Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of A Mind at Play by Jimmy Soni and Rob Goodman

During his nearly 50-year career in mathematics and electrical engineering, Claude Elwood Shannon wrote more than 100 research papers and books. Three of them stand out as seminal works in three different disciplines: computer circuit design (Shannon 1938), information theory (Shannon 1948), and cryptology (Shannon 1945, 1949). These papers arguably laid the foundation for the modern digital world. Along with Alan Turing, it may be said that Claude Shannon did indeed help invent the information age. Jimmy Soni and Rob Goodman have produced a workmanlike biography of Claude Shannon that gives us the best (and longest) glimpse yet into Shannon’s life and mind. This review will talk about Soni and Goodman’s book but will focus on those three seminal works. Claude Shannon was born in Petoskey, Michigan on 30 April 1916, the younger of two children of Claude and Mabel Shannon. His family later moved to Gaylord, Michigan, and that is where the young Claude grew up and finished high school. Claude was always a tinkerer, taking things apart and putting them together and making new, interesting devices that struck his fancy (he constructed a telegraph line to a friend’s house using the barbed wire fence that ran between them), and blessed with an insatiable curiosity that would stay with him his entire life. Shannon graduated a year early from Gaylord High School in 1932 and moved on to the University of Michigan, Ann Arbor, where he did a double major in mathematics and electrical engineering. During his senior year at Michigan, he spotted a notice on a bulletin board for an assistantship at MIT working with Vannevar Bush on his Differential Analyzer, probably the most famous analog computer of its time. He applied and was accepted. In fall 1936, Shannon arrived in Cambridge, Massachusetts to work with Bush and start his graduate program in electrical engineering. At the time, Vannevar Bush was the Dean of the MIT School of Engineering and one of the most famous and well-connected research scientists in the United States. none defined
Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of α-subunits in lung alveolar cells.

Catecholamines promote lung edema clearance via β-adrenergic-mediated stimulation of active Na+ transport across the alveolar epithelium. Because alveolar epithelial type II cell Na+-K+-ATPase contributes to vectorial Na+ flux, the present study was designed to investigate whether Na+-K+-ATPase undergoes acute changes in its catalytic activity in response to β-adrenergic-receptor stimulation. Na+-K+-ATPase activity increased threefold in cells incubated with 1 μM isoproterenol for 15 min, which also resulted in a fourfold increase in the cellular levels of cAMP. Forskolin (10 μM) also stimulated Na+-K+-ATPase activity as well as ouabain binding. The increase in Na+-K+-ATPase activity was abolished when cells were coincubated with a cAMP-dependent protein kinase inhibitor. This stimulation, however, was not due to protein kinase-dependent phosphorylation of the Na+-K+-ATPase α-subunit; rather, it was the result of an increased number of α-subunits recruited from the late endosomes into the plasma membrane. The recruitment of α-subunits to the plasma membrane was prevented by stabilizing the cortical actin cytoskeleton with phallacidin or by blocking anterograde transport with brefeldin A but was unaffected by coincubation with amiloride. In conclusion, isoproterenol increases Na+-K+-ATPase activity in alveolar type II epithelial cells by recruiting α-subunits into the plasma membrane from an intracellular compartment in an Na+-independent manner.
Analytical color fluorescence electron microscopy observation of laser diodes

Laser diodes with the multilayer heterostructure have been observed in cathodoluminescence (CL) images using an analytical color fluorescence electron microscope. An AlGaInP/GaInP chip, which is commercially available as 670 nm red laser diode, emits red CL from a part of the p-AlGaInP layer just above the p-GaInP layer and between the n-GaAs blocking layers. A chip that has no blocking layers emits only very weak red CL, which indicates the strong relation of CL with laser emission. In images of a CdZnSe/ZnSe diode that emits 530 nm blue laser light at room temperature, a blue CL emission appears which is much stronger in the n-type region, in particular in the n-ZnSSe cladding layer, than in the p-type region
Qualitative and quantitative interpretation of SEM image using digital image processing

