Miracle-dz/UniFAR-FTUs huggingface dataset:
The introduction of strain and its effects on the structure and stability of T4 lysozyme.

In order to try to better understand the role played by strain in the structure and stability of a protein a series of "small-to-large" mutations was made within the core of T4 lysozyme. Three different alanine residues, one involved in backbone contacts, one in side-chain contacts, and the third adjacent to a small cavity, were each replaced with subsets of the larger residues, Val, Leu, Ile, Met, Phe and Trp. As expected, the protein is progressively destabilized as the size of the introduced side-chain becomes larger. There does, however, seem to be a limit to the destabilization, suggesting that a protein of a given size may be capable of maintaining only a certain amount of strain. The changes in stability vary greatly from site to site. Substitution of larger residues for both Ala42 and Ala98 substantially destabilize the protein, even though the primary contacts in one case are predominantly with side-chain atoms and in the other with backbone. The results suggest that it is neither practical nor meaningful to try to separate the effects of introduced strain on side-chains from the effects on the backbone. Substitutions at Ala129 are much less destabilizing than at sites 42 or 98. This is most easily understood in terms of the pre-existing cavity, which provides partial space to accommodate the introduced side-chains. Crystal structures were obtained for a number of the mutants. These show that the changes in structure to accommodate the introduced side-chains usually consist of essentially rigid-body displacements of groups of linked atoms, achieved through relatively small changes in torsion angles. On rare occasions, a side-chain close to the site of substitution may change to a different rotamer. When such rotomer changes occur, they permit the structure to dissipate strain by a response that is plastic rather than elastic. In one case, a surface loop moves 1.2 A, not in direct response to a mutation, but in an interaction mediated via an intermolecular contact. It illustrates how the structure of a protein can be modified by crystal contacts.
Feasibility determination in presence of multiple performance measure constraints

A lot of problems in control engineering aim at solving discrete-event systems in presence of performance measure constraints. In many cases, these problems are most suitable to be modeled as constrained simulation optimization, and a key question for solving these problems is to efficiently and accurately select all the feasible designs from a finite set of design alternatives. In this paper, we consider the feasibility determination problem in presence of multiple performance measure constraints. By making some asymptotic approximation, we derive the optimal solution to maximize the expected number of correct selection for all the designs. A corresponding sequential selection procedure is designed for implementation. Numerical testing shows that our approach considerably enhances the simulation efficiency.
Partial Nephrogenic Diabetes Insipidus in a Burned Patient Receiving Sevoflurane Sedation With an Anesthetic Conserving Device—A Case Report

Objective:To describe a case of partial nephrogenic diabetes insipidus in a burned patient after prolonged delivery of low inspired concentrations of sevoflurane via an Anesthetic Conserving Device. Data Sources:Clinical observation. Study Selection:Case report. Data Extraction:Relevant clinical information. Data Synthesis:A 34-year-old man was admitted with burns covering 52% of his total body surface area. Mechanical ventilation was provided during sedation with continuous infusions of sufentanil and midazolam. Sedation became increasingly difficult, and in order to limit administration of IV agents, sevoflurane was added to the inspiratory gas flow. This was provided using an Anesthetic Conserving Device and continued for 8 days. The patient rapidly developed polyuria and hypernatremia with an inappropriate decrease in urinary osmolality. Administration of desmopressin resulted in only a modest effect on renal concentrating ability. After cessation of sevoflurane, all variables returned to normal within 5 days. The results of further investigations (cerebral computed tomographic scan, cerebral magnetic resonance imaging, and serum arginine vasopressin concentration) were compatible with a diagnosis of partial nephrogenic diabetes insipidus. The temporal sequence of clinical findings in relation to sevoflurane administration suggests that the sevoflurane was the probable underlying cause. Conclusions:Clinicians should be aware of the possibility of sevoflurane-induced diabetes insipidus not only during general anesthesia but also in the intensive care setting of sedation in critically ill patients. This is especially important in patients, such as those with severe burns, in whom preserved renal concentrating ability is important to ensure compensation for extrarenal fluid losses.
Scheduling in Networks with Time Dependent Arc Lengths Based on a Loop Finder Algorithm

path problem has to be solved to get the project duration. There are many generalizations in this theme. One of these is applying time dependent process durations. This potential is very important because this is the key to use calendars in schedules. An other one is applying maximal constraints which result loops in the schedule. If these two potentials are allowed together, the prefix of length of the loops can change according the start time. An algorithm has been already presented for this problem. This study is an opportunity to accelerate it.
Observations on the development and structure of the vitelline membrane of the hen's egg: an electron microscope study.

