Actual Entry Research Articles

Real-time imaging of transcriptional activation in live cells reveals rapid up-regulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative cellular senescence.

Cellular replicative senescence is a permanent growth arrest state that can be triggered by telomere shortening. The cyclin-dependent kinase (Cdk) inhibitor p21(CIP1/WAF1) (p21), encoded by the CDKN1A gene, is a critical cell cycle regulator whose expression increases as cells approach senescence. Although the pathways responsible for its up-regulation are not well understood, compelling evidence indicates that the upstream triggering event is telomere dysfunction. Studies of replicative senescence have been complicated by the asynchrony of its onset, which is caused by the continuous and stochastic variability in individual cell lifespans. In fact, the actual entry into senescence has never been observed in a single unperturbed cell. We report here a new in vitro human model system that allows entry into senescence to be monitored in real-time in individual viable cells. We used homologous recombination to generate non-immortalized fibroblast cells with the enhanced yellow fluorescence protein (EYFP) gene knocked into one CDKN1A gene copy, allowing promoter activity to be visualized as fluorescence intensity. Gamma irradiation, DNA-damaging drugs, expression of p14(ARF) or oncogenic Ras, and replicative exhaustion all resulted in elevated EYFP expression, demonstrating its proper control by physiological signalling circuits. Analysis by time-lapse microscopy of cultures approaching replicative senescence revealed that p21 levels rise abruptly in individual aging cells and remain elevated for extended periods of time.

Entry in Emulsion Polymerization: Effects of Initiator and Particle Surface Charge

The rate coefficient for radical entry into latex particles in emulsion polymerizations is measured for styrene systems in which the entering species are anionic (from persulfate) and cationic (from 2,2‘-azobis(2-methylpropionamidine) dihydrochloride, or V-50). These entry rate coefficients ρ are obtained by measuring rates in seeded emulsion polymerizations where the seeds have either cationic or anionic groups on the surface; “zero-one” conditions are employed, because these offer the advantage that particle size is sufficiently small (≈70 nm diameter) that intraparticle termination is not rate-determining. Data comprise steady-state rates with chemical initiator, combined with loss rates obtained using γ-radiolysis initiation and following the relaxation behavior after removal from the radiation source. Values for ρ as a function of initiator concentration can be meaningfully compared for different initiators through the dependence of initiator efficiency fentry on primary radical generation rate (radical flux). For the anionic latex, this dependence is seen to differ depending on the nature of the initiator used. This may be explained by the entry model [Maxwell, I. A.; Morrison, B. R.; Napper, D. H.; Gilbert, R. G. Macromolecules 1991, 24, 1629] wherein the rate-determining steps in entry are assumed to be only aqueous-phase propagation and termination to form surface-active z-meric oligomeric radicals; entry is solely by z-mers, for which actual entry into the particle is so fast as not to be rate-determining. The cationic latex shows a high rate of spontaneous initiation, which can be explained in terms of amidino radical chemistry; this can be reduced by heat treatment. Accurate fentry values are obtained using the heat-treated cationically stabilized latex for seeded studies. The fentry data are also consistent with the model for both cationic and anionic species entering the cationic latex. Values of z so inferred (≈2 for persulfate, ≈1 for amidinium) can be understood in terms of the hydrophobic free energy of these species. The results refute alternative models in the literature that suppose entry is controlled by double-layer (colloidal) interactions, surfactant displacement, or diffusion control.

A Dictionary of Samaritan Aramaic (review)

The Jewish Quarterly Review, XCIlI, Nos. 3-4 (January-April, 2003) 629-630 Abraham Tal. A Dictionary ofSamaritan Aramaic. Handbuch der Orientalistik , erste Abteilung: Der nahe und mittlere Osten. Leiden: E. J. Brill, 2000. Vol. 1: pp. xliii + 446; vol. 2: pp. xliv + 524. The Aramaic preserved in Samaritan manuscripts has long been one of the most poorly known of the various late Aramaic dialects. Grammatical studies, dictionaries, and reliable editions of many of the texts have all been lacking until recently. Due largely to the work of the Israeli scholar Zeev Ben-Hayyim and his student, Abraham Tal, the lacunae have gradually been filled. (A substantial but controversial grammar was prepared by R. Macuch and appeared as Grammatik des samaritanischen Aramaeisch, Berlin, 1982.) Ben-Hayyim worked for many years preparing a dictionary of Samaritan Aramaic, whose target language was Modern Hebrew. The addition of Tal to the project ultimately led to the appearance of this two-volume work under his name alone. Although its title is English, this is still a Hebrew work, paginated and typeset from the right, with awkward and incomplete English glosses and many typographical errors in both the Hebrew and the English. These features are not choices destined to win approbation for the editorial department of E. J. Brill. The following major texts are treated in this dictionary: first, the Samaritan Targum, in its two major and distinct types (J and A) as delineated by Tal in his The Samaritan Targum of the Pentateuch (Tel-Aviv, 1983). Second , the midrashic text Memar MarqaJTibat Marqe, as recently edited by Ben-Hayyim in his 1988 Hebrew edition. Third, the liturgical texts, as first published by A. Cowley, The Samaritan Liturgy (Oxford, 1909), and studied by Ben-Hayyim in volume 3b of his monumental The Literary and Oral Traditions of Hebrew and Aramaic amongst the Samaritans (Jerusalem , 1957-87). Fourth, The Chronicle of Asatir, also previously published by Ben-Hayyim (in Tarbiz 14 [1943]: 104-125, 174-190; 15 [1994]: 7187 , 128). The language of many of the later texts is mixed, combining Hebrew and Arabic terms and phrases with Aramaic material. The dictionary explicitly includes such material, as well as obvious scribal errors. But with care the user should still be able to extract authentic Aramaic vocabulary. The organization of the dictionary is highly conservative. All words are arranged under their supposed roots, even loanwords, resulting in some very strange phenomena. On p. 680, for example, a lemma, 'twa, is glossed as "receptacle for liquid," and underneath the actual entry appears: "cup, pot pnv ,

Kinetics and mechanism of rhenium-catalyzed oxygen atom transfer from pyridine N-oxides to phosphines.

The oxygen atom transfer (OAT) reaction cited does not occur on its own in >10 h. Oxorhenium(V) compounds having the formula MeReO(dithiolate)PZ(3) catalyze the reaction; the catalyst most studied was MeReO(mtp)PPh(3), 1, where mtpH(2) = 2-(mercaptomethyl)thiophenol. The mechanism was studied by multiple techniques. Kinetics (initial-rate and full-time-course methods) established this rate law: v = k(c)[1][PyO](2)[PPh(3)](-1). Here and elsewhere PyO symbolizes the general case XC(5)H(4)NO and PicO that with X = 4-Me. For 4-picoline, k(c) = (1.50 +/- 0.05) x 10(4) L mol(-1) s(-1) in benzene at 25.0 degrees C; the inverse phosphine dependence signals the need for the removal of phosphine from the coordination sphere of rhenium prior to the rate-controlling step (RCS). The actual entry of PPh(3) into the cycle occurs in a fast step later in the catalytic cycle, after the RCS; its relative rate constants (k(4)) were evaluated with pairwise combinations of phosphines. Substituent effects were studied in three ways: for (YC(6)H(4))(3)P, a Hammett correlation of k(c) against 3sigma gives the reaction constant rho(c)(P) = +1.03, consistent with phosphine predissociation; for PyO rho(c)(N) = -3.84. It is so highly negative because PyO enters in three steps, each of which is improved by a better Lewis base or nucleophile, and again for (YC(6)H(4))(3)P as regards the k(4) step, rho(4) = -0.70, reflecting its role as a nucleophile in attacking a postulated dioxorhenium(VII) intermediate. The RCS is represented by the breaking of the covalent N-O bond within another intermediate inferred from the kinetics, [MeReO(mtp)(OPy)(2)], to yield the dioxorhenium(VII) species [MeRe(O)(2)(mtp)(OPy)]. A close analogue, [MeRe(O)(2)(mtp)Pic], was identified by (1)H NMR spectroscopy at 240 K in toluene-d(8). The role of the "second" PyO in the rate law and reaction scheme is attributed to its providing nucleophilic assistance to the RCS. Addition of an exogenous nucleophile (tetrabutylammonium bromide, Py, or Pic) caused an accelerating effect. When Pic was used, the rate law took on the new form v = k(NA)[1][PicO][Pic][PPh(3)](-1); k(NA) = 2.6 x 10(2) L mol(-1) s(-1) at 25.0 degrees C in benzene. The ratio k(c)/k(NA) is 58, consistent with the Lewis basicities and nucleophilicities of PicO and Pic.

Should U.S. Military Recruiters Write Off the College-Bound?

This article examines trends and relationships involving high school seniors' military service plans, their college plans, and their actual entry into military service. Crosssectional and longitudinal data from the Monitoring the Future project show that, although individuals planning to complete college are less likely than average to plan on military service, the upward trend in college plans cannot account for many of the yearto-year changes in military propensity. Moreover, it now appears that the majority of young men expecting to enter military service also expect to complete a four-year college program. Most important, planning for college does not reduce enlistment rates among high propensity males, although for some of them it may delay entry by several years. These findings suggest that educational incentives for military service are now particularly important, given the high proportions of potential recruits with college aspirations.

Better Service Through Flexible Rules: Cataloging a Collection of Annual Reports in a Most Un-CONSER-Like Manner

ABSTRACT University Library at Indiana University-Purdue University Indianapolis (IUPUI) acquired a large and unique collection of foundation annual reports. It was decided that cataloging them as serials, with the attendant problems of successive entry maintenance and access, was not acceptable. The reports for each foundation were treated as a collection with a unifying, made-up main title and update-able holdings (245 $f). The concept of main entry was retained, but the actual entry changes when the foundation name changes. The authors conclude with a call to make rules 21.3B1 and 21.2C1 optional.

Haematologists' approaches to the management of adolescents and young adults with acute leukaemia.

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.

Haematologists' approaches to the management of adolescents and young adults with acute leukaemia

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15–29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non‐entry. Data were linked to MRC trials data to determine the proportion of patients aged 15–29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty‐two per cent of haematologists stated that they entered patients ‘always’ or ‘whenever possible’ for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non‐trial protocol, and concern about workload and ethical approval.

PrP(C) expression in the peripheral nervous system is a determinant of prion neuroinvasion.

Transmissible spongiform encephalopathies are often propagated by extracerebral inoculation. The mechanism of spread from peripheral portals of entry to the central nervous system (neuroinvasion) is complex: while lymphatic organs typically show early accumulation of prions, and B-cells and follicular dendritic cells are required for efficient neuroinvasion, actual entry into the central nervous system occurs probably via peripheral nerves and may utilize a PrP(C)-dependent mechanism. This study shows that transgenic mice overexpressing PrP(C) undergo rapid and efficient neuroinvasion upon intranerval and footpad inoculation of prions. These mice exhibited deposition of the pathological isoform of the prion protein (PrP(Sc)) and infectivity in specific portions of the central and peripheral sensory pathways, but almost no splenic PrP(Sc) accumulation. In contrast, wild-type mice always accumulated splenic PrP(Sc), and had widespread deposition of PrP(Sc) throughout the central nervous system even when prions were injected directly into the sciatic nerve. These results indicate that a lympho-neural sequence of spread occurs in wild-type mice even upon intranerval inoculation, while overexpression of PrP(C) leads to substantial predilection of intranerval over lymphoreticular spread. The rate of transport of infectivity in peripheral nerves was ca. 0.7 mm per day, and prion infectivity titres of sciatic nerves were much higher in tga20 than in wild-type mice, suggesting that overexpression of PrP(C) modulates the capacity for intranerval transport.

The Elusive Mirage: Competition Regulation and Telecommunications, 1997–2000

This paper looks at the operation of telecommunications-specific competition regulation pursuant to the 1997 legislation, on the eve of a review of the 1997 legislation by the Productivity Commission. The central thesis is that the ‘brave new world’ created by the 1997 legislation, of industry self-regulation of terms and conditions of access to declared telecommunications services, has been an inhospitable land for new entrants. Neither the access nor the competitive conduct provisions have operated in the way intended by the policy-makers and anticipated by new entrants at the time of introduction of the 1997 legislation. The tools of competitive conduct regulation at the retail level have proven cumbersome and susceptible to challenge. Instead of a rapid withering away of market power under threatened or actual market entry, the emergence of the Internet and commercial deployment of digital subscriber line (DSL) technologies has meant that Telstra's ability to cross-market leverage may actually have increased and extended beyond the telephony sphere. Finally, the paper identifies key issues for the Productivity Commission's review.

Sunk costs, entry, and the timing of cost-reducing investment

The traditional IO literature asserts that firms with monopoly power produce less efficiently than competitive firms and that they often reduce costs only after entry delivers a `wake-up call'. A model with sunk costs and uncertainty can explain this phenomenon. If becoming more efficient entails sunk costs, incumbents have an incentive to wait until a competitor's efficiency is revealed by actual entry before deciding whether to make the investment. This `uncertainty resolution' incentive can outweigh incumbents' incentives to attempt entry preemption.

