bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivating pentapeptide insertions in the fission yeast replication factor C subunit Rfc2 cluster near the ATP‐binding site and arginine finger motif
Authors: Gray Fiona C. , Whitehead Kathryn A. , MacNeill Stuart A.
Published: July 2009

Replication factor C (RFC) plays a key role in eukaryotic chromosome replication by acting as a loading factor for the essential sliding clamp and polymerase processivity factor, proliferating cell nuclear antigen (PCNA). RFC is a pentamer comprising a large subunit, Rfc1, and four small subunits, Rfc2–Rfc5. Each RFC subunit is a member of the AAA+family of ATPase and ATPase‐like proteins, and the loading of PCNA onto double‐stranded DNA is an ATP‐dependent process. Here, we describe the properties of a collection of 38 mutant forms of the Rfc2 protein generated by pentapeptide‐scanning mutagenesis of the fission yeastrfc2gene. Each insertion was tested for its ability to support growth in fission yeastrfc2Δ cells lacking endogenous Rfc2 protein and the location of each insertion was mapped onto the 3D structure of budding yeast Rfc2. This analysis revealed that the majority of the inactivating mutations mapped in or adjacent to ATP sites C and D in Rfc2 (arginine finger and P‐loop, respectively) or to the five‐stranded β sheet at the heart of the Rfc2 protein. By contrast, nonlethal mutations map predominantly to loop regions or to the outer surface of the RFC complex, often in highly conserved regions of the protein. Possible explanations for the effects of the various insertions are discussed.
High negative charge‐to‐size ratio in polyphosphates and heparin regulates factor VII‐activating protease
Authors: Muhl Lars , Galuska Sebastian P. , Öörni Katariina , Hernández‐Ruiz Laura , Andrei‐Selmer Luminita‐Cornelia , Geyer Rudolf , Preissner Klaus T. , Ruiz Felix A. , Kovanen Petri T. , Kanse Sandip M.
Published: July 2009

Factor VII‐activating protease (FSAP) circulates as an inactive zymogen in the plasma. FSAP also regulates fibrinolysis by activating pro‐urokinase or cellular activation via cleavage of platelet‐derived growth factor BB (PDGF‐BB). As the Marburg I polymorphism of FSAP, with reduced enzymatic activity, is a risk factor for atherosclerosis and liver fibrosis, the regulation of FSAP activity is of major importance. FSAP is activated by an auto‐catalytic mechanism, which is amplified by heparin. To further investigate the structural requirements of polyanions for controlling FSAP activity, we performed binding, activation and inhibition studies using heparin and derivatives with altered size and charge, as well as other glycosaminoglycans. Heparin was effective in binding to and activating FSAP in a size‐ and charge density‐dependent manner. Polyphosphate was more potent than heparin with regard to its interactions with FSAP. Heparin was also an effective co‐factor for inhibition of FSAP by plasminogen activator inhibitor 1 (PAI‐1) and antithrombin, whereas polyphosphate served as co‐factor for the inhibition of FSAP by PAI‐1 only. For FSAP‐mediated inhibition of PDGF‐BB‐induced vascular smooth muscle cell proliferation, heparin as well as a polyphosphate served as efficient co‐factors. Native mast cell‐derived heparin exhibited identical properties to those of unfractionated heparin. Despite the strong effects of synthetic polyphosphate, the platelet‐derived material was a weak activator of FSAP. Hence, negatively charged polymers with a high charge‐to‐size ratio are responsible for the activation of FSAP, and also act as co‐factors for its inhibition by serine protease inhibitors.
YidC is required for the assembly of the MscL homopentameric pore
Authors: Pop Ovidiu I. , Soprova Zora , Koningstein Gregory , Scheffers Dirk‐Jan , van Ulsen Peter , Wickström David , de Gier Jan‐Willem , Luirink Joen
Published: July 2009

The mechanosensitive channel with large conductance (MscL) of Escherichia coli is formed by a homopentameric assembly of MscL proteins. Here, we describe MscL biogenesis as determined using in vivo approaches. Evidence is presented that MscL is targeted to the inner membrane via the signal recognition particle (SRP) pathway, and is inserted into the lipid bilayer independently of the Sec machinery. This is consistent with published data. Surprisingly, and in conflict with earlier data, YidC is not critical for membrane insertion of MscL. In the absence of YidC, assembly of the homopentameric MscL complex was strongly reduced, suggesting a late role for YidC in the biogenesis of MscL. The data are consistent with the view that YidC functions as a membrane‐based chaperone ‘module’ to facilitate assembly of a subset of protein complexes in the inner membrane of E. coli.
Mechanisms and kinetics of human arylamineN‐acetyltransferase 1 inhibition by disulfiram
Authors: Malka Florence , Dairou Julien , Ragunathan Nilusha , Dupret Jean‐Marie , Rodrigues‐Lima Fernando
Published: July 2009

Disulfiram has been used for decades to treat alcoholism. Its therapeutic effect is thought to be mediated by the irreversible inhibition of aldehyde dehydrogenase. Recent reports have indicated new therapeutic uses of disulfiram, in particular in human cancers. Although the biochemical mechanisms that underlie these effects remain largely unknown, certain enzymes involved in cancer processes have been reported to be targeted by disulfiram. ArylamineN‐acetyltransferase 1 (NAT1) is a xenobiotic‐metabolizing enzyme that biotransforms aromatic amine drugs and carcinogens. In addition to its role in xenobiotic metabolism, several studies have suggested that NAT1 is involved in other physiological and/or pathological processes, such as folate metabolism or cancer progression. In this report, we provide evidence that human NAT1 is a new enzymatic target of disulfiram. We found that disulfiram at clinically relevant concentrations impairs the activity of endogenous NAT1 in human cancer cells. Further mechanistic and kinetic studies indicated that disulfiram reacts irreversibly with the active site cysteine residue of NAT1, leading to its rapid inhibition (IC50 = 3.3 ± 0.1 μmandki = 6 × 104 m−1·min−1).
THE FIRST MAN AND THE COMPANY MAN: THE COMMON GOOD, TRANSCENDENCE, AND MEDIATING INSTITUTIONS
Authors: FORT TIMOTHY L.
Published: July 2009

An enormous oblivion spread over them, and actually that was what this land gave out, what fell from the sky with the night over the three men returning to the village, their hearts made anxious by the approach of night, filled with that dread that seizes all men in Africa when the sudden evening descends on the sea, on the rough mountains and the high plateaus, the same holy dread that has the same effect on the slopes of Delphi's mountain, where it makes temples and altars emerge. But on the land of Africa the temples have been destroyed, and all that is leR is this soft unbearable burden of the heart.
THE WRONG WAY TO MANDALAY: THE MASSACHUSETTS SELECTIVE PURCHASING ACT AND THE CONSTITUTION
Authors: DHOOGE LUCIENJ
Published: July 2009

The United States cannot and should not approach the world as fifty states and thousands of municipalities who embark on setting their own foreign policy whenever it suits them.1

It's a core principle of democracy that the federal government should not intrude on state powers to spend local tax dollars unless there's an overwhelming federal interest at stake.2
WINE WARS—DIRECT SHIPMENT OF WINE: THE TWENTY‐FIRST AMENDMENT, THE COMMERCE CLAUSE, AND CONSUMERS’RIGHTS
Authors: Martin Susan Lorde
Published: July 2009

The transportation or importation into any State, Territory, or possession of the United States for delivery or use therein of intoxicating liquors, in violation of the laws thereof, is hereby prohibited.1
A NATURAL LAW DEFENSE TO THE EMPLOYMENT LAW QUESTION: A RESPONSE TO RICHARD EPSTEIN
Authors: Macdonald James E. , Beck‐Dudley Catyn L.
Published: July 2009

Every individual is continually exerting himself to find out the most advantageous employment for whatever capital he can demand. It is his own advantage, indeed, and not that of the society which he has in view. But the study of his own advantage naturally, or rather necessarily, leads him to prefer that employment which is most advantageous tothe society.1

The modern laborer, … instead of rising with the progress of industry, sinks deeper and deeper below the conditions of existence of his own class. He becomes a pauper, and pauperism develops more rapidly than population and wealth.2

Eveyone has the right to work to free choice Of employment, to just and favorable conditions of work and to protection against unemployment. Eveyone, without any discrimination, has the right to equal pay for equal work. Everyone who works has the right to just and favorable remuneration ensuring for himself and his family an existence worthy of human dignity, and supplemented if necessary, other means of social protection. Everyone has the right to form and to join trade unions for the protection of his interests. Evereyone has the right to rest and leisure, including reasonable limitation of working hours and periodic holiday with pay.3
INTEGRATIVE SOCIAL CONTRACTS THEORY: ETHICAL IMPLICATIONS OF MARKETING CREDIT CARDS TO U.S. COLLEGE STUDENTS
Authors: Lucas Laurie A.
Published: July 2009

It may be said that to take advantage of a man's credulity, to exploit his misapprehensions, to capitalize on his ignorance is morally reprehensible—and this may well be the case I do not know.—Nicholas Samstag in The Engineering of Consent1
Interactions between Fusarium species from sugarcane and the stalk borer, Eldana saccharina (Lepidoptera: Pyralidae)
Authors: McFarlane S.A. , Govender P. , Rutherford R.S.
Published: July 2009

In this study, beneficial relationships between Fusarium species in sugarcane and the stalk borer, Eldana saccharina (Lepidoptera: Pyralidae) were demonstrated in vitro. In addition, Fusarium species with antagonistic properties were found to inhabit sugarcane. Attenuated Fusarium isolates from sugarcane stalks collected across the South African sugar industry were incorporated into diet formulated to mass rear E. saccharina. Of the over 200 Fusarium isolates obtained, 10 that significantly improved the survival and development of E. saccharina larvae and considered to be beneficial were selected for further study, as were 10 that were detrimental or antagonistic to the stalk borer. Twelve of the selected isolates were identified as F. sacchari by direct sequencing of translation elongation factor‐1α fragments, eight of which resulted in reduced numbers of surviving larvae and significantly lower larval masses. F. proliferatum isolates resulted in increased survival and mass of E. saccharina and three of the five isolates assigned to the F. pseudonygamai group enhanced E. saccharina development. Results from olfactory choice experiments suggested the production of attractive and repellent metabolites by certain isolates. Findings from this study may offer additional or alternative strategies for managing E. saccharina infestation of sugarcane.
Vitamin D as a Novel Nontraditional Risk Factor for Mortality in Hemodialysis Patients
Authors: Pečovnik‐Balon Breda , Jakopin Eva , Bevc Sebastjan , Knehtl Masa , Gorenjak Maksimiljan
Published: July 2009

We examined the prevalence of vitamin D deficiency in hemodialysis patients and tested the hypothesis that decreased levels of 25‐hydroxyvitamin D (25D) are associated with an increased risk for early all‐cause mortality. One hundred and two patients, 57 (56%) men and 45 (44%) women, mean age 60.5 ± 13.1 years, were included in our study. Serum calcium and phosphorus levels were measured by routine laboratory methods. Parathyroid hormone (PTH) was measured by immunoassay and 25D by enzyme immunoassay. Patients were divided into two groups depending on the serum concentration of 25D: below or above 50 nmol/L. Survival rates were analyzed using the Kaplan–Meier survival curves. The Cox regression model was used to define potential variables effecting all‐cause mortality. The mean level of 25D in all patients was 58 ± 35.6 nmol/L, 52% of patients had 25D levels >50 nmol/L and 48% had levels of 10.5–50 nmol/L. Compared with men, women were more likely to be 25D deficient (67% vs. 37%; P = 0.005). Patients were observed from the date of laboratory measurement until their death or to a maximum of 730 days. Kaplan–Meier survival analysis showed that mortality in patients was significantly higher in the group with 25D levels ≤50 nmol/L (P < 0.033). With Cox multivariable regression modeling, the PTH level (P < 0.029) turned out to be the only predictor of mortality in our patients. Using the definitions recommended in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, we found that our hemodialysis patients on average have vitamin D insufficiency. Our results indicate that patients with 25D levels ≤50 nmol/L are associated with higher all‐cause early mortality.
Intima Media Thickness and Endothelial Function in Chronic Hemodialysis Patients
Authors: Rus Rina , Buturović‐Ponikvar Jadranka
Published: July 2009

The purpose of our study was to evaluate the intima‐media thickness (IMT) of the carotid and brachial arteries, flow‐mediated dilatation (FMD), and nitroglycerin‐mediated dilatation (NMD) in diabetic and non‐diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty‐eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1–340 months. Using B‐mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 ± 0.99 vs. 6.69 ± 2.37 mm; NMD 9.1 ± 1.95 vs. 11.23 ± 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.
Guillain–Barré Syndrome Treated by Membrane Plasma Exchange and/or Immunoadsorption
Authors: Marn Pernat Andreja , Buturović‐Ponikvar Jadranka , Švigelj Viktor , Ponikvar Rafael
Published: July 2009

In this report, we evaluate the success of immunoadsorption and plasma membrane exchange treatment in patients with severe Guillain–Barré syndrome (GBS), and describe one case successfully treated by immunoadsorption after failure of plasma exchange therapy. Nineteen severely paralyzed GBS patients, aged 14–76 years, who were treated between 1998 and 2008, were retrospectively studied. They underwent 161 immunoadsorption and 119 plasma exchange procedures. In severe GBS, 4–30 immunoadsorption and 5–31 plasma exchange sessions were needed. Among 16 patients on mechanical ventilation, 11 recovered from disability completely, while in one patient mild muscle weakness persisted after one year. One patient suffered from ischemic stroke, two patients died after weaning from mechanical ventilation. One death was believed to be procedure‐unrelated, the other patient died from sepsis. Four patients were lost to follow‐up. We treated a 14‐year‐old, mechanically‐ventilated patient using two different apheresis methods. After failure of 31 membrane plasma exchanges over 34 days, the patient was then switched to the immunoadsorption apheresis method, receiving seven sessions in 15 days. He no longer required assisted ventilation and recovered from the disability completely. A high number of immunoadsorption as well as membrane plasma exchange treatments can be safely and effectively applied in severe GBS patients. Our patients often needed, and were provided with, more than the currently arbitrarily accepted four apheresis sessions before good clinical recovery was achieved. For non‐responders to plasma exchange treatment, immunoadsorption may be the first‐line therapy.
Treatment of Hyperlipidemic Acute Pancreatitis With Plasma Exchange: A Single‐Center Experience
Authors: Gubenšek Jakob , Buturović‐Ponikvar Jadranka , Marn‐Pernat Andreja , Kovač Janko , Knap Bojan , Premru Vladimir , Ponikvar Rafael
Published: July 2009

Of the cases of acute pancreatitis, 1–7% are caused by severe hypertriglyceridemia and can be treated with plasma exchange (PE). We report on a large series of patients with acute hyperlipidemic pancreatitis (HLP) treated with PE. In the 1992–2008 period, 50 patients (45 ± 8 years old, 92% male) with acute HLP were treated with PE, during which 1–2 plasma volumes were exchanged. Heparin was used as anticoagulant in 85% of the procedures, and citrate in the rest. Cholesterol and triglycerides were measured before and after PE. In the 2003–2008 cohort of 40 patients, we retrospectively recorded an Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the first PE session, hospital mortality, and length of hospital stay. A total of 79 PE treatments were done, 1–5 per patient. The volume exchanged was 4890 ± 1300 mL over a duration of 3.5 ± 2 h. During the first PE, the triglycerides were lowered from 58.9 ± 40.8 to 10.8 ± 10.8 mmol/L, and the total cholesterol was lowered from 20.0 ± 7.6 to 5.7 ± 4.3 mmol/L. In 10% of the procedures the plasmafilter was replaced, and in 3% the filter was clotted. Hypotension occurred in 3% of PE and there was one case of gastrointestinal bleeding after PE with heparin anticoagulation. In the 2003–2008 cohort, the median APACHE II score was 5 (range 0–15), the median overall hospital stay was 18 days (range 3–142 days) and the hospital mortality was 15%. To conclude, in acute hyperlipidemic pancreatitis, one to two plasma exchanges effectively reduce the serum triglyceride level. There is a low rate of procedure‐related complications. A mortality rate of 15% is considerable.
Membrane Plasma Exchange for the Treatment of Thrombotic Thrombocytopenic Purpura
Authors: Marn Pernat Andreja , Buturović‐Ponikvar Jadranka , Kovač Janko , Knap Bojan , Premru Vladimir , Benedik Miha , Varl Janez , Škofic Nataša , Gubenšek Jakob , Kersnič Boštjan , Ponikvar Rafael
Published: July 2009

The aim of our report is to present our 11‐year experience with therapeutic membrane plasma exchange therapy for the treatment of idiopathic thrombotic thrombocytopenic purpura syndrome (TTP). In 56 patients, membrane plasma exchange therapy was initiated immediately and performed once or twice daily until the platelet count normalized. During each plasma exchange procedure, 1–1.5 plasma volumes (3606 ± 991 mL) were replaced with fresh frozen plasma. In 37 females and 19 males (44 ± 21 years), 1066 plasma exchange procedures were performed. The average duration of treatment was 23 ± 17 days. The average number of plasma exchanges was 19 ± 17 per patient. Renal impairment was detected in 36% of patients. At the initiation of plasma exchange treatment, the average platelet count was 31 ± 30 × 109/L and reached 199 ± 95 × 109/L thereafter. Fifty‐two of 56 (93%) patients demonstrated an excellent response to plasma exchange therapy, of whom 48 patients (86%) attained complete remission with a platelet count of more than 100 × 109/L. Four patients died soon after the initiation of plasma exchange therapy, when only 1–3 procedures had been performed. During the follow‐up period, six patients with complete remission had 1–5 subsequent relapses each year. One of them died of acute hemolytic reaction during the tapering of plasma exchange procedures. Three patients underwent additional splenectomy. Our experience with primary TTP supports the plasma exchange treatment with fresh frozen plasma as a mandatory, up‐to‐date therapy. Close monitoring during all 1066 procedures showed no serious side‐effects.
Hemodialysis Catheters With Citrate Locking in Critically Ill Patients With Acute Kidney Injury Treated With Intermittent Online Hemofiltration or Hemodialysis
Authors: Škofic Nataša , Buturović‐Ponikvar Jadranka , Kovač Janko , Premru Vladimir , Knap Bojan , Marn Pernat Andreja , Kersnič Boštjan , Gubenšek Jakob , Ponikvar Rafael
Published: July 2009

The purpose of the study was to compare the long‐term catheter‐related complications associated with temporary untunneled hemodialysis catheters, locked with citrate in the interdialysis period, inserted in critically ill patients with acute kidney injury, between different catheter insertion sites (femoral vs. jugular and subclavian) and catheter types (single‐lumen [SL] vs. double‐lumen [DL]). In a retrospective clinical study, the long‐term catheter‐related complications in 290 critically ill patients treated with intermittent high‐volume online hemofiltration or hemodialysis between December 2004 and January 2008 were analyzed. Among 534 inserted catheters, 493 (92.3%) were femoral, 29 (5.4%) jugular, and 12 (2.3%) subclavian; 304 (56.9%) were SL and 230 (43.1%) were DL. There were 125 (20.3/1000 catheter days [c.d.]) thrombotic complications, while infectious complications were exceptionally rare, that is, only 13 (2.1/1000 c.d.), of which 10 (1.6/1000 c.d.) were possible catheter‐related bloodstream infections and 3 (0.5/1000 c.d.) exit‐site infections. The incidence rate of all thrombotic complications was significantly lower in all jugular and subclavian vs. all femoral catheters (7.7/1000 c.d. vs. 21.8/1000 c.d., P = 0.01), and in all SL vs. DL catheters (11.4/1000 c.d. vs. 32.2/1000 c.d., P < 0.001). The incidence rate of any possible catheter‐related bloodstream and exit‐site infections was not significantly different in all jugular and subclavian vs. all femoral catheters, neither in femoral SL vs. DL catheters. The major long‐term catheter‐related complications were thrombotic, and significantly more frequent in DL vs. SL catheters. Infectious complications were exceptionally rare, most probably due to the strict catheter care protocol, as well as the routine use of a citrate catheter lock and antibiotic ointment at the catheter exit‐site.
Surgical Salvage of Thrombosed Native Arteriovenous Fistulas for Hemodialysis by Interventional Nephrologists
Authors: Ponikvar Rafael
Published: July 2009

The purpose of this retrospective clinical study with prospective data collection was to evaluate the outcomes of patients with native arteriovenous fistula (AVF) thrombosis after surgical thrombectomy performed by surgically skilled interventional nephrologists. In 111 hemodialysis patients (66 men [59%], aged 59 ± 16 [20–87] years), acute thrombosis of the native forearm or arm AVF occurred. The primary patency before thrombosis was 4.0 ± 4.7 years (range 1.2–28). Thrombectomies were performed as outpatient procedures under local anesthesia (2% lidocaine), using microsurgical instruments and magnifying glasses. The total number of surgical procedures was 128–91 thrombectomies with reanastomosis and 37 thrombectomies alone. In a few cases, angioplasty with stenting and “jump grafts” were used (because of outflow stenosis). The time between thrombosis and surgery was 3.7 ± 8.6 days (range 0–64), and the number of surgeries to maintain secondary patency was 1.15 ± 0.47 (range 1–4). The immediate success rate was 93.8% (120/128); 7/8 of failures were in the “thrombectomy alone” group. The post‐interventional secondary patency rate at one year was 68%, and in the “thrombectomy with reanastomosis” and “thrombectomy alone” subgroups it was 73% and 54%, respectively. A better outcome with thrombectomy and reanastomosis was achieved in the AVF with perianastomotic stenosis. It seems that intima‐media thickening of a new anastomosis was less pronounced because of previous remodeling of the fistula vein. Surgical salvage of a thrombosed AVF performed by an interventional nephrologist was shown to be a safe procedure, significantly prolonging AVF function and avoiding hemodialysis catheter insertion in many cases. Thrombectomy with reanastomosis was more successful than simple thrombectomy.
Slovenian Renal Replacement Therapy Registry: Excerpts From the 2006 Annual Report
Authors: Buturović‐Ponikvar Jadranka ,   Slovenian Renal Replacement Therapy Registry Group
Published: July 2009

The total number of end‐stage renal disease patients treated by renal replacement therapy (RRT) in Slovenia on 31 December 2006 was 1835, that is, 913 per million population (pmp). Of these patients, 1271 (69%) were treated by hemodialysis, 102 (6%) by peritoneal dialysis, and 461 (25%) had a functioning kidney graft. Two hundred and forty‐nine incident patients, 124 pmp (at day one), started RRT: median age 66 years, 60% men, 30.5% diabetics. Of the hemodialysis patients, 77% were dialyzed in hospital and 23% in private dialysis centers. Hemodiafiltration was used in 38% of the hemodialysis patients. The vascular accesses were native arteriovenous fistulas in 84%, polytetrafluoroethylene grafts in 5%, and hemodialysis catheters in 11% of patients. The crude death rate of dialysis patients was 14.7%, of transplant recipients 1.35%, of both dialysis and transplant patients 11.4%. The number of patients positive for hepatitis B or C viruses is stable and low at 2.3% of the dialysis patients.
Global Sensitivity Analysis Techniques for Probabilistic Ground Water Modeling
Authors: Mishra Srikanta , Deeds Neil , Ruskauff Greg
Published: July 2009

Global sensitivity analysis techniques are better suited for analyzing input‐output relationships over the full range of parameter variations and model outcomes, as opposed to local sensitivity analysis carried out around a reference point. This article describes three such techniques: (1) stepwise rank regression analysis for building input‐output models to identify key contributors to output variance, (2) mutual information (entropy) analysis for determining the strength of nonmonotonic patterns of input‐output association, and (3) classification tree analysis for determining what variables or combinations are responsible for driving model output into extreme categories. These techniques are best applied in conjunction with Monte Carlo simulation‐based probabilistic analyses. Two examples are presented to demonstrate the applicability of these methods. The usefulness of global sensitivity techniques is examined vis‐a‐vis local sensitivity analysis methods, and recommendations are provided for their applications in ground water modeling practice.
Calibration of Parameter Fields Consisting of Multiple Statistical Populations
Authors: Janssen Gijs M.C.M. , Valstar Johan R.
Published: July 2009

If a parameter field to be calibrated consists of more than one statistical population, usually not only the parameter values are uncertain, but the spatial distributions of the populations are uncertain as well. In this study, we demonstrate the potential of the multimodal calibration method we proposed recently for the calibration of such fields, as applied to real‐world ground water models with several additional stochastic parameter fields. Our method enables the calibration of the spatial distribution of the statistical populations, as well as their spatially correlated parameterization, while honoring the complete prior geostatistical definition of the multimodal parameter field. We illustrate the implications of the method in terms of the reliability of the posterior model by comparing its performance to that of a “conventional” calibration approach in which the positions of the statistical populations are not allowed to change. Information from synthetic calibration runs is used to show how ignoring the uncertainty involved in the positions of the statistical populations not only denies the modeler the opportunity to use the measurement information to improve these positions but also unduly influences the posterior intrapopulation distributions, causes unjustified adjustments to the cocalibrated parameter fields, and results in poorer observation reproduction. The proposed multimodal calibration allows a more complete treatment of the relevant uncertainties, which prevents the abovementioned adverse effects and renders a more trustworthy posterior model.
MTBE, TBA, and TAME Attenuation in Diverse Hyporheic Zones
Authors: Landmeyer James E. , Bradley Paul M. , Trego Donald A. , Hale Kevin G. , Haas Joseph E.
Published: July 2009

Groundwater contamination by fuel‐related compounds such as the fuel oxygenates methyl tert‐butyl ether (MTBE), tert‐butyl alcohol (TBA), and tert‐amyl methyl ether (TAME) presents a significant issue to managers and consumers of groundwater and surface water that receives groundwater discharge. Four sites were investigated on Long Island, New York, characterized by groundwater contaminated with gasoline and fuel oxygenates that ultimately discharge to fresh, brackish, or saline surface water. For each site, contaminated groundwater discharge zones were delineated using pore water geochemistry data from 15 feet (4.5 m) beneath the bottom of the surface water body in the hyporheic zone and seepage‐meter tests were conducted to measure discharge rates. These data when combined indicate that MTBE, TBA, and TAME concentrations in groundwater discharge in a 5‐foot (1.5‐m) thick section of the hyporheic zone were attenuated between 34% and 95%, in contrast to immeasurable attenuation in the shallow aquifer during contaminant transport between 0.1 and 1.5 miles (0.1 to 2.4 km). The attenuation observed in the hyporheic zone occurred primarily by physical processes such as mixing of groundwater and surface water. Biodegradation also occurred as confirmed in laboratory microcosms by the mineralization of U‐ 14C‐MTBE and U‐14C‐TBA to 14CO2 and the novel biodegradation of U‐ 14C‐TAME to 14CO2 under oxic and anoxic conditions. The implication of fuel oxygenate attenuation observed in diverse hyporheic zones suggests an assessment of the hyporheic zone attenuation potential (HZAP) merits inclusion as part of site assessment strategies associated with monitored or engineered attenuation.
Current state and perspectives of producing biodiesel‐like compounds by biotechnology
Authors: Uthoff Stefan , Bröker Daniel , Steinbüchel Alexander
Published: July 2009

The global demand for crude oil is expected to continue to rise in future while simultaneously oil production is currently reaching its peak. Subsequently, rising oil prices and their negative impacts on economy, together with an increased environmental awareness of our society, directed the focus also on the biotechnological production of fuels. Although a wide variety of such fuels has been suggested, only the production of ethanol and biodiesel has reached a certain economic feasibility and volume, yet. This review focuses on the current state and perspectives of biotechnological production of biodiesel‐like compounds. At present by far most of the produced biodiesel is obtained by chemical transesterification reactions, which cannot meet the demands of a totally ‘green’ fuel production. Therefore, also several biotechnological biodiesel production processes are currently being developed. Biotechnological production can be achieved by purified enzymes in the soluble state, which requires cost‐intensive protein preparation. Alternatively, enzymes could be immobilized on an appropriate matrix, enabling a reuse of the enzyme, although the formation of by‐products may provide difficulties to maintain the enzyme activity. Processes in presence of organic solvents like t‐butanol have been developed, which enhance by‐product solubility and therefore prevent loss of enzyme activity. As another approach the application of whole‐cell catalysis for the production of fatty acid ethyl esters, which is also referred to as ‘microdiesel’, by recombinant microorganisms has recently been suggested.
ORIGINAL ARTICLE: Size‐selective fishing gear and life history evolution in the Northeast Arctic cod
Authors: Jørgensen Christian , Ernande Bruno , Fiksen Øyvind
Published: July 2009

Industrial fishing has been identified as a cause for life history changes in many harvested stocks, mainly because of the intense fishing mortality and its size‐selectivity. Because these changes are potentially evolutionary, we investigate evolutionarily stable life‐histories and yield in an energy‐allocation state‐dependent model for Northeast Arctic codGadus morhua. We focus on the evolutionary effects of size‐selective fishing because regulation of gear selectivity may be an efficient management tool. Trawling, which harvests fish above a certain size, leads to early maturation except when fishing is low and confined to mature fish. Gillnets, where small and large fish escape, lead to late maturation for low to moderate harvest rates, but when harvest rates increase maturation age suddenly drops. This is because bell‐shaped selectivity has two size‐refuges, for fish that are below and above the harvestable size‐classes. Depending on the harvest rate it either pays to grow through the harvestable slot and mature above it, or mature small below it. Sustainable yield on the evolutionary time‐scale is highest when fishing is done by trawling, but only for a small parameter region. Fishing with gillnets is better able to withstand life‐history evolution, and maintains yield over a wider range of fishing intensities.
ORIGINAL ARTICLE: Implications of fisheries‐induced evolution for stock rebuilding and recovery
Authors: Enberg Katja , Jørgensen Christian , Dunlop Erin S. , Heino Mikko , Dieckmann Ulf
Published: July 2009

Worldwide depletion of fish stocks has led fisheries managers to become increasingly concerned about rebuilding and recovery planning. To succeed, factors affecting recovery dynamics need to be understood, including the role of fisheries‐induced evolution. Here we investigate a stock’s response to fishing followed by a harvest moratorium by analyzing an individual‐based evolutionary model parameterized for Atlantic codGadus morhuafrom its northern range, representative of long‐lived, late‐maturing species. The model allows evolution of life‐history processes including maturation, reproduction, and growth. It also incorporates environmental variability, phenotypic plasticity, and density‐dependent feedbacks. Fisheries‐induced evolution affects recovery in several ways. The first decades of recovery were dominated by demographic and density‐dependent processes. Biomass rebuilding was only lightly influenced by fisheries‐induced evolution, whereas other stock characteristics such as maturation age, spawning stock biomass, and recruitment were substantially affected, recovering to new demographic equilibria below their preharvest levels. This is because genetic traits took thousands of years to evolve back to preharvest levels, indicating that natural selection driving recovery of these traits is weaker than fisheries‐induced selection was. Our results strengthen the case for proactive management of fisheries‐induced evolution, as the restoration of genetic traits altered by fishing is slow and may even be impractical.
SYNTHESIS: Life history change in commercially exploited fish stocks: an analysis of trends across studies
Authors: Sharpe Diana M. T. , Hendry Andrew P.
Published: July 2009

Age and size at maturation have declined dramatically in many commercial fish stocks over the past few decades – changes that have been widely attributed to fishing pressure. We performed an analysis of such trends across multiple studies, to test for the consistency of life history changes under fishing, and for their association with the intensity of exploitation (fishing mortality rate). We analyzed 143 time series from 37 commercial fish stocks, the majority of which originated from the North Atlantic. Rates of phenotypic change were calculated for two traditional maturation indices (length and age at 50% maturity), as well as for probabilistic maturation reaction norms (PMRNs). We found that all three indices declined in heavily exploited populations, and at a rate that was strongly correlated with the intensity of fishing (for length at 50% maturity and PMRNs). These results support previous assertions that fishing pressure is playing a major role in the life history changes observed in commercial fish stocks. Rates of change were as strong for PMRNs as for age and size at 50% maturity, which is consistent with the hypothesis that fishing‐induced phenotypic changes can sometimes have a genetic basis.
ORIGINAL ARTICLE: Avoidance of fisheries‐induced evolution: management implications for catch selectivity and limit reference points
Authors: Hutchings Jeffrey A.
Published: July 2009

I examined how the fitness (r) associated with early‐ and late‐maturing genotypes varies with fishing mortality (F) and age‐/size‐specific probability of capture. Life‐history data on Newfoundland’s northern Atlantic cod (Gadus morhua) allowed for the estimation of r for individuals maturing at 4 and 7 year in the absence of fishing. Catch selectivity data associated with four types of fishing gear (trap, gillnet, handline, otter trawl) were then incorporated to examine how r varied with gear type and with F. The resulting fitness functions were then used to estimate the F above which selection would favour early (4 year) rather than delayed (7 year) maturity. This evolutionarily‐sensitive threshold, Fevol, identifies a limit reference point somewhat similar to those used to define overfishing (e.g., Fmsy, F0.1). Over‐exploitation of northern cod resulted in fishing mortalities considerably greater than those required to effect evolutionary change. Selection for early maturity is reduced by the dome‐shaped selectivities characteristic of fixed gears such as handlines (the greater the leptokurtosis, the lower the probability of a selection response) and enhanced by the knife‐edged selectivities of bottom trawls. Strategies to minimize genetic change are consistent with traditional management objectives (e.g., yield maximization, population increase). Compliance with harvest control rules guided by evolutionarily‐sensitive limit reference points, which may be achieved by adherence to traditional reference points such as Fmsy and F0.1, should be sufficient to minimize the probability of fisheries‐induced evolution for commercially exploited species.
ORIGINAL ARTICLE: Mitigating fisheries‐induced evolution in lacustrine brook charr (Salvelinus fontinalis) in southern Quebec, Canada
Authors: Okamoto Kenichi W. , Whitlock Rebecca , Magnan Pierre , Dieckmann Ulf
Published: July 2009

Size‐selective mortality caused by fishing can impose strong selection on harvested fish populations, causing evolution in important life‐history traits. Understanding and predicting harvest‐induced evolutionary change can help maintain sustainable fisheries. We investigate the evolutionary sustainability of alternative management regimes for lacustrine brook charr (Salvelinus fontinalis) fisheries in southern Canada and aim to optimize these regimes with respect to the competing objectives of maximizing mean annual yield and minimizing evolutionary change in maturation schedules. Using a stochastic simulation model of brook charr populations consuming a dynamic resource, we investigate how harvesting affects brook charr maturation schedules. We show that when approximately 5% to 15% of the brook charr biomass is harvested, yields are high, and harvest‐induced evolutionary changes remain small. Intensive harvesting (at approximately >15% of brook charr biomass) results in high average yields and little evolutionary change only when harvesting is restricted to brook charr larger than the size at 50% maturation probability at the age of 2 years. Otherwise, intensive harvesting lowers average yield and causes evolutionary change in the maturation schedule of brook charr. Our results indicate that intermediate harvesting efforts offer an acceptable compromise between avoiding harvest‐induced evolutionary change and securing high average yields.
Lymphocyte‐Bound Complement Activation Products as Biomarkers for Diagnosis of Systemic Lupus Erythematosus
Authors: Liu Chau‐Ching , Kao Amy H. , Hawkins Douglas M. , Manzi Susan , Sattar Abdus , Wilson Nicole , Ahearn Joseph M.
Published: July 2009

Systemic lupus erythematosus (SLE) is frequently misdiagnosed due to the lack of definitive diagnostic tests. The purpose of this study was to determine specifically whether complement activation products (CAP) are deposited on lymphocytes of SLE patients and whether lymphocyte‐bound CAP (LB‐CAP) may serve as novel biomarkers for the diagnosis of SLE. We conducted a cross‐sectional study of 224 patients with SLE, 179 patients with other diseases, and 114 healthy controls. LB‐CAP on peripheral blood lymphocytes was measured by flow cytometry. Diagnostic utility of LB‐CAP was determined by receiver operating characteristic (ROC) analysis. Significantly elevated levels of C4d and C3d were detected specifically on T and B lymphocytes (designated T‐C4d, T‐C3d, B‐C4d, and B‐C3d) of SLE patients. As diagnostic tools, T‐C4d and B‐C4d, respectively, were 56% sensitive/80% specific and 60% sensitive/82% specific in differentiating SLE from other diseases. Moreover, compared with measurement of anti‐dsDNA, serum C3, or serum C4, measurement of T‐C4d/B‐C4d was significantly more sensitive in identifying SLE patients during a single clinic visit. This is the first investigation of lymphocytes bearing complement activation products in human disease. T‐C4d and B‐C4d have high diagnostic sensitivity and specificity for SLE and may have added value to current laboratory tests for SLE diagnosis.
Direct Concentration Approach of Moisture Diffusion and Whole-Field Vapor Pressure Modeling for Reflow Process—Part I: Theory and Numerical Implementation
Authors: Xie B. , Fan X. J. , Shi X. Q. , Ding H.
Published: July 2009

Moisture concentration is discontinuous at interfaces when two materials, which have different saturated moisture concentrations, are joined together. In order to perform moisture diffusion modeling in a multimaterial system such as electronic packages, normalization methods have been commonly used to remove the discontinuity of moisture concentration at interfaces. However, such treatments cannot be extended to a reflow process, in which ambient temperature and/or humidity vary with time. This paper develops a direct concentration approach, with which the moisture concentration is used as a field variable directly. Constraint equations are applied to meet the interface continuity requirements. Further in this paper, a simplified vapor pressure model based on a multiscale analysis is developed. The model considers the phase change in moisture, and links the macroscopic moisture concentration to the moisture state at a microscopic level. This model yields the exact same results with the original vapor pressure model (Fan, et al., 2005, “A Micromechanics Based Vapor Pressure Model in Electronic Packages,” ASME J. Electron. Packag., 127(3), pp. 262–267). The new model does not need to relate to a reference temperature state. Numerical implementation procedures for calculating moisture concentration and ensuing vapor pressure, which are coupled with temperature analysis, are presented in this paper.
Thermal Analysis of Miniature Low Profile Heat Sinks With and Without Fins
Authors: Egan V. , Walsh P. A. , Walsh E. , Grimes R.
Published: July 2009

Reliable and efficient cooling solutions for portable electronic devices are now at the forefront of research due to consumer demand for manufacturers to downscale existing technologies. To achieve this, the power consumed has to be dissipated over smaller areas resulting in elevated heat fluxes. With regard to cooling such devices, the most popular choice is to integrate a fan driven heat sink, which for portable electronic devices must have a low profile. This paper presents an experimental investigation into such low profile cooling solutions, which incorporate one of the smallest commercially available fans in series with two different heat sink designs. The first of these is the conventionally used finned heat sink design, which was specifically optimized and custom manufactured in the current study to complement the driving fan. While the second design proposed is a novel “finless” type heat sink suitable for use in low profile applications. Together the driving fan and heat sinks combined were constrained to have a total footprint area of 465 mm2 and a profile height of only 5 mm, making them ideal for use in portable electronics. The objective was to evaluate the performance of the proposed finless heat sink design against a conventional finned heat sink, and this was achieved by means of thermal resistance and overall heat transfer coefficient measurements. It was found that the proposed finless design proved to be the superior cooling solution when operating at low fan speeds, while at the maximum fan speed tested of 8000 rpm both provided similar performance. Particle image velocimetry measurements were used to detail the flow structures within each heat sink and highlighted methods, which could further optimize their performance. Also, these measurements along with corresponding global volume flow rate measurements were used to elucidate the enhanced heat transfer characteristics observed for the finless design. Overall, it is shown that the proposed finless type heat sink can provide superior performance compared with conventional finned designs when used in low profile applications. In addition a number of secondary benefits associated with such a design are highlighted including lower cost, lower mass, lower acoustics, and reduced fouling issues.
Laser-Based Target Preparation in 3D Integrated Electronic Packages
Authors: Martens Stefan , Mack Walter , Courtade Frédéric , Perdu Philippe , Wilde Juergen , Voelklein Friedemann
Published: July 2009

The trend toward 3D integration in electronic packaging requires that failure analysis procedures and target preparation methods are adapted from conventional discrete packages to these emerging packaging technologies. This paper addresses the feasibility of laser-based target preparation in 3D integrated devices, especially stacked-die packages. Various laser technologies such as ultrashort-pulse lasers, excimer lasers, and diode-pumped solid-state (DPSS) lasers with different wavelengths and pulse durations were evaluated. In particular, it was found that ultrashort-pulse lasers with pulse durations in the femtosecond range were not suitable for ablation of the molding compound (MC). Picosecond lasers were applicable with certain constraints. It was found that for MCs with high filler content, DPSS lasers with pulse durations in the nanosecond range were the best choice. For the removal of stacked silicon dies, the laser wavelength was the most important factor in artifact-free thinning. Laser cross sections through several silicon dies with remarkably small heat-affected zones were also demonstrated. The distinct removal of the MC, silicon dies, and metal interconnected with a single laser source offers new opportunities for laser-based target preparation in 3D integrated electronic packaging devices.