Stages in the development of the outer layer of the vitelline membrane of a hen's egg have been observed in an egg found in the infundibulum of a sacrificed White Leghorn hen. Tissue from the infundibulum and the underlying egg yolk material was taken at increasing distances from the upper end of the egg and the relationship between the secretory cells of the infundibulum and the vitelline mem-brane observed. The structure of the vitelline membrane in ova just liberated from the ovary and not yet in the oviduct and that of the vitelline membrane in new-laid eggs from other White Leghorn hens were observed for comparison.
Proteome-wide Dysregulation by PRA1 Depletion Delineates a Role of PRA1 in Lipid Transport and Cell Migration*

We have previously identified prenylated Rab acceptor 1 (PRA1) as a novel cellular interacting partner for Epstein-Barr virus-encoded oncoprotein, latent membrane protein 1 (LMP1). The intracellular trafficking and full signaling of LMP1 requires its interaction with PRA1. To further explore the role of PRA1 in Epstein-Barr virus-associated nasopharyngeal carcinoma (NPC) cells, we generated several PRA1-knockdown cell clones, which exhibited altered cell morphology and increased cell motility. We identified proteins differentially expressed in the knockdown clones by means of isobaric mass tags labeling coupled with multidimensional liquid chromatography-mass spectrometry. We validated a panel of proteins, which showed consistent up-regulation in PRA1-knockdown clones and participated in regulating lipid homeostasis and cell migration. Immunofluorescence staining further revealed altered localization of these proteins and accumulation of intracellular cholesterol in PRA1-knockdown clones. These effects were phenocopied by treatment with a cholesterol transport inhibitor, U18666A. Moreover, overexpressed PRA1 was able to alleviate the dysregulation of these affected proteins either from PRA1 knockdown or U18666A treatment, implying a role for PRA1 in regulating the levels of these affected proteins in response to altered cholesterol homeostasis. We further demonstrated that LMP1 expression caused PRA1 sequestration in NPC cells, leading to a consequence reminiscent of PRA1 knockdown. Finally, the immunohistochemistry showed a physiological relevance of the PRA1-associated proteome-wide changes in NPC biopsy tissues. In sum, our findings delineated novel roles of PRA1 in lipid transport and cell migration, and provided additional insights into the molecular basis of NPC morphogenesis, namely a consequence of LMP1-PRA1 interaction.
Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy.

PURPOSE To evaluate the relationships between optic disc measurements, obtained by an optical coherence tomograph and a confocal scanning laser ophthalmoscope, and myopia. METHODS One hundred thirty-three eyes from 133 healthy subjects with mean spherical equivalent -6.0 +/- 4.2 D (range, -13.13 to +3.25 D) were analyzed. Optic disc measurements including disc area, rim area, cup area, cup-to-disc area, and vertical and horizontal ratios were obtained with an optical coherence tomograph (StratusOCT; Carl Zeiss Meditec Inc., Dublin, CA) and a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT 3; Heidelberg Engineering, GmbH, Dossenheim, Germany). The modified axial length method derived from prior published work was used to correct the OCT measurements for ocular magnification. Bland-Altman plots were used to evaluate the agreement for each optic disc parameter. Associations between optic disc area and axial length/spherical equivalent were evaluated by linear regression analysis. RESULTS Disc area increased with the axial length/negative spherical equivalent in the HRT and the corrected OCT measurements although opposite directions of associations were found when the OCT measurements were not corrected for magnification. The difference of the corrected OCT and HRT disc area (corrected OCT disc area minus HRT disc area) was correlated with the axial length (r = 0.195, P = 0.025). When the ametropia was limited to -8.0 to +4.0 D, the correlations became insignificant in the HRT. Using the corrected OCT measurements, disc area, rim area, and cup area, cup-to-disc area, and cup-to-disc horizontal and vertical ratios were significantly larger than those measured by the HRT, with a span of 95% limits of agreement at 1.99, 1.33, and 1.86 mm(2) for the areas, 0.34, 0.53, and 0.58 for the ratios, respectively. CONCLUSIONS While optic disc area generally increased with the axial length and myopic refraction, the HRT measurements demonstrated that optic disc size was largely independent of axial length and refractive error between -8 and +4 D. OCT may overestimate optic disc size in myopic eyes and results in poor agreement between the two instruments.
Torque feedback control of dry friction clutches for a dissipative passive haptic interface

The control of a passive dissipative haptic interface using electromagnetic dry friction clutches as actuators is considered. The performance of the device is currently limited by the actuator performance. A dynamic simulation of the system indicates that the actuator torque may be better controlled with torque feedback, resulting in improved path-following performance of the haptic interface. Experimental tests are presented which illustrate the validity of the simulation and feasibility of implementing torque feedback control on the system clutches.
Genomics of natural bird populations: a gene‐based set of reference markers evenly spread across the avian genome

