Alex Chen

World Wide Web (Web) documents, once delivered in a form that remained constant whilst viewed, are now often dynamic, with sections of a page able to change independently (and not requiring a full page reload), either automatically or as a result of user interaction. In order ...

Molecular descriptors and fingerprints have been routinely used in QSAR/SAR analysis, virtual drug screening, compound search/ranking, drug ADME/T prediction and other drug discovery processes. Since the calculation of such quantitative representations of molecules may require substantial computational skills and efforts, several tools have been previously developed to make an attempt to ease the process. However, there are still several hurdles for users to overcome to fully harness the power of these tools. First, most of the tools are distributed as standalone software or packages that require necessary configuration or programming efforts of users. Second, many of the tools can only calculate a subset of molecular descriptors, and the results from multiple tools need to be manually merged to generate a comprehensive set of descriptors. Third, some packages only provide application programming interfaces and are implemented in different computer languages, which pose additional c...

In Washington, DC, the vast majority of children have health insurance. Yet District children often lack sufficient access to medical care and face significant health threats from chronic conditions and risk factors such as exposure to violence in schools and neighborhoods. ...

Immunoglobulin G (IgG) antibodies that trap viruses in cervicovaginal mucus (CVM) via adhesive interactions between IgG-Fc and mucins have recently emerged as a promising strategy to block vaginally transmitted infections. The array of IgG bound to a virus particle appears to trap the virus by making multiple weak affinity bonds to the fibrous mucins that form the mucus gel. However, the antibody characteristics that maximize virus trapping and minimize viral infectivity remain poorly understood. Toward this goal, we developed a mathematical model that takes into account physiologically relevant spatial dimensions and time scales, binding, and unbinding rates between IgG and virions and between IgG and mucins, as well as the respective diffusivities of virions and IgG in semen and CVM. We then systematically explored the IgG-antigen and IgG-mucin binding and unbinding rates that minimize the flux of infectious HIV arriving at the vaginal epithelium. Surprisingly, contrary to common intuition that infectivity would drop monotonically with increasing affinities between IgG and HIV, and between IgG and mucins, our model suggests maximal trapping of HIV and minimal flux of HIV to the epithelium are achieved with IgG molecules that exhibit (i) rapid antigen binding (high k on) rather than very slow unbinding (low k off), that is, high-affinity binding to the virion, and (ii) relatively weak affinity with mucins. These results provide important insights into the design of more potent "mucotrapping" IgG for enhanced protection against vaginally transmitted infections. The model is adaptable to other pathogens, mucosal barriers, geometries, and kinetic and diffusional effects, providing a tool for hypothesis testing and producing quantitative insights into the dynamics of immune-mediated protection.

Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging. In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14(C)-L-arginine to 14(C)-L-citrulline. Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant pos...

Knowing the binding strength between a drug and its target is a key factor in determining the effectiveness of a drug. Electrospray ionization-mass spectrometry (ESI- MS), a highly sensitive analytical tool, can be used to study drug-target binding. Coupled with flow injection analysis (FIA), ESI-MS binding determinations can be performed faster and more precisely than traditional techniques. Yet, the ESI process can perturb solution binding and introduce error into the measurement. Consequently, a continuously stirred tank reactor (CSTR) arrangement was developed to address this limitation. As a FIA device, the CSTR produces a consistent exponential decay of analyte concentration from a single sample injection. Several experiments are needed to characterize the CSTR before it can be used for ESI-MS binding determinations. First, algorithms describing the analyte independent nature of exponential decay under constant flow rate conditions were validated in a single phase device. Next...

This paper focuses on the relationship between acoustic attenuation and solid content in a liquid carrier. Using such a relationship, two techniques were discussed to enable precise measurements for different concentrations of Kaolin in water. The first technique uses the fast-Fourier-transform (FFT) amplitude, while the second technique uses the attenuation coefficient's gradient to discriminate the different concentrations. In the past,

Secretory immunoglobulin A (sIgA), a dimeric antibody found in high quantities in the gastrointestinal mucosa, is broadly associated with mucosal immune protection. A distinguishing feature of sIgA is its ability to crosslink pathogens, thereby creating pathogen/sIgA aggregates that are too large to traverse the dense matrix of mucin fibers in mucus layers overlying epithelial cells and consequently reducing infectivity. Here, we use modeling to investigate this mechanism of "immune exclusion" based on sIgA-mediated agglutination, in particular the potential use of sIgA to agglutinate HIV in cervicovaginal mucus (CVM) and prevent HIV transmission. Utilizing reported data on HIV diffusion in CVM and semen, we simulate HIV collision kinetics in physiologically-thick mucus layers-a necessary first step for sIgA-induced aggregation. We find that even at the median HIV load in semen of acutely infected individuals possessing high viral titers, over 99% of HIV virions will penet...

In our current food supply, sugar substitutes are widely used in beverages and other food products. However, there is limited information about the link between dietary consumption of sugar substitutes and stroke to date. This study sought to determine the effect of various sugar substitutes on the cerebral ischemic injury and endothelial progenitor cells, which have been implicated to play an important role in vascular repair and revascularization in ischemic brain tissues, in mice. After treatment with sucrose and various sugar substitutes (the doses are in the range of corresponding acceptable daily intake levels) and vehicle for 6 weeks, mice were subjected to permanent left middle cerebral artery occlusion, and the infarct volumes, angiogenesis, and neurobehavioral outcomes were determined. In addition, the number and function of endothelial progenitor cells were also examined. After long-term treatment with fructose, erythritol (sugar alcohols), acesulfame K (artificial sweete...

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of wal...

Parkinson's disease (PD) is the most common motor neurodegenerative disorder. Olfactory dysfunction is a prevalent feature of PD. It often precedes motor symptoms by several years and is used in assisting PD diagnosis. However, the cellular and molecular bases of olfactory dysfunction in PD are not known. The fruit fly Drosophila melanogaster, expressing human alpha-synuclein protein or its mutant, A30P, captures several hallmarks of PD and has been successfully used to model PD in numerous studies. First, we report olfactory deficits in fly expressing A30P (A30P), showing deficits in two out of three olfactory modalities, tested--olfactory acuity and odor discrimination. The remaining third modality is odor identification/naming. Second, oxidative stress is an important environmental risk factor of PD. We show that oxidative stress exacerbated the two affected olfactory modalities in younger A30P flies. Third, different olfactory receptor neurons are activated differentially by...

Eliciting broadly neutralizing antibodies (bnAb) in cervicovaginal mucus (CVM) represents a promising "first line of defense" strategy to reduce vaginal HIV transmission. However, it remains unclear what levels of bnAb must be present in CVM to effectively reduce infection. We approached this complex question by modeling the dynamic tally of bnAb coverage on HIV. This analysis introduces a critical, timescale-dependent competition: to protect, bnAb must accumulate at sufficient stoichiometry to neutralize HIV faster than virions penetrate CVM and reach target cells. We developed a model that incorporates concentrations and diffusivities of HIV and bnAb in semen and CVM, kinetic rates for binding (kon) and unbinding (koff) of select bnAb, and physiologically relevant thicknesses of CVM and semen layers. Comprehensive model simulations lead to robust conclusions about neutralization kinetics in CVM. First, due to the limited time virions in semen need to penetrate CVM, subst...

In chemoinformatics and bioinformatics fields, one of the main computational challenges in various predictive modeling is to find a suitable way to effectively represent the molecules under investigation, such as small molecules, proteins and even complex interactions. To solve this problem, we developed a freely available R/Bioconductor package, called Compound-Protein Interaction with R (Rcpi), for complex molecular representation from drugs, proteins and more complex interactions, including protein-protein and compound-protein interactions. Rcpi could calculate a large number of structural and physicochemical features of proteins and peptides from amino acid sequences, molecular descriptors of small molecules from their topology and protein-protein interaction and compound-protein interaction descriptors. In addition to main functionalities, Rcpi could also provide a number of useful auxiliary utilities to facilitate the user's need. With the descriptors calculated by this pa...

Given the difficulty in finding a cure for HIV/AIDS, a promising prevention strategy to reduce HIV transmission is to directly block infection at the portal of entry. The recent Thai RV144 trial offered the first evidence that an antibody-based vaccine may block heterosexual HIV transmission. Unfortunately, the underlying mechanism(s) for protection remain unclear. Here we theoretically examine a hypothesis that builds on our recent laboratory observation: virus-specific antibodies (Ab) can trap individual virions in cervicovaginal mucus (CVM), thereby reducing infection in vivo. Ab are known to have a weak-previously considered inconsequential-binding affinity with the mucin fibers that constitute CVM. However, multiple Ab can bind to the same virion at the same time, which markedly increases the overall Ab-mucin binding avidity, and creates an inheritable virion-mucin affinity. Our model takes into account biologically relevant length and timescales, while incorporating known HIV-Ab affinity and the respective diffusivities of viruses and Ab in semen and CVM. The model predicts that HIV-specific Ab in CVM leads to rapid formation and persistence of an HIV concentration front near the semen/CVM interface, far from the vaginal epithelium. Such an HIV concentration front minimizes the flux of HIV virions reaching target cells, and maximizes their elimination upon drainage of genital secretions. The robustness of the result implies that even exceedingly weak Ab-mucin affinity can markedly reduce the flux of virions reaching target cells. Beyond this specific application, the model developed here is adaptable to other pathogens, mucosal barriers, and geometries, as well as kinetic and diffusional effects, providing a tool for hypothesis testing and producing quantitative insights into the dynamics of immune-mediated protection.

ABSTRACT This paper starts by establishing a list of the main physical and empirical laws that have been proposed for modeling landscape evolution. Then it proposes a detailed mathematical discussion of several classic landscape evolution models. This discussion permits to distinguish a priori laws from a posteriori laws governing landscape evolution. While the first kind of law relies on physical principles, the second kind stems from the observation of actual stable landscapes. It emerges from the analysis of several models that the a posteriori laws are often used to create hybrid models combining fundamental physical laws with empirical modeling. Such models can be valid near equilibrium. Nevertheless, this situation is not satisfactory from a mathematical standpoint. One would like to be able to deduce the a posteriori laws from a mathematical analysis, or at the very least to observe them from numerical simulations using only a priori physical laws. Such a mathematical and numerical research programme is sketched here. We propose a minimal landscape model coping with the main features of all models. This model singles out three spatially distributed scalar state variables, namely the landscape elevation, the water elevation, and the sediment concentration in water. These state variables are linked by three partial differential equations coping with the three main features identified in the literature as the main phenomena shaping a landscape: erosion, sedimentation and creep, and respecting conservation laws for water and sediment. Based on these equations, the first numerical simulations confirm that valley formation and drainage network formation can be simulated on virgin artificial landscapes. A first surprising result seems to emerge from these simulations: the valley spacing depends not only on a relation between the creep and erosion parameters, but is also strongly influenced by the sedimentation rate and by the rainfall intensity. The conjectured mathematical instability and non-uniqueness of landscape evolution is illustrated numerically. On the other hand numerical stability of real landscape topographies under realistic values for their evolution is also observed. The overall modeling and numerical tests suggest that existence and partial regularity results might be obtained under minimal assumptions (such as a positive rain density or a positive creep model).

1. ABSTRACT The JPL-led CSP Consortium of enterprises representing government agencies and private companies has joined together to pool in-kind resources for developing the quality and reliability of chip scale packages (CSPs) for a variety of projects. Since last year, more than 150 test vehicles, single- and double-sided, have been assembled and are presently being subjected to various environmental tests.

... Sherif Galal, Hui Zheng, Khaled Abdelfattah, Vinay Chandrasekhar, Iuri Mehr, ... 7. ACKNOWLEDGMENT The authors would like to thank Choon Fewn Tiong and Boonma Ruchirojampai for Layout help and Edison Jiang for Lab testing and characterization. ...

The purpose of this work was to report dosimetric experience with 2 kinds of multilumen balloon (MLB), 5-lumen Contura MLB (C-MLB) and 4-lumen MammoSite MLB (MS-MLB), to deliver accelerated partial-breast irradiation, and compare the ability to achieve target coverage and control skin and rib doses between 2 groups of patients treated with C-MLB and MS-MLB brachytherapy. C-MLB has 5 lumens, the 4 equal-spaced peripheral lumens are 5mm away from the central lumen. MS-MLB has 4 lumens, the 3 equal-spaced peripheral lumens are 3mm away from the central lumen. In total, 43 patients were treated, 23 with C-MLB, and 20 with MS-MLB. For C-MLB group, 8 patients were treated with a skin spacing < 7mm and 12 patients with rib spacing < 7mm. For MS-MLB group, 2 patients were treated with a skin spacing < 7mm and 5 patients with rib spacing < 7mm. The dosimetric goals were (1) ≥ 95% of the prescription dose (PD) covering ≥ 95% of the target volume (V95% ≥ 95%), (2) maximum skin dose...

ABSTRACT Recently, much work has been performed on CBIR (content based image retrieval) that treats images as single data domain. However, in our highly digitized society, information is being supplied in multiple domains where the data is linked across domains. For example, a web site does contain images, but it may also contain text, hyperlinks, documents, sound files, movies, and other domains of data. Performing recall operations within single domains eliminates the possibility of employing cross-domain inferences. In this work, a multi-domain search space is presented in with two domains: speech and facial images. A single search space is created that contains data from these vastly different domains and cross-domain inferences are allowed. In other words, queries in the speech domain can retrieve image data even if there was no hard link between these data samples. Generation of multidomain search spaces will eventually expand CBIR systems to include data from a variety of sources.