Type 1s Research Articles

Abstract P352: Transcriptomic Effects of Prolonged Diet-Induced Obesity in Subtypes of Agouti-Related Peptide Neurons of the Hypothalamic Arcuate Nucleus

Obesity is the greatest impediment to improving cardiovascular health. Despite many methods to lose weight, few people can keep it off in the long-term. The adaptation (suppression) of resting metabolic rate (RMR) appears to mediate weight re-gain after weight loss, yet the neurobiology that controls RMR remains unclear. Previously we published that the angiotensin II type 1 receptor (AT 1 R/ Agtr1a ) within Agouti-related peptide (AgRP/ Agrp ) neurons of the arcuate nucleus of the hypothalamus (ARC) is critical for integrative control of RMR. In the ARC, AT 1 R is only expressed by a subset of AgRP neurons (“Type 1”). In lean animals, AT 1 R inhibits this cell via a β-arrestin-1/Gαi-coupled cascade ("Type 1i”). Prolonged diet-induced obesity (DIO) causes RMR adaptation and is associated with a spontaneous G protein cascade switch by AT 1 R in the Type 1 neuron, in which AT 1 R activation begins stimulating the cell via the Gαq-coupled cascade (“Type 1s”). Our ongoing work aims to clarify the molecular mechanisms that govern AT 1 R coupling to Gαi versus Gαq within Type 1 AgRP neurons. First, using a dual-reporter mouse with tdTomato in AT 1 R-expressing cells plus green fluorescent protein in somatostatin (SST/ Sst )-expressing cells, we confirmed that SST expression is a selective marker of the Type 1 subtype of ARC AgRP neurons. Second, we reanalyzed our previously published single-nucleus RNA sequencing dataset describing the mouse ARC following prolonged DIO (PMC7347451) to explore the effects of DIO upon the transcriptomic profiles of AgRP neuron subtypes. Of 26 cell types initially identified, one cluster strongly expressed both Sst and Agrp (Cluster 5). Sub-clustering of Cluster 5 identified four cell types with strong Agrp expression (subclusters 0, 2, 5, and 6). Subcluster 6 may represent the Type 1i subtype due to high Sst expression, as well as enrichment for signatures of Gαi signaling events . Subcluster 6 also had very few DIO-induced differentially expressed genes (up=3, down=2). Interestingly, Subcluster 2 was comprised almost exclusively of nuclei from the DIO group (95%). Subcluster 2 was more closely related to Subcluster 6 than the other Agrp subclusters in the cluster phylogenetic tree, leading us to hypothesize that this cluster represents the DIO-induced Type 1s subtype. These data identify novel markers of AgRP neuron subtypes within the ARC, and a possible transcriptomic signature of subtype switching induced by prolonged DIO.

The Application of Machine Learning to Quasar and Seyfert Classification

Machine learning can be utilized to classify spectra flagged as Active Galactic Nuclei (AGNs) belonging to Seyferts or Quasars, expediting data collection and aiding in analyzing the AGN types. While many properties of Seyferts and Quasars can be used as feature points in training a machine learning model, one relatively available property with high information density is the spectra of the AGN types. This paper aims to describe the training and results of a K-Nearest Neighbors and a Dense Neural Network machine learning model built to classify AGNs as Seyfert type 1s, Seyfert type 2s, or Quasars.

Multiwavelength Spectral Energy Distribution Analysis of X-Ray Selected Active Galactic Nuclei at z = 0.2–0.8 in the Stripe 82 Region

We perform a systematic, multiwavelength spectral energy distribution (SED) analysis of X-ray detected active galactic nuclei (AGNs) at z = 0.2–0.8 with Sloan Digital Sky Survey (SDSS) counterparts in the Stripe 82 region, consisting of 60 type 1 and 137 type 2 AGNs covering a 2–10 keV luminosity range of 41.6<logLx<44.7 . The latest CIGALE code, where dusty polar components are included, is employed. To obtain reliable host and AGN parameters in type 1 AGNs, we utilize the image-decomposed optical SEDs of host galaxies by Li et al. based on the Subaru Hyper-Suprime Cam images. The mean ratio of black hole masses (M BH) and stellar masses (M stellar) of our X-ray detected type 1 AGN sample, log(MBH/Mstellar)=−2.7±0.5 , is close to the local relation between BH and stellar masses as reported by Li et al. for SDSS quasars. This ratio is slightly lower than that found for more luminous ( logLbol>45 ) type 1 AGNs at z ∼ 1.5. This can be explained by the AGN luminosity dependence of log(MBH/Mstellar) , which little evolves with redshift. We confirm the trend that the UV-to-X-ray slope (α OX) or X-ray-to-bolometric correction factor (κ 2–10) increases with AGN luminosity or Eddington ratio. We find that type 1 and type 2 AGNs with the same luminosity ranges share similar host stellar mass distributions, whereas type 2s tend to show smaller AGN luminosities than type 1s. This supports the luminosity-dependent (or Eddington-ratio-dependent) unified scheme.

The Type 1 and Type 2 AGN dichotomy according to their ZTF optical variability

ABSTRACT The scarce optical variability studies in spectrally classified Type 2 active galactic nuclei (AGNs) have led to the discovery of anomalous objects that are incompatible with the simplest unified models (UMs). This paper focuses on the exploration of different variability features that allow to distinguish between obscured, Type 2 AGNs and the variable, unobscured Type 1s. We analyse systematically the Zwicky Transient Facility, 2.5-yr-long light curves of ∼15 000 AGNs from the Sloan Digital Sky Survey Data Release 16, which are generally considered Type 2s due to the absence of strong broad emission lines (BELs). Consistent with the expectations from the UM, the variability features are distributed differently for distinct populations, with spectrally classified weak Type 1s showing one order of magnitude larger variances than the Type 2s. We find that the parameters given by the damped random walk model lead to broader H α equivalent width for objects with τg &amp;gt; 16 d and long-term structure function SF∞, g &amp;gt; 0.07 mag. By limiting the variability features, we find that ∼11 per cent of Type 2 sources show evidence for optical variations. A detailed spectral analysis of the most variable sources (∼1 per cent of the Type 2 sample) leads to the discovery of misclassified Type 1s with weak BELs and changing-state candidates. This work presents one of the largest systematic investigations of Type 2 AGN optical variability to date, in preparation for future large photometric surveys.

Abstract 114: Metabolic Adaptation During Obesity Is Associated With G Protein Switching By The Angiotensin At1a Receptor In Agrp Neurons

Obesity represents the single greatest impediment to continued improvements in hypertension and cardiovascular disease. Prolonged obesity is associated with “Resting Metabolic Rate (RMR) adaptation” (ie, reduced RMR relative to body composition), and RMR adaptation is proposed to explain resistance to weight loss / weight maintenance after obesity is established. Previously we showed that angiotensin II (ANG) Agtr1a (AT1A) receptors expressed in Agouti-related peptide (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) are required for integrative control of RMR. We hypothesize that changes in AT1A signaling in AgRP cells underlie the development of RMR adaptation. ARC slices from mice expressing tdTomato in AgRP cells ( Agrp -Cre x Ai9) were used for cell-attached voltage clamp recording of AgRP neurons. ANG inhibited ~33% of AgRP neurons via an AT1A-dependent mechanism (deemed a “Type 1i” response, which was inhibitable by losartan (LOS) or genetic deletion of AT1A; Firing rate; aCSF:0.85 ± 0.03 vs ANG:0.20 ± 0.04 vs ANG+LOS:0.91 ± 0.11 Hz, p&lt;0.05) that was also blocked by the Gαi inhibitor, pertussis toxin (PTX), but not by the Gαq inhibitor, BIM-46187 (Δ Firing rate: PTX: -0.39 ± 0.09 Hz, p&lt;0.05 vs BIM: 0.10 ± 0.09 Hz). After 10 weeks of high-fat feeding, roughly half of Type 1 cells exhibited a spontaneous switch from the ANG/AT1A-mediated inhibitory (Type 1i) response to an ANG/AT1A-mediated stimulatory response (“Type 1s”; Firing rate; aCSF: 0.86 ± 0.03 vs ANG:1.10 ± 0.12 vs ANG+LOS:0.82 ± 0.03 Hz, p&lt;0.05), which was blocked by BIM-46187, but not by PTX (Δ Firing rate: PTX: 0.07 ± 0.06 Hz vs BIM: 0.49 ± 0.06 Hz, p&lt;0.05). AAV delivery of Cre-inducible DREADDs into the ARC of lean Agtr1a -Cre mice was then used to study the effects of Gαi vs Gαq signaling in Type 1 AgRP cells upon RMR control. Activation of the Gαi-coupled hM4Di DREADD in AT1A-expressing cells of the ARC was sufficient to increase RMR (+25% from baseline, n=8-10, p&lt;0.05), but activation of a Gαq-coupled DREADD had no effect. We conclude (i) that the AT1A receptor is expressed by a unique subtype of AgRP neuron; (ii) that inhibitory AT1A-Gαi signaling in the Type 1 AgRP cell stimulates RMR; and (iii) that loss of AT1A-Gαi coupling in these cells is sufficient to explain obesity-associated RMR adaptation.

“No-one realises what we go through as Type 1s”: A qualitative photo-elicitation study on coping with diabetes

AimsType 1 diabetes (T1D) has physical, emotional, and social consequences and little is known how adults cope with the condition long term. This research aimed to use a novel photo-elicitation technique to gain in-depth insight into the personal coping experiences of adults living with T1D. MethodsIn-depth photo elicitation interviews were employed to collect data and transcripts were analysed using thematic analysis. ResultsParticipant-led data revealed an overarching theme of the relentlessness of the condition. Continuous self-management tasks infiltrated participants’ lives and had a significant impact on coping experiences. A range of techniques and resources were used to cope including using alarms and reminders, diabetes technology, interpersonal relationships, supportive healthcare services and seeking a mind–body balance. ConclusionsTechnology shows promise for easing the burden of the condition, expert-led online support would be of benefit, and peer support should be prioritised within interventions for adults with T1D.

Application of the Screened Hydrogenic Model to Light Atoms

The purpose of this work was to develop a Screened Hydrogenic Model (SHM) to accurately calculate the electron energies for light atoms and ions with up to ten electrons for atomic numbers up to 18. The total energy of an atom or ion was calculated with effective nuclear charges and screening parameters for each electron type (1s, 2s and 2p) within a specific electron configuration. Multiple energy states, centered at the total energy, were calculated for electron configurations that have Russell-Saunders coupling. The energy of each electron included its relativistic energy, EREL, but close overall agreement between the calculated and experimental energies of multi-electron configurations required that the one-electron expression for EREL be modified in a simple manner. In the present work, 98% of the 587 calculated energies for light atoms/ions have a relative error within ±0.1% of the corresponding experimental energies. The effective nuclear charges described in this work allow hydrogen-like wave functions to be defined for the electrons within a multi-electron configuration. The SHM, described in this work, is available for future calculations involving light atoms and ions.

Characteristics of Currents in Upward Lightning Flashes Initiated From the Gaisberg Tower

We examined the occurrence characteristics of the lightning observed at the Gaisberg Tower (GBT) in the years 2000 to 2018 and analyzed current waveforms (measured using a 0.25-mΩ shunt) of upward flashes initiated from the tower. During this period, 865 flashes were recorded at the GBT, of which 823 (95%) were upward and 4 (0.5%) were downward. For 18 flashes, the current waveforms were ambiguous and for 20 flashes they were unsuitable for analysis. Of the 823 upward flashes, 651 (79%) were negative, 35 (4.3%) were positive, and 137 (17%) were bipolar. The median initial stage (IS)-current durations in upward negative, positive, and bipolar flashes were 275, 96, and 282 ms, respectively. The median IS-current peaks in these flashes were 1.4, 3.2, and 1.8 kA, respectively. We expanded the traditional classification of bipolar flashes to include five categories. Of the 137 bipolar flashes, 45% were of Type 1S (single reversal of current polarity during IS), 47% of Type 1M (multiple reversals of current polarity during IS), 5.1% of Type 2 [different polarities of current during IS and return stroke (RS)], 1.5% of Type 3 (RSs of different polarities), and 0.73% (one flash) of Type 4 (different polarities of RS and the following continuing current).

Active galactic nuclei at high redshifts: properties and environment of Type 1 and 2 AGNs

We explore host galaxy properties and environment of a sample of Type 1 and 2 active galactic nuclei (AGN) taken from the COSMOS2015 catalog, within 0.3 $\leq z \leq$ 1.1 selected for their emission in X-rays, optical spectra and SED signatures. We find different properties of host galaxies of distinct AGNs: Type 1 AGNs reside in blue, star-forming and less massive host galaxies compared to Type 2. The majority of the AGNs have intermediate X-ray luminosities, $10^{42}\leq L_X<10^{44}$ \ergs, while only a few have X-ray luminosities ($L_X > 10^{44}$ \ergs) as those observed in QSOs. Non-parametric morphological analysis show that the majority of Type 1 AGN hosts are elliptical or compact galaxies, while Type 2 AGN host present more scatter, from spirals, irregulars and elliptical galaxies. The environment of the different AGN types are similar except at small scales ($r_p<$100 kpc), where Type 2 AGNs have more neighbour galaxies than Type 1s. Galaxies located close to Type 2 AGNs ($\sim$100 kpc) tend to have redder colours, and are more massive compared to the local environment of Type 1s. The observed differences in the environment and host galaxy properties of Type 1 and 2 AGN types show that the obscuration due to the presence of gas and dust may be distributed in larger galactic-scales, possibly originated by galaxy interactions or mergers.

Von Willebrand Factor (VWF) Propeptide and Factor VIII (FVIII) Levels Identify the Contribution of Decreased Synthesis and/or Increased Clearance Mechanisms in the Pathogenesis of Type 1 Von Willebrand Disease (VWD) in the Zimmerman Program

