cssi/SciSciGPT-SciSciNet huggingface dataset:
Influence of intravenous administration of nucleoside-coupled spleen cells on murine lupus nephritis in female (NZB×NZW)F1 mice

In this study, we examine the influence of the intravenous administration of nucleoside-coupled spleen cells on the spontaneous development of murine lupus nephritis in young and adult BWF1 mice. In both age groups, this treatment failed to affect the autoimmune disease. Rather, in young mice administration of nucleoside-coupled spleen cells accelerates the appearance of anti-DNA antibody suggesting that BWF1 have a specific defect in the immunoregulation of anti-DNA antibody production. The significance of this finding for the pathogenesis of the disease in BWF1 mice is discussed.
Effects of Cold Periods on the Stimulus-Response System of Phycomyces

The sporangiophores of Phycomyces do not exhibit phototropic responses when growth is arrested reversibly by cooling to 1°C. Unilateral UV stimuli (254 nm) applied during cold periods are stored for at least 2 hr and produce tropic responses away from the light after warm-up. During the cold period dark adaptation proceeds at a rate which decreases with the temperature.
Interstrain variation in the deoxynucleotide composition of Cryptococcus neoformans: Nucleotide composition of Cryptococcus neoformans

The deoxynucleotide (dNMP) composition of ten strains of C. neoformans was analysed by 32P-labelling and two-dimensional thin-layer chromatography. This technique is very sensitive for detecting rare deoxynucleotide adducts and analogues (minor bases) in DNA. The results indicate considerable variation among strains in DNA nucleotide composition.
Hypoglossal and phrenic responses to central respiratory inhibition in piglets.

Neonatal apnea is characterized by decreased neural output to the ventilatory muscles, and frequently associated with upper airway obstruction. We sought to characterize: (1) the role of central chemosensitive structures at the ventral medullary surface (VMS) in modulating hypoglossal and phrenic neural output, and (2) the recovery of hypoglossal and phrenic neural output during simulated central apnea. We studied 14 anesthetized, paralyzed, ventilated piglets aged 14–21 days and performed VMS cooling to inhibit central neural pathways mediating CO2 sensitivity. Phrenic and hypoglossal ENGs and end-tidal CO2 were continuously recorded. During CO2 rebreathing, hypoglossal activity was always more sensitive than phrenic activity to the inhibitory effects of VMS cooling. When phrenic apnea was induced by VMS cooling, and followed by discontinuation of ventilation for 60 sec in order to induce simultaneous hypercapnia and hypoxia, reapperance of hypoglossal ENG was delayed and recovery was significantly suppressed when compared to phrenic ENG. Therefore, attenuated central chemosensitivity during early postnatal life appears to preferentially inhibit neural output responsible for upper airway patency, and may predispose to upper airway obstruction during recovery from neonatal apnea.
Neutron and gamma ray detection for border security applications

Countries around the world are deploying radiation detection instrumentation to interdict the illegal shipment of radioactive material crossing international borders. These efforts include deployments in the U.S. and in a number of other countries by governments and international organizations. Most deployed radiation portal monitor systems are based on plastic scintillator for gamma-ray detection and 3He tubes for neutron detection. The approach to this homeland security application, and lessons learned, are discussed.
Enhancing web page skimmability

Information overload on the Web and limited reading time force users to skim read web pages. For non-native English readers, it is challenging to understand first-hand information written in English under time constraints. Traditional readability enhancement research has focused on enhancing reading comprehension and user satisfaction, but average reading times for non-native readers have remained the same or even worse. In this paper, we investigate useful techniques for readers when reading web pages under time constraints, i.e., having skim reading capability. We propose two techniques to help non-native readers to skim read web pages: (1) content spotlight, masking and filtering; and (2) semantic data extraction and in-place translation. Froggy GX is a prototype system that implements proposed techniques to provide skim-reading support for non-native readers.
Systems Analysis for Designing Reproductive Management Programs to Increase Production and Profit in Dairy Herds

Abstract Relative economic merits of three heat detection rates and three conception rates were evaluated by mathematical modeling and dynamic simulation. Three heat detection programs evaluated were: a) poor, with no specific time set aside for detection and detection rate of .35; b) average, with two 45-min observations each day and detection rate of .55; c) good, with three 45-min observations each day and detection rate of .75. Changing heat detection program from poor to average and average to good decreased days open from 136 to 119 and to 105. Corresponding increases in net return per cow per year were $60 and $4. Three breeding programs evaluated were: a) poor, direct service by an inexperienced inseminator and conception rate of .42; b) average, professional artificial inseminator servicing the cows with a single insemination at each service and conception rate of .50; c) good, professional artificial inseminator using two inseminations during each service period and conception rate of .58. Changing breeding program from poor to average and average to good decreased days open from 123 to 119 and to 115. Corresponding changes in net return per cow per year were an increase of $39 and a decrease of $7.
Molecular Dynamics Simulations of Diffusion in Mesoporous Glass