The aim of the this study is improvement of qualitative and quantitative analysis of scanning electron microscope micrographs by development of computer program, which enables automatic crack analysis of scanning electron microscopy (SEM) micrographs. Micromechanical tests of pneumatic ventricular assist devices result in a large number of micrographs. Therefore, the analysis must be automatic. Tests for athrombogenic titanium nitride/gold coatings deposited on polymeric substrates (Bionate II) are performed. These tests include microshear, microtension and fatigue analysis. Anisotropic surface defects observed in the SEM micrographs require support for qualitative and quantitative interpretation. Improvement of qualitative analysis of scanning electron microscope images was achieved by a set of computational tools that includes binarization, simplified expanding, expanding, simple image statistic thresholding, the filters Laplacian 1, and Laplacian 2, Otsu and reverse binarization. Several modifications of the known image processing techniques and combinations of the selected image processing techniques were applied. The introduced quantitative analysis of digital scanning electron microscope images enables computation of stereological parameters such as area, crack angle, crack length, and total crack length per unit area. This study also compares the functionality of the developed computer program of digital image processing with existing applications. The described pre‐ and postprocessing may be helpful in scanning electron microscopy and transmission electron microscopy surface investigations.
Minimizing Risk Associated With Older Liver Donors by Matching to Preferred Recipients: A National Registry and Validation Study

Background Allografts from older liver donors (OLDs), 70 years or older are often discarded for fear of inferior outcomes. We previously identified “preferred recipients” who did not suffer the higher risk of graft loss and mortality associated with OLDs. Preferred recipients were first-time, non-status 1 registrants older than 45 years, body mass index less than 35, indication other than hepatitis C, and cold ischemia time less than 8 hours. Methods We assessed the validity of the preferred recipient construct in a larger, more recent cohort (38 891 patients, 2006-2013). We compared recipients of OLD grafts to recipients of average liver donors (ALDs, age = 40-69) and ideal liver donors (ILDs, age = 18-39) grafts using multilevel Cox regression adjusting for recipient and transplant factors. Results The use of OLD grafts in preferred recipients has increased from 2006 to 2013 (P = 0.02). Preferred recipients Model for End-Stage Liver Disease scores ranged 6 to 40. Preferred recipients had similar 5-year all-cause graft loss (ACGL) with OLD versus ALD and ILD grafts (25.4% vs 24.5% and 21.6%). Conversely, nonpreferred recipients had higher 5-year ACGL with OLD versus ALD and ILD grafts (41.4% vs 32.9% and 25.6%). After adjustment, preferred recipients had similar graft loss with OLD versus ALD grafts (hazard ratio [HR], 0.921.081.27; P = 0.3) and ILD grafts (HR, 0.981.161.39, P = 0.09); however, nonpreferred recipients had higher ACGL risk with OLD grafts versus ALD (HR, 1.281.411.56, P < 0.001) and ILD grafts (HR, 1.501.671.86, P < 0.001). Similar trends are seen with mortality. Conclusions Because preferred recipients comprise 43.3% (n = 2916) of the current waitlist and span the full range of Model for End-Stage Liver Disease scores, transplanted OLD allografts could be distributed without added risk of graft loss or mortality.
Exploring Epitope-Focused Vaccine Development: Design of Epitope Scaffolds and Nanoparticle Presentation Platforms, and Computational Prediction of Conformational Epitopes

Exploring epitope-focused vaccine development: design of epitope scaffolds and nanoparticle presentation platforms, and computational prediction of conformational epitopes Sergey Vitalyevich Menis Chair of the Supervisory Committee: Dr. William R. Schief Jr. Biochemistry Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) evolved a number of defense strategies to evade protective mechanisms of the immune system. Classical vaccine approaches have failed to elicit a protective response for these targets. Epitope Scaffolding is a theoretically attractive immunogen design strategy, which isolates known protective epitopes from their environments while stabilizing relevant conformations, as defined by a neutralizing antibody. In this work, we extend previous epitope scaffolding methods to scaffold a known protective HCV epitope and introduce preliminary immunization results. Additionally, in light of several mixed, protein and glycan, epitopes described for HIV, we apply the scaffolding strategy to an anti-HIV broadly neutralizing antibody – PG9. Next, using a derivative of an HIV envelope glycoprotein, we describe the development of a novel multimerization platform and illustrate potential applications. Finally, a computational protocol was developed to identify antibody accessible epitopes on flexible, glycosylated proteins.
Interactive and coordinated visualization approaches for biological data analysis

The field of computational biology has become largely dependent on data visualization tools to analyze the increasing quantities of data gathered through the use of new and growing technologies. Aside from the volume, which often results in large amounts of noise and complex relationships with no clear structure, the visualization of biological data sets is hindered by their heterogeneity, as data are obtained from different sources and contain a wide variety of attributes, including spatial and temporal information. This requires visualization approaches that are able to not only represent various data structures simultaneously but also provide exploratory methods that allow the identification of meaningful relationships that would not be perceptible through data analysis algorithms alone. In this article, we present a survey of visualization approaches applied to the analysis of biological data. We focus on graph-based visualizations and tools that use coordinated multiple views to represent high-dimensional multivariate data, in particular time series gene expression, protein-protein interaction networks and biological pathways. We then discuss how these methods can be used to help solve the current challenges surrounding the visualization of complex biological data sets.
Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study.

