Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems Analysis of Cancer Cell Heterogeneity in Caspase-dependent Apoptosis Subsequent to Mitochondrial Outer Membrane Permeabilization*

Background: Computational systems models may allow understanding of progression and impairment of apoptosis based on quantitative protein profiles. Results: We found apoptosis to be impaired in some cell lines after MOMP, which can be understood by our systems model “APOPTO-CELL”. Conclusion: APOPTO-CELL helps to understand heterogeneity in apoptosis execution after MOMP. Significance: APOPTO-CELL may help to assess cancer-specific efficacy of chemotherapeutics that induce apoptosis. Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac−/−, similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAPAdv) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP.
MAC aggregation resilient to DoS attacks

In today's and future building management systems, scores of cheap low-power sensors report measurements, such as temperature, electricity consumption and other parameters, to a control node. To save power and reduce deployment costs, it is often the case that data is sent wirelessly, and sensors serve as relay nodes that retransmit messages from other, more remote sensors. To prevent en route accidental and malicious data corruption, each message is authenticated with a MAC (Message Authentication Code), keyed with a key known to the generating sensor and the control node.
Visualization of Generalized Voronoi Diagrams

Voronoi diagrams are an important data structure in computer science. However well studied mathematically, understanding such diagrams for different metrics, orders, and site shapes is a complex task. We propose a new method to visualize k-order diagrams and give an efficient adaptive implementation for this method. The algorithm is easy to customize for different metrics and site shapes. Its real-time performance makes it suitable for interactive planning and analysis of complex Voronoi configurations in 2D.We illustrate the method for different combinations of metrics and site shapes.
Hybrid binary rewriting for memory access instrumentation

Memory access instrumentation is fundamental to many applications such as software transactional memory systems, profiling tools and race detectors. We examine the problem of efficiently instrumenting memory accesses in x86 machine code to support software transactional memory and profiling. We aim to automatically instrument all shared memory accesses in critical sections of x86 binaries, while achieving overhead close to that obtained when performing manual instrumentation at the source code level. The two primary options in building such an instrumentation system are static and dynamic binary rewriting: the former instruments binaries at link time before execution, while the latter binary rewriting instruments binaries at runtime. Static binary rewriting offers extremely low overhead but is hampered by the limits of static analysis. Dynamic binary rewriting is able to use runtime information but typically incurs higher overhead. This paper proposes an alternative: hybrid binary rewriting. Hybrid binary rewriting is built around the idea of a persistent instrumentation cache (PIC) that is associated with a binary and contains instrumented code from it. It supports two execution modes when using instrumentation: active and passive modes. In the active execution mode, a dynamic binary rewriting engine (PIN) is used to intercept execution, and generate instrumentation into the PIC, which is an on-disk file. This execution mode can take full advantage of runtime information. Later, passive execution can be used where instrumented code is executed out of the PIC. This allows us to attain overheads similar to those incurred with static binary rewriting. This instrumentation methodology enables a variety of static and dynamic techniques to be applied. For example, in passive mode, execution occurs directly from the original executable save for regions that require instrumentation. This has allowed us to build a low-overhead transactional memory profiler. We also demonstrate how we can use the combination of static and dynamic techniques to eliminate instrumentation for accesses to locations that are thread-private.
Distributed MAC for connectivity maximization of interference limited un-coordinated DSA networks

In this paper, we propose a medium access control (MAC) protocol to maximize the connectivity for an un-coordinated secondary dynamic spectrum access network under the signal to interference and noise ratio (SINR) regime. We use concepts from percolation theory to obtain the optimal deployment density for secondary nodes. We argue that the optimal connectivity under the SINR regime can be improved if a fraction of the nodes transmit at a given time. Thus, the proposed MAC is based on distributed Time Division Multiple Access (TDMA) where all nodes randomly choose a time slot to transmit on, a phenomenon similar to the Poisson blinking model. We find the optimal number of slots for the super-frame that includes the sensing, contention, and transmission phases. The performance of the proposed MAC is evaluated via simulations. We show how the proposed MAC adaptively adjusts the super-frame as the density of secondary varies. We also show the connectivity and throughput achieved for various network settings1.
Architecting tacit information in conceptual data models for requirements process improvement

Despite extensive work in the field of Requirements Engineering, ineffective requirements remains a major antecedent to the failure of projects. Requirements Engineering (RE) refers to the body of methods associated with elucidating the needs of a client, when considering the development of a new system or product. In the literature, challenges in RE have been mainly attributed to insufficient client input, incomplete requirements, evolving requirements and lack of understanding of the domain. Accordingly, this has raised the need for methods of effectively eliciting, analysing and recording requirements. In the literature, promising methods have been proposed for using ethnography to improve methods for elicitation because of its strong qualitative and quantitative qualities in understanding human activities. There has also been success with the use of Model Driven Engineering techniques for analysing, recording and communicating requirements through the use of Conceptual Data Models (CDM), to provide a shared understanding of the domain of a system. However, there has been little work that has attempted to integrate these two areas either from an empirical or theoretical perspective. In this thesis, we investigate how ethnographic research methods contribute to a method for data analysis in RE. Specifically, we consider the proposition that a CDM based on explicit and implicit information derived from ethnographic elicitation, will lead to design solutions that more closely match the expectations of clients. As a result of our investigation, this thesis presents the following key contributions: (i) the introduction of an ethnographic approach to RE for elicitation and verification (ii) a rich CDM metamodel and modeling language necessary for defining and recording ethnographic analyses based on implicit and explicit information (iii) a method for mapping CDM’s to high level architectural abstractions called ecologies. To compliment this work, an evaluation case study is provided that demonstrates a real world application of this work.
Labor Market Opportunities and Education Choice of Male Black and White Youths

This paper compares the decision on education attainment by male black and white youths, paying particular attention to labor market opportunities as determinants of their decision. If black youths perceive racial discrimination against them in the labor market, the incentives for them to invest in education are dierent from those of white youths. We construct race-specic age-earnings proles and employment probabilities at dierent levels of education across metropolitan areas, and estimate an education choice model that incorporates these measures of labor market opportunities. Then we simulate the hypothetical situation in which black youths and white youths have access to the same labor market opportunities, to learn how the education gap between the two groups would change if they receive the same treatment in the labor market. We cannot nd evidence to support that inferior labor market opportunities contributed to the lower education attainment of black youths.
A Hybrid Transformation and Filtering Approach for Speech Enhancement with Time Domain Pitch Synchronous Overlap-add

The main goal of Speech enhancement is to enhance the performance of speech communication systems in noisy environments. The problem of enhancing speech which is corrupted by noise is very large, although a lot of techniques have been introduced by the researchers over the past years. This problem is more severe when there is no additional information on the nature of noise degradation is available in which case the enhancement technique must utilize only the specific properties of the speech and noise signals. Signal representation and enhancement in cosine transformation is observed to provide significant results. Discrete Cosine Transformation has been widely used for speech enhancement. In this research study, instead of DCT, a hybrid technique called DCTSLT which is the combination of Discrete Cosine Transform (DCT) and Slantlet Transform (SLT) is proposed for continuous energy compaction along with critical sampling and flexible window switching. In order to deal with the issue of frame to frame deviations of the Cosine Transformations, the proposed transform is combined with Time Domain Pitch Synchronous Overlap-Add (TD-PSOLA) method. Moreover, in order to improve the performance of noise reduction of the system, a Hybrid Vector Wiener Filter approach (HVWF) is used in this study. Experimental result shows that the proposed system performs well in enhancing the speech as compared with other techniques.
Experiences using cooperative interactive storyboard prototyping

T h e i n t e r f a c e s o f c o m p u t e r s y s t e m s e m b e d d e d in c e r t a i n t y p e s o f c o n s u m e r e l e c t r o n i c p r o d u c t s a r e f r e q u e n t l y t a r g e t s o f c r i t i c i s m . P e r h a P S t h e m o s t f r e q u e n t l y c i t e d e x a m p l e s o f p o o r u s e r i n t e r f a c e s (UIS) a r e t h o s e a s s o c i a t e d w i t h v i d e o c a s s e t t e r e c o r d e r s (VCRS).
XPath query evaluation: improving time and space efficiency

Contemporary XPath query engines evaluate queries in time exponential in the sizes of input queries, a fact that has gone unnoticed for a long time. Recently, the first main-memory evaluation algorithm for XPath 1.0 with polynomial time combined complexity, i.e., which runs in polynomial time both with respect to the size of the data and the queries, has been published (cf. [G. Gottlob, et al., (2002)]. We present several important improvements and extensions of that work, including new XPath processing algorithms with improved time and space efficiency. Moreover, we define a very large and practically relevant fragment of XPath for which a further optimized form of query evaluation is possible. Apart from its immediate relevance for XPath query processing, our work also sheds new light at those features of XPath 1.0 which are most costly relative to their practical usefulness.
270-MHz 1H nuclear-magnetic-resonance study of Met-enkephalin in water. Conformational behaviour as a function of pH.

1H spectra at 270 MHz of the Met-enkephalin pentapeptide (Tyr-Gly-Gly-Phe-Met) in aqueous solution, as a function of pH and of temperature, are reported. The analysis of the chemical shifts, line widths, coupling constants and rotamer populations around χ1 and χ2, suggests the existence of three conformational regions in the pH range 1–10, due to some rearrangements of the first two amino acids, Tyr-1 and Gly-2. A first conformational transition occurs corresponding to the N-terminus titration, with an exchange rate between conformational states which is not too fast. The second transition occurs concomitantly with the phenolic group titration. The conformational states of the cationic and zwitterionic forms are probably very similar and are characterized by the absence of intramolecular hydrogen bonds and of head-to-tail interactions. A bent structure, with the Tyr-1 ring Facing the Gly-2 could contribute to the equilibrium of the conformational states of Met-enkephalin in the pH range 8–10. This structure could be destabilized as a consequence of the phenolic group deprotonation. The Met-5 and Phe-4 residues appear to have little sensitivity to the conformational transitions of the backbone and both show a settling of the side chains corresponding to the carboxyl group titration, thus showing a reciprocal steric hindrance. The temperature coefficients of the chemical shifts of amide protons at acidic pH are in the range of solvated peptides. In the temperature range 0–75°C, the 3JαNH coupling constants were independent of temperature.
Approximating extent measures of points

We present a general technique for approximating various descriptors of the extent of a set <i>P</i> of <i>n</i> points in R<sup><i>d</i></sup> when the dimension <i>d</i> is an arbitrary fixed constant. For a given extent measure μ and a parameter ϵ > 0, it computes in time <i>O</i>(<i>n</i> + 1/ϵ<sup><i>O</i>(1)</sup>) a subset <i>Q</i> ⊆ <i>P</i> of size 1/ϵ<sup><i>O</i>(1)</sup>, with the property that (1 − ϵ)μ(<i>P</i>) ≤ μ(<i>Q</i>) ≤ μ(<i>P</i>). The specific applications of our technique include ϵ-approximation algorithms for (i) computing diameter, width, and smallest bounding box, ball, and cylinder of <i>P</i>, (ii) maintaining all the previous measures for a set of moving points, and (iii) fitting spheres and cylinders through a point set <i>P</i>. Our algorithms are considerably simpler, and faster in many cases, than previously known algorithms.
The GM-CSF receptor family: Mechanism of activation and implications for disease

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pluripotent cytokine produced by many cells in the body, which regulates normal and malignant hemopoiesis as well as innate and adaptive immunity. GM-CSF assembles and activates its heterodimeric receptor complex on the surface of myeloid cells, initiating multiple signaling pathways that control key functions such as cell survival, cell proliferation, and functional activation. Understanding the molecular composition of these pathways, the interaction of the various components as well as the kinetics and dose-dependent mechanics of receptor activation provides valuable insights into the function of GM-CSF as well as the related cytokines, interleukin-3 and interleukin-5. This knowledge provides opportunities for the development of new therapies to block the action of these cytokines in hematological malignancy and chronic inflammation.
Non‐Linear Rheology of Polymer Melts

The continuous demand for high performance products is the driving force for the development of state‐of‐the‐art materials with outstanding processability and mechanical strength. In order to fulfill these properties, an appropriate tailoring of the molecular structure is a requirement. Such tailoring can only be achieved provided that suitable and sensitive characterization techniques are available. The dominance of complex flows in most of the industrial processes requires the understanding of the rheological properties under the non‐linear viscoelastic regime. Within the present work Large Amplitude Oscillatory Shear (LAOS) will be applied to a series of industrial polypropylene and polyethylene based materials. This work will provide additional insights on the relationship between given rheological parameters from LAOS flow (|G′1/G′3|) and molecular topology. The use of the third order Chebyshev elastic and viscous coefficients, e3 and v3, provided an understanding of the physical nature of the non‐li.
Inferring Orthologs: Open Questions and Perspectives

With the increasing number of sequenced genomes and their comparisons, the detection of orthologs is crucial for reliable functional annotation and evolutionary analyses of genes and species. Yet, the dynamic remodeling of genome content through gain, loss, transfer of genes, and segmental and whole-genome duplication hinders reliable orthology detection. Moreover, the lack of direct functional evidence and the questionable quality of some available genome sequences and annotations present additional difficulties to assess orthology. This article reviews the existing computational methods and their potential accuracy in the high-throughput era of genome sequencing and anticipates open questions in terms of methodology, reliability, and computation. Appropriate taxon sampling together with combination of methods based on similarity, phylogeny, synteny, and evolutionary knowledge that may help detecting speciation events appears to be the most accurate strategy. This review also raises perspectives on the potential determination of orthology throughout the whole species phylogeny.
Glial Cell Line-Derived Neurotrophic Factor-Transfected Placenta-Derived Versus Bone Marrow-Derived Mesenchymal Cells for Treating Spinal Cord Injury

Background Placenta-derived mesenchymal stem cells (PMSCs) were isolated from placenta and had differentiation and self-renewal potential. We transfected PMSCs with glial cell line-derived neurotrophic factor (GDNF) and compared their effect for repairing spinal cord injury (SCI) with that of GDNF-transfected bone marrow-derived mesenchymal stem cell (BMSC). Material/Methods The PMSCs were isolated from Sprague-Dawley rat placenta; BMSCs were isolated from Sprague-Dawley rat thigh bone marrow. Primary cultured BMSCs and PMSCs were uniformly spindle-shaped. Flow cytometry indicated that both cell types were CD29- and CD90-positive and CD34- and CD45-negative, confirming that they were MSCs. The PMSCs and BMSCs were transfected with recombinant lentivirus containing the GDNF gene in vitro. PMSC and BMSC viability was increased after transfection, and GDNF expression was increased until 10 d after transfection. SCI was created in the rats (n=64) and was repaired using transfected PMSCs and BMSCs or untransfected PMSCs and BMSCs. Results The transfected PMSCs and BMSCs repaired the SCI. Flow cytometry, histology, immunohistochemical, kinesiology properties, and Basso-Beattie-Bresnahan locomotion score measurements determined no significant difference between transfected PMSCs and BMSCs at 7, 14, and 21 d post-transplantation (P>0.05); the injury healed better in transfected PMSCs and BMSCs than in untransfected PMSCs and BMSCs (P<0.05). Conclusions MSCs have similar biology characteristics and capacity for SCI repair to BMSCs and can be used as a new resource for treating SCI.
Red blood cell concentrates treated with the amustaline (S‐303) pathogen reduction system and stored for 35 days retain post‐transfusion viability: results of a two‐centre study

Pathogen reduction technology using amustaline (S‐303) was developed to reduce the risk of transfusion‐transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second‐generation process and stored for 35 days was evaluated in two different blood centres.
Analyzing and visualizing ancient Maya hieroglyphics using shape: From computer vision to Digital Humanities

Maya hieroglyphic analysis requires epigraphers to spend a significant amount of time browsing existing catalogs to identify individual glyphs. Automatic Maya glyph analysis provides an efficient way to assist scholars’ daily work. We introduce the Histogram of Orientation Shape Context (HOOSC) shape descriptor to the Digital Humanities community. We discuss key issues for practitioners and study the effect that certain parameters have on the performance of the descriptor. Different HOOSC parameters are tested in an automatic ancient Maya hieroglyph retrieval system with two different settings, namely, when shape alone is considered and when glyph co-occurrence information is incorporated. Additionally, we developed a graph-based glyph visualization interface to facilitate efficient exploration and analysis of hieroglyphs. Specifically, a force-directed graph prototype is applied to visualize Maya glyphs based on their visual similarity. Each node in the graph represents a glyph image; the width of an edge indicates the visual similarity between the two according glyphs. The HOOSC descriptor is used to represent glyph shape, based on which pairwise glyph similarity scores are computed. To evaluate our tool, we designed evaluation tasks and questionnaires for two separate user groups, namely, a general public user group and an epigrapher scholar group. Evaluation results and feedback from both groups show that our tool provides intuitive access to explore and discover the Maya hieroglyphic writing, and could potentially facilitate epigraphy work. The positive evaluation results and feedback further hint the practical value of the HOOSC descriptor.
A compartmentalized microfluidic neuromuscular co-culture system reveals spatial aspects of GDNF functions

ABSTRACT Bidirectional molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. The molecular mechanisms underlying such communication are of keen interest and could provide new targets for intervention in motoneuron disease. Here, we developed a microfluidic platform with motoneuron cell bodies on one side and muscle cells on the other, connected by motor axons extending through microgrooves to form functional NMJs. Using this system, we were able to differentiate between the proximal and distal effects of oxidative stress and glial-derived neurotrophic factor (GDNF), demonstrating a dying-back degeneration and retrograde transmission of pro-survival signaling, respectively. Furthermore, we show that GDNF acts differently on motoneuron axons versus soma, promoting axonal growth and innervation only when applied locally to axons. Finally, we track for the first time the retrograde transport of secreted GDNF from muscle to neuron. Thus, our data suggests spatially distinct effects of GDNF – facilitating growth and muscle innervation at axon terminals and survival pathways in the soma.