Characterizing First Arrival Position Channels: Noise Distribution and Capacity Analysis

This paper addresses two fundamental problems in diffusive molecular communication: characterizing the first arrival position (FAP) density and bounding the information transmission capacity of FAP channels. Previous studies on FAP channel models, mostly captured by the density function of noise, have been limited to specific spatial dimensions, drift directions, and receiver geometries. In response, we propose a unified solution for identifying the FAP density in molecular communication systems with fully-absorbing receivers. Leveraging stochastic analysis tools, we derive a concise expression with universal applicability, covering any spatial dimension, drift direction, and receiver shape. We demonstrate that several existing FAP density formulas are special cases of this innovative expression. Concurrently, we establish explicit upper and lower bounds on the capacity of three-dimensional, vertically-drifted FAP channels, drawing inspiration from vector Gaussian interference channels. In the course of deriving these bounds, we unravel an explicit analytical expression for the characteristic function of vertically-drifted FAP noise distributions, providing a more compact characterization compared to the density function. Notably, this expression sheds light on a previously undiscovered weak stability property intrinsic to vertically-drifted FAP noise distributions.Comment: 30 pages; 3 figures, 1 table; this paper is submitted to IEEE Transactions on Communication

The Influence of Type 2 Diabetes and Glucose-Lowering Therapies on Cancer Risk in the Taiwanese

Objective. To investigate the association between type 2 diabetes, glucose-lowering therapies (monotherapy with either metformin, sulphonylurea or insulin) and cancer risk in Taiwan. Methods. Using Taiwan's National Health Research Institutes database of 1,000,000 random subjects from 2000–2008, we found 61777 patients with type 2 diabetes (age ≥20 years) and 677378 enrollees with no record of diabetes. Results. After adjusting for age and sex, we found patients with diabetes to have significantly higher risk of all cancers (OR: 1.176; 95% CI: 1.149–1.204, P < 0.001). Diabetic patients treated with insulin or sulfonylureas had significantly higher risk of all cancers, compared to those treated with metformin (OR: 1.583; 95% CI: 1.389–1.805, P < 0.001 and OR: 1.784; 95% CI: 1.406–2.262, P < 0.001). Metformin treatment was associated with a decreased risk of colon and liver cancer compared to sulphonylureas or insulin treatment. Sulfonylureas treatment was associated with an increased risk of breast and lung cancer compared to metformin therapy. Conclusions. Taiwanese with type 2 diabetes are at a high risk of breast, prostate, colon, lung, liver and pancreatic cancer. Those treated with insulin or sulfonylureas monotherapy are more likely to develop colon and liver cancer than those treated with metformin

Crystallization of Adenylylsulfate Reductase from Desulfovibrio gigas: A Strategy Based on Controlled Protein Oligomerization

Adenylylsulfate reductase (adenosine 5′-phosphosulfate reductase, APS reductase or APSR, E.C.1.8.99.2) catalyzes the conversion of APS to sulfite in dissimilatory sulfate reduction. APSR was isolated and purified directly from massive anaerobically grown Desulfovibrio gigas, a strict anaerobe, for structure and function investigation. Oligomerization of APSR to form dimers–α_2β_2, tetramers–α_4β_4, hexamers–α_6β_6, and larger oligomers was observed during purification of the protein. Dynamic light scattering and ultracentrifugation revealed that the addition of adenosine monophosphate (AMP) or adenosine 5′-phosphosulfate (APS) disrupts the oligomerization, indicating that AMP or APS binding to the APSR dissociates the inactive hexamers into functional dimers. Treatment of APSR with β-mercaptoethanol decreased the enzyme size from a hexamer to a dimer, probably by disrupting the disulfide Cys156—Cys162 toward the C-terminus of the β-subunit. Alignment of the APSR sequences from D. gigas and A. fulgidus revealed the largest differences in this region of the β-subunit, with the D. gigas APSR containing 16 additional amino acids with the Cys156—Cys162 disulfide. Studies in a pH gradient showed that the diameter of the APSR decreased progressively with acidic pH. To crystallize the APSR for structure determination, we optimized conditions to generate a homogeneous and stable form of APSR by combining dynamic light scattering, ultracentrifugation, and electron paramagnetic resonance methods to analyze the various oligomeric states of the enzyme in varied environments

A rare complication in a child undergoing chemotherapy for acute lymphoblastic leukemia: Superior sagittal sinus thrombosis

AbstractWe report the case of a 4-year-old boy with acute lymphoblastic leukemia in high-risk group who suffered from generalized tonic-colonic seizure evolving into status epilepticus, and subsequent left hemiparesis during his first reinduction chemotherapy, consisting of dexamethasone, vincristine, l-asparaginase, and epirubicin. Superior sagittal sinus and cerebral venous thrombosis, predominantly in right side, were proved by brain magnetic resonance imaging. After aggressive treatment with low-molecular weight heparin (LMWH), left hemiparesis improved in 1 week. And he was fully ambulatory 3 weeks later. The second cycle of reinduction chemotherapy was conducted smoothly with the concomitant use of LMWH. This case illustrates the strong correlation of the rare thrombotic complication, superior sagittal sinus thrombosis, and hypercoagulable status secondary to combination use of l-asparaginase and corticosteroid. Early and vigilant recognition of superior sagittal sinus thrombosis and prompt anticoagulation with LMWH may prevent further neurological damage

The role of nitric oxide in the outgrowth of trophoblast cells on human umbilical vein endothelial cells

AbstractObjectiveEmbryo implantation is a complex process that requires coordinated trophoblast–endometrial interactions. Previous studies demonstrated that the identification of nitric oxide synthase (NOS) in trophoblast cells and the remodeling of the implantation process by nitric oxide (NO) support the important role of NO during implantation. However, the role of NO in trophoblast–endometrial interactions is unclear and is therefore examined in this study.Materials and methodsWe cocultured BeWo trophoblast spheroids with human umbilical vein endothelial cell (HUVEC) monolayers to mimic the trophoblast–endometrial interaction. Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), a competitive inhibitor of NOS, and sodium nitroprusside (SNP), an NO donor, were used to test the role of NO in the trophoblast–endometrial interaction.Resultsl-NAME diminished spheroid expansion on HUVEC monolayers in a concentration-dependent manner (p < 0.05). However, trophoblast spreading on HUVEC-free culture surfaces was unaffected by l-NAME treatment (p > 0.05). Significant suppression of spheroid expansion was found at the higher dose (1mM) of SNP (p < 0.05).ConclusionNO may be needed in the process of implantation, and an adequate but not overly NO-containing environment might be an important factor for successful implantation. This finding is worthy of further investigation

Autophagy Inhibition Enhances Apoptosis Induced by Dioscin in Huh7 Cells

Extensive research results support the application of herbal medicine or natural food as an augment during therapy for various cancers. However, the effect of dioscin on tumor cells autophagy has not been clearly clarified. In this study, the unique effects of dioscin on autophagy of hepatoma cells were investigated. Results found that dioscin induced caspase-3- and -9-dependent cell apoptosis in a dose-dependent manner. Moreover, inhibition of ERK1/2 phosphorylation significantly abolished the dioscin-induced apoptosis. In addition, dioscin triggered cell autophagy in early stages. With autophagy inhibitors to hinder the autophagy process, dioscin-induced cell apoptosis was significantly enhanced. An inhibition of caspase activation did not affect the dioscin-induced LC3-II protein expression. Based on the results, we believed that while apoptosis was blocked, dioscin-induced autophagy process also diminished in Huh7 cells. In conclusion, this study indicates that dioscin causes autophagy in Huh7 cells and suggests that dioscin has a cytoprotective effect

GenEpi: gene-based epistasis discovery using machine learning.

BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P &lt; 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P &lt; 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis

The iNOS/Src/FAK axis is critical in Toll-like receptor-mediated cell motility in macrophages

AbstractThe Toll-like receptors (TLRs) play a pivotal role in innate immunity for the detection of highly conserved, pathogen-expressed molecules. Previously, we demonstrated that lipopolysaccharide (LPS, TLR4 ligand)-increased macrophage motility required the participation of Src and FAK, which was inducible nitric oxide synthase (iNOS)-dependent. To investigate whether this iNOS/Src/FAK pathway is a general mechanism for macrophages to mobilize in response to engagement of TLRs other than TLR4, peptidoglycan (PGN, TLR2 ligand), polyinosinic–polycytidylic acid (polyI:C, TLR3 ligand) and CpG-oligodeoxynucleotides (CpG, TLR9 ligand) were used to treat macrophages in this study. Like LPS stimulation, simultaneous increase of cell motility and Src (but not Fgr, Hck, and Lyn) was detected in RAW264.7, peritoneal macrophages, and bone marrow-derived macrophages exposed to PGN, polyI:C and CpG. Attenuation of Src suppressed PGN-, polyI:C-, and CpG-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by the reintroduction of siRNA-resistant Src. Besides, knockdown of FAK reduced the mobility of macrophages stimulated with anyone of these TLR ligands. Remarkably, PGN-, polyI:C-, and CpG-induced Src expression, FAK Pi-Tyr861, and cell mobility were inhibited in macrophages devoid of iNOS, indicating the importance of iNOS. These findings corroborate that iNOS/Src/FAK axis occupies a central role in macrophage locomotion in response to engagement of TLRs