Miracle-dz/UniFAR-FTUs huggingface dataset:
Theory of Kinetic Partitioning in Protein Folding (With Application to Prions)

In this paper we study the phenomenon of kinetic partitioning when a polypeptide chain has two ground state conformations one of which is more kinetically reachable than the other. This question is relevant to understand the phenomenology of prions, proteins which exist in the cell in non-pathogenic $\alpha$-helical conformation but under certain circumstances may transform into pathogenic $PrP^{Sc}$ state featuring increased $\beta$-sheet content. We designed sequences for lattice model proteins having two different conformations of equal energy corresponding to the global energy minimum. Folding simulations revealed that one of these conformations was indeed much more kinetically accessible than the other. We found that the number and strength of local contacts in the ground state conformation is the major factor which determines which conformation is reached faster: The greater the number of local contacts the more kinetically reachable a conformation is. We present simple statistical-mechanical arguments to explain these findings. The presented results are in a clear agreement with experimental data on prions and other proteins exhibiting kinetic partitioning.
Regulation of von Willebrand factor-platelet interactions

Summary The formation of thrombi is a multistep process involving several components, including von Willebrand factor (VWF). VWF is an adhesive multimeric protein, which acts as a molecular bridge between the subendothelial matrix and the glycoprotein Ib/IX/V receptor complex. Furthermore, VWF promotes the expansion of the platelet plug by cross-linking platelets via binding to integrin αIIbβ3. In terms of thrombus formation, it is essential that VWF-platelet interactions occur timely, that is: it should happen not too early or too late. Given the co-existence of VWF and platelets in the circulation, this implies that there must be regulatory mechanisms that prevent premature formation of VWF-rich platelet aggregates that could occlude the vasculature. Indeed, several mechanisms have been identified at the level of VWF, which are dedicated to the prevention of excessive VWF-platelet interactions following endothelial release of VWF (which may include limited exposure to shear stress, the presence of Mg2+ ions, inhibition of VWF-platelet interactions by endothelial proteins, ADAMTS13-mediated proteolysis) and of circulating VWF-platelet aggregates during normal circulation (shielding of the platelet-binding A1 domain by other regions of the VWF molecule, inhibition of VWF-platelet interactions by β2-glycoprotein I). In the present review an overview of these mechanisms will be discussed.
Drones and Privacy

Drones, also referred to as UAV's (Unmanned Aerial Vehicle), are an aircraft without a human pilot. Drones have been used by various military organisations for over a decade, but in recent years drones a have been emerging more and more in commercial and recreational capacity. The paper is aimed at drone and UAV technology capabilities and how they could and are currently effecting privacy laws globally in comparison to those currently in the Rep. of Ireland. Being investigated is the collection, retention and purpose of which civilian's information is being gathered. The authors also discuss the laws preventing the development and evolution of drone technology in the US in comparison to the Rep. of Ireland.
Latitudinal variations of trace gas concentrations in the free troposphere measured by solar absorption spectroscopy during a ship cruise

The latitudinal variations of atmospheric trace gas column abundances have been measured during a ship cruise between 57°N and 45°S on the central Atlantic. The measurements were performed in October 1996 using high-resolution solar absorption spectroscopy in the infrared. The analysis method employed permits the retrieval of the total column densities of 20 different trace gases and for a few compounds the vertical mixing ratio profiles. For CH4 an interhemispheric difference of 3% was observed. The total columns of the shorter-lived trace gases CO and C2H6, analyzed between 57°N and 45°S, reveal a slight maximum in the tropics and a substantial increase north of 45°N. The total columns of C2H2 and HCN, detectable between 30°N and 30°S, reveal a maximum in the tropics of the Southern Hemisphere. For CH2O, studied between 57°N and 45°S, a well-pronounced maximum is observed in the tropics. The profile retrieval gives high mixing ratios for CO, C2H6, and O3 north of 40°N in the lower troposphere. In the tropics high concentrations are found for all three compounds in the entire troposphere, even above 12 km. The measurements have been used to estimate averaged mixing ratios of the trace gases for the free troposphere between 0 and 12 km. In the tropics the data give high values: for example, more than 200 pptv for HCN, 750 pptv for CH2O, 100 ppbv for CO and 100 pptv for C2H2. These values are comparable to or higher than what has been observed at midlatitudes, indicating the importance of biomass burning emissions on the tropospheric composition.
IMPACT OF A MEDIATING ROLE OF REPURCHASE INTENTIONS ON CUSTOMER RETENTION

Research in the area of packaged tour services, provided by the national and foreign tour operators has concentrated on mutual relationships among tourist-perceived service quality, satisfaction and repurchase intentions. However, little research in this domain has been done to explain the impact of repurchase intentions of experienced tourists on the relation between perceived quality of service and their satisfaction. This model was tested using substantial data set of experienced tourists with time span of three years. While previous literature has suggested that quality perceptions impose direct effect on tourist satisfaction, this study shows that such effect is more powerful when mediated by repurchase intentions of experienced tourists. The quality of packaged tour services mediated by repurchase intentions of the experienced tourist is expected to be paramount for the retention of the tourist in the long term. KEY WORDS: repurchase intentions, quality, packaged service, services chain, tour operator, retention, tourist satisfaction.
Transporting functions across ornaments

Programming with dependent types is a blessing and a curse. It is a blessing to be able to bake invariants into the definition of datatypes: we can finally write correct-by-construction software. However, this extreme accuracy is also a curse: a datatype is the combination of a structuring medium together with a special purpose logic. These domain-specific logics hamper any effort of code reuse among similarly structured data. In this paper, we exorcise our datatypes by adapting the notion of ornament to our universe of inductive families. We then show how code reuse can be achieved by ornamenting functions. Using these functional ornaments, we capture the relationship between functions such as the addition of natural numbers and the concatenation of lists. With this knowledge, we demonstrate how the implementation of the former informs the implementation of the latter: the user can ask the definition of addition to be lifted to lists and she will only be asked the details necessary to carry on adding lists rather than numbers. Our presentation is formalised in a type theory with a universe of datatypes and all our constructions have been implemented as generic programs, requiring no extension to the type theory.
Adaptive Backstepping Neural Network Control for Mechanical Pumps

In this paper, an Adaptive Backstepping Neural Network control approach is used for a class of affine nonlinear systems which describe the pump model in the strict feedback form. The close loop signals are semi globally uniformly ultimately bounded and the output of the system is proven to follow a desired trajectory. Simulation results are presented to show the effectiveness of the approach proposed in order to control the pump output.
Multiple signaling pathways regulate contractile activity‐mediated PGC‐1α gene expression and activity in skeletal muscle cells

PGC‐1α is an important transcriptional coactivator that plays a key role in mediating mitochondrial biogenesis. Within seconds of the onset of contractile activity, a number of rapid cellular events occur that form part of the initial signaling processes involved in PGC‐1α gene regulation, such as elevations in cytoplasmic calcium, AMPK and p38 activation, and elevated ROS production. We observed that basal levels of PGC‐1α promoter activity were more sensitive to resting Ca2+ levels, compared to ROS, p38 or, AMPK signaling. Moreover, enhanced PGC‐1α transcription and post‐translational activity on DNA were a result of the activation of multiple signal transduction pathways during contractile activity of myotubes. AMPK, ROS, and Ca2+ appear to be necessary for the regulation of contractile activity‐induced PGC‐1α gene expression, governed partly through p38 MAPK and CaMKII activity. Whether these signaling pathways are arranged as a linear sequence of events, or as largely independent pathways during contractile activity, remains to be determined.
Identification of a Receptor-Binding Domain of the Spike Glycoprotein of Human Coronavirus HCoV-229E

ABSTRACT Human coronavirus HCoV-229E uses human aminopeptidase N (hAPN) as its receptor (C. L. Yeager et al., Nature 357:420-422, 1992). To identify the receptor-binding domain of the viral spike glycoprotein (S), we expressed soluble truncated histidine-tagged S glycoproteins by using baculovirus expression vectors. Truncated S proteins purified by nickel affinity chromatography were shown to be glycosylated and to react with polyclonal anti-HCoV-229E antibodies and monoclonal antibodies to the viral S protein. A truncated protein (S547) that contains the N-terminal 547 amino acids bound to 3T3 mouse cells that express hAPN but not to mouse 3T3 cells transfected with empty vector. Binding of S547 to hAPN was blocked by an anti-hAPN monoclonal antibody that inhibits binding of virus to hAPN and blocks virus infection of human cells and was also blocked by polyclonal anti-HCoV-229E antibody. S proteins that contain the N-terminal 268 or 417 amino acids did not bind to hAPN-3T3 cells. Antibody to the region from amino acid 417 to the C terminus of S blocked binding of S547 to hAPN-3T3 cells. Thus, the data suggest that the domain of the spike protein between amino acids 417 and 547 is required for the binding of HCoV-229E to its hAPN receptor.
Closed-Loop Control of FES-Assisted Arm-Free Paraplegic Standing: A Feasibility Study

Using a simplified model of quiet standing, we demonstrated analytically that a proportional-derivative (PD) controller can mimic the physiologic control strategy applied by healthy individuals during quiet standing. In a second step, utilizing transcutaneous functional electrical stimulation (FES) of the ankle extensors in experiments with a spinal cord injured subject, it was verified that the PD controller can, in fact, compensate for long neurological delays and muscle nonlinearities. The third phase of this study was focused on better understanding the nonlinear dynamics of quiet standing. In particular, a realistic model of quiet standing was developed that could be stabilized by actuating six out of twelve degrees of freedom (DOF). A PD plus gravity compensator was used to control these six DOF, and asymptotic stability was demonstrated using Lyapunov stability analysis. These results suggest that quiet standing can be achieved in paraplegic individuals by controlling only six DOF in the lower limbs using FES, and that a PD plus gravity compensator should be able to stabilize the system despite long neurological delays and muscle nonlinearities
A Versatile Emulator for the Aging Effect of Non-volatile Memories: The Case of NAND Flash

This work presents a versatile and flexible FPGA-based platform, designed for accurate emulation of the aging effect of non-volatile memories. The emulator is based on a reconfigurable hardware-software architecture which enables the accurate representation of various non-volatile memory technologies, like NAND Flash and PCM. The proposed architecture can be used for emulating memories at the cell, chip and system level, while the proposed hardware platform can be used as a valuable tool for the development and evaluation of memory-related algorithms and techniques. In this paper, we analyze the architecture of the non-volatile memory emulator, focusing mainly on the NAND Flash case, we present details about its internal functionality and, using experimental results, we demonstrate the high accuracy achieved when it is used to emulate a specific NAND Flash chip.
Discriminative Methods for Noise Robust Speech Reacognition : A CHiME Challenge

The recently introduced second CHiME challenge is a difficult twomicrophone speech recognition task with non-stationary interference. Current approaches in the source-separation community have focused on the front-end problem of estimating the clean signal given the noisy signals. Here we pursue a different approach, focusing on state-of-the-art ASR techniques such as discriminative training and various feature transformations, in addition to simple noise suppression methods based on prior-based binary masking with estimated angle of arrival. In addition, we propose an augmented discriminative feature transformation that can introduce arbitrary features to a discriminative feature transform, an efficient combination method of Discriminative Language Modeling (DLM) and Minimum Bayes Risk (MBR) decoding in an ASR post-processing stage, and preliminarily investigate the effectiveness of deep neural networks for reverberated and noisy speech recognition. Using these techniques we present a benchmark on the middlevocabulary subtask of CHiME challenge, showing their effectiveness for this task. Promising results were also obtained for the proposed augmented feature transformation and combination of DLM and MBR decoding. A part of the training code has been released as an advanced ASR baseline, using the Kaldi speech recognition toolkit. International Workshop on Machine Listening in Multisource Environments (CHiME) This work may not be copied or reproduced in whole or in part for any commercial purpose. Permission to copy in whole or in part without payment of fee is granted for nonprofit educational and research purposes provided that all such whole or partial copies include the following: a notice that such copying is by permission of Mitsubishi Electric Research Laboratories, Inc.; an acknowledgment of the authors and individual contributions to the work; and all applicable portions of the copyright notice. Copying, reproduction, or republishing for any other purpose shall require a license with payment of fee to Mitsubishi Electric Research Laboratories, Inc. All rights reserved. Copyright c ©Mitsubishi Electric Research Laboratories, Inc., 2013 201 Broadway, Cambridge, Massachusetts 02139
Optimal strategies for literature search

With the large number of urological journals now indexed in online search engines, just reading a few journals will not keep urologists up to date on the latest developments. This paper proposes search strategies to quicken the search and retrieval of the required literature, so that the best evidence may be used to guide practice. This survey of optimal strategies begins with framing the inquiry so the search engine returns results within an accurate scope. The researcher must also isolate the type of evidence appropriate for the scenario and determine its validity. Finally, regardless of the extent of their institution's subscriptions, researchers should be able to attain the complete document. Besides search strategies, this article extensively reviews sources of information valuable to urologists, including databases and web links.
TapBack: towards richer mobile interfaces in impoverished contexts

Much of the mobile work by HCI researchers explores a future world populated by high-end devices and relatively affluent users. This paper turns to consider the hundreds of millions of people for whom such sophistication will not be realised for many years to come. In developing world contexts, people will continue to rely on voice-primary interactions due to both literacy and economic reasons. Here, we motivate research into how to accommodate advanced mobile interface techniques while overcoming the handset, data-connection and user limitations. As a first step we introduce TapBack: back-of-device taps to control a dialled-up, telephone-network-based voice service. We show how these audio gestures might be recognised over a standard telephone connection, via users' existing low-end devices. Further, in a longitudinal deployment, the techniques were made available on a live voice service used by rural Indian farmers. Data from the study illustrates the desire by users to adopt the approach and its potential extensions.
Modular neuropile organization in the Drosophila larval brain facilitates identification and mapping of central neurons

Elucidating how neuronal networks process information requires identification of critical individual neurons and their connectivity patterns. For this purpose, we used the third‐instar Drosophila larval brain and applied reverse‐genetic tools, immunolabeling procedures, and 3D digital reconstruction software. Consistent topological definition of neuropile compartments in the larval brain can be obtained through simple fluorescence‐immunolabeling methods. The modular neuropiles can be used as a fiducial framework for mapping the projection patterns of individual neurons labeled with green fluorescent protein (GFP). GFP‐labeled neurons often exhibit dendrite‐like arbors as well as clustered varicose terminals on neurite branches that innervate identifiable neuropile compartments. We identified candidate cholinergic interneurons in genetic mosaic brains that overlap with the larval optic nerve terminus. By using the neuropile framework, we demonstrate that the candidate visual interneurons are not a subset of the previously identified circadian pacemaker neurons that also contact the larval optic nerve terminus; they may represent parallel pathways in the processing of visual inputs. Thus, in the Drosophila larval brain, modular neuropiles can be used as a framework for systematically identifying, mapping, and classifying interneurons; understanding their roles in behavior can then be pursued further. J. Comp. Neurol. 499:583–602, 2006. © 2006 Wiley‐Liss, Inc.
A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase

Significance Pyrrolysine, the 22nd amino acid, is found in few proteins. One, the trimethylamine methyltransferase MttB, forms a small portion of a large family of proteins. Most in this family lack pyrrolysine and have no known activity. We show that one such protein, MtgB, is a glycine betaine methyltransferase, providing functional context that may explain the relationship between family members with and without pyrrolysine. Close relatives of MtgB are encoded in many of the abundant bacteria in the oceans, as well as different microbes undertaking symbioses ranging from plants to humans. This finding implies that MtgB might partake in a widespread and underappreciated pathway of GB metabolism contributing significantly to global carbon and nitrogen cycling as well as human health. COG5598 comprises a large number of proteins related to MttB, the trimethylamine:corrinoid methyltransferase. MttB has a genetically encoded pyrrolysine residue proposed essential for catalysis. MttB is the only known trimethylamine methyltransferase, yet the great majority of members of COG5598 lack pyrrolysine, leaving the activity of these proteins an open question. Here, we describe the function of one of the nonpyrrolysine members of this large protein family. Three nonpyrrolysine MttB homologs are encoded in Desulfitobacterium hafniense, a Gram-positive strict anaerobe present in both the environment and human intestine. D. hafniense was found capable of growth on glycine betaine with electron acceptors such as nitrate or fumarate, producing dimethylglycine and CO2 as products. Examination of the genome revealed genes for tetrahydrofolate-linked oxidation of a methyl group originating from a methylated corrinoid protein, but no obvious means to carry out corrinoid methylation with glycine betaine. DSY3156, encoding one of the nonpyrrolysine MttB homologs, was up-regulated during growth on glycine betaine. The recombinant DSY3156 protein converts glycine betaine and cob(I)alamin to dimethylglycine and methylcobalamin. To our knowledge, DSY3156 is the first glycine betaine:corrinoid methyltransferase described, and a designation of MtgB is proposed. In addition, DSY3157, an adjacently encoded protein, was shown to be a methylcobalamin:tetrahydrofolate methyltransferase and is designated MtgA. Homologs of MtgB are widely distributed, especially in marine bacterioplankton and nitrogen-fixing plant symbionts. They are also found in multiple members of the human microbiome, and may play a beneficial role in trimethylamine homeostasis, which in recent years has been directly tied to human cardiovascular health.
Importancia de los genes fur y thyA en la patogenia de Haemophilus parasuis

Haemophilus parasuis es un miembro de la familia Pasteurellaceae y un importante patogeno del tracto respiratorio porcino, causante de la enfermedad de Glasser. En la actualidad, esta enfermedad es una de las que tiene mayor incidencia en el sector porcino con una elevada repercusion economica. Por este motivo, es necesario estudiar la biologia molecular de este patogeno para poder desarrollar vacunas mas eficientes que las existentes hasta el presente. Para abordar dicho estudio es imprescindible disponer de algun proceso de transferencia genetica eficaz en H. parasuis. No obstante, dado el desconocimiento que se tenia de dicho patogeno, no se conocia ningun mecanismo natural o de laboratorio que permitiera introducir DNA en H. parasuis. Por ello, el primer objetivo del presente trabajo ha sido desarrollar un metodo de transferencia genetica en H. parasuis que permita estudiar posteriormente los genes implicados en su virulencia y en la colonizacion del hospedador. En la presente tesis se ha demostrado por vez primera que H. parasuis es capaz de transformar de forma natural si el DNA exogeno contiene la secuencia ACCGAACTC, la cual es muy similar al motivo ACCGCACTT descrito en H. influenzae como Uptake Signal Sequence. Ademas, se ha optimizado este proceso, determinando las concentraciones mas adecuadas de celulas bacterianas, AMPc y DNA transformante, asi como el tiempo de incubacion. Un segundo objetivo de este trabajo ha sido averiguar el papel de la timidilato sintasa, enzima clave en la sintesis de desoxitimidina monofosfato (dTMP), en la virulencia de H. parasuis. Para ello, se ha construido un mutante knockout en el gen thyA de H. parasuis y se ha determinado la capacidad de colonizacion y la inmunogeniciad de la cepa salvaje y de dicho mutante thyA en un modelo animal de cobayas. Los resultados han mostrado que la cepa defectiva en la enzima timidilato sintasa tienen una menor capacidad de colonizacion, a pesar de que es capaz de inducir una respuesta inmune en el animal. Por ello, el mutante thyA de H. parasuis puede ser un buen candidato para el desarrollo de futuras vacunas. Finalmente, en este trabajo se ha estudiado la importancia de la proteina Fur en la virulencia de H. parasuis. Dicha proteina es un regulador pleiotropico que, entre otras funciones, controla los mecanismos implicados en la captacion de hierro. Para abordar esta parte del trabajo se propuso la construccion de un mutante de H. parasuis defectivo en la proteina Fur. Los resultados obtenidos han mostrado claramente que dicha proteina es esencial para la viabilidad de esta bacteria. Asi, se ha determinado el entorno genetico del gen fur y se ha confirmado la no viabilidad de los mutantes fur mediante la obtencion de cepas merodiploides.