bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of DNA mass on multiple displacement whole genome amplification and genotyping performance
Authors: Bergen Andrew W , Qi Ying , Haque Kashif A , Welch Robert A , Chanock Stephen J 
Published: September 2005

Abstract

Background
Whole genome amplification (WGA) promises to eliminate practical molecular genetic analysis limitations associated with genomic DNA (gDNA) quantity. We evaluated the performance of multiple displacement amplification (MDA) WGA using gDNA extracted from lymphoblastoid cell lines (N = 27) with a range of starting gDNA input of 1–200 ng into the WGA reaction. Yield and composition analysis of whole genome amplified DNA (wgaDNA) was performed using three DNA quantification methods (OD, PicoGreen® and RT-PCR). Two panels of N = 15 STR (using the AmpFlSTR® Identifiler® panel) and N = 49 SNP (TaqMan®) genotyping assays were performed on each gDNA and wgaDNA sample in duplicate. gDNA and wgaDNA masses of 1, 4 and 20 ng were used in the SNP assays to evaluate the effects of DNA mass on SNP genotyping assay performance. A total of N = 6,880 STR and N = 56,448 SNP genotype attempts provided adequate power to detect differences in STR and SNP genotyping performance between gDNA and wgaDNA, and among wgaDNA produced from a range of gDNA templates inputs.

Results
The proportion of double-stranded wgaDNA and human-specific PCR amplifiable wgaDNA increased with increased gDNA input into the WGA reaction. Increased amounts of gDNA input into the WGA reaction improved wgaDNA genotyping performance. Genotype completion or genotype concordance rates of wgaDNA produced from all gDNA input levels were observed to be reduced compared to gDNA, although the reduction was not always statistically significant. Reduced wgaDNA genotyping performance was primarily due to the increased variance of allelic amplification, resulting in loss of heterozygosity or increased undetermined genotypes. MDA WGA produces wgaDNA from no template control samples; such samples exhibited substantial false-positive genotyping rates.

Conclusion
The amount of gDNA input into the MDA WGA reaction is a critical determinant of genotyping performance of wgaDNA. At least 10 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain wgaDNA TaqMan® SNP assay genotyping performance equivalent to that of gDNA. Over 100 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain optimal STR genotyping performance using the AmpFlSTR® Identifiler® panel from wgaDNA equivalent to that of gDNA.
Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons
Authors: Tenenbaum Alexander , Motro Michael , Fisman Enrique Z 
Published: September 2005

Abstract
There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs – the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan – (alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.
Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage
Authors: Strappe Padraig M , Hampton David W , Brown Douglas , Cachon-Gonzalez Begona , Caldwell Maeve , Fawcett James W , Lever Andrew ML 
Published: September 2005

Abstract

Background
Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS). Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector) and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells.

Results
HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors.

Conclusion
This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.
Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report
Authors: Husain Mustafa M , Stegman Diane , Trevino Kenneth 
Published: September 2005

Abstract

Background
Depression during pregnancy can have significant health consequences for the mother and her infant. Antidepressant medications, which pass through the placenta, may increase the risk of low birth weight and preterm delivery. The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy may induce serotonergic symptoms in the infant after delivery. Antidepressant medications in breast milk may also be passed to an infant. Vagus nerve stimulation (VNS) therapy is an effective non-pharmacologic treatment for treatment-resistant depression (TRD), but little information exists regarding the use of VNS therapy during pregnancy.

Case presentation
The patient began receiving VNS therapy for TRD in March 1999. The therapy was effective, producing substantial reductions in depressive symptoms and improvement of function. In 2002, the patient reported that she was pregnant. She continued receiving VNS therapy throughout her pregnancy, labor, and delivery, which enabled the sustained remission of her depression. The pregnancy was uneventful; a healthy daughter was delivered at full term.

Conclusion
In this case, VNS therapy provided effective treatment for TRD during pregnancy and delivery. VNS was safe for the patient and her child.
Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement
Authors: Woo Patricia , Wilkinson Nicholas , Prieur Anne-Marie , Southwood Taunton , Leone Valentina , Livermore Polly , Wythe Helena , Thomson David , Kishimoto Tadamitsu 
Published: September 2005

AbstractEighteen Caucasian (white, Middle East and Asian) children diagnosed by paediatric rheumatologists in the UK and France as having systemic juvenile idiopathic arthritis (sJIA) were enrolled in this open label, single dose trial. All patients had evidence of continued symptoms and disease activity for at least three months while receiving >0.2 mg/kg/day of prednisolone, or its equivalent, prior to recruitment. Twelve patients also received methotrexate (≤20 mg/m2/week). The patients were divided into three groups receiving 2, 4 or 8 mg/kg of MRA (tocilizumab) by intravenous infusion. No evidence of dose-limiting toxicity was observed and there were no dose-limiting safety issues. MRA appeared to be dramatically effective, with clinical and laboratory responses observed by 48 h post infusion, and these improvements continued well after serum MRA was undetectable. Eleven patients achieved the JIA definition of improvement (at least 3 of 6 core set criteria with a 30% improvement and no more than one worsened by 30%) and eight achieved ≥50% improvement. There were no observable differences with age. Clinical improvement in these children was observed for up to eight weeks, supporting the hypothesis that IL-6 is a key cytokine in the upregulation of genes crucial in the inflammation processes of sJIA, and the possibility of sequestration of MRA in the extra-vascular compartment needs to be considered.
Unconventional mechanisms control cyclic respiratory gas release in flyingDrosophila
Authors: Lehmann Fritz-Olaf , Heymann Nicole 
Published: September 2005

SUMMARYThe high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight,instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency(0.37±0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping,but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.
Perfusion of the isolated trout heart coronary circulation with red blood cells: effects of oxygen supply and nitrite on coronary flow and myocardial oxygen consumption
Authors: Jensen F. B. , Agnisola C. 
Published: September 2005

SUMMARYA method for perfusion of the isolated trout heart coronary circulation with red blood cells (RBCs) was developed. The method was used to analyse the influence of RBC perfusion on myocardial O2 supply and O2 consumption and to test the hypothesis that nitrite is converted to vasoactive nitric oxide in the RBC-perfused coronary circulation. Perfusion with RBCs significantly increased myocardial O2 supply and O2 consumption by increasing the incoming O2concentration and the O2 extraction. Coronary flow did not differ between RBC perfusion and saline perfusion, but RBC perfusion established a strong linear increase in myocardial O2 consumption with coronary flow. Nitric oxide was measured in the atrial effluent of the preparation. Perfusion with saline under hypoxic conditions was associated with NO production. The nitric oxide synthase inhibitor L-NA obliterated this NO production and significantly decreased coronary flow, showing that the NO was vasoactive and probably of endothelial origin. RBC perfusion at low PO2 similarly caused an L-NA-inhibitable NO production. The change in NO production upon subsequent nitrite addition, by contrast, was not inhibited by L-NA. Nitrite entered trout erythrocytes independent of degree of oxygenation, but the O2 saturation of RBCs showed a major decrease in the coronary circulation, and[NO2-] decreased while methaemoglobin rose, suggesting that deoxyHb-mediated reduction of nitrite to NO may have occurred. However,other possibilities (e.g. NO2-→NO conversion in myocardial cells) cannot be excluded. The NO formation associated with nitrite had no effect on coronary flow, possibly because NO was produced after the resistance vessels.
Does daily activity level determine muscle phenotype?
Authors: Hodgson John A. , Roy Roland R. , Higuchi Norio , Monti Ryan J. , Zhong Hui , Grossman Elena , Edgerton V. Reggie 
Published: September 2005

SUMMARYThe activation level of a muscle is presumed to be a major determinant of many mechanical and phenotypic properties of its muscle fibers. However, the relationship between the daily activation levels of a muscle and these properties has not been well defined, largely because of the lack of accurate and sustained assessments of the spontaneous activity levels of the muscle. Therefore, we determined the daily activity levels of selected rat hindlimb muscles using intramuscular EMG recordings. To allow comparisons across muscles having varying activity levels and/or muscle fiber type compositions,we recorded EMG activity in a predominantly slow plantarflexor (soleus), a predominantly fast plantarflexor (medial gastrocnemius, MG), a predominantly fast ankle dorsiflexor (tibialis anterior, TA) and a predominantly fast knee extensor (vastus lateralis, VL) in six unanesthetized rats for periods of 24 h. EMG activity levels were correlated with the light:dark cycle, with peak activity levels occurring during the dark period. The soleus was the most active and the TA the least active muscle in all rats. Daily EMG durations were highest for soleus (11–15 h), intermediate for MG (5–9 h) and VL (3–14 h) and lowest for TA (2–3 h). Daily mean EMG amplitudes and integrated EMG levels in the soleus were two- to threefold higher than in the MG and VL and seven- to eightfold higher than in the TA. Despite the three- to fourfold difference in activation levels of the MG and VL vs the TA, all three predominantly fast muscles have been reported to have a similar, very low percentage of slow fibers. Comparing these relative EMG levels to the published fiber type profiles of these muscles yields a very poor relationship between daily activity level and fiber type composition in the same muscles across several species. Although it is clear that changing the levels of activity can modulate the expression of the myosin phenotype,these results indicate that factors other than activation must play critical roles in determining and maintaining normal phenotypic properties of skeletal muscle fibers.
Sulphonylurea sensitivity and enriched expression implicate inward rectifier K+ channels inDrosophila melanogasterrenal function
Authors: Evans Jennifer M. , Allan Adrian K. , Davies Shireen A. , Dow Julian A. T. 
Published: September 2005

SUMMARYInsect Malpighian (renal) tubules are capable of transporting fluid at remarkable rates. Secondary active transport of potassium at the apical surface of the principal cell must be matched by a high-capacity basolateral potassium entry route. A recent microarray analysis of Drosophilatubule identified three extremely abundant and enriched K+ channel genes encoding the three inward rectifier channels of Drosophila: ir, irk2 and irk3. Enriched expression of inward rectifier channels in tubule was verified by quantitative RT-PCR, and all three IRKs localised to principal cells of the main segment (and irand irk3 to the lower tubule) by in situ hybridisation,suggesting roles both in primary secretion and reabsorption. A new splice form of irk2 was also identified. The role of inward rectifiers in fluid secretion was assessed with a panel of selective inhibitors of inward rectifier channels, the antidiabetic sulphonylureas. All completely inhibited fluid secretion, with IC50s of 0.78 mmol l-1 for glibenclamide and approximately 5 mmol l-1 for tolbutamide, 0.01 mmol l-1 for minoxidil and 0.1 mmol l-1 for diazoxide. This pharmacology is consistent with a lower-affinity class of inward rectifier channel that does not form an obligate multimer with the sulphonylurea receptor (SUR), although effects on non-IRK targets cannot be excluded. Glibenclamide inhibited fluid secretion similarly to basolateral K+-free saline.Radiolabelled glibenclamide is both potently transported and metabolised by tubule. Furthermore, glibenclamide is capable of blocking transport of the organic dye amaranth (azorubin S), at concentrations of glibenclamide much lower than required to impact on fluid secretion. Glibenclamide thus interacts with tubule in three separate ways; as a potent inhibitor of fluid secretion,as an inhibitor (possibly competitive) of an organic solute transporter and as a substrate for excretion and metabolism.
A computational study of the aerodynamics and forewing-hindwing interaction of a model dragonfly in forward flight
Authors: Wang Ji Kang , Sun Mao 
Published: September 2005

SUMMARYThe aerodynamics and forewing-hindwing interaction of a model dragonfly in forward flight are studied, using the method of numerically solving the Navier-Stokes equations. Available morphological and stroke-kinematic parameters of dragonfly (Aeshna juncea) are used for the model dragonfly. Six advance ratios (J; ranging from 0 to 0.75) and, at each J, four forewing-hindwing phase angle differences(γd; 180°, 90°, 60° and 0°) are considered. The mean vertical force and thrust are made to balance the weight and body-drag, respectively, by adjusting the angles of attack of the wings, so that the flight could better approximate the real flight.At hovering and low J (J=0, 0.15), the model dragonfly uses separated flows or leading-edge vortices (LEV) on both the fore- and hindwing downstrokes; at medium J (J=0.30, 0.45), it uses the LEV on the forewing downstroke and attached flow on the hindwing downstroke; at high J (J=0.6, 0.75), it uses attached flows on both fore- and hindwing downstrokes. (The upstrokes are very lightly loaded and, in general, the flows are attached.)At a given J, at γd=180°, there are two vertical force peaks in a cycle, one in the first half of the cycle, produced mainly by the hindwing downstroke, and the other in the second half of the cycle, produced mainly by the forewing downstroke; atγ d=90°, 60° and 0°, the two force peaks merge into one peak. The vertical force is close to the resultant aerodynamic force[because the thrust (or body-drag) is much smaller than vertical force (or the weight)]. 55-65% of the vertical force is contributed by the drag of the wings.The forewing-hindwing interaction is detrimental to the vertical force (and resultant force) generation. At hovering, the interaction reduces the mean vertical force (and resultant force) by 8-15%, compared with that without interaction; as J increases, the reduction generally decreases (e.g. at J=0.6 and γd=90°, it becomes 1.6%). A possible reason for the detrimental interaction is as follows: each of the wings produces a mean vertical force coefficient close to half that needed for weight support, and a downward flow is generated in producing the vertical force; thus, in general, a wing moves in the downwash-velocity field induced by the other wing, reducing its aerodynamic forces.
Sizing Backbone Internet Links
Authors: Heyman Daniel P. 
Published: September 2005

One of the distinguishing features of a backbone link is that it is designed to carry traffic from a large number of end users. This results in a Normal distribution for the number of bytes or packets that arrive in a fixed-length time interval. Based on this observation, which is substantiated by data analysis, we present a simple model for the steady-state loss probability that can be solved in closed form. This model assumes that there is no buffer, so that issues raised by the correlation of counts that is characteristic of packet traffic are bypassed.The longest interval that captures the relevant statistical fluctuations of backbone traffic is one second. Data collection on live commercial networks is costly, so byte and packet counts are usually collected over much longer time intervals; five minutes is a lower bound. This creates no problem in estimating the mean of the Normal distribution, but it makes direct estimation of the variance for one-second counts infeasible. Routers collect flow data; flows are analogous to “calls” in telephony. By modeling the number of active flows as an M/G/∞ queue and assuming that packets in a flow are spread uniformly in time, an equation for the variance of (say) one-second counts in terms of measured quantities is derived. The efficacy of this formula is demonstrated by applying it to data.