 months: 57 (92 per cent) of 62 placental cotyledon samples from aborting and non‐aborting goats, and 10 (30 per cent) of 33 fetal samples were positive by the IS1111 PCR assay.
Observational study of 14 cases of chronic pancreatitis in dogs
Authors: Watson P. J. , Archer J. , Roulois A. J. , Scase T. J. , Herrtage M. E.
Published: December 2010

This study reports the clinical, clinicopathological and ultrasonographic findings from dogs with chronic pancreatitis (CP). Fourteen dogs with clinical signs consistent with CP and histological confirmation of the disease were evaluated. Abdominal ultrasound and clinical pathology results were recorded. Sensitivities of pancreatic enzymes for diagnosis of CP were calculated with two different cut‐off values. The mean age of affected dogs was 9.1 years. Spaniels were the most common breed with CP, representing seven of the 14 dogs in this study. CP was histologically severe in nine cases. Most dogs showed chronic low‐grade gastrointestinal signs and abdominal pain. Five dogs had exocrine pancreatic insufficiency and five dogs had diabetes mellitus. The sensitivity of elevated trypsin‐like immunoreactivity for CP was 17 per cent. The sensitivities of canine pancreatic lipase immunoreactivity, lipase and amylase for CP were 44 to 67 per cent or 14 to 28 per cent depending on the cut‐off value used. Cholesterol was elevated in 58 per cent of samples. Liver enzymes were often elevated. The pancreas appeared abnormal on 56 per cent of ultrasound examinations. Ten dogs had died by the end of the study period; only one case was due to CP.
Need for a new kind of partnership on animal health
Authors: Radcliffe R.
Published: December 2010

The report from the England Advisory Group on Responsibility and Cost Sharing recommends a new approach built around the idea of an England Partnership Board. Rosemary Radcliffe, the group's chair, gives her perspective
The evolutionary significance of a Lower Cambrian trace-fossil assemblage from the Meguma terrane, Nova Scotia
Authors: Gingras Murray K. , Waldron John W.F. , White Chris E. , Barr Sandra M.
Published: December 2010

We report a diverse assemblage of trace fossils from the Lower(?) Cambrian High Head member of the Church Point Formation near Yarmouth, Nova Scotia. Based on the presence of sharp-based beds, load casts, and flute casts, along with other sedimentological criteria, the strata are interpreted to have a turbidite origin. Other characteristics, including wrinkle structures and high fidelity of trace-fossil preservation, suggest that the inter-episode biotope was influenced by the presence of biomats. The trace-fossil assemblage includes (in approximate order of abundance) Planolites , Helminthopsis , Oldhamia , Chondrites , Gordia , Cladichnus , Psammichnites gigas , Treptichnus , Phycodes , Lorenzinia , Palaeophycus , and Teichichnus . Trace fossils are increasingly abundant upwards in the section, but they are ultimately mitigated by an increase in (inferred) sedimentation rates. The trace-fossil assemblage, which bears many similarities to other Lower Cambrian locales (e.g., Puncoviscana Formation of northwest Argentina, Chapel Island Formation of southeastern Newfoundland), and the distribution of ichnofossils strongly support an earliest Cambrian age for the studied strata. More importantly, evolutionary trends can be interpreted from the trace-fossil assemblage, namely (1) an increase in size and diversity of animals in deep water; (2) an expansion of motile strategies used to coexist with biomats; and, (3) increasingly complex mining strategies below the sediment-biomat interface.
Effect of depth on seismic response of circular tunnels
Authors: Cilingir Ulas , Madabhushi S. P. Gopal
Published: December 2010

Tunnels in seismically active areas are vulnerable to adverse effects of earthquake loading. Recent seismic events have shown that there is a need to validate current design methods to better understand the deformation mechanisms associated with the dynamic behaviour of tunnels. The research described in this paper consists of physical and numerical modelling of circular tunnels with dynamic centrifuge experiments and complementary finite element simulations. The aim is to develop an understanding of the effects of tunnel depth on the seismic behaviour of tunnels. Tunnels with different depth-to-diameter ratios were tested in dry, loose silica sand. Accelerations around the tunnel and earth pressures on the lining were measured. A high-speed digital camera was used to record soil and lining deformations. Particle image velocimetry analyses were carried out on the recorded images to measure the deformations. Complementary dynamic finite element simulations were also conducted with a code capable of managing contact simulations at the soil–lining interface. Measurement of centrifuge experiments and finite element analyses show that the tunnel shifts from a static equilibrium to a dynamic equilibrium state as soon as the earthquake starts. The nature of the dynamic equilibrium, however, is difficult to predict using conventional analysis methods.
Numerical modelling of borehole water-inflow tests in the foundation of the Alqueva arch dam
Authors: Farinha M. L.B. , Lemos J. V. , Maranha das Neves E.
Published: December 2010

Borehole water-inflow tests allow measurement of discharges and water pressures in isolated sections of drains and piezometric boreholes. A series of water-inflow tests and water electrical conductivity analyses were carried out in an area of the foundation of an arch dam. Detailed three-dimensional (3D) numerical models developed for the analyses of the test data in two foundation areas are presented. Results of rock mass permeability tests and areas where seepage paths cross each drain, identified with both water-inflow tests and water electrical conductivity analyses, were taken into account. Models were validated against flow rates and water pressures recorded in situ. By examining water-inflow tests using numerical models, the main flow processes are identified and quantified. Test results and conclusions drawn from the detailed 3D models were used to elaborate a global model of the foundation. The present study shows that borehole water-inflow tests add valuable information to the usual monitoring data, which improves our ability to analyse the behaviour of concrete dam foundations. It is also concluded that although discontinuum models provide a more natural representation of flow in jointed rock masses, equivalent continuum models can still be used successfully to study both global and local hydraulic behaviour of dam foundations.
GENERALIZED JACOBI ELLIPTIC ONE-MONOPOLE: TYPE A
Authors: TEH ROSY , WONG KHAI-MING , LIM KOK-GENG
Published: December 2010

We present a new classical generalized one-monopole solution of the SU(2) Yang–Mills–Higgs theory with the Higgs field in the adjoint representation. We show that this generalized solution with θ-winding number m = 1 and ϕ-winding number n = 1 is an axially symmetric Jacobi elliptic generalization of the 't Hooft–Polyakov one-monopole. We construct this axially symmetric one-monopole solution by generalizing the large distance asymptotic solution of the 't Hooft–Polyakov one-monopole to the Jacobi elliptic functions and solving the second-order equations of motion numerically when the Higgs potential is vanishing and nonvanishing. These solutions are regular non-BPS finite energy solutions.
SUMMING RADIATIVE CORRECTIONS TO THE EFFECTIVE POTENTIAL
Authors: CHISHTIE F. A. , HANIF T. , JIA JUNJI , McKEON D. G. C. , SHERRY T. N.
Published: December 2010

When one uses the Coleman–Weinberg renormalization condition, the effective potential V in the massless [Formula: see text] theory with O(N) symmetry is completely determined by the renormalization group functions. It has been shown how the (p + 1) order renormalization group function determine the sum of all the N p LL order contribution to V to all orders in the loop expansion. We discuss here how, in addition to fixing the N p LL contribution to V, the (p + 1) order renormalization group functions can also be used to determine portions of the N p+n LL contributions to V. When these contributions are summed to all orders, the singularity structure of V is altered. An alternate rearrangement of the contributions to V in powers of ln ϕ, when the extremum condition V′(ϕ = v) = 0 is combined with the renormalization group equation, show that either v = 0 or V is independent of ϕ. This conclusion is supported by showing the LL , …, N 4 LL contributions to V become progressively less dependent on ϕ.
PHOTOINDUCED LASER EFFECTS IN INDIUM NITRIDE FILM
Authors: WANG Z. P. , GU C. M. , SHEN W. Z.
Published: December 2010

The optical nonlinear absorption properties in sputtering Indium nitride ( InN ) film were investigated under the excitations of nanosecond, picosecond and femtosecond pulsed lasers by open-aperture transmission Z-scan technique (TZ-scan). Under the condition of hν > Eg, the saturable absorption (SA) phenomena induced by one-photon transition were observed in both nanosecond and picosencond pulsed TZ-scan measurements. When 2hν > Eg > hν, the film presented SA due to the two-photon transition under the excitation of picosecond laser. However, at femtosecond 800 nm, the film showed the two-photon absorption (TPA) instead of SA, and the TPA coefficient tended to a saturable value as the excitation intensity increased. The results indicate that the InN film is a kind of good saturable absorber.
ENTROPY AND SPECIFIC HEAT FOR OPEN SYSTEMS IN STEADY STATES
Authors: HUANG X. L. , CUI B. , YI X. X.
Published: December 2010

The fundamental assumption of statistical mechanics is that the system is equally likely in any of the accessible microstates. Based on this assumption, the Boltzmann distribution is derived and the full theory of statistical thermodynamics can be built. In this paper, we show that the Boltzmann distribution in general cannot describe the steady state of an open system. Based on the effective Hamiltonian approach, we calculate the specific heat, the free energy and the entropy for an open system in steady states. Examples are illustrated and discussed.
MINING ASSOCIATIONS IN HEALTH CARE DATA USING FORMAL CONCEPT ANALYSIS AND SINGULAR VALUE DECOMPOSITION
Authors: ASWANI KUMAR CH. , SRINIVAS S.
Published: December 2010

In recent times Formal Concept Analysis (FCA), in which the data is represented as a formal context, has gained popularity for Association Rules Mining (ARM). Application of ARM in health care datasets is challenging and a highly rewarding problem. However, datasets in the medical domain are of high dimension. As the dimensionality of dataset increases, size of the formal context as well as complexity of FCA based ARM also increases. To handle the problem of high dimensionality and mine the associations, we propose to apply Singular Value Decomposition (SVD) on the dataset to reduce the dimensionality and apply FCA on the reduced dataset for ARM. To demonstrate the proposed method, experiments are conducted on Tuberculosis (TB) and Hypertension (HP) datasets. Results indicate that with fewer concepts, SVD based FCA has achieved the performance of FCA on TB data and performed better than FCA on HP data.
INDIA'S APPROACH TO ELIMINATING PLASMODIUM FALCIPARUM MALARIA: A MODELING PERSPECTIVE
Authors: MARTCHEVA MAIA , HOPPENSTEADT FRANK
Published: December 2010

Approximately one-third of the world's population that is at risk to malaria lives in India. Plasmodium falciparum, a deadly form of malaria, accounts for about 50% of the cases there. Since 1940s, India has used a number of programs to combat the disease with variable success. Since 1998, the total numbers of malaria cases, and in particular P. falciparum cases, have been steadily declining, making India one of the success stories among the countries supported by the Roll Back Malaria (RBM) Partnership. This article considers India's P. falciparum control methods from the perspective of a Ross-MacDonald type model. The model is fitted to the P. falciparum cases in India over the period 1983–2009. We focus on the disease reproduction number as being a measure of success of programs. Before the start of RBM measures, the disease reproduction number was [Formula: see text], meaning that the incidence of disease was increasing among the population. With the new control measures [Formula: see text], suggesting that P.falciparum cases may be declining to zero but extremely slowly. The model here projects 0.734 million cases of P. falciparum malaria for 2010, down from 1.14 million cases in 2000. This impressive 36% decrease falls somewhat short of the RBM's goal of 50% reduction. However, a sensitivity analysis of the disease reproduction number done here suggests that India's control programs do apply controls at the most critical points in the disease cycle; namely, mosquito biting rates, mosquito mortality, and treatment of infected humans. This suggests that as more resources become available, they should be applied to strengthen these controls. The novelty here is in fitting recent data on malaria from India to derive current values of the disease reproduction number.
Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis
Authors: Hokari Ryota , Kurihara Chie , Nagata Nanae , Aritake Kosuke , Okada Yoshikiyo , Watanabe Chikako , Komoto Shunsuke , Nakamura Mitsuyasu , Kawaguchi Atsushi , Nagao Shigeaki , Urade Yoshihiro , Miura Soichiro
Published: December 2010

