Computed Tomographic and Histopathologic Studies of Lung Function Immediately in Canine Neonates.

Background: The lung tissue in newborn canine neonates is still in a morphologically and functionally immature, canalicular-saccular stage. True alveoli are only formed postnatally. The aim of this study was to analyze the spatial and temporal development of the ventilation of the lung tissue in vital canine neonates during the first 24 h post natum (p.

Spanning tree model and the assembly kinetics of RNA viruses.

Single-stranded RNA (ssRNA) viruses self-assemble spontaneously in solutions that contain the viral RNA genome molecules and viral capsid proteins. The self-assembly of empty capsids can be understood on the basis of free energy minimization. However, during the self-assembly of complete viral particles in the cytoplasm of an infected cell, the viral genome molecules must be selected from a large pool of very similar host messenger RNA molecules and it is not known whether this also can be understood by free energy minimization.

Exact expressions for the partition function of the one-dimensional Ising model in the fixed-M ensemble.

We obtain exact closed-form expressions for the partition function of the one-dimensional Ising model in the fixed-M ensemble, for three commonly used boundary conditions: periodic, antiperiodic, and Dirichlet. These expressions allow for the determination of fluctuation-induced forces in the canonical ensemble, which we term Helmholtz forces. The thermodynamic expressions and the calculations flowing from them should provide insights into the nature and behavior of fluctuation-induced forces in interesting and as-yet unexplored regimes.

Endocytosis at extremes: Formation and internalization of giant clathrin-coated pits under elevated membrane tension.

Internalization of clathrin-coated vesicles from the plasma membrane constitutes the major endocytic route for receptors and their ligands. Dynamic and structural properties of endocytic clathrin coats are regulated by the mechanical properties of the plasma membrane. Here, we used conventional fluorescence imaging and multiple modes of structured illumination microscopy (SIM) to image formation of endocytic clathrin coats within live cells and tissues of developing fruit fly embryos.

ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation.

Objective: Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas.

Using Bayesian Belief Networks to Investigate Farmer Behavior and Policy Interventions for Improved Nitrogen Management.

Increasing farmers' adoption of sustainable nitrogen management practices is crucial for improving water quality. Yet, research to date provides ambiguous results about the most important farmer-level drivers of adoption, leaving high levels of uncertainty as to how to design policy interventions that are effective in motivating adoption. Among others, farmers' engagement in outreach or educational events is considered a promising leverage point for policy measures.

Packaging contests between viral RNA molecules and kinetic selectivity.

The paper presents a statistical-mechanics model for the kinetic selection of viral RNA molecules by packaging signals during the nucleation stage of the assembly of small RNA viruses. The effects of the RNA secondary structure and folding geometry of the packaging signals on the assembly activation energy barrier are encoded by a pair of characteristics: the wrapping number and the maximum ladder distance. Kinetic selection is found to be optimal when assembly takes place under conditions of supersaturation and also when the concentration ratio of capsid protein and viral RNA concentrations equals the stoichiometric ratio of assembled viral particles.

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

Purpose: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line.

Patients And Methods: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts.

Autophagy in host stromal fibroblasts supports tumor desmoplasia.

Growing evidence demonstrates that macroautophagy/autophagy in the host stroma influences the tumor microenvironment. We have uncovered that autophagy in host stromal fibroblasts is compulsory to initiate and maintain the desmoplastic fibrotic response that fosters mammary tumor progression. Genetic loss of fibroblast autophagy impedes COL1A/type 1 collagen secretion, which is required for the development of a stiff tissue matrix permissive for mammary tumor growth.

Autophagy in stromal fibroblasts promotes tumor desmoplasia and mammary tumorigenesis.

Autophagy inhibitors are currently being evaluated in clinical trials for the treatment of diverse cancers, largely due to their ability to impede tumor cell survival and metabolic adaptation. More recently, there is growing interest in whether and how modulating autophagy in the host stroma influences tumorigenesis. Fibroblasts play prominent roles in cancer initiation and progression, including depositing type 1 collagen and other extracellular matrix (ECM) components, thereby stiffening the surrounding tissue to enhance tumor cell proliferation and survival, as well as secreting cytokines that modulate angiogenesis and the immune microenvironment.

EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas.

Context: Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior.

Objective: We evaluated lapatinib, an ErbB1-epidermal growth factor receptor (EGFR)/ErbB2 or human EGFR2 (HER2) tyrosine kinase inhibitor (TKI), in aggressive prolactinomas.

A phase I trial of surgical resection with Gliadel Wafer placement followed by vaccination with dendritic cells pulsed with tumor lysate for patients with malignant glioma.

High grade gliomas are associated with poor prognosis and high mortality. Conventional treatments and management of high grade gliomas have shown little improvement in 5-year overall survival. This phase I trial evaluated the safety, immunogenicity, and potential synergy of surgical resection with Gliadel Wafer implantation, followed by autologous tumor lysate-pulsed dendritic cell (DC) vaccine in patients with malignant glioma.

Invariant theory and orientational phase transitions.

The Landau theory of phase transitions has been productively applied to phase transitions that involve rotational symmetry breaking, such as the transition from an isotropic fluid to a nematic liquid crystal. It even can be applied to the orientational symmetry breaking of simple atomic or molecular clusters that are not true phase transitions. In this paper, we address fundamental problems that arise with the Landau theory when it is applied to rotational symmetry breaking transitions of more complex particle clusters that involve order parameters characterized by larger values of the l index of the dominant spherical harmonic that describes the broken symmetry state.

Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial.

Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application is limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated by an oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection of recurrent high-grade glioma.

Kirigami and the Caspar-Klug construction for viral shells with negative Gauss curvature.

In this work we extend the Caspar-Klug construction to the archaeal viruses, which in recent years have captured the attention of many researchers for their ability to thrive in extreme environments. We assume that the shells of archaeal viruses are composed of hexamers and pentamers-as is true for icosahedral viruses-together with heptamers, necessary to introduce negative Gauss curvature. Following the original work of Caspar and Klug, we first construct models capable of reproducing the shape observed in electron microscopy images of archaeal viruses.

Blockade of a Laminin-411-Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk.

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (α4β1γ1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc.

Profiles of brain metastases: Prioritization of therapeutic targets.

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors.

Smectic viral capsids and the aneurysm instability.

The capsids of certain Archaea-infecting viruses undergo large shape changes, while maintaining their integrity against rupture by osmotic pressure. We propose that these capsids are in a smectic liquid crystalline state, with the capsid proteins assembling along spirals. We show that smectic capsids are intrinsically stabilized against the formation of localized bulges with non-zero Gauss curvature while still allowing for large-scale cooperative shape transformation that involves global changes in the Gauss curvature.

Ground state instabilities of protein shells are eliminated by buckling.

We propose a hybrid discrete-continuum model to study the ground state of protein shells. The model allows for shape transformation of the shell and buckling transitions as well as the competition between states with different symmetries that characterize discrete particle models with radial pair potentials. Our main results are as follows.

Nonregenerative immune-mediated anemia associated with a diffuse large B-cell lymphoma in a captive jaguar (Panthera onca).

An 18-year-old male castrated jaguar (Panthera onca) was presented with anorexia and continuous bleeding from the oral cavity after a history of fighting with the partner animal. Clinical evaluation revealed ulcerating lesions on the gingiva and hard palate and a hematoma on the tongue. Computed tomography of the head and endoscopic examination of the esophagus and stomach were unremarkable.

Manipulation and amplification of the Casimir force through surface fields using helicity.

We present both exact and numerical results for the behavior of the Casimir force in O(n) systems with a finite extension L in one direction when the system is subjected to surface fields that induce helicity in the order parameter. We show that for such systems, the Casimir force in certain temperature ranges is of the order of L^{-2}, both above and below the critical temperature, T_{c}, of the bulk system. An example of such a system would be one with chemically modulated bounding surfaces, in which the modulation couples directly to the system's order parameter.

Intravascular T-cell lymphoma in a patas monkey ().

A 9-year-old female captive patas monkey () presented with poor general condition, inability to stand, petechiae, anaemia, thrombocytopenia, and leukocytosis. Due to poor response to treatment, the animal was euthanized 16 days later. Postmortem examination revealed hemorrhages in several organs and bilateral cerebral infarctions.