bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Water Solubility Data on the Basis of HYBOT Descriptors. Part 3. Solubility of Solid Neutral Chemicals and Drugs
Authors: Raevsky Oleg A. , Raevskaja Olga E. , Schaper Klaus‐Jürgen
Published: July 2004

A detailed QSPR investigation of the water solubility (logS) of 1063 solid neutral chemicals, agrochemicals, drugs and prodrugs has been carried out. The application of the “General Solubility Equation” of Yalkowskyet al.resulted in a correlation between experimental and calculated solubility with rather modest statistic criteria. It was found that 191 compounds (18%) have calculated logS with deviations above one logarithmic unit. A comparison of experimental values with those calculated by an equation previously derived for liquid chemicals demonstrates that a part of the total set of compounds containing certain substructures such as chloroalkyls, phenyls, biphenyls, nitrogen (acyclic and in cycles), benzanthracenes, phenols, and chemicals with ether, ester, and N,N‐disubstituted carboxamide groups obey to the equation for liquids. Not unexpectedly, the other part of compounds containing both strong H‐bond acceptor and donor groups is essentially less soluble than calculated for compounds in the liquid state. It is proposed that this low solubility is connected with a specific H‐bond association of these compounds in their crystal lattice.
Dynamic Method of Determination of Octanol‐Water Partition Coefficient of 2,4‐Dihydroxythiobenzanilides in QSAR Studies
Authors: Persona Andrzej , Marczewska Barbara , Fekner Zygmunt , Senczyna Bogdan , Matysiak Joanna , Niewiadomy Andrzej
Published: July 2004

The dynamic method to determine the octanol‐water partition coefficient of 2,4‐dihydroxythiobenzanilides on the basis of the spectrophotometrical data was used. The spectrophotometric investigations of lipophilicity were based on the changes of absorbance in time as the result of permeation of analyte from the aqueous to the octanol phase. The interpretation of the data was based on the reference equation for the correlation of the experimental results and the calculated values obtained from the calibration process (log Pτ). The calculated log P values from three different approaches were used comparatively. The best correlation between the experimental log P values and those determined according to the Broto's method was found. The linear relationships between log P obtained in different ways and the logarithmically transformed 1/MIC values are presented. The strains of dermatophytes, moulds and yeasts were used as bioindicators. In comparison to the experimentally obtained log Pτ, the calculated log P values correlated better with bioactivity. Significantly higher correlation was found with the fungistatic activity determined on moulds and yeasts than on dermatophytes.
Unified analytical treatment of two‐electron multicenter integrals of central and noncentral interaction potentials over Slater orbitals
Authors: Guseinov I. I.
Published: July 2004

The complete orthonormal sets of Ψα‐exponential‐type orbitals (ETOs) (α = 1, 0, −1, −2, …) introduced by the author for expanding Slater‐type orbitals (STOs) enable two‐electron multicenter integrals of arbitrary central and noncentral interaction potentials (CIPs and NCIPs) to be reduced to one‐center two‐electron integrals. These one‐center integrals are advantageously reduced using Fourier convolution methods. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Role of Preoperative Transcatheter Arterial Chemoembolization for Resectable Hepatocellular Carcinoma: Relation between Postoperative Course and the Pattern of Tumor Recurrence
Authors: Sugo Hiroyuki , Futagawa Shunji , Beppu Tomoe , Fukasawa Masaki , Kojima Kuniaki
Published: July 2004

The effects of preoperative transcatheter arterial chemoembolization (TACE) were retrospectively evaluated in patients with resectable hepatocellular carcinoma (HCC). A total of 227 patients who underwent hepatectomy for HCC were studied (146 underwent preoperative TACE and 81 did not). We compared operative outcome, mortality, and disease‐free survival between TACE and non‐TACE groups. We also compared the pattern of recurrence and postrecurrence survival between subgroups according to staging. Of the 227 patients, 105 with tumor stage I‐II were assigned to group A (group A/TACE,n= 69; group A/non‐TACE,n= 36), and the remaining 122 with tumor stage III‐IV were assigned to group B (group B/TACE,n=77; group B/non‐TACE,n=45). Complete necrosis was found to be more frequent in the TACE group (p< 0.01). Operating time, blood loss, and mortality did not differ between those who did and did not undergo preoperative TACE. TACE did not significantly improve disease‐free survival within either the entire TACE group or group A/TACE. In contrast, in group B/TACE the disease‐free survival rates were significantly higher than in group B/non‐TACE. Furthermore, both extrahepatic metastasis and diffuse intrahepatic metastasis were significantly more frequent in group B/non‐TACE than in group B/TACE. The preoperative TACE also improved the postrecurrence survival in group B. We speculate that preoperative TACE reduced tumor recurrence and that it might confer a survival advantage after surgery, particularly in patients with advanced HCC. In addition, it is expected that this procedure may improve the pattern of tumor recurrence when it does occur.
High Dose Intravenous Immunoglobulin G Pretreatment: Effect on Lipid Peroxidation and Reperfusion Injury to the Liver
Authors: Giakoustidis Dimitrios , Papageorgiou George , Kostopoulou Evanthia , Iliadis Stavros , Giakoustidis Alexandros , Kontos Nikolas , Tsantilas Dimitrios , Botsoglou Nikolaos
Published: July 2004

The aim of this study was to examine the effect of intravenous immunoglobulin G (IVIG) compared with that of gadolinium chloride (GdCl3) in the inhibition of Kupffer cell activation on lipid peroxidation after severe total hepatic ischemia/reperfusion (I/R). Male Wistar rats (n = 40) were randomly divided into four equal groups: a sham‐operation group, a control I/R group, and two I/R groups pretreated with either IVIG or GdCl3 intravenously. Following 60 minutes of total hepatic ischemia and 120 minutes of reperfusion, the rats were sacrificed and liver and blood samples collected. Additional animals (n = 80) were followed up for survival rate determination. Results showed that I/R decreased the survival rate to 10%, increased the levels of aspartate (AST) and alanine (ALT) transaminase and lactate dehydrogenase (LDH) in serum to 2487, 2189, and 4236 IU/L, respectively, and increased malondialdehyde (MDA) levels in liver to 1.552 nmol/g compared with 1.114 nmol/g in the sham operation group. Pretreatment with GdCl3 increased the survival rate to 50% and decreased the levels of AST, ALT, and LDH in serum to 1496, 1298, and 3245 IU/l, respectively. Pretreatment with IVIG increased the survival rate to 60% and decreased the levels of AST, ALT, and LDH in serum to 449, 367, and 1456 IU/l, respectively, and the levels of MDA in liver to 1.153 and 1.148 nmol/g for GdCl3 and IVIG respectively. Histologic examination showed protection of liver parenchyma in the animals treated with GdCl3 or IVIG.
Higher Age Predicts Adverse Outcome and Readmission after Coronary Artery Bypass Grafting
Authors: Järvinen Otso , Huhtala Heini , Laurikka Jari , Tarkka Matti R.
Published: July 2004

The present prospective clinical study was carried out to investigate the effect of age on mortality, morbidity, and readmission rates after coronary artery bypass grafting (CABG). Data on 1131 consecutive CABG patients were collected in a surgical center and in all 18 secondary referral hospitals up to 3 months after discharge. Analysis was based on three age groups: 64 years or less (510 patients), 65 to 74 years (448 patients), and 75 years or more (173 patients). Thirty‐day mortality rates were 1.6% for the youngest, 5.4% for the middle age group, and 6.9% for the oldest. Major complications occurred in 10.8%, 21.2%, and 24.9% of these patients, respectively. Higher age was associated with more readmissions to health care facilities: The oldest patients had a rate twice as high as those in the youngest group (34.5% vs. 18.6%). Atrial fibrillation (15.4%), chest pain (10.6%), and congestive heart failure (8.5%) were the most common reasons for readmission. In conclusion, elderly patients, who are often suboptimal candidates for CABG, have higher 30‐day mortality, higher morbidity, longer length of stay in health care facilities, and an increased risk of readmission within 3 months after CABG; age was an independent predictor of 30‐day mortality and postdischarge readmission. Despite the higher risk of adverse events after surgery, three out of four elderly patients recover uneventfully.
Evaluation of Early Marrow Response in Childhood Aneuploid Acute Lymphoblastic Leukemia: Flow Cytometric DNA Analysis versus Standard Morphology
Authors: Finn Laura S. , Hawkins Douglas S. , Rutledge Joe C. , Patterson Kathleen
Published: July 2004

Despite improved survival rates for childhood acute lymphoblastic leukemia (ALL), the relapse rate remains at 20–30%. Early peripheral blood and bone marrow (BM) responses have been associated with more favorable outcomes; all current children's cancer group (CCG) protocols for ALL require BM evaluation at days 7 and 14 with subsequent therapy based on the results. Morphologic interpretation of aspirate smears during induction chemotherapy is challenging, as the samples are often hypocellular, excessively friable, and cytologically altered by drugs. We have shown discordancy of day 7 and 14 BM lymphoblast counts using morphologic and flow cytometric immunophenotypic analyses (FC). The aim of our study was to determine the utility, reliability, and cost effectiveness of lymphoblast enumeration using DNA content analysis by flow cytometry (DNA-FC) and to further demonstrate the subjectivity of morphologic review. All new cases of ALL had DNA-FC and FC analyses. The percentage of lymphoblasts as determined by both methods was compared for 82 aneuploid cases. Three pathologists independently reviewed aspirate smears from 39 bone marrow samples of aneuploid ALL that were obtained during early induction. These results were compared among themselves and with the results obtained by DNA-FC. We found excellent correlation between the percentage of lymphoblasts as determined by DNA-FC and FC (R 2 = 0.97) over a range of 0 to 99%. Pathologic review agreed with the DNA-FC, on average, 68%. The sensitivity, specificity, and positive and negative predictive values of morphologic review, averaged 53, 84, 78, and 63%, respectively, when using DNA-FC as the “gold standard.” All three pathologists achieved agreement of lymphoblast percentage by morphology in 72%. In our laboratory, the use of DNA-FC equates to one-sixth the time and one-half the price of FC per exam. We have shown a strong correlation between blast counts determined by DNA-FC and FC. DNA-FC is an objective, economical, and reliable method to assess early response in induction marrows from aneuploid ALL where morphology is often uninterpretable. This test is highly reproducible and available at most pediatric institutions. Prospective studies need to be employed to evaluate the effect of more definitive methods (DNA-FC and FC) of assessing the early response in bone marrows on prognosis.
Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants
Authors: Rodríguez Maria M. , Gómez Alexander H. , Abitbol Carolyn L. , Chandar Jayanthi J. , Duara Shahnaz , Zilleruelo Gastón E.
Published: July 2004

Until now oligonephropathy to indicate “too few nephrons” has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight ≤ 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < 40 days vs. long survival ≥40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age ( r = 0.87; P < 0.001). Active glomerulogenesis with “basophilic S-shaped bodies” was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving ≥40 days with RF were significantly less than RGC of those with long survival and no RF ( P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman's capsule area compared to all other groups ( P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.
High-Resolution Ultrasonic Spectroscopy for Analysis of Industrial Emulsions and Suspensions
Authors: Smyth Cormac , Kudryashov Evgeny , O'Driscoll Breda , Buckin Vitaly
Published: July 2004

This article describes the application of high-resolution ultrasonic spectroscopy (HR-US) for the analysis of industrial emulsions and suspensions. The benefits of HR-US are discussed, including the ability to perform a direct analysis of emulsions and suspensions, which would otherwise be impossible, require significantly more effort in the laboratory, or produce erroneous results. The HR-US 102 spectrometer is also introduced. Manufacture of this laboratory-scale instrument is now possible due to recent technological advances in HR-US. The article outlines the principles of the HR-US technique and illustrates the application of the HR-US 102 spectrometer for analysis of absorption of ligands on the surface of particles, thermal stability, and effects of thermal history on microstructure of emulsions, crystallization, and particle sizing in diluted and concentrated emulsions.
Primary productivity in the central equatorial Pacific (3°S 130°W) during GasEx‐2001
Authors: Strutton Peter G. , Chavez Francisco P. , Dugdale Richard C. , Hogue Victoria
Published: July 2004

Measurements of chlorophyll concentration, phytoplankton productivity, and nutrient dynamics were made during the GasEx‐2001 cruise to the equatorial Pacific in February 2001. During the core measurement period of the experiment, a parcel of water was tracked over a 16‐day period in order to close the mixed layer carbon budget. Chlorophyll concentration averaged 0.16 mg m−3 and integrated mixed layer primary productivity increased from 10 to 50 mmolC m−2 d−1, concomitant with a shoaling of the thermocline. The mean f ratio (ratio of new to primary production) decreased from 0.17 at the surface to 0.04 at 60 m, and the ratio of silicate to nitrate uptake by phytoplankton was 0.8. These results are close to or slightly lower than climatological values, and are consistent with moderate productivity in an iron‐silicate co‐limited environment. Fast repetition rate (FRR) fluorometry indicated that the effects of iron limitation increased with distance from the equator, the origin of upwelled iron. Measured chlorophyll concentrations were used to calculate the attenuation of solar irradiance, which facilitated a more accurate simulation of mixed layer temperature in a separate physical study. The productivity data presented here were incorporated into a carbon budget of the mixed layer, which derived a gas transfer velocity in excellent agreement with direct CO2 flux measurements.
Utilizing the ASPeCt sea ice thickness data set to evaluate a global coupled sea ice–ocean model
Authors: Timmermann Ralph , Worby Anthony , Goosse Hugues , Fichefet Thierry
Published: July 2004

Simulated sea ice thickness in the ORCA2‐LIM coupled sea ice–ocean model is compared with thicknesses from the Antarctic Sea Ice Processes and Climate (ASPeCt) database. We find a qualitative agreement of the large‐scale patterns of ice thickness distribution. Regional averages for the various sectors of the Southern Ocean yield a very good correspondence between observations and model data. Exceptions are the eastern Bellingshausen and northwestern Weddell Seas. A poor representation of the Antarctic Peninsula in the atmospheric forcing data and the related overestimation of westerly winds in this region lead to a spurious accumulation of sea ice on the western side of the peninsula and to an underestimation of sea ice coverage on the eastern side. Since the spatial scale of observations is not comparable to the size of a model grid cell, there is little agreement between individual observations and the corresponding model ice thicknesses. A model analysis of the seasonal and interannual variability indicates that the ASPeCt data underestimate the climatological ice thickness in the central and southern Weddell Sea and the eastern Ross Sea by up to 1 m. Because of a winter bias in the observations an overestimation of similar magnitude is expected in the Bellingshausen Sea. Ice thickness data in most of the Indo‐Pacific sector appear to be representative for the long‐term climatology. A model estimate of the bias is used to compute a revised distribution of climatological sea ice thickness.
Laboratory drilling under Martian conditions yields unexpected results
Authors: Zacny K. A. , Quayle M. C. , Cooper G. A.
Published: July 2004

Current plans to drill boreholes in the surface of Mars suppose that diamond drill bits will be used on drilling equipment developing drilling power of 100 W or less. Such drilling produces very fine cuttings. At Martian ambient pressure, it has been shown that quite small gas flows are capable of clearing these cuttings from the hole. For example, the release of 1 L of gas compressed to 50 torr is capable of removing 25 g of cuttings from a borehole 50 mm in diameter and at least 250 mm deep. Generating such volumes of gas by compressing the Martian atmosphere would not be difficult. Alternatively, the required volume of gas could be provided by the sublimation of ice trapped in the pore spaces of soil or rock in the Martian surface. Once heated by the friction of the drill bit, the ice transforms into vapor, and blows the cuttings out of the hole. Since the cuttings are, in effect, freeze‐dried, they do not choke the drill bit or hole, with the result that the drilling efficiency is much greater than under terrestrial pressures and temperatures.
Investigation of diamond‐impregnated drill bit wear while drilling under Earth and Mars conditions
Authors: Zacny K. A. , Cooper G. A.
Published: July 2004

Experiments conducted on a dry and a water‐saturated rock under Martian and Earth atmospheric pressures revealed two different wear behaviors in diamond‐impregnated drill bits. When the rock was saturated, drilling under Martian pressure caused the water in contact with the rotating bit to vaporize. Since the volumetric expansion of the liquid water or ice as it turned into a vapor was 170,000, the continuous flow of water vapor cleared the cuttings out of the hole. Thus the bit matrix was always exposed to abrasive wear by the rock cuttings and was continually wearing down and exposing new diamonds to the rock. When the rock was dry, an accumulation of rock cuttings protected the matrix from abrasive wear. Since fresh diamonds were not exposed in a timely manner, the rate of penetration dropped. Both rock conditions, namely, dry or water saturated, may exist on Mars. This adds to the complexity of the drill bit design as, ideally, a bit should penetrate the rock irrespective of whether it is dry or water saturated. The “fail‐safe” bit would have a very soft matrix to always produce some rock penetration at the expense of potential excessive bit wear and shallower than anticipated hole depth.
Uplift of the western Altiplano plateau: Evidence from the Precordillera between 20° and 21°S (northern Chile)
Authors: Victor Pia , Oncken Onno , Glodny Johannes
Published: July 2004

We present a quantitative reconstruction of uplift of the western flank of the Altiplano plateau (central Andes), one of the largest monoclines on the Earth, on the basis of an analysis of tectonic structures, syntectonic deposits, and geophysical data. Uplift occurred on a west vergent, slowly propagating system of high‐angle reverse faults merging into a joint detachment that ramps down to midcrustal levels below the plateau edge. The upper ramps determine local fold geometries while the lower ramp controls large‐scale surface tilting and uplift. At 20°S, this fault system was active between ∼30 Ma and 5–10 Ma, with maximum shortening rates of 0.22 mm/yr between 17 and 10 Ma. It generated some 2600 m of surface uplift with only minor shortening of ∼3000 m. Its activity was largely synchronous to eruption of large‐volume ignimbrites from a midcrustal source. Geophysical data indicate that the fault system localized deformation at the boundary between a cool, strong forearc crust and a presumably fluid‐rich and/or partially molten zone underneath the plateau area. The systematic relation between crustal melting and shortening with uplift at the western plateau margin can be traced along most of the plateau flank, with a stepwise decrease in age of deformation and magmatism toward the south indicating discontinuous addition of plateau segments. Crustal thickening to as much as 70 km from westward underthrusting in the back arc parts of the plateau isostatically compensated the tectonic surface uplift and monocline formation with respect to a stable forearc, which only reacted with minor tilting.
Increased ACTH and corticosterone secretion induced by different methods of paradoxical sleep deprivation
Authors: SUCHECKI DEBORAH , LOBO LETÍCIA , HIPÓLIDE DÉBORA , TUFIK SERGIO
Published: July 2004