The pathogenesis of ulcerative colitis (UC) is unclear, but enhancement of disease activity by usage of nonsteroidal anti-inflammatory drugs suggests involvement of prostanoid in its pathophysiology. However, biological effect of prostaglandin (PG) D2on intestinal inflammation remains unknown. We investigated the expression of enzymes for PGD2synthesis, prostaglandin D synthase (PGDS), and its relation to the activity of colitis in UC patients. The role of lipocalin-type PGDS (L-PGDS) using a murine colitis model was also assessed. Tissue samples were obtained by colonic biopsies from patients with UC. Expression levels of mRNAs for L-PGDS and hematopoietic-type PGDS were investigated by quantitative RT-PCR. COX-2 and L-PGDS expression was investigated by immunohistochemistry. Localization of L-PGDS expression was also determined by in situ hybridization. In experimental study, mice were treated with dextran sodium sulfate in the drinking water to induce colitis. The degree of colonic inflammation was compared with L-PGDS−/−mice and control mice. The level of L-PGDS mRNA expression was increased in UC patients in parallel with disease activity. Colocalization of L-PGDS and cyclooxygenase (COX) 2 was observed in lamina proprial infiltrating cells and muscularis mucosa in UC patients. The level of hematopoietic PGDS mRNA expression did not differ from control mucosa. Dextran sodium sulfate treatment to L-PGDS−/−mice showed lower disease activity than control mice. We reported for the first time the presence of L-PGDS in the COX-2-expressing cells in the mucosa of active UC patients and that only L-PGDS increased with disease activity. An animal model study suggests that PGD2derived from L-PGDS-expressing cells plays proinflammatory roles in colitis.
Left ventricular systolic torsion correlates global cardiac performance during dyssynchrony and cardiac resynchronization therapy
Authors: Lamia Bouchra , Tanabe Masaki , Tanaka Hidekazu , Kim Hyung Kook , Gorcsan John , Pinsky Michael R.
Published: December 2010

Left ventricular (LV) systolic torsion is a primary mechanism contributing to stroke volume (SV). We hypothesized that change in LV torsion parallels changes in global systolic performance during dyssynchrony and cardiac resynchronization therapy (CRT). Seven anesthetized open chest dogs had LV pressure-volume relationship. Apical, basal, and mid-LV cross-sectional echocardiographic images were studied by speckle tracking analysis. Right atrial (RA) pacing served as control. Right ventricular (RV) pacing simulated left bundle branch block. Simultaneous RV-LV free wall and RV-LV apex pacing (CRTfw and CRTa, respectively) modeled CRT. Dyssynchrony was defined as the time difference in peak strain between earliest and latest segments. Torsion was calculated as the maximum difference between the apical and basal rotation. RA pacing had minimal dyssynchrony (52 ± 36 ms). RV pacing induced dyssynchrony (189 ± 61 ms, P < 0.05). CRTa decreased dyssynchrony (46 ± 36 ms, P < 0.05 vs. RV pacing), whereas CRTfw did not (110 ± 96 ms). Torsion during baseline RA was 6.6 ± 3.7°. RV pacing decreased torsion (5.1 ± 3.6°, P < 0.05 vs. control), and reduced SV, stroke work (SW), and dP/d tmax compared with RA (21 ± 5 vs. 17 ± 5 ml, 252 ± 61 vs. 151 ± 64 mJ, and 2,063 ± 456 vs. 1,603 ± 424 mmHg/s, respectively, P < 0.05). CRTa improved torsion, SV, SW, and dP/d tmax compared with RV pacing (7.7 ± 4.7°, 23 ± 3 ml, 240 ± 50 mJ, and 1,947 ± 647 mmHg/s, respectively, P < 0.05), whereas CRTfw did not (5.1 ± 3.6°, 18 ± 5 ml, 175 ± 48 mJ, and 1,699 ± 432 mmHg/s, respectively, P < 0.05). LV torsion changes covaried across conditions with SW ( y = 0.94 x+12.27, r = 0.81, P < 0.0001) and SV ( y = 0.66 x+0.91, r = 0.81, P < 0.0001). LV dyssynchrony changes did not correlate with SW or SV ( r = −0.12, P = 0.61 and r = 0.08, P = 0.73, respectively). Thus, we conclude that LV torsion is primarily altered by dyssynchrony, and CRT that restores LV performance also restores torsion.
Human soleus muscle architecture at different ankle joint angles from magnetic resonance diffusion tensor imaging
Authors: Sinha Usha , Sinha Shantanu , Hodgson John A. , Edgerton Reggie V.
Published: December 2010

