cssi/SciSciGPT-SciSciNet huggingface dataset:
Noncontinuum solvent effects upon the intrinsic free-energy barrier for electron-transfer reactions

A phenomenological electrochemical approach is outlined by which noncontinuum contributions to the outer-shell intrinsic barrier to electron transfer, ..delta..G/sub os//sup */, resulting from specific reactant-solvent interactions can be estimated from the measured dependence of the formal potential upon the molecular and structural properties of the solvent. A simplified derivation, based on electrochemical half-reactions, of the conventional dielectric continuum expression is given in order to clarify the physical origins of the outer-shell intrinsic barrier and to identify likely additional noncontinuum components. Numerical calculations for amine and other redox couples involving specific ligand-solvent interactions indicate that the noncontinuum contributions to ..delta..G/sub os//sup */ for both homogeneous and electrochemical exchange reactions can be surprisingly small (typically approximately less than or equal to 1-2 kcal mol/sup -1/) even when the thermodynamics of ion solvation are in severe disagreement with the dielectric continuum (Born) predictions. An additional noncontinuum component associated with vibrational distortions of outer-shell solvent may be significant for multicharged aquo complexes and other reactants engaging in strong ligand-solvent hydrogen bonding. 50 references, 3 figures, 1 table.
Skeletal Muscle Abnormalities and Genetic Factors Related to Vertical Talus

Background/rationale Congenital vertical talus is a fixed dorsal dislocation of the talonavicular joint and fixed equinus contracture of the hindfoot, causing a rigid deformity recognizable at birth. The etiology and epidemiology of this condition are largely unknown, but some evidence suggests it relates to aberrations of skeletal muscle. Identifying the tissue abnormalities and genetic causes responsible for vertical talus has the potential to lead to improved treatment and preventive strategies.
Axonal degeneration in the Trembler‐j mouse demonstrated by stimulated single‐fiber electromyography

The Trembler-j (Tr-j) mouse is a naturally occurring mutant with a point mutation in the peripheral myelin protein-22 gene causing severe peripheral nerve demyelination. It is a genetically homologous murine model for Charcot-Marie-Tooth disease type 1A (CMT 1A). Our prior pilot studies using stimulated single-fiber needle electromyograpy (SSFEMG) showed increased jitter in 60-day-old Tr-j mice compared to age-matched, wildtype animals. The aim of this study was to better elucidate the etiology of increased jitter in Tr-j mice and test the following hypotheses: (1) the increased jitter in Tr-j mice is due to turnover of endplates secondary to axonal degeneration with reinnervation and not to conduction block secondary to demyelination of motor nerve axons; and (2) aging Tr-j mice demonstrate increased jitter and fiber density compared with younger mutant mice due to progressive motor axon loss. SSFEMG studies performed on 60- and 140-day-old mice indicated that average mean consecutive difference (MCD) and fiber density estimates (FDE) were significantly increased in Tr-j mice at both ages compared to age-matched wildtypes. FDE also increased substantially in older mutant mice. Intraperitoneal neostigmine injections produced significant reductions in average MCD in Tr-j mice, suggesting that impaired neuromuscular transmission is an early pathologic feature in these mice and likely reflects distal axonal degeneration. Our findings corroborate our prior pilot study, although in a much larger number of animals across a wider age span. Our study also indicates that SSFEMG, performed in a serial fashion, is a useful, noninvasive method of detecting progressive axon loss in this murine model of CMT 1A. This technique may be a valuable tool to study the affects of genetic or pharmaceutical interventions in murine models of peripheral neuropathy. Muscle Nerve, 2007.
Interstitial high-dose-rate brachytherapy boost: the feasibility and cosmetic outcome of a fractionated outpatient delivery scheme.

Abstract Purpose: To evaluate the feasibility, potential toxicity, and cosmetic outcome of fractionated interstitial high dose rate (HDR) brachytherapy boost for the management of patients with breast cancer at increased risk for local recurrence. Methods and Materials: From 1994 to 1996, 18 women with early stage breast cancer underwent conventionally fractionated whole breast radiotherapy (50–50.4 Gy) followed by interstitial HDR brachytherapy boost. All were considered to be at high risk for local failure. Seventeen had pathologically confirmed final surgical margins of less than 2 mm or focally positive. Brachytherapy catheter placement and treatment delivery were conducted on an outpatient basis. Preplanning was used to determine optimal catheter positions to enhance dose homogeneity of dose delivery. The total HDR boost dose was 15 Gy delivered in 6 fractions of 2.5 Gy over 3 days. Local control, survival, late toxicities (LENT-SOMA), and cosmetic outcome were recorded in follow-up. In addition, factors potentially influencing cosmesis were analyzed by logistic regression analysis. Results: The minimum follow-up is 40 months with a median 50 months. Sixteen patients were alive without disease at last follow-up. There have been no in-breast failures observed. One patient died with brain metastases, and another died of unrelated causes without evidence of disease. Grade 1–2 late toxicities included 39% with hyperpigmentation, 56% with detectable fibrosis, 28% with occasional discomfort, and 11% with visible telangiectasias. Grade 3 toxicity was reported in one patient as persistent discomfort. Sixty-seven percent of patients were considered to have experienced good/excellent cosmetic outcomes. Factors with a direct relationship to adverse cosmetic outcome were extent of surgical defect ( p = 0.00001), primary excision volume ( p = 0.017), and total excision volume ( p = 0.015). Conclusions: For high risk patients who may benefit from increased doses, interstitial HDR brachytherapy provides a convenient outpatient method for boosting the lumpectomy cavity following conventional whole breast irradiation without overdosing normal tissues. The fractionation scheme of 15 Gy in 6 fractions over 3 days is well tolerated. The volume of tissue removed from the breast at lumpectomy appears to dominate cosmetic outcome in this group of patients.
A philosopher looks at quantum mechanics (again)

