bluuebunny/crossref_metadata_2025 huggingface dataset:
New Efficient Petri Nets Reductions for Parallel Programs Verification
Authors: HADDAD Serge , PRADAT-PEYRE Jean-François
Published: March 2006

Structural model abstraction is a powerful technique for reducing the complexity of a state based enumeration analysis. We present in this paper new efficient Petri nets reductions. First, we define "behavioural" reductions (i.e. based on conditions related to the language of the net) which preserve a fundamental property of a net (i.e. liveness) and any formula of the (action-based) linear time logic that does not observe reduced transitions of the net. We show how to replace these conditions by structural or algebraical ones leading to reductions that can be efficiently checked and applied whereas enlarging the application spectrum of the previous reductions. At last, we illustrate our method on a significant and typical example of a synchronisation pattern of parallel programs.
THE PRICE OF ANARCHY FOR RESTRICTED PARALLEL LINKS
Authors: GAIRING MARTIN , LÜCKING THOMAS , MAVRONICOLAS MARIOS , MONIEN BURKHARD
Published: March 2006

In the model of restricted parallel links, n users must be routed on m parallel links under the restriction that the link for each user be chosen from a certain set of allowed links for the user. In a (pure) Nash equilibrium, no user may improve its own Individual Cost (latency) by unilaterally switching to another link from its set of allowed links. The Price of Anarchy is a widely adopted measure of the worst-case loss (relative to optimum) in system performance (maximum latency) incurred in a Nash equilibrium.

In this work, we present a comprehensive collection of bounds on Price of Anarchy for the model of restricted parallel links and for the special case of pure Nash equilibria. Specifically, we prove:

• For the case of identical users and identical links, the Price of Anarchy is [Formula: see text].

• For the case of identical users, the Price of Anarchy is [Formula: see text].

• For the case of identical links, the Price of Anarchy is [Formula: see text], which is asymptotically tight.

• For the most general case of arbitrary users and related links, the Price of Anarchy is at least m – 1 and less than m.

The shown bounds reveal the dependence of the Price of Anarchy on n and m for all possible assumptions on users and links.
IMPLEMENTATION AND PERFORMANCE EVALUATION OF A PARALLELIZATION OF ESTIMATION OF BAYESIAN NETWORK ALGORITHMS
Authors: MENDIBURU A. , MIGUEL-ALONSO J. , LOZANO J. A.
Published: March 2006

This paper presents, discusses and evaluates parallel implementations of a set of algorithms designed for optimization tasks: Estimation of Bayesian Network Algorithms (EBNAs). These algorithms belong to the family of Evolutionary Computation. Two different APIs have been combined: message passing and threads, with the aim of obtaining good performance levels in a wide range of parallel machines. Our approach has been to analyze the most computationally intensive sections of sequential implementations of EBNAs, and then to parallelize those sections using a master-worker design pattern. This way the resulting program exhibits exactly the same behavior of the sequential one, but runs faster. To evaluate our proposal, we have chosen a complex scenario where EBNAs can be applied: Feature Subset Selection (FSS) for supervised classification problems. For the experiments, three computing systems have been tested: two different clusters built from commodity components, and an 8-way multiprocessor. Programs have been executed on the target machines using different combination of message-passing processes and threads. Achieved performance is excellent, with efficiency around 1. These encouraging results do widen the spectrum of problems (and problem sizes) that can be solved, in reasonable times, with EBNAs.
THE ROLLING BELTS INJURIES IN CHILDHOOD
Authors: Tükenmez Mehmet , Tezeren Gunduz , Perçýn Sıtkı , Demirel Hüseyin
Published: March 2006

Rolling belt injuries are commonly seen in the summer when the tractors and water pumps work in agricultural fields. These machines' rolling belts may attract children and entrap their hands. The injuries frequently affect soft tissues and bone of volar side of their hands. Amputations may be seen.

In the present study, 45 patients with rolling belt injuries were retrospectively analysed. It was observed that 133 fingers of 42 patients and three hands (Zone III) of three patients were surgically treated. The treatment included primary closure of the lacerations, tendon/nerve repair, fixation of fractures, grafting, and local or cross-arm or groin flaps. Stump closure procedures were performed in 21 fingers with total amputations or non-viable tissues. The injuries in most of the cases were localised at Zones I and II. We performed revascularisation procedures in five fingers. Only one of them stayed alive (20%). Our results revealed that 13 cases were good, 21 were fair and 11 were poor to according to Gorsche and Wood criteria.

These injuries cause the burns and defects on digital arteries-veins as well as flexor tendons. Frequently, phalanx fractures and finger amputations may occur. Also, the skin defects are common. The treatment of rolling belt injuries is difficult, quite expensive, and the outcomes are not always satisfactory.
CLASSIFICATION AND TREATMENT OF HAMATE FRACTURES
Authors: Hirano Kenichi , Inoue Goro
Published: March 2006

Twenty-nine patients with hamate fractures were treated. The two main types of hamate fractures are hook fractures (type 1) and body fractures (type 2). We sub-divided type 2 fractures according to the fracture line into coronal, type 2a and transverse, type 2b. There were 15 type 1, 11 type 2a and three type 2b fractures. For type 1, nine were treated with excision, one with open reduction and internal fixation (ORIF) and five with cast immobilisation, in which two resulted in non-union followed by excision. For type 2, five type 2a cases were treated with ORIF and the others with closed reduction and pinning.

Most of the patients had satisfactory results at the seventh month follow-up. However, those with associated neurovascular and musculotendinous injuries were likely to have unfavourable results. On the basis of study findings, it appears that functional results are influenced mainly by the associated soft tissue damage.
FUNCTIONAL RESULTS POST-TRIANGULAR FIBROCARTILAGE COMPLEX RECONSTRUCTION WITH EXTENSOR CARPI ULNARIS WITH OR WITHOUT ULNAR SHORTENING IN CHRONIC DISTAL RADIOULNAR JOINT INSTABILITY
Authors: Shih Jui-Tien , Lee Hung-Maan
Published: March 2006

From September 1996 to September 2001, 37 adult patients were diagnosed with chronic triangular fibrocartilage complex (TFCC) tears with distal radioulnar joint (DRUJ) instability in our clinic. They had all received the procedure of TFCC reconstruction with partial extensor carpi ulnaris (ECU) combined with or without ulnar shortening. There were 36 males and one female in the study with a mean age of 22.4 years. The follow-up period ranged from 25 to 48 months with a mean of 36.2 months. All patients received the rehabilitation programme and were re-examined at our outpatient department. The results were graded according to the Mayo Modified Wrist Score. Eleven of the 37 patients rated their wrists "excellent", 22 rated "good", and four rated "fair". Overall, a total of 33 patients (89%) rated satisfactorily and returned to work or sport activities. Therefore, TFCC reconstruction with partial ECU tendon combined with or without ulnar shortening procedure is an effective method for post-traumatic chronic TFCC tears with DRUJ instability suggested by this study.
GIANT CELL TUMOUR OF THE DISTAL PHALANX OF THE HAND
Authors: Slesarenko Yury A. , Sampson Steven P. , Gould Elaine S.
Published: March 2006

Giant cell tumour of bone in the phalanx of the hand is extremely rare. A case of giant cell tumour of distal phalanx treated with a ray amputation is presented.
SIMULTANEOUS DISLOCATIONS OF THE CARPOMETACARPAL JOINTS: A CASE REPORT
Authors: Slesarenko Yury A. , Wang Edward D. , Most Mathew J.
Published: March 2006

A case of simultaneous dislocations of the carpometacarpal joints is reported. Closed reduction and splinting produced a good result.
LATERAL ARM FREE FLAPS IN THE DEFECTS OF THE UPPER EXTREMITY — A REVIEW OF 72 CASES
Authors: Akinci M. , Ay Ş , Kamiloglu S. , Erçetin Ö.
Published: March 2006

Lateral arm flaps are versatile in the use of upper extremity moderate-sized defects with little morbidity and with acceptable cosmesis. The conditions are outlined in a series of 74 lateral arm flaps performed on 72 patients and the results are given. Five patients were operated on as emergencies, 12 were operated within the first 72 hours of injury and 57 patients were treated electively. Skin defects were between 6 × 4 cm and 20 × 9 cm . Five (7%) flaps were lost due to venous thrombosis, three that sustained a high-voltage electric burn. Two other patients that were treated for a high-voltage electric burn had a successful revision of the anastomosis site in the early post-operative duration. One flap was abandoned due to very thin pedicle and obesity of the patient. A higher failure rate is encountered most frequently with the cases of high-voltage electric burn. To deal with this problem, a modified approach such as an extended approach and/or including the forearm skin to the flap is recommended during the flap harvest. For a longer pedicle to be anatomized more proximally, perforator flaps with longer pedicles may be used as an alternative.
A CHRONIC NOCARDIAL INFECTION FOLLOWING CONSERVATIVE TREATMENT OF A HIGH PRESSURE INJECTION INJURY OF AIR
Authors: Lee J. Y. L. , Yong F. C.
Published: March 2006

We present a case of recurrent cutaneous nocardiosis following a high pressure air injection injury which was treated conservatively. The patient subsequently developed multiple chronic granulomatous nodules in the palm and dorsum of the hand requiring repeated surgical debridements and long term antibiotics for complete resolution. Some reports suggest that high pressure injection injuries of air or water run a benign course and may be treated conservatively. However, inoculation by high pressure injection injury of air or water may result in chronic infections, which cause significant morbidity and are a therapeutic challenge. Although uncommon, they may be avoided by adherence to established treatment principles which include prompt recognition, realisation of its severity and aggressive treatment by open wound management, even for seemingly innocuous trauma or inoculum.
SUPERFICIAL RADIAL NERVE COMPRESSION CAUSED BY A PAROSTEAL LIPOMA OF PROXIMAL RADIUS: A CASE REPORT
Authors: Tzeng Chung-Yuh , Lee Tu-Sheng , Chen I-Chen
Published: March 2006

The superficial radial nerve might be compressed or injured at various anatomical sites along its course in the forearm. Most of the superficial radial nerve neuropathy are caused by pathological lesions such as trauma, a mass or tight band at the distal third of the forearm. Wartenberg's syndrome is the most common cause of sensory radial entrapment at the distal forearm. Compression of superficial radial nerve occurring at the proximal third of forearm is unusual. We present a rare case of superficial radial nerve compression due to a parosteal lipoma of proximal radius. Results of complete physical and radiological examinations are also presented. Surgical intervention of the tumour mass was performed for nerve decompression. The patient reported total relief of the neurological symptom post-operatively. This rare case demonstrates the unique characteristics of parosteal lipoma with unusual superficial radial nerve neuropathy at the proximal radius. This report reminds us that there is the possibility of superficial nerve compression caused by tumour mass over the proximal third of forearm.
MECHANICAL STRENGTH AND OPTIMAL SITE OF PLACEMENT OF A THREADED BONE SCREW ASSESSED ON THE BASIS OF THE SCREW BREAKAGE FOR NON-UNION OF THE SCAPHOID: A BIOMECHANICAL STUDY
Authors: Takase Katsumi , Yamamoto Kengo
Published: March 2006

We have performed the surgical procedure on the patients with the fracture of the scaphoid using mini-acutrak screws (ACUMED, Inc.).

A 25-year-old man was injured in a fall. Surgical treatment for non-union of the scaphoid using a mini-acutrak screw was performed. However, this screw was broken, despite the absence of any obvious trauma mechanism. A structural examination was performed with a metal microscope and a hardness test was performed. A hardness evaluation was conducted on this broken screw and similar screws. Cannulated screws having diameters of 2.7 and 3.5 mm were also evaluated in the strength test as controls for comparison.

The breakage of screw occurred due to fatigue. The screw provides the strength equivalent to that of a 3.5 mm cannulated screw but the bending strength of the head end portion in which the breakage occurred was assumed to be the strength of about one-third that of the intermediate portion.
EXTENSOR POLLICIS LONGUS TENDON RUPTURE AS A RESULT OF SCAPHOLUNATE DISSOCIATION: A CASE REPORT
Authors: Shigematsu Koji , Yajima Hiroshi , Takakura Yoshinori
Published: March 2006

A 39-year-old patient was presented with, to our knowledge, the first ever diagnosed case of extensor pollicis longus (EPL) tendon rupture as a result of scapholunate (S-L) dissociation. Arthroscopic findings showed that the dorsal aspect of the S-L ligament was ruptured and severe synovitis was revealed around the S-L joint. Direct observation revealed synovium at the rupture site of the EPL tendon. After careful resection of this synovium, an aperture in the S-L joint was observed. Thus, it was considered that the synovium in the S-L joint was connected to the rupture site of the EPL tendon, passing through the dorsal capsule of the S-L joint. The ruptured EPL tendon was reconstructed with extensor indicis proprius tendon transfer, and S-L dissociation was treated with a bone-retinaculum-bone autograft taken from the third dorsal compartment region.
TREATMENTS OF OSTEOARTHRITIS OF THE DISTAL RADIOULNAR JOINT: LONG-TERM RESULTS OF THREE PROCEDURES
Authors: Minami Akio , Iwasaki Norimasa , Ishikawa Jun-ichi , Suenaga Naoki , Yasuda Kazunori , Kato Hiroyuki
Published: March 2006

Sixty-one wrists in 61 patients with osteoarthritis of the distal radioulnar joint treated by three consecutive procedures (20 Darrach, 25 Sauvé-Kapandji and 16 hemiresection-interposition arthroplastic procedures) were retrospectively evaluated. We preferred to perform Darrach's procedure in even the early stages of osteoarthritis of the distal radioulnar joint prior to introduction of Sauvé-Kapandji and hemirestion-interposition arthroplastic procedures. Subsequently the hemirestion-interposition arthroplasty was indicated when the triangular fibrocartilage cartilage was intact or could be reconstructed and the Sauvé-Kapandji when the triangular fibrocartilage complex could not be reconstructed or there was positive ulnar variance of more than 5 mm even though the triangular fibrocartilage complex was functional. Patient's age at operation averaged 59.8 years. There were 36 men and 25 women. There were 38 primary and 23 secondary osteoarthritis cases. Post-operative pain, range of motion, grip strength, return to work status; and radiographic results were evaluated. At the five- to 14-year (average, ten years) follow-up evaluation, relief of pain from Darrach procedure was inferior to the Sauvé-Kapandji procedure and hemiresection-interposition arthroplasty although this was not statistically significant. After both the Sauvé-Kapandji procedure and hemiresection-inteposition arthroplasty, post-operative improvements in flexion and extension of the wrist had statistical significance. Post-operative improvements in pronation and supination of the forearm showed statistical significances after all procedures. Improvements of post-operative grip strength and return to an original job in the Sauvé-Kapandji procedure and hemiresection-interposition arthroplasty were statistically superior to those with a Darrach's procedure. There were many post-operative complications following the Darrach's procedure. Darrach's procedure is better indicated for severe osteoarthritic changes of the distal radioulnar joint in elderly patients. We believe the operative indications between the Sauvé-Kapandji procedure and hemiresection-interposition arthroplasty are best determined prior to surgery by the existence and status of the triangular fibrocartilage complex and the amount of the positive ulnar variance.
NEURAL FIBROLIPOMA OF THE ULNAR NERVE IN THE HAND: A CASE REPORT
Authors: YıLdırım Serkan
Published: March 2006