Laboratory diagnosis of VWD is challenging, with multiple tests required to obtain an accurate assessment. Plasma VWF level represents a balance between synthesis, secretion, and clearance. Although synthesized together, VWFpp and VWF circulate in plasma independently with differing half-lives. Plasma VWFpp level is used to assess synthesis/secretion, VWFpp/VWF:Ag ratio to indicate clearance of VWF, and FVIII/VWF:Ag ratio to assess VWF synthesis and clearance.We sought to identify the underlying VWD pathophysiology in subjects enrolled in the Zimmerman Program including 245 healthy controls, 175 "low VWF" (VWF:Ag 30-50), 69 type 1 (VWF:Ag<30), 57 type 1C (VWF:Ag<30 and VWFpp/VWF:Ag>3), and 9 type 1-severe (1S) (VWF:Ag<5). FVIII levels were significantly reduced (p < 0.0001) in VWD subjects compared to controls. The mean FVIII/VWF:Ag ratio in "low VWF" (1.5), types 1 (2.4), 1C (2.9), and 1S (8.7) were significantly different from controls (p < 0.0001). VWFpp levels in all subjects were significantly lower than controls with type 1S subjects demonstrating the most reduced levels. The mean VWFpp/VWF:Ag was significantly increased compared to controls in type 1 (1.9) and 1C (8.4) subjects.VWFpp level, VWFpp/VWF:Ag and FVIII/VWF:Ag were used to define the underlying pathophysiology in VWD subtypes. A VWFpp/VWF:Ag > 3.0 indicates increased VWF clearance. VWFpp level < 50 IU/dL or FVIII/VWF:Ag > 2.0 indicate reduced VWF synthesis/secretion. A combination of increased clearance/reduced secretion may be identified or neither mechanism. Only 9% of "low VWF" subjects had increased FVIII/VWF:Ag, while 15% had decreased VWFpp suggesting reduced secretion. Other unidentified mechanisms may explain the majority of these "low VWF" cases. In type 1, 38 had increased FVIII/VWF:Ag and 48 had reduced VWFpp indicating reduced secretion in 55-70% of cases. In type 1C, all had increased VWFpp/VWF:Ag, 44 had increased FVIII/VWF:Ag and 19 reduced VWFpp. Reduced secretion may play a role in 33 -77% of these subjects, in addition to increased VWF clearance. All 9 type 1S had reduced VWFpp and 8/9 had increased FVIII/VWF, indicating a reduced secretion mechanism in nearly all cases.To assess the influence of sequence variant (SV) location on VWF synthesis/secretion, levels were analyzed by presence or absence of SV and SV location by VWF domain. 62% of the VWD cohort had SV identified (23% with >1 SV) while 38% had no SV. Of those with SV, 52% had increased FVIII/VWF:Ag and 48% had decreased VWFpp, suggesting reduced secretion; 31% had increased VWFpp/VWF:Ag indicative of increased clearance; and 32% had neither mechanism. In the group with no SV, only 7% had increased FVIII/VWF:Ag and 17% had decreased VWFpp while 77% had neither mechanism identified.Of those subjects with reduced secretion as indicated by increased FVIII/VWF:Ag, the majority of SV were found in A1 (29%), D3 (22%) and D1 (13%) which was similar to those with reduced secretion indicated by decreased VWFpp level in A1 (25%), D3 (21%) and D1 (15%). An increased VWFpp/VWF:Ag ratio predicting increased clearance was found in patients with SV in D3, A1 and D4 domains. Patients with both increased clearance and reduced secretion had SV in A1 (53%), D3 (19%) and D4 (11%). Subjects who had neither mechanism identified had SV in A2 (25%), C1-C6 (18%) and D2 (16%), suggesting these SV are associated with other, yet unidentified mechanisms.Although VWFpp level and FVIII/VWF:Ag are both thought to indicate VWF synthesis/secretion, some discrepancies were observed. VWFpp level may be the more specific marker, as VWFpp and VWF share a common precursor protein. Reduced secretion plays a role in nearly all type 1S, 70% of type 1, and 15% of "low VWF" subjects. Additionally, SV in A1, D3, and D4 may be associated with decreased secretion and/or increased clearance while those in D1 may be associated with decreased secretion alone. No SV were found in 85% of "low VWF" subjects that is consistent with the observation that the majority of these cases (81%) had neither decreased secretion nor increased clearance mechanisms identified. The mechanistic cause of bleeding in these patients remains undefined. Assay of VWFpp and corresponding VWF:Ag ratios may help to define the underlying mechanism in VWD subjects and identify true type 1C VWD patients, which is clinically important for therapeutic treatment. DisclosuresFlood:CSL Behring: Consultancy; Baxalta: Consultancy. Friedman:Shire: Consultancy; NovoNordisk: Consultancy; CSL Behring: Consultancy; Alexion: Speakers Bureau.

Clustering, cosmology and a new era of black hole demographics– II. The conditional luminosity functions of Type 2 and Type 1 active galactic nuclei

The orientation-based unification model of active galactic nuclei (AGNs) posits that the principle difference between obscured (Type 2) and unobscured (Type 1) AGNs is the line-of-sight into the central engine. If this model is correct than there should be no difference in many of the properties of AGN host galaxies (e.g., the mass of the surrounding dark matter haloes). However, recent clustering analyses of Type 1 and Type 2 AGNs have provided some evidence for a difference in the halo mass, in conflict with the orientation-based unified model. In this work, a method to compute the Conditional Luminosity Function (CLF) of Type 2 and Type 1 AGNs is presented. The CLF allows many fundamental halo properties to be computed as a function of AGN luminosity, which we apply to the question of the host halo masses of Type 1 and 2 AGNs. By making use of the total AGN CLF, the Type 1 X-ray luminosity function, and the luminosity-dependent Type 2 AGN fraction, the CLFs of Type 1 and 2 AGNs are calculated at $z\approx 0$ and $0.9$. At both $z$, there is no statistically significant difference in the mean halo mass of Type 2 and 1 AGNs at any luminosity. There is marginal evidence that Type 1 AGNs may have larger halo masses than Type 2s, which would be consistent with an evolutionary picture where quasars are initially obscured and then subsequently reveal themselves as Type 1s. As the Type 1 lifetime is longer, the host halo will increase somewhat in mass during the Type 1 phase. The CLF technique will be a powerful way to study the properties of many AGNs subsets (e.g., radio-loud, Compton-thick) as future wide-area X-ray and optical surveys substantially increase our ability to place AGNs in their cosmological context.