The effect of gas−solid intrapore potential and surface roughness on diffusion in a single capillary was investigated by molecular dynamics simulations. Calculations were carried out for nitrogen and isobutane under free molecular flow conditions in pores of diameter 4−14 A at temperatures of 200−800 K. The gases were treated as Lennard-Jones atoms and the pore surface was taken as cylindrical, exerting a 9−3 potential. No energy transfer was considered between the gas and solid, but interaction with the roughened pore wall provided the scattering required for diffusive transport. Two effects of the gas−solid potential were examined in some detail. One is the enhanced intrapore gas concentration which increases the flux, and the other is the bending of the molecular trajectories which decreases the flux. In pores of radius 20 A, both effects were significant for temperatures as high as 500 K and were enhanced as the temperature decreased. For nitrogen, the two effects partially canceled each other over the temperature range examined, resulting in a temperature dependence similar to that of Knudsen diffusion. For isobutane, the partitioning effect dominated the path curvature effect at temperatures as high as 500 K.
Chemical approaches to controlling intracellular protein degradation.

A major goal of post-genomic research is to understand and control the function of specific proteins within the proteome. The fields of genetics, genomics, and chemical genetics attempt to study this problem from two fundamentally different approaches. The traditional genetic approach or genomic analysis involves the observation of a particular phenotype, identification of the molecule(s) responsible for that phenotype, and subsequent analysis and manipulation of the corresponding genetic sequence. In contrast, chemical genetics attempts to use small molecules as probes to perturb signaling pathways at the molecular level in the hopes of identifying novel proteins responsible for a particular phenotype. These two distinct approaches (among others) have yielded huge advances in the understanding of protein function. Despite their differences, these fields share the same strategy of inactivation of a protein to study its function. Regulation of protein expression can be described as occurring on three basic levels. First, at the genetic level, the strength of a promoter determines the level of a particular gene product. Second, at the post-transcriptional level, stability of mRNA levels lead to increased production of a protein. Finally, at the post-translational level, modifications such as gly-cosylation, phosphorylation, or degradation significantly affect both intracellular levels and the activity of a protein. The most effective way to study the function of a protein has traditionally been to observe the phenotypic change in its absence. Therefore, methods at each of these three levels have been developed to disrupt protein expression. Many ways to control protein function are known, including inducible transcription[1] and methods that affect post-translational modifications[2–4] or inhibit degradation.[5] Although these methods are effective, they are fundamentally different from strategies that lower protein levels post-translationally. As genetic knockout methodology is well understood, this review focuses on recent advances in protein inactivation at the post-translational level, specifically comparing novel chemical and biochemical methods to the post-transcriptional method of inactivation, RNA interference (RNAi).
Physical and sexual function in women with chronic kidney disease

Abstract Background: Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown. Methods: To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m 2 ), moderate (estimated GFR, 30 to 44 mL/min/1.73 m 2 ), and severe (estimated GFR, 2 ) according to a modification of recently established classification guidelines. Results: Mean age of study participants was 67 ± 7 years, and mean estimated GFR was 61 ± 14 mL/min/1.73 m 2 . In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m 2 than in women with an estimated GFR of 60 mL/min/1.73 m 2 or greater ( P
The role of response set in tests of unlearning

Evidence for the unlearning of first-list associations (A-B) during acquisition of a second list (A-C) has been obtained in unpaced tests of modified free recall (MMFR) in which S is required to reproduce both responses to each of the stimuli. The present experiment investigates the extent to which the loss of first-list associations in MMFR is attributable to a set established during IL and carried over into MMFR, viz., to restrict overt responses to those correct in the second list. In order to maximize the set to give first-list responses, a non-learning task was introduced between the end of IL and MMFR which required active recitation of all first-list associations. Comparison with appropriate control groups shows that (a) the set-inducing procedure increased the dominance of available first-list responses as indexed by the order of recall, but (b) had no effect on the number of such responses recalled, i.e., left the amount of RI unchanged. It appears unlikely, therefore, that a loss of set is responsible for the reduced availability of first-list associations in MMFR.
A comparison of the hemodynamic and ventilatory effects of abdominal insufflation with helium and carbon dioxide in young swine