The author reports an unusual case of neural fibrolipoma (lipofibromatous hamartoma) of the ulnar nerve in the hand. A 20-year-old man presented with a fusiform soft tissue mass in his right hand. Neurological examination was normal except to minimal pain on palpation. Surgical exploration revealed that ulnar nerve and its digital branches were infiltrated by fibrofatty tissues. Fibrofatty tissues were dissected and removed from the nerve by microsurgical technique. Histological examination confirmed the diagnosis as a lipofibromatous hamartoma of the nerve. The result of surgical debulking was satisfactory.
THE "U-LIGAMENT" FOR COLLATERAL LIGAMENT RECONSTRUCTION IN DUPLICATE THUMB
Authors: Coombs C. J. , Richardson P. W. , Johnstone B. R. , Tan S. C.
Published: March 2006

Duplicate thumb is a common congenital difference with complex management. Surgical treatment includes reconstruction of the collateral ligaments to optimise future function and cosmesis. We present the use of the "U-ligament" to further refine collateral ligament reconstruction. We have found it to be a simple and reliable technique.
REPRESENTATIONS OF ${\rscr B}^a (E)$
Authors: MUHLY PAUL S. , SKEIDE MICHAEL , SOLEL BARUCH
Published: March 2006

We present a short and elegant proof of the complete theory of strict representations of the algebra [Formula: see text] of all adjointable operators on a Hilbert [Formula: see text]-module E by operators on a Hilbert [Formula: see text]-module F. An analogue for W*-modules and normal representations is also proved. As an application we furnish a new proof of Blecher's Eilenberg–Watts theorem.
REMARK ON THE INTEGRATION BY PARTS FORMULA FOR THE $\phi_3^4$-QUANTUM FIELD MODEL
Authors: ALBEVERIO SERGIO , LIANG SONG , ZEGARLINSKI BOGUSLAV
Published: March 2006

An integration by parts formula for the measure μ of the Euclidean [Formula: see text]-quantum field model is proven. It is also proven that the regularized logarithmic derivative of μ when the regularization is removed does not converge in L2(μ).
DISSIPATIVE BACKWARD STOCHASTIC DIFFERENTIAL EQUATIONS IN INFINITE DIMENSIONS
Authors: CONFORTOLA FULVIA
Published: March 2006

We prove an existence and uniqueness result for a class of backward stochastic differential equations (BSDE) with dissipative drift in Hilbert spaces. We also give examples of stochastic partial differential equations which can be solved with our result.
PROFILE OF WOMEN ENTREPRENEURS IN A WAR-TORN AREA: CASE STUDY OF NORTH EAST SRI LANKA
Authors: AYADURAI SELVALAMAR , SOHAIL M. SADIQ
Published: March 2006

This study examines the demographic profile of "Tamil" women entrepreneurs in the North East of Sri Lanka who became entrepreneurs as a result of war. Five main areas of interest were examined, namely, (i) characteristics of these women; (ii) factors that spurred them into entrepreneurship; (iii) their challenges; (iv) their measures of success; and (v) their demographic profile. Findings indicate that a large percentage of these women were highly entrepreneurial who were motivated into business to achieve a higher standard of living, be self-reliant and support their families. Most of these women were married with children and, and because many had lost their husbands to the war, saw business as a means to an end. A large majority of these women were in business for the first time and rated their businesses as successful ventures. Their measures of success were self-fulfillment and a balance between family and work. The findings of this research are important because the women entrepreneurs of the North East are seen as a powerful driving force for the economic development of the country.
VENTURE OPPORTUNITY EVALUATIONS: COMPARISONS BETWEEN VENTURE CAPITALISTS AND INEXPERIENCED PRE-NASCENT ENTREPRENEURS
Authors: BISHOP KAREN , NIXON ROBERT D.
Published: March 2006

Although we know something about how venture capitalists' (VCs) evaluate opportunities, little is known about entrepreneurs' evaluation processes before venture creation. Opportunity evaluation beliefs are antecedents to goal choice or pre-nascent activities and are different from opportunity exploitation behaviors, which are goal striving or nascent activities. Results show that inexperienced pre-nascent entrepreneurs have not institutionalized VCs criteria as common knowledge and that evaluation criteria are used differently due to differences in learning and experience. Criteria common to VCs were not all predictive for any pre-nascent individual but, as a group, all VC criteria significantly predicted evaluations of potential success.
RISK MANAGEMENT IN PRIVATE EQUITY FUNDS: A COMPARATIVE STUDY OF INDIAN AND FRANCO-GERMAN FUNDS
Authors: KUT CAN , SMOLARSKI JAN
Published: March 2006

