Miracle-dz/UniFAR-FTUs huggingface dataset:
Anatomy of the human sinus node

Following the physiologic studies of the cardiac pacemaker by Wenckebach (’06) and others in the last part of the 19th century, Arthur Keith and his medical student assistant, Martin Flack, were the first to make an anatomic description of the “sino-auricular” node. A charming account of this great discovery was given by Keith (’42) in his commentary on the Hunterian Lecture delivered by Davies in 1942. As has been recently pointed out by Hudson (’60), one is still humbled and fascinated, even after the passage of over 50 years, by the meticulous details of the original work of Keith and Flack. A number of excellent subsequent anatomic studies of the sinus node have been made (Baird and Robb, ’50; Blair and Davies, ’34-’35; Burian, ’24-’25; Copenhaver and Truex, ’52; Davies, ’42; Field, ’51; Flack, ’lo-’11; Glomset and Glomset, ’40; Halpern, ’55; Koch, ’09; Koch, ’11; Lev, ’60; Lumb and Shacklett, ’60; Mackenzie, ’13; Monckeberg, ’21; Nonidez, ’43; Pace, ’24; Read, Hegre and Russi, ’53; Robb, Kaylor and Turman, ’48; Schiebler, Stark and Caesar, ’56; Shaner, ’29-’30; Stotler and McMahon, ’47; Todd, ’28; Walls, ’47). However, because of contradictory observations it is not unfair to suggest that as much confusion as clarification has been added to our knowledge. For example, there is no uniform use of a name for the pacemaker of the heart. Sino-auricular (or sinu-auricular) node, sino-atrial node, and the node of Keith and Flack have been among those more commonly used. In vernacular language the commonest name employed is probably “sinus node,” but perhaps in an effort at more elegance for the written word this brief term is seldom employed there. Walmsley (’29) conspicuously departed from this practice and consistently refers to the structure as the “sinus node. ” In addition to its attractive brevity, this term has other reasoris to recommend its usage. From embryological studies i t is known that the ultimate cardiac pacemaker originates in the sinus venosus (Patten, ’49) and not in the atrium or auricle. Additionally, neither “sino-auricular” nor “sinoatrial” is correct in the strictest anatomic sense, for the node extends from the auriculo-caval junction back to the atrio-caval junction. It is suggested that Walmsley’s simpler term “sinus node,” which is both brief and accurate, be accepted as the standard name for the pacemaker of the heart.
Bacteriology and chemical composition of renal calculi accompanying urinary tract infection

Bacteriological study of pre-operative urine and stone along with chemical analysis of stones have been perforned in 100 cases of urolithiasis. Although the rate of infection accompanying stone formation is more in female (50%) in comparison to male (27.9%) but over­all incidence of stone formation is more in male (86%). The crushed stone core culture was positive in 31 cases (31 %) and out of these cases, 23 cases (74.19%) showed positive urine culture. 15 cases (48.38%) of stone positive culture showed same organism which were also isolated from pre-operative urine culture whereas 8 (25.80%) cases of culture positive stones showed dif­ferent micro-organisms than pre-operative urine cul­ture. Chemical analysis revealed increased incidence of mixed stone composed of calcium oxalate and cal­cium phosphate (51 %). The occurence of pure triple phosphate stone was only 13%. The commonest pathogen recovered from pre-operative urine culture and stone culture was E.coli (32.25% and 21.73%)followed by Pseudomonas (22.58% and 17.39%) from mixed stones composed of calcium oxalate with cal­cium phosphate and triple phosphate. Out of 31 infection stones, 13 stones which were composed mainly of triple phosphate showed highest incidence of infection (84.62%).
Diverse two-cysteine photocycles in phytochromes and cyanobacteriochromes

Phytochromes are well-known as photoactive red- and near IR-absorbing chromoproteins with cysteine-linked linear tetrapyrrole (bilin) prosthetic groups. Phytochrome photoswitching regulates adaptive responses to light in both photosynthetic and nonphotosynthetic organisms. Exclusively found in cyanobacteria, the related cyanobacteriochrome (CBCR) sensors extend the photosensory range of the phytochrome superfamily to shorter wavelengths of visible light. Blue/green light sensing by a well-studied subfamily of CBCRs proceeds via a photolabile thioether linkage to a second cysteine fully conserved in this subfamily. In the present study, we show that dual-cysteine photosensors have repeatedly evolved in cyanobacteria via insertion of a second cysteine at different positions within the bilin-binding GAF domain (cGMP-specific phosphodiesterases, cyanobacterial adenylate cyclases, and formate hydrogen lyase transcription activator FhlA) shared by CBCRs and phytochromes. Such sensors exhibit a diverse range of photocycles, yet all share ground-state absorbance of near-UV to blue light and a common mechanism of light perception: reversible photoisomerization of the bilin 15,16 double bond. Using site-directed mutagenesis, chemical modification and spectroscopy to characterize novel dual-cysteine photosensors from the cyanobacterium Nostoc punctiforme ATCC 29133, we establish that this spectral diversity can be tuned by varying the light-dependent stability of the second thioether linkage. We also show that such behavior can be engineered into the conventional phytochrome Cph1 from Synechocystis sp. PCC6803. Dual-cysteine photosensors thus allow the phytochrome superfamily in cyanobacteria to sense the full solar spectrum at the earth surface from near infrared to near ultraviolet.
Limited Value of Fluorine-18-Fluorodeoxyglucose PET for the Differential Diagnosis of Focal Liver Lesions in Patients with Chronic Hepatitis C Virus Infection

Summary Aim: The differentiation of HCC from liver metastasis or benign disorders by imaging studies based upon morphological aspects may be difficult. Method: In order to evaluate the role of tumour metabolism, we performed FDG-PET (whole-body PET and transmission-corrected regional scans of the liver as well as the SUV determined 60 min after injection of FDG) in ten consecutive patients with HCV-associated focal liver lesions. Definite diagnosis was established after ultrasound-guided liver biopsy followed by histopathological examination. These results were compared with ultrasound, computed tomography, serum anti- p53, and p53 protein expression. Results: The histologic examination revealed a HCC in five patients, regenerative nodules in three patients, and liver metastasis (primary malignancy: one adenocarcinoma and one neuroendocrine tumour) in the remaining two patients. Three of ten lesions were detectable by FDG-PET: two HCCs and one metastatic adenocarcinoma. Seven lesions were not distinguishable by FDG-PET (three HCCs, three regeneration nodules and one metastatic neuroendocrine tumour). In each patient hepatic lesions were visible either by ultrasound or CT. Both tumours (metastatic adenocarcinoma, moderately well-differentiated HCC) with the strongest expression of p53 also presented with highly increased FDG uptake. Conclusions: FDG-PET is not superior to ultrasound or CT and therefore does not allow the non-invasive differentiation of HCV-associated focal liver lesions. Tissue-diagnosis by means of liver-biopsy followed by histopathological examination remains the gold-standard for the differentiation of HCV-related liver lesions. The finding of the relationship of p53 protein overexpression with the SUV needs further confirmation.
Proof of two Divisibility Properties of Binomial Coefficients Conjectured by Z.-W. Sun

For all positive integers n, we prove the following divisibility properties: $$(2n+3){2n\choose n} | 3{6n\choose 3n}{3n\choose n}, and (10n+3){3n\choose n} | 21{15n\choose 5n} {5n\choose n}. $$ This confirms two recent conjectures of Z. -W. Sun. Some similar divisibility properties are given. Moreover, we show that, for all positive integers m and n, the product $am{am+bm-1\choose am}{an+bn\choose an}$ is divisible by m+n. In fact, the latter result can be generalized to the q-binomial coefficients and q-integers case, which generalizes the positivity of q-Catalan numbers. We also propose several related conjectures.
Lymph node biopsies: a hospital based retrospective study.

INTRODUCTION Lymphadenopathy is a common clinical finding at the outpatient setting that may be caused by a vast array of disease processes. METHODS A retrospective study to analyze the histopathological diagnosis of lymph node biopsies with respect to age, sex, and site was conducted. All the lymph nodes sent for histopathological examination from August 2003 to 2007 were included. RESULTS Of all patients with enlarged lymph nodes, 49% were males (mean age: 34.52 years) and 51% were females (mean age: 38.1 years). The most common diagnosis was tubercular lymphadenitis (42%), followed by non-specific (reactive) lymphadenitis (23%), metastatic deposits (10%), non-specific granuloma (3%), NHL (2%), and lymphadenitis due to various other causes (7%). Thirteen percent of the biopsied lymph nodes were normal in morphology. Most common site of lymph node enlargement was neck (44%) followed by mesentery (19%) and axilla (16%). Most of the patients were in the age group of 21-30 years (20%). CONCLUSIONS The neck lymph nodes were the most commonly sent nodes for histopathological examination and tuberculosis was the most common diagnosis.
An inquiry into the human mind

Copyright © 2010–2015 All rights reserved. Jonathan Bennett [Brackets] enclose editorial explanations. Small ·dots· enclose material that has been added, but can be read as though it were part of the original text. Occasional •bullets, and also indenting of passages that are not quotations, are meant as aids to grasping the structure of a sentence or a thought. Every four-point ellipsis . indicates the omission of a short passage that seems to present more difficulty than it is worth. Longer omissions are reported beween square brackets in normal-sized type. First launched: September 2005 Last amended: July 2007
The State of Research for AIDS-Associated Opportunistic Infections and the Importance of Sustaining Smaller Research Communities

University of Kentucky, Department of Microbiology, Immunology and Molecular Genetics, Lexington, Kentucky, USAa; University of Cincinnati, Department of Biological Sciences, Cincinnati, Ohio, USAb; Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Tufts University, Boston, Massachusetts, USAc; Albert Einstein College of Medicine, Bronx, New York, USAd; and University of Cincinnati College of Medicine and the Cincinnati VAMC, Cincinnati, Ohio, USAe
Effect and mechanism of melatonin's action on the proliferation of human umbilical vein endothelial cells

Abstract: Melatonin is the major secretory product of the pineal gland and is considered an important natural oncostatic agent. The anticancer activity of melatonin is due to its immunomodulatory, anti‐proliferative and antioxidative effects. At present there are no direct data available as to melatonin's possible influence on angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. The current study investigated the influence of melatonin on angiogenesis. Human umbilical vein endothelial cells (HUVECs) were cultured, identified, and purified. Cell growth and viability, DNA fragmentation and cell cycle analyses were determined. To elucidate the mechanism of action of melatonin, Western blot analyses for P53, Bax and Bcl‐2 expression were carried out. The results demonstrate the anti‐proliferative and apoptosis‐inducing effects of melatonin; these changes were associated with cell cycle arrest, upregulation of P53 and Bax and downregulation of Bcl‐2. Taken together, our data showed that melatonin in high concentrations markedly reduces HUVECs proliferation, induces cellular apoptosis, and modulates cell cycle length. P53 and Bax/Bcl‐2 expression changes may be involved in these actions of melatonin.
Molecular characterization of male breast cancer by standardized quantitative RT-PCR analysis: First large genomic study of 347 male breast cancers compared to 82,434 female breast cancers.

549 Background: Because male breast cancer (BC) is rare, there is little known about the disease and treatment is extrapolated from female BC. Newer molecular technologies have not been used to profile male BC. We report here a study of quantitative gene expression by gender status in tumor specimens submitted for Recurrence Score testing. METHODS All estrogen receptor positive tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through December 2008 were included. Quantitative expression for each gene was measured by the 21 gene oncotype DX assay on a scale from 0 to 15 (relative to reference genes), where a one unit increment is associated with a 2-fold change in expression. RESULTS There were 347 male and 82,434 female BCs. The males were older (mean age 63.8 vs 57.4 yrs). Standard histopathology was similar, although slightly more male BCs were ductal (83% vs 78%). Like female BC, there was a wide variation in gene expression in male BC. The distribution of RS in males and females was similar - RS mean (±SD) 18.1 (±11.2) in males and 19.1 (±10.2) in females (p = NS). The proportion of tumors with RS <18, 18 - 30, and ≥ 31 was 53.6%, 35.2%, and 11.2% in males and 53.4%, 36.3%, and 10.3% in females. Although the patterns of expression of the Oncotype DX genes were more similar than different in males and females some differences were notable. Mean expression of ER, PR, and SCUBE2 were 0.5 units higher in males. Mean expression of the proliferation genes, Ki-67, MYBL2, Survivin, Cyclin B1, and STK15, were 0.5 units higher in males. Mean expression of STMY3 was 0.9 units higher in males. Of note, whereas the level of quantitative ER significantly increased with increasing patient age in females (0.4 units per decade), little increase was observed in males (<0.1 units per decade). CONCLUSIONS This large genomic study of male BC reveals a heterogeneous biology as measured by the standardized quantitative oncotype DX breast cancer assay, similar to that observed in female BC. Some differences, which may reflect the differences in hormone biology between males and females, were noted and deserve further study. [Table: see text].
Mechanisms and physiological role of enhancement of mGlu5 receptor function by group II mGlu receptor activation in rat perirhinal cortex

In this study we have investigated mechanisms underlying enhancement by group II metabotropic glutamate (mGlu) receptors of group I mGlu receptor‐induced calcium mobilization. Inhibition of protein kinase A (PKA) caused an enhancement of mGlu5 receptor‐mediated calcium mobilization and occluded the enhancement by group II mGlu receptors. A peptide (Ht31) that prevents interaction between A‐kinase anchoring protein (AKAP) and PKA also enhanced mGlu5‐mediated calcium mobilization. Enhancement of mGlu5 function, by inhibition of PKA or by activation of group II mGlu receptors, was prevented by the protein phosphatase 2B (PP2B) inhibitor cyclosporin A. Furthermore, the enhancement by activation of group II mGlu receptors was prevented by raising intracellular cAMP. These results suggest that the regulation by PKA and PP2B of phosphorylation of a substrate on mGlu5 and/or on group II mGlu receptors is intimately involved in the mechanisms underlying interaction between group II mGlu and mGlu5 receptors. Long‐term depression (LTD) in perirhinal cortex requires group I, group II and NMDA receptor activation at resting membrane potentials but does not require group II mGlu receptor activation at depolarized potentials. We previously suggested that interaction between group I and group II mGlu receptors is required for induction of LTD at resting potentials. In support of this, we demonstrate in perirhinal cortex slices that blocking mechanisms underlying mGlu receptor synergy (by raising intracellular cAMP or by inhibition of PP2B) selectively prevented LTD at resting membrane potentials. This study thus provides a potential explanation for the co‐requirement in LTD of group I and group II mGlu receptor activation. Similar mechanisms of synergistic interaction may also be important in other physiological processes dependent on mGlu receptors.
Analyse syntaxique et semantique avec evaluation d'attributs dans un demi-anneau application a la linguistique calculatoire

Le but est de proposer des algorithmes de calcul de forets d'analyse decorees par des attributs verifiant la structure algebrique de demi-anneau et applicables a differents formalismes de la linguistique calculatoire. Le point de depart est l'analyse syntaxique non-contextuelle generale (incluant donc les grammaires ambigues). Une strategie d'analyse est presentee sous la forme d'un automate a pile non-deterministe, qui est ensuite interprete par programmation dynamique. Cette technique s'applique sur des calculs recursifs a condition que chaque sous-calcul puisse etre identifie par un indice. Le mecanisme consiste a tabuler les resultats, en n'effectuant chaque sous-calcul qu'une fois. Il en resulte une complexite (en temps et en espace) cubique pour les algorithmes de reconnaissance syntaxique. Cette methode est etendue a l'analyse stochastique, pour laquelle nous proposons une generalisation des theoremes d'adequation entre les calculs operationnels de probabilites et leur definition par la grammaire probabiliste. Les quantites calculees sont les probabilites de prefixe, de sous-chaine, et le calcul du meilleur arbre. Quatre strategies sont presentees : earley, left corner, lr et extended lr. La theorie des series de puissance algebriques est utilisee pour formaliser la decoration d'une grammaire dans un demi-anneau abstrait. L'analyse s'exprime alors comme le calcul du coefficient d'un mot pour la serie formelle definie par la grammaire decoree, ce qui revient a resoudre un systeme d'equations au point fixe. Nous donnons des conditions qui assurent la solvabilite du systeme, et montrons qu'on peut le resoudre en utilisant la programmation dynamique. Les quatre algorithmes stochastiques sont alors reformules pour calculer une decoration dans un demi-anneau abstrait. Enfin nous montrons que les grammaires de clauses definies et les grammaires a structure de traits peuvent etre decrites comme des grammaires non-contextuelles decorees dans un demi-anneau.
Predictors for postoperative esophageal stricture after balloon-based radiofrequency ablation for early esophageal squamous neoplasia: a multicenter validation study