Abstract‘A Philosopher Looks at Quantum Mechanics’ (Putnam [1965]) explained why the interpretation of quantum mechanics is a philosophical problem in detail, but with only the necessary minimum of...
A Developmental Exploration of the Fear of Success Phenomenon as Cultural Stereotype.

Given prior research suggesting that “fear of success” may be a function of cultural expectations rather than an intrapsychic motive held by women, this cultural phenomenon was placed in juxtaposition with reactions to women and men failing. It was expected that women would not be rated negatively for failure. It was also expected that in a sample of third, sixth, ninth, and twelfth graders, younger children would be more dogmatic than older children in applying cultural stereotypes to these situations. The children responded on semantic differential scales to the cue of Anne (John) succeeding (failing) in medical school. The children rated a successful person much happier than one who failed, and the sex of the person succeeding or failing was entirely irrelevant. However, the results were as predicted for niceness: A woman was somewhat less nice than a man when they both succeeded, but a man was much less nice when they both failed. In addition, there were no interactions with the age or sex of the respondents. Thus, sex-role expectations are relevant to some attributes of individuals but not others, and these expectations are well established and easily applied as early as third grade.
Interspecific Pollen Loss by Hummingbirds Visiting Flower Mixtures: Effects of Floral Architecture

Tropical hummingbirds often forage in mixtures of several plant species. As a result, pollen is often transferred among heterospecific flowers. The "Sexual Architecture Hypothesis," a paradigm of pollination ecology and angiosperm evolution, suggests that the severity of such interspecific pollen transfer should reflect the similarity in the archi- tecture of sexual structures (specifically, placement of stigma and anthers) among the flowers involved. We evaluated the hypothesis with six species of Costa Rican cloud-forest plants varying greatly in sexual architecture but all pollinated by the same hummingbird, Lam- pornis calolaema. Captive Lampornis visited five long-styled, "pollen-donor" flowers of distylous, self-incompatible Palicourea lasiorrachis (Rubiaceae), then 20 short-styled re- cipient flowers of Palicourea, with or without five flowers of a second species intervening. We assessed intraspecific pollen transfer from Palicourea donors by counting pollen tubes in styles of the recipients. We examined interspecific pollen transfer between Palicourea and each of the five. other species by counting heterospecific grains deposited on stigmas of Palicourea recipients, and Palicourea grains deposited on stigmas and anthers of the heterospecific flowers. In a separate experiment, we examined how mixed-species flower visits modified the pollen loads actually carried by birds. Results did not uphold the Sexual Architecture Hypothesis. A single visit to any hetero- specific flower greatly affected the hummingbird's prior load of Palicourea pollen, re- gardless of where the second species placed its own pollen on the bird. Interspecific pollen transfer occurred consistently, but (1) heterospecific grains usurped little space on stigmas of Palicourea recipients and had no discernible effect on pollen-tube growth, whereas (2) few Palicourea grains landed specifically on anthers and stigmas of heterospecific flowers. Instead, numerous Palicourea grains apparently were scraped off on other floral structures such as the corolla. Consequently, every species of intervening flowers, regardless of its sexual architecture per se, strongly reduced pollen transfer from donor to recipient Pali- courea flowers, on average by 76%. In fact, the most drastic reductions resulted from the two species whose sexual architectures least resembled that of Palicourea. Results imply that "pollen scraping" by floral structures other than anthers and stigmas may be important and widespread among some animal-pollinated flowers. Thus, except in cases where no other floral structures contact pollinators, the positions of anthers and stigmas alone may have little bearing on the severity of interspecific pollen transfer and competitive interactions among plants sharing pollinators.
Actions of the anti-cancer drug suberoylanilide hydroxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures

Micro- and nanotechnologies are increasingly being applied in cancer research. Here we report the effects of an experimental breast cancer agent, SAHA, on the cytoarchitecture and adherence of MDA-MB-231 metastatic human breast cancer cells on flat silicon surfaces and in three dimensional (3-D) isotropic silicon microstructures. The 3-D silicon microstructure were fabricated using a single mask and single etch step process to yield arrays of star- and circular-shaped microchambers 151-168 microm in diameter and 53-68 microm deep. There was a marked expansion of the microtubule network, an increase in mean cell area and mean cell length in response to SAHA. SAHA also decreased the nuclear-to-cytoplasmic area (N/C). Atomic force microscopy (AFM) showed there was no change in cellular elasticity over the nuclear region in response to SAHA. The alterations in cytoarchitecture produced by SAHA were associated with changes in the mode of adhesion of the cells in silicon microstructures. In contrast to control cells which conformed to the microstructures, SAHA caused cells to stretch and attach to the microstructures through actin-rich cell extensions. We conclude that isotropically etched silicon microstructures comprise microenvironments that discriminate metastatic mammary cancer cells in which cytoskeletal elements reorganized in response to the anti-cancer agent SAHA.
Ineffectiveness of sexually arousing stimulation after hypothalamic lesions in the rat

Abstract Lesions of the medial forebrain bundle interrupted copulatory behavior of male rats. Female replacement, handling and tail shock elicited behavioral arousal and sexual approach in lesioned animals, but failed to induce copulation.
Ribosomal protein gene expression is cell type specific during development in Dictyostelium discoideum.

Abstract Starvation for amino acids initiates the developmental cycle in the cellular slime mold, Dictyostelium discoideum. Upon starvation one of the earliest developmental events is the selective loss of the ribosomal protein mRNAs from polysomes. This loss depends upon sequences in the 5′ non-translated leader of the ribosomal protein (r-protein) mRNAs. Here evidence is presented which indicates that those cells which will become prestalk cells express the ribosomal protein genes during development under starvation conditions. Cells which enter the prespore pathway shut off r-protein synthesis. The promoter and 5′ non–translated leader sequences from two ribosomal protein genes, the rp-L11 and the rp–S9 genes, are fused to the Escherichia coli β-galactosidase reporter gene. While β-galactosidase enzyme activity is detected in situ in most growing cells, by 15 h of development β-galactosidase enzyme activity is largely lost from the prespore cells although strong β-galactosidase enzyme activity is present in the prestalk cells. These observations suggest the possibility that the ribosomal protein mRNAs are excluded from polysomes in a cell-type-specific manner.
Prefrontal Electrophysiologic “Noise” and Catechol-O-Methyltransferase Genotype in Schizophrenia

Background Increased variability of stimulus-induced prefrontal electromagnetic activity ("noise") has been associated with genetic risk for schizophrenia. On the basis of animal experiments and computational models, we have predicted that this prefrontal "noise" phenotype would be related to variation in prefrontal dopamine (DA) signaling, which itself might be abnormal in schizophrenia. In the present study, the effect of a functional single nucleotide polymorphism (val 108/158 met) within the catechol- O -methyltransferase (COMT) gene on prefrontal "noise" was examined, because the COMT enzyme is involved in cortical synaptic dopamine metabolism and weakly predictive of risk for schizophrenia. Methods A Caucasian sample comprising 112 unrelated normal subjects, 83 schizophrenic probands, and 87 of their unaffected siblings was investigated, all of whom had measures of prefrontal "noise" estimated from event-related electroencephalogram during an auditory oddball task. Results The val 108/158 met genotype was significantly associated with prefrontal "noise"; homozygous Val-carriers had greatest prefrontal "noise" values; odds ratio (OR) = 2.37 (95% confidence interval [CI] 1.37–4.10), p = 003. The genotype-phenotype association was stronger when only considering male subjects with an OR=3.37 (95% CI: 1.63–6.98), p = 002. Conclusions The results suggest that COMT genotype impacts the level of prefrontal physiologic "noise."
881 ERYTHROCYTE PYRIMIDINE 5′ NUCLEOTIDASE ISOENZYMES IN CONGENITAL DEFICIENCY AND IN LEAD EXPOSURE

Red blood cell (rbc) pyrimidine 5' nucleotidase deficiency (P5N) is a cytosolic enzyme system that dephosphorylates CMP, UMP, dCMP, dUMP and dTMP. The kinetics and metallosensitivities of enzyme activity were determined in normal subjects, congenital pyrimidine 5' nucleotidase deficiency (PND) and subjects with increased blood lead. The apparent Michaelis constants and Kmax suggest 3 isoenzymes of decreasing substrate affinity for 1) dUMP and dCMP, 2) dTMP, 3) UMP and CMP. In PND, activity with UMP and CMP is 50% inhibition at 10−4) is more evident in normal rbc than PND. In rbc from lead exposed subjects, rbc P5N activity with UMP as substrate is directly correlated with the level of blood lead.
Fundamentals of carbocation chemistry in alkene polymerization and alkylative or oxidative alkane condensations

Some fundamental aspects of carbocation chemistry are discussed in their relationship to our better understanding of carbocationic olefin polymerization and alkane condensation reactions including those of methane. Whereas trivalent alkyl cations, i.e. R3C+ play the key role in the former, the latter is made possible through the intermediacy of five coordinate carbocations of the CH5+ type. In conventional acid catalyzed reactions carbocations are always in equilibrium with their corresponding olefins, whereas under superacidic, stable ion conditions carbocations can be generated and reacted free of such equilibria. The chemical consequences of these differences are discussed in polymerization, as well as in alkylative or oxidative alkane condensation reactions.
Coronary vasoconstriction induced by mental stress (simulated public speaking).

