Bacteriophages are synergistic with bacterial interference for the prevention of Pseudomonas aeruginosa biofilm formation on urinary catheters.

AIMS: We hypothesized that pretreating urinary catheters with benign Escherichia coli HU2117 plus an antipseudomonal bacteriophage (ΦE2005-A) would prevent Pseudomonas aeruginosa biofilm formation on catheters--a pivotal event in the pathogenesis of catheter-associated urinary tract infection (CAUTI). METHODS AND RESULTS: Silicone catheter segments were exposed to one of four pretreatments (sterile media; E. coli alone; phage alone; E. coli plus phage), inoculated with P. aeruginosa and then incubated up to 72 h in human urine before rinsing and sonicating to recover adherent bacteria. Pseudomonas aeruginosa adherence to catheters was almost 4 log(10) units lower when pretreated with E. coli plus phage compared to no pretreatment (P < 0.001) in 24-h experiments and more than 3 log(10) units lower in 72-h experiments (P < 0.05). Neither E. coli nor phage alone generated significant decreases. CONCLUSIONS: The combination of phages with a pre-established biofilm of E. coli HU2117 was synergistic in preventing catheter colonization by P. aeruginosa. SIGNIFICANCE AND IMPACT OF THE STUDY: We describe a synergistic protection against colonization of urinary catheters by a common uropathogen. Escherichia coli-coated catheters are in clinical trials; adding phage may offer additional benefit.

Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.

BACKGROUND: Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. OBJECTIVES: To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). ANIMALS: Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). METHODS: Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. RESULTS: A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.

Missense mutation in PFKM associated with muscle-type phosphofructokinase deficiency in the Wachtelhund dog.

Hereditary muscle-type phosphofructokinase (PFK) deficiency causing intermittent hemolytic anemia and exertional myopathy due to a single nonsense mutation in PFKM has been previously described in English Springer and American Cocker Spaniels, Whippets, and mixed breed dogs. We report here on a new missense mutation associated with PFK deficiency in Wachtelhunds. Coding regions of the PFKM gene were amplified from genomic DNA and/or cDNA reverse-transcribed from RNA of EDTA blood of PFK-deficient and clinically healthy Wachtelhunds and control dogs. The amplicons were sequenced and compared to the published canine PFKM sequence. A point mutation (c.550C>T, in the coding sequence of PFKM expressed in blood) was found in all 4 affected Wachtelhunds. This missense mutation results in an amino acid substitution of arginine (Arg) to tryptophan (Trp) at position 184 of the protein expressed in blood (p.Arg184Trp). The mutation is located within an alpha-helix, and based on the SIFT analysis, this amino acid substitution is not tolerated. Amplifying the region around this mutation and digesting the PCR fragment with the restriction enzyme MspI, produces fragments that readily differentiate between PFK-deficient, carrier, and normal animals. Furthermore, we document 2 additional upstream PFKM exons expressed in canine testis but not in blood. Despite their similar phenotypic appearance and use for hunting, Wachtelhunds and English Springer Spaniels are not thought to have common ancestors. Thus, it is not surprising that different mutations are responsible for PFK deficiency in these breeds. Knowledge of the molecular basis of PFK deficiency in Wachtelhunds provides an opportunity to screen and control the spread of this deleterious trait.

Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women.

We examined the effects of exercise intensity and training on rates of lipolysis, plasma free fatty acid (FFA) appearance (R(a)), disappearance (R(d)), reesterification (R(s)), and oxidation (R(oxP)) in postmenopausal (PM) women. Ten sedentary but healthy women (55 ± 0.6 yr) completed 12 wk of supervised endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (Vo(2peak))]. Flux rates were determined by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H(5)]glycerol during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% Vo(2peak) (PRE)] and two posttraining exercise trials [at power outputs that elicited 65% pretraining Vo(2peak) (absolute training; ABT) and 65% posttraining Vo(2peak) (relative training; RLT)]. Initial body weights (68.2 ± 4.5 kg) were maintained over the course of study. Training increased Vo(2peak) by 16.3 ± 3.9% (P < 0.05) (Zarins ZA, Wallis GA, Faghihnia N, Johnson ML, Fattor JA, Horning MA and Brooks GA. Metabolism 58: 9: 1338-1346, 2009). Glycerol R(a) and R(d) were elevated in the RLT trial (P < 0.05), but not the ABT trial after training. Rates of plasma FFA R(a), R(d), and R(oxP) were elevated during the ABT compared with PRE trial (P < 0.05). FFA R(s) accounted for most (50-70%) of R(d) during exercise; training reduced FFA R(s) during ABT, but not RLT compared with PRE. We conclude that, despite the large age-related decrease in metabolic scope in PM women, endurance training increases the capacities for FFA mobilization and oxidation during exercises of a given power output. However, after menopause, total lipid oxidation capacity remains low, with reesterification accounting for most of FFA R(d).

