Growth processes of snow

Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Meteorology and Physical Oceanography, 1983.Microfiche copy available in Archives and Science.Vita.Bibliography: leaves 189-192.by Kwok-Wai Kenneth Lo.Sc.D

Multi-Scale Attention-based Multiple Instance Learning for Classification of Multi-Gigapixel Histology Images

Histology images with multi-gigapixel of resolution yield rich information for cancer diagnosis and prognosis. Most of the time, only slide-level label is available because pixel-wise annotation is labour intensive task. In this paper, we propose a deep learning pipeline for classification in histology images. Using multiple instance learning, we attempt to predict the latent membrane protein 1 (LMP1) status of nasopharyngeal carcinoma (NPC) based on haematoxylin and eosin-stain (H&E) histology images. We utilised attention mechanism with residual connection for our aggregation layers. In our 3-fold cross-validation experiment, we achieved average accuracy, AUC and F1-score 0.936, 0.995 and 0.862, respectively. This method also allows us to examine the model interpretability by visualising attention scores. To the best of our knowledge, this is the first attempt to predict LMP1 status on NPC using deep learning

Discordance between lung function of Chinese university students of 20-year-old established norms

Objective: We examined the validity of the 20-year-old established Asian norms for pulmonary function in a contemporary cohort of Hong Kong Chinese university students. Design and participants: Pulmonary function testing was conducted in university students (n = 805). Setting: A university campus in Hong Kong. Measurements and results: Parameters recorded included gender, age, height, weight, standard lung function variables (ie, FEV1, FVC, and peak expiratory flow rate [PEFR]), and exhaled carbon monoxide (CO) level. Subjects completed a questionnaire on pulmonary health, smoking history, and their dietary and exercise habits within 3 months of the study. Data were compared with the established norms for lung function for Chinese persons from Hong Kong. On average, subjects were taller than those reported in the original cohort, on whom the established norms are based; however, FEV1, FVC, and PEFR were lower. As predicted, the exhaled CO level was higher in smokers. Those who exercised regularly had a higher FEV1 and FVC, and reported fewer respiratory complaints. Conclusions: Our findings support the idea that lung function norms not only differ across ethnic groups, but that they may be susceptible to change over a single generation within an ethnic group living in the same geographic region. Assuming the equivalence of our testing methods and those on which established norms are based, our findings shed further insight into the dynamic nature of lung function, and have implications regarding the definition of normal pulmonary function and its variance over the short term. <br /

Comparative transcriptomics of multidrug-resistant Acinetobacter baumannii in response to antibiotic treatments

Abstract Multidrug-resistant Acinetobacter baumannii, a major hospital-acquired pathogen, is a serious health threat and poses a great challenge to healthcare providers. Although there have been many genomic studies on the evolution and antibiotic resistance of this species, there have been very limited transcriptome studies on its responses to antibiotics. We conducted a comparative transcriptomic study on 12 strains with different growth rates and antibiotic resistance profiles, including 3 fast-growing pan-drug-resistant strains, under separate treatment with 3 antibiotics, namely amikacin, imipenem, and meropenem. We performed deep sequencing using a strand-specific RNA-sequencing protocol, and used de novo transcriptome assembly to analyze gene expression in the form of polycistronic transcripts. Our results indicated that genes associated with transposable elements generally showed higher levels of expression under antibiotic-treated conditions, and many of these transposon-associated genes have previously been linked to drug resistance. Using co-expressed transposon genes as markers, we further identified and experimentally validated two novel genes of which overexpression conferred significant increases in amikacin resistance. To the best of our knowledge, this study represents the first comparative transcriptomic analysis of multidrug-resistant A. baumannii under different antibiotic treatments, and revealed a new relationship between transposons and antibiotic resistance

Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK

AbstractThe hepatocyte growth factor (HGF) receptor, Met, is frequently overexpressed in nasopharyngeal cancer (NPC). Here, we showed for the first time that human NPC cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. The downregulation of Met by small interfering RNA decreased tumor cell invasion/migration. HGF significantly increased matrix metalloproteinase-9 production. This was inhibited by blocking phosphatidylinositide 3-kinase (PI3K) and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways. We also demonstrated that PI3K induced activation of JNK, with Akt as a potential point of this cross-talk. These results provide new insights into the molecular mechanism responsible for NPC progression and metastasis

Unidirectional Microwave Transduction with Chirality Selected Short-Wavelength Magnon Excitations

Nonreciprocal magnon propagation has recently become a highly potential approach of developing chip-embedded microwave isolators for advanced information processing. However, it is challenging to achieve large nonreciprocity in miniaturized magnetic thin-film devices because of the difficulty of distinguishing propagating surface spin waves along the opposite directions when the film thickness is small. In this work, we experimentally realize unidirectional microwave transduction with sub-micron-wavelength propagating magnons in a yttrium iron garnet (YIG) thin film delay line. We achieve a non-decaying isolation of 30 dB with a broad field-tunable band-pass frequency range up to 14 GHz. The large isolation is due to the selection of chiral magnetostatic surface spin waves with the Oersted field generated from the coplanar waveguide antenna. Increasing the geometry ratio between the antenna width and YIG thickness drastically reduces the nonreciprocity and introduces additional magnon transmission bands. Our results pave the way for on-chip microwave isolation and tunable delay line with short-wavelength magnonic excitations.Comment: 6 pages, 4 figure

Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)

<p>Abstract</p> <p>Background</p> <p>Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable.</p> <p>Methods</p> <p>The preparation of novel polyethylene glycol (PEG) derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1). rhArg1 expressed in <it>Escherichia coli </it>was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo.</p> <p>Results</p> <p>Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000) coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg_{5,000 mw}) had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC) cell lines. It was considerably more effective than 4 other pegylated conjugates prepared.</p> <p>Conclusion</p> <p>Valuable data on the optimization of the pegylation procedure and choice of ligand that best stabilizes the enzyme arginase 1 are presented, a protocol that should equally fit many other enzymes and proteins. It is a long lasting arginine-depleting enzyme in vivo which will greatly improve its use in anti-cancer therapy.</p

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.</p