Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock

Phosphorylation of a motif that binds to ankyrin repeat domains switches its binding preference to 14-3-3 proteins. Fitting Protein Keys to Multiple Protein Locks The ankyrin repeat motif is a 33-residue sequence that is important for mediating protein-protein interactions. ANKRA2 contains five such motifs, and it binds to histone deacetylase 4 (HDAC4), among other targets. Through peptide-binding arrays, mutagenesis studies, and x-ray crystallography, Xu et al. showed that the middle three ankyrin repeat domains of ANKRA2 form hydrophobic pockets that accommodate the linear arrangement of specific residues in the binding motif of HDAC4, similar to the way in which the tumblers of a lock accept a key. Phosphorylation of a serine residue within the ANKRA2-binding motif of HDAC4 attenuated the ANKRA2-HDAC4 interaction but enabled HDAC4 to bind to 14-3-3 proteins, which inhibit HDAC activity by sequestering HDACs in the cytoplasm. Proteome-wide screening identified other proteins with similar serine-containing, ankyrin domain–binding motifs, which suggests that phosphorylation acts as a switch that determines the binding preference of this motif in a signal-dependent manner. Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X–associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.
Proteomic profiling of tumor cells after induction of telomere dysfunction

Cell division in the absence of telomerase causes progressive telomere shortening which ultimately leads to telomere dysfunction and initiation of genome instability. In order to identify factors related to loss of telomere function, the effects of telomerase inhibition on the proteome of five tumor cell lines were followed by SELDI‐TOF‐MS. Five differentially expressed protein peaks (p<0.01) were found in a total of 60 clones of five cell lines representing four tissues (lung, breast, prostate, and colon) in which telomerase was inhibited by retroviral overexpression of a dominant negative (DN) mutant of human telomerase reverse transcriptase (hTERT). Among these, a 11.3 kDa peak diminished in DN‐hTERT clones was identified as histone H4 by nanoflow‐HPLC‐MS/MS. Immunoblot analysis not only confirmed the decline of histone H4, but also of other core histone proteins including histone H3. Furthermore, upregulation of several cytokeratins was found to be associated with telomere attrition. In conclusion, loss of telomere function is associated with alterations in the proteome which may represent novel biomarkers for the detection of replicative senescence.
KINESTHETIC RECALL OF CHILDREN WITH ATHETOID and SPASTIC CEREBRAL PALSY and OF NON‐HANDICAPPED CHILDREN

Twenty‐four children with spastic or athetoid quadriplegic cerebral palsy were paired according to severity of motor disability and age, then matched with 12 non‐handicapped children of similar ages. The children were tested with a standard kinesthesiométér and two kinds of scores were recorded. Absolute Error scores reflected the children's deviation from the target and Total Movement scores reflected their over‐all range of movement. There were significant differences between groups in Absolute Error scores, with the cerebral‐palsied children performing worse than the controls and the spastic children worse than the athetoid children. All three groups tended to underestimate the targets and there were no significant differences in Total Movement scores.
Interplay between Autophagy, Exosomes and HIV-1 Associated Neurological Disorders: New Insights for Diagnosis and Therapeutic Applications

The autophagy–lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through the release to the extracellular environment of exosomes. Since exosomes can be transferred from one cell to another, secretion of unwanted material to the extracellular environment in exosomes may have an impact, which can be beneficial or detrimental, in neighboring cells. Exosome secretion is under the influence of the autophagic system, and stimulation of autophagy can inhibit exosomal release and vice versa. Neurons are particularly vulnerable to degeneration, especially as the brain ages, and studies indicate that imbalances in genes regulating autophagy are a common feature of many neurodegenerative diseases. Cognitive and motor disease associated with severe dementia and neuronal damage is well-documented in the brains of HIV-infected individuals. Neurodegeneration seen in the brain in HIV-1 infection is associated with dysregulation of neuronal autophagy. In this paradigm, we herein provide an overview on the role of autophagy in HIV-associated neurodegenerative disease, focusing particularly on the effect of autophagy modulation on exosomal release of HIV particles and how this interplay impacts HIV infection in the brain. Specific autophagy–regulating agents are being considered for therapeutic treatment and prevention of a broad range of human diseases. Various therapeutic strategies for modulating specific stages of autophagy and the current state of drug development for this purpose are also evaluated.
Comparative neurotoxicity of angiographic contrast media

