Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the segmental stability of helical peptides by isotope‐edited infrared spectroscopy

Isotope‐edited infrared spectroscopy has the ability to probe the segmental properties of long biopolymers. In this work, we have compared the infrared spectra of a model helical peptide (12C) Ac‐W‐(E‐A‐A‐A‐R)6‐A‐NH2, described originally by Merutka et al. ( Biochemistry 1991;30:4245–4248 ) and three derivatives that are 13C labeled at the backbone carbonyl of alanines. The locations of six isotopically labeled alanines are at the N‐terminal, C‐terminal, and the middle two repeating units of the peptide. Variation in temperature from 1° to 91°C transformed the peptides from predominantly helical to predominantly disordered state. Amplitude and position of the infrared amide I′ absorption bands from 12C‐ and 13C‐labeled segments provided information about the helical content. Temperature dependence of infrared spectra was used to estimate segmental stability. As a control measure of overall peptide stability and helicity (independent of labeling), the temperature dependence of circular dichroism spectra in the far‐UV range at identical conditions (temperature and solvent) as infrared spectra was measured. The results indicate that the central quarter of the 32 amino acids helix has the maximal helicity and stability. The midpoint of the melting curve of the central quarter of the helix is 5.4 ± 0.8°C higher than that of the termini. The N‐terminal third of the helix is more helical and is 2.0 ± 1.4°C more stable than the C‐terminus. Proteins 2001;45:81–89. © 2001 Wiley‐Liss, Inc.
Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.
Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review

A recent meta‐analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic‐induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia.
An architecture for reflexive autonomous vehicle control

We describe a software architecture to support the planning and control requirements of an autonomous land vehicle. This architecture is designed specifically to handle diverse terrain with maximal speed, efficacy and versatility through the use of a library of reflexive strategies specialized to particular needs. A hierarchy of control is built in which lower level modules perform tasks requiring greatest immediacy while higher level modules perform tasks involving greater assimilation of sensor data. With all levels of the hierarchy operating in parallel, higher level modules perform selective activation and deactivation of lower level responses with limited interference from demands for immediacy, allowing the system to exploit the advantages of both immediate and assimilated data. The reflexive component of this system has been demonstrated both in a detailed real-time simulation and on a small indoor robotic vehicle.
CAPON modulates cardiac repolarization via neuronal nitric oxide synthase signaling in the heart

Congenital long- or short-QT syndrome may lead to life-threatening ventricular tachycardia and sudden cardiac death. Apart from the rare disease-causing mutations, common genetic variants in CAPON, a neuronal nitric oxide synthase (NOS1) regulator, have recently been associated with QT interval variations in a human whole-genome association study. CAPON had been unsuspected of playing a role in cardiac repolarization; indeed, its physiological role in the heart (if any) is unknown. To define the biological effects of CAPON in the heart, we investigated endogenous CAPON protein expression and protein–protein interactions in the heart and performed electrophysiological studies in isolated ventricular myocytes with and without CAPON overexpression. We find that CAPON protein is expressed in the heart and interacts with NOS1 to accelerate cardiac repolarization by inhibition of L-type calcium channel. Our findings provide a rationale for the association of CAPON gene variants with extremes of the QT interval in human populations.
The formation of ultra-compact dwarf galaxies and nucleated dwarf galaxies

Ultra compact dwarf galaxies (UCDs) have similar properties as massive globular clusters or the nuclei of nucleated galaxies. Recent observations suggesting a high dark matter content and a steep spatial distribution within groups and clusters provide new clues as to their origins. We perform high-resolution N-body/smoothed particle hydrodynamics simulations designed to elucidate two possible formation mechanisms for these systems: the merging of globular clusters in the centre of a dark matter halo, or the massively stripped remnant of a nucleated galaxy. Both models produce density profiles as well as the half light radii that can fit the observational constraints. However, we show that the first scenario results to UCDs that are underluminous and contain no dark matter. This is because the sinking process ejects most of the dark matter particles from the halo centre. Stripped nuclei give a more promising explanation, especially if the nuclei form via the sinking of gas, funneled down inner galactic bars, since this process enhances the central dark matter content. Even when the entire disk is tidally stripped away, the nucleus stays intact and can remain dark matter dominated even after severe stripping. Total galaxy disruption beyond the nuclei only occurs on certain orbits and depends on the amount of dissipation during nuclei formation. By comparing the total disruption of CDM subhaloes in a cluster potential we demonstrate that this model also leads to the observed spatial distribution of UCDs which can be tested in more detail with larger data sets.
(−)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium falciparum Hsp70 Chaperones and Abrogates Their Association with Functional Partners

Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70 isoforms. Two (PfHsp70-1 and PfHsp70-z) of these localize to the parasite cytosol. PHsp70-1 is known to occur in a functional complex with another chaperone, PfHsp90 via a co-chaperone, P. falciparum Hsp70-Hsp90 organising protein (PfHop). (−)-Epigallocatechin-3-gallate (EGCG) is a green tea constituent that is thought to possess antiplasmodial activity. However, the mechanism by which EGCG exhibits antiplasmodial activity is not fully understood. A previous study proposed that EGCG binds to the N-terminal ATPase domain of Hsp70. In the current study, we overexpressed and purified recombinant forms of two P. falciparum cytosol localized Hsp70s (PfHsp70-1 and PfHsp70-z), and PfHop, a co-chaperone of PfHsp70-1. Using the surface plasmon resonance approach, we demonstrated that EGCG directly binds to the two Hsp70s. We further observed that binding of EGCG to the two proteins resulted in secondary and tertiary conformational changes. In addition, EGCG inhibited the ATPase and chaperone function of the two proteins. Furthermore, EGCG abrogated association of the two Hsp70s with their functional partners. Using parasites cultured in vitro at the blood stages, we observed that 2.9 µM EGCG suppressed 50% P. falciparum parasite growth (IC50). Our findings demonstrate that EGCG directly binds to PfHsp70-1 and PfHsp70-z to inhibit both the ATPase and chaperone functions of the proteins. Our study constitutes the first direct evidence suggesting that the antiplasmodial activity of EGCG is at least in part accounted for by its inhibition of Hsp70 function.
Longitudinal Investigation of Smoking Initiation and Relapse Among Younger and Older US Military Personnel.

OBJECTIVES We examined whether military service, including deployment and combat experience, were related to smoking initiation and relapse. METHODS We included older (panel 1) and younger (panel 2) participants in the Millennium Cohort Study. Never smokers were followed for 3 to 6 years for smoking initiation, and former smokers were followed for relapse. Complementary log-log regression models estimated the relative risk (RR) of initiation and relapse by military exposure while adjusting for demographic, health, and lifestyle factors. RESULTS Deployment with combat experience predicted higher initiation rate (panel 1: RR = 1.44; 95% confidence interval [CI] = 1.28, 1.62; panel 2: RR = 1.26; 95% CI = 1.04, 1.54) and relapse rate (panel 1 only: RR = 1.48; 95% CI = 1.36, 1.62). Depending on the panel, previous mental health disorders, life stressors, and other military and nonmilitary characteristics independently predicted initiation and relapse. CONCLUSIONS Deployment with combat experience and previous mental disorder may identify military service members in need of intervention to prevent smoking initiation and relapse.
Consistency : a Factor which Links the Usability of Individual Interaction Components Together

An underlying assumption of component-based software engineering for interactive systems is that the overall usability of a new assembled device mainly depends on the usability of its individual components. This paper challenges this assumption by presenting findings of a series of lab experiments in which 48 subjects operated several consumer devices. The experiments focussed on the effect inconsistency may have on the usability of individual components. The results indicate that inconsistency could cause components, in the same or in higher layers, to activate an inappropriate mental model for other components. Furthermore, the application domain also seems to have an effect on the subjects’ understanding of the functionality a component provides.
Shape oscillations of non-adhering fibroblast cells

We demonstrate that 3T3 fibroblast cells can exhibit periodic shape oscillations following a loss of cell-substrate adhesion. The oscillatory behavior can last many hours at a constant frequency, and can be switched off and on using chemical agents. We show that the oscillation frequency increases with increasing acto-myosin contractility. The oscillations also cease when extracellular calcium is depleted or when a blocker of calcium channels is introduced. We propose a theoretical description of the oscillations based on an instability of the cortical actin layer. The cortical actin layer is described using the hydrodynamic theory of active gels. We assume that calcium enters the cell via mechanically gated channels and that an increase of the calcium density increases the acto-myosin contractility in the cortical layer. The theory provides a stability diagram for the actin cortical layer showing an oscillatory instability and gives a good description of the oscillation period. We also discuss the connections between these oscillations and other oscillations observed after depolymerization of the microtubules and with the formation of blebs.
Dihaploidy yields diploid apomicts and parthenogens in Erigeron (Asteraceae).

UNLABELLED • PREMISE OF THE STUDY Dihaploids result when tetraploids produce reduced eggs that develop without fertilization into diploid progeny. This process is useful for reducing genome complexity and studying trait expression at different ploidal levels. In this study we evaluated genetic inheritance and expression of diplospory (D) and parthenogenesis (P) in a population of dihaploids produced by tetraploid apomictic Erigeron• METHODS From 400 mostly maternal (tetraploid) progeny, we identified 64 (16%) dihaploids with 2n = 18 (53 plants) or 2n = 19 (11 plants). Differential interference contrast (DIC) imaging of ovules was used to evaluate megasporogenesis (meiosis vs. diplospory) and capacity for parthenogenetic embryo development. Seed production was estimated as the proportion of filled seeds. • KEY RESULTS For 60 analyzed dihaploids, diplospory vs. meiosis segregated approximately 1: 1 (P = 0.44) while all exhibited parthenogenetic embryo development. Parthenogenesis for meiotic progeny (n = 27) was observed in approximately 50% of ovules. Apomictic dihaploids (combining D and P; n = 33) produced seeds with mean 24.8% (range 1.3-74.4%) of total flowers. • CONCLUSIONS The dihaploid population consisted of half apomicts (D + P) and half parthenogens (P only). We infer that formation of dihaploid seeds requires the parthenogenesis locus. The highest seed values obtained for diploid apomicts are comparable to those recorded for wild type polyploid apomicts. This is one of the first reports of diploid apomixis in the Asteraceae and it demonstrates that both diplospory and parthenogenesis can be transmitted and expressed at a high level in the diploid condition.
Neuroepidemiologic Trends in 105 US Cases of Pediatric Opsoclonus-Myoclonus Syndrome

Opsoclonus-myoclonus syndrome (OMS) is a rare, autoimmune neurological disorder that is poorly recognized and undertreated. Neuroblastoma is found in one half of the cases. Because of the high incidence of spontaneous regression of neuroblastoma, it is unknown whether not finding a tumor means there was none. To define demographic trends and the standard of care in the first large series of OMS, 105 children were recruited over a 13-year period in a retrospective questionnaire survey. Children with and without a tumor differed little in viral-like prodrome and neurological symptoms. Earliest neurological symptoms were staggering and falling, leading to a misdiagnosis of acute cerebellitis. Later symptoms included body jerks, drooling, refusal to walk or sit, speech problems, decreased muscle tone, opsoclonus, and inability to sleep. Tumor resection alone did not provide adequate therapy for most. Adrenocorticotropic hormone (ACTH), prednisone, and intravenous immunoglobulin were used with equal frequency, but ACTH was associated with the best early response. More than one half of the children had relapses. Residual behavioral, language, and cognitive problems occurred in the majority. The delay in diagnosis (11 weeks) and initiation of treatment (17 weeks) is unacceptably long.
Life stress and depression in a tribal area of Pakistan

Background Depression is common in Pakistan but no research on this subject has been reported from the North West Frontier Province (NWFP), host to numerous Afghan refugees. Aims To measure depressive symptoms and associated features in a population-based sample. Method A Pushto translation of the Self Reporting Questionnaire (SRQ) was administered to 471 adults living in a village in one of the federally administered tribal areas. Respondents were also assessed with a life events checklist for social problems, a social support questionnaire and the Brief Disability Questionnaire. Results Sixty per cent (95/158) of women and 45% (140/313) of men scored 9 or more on the SRQ. High SRQ score was associated with few years of education, higher social problem score, less social support and greater disability. High social problem score was the strongest correlate. Conclusions This population reports more depressive symptoms than other communities in Pakistan and this probably reflects the very high degree of social stress experienced in the NWFP, which has been affected by years of turmoil in neighbouring Afghanistan.
Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms

Two isoforms of glutamic acid decarboxylase (GAD67 and GAD65) and their mRNAs were localized in the rat brain by immunohistochemistry and nonradioactive in situ hybridization methods with digoxigenin-labeled cRNA probes. In most brain regions, both GAD isoforms were present in neuronal cell bodies as well as axon terminals. A few populations of neurons, such as those in the reticular nucleus of the thalamus, exhibited similar cell body labeling for both GADs. However, in many brain regions, the cell bodies that were immunoreactive for GAD67 were often more numerous than those that were immunoreactive for GAD65. In contrast, the density (quantity) of GAD65-immunoreactive axon terminals was higher than that of GAD67-immunoreactive terminals. Strong parallels were observed between the intensity of immunohistochemical labeling of cell bodies and the levels of mRNA labeling for both GAD isoforms. Many groups of GAD-containing cell bodies were distinctly labeled for GAD67, and these same groups of neurons were heavily labeled for GAD67 mRNA. Such neurons included Purkinje cells of the cerebellar cortex, nonpyramidal cells in the cerebral cortex, and neurons of the reticular nucleus of the thalamus. Similar parallels in labeling were observed for GAD65 and its mRNA. Distinct cell body labeling for the protein and associated high levels of GAD65 mRNA were found in neurons of the reticular nucleus of the thalamus and periglomerular cells in the olfactory bulb. However, many cell bodies were not readily labeled for GAD65 with immunohistochemical methods. Such absence or weakness of cell body labeling for the protein was associated with low or moderate levels of GAD65 mRNA. Even though light cell body staining was frequently observed for GAD65 and its mRNA, strong axon terminal labeling for GAD65 was present. Thus, in the deep cerebellar nuclei to which the Purkinje cells of the cerebellar cortex project, strong terminal labeling was observed for both GAD isoforms even though only light cell body labeling of the Purkinje cells was obtained for GAD65 and its mRNA. The findings suggest that the two isoforms of GAD are present in most classes of GABA neurons but that they are not similarly distributed within the neurons. GAD67 is present in readily detectable amounts in many GAD-containing cell bodies whereas GAD65 is particularly prominent in many axon terminals. In addition, neurons that express either form of GAD mRNA also express the corresponding protein. Levels of labeling for the GAD mRNAs suggest that, under normal conditions, the synthesis of GAD65 is frequently lower than that of GAD67. (ABSTRACT TRUNCATED AT 400 WORDS)
Efficient Process Optimization

A computer-based system for modelling and optimizing processes is presented. The Design Structure Matrix (DSM) process representation was used to model the processes due to its compact, generic and easily quantifiable nature. The system is capable of calculating a number of process performance metrics that are focussed towards determining the degree of iteration and concurrency within the process, however, the system is easily extendible to include other process performance measurements. The paper describes the use of a Genetic Algorithm (GA) to optimise the sequence of activities with the focus of reducing the amount of iteration by reducing the number of feedback loops and hence reducing the number of initial guesses that are needed in order to undertake highly dependent tasks. Previous investigations have attempted to define a generic structure for combinatorial optimisation using GAs [Todd, D. (1997). Multiple Criteria Genetic Algorithms in Engineering Design and Operation, Ph.D. Thesis, Engineering Design Centre, University of Newcastle upon Tyne, UK. ],however this paper demonstrates that the structure of the GA is intrinsically tied to the domain. The focus of this paper was an investigation to determine the most efficient and timely structure for the GA with respect to process optimisation. Additional criteria are included within the system and it is has been demonstrated that the structure is applicable for these criteria. It is therefore assumed that if the criteria are dependent upon the matrix representation, in particular, the sequence of the activities and dependencies, then the GA structure will remain applicable. This assumption was demonstrated to be correct when the DSM and GA were used with the same GA structure to optimise component modularity using different optimisation criteria [Whitfield R.I. , Smith J.S. and Duffy A.H. B. (2002). Identifying Component Modules, Seventh International Conference on Artificial Intelligence in Design AID'02, Cambridge, UK,15-17 July 2002. ]. The results indicated that the independent position based crossover and shift mutation operators with 60 and 20% probabilities respectively was the most successful structure for the GA. A relationship between the number of activities and the number of evaluations was determined and may be used to eliminate unnecessary computation in future investigations.
Quantum two-dimensional calculation of time constants of random telegraph signals in metal-oxide-semiconductor structures

The thermal and gate-voltage dependencies for the capture and emission times of random telegraph signals have been theoretically analyzed in a Si-SiO2 interface. A quasi-two-dimensional treatment of the interaction between a neutral near-interface oxide trap and an electron in the subband of the inversion layer has been developed to obtain expressions for the capture and emission times where the influence of the trap parameters ~energy depth, distance to the interface, and electron-phonon coupling factor! is clearly shown. This analysis combines multiphonon-emission theory, tunnel transition probability and the electrostatic Coulomb barrier effect, allowing us to reproduce experimental data for traps in different devices, temperatures, and bias conditions. As a result, trap distances to the interface, trap energy levels, and electron-phonon couplings have been calculated. The character of single electron transitions in this process let us show that the ground and first excited subbands, with similar capture and emission times, are the most important contributors to the phenomenon. @S0163-1829~97! 07039-2#