Abstract The present study demonstrates that potent mental stress, such as that produced in response to the simulated public speaking task, results in an increase in heart rate and blood pressure, and vasoconstriction of normal coronary artery segments in patients with and without angiographically demonstrable coronary artery disease.
Design and Implementation of the Normalized Comprehensive Alarming System in Guangzhou Fire Department Command Center

The fire department command center is the fire command dispatching hub, the brains of strategic decisions and the information center, which affects the effectiveness of fire fighting and rescue work directly. The urgent, difficult, high-risk, important rescue missions are increasing, and fire department command center, information communication means and vehicle equipment modernization degree unceasing enhancement. The demands on the normalized comprehensive alarming system will only get more pressing. This article focuses on the design and implementation of the normalized comprehensive alarming system in Guangzhou Fire Department Command Center.
Organic halogenated contaminants in mother-fetus pairs of harbor seals (Phoca vitulina richardii) from Alaska, 2000–2002

This study measured organochlorine pesticides (OCPs) including hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), heptachlor and dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs) and polybrominated diphenyl ethers (PBDEs) in tissues of six mother-fetus pairs of harbor seals that were hunted for subsistence in Alaska waters of the Northern Pacific Ocean. These data suggest that significant amounts of these contaminants were transferred from mother harbor seals to fetuses during pregnancy and distributed among fetal organs. The tissue distribution depended on the chemical groups, the specific compounds in the groups and the target organs. Concentration profiles of ∑OCPs, ∑PCBs, ∑PCNs and ∑PBDEs were remarkably similar among maternal blubber, liver, and placenta, fetal blubber, and liver (except for HCHs), possibly indicating that the placenta did not serve as a barrier for all of the compounds analyzed. DDTs, HCB, HCHs, PCBs and PBDEs could penetrate the placenta and accumulate in the blubber of the fetus in utero, while HCHs, PCBs and PBDEs penetrated the placenta and accumulated more preferentially in the fetal liver than in the fetal brain in comparison with DDTs and HCB. Heptachlor and PCNs penetrated the placenta and accumulated in the fetal liver and brain instead of fetal blubber. Similar maternal transfer trends for OCPs, PCBs, PCNs and PBDEs were shown by fetal to maternal (FM) blubber ratios and FM liver ratios. Prenatal transfer of these toxic contaminants from mothers to fetus presumably through the placenta may pose health risks to the fetus during early development.
Kidney N-Acetylgalactosamine (GalNAc)-1-phosphate Kinase, a New Pathway of GalNAc Activation

A new enzyme that phosphorylates GalNAc at position 1 to form GalNAc-α-1P was purified ∼1275-fold from the cytosolic fraction of pig kidney, and the properties of the enzyme were determined. The kinase is quite specific for GalNAc as the phosphate acceptor and is inactive with GlcNAc, ManNAc, glucose, galactose, mannose, GalN, and GlcN. This enzyme is clearly separated from galactokinase by chromatography on phenyl-Sepharose. The GalNAc kinase has a pH optimum between 8.5 and 9.0 and requires a divalent cation in the order Mg2+ > Mn2+ > Co2+, with optimum Mg2+ concentration at ∼5 mM. The enzyme was most active with ATP as the phosphate donor, but slight activity was observed with ITP, acetyl-P, and phosphoenolpyruvate. Enzyme activity was highest in porcine and human kidney and porcine liver, but was low in most other tissues. Cultured HT-29 cells also had high activity for this kinase. The purified enzyme fraction was incubated with azido-[32P]ATP, exposed to UV light, and run on SDS gels. A 50-kDa protein was labeled, and this labeling showed saturation kinetics with increasing amounts of the probe and was inhibited by unlabeled ATP. Although the most purified GalNAc kinase preparation still had two bands that labeled with ATP, maximum labeling of the 50-kDa protein, but not the 66-kDa band, was coincident with maximum GalNAc kinase activity on a column of DEAE-Cibacron blue. On Sephacryl S-300, the native enzyme has a molecular mass of 48-51 kDa, indicating that the active kinase is a monomer. The product of the reaction was characterized as GalNAc-α-1-P by various chemical procedures.
Context memories and reactivation: constraints on the reconsolidation hypothesis

Recent evidence suggests that the maintenance of a reactivated contextual-fear memory requires a protein-synthesis-dependent reconsolidation process in the hippocampus (K. Nader, 2003). In contrast, the authors report a systematic set of experiments that failed to find evidence that the rat's reactivated memory for context becomes labile and requires a new protein to restabilize. Although injecting the protein-synthesis inhibitor into the dorsal hippocampus or intracerebroventricularly following the reactivation of the context memory had no effect, these same treatments did impair the initial consolidation of the context memory and the consolidation of a contextual-fear memory. These results suggest that there may be important constraints determining when a reactivated memory requires reconsolidation. The authors offer 2 hypotheses about the nature of these constraints.
Dynamic patent licensing

