Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure, Folding Dynamics, and Amyloidogenesis of D76N β2-Microglobulin

Background: We recently discovered the first natural human β2-microglobulin variant, D76N, as an amyloidogenic protein. Results: Fluid flow on hydrophobic surfaces triggers its amyloid fibrillogenesis. The α-crystallin chaperone inhibits variant-mediated co-aggregation of wild type β2-microglobulin. Conclusion: These mechanisms likely reflect in vivo amyloidogenesis by globular proteins in general. Significance: Our results elucidate the molecular pathophysiology of amyloid deposition. Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin (β2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition.
Structure of the tarsi in some stenus species (coleoptera, staphylinidae): External morphology, ultrastructure, and tarsal secretion

SEM studies show that the differentiation among Stenus species with respect to the formation of the tarsi (wide bilobed vs. slender tarsomeres) takes place with a considerable augmentation of tarsal ventral setae in wide bilobed tarsomeres. The structural diversity of ventral tarsal setae among and within species is discussed with respect to 1) their different roles as mechanosensilla and tenent setae, respectively, and 2) the different selection pressures in terms of adhesive requirements along the longitudinal tarsus axis. The tarsi are provided with four groups of tarsal mechanosensilla, comprising hair and bristle sensilla, campaniform sensilla, and scolopidia. The tarsus wall is supported by an epidermis, which forms three different types of glands pouring their secretion via different exit paths onto the outer cuticle. The organization and ultrastructure of each of these glands is described. Only one (unicellular) gland is directly associated with the ventral tenent setae and is thus considered to form the main part of the adhesive secretion. The beetles appear to release the tarsal secretion through mediation of the tenent setae, which contains a lipid and a proteinaceous fraction. I propose that the secretion is discharged to the outside via a system of very fine pore canals in the wall of the setal shaft. Gas chromatography and infrared spectroscopy revealed that the lipid fraction of the secretion is a mixture of unsaturated fatty acid glycerides and aliphatic hydrocarbons whose spectra are similar to those of extractions of the superficial lipid coating of the body surface. J. Morphol. 255:24–43, 2003. © 2002 Wiley‐Liss, Inc.
Competing Reflexive Models of Regional Speech in Northern Ohio

Campbell-Kibler (2012) argued that the “northern” or Cleveland accent has been developing as a register (Agha 2003, 2007) in Ohio, primarily positioned as an unstigmatized and idiosyncratic form of linguistic difference from an imagined central Ohio norm. The current study examines northern Ohioans’ orientation to this construct within a larger understanding of their sociolinguistic imagining of Ohio. Northerners are found to share many language ideologies with other Ohioans, including a focus on north-to-south variation, an emphasis on rural versus urban language difference, and a belief in the local existence of unaccented, educated, normative speech. They differ from other Ohioans in sometimes conceptualizing urban speech as standard, failing to mark central Ohio as a distinct region, and subdividing the northeast (their own region) in a Cleveland-centered small region and a larger northeast corner of the state. Most importantly, they differ from central Ohioans in their treatment of the linguistic difference between central and northern Ohio, i.e., the Inland North/Midland dialect boundary (Labov, Ash & Boberg 2006). Forty-two percent of northerners and 52 percent of others fail to construct a perceptual boundary between central and northeast Ohio, while 27 percent and 48 percent respectively indicate the north as the divergent speech area. Northerners differ, however, in having a third group (31 percent), who position their own speech as normative and the central Ohio speech as marked, counter to the discourses of central Ohioans. These results support Agha’s (2007) point that individuals’ stakes in particular reflexive models are a key influence on models’ circulation and further show the importance of “unremarkable” as a context-bound and often valuable sociolinguistic meaning, rather than a lack of meaning.
Standardization of shape memory alloy test methods toward certification of aerospace applications

The response of shape memory alloy (SMA) components employed as actuators has enabled a number of adaptable aero-structural solutions. However, there are currently no industry or government-accepted standardized test methods for SMA materials when used as actuators and their transition to commercialization and production has been hindered. This brief fast track communication introduces to the community a recently initiated collaborative and pre-competitive SMA specification and standardization effort that is expected to deliver the first ever regulatory agency-accepted material specification and test standards for SMA as employed as actuators for commercial and military aviation applications. In the first phase of this effort, described herein, the team is working to review past efforts and deliver a set of agreed-upon properties to be included in future material certification specifications as well as the associated experiments needed to obtain them in a consistent manner. Essential for the success of this project is the participation and input from a number of organizations and individuals, including engineers and designers working in materials and processing development, application design, SMA component fabrication, and testing at the material, component, and system level. Going forward, strong consensus among this diverse body of participants and the SMA research community at large is needed to advance standardization concepts for universal adoption by the greater aerospace community and especially regulatory bodies. It is expected that the development and release of public standards will be done in collaboration with an established standards development organization.
T‐cell “induced‐self” MHC class I/peptide complexes may enable “de novo” tolerance induction to neo‐antigens occurring outside of the thymus

The hair follicle (HF) epithelium can present self‐antigens to cognate CD8+ T cells. These cells express periodically during the hair cycle arising or age‐related immunogenic proteins including HF‐specific neo‐antigens. We propose that IFN‐gamma derived from the respective antigen‐specific T cells spotting the particular self‐peptides may thereby significantly induce and alter self‐antigen presentation (“induced‐self”). This induction, at first, may silence T cells, including neo‐epitope‐specific T cells. As the thymus cannot significantly recapitulate neo‐epitopes evolving in the periphery, we propose that peripheral tissue‐specific induction of MHC molecules presenting exactly these neo‐epitopes by self‐MHC/peptide‐reactive CD8+ T cells is a key element of self‐tolerance. Subsequently, however, the local perpetuation and modification of the same crosstalk in the context of HF immune privilege collapse can invite HF immunopathology, as typically seen in alopecia areata. This concept may essentially complement thymus‐based regulation models of self/non‐self‐discrimination beyond “missing‐self” to the fine‐tuned “induced‐self” to ensure peripheral needs to maintain self‐tolerance in the case of “danger” and any “alteration of self”.
The Future of Policy Transfer Research

The fact that three contributions address the state of policy transfer research and, to an extent, our contribution to it, suggests that we emphasised, although we did not ‘discover’, an important aspect of contemporary policy making. Here, we shall briefly discuss some of the issues about our work raised in these contributions before turning to our main concern, a focus upon some of the ways in which policy transfer research might usefully develop.
Degrees of freedom region of MIMO interference channel with imperfect current and delayed CSIT

In this paper, we study the degrees of freedom (DoF) of the two-user time-correlated multiple-input-multiple-output (MIMO) interference channel (IC), under realistic assumptions. In particular, the transmitters have imperfect knowledge of the current and the delayed channel state information (CSI). The novelty of this study relies upon the fact that this is the first time, within the literature of IC, that imperfect CSI is addressed for such a case. The delayed CSI at the transmitter (CSIT) is assumed to be more accurate than the current value. We identify the DoF region, which provides an insight on the behaviour of the DoF as a function of the varying qualities of the current and the delayed channel. It is also worth mentioning that any knowledge of imperfect delayed CSIT can also be utilized. Furthermore, an achievability scheme is proposed for each vertex in DoF region. Finally, simulation of the proposed scheme verifies our results.
Voxel‐based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia

Amblyopia, sometimes called “lazy eye,” is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience‐dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7–12 years and 18–35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high‐resolution MRI brain images were analyzed quantitatively with optimized voxel‐based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region‐of‐interest analysis. For the children with amblyopia, additional gray matter reductions in parietal‐occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia. Hum Brain Mapp 25:222–236, 2005. © 2005 Wiley‐Liss, Inc.
Intuitive Learnability of Touch Gestures for Technology-Naïve Older Adults

Touch-based interactions, if intuitive and natural, should be highly learnable. However, the learnability of touch gestures as a computer interaction modality cannot be taken for granted and should be evaluated empirically. This is especially true when technology-naive older adults are concerned, given the psychological and physical constraints associated with this age range. To investigate this issue, we conducted a study with 17 technology-naive older adults, whose experience with technology was mostly limited to making calls with mobile phones. Specifically, the participants were presented with three simple digital games on an interactive tabletop surface and asked to play the games on their own with minimal instruction or help. The first two games required the use of a drag gesture whereas the third game required the use of a rotate gesture. The main research question was whether the older adults could learn the gestures effectively and efficiently. A set of variables such as task duration and gesture accuracy were measured. Results showed that the learnability of a drag gesture was relatively high and that the participants could transfer this skill across the games. In contrast, the learnability of a rotate gesture was low and most of the participants failed to demonstrate any improvement over the tasks of the game. These findings partially corroborate those of earlier work. Implications for future work are drawn, especially exploring the potential of social interactions between older adults for enhancing the learning effects.
Arterial baroreflex control of heart rate in the conscious rat.

Angiotensin II, methoxamine and phenylephrine were evaluated in two tests of reflex responsiveness that involve arterial pressure increases (delta BP) and reflex bradycardia (delta HR). First, bolus injections produced comparable ratios (delta HR/delta BP, in beats . min-1 . mmHg-1) for the three agents: 1.69 +/- 0.31, 1.80 +/- 0.30, and 1.59 +/- 0.32, respectively (SE, n = 6). All three agents also had some undesirable direct chronotropic effects on the heart. Phenylephrine and methoxamine produced rapid and predictable pressure changes and were stable in solution. Blockade by atropine and propranolol was used to show that the bradycardia after bolus injection has an early component (1 s after pressure maximum) that is wholly parasympathetic. In the second test, 5-min infusions of the three agents produced comparable final delta HR/delta BP ratios: 2.0 +/- 0.3, 2.2 +/- 0.5, and 2.3 +/- 0.2 for angiotensin, methoxamine, and phenylephrine, respectively (n = 6). delta HR in this case had a predominant (estimated 67% of total) beta-adrenergic component. Therefore, rapid vagal control of heart rate in the conscious rat is temporary; it is replaced and strengthened in time by a more slowly developing beta-adrenergic component. Bolus injection and infusion of vasopressors can be conveniently used in combination to more fully quantitate heart rate responsiveness in conscious animals that have implanted arterial and venous catheters.
Let Me Count the Ways

Alternative views of computer-mediated communication suggest that it is devoid of affective cues and interpersonal expression, or that the translation of affect into verbal cues facilitates relational communication. Little research has examined basic affective communication online, mirroring a dearth of empirical research identifying spontaneous affective verbal cues in face-to-face interaction. An experiment prompted participants to enact greater or lesser affinity in face-to-face or synchronous computer chat dyads in order to assess the proportion of affect expressed verbally online compared to that which is verbal offline and the specific behaviors that account for affective communication in each channel.Partners’ ratings demonstrated affective equivalency across settings. Analyses of the verbal, kinesic, and vocalic behaviors of face-to-face participants and verbal transcripts from computer sessions revealed specific cues in each condition that led to these ratings. Results support a primary but previously untested proposition in the social information processing theory of mediated interaction.
An application of nonprarametric Cox regression model in reliability analysis: a case study

The contribution deals with an application of the nonparametric version of Cox regression model to the analysis and modeling of the failure rate of technical devices. The objective is to recall the method of statistical analysis of such a model, to adapt it to the real-case study, and in such a way to demonstrate the flexibility of the Cox model. The goodness-of-fit of the model is tested, too, with the aid of the graphical test procedure based on generalized residuals.
MPI 2015-Flooding in Porous Media

The removal of pollutants such as sulfur dioxide (SO2) from industrial exhaust before release into the atmosphere is of considerable environmental interest. One means of removing SO2 is through a chemical reaction with water vapor in a porous filter composed of specially-designed solid particles or fibers. A product of this reaction is sulfuric acid which forms in the pore space of the filter. We discuss a mathematical description of this chemical reaction and develop models for transport of SO2 in a porous filter and for the accompanying fluid production. Our goal is to improve the understanding of how transport and reaction processes occur and how the generation of fluid impacts the effectiveness of the filter. Flooding, which occurs when fluid in the pore space makes its way to the exterior of the filter, is of particular interest. Mathematical and computational models developed here may aid in understanding the underlying transport and reaction mechanisms and in improving filter efficiency.
Organization of choline acetyltransferase-containing structures in the forebrain of the rat

The cholinergic structures in the forebrain of the rat were studied immunohistochemically with a monoclonal antibody to choline acetyltransferase (ChAT) which has proven to be particularly suited to reveal the trajectory of ChAT-positive fibers and their terminations. The habenulo-interpeduncular tract contained the most distinctly ChAT- positive fibers. Here, ChAT-positivity was demonstrated in the perikarya, fibers and terminal field. From the basal forebrain, ChAT- positive fiber bundles could be followed rostrally to the olfactory bulb, dorsomedially to the neocortex and hippocampus, and dorsocaudally to the hippocampus. Terminations of ChAT-positive fibers in these regions were either boutons terminaux (in the interpeduncular nucleus), finely granular (in the hippocampus) or a network of varicose fibers (in the olfactory bulb and neocortex). Cholinergic terminal fields were also demonstrated in the following regions: the nucleus of the lateral olfactory tract, the olfactory tubercle, the pyriform cortex, the lateral nucleus and part of the basal nucleus of the amygdala, the caudate-putamen, the nucleus accumbens, some thalamic nuclei, and the suprachiasmatic nucleus of the hypothalamus. In most of these regions, ChAT-positivity appeared as either fine granules or a meshwork of varicose fibers.
A Comparative Analysis of the Addition and Subtraction of Fractions in Textbooks from Three Countries

In this paper, we report on a comparison of the treatment of addition and subtraction of fractions in primary mathematics textbooks used in Cyprus, Ireland, and Taiwan. To this end, we use a framework specifically developed to investigate the learning opportunities afforded by the textbooks, particularly with respect to the presentation of the content and the textbook expectations as manifested in the associated tasks. We found several similarities and differences among the textbooks regarding the topics included and their sequencing, the constructs of fractions, the worked examples, the cognitive demands of the tasks, and the types of responses required of students. The findings emphasized the need to examine textbooks in order to understand differences in instruction and achievement across countries. Indeed, we postulate that within a given country there may exist a recognizable “textbook signature. ” We also draw on the results and the challenges inherent in our analysis to provide suggestions and directions for future textbook analysis studies.
The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1–5 studies

Liraglutide is a new glucagon‐like peptide‐1 (GLP‐1) receptor agonist and a true GLP‐1 analogue. After successful phase 2 studies, liraglutide was assessed in a series of phase 3 trials [(Liraglutide Effect and Action in Diabetes (LEAD)] designed to demonstrate efficacy and safety across the continuum of type 2 diabetes antihyperglycaemic care, both as monotherapy and in combination with commonly used oral antidiabetic drugs (OADs). The LEAD programme also compared liraglutide with other OADs. As a monotherapy, liraglutide demonstrated significant improvements in glycaemic control in comparison with glimepiride. When combined with one or two OADs, reductions in haemoglobin A1c, fasting plasma glucose and postprandial glucose were generally greater with liraglutide than with comparators. Throughout the trials, liraglutide was associated with weight reduction; in most instances, the reduction from baseline was significantly greater than that seen with comparators. Improvements in assessments of beta‐cell function were consistently shown with liraglutide treatment across all trials. Furthermore, reductions in systolic blood pressure were reported. Liraglutide was associated with a low risk of hypoglycaemia and was generally well tolerated. The majority of adverse effects were gastrointestinal, the most frequent of which was nausea.
Exogenous Shocks or Endogenous Constructions? The Meanings of Wars and Crises

This symposium addresses the role of wars and crises as mechanisms of international change. Over the past two decades, the international system has undergone a number of remarkable transformations, from the end of the Cold War to the emergence of an ongoing ‘‘War on Terror,’’ and from the collapse of statist development models to the emergence of a contested—if evolving—neoliberal ‘‘Washington Consensus. ’’ This volatility exceeds any underlying shifts in economic structures or the distribution of capabilities, and raises important questions regarding the roles of agency, uncertainty, and ideas in advancing change. In this introduction we examine the role of wars and economic crises as socially constructed openings for change. We attempt three things: to critique materialist approaches in the security and political economy issue areas, to outline the distinctive contribution that an agent-centered constructivist understanding of such events offers, and to offer a framework for the study of such events, one which highlights an expanded range of elite-mass interactions. 1929. 1945. 1973. 1989. 2001. One scarcely need identify the events to which these dates refer. One ‘‘knows them when one sees them’’ as ‘‘turning points’’ when old orders ended and new ones began to emerge. Over the past several years, the importance of such events has been examined by a range of international relations scholars offering either materialist analyses of international relations ‘‘after victory’’ and in the context of ‘‘hard times,’’ or more constructivist analyses of ‘‘constitutive wars’’ and the importance of ‘‘socialpolitik. ’’ 1 Such Author’s note: For their comments and criticisms of this effort, we thank Lisa Baglione, Jacqueline Best, Bruce Cronin, Colin Hay, Ronald Krebs, Jennifer Lobasz, the late Steve Poe, and Alexander Wendt. The usual disclaimers apply. 1