Molecular assessment of salt-tolerant, perchlorate- and nitrate-reducing microbial cultures.

The microbial ecology of enrichment cultures adapted to the removal of perchlorate and nitrate from high salt solutions and ion-exchange brines was examined over a period of four years using denaturing gradient gel electrophoresis and total DNA extraction with cloning and in each case partial sequencing of the 16S rDNA genes. The cultures studied were a result of enrichment from marine sediment inoculum initiated in 2001. The resulting enrichment cultures were fed perchlorate, or perchlorate and nitrate, in a 3% (w/v) NaCl defined medium or ion-exchange brines (5.6% NaCl) containing perchlorate and nitrate with acetate as the electron donor. All of the sequences' closest matches in the NCBI GenBank database were to marine or salt-tolerant organisms. Strains belonging to the genera Halomonas or Marinobacter were found to dominate in cultures that were fed nitrate in addition to perchlorate, but were effectively absent from cultures fed perchlorate alone. The cultures fed perchlorate as the sole electron acceptor were relatively diverse with the dominant sequences belonging to the genera Dechloromarinus and Denitromonas. A study examining the effects of growing the cultures on different electron acceptors to the cultures revealed that Denitromonas may be more dominant than Dechloromarinus as the salt-tolerant, perchlorate-reducing organism.

Application of ceramic membranes with pre-ozonation for treatment of secondary wastewater effluent.

Membrane fouling is an inevitable problem when microfiltration (MF) and ultrafiltraion (UF) are used to treat wastewater treatment plant (WWTP) effluent. While historically the use of MF/UF for water and wastewater treatment has been almost exclusively focused on polymeric membranes, new generation ceramic membranes were recently introduced in the market and they possess unique advantages over currently available polymeric membranes. Ceramic membranes are mechanically superior and are more resistant to severe chemical and thermal environments. Due to the robustness of ceramic membranes, strong oxidants such as ozone can be used as pretreatment to reduce the membrane fouling. This paper presents results of a pilot study designed to investigate the application of new generation ceramic membranes for WWTP effluent treatment. Ozonation and coagulation pretreatment were evaluated to optimize the membrane operation. The ceramic membrane demonstrated stable performance at a filtration flux of 100 gfd (170LMH) at 20 degrees C with pretreatment using PACl (1mg/L as Al) and ozone (4 mg/L). To understand the effects of ozone and coagulation pretreatment on organic foulants, natural organic matter (NOM) in four waters - raw, ozone treated, coagulation treated, and ozone followed by coagulation treated wastewaters - were characterized using high performance size exclusion chromatography (HPSEC). The HPSEC analysis demonstrated that ozone treatment is effective at degrading colloidal NOMs which are likely responsible for the majority of membrane fouling.

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue.

BACKGROUND: Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue. METHODS: Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between -195 and -45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined. RESULTS: The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra- and inter-observer difference was small for both AAT (-1.85+/-1.28% and 7.85+/-6.08%; respectively) and TAT (3.56+/-0.83% and -4.56+/-0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, P<0.0001 and P=0.009), waist circumference (r=0.49 and 0.57, P<0.0001 for both) and body mass index (r=0.47 and 0.58, P<0.0001 for both). CONCLUSION: Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes.

Kinetics of nitrate and perchlorate reduction in ion-exchange brine using the membrane biofilm reactor (MBfR).

Several sources of bacterial inocula were tested for their ability to reduce nitrate and perchlorate in synthetic ion-exchange spent brine (30-45 g/L) using a hydrogen-based membrane biofilm reactor (MBfR). Nitrate and perchlorate removal fluxes reached as high as 5.4 g Nm(-2)d(-1) and 5.0 g ClO(4)m(-2)d(-1), respectively, and these values are similar to values obtained with freshwater MBfRs. Nitrate and perchlorate removal fluxes decreased with increasing salinity. The nitrate fluxes were roughly first order in H(2) pressure, but roughly zero-order with nitrate concentration. Perchlorate reduction rates were higher with lower nitrate loadings, compared to high nitrate loadings; this is a sign of competition for H(2). Nitrate and perchlorate reduction rates depended strongly on the inoculum. An inoculum that was well acclimated (years) to nitrate and perchlorate gave markedly faster removal kinetics than cultures that were acclimated for only a few months. These results underscore that the most successful MBfR bioreduction of nitrate and perchlorate in ion-exchange brine demands a well-acclimated inoculum and sufficient hydrogen availability.

Fluidized bed reactor for the biological treatment of ion-exchange brine containing perchlorate and nitrate.

The removal of perchlorate and nitrate from contaminated drinking water using regenerable ion-exchange processes produces a high salt brine (3-10% NaCl) laden with high concentrations of perchlorate and nitrate. This bench-scale research describes the operation of acetate-fed granular activated carbon (GAC) based fluidized bed reactors (FBR) for perchlorate-only, and combined nitrate and perchlorate removal from synthetic brine (6% NaCl). The GAC was inoculated with a salt-tolerant culture developed by the authors and used previously in batch systems. An FBR was an effective design for perchlorate reduction and exhibited first-order degradation kinetics with respect to perchlorate concentrations. Nitrate was also removed by the organisms in the column and had no negative effects on the removal of perchlorate using the FBR design. However, at higher concentrations of nitrate the FBR was more difficult to operate due to loss of carbon and biomass from the formation of nitrogen bubbles and the high recycle flow rates needed.

Perchlorate and nitrate treatment by ion exchange integrated with biological brine treatment.

Groundwater contaminated with perchlorate and nitrate was treated in a pilot plant using a commercially available ion exchange (IX) resin. Regenerant brine concentrate from the IX process, containing high perchlorate and nitrate, was treated biologically and the treated brine was reused in IX resin regeneration. The nitrate concentration of the feed water determined the exhaustion lifetime (i.e., regeneration frequency) of the resin; and the regeneration condition was determined by the perchlorate elution profile from the exhausted resin. The biological brine treatment system, using a salt-tolerant perchlorate- and nitrate-reducing culture, was housed in a sequencing batch reactor (SBR). The biological process consistently reduced perchlorate and nitrate concentrations in the spent brine to below the treatment goals of 500 microg ClO4(-)/L and 0.5mg NO3(-)-N/L determined by equilibrium multicomponent IX modeling. During 20 cycles of regeneration, the system consistently treated the drinking water to below the MCL of nitrate (10 mgNO3(-)-N/L) and the California Department of Health Services (CDHS) notification level of perchlorate (i.e., 6 microg/L). A conceptual cost analysis of the IX process estimated that perchlorate and nitrate treatment using the IX process with biological brine treatment to be approximately 20% less expensive than using the conventional IX with brine disposal.

Heat capacity of the liquid-liquid mixture nitrobenzene and dodecane near the critical point.

The heat capacity of the liquid-liquid mixture nitrobenzene-dodecane has been measured for the first time near its upper critical consolute point using an adiabatic calorimeter. The theoretical expression for the heat capacity near the critical point was applied to our combined data runs. The critical exponent alpha was determined to be 0.124+/-0.006, which was consistent with theoretical predictions. When alpha was fixed at its theoretical value of 0.11, our value for the amplitude ratio A(+)A(-)=0.58+/-0.02 was consistent with experimental determinations and theoretical predictions. However, the two-scale-factor universality ratio X, now consistent among experiments and theories with a value between 0.019 and 0.020, was violated in this system when using a previously published value for the correlation length.

Feeding patterns in a small-bodied nocturnal folivore (Avahi laniger) and the influence of leaf chemistry: a preliminary study.

We present data on feeding patterns in Avahi laniger and compare these data to temporal variations in leaf chemistry. Because A. laniger is one of the smallest folivorous primates and has a monogastric stomach, we hypothesized that this lemur would display behavioural adaptations to a leaf-based diet by scheduling feeding times when leaves were of highest quality. Data were collected from May to August 2004 at the Vatoharanana site in Ranomafana National Park, Madagascar. A. laniger fed during different time periods despite leaf carbohydrate and protein concentrations exhibiting little variation throughout the night. Although tannin concentrations exhibited temporal fluctuations, they did not covary with A. laniger feeding times. We suggest that A. laniger feeding times cannot be explained entirely by variations in leaf chemistry.

Doublets and low-frequency fatigue in potentiated human muscle.

AIM: To test the hypothesis that doublets compensate for low-frequency fatigue. Doublets increase force output from muscles stimulated at low frequencies. Low-frequency fatigue is a decline in the force elicited by low-frequency stimulation. METHODS: Human flexor carpi radialis muscles were stimulated with 20 Hz trains with and without an initial doublet and with and without low-frequency fatigue and the resulting force response measured. RESULTS: An initial doublet caused an increase in the maximum rate of force rise of 179.6 +/- 27.9% in rested and 242.9 +/- 37.7% in muscles with low-frequency fatigue, and a substantial enhancement in force in the first three inter-pulse intervals after the extra pulse. The magnitude and time course of the early doublet enhancement were very similar regardless of low-frequency fatigue, consistent with current theories regarding the mechanisms of the doublet effect and of low-frequency fatigue. By the end of the 1 s stimulus train, force enhancement was insignificant in rested muscles and was small and subject-dependent in muscles with low-frequency fatigue (17.3 +/- 8.1% of force without a doublet), reducing the force deficit by 25.2 +/- 5.5%. CONCLUSIONS: The time course of doublet force enhancement implies that an initial doublet may effectively compensate for the deficit in rate of force rise in muscles with low-frequency fatigue, but may not compensate for force deficits beyond the first few inter-pulse intervals.

14C activity and global carbon cycle changes over the past 50,000 years.

A series of 14C measurements in Ocean Drilling Program cores from the tropical Cariaco Basin, which have been correlated to the annual-layer counted chronology for the Greenland Ice Sheet Project 2 (GISP2) ice core, provides a high-resolution calibration of the radiocarbon time scale back to 50,000 years before the present. Independent radiometric dating of events correlated to GISP2 suggests that the calibration is accurate. Reconstructed 14C activities varied substantially during the last glacial period, including sharp peaks synchronous with the Laschamp and Mono Lake geomagnetic field intensity minimal and cosmogenic nuclide peaks in ice cores and marine sediments. Simulations with a geochemical box model suggest that much of the variability can be explained by geomagnetically modulated changes in 14C production rate together with plausible changes in deep-ocean ventilation and the global carbon cycle during glaciation.

Patient evaluation of the hotel function of hospitals.

BACKGROUND: A means of measuring patient satisfaction is essential in the effort to improve the quality of health care delivered in our nation's hospitals. Accurate feedback allows employers to better meet patients' needs and allows hospital administrators to improve service delivery. Patients are empowered by having a voice in the manner in which their health care is delivered. Moreover, improving the efficiency of the health care delivery system decreases health care costs. Hospital comparisons can be made readily available to a large audience through the Internet, resulting in empowerment of the patient and a universal improvement in hospital care. This is the first multi-institutional analysis of patient satisfaction among New York City and northern New Jersey area tertiary care hospitals. In this study, we evaluated the patient-assessed hotel function of hospitals in a single geographic region to determine whether clinically and statistically significant differences would be revealed that could provide beneficial information to stakeholders in the healthcare system. METHODS: Patients (n = 261) who had spent a night during the past year in one of eleven hospitals within 60 miles of New York City were chosen at random from doctors' waiting rooms. On average, 24 patients from each hospital were surveyed. They were asked to complete a questionnaire that rated the various departments in the hospital on qualities such as courtesy, promptness, and cleanliness. The questionnaire also rated important characteristics of the patient experience, such as the ease of parking and the taste of the food. Each item on the survey was coded on a scale of 1 to 10 with 10 being the most positive response. The 26 specific questions were divided into 14 domains. Averages in each domain were compared by gender, age, and hospital identity, attractiveness, and setting. All statistical calculations were performed using SPSS/PC, and means were compared using t-tests. RESULTS: Analysis designed to evaluate outcomes between each of the possible 54 pairs of hospitals comparisons revealed statistically significant differences as often as 44% of the time in some outcomes measures (logistics), but as rarely as 7% of the time in others (billing function). Clinically significant differences (>2 units per scale) were frequently evident, although the ranges differed dramatically depending on the domains surveyed. Although age, gender, and race/ethnicity were generally not predictive of satisfaction, non-urban setting was correlated with greater patient satisfaction. CONCLUSION: By having access to patient satisfaction comparisons among hospitals, patients are empowered to make better choices, employers can identify and adapt to patient preferences, and administrators can improve the services delivered and decrease health care costs by improving efficiency. Although our study was somewhat limited by patient selection biases, the study's results suggest that Internet-based tools of comparison will enable patients to make free and informed decisions about their health care by comparing local hospitals and voting on their impressions of the facilities from which they receive care.

Glacial surface temperatures of the southeast Atlantic Ocean.

A detailed record of sea surface temperature from sediments of the Cape Basin in the subtropical South Atlantic indicates a previously undocumented progression of marine climate change between 41 and 18 thousand years before the present (ky B.P.), during the last glacial period. Whereas marine records typically indicate a long-term cooling into the Last Glacial Maximum (around 21 ky B.P.) consistent with gradually increasing global ice volume, the Cape Basin record documents an interval of substantial temperate ocean warming from 41 to 25 ky B.P. The pattern is similar to that expected in response to changes in insolation owing to variations in Earth's tilt.

Ischemia causes muscle fatigue.

The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia.

PURPOSE: The aim of the present study was to evaluate the effect of the cyclosporine derivative valspodar (PSC 833; Amdray, Novartis Pharma, Basel, Switzerland) on the concentration of daunorubicin (dnr) in leukemic blast cells in vivo during treatment. PATIENTS AND METHODS: Ten patients with acute myeloid leukemia (AML) were included. Leukemic cells from seven of the patients were P-glycoprotein (Pgp)-positive. dnr 100 mg/m(2) was given as a continuous infusion over 72 hours. After 24 hours, a loading dose of valspodar was given, followed by a 36-hour infusion of 10 mg/kg per 24 hours. Blood samples were drawn at regular intervals, and concentrations of dnr and its main metabolite, daunorubicinol, in plasma and isolated leukemic cells were determined by high-pressure liquid chromatography. RESULTS: The mean dnr concentrations in leukemic cells 24 hours after the start of infusion (before valspodar) were 18.8 micromol/L in Pgp-negative samples and 13.5 micromol/L in Pgp-positive samples. After 8 hours of valspodar infusion, these values were 25.8 and 24.0 micromol/L, respectively. The effect of valspodar was evaluated from the ratio of the area under the curve (AUC) for dnr concentration versus time in leukemic cells to the AUC for dnr concentration against time in the plasma. For the seven patients with Pgp-positive leukemia, the mean ratio increased by 52%, from 545 on day 1 to 830 on day 2 (P<.05) when valspodar was given. In the three patients with Pgp-negative leukemia, no significant difference was observed. CONCLUSION: These results strongly suggest that valspodar, by interacting with Pgp, can increase the cellular uptake of dnr in leukemic blasts in vivo.

Synchronous radiocarbon and climate shifts during the last deglaciation.

Radiocarbon data from the Cariaco Basin provide calibration of the carbon-14 time scale across the period of deglaciation (15,000 to 10, 000 years ago) with resolution available previously only from Holocene tree rings. Reconstructed changes in atmospheric carbon-14 are larger than previously thought, with the largest change occurring simultaneously with the sudden climatic cooling of the Younger Dryas event. Carbon-14 and published beryllium-10 data together suggest that concurrent climate and carbon-14 changes were predominantly the result of abrupt shifts in deep ocean ventilation.

How animals move: an integrative view.

Recent advances in integrative studies of locomotion have revealed several general principles. Energy storage and exchange mechanisms discovered in walking and running bipeds apply to multilegged locomotion and even to flying and swimming. Nonpropulsive lateral forces can be sizable, but they may benefit stability, maneuverability, or other criteria that become apparent in natural environments. Locomotor control systems combine rapid mechanical preflexes with multimodal sensory feedback and feedforward commands. Muscles have a surprising variety of functions in locomotion, serving as motors, brakes, springs, and struts. Integrative approaches reveal not only how each component within a locomotor system operates but how they function as a collective whole.