Miracle-dz/UniFAR-FTUs huggingface dataset:
Peroxynitrite modification of protein thiols: oxidation, nitrosylation, and S-glutathiolation of functionally important cysteine residue(s) in the sarcoplasmic reticulum Ca-ATPase.

Skeletal muscle contraction and relaxation is efficiently modulated through the reaction of reactive oxygen-nitrogen species with sarcoplasmic reticulum protein thiols in vivo. However, the exact locations of functionally important modifications are at present unknown. Here, we determine by HPLC-MS that the modification of one (out of 24) Cys residue of the sarcoplasmic reticulum (SR) Ca-ATPase isoform SERCA1, Cys(349), by peroxynitrite is sufficient for the modulation of enzyme activity. Despite the size and nature of the SR Ca-ATPase, a 110 kDa membrane protein, identification and quantitation of Cys modification was achieved through labeling with 4-(dimethylamino)phenylazophenyl-4'-maleimide (DABMI) and/or N-(2-iodoethyl)trifluoroacetamide (IE-TFA) followed by an exhaustive tryptic digestion and on-line HPLC-UV-electrospray MS analysis. The reaction with IE-TFA generates aminoethylcysteine, a new trypsin cleavage site, which allows the production of specific peptide fragments that are diagnostic for IE-TFA labeling, conveniently identified by mass spectrometry. Exposure of the SR Ca-ATPase to low concentrations (0.1 mM) of peroxynitrite resulted in the fully reversible chemical modification of Cys at positions 344, 349, 471, 498, 525, and 614 (nitrosylation of Cys(344) and Cys(349) was seen), whereas higher concentrations of peroxynitrite (0.45 mM) additionally affected Cys residues at positions 636, 670, and 674. When the SR Ca-ATPase was exposed to 0.45 mM peroxynitrite in the presence of 5.0 mM glutathione (GSH), thiol modification became partially reversible and S-glutathiolation was detected for Cys residues at positions 344, 349, 364, 498, 525, and 614. The extent of enzyme inactivation (determined previously) quantitatively correlated with the loss of labeling efficiency (i) of a single Cys residue and (ii) of the tryptic fragment containing both Cys(344) and Cys(349). Earlier results had shown that the independent selective modification of Cys(344) is functionally insignificant [Kawakita, M. , and Yamashita, T. (1987) J. Biochem. (Tokyo) 102, 103-109]. Thus, we conclude that modification of only Cys(349) is responsible for the modulation of the SR Ca-ATPase activity by peroxynitrite.
Utilization and efficacy of internet-based eHealth technology in gastroenterology: a systematic review

Abstract Objective. While there have been several reviews exploring the outcomes of various eHealth studies, none have been gastroenterology-specific. This paper aims to evaluate the research conducted within gastroenterology which utilizes internet-based eHealth technology to promote physical and psychological well-being. Material and methods. A systematic literature review of internet-based eHealth interventions involving gastroenterological cohorts was conducted. Searched databases included: EbSCOhost Medline, CINAHL, and PsycINFO. Inclusion criteria were studies reporting on eHealth interventions (both to manage mental health problems and somatic symptoms) in gastroenterology, with no time restrictions. Exclusion criteria were non-experimental studies, or studies using only email as primary eHealth method, and studies in language other than English. Results. A total of 17 papers were identified; seven studies evaluated the efficacy of a psychologically oriented intervention (additional two provided follow-up analyses exploring the original published data) and eight studies evaluated disease management programs for patients with either irritable bowel syndrome, inflammatory bowel disease (IBD) or celiac disease. Overall, psychological eHealth interventions were associated with significant reductions in bowel symptoms and improvement in quality of life (QoL) that tended to continue up to 12 months follow up. The eHealth disease management was shown to generally improve QoL, adherence, knowledge about the disease, and reduce healthcare costs in IBD, although the studies were associated with various methodological problems, and thus, this observation should be confirmed in well-designed interventional studies. Conclusions. Based on the evidence to date, eHealth internet-based technology is a promising tool that can be utilized to both promote and enhance gastrointestinal disease management and mental health.
A study of the control of glycolate excretion in chlorella.

