Two little girls in blue: waltz song

https://digitalcommons.ithaca.edu/sheetmusic/1073/thumbnail.jp

And then there were four: a study of UK market concentration - causes, consequences and the scope for market adjustment

While concentration measures are a good indicator of market structure, the link with competitiveness is more complex than often assumed. In particular, the modern theory of industrial organisation makes no clear statement regarding the impact of concentration on competition - the focus of this paper is concentration and no inferences are made about competitive aspects of the market. The extent and nature of concentration within the UK listed company audit market as at April, 2002 and, pro forma, after the collapse of Andersen is documented and analysed in detail (by firm, market segment and industry sector). The largest four firms held 90 per cent of the market (based on audit fees) in 2002, rising to 96 per cent with the demise of Andersen. A single firm, Pricewaterhouse-Coopers, held 70 per cent or more of the share of six out of 38 industry sectors, with a share of 50 per cent up to 70 per cent in a further seven sectors. The provision of non-audit services (NAS) by incumbent auditors is also considered. As at April 2002, the average ratio of non-audit fees (paid to auditor) to audit fees was 208 per cent, and exceeded 300 per cent in seven sectors. It is likely, however, that disposals by firms of their management consultancy and outsource firms, combined with the impact of the Smith Report on audit committees will serve to reduce these ratios. Another finding is that audit firms with expertise in a particular sector appeared to earn significantly higher nonaudit fees from their audit clients in that sector. The paper thus provides a solid empirical basis for debate. The subsequent discussion considers the implications for companies and audit firms of the high level of concentration in the current regulatory climate, where no direct regulatory intervention is planned

Stable isotope analysis of soft tissues from mummified human remains

Mummies are faunal remains that include the preservation of soft tissues, such as skin, muscle, nails and hair as well as bone. These soft tissues are generally rich in collagen or keratin proteins and thus provide potentially suitable material for stable isotope studies. When preserved, such tissues can provide high-resolution information about the diet and migration of humans in the weeks and months before death. Hair, nails and soft tissue provide short-term (months) dietary information in contrast to bone which will represent 5–20 years of dietary history prior to death, depending on the bone analysed. Such high-resolution data can answer questions on the season of death, seasonality of food resources and the movement and relocation of people. This review begins with a summary of the most common isotope techniques (13C/12C, 15N/14N) and the tissues concerned, followed by an analysis of the key questions that have been addressed using these methods. Until relatively recently work has focused on bulk protein isotope analysis, but in the last 10 years this has been expanded to on-line compound-specific amino acid analysis and to a wider variety of isotopes (18O/16O, 2H/1H and 34S/32S) and these applications are also discussed

Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial

<p>ABSTRACT</p> <p>Purpose</p> <p>Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity.</p> <p>Experimental design</p> <p>286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31). Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated.</p> <p>Results</p> <p>No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS) and overall survival (OS) did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values < 0.001 for all associations) and significant linkage disequilibrium among these was indicated.</p> <p>Conclusion</p> <p>No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.</p

Potencijalna upotreba izotopa važnih za okoliš u ispitivanju migracije onečišćujućih tvari

This article presents the use of natural abundance stable isotope (hydrogen, carbon, nitrogen, oxygen, chlorine) analysis data as a tool for providing important information about the origin of contaminants, the contribution of different sources to a multi-source plume, characterisation of their complex transport (rate and mechanisms) and for evaluating the success of contaminated site remediation. Isotopic signatures of contaminants are useful tracers of their sources, while isotopic fractionation can be used to quantitatively assess the progress of an environmental process such as biodegradation. This new isotopic approach is reliable and can offer more information than traditional techniques in pollutant migration studies, particularly after waste disposal. During biological degradation of any organic compound, molecules containing lighter isotopes are degraded, and the portion of heavier isotopes in the substrate is increased, identifying specific microbial roles in biogeochemical cycling. Since isotopic fractionation is proportional to degradation, depending on the type of contamination, a microbial degradation of 50 % to 99 % of the initial concentration can be quantified using isotope ratio measurements.Cilj ovog rada je da se prikaže korištenje podataka analize prirodne obilnosti stabilnih izotopa (vodika, ugljika, dušika, kisika i klora) kao alata za dobivanje važnih informacija o porijeklu onečišćujućih tvari, doprinosu različitih multikomponentnih onečišćivača, karakterizaciji njihova kompleksnog transporta (brzine i mehanizma) i praćenja uspjeha remedijacije onečišćenih mjesta. Izotopski sadržaji onečišćujućih tvari koriste se kao traseri za određivanje njihovih izvora, dok se izotopsko frakcioniranje može iskoristiti za kvantitativnu procjenu toka procesa kao što je biodegradacija. Takav nov izotopski pristup je pouzdan i nudi više informacija od tradicionalnih tehnika kontrole putovanja onečišćivala, napose nakon odlaganja opasnog otpada na zemljištu. Za vrijeme biodegradacije nekog organskog spoje molekule koje sadržavaju lake izotope lakše se degradiraju, a dio težih izotopa u supstratu se povećava, što upućuje na mikrobiološku ulogu u biokemijskom ciklusu. Kako je izotopsko frakcioniranje proporcionalno degradaciji zavisno od tipa onečišćenja, korištenjem podataka mjerenja izotopskih odnosa može se procijeniti mikrobiološka degradacija od 50 % do 99 % od početne koncentracije

Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy

Managed Metapopulations: Do Salmon Hatchery ‘Sources’ Lead to In-River ‘Sinks’ in Conservation?

Maintaining viable populations of salmon in the wild is a primary goal for many conservation and recovery programs. The frequency and extent of connectivity among natal sources defines the demographic and genetic boundaries of a population. Yet, the role that immigration of hatchery-produced adults may play in altering population dynamics and fitness of natural populations remains largely unquantified. Quantifying, whether natural populations are self-sustaining, functions as sources (population growth rate in the absence of dispersal, λ>1), or as sinks (λ<1) can be obscured by an inability to identify immigrants. In this study we use a new isotopic approach to demonstrate that a natural spawning population of Chinook salmon, (Oncorhynchus tshawytscha) considered relatively healthy, represents a sink population when the contribution of hatchery immigrants is taken into consideration. We retrieved sulfur isotopes (34S/32S, referred to as δ34S) in adult Chinook salmon otoliths (ear bones) that were deposited during their early life history as juveniles to determine whether individuals were produced in hatcheries or naturally in rivers. Our results show that only 10.3% (CI = 5.5 to 18.1%) of adults spawning in the river had otolith δ34S values less than 8.5‰, which is characteristic of naturally produced salmon. When considering the total return to the watershed (total fish in river and hatchery), we estimate that 90.7 to 99.3% (CI) of returning adults were produced in a hatchery (best estimate = 95.9%). When population growth rate of the natural population was modeled to account for the contribution of previously unidentified hatchery immigrants, we found that hatchery-produced fish caused the false appearance of positive population growth. These findings highlight the potential dangers in ignoring source-sink dynamics in recovering natural populations, and question the extent to which declines in natural salmon populations are undetected by monitoring programs

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed