Showing papers by "University of Grenoble published in 2001"

Confounding and effect modification in the short-term effects of ambient particles on total mortality: Results from 29 European cities within the APHEA2 project

Abstract: We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.

Regularization of Wavelet Approximations

Abstract: In this paper, we introduce nonlinear regularized wavelet estimators for estimating nonparametric regression functions when sampling points are not uniformly spaced. The approach can apply readily to many other statistical contexts. Various new penalty functions are proposed. The hard-thresholding and soft-thresholding estimators of Donoho and Johnstone are specific members of nonlinear regularized wavelet estimators. They correspond to the lower and upper envelopes of a class of the penalized least squares estimators. Necessary conditions for penalty functions are given for regularized estimators to possess thresholding properties. Oracle inequalities and universal thresholding parameters are obtained for a large class of penalty functions. The sampling properties of nonlinear regularized wavelet estimators are established and are shown to be adaptively minimax. To efficiently solve penalized least squares problems, nonlinear regularized Sobolev interpolators (NRSI) are proposed as initial estimators, wh...

Electrowetting : a recent outbreak

Abstract: This paper deals with recent developments of electrowetting, i.e. the facility of modifying the spreading of a liquid on a substrate by bringing electrostatic charges on the latter. This field of research is currently seeing a revival, particularly since the interspersing of an insulator to prevent charge leaking from the substrate interface, greatly improves this phenomenon. Such electrowetting on an insulator coated electrode (EICE) concerns the majority of recent work. Some of the present studies concern the limitations of this phenomenon, whose physics is not yet fully understood, whilst others exploit EICE, either for various academic purposes or in practical situations. These are presented in the last paragraph, as well as applications of classical electrowetting.

Semi-continuity of complex singularity exponents and Kähler–Einstein metrics on Fano orbifolds

Abstract: We introduce complex singularity exponents of plurisubharmonic functions and prove a general semi-continuity result for them. This concept contains as a special case several similar concepts which have been considered e.g. by Arnold and Varchenko, mostly for the study of hypersurface singularities. The plurisubharmonic version is somehow based on a reduction to the algebraic case, but it also takes into account more quantitative informations of great interest for complex analysis and complex differential geometry. We give as an application a new derivation of criteria for the existence of Kahler–Einstein metrics on certain Fano orbifolds, following Nadel's original ideas (but with a drastic simplication in the technique, once the semi-continuity result is taken for granted). In this way, three new examples of rigid Kahler–Einstein Del Pezzo surfaces with quotient singularities are obtained.

Mirthful laughter induced by subthalamic nucleus stimulation.

Abstract: High-frequency stimulation of the subthalamic nucleus (STN) improves the motor signs of Parkinson's disease (PD). The three main components (motor, associative, and limbic) of the cortical-basal ganglia-cortical circuits pass through the STN. It is not known whether STN stimulation can influence the limbic loop. We present two PD patients in whom acute stimulation of an electrode located in the STN using high stimulation parameters (50% higher than therapeutic) induced funny associations, leading to infectious laughter and hilarity, whereas the therapeutic parameters induced a hypomanic behavior and marked improvement of akinesia. Our report suggests that the STN, with its sensorimotor, cognitive, and limbic parts is not only involved in motor, but also in psychomotor regulation.

X-Ray Structure of Sensory Rhodopsin II at 2.1 A Resolution

Abstract: Sensory rhodopsins (SRs) belong to a subfamily of heptahelical transmembrane proteins containing a retinal chromophore. These photoreceptors mediate the cascade of vision in animal eyes and phototaxis in archaebacteria and unicellular flagellated algae. Signal transduction by these photoreceptors occurs by means of transducer proteins. The two archaebacterial sensory rhodopsins SRI and SRII are coupled to the membrane-bound HtrI and HtrII transducer proteins. Activation of these proteins initiates phosphorylation cascades that modulate the flagellar motors, resulting in either attractant (SRI) or repellent (SRII) phototaxis. In addition, transducer-free SRI and SRII were shown to operate as proton pumps, analogous to bacteriorhodopsin. Here, we present the x-ray structure of SRII from Natronobacterium pharaonis (pSRII) at 2.1-Å resolution, revealing a unique molecular architecture of the retinal-binding pocket. In particular, the structure of pSRII exhibits a largely unbent conformation of the retinal (as compared with bacteriorhodopsin and halorhodopsin), a hydroxyl group of Thr-204 in the vicinity of the Schiff base, and an outward orientation of the guanidinium group of Arg-72. Furthermore, the structure reveals a putative chloride ion that is coupled to the Schiff base by means of a hydrogen-bond network and a unique, positively charged surface patch for a probable interaction with HtrII. The high-resolution structure of pSRII provides a structural basis to elucidate the mechanisms of phototransduction and color tuning.

DNA methylation profiles of lung tumors.

Abstract: Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor beta-2 (RAR beta), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.

HD 80606 b, a planet on an extremely elongated orbit ?

Abstract: We report the detection of a planetary companion orbiting the solar-type star HD 80606, the brighter component of a wide binary with a projected separation of about 2000 AU. Using high-signal spectroscopic observations of the two components of the visual binary, we show that they are nearly identical. The planet has an orbital period of 111.8 days and a minimum mass of 3:9MJup .W ithe = 0.927, this planet has the highest orbital eccentricity among the extrasolar planets detected so far. We nally list several processes this extreme eccentricity could result from.

Dynamical modeling of large scale asymmetries in the beta Pictoris dust disk

Abstract: We report a new and complete model of the Pictoris disk, which succeeds in accounting for both the surface brightness distribution, warp characteristics, the outer \butterfly" asymmetry as observed by HST/STIS in scattered light, as well as the infrared emission. Our model includes the presence of a disk of planetesimals extending out to 120{150 AU, perturbed gravitationally by a giant planet on an inclined orbit, following the ap- proach of Mouillet et al. (1997b). At any time, the planetesimal disk is assumed to be the source of a distribution of grains produced through collisional evolution, with the same initial orbital parameter distribution. The steady state spatial grain distribution is found incorporating the eects of radiation pressure which can cause the distri- bution of the smallest particles to become very distended. With realistic assumptions about the grains' chemical properties, the modeling conrms the previously evident need for an additional population of hot grains close to the star, to account for the 12m fluxes at short distances from the star. It also indicates that this population cannot explain the outer 12m flux distribution when the eects of gravity and radiation pressure determine the distribution. Very small grains, produced by collisions among aggregates, are tentatively proposed to account for this 12m outer emission.

Observation of Equipartition of Seismic Waves

Abstract: Equipartition is a first principle in wave transport, based on the tendency of multiple scattering to homogenize phase space. We report observations of this principle for seismic waves created by earthquakes in Mexico. We find qualitative agreement with an equipartition model that accounts for mode conversions at the Earth’s surface.

Seismoelectric wave conversions in porous media: Field measurements and transfer function analysis

Abstract: We present a series of field experiments showing the transient electric fields generated by a seismic excitation of the subsurface. After removing the powerline noise by adaptive filtering, the most prominent feature of the seismoelectric recordings is the presence of electric signals very similar to conventional seismic recordings. In one instance, we identified small-amplitude precursory electromagnetic disturbances showing a polarity reversal on either side of the shotpoint. Concentrating on the dominant seismoelectric effect, we theoretically show that the electric field accompanying the compressional waves is approximately proportional to the grain acceleration. We also demonstrate that the magnetic field moving along with shear waves is roughly proportional to the grain velocity. These relationships hold true as long as the displacement currents are much smaller than the conduction currents (diffusive regime), which is normally the case in the low-frequency range used in seismic prospecting. Furthermore, the analytical transfer functions thus obtained indicate that the electric field is mainly sensitive to the salt concentration and dielectric constant of the fluid, whereas the magnetic field principally depends on the shear modulus of the framework of grains and on the fluid's viscosity and dielectric constant. Both transfer functions are essentially independent of the permeability. Our results suggest that the simultaneous recording of seismic, electric, and magnetic wavefields can be useful for characterizing porous layers at two different levels of investigation: near the receivers and at greater depth.

Accumulation forms of Zn and Pb in Phaseolus vulgaris in the presence and absence of EDTA.

Abstract: The internalized speciation of Zn and Pb in roots and leaves of Phaseolus vulgaris grown in zinc sulfate, zinc EDTA, lead nitrate, and lead EDTA solutions were studied by electron microscopy (Zn) and extended X-ray absorption fine structure (EXAFS) spectroscopy (Zn and Pb). Zn was predominantly present as Zn phosphate dihydrate in the roots and leaves of the plant regardless of its form in solution. Pb was predominantly found in the leaves as cerussite (lead carbonate) when the plant was grown in Pb nitrate solution and as a mixture of PbEDTA and an undetermined species in contact with PbEDTA solution. Therefore, Phaseolus vulgaris is able to dissociate totally (Zn) or partly (Pb) the two metal-EDTA complexes from the nutrient solution and to bind these metals in other forms.

Fourth updated ESACP consensus report on diagnostic DNA image cytometry.

Abstract: A task force of experts in the field of diagnostic DNA image cytometry, invited by the ESACP, and further scientists or physicians revealing experience in that diagnostic procedure (names are given in Addendum A), agreed upon the following 4th updated Consensus Report on Standardised Diagnostic DNA Image Cytometry during the 7th International Congress of that society in Caen, 2001. This report is based on the three preceding ones [6,14,17]. It deals with the following items:- Critical review and update of the definitions given in the 1997 Consensus Update;- Review and detailed description of basic terms, principles and algorithms for diagnostic interpretation;- Recommendations concerning diagnostic or prognostic applications in specific fields of tumour pathology. This update is not aimed to substitute the 1997 consensus, but to make necessary addenda and give more detailed descriptions of those items not unequivocally to interpret by potential users of the methodology.

Increased lipid peroxidation in patients with pulmonary hypertension.

Abstract: Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of isoprostaglandin F2 α type III (iPF2 α-III), an F2-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF2 α-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF2 α-III levels were measured by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were investigated for response to inhaled NO challenge. Urinary iPF2 α-III levels in PHT patients (225 ± 27 pmol/mmol creatinine) were 2.3 times as high as in controls (97 ± 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial pressure variation and the pulmonary vascular resistance variation in response to inhaled NO were ...

Price Bubbles in Laboratory Asset Markets with Constant Fundamental Values

Abstract: We construct asset markets that are similar to those studied by Smith, Suchanek and Williams (Econometrica. 56, 1119–1151) in which bubbles and crashes tended to occur. The main difference between the markets studied here and those studied by Smith et al. is that in the markets studied here, the fundamental value of the asset is constant over the entire life of the asset. In four of the eight sessions reported here, we observe bubbles, which are prices considerably higher than fundamental values. The data suggest that the frequent payment of dividends is a major cause of bubble formation. The property that the fundamental value remains constant over the course of the trading horizon is not sufficient to eliminate the possibility of a bubble.

Pseudo-effective line bundles on compact kähler manifolds

Abstract: The goal of this work is to pursue the study of pseudo-effective line bundles and vector bundles Our first result is a generalization of the Hard Lefschetz theorem for cohomology with values in a pseudo-effective line bundle The Lefschetz map is shown to be surjective when (and, in general, only when) the pseudo-effective line bundle is twisted by its multiplier ideal sheaf This result has several geometric applications, eg to the study of compact Kahler manifolds with pseudo-effective canonical or anti-canonical line bundles Another concern is to understand pseudo-effectivity in more algebraic terms In this direction, we introduce the concept of an "almost" nef line bundle, and mean by this that the degree of the bundle is nonnegative on sufficiently generic curves It can be shown that pseudo-effective line bundles are almost nef, and our hope is that the converse also holds true This can be checked in some cases, eg for the canonical bundle of a projective 3-fold From this, we derive some geometric properties of the Albanese map of compact Kahler 3-folds

Hst/nicmos2 coronagraphic observations of the circumstellar environment of three old pms stars: hd 100546, sao 206462 and mwc 480

Abstract: The close environment of four old Pre-Main Sequence stars has been observed thanks to the coronagraphic mode of the HST/NICMOS2 camera at m. In the course of this program, a cir cum stel lar annulus around HD 141569 was detected and has already been presented in Augereau et al. ([CITE]b). In this paper, we report the detection of an elliptical structure around the Herbig Be star HD 100546 extending from the very close edge of the co mask (∼ 50 AU) to 350-380 AU (3.5-3.8″) from the star. The axis ratio gives a disk inclination of to the line-of-sight and a position angle of , measured east of north. At 50 AU, the disk has a surface brightness between 10.5 and 11 mag/arcsec2 , then follows a radial power law up to 250-270 AU and finally falls as . The inferred optical thickness suggests that the disk is at least marginally optically thick inside 80 AU and optically thin further out. Combined with anisotropic scattering properties, this could explain the shape of a brightness asymmetry observed along the minor axis of the disk. This asymmetry needs to be confirmed. The cir cum stel lar disks around SAO 206462 and MWC 480 are not resolved, leading to constraints on the dust distribution. A tight binary system separated by only is nevertheless detected in the close vicinity of SAO 206462.

Structural determinants of spectral tuning in retinal proteins - Bacteriorhodopsin vs sensory rhodopsin II

Abstract: The mechanism of spectral tuning in the rhodopsin family of proteins, that act as light-driven proton (ion) pumps and light detectors, has been investigated by a combined ab initio quantum mechanical/molecular mechanical technique. Calculations are performed on two members of the family, bacteriorhodopsin (bR) and sensory rhodopsin II (sRII), for which crystal structures of high resolution are available, to explore the physical mechanisms of spectral tuning. Despite a high degree of similarity in the three-dimensional structure, electrostatic environments in bR and sRII differ sufficiently to shift absorption maxima of their common chromophore, a retinal bound to a lysine via a protonated Schiff base, from 568 nm in bR to 497 nm in sRII. This spectral shift, involving the electronical ground state (S0) and first excited state (S1) of retinal, is predicted correctly within 10 nm. The spectral shift can be attributed predominantly to a change in polarization of the S1 state, and is induced predominantly by ...

Review of the functional surgical treatment of dystonia

Abstract: A review of functional surgery for dystonia is presented. Recently renewed interest in stereotaxy for dystonia has followed the resurgence of pallidotomy and the introduction of deep brain stimulation (DBS) in Parkinson's disease (PD) in the early 1990s. However, even since the 1950s, small series of patients treated with ablative surgery have been carefully studied, providing useful information, notably regarding the tolerability of surgery. In the setting of dystonia, thalamotomy was first performed with substantial benefits, but some authors outlined the great variability in outcome, and the high incidence of operative side-effects. In the 'modern' era of functional surgery for movement disorders, the globus pallidus internus (GPi) has emerged to be currently the best target for dystonia, based on small series of patients published in the last few years. Both bilateral posteroventral pallidotomy (PVP) and bilateral pallidal stimulation, performed by several teams, have benefited a variety of patients with severe dystonia, the most dramatic improvements being seen in primary dystonia with a mutation in the DYT1 gene. Whereas patients with secondary dystonia have often shown a lesser degree of improvement, some publications have nevertheless reported major benefit. There is today a strong need for carefully controlled studies comparing secondary and primary dystonia, DYT1 and non-DYT1 dystonia, ablative surgery and DBS, with additional assessment of neuropsychological changes, especially in children treated with bilateral pallidal procedures.

A System To Assess the Semantic Content of Student Essays.

Abstract: This paper presents Apex, a system that can automatically assess a student essay based on its content. It relies on Latent Semantic Analysis, a tool which is used to represent the meaning of words as vectors in a high-dimensional space. By comparing an essay and the text of a given course on a semantic basis, our system can measure how well the essay matches the text. Various assessments are presented to the student regarding the topic, the outline and the coherence of the essay. Our experiments yield promising results.

Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999–2000)

Abstract: Aims/hypothesis. Improvements in islet transplantation require clinical series large enough to implement controlled new strategies. The goal of this study was to demonstrate the feasibility of a multicentre network for islet transplantation in Type I (insulin-dependent) diabetic patients. Methods. The five centres (Besancon, Geneva, Grenoble, Lyon, Strasbourg) of the GRAGIL network allow pancreas procurement, recipient recruitment, transplantation procedure and follow-up. Islet isolation is, however, performed in one single laboratory (Geneva). Pancreata were procured in each of the five centres and transported to Geneva with an ischaemia time of less than 8 hours. Islets were isolated using a standard automated method. If the islet number was too low for a graft ( 6 months) received 9030 ± 1090 islet-equivalent/kg with a median purity of 63 %. The number of pancreata required for each graft was 1 (n = 5) or 2 (n = 5). At the completion of a 12 month follow-up, we observed 0 % primary nonfunction, 50 % graft survival and 20 % insulin-independence. Conclusions/interpretation. This study demonstrates the interest and the feasibility of a multicentre collaboration in human islet transplantation. [Diabetologia (2001) 44: 859–864]

Asymmetries in the HD 141569 circumstellar disk

Abstract: We present HST/STIS coronagraphic observations of the disk around HD 141569. The data, with a spatial resolution and signal to noise higher than those previously obtained with HST/NICMOS2 allow a more detailed insight in the system. They reveal a very structured system, in which two ring-like structures at distances 200 and 325 AU from the star are the most prominent features. The region between 125 and 175 AU is clearly devoid of material. An arc-like structure is also detected at about 250 AU, as well as a diffuse extended emission, both on the North side of the disk. The system appears to be highly asymmetrical, both with respect to its major and minor axes. Surprisingly, the brightness asymmetry with respect to both axes in the inner and outer parts of the disk is reversed. Possible explanations to the asymmetries include anisotropic scattering and/or non axisymmetrical distribution of the dust within the system. It is shown that anisotropic scattering cannot alone be responsible for all observed asymmetries. It is concluded that HD 141569 disk is non axi-symmetrical. Eventhough no detailed modeling is given in this observational paper, it is probable that the sculpting and brightness properties of the disk are due to the gravitational perturbation of a massive body.

On orbit closures of spherical subgroups in flag varieties

Abstract: Let $ \cal F $ be the flag variety of a complex semi-simple group G, let H be an algebraic subgroup of G acting on $ \cal F $ with finitely many orbits, and let V be an H-orbit closure in $ \cal F $ . Expanding the cohomology class of V in the basis of Schubert classes defines a union V0 of Schubert varieties in $ \cal F $ with positive multiplicities. If G is simply-laced, we show that these multiplicities are equal to the same power of 2. For arbitrary G, we show that V0 is connected in codimension 1. If moreover all multiplicities are 1, we show that the singularities of V are rational and we construct a flat degeneration of V to V0 in $ \cal F $ . Thus, for any effective line bundle L on $ \cal F $ , the restriction map $ {H}^0({\cal F}, {\rm L}) \to {H}^0({\rm V, L} $ is surjective, and $ {H}^n({\rm V, L}) = 0 $ for all $ n \geq 1 $ .

Optimized mixtures of recombinant Humicola insolens cellulases for the biodegradation of crystalline cellulose.

Abstract: The digestion of bacterial cellulose ribbons by ternary mixtures of enzymes consisting of recombinant cellulases (two cellobiohydrolases, Cel6A and Cel7A, and the endoglucanase Cel45A) from Humicola insolens was investigated over a wide range of mixture composition. The extent of digestion was followed by soluble sugar release (saccharification) analysis together with transmission electron microscopy (TEM) observations. It was found that the addition of minute quantities of Cel45A induced a spectacular increase in saccharification of the substrate with either Cel7A or the mixture of Cel6A and Cel7A. Conversely, only a moderate saccharification resulted from the mixing of Cel45A and Cel6A. This difference is believed to originate from (1) the occasional endo character of Cel6A and (2) the competition of Cel6A and Cel45A for the substrate sites that are sensitive to endo activity. Interestingly, the mixture of enzymes giving rise to the highest saccharification rate did not always correspond to mixtures of enzymes generating the highest synergy. TEM images revealed that the bacterial cellulose ribbons became at the same time cut and narrowed down under the action of an optimized mixture of the three enzymes.

Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B‐cell lymphoma and multiple myeloma

Abstract: 1q rearrangement is a remarkably frequent secondary chromosomal change in both non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), where it is associated with tumor progression. To gain insight into 1q rearrangement-associated disease mechanisms, we used fluorescence in situ hybridization (FISH) to search for recurring 1q breaks in 35 lymphoma samples (31 NHL patients and 4 lymphoma-derived cell lines) as well as 22 MM patients with cytogenetically determined 1q abnormalities. Strikingly, dual-color FISH analysis with chromosome 1 centromere and 1q12-specific probes identified constitutive heterochromatin band 1q12 as the single most frequent breakpoint site in both NHL and MM (39% and 89% of 1q breaks, respectively). These rearrangements consistently generated aberrant heterochromatin/euchromatin junctions and gain of 1q12 material. A further 30% of NHL 1q breaks specifically involved two other novel, closely spaced sites (clusters I and II) within a 2.5 Mb region of proximal 1q21 (D1S3620 to D1S3623). A possible association between these sites and NHL subtype was evident; the cluster I rearrangement was frequent in follicular and diffuse large cell lymphoma, whereas the cluster II rearrangement was more frequently observed in diffuse small-cell lymphoma (2/2 marginal zone lymphomas, 1/2 atypical chronic lymphocytic leukemias, and 1 lymphoplasmacytic lymphoma in this series). Candidate oncogenes bordering this interval (BCL9 and AF1Q) were not rearranged in any patient except one (AF1Q). This study provides the first evidence of involvement of 1q12 constitutive heterochromatin in the pathogenesis of NHL and MM and indicates proximal 1q21 to be of specific pathological significance in NHL.