Active/Transfer Learning with Medical Imaging

We\u27ve developed a robust web application to assist researchers in improving the accuracy of their Machine Learning Models. The system provides an image labeling web interface so that researchers can label and classify the models, and multiple data visualizations that help researchers identify and resolve inconsistencies between the classifications determined by their models and user feedback

Achieving Minimum Coverage Breach under Bandwidth Constraints in Wireless Sensor Networks

This paper addresses the coverage breach problem in wireless sensor networks with limited bandwidths. In wireless sensor networks, sensor nodes are powered by batteries. To make efficient use of battery energy is critical to sensor network lifetimes. When targets are redundantly covered by multiple sensors, especially in stochastically deployed sensor networks, it is possible to save battery energy by organizing sensors into mutually exclusive subsets and alternatively activating only one subset at any time. Active nodes are responsible for sensing, computing and communicating. While the coverage of each subset is an important metric for sensor organization, the size of each subset also plays an important role in sensor network performance because when active sensors periodically send data to base stations, contention for channel access must be considered. The number of available channels imposes a limit on the cardinality of each subset. Coverage breach happens when a subset of sensors cannot completely cover all the targets. To make efficient use of both energy and bandwidth with a minimum coverage breach is the goal of sensor network design. This paper presents the minimum breach problem using a mathematical model, studies the computational complexity of the problem, and provides two approximate heuristics. Effects of increasing the number of channels and increasing the number of sensors on sensor network coverage are studied through numerical simulations. Overall, the simulation results reveal that when the number of sensors increases, network lifetimes can be improved without loss of network coverage if there is no bandwidth constraint; with bandwidth constraints, network lifetimes may be improved further at the cost of coverage breach

Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.

Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets

Analysis of nucleosome positioning landscapes enables gene discovery in the human malaria parasite Plasmodium falciparum.

BackgroundPlasmodium falciparum, the deadliest malaria-causing parasite, has an extremely AT-rich (80.7 %) genome. Because of high AT-content, sequence-based annotation of genes and functional elements remains challenging. In order to better understand the regulatory network controlling gene expression in the parasite, a more complete genome annotation as well as analysis tools adapted for AT-rich genomes are needed. Recent studies on genome-wide nucleosome positioning in eukaryotes have shown that nucleosome landscapes exhibit regular characteristic patterns at the 5'- and 3'-end of protein and non-protein coding genes. In addition, nucleosome depleted regions can be found near transcription start sites. These unique nucleosome landscape patterns may be exploited for the identification of novel genes. In this paper, we propose a computational approach to discover novel putative genes based exclusively on nucleosome positioning data in the AT-rich genome of P. falciparum.ResultsUsing binary classifiers trained on nucleosome landscapes at the gene boundaries from two independent nucleosome positioning data sets, we were able to detect a total of 231 regions containing putative genes in the genome of Plasmodium falciparum, of which 67 highly confident genes were found in both data sets. Eighty-eight of these 231 newly predicted genes exhibited transcription signal in RNA-Seq data, indicative of active transcription. In addition, 20 out of 21 selected gene candidates were further validated by RT-PCR, and 28 out of the 231 genes showed significant matches using BLASTN against an expressed sequence tag (EST) database. Furthermore, 108 (47%) out of the 231 putative novel genes overlapped with previously identified but unannotated long non-coding RNAs. Collectively, these results provide experimental validation for 163 predicted genes (70.6%). Finally, 73 out of 231 genes were found to be potentially translated based on their signal in polysome-associated RNA-Seq representing transcripts that are actively being translated.ConclusionOur results clearly indicate that nucleosome positioning data contains sufficient information for novel gene discovery. As distinct nucleosome landscapes around genes are found in many other eukaryotic organisms, this methodology could be used to characterize the transcriptome of any organism, especially when coupled with other DNA-based gene finding and experimental methods (e.g., RNA-Seq)

The contribution of Alu exons to the human proteome.

BackgroundAlu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins.ResultsWe adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products.ConclusionsOur data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution

Fully Printed, Flexible, Phased Array Antenna for Lunar Surface Communication

NASAs future exploration missions focus on the manned exploration of the Moon, Mars, and beyond, which will rely heavily on the development of a reliable communications infrastructure from planetary surface-to-surface, surface-to-orbit, and back to Earth. Flexible antennas are highly desired in many scenarios. Active phased array antennas (active PAAs) with distributed control and processing electronics at the surface of an antenna aperture offer numerous advantages for radar communications. Large-area active PAAs on flexible substrates are of particular interest in NASA s space radars due to their efficient inflatable package that can be rolled up during transportation and deployed in space. Such an inflatable package significantly reduces stowage volume and mass. Because of these performance and packaging advantages, large-area inflatable active PAAs are highly desired in NASA s surface-to-orbit and surface-to-relay communications. To address the issues of flexible electronics, a room-temperature printing process of active phased-array antennas on a flexible Kapton substrate was developed. Field effect transistors (FETs) based on carbon nanotubes (CNTs), with many unique physical properties, were successfully proved feasible for the PAA system. This innovation is a new type of fully inkjet-printable, two-dimensional, high-frequency PAA on a flexible substrate at room temperature. The designed electronic circuit components, such as the FET switches in the phase shifter, metal interconnection lines, microstrip transmission lines, etc., are all printed using a special inkjet printer. Using the developed technology, entire 1x4, 2x2, and 4x4 PAA systems were developed, packaged, and demonstrated at 5.3 GHz. Several key solutions are addressed in this work to solve the fabrication issues. The source/drain contact is developed using droplets of silver ink printed on the source/drain areas prior to applying CNT thin-film. The wet silver ink droplets allow the silver to wet the CNT thin-film area and enable good contact with the source and drain contact after annealing. A passivation layer to protect the device channel is developed by bonding a thin Kapton film on top of the device channel. This film is also used as the media for transferring the aligned CNT thin-film on the device substrate. A simple and cost-effective technique to form multilayer metal interconnections on flexible substrate is developed and demonstrated. Contact vias are formed on the second substrate prior to bonding on the first substrate. Inkjet printing is used to fill the silver ink into the via structure. The printed silver ink penetrates through the vias to contact with the contact pads on the bottom layer. It is then annealed to form a good connection. One-dimensional and two-dimensional PAAs were fabricated and characterized. In these circuits, multilayer metal interconnects were used to make a complete PAA system

<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle

Fatty Liver Education Promotes Physical Activity in Vulnerable Groups, Including Those With Unhealthy Alcohol Use

Background and aimsFatty liver disease (FLD), alcohol-associated and metabolically associated, often coexists. Increase in physical activity is associated with metabolic health and decreased FLD. We aimed to identify factors associated with physical activity and its improvement following FLD education in a racially diverse, vulnerable population.MethodsFrom February 19, 2020 to December 30, 2022, 314 adults with FLD at safety-net hepatology clinics in San Francisco were surveyed at baseline, immediately after FLD education, and at 6-month follow-up. After collecting clinical and sociodemographic data, logistic regression (adjusted for age, sex, and race/ethnicity) assessed factors associated with physical activity at baseline and its improvement following education.ResultsParticipant characteristics in those without vs with any physical activity were median age 49 vs 55 years, 64% vs 56% female, 66% vs 53% Hispanic race/ethnicity, 75% vs 55% obese, and 30% vs 22% consumed heavy alcohol, respectively. On multivariable analysis, older age was the only significant factor associated with physical activity at baseline (relative risk ratio 1.37 per decade increase, 95% confidence interval [CI] 1.07-1.75). Hispanic (vs non-Hispanic) participants had a significantly higher odds of improvement in physical activity (vs no change) 6 months after education (odds ratio 2.36, 95% CI 1.27-4.39). Among those with suboptimal or no physical activity at baseline, participants who consumed heavy alcohol (vs no drinking) had a significantly higher likelihood of achieving optimal physical activity following education (relative risk ratio 1.98, 95% CI 1.05-3.74).ConclusionDespite social and structural barriers, FLD education increased uptake of physical activity in vulnerable populations, especially among Hispanic individuals and those consuming heavy alcohol. Implementation of patient-centered education is important for FLD management

Bifurcation analysis and optical soliton perturbation with Radhakrishnan–Kundu–Lakshmanan equation

This paper addresses RadhakrishnanâKunduâLakshmanan equation that arises in the study of soliton dynamics in optical fibers. The bifurcation analysis is carried out and the phase portraits are displayed. The complete discriminant analysis also leads to solitons and other solutions to the model

Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug ratio (P &amp;lt; 0.001). Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects.Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically.Keywords: repeated focused ultrasound, interleukin-4 receptor, blood-brain barrier, brain tumor, target drug deliver