cssi/SciSciGPT-SciSciNet huggingface dataset:
Ridaforolimus in advanced or metastatic soft tissue and bone sarcomas

Patient outcomes remain poor for advanced or metastatic soft tissue sarcomas (STS) and bone sarcomas despite a growing number of clinical trials involving single- and multi-agent chemotherapy. mTOR is an intracellular kinase that plays a central role in regulating cell growth, metabolism, survival and proliferation. mTOR inhibitors including temsirolimus, everolimus and ridaforolimus have demonstrated broad anticancer activity. Ridaforolimus is a non-prodrug analog of rapamycin (sirolimus) with conserved affinity for mTOR but improved solubility, stability and bioavailability when compared with sirolimus. Early clinical trials reveal a reproducible and predictable pharmacokinetic profile, a potent, rapid and prolonged target inhibition and an acceptable safety and tolerability profile. Phase II and III trials of ridaforolimus have produced promising clinical activity against advanced sarcomas and will be presented.
Leukocytes from multiple sclerosis patients respond to α- and γ-interferons

Summary Blood mononuclear leukocytes from multiple sclerosis (MS) patients were evaluated for reactivity to α- or γ-interferon (IFN), using a response whereby IFN-treated (primed) cells synthesize higher levels of IFN than untreated cells. Leukocytes were treated in vitro with natural α-IFN, recombinant α-IFN, recombinant γ-IFN, or no IFN, then exposed to measles virus to induce IFN synthesis. With no IFN treatment, IFN production by cells from the MS patients was significantly less than nomral ( P ≤ 0.025). However, with IFN treatment, cells from MS patients were primed as well as cells from normal controls: IFN synthesis for the MS patients' cells was increased 10–11-fold with either α-IFN preparation and 3.6-fold with γ-IFN. These findings verify the presence of leukocyte reactivity to α-IFN and provide the first demonstration of responsiveness to γ-IFN in MS.
Tegmental brain stimulation as a UCS in conditioned response suppression

Electrical stimulation of the mesencephalic reticular area was shown to be an effective UCS in a conditioned suppression paradigm. Of 11 rats tested, five completely suppressed, four displayed intermediate suppression, and two did not suppress, although Ss ceased to respond when the same ICS was used in punishment. Several CS-UCS intervals were used but because of high within and between S variability, no consistent relationship between CS-UCS interval and suppressive behavior was found. It was concluded that tegmental ICS may possess different reinforcing properties than foot shock.
Role of Proinflammatory Cytokines and Redox Homeostasis in Exercise-Induced Delayed Progression of Hypertension in Spontaneously Hypertensive Rats

Hypertension is a well-known risk factor for various cardiovascular diseases. Recently, exercise has been recommended as a part of lifestyle modification for all hypertensive patients. However, the precise mechanisms of exercise training (ExT)-induced effects on the development of hypertension are poorly understood. Therefore, we hypothesized that chronic ExT would delay the progression of hypertension in young spontaneously hypertensive rats (SHRs). In addition, we explored whether the beneficial effects of chronic ExT were mediated by reduced proinflammatory cytokines and improved redox status. We also investigated the involvement of nuclear factor-kappaB in exercise-induced effects. To test our hypotheses, young normotensive (Wistar-Kyoto) and SHRs were given moderate-intensity ExT for 16 weeks. Blood pressure was determined by the tail-cuff method, and cardiac function was assessed by echocardiography. Myocardial total reactive oxygen species and superoxide production were measured by electron paramagnetic resonance spectroscopy; tumor necrosis factor-alpha, interleukin-1beta, gp91(phox), and inducible NO synthase by real-time PCR; and nuclear factor kappaB activity by electrophoretic mobility shift assay. Chronic ExT in hypertensive rats resulted in significantly reduced blood pressure, reduced concentric hypertrophy, and improved diastolic function. ExT significantly reduced proinflammatory cytokines and inducible NO synthase, attenuated total reactive oxygen species and superoxide production, and increased antioxidants in SHRs. ExT also resulted in increased NO production and decreased nuclear factor kappaB activity in SHRs. In summary, chronic ExT delays the progression of hypertension and improves cardiac function in young SHRs; these ExT-induced beneficial effects are mediated by reduced proinflammatory cytokines and improved redox homeostasis via downregulation of nuclear factor-kappaB.
Private Weather Organizations and the Founding of the United States Weather Bureau

