Miracle-dz/UniFAR-FTUs huggingface dataset:
Production and Characterization of Improved Adenovirus Vectors with the E1, E2b, and E3 Genes Deleted

ABSTRACT Adenovirus (Ad)-based vectors have great potential for use in the gene therapy of multiple diseases, both genetic and nongenetic. While capable of transducing both dividing and quiescent cells efficiently, Ad vectors have been limited by a number of problems. Most Ad vectors are engineered such that a transgene replaces the Ad E1a, E1b, and E3 genes; subsequently the replication-defective vector can be propagated only in human 293 cells that supply the deleted E1 gene functions intrans. Unfortunately, the use of high titers of E1-deleted vectors has been repeatedly demonstrated to result in low-level expression of viral genes still resident in the vector. In addition, the generation of replication-competent Ad (RCA) by recombination events with the E1 sequences residing in 293 cells further limits the usefulness of E1-deleted Ad vectors. We addressed these problems by isolating new Ad vectors deleted for the E1, E3, and the E2b gene functions. The new vectors can be readily grown to high titers and have several improvements, including an increased carrying capacity and a theoretically decreased risk for generating RCA. We have also demonstrated that the further block to Ad vector replication afforded by the deletion of both the E1 and E2b genes significantly diminished Ad late gene expression in comparison to a conventional E1-deleted vector, without destabilization of the modified vector genome. The results suggested that these modified vectors may be very useful both for in vitro and in vivo gene therapy applications.
The Essence of the Family Critical Illness Experience and Nurse-Family Meetings

Nursing care of families is essential to strong family support and maintenance of family health during a critical illness. Secondary data analysis of interviews conducted with 11 families with a family member in the intensive care unit revealed two essences: the family critical illness experience and the family vision for the kind of care families required and desired from nurses. The purpose of this article was to explicate the essence of these phenomena and their implications for family nursing practice. Findings affirm the need for a family intervention described in the literature, that of regularly scheduled nurse—family meetings. Although developed for work with families experiencing a chronic illness, bringing families together and inviting meaningful conversation about their experiences is appropriate for families experiencing critical illness. Nurse—family meetings acknowledge suffering and vulnerability of families when a loved one is critically ill and afford families an opportunity for honest sensitive communication with nurses.
Modified Symbiotic Evolutionary Learning for Type-2 Fuzzy System

This paper proposes a new modified symbiotic evolutionary learning method (SET2) for fine-tuning the parameters of a type-2 fuzzy system. The paper uses a group-based symbiotic evolutionary approach. Instead of evolving the individual rules and assigning the fitness values for each rule, the membership function parameters and the rules are evolved as individual groups. This method improves the exploration of the solution space, and optimizes the rule, base count and the most influencing input parameters in each rule which is difficult to obtain in conventional symbiotic evolutionary learning approach. The paper also proposes a method to obtain the similarity measure of the membership functions. In order to demonstrate the efficiency of the proposed learning method, it is deployed in a simulated urban traffic network to obtain the optimal signal timings in a distributed manner. The proposed SET2 signal control was tested for various traffic conditions experienced in a section of the Central Business District of Singapore. A comparison of the average time delay and speed of vehicles indicated that SET2 signal control performed significantly better than the benchmark signal controls such as GLIDE, hierarchical multiagent system, and geometric fuzzy multiagent system. The test bed also showcased the performance of the modified learning method in a distributed environment.
Erkek İnfertilitesinde Spermatozoon DNA Hasarının Rolü ve Önemi