Mars Pathfinder Entry Temperature Data, Aerothermal Heating, and Heatshield Material Response

The Mars Pathe nder probe contained instrumentation that measured heatshield temperatures during entry. A description of the experiment, the data, and an analysis of the entry environment and material response are presented. Navier ‐Stokes forebody heating calculations show a peak unblown radiative-equilibrium heat e ux of 118W/cm 2 at thestagnation point and120 W /cm 2 on theshoulderforturbulente ow. Theheatload is3.8 kJ /cm 2 on thenose,decreases along thefrustum,then increasesto 2.7 ‐3.1kJ/cm 2 on theshoulder depending on the onset time forturbulence. One-dimensional charringmaterialresponseiscalculated using threedifferentmodels.Stagnationpoint temperature data are consistent with about 85% of fully catalytic laminar heating. Shoulder temperature data are inconclusive, but are consistent with fully catalytic laminar heating or with 85% of fully catalytic heating with early onset of turbulence. Aft temperature data indicate a peak heat e ux and heat load of about 1.3 W /cm2 and 70 J/cm 2 , respectively. The aft heating proe le is about 20 s longer than the forebody heating proe le. Bondline temperaturedata, although not useful forquantitative analysis of aerothermal heating, clearly showtheheatshield had adequate thickness margins for the actual entry.

Vertical differentiation: Entry and market coverage with multiproduct firms

We consider a multiproduct monopoly producing many qualities of the same product in a market where the consumers' income distribution is sufficiently wide so as to rule out the case of a natural monopoly. In this context, Mussa and Rosen (1978, Journal of Economic Theory 18, 301–317) show that a protected monopolist may decide to leave part of the market unserved. Here, we examine whether entry threats are sufficient to induce complete market coverage. We assume that the number of qualities in the incumbent's product line is endogenously determined and that both the incumbent and the entrant face the same fixed cost of introducing a new quality. Thus, an increase in the fixed cost does not necessarily make entry more difficult. As it turns out, there are disjoint intervals of the fixed cost for which the monopolist's optimal policy is sufficient to deter entry even if it implies that part of the market remains uncovered. When entry is not blockaded, the monopolist may find it profitable to react to entry threats by upgrading his intermediate qualities. The resulting higher prices will discourage more consumers from purchasing the product. Hence, while actual entry would have resulted in complete market coverage, potential entry may not improve, and in many cases may worsen, the extent of market coverage.

Survival of Firms over the Product Life Cycle

While entry and exit of firms have for long been recognized as two of the major determinants of market structure, empirical work on the subject has lagged behind for lack of adequate data. Of late, access to new data bases and the increasing use of Census of Manufactures data have enabled researchers to investigate the entry and exit of firms as well as their performance subsequent to entry. Dunne, Roberts and Samuelson use Census data for U.S. manufacturing industries [11; 12], while Baldwin and Gorecki do the same for Canadian manufacturing industries [7]. Some studies have used Small Business Administration data to track survival of firms over a ten year period [4; 5; 23; 25]. Survival of firms has also been studied as a side issue to growth of firms [16; 13]. While more is known now than ever before on survival of firms subsequent to their entry, most of the studies are cross sectional in nature and also consider entire industries rather than product markets where the actual entry and exit of firms occur. This study focuses on firm survival in product markets over the span of life of the product and considers the impact of firm attributes and the effect of evolution of markets on firm survival.

Effects of Poly(acrylic acid) Electrosteric Stabilizer on Entry and Exit in Emulsion Polymerization

A methodology developed to obtain rate coefficients for entry and exit (desorption) in emulsion polymerizations was applied to systems stabilized electrosterically by a copolymer of acrylic acid and styrene embedded in a styrene seed particle. This was grown as a second-stage procedure, by adding styrene and acrylic acid to a styrene seed and then polymerizing. Rate coefficients for entry (ρ) and exit (k ) for subsequent homopolymerization of the resulting latices with styrene were obtained from the time dependence of the approach to steady state using both chemical and γ-radiolytic initiation; the latter was used in relaxation mode, which measures k directly. Compared to the same latices with an electrostatic stabilizer, at pH 7 the electrosteric stabilizer greatly reduced both ρ and k. When ionic strength was increased, ρ increased relative to that found for electrosterically stabilized latex in the absence of added electrolyte. For electrostatically-stabilized latices, entry is supposed to occur by aqueous-phase propagation to a critical degree of polymerization z which then undergoes irreversible entry; the present data for electrostatically-stabilized latices support this model, including its prediction that ρ be independent of particle size, all other things being equal. The decrease in ρ in the electrosterically-stabilized latices is ascribed to a layer through which diffusion of a z-mer is slow, so that it may be terminated prior to actual entry. For electrostatically-stabilized latices, exit is supposed to occur by transfer, resulting in a monomeric radical which exits by diffusing through the aqueous phase, this event competing with intraparticle propagation; the decrease k in the electrosterically-stabilized latices (also seen in other polymerically-stabilized systems) can be interpreted by assuming that aqueous-phase diffusion slower in the hairy layer.

Advertising, Barriers to Entry and Competition Policy

The controversy as to whether or not advertising impairs the efficient functioning of markets because it acts as a “barrier” to new firms wishing to enter a market has once again attracted the interest of the UK competition authorities. Looks at the advertising and barrier to entry issue as seen in a number of Monopolies and Mergers Commission investigations. Concludes that the conventional negative view of advertising needs to be tempered by the positive role played by advertising in facilitating actual entry, and suggests that insofar as there are a number of other factors which may inhibit market entry it is necessary to look at this issue “in the round” rather than from one narrow perspective.

Summary of Lower Body Negative Pressure Experiments During Space Flight

This paper summarizes the lower body negative pressure experiments performed in space, beginning with the experiments conducted on Skylab, because this program provided the most cardiovascular physiology data for United States space flight. Data obtained during studies of lower body negative pressure for use as a countermeasure after months of Russian space flight are also presented. Lower body negative pressure experiments conducted aboard Space Shuttle flights provide data about the deadaptation response of the cardiovascular system to orthostatic stress occurring during periods of zero gravity, and about protection against postflight orthostatic intolerance. Data obtained using Russian and American lower body negative pressure devices indicate that, when a crew member stands, as opposed to being supported by a seat or saddle as in the American device, there may be a slight detrimental effect in terms of the cardiovascular response to this orthostatic stress. Comparison of heart rate and blood pressure response to entry and landing of the Shuttle indicate that, although lower body negative pressure is a different stress and is applied in a different manner, the maximum heart rates during lower body negative pressure are reached at approximately the same point that the maximum heart rates are reached during entry and landing. Thus, the use of a lower body negative pressure stress in flight is a fairly good predictor of the cardiovascular response to the actual entry and landing of the Shuttle.

A Simple and Inexpensive Method for Determining Stream Discharge from a Streambank

ABSTRACT A detailed protocol for the determination of stream discharge is presented which requires neither a current meter nor actual entry into streamwater. The protocol represents a modification of the flotation method of discharge determination and was devised in response to the need for a simple, inexpensive, “bank-side” technique for estimation of stream flow. Discharge is determined through measurements of a stream's cross-sectional area and surface velocity. In tests at high and low flows, mean discharges determined by the proposed flotation method were not significantly different from those calculated using a standardized, current-meter method. This suggested that me proposed flotation method (a 10–20 min procedure) could be used with reasonable accuracy to determine discharge in small to moderate-sized streams.

Sequential entry, industry structure and welfare

In this paper we reexamine the relationship between potential competition, industry structure and welfare in a market subject to a sequential entry threat where firms can make quantity commitments and have access to a constant returns technology. It is shown that, provided entry is not blockaded, the incumbent(s) will either prevent entry or allow all the potential entrants in. Furthermore, actual entry may decrease but social welfare never goes down with more potential entrants. Nevertheless, with a finite number of potential entrants, policies which lower the cost of entry need not be beneficial in welfare terms.

Alfred Tarski's work in set theory

Alfred Tarski started contributing to set theory at a time when the Zermelo-Fraenkel axiom system was not yet fully formulated and as simple a concept as that of the inaccessible cardinal was not yet fully defined. At the end of Tarski's career the basic concepts of the three major areas and tools of modern axiomatic set theory, namely constructibility, large cardinals and forcing, were already clearly defined and were in the midst of a rapid successful development. The role of Tarski in this development was somewhat similar to the role of Moses showing his people the way to the Promised Land and leading them along the way, while the actual entry of the Promised Land was done mostly by the next generation. The theory of large cardinals was started mostly by Tarski, and developed mostly by his school. The mathematical logicians of Tarski's school contributed much to the development of forcing, after its discovery by Paul Cohen, and to a lesser extent also to the development of the theory of constructibility, discovered by Kurt Gödel. As in other areas of logic and mathematics Tarski's contribution to set theory cannot be measured by his own results only; Tarski was a source of energy and inspiration to his pupils and collaborators, of which I was fortunate to be one, always confronting them with new problems and pushing them to gain new ground.Tarski's interest in set theory was probably aroused by the general emphasis on set theory in Poland after the First World War, and by the influence of Wactaw Sierpinski, who was one of Tarski's teachers at the University of Warsaw. The very first paper published by Tarski, [21], was a paper in set theory.