Miracle-dz/UniFAR-FTUs huggingface dataset:
Danger signals – damaged-self recognition across the tree of life

Multicellular organisms suffer injury and serve as hosts for microorganisms. Therefore, they require mechanisms to detect injury and to distinguish the self from the non-self and the harmless non-self (microbial mutualists and commensals) from the detrimental non-self (pathogens). Danger signals are “damage-associated molecular patterns” (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells. Seemingly ubiquitous DAMPs are extracellular ATP or extracellular DNA, fragmented cell walls or extracellular matrices, and many other types of delocalized molecules and fragments of macromolecules that are released when pre-existing precursors come into contact with enzymes from which they are separated in the intact cell. Any kind of these DAMPs enable damaged-self recognition, inform the host on tissue disruption, initiate processes aimed at restoring homeostasis, such as sealing the wound, and prepare the adjacent tissues for the perception of invaders. In mammals, antigen-processing and -presenting cells such as dendritic cells mature to immunostimulatory cells after the perception of DAMPs, prime naïve T-cells and elicit a specific adaptive T-/B-cell immune response. We discuss molecules that serve as DAMPs in multiple organisms and their perception by pattern recognition receptors (PRRs). Ca2+-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life. Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.
Enhanced enteral bioavailability of vancomycin using water-in-oil-in-water multiple emulsion incorporating highly purified unsaturated fatty acid.

The aim of this study was to evaluate the potential of an emulsion incorporating unsaturated fatty acids to improve the mucosal absorption of poorly absorbed drugs from rat intestinal loops in situ, using a water-in-oil-in-water (W/O/W) multiple emulsion. Vancomycin hydrochloride (VCM) was used as a model drug with low oral bioavailability. The entrapment efficiency of VCM in the emulsion was approximately 60% and remained constant over storage for 1 month at 4 degrees C. The emulsion incorporating C18 unsaturated fatty acids or docosahexaenoic acid (DHA) markedly enhanced VCM absorption after colonic and rectal dosing. The effectiveness of DHA on VCM colonic absorption improvement was the same as that of oleic acid, and less than that of linoleic and linolenic acids. For rectal dosing, bioavailability was similar among various emulsions, in the range 40-50%. The effect of the emulsion incorporating oleic acid or DHA on improving VCM enteral bioavailability was not increased proportional to the incorporated amount. The electrical resistance of membranes was not changed by the incorporation of various fatty acids in emulsions. Our results indicated that W/O/W emulsions incorporating C18 unsaturated fatty acid or DHA were useful carriers for improving the absorption of poorly absorbable drugs via the intestinal tract without gross changes to tight junction function.
Type VI secretion and bacteriophage tail tubes share a common assembly pathway

The Type VI secretion system (T6SS) is a widespread macromolecular structure that delivers protein effectors to both eukaryotic and prokaryotic recipient cells. The current model describes the T6SS as an inverted phage tail composed of a sheath‐like structure wrapped around a tube assembled by stacked Hcp hexamers. Although recent progress has been made to understand T6SS sheath assembly and dynamics, there is no evidence that Hcp forms tubes in vivo. Here we show that Hcp interacts with TssB, a component of the T6SS sheath. Using a cysteine substitution approach, we demonstrate that Hcp hexamers assemble tubes in an ordered manner with a head‐to‐tail stacking that are used as a scaffold for polymerization of the TssB/C sheath‐like structure. Finally, we show that VgrG but not TssB/C controls the proper assembly of the Hcp tubular structure. These results highlight the conservation in the assembly mechanisms between the T6SS and the bacteriophage tail tube/sheath.
The Story of the Amulet : A Brief History of Asynchronous Events in Manchester

This presents an overview of the significant achievements in Asynchronous Logic over the last quarter of a century at the University of Manchester. Including the Amulet (and subsequent) asynchronous Microprocessors, the synthesis tools Balsa and Teak, the MARBLE and Chain on-chip Interconnects, together with research arising from external collaborations with the University of Newcastle. 1 Pre-history an Overview by Steve Furber The Amulet story begins in 1989. Through the 1980s I (SBF) worked at Acorn Computers Ltd in Cambridge, UK, where I was a designer of the BBC Microcomputer and the ARM (then “Acorn RISC Machine”) 32-bit RISC microprocessor. We didn’t publish much, but one paper we published was on the ARM3 the first ARM with an on-chip cache at VLSI’89 in Munich [7]. At that conference I was struck by a paper [14] presented by Craig Mudge, then CEO of Austek Microsystems Ltd based in Adelaide. This was my first exposure to asynchronous design, and of course Mudge’s paper cited Ivan Sutherland’s Turing Award paper [19] which really sold the concept to me. Over the following year I doodled some ideas on the possible design of an asynchronous version of the ARM based on Sutherland’s micropipelines approach. This was around the time the EU launched the OMI Open Microprocessor systems Initiative which was in part stimulated by input from Acorn. When I accepted the ICL Chair at Manchester, to which I moved on 1st August 1990, Acorn was generous in allowing me to take with me to Manchester a part of an early OMI project that I had been involved in developing at Acorn the OMI-MAP project. OMI-MAP provided the early funding that got the Amulet (asynchronous ARM) research off the ground at Manchester. The University allocated a lectureship appointment linked to my chair, to which Jim Garside was appointed, and OMI-MAP funded the appointment of Nigel Paver and Paul Day as post-docs. In addition, existing academic staff joined in Doug Edwards, Linda Brackenbury and Viv Woods, bringing in additional perspectives and new funding, all of which enabled the Amulet group to grow to critical mass. Why “Amulet”? Well, in searching for a group or project name you have to start somewhere, and writing down keywords on a whiteboard is one way to start. “Asynchronous”, “Manchester University”,“Low-Energy Technology”? 155 x 238 mm 120 Doug Edwards et al.
High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets

Novel high-throughput analyses in molecular biology allow sensitive and rapid identification of disease-related genes and drug targets. We have used quantitative real-time reverse transcription-PCR reactions (n = 23,000) to analyze expression of all human receptor tyrosine kinases (n = 56) in malignant tumors (n = 313) of different origins and normal control samples (n = 58). The different tumor types expressed very different numbers of receptor tyrosine kinases: whereas brain tumors and testicular cancer expressed 50 receptor tyrosine kinases, acute myeloid leukemia (AML) samples expressed only 20 different ones. Specimens of similar tumor origin exhibited characteristic receptor tyrosine kinase expression patterns and were grouped together in hierarchical cluster analyses. When we focused on specific tumor entities, receptor tyrosine kinases were identified that were disease and/or stage specific. Leukemic blasts from AML bone marrow samples differed significantly in receptor tyrosine kinase expression compared with normal bone marrow and purified CD34+ cells. Among the differentially expressed receptor tyrosine kinases, we found FLT3, c-kit, CSF1 receptor, EPHB6, leukocyte tyrosine kinase, and ptk7 to be highly overexpressed in AML samples. Whereas expression changes of some of these were associated with altered differentiation patterns (e.g., CSF1 receptor), others, such as FLT3, were genuinely overexpressed in leukemic blasts. These data and the associated database (http://medweb.uni-muenster.de/institute/meda/research/) provide a comprehensive view of receptor tyrosine kinase expression in human cancer. This information can assist in the definition of novel drug targets.
Exploring interactive curve and surface manipulation using a bend and twist sensitive input strip

We explore a new input device and a set of interaction techniques to facilitate direct manipulation of curves and surfaces. The input device, called ShapeTapeTM, is a continuous bend and twist sensitive strip that encourages manipulations that use both hands and, at times, all 10 fingers. We explore this input and interaction design space through a set of usage scenarios for creating and editing curves and surfaces as well as consider general interactions such as command access and camera controls. This investigation is carried out by extending Alias|wavefront’s modeling and animation package, Maya. CR
Bladder cancer.

Identification of genetic alterations in bladder cancer is proceeding very rapidly. The most common genetic alteration identified to date in bladder cancer is loss of heterozygosity of chromosome 9, suggesting a possible tumor-suppressor gene on this chromosome. Because none of the Ta tumors showed loss of heterozygosity of 9p, it may be possible to speculate that inactivation of a gene located on 9q may be the earlier event. The genes p53 and pRb have been associated with disease progression and survival; what is more important is that this effect is more pronounced if both markers are altered. One may postulate from these results that the loss of the function of wild-type p53 allows cells with DNA damage to proceed through the cell cycle, replicating genetic errors. Similarly, loss of normal pRb disrupts regulation of cell cycle, and thus decreased pRb expression in bladder cancer correlates with increased mitotic index. It has been shown that adjuvant chemotherapy affects favorably only those patients with p53-altered tumors with regard to decreased risk of recurrence and increased survival. Thus, p53 may be useful not only in predicting the aggressive nature of the tumor, but also in identifying patients who will not benefit from chemotherapy. Significant tumor reduction and a high local control rate were clearly demonstrated by a combination of radiation and radiosensitizing agents. Although promising survival rates with intact bladders have been reported, only a selected group of patients with muscle-invasive disease may benefit from this approach. Further studies in molecular genetics surely will enable a more refined approach for selecting treatment modalities in bladder cancer.
Real time motion generation and control for biped robot -4th report: Integrated balance control-

A controller for biped running has to consider varying vertical ground reaction force while satisfying the horizontal ground reaction force and moment limits. We propose a design technique for feedback gains to stabilize the upper body position under varying vertical ground reaction force. We also propose an extended model ZMP control method which uses horizontal and rotational acceleration of the upper body and step duration change to generate moments to handle disturbances too large to be handled by ground reaction force control. Combining these techniques, robust biped running is achieved.
Time-varying FIR equalization for doubly selective channels

We propose a time-varying (TV) finite impulse response (FIR) equalizer for doubly selective (time- and frequency-selective) channels. We use a basis expansion model (BEM) to approximate the doubly selective channel and to design the TV FIR equalizer. This allows us to turn a complicated equalization problem into an equivalent simpler equalization problem, containing only the BEM coefficients of both the doubly selective channel and the TV FIR equalizer. The minimum mean-square error (MMSE) as well as the zero-forcing (ZF) solutions are considered. Comparisons with the block linear equalizer (BLE) are made. The TV FIR equalization we propose here unifies and extends many previously proposed serial equalization approaches. In contrast to the BLE, the proposed TV FIR equalizer allows a flexible tradeoff between complexity and performance. Moreover, through computer simulations, we show that the performance of the proposed MMSE TV FIR equalizer comes close to the performance of the ZF and MMSE BLE, at a point where the design as well as the implementation complexity are much lower.
High‐resolution proglacial lake records of pre‐Little Ice Age glacier advance, northeast Greenland

Understanding Arctic glacier sensitivity is key to predicting future response to air temperature rise. Previous studies have used proglacial lake sediment records to reconstruct Holocene glacier advance–retreat patterns in South and West Greenland, but high‐resolution glacier records from High Arctic Greenland are scarce, despite the sensitivity of this region to future climate change. Detailed geochemical analysis of proglacial lake sediments close to Zackenberg, northeast Greenland, provides the first high‐resolution record of Late Holocene High Arctic glacier behaviour. Three phases of glacier advance have occurred in the last 2000 years. The first two phases (c. 1320–800 cal. a BP) occurred prior to the Little Ice Age (LIA), and correspond to the Dark Ages Cold Period and the Medieval Climate Anomaly. The third phase (c. 700 cal. a BP), representing a smaller scale glacier oscillation, is associated with the onset of the LIA. Our results are consistent with recent evidence of pre‐LIA glacier advance in other parts of the Arctic, including South and West Greenland, Svalbard, and Canada. The sub‐millennial glacier fluctuations identified in the Madsen Lake succession are not preserved in the moraine record. Importantly, coupled XRF and XRD analysis has effectively identified a phase of ice advance that is not visible by sedimentology alone. This highlights the value of high‐resolution geochemical analysis of lake sediments to establish rapid glacier advance–retreat patterns in regions where chronological and morphostratigraphical control is limited.
Myosin mRNA accumulation and myofibrillogenesis at the myotendinous junction of stretched muscle fibers

Myofiber growth and myofibril assembly at the myotendinous junction (MTJ) of stretch-hypertrophied rabbit skeletal muscle was studied by in situ hybridization, immunofluorescence, and electron microscopy. In situ hybridization identified higher levels of myosin heavy chain (MHC) mRNA at the MTJ of fibers stretched for 4 d. Electron microscopy at the MTJ of these lengthening fibers revealed a large cytoplasmic space devoid of myofibrils, but containing polysomes, sarcoplasmic reticulum and T-membranes, mitochondria, Golgi complexes, and nascent filament assemblies. Tallies from electron micrographs indicate that myofibril assembly in stretched fibers followed a set sequence of events. (a) In stretched fiber ends almost the entire sarcolemmal membrane was electron dense but only a portion had attached myofibrils. Vinculin, detected by immunofluorescence, was greatly increased at the MTJ membrane of stretched muscles. (b) Thin filaments were anchored to the sarcolemma at the electron dense sites. (c) Thick filaments associated with these thin filaments in an unregistered manner. (d) Z-bodies splice into thin filaments and subsequently thin and thick filaments fall into sarcomeric register. Thus, the MTJ is a site of mRNA accumulation which sets up regional protein synthesis and myofibril assembly. Stretched muscles also lengthen by the addition of myotubes at their ends. After 6 d of stretch these myotubes make up the majority of fibers at the muscle ends. Essentially all these myotubes repeat the developmental program of primary myotubes and express slow MHC. MHC mRNA distribution in myotubes is disorganized as is the distribution of their myofibrils.
A SIMPLE PROOF OF A BASIC THEOREM ON ITERATED RANDOM FUNCTIONS

We present a transparent proof of existence of a stationary probability for a Markov chain constructed by random iterations of functions on a complete separable metric space. Our proof is to be compared with that given under equivalent assumptions by Diaconis and Freedman [1, pp. 58-63]. We just use contraction properties of the two linear operators naturally associated with the Markov chain considered.
Retrorectal Tumors: The Choice of Surgical Approach Based on a New Classification

Because retrorectal-presacral tumors differ in histologic origin, symptoms, and prognosis, and often involve various neighboring structures, successful treatment of this heterogeneous group of tumors depends on the surgical approach chosen and the specialist surgeons involved. We investigated whether a new classification of retrorectal tumors based on findings from CT and MRI would simplify presurgical planning. The clinical records of a series of 34 patients who underwent surgery for retrorectal tumors from 1989 to 2003 were reviewed. Two radiologists, who were blind to the patients’ records, separately reviewed the preoperative CT and MRI findings and classified tumors according to whether they arose from the presacral area (Group 1), sacrum or spinal cord growing anteriorly (Group 2), or rectum growing posteriorly (Group 3). The preoperative CT and MRI findings for the retrorectal tumors yielded the information required to allow surgery to be properly planned (surgical approach and need to involve various specialist surgeons) in nearly all cases: 17 of the 18 patients (94.5%) with tumors arising from the retrorectal space, all 12 of those with tumors arising from the sacrum or spinal cord, and all four of those with rectal tumors. With the findings yielded by currently available CT and MRI techniques, retrorectal tumors can be anatomically and topographically classified preoperatively so as to allow surgery to be adequately planned in advance and thus optimize the surgical resection.
Improving Security in Internet of Things with Software Defined Networking

Future Internet of Things (IoT) will connect to the Internet billions of heterogeneous smart devices with the capacity of interacting with the environment. Therefore, the proposed solutions from an IoT networking perspective must take into account the scalability of IoT nodes as well as the operational cost of deploying the networking infrastructure. This will generate a huge volume of data, which poses a tremendous challenge both from the transport, and processing of information point of view. Moreover, security issues appear, due to the fact that untrusted IoT devices are interconnected towards the aggregation networks. In this paper, we propose the usage of a Software- Defined Networking (SDN) framework for introducing security in IoT gateways. An experimental validation of the framework is proposed, resulting in the enforcement of network security at the network edge.
Carrier Frequency Offset Estimation for Multi-User MIMO OFDM Uplink Using CAZAC Sequences

In the uplink of multi-user multiple input multiple output (MIMO) orthogonal frequency division multiplexing (OFDM) systems, there are multiple carrier frequency offsets (CFO's) from the multiple users. In this paper, we study algorithms to estimate these multiple CFO values. We first derive the maximum likelihood (ML) estimator and show that the complexity of the ML estimator increases exponentially with the number of users so that the estimator is not suitable for practical implementations. To reduce the complexity, we propose a suboptimal algorithm using constant amplitude zero autocorrelation (CAZAC) sequences. The complexity of the proposed method increases only linearly with the number of users. Using computer simulations, we compare the performance using CAZAC training sequences with that using the m sequence and the short training field (STF) of the IEEE 802.11n systems. The results show that in the low to medium SNR regions, the performance using CAZAC sequences is very close to the single-user Cramer-Rao bound. For high SNR regions, an error floor exists due to multiple access interference (MAI). The error floor using CAZAC sequences is more than 10 times smaller compared to the error floor using the other two sequences.
Local stability and robustness of sparse dictionary learning in the presence of noise

A popular approach within the signal processing and machine learning communities consists in modelling signals as sparse linear combinations of atoms selected from a learned dictionary. While this paradigm has led to numerous empirical successes in various fields ranging from image to audio processing, there have only been a few theoretical arguments supporting these evidences. In particular, sparse coding, or sparse dictionary learning, relies on a non-convex procedure whose local minima have not been fully analyzed yet. In this paper, we consider a probabilistic model of sparse signals, and show that, with high probability, sparse coding admits a local minimum around the reference dictionary generating the signals. Our study takes into account the case of over-complete dictionaries and noisy signals, thus extending previous work limited to noiseless settings and/or under-complete dictionaries. The analysis we conduct is non-asymptotic and makes it possible to understand how the key quantities of the problem, such as the coherence or the level of noise, can scale with respect to the dimension of the signals, the number of atoms, the sparsity and the number of observations.
lgtC Expression Modulates Resistance to C4b Deposition on an Invasive Nontypeable Haemophilus influenzae1

We have previously shown that C3 binding to serum-resistant nontypeable Haemophilus influenzae (NTHi) strain R2866 is slower than C3 binding to a serum-sensitive strain. Ab-dependent classical pathway activation is required for complement-dependent killing of NTHi. To further characterize the mechanism(s) of serum resistance of R2866, we compared binding of complement component C4b to R2866 with a serum-sensitive variant, R3392. We show that C4b binding to R2866 relative to R3392 was delayed, suggesting regulation of the classical pathway of complement. Increased C4b deposition on R3392 was independent of the amount and subclass of Ab binding, suggesting that an impediment to C4b binding existed on R2866. Immunoblotting and mass spectrometry indicated that lipooligosaccharide and outer membrane proteins P2 and P5 were targets for C4b. P2 and P5 sequences and expression levels were similar in both strains. Insertional inactivation of the phase-variable lipooligosaccharide biosynthesis gene lgtC in R2866 augmented C4b deposition to levels seen with R3392 and rendered the bacteria sensitive to serum and whole blood. These results suggest a direct role of lgtC expression in the inhibition of C4b deposition and consequent serum resistance of R2866. Alteration of surface glycans of NTHi may be a critical event in determining the ability of a strain to evade host defenses and cause disseminated infection.