The orientation of muscle fibers influences the physiological cross-sectional area, the relationship between fiber shortening and aponeurosis shear, and the total force produced by the muscle. Such architectural parameters are challenging to determine particularly in vivo in multicompartment structures such as the human soleus with a complex arrangement of muscle fibers. The objective of this study was to map the fiber architecture of the human soleus in vivo at rest in both neutral and plantarflexed ankle positions using an MRI-based method of diffusion tensor imaging (DTI). Six subjects were imaged at 3 Tesla with the foot at rest in the two ankle positions. Eigenvalues, fractional anisotropy (FA), and eigenvector orientations of fibers in the different soleus subcompartments were evaluated after denoising of the diffusion tensor. The fiber architecture from DTI was similar to earlier studies based on a 3D fiber model from cadavers. The three eigenvalues of the diffusion tensor increased by ∼14% on increasing the joint plantarflexion angle in all of the soleus subcompartments, whereas FA showed a trend to decrease in the posterior and marginal soleus and to increase in the anterior soleus. The angle change in the lead eigenvector between the two foot positions was significant: ∼41° for the posterior soleus and ∼48° for the anterior soleus. Fibers tracked from the subcompartments support these changes seen in the eigenvector orientations. DTI-derived, subject-specific, muscle morphological data could potentially be used to model a more complete description of muscle performance and changes from disease.
Dynamic nonlinearity of lung tissue: effects of strain amplitude and stress level
Authors: Pinart Mariona , Faffe Débora S. , Sapiña Marta , Romero Pablo V.
Published: December 2010

Lung tissue presents substantial nonlinear phenomena not accounted for by linear models; however, nonlinear approaches are less available. Our aim was to characterize the behavior of total harmonic distortion, an index of nonlinearity, in lung tissue strips under sinusoidal deformation at a single frequency as a function of strain amplitude and operational stress. To that end, lung parenchymal strips from healthy rats ( n = 6) were subjected to sinusoidal deformation (1 Hz) at different strain amplitudes (Δε = 4, 8, 12, 16, and 20%) and operating stresses (σop = 6, 8, 10, 12, 14, and 16 hPa). Additional rats ( n = 9) were intratracheally instilled with saline or bleomycin (2.5 U/kg, 3 times 1 wk apart), killed 28 days after the last instillation, and their lung tissue strips were studied at 5 and 10 hPa σop and 5% Δε. In both cases, harmonic distortion (HD%) of input (strain) and output (stress) signals were determined. In healthy strips, HD% increased linearly with Δε, stress amplitude, and minimum stress by cycle variations, but showed no significant change with σop levels. A prediction model could be determined as a function of operational stress and stress amplitude. Harmonic distortion was significantly increased in bleomycin-treated strips compared with controls and showed positive correlation with E behavior in both normal and diseased strips. We concluded that HD% can be useful as a single and simple parameter of lung tissue nonlinearity.
Cancer Causes Cardiac Atrophy and Autophagy in a Sexually Dimorphic Manner
Authors: Cosper Pippa F. , Leinwand Leslie A.
Published: December 2010

Approximately one-third of cancer deaths are caused by cachexia, a severe form of skeletal muscle and adipose tissue wasting that affects men more than women. The heart also undergoes atrophy in cancer patients, but the mechanisms and the basis for apparent sex differences are unclear. In a mouse colon-adenocarcinoma model, cancer causes a loss of cardiac mass due to a decrease in cardiac myocyte size that is associated with reduced levels of all sarcomeric proteins. Unlike skeletal muscle cachexia, atrophic hearts do not upregulate the ubiquitin-proteasome system or its activity but increase autophagy. Thus, cancer causes cardiac atrophy by a mechanism distinct from that in skeletal muscle. Male tumor-bearing mice have a more severe phenotype than females, including greater cardiac mass loss and mortality, a more robust pro-inflammatory response to the tumor, and greater cardiac autophagy. In females, estrogen protects against cancer-induced cardiac atrophy and body weight loss by signaling through its receptor. Sex differences in cardiac atrophy need to be considered during the treatment of patients suffering from chemotherapy-induced cardiomyopathy to prevent exacerbation of cardiac dysfunction. Cancer Res; 71(5); 1710–20. ©2010 AACR.
A Hypoxia- and α-Fetoprotein–Dependent Oncolytic Adenovirus Exhibits Specific Killing of Hepatocellular Carcinomas
Authors: Kwon Oh-Joon , Kim Pyung-Hwan , Huyn Steven , Wu Lily , Kim Minjung , Yun Chae-Ok
Published: December 2010

Purpose: Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE).

