cssi/SciSciGPT-SciSciNet huggingface dataset:
A new type of DNA minor-groove complex: carbazole dication-DNA interactions.

The effect of opportunistic infections (OI) on immune-compromised populations has been known for decades, but the recent AIDS epidemic has sparked renewed interest in the development of new anti-OI agents. The mechanism of action of a series of cationic unfused-aromatic anti-OI drugs is believed to involve binding of the drug to AT sequences in the minor groove of DNA. Some new anti-OI drug candidates have been synthesized with fused aromatic ring systems (e.g. carbazoles) that do not resemble the classical paradigm for minor-groove interactions at AT sequences in DNA. To characterize the DNA interactions of these compounds, we have used UV-vis absorbance, fluorescence, kinetic measurements, and circular dichroism in conjunction with NMR spectroscopy to evaluate the structure of the complexes formed between the carbazoles and DNA. Application of these methods to carbazoles substituted at either the 3,6 or 2,7 positions with cationic imidazoline groups gave conclusive, but very surprising, evidence that both compounds bind strongly in the minor groove at AT DNA sequences. NMR and molecular modeling of the complexes formed between the 3,6- and 2,7-carbazoles and the self-complementary oligomer d(GCGAATTCGC) have been used to establish structural details for the minor-groove complex. These results have been used as constraints for molecular modeling calculations to construct models of the minor-groove-carbazole complexes and to draw conclusions regarding the molecular basis for the effects of substituent position on carbazole-DNA affinities. The surprising result is that the 2,7 carbazole binds in AT sequences with hydrogen bonds involving one imidazoline group and the carbazole NH. The 3,6-carbazole compound binds in a more "classical" model that uses both imidazoline groups for H-bonding while the carbazole NH points out of the minor groove. The carbazoles thus form a new type of DNA minor groove complex and their excellent biological activities indicate that a variety of fused-ring minor-groove binding agents should be investigated.
Quantitative assessment of in vivo focused ultrasound induced blood-brain barrier opening using magnetic resonance imaging

Delivery of therapeutic compounds to the brain is limited, because due to their molecular size they cannot cross the blood-brain barrier (BBB). Focused ultrasound (FUS) after administration of microbubbles into the blood-stream has been shown to open the BBB locally, non- invasively and reversibly. In this study, we investigated the time required for BBB's permeability at the sonicated region to revert to its initial condition. BBB opening has also been shown to be induced safely for a variety of sonicating parameters. The group of parameters tested was as follows: Pulse Repetition Frequency 10Hz, 20% duty cycle, pulse length 20ms, two sets of 30s sonication with a 30s delay between, with peak-rarefactional pressure of 0.30MPa. Contrast-enhanced high-resolution MRI (9.4 T) revealed BBB opening and allowed for the monitoring of the slow permeation of gadolinium in the hippocampus. BBB closing appeared to occur within a maximum of 5 days after sonication at the aforementioned parameters. The timeline of BBB closing will allow for time wise more efficient delivery of therapeutic compounds to the brain, as well as critical guidance for repeated drug administration over a period of time when necessary.
Archean geochemistry of formaldehyde and cyanide and the oligomerization of cyanohydrin.

The sources and speciation of reduced carbon and nitrogen inferred for the early Archean are reviewed in terms of current observations and models, and known chemical reactions. Within this framework hydrogen cyanide and cyanide ion in significant concentration would have been eliminated by reaction with excess formaldehyde to form cyanohydrin (glycolonitrile), and with ferrous ion to formferrocyanide. Natural reactions of these molecules would under such conditions deserve special consideration in modeling of primordial organochemical processes. As a step in this direction, transformation reactions have been investigated involving glycolonitrile in the presence of water. We find that glycolonitrile, formed from formaldehyde and hydrogen cyanide or cyanide ion, spontaneously cyclodimerizes to 4-amino-2-hydroxymethyloxazole. The crystalline dimer is the major product at low temperatue (approximately 0 C); the yield diminishes with increasing temperature at the expense of polymerization and hydrolysis products. Hydrolysis of glycolamide and of oxazole yields a number of simpler organic molecules, including ammonia and glycolamide. The spontaneous polymerization of glycolonitrile and its dimer gives rise to soluble, cationic oligomers of as yet unknown structure, and, unless arrested, to a viscous liquid, insoluble in water. A loss of cyanide by reaction with formaldehyde, inferred for the early terrestrial hydrosphere and cryosphere would present a dilemma for hypotheses invoking cyanide and related compounds as concentrated reactants capable of forming biomolecular precursor species. Attempts to escape from its horns may take advantage of the efficient concentration and separation of cyanide as solid ferriferrocyanide, and most directly of reactions of glycolonitrile and its derivatives.
Proposed Method to Assess Timber Harvesting Roads

Timber harvesting roads, skid roads, and truck roads have been identified as major sources of stream sedimentation during logging operations. Researchers have stated that the planning for timber harvesting road networks is key to reducing these erosion and stream sedimentation sources. One impediment to reducing stream sedimentation is that planners do not have a was to quantify road network sufficiency and efficiency, particularly for those networks used by rubber-tired skidders during cable skidding operations. Reach capacity and excess reach capacity are proposed as ways to measure road network sufficiency and efficiency. Reach capacity is defined as the percent of a tract covered by a zone of specified distance around each road segment. Reach capacity is a measure of that portion of the tract that can be reached with a winch cable from the road system to move trees to the road for skidding. Excess reach capacity is the total area of all possible road zone overlaps expressed as a percentage of the reac...
The First Lesson in a Beginning Class

Author's summary.— A suggestion to use numbers as the first step to teach pronunciation of a foreign tongue.
Animal model for evaluating the effect of systemic estrogen deficiency on residual ridge resorption

The rate of resorption of residual ridges after tooth extraction varies amongsubjects. Despite many human studies, the etiologic factors of severe forms of resorption of residual ridges are unknown and probably multifactorial. To facilitate investigations of resorption of residual ridges, it is preferable to use an animal model with a dentoalveolar component similar to that of human beings. This study developed a rapid, nonhuman primate model in which one could measure resorption of residual ridges at the most critical period, with the least amount of time, minimal operation, and the least interference with normal nutrition. Three female Macaca fascicularis monkeys, 7 to 9 years old, were selected for simple extraction of four maxillary incisors, four mandibular incisors, and two mandibular canines. Lateral cephalographs were taken at weeks 0, 1, 2 to 3, 5 to 6, 8 to 9, 11 to 12, and 26 to 28 after extraction with a newly constructed cephalostat that allowed easy reproductibility of animal placement in the prone position. Height and area measurements were made of maxillary and mandibular anterior residual ridges in the superimposed cephalographs. Sequential mean bone loss data produced bone loss curves similar to those observed in humans. One animal underwent ovariectomy. The plasma levels of both estrogen and progesterone decreased over 25 days and stayed below the detection limits thereafter. Tooth extraction was done 4 weeks after the ovariectomy and the bone resorption pattern was able to be observed longitudinally with the newly established monkey cephalostat. The results indicated that Macaca fascicularis need not be sacrificed when used in longitudinal studies of resorption of residual ridges in a relatively short period of experimental time. This model can provide an excellent opportunity to investigate a causal relationship between the rate of resorption of residual ridges and predisposing systemic factors such as estrogen deficiency.
Effect of 9-(4-hydroxybutyl)-N2-phenylguanine (HBPG), a thymidine kinase inhibitor, on clinical recurrences of ocular herpetic keratitis in squirrel monkeys

Abstract 9-(4-Hydroxybutyl)- N 2 -phenylguanine (HBPG) is a new viral thymidine kinase inhibitor that we tested for the ability to prevent recurrences of herpetic keratitis. Eighteen squirrel monkeys ( Saimiri scuireus ) were infected in both corneas with the Rodanus strain of herpes simplex virus type 1 (HSV-1). All corneas showed typical dendritic keratitis 3 days after infection, followed by spontaneous healing. On day 21, the monkeys were randomized into two coded groups and ocular examinations were begun. One group received intraperitoneal (i.p.) injections of HBPG, 150 mg/kg, in a corn oil suspension every 8 h, and the other group received i.p. injections of the corn oil vehicle only. On day 22, recurrences were induced by reducing the temperature of the room in the late afternoon so that a low of 18°C was achieved during the night. After the morning treatment, room temperature was raised to the normal ambient temperature (24–27°C), and treatment was discontinued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as before. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at which point the code was broken. We found that the HBPG treatment significantly reduced the number of corneas with recurrences during the treatment periods, compared with recurrences in untreated, cold-stressed animals ( P =0.01).
Visualization of Nuclear and other Non-commercial Materials Using Megavoltage X-ray Technology

Abstract The megavoltage X-ray technology is utilized for detecting nuclear materials in cargo containers. An interlaced response is obtained by switching between 6MeV and 9 MeV beams. By measuring the penetration levels of cargo contents, the major materials representing the threat group and some non-commercial materials can be visualize via an stationary wavelet algorithm. The experiments have been performed with Linatron K9 designed by Varian Security and Inspection Products.
Children's Occupational Sex-Role Stereotyping in 1994:

To update the basis of the explanation of how elementary children evaluate the capability of males versus females to perform occupations which are dominated by males, females, or are gender balanced (neutral) in the workforce 180 girls and 200 boys in Grades 1, 2, and 3 completed a questionnaire indicating which of 39 occupations were mostly done by women, by either, or by men on a 5-point scale. The most and least stereotyped occupations were very like gender-occupational data from 1972 and 1983 and reflected the actual sex-typing in the labor force. Sex and grade differences were noted for male occupations but not for female occupations. Some differences from 1977 data of Garrett, et al. were noted. The neutral status of some occupations appeared to assume a male worker.
Auranofin in the treatment of juvenile rheumatoid arthritis

Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during an open-ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg/day; incremental increases to 0.2 mg/kg/day were allowed. Aspirin (80 mg/kg/day), tolmetin (20 to 40 mg/kg/day), and naproxen (400 to 600 mg/m 2 /day) were allowed as rapidly acting anti-inflammatory agents. All patients attained measurable plasma concentrations of gold during the study. Clinically significant improvement (greater than 25%) occurred in more than half the patients with regard to the number and severity of joints with swelling. pain on motion, and tenderness. The number of joints with active arthritis decreased by at least 25% in nine of the 19 patients. Group mean changes between the initial and final visit indicated improvement in all articular disease indices measured. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25%. The group given the higher dosage had a greater proportion of responders with decreases in erythrocyte sedimentation rate. Four of six patients whose sera contained rheumatoid factor showed decreases in its titier. Discontinuation of auranofin was necessary in two patients because of headaches and because of hematuria and anemia associated with a severe flare of polyarticular disease, respectively. The results from this trial are sufficiently encouraging to merit a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.
AIR FLOW AND HEAT TRANSFER IN A TEMPERATURE-CONTROLLED OPEN TOP ENCLOSURE

A large 12-meter-diameter open top enclosure (OTE) equipped with two unique belowground and above ground heating systems was built and intensively tested in Oak Ridge, TN, USA. The OTE is a prototype for use within an environmental change experiment, in which replica units will be built in Minnesota to assess the response of northern peatland ecosystems to increases in temperature and elevated atmospheric CO2. For several months, temperatures, energy, wind speed and relative humidity were monitored throughout the enclosure space to assess the enclosure performance and efficiency. In parallel, Computational Fluid Dynamics (CFD) simulations were performed with ANSYS-CFX to investigate the impacts of external wind, buoyancy, and OTE design on the temperatures achieved within the enclosure. The addition of a frustum that partially reduced the top opening was also investigated experimentally and numerically. The OTE is capable of achieving a temperature differential of at least +6°C for air using a combination of 8 electrical heaters. Differential temperatures were sustained for several months. The experimental data and the numerical results showed that the addition of a frustum dramatically decreases the operating cost of the OTE and leads to better control over the differential air temperature in the enclosure. Buoyancy forces and winds heavily impacted enclosure performance. It was also found that the heating efficiency of the OTE depends mainly on the wind speed, and that there exists a critical wind speed at which the heating efficiency is the highest.Copyright © 2012 by ASME
The Capacity of Noncoherent Continuous-Phase Frequency Shift Keying

Capacity analysis is used to determine the fundamental tradeoff between power and spectral efficiency for coded continuous-phase frequency shift keying (CPFSK). The modulation may use an arbitrary modulation index h and the number of tones M may be any power of two. Detection is noncoherent and the channel is either AWGN or fully-interleaved (ergodic) Reyleigh fading. Numerical results demonstrate the advantage of using nonorthogonal modulation and multiple tones when the bandwidth requirement is tight.
Effects of Combined Stresses on Fracture of Alumina and Graphite

A unique method was developed for mechanical testing of brittle materials to create an unlimited number of stress ratios in the tension-tension and tension-compression quadrants. The stress states are achieved by internal and external pressurization of tubular specimens in a special pressure vessel. Failure envelopes were determined for polycrystalline alumina and fine-grained isotropic graphite. The modified maximum strain energy and Coulomb-Mohr theories fit the data best; these theories should be plotted as bands representing probability of failure. The biaxial tensile strengths of alumina and graphite are lower than their uniaxial tensile strengths; the tensile strengths decrease as the compressive stress in the orthogonal directions increases.
ODERACS preflight optical calibration

Detection and measurement of small space debris objects are vital to verify the validity of debris models for the low Earth orbit (LEO) environment. Calibration of optical instruments is necessary so that reliable estimates of the size and albedo of man-made orbiting objects can be found. The Orbital Debris Radar Calibration Spheres (ODERACS) project is being conducted by NASA and the DoD to calibrate both radar and optical tracking facilities for small objects. This paper discusses the pre-flight optical calibration of the spheres. The purpose of this study is to determine the spectral reflectivity, scattering characteristics and albedo for the visible wavelength region. The measurements are performed by illuminating the flight spheres with a collimated beam of light, and measuring the reflected visible light over possible phase angles. This allows one to estimate the specular and scattering characteristics as well as the albedo. Tests were conducted on several flight and test metal spheres with varying diameters and surface characteristics. The polished metal spheres are shown to be very good specular reflectors, while the diffuse surfaces exhibit both specular and scattering reflection characteristics.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Generation of the R2 Subunit of Ribonucleotide Reductase by Intein Chemistry: Insertion of 3-Nitrotyrosine at Residue 356 as a Probe of the Radical Initiation Process†

Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. The enzyme is composed of two subunits: R1 and R2. R1 contains the active site for nucleotide reduction and the allosteric effector sites that regulate the specificity and turnover rate. R2 contains the diferric-tyrosyl (Y•) radical cofactor that initiates nucleotide reduction by a putative long-range proton-coupled electron transfer (PCET) pathway over 35 A. This pathway is thought to involve specific amino acid radical intermediates (Y122 to W48 to Y356 within R2 to Y731 to Y730 to C439 within R1). In an effort to study radical initiation, R2 (375 residues) has been synthesized semisynthetically. R2 (residues 1−353), attached to an intein and a chitin binding domain, was constructed, and the protein was expressed (construct 1). This construct was then incubated with Fe2+ and O2 to generate the diferric-Y• cofactor, and the resulting protein was purified using a chitin aff...
On the relative sensitivity of mass-sensitive chemical microsensors

In this work, the chemical sensitivity of mass-sensitive chemical microsensors with a uniform layer sandwich structure vibrating in their lateral or in-plane flexural modes is investigated. It is experimentally verified that the relative chemical sensitivity of such resonant microsensors is -to a first order- independent of the microstructure's in-plane dimensions and the flexural eigenmode used, and only depends on the layer thicknesses and densities as well as the sorption properties of the sensing film. Important implications for the design of mass-sensitive chemical microsensors are discussed, whereby the designer can focus on the layer stack to optimize the chemical sensitivity and on the in-plane dimensions and mode shape to optimize the resonator's frequency stability.
Prescribing the length of parametric curves

Abstract Theorems and corresponding algorithms are presented which produce a parametric curve of a specified arc length subject to certain constraints. Extraneous inflection points are avoided. The problem is reduced to expressing the arc length as a function of a single variable. A general theorem is presented which gives conditions under which the arc length function is convex or strictly convex. It is also shown that initial parameters may be automatically chosen so that the secant method will produce a solution to this problem with performance comparable to the Newton-Raphson method. Earlier results of one of the authors for Bezier polynomial curves are strengthened and extended using these results.
The Softness Parameters of Ions. Prediction of the Occurrence of Miscibility Gaps in Molten Salt Mixtures

Softness parameters σM for cations and σX for anions, have been calculated as dimensionless quantities for approx. 90 cations and 18 anions. They are given by σM = [σA (Mm+) - σA(H+)]/σA(H+) and σX = [σB(Xa−) - σB(OH−)]/σA(H+) where σA = [σIi(M) + ΔH0h(Mm+)]/m and σB = [-Ea(X) + ΔH0h(Xa−)]/a are Ahrland's parameters. The new normalized and comparative (to the test ions H+ and OH−) softness parameters are positive for soft ions and negative for hard ones. These parameters, obtained independently, are used with a four-coefficient equation to calculate coordinate bond energies for metal halides with acceptable accuracy. Considerations of the average coordination in reciprocal molten salt mixture lead to an expression for the metathesis energy change as proportional to the product of the differences in softness parameters of the two cations and the two anions. An empirical one-coefficient equation involving the softness parameters is proposed to deal with next-nearest-neighbor interactions in binary common-ion molten salt mixtures. These relationships are then used with Blander and Topol's equation to predict the occurrence of irascibility gaps in uni-univalent reciprocal salt mixtures. The gaps found in other systems are also discussed in terms of the softness of the constituent ions.
SPM-Based 2R Regenerative 10Gbps Optically Linearly Controlled Delay Line with 0ps to 170ps Tuning Range

We demonstrate a 2R regenerative optical delay line with error-free operation, 1 dB negative sensitivity penalty for degraded 10 Gbps RZ packets. Its time delay can be linearly tuned from 0 ps to 170 ps with maintained original wavelength.
STM observations of two-dimensional condensed layers on solid electrodes

Abstract Two-dimensional condensed monolayers formed electrochemically on highly oriented pyrolitic graphite (HOPG) have been imaged using STM techniques. The formation process involves electrochemical adsorption followed by a phase transition to the condensed state which is controlled by the electrode potential. The resulting layered structures are well ordered and free of defects. In this work, the electrochemistry of condensed layers is briefly reviewed from a thermodynamic perspective. Recent STM studies are discussed and shown to confirm some of the earlier conclusions about condensed monolayer structures. It is also shown that the structure and the composition of a single phase of a condensed layer changes with electrode potential and the composition of the electrolyte for the cases of adenine and guanine on HOPG. Possible applications in the formation of structured films for nanotechnology are discussed.
Isoform- and Species-specific Control of Inositol 1,4,5-Trisphosphate (IP3) Receptors by Reactive Oxygen Species

Reactive oxygen species (ROS) stimulate cytoplasmic [Ca2+] ([Ca2+]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2⨪) on IP3R-mediated Ca2+ signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca2+]c spikes and frequency-modulated oscillations evoked by a O2⨪ donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. The [Ca2+]c signal was mediated by ER Ca2+ mobilization. X+XO added to permeabilized cells promoted the [Ca2+]c rise evoked by submaximal doses of IP3, indicating that O2⨪ directly sensitizes IP3R-mediated Ca2+ release. In response to X+XO, DT40 cells lacking two of three IP3R isoforms (DKO) expressing either type 1 (DKO1) or type 2 IP3Rs (DKO2) showed a [Ca2+]c signal, whereas DKO expressing type 3 IP3R (DKO3) did not. By contrast, IgM that stimulates IP3 formation, elicited a [Ca2+]c signal in every DKO. X+XO also facilitated the Ca2+ release evoked by submaximal IP3 in permeabilized DKO1 and DKO2 but was ineffective in DKO3 or in DT40 lacking every IP3R (TKO). However, X+XO could also facilitate the effect of suboptimal IP3 in TKO transfected with rat IP3R3. Although in silico studies failed to identify a thiol missing in the chicken IP3R3, an X+XO-induced redox change was documented only in the rat IP3R3. Thus, ROS seem to specifically sensitize IP3Rs through a thiol group(s) within the IP3R, which is probably inaccessible in the chicken IP3R3.
Embryonic and Early Postnatal Abnormalities Contributing to the Development of Hippocampal Malformations in a Rodent Model of Dysplasia

While there are many recent examples of single gene deletions that lead to defects in cortical development, most human cases of cortical disorganization can be attributed to a combination of environmental and genetic factors. Elucidating the cellular or developmental basis of teratogenic exposures in experimental animals is an important approach to understanding how environmental insults at particular developmental junctures can lead to complex brain malformations. Rats with prenatal exposure to methylazoxymethanol (MAM) reproduces many anatomical features seen in epilepsy patients. Previous studies have shown that heterotopic clusters of neocortically-derived neurons exhibit hyperexcitable firing activity and may be a source of heightened seizure susceptibility, however the events that lead to the formation of these abnormal cell clusters is unclear. Here, we used a panel of molecular markers and birthdating studies to show that in MAM-exposed rats, the abnormal cell clusters (heterotopia) first appear postnatally in the hippocampus (P1–P2) and that their appearance is preceded by a distinct sequence of perturbations in neocortical development: (i) disruption of the radial glial scaffolding with premature astroglial differentiation and (ii) thickening of the marginal zone with redistribution of Cajal-Retzius neurons to deeper layers. These initial events are followed by disruption of the cortical plate and appearance of subventricular zone nodules. Finally, we observed the erosion of neocortical subventricular zone nodules into the hippocampus around parturition followed by migration of nodules to hippocampus. We conclude that prenatal MAM exposure disrupts critical developmental processes and prenatal neocortical structures ultimately resulting in neocortical disorganization and hippocampal malformations.
Alkyl substituent effects on reductive elimination reactions in zirconocene alkyl hydride complexes. Manipulation of the alkyl steric environment allows the synthesis of a zirconocene dinitrogen complex

The rate of reductive elimination as a function of alkyl ligand has been measured for a series of zirconocene alkyl hydride complexes, Cp*Cp‘ ‘Zr(R)H (Cp* = η5-C5Me5, Cp‘ ‘ = η5-C5H3-1,3-(SiMe3)2, R = CH3, CH2(CH2)2CH3, CH2(CH2)6CH3, CH2cC6H11, CH2CHMe2, CH2CMe3), where the steric disposition of the alkyl ligand has been systematically varied. The rate of reductive elimination increases modestly as the steric bulk of the alkyl ligand is increased. This trend is attributed to ground state destabilization arising from unfavorable steric interactions between the alkyl ligand and the cyclopentadienyl substituents. The effect is magnified when more voluminous cyclopentadienyl ligands are incorporated into the metallocene framework. Thus, the Cp*Cp‘ ‘‘Zr(R)H (Cp‘ ‘‘ = η5-C5H2-1,2,4-(SiMe3)3, R = CH3, CH2(CH2)2CH3, CH2(CH2)6CH3) series of alkyl hydride complexes lose alkane more readily than the corresponding Cp*Cp‘ ‘Zr(R)H complexes. In addition, the rate of reductive elimination has also been examined for Cp*C...
Maximum achievable aspect ratio in deep reactive ion etching of silicon due to aspect ratio dependent transport and the microloading effect

When etching high-aspect-ratio silicon features using deep reactive ion etching (DRIE), researchers find that there is a maximum achievable aspect ratio, which we define as the critical aspect ratio, of an etched silicon trench using a DRIE process. At this critical aspect ratio, the apparent etch rate (defined as the total depth etched divided by the total elapsed time) no longer monotonically decreases as the aspect ratio increases, but abruptly drops to zero. In this paper, we propose a theoretical model to predict the critical aspect ratio and reveal its causal mechanism. The model considers aspect ratio dependent transport mechanisms specific to each of the reactant species in the three subprocesses of a time-multiplexed etch cycle: deposition of a fluorocarbon passivation layer, etching of the fluorocarbon polymer at the bottom of the trench, and the subsequent etching of the underlying silicon. The model predicts that the critical aspect ratio is defined by the aspect ratio at which the polymer etc...
Pretravel compensation for horizontally oriented touch trigger probes with straight styli

Abstract Touch trigger probes are devices through which coordinate measuring machines (CMMs) and machine tools collect dimensional measurement data in modern manufacturing environments. Advances in machine accuracy and tighter part tolerances leave probe error as one of the major error sources in these dimensional measurement processes. Pretravel accounts for the majority of touch trigger probe errors and is caused by bending deflection of the probe stylus shaft. A pretravel model for horizontally oriented touch trigger probes is described in this paper. A trigger force model based on the principle of mechanics is derived and used to develop the pretravel model, and the model accounts for bending deflection of the stylus shaft at the trigger instant. Pretravel is modeled as a function of probe design parameters (such as stylus length, tripod leg length, and stylus material) and probe operating parameters (such as spring force setting and probe approach direction). In applying the model to predict probe pretravel, only one model parameter needs to be calculated from 24 points of experimental probe data. In addition, the influence of probe approach speed on probe pretravel and model applicability has been investigated in this paper. The model is robust and can be implemented by means of a software correction module, which can be incorporated into machine systems.
The role of actin sulfhydryls in actin-myosin interaction.

Abstract 1. 1.|Rabbit white skeletal and dog cardiac actins combined fully with the heavy meromyosins at 4 °C and low ionic strength (I 0.03); the complexes (actin-heavy meromyosin) were mostly in a heavy component which settled rapidly during rotor acceleration. Increasing the temperature to 24 °C favored formation of the heavy component while increasing the ionic strength to I 0.3 decreased formation of the heavy component. 2. 2.|Modification of actin with p-mercuribenzoate (PCMB) generally reduced the heavy component and viscosity but did not interfere with actin-heavy meromyosin combination. Modification with iodoacetamide or N-ethylmaleimide had similar effects. 3. 3.|Addition of ATP reduced viscosity and eliminated the heavy component at levels which partially dissociated actin-heavy meromyosin. 4. 4.|Modification of heavy meromyosin with PCMB inhibited combination with actin. 5. 5.|The characteristics of interaction of the cardiac proteins varied less with temperature but more with ionic strength than those of skeletal proteins.
Evidence that potassium channels mediate the effects of serotonin on the ocular circadian pacemaker of Aplysia

The eye of the marine mollusk Aplysia californica contains a photo-entrainable circadian pacemaker that drives an overt circadian rhythm of spontaneous compound action potentials in the optic nerve. Serotonin is known to influence the phase of this ocular rhythm. The aim of the present study was to evaluate whether potassium channels are involved in effects on the ocular circadian rhythm. Our experimental approach was to study the effect of the potassium channel antagonist barium on serotonin-induced phase shifts of this rhythm. The application of barium was found to block serotonin-induced phase shifts whereas barium alone did not cause significant phase shifts. The effects of barium were found to be dose dependent. In addition, barium blocked forskolin-induced phase advances but did not interfere with serotonin-induced increases in cAMP content. Finally, barium antagonized serotonin-induced suppression of compound action potential activity. These results are consistent with a model in which the application of serotonin phase shifts the ocular pacemaker by causing a membrane hyperpolarization which is mediated by a cAMP-dependent potassium conductance.
Direct quantification of autologous serum albumin leakage after burn injury in mice

The current technique determining the extent of capillary leakage after injury is to measure the leakage of dye-labeled foreign albumin. A recent report, however, demonstrated that albumin leakage is dependent upon the type of fluorescent dye used for labeling. We chose to develop and test a technique for determining the extent of vascular albumin leakage after burn injury without the use of dyes. Skin and blood samples were harvested at 3h and 7 days after burn injury in mice. Total skin lysates and extracts as well as sera were analyzed for albumin leakage. Coomassie staining and Western blot analyses of skin preparations followed by the densitometric measurement revealed increased levels of albumin, suggesting that the leakage of serum albumin started within 3h after burn injury. Instead of employing dye-labeled foreign albumin, the use of SDS-polyacrylamide gel electrophoresis of tissue extracts followed by Coomassie staining will allow for a simple and direct quantification of autologous albumin leakage due to burn as well as other types of injury.
Specific chemical labeling of DNA fragments

We describe a simple method for specific chemical labeling of DNA fragments at their 3'-termini. The procedure includes enzymatic addition of 4-thiouridine, followed by reaction in mild non-denaturing conditions with the highly reactive alpha-haloacetamido derivatives of several chemical labels. The attached reporter molecule can be removed by extended treatment with beta-mercaptoethanol. Among the potential applications of this labeling method is the study of specific protein-DNA interactions in solution.
Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats

Determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host–virus systems. Using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among New World bats. Episodic bursts of positive selection were detected in several viral proteins, including regions associated with host cell interaction and viral replication. Host shifts involved unique sets of substitutions, and few sites exhibited repeated evolution across adaptation to many bat species, suggesting diverse genetic determinants over host range. Combining these results with genetic reconstructions of the demographic histories of individual viral lineages revealed that although rabies viruses shared consistent three-stage processes of emergence in each new bat species, host shifts involving greater numbers of positively selected substitutions had longer delays between cross-species transmission and enzootic viral establishment. Our results point to multiple evolutionary routes to host establishment in a zoonotic RNA virus that may influence the speed of viral emergence.
In vitro incubation of low-density lipoproteins with inflammatory cells causes enhanced degradation by macrophages in culture.