Abstract This paper shows one way a fixed fee can dominate an auction. If no one knows whether the innovation will succeed or not when it appears, and if its life exceeds the life of the patent, then selling one licence by fixed fee maximizes inventor profit for some probabilities of success. The reason is a nonlicensee is better off when a rival buys a license because this reveals the nature of the innovation. If it succeeds, the nonlicensee can adopt in the future, after the patent has expired. This expected future gain can outweigh the expected loss during the life of the patent.
Did Henry Ford mean to pay efficiency wages

In the past two decades economists have developed efficiency wage theories, which suggest a link between wage rates and worker productivity, while attempting to explain the existence of involuntary unemployment in equilibrium labor markets. Henry Ford's 1914 announcement of the five-dollar day, an overnight doubling of wage rates, is regularly used as the textbook application of efficiency wage theories put into practice. While previous research demonstrates that the effects of the five-dollar day were largely consistent with those predicted by efficiency wage theories, Ford's wage policy was principally motivated by the fallacious wage-aggregate demand link expressed by the so-called“high-wage doctrine”-a belief that many economists claim significantly contributed to the unemployment problem of the 1930s. In addition to exploring Ford's high-wage motives, I discuss the role Ford's wage statements and policies played in the acceptance and implementation of high-wage public policies during the Great Depression.
Recursive solution of Liouville's equation

Abstract The evolution of a density in phase space may be expressed as the intensity of a time-dependent wave function of coordinates and their momenta, which satisfies the classical Liouville equation and whose power spectrum is stable according to the black body theorem of von Laue. Formulated in this way, the evolution of phase space densities can be obtained from the recursion method which expands their power spectra, with respect to Liouville's equation, in continued fractions, and for which the positivity of the phase space density is preserved in all approximations. To demonstrate this method, we present its application to three simple one-dimensional systems: a harmonic oscillator, an inverted oscillator, and motion under a Gaussian potential.
Adverse gastrointestinal effects of NSAIDs: consequences and costs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely consumed medications. They are available by prescription and 'over the counter'. The same pharmacological properties which make them effective in the treatment of a variety of painful and/or arthritic conditions are responsible for a variety of adverse gastrointestinal effects, ranging from relatively mild dyspepsia to potentially lethal gastrointestinal (GI) bleeding and perforated ulcers. Yearly medical costs of GI complications associated with the use of NSAIDs are very high and likely to increase with the growth of the ageing US population. A review of the literature (1970-2000) on consequences and costs of NSAID-associated GI adverse effects, including iatrogenic cost factors of NSAIDs, was performed. The results were tabulated and compared. Knowledge and comparison of the consequences and costs of NSAID-associated GI adverse effects in various populations and across various health care systems are important for clinical care, pharmacoeconomics and policy arenas.
Evaluating the grid impact of plug-in electric vehicles using dynamic commuting profiles

We analyze the actual commuting profiles of vehicles in the US and develop a statistical model to fit the observed data. Subsequently, this model is leveraged in a simulation framework to simulate the behavior of fleets of Plug-in Electric Vehicles (PEV), analyze their impact on the grid and, compute the effective load carrying capacity (ELCC) contributed by PEVs. We develop methodologies to quantify ELCC impact of various scenarios, including (1) restrictions on when PEVs can be charged or discharged, and (2) how the commuting times are distributed throughout the day. The model is run with 4-year actual load data from New York City (NYC) and PEV performance specifications of Chevy Volt to obtain ELCC contribution figures for PEV fleet sizes going up to 50% penetration. Our results show that up to 7% of peak capacity in NYC can be supplied by PEVs at a 25% penetration level.
California ground squirrel (Spermophilus beecheyi) defenses against rattlesnake venom digestive and hemostatic toxins

Previous studies have shown that some mammals are able to neutralize venom from snake predators. California ground squirrels (Spermophilus beecheyi) show variation among populations in their ability to bind venom and minimize damage from northern Pacific rattlesnakes (Crotalus oreganus), but the venom toxins targeted by resistance have not been investigated. Four California ground squirrel populations, selected for differences in local density or type of rattlesnake predators, were assayed for their ability to neutralize digestive and hemostatic effects of venom from three rattlesnake species. In Douglas ground squirrels (S. b. douglasii), we found that animals from a location where snakes are common showed greater inhibition of venom metalloprotease and hemolytic activity than animals from a location where snakes are rare. Effects on general proteolysis were not different. Douglas ground squirrels also reduced the metalloprotease activity of venom from sympatric northern Pacific rattlesnakes (C. o. oreganus) more than the activity of venom from allopatric western diamondback rattlesnakes (C. atrox), but enhanced the fibrinolysis of sympatric venom almost 1.8 times above baseline levels. Two Beechey ground squirrel (S. b. beecheyi) populations had similar inhibition of venoms from northern and southern Pacific rattlesnakes (C. o. helleri), despite differences between the populations in the locally prevalent predator. However, the venom toxins inhibited by Beechey squirrels varied among venom from Pacific rattlesnake subspecies, and between these venoms and venom from allopatric western diamondback rattlesnakes. Blood plasma from Beechey squirrels showed highest inhibition of metalloprotease activity of northern Pacific rattlesnake venom, general proteolytic activity and hemolysis of southern Pacific rattlesnake venom, and hemolysis by allopatric western diamondback venom. These results reveal previously cryptic variation in venom activity against resistant prey that suggests reciprocal adaptation at the molecular level.
Chemotherapy treatment for older women with metastatic breast cancer: what is the evidence?

Abstract While the over-representation of the elderly in the breast cancer population is projected to dramatically increase within the next two decades, data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) remain very limited. The aim of the present study is to investigate whether elderly patients included in clinical studies for MBC are representative of the population seen during usual clinical practice. Firstly, a review of the literature was performed identifying 39 publications about chemotherapy for MBC focusing on elderly patients and we examined patient characteristics in each of these publications. Comparison of the age distribution of patients included in these studies with that of a large cohort of consecutive MBC patients aged 65years who received chemotherapy in our institution over the last ten years ( n =573) indicated that trials tend to include relatively younger patients. Furthermore, criteria to assess external validity of the results are seldom reported. Possible ways to improve the applicability of results such as increasing the minimum age for inclusion and the use of CGA are proposed.
Computing real roots of a polynomial in Chebyshev series form through subdivision

An arbitrary polynomial of degree N, fN (x), can always be represented as a truncated Chebyshev polynomial series ("Chebyshev form"). This representation is much better conditioned than the usual "power form" of a polynomial. We describe two families of algorithms for finding the real roots of fN in Chebyshev form. We briefly review existing companion matrix methods--robust, but relatively expensive. We then describe a broad family of new rootfinders employing subdivision. These new methods partition the canonical interval, x ∈ [-1, 1], into Ns subintervals and approximate fN by a low degree Chebyshev interpolant on each subdomain. We derive a rigorous error bound that allows tight control of the error in these local approximations. Because the cost of companion matrix methods grows as the cube of the degree, it is much less expensive for N > 50 to calculate the roots of many low degree polynomials, one polynomial on each subdivision, than to directly compute the roots of a single polynomial of high degree.
Reconstitution of the Signal-Transduction Bicyclic Cascade Responsible for the Regulation of Ntr Gene Transcription in Escherichia coli†

Nitrogen-regulation of gene transcription in Escherichia coli results from the regulation of the phosphorylation state of the enhancer-binding transcription factor NRI (NtrC). We examined the regulation of NRI phosphorylation in a reconstituted bicyclic cascade system containing four regulatory proteins: NRI, the signal-transducing uridylyltransferase/uridylyl-removing enzyme (UTase/UR), its substrate the signal transduction protein PII, and the kinase/phosphatase NRII (NtrB), which is a PII receptor that phosphorylates and dephosphorylates NRI. In this reconstituted system, the phosphorylation state of NRI was regulated reciprocally by the small molecule effectors glutamine, which prevented the accumulation of NRI-P, and 2-ketoglutarate, which caused accumulation of NRI-P. Regulation of the bicyclic system by glutamine was exclusively due to sensation and signal-transduction by the UTase/UR-PII monocycle, which was observed to function essentially as a glutamine-sensing apparatus. In contrast, regulation of NRI phosphorylation by 2-ketoglutarate, which binds to PII, was due to direct regulation of the NRII-PII interaction and the rate of NRI-P dephosphorylation. Thus, the PII protein transduces the glutamine signal to the NRII-NRI monocycle in the form of its uridylylation state and is also the receptor of the antagonistic 2-ketoglutarate signal, which blocks the activity of unmodified PII.
On the solvability of multipoint boundary value problems for discrete systems at resonance

We study nonlinear discrete-time boundary value problems at resonance. Criteria for the existence of solutions are established via topological degree theory and the Lyapunov–Schmidt procedure.
Traumatic rupture of the coracoacromial ligament

This is a case report of an arthroscopically diagnosed injury to the coracoacromial ligament at the undersurface of the acromion. To our knowledge, this has not been previously described. Traumatic avulsion of this ligament may represent a source of subacromial impingement that has not been recognized.
Accurate Determination of Object Position from Imprecise Data

The problem of accurate determination of object position from imprecise and excess measurement data arises in kinematics, biomechanics, robotics, CAD/CAM and flight/vehicle simulator design. Several methods described in the literature are reviewed. Two new methods which take advantage of the modern matrix oriented software (e.g., MATLAB, IMSL, EISPACK) are presented and compared with a basic method. It is found that both of the proposed decomposition methods (I: SVD/QR and II: SVD/QS) give better absolute results than a basic method available from the text books. On a relative basis, the second method (SVD/QS Decomposition) gives slightly better results than the first method (SVD/QR Decomposition). Examples are presented for the cases when the points chosen are nearly dependent and when the independent points have small the points chosen their coordinates.
Increase of polyphenol oxidase and decrease of polyamines correlate with tissue browning in Virginia pine (Pinus virginiana Mill.)

Abstract Tissue browning seriously decreases in vitro regeneration from callus cultures in some of woody plants, especially plant regeneration via organogenesis in pine species. Although most of callus cultures turn to brown, a few of them do not become brown during the process of in vitro regeneration in Virginia pine ( Pinus virginiana Mill.). We have recently identified a browning callus line and a non-browning callus line in Virginia pine. For understanding the molecular mechanism of tissue browning in pine, lipid peroxidation, polyphenol oxidase, antioxidant enzymes, and polyamines in the browning callus and the non-browning callus were quantitatively analyzed. An increment in lipid peroxidation and polyphenol oxidase and a decrease in antioxidant enzymes ascorbate peroxidase (APOX), glutathione reductase (GR) and superoxide dismutase (SOD) activities were observed in the browning calluses, compared to the non-browning calluses. Antioxidant enzyme activity decreased rapidly soon after the start of the culture period, especially between the third and fourth weeks of culture. Concentrations of the fraction of soluble amines were different. Putrescine (Put) was reduced 63.8–71.5% in the browning tissue, spermidine (Spd) was decreased to 47–65.6%, and spermine (Spm) content was decreased to 62.3–74.5%, at the third and fifth week of culture, respectively. Our results demonstrated that tissue browning is associated with both accumulation of polyphenol oxidase and decrease of putrescine, spermidine, and spermine in browning calluses, which inhibited callus growth, shoot differentiation, and rooting of shoots derived from browning tissues in Virginia pine. However, more research is necessary to elucidate their precise role in tissue browning in different species.
Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and fibrotic activity.

ANG II is a potent renal vasoconstrictor and profibrotic factor and its activity is enhanced by oxidative stress. We sought to determine whether renal oxidative stress was persistent following recovery from acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) injury in rats and whether this resulted in increased ANG II sensitivity. Rats were allowed to recover from bilateral renal I/R injury for 5 wk and renal blood flow responses were measured. Post-AKI rats showed significantly enhanced renal vasoconstrictor responses to ANG II relative to sham-operated controls and treatment of AKI rats with apocynin (15 mM, in the drinking water) normalized these responses. Recovery from AKI for 5 wk resulted in sustained oxidant stress as indicated by increased dihydroethidium incorporation in renal tissue slices and was normalized in apocynin-treated rats. Surprisingly, the renal mRNA expression for common NADPH oxidase subunits was not altered in kidneys following recovery from AKI; however, mRNA screening using PCR arrays suggested that post-AKI rats had decreased renal Gpx3 mRNA and an increased expression other prooxidant genes such as lactoperoxidase, myeloperoxidase, and dual oxidase-1. When rats were infused for 7 days with ANG II (100 ng·kg−1·min−1), renal fibrosis was not apparent in sham-operated control rats, but it was enhanced in post-AKI rats. The profibrotic response was significantly attenuated in rats treated with apocynin. These data suggest that there is sustained renal oxidant stress following recovery from AKI that alters both renal hemodynamic and fibrotic responses to ANG II, and may contribute to the transition to chronic kidney disease following AKI.
Potential evapotranspiration from forest and pasture in the tropics: A case study in Kona, Hawai‘i

Forest conversion in tropical montane landscapes is widespread and has potentially large implications for both biological and physical processes. Understanding the ecohydrologic processes that affect water can help efforts to predict the downstream effects of parcel-scale land use change. Differences in evapotranspiration between trees and grasses in humid, low wind environments are understudied, however. We analyze predictions of the Penman–Monteith model of potential evapotranspiration (PET) based on hourly meteorological inputs and direct measurements of stomatal resistance for leeward Hawai‘i Island. While evapotranspiration is very low in all of these forest and pasture ecosystems, modeled PET from pasture is higher than is PET from forest. The balance between aerodynamically and stomatally controlled evapotranspiration differs significantly between the two vegetation types in such a way that the weighted sum of the two components yields lower overall PET at the forest sites. The interaction of aerodynamic and stomatal control on PET, in conjunction with tropical meteorology characterized by low wind speeds and low vapor pressure deficit (VPD) causes this unexpected phenomenon. Vegetation structure plays an important role: evapotranspiration from forest is increased considerably by contributions from the understory, while the shorter the stature of pasture grass, the higher its rate of PET. In tropical regions that do not experience water stress, grassland has the potential to transport as much or more water vapor to the atmosphere than does forest.
A DNA element regulates drug tolerance and withdrawal in Drosophila.

Drug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca2+ activated K+ channel gene. After drug clearance this change produces a withdrawal phenotype—increased seizure susceptibility. The drug-induced histone modification profile identified the 6b element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the allele, sloΔ6b, that reacts more strongly to the drug with increased induction, a massive increase in the duration of tolerance, and an increase in the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b element is a homeostatic regulator of BK channel gene expression and is the first cis-acting DNA element shown to specifically affect the duration of a drug action.
Structural Modeling of a Novel CAPN5 Mutation that Causes Uveitis and Neovascular Retinal Detachment

CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new CAPN5 mutation to ADNIV and model the three-dimensional structure of the resulting mutant protein. In our study, a kindred with inflammatory vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and protein structural modeling to investigate the disease-causing mutation. Two daughters of an affected mother demonstrated symptoms of stage III ADNIV, with posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal neovascularization, retinal degeneration, and cataract. The women also harbored a novel guanine to thymine (c.750G>T, p.Lys250Asn) missense mutation in exon 6 of CAPN5, a gene that encodes a calcium-activated cysteine protease, calpain-5. Modeling based on the structures of all known calpains revealed the mutation falls within a calcium-sensitive flexible gating loop that controls access to the catalytic groove. Three-dimensional modeling placed the new mutation in a region adjacent to two previously identified disease-causing mutations, all three of which likely disrupt hydrogen bonding within the gating loop, yielding a CAPN5 with altered enzymatic activity. This is the third case of a CAPN5 mutation leading to inherited uveitis and neovascular vitreoretinopathy, suggesting patients with ADNIV features should be tested for CAPN5 mutations. Structural modeling of novel variants can be used to support mechanistic consequences of the disease-causing variants.
Amphiphilic block copolymer as a crystal habit modifier

The purpose of this study is to evaluate amphiphilic block copolymers, a new class of additives, for the habit modification of pharmaceuticals. The additive chosen is poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA). The model compound chosen is tolazamide, an oral hypoglycemic pharmaceutical agent. Crystallization was carried out in aqueous media by pH adjustment, with or without additives. PEG-b-PLA was found to be very effective in modifying the crystal habit of tolazamide. The habit changed from a needle shape to a plate shape at a concentration of 12.5 μg/mL. This change in habit required both blocks and could not be achieved in the presence of either block alone. A small amount of copolymer (0.55% weight) was found on/in tolazamide particles crystallized in the presence of 30 μg/mL of copolymer. Washing the crystals with toluene effectively removed the copolymer. It is thus concluded that the block copolymer is mainly adsorbed on the crystal surface(s) rather than being incorporated into the lattice of tolazamide crystals. The recrystallized tolazamide is of the same crystal form as that of the original solid, regardless of the concentration of the copolymer used.
Recurrent Benign Müllerian Papilloma of the Cervix

A 4-year-old girl with a recurrent benign cervical mullerian papilloma is presented. Benign mullerian papillomas are rare cervical and vaginal lesions of childhood, with only two recurrences previously reported. This lesion was originally biopsied and later rebiopsied and completely fulgarated with electrocautery. One year later, the lesion recurred and was biopsied but not completely excised because of concern that complete excision of this benign, asymptomatic lesion would cause significant damage to her cervix. A review of the literature on this subject is presented.
Crystallographic report: Triorganotin 2‐(p‐chlorophenyl)‐3‐methylbutyrates

The crystal structures of two triorganotin butyrates were determined. Tricyclohexyltin 2-(p-chlorophenyl)-3-methylbutyrate was determined to have a distorted tetrahedral geometry. Trimethyltin 2-(p-chlorophenyl)-3-methylbutyrate, on the other hand, was found to be polymeric in nature with a trigonal bipyramidal configuration. The three methyl groups are located in the equatorial positions with the axial positions occupied by oxygen atoms from two different carboxylate groups. Copyright © 2003 John Wiley & Sons, Ltd.
A minicomputer program for the resolution of response frequency and latency in classical conditioning preparations

This classical conditioning program is capable of controlling stimulus events and recording response data in experiments using the rabbit’s nictitating membrane and/or iaw-movement responses. The main features of the program, implemented on the PDP·12 computer, are the ability to resolve response latency within a 1 msec error range and to display the response topography on the computer’s cathode ray tube. The extreme accuracy in latency measurement cannot be duplicated either by conventional hand-scoring methods involving oscillographic records or by other minicomputer conditioning programs.
Genes and pseudogenes for rat U3A and U3B small nuclear RNA

We report here the isolation and primary structure of two genes encoding rat U3 small nuclear RNA. One of the genes encodes U3B RNA; the other encodes an RNA which is almost identical to U3A RNA. Both genes are expressed after microinjection into the nuclei of Xenopus laevis oocytes and can direct the accumulation of mature U3 RNA as well as longer transcripts which may be the U3 precursors. We have also isolated and sequenced four other regions of the rat genome homologous to U3 RNA. One of these almost certainly represents a second U3B gene; the other three are pseudogenes which appear to have been generated by the reverse flow of genetic information from U3 RNA back into the genome. Using genomic blotting techniques, we show that the rat U3 genes are present in only a few copies per haploid genome and are probably not closely linked to one another.
The use of a surgical splint in the treatment of oral carcinoma

Abstract A case has been presented to illustrate a technique of using an acrylic guide for the placement of radium needles in the treatment of an oral carcinoma. The appliance allows for the proper spacing and parallelism of the needles to ensure efficient radiation of the lesion.
Some linear nonautonomous control problems with quadratic cost

Abstract In this paper we consider two similar nonautonomous linear control problems which have quadratic cost functionals. We give necessary conditions for the problems to be optimized over an infinite interval and prove that the optimal controls are linear feedback controls. If the first problem is set in a real Hilbert space the feedback controls generate a uniformly asymptotically stable evolutionary process. In the second problem the controls generate an asymptotically stable system of neutral functional differential equations.