Domain Distribution of Type 1 VWD Sequence Variants and Impact on Clinical and Laboratory Phenotype in the Zimmerman Program

Type 1 von Willebrand disease (VWD) is a common inherited bleeding disorder, characterized by a quantitative deficiency of von Willebrand factor (VWF). The molecular basis continues to merit exploration, especially since the genetic cause has not been determined in 30-40% of cases in previous studies. As part of the Zimmerman Program for the Molecular and Biology of VWD (ZPMCB-VWD) study, we sought to identify the sequence variants (SV) within the VWF gene that result in type 1 VWD and correlate these to clinical laboratory phenotype and clinical severity and determine the frequency of type 1 subjects who do not have a gene defect. We also wanted to examine the types of sequence variants that cause type 1, type 1-Severe (1S), type 1C and low VWF (LVWF), and determine the influence of SV location on VWF levels and risk of bleeding. 310 type 1 Index Cases (IC) enrolled in the ZPMCB-VWD were analyzed, including 69 type 1 (VWF:Ag&lt;30), 9 type 1S (VWF:Ag&lt;5), 57 type 1C (VWF:Ag&lt;30; VWFpp/VWF:Ag&gt;3), and 175 LVWF (VWF:Ag or VWF:RCo 30-50). Bleeding symptoms were quantified using the ISTH bleeding score (ISTH BS). Clinical VWF testing was done in a central laboratory at BloodCenter of Wisconsin and included FVIII, VWF:Ag, VWF:RCo, VWFpp, and VWF:CB. Full-length VWF sequencing was performed, including 5' and 3' regions and intron/exon boundaries. SV found in &gt;1% of the healthy control population were excluded from this analysis. Mutation negative cases were further investigated by comparative genomic hybridization (CGH) to identify any large deletions or duplications in the VWF gene. SV or large deletions were identified in 62% (n=192) of this cohort with quantitative VWF deficiency, whereas 38% (n=118) had no variants found. Of those with no sequence variant identified, 10% were type 1, 5% type 1C and 85% LVWF. There were 142 SV found in this cohort. 75% of the subjects had missense mutations, 8% small insertions/deletions, 9% splice site mutations, 3% nonsense mutations and 1% large deletions. The median number of SV found in individuals was 1, however 23% had more than 1 SV present (range 1 to 4). Mean VWF:Ag (IU/dl) was examined to determine the influence of SV location on levels and median ISTH BS was assessed as a measure of bleeding severity by domain: Table.VWF DomainD1D2D'D3A1A2A3D4C1-C6CKNone# Subjects24343460251324304118VWF:Ag (IU/dl)18211614311221253839ISTH BS5665495515 Type 1S subjects had SV that were enriched in D1, D2 and A3 domains. 52% of type 1C variants were found in the A1 domain followed by 19% in D'D3 and 17% in D4. Both type 1 and LVWF subjects had SV that were evenly distributed throughout the gene, but LVWF had the majority of SV found in the A2, D2 and C1-C6 domains. Type 1S subjects showed a difference in mutation type compared to rest of the type 1 cohort with 31% intronic/splice site mutations, 19% nonsense mutations, 19% insertions/deletions and only 25% missense mutations. In contrast, missense mutations accounted for 68% of the mutations in type 1, 91% in type 1C and 80% in LVWF. The presence of predominantly truncating or loss of function variants in type 1S correlates with lower VWF levels and increased bleeding. In conclusion, we found that 62% of our type 1 cohort did have potentially causative SVs identified, with the majority caused by missense mutations (75%). Type 1C and type 1S tend to have SV isolated in certain domains whereas SV in type 1 and LVWF tend to be spread throughout the gene. SVs in the A3 domain demonstrated the lowest VWF:Ag (12 IU/dl) and highest ISTH BS (9) while changes in the CK domain had the highest VWF:Ag (38 IU/dl) and lowest ISTH BS (1). SVs or large deletions were not found in 38% of this cohort, indicating that other molecular factors either intronic or outside of the VWF gene may be the cause of low VWF and bleeding in these subjects. Disclosures Friedman: CSL Behring: Consultancy; Instrumentation Laboratories: Consultancy; Novo Nordisk: Consultancy; Alexion: Speakers Bureau. Gill:Baxalta, Bayer, and CSL-Behring: Membership on an entity's Board of Directors or advisory committees.

Extremely red quasars from SDSS, BOSS andWISE: classification of optical spectra

Quasars with extremely red infrared-to-optical colours are an interesting population that can test ideas about quasar evolution as well as orientation, obscuration and geometric effects in the so-called AGN unified model. To identify such a population we match the quasar catalogues of the Sloan Digital Sky Survey (SDSS), the Baryon Oscillation Spectroscopic Survey (BOSS) to the Wide-Field Infrared Survey Explorer (WISE) to identify quasars with extremely high infrared-to-optical ratios. We identify 65 objects with r(AB)-W4(Vega)>14 mag (i.e., F_nu(22um)/F_nu(r) > ~1000). This sample spans a redshift range of 0.28<z<4.36 and has a bimodal distribution, with peaks at z~0.8 and z~2.5. It includes three z>2.6 objects that are detected in the W4-band but not W1 or W2 (i.e., W1W2-dropouts). The SDSS/BOSS spectra show that the majority of the objects are reddened Type 1 quasars, Type 2 quasars (both at low and high redshift) or objects with deep low-ionization broad absorption lines (BALs) that suppress the observed r-band flux. In addition, we identify a class of Type 1 permitted broad-emission line objects at z~2-3 which are characterized by emission line rest-frame equivalent widths (REWs) of >~150Ang , much larger than those of typical quasars. In particular, 55% (45%) of the non-BAL Type 1s with measurable CIV in our sample have REW(CIV) > 100 (150)Ang, compared to only 5.8% (1.3%) for non-BAL quasars in BOSS. These objects often also have unusual line ratios, such as very high NV/Ly-alpha ratios. These large REWs might be caused by suppressed continuum emission analogous to Type 2 quasars; however, there is no obvious mechanism in standard Unified Models to suppress the continuum without also obscuring the broad emission lines.

Mixed mode oscillations in a conceptual climate model

Much work has been done on relaxation oscillations and other simple oscillators in conceptual climate models. However, the oscillatory patterns in climate data are often more complicated than what can be described by such mechanisms. This paper examines complex oscillatory behavior in climate data through the lens of mixed-mode oscillations. As a case study, a conceptual climate model with governing equations for global mean temperature, atmospheric carbon, and oceanic carbon is analyzed. The nondimensionalized model is a fast/slow system with one fast variable (corresponding to ice volume) and two slow variables (corresponding to the two carbon stores). Geometric singular perturbation theory is used to demonstrate the existence of a folded node singularity. A parameter regime is found in which (singular) trajectories that pass through the folded node are returned to the singular funnel in the limiting case where ϵ=0. In this parameter regime, the model has a stable periodic orbit of type 1s for some s>0. To our knowledge, it is the first conceptual climate model demonstrated to have the capability to produce an MMO pattern.

Do the spectral energy distributions of type 1 active galactic nuclei show diversity?

We create broadband SEDs of 761 type 1 AGN. The Scott et al. sample, created by a cross-correlation of the optical SDSS DR5 quasar catalogue and the 2XMMi catalogue of serendipitous X-ray sources, is further matched with the FIRST catalogue of radio sources, the WISE MIR all-sky data release, the 2MASS NIR point source catalogue, the UKIDSS DR9 Large Area Survey and the GALEX all-sky and medium UV imaging surveys. This allows broadband SEDs covering log(nu)~9.2-18.1 to be created. We investigate variations in the SED shape by binning a subsample of 237 AGN with the best quality SEDs according to their X-ray spectral parameters, their AGN sub-type and their luminosity, black hole mass and Eddington ratio. The AGN sub-populations show some significant differences in their SEDs; X-ray absorbed AGN show a deficit of emission at X-ray/UV frequencies and an excess in the MIR consistent with absorption and re-emission, radio-loud AGN show increased radio and X-ray emission, consistent with the presence of a jet component in addition to the emission seen from radio-quiet AGN and the SEDs of NLS1s only differ from other type 1s in the X-ray regime, suggesting any physical differences are limited to their X-ray emitting region. Binning the AGN according to underlying physical parameters reveals more subtle differences in the SEDs. The X-ray spectral slope does not appear to have any influence or dependence on the multiwavelength emission in the rest of the SED. The contribution of X-rays to Lbol is lower in higher luminosity sources, and relatively more emission in the optical/UV is seen in AGN with higher Lx. Variations in the relative flux and peak frequency of the BBB are observed and may suggest higher inner disc temperatures with increasing accretion rates. Overall, we find that the diversity in the SED shapes is relatively small, and we find no apparent single driver for the variations.

