Formal deformations and their categorical general fibre

We study the general fibre of a formal deformation over the formal disk of a projective variety from the view point of abelian and derived categories. The abelian category of coherent sheaves of the general fibre is constructed directly from the formal deformation and is shown to be linear over the field of Laurent series. The various candidates for the derived category of the general fibre are compared. If the variety is a surface with trivial canonical bundle, we show that the derived category of the general fibre is again a linear triangulated category with a Serre functor given by the square of the shift functor

Localizations of the Category of A∞ Categories and Internal Homs

We prove that the localizations of the categories of dg categories, of cohomologically unital and strictly unital A 1e categories with respect to the corresponding classes of quasi-equivalences are all equivalent. Moreover we show that the last two localizations are equivalent to the corresponding quotients by the relation of being isomorphic in the cohomology of the A 1e category of A 1e functors. As an application we give a complete proof of a claim by Kontsevich stating that the category of internal Homs for two dg categories can be described as the category of strictly unital A 1e functors between them

A categorical invariant for cubic threefolds

Abstract We prove a categorical version of the Torelli theorem for cubic threefolds. More precisely, we show that the non-trivial part of a semi-orthogonal decomposition of the derived category of a cubic threefold characterizes its isomorphism class

A high sensitivity process variation sensor utilizing sub-threshold operation

In this paper, we propose a novel low-power, bias-free, high-sensitivity process variation sensor for monitoring random variations in the threshold voltage. The proposed sensor design utilizes the exponential current-voltage relationship of sub-threshold operation thereby improving the sensitivity by 2.3X compared to the above-threshold operation. A test-chip containing 128 PMOS and 128 NMOS devices has been fabricated in 65nm bulk CMOS process technology. A total of 28 dies across the wafer have been fully characterized to determine the random threshold voltage variations

Arithmetically Cohen-Macaulay bundles on cubic threefolds

We study arithmetically Cohen Macaulay bundles on cubic threefolds by using derived category techniques. We prove that the moduli space of stable Ulrich bundles of any rank is always non-empty by showing that it is birational to a moduli space of semistable torsion sheaves on the projective plane endowed with the action of a Clifford algebra. We describe this birational isomorphism via wall-crossing in the space of Bridgeland stability conditions, in the example of instanton sheaves of minimal charge

CHF6001 Inhibits NF-κB activation and neutrophilic recruitment in LPS-induced lung inflammation in mice

Inhibitors of phosphodiesterase 4 (PDE4) are potent anti-inflammatory agents, inhibiting the production of inflammatory mediators through the elevation of intracellular cAMP concentrations. We studied the activity of a novel PDE4 inhibitor, CHF6001, both in vitro in human cells and in vivo, using bioluminescence imaging (BLI) in mice lung inflammation. Mice transiently transfected with the luciferase gene under the control of an NF-\u3baB responsive element (NF-\u3baB-luc) have been used to assess the in vivo anti-inflammatory activity of CHF6001 in lipopolysaccharide (LPS)-induced lung inflammation. BLI as well as inflammatory cells and the concentrations of pro-inflammatory cytokines were monitored in bronchoalveolar lavage fluids (BALF) while testing in vitro its ability to affect the production of leukotriene B4 (LTB4), measured by LC/MS/MS, by LPS/LPS/N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated human blood. CHF6001 inhibited the production of LTB4 in LPS/fMLP-activated human blood at sub-nanomolar concentrations. LPS-induced an increase of BLI signal in NF-\u3baB-luc mice, and CHF6001 administered by dry powder inhalation decreased in parallel luciferase signal, cell airway infiltration, and pro-inflammatory cytokine concentrations in BALF. The results obtained provide in vitro and in vivo evidence of the anti-inflammatory activity of the potent PDE4 inhibitor CHF6001, showing that with a topical administration that closely mimics inhalation in humans, it efficiently disrupts the NF-\u3baB activation associated with LPS challenge, an effect that may be relevant for the prevention of exacerbation episodes in chronic obstructive pulmonary disease subjects

Effect of temperature on superconducting nanowire single-photon detector noise

Today Superconducting Nanowire Single-Photon Detectors (SNSPDs) are commonly used in different photon-starved applications, including testing and diagnostics of VLSI circuits. Detecting very faint signals in the near-infrared wavelength range requires not only good detection efficiency, but also very low Dark Count Rate (DCR) and jitter. For example, low noise is crucial to enable ultra-low voltage optical testing of integrated circuits. The effect of detector temperature and background thermal radiation on the noise of superconducting single-photon detectors made of NbN meanders is studied in this paper. It is shown that two different regimes can be identified in the DCR vs. bias current characteristics. At high bias, the dark count rate is dominated by the intrinsic noise of the detector, while at low bias current it is dominated by the detection of stray photons that get onto the SNSPD. Changing the detector temperature changes its switching current and only affects the high bias branch of the characteristics: a reduction of the DCR can be achieved by lowering the SNSPD base temperature. On the other hand, changing the temperature of the single-photon light source (e.g. the VLSI circuit under test) only affects the low bias regime: a lower target temperature leads to a smaller DCR. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.United States. Air Force Research Laboratory. Intelligence Advanced Research Projects Activity (IARPA ) (contract number FA8650-11-C_7105

Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the aberrant accumulation of extracellular matrix in the lungs. nintedanib is one of the two FDA-approved drugs for IPF treatment; however, the exact pathophysiological mechanisms of fibrosis progression and response to therapy are still poorly understood. In this work, the molecular fingerprint of fibrosis progression and response to nintedanib treatment have been investigated by mass spectrometry-based bottom-up proteomics in paraffin-embedded lung tissues from bleomycin-induced (BLM) pulmonary fibrosis mice. Our proteomics results unveiled that (i) samples clustered depending on the tissue fibrotic grade (mild, moderate, and severe) and not on the time course after BLM treatment; (ii) the dysregulation of different pathways involved in fibrosis progression such as the complement coagulation cascades, advanced glycation end products (AGEs) and their receptors (RAGEs) signaling, the extracellular matrix-receptor interaction, the regulation of actin cytoskeleton, and ribosomes; (iii) Coronin 1A (Coro1a) as the protein with the highest correlation when evaluating the progression of fibrosis, with an increased expression from mild to severe fibrosis; and (iv) a total of 10 differentially expressed proteins (padj-value ≤ 0.05 and Fold change ≤-1.5 or ≥1.5), whose abundance varied in the base of the severity of fibrosis (mild and moderate), were modulated by the antifibrotic treatment with nintedanib, reverting their trend. Notably, nintedanib significantly restored lactate dehydrogenase B (Ldhb) expression but not lactate dehydrogenase A (Ldha). Notwithstanding the need for further investigations to validate the roles of both Coro1a and Ldhb, our findings provide an extensive proteomic characterization with a strong relationship with histomorphometric measurements. These results unveil some biological processes in pulmonary fibrosis and drug-mediated fibrosis therapy

Monitoring inflammation and airway remodeling by fluorescence molecular tomography in a chronic asthma model

Background: Asthma is a multifactorial disease for which a variety of mouse models have been developed. A major drawback of these models is represented by the transient nature of the airway pathology peaking 24-72h after challenge and resolving in 1-2weeks. We characterized the temporal evolution of pulmonary inflammation and tissue remodeling in a recently described mouse model of chronic asthma (8week treatment with 3 allergens: Dust mite, Ragweed, and Aspergillus; DRA). Methods: We studied the DRA model taking advantage of fluorescence molecular tomography (FMT) imaging using near-infrared probes to non-invasively evaluate lung inflammation and airway remodeling. At 4, 6, 8 or 11weeks, cathepsin- and metalloproteinase-dependent fluorescence was evaluated in vivo. A subgroup of animals, after 4weeks of DRA, was treated with Budesonide (100\u3bcg/kg intranasally) daily for 4weeks. Results: Cathepsin-dependent fluorescence in DRA-sensitized mice resulted significantly increased at 6 and 8weeks, and was markedly inhibited by budesonide. This fluorescent signal well correlated with ex vivo analysis such as bronchoalveolar lavage eosinophils and pulmonary inflammatory cell infiltration. Metalloproteinase-dependent fluorescence was significantly increased at 8 and 11weeks, nicely correlated with collagen deposition, as evaluated histologically by Masson's Trichrome staining, and airway epithelium hypertrophy, and was only partly inhibited by budesonide. Conclusions: FMT proved suitable for longitudinal studies to evaluate asthma progression, showing that cathepsin activity could be used to monitor inflammatory cell infiltration while metalloproteinase activity parallels airway remodeling, allowing the determination of steroid treatment efficacy in a chronic asthma model in mice