In late-twentieth-century America, both the National Weather Service and private weather organizations provide weather services. Although commercially successful, private weather organizations do not bear the full costs of supplying their services, since they receive nearly all oftheir meteorological data from the National Weather Service at essentially zero cost. I No private weather organization in the United States owns a weather satellite, for example. Any investigation into the socially optimal system of delivering weather-information services requires an understanding ofthe historical provision ofthose services. On 9 February 1870 President Ulysses S. Grant signed the Congressional joint resolution authorizing the Secretary of War to establish a network of observation stations in order to provide storm warnings on the Great Lakes and the Atlantic Seaboard.2 The Army Signal Service began providing storm warnings and forecasts the following year for no fee. Did the establishment of the United States Weather Bureau in 1870 replace an already existing weather-forecast system? Were private weather organizations unsuccessful in collecting enough revenue to cover their costs? Or did the growth of commerce, especially on the Great Lakes and the Atlantic Seaboard, raise the expected value of storm warnings enough so that by the late 1870s, a private weather organization of efficient scale would have been created in the absence of the Weather Bureau? This note provides answers to these questions. Two general hypotheses offer differing explanations as to why the government, rather than a private organization, provided the first self-sustaining weather forecast service in the United States. First, weather forecasts may possess qualities characterizing a public good. If the nonrivalrous or nonexcludable nature of weather information was severe enough, private organizations may have been unable to support a socially useful service, or the private service may have been inefficiently limited in size. Second, investors and potential users may not have been convinced initially that the available technology could provide a valuable service. One extension of this view is that the Federal government could test the feasibility of a weather forecasting system more cheaply or was persuaded more readily, for political or scientific reasons, that weather forecasts were both feasible and worthwhile.
Double bond location in polyenoic fatty esters through partial oxymercuration

A rapid micro-procedure has been developed to locate double bonds in fatty acid methyl esters containing from one to four double bonds. Reaction of the ester with an equal molar amount of mercuric acetate in methanol and reduction with sodium borohydride, followed by hydrogenation, produce a mixture of monomethoxy alkanoates. The mass spectrum of this mixture is simpler and more definitive than that from the completely methoxylated polyenoate. Only one methoxyl group is present per molecule, and the mass spectrum of the mixture is indicative of all olefinic positions. Four intense ions are observed for all double bonds examined, except Δ3, where the double bond is represented, by only two ions. Hydrogenation in a gas chromatograph reduces total analysis time to 1 hr.
Sustainable innovation through an entrepreneurship lens

Sustainable innovation is an emerging and fundamental force for change in business and society. Its potential to transform technology, products and markets distinguishes it as an area of entrepreneurial opportunity and a force of ‘creative destruction’ as defined by economist Joseph Schumpeter (1934). Walden Paddlers is a case example of Schumpeterian creative destruction in the area of sustainable innovation. By examining the process by which product and process innovations were achieved by this startup virtual corporation we gain a broader comprehension of how environmental and sustainability considerations can be successfully integrated into business strategy. The company is studied from idea generation through successful launching and management. Key to understanding the outcome was the environmentally related opportunity and the process through which the entrepreneur created innovation through the cultivation and leadership of a network of players. Two premises underlie the analysis: (i) by focusing on opportunity and innovation, the entrepreneurial field offers insights into the relationship between business and the natural environment; (ii) studies of startup entrepreneurial firms implementing environmental and sustainable strategies provide important data that add to our rapidly evolving body of knowledge about the relationship between corporate behavior and the environment. Copyright © 2000 John Wiley & Sons, Ltd. and ERP Environment
Cooperative dislocation generation and the brittle-to-ductile transition

The characteristic features of the brittle-to-ductile transition are explained using a model of cooperative dislocation generation. In two dimensions, the onset of the ductile behavior corresponds to a thermally-driven, stress-assisted dissociation of many atomic-size dislocation dipoles in the vicinity of the crack tip above a critical temperature Tc. The instability is caused by thermally induced screening of dislocation interactions as in the Kosterlitz-Thouless phase transition. However, the critical temperature is well below the melting temperature in the presence of a stress. The nature of dislocation dynamics in the vicinity of the crack tip is also described and its role in the onset of the cooperative instability is examined. The origin of the correlation between the strain-rate dependence of the transition temperature and the temperature dependence of dislocation mobility is explained.
Disparity determination using multilevel products

We determined the overall disparity from stereo images using multiscale products of disparity values. Using the wavelet transform, we used a multiresolution analysis to calculate disparity values from stereo images at different scales. Forming the product of disparities and rescaling resulted in a disparity map that was directly related to depth. Using a multiresolution approach allowed us to more accurately determine disparity by examining the consistency of results through different scales. Using this approach could form the basis of an effective method for depth estimation.
Misused Product Costing in the American Railroad Industry: Southern Pacific Passenger Service between the Wars

Reflecting recent studies that have highlighted the importance of product cost accounting, this article traces the resistance of American railroad managers to the tool, despite growing pressure from academic and engineering economists. This study reveals widespread misunderstanding among managers about the nature of railroad costs, particularly misconceptions about the proportion of fixed and variable costs and the definition of direct costs. It illustrates the impact of these misapprehensions through a detailed examination of Southern Pacific's interwar passenger strategy.
Structure and propagation of laminar flamesnear a heat sink

Abstract This paper presents the results obtained in a theoretical investigation of the problem of laminar flame propagation near a heat sink, the temperature of which may be either high or low as far as the chemical reaction rate is concerned. The results presented consist of two parts: first, effects on the burning velocity of an adiabatic laminar flame due to a change in the temperature of the unburnt mixture; and secondly, effects on the structure and the burning velocity of a laminar flame when the rate of heat loss per unit volume inside the flame in the direction normal to the mixture velocity and the raw of heat loss per unit area at the hot boundary in the direction parallel to the flow are prescribed by arbitrary functions. In all cases, the burning velocity is found to vary approximately with the temperature of the combustion product at the hot boundary according to an expression of the following form S u ∼ exp (−T c /T b ) where S u is the burning velocity. T b is the temperature of the combustion product, and T e is a characteristic temperature, the value of which depends on the specific case under consideration. Some of these observations have also been found to agree with the experimental results. For the special case where heat loss occurs only at the hot boundary in the direction parallel to the flow, there is a lower limit for the temperature of the combustion product, below which no steady-state solution for the burning velocity can be found. This limit is in addition to the one deduced from stability considerations.
Non-invasive measurement of chemotherapy drug concentrations in tissue: preliminary demonstrations of in vivo measurements.

Measurements of the tissue concentrations of two chemotherapy agents have been made in vivo on an animal tumour model. The method used is based on elastic-scattering spectroscopy (ESS) and utilizes a fibre-optic probe spectroscopic system. A broadband light source is used to acquire data over a broad range of wavelengths and, therefore, to facilitate the separation of absorptions from various chromophores. The results of the work include measurements of the time course of the drug concentrations as well as a comparison of the optical measurements with high-performance liquid chromatography (HPLC) analysis of the drug concentrations at the time of sacrifice. It is found that the optical measurements correlate linearly with HPLC measurements, but give lower absolute values.
Nerve growth factor signaling regulates motility and docking of axonal mitochondria.

Axonal transport is thought to distribute mitochondria to regions of the neuron where their functions are required [1]. In cultured neurons, mitochondrial transport responds to growth cone activity, and this involves both a transition between motile and stationary states of mitochondria and modulation of their anterograde transport activity [2]. Although the exact cellular signals responsible for this regulation remain unknown, we recently showed that mitochondria accumulate in sensory neurons at regions of focal stimulation with NGF and suggested that this involves downstream kinase signaling [3]. Here, we demonstrate that NGF regulation of axonal organelle transport is specific to mitochondria. Quantitative analyses of motility show that the accumulation of axonal mitochondria near a focus of NGF stimulation is due to increased movement into bead regions followed by inhibition of movement out of these regions and that anterograde and retrograde movement are differentially affected. In axons made devoid of F-actin by latrunculin B treatment, bidirectional transport of mitochondria continues, but they can no longer accumulate in the region of NGF stimulation. These results indicate that intracellular signaling can specifically regulate mitochondrial transport in neurons, and they suggest that axonal mitochondria can respond to signals by locally altering their transport behavior and by undergoing docking interactions with the actin cytoskeleton.
Calculation of the Unsteady Gas Flow Around a Projectile Moving Through a Gun Barrel

The calculation of gas flow during the motion of a projectile in the gun barrel is a complicated computational task due of the presence of numerous factors, such as nonisothermicity, turbulence, changes in the shape of the computational domain with time, etc. In this study, an attempt to calculate the characteristics of gas flow around a projectile during the motion of the projectile in the gun barrel is undertaken. The flow is considered axisymmetrical, nonstationary, nonisothermal, compressible, and turbulent. For calculating the flow around the projectile, the finite volume method was employed. During the motion of the projectile, the flow pattern behind it changed from subsonic to supersonic. The results of the calculations are represented in figures depicting the flow at different moments of time. The figures show the fields of velocity, pressure and density, as well as the appearance of shock waves inside the gun barrel at subsonic and supersonic speeds.Copyright © 2003 by ASME
Universal Approach for Scaling the ac Conductivity in Ionic Glasses

In a recent Letter, Roling et al. [Phys. Rev. Lett. 78, 2160 (1997)] proposed a novel scaling approach, requiring no arbitrary parameters, for the analysis of the ac conductivity resulting from ionic motion in glasses. However, this approach cannot be applied to alkali germanate glasses whose alkali content varies by more than a decade, since changes which occur in the ion hopping length that accompany the changing alkali content are not incorporated. Here, I show that these changes can be incorporated into a universally valid approach which successfully scales the ac conductivity of sodium germanate glasses as well as two additional ionic systems without the introduction of arbitrary parameters.
The formation of cyclic sesquiterpenes from farnesyl pyrophosphate by prenyltransferase

Abstract Prenyltransferase, which normally catalyzes the 1′-4 condensation which is the basic polymerization of polyterpenoid and cholesterol biosynthesis, also mediates a pyrophosphate-dependent solvolysis of its substrates. We had previously shown that this was an aberration of the normal reaction and that dimethylallyl alcohol and geraniol were liberated from their pyrophosphate esters (C. D. Poulter and H. C. Rilling, 1976, Biochemistry 15 , 1079–1085) . Enzymatic solvolysis of farnesyl pyrophosphate yielded farnesol, nerolidol, and hydrocarbons. We now demonstrate that the hydrocarbons produced are cyclic Sesquiterpenes such as the germacrenes and the humulenes. We postulate that this results from the structure of the catalytic site which is shaped so that the 9,10 double bond of farnesyl pyrophosphate is forced back over its carbinol carbon. As a result, the carbonium ion which is produced by the enzyme at C-1, by pyrophosphate-induced initiation, can now react with the ω-terminal double bond. This finding strongly supports our proposal for the mechanism for termination of this polymerization reaction catalyzed by prenyltransferase.
RSC functions as an early double-strand-break sensor in the cell's response to DNA damage.

Summary The detection of a DNA double-strand break (DSB) is necessary to initiate DSB repair. Several proteins, including the MRX/N complex, Tel1/ATM (ataxia telangiectasia mutated), and Mec1/ATR (ATM and Rad3 related), have been proposed as sensors of DNA damage, yet how they recognize the breaks is poorly understood. DSBs occur in the context of chromatin, implicating factors capable of altering local and/or global chromatin structure in the cellular response to DNA damage, including DSB sensing. Emerging evidence indicates that ATP-dependent chromatin-remodeling complexes function in DNA repair [1–3]. Here we describe an important and novel early role for the RSC ATP-dependent chromatin remodeler linked to DSB sensing in the cell's DNA-damage response. RSC is required for full levels of H2A phosphorylation because it facilitates the recruitment of Tel1/ATM and Mec1/ATR to the break site. Consistent with these results, we also show that Rsc2 is needed for efficient activation of the Rad53-dependent checkpoint, as well as for Cohesin's association with the break site. Finally, Rsc2 is needed for the DNA-damage-induced changes in nucleosome structure surrounding the DSB site. Together, these new findings functionally link RSC to DSB sensing, highlighting the importance of ATP-dependent chromatin-remodeling factors in the cell's early response to DNA damage.
METABOLISM OF THE STERIOD HORMONES, METABOLISM OF PROGESTERONE AND RELATED STEROIDS1

PREVIOUS in vivo studies in humans have indicated that progesterone may be reduced to and excreted as pregnanediol-3(α),20(α) (Venning and Browne, 1937; Buxton and Westphal, 1938; Hamblen et al., 1940; Dorfman et al., 1948) and pregnanol-3(α)-one-3 (Dorfman et al., 1948; Venning, 1947). We have now been able to show that allopregnanediol-3(α),20(α) is also a metabolite of progesterone. Some theoretical intermediates between progesterone and the saturated diols have also been investigated. Among these are pregnanedione-3,20 and allopregnanedione-3,20. Pregnanedione-3,20 was shown to be converted to pregnanediol-3(α),20(α) while allopregnanedione-3,20 was converted to allopregnane-diol-3(α),20(a:) as well as allopregnanediol-3(β),20(α). As a final part of this study Δ5-pregenol-3(β)-one-20, which has been isolated from hog testes (Ruzicka and Prelog, 1943; Haines et al., 1948) was studied in women. Previously Pearlman and Pincus (1946) reported the conversion of pregnenolone to pregnanediol-3(α),20(α) in a ...
Bioaccumulation of chromium in red swamp crayfish (Procambarus clarkii)

Abstract Crayfish were exposed to a range of potassium dichromate concentrations (0.15, 0.30, 3.0 and 30 mg l−1) for periods up to 7 weeks. Chromium bioaccumulation in all tissues over the 7 week exposure period was not consistently time- and dose-dependent. The order of distribution of chromium into the various tissues was dependent upon the exposure concentration of the metal. Chromium clearance studies conducted 1 and 3 weeks following exposure demonstrated a concentration reduction in most tissues only at the highest exposure concentration of chromium (30 mg l−1). Histological studies demonstrated damage to both the gills and hepatopancreas at the lowest exposure concentration. The results suggest that the red swamp crayfish, Procambarus clarkii, is a useful biomarker for chromium exposure.
An Analytical Heat Conduction Modeling in Spherical Powder as Rapid Prototyping with Low Frequency SEDS

The analytical two dimensional temperature field for a spherical metal powder particle subjected to Gaussian heat flux is derived. The particle is considered to be spherical, homogeneous and isotropic with time-independent thermal properties. The heat transfer equation is solved, the temperature distribution in the spherical particle is then derived, and the 3-D temperature charts are drawn. And finally, the results are compared with available resources and good agreements have been observed. As several conduction heat transfer problems can be modeled by a sphere subjected to Gaussian heat flux, the results are used to approximate the problems and the time consuming complex numerical calculations avoided. A Good example for this problem is Rapid prototyping with low frequency Selective Electrical Discharge Sintering (SEDS). In SEDS, electrical plasma arcs provide the thermal energy for initial binding. Binding is a heat transfer process from the energy source to the raw material which cause the separated ...
BEHAVIORAL PATTERNS AND LESION SITES ASSOCIATED WITH IMPAIRED PROCESSING OF LEXICAL AND CONCEPTUAL KNOWLEDGE OF ACTIONS

To further investigate the neural substrates of lexical and conceptual knowledge of actions, we administered a battery of six tasks to 226 brain-damaged patients with widely distributed lesions in the left and right cerebral hemispheres. The tasks probed lexical and conceptual knowledge of actions in a variety of verbal and non-verbal ways, including naming, word-picture matching, attribute judgments involving both words and pictures, and associative comparisons involving both words and pictures. Of the 226 patients who were studied, 61 failed one or more of the six tasks, with four patients being impaired on the entire battery, and varied numbers of patients being impaired on varied combinations of tasks. Overall, the 61 patients manifested a complex array of associations and dissociations across the six tasks. The lesion sites of 147 of the 226 patients were also investigated, using formal methods for lesion-deficit statistical mapping and power analysis of lesion overlap maps. Significant effects for all six tasks were found in the following left-hemisphere regions: the inferior frontal gyrus; the ventral precentral gyrus, extending superiorly into what are likely to be hand-related primary motor and premotor areas; and the anterior insula. In addition, significant effects for 4-5 tasks were found in not only the regions just mentioned, but also in several other left-hemisphere areas: the ventral postcentral gyrus; the supramarginal gyrus; and the posterior middle temporal gyrus. These results converge with previous research on the neural underpinnings of action words and concepts. However, the current study goes considerably beyond most previous investigations by providing extensive behavioral and lesion data for an unusually large and diverse sample of brain-damaged patients, and by incorporating multiple measures of verb comprehension. Regarding theoretical implications, the study provides new support for the Embodied Cognition Framework, which maintains that conceptual knowledge is grounded in sensorimotor systems.
Neutron diffraction and ion-channeling investigations of atomic displacements in YBa2Cu3O7-δ between 10 and 300 K

Abstract Neutron powder diffraction was used to investigate the structural and vibrational properties of a single-phase ceramic specimen of YBa 2 Cu 3 O 7-δ in the temperature range from 10 to 300 K. Measurements were taken at closely-spaced (10 K) intervals between 50 and 150 K, and the data were defined to a precision equal to or exceeding that achieved in previous studies. No clear evidence is found for an anomalous change in any of the structural parameters, including the orthorhombicity parameter, 2( b - a )/( a + b ), in the vicinity of T c . The vibrational properties obtained from the neutron diffraction data are compared with previous results from ion-channeling in single-crystals of YBa 2 Cu 3 O 7-δ , these latter results revealed a clear anomaly at T c in displacements of the Cu(1), Cu(2) and O(4) atoms in the a - b plane. The average vibrational properties of the lattice atoms determined from the two techniques agree quite well, showing an overall decrease in the apparent vibrational amplitude from 300 to 100 K, followed by a further drop as the temperature is lowered through T c . The evidence for an abrupt change (≈0.015 A) in displacement amplitude at T c is clearly much stronger in the channeling results; the magnitude of any anomaly in the diffraction results approaches the statistical uncertainty. The absence of a clear abrupt change in the neutron results at T c suggests that the ion channeling anomaly is not due to an overall reduction in average vibration, amplitude, but arises instead from a strongly correlated sequence of Cu and O (4) displacements appearing in the superconducting state.
Anatomical and physiological relationships between the anterior cerebellar vermis and the pontine parabrachial nucleus in the rabbit

The anatomical connections between the midline cerebellum and the pontine parabrachial nucleus (PBN) were investigated in the rabbit using anterograde and retrograde axonal transport techniques. Small injections (20-50 nl) of cholera toxin conjugated to horseradish peroxidase (CT-HRP) or wheat germ agglutinin conjugated HRP (WGA-HRP) into the cortex of the anterior cerebellar vermis resulted in retrograde and anterograde-like label in the PBN. Focal injections of tracer into the PBN resulted in anterogradely labeled processes in the ACV and retrogradely labeled a small, but distinct group of Purkinje cells within the anterior vermis. Focal injections into the rostral fastigial nuclei (FN) resulted in anterograde-like label in the PBN, and PBN injections labeled FN neurons. Furthermore, the projection from the PBN to ACV is effective in driving cerebellar neurons as electrical microstimulation of the PBN evoked short-latency, phasic responses in ACV Purkinje cells. These experiments generated anatomical and physiological evidence for the existence of a neuroanatomical circuit connecting the midline cerebellum (ACV, FN) with the PBN, that may serve as a functional interface between the midline cerebellum and other brain stem nuclei with cardiovascular function, particularly with respect to the midline cerebellar role in classically conditioned cardiovascular responses.
The application of contact mechanics to rail profile design and rail grinding

Abstract While many railway engineers are exploring the benefits of the latest lubrication technologies, bogie types and metallurgies, the wheel/rail (w/r) contact mechanics are often overlooked or poorly controlled. But the geometry of the w/r contact permeates every facet of the w/r interaction, having profound effects on wear, fatigue, corrugation, stability and derailment potential. A pummelling model is being developed at the NRC Centre for Surface Transportation Technology to quantify the performance of rail profiles when loaded by a large number of measured new and worn wheels. Typical results are shown for the RE136-10″, UIC60 and RE141 rail profiles. Contact mechanics principles are further applied in a discussion of several aspects of rail grinding, including surface roughness, facet width and rail grinding interval.
EVI5 is a novel centrosomal protein that binds to α- and γ-tubulin

The human EVI5 protein carries a TBC domain indicative of Rab GTPase activating protein (GAP) activity, and an extensive coiled-coil motif in the C-terminal region. EVI5 is ubiquitously expressed in adult, fetal, and cancer tissues and exists as two mRNA species resulting from differential use of polyadenylation signals. Western blot analysis suggests that different molecular weight protein species are probably generated by posttranslational modification. FPLC analysis demonstrates that EVI5 protein can form dimers and confocal microscopy indicates that EVI5, in addition to a diffuse localization in the nucleus, also preferentially localizes to the pericentriolar material in interphase cells. Immunoprecipitation and GST pull-down experiments demonstrate that EVI5 exists in complexes with both α- and γ-tubulin. Both interactions are localized to the N-terminal part of the EVI5 protein. Thus, EVI5 is a novel centrosomal protein with a complex expression pattern and subcellular localization, possibly involved in centrosome stability and dynamics.
The Wind from the East: French Intellectuals, the Cultural Revolution, and the Legacy of the 1960s

Richard Wolin, The Wind from the East: French Intellectuals, the Cultural Revolution, and the Legacy of the 1960s (2010), xiv + 400 (Princeton University Press, Princeton, £24.95/$35.00). Richard W...
Neptunium Incorporation into Uranium(Vi) Compounds formed During Aqueous Corrosion of Neptunium-Bearing Uranium Oxides

We report results of experimental studies on the behavior of Np during aqueous corrosion of unirradiated Np-bearing U oxides. Np-doped U oxides were reacted in humid air at 90°C and 150°C for several weeks within sealed stainless-steel vessels. Reacted solids were examined by scanning and transmission electron microscopies (SEM and TEM), electron energy-loss spectroscopy (EELS), and X-ray powder diffraction (XRD). Dehydrated schoepite, (UO2)O0.25-z(OH) 1.5+2z (0 ≤z ≤0.15), is the predominant U(VI) compound formed in these experiments. Preliminary EELS analysis on crushed grains verify that dehydrated schoepite formed at 150°C contains up to approximately 2 wt.% Np, corresponding to a maximum Np:U molar ratio of approximately 1:40. These are maximum values because the degree to which surface-sorbed Np is present on the grains analyzed is not yet known. Crystalline NpO2 also precipitated during these experiments, and the concentration of Np in dehydrated schoepite may represent the maximum amount of Np that can be incorporated into dehydrated schoepite under the experimental conditions.
Kant's Fact of Reason as Source of Normativity

Abstract In The Sources of Normativity, Christine M. Korsgaard argues that unconditional obligation can be accounted for in terms of practical identity. My argument in this paper is that practical identity cannot play this foundational role. More specifically, I interpret Korsgaard's argument as beginning with something analogous to Kant's fact of reason, viz. with the fact that our minds are reflective. I then try to show that her determination of this fact is inadequate and that this causes the argument concerning practical identity to fail. Finally, I argue that a conception of the fact of reason more in line with what I take to be Kant's own is necessary to account for unconditional obligation.
Men and women in the clergy: Stresses, strains, and resources

This essay reports a program of research as the occupational and personal stress experienced by contemporary American clergy. Three studies are reported. In the first survey a group of largely Roman Catholic religious reported less stress than the general population. In a replication of this investigation on over 510 Protestant clergy this impression of less experienced stress and greater personal resources was confirmed. In the most recent study of clergy in Southern California, a mixed picture was observed. Although the impression of less overall stress was confirmed, great differences in layclery role expectations were observed.
Closed-form kinetic parameter estimation using wavelets

This paper uses the method of integration by parts to convert a differentiation equation into an equation that does not contain any derivatives. A linear estimation model is set up and a closed-form estimation solution is obtained.
Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study.

Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. Background Collapsing glomerulopathy (CG) is a pattern of renal injury that is seen in association with HIV infection and that is increasingly recognized in non-HIV patients. Methods A review of native kidney biopsies with CG that were diagnosed between 1979 and 1997 in 18 HIV and 42 non-HIV patients is provided. Results HIV and non-HIV patients with CG were similar in terms of age, sex ratio, serum creatinine, proteinuria, the extent of collapsing and sclerosing glomerular lesions, and interstitial damage. A slight female predominance was found in both groups. In contrast to non-HIV patients, the HIV group was characterized by a high prevalence of blacks (94 vs. 57%), frequent tubuloreticular inclusions (76 vs. 29%), and microcystic tubular changes (72 vs. 40%). In 13 non-HIV patients, CG was associated with a systemic lupus erythematosus (SLE)-like disease (5), hepatitis C virus (HCV) infection (3), HTLV-I infection, MCTD, acute monoblastic leukemia, multiple myeloma, and cerebral arteritis. Overall, the renal survival of human immunodeficiency virus (HIV) and non-HIV patients with CG was not significantly different. Cox regression revealed that HIV infection had an adverse effect on short-term renal survival, with other significant risk factors being extensive interstitial fibrosis, high serum creatinine, proteinuria, and a low percentage of glomeruli with collapse. The slope of reciprocal creatinine was best predicted by the degree of proteinuria. Serum creatinine correlated with the extent of interstitial fibrosis, the male gender, and the percentage of glomeruli with collapse. Proteinuria was best predicted by the extent of effacement of podocyte foot processes. Conclusions CG shares many clinicopathological similarities in HIV and non-HIV patients. In some non-HIV patients, CG was associated with autoimmune diseases, lymphoproliferative disorders, and viral infections.
Measurements of Close Encounters in H-on-H, H-on-H 2 , and H - -on-H Collisions

Close encounters are studied in the collision of hydrogen atoms with hydrogen atoms at incident energies of 2 to 60 keV. Those incident particles which are scattered through an angle of 1.5\ifmmode^\circ\else\textdegree\fi{} or 3\ifmmode^\circ\else\textdegree\fi{} are examined to find the fraction ${P}_{+1}$ which have lost an electron in the encounter, the fraction ${P}_{0}$ which have remained neutral, and the fraction ${P}_{\ensuremath{-}1}$ which have captured an electron. The ${P}_{\ensuremath{-}1}$ component, which is a measure of the reaction H + H \ensuremath{\rightarrow} ${\mathrm{H}}^{\ensuremath{-}}$ + ${\mathrm{H}}^{+}$, is everywhere low, at these scattering angles, never exceeding 4%, but it does show an interesting oscillatory structure. This quantity has a maximum evident at 7.5 keV and suggested maxima at 50 and 3.5 keV. Similar measurements are made for the H-on-${\mathrm{H}}_{2}$ collision, and these show a peak in the ${\mathrm{H}}^{\ensuremath{-}}$ production at 12 keV. For the ${\mathrm{H}}^{\ensuremath{-}}$ -on-H collision, measurements of ${P}_{+1}$, ${P}_{0}$, and ${P}_{\ensuremath{-}1}$ are made where the fast particle is scattered through 1.2\ifmmode^\circ\else\textdegree\fi{}. No oscillatory structure is seen in this case for incident energies between 2 and 50 keV.
The EDAM project: Mining atmospheric aerosol datasets

There is a great need to better understand the sources, dynamics, and compositions of atmospheric aerosols. The traditional approach for particle measurement, collecting bulk samples of particulates on filters, is not adequate for studying particle dynamics and real-time correlations. This has led to the development of a new generation of real-time instruments that provide continuous or semicontinuous streams of data about certain aerosol properties. However, these instruments have added a significant level of complexity to atmospheric aerosol data and dramatically increased the amounts of data to be collected, managed, and analyzed. Our ability to integrate the data from all of these new and complex instruments now lags far behind our data-collection capabilities, and severely limits our ability to understand the data and act upon it in a timely manner. In this article, we present an overview of EDAM (Exploratory Data Analysis and Management), a joint project between researchers in Atmospheric Chemistry and Computer Science. Important objectives include environmental monitoring and data quality assurance, and real-time data mining offers great potential. While atmospheric aerosol analysis is an important and challenging domain, our objective is to develop techniques that have broader applicability. © 2005 Wiley Periodicals, Inc. Int J Int Syst 20: 759–787, 2005.
Weaving the fabric of social interaction: Articulating developmental psychology and cognitive neuroscience in the domain of motor cognition

In this article, we bring together recent findings from developmental science and cognitive neuroscience to argue that perception-action coupling constitutes the fundamental mechanism of motor cognition. A variety of empirical evidence suggests that observed and executed actions are coded in a common cognitive and neural framework, enabling individuals to construct shared representations of self and other actions. We review work to suggest that such shared representations support action anticipation, organization, and imitation. These processes, along with additional computational mechanisms for determining a sense of agency and behavioral regulation, form the fabric of social interaction. In addition, humans possess the capacity to move beyond these basic aspects of action analysis to interpret behavior at a deeper level, an ability that may be outside the scope of the mirror system. Understanding the nature of shared representations from the vantage point of developmental and cognitive science and neuroscience has the potential to inform a range of motor and social processes. This perspective also elucidates intriguing new directions and research questions and generates specific hypotheses regarding the impact of early disorders (e.g., developmental movement disorders) on subsequent action processing.
Extracellular field signatures of CA1 spiking cell assemblies during sharp wave-ripple complexes

Although postsynaptic and transmembrane currents over local neuronal populations are considered the main factors for shaping local field potential (LFP) and current source density (CSD) fluctuations [1], high-frequency oscillatory LFPs can also be shaped by extracellular action potentials of pyramidal cell populations [2]. Sharp wave-ripple complexes (SWRs) are typical examples of such high-frequency oscillatory events, observed in hippocampal LFPs during deep sleep and awake immobility. They consist of an extensive depolarization in the CA1 dendritic layer (sharp wave) arising from population bursts in CA3, accompanied by a ~150-200 Hz LFP oscillation in the CA1 pyramidal layer (ripple). During SWRs, temporal firing patterns of correlated place cells, acquired during wakeful exploration, are replayed in fast-scale, providing a strong indication for the participation of SWRs in memory consolidation. Yet the particular effects of these pattern replays on the hippocampal extracellular field are largely unknown. How are the different ensembles of spiking cells encoded in the emerging ripple-LFPs? Here, we study this association through both a modeling and an experimental approach.
(Ap)pointing the canon Rousseau's Émile, visions of the state, and education

Jean-Jacques Rousseau’s Emile, ou de I’Education (Emile, or on Education) has been described by Rousseau scholars in latter twentieth century English-language philosophy as an educational classic. In 1995 Robert Wokler argued that together with Montesquieu, Hume, Smith, and Kant among his contemporaries, Rousseau had exerted the most profound influence on modern European intellectual history, “perhaps even surpassing anyone else of his day." For Wokler Emile is “the most significant work on education after Plato’s Republic.” Earlier in 1977, Allan Bloom questioned why Emile had not been the subject of analysis in philosophy relative to the rest of Rousseau‘s work, for “Emile is truly a great book, one that lays out for the first time and with the greatest clarity and vitality the modern way of posing the problems of psychology.” Bloom also saw Emile as “one of those rare total or synoptic books... a book comparable to Plato’s Republic, which it is meant to rival or supersede” and argued that Rousseau himself was at the source of a new tradition: “Whatever else Rousseau may have accomplished, he presented alternatives available to man more comprehensively and profoundly and articulated them in the form which has dominated discussion since his time." Even Peter Gay’s earlier commentary on John Locke and education in 1964 could not escape this central positioning of the text. The significance of Locke’s Some Thoughts on Education is weighed in relation to its impact on Rousseau‘s Emile. For Gay, the latter is “probably the most influential revolutionary tract on education that we have.”
Development of a marine aquaculture research complex

Abstract The new Environmental Systems Laboratory of the Woods Hole Oceanographic Institution was designed to be capable of performing a wide spectrum of research in the fields of marine aquaculture, water pollution control and coastal biology. Discussed are the setting of requirements, approaches adopted, design problems encountered, experiences to date and the unique physical plant.
Atypical childhood Wilson's disease

Wilson's disease is a genetic disorder of copper metabolism with a hepatic or neurologic presentation. A hepatic presentation is more common in young children. Neurologic Wilson's disease often manifests as a movement disorder with dystonia, tremor, and dysarthria. Psychiatric or behavioral symptoms can also be a presenting feature of Wilson's disease. We describe an atypical neurologic presentation in a prepubertal child with minimal hepatic involvement; in which transient hemiparesis and encephalopathy dominated her initial neurologic presentation. Brain magnetic resonance imaging revealed extensive cortical and subcortical signal change, in addition to the classical basal ganglia signal abnormality observed in Wilson's disease. She was treated with oral tetrathiomolybdate anticopper therapy, followed by zinc maintenance. Her clinical status and brain imaging improved considerably at 1 year after treatment initiation. Neurologic Wilson's disease may have diverse presentations, and should be considered in children who present with cortical features and signal change on magnetic resonance imaging.
Cholesterol Addition to ER Membranes Alters Conformation of SCAP, the SREBP Escort Protein that Regulates Cholesterol Metabolism

Sterol accumulation in membranes blocks the exit of SCAP from the ER, preventing SREBP cleavage and reducing cholesterol synthesis. Sterols act through SCAP's sterol-sensing domain by an obscure mechanism. Here, we show that addition of cholesterol to ER membranes in vitro causes a conformational change in SCAP, detected by the unmasking of closely spaced trypsin cleavage sites. Two mutant forms of SCAP (Y298C and D443N) that are refractory to sterol regulation in vivo are also refractory to sterol-induced conformational change in vitro. 25-hydroxycholesterol, a potent regulator of SCAP in vivo, fails to change SCAP's conformation in vitro, suggesting that oxysterols act in intact cells by translocating cholesterol from plasma membrane to ER. These studies demonstrate an in vitro effect of cholesterol on the sterol regulatory machinery.
Novel design of multiband branch-line coupler using multiband transmission lines

In this article, a novel multiband branch-line coupler employing multiband transmission lines is designed to operate at three different frequencies. To realize multiband operations, a Pi-type-based multiband transmission line network with open- and short-ended stubs is employed. Specifically, the Pi-type line is applied to realize the dual-band operation at the first two working frequencies. For the third operating frequency, the open- and short-ended stubs are tapped at the center of the Pi-type line. ABCD-matrix is employed to derive the design formulas for the proposed triband transmission line. To verify the design concept, a planar coupler operating at 1/2.5/4.5GHz is designed and fabricated. The simulation and measurement results show good agreement with the design theory. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:2841–2845, 2014
Topography of the human motor potential

Abstract The motor potential (MP) accompanying voluntary movements is maximal over Rolandic cortex and shows a somatotopic distribution for contractions of various muscles similar to that obtained by cortical stimulation. The MP field distribution was shown to be compatible with its generation by a source of comparable size to the excitable motor cortex. The late component of the somato-sensory evoked response (SER) elicited by peripheral nerve stimulation had a similar distribution, but extended slightly posterior to that of the MP. These differences in distribution between the SER and the P2 component of the MP, presumed to represent afferent input from joint and muscle receptors, are attributed to the predominantly post-central projection of the cutaneous afferents which are also activated by electrical stimulation of peripheral nerve.