cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacokinetic and Pharmacodynamic Perspectives on the Clinical Drug Development of Panitumumab

Panitumumab is a recombinant, fully human IgG2 monoclonal antibody directed against the epidermal growth factor receptor (EGFR). It is indicated for use as monotherapy in the treatment of patients with EGFR-expressing metastatic colorectal cancer after disease progression with standard chemotherapy. The currently indicated dose is 6mg/kg given every 2 weeks. Panitumumab is mainly distributed into the vascular space and exhibits nonlinear pharmacokinetics that are consistent with target-mediated drug disposition, involving saturable binding to EGFR and subsequent internalization and degradation inside the cells. Panitumumab is also cleared in a linear fashion by the reticuloendothelial system, similarly to other endogenous immunoglobulins. After single-dose administration of panitumumab as a 1-hour intravenous infusion, the area under the serum concentration-time curve increases in a greater-than-dose-proportional manner asthe dose increases from 0.75 to 5mg/kg; however, at doses above 2mg/kg, the exposure to panitumumab increases in a dose-proportional manner. Panitumumab pharmacokinetics are not meaningfully affected by the tumour type, EGFR membrane expression, tumour KRAS mutation, sex, age, race or renal or hepatic dysfunction. In addition, irinotecan-containing and paclitaxel/carboplatin-containing chemotherapeutic regimens do not appear to affect panitumumab pharmacokinetics. The results of population pharmacokinetic analyses have shown that bodyweight is the most influential covariate on panitumumab exposure, supporting the current use of bodyweight-adjusted doses (mg/kg). The relationship between the weekly dose of panitumumab and skin rash, an on-target pharmacodynamic effect of EGFR inhibition, reaches a plateau at 2.5 mg/kg, indicating that this is the optimal weekly dose. Two less-frequent dosing regimens (6 mg/kg given every 2 weeks and 9mg/kg given every 3 weeks) achieve steady-state serum trough concentrations similar to those achievedby 2.5mg/kg given every week, ensuring maximal EGFR coverage. Anti-panitumumab antibody production is uncommon and does not appear to have an impact on the pharmacokinetics of panitumumab.
Detailed Kinetic Modeling of Iron Nanoparticle Synthesis from the Decomposition of Fe(CO)5

A detailed chemical kinetic model for gas-phase synthesis of iron nanoparticles is presented in this work. The thermochemical data for Fen clusters (n ≥ 2), iron carbonyls, and iron-cluster complexes with CO were computed using density functional theory at the B3PW91/6-311+G(d) level of theory. Chemically activated and fall-off reaction rates were estimated by the QRRK method and three-body reaction theory. Kinetic models were developed for two pressures (0.3 and 1.2 atm) and validated against literature shock-tube measurements of Fe concentrations and averaged nanoparticle diameters. The new model indicates that the nanoparticle formation chemistry is much more complex than that assumed in earlier studies. For the important temperature range near 800 K in a CO atmosphere, the Fe atom formation and consumption are largely controlled by the chemistry of Fe(CO)2, especially the reactions Fe(CO)2 ⇌ FeCO + CO, Fe + Fe(CO)2 ⇌ Fe2CO + CO, and Fe(CO)2 + Fe(CO)2 ⇌ Fe2(CO)3 + CO. The decomposition of Fe(CO)5 is re...
Can and does the pomeron occur more than once in a single process

Abstract A study of high energy diffractive amplitudes (the elastic amplitude being a special case), has revealed the following regularities at small momentum transfers: (a) they all tend to be almost purely imaginary, and (b) they all have the same energy dependence, leading to universal, constant (modulo logarithms) cross sections at high energies. In this paper, it is assumed that these regularities are produced by an underlying, common mechanism, which is defined as the pomeron. The question then addressed is whether the pomeron, so defined, can and does occur more than once in a single process. It is demonstrated that various models for the pomeron (involving Regge poles, Regge cuts, geometric ideas like diffraction, etc.) lead to different answers to this question, none of them quantitative. By contrast, the introduction of the pion-pole dominance (PPD) hypothesis is shown to lead to a model-independent quantitative answer. Assuming just the above definition of the pomeron, the PPD hypothesis predicts certain processes that must be termed multi-pomeron by the advocates of all models, and provides estimates for their cross sections. The predictions of this hypothesis are compared with experiment. It is shown that PPD leads to, and sets lower bounds for, inclusive triple-pomeron cross sections assuming no more than our general definition of the pomeron. It is pointed out that the repetition of the pomeron, guaranteed by PPD, may be used to set upper bounds on asymptotic total cross sections. The crucial property of the result, that total cross sections must eventually die away, is that it does not rely on any model-dependent property of the pomeron, such as factorization.
Tales of poly(A): a review

Abstract Until recently, evidence to support a translational role for the 3′-poly(A) tract of eukaryotic mRNAs has been mostly indirect, including: a correlation between the adenylation status of individual mRNAs and their translatability in vivo or in vitro, the demonstration that exogenously added poly(A) is a potent competitive inhibitor of the translation of poly(A) + mRNA, but not poly(A) − mRNAs in vitro, and a correlation between the abundance and stability of poly(A)-binding proteins (PABPs) and the rate of translational initiation in vivo. However, more recent studies demonstrate directly that poly(A) + mRNAs can initiate translation more efficiently than poly(A) − mRNAs, and indicate that this effect is: (i) targeted to the formation of 80S initiation complexes, and (ii) likely to be mediated by the cytoplasmic PABP. We suggest that the 3′-poly(A) tail should be considered a translational enhancer which may stimulate translational initiation in much the same way that transcriptional enhancers are thought to stimulate transcriptional initiation.
Acute low-level formaldehyde behavioural and neurochemical toxicity in the rat

The purpose of the present study was to determine the effects of low-level formaldehyde exposure upon behavior and neurochemistry in the male rat. Rats were exposed to either air or formaldehyde vapor (5, 10 or 20 parts per million) for 3 hours on 2 consecutive days during which behavioral observations were made. Following the second exposure session the rats were sacrificed and their brains analyzed for norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites. Formaldehyde exposure resulted in decreased motor activity and neurochemical changes in dopamine and 5-hydroxytryptamine neurons.
The Role of Value in Strategies Based on Anticipated Earnings Surprise

The author shows that the strategy of buying stocks where the most positive earnings surprises are expected is more effective for high E/P (i.e., value) stocks than for low E/P (i.e., glamour) stocks. Conversely, the strategy of selling short stock where the most negative earnings of surprises are expected is more effective for low E/P stocks than for high E/P stocks. These results hold after controlling for firm size, forecast horizon, stock price momentum, and the number of analyst forecast. To the extent that the results for strategies based on expected earnings surprises are driven by value stocks that react strangely for favorable information, the interpretation of the strategies9 success may be that they are forms of value strategies.
Hyperjacobians, Determinantal Ideals and Weak Solutions to Variational Problems

The problem of classifying homogeneous null Lagrangians satisfying an nth order divergence identity is completely solved. All such differential polynomials are affine combinations of higher order Jacobian determinants, called hyperjacobians, which can be expressed as higher dimensional determinants of higher order Jacobian matrices. Special cases, called transvectants, are of importance in classical invariant theory. Transform techniques reduce this question to the characterization of the symbolic powers of certain determinantal ideals. Applications to the proof of existence of minimizers of certain quasi-convex variational problems with weakened growth conditions are discussed.
Chloroplast DNA Rearrangements Are More Frequent When a Large Inverted Repeat Sequence Is Lost

We examined the arrangement of sequences common to seven angiosperm chloroplast genomes. The chloroplast DNAs of spinach, petunia and cucumber are essentially colinear. They share with the corn chloroplast genome a large inversion of approximately 50 kb relative to the genomes of three legumes--mung bean, pea and broad bean. There is one additional rearrangement, a second, smaller inversion within the 50 kb inversion, which is specific to the corn genome. These two changes are the only detectable rearrangements that have occurred during the evolution of the species examined (corn, spinach, petunia, cucumber and mung bean) whose chloroplast genomes contain a large inverted repeat sequence of 22-25 kb. In contrast, we find extensive sequence rearrangements in comparing the pea and broad bean genomes, both of which have deleted one entire segment of the inverted repeat, and also in comparing each of these to the mung bean genome. Thus there is a relatively stable arrangement of sequences in those genomes with the inverted repeat and a much more dynamic arrangement in those that have lost it. We discuss several explanations for this correlation, including the possibility that the inverted repeat may play a direct role in maintaining a conserved arrangement of chloroplast DNA sequences.
Low-rank representation of neural activity and detection of submovements

In this study, Robust Principal Component Analysis (RPCA) is applied to neural spike datasets to extract neural signatures that signify the onset of submovements, a type of motor primitive. Given neural activity recorded from rhesus macaques during a set of reaches between targets in a horizontal plane, we aim to identify common event-related neural features and validate submovement-based motor primitives inferred from the hand velocity profiles. Such features represent common dynamic patterns across many experimental trials and may be used as a signature to detect discrete events such as submovement onset. We present RPCA, a method well suited for extracting data matrices' low-rank component and this method allows (1) removal of task-irrelevant signal from data, (2) identification of task-related dynamic patterns, and (3) detection of submovements. We also explored using the Random Projection (RP) technique and applying RP to data prior to applying RPCA improved the submovement prediction performance by de-sparsifying neural data while preserving certain statistical characteristics of aggregate neural activity.
The Effects of the Number of Options per Item and Student Ability on Test Validity and Reliability

Reliability and validity of multiple-choice examinations were computed as a function of the number of options per item and student ability for junior class parochial high school students administer...
The accurate calibration of infants' scanning records☆

Abstract The visual scanning characteristics of 10 infants were assessed repeatedly over the 2- to 14-week age period, using a bright-pupil/corneal reflection technique. The present report focuses on the calibration process—a procedure by which stimulus figures are mapped onto the raw scanning data. It is concluded that the major calibration parameters vary significantly among infants, and therefore separate calibration data must be collected on each infant if errors on the order of several degrees of visual angle are to be avoided. Moreover, it was found that infants' saccades often are not directed accurately toward the attracting stimulus, and hence repeated calibration trials are required for the precise determination of parameter values. After about 6 weeks of age, the parameter values established for a given infant remained largely invariant. During the initial weeks of life, however, parameter values occasionally changed, apparently because very young infants sometimes will center the image of an attracting stimulus about some extrafoveal location. This raises an additional complexity when interpreting the scanning records of very young infants.
An experimental study of the oscillatory flow structure of tone-producing supersonic impinging jets

An experimental investigation into the structure of a supersonic jet impinging on a large plate is presented. Digital particle image velocimetry (DPIV), shadowgraph photography and acoustic measurements are used to understand the relationship between the unsteady jet structure and the production of tones for nozzle-to-plate spacings between 1 and 5 nozzle exit diameters at a nozzle–pressure ratio equal to 4. Results indicate that the instability of the jet depends on the location of the plate in the shock cell structure of the corresponding free jet and the strength of the standoff shock wave, rather than on the occurrence of recirculation zones in the impingement region. Phase-locked studies show streamwise displacements of the stand-off shock wave, a moving recirculation zone in the subsonic flow in front of the plate, and significant oscillations of both the compression and expansion regions in the peripheral supersonic flow when tones are produced. Sound is shown to be generated by periodic pulsing of the wall jet boundary resulting from periodic motion of the flow in the impingement and near-wall regions of the flow.
MONOPOLE ACCRETION BY COSMIC STRINGS

We study the accretion of super-heavy magnetic monopoles around cosmic string loops in the very early universe. For sufficiently massive monopoles, a possible result of this accretion process is the formation of monopole-black holes, leading ultimately to a monopole-to-photon ratio comparable to the limits required by neutron star observations.
Aluminide coating on directional γ′-δ eutectics

Abstract The relations between the process variables and the coating microstructure were studied for aluminide-coated γ'-δ directional eutectics. A spectrum of coating microstructures was obtained depending on the choice of the process variables. The process variables were the aluminizing and homogenizing temperatures, the homogenizing time and the activity of aluminum in the coating pack. The microstructures were described with reference to the NiAlNb ternary phase diagram and the diffusion of the aluminum and the nickel atoms.
The effects of ultraviolet irradiation on wound contraction in the hairless guinea pig

Abstract Ultraviolet radiation has been shown to alter wound tensile strength and evoke a number of intracellular changes in fibroblasts. We examined the effects of relatively high doses of ultraviolet radiation on subsequent wound contraction of circular wounds in the hairless guinea pig model. Female hairless guinea pigs were divided into two experimental groups receiving 80 J/cm 2 or 480 J/cm 2 every other day for 16 weeks. Age-matched unirradiated animals were used as controls. After exposure, all animals had either a 4 mm punch biopsy (80 J/cm 2 ) or a 2.4 cm diameter ((480 J/cm 2 ) Groups 3 and 4) circular area excised from the dorsum. The extent of wound enlargement immediately following wounding of the irradiated animals was decreased as compared to the controls. The rate of wound contraction was significantly lower during early stages of wound contraction in each group of irradiated animals, and wound contraction was significantly slower overall in both groups of irradiated animals compared to controls.
The Zoo: 150 years of research

In the 150 years since its inception, the Zoological Society has developed from a collection of curiosities on which only observational research was carried out, to one of the world's most comprehensive collections of animal species, with two attached experimental research institutes. Dr Harrison Matthews traces the evolution of the Zoo from the time when the idea first occurred to Sir Stamford Raffles on a visit to the Jardin des Plantes in Paris.
Proposed far-infrared difference-frequency generation using the Lorentz nonlinearity of a solid-state plasma

A calculation is made of the efficiency of laser difference-frequency power generation in the far infrared by reflection from the surface of metals and semiconductors. It is assumed that the essential nonlinearity is that associated with the Lorentz force on conduction electrons for which P^{NLS} = \alpha(E_{L} \times H_{L}) . It is shown that, when two 1-kW separately tuned CO 2 lasers are used as primary sources, as much as 10-4watts in the 100-1000 \mu range may be generated under favorable conditions. No phase matching of primary and difference-frequency waves is required.
Cyclotron production of NCA 99mTc and 99Mo. An alternative non-reactor supply source of instant 99mTc and 99Mo----99mTc generators

The direct production of no-carrier-added (NCA) 6.02 h 99mTc and of 66 h 99mMo using proton beams of natural Mo targets was investigated. The major objective of this work was to evaluate the potential of utilizing high-intensity proton accelerators as a supply source of 99mTc and 99Mo for use in diagnostic nuclear medicine. The excitation functions for the production of the directly-made 99mTc via the 100Mo(p, 2n)99mTc (Q = -7.85 MeV) reaction, and of its parent 99Mo via the 100Mo(p, pn) 99Mo (Q = -8.30 MeV) and 100Mo(p, 2p)99mNb(15 s)----99Mo (Q = -11.14 MeV) reactions, were measured in the 68-8 MeV energy range. Single and cumulative yields for 99mTc and 99Mo, and for other Tc, Mo, Zr, Nb and Y radiocontaminants were also determined. The prospects of integrating the use of enriched 100Mo targets with high-intensity, dual beam, H- accelerators was analyzed. The potential of this combined method to replace or complement the current reactor-based supply sources of 99Mo----99mTc generators, is also discussed. Finally, a brief analysis is made on the potential use of this combined technology to support the anticipated expansion of nuclear medicine in developing nations.
The vascular plant collections of R. S. Williams from Bolivia and Peru (1901–1902): Addenda et corrigenda

Notes that augment an earlier essay on R. S. Williams’ botanical activities and the distribution of his collections from Bolivia and Peru are presented. Twelve species based on Williams’ vascular plant collections are added to a catalog that was previously published. Synonymies of an additional 22 taxa are corrected or updated. Notes also are provided concerning the typification or orthography of two species.
High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux.

Abstract Background: Pseudomonas aeruginosa is intrinsically resistant to high levels of triclosan. Methods: Using the agar incorporation method and defined mutant strains, the contribution of multidrug efflux pumps to high-level (>1000 μg/mL) triclosan resistance in P aeruginosa was assessed. Results: The results showed that the ability of P aeruginosa to survive in the presence of triclosan concentrations in excess of 1000 μg/mL is solely attributable to the expression of efflux pumps. (Am J Infect Control 2003;31:124-7.)
Anomalous Magnetoconductance in Silicon Surfaces

The effect of a tangential magnetic field on the surface transport properties of silicon has been studied at low temperatures. An anomalous variation in conductance, with $\frac{\ensuremath{\delta}G}{{G}_{0}}g1$ and negative magnetoresistance, has been observed in samples with bulk resistivities in excess of 100 \ensuremath{\Omega} cm.
Human identification experiments using acoustic micro-Doppler signatures

Active acoustic scene analysis is a promising approach to distributed persistent surveillance in sensor networks. We report on the design of bandpass sampling technique for an acoustic micro-Doppler sonar to reduce the data rate to as low as 85 kbps. We then explore the use of Gaussian mixture models for human identification. We compare the classification performances using different feature vectors and from different sampling schemes. We show that the use of differential cepstral vectors of context length 2 improves the classification accuracy. We also show that the classification performance of the bandpass sampling system with an 8-bit resolution is still over 90% on a database consisting of 160 gait signatures from 8 individuals.
Resolution analysis for Gradient Direction Matching of object model edges to overhead images

The problem of computer-assisted broad area search for specific objects of interest in overhead images is considered. To this end, we present a novel efficient Gradient Direction Matching (GDM) algorithm that matches gradient directions associated with object edges to pixel gradient directions (as opposed to image edges, which are less reliable). GDM seamlessly integrates information associated with pixel location and orientation in such a way that the FFT can be exploited for computational efficiency, and it inherently rejects background clutter. The effects of spatial resolution on GDM statistical performance are studied empirically with the goal of gaining insight into how far GDM computational cost can be reduced before matching performance becomes too severely compromised.
Short‐Crack Fracture Toughness of Silicon Carbide

The fracture toughness of four different silicon carbides was measured using single-edge precracked beam (SEPB) and indentation/strength techniques. Two were development grades with similar microstructures and chemistries, and yet exhibited different fracture modes. The grade that exhibited a predominantly intergranular fracture had an SEPB fracture toughness (6.4 MPaOm) 88% higher than the one that showed primarily a transgranular fracture (3.4 MPaOm). The higher fracture toughness was associated with a modest increase in average strength (25%), although there was a significant increase in the Weibull modulus (11–32). Fracture toughness at short crack lengths was assessed by an indentation method that used fracture strengths, crack lengths at fracture, and a new method of estimating the constant d that characterizes the residual driving force of the plastic zones based on the stable growth of the indentation cracks from the initial (c0) to the instability (c ) lengths. The results showed a rising crack-growth-resistance behavior for the grade exhibiting intergranular fracture, while the grade showing transgranular fracture had a flat crackgrowth resistance. Tests on two commercial grades of silicon carbide showed similar behaviors associated with the respective fracture modes.
VpsT Is a Transcriptional Regulator Required for Expression of vps Biosynthesis Genes and the Development of Rugose Colonial Morphology in Vibrio cholerae O1 El Tor

ABSTRACT Vibrio cholerae switches between smooth and rugose colonial variants. The rugose variant produces more vibrio polysaccharides (VPSEl Tor) and forms well-developed biofilms. Both phenotypes depend on expression of vps biosynthesis genes. We identified a positive transcriptional regulator of vps gene expression, VpsT, which is homologous to response regulators of two-component regulatory systems. Disruption of vpsT in the rugose variant yields smooth colonies, prevents formation of mature biofilms, and decreases vps gene expression. The interaction between VpsT and VpsR, a previously identified positive regulator of vps genes, was also investigated.
The effect of pre-smoothing functional data on cluster analysis

We investigate the possible benefits of pre-smoothing functional data before performing a cluster analysis. A simulation study compares the accuracy of clustering results on the basis of the use of unsmoothed functional data—and two smoothed versions of the data—as the inputs in a clustering algorithm. Smoothing is usually found to produce a more accurate clustering, with the best results arising from a novel James–Stein-type shrinkage adjustment to the standard linear smoother. Two real functional data sets are clustered using the competing methods to illustrate the procedure.
Bit error probability for space-time block code with coherent and differential detection

Exact, closed-form expressions of bit error probability (BEP) are derived for space-time block codes (STBC) based on Alamouti's (1998) scheme and utilizing M-ary phase shift keying (MPSK) modulation. The analysis is carried out for the slow, flat fading Rayleigh channel with coherent detection and with differential encoding/decoding. With these closed-form expressions, we prove that a signal to noise ratio (SNR) loss of approximately 3 dB is paid for deferential detection compared to coherent detection. Numerical results are provided for analysis and simulations for BPSK and QPSK modulations.
THE EFFECT OF A TREMATODE PARASITE ( MICROPHALLUS SP. ) ON THE RESPONSE OF THE FRESHWATER SNAIL POTAMOPYRGUS ANTIPODARUM TO LIGHT AND GRAVITY

Summary Parasites often ine uence the behavior of their hosts in ways that increase the probability of transmission of the parasite. The digenetic trematode Microphallus sp. has been demonstrated to alter the behavior of the New Zealand freshwater snail Potamopyrgus antipodarum in a way that increases the probability that infected snails will be eaten by the e nal host (waterfowl). Infected snails are found foraging on top of rocks more often in the early morning when waterfowl are feeding and less often in the afternoon when unsuitable hosts (e sh) are feeding. The mechanism(s) that the parasite utilizes to produce this behavioral change is not known. The present study investigated three possible behaviors (phototaxis, geotaxis, and photokinesis) that the parasite could alter that may account for the behavioral change seen in the e eld. Infected and uninfected snails were assessed in terms of their orientation to light (phototaxis), orientation to gravity (geotaxis), and movement in response to light (photokinesis). There was no evidence of phototactic behaviors in either infected or uninfected snails. However, uninfected snails were found to positively orient towards gravity, while infected snails did not. Also, both infected and uninfected snails were found to be positively photokinetic (they move faster in the light than in the dark), but Microphallusinfected snails were found to move more slowly than uninfected snails. The differences found between infected and uninfected snails may be part of the manipulative effort of the parasite, but by themselves the differences are not sufe cient to explain the patterns observed in the e eld.
Inducibility of Atrial Fibrillation Before and After Radiofrequency Catheter Ablation of Accessory Atrioventricular Connections

fInducibility of Atrial Fibrillation. Introduction: The purpose of this study was to evaluate the inducihility of atrial fihrillation in patients with an accessory atrioventricular connection (AAVC) and to determine if the inducihility of atrial fihrillation is altered after successful radiofrequency catheter ahlation of the AAVC. Methods and Results: Thirty-seven patients with an AAVC and 36 control patients were prospectively evaluated using a standardized atrial pacing protocol. The high right atrium was paced using a 25-heat drive train, 1.5-second intertrain pause, 10-mA pulse amplitude, and 2msec pulse duration at cycle lengths of 250 to 100 msec, in 10-msec decrements. Pachig was performed twice at each cycle length. Thirty patients with an AAVC underwent repeat atrial overdrive pacing after successful radiofrequency ahlation of the AAVC. Atrial fihrillation was induced in 26 (70%) patients with an AAVC and 22 (61%) controls (P = NS). Atrial flutter was induced In 11 (30%) patients with an AAVC and 13 (36%) controls (P = NS). The cumulative percentage of patients with atrial lihrillation/flutter induced at each pacing cycle length wa.s the same in each group. There was no difference in the duration of atrial fihrillatiDn/flutler hetween control patients and patients with an AAVC. Among the 30 patients who underwent repeat atrial overdrive pacing after radiofrequency ahlation of an AAVC, there was no difference in the inducihility or duration of atrial fibril la tion/at rial flutter after ablation compared to baseline. Conclusion: These findings indicate that the vulnerability of the atrium to Hhrillate in response to atrial pacing is independent of the presence of an AAVC./J Catdiovasc Electrophys
Fast hazard detection in combinational circuits

In designing asynchronous circuits it is critical to ensure that cir-cuits are free of hazards in the specified set of input transitions. In this paper, two new algorithms are proposed to determine if a com-binational circuit is hazard-free without exploring all its gates, thus providing more efficient hazard detection. Experimental results in-dicate that the best new algorithm on average visits only 20.7% of the original gates, with an average runtime speedup of 1.69 and best speedup of 2.27 (for the largest example.
On the properties of discrete adjoints of numerical methods for the advection equation

This paper discusses several aspects related to the consistency of the discrete adjoints of upwind numerical schemes. Both linear (finite differences, finite volumes) and nonlinear (slope and flux-limited) discretizations of the one-dimensional advection equation are considered. The analysis is focused on uniform meshes and on explicit numerical schemes. We show that the discrete adjoints may lose consistency near the points where upwinding changes, near inflow boundaries where another numerical scheme is employed, and near the locations where the slope/flux limiter is active in the forward simulation. Numerical results are presented to support the theoretical analysis. Copyright © 2007 John Wiley & Sons, Ltd.
Formal Charge Model for Predicting Structures, Acid-Base, and Ion Exchange Properties of Mixed Oxides

The range of mixed-oxide materials used in ion exchange and catalytic materials is rapidly expanding from aluminosilicates such as zeolites and clays into materials whose structure and chemical properties are more difficult to predict and understand. A simple model based on local charge has been developed to predict distributions of local bonding configurations of both cations and anions in mixed oxides. The model, illustrated for the case of silicotitanates, provides qualitative predictions regarding both the acid-base and ion exchange properties of such materials as a function of composition.
A DISTRIBUTION MODEL FOR EGG DEVELOPMENT IN MOUNTAIN PINE BEETLE

Mountain pine beetle ( Dendroctonus ponderosae Hopkins) population dynamics, as well as potential for outbreaks and resulting tree mortality, are related in part to habitat temperature. As a first step in development of a life-stage, event-oriented simulation model, we have modeled the temperature-dependent development of the egg stage. The completed model includes a full description of variation in developmental rates and is capable of predicting duration and eclosion patterns for any temperature regime. This model was parameterized using data obtained from constant-temperature experiments at temperatures of 8, 10, 12.5, 15, 20, 25, and 30°C. Validation experiments were conducted for constant temperatures of 15, 17.5, 22.5, and 27.5°C and for variable-temperature regimes of 15±5 and 15±10°C. Validation results indicated that the model is capable of accurately describing the emergence curve for constant temperatures below 27.5°C. The model also faithfully represents emergence under variable temperatures of 15 ± 10°C. Potential reasons for lack of model fidelity in describing emergence at constant high temperatures and for 15 ± 5°C are discussed in the text.
Medicine Unplugged: The Future of Laboratory Medicine

We live amidst a digital revolution occurring in mobile healthcare. The remarkable and explosive progress in wireless medical devices has been catalyzed by the software of apps and the hardware of “adds.” Wireless diagnostics tools such as the AliveCor smartphone-enabled electrocardiograph, the vScan pocket ultrasound, and the CellScope smartphone-based otoscope are poised to deliver diagnostic information faster, cheaper, and at the point-of-care (POC).4 Leveraging the power of >6 billion active cell phones, a number far greater than the number of toothbrushes or toilets in the world, these devices can be used anywhere there is a mobile signal, thereby achieving a “flattening” of the Earth with respect to access to mobile-health technologies (1). Now, the convergence of smartphones and innovative biosensors based on microfluidics and microelectronics is tackling the next big challenge for wireless health: portable biochemical analysis in the form of a handheld lab-on-a-chip (LOC). Capable of accommodating a wide range of testing modalities—from analytical chemistry to microscopy to POC genomics—LOC systems represent a new model for laboratory medicine, in which a smartphone-enabled portable laboratory is brought to the patient instead of the patient being brought to the laboratory. We examine recent advancements in mobile diagnostics enabled by microfluidics and LOC technologies for POC clinical testing. Vinod Khosla, the prominent venture capitalist, recently opined that in the future a combination of innovative algorithms and next-generation diagnostic devices could replace 80% of doctors (2). This radical prediction reflects the fact that the current wireless health ecosystem is home to a growing network of distributed health data procured by an array of diagnostic devices. Aggregation and algorithmic processing of the data will ultimately be necessary to create artificial-intelligence and decision support for patients and the medical community. Consequently, there is enormous interest and investment in wireless diagnostics, as exemplified by the …
Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

Purpose Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m2 in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine. Results Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P...
Advising incoming CS students for what lies ahead

In the mid 1980's freshmen at two universities were surveyed and their responses about computer science courses were compared with their responses about other freshmen courses…students were more likely to report reality shock, confusion, control attempts, anger, and withdrawal in their computing courses than in other courses [1]. Today computer science departments still experience some of the highest dropout rates of all disciplines with a range from 25% to over 50% attrition by the end of the first year. This panel was formed to discuss the various advising methods used by schools to attempt to prepare the students for the rigors of what their first year experience in computer science courses will involve. Helping the student understand what will be required of them goes a long way toward assuring the students success in the computer science major. Can more be done? Are any schools doing innovative approaches to this problem?
Thyrotropin Receptor-Adenylate Cyclase System in Hurthle Cell Neoplasms*

Hurthle cell neoplasms are thought to arise from the follicular cells of the thyroid gland, although some studies suggest that they originate from the parafollicular cells. We studied tissue from five patients (three men and two women, aged 33–72 yr) with Hurthle cell neoplasms (four adenomas and one carcinoma) to determine whether Hurthle cell neoplasms have an intact TSH receptor-adenylate cyclase (AC) system and, if so, whether it differs in benign and malignant Hurthle cell and neoplasms. Binding of [125I]bovine (b) TSH and an AC response to TSH occurred in all four Hurthle cell adenomas. In three of these tumors, there was good binding and a relatively good correlation between the concentration of bTSH producing half-maximal inhibition of [125I]bTSH binding (4.8 mU/ml) and the TSH concentration causing half-maximal stimulation of AC (2.2 mU/ml). There was also a 2- to 5-fold increase in AC activity in response to bTSH (300 mU/ml), a value comparable to that which occurs in follicular thyroid neoplasm...
Preparation of carbazole-3,6-d2 and carbazole-1,3,6,8-d4

Carbazole-3,6-d2 and carbazole-1,3,6,8-d4 were prepared by reduction of the corresponding di- and tetrabromocarbazoles in alkaline ethanol with deuterium gas and Pd/C catalyst.
Liver Disease in Patients After the Fontan Operation

We reviewed records of all patients with an initial Fontan operation or revision from 1973 to 2012 at our institution (n = 1,138); 195 patients had postoperative liver data available. Cirrhosis was identified by histopathology or characteristic findings on imaging with an associated diagnosis of cirrhosis by a hepatologist. Of 195 patients with biopsy or imaging, 10-, 20-, and 30-year freedom from cirrhosis was 99%, 94%, and 57%, respectively. There were 40 of 195 patients (21%) diagnosed with cirrhosis (mean age at Fontan 10.7 ± 8 years). On multivariate analysis, hypoplastic left heart syndrome was associated with increased risk of cirrhosis (n = 2 of 16, p = 0.0133), whereas preoperative sinus rhythm was protective (p = 0.009). Survival after diagnosis of cirrhosis was 57% and 35%, at 1, and 5 years, respectively. The cause of death was known for 9 patients (5 multiorgan failure, 2 liver failure, and 2 heart failure). In conclusion, there is an incremental occurrence of cirrhosis after the Fontan, which should be considered when designing follow-up protocols for patients after Fontan operation.
Impulsivity and Suicidal Behavior: How You Define It Matters

Impulsivity is inconsistently defined in the literature. While there are some clear operationalizations of the trait of impulsivity, there is no consensus about the impulsivity of a specific suicidal behavior. Using a sample of 131 suicide attempters identified in a county emergency room, we used interviewer ratings from the Suicide Attempt Self-Injury Interview (SASII) and the Borderline Personality Disorder (BPD) trait impulsivity criterion from the Structured Clinical Interview for the DSM-IV Axis-II (SCID-II) to examine seven core constructs most commonly used in the literature on impulsivity of suicidal behavior. These constructs are resisting the urge/delaying, planning, trait impulsivity, communication to others, leaving a suicide note, the ability to be rescued, and intoxication. Comparison of these constructs shows relatively small relationships between them, and they clearly do not represent the same underlying concept. The ability of these constructs to predict intent and lethality of the index...
Altered E-C coupling in triads isolated from malignant hyperthermia-susceptible porcine muscle.

Triad vesicles were isolated from normal (N) and homozygous malignant hyperthermia-susceptible (MHS) porcine skeletal muscle, and two types of sarcoplasmic reticulum Ca2+ release were investigated:...
The Ground State of Liquid He4

In a recent study of liquid He/sup 4/ (Wu and Feenberg, Phys. Rev. 122,739) the virial theorem was used to determine the range and strength parameters in several 6-n type interatomic potentials. Comments are presented on the criticism of the study by Hiroike (Prog. Theor. Phys. 27,342.). (W.D.M.)
Identification of Plasmodium falciparum specific translation inhibitors from the MMV Malaria Box using a high throughput in vitro translation screen

A major goal in the search for new anti-malarial compounds is to identify new mechanisms of action or new molecular targets. While cell-based, growth inhibition-based screening have enjoyed tremendous success, an alternative approach is to specifically assay a given pathway or essential cellular process. Here, this work describes the development of a plate-based, in vitro luciferase assay to probe for inhibitors specific to protein synthesis in Plasmodium falciparum through the use of an in vitro translation system derived from the parasite. Using the Medicines for Malaria Venture’s Malaria Box as a pilot, 400 bioactive compounds with minimal human cytotoxicity profiles were screened, identifying eight compounds that displayed greater potency against the P. falciparum translation machinery relative to a mammalian translation system. Dose–response curves were determined in both translation systems to further characterize the top hit compound (MMV008270). This assay will be useful not only in future anti-malarial screening efforts but also in the investigation of P. falciparum protein synthesis and essential processes in P. falciparum biology.
Laboratory evaluation of BAY SIR 8514 against the house fly (Diptera: Muscidae): effects on immature stages and adult sterility.

Medium containing eggs or 1st, 2nd, or 3rd instars of Musca domestica L. was treated with BAY SIR 8514 (2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide), and its effects were evaluated on the basis of percent forming puparia, percent deformity, percent eclosion, and larval length at 48 and 72 h of development. Rates (g of AI/0.09m2) evaluated ranged from 0.0263 to 0.0066 g for 25 WP and 0.0263 to 0.0016 g for 0.5 EC. Mortality, as reflected by percentage of larvae forming puparia, was greatest in treatments of the egg and 1st instars for both WP and EC formulations; treated 2nd instars were less affected, with 36 to 66% of larvae forming puparia. The number of puparia from treated 3rd instars and untreated larvae was about equal. Deformed puparia were elongated, shortened, or “C” shaped; amount of deformity was greatest following treated eggs or 1st instars and decreased with maturity of stage treated. Eclosion was greatly inhibited by all treatments; only random and isolated occurences of eclosion were observed except at the lowest rate of EC and never exceeded 13%. No adults from treated medium survived beyond 5 days posteclosion, and none produced eggs for rearing. Larval growth (as determined by length of larvae) was significantly retarded in all treated stages except the 3rd instar. No ovicidal activity was exhibited by BAY SIR 8514 to eggs topically treated at 2,500 ppm; treatments of pupa ria at the same rate had no significant effect on adult emergence or fertility. There was a significant degree ( P = 0.05) of sterility induced in adult flies for up to 21 days (only 27.1% hatch) after exposure to a granulated sugar and WP bait at concentrations as low as 0.0156%. Sterility induced by contact with treated paper (0.5 EC) was not as permanent as exposure to bait, except at the highest rate of 0.0376 g of AI/0.09m2, and then results were comparable only to 14 days post treatment.
Stimulus “Fractionation” in Paired-Associate Learning

It has been suggested that Ss may use only a portion of the nominal stimulus as a cue in paired-associate learning. Non-overlapping consonant trigram stimuli were used in such learning with numerals as responses. When the pairs had been learned, individual letters were presented and Ss were required to respond with the appropriate number. Results support the hypothesis that Ss had learned to respond to only part of the stimulus compound. Responses to letters which had been in the initial and final positions in the trigrams were correct significantly more often than responses to medial letters.
Ionization-Dependent Behavior of Transmembrane Helices that Incorporate Glu or Tyr Residues

GWALP23 (acetyl-GGALW5LALALALALALALW19LAGA-amide) is a constructive low-dynamic model peptide for investigations of single-residue influence on protein-lipid interactions and the properties of membrane-spanning helices (J. Biol. Chem. 285, 31723). To investigate the pH dependence, ionization behavior and orientational constraints when potentially negatively charged glutamic acid side chains are present, we have substituted a single Leu residue with Glu at different positions and incorporated specific 2H-Ala labels in the core GWALP23 or Y5GWALP23. Solid state NMR experiments show well defined 2H-Ala quadrupolar splittings for Y5GWALP23-E14 over the pH range of 6 to 10, suggesting that the peptide helix is well oriented in DLPC and DOPC lipid bilayers. Spectral changes are evident above pH 11 (in ether-lipid bilayers), but the titration of the Glu is uncertain because the Tyr residue itself appears to titrate around pH 11.5. GWALP23-E14 shows no spectral changes over the pH range 6.0 to 11.5, yet a change in quadrupolar splittings is observed at pH 13. The combined results suggest that the Glu residue may titrate with a pKa near 12. In bilayers of DLPC and DOPC, GWALP23-E16 shows similar trend and is suggested to have a pKa of around 12. The rather modest shifts in the 2H quadrupolar splittings, nevertheless, suggest that the orientation of the transmembrane helix actually may change rather little at high pH. It is conceivable that the close proximity of either E14 or E16 to W19 could provide stability to the neutral peptide helix and perhaps influence the results. We additionally are investigating the possibilities for helix unwinding near the ends of these peptides.
Acceptability of Female Condom Among Female Sex Workers

Objective To understand the acceptability of the female condom among female sex workers (FSWs) and its influencing factors. Method Qualitative survey method was adopted to evaluate the acceptability of female condom among FSWs. Results Most FSWs(25/27)thank the female condom was superior in quality, but it looked bad(19/27), or inconvenient to use (11/27)and made users uncomfortable(24/27). Conclusion The proportion of thinking the female condom inconvenient to use is high, so promoting the female condom is Certainly difficult.
Determining the Conformational Landscape of σ and π Coupling Using para-Phenylene and “Aviram–Ratner” Bridges

The torsional dependence of donor–bridge–acceptor (D–B–A) electronic coupling matrix elements (HDA, determined from the magnetic exchange coupling, J) involving a spin SD = 1/2 metal semiquinone (Zn-SQ) donor and a spin SA = 1/2 nitronylnitroxide (NN) acceptor mediated by the σ/π-systems of para-phenylene and methyl-substituted para-phenylene bridges and by the σ-system of a bicyclo[2.2.2]octane (BCO) bridge are presented and discussed. The positions of methyl group(s) on the phenylene bridge allow for an experimentally determined evaluation of conformationally dependent (π) and conformationally independent (σ) contributions to the electronic and magnetic exchange couplings in these D–B–A biradicals at parity of D and A. The trend in the experimental magnetic exchange couplings are well described by CASSCF calculations. The torsional dependence of the pairwise exchange interactions are further illuminated in three-dimensional, “Ramachandran-type” plots that relate D–B and B–A torsions to both electronic a...
Lymph Node Reactivity. III. Lymphomas and Allied Diseases

A study was made of the ammoniacal silver staining of the cells of Hodgkin’s disease, lymphosarcoma, follicular lymphoma, acute leukemia and chronic leukemia as seen in routine 5 µ. paraffin sections. With the exception of chronic lymphatic leukemia, the cells of lymphomas and allied diseases exhibited minimal staining. These data were compared with the ammoniacal silver staining of normal lymph nodes and the enhanced staining of nonneoplastic proliferations in developing and reactive lymph nodes.