Venture capitalist and buy-out funds are often considered experts at investing in high-risk projects and companies. To be successful investors, private equity funds must therefore manage the many aspects of risk that are associated with investing in non-public enterprises. This study examines how Indian private equity funds manage several dimensions of risk in comparison to non-Anglo-Saxon funds. We analyze risk management preferences in Indian and Franco-German funds in pre- and post-investment stages. The results, which are discussed in detail, show significant differences between the two groups.
IMPACT OF HUMAN RESOURCE MANAGEMENT: SME PERFORMANCE IN VIETNAM
Authors: KING-KAUANUI SANDRA , NGOC SU DANG , ASHLEY-COTLEUR CATHERINE
Published: March 2006

In its transition from a centrally planned economy to a market economy, Vietnam has achieved remarkable success. During this transition, Vietnam businesses have implemented a number of HRM practices used primarily by companies in Western cultures. This study specifically investigates the impact of three HRM practices: training, performance appraisal systems and incentive pay, on firm performance to determine if results mirror those obtained in the more highly developed economies of the West. A sample of 200 Hanoi manufacturing SMEs was surveyed regarding their practices in these areas. The result provides empirical support that training, performance appraisal and incentive compensation have positive effects on Vietnamese SME performance, with incentive compensation having the greatest impact.
Redistribution of connexin43 in regional acute ischemic myocardium: influence of ischemic preconditioning
Authors: Vetterlein Friedrich , Mühlfeld Christian , Cetegen Cenk , Volkmann Rolf , Schrader Christina , Hellige Gerhard
Published: March 2006

Connexins are known to play an essential role in the ischemic preconditioning (IP) of the heart; their functional role in this process, however, has not been clearly defined. For this reason, anesthetized rats were subjected to regional myocardial ischemia, with or without IP or reperfusion. In frozen sections of hearts, fluorescence immunohistochemical staining for connexin43 (Cx43) was performed. In contrast to undisturbed zones, tissue that had been subjected to ischemia revealed Cx43 immunostaining not only in the gap junctions but also in a conspicuous pattern in the free cellular membranes of the myocytes. In myocardium that was exposed to IP only, the ratio of immunofluorescence intensity in the free cellular membrane to that in the interior of the cell was 1.22 ± 0.04 (ratio in non-ischemia-exposed area = 1.04 ± 0.01). When 15 or 45 min of permanent ischemia followed IP, the effect became more evident (ratio = 1.31 ± 0.03 and 1.46 ± 0.03, respectively) and proved to be significantly greater than in the corresponding non-IP groups (ratio = 1.16 ± 0.03 and 1.30 ± 0.03, respectively, P < 0.01). Reperfusion led to an overall weakening of fluorescence intensities and a disappearance of the observed IP-specific differences. We conclude that IP initiates a redistribution of Cx43 from its natural position in the gap junctions toward the free plasma membrane, thereby improving the cell's chance of survival during the subsequent phase of prolonged ischemia by an unknown, supposedly gap junction-independent, mechanism.
Early exposure to a nonhygienic environment alters pulmonary immunity and allergic responses
Authors: George Caroline L. S. , White Misty L. , Kulhankova Katarina , Mahajan Aditya , Thorne Peter S. , Snyder Jeanne M. , Kline Joel N.
Published: March 2006

The hygiene hypothesis suggests that early life exposure to a nonhygienic environment that contains endotoxin reduces the risk of developing allergic diseases. The mechanisms underlying the hygiene hypothesis are unclear and may involve subtle immune system interactions that occur during maturation. Experimental objectives of this study were to use a novel animal model to test the hygiene hypothesis and to characterize early life immune system responses to a nonhygienic environment. Mice were reared in corn dust, a grain-processing byproduct with a high-endotoxin content and microbial products or in a low-endotoxin environment. The influence of early or later life exposure to corn dust on a subsequent allergen stimulus (ovalbumin) was assessed by bronchoalveolar lavage (BAL) cell analysis, lung histology, serum IgE, and BAL cytokine measurements. The influence of the corn dust environment on the developing pulmonary immune system was assessed by BAL cell analysis and immunostaining of lung tissue. The corn dust environment contained significantly more endotoxin ( P < 0.001), and the dust exposures attenuated the cellular inflammatory response to ovalbumin in the adult mouse ( P < 0.01) but did not reduce serum IgE levels or alter baseline BAL fluid proinflammatory cytokine levels. The corn dust environment did not induce significant neutrophilia in lavage fluid but significantly increased the number of antigen-presenting cells in alveolar walls early in life by ∼37%. In conclusion, exposure to a nonhygienic environment did not induce significant airway neutrophilia, yet altered the population of immunologically active cells in the lung and reduced subsequent allergic inflammation.
Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
Authors: Homer Robert J. , Zhu Zhou , Cohn Lauren , Lee Chun Gun , White Wendy I. , Chen Suping , Elias Jack A.
Published: March 2006

