bluuebunny/crossref_metadata_2025 huggingface dataset:
ORIGINAL ARTICLE: Glycodelin A Induces a Tolerogenic Phenotype in Monocyte‐Derived Dendritic Cells In vitro
Authors: Scholz Christoph , Toth Bettina , Brunnhuber Regina , Rampf Elisabeth , Weissenbacher Tobias , Santoso Laura , Friese Klaus , Jeschke Udo
Published: November 2008

Problem  Successful mammalian pregnancy requires a delicate immunological balance at the feto‐maternal interface that allows the semi‐allogeneic fetus to grow, while protecting mother and child from environmental pathogens. As in other mucosal tissues, antigen‐recognition and ‐handling by professional antigen‐presenting cells such as dendritic cells (DC) determine the course of the subsequent immune response. DC at the feto‐maternal interface help shape this immunological equilibrium. Endometrial tissue secretes high quantities of glycodelin A (GdA) during the so‐called fertile window (i.e. the time of implantation of the blastocyst).

Method of study  We investigated the effect of GdA on monocyte‐derived DC (moDC) regarding surface marker expression, endopinocytotic activity, cytokine profile as well as lymphoproliferative activity.

Results  Upon pretreatment with GdA and subsequent maturation with tumor necrosis factor‐α and interleukin (IL)‐1β, moDC displayed a reduced expression of costimulatory molecules, an unchanged major histocompatibility complex‐II expression and persistence of DC‐SIGN positive cells. GdA‐pretreated moDC had a higher endopinocytotic activity, an increased IL‐10 production and a dose‐dependent reduction in lymphoproliferative activity. GdA incubation alone did not alter the immature phenotype.

Conclusion  Our results suggest a model in which the human endometrium secretes high quantities of GdA during implantation and thereby helps to shape the unique immunological interaction between mother and fetus via decidual DC.
ORIGINAL ARTICLE: Ecology of Danger‐Dependent Cytokine‐Boosted Spontaneous Abortion in the CBA × DBA/2 Mouse Model: II Fecal LPS Levels in Colonies with Different Basal Abortion Rates
Authors: Clark David A. , Chaouat Gerard , Banwatt Daljeet , Friebe Asreid , Arck Petra C.
Published: November 2008

Problem  Previous data have shown that ‘danger’ signals, such as bacterial lipopolysaccharide (LPS) acting via toll‐like receptors (TLR), are conditions antecedent to early pregnancy failure in several murine abortion models. Indeed, the abortion rate increased in the CBA × DBA/2 model after injection of tumor necrosis factor‐α (TNF‐α) + interferon (IFN‐γ) on gestation day (GD) 7.5 only if the LPS–TLR signaling pathway was intact. High rates of cytokine‐boosted abortion >80% loss can be demonstrable in certain animal colonies that have a high endogenous (spontaneous) rate of resorption (30–50%). A specific role for LPS on GD 0.5 determines the endogenous loss rate and on GD 6.5 the responsiveness to cytokine boosting of losses. Th1 cytokines (or the stress that induces these cytokines) increase intestinal permeability and absorption of luminal contents. It was predicted that intestinal availability of LPS was a major factor in the endogenous and cytokine‐boosted resorption rates.

Method of study  A fixed weight of fresh mouse droppings from CBA/J female mice house in a high‐abortion‐rate (30–40%) colony at Clamart, France was homogenized and filtered. Fresh mouse droppings from a low‐abortion‐rate (10–15%) colony in Berlin, Germany were similarly processed. LPS was assayed using the Limulus amoebocyte lysate bioassay.

Results  To our surprise, there was no significant difference in LPS content of fecal samples from the two colonies.

Conclusion  A high endogenous rate of abortion and cytokine (or stress) boosted abortion in the CBA × DBA/2 model is not explained by the LPS content of feces. Possible explanations include: fecal LPS does not reflect small intestinal LPS, there are additional TLR signals besides LPS that are important and endogenous stress levels may be higher in high‐abortion‐rate colonies, so permeability of the intestine (and Th1 cytokine levels) may be already higher. These data have implications for studies on the role of flora in human pregnancy problems.
Human Rights and Pluralism in Catholic Social Thought
Authors: McCarthy David Matzko
Published: November 2008

The essay argues that a Catholic tradition of natural law and its conception of human rights depend on the continuing life of institutions that stand apart from and sustain standards of justice independent from the modern state and its corresponding economy. Christians contribute to a defense of human rights precisely as members of their Churches, through their social and institutional presence across the globe. Catholic social thought deals with matters of human rights from within a tradition of natural law that assumes a common human end, a common good. This ecclesiological tradition of the human good is precisely what Catholics have to offer in a context of pluralism. The Church has a task of sustaining institutions where its practical rationality about human goods offers a practical alternative in a world where the self-interest of states and purely economic interests win the day.
Shakespeare Now: The Function of Presentism at the Critical Time
Authors: Holbo John
Published: November 2008

