Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of carboplatin with carrier human erythrocytes

The antineoplastic drug Carboplatin (CBDCA) was encapsulated in human erythrocytes by means of transient hypotonic hemolysis, followed by isotonic resealing. Up to 5 mg/ml of packed cells could be entrapped, with about 70% cell recovery. In vitro incubation of the CBDCA‐loaded erythrocytes in autologous plasma caused a very slow release of the drug from the cells (12% approximately in 3 h). The encapsulation conditions, performed at a low hematocrit, in order to obtain high amounts of the drug inside the carriers, impaired the metabolic properties of the loaded erythrocytes significantly. In particular, an almost complete disappearance of GSH was observed. Analysis of the intraerythrocytic metabolism of CBDCA showed that, in spite of its relatively high stability in aqueous solutions, in hemolysates and in the loaded erythrocytes a significant percentage of CBDCA is rapidly converted to other species that still retain an antiproliferative activity in vitro. This fast conversion could be extensively inhibited by previous conversion of oxyhemoglobin to methemoglobin or carbomonoxyhemoglobin, suggesting an important role of heme iron in this process. Encapsulation of CBDCA in selectively targeted human erythrocytes may represent a therapeutic strategy for increasing the drug concentration in specific organs, notably liver.
Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

Abstract The epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.
Screening for osteoporosis in men receiving androgen deprivation therapy.

To the Editor: Prostate cancer is the most common cancer in men. One in 2 men with prostate cancer is expected to receive androgen deprivation therapy (ADT). Use of ADT is associated with accelerated bone loss and an increased risk of fractures. To better characterize fracture risk and optimize bone health, a bone mineral density (BMD) test has been recommended prior to ADT initiation since 2006 in Canada and elsewhere. Low rates of BMD use have been reported by single centers. We examined the rate of BMD testing in men starting ADT in the province of Ontario, Canada, between 1995 and 2008. Methods. We identified men aged 66 years or older who were starting ADT for prostate cancer, using linked administrative databases at the Institute for Clinical Evaluative Sciences in Ontario, Canada (population approximately 11 million) and the Ontario Cancer Registry as previously described. These databases have been shown to be 85% to 99% complete and accurate. Men diagnosed between January 1, 1995, and December 31, 2008, and receiving at least 6 months of continuous medical ADT (luteinizing–hormone-releasing hormone agonists, antiandrogens, or both) or undergoing orchiectomy were included. The BMD tests used dual x-ray absorptiometry within 2 years of starting ADT and were captured using outpatient claims. Sociodemographic characteristics, comorbidity information (including prior diagnoses of osteoporosis and fragility fractures, ie, hip, spine, or wrist), and prior bisphosphonate use were obtained from inpatient and outpatient records using specific diagnostic, procedure, and claims codes as previously described. We examined whether a BMD test was performed over time using counts (per 100 person-years) and multivariable logistic regression using SAS version 9.2 (SAS Institute Inc). Level of significancewasa P valueof less than . 05andstatistical tests were2-sided.Studyapprovalwasobtainedfromtheinstitutional research ethics board; individual patient consent was waived. Results. We identified 33 036 men (mean age: 76.0 years; range: 66-100 years) with prostate cancer who initiated ADT during the study period. A prior BMD test was performed in 1591 men (4.8%), 1332 (4.0%) had a prior diagnosis of osteoporosis, 1053 (3.2%) had a prior fragility fracture, and 808 (2.4%) were taking bisphosphonates at baseline. The use of BMD tests within 2 years of starting ADT ranged from 0.5 per 100 person-years in 1995 to 18.0 per 100 personyears in 2008 (FIGURE). Even among ADT users at high risk of osteoporosis (prior fragility fractures) or fractures (prior diagnosis of osteoporosis), BMD test ordering remained low, never reaching 50% of patients (Figure). Predictors of greater BMD testing included younger age, not living in a rural area, later start year of ADT, prior osteoporosis, prior BMD test, prior bisphosphonate use, and having a regular primary care physician (all P .01) (TABLE).
The Bunyamwera virus nonstructural protein NSs inhibits viral RNA synthesis in a minireplicon system.

The small (S) genomic segment of Bunyamwera virus (family Bunyaviridae, genus Bunyavirus) encodes the nucleocapsid protein, N, and a nonstructural protein, NSs, in overlapping reading frames. In order to elucidate the function of NSs, we established a plasmid-based minireplicon system using mammalian cells that express large amounts of T7 RNA polymerase. Expression of N, the viral polymerase protein (L), and a minireplicon containing a reporter gene was sufficient to reconstitute functional virus nucleocapsids. Coexpression of NSs, however, led to a dose-dependent decrease in reporter activity without affecting expression of controls. The inhibition could not be reversed by overexpression of N, L or the minireplicon, indicating that the NSs effect was not caused by a reduction in virus gene expression. The NSs proteins of two other members of the Bunyavirus genus, Guaroa virus and Lumbo virus, were also inhibitory in our system. The intracellular localisation of Bunyamwera virus NSs was investigated and found to be predominantly cytoplasmic, but intranuclear inclusion was also detected. Taken together, these data suggest that, in mammalian cells, the bunyavirus NSs protein controls the activity of the viral polymerase by a highly conserved mechanism.
Reconstructive gastric surgery

Among 173 patients undergoing reconstructive gastric operations, including 115 patients who received Roux‐en‐Y gastrojejunostomy, 25 with jejunal interpositions, 11 with conversion of Billroth II to Billroth I, 8 with closure of gastroenterostomy, 5 with pyloric reconstruction and 9 with other operations, only 2 immediate postoperative mortalities occurred. A perfect or good result was obtained in 108 of 156 patients (69 per cent) at long term follow‐up, while a fair result was achieved in 35 patients (22 per cent) and a poor result in 13 patients (9 per cent). We concluded that reconstructive gastric operations were safe and had clearly improved 7 of 10 patients in this series.
Aging and the hypothalamus-pituitary-adrenocortical axis, with special reference to the dog.

Aging affects the hypothalamus-pituitary-adrenocortical (HPA) system in various ways. It affects the receptors for glucocorticosteroids in the limbic system, the hypothalamus and the pituitary; the basal and stress-induced secretion of proopiomelanocortin-derived peptides and glucocorticoids; and the neuronal integrity, especially in the hippocampus. The homeostatic actions of glucocorticoids occur through the glucocorticoid and the mineralocorticoid receptors. It has been hypothesized that the balance between these two receptors, which are co-localized in the hippocampus, determines the basal HPA activity and the magnitude of the response to challenges. Feedback actions of glucocorticoids are mediated via glucocorticoid receptors in the hypothalamus and the pituitary. In aged rats many changes in the binding capacity of the mineralocorticoid receptor and glucocorticoid receptor and in the regulation of the HPA activity have been reported, but the findings often seem contradictory. The only consistent finding has been that the binding capacity of mineralocorticoid receptor in the hippocampus is reduced. The number of glucocorticoid receptors may be increased, reduced or unchanged in senescent rats. In old dogs the receptor changes were largely confined to mineralocorticoid receptor, there being a 60% reduction in the binding capacity in the limbic system, but glucocorticoid receptor was unchanged in all brain regions. Senescent dogs also had an increased basal secretion of ACTH, and of cortisol. The old dogs had exaggerated responses to stress and to administered corticotropin-releasing hormone, but the termination of the response by the feedback mechanism was unchanged. (ABSTRACT TRUNCATED AT 250 WORDS)
Impaired integration of object knowledge and visual input in a case of ventral simultanagnosia with bilateral damage to area V4

This study examines how brain damage can affect the cognitive processes that support the integration of sensory input and prior knowledge during shape perception. It is based on the first detailed study of acquired ventral simultanagnosia, which was found in a patient (M.T.) with posterior occipitotemporal lesions encompassing V4 bilaterally. Despite showing normal object recognition for single items in both accuracy and response times (RTs), and intact low-level vision assessed across an extensive battery of tests, M.T. was impaired in object identification with overlapping figures displays. Task performance was modulated by familiarity: Unlike controls, M.T. was faster with overlapping displays of abstract shapes than with overlapping displays of common objects. His performance with overlapping common object displays was also influenced by both the semantic relatedness and visual similarity of the display items. These findings challenge claims that visual perception is driven solely by feedforward mechanisms and show how brain damage can selectively impair high-level perceptual processes supporting the integration of stored knowledge and visual sensory input.
Elucidating the Germination Transcriptional Program Using Small Molecules1[W][OA]

The transition from seed to seedling is mediated by germination, a complex process that starts with imbibition and completes with radicle emergence. To gain insight into the transcriptional program mediating germination, previous studies have compared the transcript profiles of dry, dormant, and germinating after-ripened Arabidopsis (Arabidopsis thaliana) seeds. While informative, these approaches did not distinguish the transcriptional responses due to imbibition, shifts in metabolism, or breaking of dormancy from those triggered by the initiation of germination. In this study, three mechanistically distinct small molecules that inhibit Arabidopsis seed germination (methotrexate, 2, 4-dinitrophenol, and cycloheximide) were identified using a small-molecule screen and used to probe the germination transcriptome. Germination-responsive transcripts were defined as those with significantly altered transcript abundance across all inhibitory treatments with respect to control germinating seeds, using data from ATH1 microarrays. This analysis identified numerous germination regulators as germination responsive, including the DELLA proteins GAI, RGA, and RGL3, the abscisic acid-insensitive proteins ABI4, ABI5, ABI8, and FRY1, and the gibberellin receptor GID1A. To help visualize these and other publicly available seed microarray data, we designed a seed mRNA expression browser using the electronic Fluorescent Pictograph platform. An overall decrease in gene expression and a 5-fold greater number of transcripts identified as statistically down-regulated in drug-inhibited seeds point to a role for mRNA degradation or turnover during seed germination. The genes identified in our study as responsive to germination define potential uncharacterized regulators of this process and provide a refined transcriptional signature for germinating Arabidopsis seeds.
PERBEDAAN ASUPAN ENERGI, PROTEIN, LEMAK, KARBOHIDRAT DAN STATUS GIZI PADA REMAJA YANG TINGGAL DI WILAYAH PERKOTAAN DAN PEDESAAN

Latar Belakang : m asalah gizi ganda tidak hanya terdapat pada masyarakat perkotaan saja akan tetapi juga terdapat pada masyarakat pedesaan. Prevalensi obesitas pada remaja tidak hanya terjadi di wilayah perkotaan (7,8%), namun juga di pedesaan (2%). Penelitian ini bertujuan untuk mengetahui perbedaan asupan energi, protein, lemak, karbohidrat dan status gizi pada remaja yang tinggal di wilayah perkotaan dan pedesaan . Metode : Rancangan penelitian ini adalah cross - sectional dengan jumlah sampel di kota 49 subjek dan di desa 45 subjek, diambil dengan metode simple random sampling. Data meliputi karakteristik subjek, asupan makanan diperoleh dari food recall 24 jam , status gizi diperoleh dari grafik persentil berdasarkan indeks massa tubuh, umur dan jenis kelamin . Analisis data dengan Mann-Whitney, dan independent t-test. Hasil : Prevalensi overweight pada remaja di wilayah perkotaan (10,2%) lebih tinggi bila dibandingkan dengan remaja di wilayah pedesaan (6,6%). Sedangkan untuk status gizi kurang pada remaja di wilayah pedesaan (31,1%) lebih tinggi bila dibandingkan dengan remaja wilayah perkotaan (8,2%). Rerata persentase asupan energi di wilayah perkotaan lebih tinggi (99,4%) dibanding di pedesaan (96,6%). Rerata persentase protein di kota (76,9%) lebih tinggi dibandingkan dengan desa (74,0%). Rerata persentase asupan lemak di kota (181,1%) lebih tinggi bila dibandingkan dengan desa (171,8%). Rerata persentase asupan karbohidrat di desa (82,5%) lebih tinggi bila dibandingkan dengan di kota (80,9%). Uji analisis perbedaan kedua subyek diperoleh hasil, asupan energi ( p= 0,108 ), asupan protein ( p= 0,254), asupan lemak (p= 0,173), asupan karbohidrat (p= 0,173), status gizi (p= 0,000). Kesimpulan : Tidak ada perbedaan asupan energi , protein, lemak dan karbohidrat pada remaja yang tinggal di wilayah perkotaan dan pedesaan (p> 0,05) . Ada perbedaan status gizi pada remaja yang tinggal di wilayah kota dan remaja di wilayah desa (p< 0.05) Kata Kunci : asupan energi; protein; lemak; karbohidrat; status gizi; remaja; perkotaan dan pedesaan
Milk lactate dehydrogenase and alkaline phosphatase as biomarkers in detection of bovinesubclinical mastitis

Currently, somatic cell count (SCC) and bacterial culture is considered as the gold standard of detecting subclinical mastitis. However, the above-mentioned tests have a low diagnostic accuracy. Therefore, for identification of infected animals, new biomarkers with high clinical accuracy are needed. The objective of this study was to determine the diagnostic value of milk lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) for the diagnosis of subclinical mastitis in dairy cows. The activities of these enzymes increase during mastitis, which make them to be the potential biomarkers for screening of mastitis. A total of 145 clinically healthy cows were randomly selected. Of these, 77 cows were considered to be affected by subclinical mastitis based on a SCC higher than 100×1000 cells/ml of milk and positive bacterial culture results of milk samples obtained from at least one of the quarters. Enzymes activities were measured in blood serum and defatted milk (centrifuged at 5000 g for 15 min at 4â) using commercial kits. Diagnostic sensitivity and specificity and cutoff points for each test were determined via receiver-operating characteristics curve. Significant (P<0.001) increases in the mean and median activities of LDH and ALP were found in the milk samples collected from cows with subclinical mastitis. Milk LDH had the most clinical accuracy with 94.8% sensitivity and 94.1% specificity at cutoff point of 109 U/L. The results of the present study showed that the measurement of LDH and ALP activities in milk samples could be used as reliable method for detection of bovine subclinical mastitis.
VARIABILIDADE TEMPORAL DA TSM DO ATLÂNTICO TROPICAL E DAS TÁBUAS DAS MARÉS PARA O PORTO DE SALVADOR-BA

A problematica do aumento do nivel do mar esta associada aos acrescimos da temperatura global, ao derretimento das geleiras e a fusao das calotas glaciais em paralelo com a expansao termica dos oceanos. As capitais do nordeste brasileiro experimentam esse tipo de problema por conta da descarga dos rios nos momentos de mare alta. Utilizando-se dados diarios de janeiro de 1990 a dezembro de 2009 da tabua das mares fornecidas pela Diretoria de Hidrografia e Navegacao (DHN) do Ministerio da Defesa, dados do mesmo periodo fornecidos pelo IBGE e dados da Temperatura da Superficie do Mar (TSM) para o Oceano Atlântico, obtidos atraves do National Centers for Environmental Prediction (NCEP), monitorou-se o nivel do mar e o comportamento da TSM, ao longo do periodo de estudo, com objetivo de analisar as tendencias dos dados de TSM para o oceano Atlântico Tropical e das variacoes das tabuas das mares estimados para o porto de Salvador-BA. Os resultados mostram que os episodios El Nino e La Nina, nos anos 1997/1998/1999, influenciaram tanto os valores das TSM no periodo, como os maximos das mares observadas, contudo o nivel medio do mar permaneceu constante durante o periodo. Embora, este fato esteja em desacordo com a teoria do aquecimento global, este pode ser um efeito inteiramente local e aponta para a necessidade de um estudo mais regionalizado. Palavras-Chave: Mudancas climaticas. Aumento do nivel do mar. Temperatura da superficie do mar.
Can the classification of personality disorders be based on behavior genetics? A comment on South and DeYoung (2013).

Comments on the article by S. C. South and N. J. DeYoung (see record 2012-01744-001). This commentary examines how behavior genetic research can be used to inform the revision of personality disorders (PDs) during the transition from DSM-IV to DSM-5. Although supportive of the proposal put forth by the work group that extreme personality traits need to be distinguished from personality disorder by the presence of disorganization in personality structure and function, South and DeYoung note the absence of behavior genetics data on the levels of personality functioning and the new general criteria for personality disorder that incorporate impairment in personality functioning as the "A criterion. " They also note, however, that literature supporting this type of definition with its focus on aspects of self-concept and interpersonal relations is rapidly growing.
Endothelin-mediated positive inotropic effect induced by reactive oxygen species in isolated cardiac muscle.

Cardiac endothelium, both coronary and endocardial, produces a number of inotropic molecules. Changes in cardiac endothelial function by substances in the superfusing blood may thus participate in the control of muscle-pump performance of the heart. Reactive oxygen species (ROS) have been implicated in normal and pathological vascular physiology by influencing vascular endothelial function. Therefore, we examined the influence of ROS on endocardial endothelial modulation of myocardial performance. Right ventricular cat papillary muscles were briefly (15 s) exposed to electrolysis-generated ROS. Peak total isometric twitch tension and peak rate of tension development increased by 7.8 +/- 0.7% (P < .05) and 9.7 +/- 1.5% (P < .05), respectively (n = 12). Isometric twitch duration was slightly increased (time from stimulus to half isometric relaxation, +2.7 +/- 0.6%; P < .05). ROS scavengers such as ascorbic acid (n = 6), superoxide dismutase and catalase (n = 8), or catalase alone (n = 6), but not superoxide dismutase alone (n = 6), blocked the inotropic effect. Interestingly, the positive inotropic effect was completely blocked by selectively damaging endocardial endothelium (Triton X-100, 0.5%, 1-s immersion, n = 7) before ROS generation and by preincubating the muscles with the endothelin-A receptor antagonist BQ 123 (n = 11). Preincubation with NG-nitro-L-arginine methyl ester and indomethacin (n = 5) or with atenolol (n = 6) did not influence the inotropic effect. (ABSTRACT TRUNCATED AT 250 WORDS)
Adaptive backstepping control for a hypersonic vehicle with uncertain parameters and actuator faults

For a hypersonic vehicle with redundant elevators, an adaptive backstepping fault-tolerant control scheme is designed for its longitudinal motion model. In the backstepping design, the dynamic surface control strategy is adopted to eliminate the explosion of complexity in calculating the derivatives of virtual control inputs by introducing two first-order filters. An appropriate controller structure is proposed and the matching conditions are derived for adaptive fault compensation for the vehicle with redundant elevators subject to uncertain actuator faults. The adaptation laws are designed to update parameter estimates to implement the adaptive controller. The closed-loop stability under the proposed adaptive actuator fault compensation scheme is analyzed. Both analytical and simulation results are given to verify the effectiveness of the design and demonstrate the desired performance for altitude and velocity control.
Analysis of p53 and NF‐κB signaling in modulating the cardiomyocyte fate during hypertrophy

Cardiac hypertrophy leading to eventual heart failure is the most common cause of mortality throughout the world. The triggering mechanisms for cardiac hypertrophy are not clear but both apoptosis and cell proliferation have been reported in sections of failing hearts. In this study, we utilized both angiotensin II (AngII) treatment of cardiomyocytes and aortic ligation in rats (Rattus norvegicus, Wistar strain) for induction of hypertrophy to understand the cellular factors responsible for activation of apoptotic or anti‐apoptotic pathway. Hypertrophy markers (ANF, β‐MHC), apoptotic proteins (Bax, Bad, Fas, p53, caspase‐3, PARP), and anti‐apoptotic or cell proliferation marker proteins (Bcl2, NF‐κB, Ki‐67) were induced significantly during hypertrophy, both in vitro as well as in vivo. Co‐localization of both active caspase‐3 and Ki‐67 was observed in hypertrophied myocytes. p53 and NF‐κBp65 binding to co‐activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF‐κB activation, and NF‐κB–p300 binding; however, NF‐κB inhibition did not inhibit apoptosis or p53–p300 binding. Blocking of either p53 or NF‐κB by specific inhibitors resulted in decrease in cell proliferation and hypertrophy markers, suggesting that p53 initially binds to p300 and then this complex recruits NF‐κB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy. J. Cell. Physiol. 226: 2543–2554, 2011. © 2010 Wiley‐Liss, Inc.