Background: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs), but the risk factors for postoperative stricture have not been elucidated. The objective of this study was to identify and validate a predictor for post-RFA stenosis. Methods: We consecutively enrolled patients with flat-type ‘large’ (length no less than 3 cm extending no less than half the circumference of the esophagus), early ESCNs, treated with balloon-based RFA (12 J/cm2–clean–12 J/cm2 regimen). The tumor and technical factors for postoperative stricture were investigated and we validated the results externally with a society-based multicenter cohort using the same ablation regimen. Results: A total of 51 patients were enrolled (30 in the development set and 21 in the validation set). The complete remission rate at 12 months was 93%, and the rates of perforation and postoperative stenosis were 0% and 17%, respectively. Patients with post-RFA stenosis had a significantly larger longitudinal tumor size (mean 115 versus 61 mm, p = 0.003). There were no significant differences in age, body mass index, tumor circumferential extension, pretreatment histological grade, treatment efficacy or size of balloon catheter between the groups with or without stenosis. The optimal cut-off value was set as 9 cm to predict post-RFA stenosis by receiver operating characteristic curve [area under curve (AUC) = 0.881], which was then confirmed to be a reliable predictor by multivariate analysis (odds ratio, 12.7, 95% confidence interval, 1.18–136.28, p = 0.03) and have a good predictive performance in the validation set (AUC = 0.876). Conclusions: The most frequent adverse event of RFA was esophageal stenosis, for which the longitudinal tumor size was a significant predictive factor. Early intervention or prevention for stricture should be applied for those with long segment (⩾9 cm) ESCNs.
Identification and Functional Analysis of Phosphorylated Tyrosine Residues within EphA2 Receptor Tyrosine Kinase*

EphA2 is a member of the Eph family of receptor tyrosine kinases. EphA2 mediates cell-cell communication and plays critical roles in a number of physiological and pathologic responses. We have previously shown that EphA2 is a key regulator of tumor angiogenesis and that tyrosine phosphorylation regulates EphA2 signaling. To understand the role of EphA2 phosphorylation, we have mapped phosphorylated tyrosines within the intracellular region of EphA2 by a combination of mass spectrometry analysis and phosphopeptide mapping using two-dimensional chromatography in conjunction with site-directed mutagenesis. The function of these phosphorylated tyrosine residues was assessed by mutational analysis using EphA2-null endothelial cells reconstituted with EphA2 tyrosine-to-phenylalanine or tyrosine-to-glutamic acid substitution mutants. Phosphorylated Tyr587 and Tyr593 bind to Vav2 and Vav3 guanine nucleotide exchange factors, whereas Tyr(P)734 binds to the p85 regulatory subunit of phosphatidylinositol 3-kinase. Mutations that uncouple EphA2 with Vav guanine nucleotide exchange factors or p85 are defective in Rac1 activation and cell migration. Finally, EphA2 mutations in the juxtamembrane region (Y587F, Y593F, Y587E/Y593E), kinase domain (Y734F), or SAM domain (Y929F) inhibited ephrin-A1-induced vascular assembly. In addition, EphA2-null endothelial cells reconstituted with these mutants were unable to incorporate into tumor vasculature, suggesting a critical role of these phosphorylation tyrosine residues in transducing EphA2 signaling in vascular endothelial cells during tumor angiogenesis.
Synthetic Peptide Dendrimers Block the Development and Expression of Experimental Allergic Encephalomyelitis1

Multiple Ag peptides (MAPs) containing eight proteolipid protein (PLP)139–151 peptides arranged around a dendrimeric branched lysine core were used to influence the expression and development of relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. The PLP139–151 MAPs were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP139–151 monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP72–84 MAP (a dendrimeric octamer composed of the 72–84 peptide) and PLP178–191 MAP (a dendrimeric octamer composed of the PLP178–191 peptide) had no treatment effect on PLP139–151-induced EAE. PLP139–151 MAP treatment initiated after clinical signs of paralysis also altered the subsequent course of EAE; it limited developing signs of paralysis and effectively limited the severity and number of disease relapses in MAP-treated mice over a 60-day observation period. PLP139–151 MAP therapy initiated before disease onset acts to limit the numbers of Th17 and IFN-γ-producing cells that enter into the CNS. However, Foxp3+ cells entered the CNS in numbers equivalent for nontreated and PLP139–151 MAP-treated animals. The net effect of PLP139–151 MAP treatment dramatically increases the ratio of Foxp3+ cells to Th17 and IFN-γ-producing cells in the CNS of PLP139–151 MAP-treated animals.