cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

1. Hair cells in whole-mount in vitro preparations of the utricular macula of the bullfrog (Rana catesbeiana) were selected according to their macular location and hair bundle morphology. The sensitivity and response dynamics of selected hair cells to natural stimulation were examined by recording their voltage responses to step and sinusoidal hair bundle displacements applied to their longest stereocilia. 2. The voltage responses of 31 hair cells to sinusoidal hair bundle displacements were characterized by their gains and phases, taken with respect to peak hair bundle displacement. The gains of Type B and Type C cells at both 0.5 and 5.0 Hz were markedly lower than those of Type F and Type E cells. Phases, with the exception of Type C cells, lagged hair bundle displacement at 0.5 Hz. Type C cells had phase leads of 25-40 degrees. At 5.0 Hz, response phases in all cells were phase lagged with respect to those at 0.5 Hz. Type C cells had larger gains and smaller phase leads at 5.0 Hz than at 0.5 Hz, suggesting the presence of low-frequency adaptation. 3. Displacement-response curves, derived from the voltage responses to 5.0-Hz sinusoids, were sigmoidal in shape and asymmetrical, with the depolarizing response having a greater magnitude and saturating less abruptly than the hyperpolarizing response. When normalized to their largest displacement the linear ranges of these curves varied from < 0.5 to 1.25 microns and were largest in Type B and smallest in Type F and Type E cells. Sensitivity, defined as the slope of the normalized displacement-response curve, was inversely correlated with linear range. 4. The contribution of geometric factors associated with the hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the lever arm between kinociliary and stereociliary displacement; 2) tip link extension/linear displacement, largely a function of stereociliary height and separation; and 3) stereociliary number, an estimate of the number of transduction channels, were considered in this analysis. The first of these factors was quantitatively more important than the latter two factors and their total contribution was largest in Type B and Type C cells. Theoretical models were also used to calculate the relation between rotary and linear displacement.(ABSTRACT TRUNCATED AT 400 WORDS).
Emerging issues in the physics and control of electromigration in SnPb and Pb-free solder bumps

Electromigration is the movement of metal atoms in the direction of current flow. It is caused by the transfer of momentum from the passing electrons to atoms in the lattice. First discovered in thin-film aluminum conductors some thirty years ago, electromigration is a significant concern for solder bumps on chip scale packages (CSP). As the understanding of solder electromigration expands, new opportunities for risk mitigation have emerged. This paper addresses the physics of electromigration in solders with particular emphasis on the time and temperature dependant factors that affect accelerated testing. Pb-based solders are contrasted with Pb-free solders by realizing that the microstructures of these solders are substantially different and the risks from electromigration are different as well.
Noble Metal Immersion Spectroscopy of Silica Alcogels and Aerogels

We have fabricated aerogels containing gold and silver nanoparticles for gas catalysis applications. The technique of immersion spectroscopy is extended to porous or heterogeneous media allowing the surface area of metal available for catalytic gas reaction to be determined. Specifically, we apply the predominant effective medium theories to the heterogeneous interlayer surrounding each particle to determine the average fractional composition of each component in this inhomogeneous layer. The technique is satisfactory for statistically random metal particle distributions but needs further modification for aggregated or surfactant modified systems. Additionally, the kinetics suggest that collective particle interactions in coagulated clusters are perturbed during silica gelation resulting in a change in the aggregate geometry.
Blood lactate responses to exercise performed on a high-speed inertial device

To assess blood lactate and performance variables obtained from high-speed exercise performed on a device (Impulse Training Systems; Newnan GA) that imposes loads without gravitational resistance, subjects (n = 45) completed two tonic and two phasic workouts. Each high-speed workout entailed two 60-second sets of seated knee- and hip-extension repetitions separated by a 90-second rest period. Pre- and five minutes post-exercise, lactate concentration was measured from a fingertip blood drop with a calibrated analyzer (Accusport, Sports Resource Group, Hawthorne, NY). Mean blood lactate values were compared with a 2(contractile mode: tonic, phasic) x 2(time) x 2 (gender) ANOVA, with repeated measures applied to workout mode and time. Resistance exercise performance variables were assessed with 2 (contractile mode: tonic, phasic) x 2 (gender) ANOVAs. With α ≤ 0.05, results showed a time (post > pre) effect for blood lactate. Exercise performance values were impacted by workout mode and gender, yet those independent variables had no impact on blood lactate. Results concur with prior resistance exercise studies that show significant blood lactate increases over time. Additional inquiry is warranted as to why gender and workout mode influenced resistance exercise performance variables, but did not impact blood lactate.
Time delay estimation for Poisson derived processes

The author treats the problem of time delay estimation for inhomogeneous filtered Poisson processes in the presence of Gaussian noise when the time delay parameter is imbedded in the intensity function of the point process. This is an important estimation problem in the synchronization of optical communications receivers, and positron emission tomography. Approximate expressions for the maximum a posteriori (MAP) and the minimum mean square error (MMSE) estimators are obtained which become increasingly accurate as the product of the filter time-width and the Poisson intensity amplitude approach zero. Large sample approximations to the bias and the MSE are presented for the approximate MAP estimator. >
Cattle distribution and behavior in southern-pine silvopasture versus open-pasture

Shade present in silvopasture systems could reduce heat stress associated with microclimatic conditions that characterize warm-weather portions of the year on the Coastal Plain of the Southeast USA. Objectives of this research were to: (1) quantify diurnal distribution patterns of landscape use and behavior of cattle in loblolly-pine (Pinus taeda) silvopasture versus open-pasture landscapes, and (2) relate observed differences in landscape use and cattle behavior patterns between the two pastures to differences in microclimatic conditions, and forage quantity and quality. The research was conducted in Chipley, Florida USA within a 5-ha cell of a loblolly-pine-bahiagrass (Paspalum notatum) silvopasture (tree age 20 year), and a 5-ha open bahiagrass pasture with unlimited access to an adjacent 1-ha wooded area. One-day observations of diurnal distribution and behavior of cattle were conducted in March, June, and September 2007; microclimatic conditions were measured, and forage quantity and quality were estimated within each landscape. Cattle utilized the landscape more evenly in the silvopasture versus the open-pasture and this difference was mainly attributed to reduced solar radiation recorded in the silvopasture. Grazing was the dominant behavior in the silvopasture while loafing was dominant in the open-pasture. Shade present in silvopasture appeared to reduce heat stress for cattle grazing during warm-weather portions of the year on the Coastal Plain of the Southeast USA. Further study is needed to determine how this reduction in heat stress influences cattle performance in southern-pine silvopasture, and the nature and extent of the interactions among animal distribution and behavior, microclimatic conditions, and forage characteristics in these systems.
Polyamide-anchored palladium(0): Catalysts for the hydrogenation of olefins and nitro compounds

Abstract The reaction of a polyamide prepared from 2,2′-bipyridine-4,4′-dicarboxylic acid and 2,6-diaminopyridine with palladium dichloride was carried out in tetrahydrofuran, resulting in formation of the polyamide Pd(II) complex [1–4]. This was reduced in alkaline methanol under hydrogen to give the polyamide Pd(0) complex, which is a very efficient catalyst for the reduction of olefins and nitro compounds.
A publish-subscribe architecture and component-based programming model for medical device interoperability

Medical devices historically have been monolithic units --- developed, validated, and approved by regulatory authorities as standalone entities. Modern medical devices increasingly incorporate connectivity mechanisms that offer the potential to stream device data into electronic health records, integrate information from multiple devices into single customizable displays, and coordinate the actions of groups of cooperating devices to realize "closed loop" scenarios and automate clinical workflows. In this paper, we describe a publish-subscribe architecture for medical device integration based on the Java Messaging Service. We provide a overview of a model-based development environment that we have built for rapidly programming device coordination scenarios. We assess the extent to which this framework is capable of supporting and complementing the Integrated Clinical Environment that has been proposed by the Medical Device Plug and Play Interoperability Project The implementation of this framework is freely available and open source. One of the primary goals of the framework is to provide researchers in acadaemia, industry, and government with an open test bed for exploring development, quality assurance, and regulatory issues related to medical device interoperability.
Visceral obesity and breast cancer risk

Background. The risk for breast cancer and the sex hormone abnormalities noted in breast cancer patients have been demonstrated in women with upper body fat obesity. The objective of this study was to determine if the visceral component of upper body fat obesity was correlated with breast cancer risk. Methods. A case-control study of 40 consecutively enrolled women with breast cancer and 40 community based age, weight, and waist circumference-matched control subjects was conducted. The areas of visceral fat, subcutaneous fat, and total fat were measured using computed tomography at the 1, -4 vertebral body. Calculations of relative risk for breast cancer were based on these fat compartments. Results. Patients with breast cancer had a significantly greater visceral fat area (P = 0.01), visceral-to-to-tal-fat area ratio (VT ratio) (P 0.24 = 9.5) (P < 0.0001) and decreasing SV ratio (≥3.64 = 1.0; <3.64 = 8.5) (P = 0.0002). Conclusions. Visceral obesity, as assessed by computed tomography, was a significant risk factor for breast cancer in women matched for age, weight, and waist circumference. Comparing the VT ratio for both groups, breast cancer patients had 45% more visceral fat compared with matched control subjects. Cancer 1994; 74: 632-9
Enzymatic determinants of DNA polymerase accuracy. Theory of coliphage T4 polymerase mechanisms.