The mammalian chitinase family includes members both with and without enzymatic activity against chitin, a product of fungal cell walls, exoskeletons of crustaceans and insects, and the microfilarial sheaths of parasitic nematodes. Two members of that family, Ym1 and acidic mammalian chitinase (AMCase), are strongly upregulated in pulmonary T helper (Th) 2 inflammation but not in Th1 inflammation. The sites of expression of these products are incompletely known. We show here that, in two different models of Th2 inflammation, Ym1 and AMCase are mutually exclusively expressed in proximal vs. distal airway epithelium, respectively, whereas both are expressed in alveolar macrophages. This regional difference along the airway corresponds to the previously noted distinction between mucus positive proximal cells and mucus negative distal cells under the same conditions. Among distal cells, AMCase colocalizes with epithelial cells expressing the Clara cell marker Clara cell secretory protein. These AMCase-expressing cells retain expression of FOXA2, a transcription factor whose downregulation in association with IL-13 signaling has previously been associated with production of mucus in proximal airway epithelial cells. These results provide evidence that secretory cells of proximal and distal airways undergo fundamentally different gene expression programs in response to allergic inflammation. Furthermore, AMCase provides the first positive molecular marker of distal Clara cell secretory protein-expressing cells under these conditions.
Identification and characterization of p63 (CKAP4/ERGIC-63/CLIMP-63), a surfactant protein A binding protein, on type II pneumocytes
Authors: Gupta Nisha , Manevich Yefim , Kazi Altaf S. , Tao Jian-Qin , Fisher Aron B. , Bates Sandra R.
Published: March 2006

Surfactant protein A (SP-A) binds to alveolar type II cells through a specific high-affinity cell membrane receptor, although the molecular nature of this receptor is unclear. In the present study, we have identified and characterized an SP-A cell surface binding protein by utilizing two chemical cross-linkers: profound sulfo-SBED protein-protein interaction reagent and dithiobis(succinimidylpropionate) (DSP). Sulfo-SBED-biotinylated SP-A was cross-linked to the plasma membranes isolated from rat type II cells, and the biotin label was transferred from SP-A to its receptor by reduction. The biotinylated SP-A-binding protein was identified on blots by using streptavidin-labeled horseradish peroxidase. By using DSP, we cross-linked SP-A to intact mouse type II cells and immunoprecipitated the SP-A-receptor complex using anti-SP-A antibody. Both of the cross-linking approaches showed a major band of 63 kDa under reduced conditions that was identified as the rat homolog of the human type II transmembrane protein p63 (CKAP4/ERGIC-63/CLIMP-63) by matrix-assisted laser desorption ionization and nanoelectrospray tandem mass spectrometry of tryptic fragments. Thereafter, we confirmed the presence of p63 protein in the cross-linked SP-A-receptor complex by immunoprobing with p63 antibody. Coimmunoprecipitation experiments and functional assays confirmed specific interaction between SP-A and p63. Antibody to p63 could block SP-A-mediated inhibition of ATP-stimulated phospholipid secretion. Both intracellular and membrane localized pools of p63 were detected on type II cells by immunofluorescence and immunobloting. p63 colocalized with SP-A in early endosomes. Thus p63 closely interacts with SP-A and may play a role in the trafficking or the biological function of the surfactant protein.
Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains
Authors: Anh Dao Bui Tran , Faisca Pedro , Desmecht Daniel J.-M.
Published: March 2006

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.
Glucagon secretion and autonomic signaling during hypoglycemia in late pregnancy
Authors: Canniff Kathryn M. , Smith Marta S. , Lacy D. Brooks , Williams Phillip E. , Moore Mary Courtney
Published: March 2006

We examined net pancreatic norepinephrine (NE) spillover, pancreatic polypeptide (PP) release, and the decrement in C-peptide to identify factors involved in the blunted counterregulatory glucagon response in pregnancy. Conscious pregnant [pregnant hypoglycemic (Ph); 3rd trimester; n = 8] and nonpregnant [nonpregnant hypoglycemic (NPh); n = 6] dogs were studied during insulin-induced (∼12-fold basal insulin concentrations) hypoglycemia (plasma glucose 3.1 mM). Additional dogs were studied during hyperinsulinemic euglycemia [nonpregnant euglycemic (NPe), n = 4; pregnant euglycemic (Pe), n = 5; plasma glucose 6 mM]. Arterial glucagon concentrations declined similarly in NPe and Pe. Areas under the curve (AUCs) of the changes in glucagon and epinephrine were seven- and threefold greater in NPh than Ph ( P < 0.05 between groups for both). Glucagon secretion fell below basal in NPe, Pe, and Ph but rose significantly in NPh. C-peptide declined 0.25 ± 0.06, 0.12 ± 0.11, 0.28 ± 0.05, and 0.13 ± 0.02 ng/ml in NPe, Pe, NPh, and Ph, respectively ( P < 0.05, NPh vs. Ph). AUCs of NE spillover were 516 ± 274, 265 ± 303, 506 ± 94, and −63 ± 79 ng, respectively ( P < 0.05, NPh vs. Ph). The AUC of PP release was approximately threefold greater in NPh than Ph ( P < 0.05) but not different between euglycemic groups. The current evidence strongly suggests that the blunting of glucagon secretion during insulin-induced hypoglycemia in pregnancy is related to generalized impairment of a number of different signals, including parasympathetic and sympathoadrenal stimuli and altered sensing of circulating and/or intraislet insulin.
Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow
Authors: Kalliokoski Kari K. , Langberg Henning , Ryberg Ann Kathrine , Scheede-Bergdahl Celena , Doessing Simon , Kjær Andreas , Kjær Michael , Boushel Robert
Published: March 2006

Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-d-[18F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-l-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow.
Regulation of Class II β-Tubulin Expression by Tumor Suppressor p53 Protein in Mouse Melanoma Cells in Response toVincaAlkaloid
Authors: Arai Katsuhiko , Matsumoto Yoshifumi , Nagashima Yuko , Yagasaki Kazumi
Published: March 2006

The continuous exposure of antimicrotubule drugs to tumors often results in the emergence of drug-resistant tumor cells with altered expression of several β-tubulin isotypes. We found that Vinca alkaloid enhanced expression of class II β-tubulin isotype (mTUBB2) in mouse B16F10 melanoma cells via alteration of the tumor suppressor p53 protein. Vincristine treatment stimulated an increase in mTUBB2 mRNA expression and promoted accumulation of this isotype around the nuclei. Transient transfection assays employing a reporter construct, together with site-directed mutagenesis studies, suggested that the p53-binding site found in the first intron was a critical region for mTUBB2 expression. Electrophoretic mobility shift assay and associated antibody supershift experiments showed that vincristine promoted release of p53 protein from the binding site. In addition, exogenous induction of TAp63γ (p51A), a homologue of p53, canceled the effect of vincristine on mTUBB2 expression. These results suggest that p53 protein may function as a suppressor of mTUBB2 expression and vincristine-mediated inhibition of p53 binding results in enhanced mTUBB2 expression. This phenomenon could be related with the emergence of drug-resistant tumor cells induced by Vinca alkaloid and may participate in determining the fate of these cells. (Mol Cancer Res 2006;4(4):247–55)
Gene Promoter Hypermethylation in Mouse Lung Tumors
Authors: Vuillemenot Brian R. , Hutt Julie A. , Belinsky Steven A.
Published: March 2006

The mouse is a good model for evaluating the efficacy of chemopreventive agents for lung cancer. Gene silencing by promoter hypermethylation is a critical component for the development and progression of lung cancer and an emerging target for preventive intervention by demethylating agents. Genes methylated in mouse lung tumors could serve as biomarkers to evaluate the effectiveness of demethylating agents for preventing lung cancer and causing gene reexpression in vivo. The purpose of the current study was to evaluate a panel of genes inactivated by promoter hypermethylation in human lung cancer for silencing by this epigenetic mechanism in murine lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), cigarette smoke, or arising spontaneously. Cadherin-13, estrogen receptor-α, progesterone receptor, and runt-related transcription factor-3 were frequently methylated in mouse lung tumor-derived cell lines, whereas cadherin-1 and suppressor of cytokine signaling-1 were not. Methylation within these four genes was associated with lack of expression that could be restored after treatment with 5-aza-2′-deoxycytidine and with methylation within the CpG island of each gene. Methylation-specific PCR revealed that methylation of these four genes occurred at prevalences of 24% to 69% in primary lung tumors arising spontaneously or induced by exposure to cigarette smoke or NNK. Estrogen receptor-α methylation was more frequent in spontaneously occurring lung cancer than cigarette smoke–induced or NNK-induced lung cancer, whereas runt-related transcription factor-3 showed the opposite relationship. Thus, genes can be targeted for inactivation by methylation, depending on exposure history. This study indicates that methylation events frequently observed in human lung cancer are recapitulated in the mouse model and identifies four potential biomarkers for assessing intervention approaches for reversing epigenetically mediated gene silencing. (Mol Cancer Res 2006;4(4):267–73)
Inflammation, a Key Event in Cancer Development
Authors: Lu Haitian , Ouyang Weiming , Huang Chuanshu
Published: March 2006

Several recent studies have identified nuclear factor-κB as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation. (Mol Cancer Res 2006;4(4):221–33)
Nuclear Factor-ĸB- and Glucocorticoid Receptor α- Mediated Mechanisms in the Regulation of Systemic and Pulmonary Inflammation during Sepsis and Acute Respiratory Distress Syndrome
Authors: Meduri G. Umberto , Muthiah Muthiah P. , Carratù Pierluigi , Eltorky Mahmoud , Chrousos George P.
Published: March 2006

