Collage Diffusion

We seek to give users precise control over diffusion-based image generation by modeling complex scenes as sequences of layers, which define the desired spatial arrangement and visual attributes of objects in the scene. Collage Diffusion harmonizes the input layers to make objects fit together -- the key challenge involves minimizing changes in the positions and key visual attributes of the input layers while allowing other attributes to change in the harmonization process. We ensure that objects are generated in the correct locations by modifying text-image cross-attention with the layers' alpha masks. We preserve key visual attributes of input layers by learning specialized text representations per layer and by extending ControlNet to operate on layers. Layer input allows users to control the extent of image harmonization on a per-object basis, and users can even iteratively edit individual objects in generated images while keeping other objects fixed. By leveraging the rich information present in layer input, Collage Diffusion generates globally harmonized images that maintain desired object characteristics better than prior approaches

Fluoroquinolone-associated tendinopathy: a case report

Fluoroquinolone-associated tendinopathy is well described. This adverse effect however does not appear to be widely known among medical practitioners. We hereby described a case of ciprofloxacin-associated tendinopathy for which the adverse drug reaction was not suspected initially and the patient was inappropriately reassured and incorrectly advised to complete the antibiotic course. Given the frequent use of fluoroquinolones in clinical practice and the potential for severe disability from tendon rupture, we consider it important to remind your readers of this uncommon but potentially devastating adverse drug reaction

Thermodynamic entropy of a many body energy eigenstate

It is argued that a typical many body energy eigenstate has a well defined thermodynamic entropy and that individual eigenstates possess thermodynamic characteristics analogous to those of generic isolated systems. We examine large systems with eigenstate energies equivalent to finite temperatures. When quasi-static evolution of a system is adiabatic (in the quantum mechanical sense), two coupled subsystems can transfer heat from one subsystem to another yet remain in an energy eigenstate. To explicitly construct the entropy from the wave function, degrees of freedom are divided into two unequal parts. It is argued that the entanglement entropy between these two subsystems is the thermodynamic entropy per degree of freedom for the smaller subsystem. This is done by tracing over the larger subsystem to obtain a density matrix, and calculating the diagonal and off-diagonal contributions to the entanglement entropy.Comment: 18 page

Clostridium perfringens Epsilon Toxin Compromises the Blood-Brain Barrier in a Humanized Zebrafish Model

This is the final version. Available on open access from Elsevier vis the DOI in this recordClostridium perfringens epsilon toxin (ETX) is hypothesized to mediate blood-brain barrier (BBB) permeability by binding to the myelin and lymphocyte protein (MAL) on the luminal surface of endothelial cells (ECs). However, the kinetics of this interaction and a general understanding of ETX's behavior in a live organism have yet to be appreciated. Here we investigate ETX binding and BBB breakdown in living Danio rerio (zebrafish). Wild-type zebrafish ECs do not bind ETX. When zebrafish ECs are engineered to express human MAL (hMAL), proETX binding occurs in a time-dependent manner. Injection of activated toxin in hMAL zebrafish initiates BBB leakage, hMAL downregulation, blood vessel stenosis, perivascular edema, and blood stasis. We propose a kinetic model of MAL-dependent ETX binding and neurovascular pathology. By generating a humanized zebrafish BBB model, this study contributes to our understanding of ETX-induced BBB permeability and strengthens the proposal that MAL is the ETX receptor.National Institute of Neurological Disorders and StrokeWilma S. and Laurence A. Tisch Foundatio

The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer

Metastatic breast cancer; PostmenopausalCàncer de mama metastàtic; PostmenopausaCáncer de mama metastásico; PostmenopausiaPurpose GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling. Methods A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 −) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status. Results Patients (N = 152) received GDC-0810 100–800 mg once daily (QD) or 300–400 mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600 mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (> 90%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring ESR1 mutations included partial responses (4% overall; 4% ESR1), stable disease (39% overall; 42% ESR1), non-complete response/non-progressive disease (13% overall; 12% ESR1), progressive disease (40% overall; 38% ESR1), and missing/unevaluable (5% overall; 5% ESR1). Clinical benefit (responses or SD, lasting ≥ 24 weeks) was observed in patients in dose escalation (n = 16, 39%) and expansion (n = 24, 22%). Conclusion GDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER + advanced/MBC, with/without ESR1 mutations, highlighting the potential for oral SERDs.This work was supported by Genentech, Inc., South San Francisco, CA. and K.J. would like to acknowledge a Memorial Sloan Kettering Cancer Center Support Grant (P30 CA008748)

Electronic origins of photocatalytic activity in d0 metal organic frameworks

Metal-organic frameworks (MOFs) containing d0 metals such as NH2-MIL-125(Ti), NH2-UiO-66(Zr) and NH2-UiO-66(Hf) are among the most studied MOFs for photocatalytic applications. Despite structural similarities, we demonstrate that the electronic properties of these MOFs are markedly different. As revealed by quantum chemistry, EPR measurements and transient absorption spectroscopy, the highest occupied and lowest unoccupied orbitals of NH2-MIL-125(Ti) promote a long lived ligand-to-metal charge transfer upon photoexcitation, making this material suitable for photocatalytic applications. In contrast, in case of UiO materials, the d-orbitals of Zr and Hf, are too low in binding energy and thus cannot overlap with the π* orbital of the ligand, making both frontier orbitals localized at the organic linker. This electronic reconfiguration results in short exciton lifetimes and diminishes photocatalytic performance. These results highlight the importance of orbital contributions at the band edges and delineate future directions in the development of photo-active hybrid solids

Managing software development information in global configuration management activities

Software Configuration Management (SCM) techniques have been considered the entry point to rigorous software engineering, where multiple organizations cooperate in a decentralized mode to save resources, ensure the quality of the diversity of software products, and manage corporate information to get a better return of investment. The incessant trend of Global Software Development (GSD) and the complexity of implementing a correct SCM solution grow not only because of the changing circumstances, but also because of the interactions and the forces related to GSD activities. This paper addresses the role SCM plays in the development of commercial products and systems, and introduces a SCM reference model to describe the relationships between the different technical, organizational, and product concerns any software development company should support in the global market

Glycosylation of mucins present in gastric juice: the effect of helicobacter pylori eradication treatment

It is suggested that gastric mucins, and in particular some specific glycan structures that can act as carbohydrate receptors, are involved in the interactions with Helicobacter pylori adhesins. The main aim of our study was to evaluate glycosylation pattern of glycoproteins of gastric juice before and at the end of eradication therapy. Gastric juices were taken from 13 clinical patients and subjected to analysis. Pooled fractions of the void volume obtained after gel filtration were subjected to ELISA tests. To assess the relative amounts of carbohydrate structures, lectins and monoclonal antibodies were used. Changes in the level of MUC 1 and MUC 5AC mucins and of carbohydrate structures, which are suggested to be receptors for Helicobacter pylori adhesins, were observed by the end of the eradication treatment. Our results support the idea about the involvement of MUC 5AC and MUC 1 with some specific sugar structures in the mechanism of Helicobacter pylori infection