Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein structural and surface water rearrangement constitute major events in the earliest aggregation stages of tau

Significance Amyloid fibril formation is a key process accompanying many neurodegenerative diseases. Oligomers formed in the early stages of aggregation have been thought to play a key role in disease effects, but their studies are challenging. We use site-specific measurements of surface water diffusion, protein segmental dynamics, and interstrand packing to track early tau protein aggregation processes in situ. Our study reveals that tau aggregation is accompanied by a dramatic structural transformation within minutes of initiating aggregation, followed by the formation of partially structured aggregation intermediates and their rearrangement into stable aggregate species with β-sheet signatures and fibrils. Our findings suggest that therapeutic intervention may focus on disrupting the earliest aggregation events occurring in solution. Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, and the mechanism of its progression is poorly understood. Here, we examine the structural and dynamic characteristics of transiently evolving protein aggregates under ambient conditions by directly probing protein surface water diffusivity, local protein segment dynamics, and interprotein packing as a function of aggregation time, along the third repeat domain and C terminus of Δtau187 spanning residues 255–441 of the longest isoform of human tau. These measurements were achieved with a set of highly sensitive magnetic resonance tools that rely on site-specific electron spin labeling of Δtau187. Within minutes of initiated aggregation, the majority of Δtau187 that is initially homogeneously hydrated undergoes structural transformations to form partially structured aggregation intermediates. This is reflected in the dispersion of surface water dynamics that is distinct around the third repeat domain, found to be embedded in an intertau interface, from that of the solvent-exposed C terminus. Over the course of hours and in a rate-limiting process, a majority of these aggregation intermediates proceed to convert into stable β-sheet structured species and maintain their stacking order without exchanging their subunits. The population of β-sheet structured species is >5% within 5 min of aggregation and gradually grows to 50–70% within the early stages of fibril formation, while they mostly anneal block-wisely to form elongated fibrils. Our findings suggest that the formation of dynamic aggregation intermediates constitutes a major event occurring in the earliest stages of tau aggregation that precedes, and likely facilitates, fibril formation and growth.
Different spatial processing for stimulus-centered and body-centered representations

The authors describe a patient who experienced two successive strokes in the right hemisphere. After the first stroke, she showed stimulus-centered left neglect confined to right space on a circle discrimination task, which resolved. After the second stroke, she showed body-centered left neglect on the same task. These observations of two types of left neglect in the same patient suggest there are at least two distinct spatial attentional systems in the brain: global and focal attentional systems.
Molecular mechanism of desensitization of the chemokine receptor CCR‐5: receptor signaling and internalization are dissociable from its role as an HIV‐1 co‐receptor

The chemokine receptor, CCR‐5, a G protein‐coupled receptor (GPCR) which mediates chemotactic responses of certain leukocytes, has been shown to serve as the primary co‐receptor for macrophage‐tropic human immunodeficiency virus type 1 (HIV‐1). Here we describe functional coupling of CCR‐5 to inhibition of forskolin‐stimulated cAMP formation via a pertussis toxin‐sensitive Gi protein mechanism in transfected HEK 293 cells. In response to chemokines, CCR‐5 was desensitized, phosphorylated and sequestered like a prototypic GPCR only following overexpression of G protein‐coupled receptor kinases (GRKs) and β‐arrestins in HEK 293 cells. The lack of CCR–5 desensitization in HEK 293 cells in the absence of GRK overexpression suggests that differences in cellular complements of GRK and/or β‐arrestin proteins could represent an important mechanism determining cellular responsiveness. When tested, the activity of CCR‐5 as an HIV‐1 co‐receptor was dependent neither upon its ability to signal nor its ability to be desensitized and internalized following agonist stimulation. Thus, while chemokine‐promoted cellular signaling, phosphorylation and internalization of CCR‐5 may play an important role in regulation of chemotactic responses in leukocytes, these functions are dissociable from its HIV‐1 co‐receptor function.
Comunidades agrícolas en el Valle de Potrerillos (NO de Mendoza) durante el Holoceno tardío: organización de la tecnología y vivienda

