Singularities and undefinitions in the calibration functions of sonic anemometers

A mathematical model of the process employed by a sonic anemometer to build up the measured wind vector in a steady flow is presented to illustrate the way the geometry of these sensors as well as the characteristics of aerodynamic disturbance on the acoustic path can lead to singularities in the transformation function that relates the measured (disturbed) wind vector with the real (corrected) wind vector, impeding the application of correction/calibration functions for some wind conditions. An implicit function theorem allows for the identification of those combinations of real wind conditions and design parameters that lead to undefined correction/ calibration functions. In general, orthogonal path sensors do not show problematic combination of parameters. However, some geometric sonic sensor designs, available in the market, with paths forming smaller angles could lead to undefined correction functions for some levels of aerodynamic disturbances and for certain wind directions. The parameters studied have a strong influence on the existence and number of singularities in the correction/ calibration function as well as on the number of singularities for some combination of parameters. Some conclusions concerning good design practices are included.

El tiempo como sustancia de la forma : una aproximación al Museo de Arte Romano de Mérida desde los presupuestos del vitalismo

El modelo dominante durante la Era Moderna asume la presencia del hombre como sujeto dentro del gran engranaje mecánico del Cosmos. Asimismo, recoge una idea acerca del ser natural dentro de la tradición ontológica iniciada por el eleatismo presocrático que concibe a éste como lo inmutable y estático frente al cambio y al movimiento, los cuales se constituyen como meras apariencias. Durante el periodo anterior a la aparición de los grandes filósofos griegos se produce una transformación en donde, de la inicial cosmología vinculada a un tiempo primordial, se pasará a una visión del Universo como ente indestructible, atemporal, inmutable, perfecto, geométrico y espacial. Si en Demócrito se admite un universo sometido al azar y a la necesidad, en Platón el Universo sólo atiende a la necesidad. Este modelo ontológico se pone en entredicho cuando el hombre ya no es concebido como pieza de un sistema más amplio, sino como centro radical del pensamiento. La condición radical del hombre es entonces su propia vida, siendo éste el concepto troncal del denominado vitalismo cuyo más influyente representante en España es José Ortega y Gasset. El estatismo del ser –del hombre- pierde sentido; en palabras del propio Ortega, “no es un ser sino un estar siendo” lo que caracteriza a la vida humana. La razón cartesiana es ahora la razón vital y su objeto de estudio no es la naturaleza sino el propio devenir, es decir, el tiempo, la historia. Este planteamiento es fundamental para comprender el edificio que es objeto de este estudio, el Museo de Arte Romano de Mérida (1980-1985) de Rafael Moneo. Por ello el concepto de tiempo es utilizado como marco y estructura de la presente tesis, a sabiendas del notorio y muy significativo papel que este edificio desempeñó en la carrera de su autor y en el panorama nacional e internacional de la arquitectura y de la museología. Este proyecto nos permite acercarnos al pensamiento de su autor a través de un edificio que, aun habiendo sido ampliamente reconocido, no cuenta con un estudio suficientemente exhaustivo que recoja la amplitud y riqueza que encierra. Esta tesis no es un compendio de lo que ya se ha investigado sobre Mérida; es una aproximación global e interpretativa cuyo sentido sólo puede concebirse al vislumbrar la estructura completa de la misma en sintonía con el "lógos" vital, histórico y narrativo que el proyecto encierra. Se revisará la concepción histórica según la cual, la configuración espacial de la forma habría tenido primacía respecto a su configuración temporal, al remitir esta última a una condición espacializada y circunstancial. La componente vicaria de la circunstancia será elevada por Ortega a la categoría de esencial, visualizando así una paradoja cuya reformulación nos lleva a la concepción de un tiempo sustancial. El diccionario de la RAE, en su tercera acepción, define la sustancia como “aquello que permanece en algo que cambia”, lo cual nos remite al pensamiento antiguo. Se mostrará que lo que permanece no necesariamente implica una concepción estática y eleática de la forma, que la arquitectura esencial no es unívocamente la arquitectura atemporal del platonismo y que cabe concebir la "firmitas" desde la atención a la "durée" bergsoniana. Al asociar tradicionalmente la sustancia con el referido estatismo, se margina al tiempo y a la duración a lo no sustancial; por ello, se tratará de aproximar los términos de tiempo y sustancia para definir la forma. Ello conllevará al estudio de las notables patologías derivadas de la asunción de un tiempo cronológico en nuestra contemporaneidad frente a las cuales, las intuiciones contenidas en Mérida, se alinearán con la actual actitud revisionista en el ámbito del pensamiento filosófico y científico. En Mérida, la memoria recogerá los aspectos de la conciencia así como los aspectos vinculados a la experiencia íntima y colectiva como soporte para la consecución de un discurso. La dualidad entre intuición e inteligencia será recogida por Moneo con idea de trascender su incomunicabilidad, mediante una operación que consistirá en la reivindicación de una memoria irreductible, cuya morada estaría incardinada en el propio tiempo de la duración y de la vida y no en la espacialidad coextensiva del presente y de la acción funcional sobre la materia. Moneo asumirá el papel de la memoria como condición central de una forma que se encarnará al concebirse como un teatro. En la respuesta a la contradicción entre el hecho físico y el efecto psíquico de la experiencia humana residirá la pertinencia de un tiempo narrativo. Será entonces el lenguaje el encargado de aportar sentido a la obra mediante el recurso fundado en la dramatización de la experiencia, es decir, a través de una conexión entre la conciencia íntima y el carácter social y colectivo intrínseco en la arquitectura. ABSTRACT TIME AS A SUBSTANCE OF FORM. AN APPROACH TO THE ROMAN ART MUSEUM OF MÉRIDA FROM THE VIEWPOINT OF VITALISM. The dominant model during the Modern Era placed man as a subject inside the great mechanism of the cosmos. It is also based in an idea about natural being within the ontological tradition initiated by the pre-Socratic Eleatism that conceives it as something immutable and static in respect with change and movement, which are considered as mere appearances. Prior to the emergence of the great Greek philosophers occurred a transformation where concepts of cosmology linked to a primordial time, changed to a view of the universe as indestructible, timeless, unchanging, perfect, geometric and spatial. If Democritus accepted a universe subjected to randomness and necessity, Plato thought that the universe only worked by necessity. This ontological model is called into question when man is not conceived as a piece of a broader system, but as a radical center of thinking. The radical condition of man then is his own life. This is the core concept of so-called Vitalism, whose most influential representative in Spain was José Ortega y Gasset. The stillness of being – of man - loses its meaning; in the words of Ortega, “it is not being but being in progress” that characterizes human life. The Cartesian reason is now the vital reason and its subject of study is no longer nature but its own evolution, in other words, time and history. This approach is fundamental to understand the building which is the subject of this study, the Museum of Roman Art in Mérida (1980-1985) by Rafael Moneo. The concept of time is used as a framework and structure of this thesis, demonstrating the notorious and very significant role this building has implied in the career of its author and in the national and international panorama of architecture and museology. This project allow us to approach the thought of its author through a building that, even whilst widely recognized, does not yet have a sufficiently comprehensive study covering its breadth and richness. This thesis is not a compendium of what already has been researched on Merida; it is a global and interpretative approach whose meaning can only be conceived as a study of its complete structure in line with the vital, historical and narrative logos the project implies. We will review the historical idea where spatial configuration of the form would have had primacy with respect to temporary configuration, because the latter refers to a spatial and circumstantial condition. The vicarious nature of the circumstance will be elevated by Ortega to the category of essential, thus showing a paradox which reformulation leads us to the conception of a substantial time. The dictionary of the Spanish Royal Academy, in its third meaning, defines substance as "that which remains in something that changes". This is a reference to ancient thought. It will be shown that what remains does not necessarily imply a static and Eleatic conception of form. It will also be shown that the essential architecture is not uniquely the timeless architecture of Platonism and that it is possible to conceive the "firmitas" parallel to the "durée" of Henri Bergson. As a result of this traditional association between substance and stillness, it marginalizes the time and the duration to the non-substantial; for this reason, we will try to approach terms of time and substance to define the shape. This will involve studying significant pathologies resulting from an assumption of chronological time in our contemporary world against which, the insights contained in Merida, will be aligned with the current revisionist attitude in the fields of philosophical and scientific thought. In Merida, memory includes aspects of consciousness as well as aspects linked to the intimate and collective experience as a foundation for the achievement of discourse. The duality between intuition and intelligence is put forward by Moneo with the idea of transcending its lack of communication, by means of a resource consisting of the vindication of an irreducible memory, whose home would be embodied in the time of duration and life and not in the coextensive spatiality of the present and in the functional action on the matter. Moneo demonstrates the role of memory as a central condition of form as a theatre. In response to the contradiction between the physical fact and the psychological effect of human experience lies the relevance of narrative time. Language then assumes the responsibility of giving meaning to the work through the dramatization of experience, i.e., through a connection between the intimate consciousness and the intrinsic social and collective character of architecture.

Instruments for analysing urban conflicts in the Global South: The case of urban transformation processes in Dakar

Physical and social transformation processes that take place in urban contexts with strong spatial growth and hardly any economic development frequently have significant adverse impacts for the affected people, which tend to be made invisible. This paper presents an analytical framework to explore different ways to approach urban transformation processes (supply side), their impacts on the set of needs of the community (demand side) and their consequences on the urban environment as a whole (context). The proposed method has been used to assess three actions related to the physical and social transformation of the largest self-made settlement in the city of Dakar, Senegal, during the 2005–2012 period. Research findings show how exogenous interests are privileged over the common good when the affected citizens are not effectively involved in decision-making processes.

Functional copies of a human gene can be directly isolated by transformation-associated recombination cloning with a small 3′ end target sequence

Unique, small sequences (sequence tag sites) have been identified at the 3′ ends of most human genes that serve as landmarks in genome mapping. We investigated whether a single copy gene could be isolated directly from total human DNA by transformation-associated recombination (TAR) cloning in yeast using a short, 3′ unique target. A TAR cloning vector was constructed that, when linearized, contained a small amount (381 bp) of 3′ hypoxanthine phosphoribosyltransferase (HPRT) sequence at one end and an 189-bp Alu repeat at the other end. Transformation with this vector along with human DNA led to selective isolations of the entire HPRT gene as yeast artificial chromosomes (YACs) that extended from the 3′ end sequence to various Alu positions as much as 600 kb upstream. These YACs were retrofitted with a NeoR and a bacterial artificial chromosome (BAC) sequence to transfer the YACs to bacteria and subsequently the BACs to mouse cells by using a Neo selection. Most of the HPRT isolates were functional, demonstrating that TAR cloning retains the functional integrity of the isolated material. Thus, this modified version of TAR cloning, which we refer to as radial TAR cloning, can be used to isolate large segments of the human genome accurately and directly with only a small amount of sequence information.

Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase

The intracellular signals governing cellular proliferation and developmental progression during lymphocyte development are incompletely understood. The tyrosine kinase Blk is expressed preferentially in the B lineage, but its function in B cell development has been largely unexplored. We have generated transgenic mice expressing constitutively active Blk [Blk(Y495F)] in the B and T lymphoid compartments. Expression of Blk(Y495F) in the B lineage at levels similar to that of endogenous Blk induced B lymphoid tumors of limited clonality, whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to preB-II transition. Expression of constitutively active Blk in the T lineage resulted in the appearance of clonal, thymic lymphomas composed of intermediate single positive cells. Taken together, these results indicate that specific B and T cell progenitor subsets are preferentially susceptible to transformation by Blk(Y495F) and suggest a role for Blk in the control of proliferation during B cell development.

The lepidopteran transposon vector, piggyBac, mediates germ-line transformation in the Mediterranean fruit fly

The piggyBac (IFP2) short inverted terminal repeat transposable element from the cabbage looper Trichoplusia ni was tested for gene transfer vector function as part of a bipartite vector–helper system in the Mediterranean fruit fly Ceratitis capitata. A piggyBac vector marked with the medfly white gene was tested with a normally regulated piggyBac transposase helper at two different concentrations in a white eye host strain. Both experiments yielded transformants at an approximate frequency of 3–5%, with a total of six lines isolated having pigmented eyes with various levels of coloration. G1 transformant siblings from each line shared at least one common integration, with several sublines having an additional second integration. For the first transformant line isolated, two integrations were determined to be stable for 15 generations. For five of the lines, a piggyBac-mediated transposition was verified by sequencing the insertion site junctions isolated by inverse PCR that identified a characteristic piggyBac TTAA target site duplication. The efficient and stable transformation of the medfly with a lepidopteran vector represents transposon function over a relatively large evolutionary distance and suggests that the piggyBac system will be functional in a broad range of insects.

A unified theory of carcinogenesis based on order–disorder transitions in DNA structure as studied in the human ovary and breast

Fourier transform-infrared/statistics models demonstrate that the malignant transformation of morphologically normal human ovarian and breast tissues involves the creation of a high degree of structural modification (disorder) in DNA, before restoration of order in distant metastases. Order–disorder transitions were revealed by methods including principal components analysis of infrared spectra in which DNA samples were represented by points in two-dimensional space. Differences between the geometric sizes of clusters of points and between their locations revealed the magnitude of the order–disorder transitions. Infrared spectra provided evidence for the types of structural changes involved. Normal ovarian DNAs formed a tight cluster comparable to that of normal human blood leukocytes. The DNAs of ovarian primary carcinomas, including those that had given rise to metastases, had a high degree of disorder, whereas the DNAs of distant metastases from ovarian carcinomas were relatively ordered. However, the spectra of the metastases were more diverse than those of normal ovarian DNAs in regions assigned to base vibrations, implying increased genetic changes. DNAs of normal female breasts were substantially disordered (e.g., compared with the human blood leukocytes) as were those of the primary carcinomas, whether or not they had metastasized. The DNAs of distant breast cancer metastases were relatively ordered. These findings evoke a unified theory of carcinogenesis in which the creation of disorder in the DNA structure is an obligatory process followed by the selection of ordered, mutated DNA forms that ultimately give rise to metastases.

Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene

Cancer is a progressive multigenic disorder characterized by defined changes in the transformed phenotype that culminates in metastatic disease. Determining the molecular basis of progression should lead to new opportunities for improved diagnostic and therapeutic modalities. Through the use of subtraction hybridization, a gene associated with transformation progression in virus- and oncogene-transformed rat embryo cells, progression elevated gene-3 (PEG-3), has been cloned. PEG-3 shares significant nucleotide and amino acid sequence homology with the hamster growth arrest and DNA damage-inducible gene gadd34 and a homologous murine gene, MyD116, that is induced during induction of terminal differentiation by interleukin-6 in murine myeloid leukemia cells. PEG-3 expression is elevated in rodent cells displaying a progressed-transformed phenotype and in rodent cells transformed by various oncogenes, including Ha-ras, v-src, mutant type 5 adenovirus (Ad5), and human papilloma virus type 18. The PEG-3 gene is transcriptionally activated in rodent cells, as is gadd34 and MyD116, after treatment with DNA damaging agents, including methyl methanesulfonate and γ-irradiation. In contrast, only PEG-3 is transcriptionally active in rodent cells displaying a progressed phenotype. Although transfection of PEG-3 into normal and Ad5-transformed cells only marginally suppresses colony formation, stable overexpression of PEG-3 in Ad5-transformed rat embryo cells elicits the progression phenotype. These results indicate that PEG-3 is a new member of the gadd and MyD gene family with similar yet distinct properties and this gene may directly contribute to the transformation progression phenotype. Moreover, these studies support the hypothesis that constitutive expression of a DNA damage response may mediate cancer progression.

Dominant transformation by mutated human ras genes in vitro requires more than 100 times higher expression than is observed in cancers

The gene-mutation-cancer hypothesis holds that mutated cellular protooncogenes, such as point-mutated proto-ras, “play a dominant part in cancer,” because they are sufficient to transform transfected mouse cell lines in vitro [Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. & Watson, J. D. (1994) Molecular Biology of the Cell (Garland, New York)]. However, in cells transformed in vitro mutated human ras genes are expressed more than 100-fold than in the cancers from which they are isolated. In view of the discrepancy between the very low levels of ras transcription in cancers and the very high levels in cells transformed in vitro, we have investigated the minimal level of human ras expression for transformation in vitro. Using point-mutated human ras genes recombined with different promoters from either human metallothionein-IIA or human fibronectin or from retroviruses we found dominant in vitro transformation of the mouse C3H cell line only with ras genes linked to viral promoters. These ras genes were expressed more than 120-fold higher than are native ras genes of C3H cells. The copy number of transfected ras genes ranged from 2–6 in our system. In addition, nondominant transformation was observed in a small percentage (2–7%) of C3H cells transfected with ras genes that are expressed less than 20 times higher than native C3H ras genes. Because over 90% of cells expressing ras at this moderately enhanced level were untransformed, transformation must follow either a nondominant ras mechanism or a non-ras mechanism. We conclude that the mutated, but normally expressed, ras genes found in human and animal cancers are not likely to “play a dominant part in cancer.” The conclusion that mutated ras genes are not sufficient or dominant for cancer is directly supported by recent discoveries of mutated ras in normal animals, and in benign human tissue, “which has little potential to progress” [Jen, J., Powell, S. M., Papadopoulos, N., Smith, K. J., Hamilton, S. R., Vogelstein, B. & Kinzler, K. W. (1994) Cancer Res. 54, 5523–5526]. Even the view that mutated ras is necessary for cancer is hard to reconcile with (i) otherwise indistinguishable cancers with and without ras mutations, (ii) metastases of the same human cancers with and without ras mutations, (iii) retroviral ras genes that are oncogenic without point mutations, and (iv) human tumor cells having spontaneously lost ras mutation but not tumorigencity.

The small GTP-binding protein Rho links G protein-coupled receptors and Gα12 to the serum response element and to cellular transformation

Receptors coupled to heterotrimeric G proteins can effectively stimulate growth promoting pathways in a large variety of cell types, and if persistently activated, these receptors can also behave as dominant-acting oncoproteins. Consistently, activating mutations for G proteins of the Gαs and Gαi2 families were found in human tumors; and members of the Gαq and Gα12 families are fully transforming when expressed in murine fibroblasts. In an effort aimed to elucidate the molecular events involved in proliferative signaling through heterotrimeric G proteins we have focused recently on gene expression regulation. Using NIH 3T3 fibroblasts expressing m1 muscarinic acetylcholine receptors as a model system, we have observed that activation of this transforming G protein-coupled receptors induces the rapid expression of a variety of early responsive genes, including the c-fos protooncogene. One of the c-fos promoter elements, the serum response element (SRE), plays a central regulatory role, and activation of SRE-dependent transcription has been found to be regulated by several proteins, including the serum response factor and the ternary complex factor. With the aid of reporter plasmids for gene expression, we observed here that stimulation of m1 muscarinic acetylcholine receptors potently induced SRE-driven reporter gene activity in NIH 3T3 cells. In these cells, only the Gα12 family of heterotrimeric G protein α subunits strongly induced the SRE, while Gβ1γ2 dimers activated SRE to a more limited extent. Furthermore, our study provides strong evidence that m1, Gα12 and the small GTP-binding protein RhoA are components of a novel signal transduction pathway that leads to the ternary complex factor-independent transcriptional activation of the SRE and to cellular transformation.

A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-ErbB signaling to actin stress fiber disassembly

The avian erythroblastosis viral oncogene (v-erbB) encodes a receptor tyrosine kinase that possesses sarcomagenic and leukemogenic potential. We have expressed transforming and nontransforming mutants of v-erbB in fibroblasts to detect transformation-associated signal transduction events. Coimmunoprecipitation and affinity chromatography have been used to identify a transformation-associated, tyrosine phosphorylated, multiprotein complex. This complex consists of Src homologous collagen protein (Shc), growth factor receptor binding protein 2 (Grb2), son of sevenless (Sos), and a novel tyrosine phosphorylated form of the cytoskeletal regulatory protein caldesmon. Immunofluorescence localization studies further reveal that, in contrast to the distribution of caldesmon along actin stress fibers in normal fibroblasts, caldesmon colocalizes with Shc in plasma membrane blebs in transformed fibroblasts. This colocalization of caldesmon and Shc correlates with actin stress fiber disassembly and v-erbB-mediated transformation. The tyrosine phosphorylation of caldesmon, and its association with the Shc–Grb2–Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes, and may define one mechanism regulating actin stress fiber disassembly in transformed cells.

Oncogenic transformation induced by the Qin protein is correlated with transcriptional repression

The retroviral oncogene qin codes for a protein that belongs to the family of the winged helix transcription factors. The viral Qin protein, v-Qin, differs from its cellular counterpart, c-Qin, by functioning as a stronger transcriptional repressor and a more efficient inducer of tumors. This observation suggests that repression may be important in tumorigenesis. To test this possibility, chimeric proteins were constructed in which the Qin DNA-binding domain was fused to either a strong repressor domain (derived from the Drosophila Engrailed protein) or a strong activator domain (from the herpes simplex virus VP16 protein). The chimeric transcriptional repressor, Qin–Engrailed, transformed chicken embryo fibroblasts in culture and induced sarcomas in young chickens. The chimeric activator, Qin–VP16, failed to transform cells in vitro or in vivo and caused cellular resistance to oncogenic transformation by Qin. These data support the conclusion that the Qin protein induces oncogenic transformation by repressing the transcription of genes which function as negative growth regulators or tumor suppressors.

Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression

Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis.

Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil

Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and cycloguanil have sparked renewed interest in the antimalarial drugs WR99210 and proguanil, the cycloguanil precursor. To investigate suggestions that WR99210 and proguanil act against a target other than the reductase moiety of the P. falciparum bifunctional DHFR–thymidylate synthase enzyme, we have transformed P. falciparum with a variant form of human DHFR selectable by methotrexate. Human DHFR was found to fully negate the antiparasitic effect of WR99210, thus demonstrating that the only significant action of WR99210 is against parasite DHFR. Although the human enzyme also resulted in greater resistance to cycloguanil, no decrease was found in the level of susceptibility of transformed parasites to proguanil, thus providing evidence of intrinsic activity of this parent compound against a target other than DHFR. The transformation system described here has the advantage that P. falciparum drug-resistant lines are uniformly sensitive to methotrexate and will complement transformation with existing pyrimethamine-resistance markers in functional studies of P. falciparum genes. This system also provides an approach for screening and identifying novel DHFR inhibitors that will be important in combined chemotherapeutic formulations against malaria.

p19Arf induces p53-dependent apoptosis during Abelson virus-mediated pre-B cell transformation

The Ink4a/Arf locus encodes p16Ink4a and p19Arf and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between p19Arf and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both p16Ink4a and p19Arf are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis. Because expression of p19Arf but not p16 Ink4a induced apoptosis in Ab-MLV-transformed pre-B cells, p19Arf appears to be responsible for these events. Consistent with the link between p19Arf and p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that p19Arf is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the p19Arf–p53 regulatory loop plays an important role in lymphoma induction.