Although there is growing interest to take genomics into the complex realms of natural populations, there is a general shortage of genomic resources and tools available for wild species. This applies not at least to birds, for which genomic approaches should be helpful to questions such as adaptation, speciation and population genetics. In this study, we describe a genome‐wide reference set of conserved avian gene markers, broadly applicable across birds. By aligning protein‐coding sequences from the recently assembled chicken genome with orthologous sequences in zebra finch, we identified particularly conserved exonic regions flanking introns of suitable size for subsequent amplification and sequencing. Primers were designed for 242 gene markers evenly distributed across the chicken genome, with a mean inter‐marker interval of 4.2 Mb. Between 78% and 93% of the markers amplified a specific product in five species tested (chicken, peregrine falcon, collared flycatcher, great reed warbler and blue tit). Two hundred markers were sequenced in collared flycatcher, yielding a total of 122.41 kb of genomic DNA sequence (12096 bp coding sequence and 110 314 bp noncoding). Intron size of collared flycatcher and chicken was highly correlated, as was GC content. A polymorphism screening using these markers in a panel of 10 unrelated collared flycatchers identified 871 single nucleotide polymorphisms (π = 0.0029) and 33 indels (mainly very short). Avian genome characteristics such as uniform genome size and low rate of syntenic rearrangements suggest that this marker set will find broad utility as a genome‐wide reference resource for molecular ecological and population genomic analysis of birds. We envision that it will be particularly useful for obtaining large‐scale orthologous targets in different species — important in, for instance, phylogenetics — and for large‐scale identification of evenly distributed single nucleotide polymorphisms needed in linkage mapping or in studies of gene flow and hybridization.
Extracellular Vesicles Act as Messengers of Macrophages Sensing Atherogenic Stimuli.

The release of vesicles by cells into the extracellular space is found in many aspects of biology, and such extracellular vesicles (EVs) are gaining increasing attention in diverse areas of biomedical research.1,2 EVs represent a heterogeneous population differing in size, number, and composition that are dependent on the type and activation state of the parental cells that release them. Based on size, EVs can be classified into apoptotic bodies (>1 µM), smaller microvesicles (100 nm–1 µm), and exosomes (<125 nm), which are derived from multivesicular bodies. The biological properties of EVs depend on their composition and the specific cargo that is carried by them, including proteins, lipids, and nucleic acids. Their ability to transfer these contents to other cells makes them important contributors to intercellular communication. In particular, the transfer of different types of noncoding RNAs by EVs has been shown to modulate target cell functions.3 See accompanying article on page 49 The function of EVs is being investigated in the context of several pathological conditions, including cardiovascular disease, in which EVs derived from various vascular cells have been studied extensively.2 They are proposed to contribute to disease pathogenesis by promoting inflammation and thrombosis via different mechanisms. On the other hand EV-associated miRNAs have also been shown to mediate protective effects on endothelium.4,5 Therefore, circulating EVs of different cellular origin are considered as candidates for biomarkers of disease activity and risk.6 Moreover, different classes of EVs have been identified …
Embryonic development in the reduced folate carrier knockout mouse is modulated by maternal folate supplementation.

BACKGROUND The reduced folate carrier (RFC1) is a ubiquitously expressed integral membrane protein that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. In this study, embryonic/fetal development is characterized in an RFC1 knockout mouse model in which pregnant dams receive different levels of folate supplementation. METHODS RFC1(+/-) males were mated to RFC1(+/-) females, and pregnant dams were treated with vehicle (control) or folic acid (25 or 50 mg/kg) by daily subcutaneous injection (0.1 mL/10 g bwt), beginning on E0.5 and continuing throughout gestation until the time of sacrifice. RESULTS Without maternal folate supplementation, RFC1 nullizygous embryos die shortly postimplantation. Supplementation of pregnant dams with 25 mg/kg/day folic acid prolongs survival of mutant embryos until E9.5-E10.5, but they are developmentally delayed relative to wild-type littermates, display a marked absence of erythropoiesis, severe neural tube and limb bud defects, and failure of chorioallantoic fusion. Fgfr2 protein levels are significantly reduced or absent in the extraembryonic membranes of RFC1 nullizygous embryos. Maternal folate supplementation with 50 mg/kg/day results in survival of 22% of RFC1 mutants to E18.5, but they develop with multiple malformations of the eyelids, lungs, heart, and skin. CONCLUSIONS High doses of daily maternal folate supplementation during embryonic/fetal development are necessary for early postimplantation embryonic viability of RFC1 nullizygous embryos, and play a critical role in chorioallantoic fusion, erythropoiesis, and proper development of the neural tube, limbs, lungs, heart, and skin.
Educating for the future: adolescent girls’ health and education in West Bengal, India

