Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival

Purpose: We reported previously that ≥5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated. Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of ≥5 CTCs/7.5 mL at each blood draw. Results: Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with ≥5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with ≥5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different. Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
Data volume reduction in high-resolution wide-swath SAR systems

High-resolution wide-swath (HRWS) synthetic aperture radar (SAR) systems are very attractive for the observation of dynamic processes on the Earth's surface, but they are also associated with a huge data volume. In order to comply with azimuth ambiguity requirements, in fact, a pulse repetition frequency (PRF) much higher than the required processed Doppler bandwidth (PBW) is often desirable. The data volume can be drastically reduced, if on-board Doppler filtering and decimation are performed prior to downlink. A finite impulse response (FIR) filter with a relatively small number of taps suffices to suppress the additional ambiguous components and recover the original impulse response. This strategy is also applicable and especially relevant to staggered SAR systems, where on-board Doppler filtering and resampling can be jointly implemented.
Scalable large‐scale fluid–structure interaction solvers in the Uintah framework via hybrid task‐based parallelism algorithms

Uintah is a software framework that provides an environment for solving fluid–structure interaction problems on structured adaptive grids for large‐scale science and engineering problems involving the solution of partial differential equations. Uintah uses a combination of fluid flow solvers and particle‐based methods for solids, together with adaptive meshing and a novel asynchronous task‐based approach with fully automated load balancing. When applying Uintah to fluid–structure interaction problems, the combination of adaptive meshing and the movement of structures through space present a formidable challenge in terms of achieving scalability on large‐scale parallel computers. The Uintah approach to the growth of the number of core counts per socket together with the prospect of less memory per core is to adopt a model that uses MPI to communicate between nodes and a shared memory model on‐node so as to achieve scalability on large‐scale systems. For this approach to be successful, it is necessary to design data structures that large numbers of cores can simultaneously access without contention. This scalability challenge is addressed here for Uintah, by the development of new hybrid runtime and scheduling algorithms combined with novel lock‐free data structures, making it possible for Uintah to achieve excellent scalability for a challenging fluid–structure problem with mesh refinement on as many as 260K cores. Copyright © 2013 John Wiley & Sons, Ltd.
Connectivity effects on energy and area for neuromorphic system with high speed asynchronous pulse mode links

Hardware neuromorphic systems are challenged to achieve biologically realistic levels of interconnectivity. When building a physical implementation of a neural net, the properties of the media immediately impose limits on the number of interconnects and available timing options. The design of any system must consider the energy and area costs associated with the physical layout of neuron core connectivity, rst, by accepting the wiring limits imposed by Rent's rule and second, by understanding the temporal overhead introduced by routing. The presented results show the energyarea trade-o for a model of a neuromorphic system with event driven interconnections. The low area overhead of the asynchronous pulse-mode links create an attractive opportunity for a digital neuromorphic system with a connectivity model closer to the existing software models of neural nets.
An Automated Image-based Method for Multi-Leaf Collimator Positioning Verification in Intensity Modulated Radiation Therapy

Intensity Modulated Radiation Therapy (IMRT) is an innovative, three-dimensional conformal radiation treatment that can deliver highly focused and precisely shaped radiation to a tumor site through the use of the Multi-Leaf Collimators (MLC). A crucial step in IMRT procedure is the verification of MLC positioning to assure the accuracy of radiation treatment delivery. In this paper, we have developed an automated image based method for MLC positioning verification using images acquired from an Electronic Portable Imaging Device. The method consists of three major steps: 1) non-linear geometric distortion correction, 2) isocenter estimation, and 3) MLC leaf boundary recovery. Preliminary experiment on real image data shows that the proposed method is both fast and robust to image artifacts such as intensity inhomogeneity and noise, making it a promising approach for replacing manual verification of MLC in the IMRT treatment.
MIT Open Access

Phylogenetic tree reconciliation is a powerful approach for inferring evolutionary events like gene duplication, horizontal gene transfer, and gene loss, which are fundamental to our understanding of molecular evolution. While duplication–loss (DL) reconciliation leads to a unique maximum-parsimony solution, duplication-transfer-loss (DTL) reconciliation yields a multitude of optimal solutions, making it difﬁcult to infer the true evolutionary history of the gene family. This problem is further exacerbated by the fact that different event cost assignments yield different sets of optimal reconciliations. Here, we present an effective, efﬁcient, and scalable method for dealing with these fundamental problems in DTL rec-onciliation. Our approach works by sampling the space of optimal reconciliations uniformly at random and aggregating the results. We show that even gene trees with only a few dozen genes often have millions of optimal reconciliations and present an algorithm to efﬁciently sample the space of optimal reconciliations uniformly at random in O ( mn 2 ) time per sample, where m and n denote the number of genes and species, respectively. We use these samples to understand how different optimal reconciliations vary in their node mappings and event assignments and to investigate the impact of varying event costs. We apply our method to a biological dataset of approximately 4700 gene trees from 100 taxa and observe that 93% of event assignments and 73% of mappings remain consistent across different multiple optima. Our analysis represents the ﬁrst systematic investigation of the space of optimal DTL rec-onciliations and has many important implications for the study of gene family evolution.
Oxidative Stress and the Use of Antioxidants in Stroke

Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA). The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS) over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease.
Nanomaterials for intracellular fluorescence imaging and sensing

This thesis explores the use of nanomaterials for bioimaging using conjugated polymer nanoparticles (CPNs) and porous silicon nanoneedles (PSNs) for intracellular biosensing. CPNs have recently started being used in biomedical research due to their outstanding optical properties, such as large extinction coefficients and high fluorescence brightness. Several strategies have been developed to stabilise their surface and provide functional groups for subsequent biomolecule conjugation. Peptides are highly customisable molecules and possess several advantages when compared to other capping ligands. A one-pot synthesis and peptide functionalisation method for CPNs using peptide amphiphiles was developed and it was shown that the presence of the peptide amphiphile did not affect the advantageous optical properties of CPNs. By using peptide amphiphiles with different characteristics, it was possible to tailor the cellular uptake of peptide-CPNs, proving the bioactivity of these nanoparticles. Importantly, none of the used peptide-CPNs demonstrated cell cytotoxicity. Other conjugated polymer (CPs) were used to synthesise peptide-CPNs of different colours, demonstrating the versatility of this method. PSNs have been developed for probing the intracellular environment for delivery or sensing. Access to the cytoplasm of cells is difficult using other methods and therefore PSNs are a suitable candidate for a biocompatible and minimally invasive approach. PSNs were functionalised to a cathepsin B (CTSB) protease cleavable peptide with an imaging moiety
The Effect of Technology-Based Interventions on Pain, Depression, and Quality of Life in Patients With Cancer: A Systematic Review of Randomized Controlled Trials

Background The burden of cancer is increasing; projections over the next 2 decades suggest that the annual cases of cancer will rise from 14 million in 2012 to 22 million. However, cancer patients in the 21st century are living longer due to the availability of novel therapeutic regimens, which has prompted a growing focus on maintaining patients’ health-related quality of life. Telehealth is increasingly being used to connect with patients outside of traditional clinical settings, and early work has shown its importance in improving quality of life and other clinical outcomes in cancer care. Objective The aim of this study was to systematically assess the literature for the effect of supportive telehealth interventions on pain, depression, and quality of life in cancer patients via a systematic review of clinical trials. Methods We searched PubMed, EMBASE, Google Scholar, CINAHL, and PsycINFO in July 2013 and updated the literature search again in January 2015 for prospective randomized trials evaluating the effect of telehealth interventions in cancer care with pain, depression, and quality of life as main outcomes. Two of the authors independently reviewed and extracted data from eligible randomized controlled trials, based on pre-determined selection criteria. Methodological quality of studies was assessed by the Cochrane Collaboration risk of bias tool. Results Of the 4929 articles retrieved from databases and relevant bibliographies, a total of 20 RCTs were included in the final review. The studies were largely heterogeneous in the type and duration of the intervention as well as in outcome assessments. A majority of the studies were telephone-based interventions that remotely connected patients with their health care provider or health coach. The intervention times ranged from 1 week to 12 months. In general, most of the studies had low risk of bias across the domains of the Cochrane Collaboration risk of bias tool, but most of the studies had insufficient information about the allocation concealment domain. Two of the three studies focused on pain control reported significant effects of the intervention; four of the nine studies focus on depression reported significant effects, while only the studies that were focused on quality of life reported significant effects. Conclusions This systematic review demonstrates the potential of telehealth interventions in improving outcomes in cancer care. However, more high-quality large-sized trials are needed to demonstrate cogent evidence of its effectiveness.
Organic molecules with propeller structures for efficient photoacoustic imaging and photothermal ablation of cancer cells

Photoacoustic (PA) imaging has recently attracted great attention due to its noninvasive and nonionizing properties and high penetration depth. This technique is particularly attractive for sentinel lymph node (SLN) imaging, which is highly desirable during sentinel lymph node biopsy for the detection of breast cancer metastasis. In this work, we report the design and synthesis of BTPETTQ with a propeller structure and a donor–acceptor–donor configuration, which exhibits strong NIR absorption, extremely weak fluorescence and a high PA signal in solution as molecular species. After being encapsulated into a polymeric matrix, BTPETTQ nanoparticles (NPs) also show excellent PA signal output, which is superior to the widely used gold nanorods based on the same mass and is also better than that from the NPs based on the core molecule of TTQ without tetraphenylethene modification. High-resolution PA imaging of SLN is achieved after injection of BTPETTQ NPs into the left paw of rats. The good photothermal conversion efficiency (40%) of BTPETTQ NPs also ensures their good performance in photothermal therapy, which is validated by the effective killing of HeLa cells upon 808 nm laser irradiation. This work demonstrates the great potential of compounds with propeller structures for PA imaging and photothermal therapy applications.
A meta-approach to investigate the variance in transport cost elasticities. A cross-national European comparison

Results from past studies on transport elasticities show a large variance. The aim of this paper is to assess key factors that influence the sensitivity of travellers to transport costs in Europe, by carrying out a comparative analysis of the different elasticity values of demand for transport that are being used in some of the different Member States. Our empirical base are elasticity studies in four different European countries, namely Norway, Finland, The Netherlands and the UK. We are dealing here with a data set consisting of a limited number of observations (i.e. elasticity study results), thus we are facing a high level of uncertainty. Therefore, our in-depth analysis of these causes is based on a meta-analytic approach. Such an approach can be used to extract lessons from a limited set of different research studies. The specific meta-analytic method used is called rough set analysis. The paper starts with a description of the concept of transport price elasticity. It succeeds with a review of the literature. Then an in- depth analysis of possible causes of variances between elasticity values across the four European countries is presented based on rough set analysis. It appears that the emerging importance from the literature of the difference between aggregate, empirical-based research methods and the use of disaggregate choice models, as well as model assumptions, for explaining the variance in elasticity values across studies are largely supported by our rough set analysis. From this analytical approach it also appears that the country involved, the number of competitive modes and type of data collected have a relative strong explanatory power for the size of elasticities.
Reinstatement of Associative Memories in Early Visual Cortex Is Signaled by the Hippocampus

The cortical reinstatement hypothesis of memory retrieval posits that content-specific cortical activity at encoding is reinstated at retrieval. Evidence for cortical reinstatement was found in higher-order sensory regions, reflecting reactivation of complex object-based information. However, it remains unclear whether the same detailed sensory, feature-based information perceived during encoding is subsequently reinstated in early sensory cortex and what the role of the hippocampus is in this process. In this study, we used a combination of visual psychophysics, functional neuroimaging, multivoxel pattern analysis, and a well controlled cued recall paradigm to address this issue. We found that the visual information human participants were retrieving could be predicted by the activation patterns in early visual cortex. Importantly, this reinstatement resembled the neural pattern elicited when participants viewed the visual stimuli passively, indicating shared representations between stimulus-driven activity and memory. Furthermore, hippocampal activity covaried with the strength of stimulus-specific cortical reinstatement on a trial-by-trial level during cued recall. These findings provide evidence for reinstatement of unique associative memories in early visual cortex and suggest that the hippocampus modulates the mnemonic strength of this reinstatement.
Strictly contractive quantum channels and physically realizable quantum computers

We study the robustness of quantum computers under the influence of errors modeled by strictly contractive channels. A channel T is defined to be strictly contractive if, for any pair of density operators p, σ in its domain, ∥Tρ-Tσ∥ 1 ≤k∥ρ-σ∥ 1 for some 0≤k< 1 (here ∥.∥ 1 denotes the trace norm). In other words, strictly contractive channels render the states of the computer less distinguishable in the sense of quantum detection theory. Starting from the premise that all experimental procedures can be carried out with finite precision, we argue that there exists a physically meaningful connection between strictly contractive channels and errors in physically realizable quantum computers. We show that, in the absence of error correction, sensitivity of quantum memories and computers to strictly contractive errors grows exponentially with storage time and computation time, respectively, and depends only on the constant k and the measurement precision. We prove that strict contractivity rules out the possibility of perfect error correction, and give an argument that approximate error correction, which covers previous work on fault-tolerant quantum computation as a special case, is possible.
cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)

The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors. The molecular mechanisms regulating the ability of the RIP proteins to transduce the stress signals remain poorly understood, but seem to rely only partially on their kinase activities. Recent studies on RIP1 and RIP2 have highlighted the importance of ubiquitination as a key process regulating their capacity to activate downstream signaling pathways. In this study, we found that XIAP, cIAP1 and cIAP2 not only directly bind to RIP1 and RIP2 but also to RIP3 and RIP4. We show that cIAP1 and cIAP2 are direct E3 ubiquitin ligases for all four RIP proteins and that cIAP1 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains. Consistently, we show that repressing cIAP1/2 levels affects the activation of NF-κB that is dependent on RIP1, -2, -3 and -4. Finally, we identified Lys51 and Lys145 of RIP4 as two critical residues for cIAP1-mediated ubiquitination and NF-κB activation.
On Maximum Coverage in the Streaming Model & Application to Multi-topic Blog-Watch

We generalize the graph streaming model to hypergraphs. In this streaming model, hyperedges are arriving online and any computation has to be done on-the-fly using a small amount of space. Each hyperedge can be viewed as a set of elements (nodes), so we refer to our proposed model as the “set-streaming” model of computation. We consider the problem of “maximum coverage”, in which k sets have to be selected that maximize the total weight of the covered elements. In the set-streaming model of computation, we show that our algorithm for maximumcoverage achieves an approximation factor of 14 . When multiple passes are allowed, we also provide a Θ(log n) approximation algorithm for the set-cover. We next consider a multi-topic blog-watch application, an extension of blogalert like applications for handling simultaneous multipletopic requests. We show how the problems of maximumcoverage and set-cover in the set-streaming model can be utilized to give efficient online solutions to this problem. We verify the effectiveness of our methods both on synthetic and real weblog data.
Orientation-specific cis complementation by bulge- and loop-mutated human immunodeficiency virus type 1 TAR RNAs

Tat activates human immunodeficiency type 1 gene expression by binding to TAR RNA. TAR comprises a partially base paired stem and hexanucleotide loop with a tripyrimidine bulge in the upper stem. In vitro, Tat binds to the bulge and upper stem, with no requirement for the loop. However, in vivo, loop sequences are critical for activation, implying that a loop binding cellular factor may be involved in the activation pathway. Given that activation appears to be a two-component system comprising a Tat-bulge interaction and a cellular factor-loop interaction, we considered that it might be possible to spatially separate the two components and retain activation. We have constructed a series of double TAR elements comprising various combinations of mutated TAR structures. Defective TARs with nucleotide substitutions in either the bulge or the loop complemented each other to give wild-type activation. However, the complementation was orientation specific, requiring the intact Tat binding site to reside on the 5'-proximal TAR. These data suggest that provided the wild-type orientation of the bulge and loop elements is retained, there is no requirement for them to coexist on the same TAR structure.