The neurotoxic effects in cerebral angiography of three iodinated ionic contrast media, nonionic iopamidol, 25% mannitol, and saline controls were compared in 25 rabbits. Diatrizoate sodium meglumine was the most toxic agent, followed by diatrizoate meglumine, iothalamate meglumine, and mannitol in terms of blood-brain barrier (BBB) disruption and coupled perfusion decline. HIPDm distribution was more sensitive than trypan blue extravasation for monitoring brain dysfunction. Iopamidol and saline controls exhibited no visual BBB breakdown or alteration in regional uptake of 1–125 HIPDm, confirming the safety of nonionic iopamidol as compared with presently used ionic contrast media.
Finding genes discriminating smokers from non-smokers by applying a growing self-organizing clustering method to large airway epithelium cell microarray data.

BACKGROUND Cigarette smoking is the major risk factor for development of lung cancer. Identification of effects of tobacco on airway gene expression may provide insight into the causes. This research aimed to compare gene expression of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9) in order to find genes which discriminate the two groups and assess cigarette smoking effects on large airway epithelium cells. MATERIALS AND METHODS Genes discriminating smokers from non-smokers were identified by applying a neural network clustering method, growing self-organizing maps (GSOM), to microarray data according to class discrimination scores. An index was computed based on differentiation between each mean of gene expression in the two groups. This clustering approach provided the possibility of comparing thousands of genes simultaneously. RESULTS The applied approach compared the mean of 7,129 genes in smokers and non-smokers simultaneously and classified the genes of large airway epithelium cells which had differently expressed in smokers comparing with non-smokers. Seven genes were identified which had the highest different expression in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1, ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be clinically notable in lung cancer studies. Furthermore, statistical discriminate analysis showed that these genes could classify samples in smokers and non-smokers correctly with 100% accuracy. With the performed GSOM map, other nodes with high average discriminate scores included genes with alterations strongly related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10. CONCLUSIONS This clustering by comparing expression of thousands of genes at the same time revealed alteration in normal smokers. Most of the identified genes were strongly relevant to lung cancer in the existing literature. The genes may be utilized to identify smokers with increased risk for lung cancer. A large sample study is now recommended to determine relations between the genes ABHD2 and ADH7 and smoking.
Differential binding of tetrodotoxin and its derivatives to voltage‐sensitive sodium channel subtypes (Nav1.1 to Nav1.7)

The development of subtype‐selective ligands to inhibit voltage‐sensitive sodium channels (VSSCs) has been attempted with the aim of developing therapeutic compounds. Tetrodotoxin (TTX) is a toxin from pufferfish that strongly inhibits VSSCs. Many TTX analogues have been identified from marine and terrestrial sources, although their specificity for particular VSSC subtypes has not been investigated. Herein, we describe the binding of 11 TTX analogues to human VSSC subtypes Nav1.1–Nav1.7.
Octopull : integrating Static Analysis with Code Reviews THESIS submitted in partial fulfillment of the requirements for the degree of MASTER OF

Teams using modern day software engineering practices often incorporate code reviews as a quality assurance step in their development. These code reviews are intended to uncover software quality defects before code changes are incorporated into the project. Certain classes of these software quality defects can be detected by so-called static analysis tools. These tools have seen increasing uptake and are found to be effective at finding relevant quality defects in these classes. Several tools to integrate the static analysis results into code review have been created, such as SCRUB and Review Bot. However, these tools were created specifically for internally used platforms and their source is not made available. In this thesis, we propose and implement a tool called Octopull, which is an open-source implementation that incorporates static analysis results in the user-interface of the GitHub platform. We evaluate the tool by performing a user-study on undergraduate students. Our study shows no significant effect of using the tool on the effectiveness of their code review sessions.
Climatological phytoplankton chlorophyll and sea surface temperature patterns in continental shelf and slope waters off the northeast U.S. coast

Satellite‐derived chlorophyll estimates from the Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) and Coastal Zone Color Scanner (CZCS), a large archive of in situ near‐surface chlorophyll data, and satellite sea surface temperature (SST) measurements were used to quantify spatial and seasonal variability of near‐surface chlorophyll and SST in middle shelf to slope waters off the coast of the U.S. Northeast. The results of empirical orthogonal function (EOF) analysis on normalized monthly fields (after temporal and spatial means were removed) show that all three chlorophyll climatologies have similar mode 1 temporal and spatial patterns in these waters. Mode 1, which explains about half of the total variability in monthly climatological images, shows that shelf waters in the Gulf of Maine (GOM) are out of phase with the mid‐Atlantic bight (MAB), with seasonally high chlorophyll concentrations in winter in the MAB and in summer in the GOM. The three chlorophyll climatologies begin to differ at higher modes (modes 2 and 3), although SeaWiFS and in situ climatologies keep similar features through mode 3. Higher modes in both SST and chlorophyll are related to the effects of tidal mixing on Georges Bank, differences in seasonal stratification between the southwestern and northeastern GOM, and the importance of the spring bloom in MAB outer shelf waters and western GOM. SST patterns during the CZCS and SeaWiFS eras are very similar, and this indicates that the observed differences between results obtained with these two sensors are probably not caused by differences in physical processes during the two satellite eras.
Binary Control Design for a Class of Bilinear Systems: Application to a Multilevel Power Converter

This brief studies the local stabilization of bilinear systems with binary inputs. A novel convex optimization procedure for the robust design of switching surfaces is proposed using convex optimization tools and linear matrix inequalities. The procedure takes into account the robustness to parametric uncertainties in the system matrices. An experimental illustration for the stabilization of a three-cell multilevel power converter is given.
All-polymer piezoeelctret energy harvester with embedded PEDOT electrode

A novel all-polymer high-aspect-ratio piezoelectret energy harvester with embedded PEDOT electrode is proposed, and its performance for low-resonant-frequency in-plane vibration energy harvesting is demonstrated. Butterfly-shaped stop valves is devised to control the PEDOT capillary flow inside the parylene channels. With the present early prototype, 5.2 V open circuit voltage and 53 nW output power have been obtained at the resonant frequency of 205 Hz with 3.0 g acceleration.
Area efficient implementation of ripple carry adder using memristor crossbar arrays

Memristor has drawn the attention of circuit designers for its non-volatility, and is considered as a viable candidate to replace CMOS technology in many applications. Another interesting characteristic of memristor is that it can be employed in crossbar array architecture that allows very high packing density. In addition to implementing high capacity storage systems, memristor can also be used to realize logic functions. In this paper, the Memristor Aided Logic (MAGIC) design style is used to map the NOR netlist of a given Boolean function to memristor crossbar arrays. Various optimization techniques have been used by scheduling the NOR gates to time steps in order to reduce the hardware cost. To illustrate the viability of the design methodology, full adder and ripple carry adder circuits have been studied and analyzed.
Lagrangian Relaxation via Ballstep Subgradient Methods

We exhibit useful properties of ballstep subgradient methods for convex optimization using level controls for estimating the optimal value. Augmented with simple averaging schemes, they asymptotically find objective and constraint subgradients involved in optimality conditions. When applied to Lagrangian relaxation of convex programs, they find both primal and dual solutions, and have practicable stopping criteria. Up until now, similar results have only been known for proximal bundle methods, and for subgradient methods with divergent series stepsizes, whose convergence can be slow. Encouraging numerical results are presented for large-scale nonlinear multicommodity network flow problems.
Design of a low-power asynchronous elliptic curve cryptography coprocessor

The current evolution of mobile devices and networked pervasive computer systems, such as wireless sensor networks, demand more and more functionality while consuming a minimum amount of energy. Security is one important need within such networked systems. With respect to this, the asynchronous design style is an accepted way of hardening crypto-cores against side-channel attacks. In this paper, we show a case study of designing a low-power asynchronous processor for elliptic-curve-cryptography. Therefore, we provide the theoretical base of this crypto-technique and a description about the applied designflow. For the evaluation, a layout has been created and compared with a synchronous implementation. The results show that even for a larger asynchronous implementation the power consumption is only one third of the synchronous one.
New height, weight and head circumference charts for British children with Williams syndrome

Aim: To produce a growth reference for British children with Williams syndrome. Methods: The children and adults recruited into the study were all affiliated to the Williams Syndrome Foundation, a parent support group founded in 1979. They have all been shown to have a deletion of chromosome 7q11.23. One growth nurse (WRS) prospectively measured the weight, height and head circumference of individuals from 19 regions in Great Britain including Scotland, England and Wales. 169 children and adults were measured on up to four occasions between 2001 and 2004 (275 measurements). In addition, retrospective data were obtained from the hospital notes of 67 of these individuals (586 measurements). Centile curves were constructed using Cole’s LMS method. Results: The centile charts differ from charts previously derived in the USA and Germany and provide more appropriate standards for the British population. Conclusions: We propose that these charts be adopted for routine clinical practice as abnormalities in growth are an important feature of this syndrome.
Microbiota Reconstitution Does Not Cause Bone Loss in Germ-Free Mice

The microbiota has been shown to be an important regulator of health and development. With regard to its effect on bone health, a previous study has suggested that gut microbes negatively impact bone density. However, we show here that this is not generalizable to all microbial communities and mouse strain backgrounds. Our results demonstrate that colonization of mice, both outbred and inbred strains, did not have a major impact on bone health. The identification of microbial communities that do not negatively impact bone health may provide a foundation for future investigations that seek to identify microbes that are either beneficial or detrimental to bone metabolism. ABSTRACT Annually, an estimated 2 million osteoporotic fractures occur in the United States alone. Osteoporosis imparts a great burden on the health care system. The identification of novel regulators of bone health is critical for developing more effective therapeutics. A previous study on the colonization of germ-free (GF) mice with a microbial community has demonstrated that bacterial colonization dramatically increases bone loss. We therefore investigated the impact of multiple microbial communities in different mice to understand how generalizable the impact of bacterial colonization is on bone health. To investigate the impact of different microbial communities on bone health in outbred and inbred mouse strains, gavage was performed on GF Swiss Webster and GF C57BL/6 mice to introduce distinct microbiotas that originated from either humans or mice. GF mice displayed a high degree of colonization, as indicated by more than 90% of the operational taxonomic units present in the starting inoculum being successfully colonized in the mice when they were examined at the end of the experiment. In spite of the successful colonization of GF mice with gut microbiota of either mouse or human origin, bone mass did not change significantly in any of the groups tested. Furthermore, static and dynamic bone parameters and osteoclast precursor and T cell populations, as well as the expression of several inflammatory markers, were mostly unchanged following microbial colonization of GF mice. IMPORTANCE The microbiota has been shown to be an important regulator of health and development. With regard to its effect on bone health, a previous study has suggested that gut microbes negatively impact bone density. However, we show here that this is not generalizable to all microbial communities and mouse strain backgrounds. Our results demonstrate that colonization of mice, both outbred and inbred strains, did not have a major impact on bone health. The identification of microbial communities that do not negatively impact bone health may provide a foundation for future investigations that seek to identify microbes that are either beneficial or detrimental to bone metabolism.
Brittany and the Atlantic Rim in the Later First Millennium BC

Recent work on the Iron Age of Brittany, in particular on the ceramics and the decorated stone stelae, has emphasized the distinctive nature of Armorican culture while demonstrating links with Continental Europe. We argue that it is possible to recognize changing axes of communication between the Atlantic faÂµade and more easterly areas first along the Loire, later along the Seine and finally, as the result of Greek exploration, along the Garonne. These changes are considered against the background of the developing socio-economic systems of west central and Mediterranean Europe.
Differential participation in whole-class discussions and the construction of marginalised identities

Previous researchers have observed differences in the quantity of teacher-pupil interactions experienced by pupils from different social backgrounds. However, there has been little attempt to explore the qualitative nature of such differences and their impact on pupil learning. In this paper I report on an ethnographic study undertaken in a Year 5 primary classroom in the UK focusing on pupil participation in whole-class discussions. I present a typology for identifying productive and non-productive interactions in order to explore the relationship between participation and pupil access to classroom learning processes. The qualitative analysis of audio and video data shows that some children engage in productive exchanges with teachers more often than others, and that this variation may be linked to an implicit set of social norms embedded in the classroomâ€™s micro-culture. The reasons behind such differences primarily relate to teacher expectations of ability and the cultural capital that pupils bring into the classroom, which both impact upon the communicative behaviour of teachers and pupils. Drawing on Lave and Wengerâ€™s theory of learning as participation in practice, I argue that patterns of unequal participation in whole-class discussions may lead to the construction of different types of pupil identities within the classroom. Pupils who are consistently involved in productive interactions come to see themselves as full participants or learners, whilst those involved in non-productive interactions find themselves marginalised from the practice of classroom learning. I conclude that, in order to tackle issues surrounding educational disadvantage, there is a need to address the systems and processes that reproduce wider social inequalities within the classroom micro-climate.