Abstract Adolescent girls in India carry a disproportionate burden of health and social risks; girls that do not finish secondary education are more likely to have an earlier age of sexual initiation, engage in risky sexual behavior, and consequentially be at greater risk of dying from pregnancy-related causes. This paper presents a comparison of girls in school and girls not in school from 665 participants in rural West Bengal, India. The social cognitive theory (SCT), a comprehensive theoretical model, was used as a framework to describe the personal, behavioral, and environmental factors affecting the lives of these adolescent girls. There were significant differences between girls in and out of school in all three categories of the SCT; girls in school were more likely to have heard of sexually transmitted diseases or infections than girls not in school (p<0.0001). Girls in school were also more likely than girls not in school to boil water before drinking (p=0.0078), and girls in school lived in dwellings with 2.3 rooms on average, whereas girls not in school lived in dwellings with only 1.7 rooms (p<0.0001). Indian adolescent girls who are not in school are disadvantaged both economically and by their lack of health knowledge and proper health behaviors when compared with girls who are still in school. In addition, to programs to keep girls in school, efforts should also be made to provide informal education to girls not in school to improve their health knowledge and behaviors.
Amyloid imaging in aged and young macaques with [11C]PIB and [18F]FDDNP

[11C]PIB and [18F]FDDNP were examined on five aged and five young adult male rhesus macaques using positron emission tomography. Both tracers showed increased accumulation in the striatum, thalamus, cingulate and pons in the aged group. Compared to [11C]PIB, [18F]FDDNP showed higher accumulation in the cortical regions of aged animals as well as young animals. Although [18F]FDDNP may have possible usefulness for imaging, including other proteins, [11C]PIB may be better for amyloid imaging owing to lower non‐specific binding. Synapse 62:472–475, 2008. © 2008 Wiley‐Liss, Inc.
T‐antigen. A prognostic indicator of high recurrence index in transitional carcinoma of the bladder

Forty biopsies from 36 patients with bladder tumors were tested for T‐antigen (TAg) expression on tumor cells on sections untreated or treated with neuraminidase; a 37.5% of tumors showed abnormal expression of TAg either as an aberrant expression, or absence of this antigen after removing sialic acid. These changes were not well correlated with histologic signs of anaplasia or infiltration, nor with other biologic properties of tumor cells such as the expression of blood group antigens (ABH). However, a practical utility of TAg in the study of bladder tumors, is suggested by the analysis of those biopsies with low‐grade low‐stage tumors, on which the abnormal expression of TAg was more discriminatory than the ABH changes in defining those patients suffering tumors with a particular aggressiveness. Circulating antibody titer was also investigated in 20 patients but all of them displayed titers in the normal range, with independence of the results observed in their corresponding bladder biopsies.
Timing recovery based on the PAM representation of CPM

A reduced-complexity decision-directed timing recovery method for continuous phase modulation (CPM) is presented. Using the well-known and popular pulse amplitude modulation (PAM) representation-or Laurent representation- of CPM, we develop two different formulations of a PAM-based timing error detector (TED). We consider the general M-ary multi-h CPM model in our development and use the family of aeronautical telemetry CPMs for our numerical examples. We show by analysis that the two TED formulations have identical ldquoS-curverdquo characteristics, and are free of false lock points, but have slightly different performance when applied to specific CPM examples, particularly in the multi-h case. There is no unanimous winner between the two formulations in all cases; however, for both formulations, we show the TEDs are able to perform close to the theoretical limit given by the modified Cramer-Rao bound. As such, the proposed TEDs provide an important synchronization component for reduced-complexity PAM-based CPM receivers that has heretofore been missing.
Using a Harmony Search Algorithm / Spiking Neural Network Hybrid for Speech Recognition in a Noisy Environment

The Harmony Search Algorithm (HSA) is a recently constructed algorithm that is based on the improvisation process that musicians often demonstrate in performances [1],[2]. In the HSA each musician plays a note in an effort to find the best harmony with his/her fellow musicians. In the context of Computer Science, this improvisation process corresponds to a decision variable (musician) generating a value in order to find a best global optimum solution (a pleasing harmony). The HSA involves three possible choices; repeating a tune or pattern exactly from memory, repeating a tune or pattern with slight variation of one or two variables (adjusting the pitch slightly), or using new random values or notes. Geem [1],[2] formalized these processes as harmony memory, pitch adjusting, and randomization. Recently the HSA has been applied to neural networks. This has been done in two ways. Firstly, by modification of the weights of the neural network by using the HSA as the network is trained, and secondly by using the HSA as a postprocessing tool as a way to reduce the chances of selecting a sub-optimal solution. We propose using the HSA in a new way and on a new generation of neural networks. Spiked Neural Networks (SNN) [3],[4],[5] encode information according to the temporal differences and correlations between spike trains. This new type of neural network is not only biologically more realistic than other neural networks; we propose that SNN have a natural symbiosis with the HSA.