Miracle-dz/UniFAR-FTUs huggingface dataset:
Description of a Versatile Peroxidase Involved in the Natural Degradation of Lignin That Has Both Manganese Peroxidase and Lignin Peroxidase Substrate Interaction Sites*

Two major peroxidases are secreted by the fungusPleurotus eryngii in lignocellulose cultures. One is similar to Phanerochaete chrysosporiummanganese-dependent peroxidase. The second protein (PS1), although catalyzing the oxidation of Mn2+ to Mn3+ by H2O2, differs from the above enzymes by its manganese-independent activity enabling it to oxidize substituted phenols and synthetic dyes, as well as the lignin peroxidase (LiP) substrate veratryl alcohol. This is by a mechanism similar to that reported for LiP, as evidenced byp-dimethoxybenzene oxidation yielding benzoquinone. The apparent kinetic constants showed high activity on Mn2+, but methoxyhydroquinone was the natural substrate with the highest enzyme affinity (this and other phenolic substrates are not efficiently oxidized by the P. chrysosporium peroxidases). A three-dimensional model was built using crystal models from four fungal peroxidase as templates. The model suggests high structural affinity of this versatile peroxidase with LiP but shows a putative Mn2+ binding site near the internal heme propionate, involving Glu36, Glu40, and Asp181. A specific substrate interaction site for Mn2+ is supported by kinetic data showing noncompetitive inhibition with other peroxidase substrates. Moreover, residues reported as involved in LiP interaction with veratryl alcohol and other aromatic substrates are present in peroxidase PS1 such as His82 at the heme-channel opening, which is remarkably similar to that of P. chrysosporiumLiP, and Trp170 at the protein surface. These residues could be involved in two different hypothetical long range electron transfer pathways from substrate (His82-Ala83-Asn84-His47-heme and Trp170-Leu171-heme) similar to those postulated for LiP.
Are there two sides to colorectal cancer?

Colorectal carcinomas (CRC) that arise proximal (right) or distal (left) to the splenic flexure exhibit differences in incidence according to geographic region, age and gender. Together with observations that tumours in the hereditary cancer syndromes HNPCC and FAP occur predominantly in the right and left colon, respectively, the existence of 2 categories of CRC based on site of origin in the large bowel was proposed more than a decade ago. Differences between normal right and left colonic segments that could favour progression through different tumourigenic pathways are summarized in this review. Accumulating evidence suggests that the risk of CRC conferred by various environmental and genetic factors is different for proximal and distal tumours. Right‐ and left‐sided tumours also exhibit different sensitivities to fluorouracil‐based chemotherapy. Such differences are probably related to the molecular characteristics of the tumours, with the microsatellite instability and CpG island methylator phenotypes being associated with right‐sided tumours and chromosomal instability with left‐sided tumours. Future molecular‐based classification systems for CRC that rely upon distinctive gene expression patterns may allow a clearer discrimination of subgroups than that provided by tumour site alone. Until then however, the existence of 2 broadly different groups of cancer defined by site of origin in the colon should be considered in the design of future epidemiologic studies as well as in the design of new clinical trials aimed at testing novel adjuvant therapies. © 2002 Wiley‐Liss, Inc.
Pathogenesis of the dawn phenomenon in patients with insulin-dependent diabetes mellitus. Accelerated glucose production and impaired glucose utilization due to nocturnal surges in growth hormone secretion.

The early-morning increase in insulin requirements of patients with insulin-dependent diabetes mellitus (IDDM) has been referred to as the "dawn phenomenon. " To determine the roles of growth hormone levels and sympathoadrenal activity in this phenomenon, we studied six subjects with IDDM on four occasions during a constant overnight infusion of insulin. In control experiments (infusion of insulin alone), plasma glucose increased from 98 +/- 5 mg per deciliter at midnight to 225 +/- 36 at 8:00 a.m. (P less than 0.001), glucose production increased by 65 per cent (P less than 0.001), and glucose clearance decreased by 50 per cent (P less than 0.001). When nocturnal surges in growth hormone secretion were prevented by infusion of somatostatin plus replacement glucagon, neither plasma glucose levels nor glucose production increased significantly, and glucose clearance did not decrease. When nocturnal surges in growth hormone secretion were simulated by hourly intravenous injections of growth hormone (15 to 100 micrograms) during infusion of somatostatin and glucagon, plasma glucose levels and glucose production increased and glucose clearance decreased to values observed in control experiments. During combined alpha- and beta-adrenergic blockade (phentolamine and propranolol), values for plasma glucose, glucose production, and glucose utilization were not significantly different from those in control experiments. Increases in plasma glucose were significantly correlated with peak plasma growth hormone concentrations (r = 0.58, P less than 0.01). We conclude that nocturnal surges in growth hormone secretion are primarily responsible for the dawn phenomenon in patients with IDDM.
Medical Use, Illicit Use and Diversion of Prescription Stimulant Medication

Abstract The objective of this study was to examine the prevalence and factors associated with the illicit use of prescription stimulants and to assess the relationship between the medical and illicit use of prescription stimulants among undergraduate college students. A Web survey was self-administered by a random sample of 9,161 undergraduate students attending a large public midwestern university in the spring of 2003. A total of 8.1% reported lifetime illicit use of prescription stimulants and 5.4% reported past year dlicit use. The number of undergraduate students who reported illicit use of prescription stimulants exceeded the number of students who reported medical use of prescription stimulants for ADHD. The leading sources of prescription stimulants for illicit use were friends and peers. Multivariate logistic regression analyses revealed several risk factors for illicit use of prescription stimulants such as being male, White, member of a social fraternity or sorority, Jewish religious affiliation, and lower grade point average. All of these characteristics were also related to medically prescribed use of prescription stimulants. Those who initiated medically prescribed use of prescription stimulants for ADHD in elementary school were generally not at increased risk for illicit use of prescription stimulants or other drugs during college as compared to those who were never prescribed stimulant medication. The present study provides evidence that the illicit use of prescription stimulants is a problem among undergraduate college students, and certain subgroups appear to be at heightened risk.
Indoor positioning in cultural heritage: Challenges and a solution

Museums are both appealing and challenging as an environment for research with novel mobile technology. Over the years, quite a few research projects explored the potential of novel technologies to support information delivery to museum visitors. Having an accurate visitor position and orientation is a key factor in the success for offering an interesting and personalized experience to visitors. Unlike outdoors positioning, in spite of numerous technologies experimented with, there is no prevailing indoor positioning solution. Each technology has its benefits as well as its limitations. In addition, museums have their own constraints when it comes to installation of equipment in their space. In the framework of the PIL project, a flexible “light weight” proximity based indoor positioning system was developed and deployed at the Hecht museum, at the University of Haifa. The positioning system was subject to the inherent limitations of the basic measurement technology. The implementation proposes a general framework for indoor positioning addressing these limitations by an abstract reasoning layer supported by a dialog with the user that is seamlessly integrated into a museum visitors' guide system.
Comparison of Ultrasound-assisted Extraction and Dynamic Maceration Over Content of Tagitinin C obtained from Tithonia diversifolia (Hemsl.) A. Gray Leaves Using Factorial Design

Background:Tithonia diversifolia belongs to the Asteraceae family. The leaves of T. diversifolia have been studied lately because of the presence of tagitinin C. Objective: Looking for an easy and inexpensive method to extract tagitinin C from T. diversifolia leaves, this work aims to conduct a screening to evaluate the influence of different experimental factors using the dynamic maceration and ultrasound-assisted extraction methods with 23 factorial design based on response surface methodology in enhancing this chemical marker extraction. Materials and Methods: The experimental factors were: extraction time (ET) of 30 and 60 minutes, solid: liquid ratio (SLR) of 5 and 10 grams/grams and ethanolic strength (ES) 48 and 96% (w/w). The experiments were done tripled. The content of tagitinin C in each produced extract was quantified by HPLC method. Results: The highest concentrations of tagitinin C obtained under the experimental design were 0.53 mg/mL and 0.71 mg/mL, respectively for dynamic maceration (DM) and ultrasound-assisted extraction (UAE) from Tithonia diversifolia powdered leaves. For the UAE method, the main parameter for higher contents of tagitinin C was the solid: liquid ratio, followed by the ethanolic strength, and the extraction time was not significant for this method. As for the DM method, all the parameters (SLR, ES, and ET) were significant for a higher content of tagitinin C. Conclusion: Based on the obtained results, it was revealed that the ultrasound-assisted extraction was more effective than dynamic maceration for tagitinin C extraction from T. diversifolia powdered leaves. Abbreviation used: DME: dynamic maceration extraction, UAE: ultrasound-assisted extraction, ET: extraction time, ES: ethanolic strength, SLR: solid:liquid ratio, Tag C: tagitinin C, HPLC: high-performance liquid chromatography.
Subsyndromal Symptoms in Bipolar Disorder: A Comparison of Standard and Low Serum Levels of Lithium

• Ninety-four patients with bipolar disorder participating in a random-assignment, double-blind, prospective maintenance trial of standard- (0.8 to 1.0 mmol/L) vs low-range (0.4 to 0.6 mmol/L) serum lithium levels were assessed to determine the presence and significance of subsyndromal symptoms during periods of remission and recovery. A significant relationship was found between prescribed serum lithium level and the probability of major affective relapse and the occurrence of subsyndromal symptoms. Patients given lithium carbonate to achieve low-range levels had 2.6 times the risk of major affective relapse as those given lithium for standard-range levels and nearly twice the risk of developing subsyndromal symptoms. Patients given the low-range therapy showed a greater variance in weekly Psychiatric Status Rating measures, and their symptoms were more likely to worsen at any time than were symptoms in their standard-level group counterparts. The first occurrence of subsyndromal symptoms increased the risk of major affective relapse fourfold. Following the onset of subsyndromal symptoms, the patients originally randomized to receive standard-range lithium therapy were still better protected from relapse than were patients randomized to receive low-range lithium treatment. Patients were two times more likely to develop depressive than hypomanic symptoms between acute episodes of illness. However, onset of hypomanic symptoms predicted subsequent major affective relapse twice as strongly as did depressive symptoms. Seventy-six percent of patients who became hypomanic had a major affective relapse, compared with 39% of patients who were subclinically depressed.
Differential Repair of the Two Major UV-Induced Photolesions in Trichothiodystrophy Fibroblasts

Defects in nucleotide excision repair have been shown to be associated with the photosensitive form of the disorder trichothiodystrophy (TTD). Most repair-deficient TTD patients are mutated in the XPD gene, a subunit of the transcription factor TFIIH. Knowledge of the kinetics and efficiency of repair of the two major UV-induced photolesions in TTD is critical to understand the role of unrepaired lesions in the process of carcinogenesis and explain the absence of enhanced skin cancer incidence in TTD patients contrarily to the xeroderma pigmentosum D patients. In this study, we used different approaches to quantify repair of UV-induced cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6–4PP) at the gene and the genome overall level. In cells of two TTD patients, repair of CPD and 6–4PP was reduced compared with normal human cells, but the reduction was more severe in confluent cells than in exponentially growing cells. Moreover, the impairment of repair was more drastic for CPD than 6–4PP. Most notably, exponentially growing TTD cells displayed complete repair 6–4PP over a broad dose range, albeit at a reduced rate compared with normal cells. Strand-specific analysis of CPD repair in a transcriptional active gene revealed that TTD cells were capable to perform transcription-coupled repair. Taken together, the data suggest that efficient repair of 6–4PP in dividing TTD cells in concert with transcription-coupled repair might account for the absence of increased skin carcinogenesis in TTD patients.
ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

Phosphatidylserine is localized exclusively to the inner leaflet of the membrane lipid bilayer of most cells, including erythrocytes. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized phosphatidylserine is a phagocytic signal for splenic macrophages. Flippases are P-IV ATPase family proteins that actively transport phosphatidylserine from the outer to inner leaflet. It has not yet been determined which of the 14 members of this family of proteins is the flippase in human erythrocytes. Herein, we report that ATP11C encodes a major flippase in human erythrocytes, and a genetic mutation identified in a male patient caused congenital hemolytic anemia inherited as an X-linked recessive trait. Phosphatidylserine internalization in erythrocytes with the mutant ATP11C was decreased 10-fold compared to that of the control, functionally establishing that ATP11C is a major flippase in human erythrocytes. Contrary to our expectations phosphatidylserine was retained in the inner leaflet of the majority of mature erythrocytes from both controls and the patient, suggesting that phosphatidylserine cannot be externalized as long as scramblase is inactive. Phosphatidylserine-exposing cells were found only in the densest senescent cells (0.1% of total) in which scramblase was activated by increased Ca2+ concentration: the percentage of these phosphatidylserine-exposing cells was increased in the patient’s senescent cells accounting for his mild anemia. Furthermore, the finding of similar extents of phosphatidylserine exposure by exogenous Ca2+-activated scrambling in both control erythrocytes and the patient’s erythrocytes implies that suppressed scramblase activity rather than flippase activity contributes to the maintenance of phosphatidylserine in the inner leaflet of human erythrocytes.
Completeness and accuracy of registration of ovarian cancer in the cancer registry of Norway

Completeness of reporting and accuracy of the diagnosis of ovarian cancer from one health region in Norway to the Cancer Registry were examined. Data kept by the Cancer Registry were evaluated against discharge diagnosis data from all 8 hospitals in the health region during the period of 1987–1996. The assessment of the accuracy of the diagnosis recorded in the Cancer Registry was based on review of all medical records in the hospital setting and on slide review of all histologic diagnoses. The overall completeness of reporting ovarian cancer to the Cancer Registry was 99.6%. The organ specific completeness of registration of histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re‐evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91% had a primary histologic diagnosis. Among 591 cases identified with a histologic diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at 92%. Coding errors were found in 2% of these cases, while in 6% of the cases it was not possible to reproduce the original diagnosis of ovarian cancer at re‐evaluation. In order to provide data of high quality for cancer surveillance a cancer registry needs several data providers, such as histopathologic laboratory reports and clinical reports. In addition, assessment of reported data through stringent quality assurance procedures within the registry are necessary for reaching a nearly 100% completeness of registration as found for ovarian cancer in the Cancer Registry of Norway. © 2002 Wiley‐Liss, Inc.
Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: A phenotype/genotype correlation

The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low‐ and high‐grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High‐level copy number changes (amplifications) become more prevalent in advanced‐stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage‐specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin‐dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage‐specific chromosomal aberrations with respect to diagnostic applications. Genes Chromosomes Cancer 25:195–204, 1999. Published 1999 Wiley‐Liss, Inc.
Deamidation of human beta B1 alters the elongated structure of the dimer.

The purpose of these experiments was to determine if truncation and deamidation alter the structure of a human lens protein, beta B1-crystallin. Recombinant wild type and a deamidated form of recombinant beta B1 were expressed in Escherichia coli. Wild type beta B1 was also enzymatically cleaved to generate a physiologically-relevant truncated beta B1. Purity and size of the expressed proteins were confirmed by SDS-PAGE and electrospray ionization mass spectrometry. Size exclusion chromatography and light scattering were used to determine aggregation states of beta B1. Protein conformations were predicted from sedimentation velocity analysis. Molecular weights of 49,000 and 54,000 Da were obtained for wild type beta B1 by sedimentation equilibrium and light scattering, respectively. A sedimentation coefficient of 2.7 S was determined for wild type beta B1. Molecular weights of 54,000 and 60,000 Da were determined for deamidated beta B1 by sedimentation equilibrium and light scattering, respectively. However, deamidated beta B1 eluted earlier than wild type beta B1 on size exclusion chromatography, with an estimated molecular weight between 78,000 and 116,000 Da. Loss of the extensions of beta B1 caused abnormal association of the protein with the stationary phase during size exclusion chromatography. Wild type beta B1 was predicted to form a dimer with an elongated structure. The earlier elution of the deamidated beta B1 dimer on size exclusion chromatography suggested the dimer was less compact. Truncation caused abnormal column interactions suggesting an altered conformation. These changes are important because truncation and deamidation occur extensively in aging human lenses and may be important for senile cataract formation.
Implementation and workflow for PET monitoring of therapeutic ion irradiation: a comparison of in-beam, in-room, and off-line techniques

An independent assessment of the dose delivery in ion therapy can be performed using positron emission tomography (PET). For that a distribution of positron emitters which appear as the result of interaction between ions of the therapeutic beam and the irradiated tissue is measured during or after the irradiation. Three concepts for PET monitoring implemented in various therapy facilities are considered in this paper. The in-beam PET concept relies on the PET measurement performed simultaneously to the irradiation by means of a PET scanner which is completely integrated into the irradiation site. The in-room PET concept allows measurement immediately after irradiation by a standalone PET scanner which is installed very close to the irradiation site. In the off-line PET scenario the measurement is performed by means of a standalone PET/CT scanner 10–30 min after the irradiation. These three concepts were evaluated according to image quality criteria, integration costs, and their influence onto the workflow of radiotherapy. In-beam PET showed the best performance. However, the integration costs were estimated as very high for this modality. Moreover, the performance of in-beam PET depends heavily on type and duty cycle of the accelerator. The in-room PET is proposed for planned therapy facilities as a good compromise between the quality of measured data and integration efforts. For facilities which are close to the nuclear medicine departments off-line PET can be suggested under several circumstances.
Natural-cycle in vitro fertilization in women aged over 44 years

Women who are 44 years of age or more are usually denied infertility treatment because of their low response to ovarian stimulation and the extremely low pregnancy rate that can be achieved. The object of this study was to assess the place of natural-cycle in vitro fertilization (IVF) in this population. From January 1996 to September 1997, all consecutive women aged 44–41 years who approached our unit seeking infertility treatment with their own oocytes were enrolled in the study. After a counselling session in which the advantage of egg donation was discussed, women who still wished to try to conceive by utilizing their own oocytes were treated according to the following protocol. Ultrasound and hormonal surveillance was carried out starting 5 days prior to the presumed ovulation day, based on previous menstrual history. Ovum pick-up was timed either by detection of the luteinizing hormone surge or by human chorionic gonadotropin administration. In total, 48 treatment cycles were conducted in 20 women. Oocyte retrieval was successful in 22 cycles. Fertilization and cleavage rates of 48% and 100%, respectively, were detected. Nine of the 12 embryos transferred were defined as grade A. One chemical and one ongoing pregnancy were achieved. We conclude that, despite the fact that high-quality embryos can be obtained in this population, the likelihood of pregnancy is low.