To test the hypothesis that the interaction between nuclear factor-ĸB (NF-ĸB) and glucocorticoid receptor α (GRα) is a key pathogenetic mechanism regulating the progression of systemic and pulmonary inflammation in sepsis and acute respiratory distress syndrome (ARDS), we used an ex vivo model of systemic inflammation. Naïve peripheral blood leukocytes (PBL) were exposed to longitudinal (days 1–10) plasma samples from ARDS patients divided into three groups based on physiological improvement and clinical outcome by days 7–10: improvers, nonimprovers-survivors, and nonimprovers-nonsurvivors. In a separate group of nonimprovers-survivors, we correlated the severity of lung histopathology with the intensity of NF-ĸB and GRα nuclear staining in immunohistochemistry analysis of lung tissue obtained by open lung biopsy. We found that exposure of naïve cells to longitudinal plasma samples led to divergent directions in NF-ĸB and GRα activation that reflected the severity of systemic inflammation. Plasma samples from improvers with declining cytokine levels over time elicited a progressive increase in all measured aspects of glucocorticoid (GC)-induced GRα-mediated activity (p = 0.0001) and a correspondent reduction in NF-ĸB nuclear binding (p = 0.0001) and transcription of TNF-α and IL-1β (regulated, GRα-driven response). In contrast, plasma samples from nonimprovers with sustained elevation in cytokine levels over time elicited only a modest longitudinal increase in GC-GRα-mediated activity (p = 0.04) and a progressive increase in NF-ĸB nuclear binding over time (p = 0.0001) that was most striking in nonsurvivors (dysregulated, NF-ĸB-driven response). By days 3–5, no overlap was observed between groups for NF-ĸB and GC-GRα nuclear binding. In immunohistochemistry analyses, lung tissues of patients with severe versus mild ARDS had a higher intensity of NF-ĸB nuclear staining (13 ± 1.3 vs. 7 ± 2.9; p = 0.01) and a lower ratio of GRα:NF-ĸB in nuclear staining (0.5 ± 0.2 vs. 1.5 ± 0.2; p = 0.007). In conclusion, we demonstrated that the ability of GC-GRα to downregulate NF-ĸB activation is critical for the resolution of systemic and pulmonary inflammation in ARDS. The findings provide a rationale for the use of prolonged GC treatment in early ARDS.
Stress-Induced versus Preovulatory and Pregnancy Hormonal Levels in Modulating Cytokine Production following Whole Blood Stimulation
Authors: Matalka Khalid Z. , Ali Dalia A.
Published: March 2006

Estradiol, progesterone, prolactin and cortisol concentrations are substantially increased during pregnancy. Also, cortisol and prolactin levels are elevated during stress. In the present study, we exposed peripheral blood to estradiol, progesterone, prolactin and cortisol alone or in combination for 24 h before stimulation with T-dependent (phytohemagglutinin, PHA) and independent activators (lipopolysaccharide, LPS) to study their immunomodulatory role in interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and IL-10 production in a whole blood model. This should be similar to in vivo exposure conditions such as long-term stress, preovulatory or pregnancy periods. The present study showed that the stress-induced and preovulatory levels of prolactin and estradiol, respectively, increased the production of IFN-γ and IL-12 levels (and IL-10 in the case of estradiol) in PHA + LPS-stimulated whole blood, and inhibited a hydrocortisone (100 nmol/l) suppressive effect on IFN-γ, IL-12 and IL-10 productions. In LPS-stimulated whole blood, however, prolactin enhanced only IL-10 production levels in a non-concentration-dependent manner. Higher prolactin levels as in pregnancy did not modulate any of the cytokines, but pregnancy estradiol concentrations only induced higher IL-10 levels in PHA + LPS-stimulated whole blood. All progesterone levels tested revealed no effect on any of the cytokines following whole blood stimulation. Our results indicate that (1) a long exposure time of prolactin and estradiol to whole blood modulates the production of cytokines in a concentration- and stimulus-dependent manner; (2) stress-induced levels of prolactin and preovulatory estradiol concentrations can regulate cortisol-induced cytokine suppression, and (3) even though the cytokine pattern is different, pregnancy estradiol and cortisol levels decreased the IFN-γ/IL-10 ratio, thereby keeping the anti-inflammatory IL-10 levels favored during pregnancy, which could be useful in regulating inflammatory-mediated autoimmune diseases.
Social Disruption Stress Exacerbates α-Galactosylceramide-Induced Hepatitis in Mice
Authors: Sonoda Junko , Chida Yoichi , Sudo Nobuyuki , Kubo Chiharu
Published: March 2006

Objective: Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag+ T cell-dependent α-galactosylceramide (α-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation, e.g. social disruption stress. Methods: Male wild-type C57BL/6 (B6) or B6 hepatitis virus type B surface antigen transgenic (HBs-tg) mice, a hepatitis B virus carrier mouse model, were exposed 3 times in 1 week to social disruption stress in which an 8-month-old aggressive male intruder was placed into their home cage (5 mice per group) for 2 h. Twelve hours after the final exposure to the stress, the wild-type and HBs-tg mice were intravenously injected with α-GalCer. Results: The stress-exposed wild-type mice exhibited significantly reduced thymus weight loss compared with the control animals. Moreover, this stress regimen led to a significant increase in serum alanine aminotransferase levels in both the wild-type and the HBs-tg mice, although the increase in the HBs-tg mice was higher than that in the wild-type mice. Conclusion: These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated α-GalCer-induced hepatitis.