Erkege bagli infertilite, genetik ve epigenetik nedenlerden kaynaklanan karmasik etiyolojili, dolveriminin normal sinirlar altinda bulunmasina sebep olan bir hastaliktir. Infertilite ile spermatozoonun genetik yapisi arasinda kuvvetli bir birliktelik bulunmaktadir. Cesitli ic ve dis kaynakli sebeplerden dolayi spermatozoonun DNA yapisinda farkli duzeylerde hasarlar meydana gelmektedir. Infertil erkeklerde spermatozoon DNA hasari yuksek olarak saptanmaktadir. Cesitli DNA hasar tamir mekanizmalari DNA’da meydana gelen hasarin tipine uygun olarak devreye girmekte ve hasar tamirinin gerceklestirilmesi sonucu genomik kararlilik korunmakta ve hucre yasamini surdurebilmektedir. H asar nedenlerinin cogalmasi , onarim mekanizmalarind aki aksakliklar gibi nedenlerle hucre olumu, fertilizasyon kapasitesinde azalma, spermatozoon genom butunlugunde bozu lma, infertilite ve mutasyonlar meydana gelebilmektedir . Spermatozoon DNA’sinda sekillenen bu hasarlarin tespiti amaciyla tek hucre jel elektroforezi, tunel, spermatozoon kromatin yapisi analizi gibi bircok metot kullanilmaktadir. Mevcut veriler isiginda, daha iyi kalitede spermatozoonlara sahip olan hayvanlarin seciminde, reproduktif biyoteknolojiler ve yardimci ureme tekniklerinde spermatozoon seciminde onemli olsa da, erkek infertilitesi tani ve tedavisinde spermatozoon DNA hasari olup olmadiginin degerlendirilmesi ayri bir onem arz etmektedir.
Biofiltration of gasoline and diesel aliphatic hydrocarbons

The ability of a biofilm to switch between the mixtures of mostly aromatic and aliphatic hydrocarbons was investigated to assess biofiltration efficiency and potential substrate interactions. A switch from gasoline, which consisted of both aliphatic and aromatic hydrocarbons, to a mixture of volatile diesel n-alkanes resulted in a significant increase in biofiltration efficiency, despite the lack of readily biodegradable aromatic hydrocarbons in the diesel mixture. This improved biofilter performance was shown to be the result of the presence of larger size (C9-C12) linear alkanes in diesel, which turned out to be more degradable than their shorter-chain (C6-C8) homologues in gasoline. The evidence obtained from both biofiltration-based and independent microbiological tests indicated that the rate was limited by biochemical reactions, with the inhibition of shorter chain alkane biodegradation by their larger size homologues as corroborated by a significant substrate specialization along the biofilter bed. These observations were explained by the lack of specific enzymes designed for the oxidation of short-chain alkanes as opposed to their longer carbon chain homologues. Implications: Biological removal of petroleum hydrocarbons from contaminated air has not become a widely used technology due to its low efficiency. This paper presents the analysis of this problem using bench-scale experiments and provides several reasons for the low biodegradation efficiency of gasoline. The results reported suggest that gasoline removal efficiency strongly depends on the substrate composition, with aromatic hydrocarbons being removed preferentially. The study also opens up a new perspective for the efficient biofiltration of diesel hydrocarbons as opposed to gasoline, as higher molecular weight n-alkanes of diesel were removed readily. By contrast, low-molecular-weight n-alkanes of gasoline turned out to be poor substrates for biofiltration, and the biological reasons for this phenomenon were suggested.
Proposta conceitual para sistema de compartilhamento de bicicletas no campus universitário da UFRN

O sistema de compartilhamento inteligente de bicicletas encontra-se na sua terceira geracao, sendo sucesso em dezenas de cidades do mundo para ajudar na mobilidade urbana. A proposta de implantacao desse sistema de compartilhamento no campus central da UFRN/Natal se assemelha a que ocorreu na cidade de Paris na Franca, onde a ciclovia recem-construida encontrava-se com uso abaixo do que era esperado. Para a implantacao desse sistema foi apresentada a ciclovia construida no campus, os possiveis usuarios do sistema, as bicicletas, as estacoes, e nestas os terminais de acesso e os engates para guardar as bicicletas, onde os melhores modelos existentes para os pontos anteriormente citados sao analisados e os mais viaveis para a realidade do campus foram propostos. Com base nessas analises realizadas com os elementos do sistema, foi estudada a viabilidade da implementacao, os custos diretos com os ativos e os custos operacionais, bem como a proposta de usar um software existente ou de desenvolver uma equipe para criacao de um software proprio, e por fim foi proposto que o sistema tivesse uma interacao com os departamentos de alguns cursos da UFRN, para desenvolver atraves deste sistema projetos de desenvolvimento e pesquisa aplicada, alem de verificar o atual meio de mobilidade publica no campus e sua interacao com outros meios de mobilidade existente, e o novo sistema proposto.
Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals

ABSTRACT The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.
Beyond False Belief: Theory of Mind in Young, Young-Old, and Old-Old Adults

Theory of mind (ToM) refers to humans' ability to recognize the existence of mental states, such as beliefs, emotions, and desires. The literature on ToM in aging and on the relationship between ToM and other cognitive functions, like executive functions, is not homogenous. The aim of the present study was to explore the course of ToM and to investigate the role of working memory, inhibition, and language on the possible age differences in ToM. To address these issues, we examined ToM using the Strange Stories task and executive function task in three age groups. Results showed that young adults outperform both old groups on the ToM stories. This difference remains significant also when controlling for working memory and inhibitory control. Our findings suggest a specific impairment in inferring mental states starting from 60 years of age that seems to be independent of changes in executive functions.
Genetic studies of ad-8 mutants in Neurospora crassa. I. Genetic fine structure of the ad-8 locus.

recent years, evidence has accumulated which indicates that genetic re'2mbination occurs not only between different loci but also between alleles within one locus (PONTECORVO 1958). A precise genetic analysis of allelic relationships within one locus is certainly an essential approach to understanding genes, since studies of allelism can help to elucidate both the structure and function of a particular gene. The present study will describe the genetic fine structure of the adenine-8 (ad-8) locus in Neurospora crassa, a locus at which a large number of mutants of independent origin are available. Some of the mutants are of spontaneous origin and others have been induced by various physical and chemical mutagens. Biochemical studies indicate that the ad-8 locus controls one reaction in the biosynthetic pathway to adenine, i.e., the conversion of inosine monophosphate to adenosine monophosphate succinate and that all ad-8 mutants lack activity for a single enzyme, adenylosuccinate synthetase. A genetic map has been established for the ad-8 locus as the result of a series of over 1,000 interallelic crosses. This map indicates the existence of numerous distinct mutational sites within the ad-8 locus. The map has proved especially useful in studies of interallelic complementation at this locus ( ISHIKAWA 1960). In addition, evidence concerning genetic fine structure has also been helpful in elucidating the nature of forward and reverse mutational events at this locus, especially in relation to the types of mutagens used.
Regulation of linear continuous-time singular systems with constrained states and controls

This article considers the constrained regulation problem (CRP) for linear continuous-time singular systems. The study consists in finding for a completely controllable singular system a linear state feedback control law that eliminates the impulsive behavior of a system and transfers asymptotically to the origin all initial states belonging to some polyhedral subset of the state space while respecting the linear constraints on state and control vectors. The proposed method gives a solution to the CRP for a singular system from a transformation that leads to a problem of positive invariance for a reduced order nonsingular one. Conditions guaranteeing the positive invariance for the whole domain of admissible controls are deduced. It is shown that the solution to the CRP is that of a nonlinear algebraic matrix equation.
Electron microscopy of whole cells in liquid with nanometer resolution

Single gold-tagged epidermal growth factor (EGF) molecules bound to cellular EGF receptors of fixed fibroblast cells were imaged in liquid with a scanning transmission electron microscope (STEM). The cells were placed in buffer solution in a microfluidic device with electron transparent windows inside the vacuum of the electron microscope. A spatial resolution of 4 nm and a pixel dwell time of 20 μs were obtained. The liquid layer was sufficiently thick to contain the cells with a thickness of 7 ± 1 μm. The experimental findings are consistent with a theoretical calculation. Liquid STEM is a unique approach for imaging single molecules in whole cells with significantly improved resolution and imaging speed over existing methods.
Oral levosimendan prevents postinfarct heart failure and cardiac remodeling in diabetic Goto-Kakizaki rats

Background Diabetes increases the risk for fatal myocardial infarction and development of heart failure. Levosimendan, an inodilator acting both via calcium sensitization and opening of ATP-dependent potassium channels, is used intravenously for acute decompensated heart failure. The long-term effects of oral levosimendan on postinfarct heart failure are largely unknown. Objective To examine whether oral treatment with levosimendan could improve cardiac functions and prevent cardiac remodeling after myocardial infarction in a rodent model of type 2 diabetes, the Goto-Kakizaki rat. Methods Myocardial infarction (MI) was induced to diabetic Goto-Kakizaki and nondiabetic Wistar rats by coronary ligation. Twenty-four hours after surgery, Goto-Kakizaki and Wistar rats were randomized into four groups: MI group without treatment, MI group with levosimendan for 12 weeks (1 mg/kg per day), sham-operated group, sham-operated group with levosimendan. Blood pressure, cardiac functions as wells as markers of cardiac remodeling were determined. Results In Goto-Kakizaki rats, MI induced systolic heart failure, pronounced cardiac hypertrophy in the remote area, and sustained cardiomyocyte apoptosis. Postinfarct cardiac remodeling was associated with increased atrial natriuretic peptide, interleukin-6 and connective tissue growth factor mRNA expressions, as well as three-fold increased cardiomyocyte senescence, measured as cardiac p16INK4a mRNA expression. Levosimendan improved cardiac function and prevented postinfarct cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and cellular senescence. Levosimendan also ameliorated MI-induced atrial natriuretic peptide, IL-6, and connective tissue growth factor overexpression as well as MI-induced disturbances in calcium-handling proteins (SERCA2, Na+–Ca2+ exchanger) without changes in diabetic status or systemic blood pressure. In nondiabetic Wistar rats, MI induced systolic heart failure; however, the postinfarct cardiac remodeling was associated with less pronounced cardiac hypertrophy, cardiomyocyte apoptosis, inflammatory reaction, and induction of cellular senescence. Levosimendan only partially prevented postinfarct heart failure and cardiac remodeling in Wistar rats. Conclusion Our findings suggest a therapeutic role for oral levosimendan in prevention of postinfarct heart failure and cardiac remodeling in type 2 diabetes and underscore the importance of sustained cardiomyocyte apoptosis and induction of cellular senescence in the pathogenesis.
Avaliação de ferramentas para detecção de interações epistáticas para fenótipos quantitativos em estudos de associação genômica ampla.

Variacoes geneticas presentes em uma populacao podem estar associadas a muitas caracteristicas como susceptibilidade a doencas em humanos (ex: diabetes, câncer, e doencas psiquiatricas). Atualmente, tecnologias de genotipagem de baixo custo, baseadas em marcadores moleculares do tipo polimorfismo de base unica Single Nucleotide Polymorphism (SNP) sao utilizados para identificar variacoes desse tipo associadas com doencas. Tais estudos, sao denominados, estudos de associacao genomica ampla, Genome Wide Association Studies (GWAS). No caso de especies de interesse agropecuario, essas variacoes geneticas estao relacionadas a caracteristicas que podem impactar ganhos de qualidade e producao. Portanto, e de extrema importância a utilizacao de novos metodos computacionais para identificacao desses marcadores, ja que isto pode contribuir para a selecao de individuos superiores, considerando os tracos fenotipicos de interesse em especies animais utilizadas em programas de melhoramento coordenados pela Empresa Brasileira de Pesquisa Agropecuaria (Embrapa).
Performance of the Afirma Gene Expression Classifier in Hürthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules.

BACKGROUND The recently introduced Afirma gene expression classifier (AGEC) provides binary results (benign or suspicious) to guide management of cytologically indeterminate thyroid nodules. The AGEC is intended to reduce unnecessary surgeries for benign nodules, and management algorithms favor surgery for suspicious results. Limited data are available on the performance of this test for Hürthle cell nodules (HCNs). This study hypothesized that a predominance of Hürthle cells leads to an increased rate of suspicious AGEC results with a potential for overtreatment, despite a relatively low risk of malignancy. METHODS The pathology databases from three tertiary care facilities were queried from 2010 to 2014 for fine-needle aspirates (FNAs) diagnosed as suspicious for Hürthle cell neoplasm (SHCN) or atypia of undetermined significance/follicular lesion of undetermined significance concerning for Hürthle cell neoplasm (AFHCN). Cytology diagnoses were rendered internally prior to AGEC testing. The patient demographics, FNA diagnosis, AGEC result, surgical procedure, and pathologic outcomes were recorded. RESULTS The cohort consisted of 134 patients with HCNs. Prior to AGEC availability, 62 patients underwent surgery: 81% (50/62) of patients had surgery, and 34% (17/50) of the resected index nodules were malignant. After introduction of the AGEC, 72 patients underwent AGEC testing: 65% (47/72) of patients had surgery, and 13% (6/46) of the resected nodules were malignant. Thirty-two percent (23/72) of patients had a benign AGEC result and did not undergo surgery, and 4% (3/72) had surgery despite a benign AGEC result with benign final pathology, whereas 63% (45/72) of patients had suspicious AGEC results, with 96% of these patients (43/45) undergoing surgery, and 14% (6/43) of these index nodules were malignant. CONCLUSIONS While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly.