bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue‐type plasminogen activator rescues neurones from serum deprivation‐induced apoptosis through a mechanism independent of its proteolytic activity
Authors: Liot Géraldine , Roussel Benoit D. , Lebeurrier Nathalie , Benchenane Karim , López‐Atalaya José P. , Vivien Denis , Ali Carine
Published: June 2006

Although the mechanism of action of tissue‐type plasminogen activator (tPA) in excitotoxic necrosis is well documented, whether this serine protease can influence the apoptotic cascade remains a subject of debate. Here, we report that tPA protects cultured cortical neurones against apoptotic cell death induced by serum deprivation, an effect associated with a reduction of caspase‐3 activation. Interestingly, blocking tPA proteolytic activity by either tPA stop or neuroserpin did not prevent this neuroprotection. Similarly, prevention of the interaction between tPA and its receptor low‐density lipoprotein receptor‐related protein (LRP) could not alter tPA anti‐apoptotic activity. Interestingly, the survival‐promoting effect of tPA was blocked by the phosphatidylinositol‐3 (PI‐3) kinase inhibitor, LY294002, but not by the mitogen‐activated protein (MAP) kinase inhibitor, U0126. In conclusion, the present demonstration of an anti‐apoptotic effect of tPA, independent of its enzymatic activity, reveals an additional level of complexity in our understanding of this critical mediator of brain physiology and pathology.
Activation of D1 dopamine receptors increases surface expression of AMPA receptors and facilitates their synaptic incorporation in cultured hippocampal neurons
Authors: Gao Can , Sun Xiu , Wolf Marina E.
Published: June 2006

Considerable evidence indicates that neuroadaptations leading to addiction involve the same cellular processes that enable learning and memory, such as long‐term potentiation (LTP), and that psychostimulants influence LTP through dopamine (DA)‐dependent mechanisms. In hippocampal CA1 pyramidal neurons, LTP involves insertion of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors into excitatory synapses. We used dissociated cultures to test the hypothesis that D1 family DA receptors influence synaptic plasticity in hippocampal neurons by modulating AMPA receptor trafficking. Brief exposure (5 min) to a D1 agonist increased surface expression of glutamate receptor (GluR)1‐containing AMPA receptors by increasing their rate of externalization at extrasynaptic sites. This required the secretory pathway but not protein synthesis, and was mediated mainly by protein kinase A (PKA) with a smaller contribution from Ca2+–calmodulin‐dependent protein kinase II (CaMKII). Prior D1 receptor stimulation facilitated synaptic insertion of GluR1 in response to subsequent stimulation of synaptic NMDA receptors with glycine. Our results support a model for synaptic GluR1 incorporation in which PKA is required for initial insertion into the extrasynaptic membrane whereas CaMKII mediates translocation into the synapse. By increasing the size of the extrasynaptic GluR1 pool, D1 receptors may promote LTP. Psychostimulants may usurp this mechanism, leading to inappropriate plasticity that contributes to addiction‐related behaviors.
Results of combination treatment with pegylated interferon and ribavirin in cirrhotic patients with hepatitis C infection
Authors: Höroldt Barbara , Haydon Geoffrey , O'Donnell Katrina , Dudley Tracey , Nightingale Peter , Mutimer David
Published: June 2006

Abstract: Background: The treatment of hepatitis C patients with advanced cirrhotic liver disease remains challenging and data on the outcome of treatment for this patient group is limited.

Results: Between September 2000 and August 2004, 61 cirrhotic patients started treatment with pegylated interferon and ribavirin (42 male, age range 29–69 years, 26 Asian). Forty‐three (70%) patients were serum hepatitis C virus (HCV) RNA negative at the end of treatment and 24 (39%) achieved a sustained virological response (SVR). SVR was achieved for 35% (6/17) of patients with genotype 1, and for 39% (16/41) with genotype 3. Caucasians with genotype 3 demonstrated a higher cure rate (SVR 10/18=56%) than Asians (SVR 6/24=25%). Failure to achieve SVR was associated with lower platelet count, neutrophil count and albumin at baseline. Twenty patients suffered clinical or laboratory decompensation, five patients required hospitalization, and two patients died. Patients who experienced hepatic decompensation were older and had baseline characteristics associated with more advanced liver disease.

Conclusion: The treatment of patients with advanced HCV is challenging, although many treated patients achieve SVR. Significant toxicity is experienced and there is treatment‐related mortality. This balance of efficacy and toxicity needs to be considered before commencing treatment.
Radio‐frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and ‘TUNEL’ study
Authors: Netto G. J. , Altrabulsi B. , Katabi N. , Martin P. , Burt K. , Levy M. , Sanchez E. , Watkins D. L. , Jennings L. , Klintmalm G. , Goldstein R.
Published: June 2006

Abstract: Background: Radio‐frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers.

Design: We evaluated 36 tumors from 35 patients with RFA‐treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt‐mediated UTP nick‐end labeling (TUNEL) was further performed to assess apoptosis in the morphologically ‘viable’ areas. A final ‘tumor cell death’ (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL.

Results: Based on H&E evaluation, 22/36 (61.1%) HCC revealed ≥90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed ≥90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA‐to‐transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with ≥90% TCD; P=0.019). There was no significant correlation between tumor grade or pre‐RFA size of the tumors and TCD rate in RFA‐treated HCC (P=0.11).

Conclusion: Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA‐induced cell injury could be associated with apoptosis.
Detection of new amino acid markers of liver trauma by proton nuclear magnetic resonance spectroscopy
Authors: Ranjan Priyadarshi , Gupta Ashish , Kumar Sandeep , Nagan Gowda Gowda Ajjapa , Ranjan Aseem , Sonker Abhinav Arun , Chandra Abhijit , Kant Rama
Published: June 2006

Abstract: Objective: We examined serum in patients of liver injury to explore the possible clinical application of abnormal micrometabolites as a marker of liver injury and severity in cases of traumatic liver damage.

Methods: Serum were screened by proton nuclear magnetic resonance spectroscopy in 96 patients with varying degree of liver injury and compared with concentrations in healthy control volunteers.

Results: Large quantities of phenylalanine and tyrosine were detected by spectroscopic analysis in patients with liver injury but not in those without liver injury (P<0.001). Proton nuclear magnetic resonance spectroscopy revealed two unique amino acids, phenylalanine and tyrosine, in the sera of the subjects with liver injury, irrespective of the extent and type of injury gauged by radiology or laparotomy. Phenylalanine spectrum was obtained in all 84 patients with liver injury (100% sensitivity) whereas tyrosine spectrum was present in 83 out of 84 patients (98.8% sensitivity) suggesting that these amino acids were specifically released in the patients of liver injury. Significant correlations were observed between phenylalanine and tyrosine concentrations and total bilirubin levels and albumin levels. Serum phenylalanine and tyrosine concentrations correlated well with imaging and laparotomy findings of liver injury.

Conclusion: Phenylanaline and tyrosine appear to be specific and new markers of liver injury.
Ring‐shaped appearance in liver‐specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers
Authors: Maruyama Hitoshi , Matsutani Shoichi , Kondo Fukuo , Yoshizumi Hiroaki , Kobayashi Satoshi , Okugawa Hidehiro , Ebara Masaaki , Saisho Hiromitsu
Published: June 2006

Abstract: Background/Aims: The aim was to clarify the features of contrast‐enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers.

Patients and methods: Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide‐band Doppler, 7/7), contrast‐enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient.

Results: Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver‐specific sonograms with a ring‐shaped appearance – peripheral enhancement with a central non‐enhanced area. Two of the three nodules showed decreased signal‐intensity in the periphery on SPIO‐enhanced MRI.

Conclusions: The ring‐shaped appearance on liver‐specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.
Nematode infection of the liver mimicking metastasis of malignant melanoma
Authors: Maier M. , Tappe D. , Töpfer C. , Rosenwald A. , Gassel H.‐J. , Timm S.
Published: June 2006

Abstract: Background: The differential diagnoses of a circumscribed mass of the liver are varied. Especially if a malignant tumor, capable of setting metastases to the liver, is known in a patient's medical history, there might be difficulties in differentiating the tumor's entity.

Casuistry: We report a case of a 40‐year‐old male with a history of malignant melanoma in whom follow‐up investigations revealed a mass in the liver.

Results: The histopathological and microbiological results, however, showed an infestation of liver tissue with nematodes. Malignant tumor cells could not be detected.

Conclusions: Roundworm‐infections of the liver can present as lesions suspicious of being malignant. Therefore, along with e.g. microhamartoma, microabscesses and hepatocellular carcinoma, infestation with nematodes should be taken into consideration.
A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade
Authors: Di Stefano Giuseppina , Fiume Luigi , Baglioni Michele , Bolondi Luigi , Busi Corrado , Chieco Pasquale , Kratz Felix , Manaresi Francesca , Pariali Milena
Published: June 2006

Abstract: Background/Aims: Doxorubicin (DOXO) was coupled to lactosaminated human serum albumin (L‐HSA) in order to enhance the drug concentration in the well differentiated hepatocellular carcinomas (HCCs), which can accumulate L‐HSA through the asialoglycoprotein receptor. In the present experiments we compared the DOXO concentrations produced by this conjugate (L‐HSA–DOXO) and by the uncoupled drug in the well, moderately, and poorly differentiated rat HCCs.

Methods: The same dose (1 μg/g) of free or L‐HSA coupled‐DOXO was injected in rats with HCCs induced by diethylnitrosamine. At different times, the animals were killed and the neoplastic nodules of liver were isolated. Their differentiation grade was determined histologically and their DOXO content was measured.

Results: Unexpectedly, we found that also in the poorly differentiated forms of HCCs, which display no or only a poor capacity of accumulating L‐HSA, the conjugate raised DOXO levels that were approximately twofold higher than those produced by the free drug.

Conclusions: The conjugate L‐HSA–DOXO could improve the potential of DOXO in the treatment of all HCCs, including the poorly differentiated tumors that are the common forms in the advanced disease for which an effective chemotherapy is particularly needed.
High prevalence of infection with a single hepatitis C virus genotype in a small rural community of Argentina
Authors: Picchio Gastón R. , Baré Patricia C. , Descalzi Valeria I. , Bussy María V. , Soria Sonia M. , Raffa María P. , Mazzencio Nancy E. , Etchehun Silvina , Cámera Juan A. , Mosier Donald E. , Villamil Federico G.
Published: June 2006

Abstract: Background: During the years preceding this study, we noticed a relatively unusual high number of individuals with elevated alanine aminotransferase (ALT) levels in O'Brien, a small rural town in Argentina. Moreover, four individuals from this town underwent liver transplantation owing to hepatitis C virus (HCV)‐induced liver cirrhosis. These findings prompted us to conduct a large population‐based survey to evaluate the prevalence of HCV in this community.

Methods and Results: A total of 1637 individuals were studied. The overall HCV‐seroprevalence was 5.7% (93/1637), being slightly higher in men (45/769; 5.9%) than in women (48/868; 5.5%). HCV seroprevalence increased with age, reaching a peak rate of 23.9% among individuals between 61 and 70 years of age. HCV RNA was present in 82.7% of all HCV seropositive individuals identified and 100% of them were infected with genotype 1b. ALT elevations were detected in 44% of HCV+ patients and were only observed among viremic individuals. Hepatitis B virus infection was also prevalent (52%) among HCV‐seropositive patients. The most common risk factor associated with HCV transmission identified was the apparent use of inadequately sterilized glass syringes by a health care provider serving the community; however, other risk factors may have also played a role in the dissemination of HCV.

Conclusions: Our findings provide an explanation for the relative high number of individuals with elevated ALT levels observed in this community and form the basis of future prospective studies on the natural history of genotype 1b infection.
Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats
Authors: Behrends Matthias , Hirose Ryutaro , Serkova Natalie J. , Coatney John L. , Bedolli Melanie , Yardi Jason , Park Yeon Ho , Niemann Claus U.
Published: June 2006

Abstract: Background/Aims: Hypothermia is known to protect against ischemia/reperfusion (I/R) injury. The mechanisms of protection are incompletely understood and a temperature threshold for protection has not been established.

Methods: In anesthetized Wistar rats, partial (70%) hepatic ischemia was applied for 45 min. Three study groups were used. Group T31 (n=6) spontaneously cooled to 31.3±0.8°C, while group T34 (n=6) spontaneously cooled to 34°C and was then maintained at 34.0±0.1°C using a heat lamp. The normothermic group (T37, n=6) was maintained at 37.1±0.3°C. Hepatic injury, inflammation, lipid peroxidation and metabolic function (using quantitative 1H‐NMR) were assessed 24 h after reperfusion.

Results: At 24 h following reperfusion, alanine aminotransferase and aspartate aminotransferase increased to 5101±2378 and 6409±4202 U/l in the normothermic T37 group (P<0.05 vs. T34 and T31), whereas transaminases in hypothermic groups (T31 and T34) were significantly lower. Severe liver necrosis was only noted with T37. Myeloperoxidase activity was increased in the T37 group when compared with hypothermic groups (223±161 (T37) vs. 16±10 (T31) and 8±5 (T34) mU/min/mg of tissue, P<0.05 vs. T31 and T34). 1H‐NMR analysis of the blood of normothermic animals revealed metabolic changes consistent with increased ischemic injury, which was almost completely ameliorated in T34 and T31 groups.

Conclusions: Mild hypothermia of 34°C is sufficient to reduce I/R injury by inhibiting the inflammatory response. Further spontaneous cooling to 31°C did not demonstrate any additional protective effect.
In vitro pH effects on in vivo recovery and survival of platelets: an analysis by the BEST Collaborative
Authors: Dumont Larry J. , AuBuchon James P. , Gulliksson Hans , Slichter Sherrill J. , Elfath M. Dean , Holme Stein , Murphy James R. , Rose Leslie E. , Popovsky Mark A. , Murphy Scott
Published: June 2006

BACKGROUND: The pH environment of stored platelet (PLT) products is recognized as an important factor and is generally used as a key surrogate measure of PLT viability. It is the only in vitro measurement that has been translated into industry standards and regulatory rules or specifications for storage of PLT products. The objective of this study was to evaluate the effect of in vitro pH on the in vivo recovery and survival of autologous PLT products.

STUDY DESIGN AND METHODS: Data from individual autologous radiolabeled PLT kinetic studies were solicited from independent laboratories. PLTs stored for at least 5 days in 100 percent autologous plasma with a pH22°C of at least 6.2 were analyzed. Data were fit to a mixed‐effects regression model with fixed effects of pH22°C, time of storage, and preparation method‐storage bag combination.

RESULTS: Eight research laboratories reported 476 individual recovery and survival results with associated pH before labeling from a variety of autologous, radiolabeled PLT kinetic studies from September 1999 to March 2005. These results are from 254 individual subjects who donated a total of 386 PLT units, with up to nine collections per subject reported. The effect of pH on either PLT recovery (p = 0.86) or survival (p = 0.55) was not significant. Time of storage and the method‐bag combination both had significant effects on these outcomes (p < 0.0001).

CONCLUSION: These data suggest that there is no relationship between in vitro pH at a pH22°C of at least 6.2 and in vivo PLT viability as measured by radiolabeled recovery and survival of autologous PLTs.
In vivo efficacy of shipped HLA‐matched platelets
Authors: Haddad Salim A. , Lichtiger Benjamin , Klein Harvey G.
Published: June 2006

BACKGROUND: Platelet (PLT) concentrates are currently stored in an incubator at 20 to 24°C with continuous gentle agitation. PLTs are routinely shipped for transfusion to thrombocytopenic patients, however. There is a concern that PLT concentrates may be adversely affected during the shipping process.

CASE REPORT: A 40‐year‐old woman with severe aplastic anemia and immune refractory to unselected PLT transfusions was transferred to a distant medical center for a hematopoietic peripheral blood progenitor cell transplant where she continued to receive HLA‐matched PLTs from her dedicated donors. Sixteen such components were collected and air‐shipped in insulated boxes to the transplant center. Thirty‐seven plateletpheresis components from the same dedicated donors had been transfused to the patient before transfer. Corrected count increments (CCIs) at the two sites were compared, with assessment of the role of HLA‐match grades. The mean interruption time of controlled agitation during shipment was approximately 10.5 hours. The mean CCI of all distant transfusions was 14,450 ± 9700 PLTs per µL·m2 per 1011 and that of local transfusions was 10730 ± 4870. The mean donor‐paired difference between CCIs at the two sites was 1140 ± 9940. At the remote location no clinically significant bleeding occurred and one posttransfusion febrile reaction was noted.

CONCLUSION: Despite the study limitations, the effectiveness, in a single patient, of leukoreduced, irradiated apheresis PLTs shipped by lengthy combined surface and airline transport is reported, as measured by posttransfusion CCIs.
TheRHCEalleleceCF: the molecular basis of Crawford (RH43)
Authors: Flegel Willy A. , Wagner Franz F. , Chen Qing , Schlanser Gloria , Frame Tom , Westhoff Connie M. , Moulds Marilyn K.
Published: June 2006

BACKGROUND:The Crawford antigen (RH43) was described in 1980. It occurred in African American people, as a low‐prevalence Rhesus antigen, who were also VS+.

STUDY DESIGN AND METHODS:Twelve blood samples were analyzed because of inquiries into discrepant reactions in routine anti‐D typing. TheRHCEalleles were determined by nucleotide sequencing from genomic DNA. The D epitope profile was determined with 60 monoclonal anti‐D. The population frequency was estimated in four major US regional blood centers.

RESULTS:The novelRHce(W16C, Q233E, L245V) allele, dubbedceCF, was found to be occurring in thecdehaplotype as cause of the reactivity with the immunoglobulin M anti‐D GAMA401. The ceCF phenotype expressed few D epitopes resembling but not matching the reaction patterns observed with other RhCE variants, like R0Har, ceRT, and ceSL. The frequency of the ceCF phenotype was 0.056 percent among African American persons and 0.007 percent in the general US population.

CONCLUSION:The novelRHce(W16C, Q233E, L245V) allele, which is a variant of the knowncesallele,RHce(W16C, L245V), occurs in a haplotype with theRHDdeletion and represents the molecular basis of the Crawford antigen.
A comparison of three rapid bacterial detection methods under simulated real‐life conditions
Authors: Schmidt Michael , Hourfar Michael K. , Nicol Sven‐Boris , Wahl Alexandra , Heck Julia , Weis Christina , Tonn Torsten , Spengler Hans‐Peter , Montag Thomas , Seifried Erhard , Roth W. Kurt
Published: June 2006

BACKGROUND: Bacterial screening of all produced platelet concentrates (PCs) is implemented in many countries to reduce the risk of transfusion‐transmitted sepsis. This study compares three rapid bacterial detection methods by imitating real‐life conditions.

STUDY DESIGN AND METHODS: The sensitivity of a solid‐phase scanning cytometer (optimized Scansystem, Hemosystem), fluorescence‐activated cell sorting (FACS) analysis, and 16S RNA in‐house nucleic acid testing (NAT) was evaluated by spiking PCs with four transfusion relevant bacteria (Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, and Escherichia coli ). Two different inocula (10 colony‐forming units [CFUs]/mL and 10 CFUs/bag) were used to simulate real‐life conditions. Samples were taken at 12, 16, 20, and 24 hours after spiking.

RESULTS: With the high inoculum, NAT had a 100 percent rate of positive testing for all four types of bacteria (10/10 replicates) at each time point. With the exception of E. coli, the sensitivity of FACS and optimized Scansystem was comparable for the high inoculum. With the low inoculum, 60 percent of E. coli, 80 percent of B. cereus, 90 percent of K. pneumoniae, and 100 percent of S. aureus were NAT‐positive 12 hours after spiking. In contrast, only 20 percent of E. coli, 10 percent of B. cereus, and 70 percent of K. pneumoniae were FACS‐positive with the low inoculum 12 hours after spiking.

CONCLUSIONS: In summary, the preliminary data revealed a higher sensitivity for NAT in comparison to FACS and optimized Scansystem under the defined study conditions. To imitate real‐life conditions, further spiking studies with a low inoculum (10 CFUs/bag) and slower growing organisms should be conducted to examine the sensitivity of available detection systems.
Efficacy of single‐dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma
Authors: Kroschinsky Frank , Hölig Kristina , Platzbecker Uwe , Poppe‐Thiede Kirsten , Ordemann Rainer , Blechschmidt Matthias , Oelschlaegel Uta , Schaich Markus , Hänel Mathias , Bornhäuser Martin , Ehninger Gerhard
Published: June 2006

BACKGROUND: A single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, whereas the experiences with pegfilgrastim in mobilization of peripheral blood progenitor cells (PBPCs) are limited.

STUDY DESIGN AND METHODS: Forty unselected patients with lymphoma or multiple myeloma were treated with different chemotherapy regimens followed by 6 mg of pegfilgrastim for mobilization of autologous PBPCs. Patients with an inadequate mobilization (blood CD34+ cells ≤ 10/µL after nadir) were given additional daily doses of 10 µg per kg unconjugated filgrastim.

RESULTS: A median blood CD34+ peak concentration of 81 per µL (range, 10‐565/µL) was found in 30 patients, who had only received pegfilgrastim, compared to 13 per µL (median, range 4‐71/µL; p < 0.001) in 10 poor mobilizing patients with additional filgrastim. The median yield of CD34+ cells was 9.8 × 106 per kg (range, 1.5‐88.1) after pegfilgrastim only versus 2.5 × 106 (range, 1.7‐7.0) in poor mobilizers. Patients who needed additional cytokine administration were those with a more extensive previous antineoplastic treatment and mobilizing regimens containing PBPC toxic agents.

CONCLUSION: The results confirm the efficacy and feasibility of PBPC mobilization with chemotherapy and single‐dose pegfilgrastim in patients with lymphoproliferative malignacies. In less heavily pretreated patients, 6 mg of pegfilgrastim after chemotherapy induced an adequate mobilization, whereas dose and schedule in patients after numerous cytotoxic regimens need further investigation.
Heritability of Indices for Cardiac Contractility in Ambulatory Recordings
Authors: KUPPER NINA , WILLEMSEN GONNEKE , BOOMSMA DORRET I. , DE GEUS ECO J.C.
Published: June 2006

Introduction: Overactivity of the sympathetic nervous system (SNS) plays a pivotal role in the development of cardiovascular disease. This involvement suggests that the genetic susceptibility to adverse cardiovascular events may derive in part from individual differences in SNS activity.

Methods and Results: To establish a genetic contribution to SNS activity, we measured sympathetic effects on cardiac contractility in 755 healthy adult twins and their singleton siblings. The preejection period (PEP) and the ratio of PEP to the left ventricular ejection time (PEP/LVET ratio) were derived from ambulatory recordings of the ECG and thorax impedance. During this type of prolonged recordings in a real life setting, the extent of cardiac sympathetic activity will vary with the demands of daily activities. Therefore, the genetic architecture of both indices was examined separately across three daytime periods (morning, afternoon, evening), and during nighttime sleep. Results showed significant genetic contribution to PEP (48–62%) over all daily periods. Heritability estimates for PEP/LVET ratio ranged between 35% and 58%. Cardiac sympathetic activity during the waking and sleep periods was largely influenced by genetic factors that were common to the entire 24‐hour period. During sleep, additional genetic influences emerged that accounted for 8% of the variance in PEP.

Conclusion: Impedance‐derived measures of sympathetic effects on cardiac contractility show substantial heritability across all periods of the day and during sleep.
Implantation of Bilateral Carotid Artery Filters to Allow Safe Removal of Left Atrial Thrombus During Ablation of Atrial Fibrillation
Authors: MARTELO SILVIA , D'AVILA ANDRÉ , FERREIRA FERNANDA , SAAD EDUARDO B.
Published: June 2006

Left atrial clot formation is a feared complication of catheter ablation for atrial fibrillation. We report a case of left atrial thrombus that formed around the circular mapping catheter before the delivery of RF. Successful retrieval of the clot was obtained by withdrawing the catheters while protecting the anterior cerebral circulation by positioning temporary carotid artery filters.
Confectionery and Conflict Resolution? What Chocolat Reveals about Mediation
Authors: Schulz Jennifer L.
Published: June 2006

A close analysis of the film Chocolat discloses a new metaphor for the mediator — the mediator as cook. The use of this metaphor throughout the film suggests new insights about mediator style and practice. Specifically, the mediator–protagonist in Chocolat demonstrates that: (1) mediations need not be voluntary to be sound, (2) non‐neutral, directive, evaluative mediators can be effective if they individualize their approaches to each disputant and dispute, and (3) effective approaches to mediation celebrate emotion and pleasure, contrary to many conflict resolution theorists who write about the importance of emotions, but do not privilege them in practice.
Electronic Negotiation: A Teaching Tool for Encouraging Student Self‐Reflection
Authors: Holtom Brooks C. , Kenworthy‐U'Ren Amy L.
Published: June 2006

As the amount of negotiation taking place electronically increases, the responsibility of negotiation instructors to prepare students to successfully operate in electronic environments grows. We believe that skills related to electronic negotiation — like many other negotiation skills — are best taught by providing students opportunities to gain firsthand experience followed by self‐reflection. For the past five years, we have used an electronic negotiation exercise to allow students to personally experience the complexities associated with negotiations completed exclusively over the Internet. Further, with the use of e‐mail and instant messaging, a powerful record emerges: a complete transcript of the negotiation encounter. After describing the preparation and structure of this exercise, we explain how to harness the power of this vehicle to lead students to significant insights through self‐reflective activities.
Functional Dissection of SseF, a Type III Effector Protein Involved in Positioning the Salmonella‐Containing Vacuole
Authors: Abrahams Garth L. , Müller Petra , Hensel Michael
Published: June 2006

Intracellular replication of Salmonella enterica requires the formation of a unique organelle termed Salmonella‐containing vacuole (SCV). The type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2–T3SS) has a crucial role in the formation and maintenance of the SCV. The SPI2–T3SS translocates a large number of effector proteins that interfere with host cell functions such as microtubule‐dependent transport. We investigated the function of the effector SseF and observed that this protein is required to maintain the SCV in a juxtanuclear position in infected epithelial cells. The formation of juxtanuclear clusters of replicating Salmonella required the recruitment of dynein to the SCV but SseF‐deficient strains were highly reduced in dynein recruitment to the SCV. We performed a functional dissection of SseF and defined domains that were important for translocation and the specific effector functions of this protein. Of particular importance was a hydrophobic domain in the C‐terminal half that contains three putative transmembrane (TM) helices. Deletion of one of these TM helices ablated the effector functions of SseF. We observed that this domain was essential for the proper intracellular positioning of the SCV to a juxtanuclear, Golgi‐associated localization. These data show that SseF, in concert with the effector proteins SifA and SseG mediate the precise positioning of the SCV by differentially modulating the recruitment of microtubule motor proteins to the SCV.
VARIATION IN GLYCOLYTIC POTENTIAL AND FRESH PORK QUALITY TRAITS ALONG THE LONGISSIMUS DORSI OF SLAUGHTER WEIGHT PIGS*
Authors: BERTOL T.M. , ELLIS M. , RITTER M.J. , MCKEITH F.K. , HAMILTON D.N.
Published: June 2006

The objective of this study was to determine the effects of loin muscle location on glycolytic potential (GP) and fresh pork quality traits. Seven sections (5‐cm thick) from approximately between the eighth rib and fourth lumbar vertebra were evaluated. Numerous quality measurements were taken within each section. Ultimate pH was similar (P > 0.05) at all locations. Drip loss decreased (P < 0.01), while subjective firmness and color scores improved (P < 0.01) toward the posterior end of the loin. Minolta L* values (Minolta, Osaka, Japan) were highest (P < 0.01) in the anterior sections. Intramuscular fat was lower, but shear force and GP were higher in the middle sections than at the extremities (P < 0.01). In conclusion, GP and pork quality traits vary throughout the longissimus dorsi. However, differences in GP among sections were of low magnitude, and ultimate pH was unaffected by loin location. For studies that require multiple measurements of GP, samples should be taken in the region of the longissimus that yielded similar values, i.e., between the 10th rib and the third lumbar vertebra.
EFFECT OF REFRIGERATED STORAGE ON PROTEOLYTIC ACTIVITY AND PHYSICOCHEMICAL AND MICROSTRUCTURAL PROPERTIES OF GIANT SQUID (DOSIDICUS GIGAS) MANTLE MUSCLE
Authors: DUBLÁN‐GARCÍA OCTAVIO , CRUZ‐CAMARILLO RAMÓN , GUERRERO‐LEGARRETA ISABEL , PONCE‐ALQUICIRA EDITH
Published: June 2006

Giant squid (Dosidicus gigas) is abundant along the Pacific Coast of Mexico. It possesses a high proteolytic activity that makes it a low‐quality food material. Squid mantle endogenous proteases were partially characterized; physicochemical and structural changes during storage at 4C were also examined. High proteolytic activity was observed at acidic and alkaline pH values. Proteases were strongly inhibited by leupeptine and pepstatin A, as well as by phenyl methyl sulfonyl fluoride, indicating the possible presence of serine, cysteine and metal proteases. Myosin heavy chain was degraded during storage, as shown on sodium dodecyl sulfate–polyacrylamide gel electrophoresis patterns, resulting in a significant decrease (P < 0.001) in muscle water‐holding capacity, texture and gelling capacity. Muscle deterioration was evident in scanning electron micrographs, where the initial compact structure loosened during storage.
EFFECTS OF MUSCLE MASS AND FIBER TYPE COMPOSITION OF LONGISSIMUS DORSI MUSCLE ON POSTMORTEM METABOLIC RATE AND MEAT QUALITY IN PIGS
Authors: RYU Y.‐C. , LEE M.‐H. , LEE S.‐K. , KIM B.‐C.
Published: June 2006

The carcass traits, the muscle fiber characteristics and the meat quality traits were evaluated using 200 crossbred pigs. The muscle mass was divided into heavy or light groups according to the carcass weight and the loin‐eye area measurements. In addition, the proportion of the fast‐twitch glycolytic muscle fiber was divided into high or normal groups according to the area percentage of type IIb fiber. Heavier pigs contained larger loin‐eye area and muscle fibers, and also had more total muscle fibers than the lighter ones. The high group showed lower muscle pH, protein solubility, and also showed higher R‐value, drip loss and lightness than the normal group. These results suggest that an increase in total fiber number combined with a higher percentage of oxidative muscle fibers has a beneficial effect on increasing the muscle mass without deteriorating the meat quality.
Heat Transfer From a Translating Droplet at High Peclet Numbers: Revisiting the Classic Solution of Kronig & Brink
Authors: Oliver Douglas L. , Souccar Adham W.
Published: June 2006

More than five decades ago Kronig and Brink published a classic analysis of transport from translating droplets. Their analysis assumed that the bulk of the resistance to transfer was in the droplet phase. It considered the limiting solution as the Peclet number became very large. Their work has been cited in many subsequent studies of droplet transfer. The present work revisits their solution using numerical techniques that were not then available. It was found that only the first mode of their solution is mathematically accurate. Hence, their solution is accurate only at large times.
Thermal Transport Due to Phonons in Random Nano-particulate Media in the Multiple and Dependent (Correlated) Elastic Scattering Regime
Authors: Prasher Ravi
Published: June 2006

Effects of multiple and dependent or correlated elastic scattering of phonons due to nanoparticles on thermal transport in random nano-particulate media (random phononic crystals) are investigated in this paper under various approximations. Multiple scattering means that the scattered wave from one particle is incident on another particle to be scattered again. Dependent scattering means far-field interference of the scattered waves due to phase difference, which is ignored in the independent scattering regime. Multiple and dependent scattering effects become important when the interparticle distance is comparable to the wavelength of phonons. Results show that multiple scattering primarily affects the velocity and density of states of phonons and dependent scattering primarily affects the mean free path of phonons. Effects of both multiple and dependent scattering increases with increasing volume fraction of nanoparticles. Modification of these parameters affects the equilibrium phonon intensity and the thermal conductivity of phonons.
Modeling and Experimental Verification of Transient/Residual Stresses and Microstructure Formation in Multi-Layer Laser Aided DMD Process
Authors: Ghosh S. , Choi J.
Published: June 2006

Despite enormous progress in laser aided direct metal/material deposition (LADMD) process many issues concerning the adverse effects of process parameters on the stability of variety of properties and the integrity of microstructure have been reported. Comprehensive understanding of the transport phenomena and heat transfer analysis is essential to predict the thermally induced residual stresses and solidification microstructure in the deposited materials. Traditional solidification theories as they apply to castings or related processes, assume either no mass diffusion in the solid (Gulliver-Scheil) or complete diffusion in the solid (equilibrium lever rule) in a fixed arm space. These are inappropriate in high energy beam processes involving significantly high cooling rates. The focus of this paper is the solute transport in multi-pass LADMD process, especially the coupling of the process scale transport with the transport at the local scale of the solid-liquid interface. This requires modeling of solute redistribution at the scale of the secondary arm spacing in the dendritic mushy region. This paper is an attempt toward a methodology of finite element analysis for the prediction of solidification microstructure and macroscopic as well as microscopic thermal stresses. The computer simulation is based on the metallo-thermo-mechanical theory for uncoupled temperature, solidification, phase transformation, and stress/strain fields. The importance of considering phase transformation effects is also verified through the comparison of the magnitudes of residual stresses with and without the inclusion of phase transformation kinetics. The simulation has been carried out for H13 tool steel deposited on a mild steel substrate.
Heat Transfer Performance During Condensation Inside Horizontal Smooth, Micro-Fin and Herringbone Tubes
Authors: Lambrechts Adriaan , Liebenberg Leon , Bergles Arthur E. , Meyer Josua P.
Published: June 2006

An experimental investigation was conducted into the heat transfer characteristics during in-tube condensation of horizontal smooth, micro-fin, and herringbone tubes. The study focused on the heat transfer coefficients of refrigerants R-22, R-134a, and R-407C inside a series of typical horizontal smooth, micro-fin, and herringbone tubes at a representative average saturation temperature of 40°C. Mass fluxes ranged from 300 to 800kg∕m2s, and vapor qualities ranged from 0.85 to 0.95 at condenser inlet, to 0.05 to 0.15 at condenser outlet. The herringbone tube results were compared with the smooth and micro-fin tube results. The average increase in the heat transfer coefficient of the herringbone tube, when compared with the smooth tube at comparable conditions, was found to be 322%, with maximum values reaching 336%. When compared with the micro-fin tube, the average increase in heat transfer coefficient was found to be 196%, with maximum values reaching 215%. Moreover, a new correlation was developed to predict the heat transfer coefficients in a herringbone and micro-fin tube. Semi-local heat transfer coefficients were calculated from the modified Wilson plot technique, using measurements of condenser subsection inlets and outlets, and from knowledge of the temperature gradient on the annulus side. The correlation predicted the semi-local heat transfer coefficients accurately, with 96% and 89% of the data points falling in the ±20% region for the herringbone tube and the micro-fin tube, respectively. The average heat transfer coefficients were accurately predicted, too, with all the data points for the herringbone tube and 83% of the data points for the micro-fin tube falling in the ±20% region. The derived heat transfer correlations can be used for design, especially for reversible heat pumps. This research proves that predicting the flow pattern during intermittent and annular flow is not a prerequisite for predicting the heat transfer accurately to within 20% of the measurements.
Steady-Periodic Green’s Functions and Thermal-Measurement Applications in Rectangular Coordinates
Authors: Cole Kevin D.
Published: June 2006

Methods of thermal property measurements based on steady-periodic heating are indirect techniques, in which the thermal properties are deduced from a systematic comparison between experimental data and heat-transfer theory. In this paper heat-transfer theory is presented for a variety of two-dimensional geometries applicable to steady-periodic thermal-property techniques. The method of Green’s functions is used to systematically treat rectangles, slabs (two dimensional), and semi-infinite bodies. Several boundary conditions are treated, including convection and boundaries containing a thin, high-conductivity film. The family of solutions presented here provides an opportunity for verification of numerical results by the use of distinct, but similar, geometries. A second opportunity for verification arises from alternate forms of the Green’s function, from which alternate series expressions may be constructed for the same unique temperature solution. Numerical examples are given to demonstrate both verification techniques for the steady-periodic response to a heated strip.
Non-Equilibrium
Phonon Distributions in Sub-100nm Silicon
Transistors
Authors: Sinha S. , Pop E. , Dutton R.
W. , Goodson K.
E.
Published: June 2006

Intense electron-phonon scattering near the peak electric field in a semiconductor device results in nanometer-scale phonon hotspots. Past studies have argued that ballistic phonon transport near such hotspots serves to restrict heat conduction. We reexamine this assertion by developing a new phonon transport model. In a departure from previous studies, we treat isotropic dispersion in all phonon branches and include a phonon emission spectrum from independent Monte Carlo simulations of electron-phonon scattering. We cast the model in terms of a non-equilibrium phonon distribution function and compare predictions from this model with data for ballistic transport in silicon. The solution to the steady-state transport equations for bulk silicon transistors shows that energy stagnation at the hotspot results in an excess equivalent temperature rise of about 13% in a 90nm gate-length device. Longitudinal optical phonons with non-zero group velocities dominate transport. We find that the resistance associated with ballistic transport does not overwhelm that from the package unless the peak power density approaches 50W∕μm3. A transient calculation shows negligible phonon accumulation and retardation between successive logic states. This work highlights and reduces the knowledge gaps in the electro-thermal simulation of transistors.
Transport Phenomena and Keyhole Dynamics during Pulsed Laser Welding
Authors: Zhou Jun , Tsai Hai-Lung , Wang Pei-Chung
Published: June 2006

Numerical and experimental studies were conducted to investigate the heat transfer, fluid flow, and keyhole dynamics during a pulsed keyhole laser welding. A comprehensive mathematical model has been developed. In the model, the continuum formulation was used to handle solid phase, liquid phase, and mushy zone during melting and solidification processes. The volume-of-fluid method was employed to handle free surfaces. The enthalpy method was used for latent heat. Laser absorptions (Inverse Bremsstrahlung and Fresnel absorption) and thermal radiation by the plasma in the keyhole were all considered in the model. The results show that the recoil pressure is the main driving force for keyhole formation. Combining with the Marangoni shear force, hydrodynamic force, and hydrostatic force, it causes very complicated melt flow in the weld pool. Laser-induced plasma plays twofold roles in the process: (1) to facilitate the keyhole formation at the initial stage and (2) to block the laser energy and prevent the keyhole from deepening when the keyhole reaches a certain depth. The calculated temperature distributions, penetration depth, weld bead size, and geometry agreed well with the corresponding experimental data. The good agreement demonstrates that the model lays a solid foundation for the future study of porosity prevention in keyhole laser welding.
Natural Convection in a Cavity With a Wavy Wall Heated From Below and Uniformly Cooled From the Top and Both Sides
Authors: Dalal Amaresh , Das Manab Kumar
Published: June 2006

In this paper, natural convection inside a two-dimensional cavity with a wavy right vertical wall has been carried out. The bottom wall is heated by a spatially varying temperature and other three walls are kept at constant lower temperature. The integral forms of the governing equations are solved numerically using finite-volume method in the non-orthogonal body-fitted coordinate system. The semi-implicit method for pressure linked equation algorithm with higher-order upwinding scheme are used. The streamlines and isothermal lines are presented for three different undulations (1, 2 and 3) with different Rayleigh number and a fluid having Prandtl number 0.71. Results are presented in the form of local and average Nusselt number distribution for a selected range of Rayleigh number (100-106).
Critical Heat Flux of Steady Boiling for Water Jet Impingement in Flat Stagnation Zone on Superhydrophilic Surface
Authors: Liu Zhenhua , Qiu Yuhao
Published: June 2006

The nucleate boiling heat transfer characteristics of a round water jet impingement in a flat stagnation zone on the superhydrophilic surface were experimentally investigated. The superhydrophilic heat transfer surface was formed by a TiO2 coating process. The experimental results were compared with those on the common metal surface. In particular, the quantificational effects of the flow conditions, heating conditions, and the coating methods on the critical heat flux (CHF) were systemically investigated. The experimental data showed that the nucleate boiling heat transfer characteristics on the superhydrophilic surface are significantly different from those on the common metal surface. The CHF of boiling on the superhydrophilic surface is greatly increased by decreasing of the solid-liquid contact angle.
Isolated haploinsufficiency of exon 1 of theSHOXgene in a patient with idiopathic short stature
Authors: Tan Y-M , Loke K-Y
Published: June 2006

This paper reports the case of a 16-year-old woman with idiopathic short stature (ISS) who was detected to be haploinsufficient in only exon 1 of the short stature homeobox-containing (SHOX) gene by RQ-PCR and had two copies of the other six exons intact. The translation of the SHOX protein and of theSHOXpromoter may be potentially affected if the deletion of exon 1 is extended further upstream. Further studies may help in determining the significance of partial exonic deletions of theSHOXgene in relation to ISS.