El Valle de Potrerillos (1.400 m snm) fue intensamente ocupado durante el Holoceno tardio por agricultores que usaron pequenas casas semi-subterraneas (Sitio Gendarmeria Casas 1 y 2). En el trabajo se presenta el registro de estos emplazamientos y de las canteras y talleres utilizados para la explotacion de materias primas liticas. Una cantera taller de riolitas y basaltos en el propio valle (Paleomedanos), y una de rocas criptocristalinas en el Piedemonte de la Precordillera donde se localizaron abrigos rocosos que muestran una secuencia de ocupacion de 2.300 a 1.000 C14 anos AP (Los Conitos). La evaluacion de los materiales liticos de acuerdo a su procedencia permite reconstruir secuencias de produccion que refieren episodios especificos en diferentes localizaciones. Las diferencias en las propiedades organizacionales de la tecnologia se han vinculado a factores como el crecimiento de poblacion, cambios en la subsistencia y sistema de asentamiento entre el Holoceno medio y tardio. Esto involucra un proceso de intensificacion en la explotacion de recursos y una reduccion en la movilidad.
Long-range liquid coarticulation in American English: a preliminary study

The sounds [r] and [l] are unique in the sense that in a word containing that sound, vowels for several syllables before and after the [r]/ [l] will be slightly [r]- or [l]-like themselves. The effect of different sounds on vowels can be measured by analyzing the specific formants, or acoustic components of vowel sounds. Previous studies have found that in British English dialects, the liquid sounds /r/ and /l/ have long-range acoustic effects, meaning that they affect the quality of vowels for several syllables before and after the liquid. In sentences that are phonetically similar except for a critical consonant (/r/ or /l/), there are significant effects on vowel formant frequencies within a range of two syllables before and after this consonant when compared to a neutral /h/ sound. The pronunciation of [r], particularly, is different in British English than in American English because they do not pronounce a [r] sound at the end of a word (e.g. car). Also, many British speakers pronounce [r] using a different part of the tongue than American speakers. The current project looks for evidence of similar effects in American English, by gathering and analyzing data of one native English speaker who was acoustically recorded pronouncing 3 repetitions of 95 target words that were similar except for a critical consonant, /r/, /l/, or /h/, in a frame sentence. This pilot study found that /r/ and /l/ have anticipatory coarticulatory effects ranging at least one syllable, and probably three syllables, although the trends for the third syllable fall slightly short of significance.
Fast and robust detection of crest lines on meshes

We propose a fast and robust method for detecting crest lines on surfaces approximated by dense triangle meshes. The crest lines, salient surface features defined via first- and second-order curvature derivatives, are widely used for shape matching and interrogation purposes. Their practical extraction is difficult because it requires good estimation of high-order surface derivatives. Our approach to the crest line detection is based on estimating the curvature tensor and curvature derivatives via local polynomial fitting.Since the crest lines are not defined in the surface regions where the surface focal set (caustic) degenerates, we introduce a new thresholding scheme which exploits interesting relationships between curvature extrema, the so-called MVS functional of Moreton and Sequin, and Dupin cyclides,An application of the crest lines to adaptive mesh simplification is also considered.
What borrowing buys us: a study of Mandarin Chinese loanword phonology

The two key questions recurring in the literature on loanword studies are: are there any general patterns of loanword adaptation, and if so, which forces drive the process(es) that result in these patterns. This dissertation readdresses these two questions on the basis of a study of loanword phonology in which Mandarin Chinese (MC) is the recipient language (RL) and English the source language (SL). It argues that factors that have not received much attention in the field have to be taken into consideration. They are input types and adapter types. In this dissertation, the roles of the two factors are put to the test. By investigating both loanword corpus data and extensive experimental results, this dissertation presents an analysis of MC loanword phonology that can account for the intricate adaptation patterns attested in a corpus of loanwords borrowed from English into MC. It moreover shows that, depending on input and/or adapter types, loanword adaptation is driven by one or more of the following grammars: the native RL phonological production grammar, the native RL perception grammar, the RL/SL interlanguage phonological production grammar and the RL/SL interlanguage perception grammar. This dissertation will be of interest to all those working on loanword adaptation, Mandarin Chinese phonology, perception and production in second language acquisition and the role of orthography in linguistics.
Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins

Tim10p, a protein of the yeast mitochondrial intermembrane space, was shown previously to be essential for the import of multispanning carrier proteins from the cytoplasm into the inner membrane. We now identify Tim9p, another essential component of this import pathway. Most of Tim9p is associated with Tim10p in a soluble 70 kDa complex. Tim9p and Tim10p co‐purify in successive chromatographic fractionations and co‐immunoprecipitated with each other. Tim9p can be cross‐linked to a partly translocated carrier protein. A small fraction of Tim9p is bound to the outer face of the inner membrane in a 300 kDa complex whose other subunits include Tim54p, Tim22p, Tim12p and Tim10p. The sequence of Tim9p is 25% identical to that of Tim10p and Tim12p. A Ser67→Cys67 mutation in Tim9p suppresses the temperature‐sensitive growth defect of tim10‐1 and tim12‐1 mutants. Tim9p is a new subunit of the TIM machinery that guides hydrophobic inner membrane proteins across the aqueous intermembrane space.
Differential Expression of Vinculin between Weakly and Highly Metastatic B16‐Melanoma Cell Lines

We previously reported on the altered expression of a third actin in mouse‐B16 melanoma associated with malignant progression. White further investigating the relationship of cytoskeletal proteins to malignancy, we found that the expression of vinculin was higher in weakly metastatic B16‐F1 cells than in highly metastatic B16‐F10 cells. By Northern blot analysis, the mRNA expression of vinculin in B16‐F1 was also shown to be higher than in B16‐F10. Immunofluorescence staining showed a clear dotted distribution of vinculin in B16‐F1, but only a weak and diffuse distribution in B16‐F10. The dotted distribution tended to be larger in B16‐F1 and when cultured on Matrigel and fibronectin than on laminin and type IV collagen. An alteration in the expression of vinculin was also observed in other cell systems. Vinculin was detected in both normal 3Y1 and in relatively weakly malignant transformed 3Y1 cell lines, while vinculin was either scarcely detected or not detected at all in more malignant cell lines. These results suggest that the suppression of vinculin is closely related to malignant progression in both the B16‐melanoma and 3Y1 cell systems.
Spectroscopic probes of muscle cross-bridge rotation.

Recent progress in the quantitative study of the mechanics, biochemistry, and molecular structure of muscle has resulted in the formulation of detailed models for the molecular mechanism of force production (reviewed in Refer­ ences 18 and 31). Most of these models involve the motions of myosin cross-bridges, which are coupled to the actin-activated ATPase cycle of myosin. Spectroscopic probes play an essential role in testing these models. In general, spectroscopic methods permit studies to be carried out under physiological or near-physiological conditions that are often inaccessible to more invasive analytical techniques such as electron microscopy or chemical analysis. The detection of site-specific signals, particularly from extrinsically introduced molecular probes attached to myosin heads, offers the kind of selectivity that is not usually possible with mechanical or x-ray diffraction studies. Most importantly, each spectroscopic technique is sensitive to its own specific physical properties, so a judicious choice of technique permits a relatively direct selection of physical parameters that are particularly relevant to contraction models. Techniques sensitive to orientation and rotational motion are particularly important, since cross-bridge rotations are the key events according to most models (18, 32). The present review surveys the recent literature on spectroscopic studies of cross-bridge orientation and rotational motion. Emphasis is placed on applica­ tions to intact or skinned fibers, although studies on myofibrils or purified myosin are also included in cases where they are of particular relevance to fiber work or where extensions of the techniques to fibers are likely. The review is divided into two main sections, optical probes and spin probes.
Human Factors for More Usable and Safer Health Information Technology: Where Are We Now and Where do We Go from Here?

Summary A wide range of human factors approaches have been developed and adapted to healthcare for detecting and mitigating negative unexpected consequences associated with technology in healthcare (i.e. technology-induced errors). However, greater knowledge and wider dissemination of human factors methods is needed to ensure more usable and safer health information technology (IT) systems. Objective: This paper reports on work done by the IMIA Human Factors Working Group and discusses some successful approaches that have been applied in using human factors to mitigate negative unintended consequences of health IT. The paper addresses challenges in bringing human factors approaches into mainstream health IT development. Results: A framework for bringing human factors into the improvement of health IT is described that involves a multi-layered systematic approach to detecting technology-induced errors at all stages of a IT system development life cycle (SDLC). Such an approach has been shown to be needed and can lead to reduced risks associated with the release of health IT systems into live use with mitigation of risks of negative unintended consequences. Conclusion: Negative unintended consequences of the introduction of IT into healthcare (i.e. potential for technology-induced errors) continue to be reported. It is concluded that methods and approaches from the human factors and usability engineering literatures need to be more widely applied, both in the vendor community and in local and regional hospital and healthcare settings. This will require greater efforts at dissemination and knowledge translation, as well as greater interaction between the academic and vendor communities.
Gender and the social construction of illness

Chapter 1: Gender and the Social Construction of Illness: Overview Chapter 2: Women Get Sicker, but Men Die Quicker: Social Epidemiology Chapter 3: Hierarchies in Health Care: Patients, Professionals, and Gender Chapter 4: Gender and Disability: Contradictions and Status Dilemmas Chapter 5: If a Situation is Defined as Real: Premenstrual Syndrome and Menopause Chapter 6: Genital Surgeries: Gendering Bodies Chapter 7: A Modern Plague: Gender and Aids Chapter 8: Healing Social Bodies in Social Worlds: Feminist Healthcare
The Wages of Wins: Taking Measure of the Many Myths in Modern Sport

**Named of one of Princeton University's Noteworthy Books in Industrial Relations for 2006** Arguing about sports is as old as the games people play. Over the years sports debates have become muddled by many myths that do not match the numbers generated by those playing the games. In The Wages of Wins, the authors use layman's language and easy to follow examples based on their own academic research to debunk many of the most commonly held beliefs about sports. In this updated version of their book, these authors explain why Allen Iverson leaving Philadelphia made the 76ers a better team, why the Yankees find it so hard to repeat their success from the late 1990s, and why even great quarterbacks like Brett Favre are consistently inconsistent. The book names names, and makes it abundantly clear that much of the decision making of coaches and general managers does not hold up to an analysis of the numbers. Whether you are a fantasy league fanatic or a casual weekend fan, much of what you believe about sports will change after reading this book.
Combining an Evolutionary Algorithm with the Multilevel Paradigm for Solving the Satisfiability Problem

The satisfiabiltiy problem refers to the task of finding a satisfying assignment that makes a Boolean expression evaluate to True. In this work, an evolutionary algorithm enhanced with the multilevel paradigm is introduced. The multilevel paradigm aims at dividing large and difficult problems into smaller ones, which are hopefully much easier to solve, and then work backward towards the solution of the original problem, using a solution from a previous level as a starting solution at the next level. Results comparing the proposed algorithm with and without the multilevel paradigm are presented.
Dual-phase pipeline circuit design automation with a built-in performance adjusting mechanism

The high speed dual phase operation domino circuit, which includes high-performance and reliable characteristics is proposed, and the circuit design technique with practical implementation is presented. The cell-based automatic synthesis flow supports the quick design of high performance chips. The test chip of a dual-phase 64 bit high-speed multiplier with a built-in performance adjustment mechanism is successfully validated using TSMC 0.18 technology. The test chip shows ×2.7 performance improvement compared to the conventional static CMOS logic design.
ANALISIS PENGARUH LOCUS OF CONTROL DAN LINGKUNGAN KERJA TERHADAP KINERJA PEGAWAI DENGAN SELF EFFICACY SEBAGAI MEDIASI (Studi pada Dinas Pertanian dan Kehutanan Kabupaten Rembang)

The purpose of this study was to determine the effect of locus of control and work environment on employee performance with self efficacy mediation. In this study the dependent variable is the employee performance, while the independent variable is the locus of control and work environment and self-efficacy as an intervening variable (mediation). This research was conducted at the Department of Agriculture and Forestry Rembang regency. The method of data collection was done by using a questionnaire that census sample totaled 103 people. The results showed that the locus of control is significant positive effect on self-efficacy but not significant effect on the employee performance, work environment significant positive effect on self-efficacy and employee performance while self-efficacy significant positive effect on employee performance and an intervening variable (mediation) between locus of control and employee performance. Keywords : locus of control, work environment, self efficacy and employee performance
Two New Term Weighting Methods for Router Syslogs Anomaly Detection

A Router's syslogs are a sequence of events observed and logged by the router. They have been widely used in the system security field. This paper focuses on detecting anomalous behaviors of routers by analyzing router syslogs. For syslog data pre-processing, hierarchical clustering based on counting cousin distance between event patterns is used to cluster events. In order to construct a time series, the length for a time window is set and every time window has a score related to the event clusters in it. Instead of simply treating every event cluster equally in a time window, we assign weights to every event cluster by using four term weighting methods. Two of them-inverse document frequency (IDF) and residual inverse document frequency (RIDF) methods - are widely used in the information retrieval field. Due to their drawbacks, this paper proposes two new weighting methods. The first method, IDFVAR, is a modification of the RIDF method and takes data distribution, frequency, and several additional factors into consideration. In the second method, IDFJMP, JMP value is proposed to evaluate the degree of sudden change of an event cluster. In order to compare those term weighting methods, experiments are done on an estimated data set. Then, we detect anomalous behaviors by using a method derived from standard deviation on the chosen time series. Finally, we conduct experiments on real router syslogs.
Performance Analysis of AIM-K-means & K-means in Quality Cluster Generation

Among all the partition based clustering algorithms K-means is the most popular and well known method. It generally shows impressive results even in considerably large data sets. The computational complexity of K-means does not suffer from the size of the data set. The main disadvantage faced in performing this clustering is that the selection of initial means. If the user does not have adequate knowledge about the data set, it may lead to erroneous results. The algorithm Automatic Initialization of Means (AIM), which is an extension to K-means, has been proposed to overcome the problem of initial mean generation. In this paper an attempt has been made to compare the performance of the algorithms through implementation