Transformer Coolers feature portable design
Installed on transformer, ForZair(TM) HeatSink auxiliary coolers immediately reduce temperature of dielectric cooling oil. Units can be transferred from one overloaded substation to another, providing relief wherever it is needed most. They employ mono-aluminum extruded fin-tubes and Cardinal transformer oil pumps with glandless design that prevents leaks. To augment cooling on 1-60 Mva OA, FA, or FOA transformers, coolers come ready for fully self-contained operations.
Efficient transformer cooling wherever and whenever you need it London, Ontario - Unifin, a world-leading supplier of cooling equipment and transformer oil pumps and valves to the Power Generation and Power Transformer industries, offers ForZair(TM) HeatSink auxiliary transformer cooler. The strong performance of this portable and highly efficient cooler allows increased overload and extends transformer life.
The ForZair(TM) HeatSink cooler can be installed on a transformer quickly to immediately reduce the temperature of the dielectric cooling oil. With its small footprint, low profile and quick-connect hoses, the ForZair(TM) HeatSink cooler can be transferred easily from one overloaded substation to another, providing quick relief wherever it is needed most.
The ForZair(TM) line of coolers feature Unifin’s unique Mono-Aluminum Extruded Fin-Tubes and the industry’s best plate fin technology, both of which provide optimal heat transfer efficiency and exceptional durability. The ForZair(TM) HeatSink coolers employ Cardinal Transformer Oil pumps, with a glandless design that prevents leaks in demanding transformer oil applications.
To augment cooling on 1Mva to 60 Mva OA, FA or FOA transformers these rugged portable coolers come ready for fully self-contained operations. The skid-mounted package is mounted on a durable frame designed for easy lifting by forklift or overhead crane.
p53 Mediates Particulate Matter-induced Alveolar Epithelial Cell Mitochondria-regulated Apoptosis
Rationale: Exposure to particulate matter (PM) causes lung cancer by mechanisms that are unknown, but p53 dysfunction is implicated.
Objective: We determined whether p53 is required for PM-induced apoptosis in both human and rodent alveolar type (AT) 2 cells.
Methods: A well-characterized form of urban PM was used to determine whether it induces mitochondrial dysfunction (mitochondrial membrane potential change [??m] and caspase-9 activation), p53 protein and mRNA expression, and apoptosis (DNA fragmentation and annexin V staining) in vitro using A549 cells and primary isolated human and rat AT2 cells. The role of p53 was assessed using inhibitors of p53-dependent transcription, pifithrin-?, and a genetic approach. In mice, the in vivo effects of PM causing p53 expression and apoptosis were assessed 72 h after a single PM intratracheal instillation.
Measurements and Main Results: PM-induced apoptosis in A549 cells was characterized by increased p53 mRNA and protein expression, mitochondrial translocation of Bax and p53, a reduction in ??m, and caspase-9 activation, and these effects were blocked by inhibiting p53-dependent transcription. Similar findings were noted in primary isolated human and rat AT2 cells. A549-?° cells that are incapable of mitochondrial reactive oxygen species production were protected against PM-induced ??m, p53 expression, and apoptosis. In mice, PM induced p53 expression and apoptosis at the bronchoalveolar duct junctions.
Conclusions: These data suggest a novel interaction between p53 and the mitochondria in mediating PM-induced apoptosis that is relevant to the pathogenesis of lung cancer from air pollution.
Keywords: apoptosis; mitochondria; p53; particulate matter; reactive oxygen species
The p53 tumor suppressor is a transcription factor that regulates the expression of genes involved in the regulation of the cell cycle, DNA repair, and apoptosis. The finding that most human cancers have alterations in p53 or one of its regulatory family members, and that p53 knockout animals have an increased incidence of cancer, supports the importance of normal p53 function (1-3). Cells respond to DNA damage by activating p53-regulated genes involved in delaying cell cycle progression to facilitate DNA repair or, if DNA damage is extensive, promoting apoptosis. Exposure to airborne particulate matter (PM) is associated with an increased risk of cardiopulmonary diseases, including lung cancer, resulting in an estimated 500,000 excess deaths worldwide each year (4-7). Despite the magnitude of the public health consequences stemming from PM exposure, the precise mechanisms underlying the pathophysiologic effects of PM have not been established. There is evidence showing that exposure of lung epithelial cells and macrophages to PM results in a generation of reactive oxygen species (ROS), DNA damage, reduction in mitochondrial membrane potential change (??m), activation of caspase-9, mitochondria-regulated apoptosis, and inflammation (8-12). Humans exposed to environmental pollution have increased levels of several markers of genotoxicity, including DNA adducts, chromosome aberrations, sister chromatid exchanges, 8-oxo-dihydro-2′-deoxyguanosine, DNA strand breaks, ras oncogene activation, and p53 expression (5, 6, 13). There is controversy about the source of ROS production that causes apoptosis after PM exposure, but accumulating evidence implicates components in PM, such as transition metals (e.g., iron, vanadium, and others), polycyclic aromatic hydrocarbons, and quinones, as well as the mitochondria of lung target cells (6). However, the molecular mechanisms by which PM induces mitochondrial dysfunction and apoptosis are unclear.
Although p53 modulates apoptosis by complex and incompletely understood mechanisms, one established pathway involves activating the mitochondria-regulated death pathway by increasing gene expression of proapoptotic stimuli (e.g., Bax, Bak, BH3-only molecules, and others) while inhibiting the expression of antiapoptotic Bcl-2 family members (1, 2, 14-16). DNA-damaging agents can also induce a direct mitochondrial effect of p53, in part due to the BH3-like activity of p53, and in part due to the DNA binding domain of p53 interacting with Bcl-xl, promoting Bax/Bak-induced outer mitochondrial membrane permeabilization (1, 2, 17, 18). Recent evidence shows that p53-upregulated modulator of apoptosis is essential for coupling the nuclear and cytoplasmic proapoptotic function of p53 (19). A mechanistic link between mitochondrial ROS production and p53-induced apoptosis has been suggested (20, 21). We recently showed that p53 mediates asbestos-induced alveolar epithelial cell (AEC) mitochondria-regulated apoptosis in part by mechanisms involving p53-dependent transcription and a direct effect of p53 on the mitochondria (22). It is unknown whether p53 has a similar role in mediating PM-induced apoptosis.
Given the above findings, we reasoned that cross-talk between p53 and the mitochondria is important in causing AEC apoptosis after exposure to PM. We show that inhibitors of p53-dependent transcription (pifithrin-?, E6 overexpression, or dominant negative p53) prevent PM-induced apoptosis resulting from reductions in ??m, caspase-9 activation, increased p53 mRNA and protein expression, and mitochondrial translocation of BAX and p53. A role for mitochondrial-derived ROS is suggested by our findings that mitochondrial dysfunction, apoptosis, and p53 protein expression are abolished in A549-?° cells that are incapable of mitochondrial ROS production. Collectively, these data suggest a novel interaction between the mitochondria and p53 in mediating PM-induced AEC apoptosis, and that mitochondria-derived ROS have an important role in activating p53. Some of the results of these studies have been previously reported in the form of an abstract (23).
Chemical Composition and Antioxidant Activities of Buds and Leaves of Capers Cultivated in Turkey
Essential oils of caper (Capparis ovata Desf. var. canescens) buds and leaves obtained by steam distillation followed by solvent extraction were analyzed by GC and GC/MS. Eighty-six compounds were identified from the caper bud extract and 100 from the caper leaf oil. The major volatile compounds found in caper bud oil were benzyl alcohol (20.4%), furfural (7.4%), ethanal methyl pentyl acetal (5.9%), 4-vinyl guaiacol (5.3%), thymol (5.1%), octanoic acid (4.8%) and methyl isothiocyanate (4.5%). The major volatile compounds found in caper leaves were methyl isothiocyanate (20.0%), thymol (15.5%), 4-vinyl guaiacol (4.3%), hexyl acetate (3.6%) and trans-theaspirane (2.6%). These oils inhibited hexanal oxidation by 80% over 40 days at the level of 200 µg/mL. Also, they inhibited oxidation of 1,1-diphenyl-2-picrylhydrazyl hydrate by over 70% at the 500 µg/mL level. The dichloromethane and methanol extracts from caper buds and leaves exhibited higher antioxidant activities than those of their essential oils in both testing systems.
Capparis ovata Desf. var. canescens, Cappasidaceae, capers, essential oil composition, methyl isothiocyanate, benzyl alcohol, thymol, antioxidant activity.
Introduction
Capparis ovata Desf. var. canescens is one of the most commonly used seasoning ingredients in Mediterranean kitchens. Certain species and varieties of capers have been cultivated in special regions of the Mediterranean. These plants show strong resistance to harsh environmental conditions and have become an important economic resource in Southern Europe in recent decades (1-3). The main producers and exporters of capers are Spain, Morocco and Italy. Recently, packed brined caper products have been exported from Turky to European countries (4,5).
Capers are used for flavoring foods such as anchovies, pasta, pizza and commenrical frozen foods. Various parts of the caper plant, especially the buds and leaves, have been used in drugs, cosmetics and foods (4). The flavor intensity is directly related to bud maturity, and capers as large as 1 cm are commonly used. Caper leaves steeped in vinegar have been used to treat ulcers (6).
Chemical studies on Capports spinosa L. have reported the presence of glycosides, such as quercetin and kaempferol (7) and an anti-inflammatory principle (8). A few other substances such as alkaloids, glucosinolate, lipids flavonoids and miscellaneous isothiocyanate glucosides have also been identified in different species of genus Capparis (9-13).
Recently, the presence of antioridants in natural plants, including herbs and spices, has received much attention as a disease preventive substance (14). Natural antioxidants of plant origin are generally classified as vitamins, phenolic compounds, or flavonoids. In addition to the use of the plant per se, volatile or flavor chemicals isolated from various plants have been shown to have certain antioxidative activities.
The volatile compounds and antioxidative activity of caper buds and leaves have not been reported prior to this study. Therefore, in the present study, the chemical compositions and antioxidant activities of the essential oils obtained from both caper (Capparis ovata Desf. var. canescens) buds and leaves were investigated.
Experimental
Plant materials: The caper (Capparis ovata Desf. van canescens) plants were planted and harvested in SelcukluKonya, Turkey.
Isolation of volatile components: Each sample of dried ground caper buds or leaves (100 g) was placed in a 3 L round-bottom flask with 1 L deionized water. The solution was steam distilled for 4 h. The distillate (900 mL) was extracted with 100 mL dichloromethane using a liquid-liquid continuous extractor for 6 h. After the extract was dried over anhydrous sodium sulfate, the solvent was removed by a rotary flash evaporator (BUCHI 461 SWITZERLAND). The distillation was stopped when the volume of extract was reduced to approximately ImL and then the solvent was further removed under a purified N^sub 2^ stream until the volume was reduced to 0.5 mL. The volatile samples obtained from caper buds and leaves were stored at 5°C until analyzed.
Direct sequential extraction of caper samples with dichloromethane and methanol: Each sample of dried ground caper buds and leaves (200 g) was mixed with 100 mL dichloromethane in a 500 mL Erlenmeyer flask. The flask was shaken in a shaking water bath at room temperature for 7 h. After the solution was filtered, the filtrate was concentrated by a rotary flash evaporator at 50°C under reduced pressure. The residual materials were placed in a 500 mL Erlenmeyer flask and 100 mL methanol was added. The flask was shaken in a shaking water bath at room temperature for 7 h. After the solution was filtered, the filtrate was concentrated by a rotary flash evaporator at 50°C. The samples obtained from caper buds and leaves were stored in dark containers at -18°C until analyzed.
Organic Valley distribution center to boost economy of southwest Wisc
After more than a year of planning and construction, Organic Valley employees, state and local officials, business leaders and community members gathered in Cashton, Wisc., July 27 to celebrate the grand-opening of a new, $17.5 million Organic Valley Distribution Center. The new facility will serve as the primary warehouse and distribution center for Organic Valley, America’s largest cooperative of organic farmers and one of the nation’s leading organic brands.
The new facility provides ample evidence that organic products have moved from a niche market into mainstream consumption, co-op officials say.
The 80,000-square-foot distribution center is located on 40 acres in the Cashton Greens Business Park, an innovative new development where businesses will create and use renewable energy, such as biomass conversion of manure and sawdust, biodiesel and wind energy. It includes an automated storage and retrieval system.
“The new Organic Valley Distribution Center is a symbol of our co-op’s growth and its ongoing commitment to creating sustainable communities through organic farming,” said co-op CEO George Siemon. “Anchoring our distribution in Cashton is a step to fulfill our mission to help bring economic vitality to rural Wisconsin.”
The facility was built using a number of “green” building practices, including fly ash in the cement, recycled cotton for insulation in the walls and recycled steel throughout the building; a white roof to reflect the sun’s heat and decrease energy costs in refrigeration; waterless urinals; and automatic faucets that recharge their batteries with the flow of water.
Systematic Colocalization Errors between Acridine Orange and EGFP in Astrocyte Vesicular Organelles
Dual-color imaging of acridine orange (AO) and EGFP fused to a vesicular glutamate transporter or the vesicle-associated membrane proteins 2 or 3 has been used to visualize a supposedly well-defined subpopulation of glutamatergic astrocytic secretory vesicles undergoing regulated exocytosis. However, AO metachromasy results in the concomitant emission of green and red fluorescence from AO-stained tissue. Therefore, the question arises whether AO and EGFP fluorescence can be distinguished reliably. We used evanescent-field imaging with spectral fluorescence detection as well as fluorescence lifetime imaging microscopy to demonstrate that green fluorescent AO monomers inevitably coexist with red fluorescing AO dimers, at the level of single astroglial vesicles. The green monomer emission spectrally overlaps with that of EGFP and produces a false apparent colocalization on dual-color images. On fluorophore abundance maps calculated from spectrally resolved and unmixed single-vesicle spectral image stacks, EGFP is obscured by the strong green monomer fluorescence, precluding the detection of EGFP. Hence, extreme caution is required when deriving quantitative colocalization information from images of dim fluorescing EGFP-tagged organelles colabeled with bright and broadly emitting dyes like AO. We finally introduce FM4-64/EGFP dual-color imaging as a remedy for imaging a distinct population of astroglial fusion-competent secretory vesicles.
Fluorescence colocalization imaging is a powerful method for exploring the targeting of molecules to intracellular compartments and to screen for their association and interaction. In such experiments, distinct fluorophores are attached to the molecular targets of interest and imaged into spectrally separated detection channels. The fluorescence intensity in each channel ideally is dominated by spatial and concentration information derived from one fluorophore only. In this case, the dual-color fluorescence intensity images then correspond to diffraction-limited fluorophore maps, which can be overlaid or displayed side-by-side and the amount of colocalization can be calculated using different estimators (1-3).
One recent application of dual-color fluorescence detection has been the identification of vesicular compartments and study of their dynamics and fusion in nonsecretory exocytoses, the primary function of which is the transfer of the organelle membrane and its embedded proteins to the cell surface rather than the release of the vesicular cargo (4), or for studying regulated secretion of vesicular compartments in nonspecialized secretory cells (5), like macrophages, tibroblasts (6) or astrocytes (7) (see, e.g., (8) for review). In contrast to presynaptic nerve terminals or neuroendocrine cells that harbor large numbers of secretory vesicles close to the plasma membrane in readiness for exocytosis, nonsecretory cells lack such obvious morphological and functional specializations. Any attempt to study the release of biologically active substances from these cells must therefore first pinpoint the right vesicular compartment among the numerous endosomes, lysosomes, caveolae, and transport carriers, which is typically done by overexpressing a suitable marker (9) and then specifically follow the fate of the identified organelle, typically by using a second fluorescent reporter of membrane fusion.
Acridine orange (AO) is a weak base and metachromatic, fluorescent cationic dye (10,11) and photosensitizer (12,13) that stains live (12,14) and fixed tissue (15,16) with variable hues of fluorescence. At the cellular level, AO relocation and color change has been widely used as a test for cell viability (17,18), and for studying pH gradients across vesicular (19-22), as well as lyso- (23-25) and endosomal (26,27) membranes.
Dilute AO solutions or AO molecules bound to polyanions and isolated from each other emit green orthochromic fluorescence. Concentrated solutions, aggregates of AO, or molecules bound close by to neighboring sites, have orange or red metachromatic fluorescence (12,28). Note that “metachromasy” is here operationally defined as the hypsochromic (shift in absorption to shorter wavelength) and hypochromic (decrease in intensity of emitted fluorescence) change in color exhibited by certain dyes in the presence of water under the following conditions: 1), increase in dye concentration; 2), temperature decrease; 3), salting out; and 4), interaction with substrates that favor water intercalation and/or proximity or stacking of dye monomers. Like thionine, methylene blue, toluidine blue, rhodamine 6G, and phronine G, AO derives its melachromatic properties from the progressive formation of dimers and higher aggregates with increasing concentration (10,11). Low temperature and ionic strength favor AO metachromasy (27,29,30). Due to these photochemical properties and because of its passive accumulation inside acidic vesicles as well as the pronounced and rapid fluorescence change associated with exocytosis, AO has been popular as a reporter of membrane fusion and vesicle release (20,31,32). The opening of the fusion pore equilibrates the acidic luminal pH, leading to the rapid dequenching of AO fluorescence, which is observed as a loss of metachromatic red fluorescence and a concomitant flash of orthochromatic green fluorescence, followed by the dissipation of AO monomers in the extracellular space.
Modified interactions between salamander life stages caused by wildfire-induced sedimentation
Ecological communities are commonly affected by natural and periodic disturbance events. These disturbances may kill organisms, change competitive outcomes, alter habitats, or introduce new species to existing communities.If a disturbance suddenly adds a new species to a community it may be possible to directly observe the effects of this new species on the interactions of existing species, particularly if the dynamics between existing species had been observed before the introduction.
The effects of wildfire as a disturbance on chaparral plant communities are well studied.Wildfires also impact animal communities but studies examining animal-fire interactions generally consider only short-term population changes in small mammals and birds.Despite studies on the physical changes to stream habitats following fire,little is known about the effects of wildfire on aquatic organisms.Wildfire may indirectly affect aquatic systems by altering the surrounding terrestrial habitat. Fires may cause loss of vegetation, producing soil instability and landslides that change stream geomorphology.After rains, suspended sediments are often higher in streams flowing through burned areas.If organisms are introduced into the stream as a result of sedimentation, interactions among members of the stream community could be modified.
We have taken advantage of a major chaparral wildfire to examine if fire indirectly impacts the feeding ecology of the California newt.Adults breed in perennial streams that flow through the chaparral communities of the Santa Monica Mountains of southern California. Adult T. torosa spend most of the year on land and return to the streams to breed each spring.
Serum sickness-like reaction to cefuroxime: a case report and review of the literature
We report a case of a 34-year-old woman who received cefuroxime, a second-generation cephalosporin, as treatment for mastitis. She subsequently developed a serum sickness-like reaction (SSLR) with a generalized pruritic rash, joint pains, and fever. She improved upon treatment with systemic steroids. SSLR is well-described to cefaclor, a second-generation cephalosporin. However, there is a paucity of reports of SSLR to other cephalosporins such as this case.
A 34-year-old Caucasian woman presented to the dermatology clinic with a 2-week history of mastitis. The patient was breast-feeding following delivery of her sixth child 7 weeks earlier. She had no other significant past medical history. She was treated with 500 mg of oral cefuroxime twice daily and had completed the 10-day prescribed course. Six days into the course of treatment, she developed a rash on the scalp, which generalized over a 5-day time span to involve extensive areas of the trunk, arms, legs, and face. The rash was very pruritic, and individual lesions, which lasted less than 24 hours, were migratory. The patient also complained of intermittent fevers to 101[degrees]F and joint pains of the elbows, knees, and smaller joints of the hands. She specifically denied wheezing or shortness of breath. Her other current medications included prenatal vitamins. At the time of her delivery, 7 weeks previous, she had received pain medications, but no antibiotics. Acetaminophen and diphenhydramine, which she had tolerated well in the past, were taken orally as needed for the rash. Her reported allergies included tetracycline, penicillin, and erythromycin, all of which had caused skin rashes. As the rash continued to worsen in extent and severity, even after the antibiotic was completed, she was treated with oral methylprednisolone for 3 days, then one dose of oral prednisone 30 mg without improvement. She was then referred to the dermatology clinic.
The patient was a thin woman who scratched frequently, but otherwise was in no apparent distress. Skin examination revealed multiple confluent and extensive blanching urticarial plaques with dermatographism on the arms, legs, trunk, and face. No mucosal erosions were present, and there was no edema of the face or extremities. No cervical, occipital, axillary, or inguinal lymphadenopathy was noted. Pulmonary and cardiac examination was unremarkable. She had no swelling or erythema of the joints. The elbows, knees, and joints of the hands exhibited full range of motion. Laboratory studies, including a complete blood count, comprehensive metabolic panel, urinalysis, erythrocyte sedimentation rate, and C3, C4, and CH50 were all within the normal limits.
She was diagnosed with a serum sickness-like reaction (SSLR) to cefuroxime and admitted for 100 mg of intravenous methylprednisolone daily and oral antihistamines. Her symptoms and rash improved within 24 hours, and she was discharged on an extended tapering dose of prednisone starting at 40 mg daily, in addition to oral hydroxyzine, oral doxepin, and topical emollients. She experienced slow but steady resolution of her symptoms over the following 4 weeks.
SSLR is a specific type of drug reaction so named because of its clinical similarity to serum sickness. True serum sickness is a type III hypersensitivity reaction in which clinical signs and symptoms result from deposition of immune complexes in the skin, joints, and other organ systems. In contrast, SSLR is not associated with demonstrable circulating immune complexes. The reaction is acute, self-limited, and has been described in association with a variety of different medications. Although many drugs have been reported to cause SSLR, antibiotics are the major group of offending agents, particularly beta-lactam and sulfonamide antibiotics.
In most cases, signs and symptoms appear about a week after initiation of therapy. The most frequent finding is cutaneous involvement, typically in the form of erythema and urticarial lesions that are often migratory. In the series reported by Hebert et al, many of the urticarial wheals had dusky to purple centers, which were morphologically suggestive of erythema multiforme
The other primary clinical feature is joint involvement. Pain and swelling of the joints is a typical finding, and is usually polyarticular. Affected joints commonly include wrists, ankles, hips, and knees, which can become so severe that patients are unable to walk.
Although fever may occur, other systemic findings are less common. In contrast to true serum sickness, renal and hepatic involvement is rare.
Despite the impressive cutaneous findings and joint symptoms, a hallmark of SSLR is the benign outcome, although some patients do require hospitalization due to their severe symptoms. Treatment is typically symptomatic, usually with antihistamines and analgesics. The use of systemic corticosteroid treatment has been described in retrospective medical record reviews and in a number of case reports, although there is no accepted standardized therapy. Reports of SSLR describe benign outcomes with no sequelae.
Geological and biological evidence for regional drainage reversal during lateral tectonic transport, Marlborough, New Zealand
A 2500 km^sup 2^ mountainous river catchment in northern South Island, New Zealand, drained southwards until the late Quaternary. The catchment is being transported laterally at c. 36 mm a^sup -1^ relative to the southern South Island by dextral strike-slip motion along the Pacific-Australian Plate boundary (Alpine Fault). This lateral motion has moved the eastern half of the catchment from a zone of uplift into a zone of subsidence over the past million years, triggering drainage reversal. Sedimentation from the catchment switched from a sedimentary basin in the SE to a basin in the north. Profiles of river terrace remnants, formed from glacial outwash, show that drainage reversal occurred in the latter stages of deposition of the oldest recognizable terrace. Clast imbrication patterns and clast petrography in that terrace indicate southward flow, whereas flow had a northerly component in younger terraces and a nearby active river. In addition, 1.6% genetic divergence of fish on either side of the new drainage divide is consistent with late Quaternary separation by drainage reversal. The timing of drainage reversal is estimated from regional terrace correlation and the magnitude of the genetic divergence to be between 100 and 200 ka bp.
River capture is a commonly invoked phenomenon during the evolution of drainage systems, especially in tectonically active areas . Erosion of bedrock associated with this type of drainage reorientation causes major changes to regional geomorphology and can even lead to enhanced localized uplift of mountains and weakening of the underlying rocks. Drainage reversal can lead to major shins in sites of deposition and accumulation of sedimentary piles both onshore and offshore. This sedimentary redirection can have economic significance if gemstones or alluvial gold are part of the sediment load. Hence, river capture and drainage reversal can be important parts of the geological history and evolution of tectonically active areas.
Despite the significance of river capture and drainage reversal to geological history, unequivocal documentation of these events is difficult. Most such events are inferred from topographic features such as river bends (’elbows of capture’) and angles of stream confluences (’barbed tributaries’), or low divides (’wind gaps’). River terraces can indicate geomorphological changes, but these are commonly fragmentary. The sedimentary record can suggest that drainage reorientation events have happened by changes in sediment thickness and/or clast type . The relationships between catchment area and downstream sedimentary sequence thickness can also suggest that capture has occurred . AU the above indicators are entirely plausible, but they can have alternative explanations as well, and quantitative definition of nature and timing of drainage reorientation remains problematic.
In this study, we report evidence for regional drainage reversal, using several of the above criteria in combination, for a river system in which these criteria are particularly well preserved. We focus on topography, river terrace geometry, stream flow directions, and provenance studies, to determine the nature and timing of the capture event. In addition, we take advantage of a new and developing genetic approach to river capture studies that also provides evidence for river capture and an estimate of the age of that capture. Finally, we examine the capture event and associated drainage reversal in the context of the tectonic evolution of the region, as the whole catchment is transported by strike-slip faulting from an area of active uplift to an area of subsidence.
Idiopathic Nonspecific Interstitial Pneumonia: An Unrecognized Autoimmune Disease?
The recognition by Katzenstein and Fiorelli (1) that nonspecific interstitial pneumonia (NSIP) was a separate histopathologic entity from idiopathic pulmonary fibrosis (IPF) created great excitement because it helped to explain why some patients with IPF have more cellular inflammation on biopsy and/or more lymphocytes in bronchoalveolar lavage fluid and respond to corticosteroid therapy. NSIP has all these features (2), in addition to unique histopathology with spatial and temporal homogeneity of fibrosis as well as a better prognosis than IPF (2, 3). However, this new diagnostic category also raised questions and generated debate; the NSIP pattern has been found in association with various underlying diseases, including hypersensitivity pneumo-nitis, drug-related lung diseases, following an episode of acute respiratory distress syndrome, and in the context of connective tissue diseases, as first noted by Katzenstein and Fiorelli (1). Another concern was that NSIP may not be one entity because the histologic pattern has been split into three subtypes-that is, cellular, mixed, and fibrotic-in both the original description and other reports (1-3), whereas the radiologic findings are also heterogeneous (4). Furthermore, patient series showed that a subset of patients with fibrotic NSIP have a clearly unfavorable prognosis similar to that of IPF during long-term follow-up (5, 6). There was also debate as to whether NSIP is an early stage of IPF rather than a distinct entity (7).
NSIP was categorized as a provisional diagnosis in the 2002 American Thoracic Society and the European Respiratory Society consensus classification of idiopathic interstitial pneumonia (8), and a special workshop was organized to address its characterization. The NSIP workshop consisted of expert pathologists, radiologists,and clinicians, and concluded that idiopathic NSIP is a distinct clinico-radiologic and pathologic entity; the final report will come out soon. However, there is still a possibility that NSIP may not be a single entity and may overlap with different conditions. Among these, connective tissue diseases are the most intriguing, because NSIP has been recognized as a major histopathologic pattern of lung involvement in scleroderma, polymyositis-dermatomyositis, or Sjögren’s syndrome (9-11). In addition, in some patients, lung involvement precedes other systemic manifestations, making the distinction between idiopathic NSIP and lung involvement of connective tissue disease impossible at the time of diagnosis.
Many studies, including the NSIP workshop, reported that a substantial number of patients with idiopathic NSIP have positive autoantibodies (12). In this context, the study by Kinder and colleagues in this issue of the Journal (pp. 691-697) is timely and provides important information (13). The authors hypothesized that idiopathic NSIP is the lung manifestation of undifferentiated connective tissue disease (UCTD), a clinical entity with symptoms and/or signs suggestive of a connective tissue disease, but not fulfilling the classification criteria for any specific diagnostic entity (14). From their medical records, they identified 28 patients with idiopathic interstitial pneumonia (IIP) who met the criteria forUCTD and compared these patients with the control group of patients with IIP (n 5 47) who did not meet the UCTD criteria. Compared with the control group, the patients with UCTD-interstitial lung disease were more likely to have ground-glass opacity on high-resolution computed tomography (HRCT) and NSIP pattern on biopsy, and less likely to have honeycombing on HRCT or usual interstitial pneumonia (UIP) on biopsy. The authors also analyzed their biopsy-proven NSIP cases and found that a majority (88%) of patients previously classified as idiopathic NSIP met the criteria for UCTD. Based on these findings, Kinder and colleagues suggest that the clinical entity of idiopathic NSIP actually appears to be a lung manifestation of UCTD.
This study has several limitations, which makes it difficult to accept the conclusion that idiopathic NSIP is UCTD. First, this clinical series was retrospective and performed in one center with a small number of subjects. The total number of evaluable patients with IIP was 75, including 28 with UCTD, and surgical lung biopsy was performed in only 53% of the subjects. Second, there was uncertainty in the diagnosis of UCTD. Even though UCTD is a relatively new entity with no definitive consensus criteria for diagnosis yet available, the classification criteria used in rheumatology are as follows: (1) signs and symptoms suggestive of a connective tissue disease, but not satisfying the criteria of any defined disease entity; (2) positive result for antinuclear antibody test; and (3) disease duration of at least 3 years (14). Because a significant proportion of the patients initially diagnosed as UCTD eventually evolve into a defined connective tissue disease, longer follow-up might permit correct classification of many patients initially given this diagnosis. The authors’ criterion for UCTD was duration of 1 year, which may be too short a follow-up period and may increase the number of false-positive cases. Furthermore, the authors modified the second criterion of the presence of antinuclear antibodies to include nonspecific inflammatory markers, such as C-reactive protein, creatine kinase, aldolase, or sedimentation rate, which are not specific for connective tissue diseases. This modification might also result in more false-positive cases. A third limitation of this study is that autoantibodies were not tested for in all subjects, especially in the control group, and, even among those tested, uniform serologic panels were not performed.
Non-ideality by sedimentation velocity of halophilic malate dehydrogenase in complex solvents
ABSTRACT We have investigated the potential of sedimentation velocity analytical ultracentrifugation for the measurement of the second virial coefficients of proteins, with the goal of developing a method that allows efficient screening of different solvent conditions. This may be useful for the study of protein crystallization. Macromolecular concentration distributions were modeled using the Lamm equation with the approximation of linear concentration dependencies of the diffusion constant, D = D deg (1 + k^sub d^c), and the reciprocal sedimentation coefficients = s deg/(1 + k^sub a^c). We have studied model distributions for their information content with respect to the particle and its non-ideal behavior, developed a strategy for their analysis by direct boundary modeling, and applied it to data from sedimentation velocity experiments on halophilic malate dehydrogenase in complex aqueous solvents containing sodium chloride and 2-methyl-2,4-pentanediol, including conditions near phase separation. Using global modeling for three sets of data obtained at three different protein concentrations, very good estimates for k^sub s^ and s deg and also for D deg and the buoyant molar mass were obtained. It was also possible to obtain good estimates for k^sub D^ and the second virial coefficients. Modeling of sedimentation velocity profiles with the non-ideal Lamm equation appears as a good technique to investigate weak inter-particle interactions in complex solvents and also to extrapolate the ideal behavior of the particle.