Presentism styles itself a distinctive critical approach to literary texts, characterized by heightened self‐critical awareness. It sees itself as complementing (rather than competing with) historicism. Its main proponents – Hugh Grady and Terence Hawkes – are Shakespearean scholars, and in several recent works, including a recent anthology (Presentist Shakespeares), they elaborate and showcase their approach. This essay argues that the likes of Grady and Hawkes have failed to face up to the simple consideration that ‘presentism’ means a species of error, or it means nothing. They have also failed to square up, satisfactorily, against what is evidently their real target: namely, post‐Theory approaches to Shakespeare. (David Kastan is a target, but his name is really more a convenient marker for the target zone, due to the title of his book: Shakespeare after Theory.) Presentism is, in effect, oblique apologetics for Theory, but fails to say anything in its defense.
Medieval Things: Materiality, Historicism, and the Premodern Object
Authors: Robertson Kellie
Published: November 2008

How do we read the premodern representation of objects? This essay surveys recent approaches to medieval literature and culture that focus attention on ‘objecthood’ and the debates that it inspired in the premodern period. This work eschews the exclusive focus on ‘subjectivity’ that was the hallmark of late twentieth‐century poststructuralist accounts of medieval literature in Britain. Subjects do not disappear in these readings, however; they are instead shown to be dialogically produced, always in conversation with things. In offering a genealogy of what has come to be known as ‘thing theory,’ this survey interrogates a number of related (but not necessarily compatible) strains of materialism, including those influenced by Marxism, phenomenology, sociology, and New Historicism. Neither a return to old positivist historical models seeking ‘the thing itself’ nor a retreat from the significant questions posed by poststructuralist theory, these object‐oriented studies all seek ways of approaching narrated things that do not render them merely ‘mirrors’ of human desires or just signs pointing us toward the ‘inner lives’ of literary personas. Instead, this work takes seriously the idea that premodern objects were endowed with an autonomy and agency that was largely misrecognized in the wake of Enlightenment empiricism. Taking Geoffrey Chaucer'sCanterbury Talesas a point of departure, this essay argues that where and how the line between human and nonhuman, subject and object, society and nature gets drawn is always an ideological process. The work surveyed here attempts to make available some of the manifold cultural pressures that influenced this permeable boundary across the Middle Ages.
The sulfur atoms of the substrate CoA and the catalytic cysteine are required for a productive mode of substrate binding in bacterial biosynthetic thiolase, a thioester‐dependent enzyme
Authors: Meriläinen Gitte , Schmitz Werner , Wierenga Rik K. , Kursula Petri
Published: November 2008

Thioesters are more reactive than oxoesters, and thioester chemistry is important for the reaction mechanisms of many enzymes, including the members of the thiolase superfamily, which play roles in both degradative and biosynthetic pathways. In the reaction mechanism of the biosynthetic thiolase, the thioester moieties of acetyl‐CoA and the acetylated catalytic cysteine react with each other, forming the product acetoacetyl‐CoA. Although a number of studies have been carried out to elucidate the thiolase reaction mechanism at the atomic level, relatively little is known about the factors determining the affinity of thiolases towards their substrates. We have carried out crystallographic studies on the biosynthetic thiolase fromZoogloea ramigeracomplexed with CoA and three of its synthetic analogues to compare the binding modes of these related compounds. The results show that both the CoA terminal SH group and the side chain SH group of the catalytic Cys89 are crucial for the correct positioning of substrate in the thiolase catalytic pocket. Furthermore, calorimetric assays indicate that the mutation of Cys89 into an alanine significantly decreases the affinity of thiolase towards CoA. Thus, although the sulfur atom of the thioester moiety is important for the reaction mechanism of thioester‐dependent enzymes, its specific properties can also affect the affinity and competent mode of binding of the thioester substrates to these enzymes.
Methamphetamine Use Is Independently Associated With Recent Risky Sexual Behaviors and Adolescent Pregnancy
Authors: Zapata Lauren B. , Hillis Susan D. , Marchbanks Polly A. , Curtis Kathryn M. , Lowry Richard
Published: November 2008

BACKGROUND:  Lifetime methamphetamine use among adolescents is estimated to be between 5% and 10%. Youth substance use in general is known to be associated with risky sexual behaviors, but the effect of methamphetamine use on recent risky sexual behaviors and adolescent pregnancy has received little attention. The purpose of this analysis was to evaluate the association between lifetime methamphetamine use and recent (past 3 months) risky sexual behaviors and lifetime adolescent pregnancy, adjusting for other substance use.

METHODS:  We analyzed data from the 2003 National Youth Risk Behavior Survey, a school‐based paper‐and‐pencil survey that assesses risky health behaviors among a nationally representative sample of 9th‐ to 12th‐grade students. Multivariable logistic regression was used to calculate adjusted odds ratios (AORs) to examine the association between methamphetamine use and being recently sexually active, having 2 or more recent sex partners, and ever being pregnant or getting someone pregnant.

RESULTS:  Lifetime methamphetamine use was reported by 7.6% of students. After adjustment for demographic covariates and lifetime use of cigarettes, alcohol, marijuana, and other illicit drugs, lifetime methamphetamine use was associated with recent sexual intercourse (AOR = 1.8, 95% confidence interval [CI] = 1.5‐2.3), having 2 or more recent sex partners (AOR = 3.0, 95% CI = 2.2‐4.2), and ever being pregnant or getting someone pregnant (AOR = 2.9, 95% CI = 2.1‐3.9).

CONCLUSIONS:  Adolescent methamphetamine use is common and is associated with recent risky sexual behaviors and adolescent pregnancy. Prevention strategies for high school students should integrate education on substance abuse, pregnancy, sexually transmitted infections, and human immunodeficiency virus.
Prevalence of Tobacco Use Among Junior High and Senior High School Students in Taiwan
Authors: Chen Ping‐Ling , Huang Weigang , Chuang Yi‐Li , Warren Charles W. , Jones Nathan R. , Asma Samira
Published: November 2008

BACKGROUND: Tobacco use is a major preventable cause of death in the world. This article describes and compares tobacco use prevalence for students attending junior high schools and senior high schools in Taiwan.

METHODS: This report uses data from the Global Youth Tobacco Survey (GYTS) completed among 4689 junior high school students and 4426 senior high school students in Taiwan in 2004‐2005. The GYTS uses a 2‐stage sampling design to produce nationally representative data for junior and senior high students in general and vocational schools.

RESULTS: Higher smoking prevalence was observed among senior high (10.1% general schools and 15.9% vocational schools) than junior high (5.5%) school students. Smoking prevalence of girls in junior high (3.2%) and senior high schools (4.6% general and 11.1% vocational) was almost as high or higher than adult females’ (4.3%) smoking rates. The pattern of smoking intensity across school years and type of school shows that the percentage of smokers who were experimenters (47.1%) was higher in junior high school and the percentage of smokers who were regular/established smokers (over 50%) was higher in senior high school.

CONCLUSIONS: Smoking prevalence described in this report shows that there are challenges facing the tobacco prevention and control program in Taiwan. The findings suggest that schools should increase their smoking initiation prevention efforts and make available cessation programs and counseling to help students quit smoking. If effective youth tobacco control programs are not developed and implemented in Taiwan, future morbidity and mortality attributed to tobacco will surely increase, especially among women.
The calcium‐conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein‐2‐induced migration of mouse neutrophils*
Authors: Damann N. , Owsianik G. , Li S. , Poll C. , Nilius B.
Published: November 2008

Aim:  The role of the calcium‐conducting ion channel transient receptor potential canonical 6 (TRPC6) in macrophage inflammatory protein‐2 (MIP‐2) induced migration of mouse neutrophils was investigated.

Methods:  Neutrophil granulocytes isolated from murine bone marrow of wild‐type (TRPC6+/+) and TRPC6 knockout (TRPC6−/−) mice were tested for the presence of TRPC6 channel expression using quantitative real‐time polymerase chain reactions and immunocytochemistry. The effect of different stimuli (e.g. MIP‐2, 1‐oleoyl‐2‐acetyl‐sn‐glycerol, formyl‐methionyl‐leucyl‐phenylalanin) on migration of isolated neutrophils was tested by two‐dimensional (2D) migration assays, phalloidin staining and intracellular calcium imaging.

Results:  We found that neutrophil granulocytes express TRPC6 channels. MIP‐2 induced fast cell migration of isolated neutrophils in a 2D cell‐tracking system. Strikingly, MIP‐2 was less potent in neutrophils derived from TRPC6−/− mice. These cells showed less phalloidin‐coupled fluorescence and the pattern of cytosolic calcium transients was altered.

Conclusions:  We describe in this paper for the first time a role for transient receptor potential (TRP) channels in migration of native lymphocytes as a new paradigm for the universal functional role of TRPs. Our data give strong evidence that TRPC6 operates downstream to CXC‐type Gq‐protein‐coupled chemokine receptors upon stimulation with MIP‐2 and is crucial for the arrangement of filamentous actin in migrating neutrophils. This is a novel cell function of TRP channel beyond their well‐recognized role as universal cell sensors.
Mechanisms of metabotropic glutamate receptor‐mediated synaptic signalling in cerebellar Purkinje cells
Authors: Hartmann J. , Konnerth A.
Published: November 2008

The metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G‐protein‐coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post‐synaptic response consisting of a Ca2+‐release signal from intracellular stores and a slow excitatory post‐synaptic potential. While it is well established that the mGluR1‐dependent Ca2+‐release signal from intracellular stores involves the activation of inositol‐trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C‐type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1‐dependent synaptic current. For the signalling pathways underlying both, Ca2+‐release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1‐dependent signalling in Purkinje neurones.
Measuring diffusion parameters in the brain: comparing the real‐time iontophoretic method and diffusion‐weighted magnetic resonance
Authors: Vorisek I. , Sykova E.
Published: November 2008

The extracellular space (ECS) diffusion parameters influence the movement of ions, neuroactive substances, hormones and metabolites in the nervous tissue. They also affect extrasynaptic transmission, a mode of signal transmission dependent solely on diffusion. This review compares in detail two methods for studying diffusion in the brain: the real‐time iontophoretic tetramethylammonium method for ECS volume fraction and tortuosity measurements and diffusion weighted‐magnetic resonance imaging for measuring the apparent diffusion coefficient of water. The results obtained using both methods under physiological conditions (post‐natal development, ageing) or in pathologies (brain injury, ischaemia) and their similarities and differences are discussed.
Neuronismo y reticulismo: neuronal–glial circuits unify the reticular and neuronal theories of brain organization
Authors: Verkhratsky A.
Published: November 2008

The neuronal doctrine, which shaped the development of neuroscience, was born from a long‐lasting struggle between reticularists, who assumed internal continuity of neural networks and neuronists, who defined the brain as a network of physically separated cellular entities, defined as neurones. Modern views regard the brain as a complex of constantly interacting cellular circuits, represented by neuronal networks embedded into internally connected astroglial syncytium. The neuronal–glial circuits endowed with distinct signalling cascades form a ‘diffuse nervous net’ suggested by Golgi, where millions of synapses belonging to very different neurones are integrated first into neuronal–glial–vascular units and then into more complex structures connected through glial syncytium. These many levels of integration, both morphological and functional, presented by neuronal–glial circuitry ensure the spatial and temporal multiplication of brain cognitive power.
When is high‐Ca2+ microdomain required for mitochondrial Ca2+ uptake?*
Authors: Spät A. , Fülöp L. , Koncz P. , Szanda G.
Published: November 2008

Ca2+ release from IP3‐sensitive stores in the endoplasmic reticulum (ER) induced by Ca2+‐mobilizing agonists generates high‐Ca2+ microdomains between ER vesicles and neighbouring mitochondria. Here we present a model that describes when such microdomains are required and when submicromolar [Ca2+] is sufficient for mitochondrial Ca2+ uptake. Mitochondrial Ca2+ uptake rate in angiotensin II‐stimulated H295R adrenocortical cells correlates with the proximity between ER vesicles and the mitochondrion, reflecting the uptake promoting effect of high‐Ca2+ peri‐mitochondrial microdomains. Silencing or inhibition of p38 mitogen‐activated protein kinase (MAPK) or inhibition of the novel isoforms of protein kinase C enhances mitochondrial Ca2+ uptake and abolishes the positive correlation between Ca2+ uptake and ER‐mitochondrion proximity. Inhibition of protein phosphatases attenuates mitochondrial Ca2+ uptake and also abolishes its positive correlation with ER‐mitochondrion proximity. We postulate that during IP3‐induced Ca2+ release, Ca2+ uptake is confined to ER‐close mitochondria, because of the simultaneous activation of the protein kinases. Attenuation of Ca2+ uptake prevents Ca2+ overload of mitochondria and thus protects the cell against apoptosis. On the other hand, all the mitochondria accumulate Ca2+ at a non‐inhibited rate during physiological Ca2+ influx through the plasma membrane. Membrane potential is higher in ER‐distant mitochondria, providing a bigger driving force for Ca2+ uptake. Our model explains why comparable mitochondrial Ca2+ signals are formed in response to K+ and angiotensin II (equipotent in respect to global cytosolic Ca2+ signals), although only the latter generates high‐Ca2+ microdomains.
The role of free fatty acids, pancreatic lipase and Ca2+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase‐deficient mice
Authors: Yang F. , Wang Y. , Sternfeld L. , Rodriguez J. A. , Ross C. , Hayden M. R. , Carriere F. , Liu G. , Schulz I.
Published: November 2008

Aim and methods:  Recurrent pancreatitis is a common complication of severe hypertriglyceridaemia (HTG) often seen in patients carrying various gene mutations in lipoprotein lipase (LPL). This study investigates a possible pathogenic mechanism of cell damage in isolated mouse pancreatic acinar cells and of pancreatitis in LPL‐deficient and in wild type mice.

Results:  Addition of free fatty acids (FFA) or of chylomicrons to isolated pancreatic acinar cells caused stimulation of amylase release, and at higher concentrations it also caused cell damage. This effect was decreased in the presence of the lipase inhibitor orlistat. Surprisingly, pancreatic lipase whether in its active or inactive state could act like an agonist by inducing amylase secretion, increasing cellular cGMP levels and converting cell damaging sustained elevations of [Ca2+]cyt to normal Ca2+ oscillations. Caerulein increases the levels of serum amylase and caused more severe inflammation in the pancreas of LPL‐deficient mice than in wild type mice.

Conclusion:  We conclude that high concentrations of FFA as present in the plasma of LPL‐deficient mice and in patients with HTG lead to pancreatic cell damage and are high risk factors for the development of acute pancreatitis. In addition to its enzymatic effect which leads to the generation of cell‐damaging FFA from triglycerides, pancreatic lipase also prevents Ca2+ overload in pancreatic acinar cells and, therefore, counteracts cell injury.
Oxygen‐dependent ion transport in erythrocytes
Authors: Bogdanova A. , Berenbrink M. , Nikinmaa M.
Published: November 2008

The present contribution reviews current knowledge of apparently oxygen‐dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed.
Complexity of Shapes and Quantitative Reasoning in Geometry
Authors: Stavy Ruth , Babai Reuven
Published: November 2008

ABSTRACT— We explored the effects of task‐related factors on reasoning processes in geometry focusing on a comparison‐of‐perimeters task in which the irrelevant feature area interferes with the reasoning process. We studied the effects of congruity, salience, and complexity on participants’ accuracy of responses and reaction times. The study shows that incongruent trials yield lower accuracy and longer reaction times than congruent ones. In addition, increasing the salience of the irrelevant feature results in a lower rate of success. Previous research suggested that a high cognitive load leads to higher interference in the incongruent condition. The current study shows that, in this condition, increasing the level of complexity of shapes associated with a higher cognitive load decreases the accuracy of responses and increases reaction times. Our findings can aid educators to select appropriate tasks and examples in their classrooms, taking into account how the level of difficulty is affected by complexity, salience, and congruity.
Neurocognitive and Temperamental Systems of Self‐Regulation and Early Adolescents’ Social and Academic Outcomes
Authors: Checa Purificación , Rodríguez‐Bailón Rosa , Rueda M. Rosario
Published: November 2008

ABSTRACT— The aim of the current study was to examine the role of individual differences in neurocognitive and temperamental systems of self‐regulation in early adolescents’ social and academic competence. Measures used in the study included the Attention Network Test, the Early Adolescence Temperament Questionnaire, a peer‐reported Social Status Questionnaire, a self‐reported measure of Schooling Skills, and information on grades obtained by the students in a variety of school subjects (n= 69 12‐year olds). Results showed that efficiency of the neurocognitive network of executive attention is related to academic outcomes, particularly in mathematics, as well as to aspects of social adjustment. Temperamental effortful control appears to be a significant predictor of all dimensions of school competence assessed in this study and mediates the relationship between social adjustment and poor schooling outcomes. These data suggest that individual differences in systems of self‐regulation are central to understanding processes of learning and social adjustment in the school.
Prevalence and Predictors of Renal Artery Stenosis in Hypertensive Patients Undergoing Elective Coronary Procedures
Authors: El‐Mawardy Ramzy H. , Ghareeb Magdy A. , Mahdy Mohsen M. , Sabet Sameh S. , Nammas Wail M.
Published: November 2008

This study explored the prevalence and predictors of renal artery stenosis in a cohort of 525 hypertensive patients referred for elective coronary procedures. Patients underwent coronary and renal arteriography. The study defined renal artery stenosis as ≥60% luminal obstruction (physiologic or hemodynamic significance was not tested). Patients were classified into groups of those with normal renal arteries, those with insignificant renal artery stenosis, and individuals with significant renal artery stenosis. The mean age was 52.6±8.5 years, and 403 (76.8%) were males. Significant renal artery stenosis was found in 3.6%. It correlated significantly with hypertension duration (P=.005), history of cerebrovascular stroke (P=.01), history of angioplasty to >1 coronary vessel (P=.003), and 3‐vessel coronary disease (P=.0003). Multivariate regression analysis identified 2‐vessel and 3‐vessel coronary artery disease as independent predictors of renal artery stenosis, with odds ratios of 4.9 and 12.1, respectively. It was concluded that invasive screening for renal artery stenosis was probably warranted only in hypertensive patients with multivessel coronary disease referred for elective coronary procedures.
Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis
Authors: Um Soo‐Jung , Lee Soo‐Keol , Yang Doo Kyung , Son Choonhee , Roh Mee Sook , Kim Ki Nam , Lee Ki‐Nam , Choi Pil Jo
Published: November 2008

Introduction:  Although gefitinib used for the treatment of non‐small‐cell lung cancer is a well‐known cause of interstitial lung disease (ILD), few case reports on erlotinib‐induced ILD have been issued. The common risk factor of both of these two drug‐induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported.

Methods:  Report of a case.

Results:  We recently experienced a case of fatal erlotinib‐induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50‐year‐old male patient was started on erlotinib as a third‐line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High‐resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib‐induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation.

Conclusion:  Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib.

Please cite this paper as: Um S‐J, Lee S‐K, Yang DK, Son C, Roh MS, Kim KN, Lee K‐N and Choi PJ. Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. The Clinical Respiratory Journal 2009; 3: 181–184.
Prevalence and Concentration of Verotoxigenic Escherichia coli O157:H7 in Adult Sheep at Slaughter from Italy
Authors: Franco A. , Lovari S. , Cordaro G. , Di Matteo P. , Sorbara L. , Iurescia M. , Donati V. , Buccella C. , Battisti A.
Published: November 2008

A 1‐year study on the animal‐level prevalence and concentration of Escherichia coli O157 in adult sheep at slaughter was performed, to collect qualitative and quantitative information on the diffusion of the pathogen in adult sheep from Italy. A total 533 samples were collected, with a similar distribution in the four seasons. For prevalence estimates, a simple random sampling technique was used. An immuno‐magnetic separation technique was used for sample screening, with enumeration of the pathogen in positive samples, along with molecular and serological identification of isolates. An overall prevalence of 7.1% (38/533, 95% CI 4.9–9.3%) was observed for fully virulent E. coli O157. A wide interval of VTEC O157 per gram was observed (<100 to 6 × 105 CFU g−1), with 28.9% (11/38) of positive samples ≥1 × 103 CFU g−1, set as the threshold for those animals defined ‘active shedders’ for the purpose of the study. Eight per cent (3/38) of animals shed >1 × 104 g−1 VTEC O157, which represents >96% of the total VTEC O157 bacteria cultured from all animals tested. The prevalence estimate of active shedders was therefore 2.1% (95% CI 0.9–3.3%). Most (34/38, 89.5%) of the positive animals were found in summer (July–September). Prevalence and concentrations of virulent VTEC O157 obtained in this study contribute to the demonstration that adult sheep represent a relevant source of environmental contamination from virulent VTEC O157, as well as a source of VTEC O157 contamination for food of ovine origin (meat and dairy products), especially during warm months.
The New Dynamics of East Asian Regional Economy: Japanese and Chinese Strategies in Asia
Authors: Komori Yasumasa
Published: November 2008

The Japan‐led flying‐geese pattern of economic development has become obsolete as an accurate description of the pattern of economic relations in East Asia. Meanwhile, the rise of China as the world's production platform has become the most significant factor in transforming the East Asian regional economy. Although the Asian financial crisis served as a major catalyst for the emergence of ASEAN+3, the China factor looms increasingly important in the subsequent development of East Asian regionalism. Despite its enhanced position in the region, however, China's new role in East Asia is clearly different from the role that Japan played at the zenith of its economic prosperity. While Japan's economic engagement in Asia was based on economic penetration by Japanese multilateral firms, China's rapid growth is still predicated upon foreign capital and technology. China's strength lies in its ability to open up its economy for trade and investment. In trade negotiations with ASEAN, China has taken the lead, surpassing Japan, a country constrained by domestic politics. However, Japan remains an important partner for ASEAN countries, not only in providing financial and developmental assistance, but also in hedging against China's dominance.
α‐Adrenergic and neuropeptide Y Y1 receptor control of collateral circuit conductance: influence of exercise training
Authors: Taylor Jessica C. , Yang H. T. , Laughlin M. Harold , Terjung Ronald L.
Published: November 2008

This study evaluated the role of α‐adrenergic receptor‐ and neuropeptide Y (NPY) Y1 receptor‐mediated vasoconstriction in the collateral circuit of the hind limb. Animals were evaluated either the same day (Acute) or 3 weeks following occlusion of the femoral artery; the 3‐week animals were in turn limited to cage activity (Sed) or given daily exercise (Trained). Collateral‐dependent blood flows (BFs) were measured during exercise with microspheres before and after α‐receptor inhibition (phentolamine) and then NPY Y1 receptor inhibition (BIBP 3226) at the same running speed. Blood pressures (BPs) were measured above (caudal artery) and below (distal femoral artery) the collateral circuit. Arterial BPs were reduced by α‐inhibition (50–60 mmHg) to ∼75 mmHg, but not further by NPY Y1 receptor inhibition. Effective experimental sympatholysis was verified by 50–100% increases (P < 0.001) in conductance of active muscles not affected by femoral occlusion with receptor inhibition. In the absence of receptor inhibition, vascular conductance of the collateral circuit was minimal in the Acute group (0.13 ± 0.02), increased over time in the Sed group (0.41 ± 0.03; P < 0.001), and increased further in the Trained group (0.53 ± 0.03; P < 0.02). Combined receptor inhibition increased collateral circuit conductances (P < 0.005), most in the Acute group (116 ± 37%; P < 0.02), as compared to the Sed (41 ± 6.6%; P < 0.001) and Trained (31 ± 5.6%; P < 0.001) groups. Thus, while the sympathetic influence of the collateral circuit remained in the Sed and Trained animals, it became less influential with time post‐occlusion. Collateral conductances were collectively greater (P < 0.01) in the Trained as compared to Sed group, irrespective of the presence or absence of receptor inhibition. Conductances of the active ischaemic calf muscle, with combined receptor inhibition, were suboptimal in the Acute group, but increased in Sed and Trained animals to exceptionally high values (e.g. red fibre section of the gastrocnemius: ∼7 ml min−1 (100 g)−1 mmHg−1). Thus, occlusion of the femoral artery promulgated vascular adaptations, even in vessels that are not part of the collateral circuit. The presence of active sympathetic control of the collateral circuit, even with exercise training, raises the potential for reductions in collateral BF below that possible by the structure of the collateral circuit. However, even with release of this sympathetic vasoconstriction, conductance of the collateral circuit was significantly greater with exercise training, probably due to the network of structurally larger collateral vessels.
Reliability-Based Design Optimization Using Response Surface Method With Prediction Interval Estimation
Authors: Kim Chwail , Choi K. K.
Published: November 2008

Since variances in the input variables of the engineering system cause subsequent variances in the product output performance, reliability-based design optimization (RBDO) is getting much attention recently. However, RBDO requires expensive computational time. Therefore, the response surface method is often used for computational efficiency in solving RBDO problems. A method to estimate the effect of the response surface error on the RBDO result is developed in this paper. The effect of the error is expressed in terms of the prediction interval, which is utilized as the error metric for the response surface used for RBDO. The prediction interval provides upper and lower bounds for the confidence level that the design engineer specified. Using the prediction interval of the response surface, the upper and lower limits of the reliability are computed. The lower limit of reliability is compared with the target reliability to obtain a conservative optimum design and thus safeguard against the inaccuracy of the response surface. On the other hand, in order to avoid obtaining a design that is too conservative, the developed method also constrains the upper limit of the reliability in the design optimization process. The proposed procedure is combined with an adaptive sampling strategy to refine the response surface. Numerical examples show the usefulness and the efficiency of the proposed method.
Construction of Semianalytical Solutions to Spur Gear Dynamics Given Periodic Mesh Stiffness and Sliding Friction Functions
Authors: He Song , Rook Todd , Singh Rajendra
Published: November 2008

Gear dynamic models with time-varying mesh stiffness, viscous mesh damping, and sliding friction forces and moments lead to complex periodic differential equations. For example, the multiplicative effect generates higher mesh harmonics. In prior studies, time-domain integration and fast Fourier transform analysis have been utilized, but these methods are computationally sensitive. Therefore, semianalytical single- and multiterm harmonic balance methods are developed for an efficient construction of the frequency responses. First, an analytical single-degree-of-freedom, linear time-varying system model is developed for a spur gear pair in terms of the dynamic transmission error. Harmonic solutions are then derived and validated by comparing with numerical integration results. Next, harmonic solutions are extended to a six-degree-of-freedom system model for the prediction of (normal) mesh loads, friction forces, and pinion/gear displacements (in both line-of-action and off-line-of-action directions). Semianalytical predictions compare well with numerical simulations under nonresonant conditions and provide insights into the interaction between sliding friction and mesh stiffness.
Consciousness and Anesthesia
Authors: Alkire Michael T. , Hudetz Anthony G. , Tononi Giulio
Published: November 2008

When we are anesthetized, we expect consciousness to vanish. But does it always? Although anesthesia undoubtedly induces unresponsiveness and amnesia, the extent to which it causes unconsciousness is harder to establish. For instance, certain anesthetics act on areas of the brain's cortex near the midline and abolish behavioral responsiveness, but not necessarily consciousness. Unconsciousness is likely to ensue when a complex of brain regions in the posterior parietal area is inactivated. Consciousness vanishes when anesthetics produce functional disconnection in this posterior complex, interrupting cortical communication and causing a loss of integration; or when they lead to bistable, stereotypic responses, causing a loss of information capacity. Thus, anesthetics seem to cause unconsciousness when they block the brain's ability to integrate information.
Slow Electron Cooling in Colloidal Quantum Dots
Authors: Pandey Anshu , Guyot-Sionnest Philippe
Published: November 2008

Hot electrons in semiconductors lose their energy very quickly (within picoseconds) to lattice vibrations. Slowing this energy loss could prove useful for more efficient photovoltaic or infrared devices. With their well-separated electronic states, quantum dots should display slow relaxation, but other mechanisms have made it difficult to observe. We report slow intraband relaxation (>1 nanosecond) in colloidal quantum dots. The small cadmium selenide (CdSe) dots, with an intraband energy separation of ∼0.25 electron volts, are capped by an epitaxial zinc selenide (ZnSe) shell. The shell is terminated by a CdSe passivating layer to remove electron traps and is covered by ligands of low infrared absorbance (alkane thiols) at the intraband energy. We found that relaxation is markedly slowed with increasing ZnSe shell thickness.
Global Protein Stability Profiling in Mammalian Cells
Authors: Yen Hsueh-Chi Sherry , Xu Qikai , Chou Danny M. , Zhao Zhenming , Elledge Stephen J.
Published: November 2008

The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of ∼8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions.
Recycling of Graphite During Himalayan Erosion: A Geological Stabilization of Carbon in the Crust
Authors: Galy Valier , Beyssac Olivier , France-Lanord Christian , Eglinton Timothy
Published: November 2008

At geological time scales, the role of continental erosion in the organic carbon (OC) cycle is determined by the balance between recent OC burial and petrogenic OC oxidation. Evaluating its net effect on the concentration of carbon dioxide and dioxygen in the atmosphere requires the fate of petrogenic OC to be assessed. Here, we report a multiscale (nanometer to micrometer) structural characterization of petrogenic OC in the Himalayan system. We show that graphitic carbon is preserved and buried in marine sediments, while the less graphitized forms are oxidized during fluvial transport. Radiocarbon dating indicates that 30 to 50% of the carbon initially present in the Himalayan rocks is conserved during the erosion cycle. Graphitization during metamorphism thus stabilizes carbon in the crust over geological time scales.
Reconstructing Farallon Plate Subduction Beneath North America Back to the Late Cretaceous
Authors: Liu Lijun , Spasojević Sonja , Gurnis Michael
Published: November 2008

Using an inverse mantle convection model that assimilates seismic structure and plate motions, we reconstruct Farallon plate subduction back to 100 million years ago. Models consistent with stratigraphy constrain the depth dependence of mantle viscosity and buoyancy, requiring that the Farallon slab was flat lying in the Late Cretaceous, consistent with geological reconstructions. The simulation predicts that an extensive zone of shallow-dipping subduction extended beyond the flat-lying slab farther east and north by up to 1000 kilometers. The limited region of flat subduction is consistent with the notion that subduction of an oceanic plateau caused the slab to flatten. The results imply that seismic images of the current mantle provide more constraints on past tectonic events than previously recognized.
"Who" Is Saying "What"? Brain-Based Decoding of Human Voice and Speech
Authors: Formisano Elia , De Martino Federico , Bonte Milene , Goebel Rainer
Published: November 2008

Can we decipher speech content (“what” is being said) and speaker identity (“who” is saying it) from observations of brain activity of a listener? Here, we combine functional magnetic resonance imaging with a data-mining algorithm and retrieve what and whom a person is listening to from the neural fingerprints that speech and voice signals elicit in the listener's auditory cortex. These cortical fingerprints are spatially distributed and insensitive to acoustic variations of the input so as to permit the brain-based recognition of learned speech from unknown speakers and of learned voices from previously unheard utterances. Our findings unravel the detailed cortical layout and computational properties of the neural populations at the basis of human speech recognition and speaker identification.
Insights into Translational Termination from the Structure of RF2 Bound to the Ribosome
Authors: Weixlbaumer Albert , Jin Hong , Neubauer Cajetan , Voorhees Rebecca M. , Petry Sabine , Kelley Ann C. , Ramakrishnan Venki
Published: November 2008

The termination of protein synthesis occurs through the specific recognition of a stop codon in the A site of the ribosome by a release factor (RF), which then catalyzes the hydrolysis of the nascent protein chain from the P-site transfer RNA. Here we present, at a resolution of 3.5 angstroms, the crystal structure of RF2 in complex with its cognate UGA stop codon in the 70
S
ribosome. The structure provides insight into how RF2 specifically recognizes the stop codon; it also suggests a model for the role of a universally conserved GGQ motif in the catalysis of peptide release.
In Vitro Levels of Interleukin 10 (IL-10) and IL-12 in Response to a Recombinant 32-Kilodalton Antigen ofMycobacterium bovisBCG after Treatment for Tuberculosis
Authors: Sai Priya V. Hari , Anuradha B. , Latha Gaddam Suman , Hasnain Seyed E. , Murthy K. J. R. , Valluri Vijaya Lakshmi
Published: November 2008

Cell-mediated immunity plays a major role in conferring protection against tuberculosis (TB) on an individual. It is not known whether the immune status correlates with the bacterial load or whether the immunity improves after treatment. Also, it may be important to monitor treatment by being able to discriminate between active disease and successfully treated TB. The main aim of this study was to investigate the usefulness of a recombinant 32-kDa antigen (r32-kDa Ag) ofMycobacterium bovisBCG (Ag85A-BCG) as a diagnostic marker in patients being treated for TB. Specifically, the in vitro T-cell assays and the release of interleukin-12 (IL-12) (Th1-type cytokine) and IL-10 (Th2-type cytokine) in response to the r32-kDa Ag of BCG were assayed in patients with either pulmonary (sputum positive/negative,n= 74) or extrapulmonary TB (n= 49) and healthy controls. The proliferative responses of stimulated cells at 0, 2 to 4, and 6 months of treatment increased and were highly significant (P< 0.000) compared to the responses in controls. The increase in IL-12 and decrease in IL-10 release suggest that there is cytokine expression modification during different stages of TB, and treatment seems to have an influence on the levels of these cytokines, suggesting an augmentation in the protective responses. The in vitro response to theM.bovisBCG r32-kDa Ag may be useful in monitoring treatment of TB.
Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines against Severe Acute Respiratory Syndrome (SARS) or SARS-Like Coronavirus in Mice
Authors: Lu Baojing , Tao Ling , Wang Ting , Zheng Zhenhua , Li Bao , Chen Ze , Huang Yi , Hu Qinxue , Wang Hanzhong
Published: November 2008

Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8
+
T cells and interleukin-2 (IL-2) mainly by CD4
+
T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.