Abstract The specificity of base selection in DNA synthesis is affected by the DNA polymerase. This paper presents a detailed model of the enzymatic reaction steps involved in template-directed DNA synthesis by DNA polymerase possessing 3′ to 5′ exonuclease activity (the T4 coliphage enzyme and polymerases I, II and III of Escherichia coli are known examples). The central assumptions of the model imply that the strength of the hydrogen bonds formed between candidate bases and the template base provide the principal discrimination criteria for both the insertion and the “editing” excision of bases. We have performed a detailed analysis of this model, and of the stochastic, sequential, single-step process of insertion and excision, which it implies, and have compared the results with experimental data reported by Bessman et al. (1974a,b) for the DNA polymerase of T4. In the present version of the model, the presence of the editing exonuclease accounts for the enzyme's contribution to the accuracy of polymerization and all binding and reaction sites on the enzyme are insensitive to differences between bases or base-pairs. The Bessman data, describing the competitive incorporation of adenine and 2-aminopurine by five allelic polymerases and spanning a spectrum of mutation rates, are well fit by this theory, and permit us to predict the effects of changes in reaction conditions and in basepairing free energy on the outcome of similar experiments.
Synthesis of active RC multiport networks with grounded ports

Abstract A synthesis procedure–easily implemented as a digital computer program– is presented whereby the network function T (s) can be realized as an active RC multiport network with grounded ports. Based on V (s) = T (s) U (s), where T (s) is a q × p matrix of real rational functions of the complex variable s, the realization requires a minimum number of grounded capacitors–n = degree { T (s)}–and no more than 2 (p+n) inverting, grounded voltage amplifiers or p+n differential output, grounded voltage amplifiers. Note: These properties of the realization are desirable if the network is to be fabricated as an integrated circuit.
Tissue Specific Expression of Different Human ReceptorTypes for Pituitary Adenylate Cyclase Activating Polypeptideand Vasoactive Intestinal Polypeptide: Implications fortheir Role in Human Physiology

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two structurally related peptides with pleiotropic physiological effects. Biochemical and cloning experiments have demonstrated that there are two structurally distinct receptors which recognize PACAP and VIP peptides with similar affinities (PACAP/VIP R-1, PACAP/VIP R-2), as well as a receptor that is specific for the PACAP peptide (PACAP-Type 1 receptor). Using a homology-based cloning strategy we have identified PACAP/VIP R-2 receptor in human adipocytes, a tissue which was not previously identified as a target for PACAP and VIP action. This receptor type recognizes PACAP-38 and VIP similar affinity with inhibition concentrations of IC50 = 6.2 +/- 4.8 nM for PACAP-38 and IC50 = 9.4 +/- 4.6 nM for VIP. Like the other two PACAP receptors types, PACAP/VIP R-2 is coupled to cAMP-mediated signal transduction pathway with effective doses ED50 = 3.2 +/- 1.6 nM and ED50 = 2.2 +/- 0.9 nM for PACAP-38 and VIP respectively. Transcripts of the common PACAP/VIP R-2 are also found in human brain and a number of peripheral tissues, such as pancreas, muscle, heart, lund, kidney, stomach and low levels in the liver. Comparison of the tissue distribution of the human PACAP/VIP R-2 to that of the other two types of human PACAP receptors (PACAP-Type 1 and the other common PACAP/VIP R-1) by RNase protection showed that each of the three PACAP receptors is expressed in a unique set of human peripheral tissues. RNA transcripts for all three PACAP receptor types are found in human heart, brain and adipose tissue, while PACAP/VIP R-2 is the only one of these three receptor types that is expressed in the pancreas and skeletal muscle. These results suggest a novel and not yet characterized role for PACAP and VIP peptides in the neuroendocrine regulation of insulin-glucose homeostasis.
Fast and Black-box Exploit Detection and Signature Generation for Commodity Software

In biology, a vaccine is a weakened strain of a virus or bacterium that is intentionally injected into the body for the purpose of stimulating antibody production. Inspired by this idea, we propose a packet vaccine mechanism that randomizes address-like strings in packet payloads to carry out fast exploit detection and signature generation. An exploit with a randomized jump address behaves like a vaccine: it will likely cause an exception in a vulnerable program’s process when attempting to hijack the control flow, and thereby expose itself. Taking that exploit as a template, our signature generator creates a set of new vaccines to probe the program in an attempt to uncover the necessary conditions for the exploit to happen. A signature is built upon these conditions to shield the underlying vulnerability from further attacks. In this way, packet vaccine detects exploits and generates signatures in a black-box fashion, that is, not relying on the knowledge of a vulnerable program’s source and binary code. Therefore, it even works on the commodity software obfuscated for the purpose of copyright protection. In addition, since our approach avoids the expense of tracking the program’s execution flow, it performs almost as fast as a normal run of the program and is capable of generating a signature of high quality within seconds or even subseconds. We present the design of the packet vaccine mechanism and an example of its application. We also describe our proof-of-concept implementation and the evaluation of our technique using real exploits.
Lattice-Fluid Model for Solvation Force Oscillations in Nonionic Fluid Films

Abstract A discrete model is proposed to explain experimentally measured oscillatory disjoining pressure isotherms. The model uses concepts from an earlier model proposed by Tarazona and Vicente (Mol. Phys.56, 557, 1985). This approach yields oscillations with period equal to exactly two molecular diameters, which is contrary to all reported experimental data. When, instead of the simplest lattice-gas description, the Sanchez-Lacombe model (J. Phys. Chem.80, 2352, 1976) is used and a molecule is allowed to occupy several lattice sites, the period agrees well with experiments. Another new feature of our model is that, instead of accounting for only nearest-neighbor repulsion, it also allows for attractive next-nearest-neighbor interactions. The model has one adjustable parameter which is used to match experimental data on oscillatory solvation forces. A generalization of the Deryagin approximation to the case when structural forces are estimated using a density functional model is obtained.
Cultural variation in response to strategic emotions in negotiations

This research examined how culture influences the effectiveness of the strategic displays of emotions in negotiations. We predicted that in cross-cultural negotiation settings, East Asian negotiators who highly regarded cultural values that are consistent with communicating respect as humility and deference would be more likely to accept an offer from an opposing party who displayed positive as opposed to negative emotion. With a sample of East Asian MBA students, the results of Study 1 confirmed this prediction. Study 2 results replicated this finding with a sample of Hong Kong executive managers and also found they were less likely to accept an offer from a negotiator displaying negative emotion than Israeli executive managers who did not hold humility and deference in such high regard. Implications for strategic display of emotions in cross-cultural settings are discussed.
Techniques for successful cardiopulmonary bypass in the calf

Abstract The calf is an excellent experimental animal, but problems in the care and management of these animals, particularly during thoracotomy and cardiopulmonary bypass, have led to a high morbidity and mortality. Pulmonary complications have been most common and have been thought to be due in part to intrinsic problems or immaturity of the lungs and pulmonary circulation of the calf. The results of this study suggest that the pulmonary problems are due primarily to unsatisfactory ventilation. High-pressure (25–30 cm. H 2 O), large-tidal-volume ventilation before and after bypass, with the lungs inflated but not ventilated during bypass, eliminated the pulmonary complications associated with cardiopulmonary bypass in the calf. Methods were developed to prevent other complications in the calf during cardiopulmonary bypass, including foaming of blood in the extracorporeal system, cardiac irritability, ventricular fibrillation, rumen distension, patent ductus arteriosus, and transition from the extracorporeal circuit. These and other techniques have allowed prolonged intrathoracic procedures and cardiopulmonary bypass in the calf with excellent survival and little postoperative morbidity.
Homograft Replacement for Isolated Left-Sided Atrioventricular Valve Insufficiency with Corrected Transposition

Abstract A 38-year-old woman is reported who had corrected transposition of the great vessels and associated left-sided atrioventricular (A-V) valve insufficiency without intracardiac septal defects. Successful resection of the tricuspid valve and implantation of a fresh aortic homograft on a support ring were carried out.
MAKING DEMOCRACY SAFE FOR THE WWORLD

Recent literature has argued that, beginning in the late 1940s, the increasing ideological competition between the Soviet Union and the United States-or, more broadly, between communism and capitalism-transformed America9s record of racial discrimination and violence into an international issue with consequences for U.S. foreign policy. This article challenges that historiography by raising questions about both the timing and the cause of the increasing importance of civil rights to the U.S. foreign policy process. It focuses roughly equally upon the damage that discrimination against Latinos in the Southwest did to the Good Neighbor Policy and the dif�culties of the World War II propaganda organization, the Of�ce of War Information, in portraying America9s racial practices to the world. To account for these examples requires us to recognize the World War II years-not the Cold War-as the decisive turning point when the history of domestic race relations could no longer be sanguinely ignored by U.S. policymakers.
An investigation of the reduction in tensile strength and fatigue life of pre-corroded 7075-T6 aluminum alloy

In aging aircraft, the synergetic interaction between corrosion and fatigue has been shown to reduce the life expectancy of aluminum alloys. The objective of this study was to quantify the effects of corrosion, in terms of mass loss per unit area, on the static strength and fatigue life of 7075-T6 aluminum alloy. This was an experimental study in which test specimens were corroded in a laboratory environment. The corrosion process was accelerated by use of a corrosion cell. Test specimens were cut from flat sheets of aluminum and covered with masking material to restrict corrosion to a confined area. After testing, the fatigue life, ultimate tensile strength (UTS), and hardness of the specimens were observed to drop significantly with small amounts of corrosion. After the initial decrease, the UTS was observed to decrease linearly with increasing corrosion levels. The fatigue life of the specimens decreased in an inverse exponential fashion as mass loss per unit area increased. The hardness values of the corroded surfaces were also observed to drop. The topology of the pits and the related subsurface damage produced areas of high stress concentration resulting in the immediate reduction of UTS and fatigue life of the specimens. Subsurface corrosion damage was responsible for the reduction in hardness.
The development of a technique for the morphometric analysis of invasion in cancer.

We describe tests of the feasibility of a reconstructive technique to discriminate between expansive growth and active cell movement in the invasion of tissues by cancer cells. The densities of cancer cells in 2210 μm2 (grid) squares of standard 6 μm fixed, stained histologic sections of a nodule and an invasive cutaneous melanoma were determined, and density maps of the tumors constructed. An abrupt transition from saturation density to zero cell density was observed at the advancing edge (towards the stratum corneum) of the tumor nodule which was consistent with a model for expansion by growth (vis a tergo). In contrast, at the advancing edge of the invasive tumor, the transition from saturation to zero density (towards the subcutaneous tissues) occurred more gradually, over approximately 400 μm, which was consistent with a model for invasion by active movement of melanoma cells. The occurrence of statistically significant “high density regions” near to the advancing edge of the invasive tumor is consistent with an invasive pattern of active movement followed by focal proliferation of the cancer cells, in a repetitious manner. It therefore appears feasible to make kinetic reconstructions of some of the events in invasion, from static quantitative observations.
Motorcycle conspicuity: effects of age and daytime running lights

Objective:This study investigated variables that may contribute to motorcycle conspicuity within a high-fidelity simulated environment. The variables included motorcycle lighting, vehicular daytime running lights (DRLs), and age of the driver of the other vehicle. Background: Research suggests that decreased levels of conspicuity associated with riding a small two-wheeled vehicle reduce the ability of other drivers to detect and respond to that vehicle effectively. This lack of conspicuity is often responsible for the frequent injuries and fatalities incurred by motorcycle riders. Method: The 75 participants who took part in this study watched a series of video clips of roadway traffic and were asked to indicate when they saw a hazardous situation, such as the presence of pedestrians, motorcycles, or traffic cones. Both motorcycle and following-vehicle lights were manipulated, and participant reaction times were collected and analyzed. Results: Analyses indicated main effects for all three variables as well as interaction effects between motorcycle lighting and vehicle-following conditions. Overall, findings showed a link between DRLs and the effective detection of motorcycles and suggested that age-related changes affect the ability to detect and respond to a motorcycle effectively. Conclusion: Although our laboratory findings corroborated previous correlational studies, further research in real-world settings, such as those with high-density traffic or under adverse environmental conditions, needs to be conducted. Application: Potential applications of this research include the assessment of appropriate lighting technology to enhance conspicuity of motorcycles and reduce the high rate of fatalities and injuries related to motorcycle crashes.
Mechanisms of autoimmune neuropathies

Our studies have focused on the mechanisms involved in blood-brain barrier and blood-nerve barrier alterations in inflammatory demyelinating diseases. The results support the conclusion that these diseases are initiated by delayed hypersensitivity reactions. They further demonstrate a role for mast cell degranulation and vasoactive amines in the peripheral nerve. In the central nervous system, our studies have documented both active and passive mechanisms of edema formation and support the conclusion that cytokines may be involved in altered blood-brain barrier permeability and inflammation. We conclude that several mechanisms of barrier breakdown are activated in the inflammatory demyelinating diseases and that alteration in endothelial cell function is a major component of disease induction.
International variation in sin stocks and its effects on equity valuation

Abstract We examine the impact of differences in time varying social views towards sin stocks across G20 nations on firm valuation and excess returns. Sin stocks have an 8% lower equity valuation in countries where society is strongly against such industries. After controlling for other factors, sin stocks have excess returns of about 1–2% annually. However, these returns are largely arbitraged away in nations without capital and investment controls, but persist in countries with capital restrictions. These results are robust to proxies for litigation risk, transparency, growth opportunities, sin measures, and alternative measures of firm valuation.
John Martin Fischer, The Metaphysics of Free Will (Oxford: Blackwell, 1994)

Etude de la position semi-compatibiliste sur la question de la liberte, de la responsabilite morale et du determinisme, developpee par J. M. Fischer dans son ouvrage intitule «La metaphysique de la volonte libre» (1994). Examinant la discussion de Fischer sur les contre-exemples de Frankfurt refutant le principe des possibilites alternatives, l'A. etudie les deux theses principales de Fischer qui sont la defense de l'incompatibilisme concernant la volonte libre (ou la possibilite d'agir autrement) et la defense du compatibilisme concernant la responsabilite morale (effective meme dans le cas ou l'on ne peut agir autrement)
The two-step model of prostaglandin signal termination: in vitro reconstitution with the prostaglandin transporter and prostaglandin 15 dehydrogenase.

Termination of prostaglandin (PG) signaling has been proposed to involve carrier-mediated uptake across the plasma membrane followed by cytoplasmic oxidation. Here, we tested this hypothesis directly by coexpressing the PG uptake carrier prostaglandin transporter (PGT) in various cell types with and without human PG 15 dehydrogenase (PG15DH). In HeLa cells, which express neither PGT nor PG15DH, exogenously added PGE2 or PGF2α were rapidly oxidized to the 13, 14-dihydro, 15-keto metabolites only when PGT and PG15DH were coexpressed, directly confirming the two-step hypothesis. Cells expressing PG15DH that were broken open formed more PG metabolites than cells in which the PGs could gain access to PG15DH only via PGT. Similar results were obtained using the human prostate cancer cell line LNCaP, in which endogenous PG15DH is induced after exposure to dihydrotestosterone. Because PGT in vivo is expressed in renal collecting duct epithelia, we also expressed PGT in Madin-Darby canine kidney cells grown on filters, where it mediated both the active uptake of PGE2 across the apical membrane and the transepithelial transport of PGE2 to the basolateral compartment. When PG15DH was coexpressed with PGT in these epithelial monolayers, about half of the PGE2 taken up apically was oxidized to 13, 14-dihydro, 15-keto-PGE2, which in turn exited the cells nondirectionally into both the apical and basolateral compartments. Our data represent reconstitution of the longstanding model of PG metabolism consisting of sequential carrier-mediated PG uptake, cytoplasmic oxidation, and diffusional efflux of the PG metabolite.
Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma

BACKGROUND: Women with HER-2 overexpressing metastatic breast carcinoma benefit from trastuzumab-based therapy, but trastuzumab does not cross the blood-brain barrier. The authors characterized central nervous system (CNS) disease in these women. METHODS: Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER-2-positive metastatic breast carcinoma at Dana-Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow-up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow-up of this cohort was 23 months. RESULTS: Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26-44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety-three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first-line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites. CONCLUSIONS: Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab-based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER-2-positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted.
BIOLOGICAL STUDIES OF THE GONADOTROPIC PRINCIPLES IN SHEEP PITUITARY SUBSTANCE1

IN A RECENT publication we described the preparation of two gonadotropic principles from sheep pituitary, namely a follicle stimulating hormone (FSH) and an interstitial cell stimulating hormone (ICSH) (i). A ioo′fold increase in activity over th potency of the dried glands was achieved for each fraction and either was found to befree of the other component up to 10 to 20 times the M.E.D. We also briefly stated that our biological studies of these two gonadotropic fractions indicated that such physiological re′sponses as synergism (activation), luteinisation and antagonism can be dem′onstrated by injecting a combination of these two factors in certain pro′portio and by various routes. In the present communication we wish to report the results of these combination experiments. Definition of Units and Standardization of FSH andICSH In order to be able to compare the biological results quantitatively we adopte the following physiological
Analysis of trace neptunium in the vicinity of underground nuclear tests at the Nevada National Security Site.

Abstract A high sensitivity analytical method for 237 Np analysis was developed and applied to groundwater samples from the Nevada National Security Site (NNSS) using short-lived 239 Np as a yield tracer and HR magnetic sector ICP-MS. The 237 Np concentrations in the vicinity of the Almendro, Cambric, Dalhart, Cheshire, and Chancellor underground nuclear test locations range from −4 to 2.6 mBq/L (6 × 10 −17 –4.2 × 10 −13 mol/L). All measured 237 Np concentrations are well below the drinking water maximum contaminant level for alpha emitters identified by the U.S. EPA (560 mBq/L). Nevertheless, 237 Np remains an important indicator for radionuclide transport rates at the NNSS. Retardation factor ratios were used to compare the mobility of 237 Np to that of other radionuclides. The results suggest that 237 Np is less mobile than tritium and other non-sorbing radionuclides ( 14 C, 36 Cl, 99 Tc and 129 I) as expected. Surprisingly, 237 Np and plutonium ( 239,240 Pu) retardation factors are very similar. It is possible that Np(IV) exists under mildly reducing groundwater conditions and exhibits a retardation behavior that is comparable to Pu(IV). Independent of the underlying process, 237 Np is migrating downgradient from NNSS underground nuclear tests at very low but measureable concentrations.
Product and process understanding to relate the effect of freezing method on glycation and aggregation of lyophilized monoclonal antibody formulations.

The objective of the study was to analyze the effect of controlled and uncontrolled freezing step of a lyophilization process on the extent of non-enzymatic glycation and aggregation of an IgG1 formulation at two concentrations (1 mg/ml and 20 mg/ml). The degree of glycation (%) was determined through boronate affinity chromatography and its effect on the formation of soluble aggregates and higher molecular weight species was studied using dynamic light scattering (DLS) and size exclusion chromatography with multi-angle light scattering (SEC-MALS). The effect of non-enzymatic glycation on the secondary structure of the formulations was also studied using circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. Results indicated that controlled nucleation yielded higher residual moisture contents and significantly lower specific surface areas for the two monoclonal antibody concentrations compared with uncontrolled nucleation cycle (p < 0.05). For the two concentrations, uncontrolled nucleation resulted in significantly higher levels of glycation compared with controlled nucleation samples (p < 0.05). Further, it was observed that higher storage temperatures (25 °C/60% RH) versus 5 °C resulted in higher glycation. Even though SEC-MALS analyses of the low concentrated formulations did not reveal the formation of higher molecular weight species, DLS analyses at two storage conditions revealed increases in the hydrodynamic radii and polydispersity index of the reconstituted formulations, suggesting the onset of formation of smaller species in the formulations. CD spectroscopy did not reveal any differences in the secondary structure of the mAb for the two concentrations after lyophilization. In conclusion, the freezing step method impacted the extent of glycation in lyophilized samples and the hydrolyzed component of sucrose was critical for increasing glycation. Even though some level of glycation was observed in lyophilized samples, the native structure of the protein was not affected. Further, it was demonstrated that storage of both lyophilized cakes and reconstituted formulations at higher temperatures could increase the extent of glycation in monoclonal antibody formulations.
On language unity and disunity

A millenary ethnic and cultural history of Italic settlements, Latin hegemonic contact, followed by isolation and external punctuations prior to unification in 1861 under one territorial and legal state created a diverse metalinguistic complex in the Italian peninsula, albeit reflected in extraordinarily rich expression in the arts and sciences as recognized in global society today. In the historicist approach, the role and effects of unity under one state over the last 150 years is recognized in contrast with the prior highly fractured situation as ‘many little states’ under varied (and lingering foreign) influence, including new linguistic (French) and ideological hegemony. The theme of this article deals specifically with the ontology of Italian ‘linguistic identity’ from a human perspective, that personal and group identification that brings us together or divides us in post-modern society toward the quest for linguistic rights as human rights. Owing to the unifying effect (largely achieved) of the It...
The Lap-Band system in the United States. One surgeon's experience with 271 patients

Background: The LAP-BAND system is considered an important bariatric surgery procedure in many countries and is rapidly gaining acceptance in the United States. Outcomes data emerging in the United States parallel European and Australian experience. The purpose of this study was to examine our experience with this procedure in the United States. Methods: Between November 2000 and September 2002, 271 patients (236 women) underwent LAP-BAND system placement. The mean age of patients was 40 years (18–63); preoperative mean body weight was 125 kg (93–192). Surgeries were performed using either the two-step (pars flaccida to perigastric) or the pars flaccida technique with three (1.1%) conversions to open procedures. Mean operative time was 42 min (23–86); average hospital stay was 1 day (4 h to 7 days). Results: The mean body mass index (BMI) decreased from a baseline of 45.3 kg/m2 (35–68) to 41.9 (n = 178), 39.5 (n = 101), 38.4 (n = 81), 36.5 (n = 72), 35.9 (n = 51), and 35.1 (n = 21) kg/m2 at 3, 6, 9, 12, 18, and 24 months, respectively, after surgery. Mean excess weight loss was 40% at 12 months and 43% at 24 months. As patients lost weight, comorbid conditions improved. No deaths occurred, no bands had to be removed, and postoperative complications were minor: 20 (7.3%) access port problems, 18 (6.6%) gastric pouch dilatations, five (1.8%) gastric slippages, and five (1.8%) stoma obstructions. All were managed conservatively or repaired laparoscopically using the original bands. Additional complications included four cases of pneumonia and one case of pulmonary embolism. One patient required reoperation because of trocar site bleeding. Conclusions: The LAP-BAND system is a safe and effective bariatric procedure leading to considerable weight loss and reduction in comorbidity.
Comparison of changes in cellulose ultrastructure during different pretreatments of poplar

One commonly cited factor that contributes to the recalcitrance of biomass is cellulose crystallinity. The present study aims to establish the effect of several pretreatment technologies on cellulose crystallinity, crystalline allomorph distribution, and cellulose ultrastructure. The observed changes in the cellulose ultrastructure of poplar were also related to changes in enzymatic hydrolysis, a measure of biomass recalcitrance. Hot-water, organo-solv, lime, lime-oxidant, dilute acid, and dilute acid-oxidant pretreatments were compared in terms of changes in enzymatic sugar release and then changes in cellulose ultrastructure measured by 13C cross polarization magic angle spinning nuclear magnetic resonance and wide-angle X-ray diffraction. Pretreatment severity and relative chemical depolymerization/degradation were assessed through compositional analysis and high-performance anion-exchange chromatography with pulsed amperometric detection. Results showed minimal cellulose ultrastructural changes occurred due to lime and lime-oxidant pretreatments, which at short residence time displayed relatively high enzymatic glucose yield. Hot water pretreatment moderately changed cellulose crystallinity and crystalline allomorph distribution, yet produced the lowest enzymatic glucose yield. Dilute acid and dilute acid-oxidant pretreatments resulted in the largest increase in cellulose crystallinity, para-crystalline, and cellulose-Iβ allomorph content as well as the largest increase in cellulose microfibril or crystallite size. Perhaps related, compositional analysis and Klason lignin contents for samples that underwent dilute acid and dilute acid-oxidant pretreatments indicated the most significant polysaccharide depolymerization/degradation also ensued. Organo-solv pretreatment generated the highest glucose yield, which was accompanied by the most significant increase in cellulose microfibril or crystallite size and decrease in relatively lignin contents. Hot-water, dilute acid, dilute acid-oxidant, and organo-solv pretreatments all showed evidence of cellulose microfibril coalescence.
Phase transformations in ion‐mixed metastable (GaSb)1−x(Ge2)x semiconducting alloys

Low energy (75–175 eV) Ar+ ion bombardment during film deposition has been used to produce well‐mixed amorphous GaSb/Ge mixtures which, when annealed, transform first to single phase polycrystalline metastable (GaSb)1−x(Ge2)x alloys before eventually transforming to the equilibrium two‐phase state. At 500 °C, for example, the annealing time ta required for the amorphous to crystalline metastable (ACM) transformation was ∼10 min, while ta for the crystalline metastable to equilibrium (CME) transformation was >6 h. The exothermic enthalpy of crystallization and the onset temperature of the ACM transition were determined as a function of alloy composition using differential thermal analysis. The thermodynamic data was then used to calculate the surface energy per unit area σ of the amorphous/metastable‐crystal interface. σ was found to exhibit a minimum between x=0.3 and 0.4. The driving energy for the transition from the crystalline metastable state to the equilibrium two‐phase state was of the order of 0.1...
Bifurcated Endovascular Grafting for Abdominal Aortic Aneurysm

= 55.4 mm) underwent bifurcated endovascular grafting (Guidant/EVT, Menlo Park, CA) over an 18-month period. We concluded that bifurcated endovascular grafting with the EVT® device provides reliable and reproducible aneurysm exclusion with short hospital recovery and low morbidity.
Topic Identification Using Wikipedia Graph Centrality

This paper presents a method for automatic topic identification using a graph-centrality algorithm applied to an encyclopedic graph derived from Wikipedia. When tested on a data set with manually assigned topics, the system is found to significantly improve over a simpler baseline that does not make use of the external encyclopedic knowledge.
Lanthanide/proline cotransport across rabbit renal brush borders

It has been suggested previously that La3+ can replace Na+ on various cotransport systems in renal brush border membranes. In the present study, we used rabbit renal brush border membrane vesicles to examine the specificity and kinetics of Ln3+/proline cotransport. Experiments were carried out under zero-trans, voltage clamped conditions using a rapid-mix/filtration technique. Initial experiments confirmed that La3+ produced the classical overshoot phenomenon. The initial rates of proline uptake relative to Na+ were Eu3+, Tb3+, Nd3+, Pr3+, Ho3+ (3.3)>Na+ (1.0)>La3+ (0.86) > choline+ (0.1). At a saturating salt concentration, uptake saturated with increasing proline concentration: theK t andJ max were 0.05mm and 17 pmol mg−1 sec−1 in Na+; and 0.28mm and 73 pmol mg−1 sec−1 in Tb3+. The higherJ max in Tb3+ indicates that the Tb3+-proline loaded carrier is more effective than the Na+-proline loaded carrier in overcoming some rate-limiting barriers in the transport process. Na+ activated proline uptake with a Hill coefficient of 1.6 and aK 0.5 of 21mm, while Tb3+ activated with a Hill coefficient of 0.88 and aK 0.5 of 28mm. The Hill coefficient for Na+ suggests two binding sites, whereas the Hill coefficient for Tb3+ may indicate negative cooperativity between the trivalent ligands at the binding sites. We conclude that lanthanides are able to substitute for Na+ on the brush border proline carrier and that the lanthanides may serve as useful probes for the ligand binding sites.
ECHO-4 Viruses: Improved Methods and Strain Selection for Identification and Serodiagnosis.

SummaryThese studies have shown that the tube neutralization identification test for ECHO-4 viruses is unreliable and that the most reliable identification method at present is the CF test. It has been demonstrated that immunization of guinea pigs and monkeys with ECHO-4 virus grown in Det.-504 human fibroblast-like cells produces an antiserum free of antibody which will react with RhMKCC antigens, thereby eliminating cell culture cross-reactions and yielding a highly specific diagnostic reaction even with virus antigens of low antigenicity. The ability of ECHO-4 antibodies to readily neutralize DuToit strain as reported by Barron and Karzon(3) has been confirmed and our strain 5705 was found to have similar properties. As suggested by these investigators, DuToit-like strains should probably be employed to detect NA in human patients' sera.
Atmospheric science: Tug of war on the jet stream

Recovery of the ozone hole and increasing greenhouse-gas concentrations have opposite effects on the jet stream. New model experiments indicate that they will cancel each other out over coming decades, leaving storm tracks at a stand still.