Chlorella pyrenoidosa cells grown on 5% CO(2) excreted glycolate when incubated in light with 10 mm bicarbonate, but excreted no glycolate under the same conditions when they were maintained on air for 7 hours prior to the assay. Incubation of 5% CO(2)-grown and air-grown cells with 10 mm isonicotinyl hydrazide or 10 mm alpha-hydroxypyridinemethane sulfonate during the assay stimulated the excretion of glycolate by CO(2)-grown cells severalfold that of air-grown cells.Adaptation of CO(2)-grown Chlorella to growth on air did not affect the levels of glycolate dehydrogenase in the cells and did not affect the rate of dark oxidation and metabolism of exogeneous (14)C-glycolate by the cells. These results indicate that the lack of glycolate excretion by air-grown or air-adapted cells of Chlorella cannot be explained by a concomitant change in the level of glycolate dehydrogenase.
Query Interactions in Database Systems

The typical workload in a database system consists of a mix of multiple queries of different types, running concurrently and interacting with each other. The same query may have different performance in different mixes. Hence, optimizing performance requires reasoning about query mixes and their interactions, rather than considering individual queries or query types. In this dissertation, we demonstrate how queries affect each other when they are executing concurrently in different mixes. We show the significant impact that query interactions can have on the end-to-end workload performance. A major hurdle in the understanding of query interactions in database systems is that there is a large spectrum of possible causes of interactions. For example, query interactions can happen because of any of the resource-related, data-related or configuration-related dependencies that exist in the system. This variation in underlying causes makes it very difficult to come up with robust analytical performance models to capture and model query interactions. We present a new approach for modeling performance in the presence of interactions, based on conducting experiments to measure the effect of query interactions and fitting statistical models to the data collected in these experiments to capture the impact of query interactions. The experiments collect samples of the different possible query mixes, and measure the performance metrics of interest for the different queries in these sample mixes. Statistical models such as simple regression and instance-based learning are used to train models from these sample mixes. This approach requires no prior assumptions about the internal workings of the database system or the nature or cause of the interactions, making it portable across systems. We demonstrate the potential of capturing, modeling, and exploiting query interactions by developing techniques to help in two database performance related tasks: workload scheduling and estimating the completion time of a workload. These are important workload management problems that database administrators have to deal with routinely. We consider the problem of scheduling a workload of report-generation queries. Our scheduling algorithms employ statistical performance models to schedule appropriate query mixes for the given workload. Our experimental evaluation demonstrates that our interaction-aware scheduling algorithms outperform scheduling policies that are typically used in database systems. The problem of estimating the completion time of a workload is an important problem, and the state of the art does not offer any systematic solution. Typically database administrators rely on heuristics or observations of past behavior to solve this problem. We propose
Comparison of three typing methods for clinical and environmental isolates of Aspergillus fumigatus

To evaluate procedures used for epidemiologic analysis of outbreaks of aspergillosis, we analyzed a collection of 35 Aspergillus fumigatus isolates using three typing methods: isoenzyme analysis (IEA), random amplified polymorphic DNA (RAPD) analysis, and restriction endonuclease analysis (REA). Twenty-one isolates were from a single hospital, with four isolates coming from different patients. Three clinical isolates came from a different hospital, and 11 clinical or environmental isolates were derived from a culture collection. With IEA, the patterns of alkaline phosphatase, esterase, and catalase discriminated nine types. In contrast, 22 types were obtained with five different RAPD primers, and 21 types could be detected with three of these (R108, R151, and UBC90). Restriction endonuclease analysis of genomic DNA, digested with either XbaI, XhoI, or SalI, detected 3, 17, and 13 different REA types, respectively, and 22 types were identified by combining the data from the XhoI and SalI REAs. Twenty-eight types were obtainable with a combination of REA, IEA, and RAPD patterns. Overall, the results pointed to substantial genetic variation among the isolates. Though two isolates had markedly distinct genotypes, their morphologic features and exoantigens were consistent with their being A. fumigatus. The analysis will help in planning epidemiologic studies of aspergillosis.
Chemokine Receptor 7 (CCR7) Gene Expression Is Regulated by NF-κB and Activator Protein 1 (AP1) in Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN)*

Background: The regulation and significance of aberrant CCR7 expression in metastatic SCCHN is poorly understood. Results: High CCR7 expression correlates with decreased patient survival. CCR7 is regulated by NF-κB and AP1 signaling pathways. Conclusion: CCR7 is a poor prognosis marker. NF-κB and AP1 signaling pathways co-regulate CCR7 expression. Significance: Understanding the regulation of CCR7 is crucial for developing therapeutic targets for treating metastatic SCCHN. The chemokine receptor CCR7 is a seven-transmembrane domain G-protein-coupled receptor that facilitates leukocyte migration to regional lymph nodes. Aberrant CCR7 expression in a number of human malignancies has been linked to pro-survival, -invasive, and -metastatic pathways. We demonstrate here that up-regulation of CCR7 in squamous cell carcinoma of the head and neck (SCCHN) patient tumors correlates with lower survival because of metastatic disease. Because of this important oncogenic phenotype, we investigated the mechanisms that regulate CCR7 expression in these tumors. Interestingly, the inflammatory transcription factor NF-κB has been associated with a more aggressive SCCHN phenotype. Immunohistochemical staining of a SCCHN tumor cohort (n = 47) strongly linked NF-κB staining and CCR7 expression in SCCHN. Thus, we investigated whether NF-κB contributes to metastatic disease by promoting CCR7 expression in SCCHN tumor cells. We characterized four novel, potential NF-κB binding sites in the 1000-bp promoter region upstream of the CCR7 gene, using luciferase, ChIP, and EMSA. However, NF-κB inhibition only resulted in partial reduction in CCR7 expression, prompting consideration of other co-regulators of CCR7. Indeed, cooperation between NF-κB and AP1 transcription factors, which are often co-activated, is crucial to the regulation of CCR7 mRNA expression in metastatic SCCHN cells. Thus, our findings support an important biological role for inflammatory NF-κB and AP1 in the regulation of CCR7 expression in metastatic SCCHN. As such, CCR7, NF-κB, and AP1 could be potentially useful therapeutic targets in controlling the progression and metastasis of SCCHN tumors.
'Gangliocytomas' of the pituitary: a heterogeneous group of lesions with differing histogenesis.

Hamartomatous or neoplastic ganglion cells in the sella turcica are an unusual cause of symptoms. They have been reported in association with a functioning or nonfunctioning pituitary adenoma, with pituitary cell hyperplasia, and occasionally as masses unassociated with an adenoma, again with variable endocrinologic findings. Fewer than 50 cases of intrasellar ganglion cell lesions have been reported in the literature, only six of them associated with Cushing's syndrome. We describe the clinicopathologic features of another eight patients, three of whom presented with acromegaly, four with apparently nonfunctioning adenohypophyseal masses, and one with Cushing's syndrome. On histology, six of them were found to have sparsely granulated growth hormone (GH)-producing adenomas with ganglion cell areas, one appeared to have a gangliocytoma not associated with an adenoma, whereas the eighth had a ganglion cell lesion in the posterior pituitary. The morphologic and immunohistochemical findings suggest that the ganglion cell component of seven of these tumors has resulted from neuronal differentiation in a GH-producing adenoma, despite the lack of demonstrable adenoma in one case. A true sellar "gangliocytoma" or hamartoma of ectopic hypothalamic-type neurons appears to be a rarer explanation for the presence of ganglion cells in a pituitary biopsy.
Perichromosomal protein Ki67 supports mitotic chromosome architecture

Although the condensin complexes and topoisomerase IIα (TopoIIα) are the central players in mitotic chromosome formation, they are insufficient for its completion, and additional factors involved in the process have been extensively sought. In this study, we examined the possibility that Ki67, a perichromosomal protein widely used as a cell proliferation marker, is one such factor. Using a combination of auxin‐inducible degron and CRISPR–Cas9‐based gene editing technologies, we generated a human HCT116 cell line in which Ki67 is rapidly depleted in a few hours. The removal of Ki67 before mitotic entry did not impact the early mitotic chromosome assembly observed in prophase but subsequently resulted in the formation of misshapen mitotic chromosomes. When Ki67 was removed after mitotic entry, preassembled rod‐shaped mitotic chromosomes became disorganized. In addition, we show that Ki67 and TopoIIα are reciprocally coimmunoprecipitated from mitotic cell extracts. These observations indicate that Ki67 aids the finalization of mitotic chromosome formation and helps maintain rod‐shaped chromosome architecture, likely in collaboration with TopoIIα. Together, these findings represent a new model in which mitotic chromosome architecture is supported both internally and externally.
How do proxy responses and proxy-assisted responses differ from what Medicare beneficiaries might have reported about their health care?

OBJECTIVE Assess proxy respondent effects on health care evaluations by Medicare beneficiaries. DATA SOURCE 110,215 respondents from the nationally representative 2001 CAHPS((R)) Medicare Fee-for-Service Survey. STUDY DESIGN/DATA COLLECTION/EXTRACTION METHODS We compare the effects of both proxy respondents and proxy assistance (reading, writing, or translating) on 23 "objective" report items and four "subjective" global measures of health care experiences using propensity-score-weighted regression. We assess whether proxy effects differ among spouses, other relatives, or nonrelatives. PRINCIPAL FINDINGS Proxy respondents provide less positive evaluations of beneficiary health care experiences than otherwise similar self-reporting beneficiaries for more subjective global ratings (average effect of 0.21 standard deviations); differences are smaller for relatively objective and specific report items. Proxy assistance differences are similar, but about half as large. Reports from spouse proxy respondents are more positive than those from other proxies and are similar to what would have been reported by the beneficiaries themselves. Standard regression techniques may overestimate proxy effects in this instance. CONCLUSIONS One should treat proxy responses to subjective ratings cautiously. Even seemingly innocuous reading, writing, and translation by proxies may influence answers. Spouses may be accurate proxies for the elderly in evaluations of health care.
Electromyography--dynamic gross anatomy: a review.

“Electromyography: Dynamic Gross Anatomy” is the first in a series of invited review articles by leaders in fields of current interest. Students often ask if anything really “new” has been discovered in gross anatomy in the last fifty years. The answer is an unqualified “yes,” and electromyography probably has provided more of this new information than any other technique. Not since the pioneering work of Duchenne in 1867 has any one man contributed so much to our knowledge of the function of the musculoskeletal system as Dr. John V. Basmajian, Professor of Medicine and Associate in Anatomy at McMaster University and Director of Rehabilitation and Continuing Care Centres of Chedoke-McMaster Hospital, Hamilton, Ontario, Canada. Since his initial publication in 1952, he has written over 200 scientific papers on electromyography. He is the author of Muscles Alive: Their Functions Revealed by Electromyography, now in its fourth edition, and the author or co-author of numerous other books on gross anatomy, kinesiology, therapeutic exercise and clinical electro-neurography. In 1965, Dr. Basmajian was one of the founders of the International Society of Electromyographic Kinesiology (now the International Society of Electrophysiologic Kinesiology), and he served as its first president. In recognition of his many contributions to the discipline, ISEK dedicated its Sixth International Congress to him. Universally recognized as the undisputed leader in the field, Professor Basmajian is the ideal person to summarize the “state of the art” for the readers of The American Journal of Anatomy.
Laparoscopic vs open appendectomy in children: outcomes comparison based on age, sex, and perforation status.

HYPOTHESIS Outcomes of laparoscopic appendectomy (LA) will be similar to open appendectomy (OA) in children of all ages. DESIGN Retrospective cohort study using discharge abstract data. SETTING Twelve regional hospitals in Southern California. PATIENTS Seven thousand six hundred fifty patients underwent appendectomy for acute appendicitis (LA = 3551, OA = 4099). INTERVENTION Laparoscopic appendectomy or OA. MAIN OUTCOME MEASURES Thirty-day morbidity (wound infection, abscess drainage, and readmission) and length of hospitalization. RESULTS Use of laparoscopy increased from 22% in 1998 to 70% in 2007. Overall, patients undergoing LA were older (mean [SD] age, 12.8 [3.2] vs 10.4 [3.7] years; P < .001) and had a lower perforation rate (24% vs 34%; P < .001). Multivariable logistic regression demonstrated a decreased odds ratio for wound infection (odds ratio, 0.6; 95% confidence interval, 0.5-0.8) and abscess drainage (odds ratio, 0.6; 95% confidence interval, 0.4-0.7) following LA compared with OA. Multivariable linear regression also showed decreased length of hospitalization following LA compared with OA. CONCLUSION Now the preferred operation for children with appendicitis, LA was associated with a decreased risk of wound infection, abscess drainage, and length of hospitalization compared with OA.
Cellular mechanisms of renal tubular transport of I-dopa and its derivatives in the rat: microperfusion studies.

