Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioengineered Tissues for Urogenital Repair in Children

The most common congenital abnormalities involve the genitourinary system. These include hypospadias, in which the urethral opening develops in an improper position, and bladder exstrophy, in which the bladder develops on the outer surface of the abdomen. Children with these conditions will require immediate and multiple reconstructive surgeries. Currently, reconstruction may be performed with native nonurologic tissues (skin, gastrointestinal segments, or mucosa), homologous tissues from a donor (cadaver or living donor kidney), heterologous tissues or substances (bovine collagen), or artificial materials (silicone, polyurethane, teflon). However, these materials often lead to complications after reconstruction, either because the implanted tissue is rejected, or because inherently different functional parameters cause a mismatch in the system. For example, replacement of bladder tissue with gastrointestinal segments can be problematic due to the opposite ways in which these two tissues handle solutes—urologic tissue normally excretes material, and gastrointestinal tissue generally absorbs the same materials. This mismatched state can lead to metabolic complications as well as infection and other issues. The replacement of lost or deficient urologic tissues with functionally equivalent ones would improve the outcome of reconstructive surgery in the genitourinary system. This goal may soon be attainable with the use of tissue engineering techniques.
Public Opinion in Olympic Cities: From Bidding to Retrospection

Whereas traditionally hosting the Olympics was viewed as a top-down decision with little public input, public opinion is becoming more important in assessing and evaluating the merits of hosting the Games. Using bid documents from 2010 to 2020, the formal role that public opinion officially plays in the bid phase following the International Olympic Committee (IOC) procedures is examined. Public opinion in the preparation stage is reviewed, which demonstrates the problem of seeking simple declarations of support (Yes/No) that obfuscate important local issues (cost, traffic, urban priorities). Shifts in public opinion during the Games themselves, as well as one and four years after the Games, provide a new perspective on resident attitudes. Using retrospective data from Vancouver 2010 and London 2012, multivariate analysis demonstrates that participation in Olympic-related events (sporting and nonsporting) was the most important predictor of attitudes toward the Games and that concerns over costs were the only concerns that were justified.
Suitability of Different Agricultural and Urban Organic Wastes as Feedstocks for the Production of Biochar—Part 1: Physicochemical Characterisation

Biochar is traditionally made from clean lignocellulosic or waste materials that create no competition for land use. In this paper, the suitability of alternative feedstocks of agricultural and urban origins are explored. A range of biochars was produced from holm oak and a selection of organic wastes, such as greenhouse wastes, greenwastes, a cellulosic urban waste, municipal press cake and pig manure. They were characterized and assessed for their potential agricultural use. The physicochemical properties of biochars were mainly driven by the characteristics of feedstocks and the pyrolysis temperature. The use of pre-treated lignocellulosic residues led to biochars with a high concentration of ash, macro and micronutrients, whereas raw lignocellulosic residues produced biochars with characteristics similar to traditional wood biochars. All biochars were found to be suitable for agricultural use according to the international standards for the use of biochars as soil amendments, with the exception of a biochar from urban origin, which presented high levels of Cr and Pb. The use of these biochars as soil amendments requires a thorough agronomical evaluation to assess their impact on soil biogeochemical cycles and plant growth.
Fatty Acid (FFA) Transport in Cardiomyocytes Revealed by Imaging Unbound FFA Is Mediated by an FFA Pump Modulated by the CD36 Protein*

Free fatty acid (FFA) transport across the cardiomyocyte plasma membrane is essential to proper cardiac function, but the role of membrane proteins and FFA metabolism in FFA transport remains unclear. Metabolism is thought to maintain intracellular FFA at low levels, providing the driving force for FFA transport, but intracellular FFA levels have not been measured directly. We report the first measurements of the intracellular unbound FFA concentrations (FFAi) in cardiomyocytes. The fluorescent indicator of FFA, ADIFAB (acrylodan-labeled rat intestinal fatty acid-binding protein), was microinjected into isolated cardiomyocytes from wild type (WT) and FAT/CD36 null C57B1/6 mice. Quantitative imaging of ADIFAB fluorescence revealed the time courses of FFA influx and efflux. For WT mice, rate constants for efflux (∼0.02 s−1) were twice influx, and steady state FFAi were more than 3-fold larger than extracellular unbound FFA (FFAo). The concentration gradient and the initial rate of FFA influx saturated with increasing FFAo. Similar characteristics were observed for oleate, palmitate, and arachidonate. FAT/CD36 null cells revealed similar characteristics, except that efflux was 2–3-fold slower than WT cells. Rate constants determined with intracellular ADIFAB were confirmed by measurements of intracellular pH. FFA uptake by suspensions of cardiomyocytes determined by monitoring FFAo using extracellular ADIFAB confirmed the influx rate constants determined from FFAi measurements and demonstrated that rates of FFA transport and etomoxir-sensitive metabolism are regulated independently. We conclude that FFA influx in cardiac myocytes is mediated by a membrane pump whose transport rate constants may be modulated by FAT/CD36.
T Cell–Independent Modulation of Experimental Autoimmune Encephalomyelitis in ADAP-Deficient Mice

The adhesion- and degranulation-promoting adaptor protein (ADAP), expressed in T cells, myeloid cells, and platelets, is known to regulate receptor-mediated inside-out signaling leading to integrin activation and adhesion. In this study, we demonstrate that, upon induction of active experimental autoimmune encephalomyelitis (EAE) by immunization with the myelin oligodendrocyte glycoprotein35–55 peptide, ADAP-deficient mice developed a significantly milder clinical course of EAE and showed markedly less inflammatory infiltrates in the CNS than wild-type mice. Moreover, ADAP-deficient recipients failed to induce EAE after adoptive transfer of myelin oligodendrocyte glycoprotein–specific TCR-transgenic T cells (2D2 T cells). In addition, ex vivo fully activated 2D2 T cells induced significantly less severe EAE in ADAP-deficient recipients. The ameliorated disease in the absence of ADAP was not due to expansion or deletion of a particular T cell subset but rather because of a strong reduction of all inflammatory leukocyte populations invading the CNS. Monitoring the adoptively transferred 2D2 T cells over time demonstrated that they accumulated within the lymph nodes of ADAP-deficient hosts. Importantly, transfer of complete wild-type bone marrow or even bone marrow of 2D2 TCR–transgenic mice was unable to reconstitute EAE in the ADAP-deficient animals, indicating that the milder EAE was dependent on (a) radio-resistant nonhematopoietic cell population(s). Two-photon microscopy of lymph node explants revealed that adoptively transferred lymphocytes accumulated at lymphatic vessels in the lymph nodes of ADAP-deficient mice. Thus, our data identify a T cell–independent mechanism of EAE modulation in ADAP-deficient mice.
Development of hepatocellular carcinoma after successful management of esophageal variceal bleeding.

BACKGROUND Endoscopic and pharmacological treatments significantly reduce recurrent esophageal variceal bleeding and improve the prognosis of cirrhotic patients. This study was aimed to evaluate the incidence, risk factors, treatment and prognosis of hepatocellular carcinoma after esophageal variceal bleeding. METHODS Patients with esophageal variceal bleeding underwent endoscopic or pharmacological treatments to arrest acute bleeding or prevent rebleeding. Concurrently, patients were followed by periodic serum alpha-fetoprotein examinations and ultrasonography, aiming at early detection and possible treatment of hepatocellular carcinoma. RESULTS Hepatocellular carcinoma developed in 79 of 370 patients (21.4%) during the 10-year follow-up. The cumulative incidence of hepatocellular carcinoma was 21.1% at the end of the third year, 39.3% at the end of the fifth year and 53.0% at the end of the tenth year. Small tumors (< or = 3 cm) were found in 64 patients (81.0%, monofocal tumors in 46 patients). Age, hepatitis B virus, hepatitis C virus, and alpha-fetoprotein level > 20 ng/mL were factors associated with the risk of hepatocellular carcinoma development by multivariate analysis using Cox regression. Tumors were actively treated in 37 of 49 Child-Pugh A and B patients (75.5%) and 2 of 30 Child-Pugh C patients (6.7%). The median survival of all patients was 2.5 (range, 0.5 to 10.0) years. Development of hepatocellular carcinoma and serum bilirubin level were significantly associated with mortality in Child-Pugh A and B patients. CONCLUSIONS Patients with esophageal variceal bleeding had a high risk of developing hepatocellular carcinoma. Surveillance on hepatocellular carcinoma could detect most tumors with small size. Hepatocellular carcinoma had an adverse impact on the survival of patients without advanced cirrhosis.
The protective effect of erythropoietin on ischaemia/reperfusion injury of liver.

BACKGROUND Besides its haematopoietic effect, erythropoietin (EPO) has multiple protective effects, i.e. antiapoptotic, antioxidant and angiogenic properties. The neuroprotective effects of EPO against ischaemia have all been demonstrated in cell culture and animal models. The aim of the study was to evaluate the effect of erythropoietin on ischaemia-reperfusion injury (I/R injury) of the liver. METHODS Forty-eight adult male Sprague-Dawley rats weighing 250-300 g were divided into three groups: group I, hepatic ischaemia-reperfusion (Hepatic I/R); group II, hepatic ischaemia-reperfusion + EPO (Hepatic I/R+ EPO); group III, sham. Hepatic ischaemia was created by placing a microvascular clamp on the hepatic pedicle for 45 minutes. EPO was given to group II at a dose of 1000 U/kg 120 minutes before the onset of the ischaemia. Blood samples and liver tissues were obtained after 45 minutes of reperfusion from half of the rats in each group. The remaining rats were killed after a 24-hour observation period and blood and tissue samples were obtained. Blood alanine aminotransferase, tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and liver tissue malondialdehyde (MDA) levels were determined. Liver tissue histopathology was also evaluated by light microscopy. RESULTS In rats with hepatic ischaemia, serum levels of ALT, TNF-alpha, IL-2 and liver tissue levels of MDA were reduced by the administration of erythropoietin and the histopathological score was also less severe. CONCLUSION This study demonstrates that pre-ischaemic administration of EPO has protective effects on hepatic I/R injury.
Analysis of electric vehicle powertrain simulators for fuel consumption calculations

In this paper, three electric vehicle (EV) powertrain simulators are analyzed by combining their modeling methodologies into a single MATLAB script file. A simplified electric vehicle powertrain (SEVP) simulator is compared with two widely used powertrain simulators, ADVISOR and FASTSim. Validation of the simulators is carried out using dynamometer test data on two models of the Nissan LEAF from the Advanced Powertrain Research Facility (APRF) of Argonne National Laboratory (ANL). The single script file approach is used to offer plug-and-play functionality with powertrain component models from the three simulators to determine their contribution to fuel consumption prediction. These test results show that a simplified powertrain model for an EV can predict EV fuel consumption to the same, (or better) level of accuracy as the state-of-the-art vehicle simulators.
The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism.

3-Methylcrotonylglycinuria is an inborn error of leucine catabolism and has a recessive pattern of inheritance that results from the deficiency of 3-methylcrotonyl-CoA carboxylase (MCC). The introduction of tandem mass spectrometry in newborn screening has revealed an unexpectedly high incidence of this disorder, which, in certain areas, appears to be the most frequent organic aciduria. MCC, an heteromeric enzyme consisting of alpha (biotin-containing) and beta subunits, is the only one of the four biotin-dependent carboxylases known in humans that has genes that have not yet been characterized, precluding molecular studies of this disease. Here we report the characterization, at the genomic level and at the cDNA level, of both the MCCA gene and the MCCB gene, encoding the MCC alpha and MCC beta subunits, respectively. The 19-exon MCCA gene maps to 3q25-27 and encodes a 725-residue protein with a biotin attachment site; the 17-exon MCCB gene maps to 5q12-q13 and encodes a 563-residue polypeptide. We show that disease-causing mutations can be classified into two complementation groups, denoted "CGA" and "CGB. " We detected two MCCA missense mutations in CGA patients, one of which leads to absence of biotinylated MCC alpha. Two MCCB missense mutations and one splicing defect mutation leading to early MCC beta truncation were found in CGB patients. A fourth MCCB mutation also leading to early MCC beta truncation was found in two nonclassified patients. A fungal model carrying an mccA null allele has been constructed and was used to demonstrate, in vivo, the involvement of MCC in leucine catabolism. These results establish that 3-methylcrotonylglycinuria results from loss-of-function mutations in the genes encoding the alpha and beta subunits of MCC and complete the genetic characterization of the four human biotin-dependent carboxylases.
Characterization of the Interaction between Retinoic Acid Receptor/Retinoid X Receptor (RAR/RXR) Heterodimers and Transcriptional Coactivators through Structural and Fluorescence Anisotropy Studies*

Retinoid receptors (RARs and RXRs) are ligand-activated transcription factors that regulate the transcription of target genes by recruiting coregulator complexes at cognate promoters. To understand the effects of heterodimerization and ligand binding on coactivator recruitment, we solved the crystal structure of the complex between the RARβ/RXRα ligand-binding domain heterodimer, its 9-cis retinoic acid ligand, and an LXXLL-containing peptide (termed NR box 2) derived from the nuclear receptor interaction domain (NID) of the TRAP220 coactivator. In parallel, we measured the binding affinities of the isolated NR box 2 peptide or the full-length NID of the coactivator SRC-1 for retinoid receptors in the presence of various types of ligands. Our correlative analysis of three-dimensional structures and fluorescence data reveals that heterodimerization does not significantly alter the structure of individual subunits or their intrinsic capacity to interact with NR box 2. Similarly, we show that the ability of a protomer to recruit NR box 2 does not vary as a function of the ligand binding status of the partner receptor. In contrast, the strength of the overall association between the heterodimer and the full-length SRC-1 NID is dictated by the combinatorial action of RAR and RXR ligands, the simultaneous presence of the two receptor agonists being required for highest binding affinity. We identified an LXXLL peptide-driven mechanism by which the concerted reorientation of three phenylalanine side chains generates an “aromatic clamp” that locks the RXR activation helix H12 in the transcriptionally active conformation. Finally, we show how variations of helix H11-ligand interactions can alter the communication pathway linking helices H11, H12, and the connecting loop L11-12 to the coactivator-binding site. Together, our results reveal molecular and structural features that impact on the ligand-dependent interaction of the RAR/RXR heterodimer with nuclear receptor coactivators.
Whole genome microarray analysis of chicken embryo facial prominences

The face is one of the three regions most frequently affected by congenital defects in humans. To understand the molecular mechanisms involved, it is necessary to have a more complete picture of gene expression in the embryo. Here, we use microarrays to profile expression in chicken facial prominences, post neural crest migration and before differentiation of mesenchymal cells. Chip‐wide analysis revealed that maxillary and mandibular prominences had similar expression profiles while the frontonasal mass chips were distinct. Of the 3094 genes that were differentially expressed in one or more regions of the face, a group of 56 genes was subsequently validated with quantitative polymerase chain reaction (QPCR) and a subset examined with in situ hybridization. Microarrays trends were consistent with the QPCR data for the majority of genes (81%). On the basis of QPCR and microarray data, groups of genes that characterize each of the facial prominences can be determined. Developmental Dynamics 239:574–591, 2010. © 2009 Wiley‐Liss, Inc.
Curcumol potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer

Combinatorial therapies that target multiple signaling pathways may provide improved therapeutic responses over monotherapies. Celecoxib and curcumol are two highly hydrophobic drugs which show bioavailability problems due to their poor aqueous solubility. In the present study, we evaluated the effects of celecoxib and curcumol alone and in combination on cell proliferation, invasion, migration, cell cycle and apoptosis induction in non-small cell lung cancer (NSCLC) cells using in vitro and in vivo experiments. Our data showed that the sensitivity of a combined therapy using low concentration of celecoxib and curcumol was higher than that of celecoxib or curcumol alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle G1 arrest, and inhibition of survival MAPK and PI3K/AKT signaling pathway contributed to the synergistic effects of this combination therapy for induction of apoptosis. Additionally, either celecoxib alone or in combination with curcumol inhibited NSCLC cell migration and invasion by suppressing FAK and matrix metalloproteinase-9 activities. Furthermore, the combined treatment reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. Our results confirm and provide mechanistic insights into the prominent anti-proliferative activities of celecoxib and/or curcumol on NSCLC cells, which provide a rationale for further detailed preclinical and potentially clinical studies of this combination for the therapy of lung cancer.
Detection of circulating gastric cancer cells in peripheral blood using real time quantitative RT-PCR.

BACKGROUND/AIMS Detection of occult cancer cells in peripheral blood or bone marrow has recently received a great deal of attention regarding the prediction of postoperative recurrence of the cancer, and for novel strategies of adjuvant therapy. This study addresses the detection of circulating tumor cells in peripheral blood in patients with gastric cancer using Quantitative RT-PCR. METHODOLOGY Common mRNA targets for RT-PCR for detection of small numbers of cancer cells in gastric cancer are CK18, CK19, CK20, and CEA. Ten milliliter of peripheral venous blood was taken from 14 healthy Japanese volunteers and 101 patients with gastric cancer. Samples were analyzed using real-time TaqMan technology and a Model 7700-sequence system. The group of gastric cancer patients included 69 individuals with curative disease on preoperative diagnosis and 32 individuals with a non-curative operation or recurrence of the disease. RESULTS The number of CK19 and CK20 mRNA copies was significantly increased in patients with a non-curative operation or recurrence of gastric cancer (CK19; p=0.0087, CK20; p=0.0022) compared with healthy volunteers. Cut-off levels of CK19 or CK20 copy numbers were determined by the maximum value of healthy volunteers. For CK19, there were 61 (88.4%) negative cases and 8 (11.6%) positive cases in 69 individuals with curative gastric cancer. There was a significant difference in tumor stages between CK19 positive and negative patients with curative disease on preoperative diagnosis. For CK20, there were 59 (85.5%) negative cases and 10 (15.5%) positive cases. There was no statistical difference between CK20 positive and negative cases for all clinicopathological factors. On postoperative day 14, there was a significant difference between positive and negative cases regarding tumor size, tumor stage, and lymph node metastasis for CK19, and tumor stage and lymph node metastasis for CK20. Five-year survival rates of patients with CK19 positive or negative cases were 50.0% or 79.0%, respectively (p=0.0347). While, for CK20, 5-year survival rates for positive cases was 51.9%, and for negative cases 78.9% (p=0.0490). CONCLUSIONS Micrometastases of gastric cancer can be detected in circulating peripheral blood using quantitative real-time RT-PCR. CK19 is a better marker than CK18, CK20 and CEA, and could be clinically useful to estimate prognosis or to make a postoperative strategy of adjuvant treatment.
Early detection and intervention of psychosis. A review

The vulnerability and hybrid models for the onset of psychosis are presented. Familial liability, perinatal and developmental factors, and decreased cognitive performance associate with psychosis in adolescence and young adulthood. Genetic predisposition connected with behavioural deviances and/or mental symptoms associate with psychotic development so strongly that monitoring and intervention are indicated. Especially, in families where one or both parents or other family members are severely mentally ill, early family-centred assessments and interventions is needed. Together with familial psychosis, deficits in adolescent and young adult social development indicate thorough assessment, intensive monitoring and often also preventive interventions. During the prodromal phase of psychosis, patients often display unspecific symptoms, such as anxiety and depression, personality disorders, abuse of alcohol or drugs. Social decline, possibly associated with neurocognitive deficits, frequently occurs in the prodromal phase or in the early course of schizophrenia. Among help-seeking patients, occurrence of the Basic Symptoms represent the early initial prodromal state, while the late initial prodome state includes attenuated psychotic symptoms, brief limited intermittent psychotic symptoms, and a first degree relative with psychotic disorder, or a schizotypal personality disorder, together with decrease global functioning. These patients suffer also from other mental symptoms and functional decline, and are clearly in need of psychiatric assessment and treatment. Intervention trials have shown that patients suffering from prodromal syndromes can be successfully treated, and onset of psychosis prevented or delayed. However, more large-scale studies and clinical case descriptions of treatment of patients with sub-threshold psychotic symptoms are needed.