Utilizing the polyvinyl sponge-implant model, we have reported in vivo modification of low-density lipoproteins (LDL) isolated from interstitial inflammatory fluid (IF) of the rabbit. Further studies on the metabolism of IF-LDL by resident mouse peritoneal macrophages (MPM), demonstrated enhanced uptake and degradation of these modified lipoproteins by scavenger mechanisms. Based upon these studies, we attempted to examine the mechanisms of these observed in vivo modifications in IF-LDL by in vitro incubation of plasma LDL with inflammatory fluid subfractions. Incubation of LDL with inflammatory cells at 37°C resulted in an increased anodal electrophoretic mobility and alteration in apolipoprotein (APO) composition. Subsequent incubation of this modified plasma LDL with MPM resulted in a significant increase in cell surface binding and an increase in the appearance of degradation products in the medium. The formation of lipid peroxides, measured as thiobarbituric acid-reacting substances (T Bars), increased with the time of LDL incubation with inflammatory cells. Conversely, incubation of LDL with cell-free, lipoprotein-deficient IF (LPDIF,d>1.210 g/ml) significantly inhibited LDL degradation by MPM. LPDIF did not alter the electrophoretic mobility of LDL or result in the appearance of T Bars in the medium. These results implicate peroxidative reactions associated with an inflammatory response as mediators of the in vivo modifications in IF-LDL which facilitates enhanced uptake via the scavenger receptor in MPM.
Determination of ion association in dilute aqueous lithium chloride and lithium hydroxide solutions to 600 °C and 300 MPa by electrical conductance measurements

The limiting molar conductances (Λ0) and ion association constants of dilute aqueous lithium chloride and lithium hydroxide solutions (<0.01 mol·kg-1) were determined by electrical conductance measurements at temperatures from 100 to 600 °C and pressures up to 300 MPa. The values of Λ0(LiCl) and Λ0(LiOH) obtained from with Shedlovsky (at densities ≥0.6 g·cm-3) and Fuoss−Hsia−Fernandez-Prini (FHFP) equations (at densities <0.6 g·cm-3) increase with increasing temperature up to 300 °C and decreasing density. Above 300 °C and densities between 0.8 and 0.5 g·cm-3 for LiCl(aq) and 0.8 to 0.6 g·cm-3 for LiOH(aq), Λ0 is nearly temperature-independent but does increase linearly with decreasing density. The molal association constants, KA(m) for both electrolytes were computed exclusively from the data ≥400 °C (at densities 0.8−0.3 for LiCl and 0.8−0.5 g·cm-3 for LiOH) by the Shedlovsky equation and can be represented as functions of temperature (Kelvin) and the logarithm of water density (ρw) as follows: log KA(...
Effects of continuous light and darkness on the eyes of the troglobitic salamander Typhlotriton spelaeus

Larval Typhlotriton spelaeus collected from five caves in Pulaski Co., Missouri, were kept as larvae or induced to transform in darkness or continuous fluorescent illumination. Larvae maintained in darkness for 215 and 279 days had smaller eyes, smaller rod inner and outer segments, and fewer metaphase figures in the genninative zone of the neural retina than comparable larvae maintained in light (258 lux). Except for visual cell size, differences were small and for each characteristic exceptions were observed. One larva kept in light showed early retinal degeneration comparable to that in transformed adults of T. spelaeus. All larvae exhibited optomotor behavior both before and after the experiment. Among animals induced to transform by L-thyroxin and maintained in darkness 111 to 366 days, visual cell and pigment epithelium degeneration was more extensive and more frequent than in animals kept for the same length of time in light (237-298 lux). In darkness the frequency of animals with retinal degeneration increased between 111 and 366 days. In light some animals exhibited pigment epithelium reduction with normal visual cells, and others had free, pigmented cells in the subretinal space. These effects were not comparable to degeneration in darkness. Eyelids covered the eyes of only a few animals in both light and dark treatments. The extent of eyelid encroachment over the eye was greater in darkness than in light. Most animals exhibited optomotor responses after experiments, but responses of animals kept in darkness were impaired in comparison to those of animals kept in light.
A Narrow‐Band Approach for Approximating the Laplace‐Beltrami Spectrum of 3D Shapes

The spectrum of the Laplace‐Beltrami operator is a useful tool for various shape analysis problems as it provides an intrinsic, Fourier‐like characterization of 3D shapes. The numerical computation of the Laplace‐Beltrami spectrum is typically based on a triangular mesh representation of the 3D surface, which makes its robustness dependent upon the quality of triangulation. In this paper, we propose an alternative approach by approximating the Laplace‐Beltrami spectrum with the Laplacian spectrum of a narrow band composed of regular cubes with the Neumann boundary condition, thus mesh quality is not an issue in our method. We validate our method by computing the spectrum of real anatomical shapes and comparing with the mesh‐based method.
Selective Defects of Visual Tracking in Progressive Supranuclear Palsy (PSP): Implications for mechanisms of motion vision

Smooth ocular tracking of a moving visual stimulus comprises a range of responses that encompass the ocular following response (OFR), a pre-attentive, short-latency mechanism, and smooth pursuit, which directs the retinal fovea at the moving stimulus. In order to determine how interdependent these two forms of ocular tracking are, we studied vertical OFR in progressive supranuclear palsy (PSP), a parkinsonian disorder in which vertical smooth pursuit is known to be impaired. We measured eye movements of 9 patients with PSP and 12 healthy control subjects. Subjects viewed vertically moving sine-wave gratings that had a temporal frequency of 16.7 Hz, contrast of 32%, and spatial frequencies of 0.17, 0.27 or 0.44 cycles/degree. We measured OFR amplitude as change in eye position in the 70-150 ms, open-loop interval following stimulus onset. Vertical smooth pursuit was studied as subjects attempted to track a 0.27 cycles/degree grating moving sinusoidally through several cycles at frequencies between 0.1 and 2.5 Hz. We found that OFR amplitude, and its dependence on spatial frequency, was similar in PSP patients (group mean 0.10 degree) and control subjects (0.11 degree), but the latency to onset of OFR was greater for PSP patients (group mean 99 ms) than control subjects (90 ms). When OFR amplitude was re-measured, taking into account the increased latency in PSP patients, there was still no difference from control subjects. We confirmed that smooth pursuit was consistently impaired in PSP; group mean tracking gain at 0.7 Hz was 0.29 for PSP patients and 0.63 for controls. Neither PSP patients nor control subjects showed any correlation between OFR amplitude and smooth-pursuit gain. We propose that OFR is spared because it is generated by low-level motion processing that is dependent on posterior cerebral cortex, which is less affected in PSP. Conversely, smooth pursuit depends more on projections from frontal cortex to the pontine nuclei, both of which are involved in PSP. The accessory optic pathway, which is heavily involved in PSP, seems unlikely to contribute to the OFR in humans.
Ties that bind: foreseeing foreclosure

Lawyers focus on whether behavior in the software industry fits into the present legal definitions for foreclosure and tying. This slant tends to cast antitrust issues as a question of judicial edicts over forbidden business tactics. While that focus is fine for some purposes, it is a narrow base from which to begin a broad discussion about competition policy in innovative markets. The one structural feature lying at the heart of vertical relationships in the IT industry is this: when firms innovate and commercialize technology, they act as both partners and competitors at the same time. Large and small firms alike do this. Although the current discussion focuses on the behavior of large firms, the author can anticipate the layman's response-that the same rules ought to apply to any size firm.
Experimental and Computational Evaluation of In-Span Hinges in Reinforced Concrete Box-Girder Bridges

During the last three decades, considerable research efforts have sought to improve the seismic design of California highway bridges. However, the in-span hinge (ISH) regions of concrete box girders have not been studied adequately. ISHs are classified as disturbed regions because of the concentrated bearing loads and the possible existence of utility and maintenance openings, which induce a three-dimensional (3D) behavior. Nevertheless, ISHs are commonly designed as two-dimensional short cantilevers, following standard procedures in “Building Code Requirements for Structural Concrete and Commentary” of the American Concrete Institute. These designs typically lead to congested reinforcement, causing constructability concerns from practical and economical aspects. In this study, the strength of current ISHs is assessed by using a combined experimental and computational approach. For the experimental part, two 1/3-scale specimens were tested at the University of California, Berkeley. The computational part ...
Radiometallated receptor-avid peptide conjugates for specific in vivo targeting of cancer cells.

Abstract New receptor-avid radiotracers are being developed for site-specific in vivo targeting of a myriad of receptors expressed on cancer cells. This review exemplifies strategies being used to design radiometallated peptide conjugates that maximize uptake in tumors and optimize their in vivo pharmacokinetic properties. Efforts to produce synthetic peptide analogues that target the following three receptor systems are highlighted: Gastrin releasing peptide (GRP), alpha-melanocyte stimulating hormone (α-MSH), and guanylate cyclase-C (GC-C) receptors.
Reduced risk of secondary leukemia with fewer cycles of dose-intensive induction chemotherapy in patients with neuroblastoma.

Background We report a prospective study of secondary leukemia (SL)/myelodysplastic syndrome (MDS) in neuroblastoma (NB) patients treated with ≥5 cycles of dose-intensive chemotherapy. Procedure NB patients received induction with high-dose cyclophosphamide (4,200 mg/m2)-doxorubicin (75 mg/m2)-vincristine (cycles 1, 2, 4, 6, 8), and high-dose cisplatin (200 mg/m2)-etoposide (600 mg/m2) (cycles 3, 5, 7). Bone marrow was examined every 1–3 months for ≥36 months, with inclusion of extensive chromosomal studies 1-3 months post-induction and 1–2×/year thereafter. Results One hundred eight four patients received 5 (n = 76), 6 (n = 45), 7 (n = 59), or 8 (n = 4) cycles. Eight patients developed SL/MDS (only one each in the 5- and 6-cycle groups), at 12–50 months, including two cases detected in surveillance studies. Among 108 patients who received ≥6 cycles, the 5-year cumulative incidence was 7.1% (95% CI: 2%, 12.2%), versus 0% among 54 patients who received 5 cycles without maintenance oral etoposide. Five-year cumulative incidences were 1.46%, 2.28%, and 8.47% among patients in the 5-, 6-, and 7-cycle groups, with fewer cycles having a significantly lower risk (P = 0.048). There was no significant association of risk with potentially leukemogenic consolidative treatments (targeted radiotherapy, myeloablative therapy, and oral etoposide). Conclusions Reducing the number of dose-intensive cycles significantly decreases the risk of SL/MDS, yielding 5-year rates matching the low range (0.4–2.2%) reported for moderate-dose combination chemotherapy regimens used against other pediatric solid tumors. Pediatr Blood Cancer 2009;53:17–22. © 2009 Wiley-Liss, Inc.