Abdominal CO2 insufflation has been shown to cause hypercarbia, acidemia, and decreased oxygenation in a pediatric animal model. Such metabolic derangements have prompted a search for alternative insufflation gases. This study compares the hemodynamic and ventilatory changes that occur during pneumoperitoneum with CO2 and helium. Four juvenile swine were intubated and given general anesthesia. Minute ventilation was adjusted to obtain a baseline Pco2 of between 32 and 36 mm Hg, and was kept constant for the duration of the experiment. The subjects initially were insufflated with CO2 or helium at a pressure of 10 mm Hg. Peak ventilatory pressure, end-tidal CO2 (ETCO2) arterial pH, Pco2, Po2, and right atrial and inferior vena caval pressures were measured before and during a 1-hour insufflation period. After desufflation, Pco2 and pH were restabilized. The same parameters were then measured during reinsufflation with the alternate gas. CO2 insufflation caused significant decreases in pH, from 7.51 +/- 0.03 to 7.32 +/- 0.06, and Po2 increased from 261 +/- 49 to 189 +/- 33 mm Hg. Pco2 increased from 35.0 +/- 1.4 to 57.9 +/- 6.3 mm Hg. ETCO2 also increased, from 29.0 +/- 2.2 to 47.2 +/- 5.0 mm Hg. Helium insufflation caused pH to decrease from 7.51 +/- 0.01 to 7.42 +/- 0.04. Pco2 increased from 32.8 +/- 0.8 to 43.5 +/- 3.9 mm Hg, and ETCO2 increased from 27.8 +/- 0.5 to 36.8 +/- 3.1 mm Hg. These alterations were significantly less than those with CO2 pneumoperitoneum. Po2 decreased as well-from 266 +/- 30 to 212 +/- 21 mm Hg. During insufflation with both gases, peak ventilatory pressure and right atrial pressure increased significantly. Abdominal insufflation with CO2 or helium causes hypercarbia, acidemia, and increased ETCO2 in this juvenile animal model. These derangements are significantly less with helium. This gas may prove to be the more suitable insufflation agent for pediatric patients.
Variability in tornado frequency associated with U.S. landfalling tropical cyclones

[1] A statistical model for tornado frequency from Gulf of Mexico landfalling tropical cyclones (TCs) is developed using TC size, intensity, recurvature, and mid-level specific humidity data. New datasets are assembled for tornado frequency and for TC size at landfall as measured by the radius of outer closed isobar and distance of tornado from the TC center. Owing to systematic undercounting of tornadoes, the model is used to reconstruct the TC tornado climatology back to 1948, and further back to 1920 using a modified model that does not include mid-level specific humidity. Relative to the previous active period for Gulf TC landfalls of 1948–1964, the active period since 1995 has seen a statistically significant increase (95% level) in median TC tornadoes and in the frequency of large TC tornado outbreaks. These changes are linked to an increase in the median size and frequency of large Gulf landfalling TCs.
Massively Parallel Computing of Traveltime In 2-D And 3-D Piecewise Homogeneous Models

This paper presents an accurate and computationally efficient method for computing the shortest raypath in a twoand three-dimensional space of discrete block models. An implementation of the algorithm on the Cray T3D Massively Parallel Processors(MPP) is proposed. The velocity distribution is discretized into homogeneous polygonal or polyhedral cells. The seeking of the shortest traveltime path between two given points can be reduced to discrete graph searching. The 3D algorithm is a straightforward extension of the 2D case, however, the computing operations in a 3D model are much more CPU intensive. The method is demonstrated with examples showing raypaths and wavefronts in 2D and 3D block models. It is indicated that the algorithm is capable of solving the optimal raypaths from di’erent source points in parallel on the MPP system.
Ion-cyclotron range of frequencies in the scrape-off-layer: fine structure radial electric fields

Gas-puff-imaging techniques are utilized to detect radial electric field structures in the scrape-off-layer (SOL) of the Alcator C-Mod tokamak via the observation of poloidal motion of advected fluctuations. When the diagnostic's field of view is magnetically connected to the ion-cyclotron range of frequencies (ICRF) active antennas, large (up to 8 km s−1) poloidal velocities are observed in a radial region encompassing both field lines terminating on and those passing in front of the antennas. The radial electric field switches sign indicating a peak in the potential profile corresponding to the transition from piercing to passing field lines. The electric field extends a few centimeters into the SOL and its local magnitude is of order Er ≈ 20–30 kV m−1. The corresponding plasma potentials scale as the square root of RF power; the poloidal structure is peaked when the field lines are connected to the top and bottom of the antenna. This structure is consistent with the presence of potential structures arising as a consequence of sheath rectification of the RF waves. The most striking result, however, is that the radial penetration λ⊥ of the potential structures is an order of magnitude larger than the basic theoretical expectation (λ⊥ ≈ 10δe, where δe is the skin depth). This substantial broadening is expected to have a strong impact on RF impurity physics. A (weak) power dependence observed in the width of the poloidal velocity features is explained as a competition between the RF induced and the background potential gradients.
Evidence for Kondo effect and crossover in electronic structure for x ∼ 0.2 of UxY1−xPd3

Abstract We present measurements of the thermoelectric power S(T) from 2 to 300 K and Hall coefficient RH at 300 K in the material UxY1−xPd3. At 300 K, S(T) is large and positive for x > 0.2. S(T) for x = 0.05, 0.1 is reminiscent of conventional Kondo alloys. The Kondo temperature, TK, is of the order of 150 K. RH (300 K) is positive for all x and exhibits a dip at x = 0.2. There is no unique evidence for non-Fermi liquid behavior for the more dilute alloys.
Spiders and Other Arthropods as Indicators in Old‐Growth Versus Logged Redwood Stands

This study, conducted in the Santa Cruz Mountains of California, provides data on the abundance and diversity of litter spiders and other arthropods in three redwood forest conditions: old growth, second growth, and tree farm. Litter spiders are linked to and reflect habitat structure and prey abundance and can act as indicators for redwood forest restoration and monitoring. There were significant declines in spider and other arthropod diversity and abundance with increased logging and decreased herb cover. The absolute and relative increase in nocturnal spiders and detritivores in unlogged sites suggests that guild structures of spiders and other arthropods can indicate forest recovery from logging disturbance. Furthermore, selectively harvested stands do not retain old-growth levels of litter arthropod diversity or abundance. This study identifies potential indicator redwood litter spiders that show higher abundances in old-growth areas, Zelotes sp. (Gnaphosidae), Xysticus sp. (Thomisidae), and Ceratinops inflata (Linyphiidae) and a possible old-growth specialist, Phrurotimpus sp. (Liocranidae). These findings strengthen the case for including soil arthropods in redwood forest monitoring and assessment and for the preservation of undisturbed forest areas.
A new spectral intermediate associated with cytochrome P-450 function in liver microsomes

The spectrophotometric examination of pigment reduction during the steady state of drug oxidative metabolism, as catalyzed by hepatic microsomes, has revealed the presence of a new spectral intermediate presumed associated with an oxygenated form of reduced cytochrome P-450. This new spectral intermediate has absorption maxima at about 440 and 590 mμ in the difference spectrum. The magnitude of this intermediate is dependent on the presence of a hydroxylatable substrate, the oxygen concentration, and the use of TPNH as the source of reducing equivalents. Further, changes in the extent of the TPNH-dependent reduction of cytochrome b5 during the steady state indicates that cytochrome b5 serves as a donor of electrons to the oxygenated form of reduced cytochrome P-450.
Distribution of Practice as a Factor Affecting Learning And/Or Performance

Earlier studies considering distribution of practice as a factor affecting learning and/or performance have employed a transfer design and consequently have failed to provide the means for refuting the contention that postrest performance was the manifestation of extended practice, a temporary performance variation, or some form of the “Hawthorne effect” rather than the result of the independent variable. The present experiment provided adequate control, and results indicated that distribution of practice was a factor affecting performance rather than learning.
Merkel cell carcinoma : Report of 10 cases and review of the literature

Abstract Background: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine skin tumor that usually arises in the head and neck or the extremities of elderly patients. Because of the limitation of retrospective data, optimal treatment is not well defined. Objective: Our purpose was to present the clinical course and treatment of 10 patients with MCC and review the published literature on MCC. Method: We conducted a retrospective analysis and obtained detailed clinical information for all 10 patients treated for MCC at our institution from 1986 through 1998. The medical literature was also reviewed for natural history and treatment recommendations using MEDLINE search. Results: Five men and 5 women received their treatment between 1986 and 1998 for MCC (5 had stage IA disease, 4 stage IB, 1 stage II). The mean age was 70.3 years (range, 47-86 years). Seven tumors were located on the head and neck and 3 on extremities. Five of 10 patients had a relapse (mean time before recurrence, 5.7 months) (range, 2 weeks-20 months); one patient had local recurrence, one had regional lymph node recurrence, and 3 had both local and regional lymph node recurrence. In 4 patients systemic metastases developed. Long survival is also noted (6 to > 164 months); 4 patients died of MCC. After initial surgery, 9 patients received radiotherapy at some point and 3 patients also received chemotherapy. Five of 10 patients had 13 previously treated or coexisting malignant neoplasms. In one patient MCC developed in a previously irradiated field. Review of 875 cases showed a male/female ratio of 1.5:1; location of tumors was as follows: head and neck, 47%; extremities, 40%; trunk, 8%; unknown primary site, 5%. Local recurrence was observed in 25%, regional lymph node involvement in 52%, distant metastasis in 34%, and MCC was a cause of death in 34%. Conclusion: MCC has a high incidence of locoregional recurrence with distant metastases that is more common with higher stage lesions. Early local management of smaller lesions results in good long-term survival. It is not known whether prophylactic lymph node dissection and/or radiation and adjuvant radiation increases survival. Long survival can be achieved after treating locoregional recurrence. The role of chemotherapy is still controversial and should be considered in patients with advanced disease and those not thought to be candidates for surgery. (J Am Acad Dermatol 2000;43:755-67.).
Antiandrogenic suppression of lymphocytic blastogenesis: in vitro and in vivo observations

Nachweis, dass die Fahigkeit zur Blastogenese der Lymphozyten gesunder junger Manner nach Reizung mit Phytohamagglutinin im peripheren Blut unterdruckt wird, wenn die Lymphozyten zusammen mit ostrogen (Diethylstilbestrol-Diphosphat) kultiviert werden.
LOW PREVALENCE OF ANEMIA AMONG NAVAJO CHILDREN

Both historical and recent evidence has suggested that iron deficiency may be common among southwestern American indians. To assess the nutritional status of young Navajo indians, nutritional histories, heights, weights, and fingerstick blood samples were collected from 576 children from 6 months to 10 years of age. Using Harvard standards, 19% of heights and 9% of weights were 97th percentile. Microhematocrit determinations demonstrated a very low prevalence of anemia: only 2% were >2 S.D. below the mean for age. Plasma iron levels were determined on 440 samples with a new spectrophotometric method using ferrozine and requiring 50μl of plasma. Less than 6% of the children had iron values <12.5μmol/l (70μg/dl). Although almost all hematocrit values were normal, children with lower hematocrits for age tended to have lower plasma irons (p<.001) and to be shorter (p<.001) and lighter (p<.03). A much higher proportion of children with iron deficiency anemia has been reported in other U.S. populations of similar economic level. The high prevalence of breastfeeding (46%), the use of iron fortified infant formulas (by history 75% of formula users), participation in food supplementation programs, and a cultural tradition that includes meat in children's regular diet may be factors in the unusually low prevalence of nutritional anemia among these Navajo children.
Pseudoexstrophy of the bladder: Case report and literature review

The authors present a case of a boy newborn who had bladder pseudoexstrophy and multiple congenital anomalies. In addition to this unusual variant of the exstrophy-epispadias complex, the patient was found to have a posterior cleft palate, an omphalocele, and an imperforate anus.
Th1/Th2 T cell sensitivity to rice in an infant

Abstract Rationale While food allergy is common in children, rice allergy is unusual in Western cultures. We report a case of T-cell mediated rice intolerance in an 11-month-old Caucasian girl. Methods/case The patient presented with vomiting after eating rice cereal, barley cereal, vanilla wafers and pudding on separate occasions. The episodes of vomiting after rice cereal were reproducible and occurred within two hours of eating rice. She did not experience respiratory symptoms or urticaria. The child's growth and physical exam were normal. Results A food allergy evaluation was initiated with skin prick tests that were negative for rice but positive for egg, milk and soy. Specific IgE was undetectable for rice, egg, peanut, wheat, walnut, codfish, milk, soybean, corn, shrimp, scallops, and clams by IgE ImmunoCAP testing. A single-blind rice food challenge was positive. The patient progressed through the eight-gram dose of rice. Within three hours from the beginning of the food challenge, the patient developed emesis that persisted for over an hour, for which she required intravenous hydration. The patient demonstrated positive in vitro lymphoproliferative responses to rice stimulation. In addition, IFN-γ, IL-10, and IL-5 synthesis was elevated to rice stimulation compared to the control subject, indicating a Th0 T-cell response to rice. Conclusions Though this patient did not demonstrate IgE antibody to rice, Th1/Th2 cell-mediated responses to rice lead to significant morbidity.
Regadenoson is a safe and well-tolerated pharmacological stress agent for myocardial perfusion imaging in post-heart transplant patients.

The safety and tolerability of regadenoson (REG), a newer adenosine A2a receptor agonist, has not been tested in orthotopic heart transplant (OHT) patients. Retrospective review of a tertiary care center experience of OHT patients who underwent a REG single-photon emission computed tomography (SPECT) study as part of the work-up for cardiac allograft vasculopathy. The control group included those same patients who had prior adenosine-based SPECT. A total of 40 patients met the above criteria. Mean time from OHT to adenosine-SPECT and REG-SPECT was 8.2 ± 4.8 years vs 9.8 ± 4.5 years, respectively (P < .001). Both vasodilators had similar side effect profiles (P = .10), produced significant heart rate acceleration and asymptomatic hypotension (P < .001). There were no episodes of bradycardia and/or AV block with REG. Despite adjustment for medication status, adenosine was still associated with more conduction abnormalities (8 vs 1 event with REG, P = .02) including five episodes of 2nd degree AV block (Mobitz type II) and three episodes of sinus pause. This is the first reported use of REG in OHT patients. REG appears to be safe and well tolerated without significant cardiovascular adverse events.
Pharmacokinetics of intravenous immunoglobulin (Gammagard) in bone marrow transplant patients

The pharmacokinetics of an intravenous immunoglobulin (IVIG), Gammagard (Baxter Healthcare Corp., Glendale, CA), were measured in 31 cytomegalovirus (CMV) antibody negative bone marrow transplant (BMT) patients as part of a multicenter efficacy trial of 2 weekly dose regimens. Since all patients lacked antibody to CMV and received only screened CMV negative blood products, the half-life of the exogenous CMV antibody could be measured with an ELISA assay. The CMV antibody titer was related to the immunoglobulin concentration using a standard curve. Compared with the 22-day half-life in normal subjects, the half-life in BMT patients was approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen. The half-life did not change over the subsequent 3 weekly doses. Peak concentrations were 3.5 +/- 1.4 and 2.6 +/- 0.7 mg/mL of IVIG in week 1 as well as 5.5 +/- 2.6 and 3.4 +/- 1.2 mg/mL in week 3 after the 250 mg/kg and 500 mg/kg, respectively. Total body clearance of IVIG was 0.61 and 0.46 mL/kg/hr for the 500 mg/kg and 250 mg/kg, respectively.
Short-term inhalation exposure to bromotrifluoromethane.

Abstract Exposure of dogs and monkeys to 10–80% bromotrifluoromethane (CBrF 3 ) caused cardiovascular and central nervous system effects which increased in severity with increasing CBrF 3 concentration. An initial fall in mean arterial blood pressure of 10–20 mm Hg at the lower CBrF 3 concentrations and 40–60 mm Hg at the higher CBrF 3 concentrations was observed. Most animals developed spontaneous cardiac arrhythmias within 1–3 min of exposure to 40% or more CBrF 3 . Arrhythmias could be produced in those animals not developing arrhythmias spontaneously by the intravenous injection of a pressor dose of epinephrine. Larger doses of epinephrine (5–10 μg/kg) caused ventricular fibrillation with cardiac arrest in dogs and, commonly, spontaneous defibrillation in monkeys. Epileptiform convulsions were seen in about 50% of the dogs exposed to 50–80% CBrF 3 while conscious. Conscious monkeys, on the other hand, became lethargic, and no convulsions were seen.
Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors.

Abstract We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3sp subsite.
Human ornithine aminotransferase complexed with L-canaline and gabaculine: structural basis for substrate recognition

Abstract Background: Ornithine aminotransferase (OAT) is a 45 kDa pyridoxal-5′-phosphate (PLP)-dependent enzyme that catalyzes the conversion of L-ornithine and 2-oxoglutarate to glutamate- δ -semialdehyde and glutamic acid, respectively. In humans, loss of OAT function causes an accumulation of ornithine that results in gyrate atrophy of the choroid and retina, a disease that progressively leads to blindness. In an effort to learn more about the structural basis of this enzyme's function, we have determined the X-ray structures of OAT in complex with two enzyme-activated suicide substrates: L-canaline, an ornithine analog, and gabaculine, an irreversible inhibitor of several related aminotransferases. Results: The structures of human OAT bound to the inhibitors gabaculine and L-canaline were solved to 2.3 A at 110K by difference Fourier techniques. Both inhibitors coordinate similarly in the active site, binding covalently to the PLP cofactor and causing a 20° rotation in the cofactor tilt relative to the ligand-free form. Aromatic–aromatic interactions occur between the bound gabaculine molecule and active-site residues Tyr85 and Phe 177, whereas Tyr55 and Arg180 provide specific contacts to the α -amino and carboxyl groups of L-canaline. Conclusions: The OAT–L-canaline complex structure implicates Tyr55 and Arg180 as the residues involved in coordinating with the natural substrate ornithine during normal enzyme turnover. This correlates well with two enzyme-inactivating point mutations associated with gyrate atrophy, Tyr55→His and Arg180→Thr. The OAT–gabaculine complex provides the first structural evidence that the potency of the inhibitor is due to energetically favorable aromatic interactions with residues in the active site. This aromatic-binding mode may be relevant to structure-based drug design efforts against other ω -aminotransferase targets, such as GABA aminotransferase.
Promoting a coupled human and natural systems approach to addressing conservation in complex mountainous landscapes of Central Asia

Global climate change, nonpoint source pollution, watershed and wildlife habitat destruction, and unsustainable development are damaging the natural world, threatening the socio-cultural integrity of communities, and jeopardizing the livelihood security of peoples worldwide. Despite the past 50 years of progress in addressing environmental damage in the United States and elsewhere, intractable problems have arisen that to date have eluded successful technological or policy responses. Solutions have been sought by recognizing that these problems are very complex and demand interdisciplinary approaches that require building effective partnerships among relevant academic institutions, governmental agencies, nongovernmental organizations, and private business, as well as levering various disciplines and traditional knowledge systems. Such thinking has evolved to now consider humans to be an integral part of nature, which is captured in the idea of the ‘human ecosystem’, where biophysical, socioeconomic, and cultural systems interact via a complex set of organizational, spatial, and temporal ‘couplings’. Within such a context, environmental problems can be viewed as coupled human and natural systems, which afford unique and novel approaches to their solutions. This paper discusses the development of the coupled systems approach as a scientific methodology, reviews its key characteristics and principles, provides an example of how it has been applied to assess conservation issues in alpine areas of Northwest Yunnan Province, China, and recommends how this scientific approach might be further developed for use in mountainous landscape regions of Central Asia and elsewhere.
Order of Exposure to High Dietary Calcium and Gray Strain Infectious Bronchitis Virus Alters Renal Function and the Incidence of Urolithiasis

Experiments were designed to determine if Gray strain infectious bronchitis virus (IBV) infection increases the incidence of urolithiasis type kidney damage when the urine is already high in Ca and relatively alkaline due to a high Ca-low available P diet (i.e., layer ration). In addition, experiments were conducted to determine the effects of Gray strain IBV on pullet renal function of 6 and 14-wk-old pullets at 2, 5, and 10 days postinoculation (PI). Blood gas parameters were measured to determine the mechanism by which layer ration decreases hydrogen ion concentration [( H+]). Urine flow rate, glomerular filtration rate, electrolyte excretion (Na, K, Ca, P), free water clearance, urine osmolality, urine [H+], and renal plasma flow (para-aminohippuric clearance) were measured to assess renal function. Gray strain IBV increased urine [H+] and decreased renal plasma flow in 6-wk-old pullets, and induced a diuresis in 14-wk-old pullets between 5 and 10 days PI. The layer ration increased Ca excretion and induced a metabolic alkalosis, thus decreasing urine [H+] and causing urolith formation. Feeding layer ration followed by Gray strain IBV infection had an additive effect on the incidence of urolithiasis and gross kidney damage. Gray strain IBV infection 8 wk prior to feeding layer ration did not induce urolithiasis. The results suggest that the additive effect of Gray strain IBV on the incidence of urolithiasis is probably due to tubular damage rather than direct changes in renal function parameters.
Non-Covalent Interactions with Dual-Basis Methods: Pairings for Augmented Basis Sets

Basis set pairings for dual-basis calculations are presented for the aug-cc-pVXZ (X = D, T, Q) series of basis sets. Fidelity with single-basis results is assessed at the second-order Moller−Plesset perturbation theory (MP2) level within the resolution-of-the-identity (RI) approximation, using the S22 set of noncovalent interactions and a series of electron affinities from the G3 set. Root-mean-squared errors for the S22 set are 0.019 kcal mol−1 or lower, with a maximum deviation of 0.44%, and errors in nuclear structures are 0.09% or lower. Cost savings of 60−93% (RI-MP2 energies) and 50−88% (RI-MP2 gradients) are demonstrated. Spin-component-scaled MP2 [SCS(MI)-MP2] scaling parameters are provided for the aug-cc-pVXZ series, and dual-basis results are shown to be consistent without reoptimization of the single-basis parameters. Explicit handling of linear dependence in the basis set projection scheme is also provided. These dual-basis pairings will be helpful for accelerating accurate Hartree−Fock, dens...
Carbon Nanofiber Nanoelectrode Array: Effect of Process Conditions on Reliability

Nanoelectrode arrays (NEA) using 1-D nanomaterials as the electrode material have shown promise for biosensing applications. Vertical, freestanding, individual carbon nanofibers (CNFs) on patterned substrates constitute one example of NEA in the literature. The development of a biosensor system using this NEA first requires reliability studies prior to undertaking system integration with microfluidics and sample handling aspects. Here, we have investigated the effect of temperature and process conditions on the diameters and quality of the CNFs using atomic force microscopy (AFM). A Taguchi approach is employed to study the temperature effect in etched and unetched CNFs using AFM followed by a statistical analysis.
Methamphetamine induces AP-1 and NF-κB binding and transactivation in human brain endothelial cells

Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity may involve alterations of cellular redox status and induction of inflammatory genes in endothelial cells. To study these hypotheses, molecular signaling pathways of METHinduced inflammatory responses via activation of redoxsensitive transcription factors were investigated in human brain microvascular endothelial cells (HBMEC). A dose-dependent depletion of total glutathione levels was detected in HBMEC exposed to METH. In addition, electrophoretic mobility shift assay (EMSA) showed significant increases in DNA binding activities of redoxresponsive transcription factors, AP-1 and NF-kB, in HBMEC treated with METH. METH-mediated AP-1 or NF-kB activation was accompanied by induction of transactivation of AP-1 or NF-kB, as measured by dual luciferase assay using specific reporter plasmids. Because NF-kB and AP-1 are known to regulate expression of inflammatory genes, expression of the gene encoding for tumor necrosis factor-a (TNF-a) was also studied in METH-treated HBMEC. A dose-dependent overexpression of the TNF-a gene was observed in HBMEC treated with METH. The importance of AP-1 and NF-k Bi n METH-induced TNF-a gene was confirmed in functional promoter studies using constructs of the TNF-a promoter with mutated AP-1 or NF-kB sites. These results indicate that METH-induced disturbances in cellular redox status and activation of AP-1 and NF-kB can play critical roles in the signaling pathways leading to upregulation of inflammatory genes in human brain endothelial cells. J. Neurosci. Res. 66:583‐591, 2001. © 2001 Wiley-Liss, Inc.
Biological Effects of Electric Shock and Heat Denaturation and Oxidation of Molecules, Membranes, and Cellular Functions

Direct exposure of cells in suspension to intense electric pulses is known to produce damages to cell membranes and supramolecular organizations of cells, and denaturation of macromolecules, much like injuries and tears seen in electric trauma patients. Thus, the system has been used as a laboratory model for investigating the biochemical basis of electric injury. An intense electric pulse can produce two major effects on cells--one caused by the field, or the electric potential, and the other by current, or the electric energy. The field-induced transmembrane potential can produce electro-conformational changes of ion channels and ion pumps and, when the potential exceeds the dielectric strength of the cell membrane (approximately 500 mV for a pulse width of a few ms), electro-conformational damages and electroporations of membrane proteins and lipid bilayers. These events lead to passage of electric current through the membrane-porated cells and to heating of cell membranes and cytoplasmic contents. The subsequent denaturation of cell membranes and cytoplasmic macromolecules brings about many complex biochemical reactions, including oxidation of proteins and lipids. The combined effects may cripple the cells beyond repair. This communication will focus on the thermal effects of electric shock. After a brief review of the current state of knowledge on thermal denaturation of soluble enzymes and muscle proteins, this paper will describe experiments on the thermal denaturation of cellular components and functions, such as nucleosomes, and the electron transport chain and ATP synthetic enzymes of the mitochondrial inner membranes. Data will show that lipid peroxidation and the subsequent loss of the energy-transducing ability of the cells may occur even at moderate temperatures between 40 degrees C and 45 degrees C. However, lipid peroxidation may be prevented with reducing reagents such as mercaptoethanol, dithiothreitol, and ascorbic acid. Reactivation of denatured cellular proteins and functions may also be possible and a strategy for doing so is discussed.
A Remote-Sensing, GIS-Based Approach to Identify, Characterize, and Model Spawning Habitat for Fall-Run Chum Salmon in a Sub-Arctic, Glacially Fed River

Abstract At northern limits of a species’ distribution, fish habitat requirements are often linked to thermal preferences, and the presence of overwintering habitat. However, logistical challenges and hydrologic processes typical of glacial systems could compromize the identification of these habitats, particularly in large river environments. Our goal was to identify and characterize spawning habitat for fall-run chum salmon Oncorhynchus keta and model habitat selection from spatial distributions of tagged individuals in the Tanana River, Alaska using an approach that combined ground surveys with remote sensing. Models included braiding, sinuosity, ice-free water surface area (indicating groundwater influence), and persistent ice-free water (i.e., consistent presence of ice-free water for a 12-year period according to satellite imagery). Candidate models containing persistent ice-free water were selected as most likely, highlighting the utility of remote sensing for monitoring and identifying salmon habi...
Magnetic and Electrostatic Focusing in the Cyclotron

A quantitative study of the magnetic and electrostatic focusing of ions being accelerated in the cyclotron is made on the basis of electric and magnetic field measurements. The relative importance of the two effects is found to depend on the energy or path radius of the circulating particles. For small energies, only the electrostatic action is effective; and it is found that actually it constitutes a defocusing action which causes the ions to move away from the central plane between the magnet pole faces and so to become lost. At larger energies the electrostatic field becomes a focusing action but also the effect becomes rapidly smaller and, if acting alone, would cause the particles to oscillate back and forth across the central plane with increasing amplitude so that a very diffuse beam would result. On the other hand, at the larger energies, the focusing due to the outward curvature of the magnetic lines of force soon predominates and becomes rapidly larger and causes the ions to oscillate about the central plane, but now with decreasing amplitude so that it is by the magnetic effect that the diffuse starting ions are focused to the concentrated beam which is actually obtained. It is shown that the amplitudes of vertical oscillation due to the electrostatic field increases with ${r}^{\frac{3}{4}}$, and that the amplitudes due to the magnetic field vary as ${(\ensuremath{-}\frac{r\ensuremath{\partial}H}{\ensuremath{\partial}r})}^{\ensuremath{-}\frac{1}{4}}$ for ions in phase. Calculations of the vertical motion of the ions as they circulate out from the center by means of a step by step process of integration indicate that the electrostatic defocusing action decreases with $\frac{d}{h}$, the ratio of electrode separation to electrode height. Thus for maximum output currents the electrode height should be as large and the separation as small as possible. The width of the beam and distribution of ions with height was measured at various distances from the center for the case of the cyclotron in use at Berkeley up to August 1937. This was done by measuring the radioactivity induced in a probe which was introduced into the beam. The widths so obtained agree within one or two mm with the widths calculated from the theory presented. Various changes in accelerator electrode design are suggested which would decrease their capacity and so enable larger high frequency input voltages to be obtained.
Intramodal blocking between olfactory stimuli in rats

The means by which olfactory systems enable the consistent recognition of biologically meaningful odors that may vary in composition over time is a central problem in olfaction. Experiments in honeybees have suggested a solution to one aspect of this problem by demonstrating that the learning of components in an odor mixture suppresses subsequent learning about additional components that are later added to that mixture. We here show, in rats, that intramodal olfactory blocking is also exhibited in vertebrates, and furthermore that the specific characteristics of this blocking are similar to those observed in intermodal blocking studies. Using an olfactory digging task, we submitted two groups of rats to the following olfactory training protocol: one group was first trained (five trials) on an odor (A), followed by five training trials on a binary mixture (A+B), while the second group was similarly trained on a different odor (C) followed by the binary mixture (A+B). After training, both groups' unrewarded responses to the mixture (A+B), odor (B), and an unconditioned control odor (X) were measured. For four out of five odor sets used in this experiment, a significant difference in digging time was observed between the responses of the two groups to odor B (P<.01), but not between their responses to the binary mixture (A+B) or to the control odor (X). These results demonstrate that pretraining rats with an odorant blocks subsequent learning about another odorant when the latter is presented simultaneously with the pretrained odorant, indicating that the components of a mixture are at least partially perceived as independent elements of this mixture.