BACKGROUND Several lines of evidence suggest that n-3 fatty acids reduce the risk of some chronic diseases, including heart disease, diabetes, and cancer. Other research, mainly in animals, also suggests a role in bone health. OBJECTIVE We aimed to investigate the association between the ratio of dietary n-6 to n-3 fatty acids and bone mineral density (BMD) in 1532 community-dwelling men and women aged 45-90 y. DESIGN Between 1988 and 1992, dietary data were obtained through self-administered food-frequency questionnaires, and BMD was measured at the hip and spine with the use of dual-energy X-ray absorptiometry. A medical history was obtained and current medication use was validated. Age- and multiple-adjusted linear regression analyses were performed. RESULTS There was a significant inverse association between the ratio of dietary linoleic acid to alpha-linolenic acid and BMD at the hip in 642 men, 564 women not using hormone therapy, and 326 women using hormone therapy; these results were independent of age, body mass index, and lifestyle factors. An increasing ratio of total dietary n-6 to n-3 fatty acids was also significantly and independently associated with lower BMD at the hip in all women and at the spine in women not using hormone therapy. CONCLUSIONS A higher ratio of n-6 to n-3 fatty acids is associated with lower BMD at the hip in both sexes. These findings suggest that the relative amounts of dietary polyunsaturated fatty acids may play a vital role in preserving skeletal integrity in older age.
Linear and nonlinear analysis of human dynamic cerebral autoregulation.

The linear dynamic relationship between systemic arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) was studied by time- and frequency-domain analysis methods. A nonlinear moving-average approach was also implemented using Volterra-Wiener kernels. In 47 normal subjects, ABP was measured with Finapres and CBFV was recorded with Doppler ultrasound in both middle cerebral arteries at rest in the supine position and also during ABP drops induced by the sudden deflation of thigh cuffs. Impulse response functions estimated by Fourier transfer function analysis, a second-order mathematical model proposed by Tiecks, and the linear kernel of the Volterra-Wiener moving-average representation provided reconstructed velocity model responses, for the same segment of data, with significant correlations to CBFV recordings corresponding to r = 0.52 ± 0.19, 0.53 ± 0.16, and 0.67 ± 0.12 (mean ± SD), respectively. The correlation coefficient for the linear plus quadratic kernels was 0.82 ± 0.08, significantly superior to that for the linear models ( P < 10-6). The supine linear impulse responses were also used to predict the velocity transient of a different baseline segment of data and of the thigh cuff velocity response with significant correlations. In both cases, the three linear methods provided equivalent model performances, but the correlation coefficient for the nonlinear model dropped to 0.26 ± 0.25 for the baseline test set of data and to 0.21 ± 0.42 for the thigh cuff data. Whereas it is possible to model dynamic cerebral autoregulation in humans with different linear methods, in the supine position a second-order nonlinear component contributes significantly to improve model accuracy for the same segment of data used to estimate model parameters, but it cannot be automatically extended to represent the nonlinear component of velocity responses of different segments of data or transient changes induced by the thigh cuff test.
Four-component model of body composition in children: density and hydration of fat-free mass and comparison with simpler models.

BACKGROUND Body composition in children is generally measured by 2-component (2C) models, which are subject to error arising from variation in fat-free mass (FFM) composition. The 4-component (4C) model, which divides body weight into fat, water, mineral, and protein, can overcome these limitations. OBJECTIVE The aims of our study were to 1) describe 4C model data for children aged 8-12 y; 2) evaluate interindividual variability in the hydration, bone mineral content, and density of FFM; 3) evaluate the success with which 2C models and bedside techniques measure body composition in this age group with use of the 4C model as a reference. DESIGN Dual-energy X-ray absorptiometry, underwater weighing, deuterium dilution, bioelectrical impedance analysis, and anthropometry were used to determine body composition in 30 children. The contribution of methodologic error to the observed variability in the hydration and density of FFM was evaluated by using propagation of error. RESULTS Mean (+/-SD) FFM density and hydration were 1.0864+/-0.0074 kg/L and 75.3+/-2.2%, respectively, and were significantly different from adult values (P < 0.02). Relative to the 4C model, deuterium dilution and dual-energy X-ray absorptiometry showed no mean bias for fatness, whereas underwater weighing underestimated fatness (P < 0.025). Fatness determined by using skinfold-thickness and bioelectrical impedance analysis measurements along with published equations showed poor agreement with 4C model data. CONCLUSIONS Biological variability and methodologic error contribute equally to the variability of FFM composition. Our findings have major implications for bedside prediction methods used for children, traditionally developed in relation to underwater weighing.
Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures.

Restitution, the lateral migration of cells over an intact basement membrane, maintains mucosal integrity. We studied the regulation of migration and proliferation of enzyme-dispersed canine oxyntic mucosa cells in primary culture. Confluent monolayers were wounded and cultured in serum-free medium, and cells migrating into the wound were counted. [3H]thymidine incorporation into DNA was studied using subconfluent cultures. Considerable migration occurred in untreated monolayers; however, epidermal growth factor (EGF), transforming growth factor (TGF)-α, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1β further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-α- or IL-1β-stimulated migration, but not the response to trefoil peptide, bFGF, or IGF-I. Exogenous TGF-β inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-β blocked the response to exogenous TGF-β and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-α-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-β inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1β enhance gastric epithelial migration, only IL-1β acted in a TGF-α-dependent fashion.
Involvement of lung interstitial proteoglycans in development of hydraulic- and elastase-induced edema.

We extracted and isolated proteoglycans from lung tissue samples obtained from three groups of anesthetized rabbits: 1) control animals (C; n= 8) killed by overdose after 180 min; 2) animals receiving an intravenous saline infusion (S; n = 4, 1.5 ml ⋅ kg-1 ⋅ min-1) for 180 min; 3) animals receiving an intravenous bolus of 200 μg of pancreatic elastase (E; n = 4), killed after 200 min. The lung dry weight-to-wet weight ratio in the three groups was 5.2 ± 0.2, 6.0 ± 0.4, and 5.6 ± 0.5, respectively. Gel-filtration analysis showed a massive fragmentation of the versican family of the extracellular matrix (ECM) in the S groups and a marked degradation of heparan sulfate-containing proteoglycans, including perlecan of the basement membrane, in the E group. The binding properties of total proteoglycans to other ECM components were lowered in both groups relative to control. The decrease in proteoglycan binding was more pronounced for collagen type IV in the E group relative to C (-93.5%, P < 0.05) and for hyaluronic acid in the S groups (-85.8%, P < 0.05). These findings suggest that elastase treatment produces a major degree of damage to the organization of basement membrane, whereas saline loading affects more markedly the architecture of interstitial ECM. Qualitative zymography performed on lung extracts showed increased gelatinase activities in both S and E groups, providing direct evidence that the activation of tissue proteinases may play a role in acute lung injury.
A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1 end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ∼14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen’s design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10−4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.
Prediction of resting energy expenditure in a large population of obese children.

BACKGROUND Recommendations for energy intake in obese children rely on accurate methods for measuring energy expenditure that cannot be assessed systematically. OBJECTIVE The aim was to establish and validate new equations for predicting resting energy expenditure (REE), specifically in obese children. DESIGN REE (indirect calorimetry) and body composition (bioelectrical impedance analysis) were measured in 752 obese subjects aged 3-18 y. The first cohort (n=471) was used to establish predictive equations, the second (and independent) cohort (n=211) was used to validate these equations, and the third cohort, a follow-up group of children who lost weight (n=70), was used to examine predictive REE in the postobese period. REE values predicted with the use of various published equations and the new established equation were compared with measured REE by using the Bland-Altman method and Student's t tests. RESULTS In cohort 1, significant determinants of the new prediction equations were fat-free mass in boys (model R2=0.79) and age and fat-free mass in girls (model R2=0.76). External validation conducted by using the Bland-Altman method and Student's t tests, in cohort 2, showed no significant difference between measured REE and predicted REE with the new equation. When already published equations were applied, systematical bias appeared with all published equations except for that of the World Health Organization. In cohort 3, the children who lost weight, almost all equations significantly underestimated REE. CONCLUSIONS These new predictive equations allow clinicians to estimate REE in an obese pediatric population with sufficient and acceptable accuracy. This estimation may be a strong basis for energy recommendations in childhood obesity.