Diagnosis of von Willebrand disease in Argentina: a single institution experience

Background: von Willebrand disease (VWD) is the most common autosomal bleeding disorder, mostly inherited as dominant trait. VWD is due to deficiency/abnormality of von Willebrand factor (VWF). The true prevalence of VWD is unknown, but estimated as 0.1% to 1% of the general population. Methods: The bleeding score (BS) was used to evaluate the bleeding status of patients presenting at our institution. Laboratory analyses include: VWF:Ag, VWF:RCo, VWF:CB, multimeric pattern, VWF propeptide, Desmopressin challenge test. Genotypic analysis comprises the study of specific exons of VWF, depending on the suspected variant. Results: We describe the main characteristics of our VWD population, including phenotypic and genotypic methods used to achieve the diagnosis. From our 2,482 patients registered, quantitative variants account for 83.2% of cases, and qualitative, 16.8% of cases. Platelet-type VWD (PT-VWD) was diagnosed in two patients and acquired von Willebrand syndrome (AVWS) in six. From quantitative variants, relative frequencies are: possible type 1, 78.7%; type 1, 14.9%; type 1S, 1.5%; type 1C, 0.4%; type 3, 1.6%. From qualitative variants: 2M, 21.9%; 2B, 10.3%; 2A, 8.4%; 2N, 3.4%; patients currently without complete diagnosis: 56%. Family history of bleeding: 64.7% of cases. Type 3, 2A and 2B VWD showed the highest major bleeding (MB) frequency. Genotypic diagnosis was reached in eight type 1C, 72 type 2M, 38 type 2B, 30 type 2A, 14 type 2N, and two PT-VWD patients. Five de novo mutations were identified among 52 families (9.61%): two mutations were associated with type 2B VWD (p.V1316M and p.S1310F), one mutation associated with type 1C (Vicenza) (p.R1205H) described in combination with p.R924Q, one deletion associated to type 1 VWD according to the ISTH VWF database (p.Pro1648fs*45) in combination with p.R1426C resulting in a 2M phenotype and one mutation related to type 2A VWD (p.Y1542D). Six patients are under prophylactic treatment due to their severe bleeding: four are type 3 VWD, one type 2M VWD, and one, the patient with p.Pro1648fs*45 and p.R1426C. Conclusions: The wide heterogeneity of clinical symptoms and laboratory data from possible type 1 VWD implies a risk for bleeding that becomes crucial in challenging situations. In our population, type 2M was found to be more frequent than the type 2A variant. DDAVP (1-deamino-8-D-arginine vasopressin) challenge test, VWF propeptide/antigen ratio and genotypic studies are useful tools for discriminating cases representing difficult diagnoses such as type 2M versus type 1C VWD. Elevated propeptide ratio, the detection of antiphospholipid antibodies, platelet-associated antibodies or anti-VWF immunoglobulins and negative genotypic screening is useful to discriminate inherited VWD from AVWS. Genotypic testing assisted discrimination between types 2B versus platelet-type-VWD and type 2N VWD versus mild hemophilia A.

THE 3.3 ㎛ PAH FEATURE AS A SFR INDICATOR: PROBING THE INTERPLAY BETWEEN SF AND AGN ACTIVITIES

We utilize AKARI's slitless spectroscopic capability to detect the <TEX>$3.3{\mu}m$</TEX> polycyclic aromatic hydrocarbons (PAHs) emission and measure star formation (SF) activity for various AKARI programs. First, we obtain <TEX>$2{\sim}5{\mu}m$</TEX> spectra of 20 flux-limited galaxies with mixed SED classes in order to calibrate the <TEX>$3.3{\mu}m$</TEX> PAH luminosity (<TEX>$L_{PAH3.3}$</TEX>) as a star formation rate (SFR) indicator. We find that <TEX>$L_{PAH3.3}$</TEX> correlates with <TEX>$L_{IR}$</TEX> as well as with the <TEX>$6.2{\mu}m$</TEX> PAH luminosity (<TEX>$L_{PAH6.2}$</TEX>). The correlations does not depend on SED classes. We find that ULIRGs deviate from the correlation between PAH luminosities and <TEX>$L_{IR}$</TEX>, while they do not for the correlation between PAH luminosities. We suggest possible effects to cause this deviation. On the other hand, how AGN activity is linked to SB activity is one of the most intriguing questions. While it is suggested that AGN luminosity of quasars correlates with starburst (SB) luminosity, it is still unclear how AGN activity is connected to SF activity based on host galaxy properties. We are measuring SFRs for the LQSONG sample consisting of reverberation mapped AGNs and PG-QSOs. This is an extension of the ASCSG program by which we investigated the connection between SB and AGN activities for Seyferts type 1s at z ~ 0.36. While we found no strong correlation between <TEX>$L_{PAH3.3}$</TEX> and AGN luminosity for these Seyferts 1s, <TEX>$L_{PAH3.3}$</TEX> measured from the central part of galaxies correlates with AGN luminosity, implying that SB and AGN activities are directly connected in the nuclear region.

X-ray spectral properties of Seyfert galaxies and the unification scheme

Aims: The unification scheme of Seyfert galaxies predicts that the observed differences between type 1 and type 2 Seyfert galaxies are solely due to the differing orientations of the toroidal-shaped obscuring material around AGN. The observed X-ray spectra of Seyfert type 2s compared to type 1s are expected to be affected by higher absorbing column density due to the edge-on view of the obscuring torus. We study the 0.5 - 10 keV X-ray spectral properties of Seyfert type 1s and type 2s with the aim to test the predictions of Seyfert unification scheme in the X-ray regime. Methods: We use an optically selected Seyfert sample in which type 1s and type 2s have matched distributions in the orientation independent parameters of AGN and host galaxy. Results: The 0.5 - 10 keV XMM-Newton pn X-ray spectra of Seyfert galaxies are in general best fitted with a model consists of an absorbed power-law, a narrow Gaussian fitted to the Fe K{\alpha} emission line and an often seen soft excess component characterized by either a thermal plasma model with temperature kT \sim 0.1 - 1.0 keV and/or a steep power-law. The 2.0 - 10 keV hard X-ray continuum emission in several Seyfert type 2s is reflection dominated and suggests the Compton-thick obscuration. Results on the statistical comparison of the distributions of the observed X-ray luminosities in the soft (0.5 - 2.0 keV) and hard (2.0 - 10.0 keV) bands, the X-ray absorbing column densities, the equivalent widths of Fe K{\alpha} line and the flux ratios of hard X-ray to [OIII] {\lambda}5007{\AA} for the two Seyfert subtypes are consistent with the obscuration and orientation based unification scheme.

TORUS AND ACTIVE GALACTIC NUCLEUS PROPERTIES OF NEARBY SEYFERT GALAXIES: RESULTS FROM FITTING INFRARED SPECTRAL ENERGY DISTRIBUTIONS AND SPECTROSCOPY

We used the CLUMPY torus models and a Bayesian approach to fit the infrared spectral energy distributions (SEDs) and ground-based high-angular resolution mid-infrared spectroscopy of 13 nearby Seyfert galaxies. This allowed us to put tight constraints on torus model parameters such as the viewing angle, the radial thickness of the torus Y, the angular size of the cloud distribution sigma_torus, and the average number of clouds along radial equatorial rays N_0. The viewing angle is not the only parameter controlling the classification of a galaxy into a type 1 or a type 2. In principle type 2s could be viewed at any viewing angle as long as there is one cloud along the line of sight. A more relevant quantity for clumpy media is the probability for an AGN photon to escape unabsorbed. In our sample, type 1s have relatively high escape probabilities, while in type 2s, as expected, tend to be low. Our fits also confirmed that the tori of Seyfert galaxies are compact with torus model radii in the range 1-6pc. The scaling of the models to the data also provided the AGN bolometric luminosities, which were found to be in good agreement with estimates from the literature. When we combined our sample of Seyfert galaxies with a sample of PG quasars from the literature to span a range of L_bol(AGN)~10^{43}-10^{47}erg/s, we found plausible evidence of the receding torus. That is, there is a tendency for the torus geometrical covering factor to be lower at high AGN luminosities than at low AGN luminosities. This is because at low AGN luminosities the tori appear to have wider angular sizes and more clouds along radial equatorial rays. We cannot, however rule out the possibility that this is due to contamination by extended dust structures not associated with the dusty torus at low AGN luminosities, since most of these in our sample are hosted in highly inclined galaxies. (Abridged)

Two types of Lyman α emitters envisaged from hierarchical galaxy formation

From multi-wavelength observations of LAEs,we know that while many LAEs appear to be young and less massive,a noticeable fraction of LAEs possess much older populations of stars and larger stellar mass.How these two classes of LAEs are concordant with the hierarchical galaxy formation scenario has not been understood clearly so far.In this paper,we model LAEs by three-dimensional cosmological simulations of dark halo merger in a CDM universe.As a result,it is shown that the age of simulated LAEs can spread over a wide range from 2*10^6yr to 9*10^8yr.Also,we find that there are two types of LAEs, in one of which the young half-mass age is comparable to the mean age of stellar component,and in the other of which the young half-mass age is appreciably shorter than the mean age.We define the former as Type 1 LAEs and the latter as Type 2 LAEs.A Type 1 corresponds to early starburst in a young galaxy,whereas a Type 2 does to delayed starburst in an evolved galaxy,as a consequence of delayed accretion of a subhalo onto a larger parent halo.Thus,the same halo can experience a Type 2 LAE-phase as well as a Type 1 LAE-phase in the merger history.Type 1s are expected to be younger than 1.5*10^8yr,less dusty,and less massive with stellar mass M*<10^8 Msun,while Type 2s are older than 1.5*10^8yr,even dustier,and as massive as M*~10^8-10^10Msun.The fraction of Type 2s in all LAEs is a function of redshift.Type 2s discriminated clearly from Type 1s in two color diagram of z'-H vs J-K.We find that the brightness distribution of LyA in Type 2s is more extended than the main stellar component,in contrast to Type 1s.This is not only because delayed starbursts tend to occur in the outskirts of a parent galaxy,but also because LyA photons are effectively absorbed by dust in an evolved galaxy.Hence,the extent of LyA emission may be an additional measure to distinguish Type 2s from Type 1s