Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryptic epitopes in N‐terminally truncated prion protein are exposed in the full‐length molecule: Dependence of conformation on pH

Prion diseases are diseases of protein conformation. Structure‐dependent antibodies have been sought to probe conformations of the prion protein (PrP) resulting from environmental changes, such as differences in pH. Despite the absence of such antibodies for full‐length PrP, a recombinant Fab (D13) and a Fab derived from mAb 3F4 showed pH‐dependent reactivity toward epitopes within the N‐terminus of N‐terminally truncated PrP(90–231). Refolding and maintaining this protein at pH ≥5.2 before immobilization on an ELISA plate inhibited reactivity relative to protein exposed to pH ≤4.7. The reactivity was not affected by pH changes after immobilization, showing retention of conformation after binding to the plate surface, although guanidine hydrochloride at 1.5–2 M was able to expose the cryptic epitopes after immobilization at pH ≥5.2. The α‐helical CD spectrum of PrP(90–231) refolded at pH 5.5 was reduced somewhat by these pH changes, with a minor shift toward β‐sheet at pH 4 and then toward coil at pH 2. No covalent changes were caused by the pH differences. This pH dependence suggests titration of an acidic region that might inhibit the N‐terminal epitopes. A similar pH dependence for a monoclonal antibody reactive to the central region identified an acidic region incorporating Glu152 as a significant participant. Proteins 2001;44:110–118. © 2001 Wiley‐Liss, Inc.
Radiocarbon Dating of Corn

Nine samples from well-dated prehistoric sites in the southwestern United States have been radiocarbon dated in order to determine the accuracy of 14C dates on corn. The results indicate that a normalized and calibrated 14C date on corn is as accurate an estimate of the sample's age as is a 14C date for any other material. This accuracy has implications not only for future selection of 14C samples but also for interpretation of existing dates on corn and on other kinds of materials.
Study on the Localization for a Rescue Robot Based on Laser Scan Matching

This paper studied the localization problem for a rescue robot based on laser scan matching and extended Kalman filtering (EKF). Scan matching method based on normal distribution transform (NDT) can avoid hard feature extraction problem by estimation of the probability distribution of laser scan data and localization can be achieved using correlation of the NDT. Based on NDT scan matching, the NDT-EKF algorithm has been proposed, which realizes fast and precise localization in rescue environment by fusing odometery data and scan matching together. The NDT-EKF algorithm has been extensively tested and experimental results show its effectiveness and robustness.
Combination, Cooperation And Selection Of Classifiers: A State Of The Art

When several classifiers are brought to contribute to the same task of recognition, various strategies of decisions, implying these classifiers in different ways, are possible. A first strategy consists in deciding using different opinions: it corresponds to the combination of classifiers. A second strategy consists in using one or more opinions for better guiding other classifiers in their training stages, and/or to improve the decision-making of other classifiers in the classification stage: it corresponds to the cooperation of classifiers. The third and last strategy consists in giving more importance to one or more classifiers according to various criteria or situations: it corresponds to the selection of classifiers. The temporal aspect of Pattern Recognition (PR), i.e. the possible evolution of the classes to be recognized, can be treated by the strategy of selection.
Total synthesis of human hepcidin through regioselective disulfide-bond formation by using the safety-catch cysteine protecting group 4,4'-dimethylsulfinylbenzhydryl.

A safety-catch cysteine protecting group, S-4,4'-dimethylsulfinylbenzhydryl (Msbh), was designed and developed to expand the capabilities of synthetic strategies for the regioselective formation of disulfide bonds in cysteine-rich peptides. The directed regioselective synthesis of human hepcidin, which contains four disulfide bonds, was undertaken and led to a high-resolution NMR structure under more physiologically relevant conditions than previously. Conversely, hepcidin synthesized with the formerly assigned vicinal disulfide-bond connectivity displayed significant conformational heterogeneity under similar conditions. The two synthetic forms of human hepcidin induced ferroportin internalization with apparent EC50 values of 2.0 (native fold, 1) and 4.4 nM (non-native fold, 2), with 2 undergoing isomerization to 1 in the presence of ferroportin expressing cells.
ATPDI: a computational definition of fingerprint singular points

In this paper, a computational definition of fingerprint singular points based on aligned tri-coloured pixel-wise directional image, called ATPDI, is presented. The traditional descriptive definitions, geometric definition, and ISO/IEC definition are explained in detail with discussion of their advantages and disadvantages. The quality of a singular point definition is measured by three factors: completeness, rotation sensibility, and precision. We used NIST-4 database for experimental tests, and the experimental results show the ATPDI does not leave cases undefined, is rotation insensitive, and can define singular points in a 2
Neuropsychiatric symptoms in patients with Alzheimer's disease with a vascular component.

OBJECTIVE Vascular changes are observed in most cases of Alzheimer's disease (AD). Observations of AD and vascular disease (VD) allow us to surmise that vascular changes may not only affect cognitive impairment in AD but may also have a negative influence on the neuropsychiatric symptoms which often occur in the course of the disease. The aim of the study was to evaluate the impact of vascular factors on the neuropsychiatric symptoms in Alzheimer's Disease. MATERIAL AND METHODS The study included 48 people with a preliminary diagnosis of Alzheimer's Disease on the basis of NINCDS/ADRDA criteria. The evaluation of impairments in cognitive functioning was carried out by means of the Alzheimer Disease Assessment Scale - the cognitive part (ADAS - cog), whereas the behavioural and psychological symptoms were evaluated by means of the Neuropsychiatric Inventory - the version adapted for residents of nursing homes for the elderly (Neuropsychiatric Inventory - Nursing Home Version) (NPI - NH). The score on the Hachinski scale was the basis for dividing the study participants into two groups - those with a mild vascular component (0-1 points on the Hachinski scale) and those with a severe vascular component (2-4 points). RESULTS The analyzed groups did not differ with respect to the intensity of cognitive impairments (ADAS-cog) or age of the participants. Scores obtained on the NPI - NH scale as well as some of its elements (depression/dysphoria and anxiety) had a discriminating value. Studies show that vascular factors are a serious risk factor for neuropsychiatric symptoms in AD. CONCLUSIONS Vascular factors in Alzheimer's Disease influence the presence of neuropsychiatric symptoms. In the course of angiogenic dementia a greater frequency in depressive disorders was shown. The most visible differences between individuals with a greater and lesser burden of vascular factors was in the realm of depressive and dysphoric disorders.
Structural insight into acute intermittent porphyria

Acute intermittent porphyria (AIP), an inherited disease of heme biosynthesis, is one of the most common types of porphyria. Reduced activity of the enzyme porphobilinogen deaminase (PBGD), which catalyzes the sequential condensation of 4 molecules of porphobilinogen to yield preuroporphyrinogen, has been linked to the symptoms of AIP. We have determined the 3‐dimensional structure of human PBGD at 2.2 Å resolution. Analysis of the structure revealed a dipyrromethane cofactor molecule covalently linked to C261, sitting in a positively charged cleft region. In addition to the critical catalytic D99, a number of other residues are seen hydrogen bonded to the cofactor and play a role in catalysis. Sequential entry of 4 pyrrole molecules into the active site is accomplished by movement of the domains around the hinges. H120P mutation resulted in an inactive enzyme, supporting the role of H120 as a hinge residue. Interestingly, some of the mutations of the human PBGD documented in patients suffering from AIP are located far away from the active site. The structure provides insights into the mechanism of action of PBGD at the molecular level and could aid the development of potential drugs for the up‐regulation of PBGD activity in AIP. — Song, G. , Li, Y. , Cheng, C, Zhao, Y. , Gao, A. , Zhang, R. , Joachimiak, A. , Shaw, N. , Liu, Z. ‐J. Structural insight into acute intermittent porphyria. FASEB J. 23, 396–404 (2009)
Direct estimation of volumes in ovarian follicles using the nucleator

The aim of the study was to evaluate the precision of the nucleator principle with regard to estimation of follicle, oocyte and antral volumes in individual follicles, as well as their average volumes in a group of follicles. Nine isolated murine ovarian follicles embedded in plastic were orientated isotropically, cut into 20 μm serial sections, and stained with hematoxylin. In each follicle the volumes of the follicle, the antrum and the oocyte were estimated in two ways, both unbiased: Firstly, in just one unique section through the follicle, viz. the section which contains the unique sampling point ‐ the nucleolus of the oocyte ‐ using the nucleator principle, and, secondly, in the complete set of follicle sections using the Cavalieri principle. Estimates using the Cavalieri, which are very precise (CEFollicle˜0.03, CEOocyte˜0.11, CEAntrum˜0.16), were interpreted as the “true” values. Therefore, the precision (estimator variation) of the nucleator estimates could be calculated. The nucleator estimates correlated well with the Cavalieri estimates: r(follicle) = 0.95; r(antrum) = 0.88; r(oocyte) = 0.83. The nucleator provides very precise estimates of the volumes of follicle, oocyte and antrum with a minimal amount of effort, since the estimates are derived from measurements in only four directions sampled in a uniform systematic way, the first direction being chosen at random, in only one section through the follicle. Moreover, it is not necessary to know the precise thickness of the section, and, finally, the estimates are expressed in correctly dimensioned terms. The estimator variation of the nucleator (CE = 0.28) is of minor importance compared to the biological variation (CV = 0.47) in this realistic sample of follicles.
Interleukins in glioblastoma pathophysiology: implications for therapy

Despite considerable amount of research, the poor prognosis of patients diagnosed with glioblastoma multiforme (GBM) critically needs new drug development to improve clinical outcomes. The development of an inflammatory microenvironment has long been considered important in the initiation and progression of glioblastoma; however, the success of developing therapeutic approaches to target inflammation for GBM therapy has yet been limited. Here, we summarize the accumulating evidence supporting a role for inflammation in the pathogenesis of glioblastoma, discuss anti‐inflammatory targets that could be relevant for GBM treatment and provide a perspective on the challenges faced in the development of drugs that target GBM inflammation. In particular, we will review the function of IL‐1β, IL‐6 and IL‐8 as well as the potential of kinase inhibitors targeting key players in inflammatory cell signalling cascades such as JAK, JNK and p38 MAPK.
Regulation of Protein Synthesis in Ventricular Myocytes by Vasopressin

Protein synthesis in H9c2 ventricular myocytes was subject to rapid inhibition by agents that release Ca2+ from the sarcoplasmic/endoplasmic reticulum, including thapsigargin, ionomycin, caffeine, and arginine vasopressin. Inhibitions were attributable to the suppression of translational initiation and were coupled to the mobilization of cell-associated Ca2+ and the phosphorylation of eIF2α. Ionomycin and thapsigargin produced relatively stringent degrees of Ca2+mobilization that produced an endoplasmic reticulum (ER) stress response. Translational recovery was associated with the induction of ER chaperones and resistance to translational inhibition by Ca2+-mobilizing agents. Vasopressin at physiologic concentrations mobilized 60% of cell-associated Ca2+ and decreased protein synthesis by 50% within 20–30 min. The inhibition of protein synthesis was exerted through an interaction at the V1 vascular receptor, was imposed at physiologic extracellular Ca2+ concentrations, and became refractory to hormonal washout within 10 min of treatment. Inhibition was found to attenuate after 30 min, with full recovery occurring in 2 h. Translational recovery did not involve an ER stress response but rather was derived from the partial repletion of intracellular Ca2+ stores. Longer exposures to vasopressin were invariably accompanied by increased rates of protein synthesis. Translational inhibition by vasopressin, but not by Ca2+-mobilizing drugs, was both preventable and reversible by treatment with phorbol ester, which reduced the extent of Ca2+ mobilization occurring in response to the hormone. Larger and more prolonged translational inhibitions occurred after down-regulation of protein kinase C. This report provides the first compelling evidence that hormonally induced mobilization of sarcoplasmic/endoplasmic reticulum Ca2+stores is regulatory upon mRNA translation.
Ship systems for natural gas liquefaction

Pregled postojecih sustava prijevoza prirodnog plina u tekucem stanju. Principi rada sustava ukapljivanja, termodinamicki procesi, tehnoloski uvjeti, prednosti i nedostaci pojedinih rjesenja.
Human thalamus contributes to perceptual stability across eye movements

We continuously move our eyes when we inspect a visual scene. Although this leads to a rapid succession of discontinuous and fragmented retinal snapshots, we perceive the world as stable and coherent. Neural mechanisms underlying visual stability may depend on internal monitoring of planned or ongoing eye movements. In the macaque brain, a pathway for the transmission of such signals has been identified that is relayed by central thalamic nuclei. Here, we studied a possible role of this pathway for perceptual stability in a patient with a selective lesion affecting homologous regions of the human thalamus. Compared with controls, the patient exhibited a unilateral deficit in monitoring his eye movements. This deficit was manifest by a systematic inaccuracy both in successive eye movements and in judging the locations of visual stimuli. In addition, perceptual consequences of oculomotor targeting errors were erroneously attributed to external stimulus changes. These findings show that the human brain draws on transthalamic monitoring signals to bridge the perceptual discontinuities generated by our eye movements.
The Cytoplasmic Region of α-1,6-Mannosyltransferase Mnn9p Is Crucial for Retrograde Transport from the Golgi Apparatus to the Endoplasmic Reticulum in Saccharomyces cerevisiae

ABSTRACT In Saccharomyces cerevisiae, Och1p and Mnn9p mannosyltransferases are localized in the cis-Golgi. Attempts to live image Och1p and Mnn9p tagged with green fluorescent protein or red fluorescent protein, respectively, using a high-performance confocal laser scanning microscope system resulted in simultaneous visualization of the native proteins in a living cell. Our observations revealed that Och1p and Mnn9p are not always colocalized to the same cisternae. The difference in the dynamics of these mannosyltransferases may reflect differences in the mechanisms for their retention in the cis-Golgi, since it has been reported that Mnn9p cycles between the endoplasmic reticulum and the cis-Golgi whereas Och1p does not (Z. Todorow, A. Spang, E. Carmack, J. Yates, and R. Schekman, Proc. Natl. Acad. Sci. USA 97:13643-13648, 2000). We investigated the localization of chimeric proteins of Mnn9p and Och1p in sec12 and erd1 mutant cells. A chimeric protein, M16/O16, which consists of the N-terminal cytoplasmic region of Mnn9p and the transmembrane and luminal region of Och1p, behaved like Mnn9p, suggesting that the N-terminal cytoplasmic region is important for the intracellular dynamics of Mnn9p. This observation is supported by results from subcellular-fractionation experiments. Mutational analysis revealed that two arginine residues in the N-terminal region of Mnn9p are important for the chimeric protein to cycle between the endoplasmic reticulum and the Golgi apparatus.
Adaptive realization of a maximum likelihood time delay estimator

This paper presents an adaptive maximum likelihood method for estimating the time difference of arrival of a source signal at two spatially separate sensors. It is well-known that the maximum likelihood technique achieves the Cramer-Rao lower bound for time delay estimation error for certain signal conditions. The /spl alpha/-/spl beta/ tracker is a heuristic mechanism that is heavily used in target tracking applications. In this work, we combine an adaptive realization of the maximum likelihood time delay estimator with the /spl alpha/-/spl beta/ tracker to obtain significant improvement in the performance of the tracker, Experimental results showing 2 to 8 dB improvement in the mean-square estimation error over the conventional /spl alpha/-/spl beta/ tracker for various signal-to-noise ratios are also included in the paper.
Navigating on web sites: Exploring the life events approach

To help users find their way on complex web sites, an adequate information architecture and navigation design is important. Currently, a navigational structure based on so-called life events is becoming increasingly popular. In close cooperation with the Dutch Tax and Customs Administration, we executed two studies (a card sort study and a comparative usability test) to investigate the attitude and experiences of the users with regard to a web site based on life events. The results of the card sort study showed that citizens do not spontaneously think about life events as a possible way to categorize and label content elements of a government web site. The results of the usability test showed that a navigational structure based on life events does not lead to more effective or efficient search processes. A web site with a navigational structure based on life events is as usable as a structure based on themes.
Flood Impacts on Road Transportation Using Microscopic Traffic Modelling Technique Contributions

The research presented in this paper proposes a novel methodology for modelling the impacts of floods on traffic. Often flooding is a complex combination of various causes (coastal, fluvial and pluvial). Further, transportation systems are very sensitive to external disturbances. There is insufficient knowledge on the interactions in these complex and dynamic systems. This paper proposes a methodology for integrating a flood model (MIKE Flood) and a traffic model (SUMO). Traffic on inundated roads will be interrupted or delayed according to the manner of flood propagation. As a consequence, some trips will be cancelled or rerouted and other trips will be indirectly affected. A comparison between the baseline and a flood scenario yields the impacts of that flood on traffic, estimated in terms of lost business hours, additional fuel consumption, and additional CO2 emissions. The outcome suggests that the proposed methodology can help to quantify the flood impact on transportation.
5-HTTLPR moderates the relation between changes in depressive and bulimic symptoms in adolescent girls: a longitudinal study.

OBJECTIVE Depression and bulimia both are associated with low serotonin levels. We examined whether the serotonin transporter gene (5-HTTLPR) moderates the relation between depressive and bulimic symptoms over time. METHOD Fifty adolescent girls with no current or past Axis I disorder were genotyped for the 5-HTTLPR gene. Twice, 6 months apart, participants completed self-report measures of depressive symptoms and bulimic symptoms. RESULTS The association between change in depressive symptoms and change in bulimic symptoms over time was significantly stronger in girls who are homozygous for the short 5-HTTLPR allele than for girls with at least one long allele. DISCUSSION This finding is consistent with previous studies documenting a relation between depressive and bulimic symptoms in adolescents. Few studies, however, considered the possible role of serotonin linking both disorders. Gaining a better understanding of developmental effects of low serotonin could help to identify high-risk individuals and provide effective prevention and intervention.
Feature Adjustment in Kernel Space when using Cross-Validation November 28 , 2017

Kernel methods are a powerful set of techniques for learning from data. One of the attractive properties of these techniques is that they rely only on a kernel function which provides the user-defined notion of similarity between two observations, to train the models. This report describes a strategy for evaluating kernel-based predictive models within a cross-validation framework when we also have a set of confounds which are used to ‘adjust’ the data based on their relationship with the data within the training sample. We show that for a linear kernel function, this adjustment can be performed in kernel space which removes the need to reload or retain the data in memory during the cross-validation procedure. Furthermore, we show how a similar strategy can be used with other kernel functions such as the Gaussian Radial Basis function. Feature Adjustment in Kernel Space when using Cross-Validation Anil Rao Janaina Mourao-Miranda
Acute Coronary Syndromes Compendium

Circulation Research is available at http://circres.ahajournals. org DOI: 10.1161/CIRCRESAHA.114. 302804 Abstract: Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non–ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply–demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into disease-modifying agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as β-blockers and inhibitors of the renin–angiotensin–aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic preand postconditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, antithrombotic agents, and the use of high-intensity statins. (Circ Res. 2014;114:1944-1958.)