The methods used to induce paradoxical sleep (PS) deprivation are believed to be stressful. In the present study, two methods were compared in regard to their ability to activate the hypothalamic‐pituitary‐adrenal (HPA) axis. Animals were placed on multiple large (MLP) or small (MSP) platforms or on single large (SLP) or small (SSP) platforms and blood sampled at the end of a 4‐day period of PS deprivation (experiment 1) or on Days 1 (short‐term) and 4 (long‐term) of PS deprivation (experiment 2). ACTH and corticosterone (CORT) levels were determined by RIA. The results of experiment 1 showed that all experimental animals presented increased ACTH response, compared to controls. CORT levels, however, were only elevated in MSP animals, suggesting increased adrenal sensitivity. Experiment 2 showed that ACTH levels of MSP animals were higher than MLP and SSP animals, and that animals placed on the multiple platform tanks showed the highest ACTH levels on Day 4 of manipulation. CORT levels were elevated in the animals kept over small platforms, and these levels where higher on Day 1 than basal and further elevated on Day 4 of PS deprivation. These results indicate that the multiple platform technique induces a distinct activation of the HPA axis, and that PS deprivation may act as an additional stressor.
Investigation on the characteristics of turbulence transport for momentum and heat in a drag-reducing surfactant solution flow
Authors: Li F.-C. , Kawaguchi Y. , Hishida K.
Published: July 2004

Simultaneous measurements of the velocity (u and ν in the streamwise and wall-normal directions, respectively) and temperature fluctuations (θ) in the thermal boundary layer were carried out for a heated drag-reducing surfactant solution flow in a two-dimensional channel by means of a two-component laser Doppler velocimetry and a fine-wire thermocouple probe. The drag-reducing fluid tested was a dilute aqueous solution of a cationic surfactant, cetyltrimethylammonium chloride (CTAC), with 30 ppm concentration. Measurements were performed for CTAC solution flows at an inlet temperature of 31 °C and at three Reynolds numbers of 3.5×104, 2.5×104, and 1.5×104, respectively, and for water flow at the Reynolds number of 2.5×104. Drag reduction (DR) and heat transfer reduction (HTR) for the three CTAC solution flows were DR(HTR)=33.0(20.2), 70.0(77.3), and 65.1(77.0) percentage, respectively. At a high HTR level, a large temperature gradient appeared when y+<50 in the measured range (the superscript “+” denotes normalization with inner variables). Temperature fluctuation intensity, θ′+, and the streamwise turbulent heat flux, u+θ+¯, were enhanced in the layer with large temperature gradient for the drag-reducing flow, whereas the wall-normal turbulent heat flux, −ν+θ+¯, was depressed throughout the measured range. The depression of −ν+θ+¯ was due to a cause similar to that of the depression of the Reynolds shear stress −u+ν+¯, i.e., in addition to the decrease of ν′+, decorrelation between the two variables occurred. The decrease of −ν+θ+¯ resulted in HTR, which was similar to that of the decrease of −u+ν+¯ resulted in DR for the drag-reducing flow by additives. The turbulence production terms, −u+ν+¯(∂U+/∂y+) and −ν+θ+¯(∂Θ+/∂y+) where U and Θ are mean velocity and temperature, were reduced in the drag-reducing CTAC solution flows. The estimated power spectra of temperature fluctuations implied that the drag-reducing surfactant additive depressed the turbulence at high frequencies or at small scales, whereas it increased the turbulent energy at low frequencies or at large scales. The profiles of the eddy diffusivities for momentum and heat in the CTAC solution flows were both decreased. The turbulent Prandtl number deviated from that of the water flow near the heated wall with a value close to the molecular Prandtl number of the solvent.
The HIV/AIDS pandemic: new ways of preventing infection in men
Authors: Short R. V.
Published: July 2004

Nelson Mandela has recently said that HIV/AIDS is the greatest health crisis in human history. At the end of 2001, UNAIDS estimated that there were 40 million people living with the infection, with 5 million new cases, and 3 million deaths per year. About half the infected individuals are men, and heterosexual intercourse is the commonest route of infection. Although condoms remain the first line of defence, they are unpopular in parts of Africa, where the pandemic is worst, so an alternative is needed. Post-coital penile hygiene has received little attention. Wiping the glans penis and inner foreskin immediately after intercourse with an acidic solution like lemon or lime juice, or even vinegar, should immediately kill the virus and might prevent infection; clinical trials are urgently needed. Several studies in Africa and India have now conclusively demonstrated a 2–7-fold protective effect of male circumcision against HIV infection. Circumcision removes the inner foreskin and the frenulum, which are the prime sites of HIV entry into the penis. Since male circumcision also protects men from human papilloma virus infection, and their wives from cervical carcinoma, the procedure should be encouraged in developed and developing countries.
Eddy Current Separation of Fine Non‐Ferrous Particles from Bulk Streams
Authors: Settimo Francesca , Bevilacqua Paolo , Rem Peter
Published: July 2004

Recovery of fine non‐ferrous metals from waste streams is a notoriously difficult problem in eddy current separation technology. Existing processes either have a low capacity or an incomplete recovery for particle sizes below 5 mm. In a new process, the particles are fed slightly wet to make them stick to the surface of the conveyor belt. The action of the magnet rotor makes the non‐ferrous particles tumble, so that they break loose from the belt and end up in front of the rotor. The new process combines a relatively high capacity with an almost complete recovery, even for heavy and poorly conducting non‐ferrous metals.
New Light on Harry Dexter White
Authors: Boughton James M.
Published: July 2004

Harry Dexter White is remembered today as the “other” founding father of the International Monetary Fund (IMF) and the World Bank, almost always as an afterthought as homage is paid to his far more renowned British counterpart, John Maynard Keynes. In the months leading up to and beyond the U.S. entry into World War II, White and Keynes independently drafted plans for a postwar stabilization fund aimed at restoring multilateral trade with convertible currencies. They traded plans in 1942 and then worked jointly on increasingly detailed proposals that led eventually to the creation of the IMF and World Bank. White is also remembered as a man who was accused of being a Soviet spy during the war, who died of a heart attack in 1948 just three days after giving a spirited and emotional public defense of his character before the House Un-American Activities Committee, and whose name was dragged out prominently five years later in an ugly battle between the Eisenhower Administration and former President Truman. Squeezed into the shadows between the luminosity of Keynes and the glaring excesses of McCarthyism, White's reputation has long been in need of a more sober inspection in the light of history.
Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep
Authors: Roelfsema Vincent , Bennet Laura , George Sherly , Wu David , Guan Jian , Veerman Marije , Gunn Alistair Jan
Published: July 2004

Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4±0.1°C to between 30 and 33°C), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal white matter 5 days after ischemia. Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41±20 vs 18±11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14±12 vs 91±51, P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4±6 vs 38±18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24±12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.
Simplified Methods for Calculating Cerebral Metabolic Rate of Oxygen Based on 17O Magnetic Resonance Spectroscopic Imaging Measurement during a Short 17O2 Inhalation
Authors: Zhang Nanyin , Zhu Xiao-Hong , Lei Hao , Ugurbil Kamil , Chen Wei
Published: July 2004

It has recently been shown that 17O magnetic resonance (MR) spectroscopic imaging at ultrahigh fields provides a reliable method for measuring CMRO2 during a short period of 17O2 gas inhalation. The mathematical (or complete) model used in the 17O MR method for calculating CMRO2 requires simultaneous measurements of multiple parameters including the concentration of H217O produced in the brain tissue from inhaled 17O2 gas (Cb), CBF, and the input function for the H217O concentration in the feeding artery (Ca). Both invasive and noninvasive measurements are involved in determining all of these parameters. In this article, two simplified methods are proposed and validated for calculating CMRO2 based on 17O MR measurement(s); the first method requires the measurements of Cb and CBF, but not Ca, and the second method only requires a single noninvasive measurement of Cb. The simplified methods were used to calculate CMRO2 in anesthetized rat brain, and the results were compared with those obtained using the complete model. The results from this work show (1) the validity of the simplified methods for quantifying CMRO2, and (2) the feasibility for establishing a completely noninvasive 17O MR approach for imaging CMRO2 in vivo.
Solid or Gaseous Circulating Brain Emboli: Are They Separable by Transcranial Ultrasound?
Authors: Darbellay Georges A. , Duff Rebecca , Vesin Jean-Marc , Despland Paul-André , Droste Dirk W. , Molina Carlos , Serena Joachim , Sztajzel Roman , Ruchat Patrick , Karapanayiotides Theodoros , Kalangos Afksendyios , Bogousslavsky Julien , Ringelstein Erich B. , Devuyst Gérald
Published: July 2004

High-intensity transient signals (HITS) detected by transcranial Doppler (TCD) ultrasound may correspond to artifacts or to microembolic signals, the latter being either solid or gaseous emboli. The goal of this study was to assess what can be achieved with an automatic signal processing system for artifact/microembolic signals and solid/gas differentiation in different clinical situations. The authors studied 3,428 HITS in vivo in a multicenter study, i.e., 1,608 artifacts in healthy subjects, 649 solid emboli in stroke patients with a carotid stenosis, and 1,171 gaseous emboli in stroke patients with patent foramen ovale. They worked with the dual-gate TCD combined to three types of statistical classifiers: binary decision trees (BDT), artificial neural networks (ANN), and support vector machines (SVM). The sensitivity and specificity to separate artifacts from microembolic signals by BDT reached was 94% and 97%, respectively. For the discrimination between solid and gaseous emboli, the classifier achieved a sensitivity and specificity of 81% and 81% for BDT, 84% and 84% for ANN, and 86% and 86% for SVM, respectively. The current results for artifact elimination and solid/gas differentiation are already useful to extract data for future prospective clinical studies.
Massive Inborn Angiogenesis in the Brain Scarcely Raises Cerebral Blood Flow
Authors: Vogel Johannes , Gehrig Mathias , Kuschinsky Wolfgang , Marti Hugo H.
Published: July 2004

The functional consequences of increased capillary densities in the brain resulting from vascular endothelial growth factor (VEGF165) overexpression are unknown. Therefore, the authors measured local CBF using the iodo-[14C]antipyrine technique in transgenic mice expressing brain-specifically sixfold higher VEGF165 levels and in nontransgenic littermates. To reveal possible compensatory vasoconstriction, CBF was also measured during severe hypercapnia (PaCO2 > 130 mm Hg). Simultaneously, local capillary density, perfusion state, and blood–brain-barrier permeability were assessed. Using the 2-[14C]deoxyglucose method, metabolic effects of VEGF overexpression could be excluded. In transgenic mice all capillaries showed normal morphology and a tight blood–brain barrier. However, 3% nonperfused capillaries in some brain structures indicate ongoing angiogenesis. Capillary density was drastically increased in transgenic mice in white matter structures (70% to 185%), the dentate gyrus (143%), and caudate nucleus (86%). In all other brain structures investigated, capillary densities were moderately increased by approximately 20%. Normocapnic CBF did not differ between transgenic and nontransgenic mice. During maximal hypercapnic vasodilation, CBF was 20% to 30% higher in transgenic mice, although only in brain structures where capillary density was increased more than twofold. These findings suggest that attenuated CBF in transgenic mice during normocapnia is only partly due to a compensatory vasoconstriction, and that microvascular networks in transgenic brains might be ineffectively constructed.
Multiplexed Cytokine Protein Expression Profiles from Spreading Depression in Hippocampal Organotypic Cultures
Authors: Kunkler Phillip E. , Hulse Raymond E. , Kraig Richard P.
Published: July 2004

Cytokines are involved in ischemic tolerance, including that triggered by spreading depression (SD), yet their roles in neuroprotection remain incompletely defined. The latter may stem from the pleiotropic nature of these signaling molecules whose complexities for interaction might be better deciphered through simultaneous measurement of multiple targeted proteins. Accordingly, the authors used microsphere-based flow cytometric immunoassays and hippocampal organotypic cultures (HOTCs) to characterize the magnitude, time course, and diversity of cytokine (interleukin [IL] 1α, IL-1β, IL-2, IL-4, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) response to SD. GM-CSF was not detected in HOTCs or media. However, SD triggered a significant, generalized increase in seven cytokines evident in HOTCs 6 hours later, with the remaining cytokine, IL-1β, becoming significantly different at 1 and 3 days. Additionally, these changes extended to include surrounding media for IL-6 and TNF-α by 1 and 3 days. This increase was localized to microglia via immunostaining for IL-1α, IL-1β, and interferon-γ. IL-10, although significantly more abundant in HOTCs 6 hours after SD, was significantly less abundant in surrounding media at that time and at 1 day. Finally, the generalized early increase in tissue cytokines later settled to a pattern at 3 days of recovery centering on changes in IL-1α, IL-1β, and TNF-α, cytokines capable of modulating ischemic injury.
Transient Focal Ischemia Affects the cAMP Second Messenger System and Coupled Dopamine D1 and 5-HT1A Receptors in the Living Monkey Brain: A Positron Emission Tomography Study Using Microdialysis
Authors: Tsukada Hideo , Fukumoto Dai , Nishiyama Shingo , Sato Kengo , Kakiuchi Takeharu
Published: July 2004

Using positron emission tomography (PET) and microdialysis, the present study showed that neuronal damages after transient focal ischemia was partly induced by hyperactivation of the cyclic adenosine 3′,5′-monophosphate (cAMP) second messenger system through modulations of dopamine D1 and serotonin 5-HT1A receptors in the living brains of cynomolgus monkeys. Occlusion of the right middle cerebral artery for 3 hours suppressed CBF in the striatum, and reperfusion induced hyperperfusion in the neocortex and striatum of the occluded side. Six hours after reperfusion, the activity of the cAMP second messenger system assayed with [11C]rolipram was significantly facilitated in the neocortex and striatum where CBF was lowered more than 40% of normal during occlusion (“ischemic” area). Seven days later, impaired dopamine D1 and 5-HT1A receptor binding, measured with [11C]SCH23390 and [ carbonyl-11C]WAY-100635, respectively, was observed in the ischemic area. Microdialysis analysis revealed that the striatal dopamine level provided a transient and marked increased during occlusion and after reperfusion, whereas the cortical serotonin level transiently increased only after reperfusion, and was at an undetectable level thereafter. Administration of rolipram (0.1 and 1 mg/kg, intravenously) during occlusion facilitated reduction of dopamine D1 binding, whereas rolipram administration 6 hours after reperfusion induced a further decrease in 5-HT1A receptor binding. These results suggest that the activation of cAMP second messenger system modulated by dopamine D1 and 5-HT1A receptors could be involved in the neuronal degeneration after transient cerebral ischemic insult.
Platelet–Leukocyte–Endothelial Cell Interactions after Middle Cerebral Artery Occlusion and Reperfusion
Authors: Ishikawa Mami , Cooper Dianne , Arumugam Thiruma V. , Zhang John H. , Nanda Anil , Granger D. Neil
Published: July 2004

The adhesion of both leukocytes and platelets to microvascular endothelial cells has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds. The objectives of this study were to (1) assess the platelet–leukocyte–endothelial cell interactions induced in the cerebral microvasculature by middle cerebral artery occlusion (MCAO)/reperfusion, and (2) define the molecular determinants of the prothrombogenic and inflammatory responses in this model of focal I/R. MCAO was induced for 1 hour in wild-type (WT) mice, WT mice treated with a monoclonal antibody (mAb) to either P-selectin or GPIIb/IIIa, and in P-selectin−/−(P-sel−/−) chimeras. Isolated platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) were administered intravenously and observed with intravital fluorescence microscopy. Leukocytes were observed after intravenous injection of rhodamine 6G. One hour of MCAO followed by 1 hour of reperfusion resulted in the rolling and adhesion of leukocytes in venules, and after 4 hours of reperfusion, the adhesion of both leukocytes and platelets was detected. Although both the P-selectin and GPIIb/IIIa mAbs significantly reduced the adhesion of leukocytes and platelets at 4 hours of reperfusion, the antiadhesive effects of the P-selectin mAb were much greater. The leukocyte and platelet adhesion responses were significantly attenuated in both P-sel−/−→WT and WT→P-sel−/− bone marrow chimeras, compared with WT→WT chimeras. Neutropenia, induced by antineutrophil serum treatment, also reduced the recruitment of leukocytes and platelets after cerebral I/R. These findings implicate a major role for both platelet-associated and endothelial cell–associated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R.
VP1 of infectious bursal disease virus is an RNA-dependent RNA polymerase
Authors: von Einem Ursula I. , Gorbalenya Alexander E. , Schirrmeier Horst , Behrens Sven-Erik , Letzel Tobias , Mundt Egbert
Published: July 2004

Segment B of the bisegmented, double-stranded RNA genome of infectious bursal disease virus (IBDV) encodes the viral protein VP1. This has been presumed to represent the RNA-dependent RNA polymerase (RdRp) as it contains motifs that are typical for the RdRp of plus-strand RNA viruses. Here it is demonstrated that baculovirus-expressed wild-type but not motif A mutated VP1 acts as an RdRp on IBDV-specific RNA templates. Thus, on a plus-strand IBDV segment A cRNA template, minus-strand synthesis occurred in such a way that a covalently linked double-stranded RNA product was generated (by a ‘copy-back’ mechanism). Importantly, enzyme activity was observed only with templates that comprised the 3′ non-coding region of plus-strand RNAs transcribed from IBDV segments A and B, indicating template specificity. RdRp activity was shown to have a temperature optimum of 37 °C and required magnesium ions for enzyme activity. Thus, it has been demonstrated unequivocally that VP1 represents the RdRp of IBDV.
Functional co-operation between the Kaposi's sarcoma-associated herpesvirus ORF57 and ORF50 regulatory proteins
Authors: Malik Poonam , Blackbourn David J. , Cheng Ming Fei , Hayward Gary S. , Clements J. Barklie
Published: July 2004

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) proteins ORF57 (also known as MTA) and ORF50 (also known as RTA) act post-transcriptionally and transcriptionally to regulate viral lytic gene expression and synergistically activate certain early and late KSHV promoters. When ORF57 and ORF50 were co-expressed, they co-operatively stimulated expression from the promoter of the immediate-early ORF50 gene itself. Co-immunoprecipitations with extracts of KSHV-infected cells showed that ORF57 and ORF50 proteins were present in the same complex. Using the pull-down assay with extracts of KSHV-infected cells, ORF50 protein was shown to interact with a glutathione S-transferase–ORF57 fusion protein. A chromatin immunoprecipitation assay showed that ORF50 promoter sequences were preferentially associated with immunoprecipitated chromatin using both anti-ORF50 and anti-ORF57 antibodies consistent with both an in vivo physical association between ORF57 and ORF50 and a potential role for ORF57 at the transcriptional level. This is the first demonstration of an interaction between these two lytic regulatory proteins in a gammaherpesvirus. Expression of ORF50 protein is sufficient to induce lytic replication in latently infected cells and may determine viral host range, spread and KS pathogenesis in vivo. A new insight into the co-ordinated activities of these two key regulatory proteins is provided in which upregulation of the ORF50 promoter with augmentation of ORF50 activity by ORF57 protein, and vice versa, would facilitate the cascade of lytic viral gene expression, thereby breaking latency. A functional and physical interaction between these two gammaherpesvirus regulatory protein counterparts could be a general feature of the herpesviruses.
Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen
Authors: Mäkitalo B. , Lundholm P. , Hinkula J. , Nilsson C. , Karlén K. , Mörner A. , Sutter G. , Erfle V. , Heeney J. L. , Wahren B. , Biberfeld G. , Thorstensson R.
Published: July 2004

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIBenv,gag,RT,rev,tatandnef, and MVA expressing HIV-1 IIIBnef,tatandrevand simian immunodeficiency virus (SIV) macJ5gag/poland vaccinia HIV-1env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.