Port d'Informació Científica

Abstract Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 2213–21. ©2017 AACR.

Deep brain stimulation (DBS) is currently tested as an experimental therapy for patients with treatment-resistant depression (TRD). Here we report on the short- and long-term (1 yr) clinical outcomes and tolerance of DBS in eight TRD patients. Electrodes were implanted bilaterally in the subgenual cingulate gyrus (SCG; Broadman areas 24-25), and stimulated at 135 Hz (90-μs pulsewidth). Voltage and active electrode contacts were adjusted to maximize short-term responses. Clinical assessments included the 17-item Hamilton Depression Rating Scale (HAMD17; primary measure), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) Scale. In the first week after surgery, response and remission (HAMD ⩽7) rates were, respectively 87.5% and 50%. These early responses were followed by an overall worsening, with a response and remission rates of 37.5% (3/8) at 1 month. From then onwards, patients showed a progressive improvement, with response and remission rates of 87.5% and 37.5%, respectively, at 6 months. The corresponding figures at 1 yr were 62.5% and 50%, respectively. Clinical effects were seen in all HAMD subscales without a significant incidence of side-effects. Surgical procedure and post-operative period were well-tolerated for all patients. This is the second independent study on the use of DBS of the SCG to treat chronic depression resistant to current therapeutic strategies. DBS fully remitted 50% of the patients at 1 yr, supporting its validity as a new therapeutic strategy for TRD.

Abstract We describe the Dark Energy Survey (DES) photometric data set assembled from the first three years of science operations to support DES Year 3 cosmologic analyses, and provide usage notes aimed at the broad astrophysics community. Y3 GOLD improves on previous releases from DES, Y1 GOLD , and Data Release 1 (DES DR1), presenting an expanded and curated data set that incorporates algorithmic developments in image detrending and processing, photometric calibration, and object classification. Y3 GOLD comprises nearly 5000 deg 2 of grizY imaging in the south Galactic cap, including nearly 390 million objects, with depth reaching a signal-to-noise ratio ∼10 for extended objects up to i AB ∼ 23.0, and top-of-the-atmosphere photometric uniformity <3 mmag. Compared to DR1, photometric residuals with respect to Gaia are reduced by 50%, and per-object chromatic corrections are introduced. Y3 GOLD augments DES DR1 with simultaneous fits to multi-epoch photometry for more robust galactic color measurements and corresponding photometric redshift estimates. Y3 GOLD features improved morphological star–galaxy classification with efficiency >98% and purity >99% for galaxies with 19 < i AB < 22.5. Additionally, it includes per-object quality information, and accompanying maps of the footprint coverage, masked regions, imaging depth, survey conditions, and astrophysical foregrounds that are used to select the cosmologic analysis samples.

Baryon Acoustic Oscillations (BAO) provide a “standard ruler ” of known physical length, making it one of the most promising probes of the nature of dark energy. The detection of BAO as an excess of power in the galaxy distribution at a certain scale requires measuring galaxy positions and redshifts. “Transversal ” (or “angular”) BAO measure the angular size of this scale projected in the sky and provide information about the angular distance. “Line-of-sight ” (or “radial”) BAO require very precise redshifts, but provide a direct measurement of the Hubble parameter at different redshifts, a more sensitive probe of dark energy. The main goal of this paper is to show that it is possible to obtain photometric redshifts with enough precision (σz) to measure BAO along the line of sight. There is a fundamental limitation as to how much one can improve the BAO 1

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.

Bone augmentation procedures are frequent today in implant patients, since an implant should be circumferentially anchored in bone at completion of bone healing to have a good long-term stability. The best documented surgical technique to achieve this goal is guided bone regeneration (GBR) utilizing barrier membranes in combination with bone fillers. This clinical review paper reflects 35 years of development and progress with GBR. In the 1990s, GBR was developed by defining the indications for GBR, examining various barrier membranes, bone grafts, and bone substitutes. Complications were identified and reduced by modifications of the surgical technique. Today, the selection criteria for various surgical approaches are much better understood, in particular, in post-extraction implant placement. In the majority of patients, biodegradable collagen membranes are used, mainly for horizontal bone augmentation, whereas bioinert PTFE membranes are preferred for vertical ridge augmentation. The leading surgeons are using a composite graft with autogenous bone chips to accelerate bone formation, in combination with a low-substitution bone filer to better maintain the augmented bone volume over time. In addition, major efforts have been made since the millenium change to reduce surgical trauma and patient morbidity as much as possible. At the end, some open questions related to GBR are discussed.

Growth is a complex process that is intimately linked to the developmental program to form adults with proper size and proportions. Genetics is an important determinant of growth, as exemplified by the role of local diffusible molecules setting up organ proportions. In addition, organisms use adaptive responses allowing modulating the size of individuals according to environmental cues, for example, nutrition. Here, we describe some of the physiological principles participating in the determination of final individual size.

BACKGROUND: Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established. METHOD: The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate. RESULTS: Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered. CONCLUSIONS: Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.

BACKGROUND: Dementia is a frequent and devastating complication in Parkinson's disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients. OBJECTIVES AND METHODS: We aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer. RESULTS: In a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex. CONCLUSIONS: The pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing.

CONTEXT: Cushing's syndrome (CS) affects cognition and memory. OBJECTIVE: Our objective was to evaluate memory and hippocampal volumes (HV) on 3-tesla magnetic resonance imaging (3T MRI) in CS patients and controls. PATIENTS AND METHODS: Thirty-three CS patients (11 active, 22 cured) and 34 controls matched for age, sex, and education underwent Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure memory tests. Gray matter and HV were calculated on 3T MRI, using FreeSurfer image analyses software. RESULTS: No differences in HV were observed between active and cured CS or controls. Memory performance was worse in CS patients than controls (P < 0.04 in active; P < 0.03 in cured CS) but did not differ among CS groups, which were therefore analyzed together; they performed worse for verbal (P = 0.02) and visual memory (P = 0.04) than controls. In 12 CS patients, memory was below normative cutoff values for verbal (n = 6, cured), visual memory (n = 10, six cured) or both (n = 4); these patients with severe memory impairments showed smaller HV compared with their matched controls (P = 0.02 with verbal impairment; P = 0.03 with visual impairment). They were older (P = 0.04), had shorter education (P = 0.02), and showed a trend toward longer duration of hypercortisolism (P = 0.07) than the remaining CS patients. Total (P = 0.004) and cortical (P = 0.03) brain gray matter volumes were decreased in CS compared with controls, indicating brain atrophy, whereas subcortical gray matter (which includes HV) was reduced only in the 12 patients with severe memory impairment. CONCLUSION: Verbal and visual memory is worse in CS patients than controls, even after biochemical cure. HV was decreased only in those whose memory scores were below normative cutoff values.

Context. Gravitational waves from black-hole (BH) merging events have revealed a population of extra-galactic BHs residing in short-period binaries with masses that are higher than expected based on most stellar evolution models – and also higher than known stellar-origin black holes in our Galaxy. It has been proposed that those high-mass BHs are the remnants of massive metal-poor stars. Aims. Gaia astrometry is expected to uncover many Galactic wide-binary systems containing dormant BHs, which may not have been detected before. The study of this population will provide new information on the BH-mass distribution in binaries and shed light on their formation mechanisms and progenitors. Methods. As part of the validation efforts in preparation for the fourth Gaia data release (DR4), we analysed the preliminary astrometric binary solutions, obtained by the Gaia Non-Single Star pipeline, to verify their significance and to minimise false-detection rates in high-mass-function orbital solutions. Results. The astrometric binary solution of one source, Gaia BH3, implies the presence of a 32.70 ± 0.82 M ⊙ BH in a binary system with a period of 11.6 yr. Gaia radial velocities independently validate the astrometric orbit. Broad-band photometric and spectroscopic data show that the visible component is an old, very metal-poor giant of the Galactic halo, at a distance of 590 pc. Conclusions. The BH in the Gaia BH3 system is more massive than any other Galactic stellar-origin BH known thus far. The low metallicity of the star companion supports the scenario that metal-poor massive stars are progenitors of the high-mass BHs detected by gravitational-wave telescopes. The Galactic orbit of the system and its metallicity indicate that it might belong to the Sequoia halo substructure. Alternatively, and more plausibly, it could belong to the ED-2 stream, which likely originated from a globular cluster that had been disrupted by the Milky Way.

We present a measurement of the extragalactic background light (EBL) based on a joint likelihood analysis of 32 gamma-ray spectra for 12 blazars in the redshift range z = 0.03-0.944, obtained by the MAGIC telescopes and Fermi-LAT. The EBL is the part of the diffuse extragalactic radiation spanning the ultraviolet, visible, and infrared bands. Major contributors to the EBL are the light emitted by stars through the history of the Universe, and the fraction of it that was absorbed by dust in galaxies and re-emitted at longer wavelengths. The EBL can be studied indirectly through its effect on very high energy photons that are emitted by cosmic sources and absorbed via γγinteractions during their propagation across cosmological distances. We obtain estimates of the EBL density in good agreement with state-of-the-art models of the EBL production and evolution. The 1σ upper bounds, including systematic uncertainties, are between 13 per cent and 23 per cent above the nominal EBL density in the models. No anomaly in the expected transparency of the Universe to gamma-rays is observed in any range of optical depth. We also perform a wavelength-resolved EBL determination, which results in a hint of an excess of EBL in the 0.18-0.62 μm range relative to the studied models, yet compatible with them within systematics.

BACKGROUND: Findings of brain structural changes in major depressive disorder are still inconsistent, partly because some crucial clinical variables have not been taken into account. AIMS: To investigate the effect of major depressive disorder on grey matter volumes. METHOD: Voxel-based morphometry was used to compare 66 patients with depression at different illness stages (22 each with first-episode, remitted-recurrent and treatment resistant/chronic depression) with 32 healthy controls. Brain volumes were correlated with clinical variables. RESULTS: Voxel-based morphometry showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus (P<0.05, family wise error-corrected). Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula. CONCLUSIONS: Frontotemporolimbic areas are smaller in the patients with severe depression and are associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting major depressive disorder on grey matter.

BACKGROUND: Smaller hippocampal volumes in major depressive disorder (MDD) have been linked with earlier onset, previous recurrences and treatment refractoriness. The aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden. METHODS: Glutamate/glutamine (Glx), N-acetylaspartate (NAA) and choline (Cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 T magnetic resonance spectroscopy scanner. Voxels were placed in the head of the right and left hippocampus. We controlled for systematic differences resulting from volume-of-interest (VOI) tissue composition and total hippocampal volume. RESULTS: Our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. Patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of Glx and NAA than controls, especially in the right hippocampal region (p ≤ 0.025). Diminished levels of Glx were correlated with longer illness duration (left VOI r = -0.34, p = 0.01). By contrast, Cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19% higher; all p ≤ 0.025) and were consistently related to longer illness duration (right VOI r = 0.30, p = 0.028; left VOI r = 0.38, p = 0.004) and more previous episodes (right VOI r = 0.46, p = 0.001; left VOI r = 0.44, p = 0.001). LIMITATIONS: The cross-sectional design and the inclusion of treated patients are the main limitations of the study. CONCLUSION: Our results support that metabolite alterations within the hippocampus are more pronounced in patients with a clinical evolution characterized by recurrences and/or chronicity and add further evidence to the potential deleterious effects of stress and depression on this region.

Context. Extended and delayed emission around distant TeV sources induced by the effects of propagation of γ ray s through the intergalactic medium can be used for the measurement of the intergalactic magnetic field (IGMF). Aims. We search for delayed GeV emission from the hard-spectrum TeV γ -ray emitting blazar 1ES 0229+200, with the goal of detecting or constraining the IGMF-dependent secondary flux generated during the propagation of TeV γ rays through the intergalactic medium. Methods. We analysed the most recent MAGIC observations over a 5 year time span, and complemented them with historic data of the H.E.S.S. and VERITAS telescopes, along with a 12-year-long exposure of the Fermi /LAT telescope. We used them to trace source evolution in the GeV–TeV band over a decade and a half. We used Monte Carlo simulations to predict the delayed secondary γ -ray flux, modulated by the source variability, as revealed by TeV-band observations. We then compared these predictions for various assumed IGMF strengths to all available measurements of the γ -ray flux evolution. Results. We find that the source flux in the energy range above 200 GeV experiences variations around its average on the 14-year time span of observations. No evidence for the flux variability is found in the 1 − 100 GeV energy range accessible to Fermi /LAT. The non-detection of variability due to delayed emission from electromagnetic cascade developing in the intergalactic medium imposes a lower bound of B &gt; 1.8 × 10 −17 G for the long-correlation-length IGMF and B &gt; 10 −14 G for an IGMF of cosmological origin. Though weaker than the one previously derived from the analysis of Fermi /LAT data, this bound is more robust, being based on a conservative intrinsic source spectrum estimate and accounting for the details of source variability in the TeV energy band. We discuss implications of this bound for cosmological magnetic fields that might explain the baryon asymmetry of the Universe.

Aims. We aim to characterize the multiwavelength emission from Markarian 501 (Mrk 501), quantify the energy-dependent variability, study the potential multiband correlations, and describe the temporal evolution of the broadband emission within leptonic theoretical scenarios. Methods. We organized a multiwavelength campaign to take place between March and July of 2012. Excellent temporal coverage was obtained with more than 25 instruments, including the MAGIC, FACT and VERITAS Cherenkov telescopes, the instruments on board the Swift and Fermi spacecraft, and the telescopes operated by the GASP-WEBT collaboration. Results. Mrk 501 showed a very high energy (VHE) gamma-ray flux above 0.2 TeV of ∼0.5 times the Crab Nebula flux (CU) for most of the campaign. The highest activity occurred on 2012 June 9, when the VHE flux was ∼3 CU, and the peak of the high-energy spectral component was found to be at ∼2 TeV. Both the X-ray and VHE gamma-ray spectral slopes were measured to be extremely hard, with spectral indices &lt; 2 during most of the observing campaign, regardless of the X-ray and VHE flux. This study reports the hardest Mrk 501 VHE spectra measured to date. The fractional variability was found to increase with energy, with the highest variability occurring at VHE. Using the complete data set, we found correlation between the X-ray and VHE bands; however, if the June 9 flare is excluded, the correlation disappears (significance &lt; 3 σ ) despite the existence of substantial variability in the X-ray and VHE bands throughout the campaign. Conclusions. The unprecedentedly hard X-ray and VHE spectra measured imply that their low- and high-energy components peaked above 5 keV and 0.5 TeV, respectively, during a large fraction of the observing campaign, and hence that Mrk 501 behaved like an extreme high-frequency-peaked blazar (EHBL) throughout the 2012 observing season. This suggests that being an EHBL may not be a permanent characteristic of a blazar, but rather a state which may change over time. The data set acquired shows that the broadband spectral energy distribution (SED) of Mrk 501, and its transient evolution, is very complex, requiring, within the framework of synchrotron self-Compton (SSC) models, various emission regions for a satisfactory description. Nevertheless the one-zone SSC scenario can successfully describe the segments of the SED where most energy is emitted, with a significant correlation between the electron energy density and the VHE gamma-ray activity, suggesting that most of the variability may be explained by the injection of high-energy electrons. The one-zone SSC scenario used reproduces the behavior seen between the measured X-ray and VHE gamma-ray fluxes, and predicts that the correlation becomes stronger with increasing energy of the X-rays.

We present a new infrared survey covering the three Euclid deep fields and four other Euclid calibration fields using Spitzer Space Telescope’s Infrared Array Camera (IRAC). We combined these new observations with all relevant IRAC archival data of these fields in order to produce the deepest possible mosaics of these regions. In total, these observations represent nearly 11 % of the total Spitzer Space Telescope mission time. The resulting mosaics cover a total of approximately 71.5 deg 2 in the 3.6 and 4.5 μm bands, and approximately 21.8 deg 2 in the 5.8 and 8 μm bands. They reach at least 24 AB magnitude (measured to 5 σ , in a 2″​​.5 aperture) in the 3.6 μm band and up to ∼5 mag deeper in the deepest regions. The astrometry is tied to the Gaia astrometric reference system, and the typical astrometric uncertainty for sources with 16 &lt; [3.6]&lt; 19 is ≲0″​​.15. The photometric calibration is in excellent agreement with previous WISE measurements. We extracted source number counts from the 3.6 μm band mosaics, and they are in excellent agreement with previous measurements. Given that the Spitzer Space Telescope has now been decommissioned, these mosaics are likely to be the definitive reduction of these IRAC data. This survey therefore represents an essential first step in assembling multi-wavelength data on the Euclid deep fields, which are set to become some of the premier fields for extragalactic astronomy in the 2020s.

Euclid will be the first space mission to survey most of the extragalactic sky in the 0.95–2.02 µm range, to a 5 σ point-source median depth of 24.4 AB mag. This unique photometric dataset will find wide use beyond Euclid’s core science. In this paper, we present accurate computations of the Euclid Y E , J E , and H E passbands used by the Near-Infrared Spectrometer and Photometer (NISP), and the associated photometric system. We pay particular attention to passband variations in the field of view, accounting for, among other factors, spatially variable filter transmission and variations in the angle of incidence on the filter substrate using optical ray tracing. The response curves’ cut-on and cut-off wavelengths – and their variation in the field of view – are determined with ~0.8 nm accuracy, essential for the photometric redshift accuracy required by Euclid. After computing the photometric zero points in the AB mag system, we present linear transformations from and to common ground-based near-infrared photometric systems, for normal stars, red and brown dwarfs, and galaxies separately. A Python tool to compute accurate magnitudes for arbitrary passbands and spectral energy distributions is provided. We discuss various factors, from space weathering to material outgassing, that may slowly alter Euclid ’s spectral response. At the absolute flux scale, the Euclid in-flight calibration program connects the NISP photometric system to Hubble Space Telescope spectrophotometric white dwarf standards; at the relative flux scale, the chromatic evolution of the response is tracked at the milli-mag level. In this way, we establish an accurate photometric system that is fully controlled throughout Euclid’s lifetime.

Abstract We report on observations of the pulsar/Be star binary system PSR J2032+4127/MT91 213 in the energy range between and with the Very Energetic Radiation Imaging Telescope Array and Major Atmospheric Gamma Imaging Cherenkov telescope arrays. The binary orbit has a period of approximately 50 years, with the most recent periastron occurring on 2017 November 13. Our observations span from 18 months prior to periastron to one month after. A new point-like gamma-ray source is detected, coincident with the location of PSR J2032+4127/MT91 213. The gamma-ray light curve and spectrum are well characterized over the periastron passage. The flux is variable over at least an order of magnitude, peaking at periastron, thus providing a firm association of the TeV source with the pulsar/Be star system. Observations prior to periastron show a cutoff in the spectrum at an energy around . This result adds a new member to the small population of known TeV binaries, and it identifies only the second source of this class in which the nature and properties of the compact object are firmly established. We compare the gamma-ray results with the light curve measured with the X-ray Telescope on board the Neil Gehrels Swift Observatory and with the predictions of recent theoretical models of the system. We conclude that significant revision of the models is required to explain the details of the emission that we have observed, and we discuss the relationship between the binary system and the overlapping steady extended source, TeV J2032+4130.