Experimental Design: We constructed Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging.

Results: Ad-HRE12/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE12/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE12/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection.

Conclusions: The results presented here show the advantages of incorporating HREs into a hAFP promoter–driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment–selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE12/hAFPΔ19 make it a promising therapeutic agent in the treatment of liver cancers. Clin Cancer Res; 16(24); 6071–82. ©2010 AACR.
The 2010 Health Care Reform Act: A Potential Opportunity to Advance Cancer Research by Taking Cancer Personally
Authors: Dalton William S. , Sullivan Daniel M. , Yeatman Timothy J. , Fenstermacher David A.
Published: December 2010

The Patient Protection and Affordable Care Act of 2010 will have a profound influence on health care in the United States, including how we conduct cancer research and cancer care delivery. For this reason, oncologists and researchers must be intimately involved in the implementation and interpretation of this important legislation. A major goal of the Act is to improve access to affordable, quality health care. An important element in achieving this goal will be to learn from patients' experiences and build the foundation for evidence-based personalized medicine. This will require a partnership among researchers, clinicians, policy makers and regulators, and patients to design an integrated information network system that will be the basis for providing the right treatment for the right patient in the right place at the right time. In this review, we will discuss the salient points of the Act that specifically affect cancer research and care, as well as highlight opportunities for oncologists and researchers to play a primary role in developing a health care system that includes personalized medicine approaches that will in turn enhance the likelihood of achieving the goals and objectives of the health care reform act. Clin Cancer Res; 16(24); 5987–96. ©2010 AACR.
Biologically Targeted Cancer Therapy and Marginal Benefits: Are We Making Too Much of Too Little or Are We Achieving Too Little by Giving Too Much?
Authors: Fojo Tito , Parkinson David R.
Published: December 2010

We describe the development and approval of biologically targeted agents in the clinic through examples chosen from the experience with inhibitors of the epidermal growth factor (EGF) and VEGF pathways. Despite extensive biological rationale for the use of these classes of molecules, marginal clinical benefits have been observed in broad patient populations, and the agents have entered into general clinical practice. We discuss why this situation is unsatisfactory because marginal general benefit may often be at the expense of toxicity to nonbenefiting or even harmed patients. Finally, we point out that emerging technologies bring the promise of allowing the identification of patients who might potentially benefit from a therapy. However, development of this technology will not move forward without broader recognition of its need by the range of stakeholders, including patients, advocates, academic and private oncologists, drug sponsors, and those who develop drugs and diagnostic tests. Clin Cancer Res; 16(24); 5972–80. ©2010 AACR.
Translating Clinical Trials into Meaningful Outcomes
Authors: LoRusso Patricia M. , Schnipper Lowell E. , Stewart David J. , Boerner Scott A. , Averbuch Steven D. , Wolf Walter
Published: December 2010

Efforts to unravel the complex biology that is necessary to develop new therapies best suited for an individual with cancer are at a crossroads with a strained health care system and an insufficient clinical trial apparatus. The resulting failures have been described as the “valley of death.” Progress into the future will require new considerations and the engagement of a broad band of stakeholders. To identify novel therapeutics that are likely to succeed in late development and to be meaningful for clinical practice, investigators will need to make a paradigm shift in designing clinical trials and endpoints while adhering to scientific rigor when interpreting results and making informed decisions. Large phase III trials that show a modest incremental benefit will continue to diminish in value for patients, clinicians, payers, and industry. Outcomes that are robust in both magnitude and application to the real world will take on increasing importance. Ensuring active participation by patients, lowering barriers to health care access, and protecting patients through health care reform are requirements for the future success of the cancer clinical research enterprise. The challenge today is to develop new approaches to translate scientific discovery into cost-effective and meaningful improvements in cancer outcomes. Clin Cancer Res; 16(24); 5951–5. ©2010 AACR.