Proximal tubular transport of L-3,4-dihydroxyphenylalanine (L-dopa) and its derivatives were studied in the rat kidney by microperfusion and capillary perfusion techniques in situ. With the use of microperfusion techniques alone, it was found that L-dopa, L-3-methoxy-4-hydroxyphenylalanine, L-tyrosine and L-phenylalanine rapidly disappeared from the perfusate. The rates of reabsorption were calculated to be 2.05 X 10(-12), 2.13 X 10(-12), 6.35 X 10(-12) and 7.14 X 10(-12) mol/cm/sec, respectively. In contrast, L-alpha-methyldopa and dopamine were only slightly reabsorbed. The permeability coefficients were calculated to be 0.35 X 10(-4) and 0.21 x 10(-4) and 0.21 x 10(-4) cm/sec, respectively. The rate of reabsorption of L-dopa was greatly reduced in the presence of L-phenylalanine in the perfusate, but was not affected by D-dopa. With the stop-flow microperfusion technique with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (deltaC) of labeled dopa was measured. When the initial concentration of 2 mM labeled L-dopa was perfused, the luminal concentration fell to a plateau level of 1.5 mM after a contact time of 20 seconds; i.e., deltaC was 0.5 mM. The net flux was much less than the efflux, suggesting the presence of a secretory or passive back flux of L-dopa. The deltaC of L-dopa was not influenced by the decarboxylase inhibitor, MK-486, and monoamine oxidase inhibitor, pheniprazine, but was significantly reduced by NaCN. Thus the reabsorption of L-dopa in the proximal convoluted tubule is an active process with great structural specificity.
Chapter 7 Induction Therapy in Multiple Myeloma

Today, multiple myeloma (MM) can be defined as a heterogenous disease composed of different clinical conditions. The differences are a result of patient related factors (age, sex, comorbidity), disease related complications (renal failure, bone disease, neuropathy, throm‐ bosis) and biological characteristics (cytogenetics, lactate dehydrogenase level, plasma cell labelling index, beta2-microglobulin, gene expression profiles). The widely used international scoring system is a powerful tool for determining survival. However, it cannot be used for treatment planning. The biological determinants of disease determined by flourescein in situ hybridization (FISH) and/or conventional cytogenetics are better tools to stratify myeloma subgroups with different survival profiles. Thus these are better tools for designing therapeutic approaches. A risk stratification of newly diagnosed MM according to FISH/Karyotyping has been recently reviewed by Rajkumar (Rajkumar, 2012).
Selective removal of Pb2+ by AlPO4

Abstract Aluminium(III) phosphate was observed to have a very high selectivity towards Pb2+ ions. Under similar conditions, the sorption capacities of the exchanger were observed to follow the order: Pb2+ > Zn2+> Ni2+ > Co2+. The potentiometric titration data were used to determine the deprotonation constants (pKa) of AlPO4 which were dependent upon the temperature and nature of the metal cations present in the aqueous phase. Different physico‐chemical methods i.e. FTIR, EPM and the wet chemical analyses were used to investigate the uptake mechanism of Pb2+ by the solid, which showed that no new solid phases were present in the solid residue after sorption of Pb2+ at pH 5. The exchange between protons from the surface and Pb2+ from solutions was found to be responsible for Pb2+sorption by aluminum(III) phosphate.
A review of the Granger-causality fallacy

Methods used to infer causal relations from data rather than knowledge of mechanisms are most helpful and exploited only if the theoretical background is insufficient or experimentation impossible. The review of literature shows that when an investigator has no prior knowledge of the researched phenomenon, no result of the Grangercausality test has any epistemic utility due to different possible interpretations. (1) Rejecting the null in one of the tests can be interpreted as either a true causal relation, opposite direction of the true causation, instant causality, time series cointegration, not frequent enough sampling, etc. (2) Bi-directional Granger causality can be read either as instant causality or common cause fallacy. (3) Non-rejection of both nulls possibly means either indirect or nonlinear causality, or no causal relation.