Measuring the flow properties of small powder samples using an avalanche tester

The feasibility of using a small-scale avalanche tester to measure the flow properties of pharmaceutical lactose powders was examined. The modes of behavior observed in larger systems were displayed and showed a clear distinction between angular, free-flowing particles and more spherical particles of similar flow characteristics. Angular Lactohale LH100 particles showed slumping behavior at a rotational frequency of 0.33 Hz that disappeared at higher frequencies. Spherical lactose powder with a similar flow function to LH100 only showed rolling behavior under the same conditions, as did more cohesive powders LH200 and LH300. Further investigation of the LH100 data using fast Fourier analysis showed that the slumping frequency was one tenth of the rotational frequency

Superconducting-coil--resistor circuit with electric field quadratic in the current

It is shown for the first time that the observed [Phys. Lett. A 162 (1992) 105] potential difference Phi_t between the resistor and the screen surrounding the circuit is caused by polarization of the resistor because of the kinetic energy of the electrons of the superconducting coil. The proportionality of Phi_t to the square of the current and to the length of the superconducting wire is explained. It is pointed out that measuring Phi_t makes it possible to determine the Fermi quasimomentum of the electrons of a metal resistor.Comment: 2 pages, 1 figur

Measuring the flow properties of small powder samples using an avalanche tester

The feasibility of using a small-scale avalanche tester to measure the flow properties of pharmaceutical lactose powders was examined. The modes of behaviour observed in larger systems were displayed and showed a clear distinction between angular, free-flowing particles and more spherical particles of similar flow characteristics. Angular Lactohale LH100 particles showed slumping behaviour at a rotational frequency of 0.33Hz which disappeared at higher frequencies. Spherical lactose powder with a similar flow function to LH100 only showed rolling behaviour under the same conditions, as did more cohesive powders LH200 and LH300. Further investigation of the LH100 data using Fast Fourier analysis showed that the slumping frequency was 1/10th of the rotational frequency

Modular Clinical Decision Support Networks (MoDN)-Updatable, interpretable, and portable predictions for evolving clinical environments.

Clinical Decision Support Systems (CDSS) have the potential to improve and standardise care with probabilistic guidance. However, many CDSS deploy static, generic rule-based logic, resulting in inequitably distributed accuracy and inconsistent performance in evolving clinical environments. Data-driven models could resolve this issue by updating predictions according to the data collected. However, the size of data required necessitates collaborative learning from analogous CDSS's, which are often imperfectly interoperable (IIO) or unshareable. We propose Modular Clinical Decision Support Networks (MoDN) which allow flexible, privacy-preserving learning across IIO datasets, as well as being robust to the systematic missingness common to CDSS-derived data, while providing interpretable, continuous predictive feedback to the clinician. MoDN is a novel decision tree composed of feature-specific neural network modules that can be combined in any number or combination to make any number or combination of diagnostic predictions, updatable at each step of a consultation. The model is validated on a real-world CDSS-derived dataset, comprising 3,192 paediatric outpatients in Tanzania. MoDN significantly outperforms 'monolithic' baseline models (which take all features at once at the end of a consultation) with a mean macro F1 score across all diagnoses of 0.749 vs 0.651 for logistic regression and 0.620 for multilayer perceptron (p < 0.001). To test collaborative learning between IIO datasets, we create subsets with various percentages of feature overlap and port a MoDN model trained on one subset to another. Even with only 60% common features, fine-tuning a MoDN model on the new dataset or just making a composite model with MoDN modules matched the ideal scenario of sharing data in a perfectly interoperable setting. MoDN integrates into consultation logic by providing interpretable continuous feedback on the predictive potential of each question in a CDSS questionnaire. The modular design allows it to compartmentalise training updates to specific features and collaboratively learn between IIO datasets without sharing any data

Hall Coefficient of Equilibrium Supercurrents Flowing inside Superconductors

We study augmented quasiclassical equations of superconductivity with the Lorentz force, which is missing from the standard Ginzburg-Landau and Eilenberger equations. It is shown that the magnetic Lorentz force on equilibrium supercurrents induces finite charge distribution and the resulting electric field to balance the Lorentz force. An analytic expression is obtained for the corresponding Hall coefficient of clean type-II superconductors with simultaneously incorporating the Fermi-surface and gap anisotropies. It has the same sign and magnitude at zero temperature as the normal state for an arbitrary pairing, having no temperature dependence specifically for the s-wave pairing. The gap anisotropy may bring a considerable temperature dependence in the Hall coefficient and can lead to its sign change as a function of temperature, as exemplified for a model d-wave pairing with a two-dimensional Fermi surface. The sign change may be observed in some high-$T_{c}$ superconductors.Comment: 7 pages, 3 figure

Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction.

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19

Role of Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein K (gK) Pathogenic CD8+ T Cells in Exacerbation of Eye Disease

HSV-1-induced corneal scarring (CS), also broadly referred to as Herpes Stromal Keratitis (HSK), is the leading cause of infectious blindness in developed countries. It is well-established that HSK is in fact an immunopathological disease. The contribution of the potentially harmful T cell effectors that lead to CS remains an area of intense study. Although the HSV-1 gene(s) involved in eye disease is not yet known, we have demonstrated that gK, which is one of the 12 known HSV-1 glycoproteins, has a crucial role in CS. Immunization of HSV-1 infected mice with gK, but not with any other known HSV-1 glycoprotein, significantly exacerbates CS, and dermatitis. The gK-induced eye disease occurs independently of the strain of the virus or mouse. HSV-1 mutants that lack gK are unable to efficiently infect and establish latency in neurons. HSV-1 recombinant viruses expressing two additional copies of the gK (total of three gK genes) exacerbated CS as compared with wild type HSV-1 strain McKrae that contains one copy of gK. Furthermore, we have shown that an 8mer (ITAYGLVL) within the signal sequence of gK enhanced CS in ocularly infected BALB/c mice, C57BL/6 mice, and NZW rabbits. In HSV-infected “humanized” HLA-A*0201 transgenic mice, this gK 8mer induced strong IFN-γ-producing cytotoxic CD8+ T cell responses. gK induced CS is dependent on gK binding to signal peptide peptidase (SPP). gK also binds to HSV-1 UL20, while UL20 binds GODZ (DHHC3) and these quadruple interactions are required for gK induced pathology. Thus, potential therapies might include blocking of gK-SPP, gK-UL20, UL20-GODZ interactions, or a combination of these strategies

Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization

Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with alpha-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis

Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization

BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225)Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225)Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225)Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225)Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225)Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice