Miracle-dz/UniFAR-FTUs huggingface dataset:
Total Excitation of the Isolated Human Heart

To obtain information concerning the time course and instantaneous distribution of the excitatory process of the normal human heart, studies were made on isolated human hearts from seven individuals who died from various cerebral conditions, but who had no history of cardiac disease. Measurements were made from as many as 870 intramural terminals.In the isolated human hearts three endocardial areas were synchronously excited 0 to 5 msec after the start of the left ventricular activity potential. These areas increased rapidly in size during the next 5 to 10 msec and became confluent in 15 to 20 msec. The left ventricular areas first excited were (1) high on the anterior paraseptal wall just below the attachment of the mitral valve; (2) central on the left surface of the interventricular septum and (3) posterior paraseptal about one third of the distance from apex to base. The last part of the left ventricle to be activated usually was the posterobasal area. Endocardial activation of the right ventricle was found to start near the insertion of the anterior papillary muscle 5 to 10 msec after onset of the left ventricular cavity potential. Septal activation started in the middle third of the left side of the interventricular septum, somewhat anteriorly, and at the lower third at the junction of the septum and posterior wall. The epicardial excitation pattern reflected the movements of the intramural excitation wave. Conduction velocity was determined in one heart by an appropriate stimulation technic. Atrial excitation, explored in two hearts, spread more or less according to concentric isochronic lines.Control studies, carried out on five canine hearts, disclosed that the pattern of ventricular excitation did not change after isolation and perfusion. However, total excitation was completed earlier in the isolated heart, and conduction velocity increased.Careful mapping illustrations are presented.
Amyloid fibers provide structural integrity to Bacillus subtilis biofilms

Bacillus subtilis forms biofilms whose constituent cells are held together by an extracellular matrix. Previous studies have shown that the protein TasA and an exopolysaccharide are the main components of the matrix. Given the importance of TasA in biofilm formation, we characterized the physicochemical properties of this protein. We report that purified TasA forms fibers of variable length and 10–15 nm in width. Biochemical analyses, in combination with the use of specific dyes and microscopic analyses, indicate that TasA forms amyloid fibers. Consistent with this hypothesis, TasA fibers required harsh treatments (e.g., formic acid) to be depolymerized. When added to a culture of a tasA mutant, purified TasA restored wild-type biofilm morphology, indicating that the purified protein retained biological activity. We propose that TasA forms amyloid fibers that bind cells together in the biofilm.
Treating astigmatism at the time of cataract surgery

Correcting astigmatism at the time of cataract surgery can be accomplished either by incisional techniques, such as use of a cataract incision for flattening or astigmatic keratotomy, or by implanting a toric intraocular lens. Both methods can reduce mild to moderate astigmatism. For correcting larger amounts of astigmatism, a combination of techniques can produce greater correction. New methods of analyzing the change induced by surgery provide a more complete understanding of the astigmatic change.
Early syntactic productivity : Evidence from dative shift q

The abstractness of children’s early syntactic representations has been questioned in the recent acquisition literature. While some research has suggested that children’s knowledge of basic constructions such as the transitive is robust and abstract at a very young age, other work has proposed that young children only have constructions that are specific to individual lexical items. The present paper seeks to resolve this discrepancy by examining children’s abstract knowledge of the English dative alternation via a production study. The studiesknowledge of the English dative alternation via a production study. The studies ask whether young children who hear a sentence like I pilked the cup to Petey know that the same meaning can be expressed with the sentence I pilked Petey the cup. This generalization is well-attested in the language that children hear and represents a strong test-case for determining the nature of children’s early syntactic representations. The results indicate that three-year-old children have productive knowledge of the English dative alternation, but that their performance can be influenced by small changes in the nature of the task. A preference for the prepositional dative form is also found and the possible reasons for this preference are discussed. 2006 Elsevier B.V. All rights reserved.
When “AA” is long but “A” is not short: speakers who distinguish short and long vowels in production do not necessarily encode a short–long contrast in their phonological lexicon

In some languages (such as Dutch), speakers produce duration differences between vowels, but it is unclear whether they also encode short versus long speech sounds into different phonological categories. To examine whether they have abstract representations for ‘short’ versus ‘long’ contrasts, we assessed Dutch listeners’ perceptual sensitivity to duration in two vowel qualities: [a] and [ɑ], as in the words maan ‘moon’ and man ‘man,’ which are realized with long and short duration respectively. If Dutch represents this phonetic durational difference as a ‘short’–‘long’ contrast in its phonology, duration changes in [a] and [ɑ] should elicit similar neural responses [specifically, the mismatch negativity (MMN)]. However, we found that duration changes evoked larger MMN amplitude for [a] than for [ɑ]. This finding indicates that duration is phonemically relevant for the maan-vowel that is represented as ‘long,’ while it is not phonemically specified for the man-vowel. We argue that speakers who in speech production distinguish a given vowel pair on the basis of duration may not necessarily encode this durational distinction as a binary ‘short’–‘long’ contrast in their phonological lexicon.
OZONE EPISODES OVER THE SOUTHEAST IBERIAN COAST: ORIGIN AND RECYCLING BETWEEN TWO SEAS

Episodes of high tropospheric ozone concentration in the southeast coast of Iberian Peninsula during 2015 were identified together with associated synoptic conditions, and their most probable origins were determined by means of different atmospheric modelling simulations and data analysis. Most of episodes in this study were associated with high pressures and temperatures, not only over the southeast coast but also over the whole southern Iberian region, which are favourable to the ozone photochemical production. The tropospheric ozone levels detected are mainly due to the transport of ozone from the Eastern Iberian coast. However, Atlantic winds through the Strait of Gibraltar also produce recycling over the study region, and locally increase the ozone levels over the southeast coast of the Iberian
Transient translocation of the cytoplasmic (endo) domain of a type I membrane glycoprotein into cellular membranes

The E2 glycoprotein of the alphavirus Sindbis is a typical type I membrane protein with a single membrane spanning domain and a cytoplasmic tail (endo domain) containing 33 amino acids. The carboxyl terminal domain of the tail has been implicated as (a) attachment site for nucleocapsid protein, and (b) signal sequence for integration of the other alpha-virus membrane proteins 6K and E1. These two functions require that the carboxyl terminus be exposed in the cell cytoplasm (a) and exposed in the lumen of the endoplasmic reticulum (b). We have investigated the orientation of this glycoprotein domain with respect to cell membranes by substituting a tyrosine for the normally occurring serine, four amino acids upstream of the carboxyl terminus. Using radioiodination of this tyrosine as an indication of the exposure of the glycoprotein tail, we have provided evidence that this domain is initially translocated into a membrane and is returned to the cytoplasm after export from the ER. This is the first demonstration of such a transient translocation of a single domain of an integral membrane protein and this rearrangement explains some important aspects of alphavirus assembly.
The Role of JAK Pathway Dysregulation in the Pathogenesis and Treatment of Acute Myeloid Leukemia

The discovery of the Janus kinase 2 (JAK2) V617F mutation has improved our understanding of the pathophysiology of myeloproliferative neoplasms such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Before discovery of the JAK2 V617F mutation, there were no specific targeted therapies for patients with myeloproliferative neoplasms. More recently, several small-molecule inhibitors have been developed that have shown therapeutic potential in the clinical setting. There is evidence that the JAK2 pathway is dysregulated in some acute myeloid leukemias and may also represent a novel therapeutic target in this disease. In this review, we describe the preclinical, clinical, and pathophysiologic evidence for using JAK inhibitors in the treatment of acute myeloid leukemias. Clin Cancer Res; 19(2); 327–35. ©2012 AACR.
A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core and the micro-environment. We discuss the broader use of this approach for other plastic systems and possible therapeutic interventions.
Chemical Studies on the Structure of Mucopeptide Isolated from Streptococcus bovis

Mucopeptides isolated from Streptococcus bovis cell walls were found to be composed of alanine, glutamic acid, lysine, and threonine in a mole ratio of 3:1:1:1. A dipeptide, Nε-lysylthreonine, was isolated from S. bovis mucopeptide by ion-exchange chromatography. This finding suggests that threonine is associated with the bridge which cross-links adjacent tetrapeptides by connecting the ε-amino group of lysine of one tetrapeptide to the carboxyl group of d-alanine of another to form the mucopeptide matrix.
Consequences of combining siRNA-mediated DNA methyltransferase 1 depletion with 5-aza-2′-deoxycytidine in human leukemic KG1 cells

5-azacytidine and 5-aza-2′-deoxycytidine are clinically used to treat patients with blood neoplasia. Their antileukemic property is mediated by the trapping and the subsequent degradation of a family of proteins, the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) leading to DNA demethylation, tumor suppressor gene re-expression and DNA damage. Here we studied the respective role of each DNMT in the human leukemia KG1 cell line using a RNA interference approach. In addition we addressed the role of DNA damage formation in DNA demethylation by 5-aza-2′-deoxycytidine. Our data show that DNMT1 is the main DNMT involved in DNA methylation maintenance in KG1 cells and in mediating DNA damage formation upon exposure to 5-aza-2′-deoxycytidine. Moreover, KG1 cells express the DNMT1 protein at a level above the one required to ensure DNA methylation maintenance, and we identified a threshold for DNMT1 depletion that needs to be exceeded to achieve DNA demethylation. Most interestingly, by combining DNMT1 siRNA and treatment with low dose of 5-aza-2′-deoxycytidine, it is possible to uncouple DNA damage formation from DNA demethylation. This work strongly suggests that a direct pharmacological inhibition of DNMT1, unlike the use of 5-aza-2′-deoxycytidine, should lead to tumor suppressor gene hypomethylation and re-expression without inducing major DNA damage in leukemia.
A community study of depression treatment and employment earnings.

OBJECTIVE Although treatment for major depression has been shown to reduce the costs of lost earnings resulting from lost work days, research has not demonstrated whether the reduction fully offsets the costs of treatment for the disorder. METHODS A statewide cohort of community residents with recent major depression, dysthymia, or substantial depressive symptoms was recruited and interviewed at baseline and at six-month and 12-month follow-ups. The cost of lost earnings was measured by lost work days multiplied by subjects' wage rates. Cost of treatment for depression was approximated using charges abstracted from provider and insurance records. Net economic cost, defined as the sum of changes in lost earnings and depression treatment costs, was examined in multiple regression analyses. RESULTS After the analyses controlled for sociodemographic characteristics, baseline severity of depression, and comorbidity, no statistically significant effect of depression treatment on net economic cost was found. This finding suggests that the cost of depression treatment was fully offset by savings from reduction in lost work days. Results from sensitivity analyses in multiple alternative scenarios support the same conclusion. CONCLUSIONS The finding of a full offset of depression treatment cost is conservative because other benefits, such as reduced pain and suffering and increased productivity while at work, were not included in the analyses. Employers who bear the cost from lost work days should encourage their employees with depressive disorders to seek treatment, even if it means paying for the entire treatment cost. Self-employed individuals with depression also will benefit even if they pay for the treatment costs themselves.
Clinical applications of wall-stress analysis in the pediatric intensive care unit

ObjectiveTo determine whether serial, noninvasive assessment of afterload, contractility, and Doppler-derived cardiac output reliably detects variations in cardiac function in unstable pediatric patients. DesignProspective, blinded clinical trial. SettingThe pediatric intensive care unit at Massachusetts General Hospital. PatientsFourteen critically ill pediatric patients. InterventionsPediatric patients meeting criteria for hemodynamic instability underwent serial echocardiograms every 6 hrs until they met exit criteria, generating 75 studies. Measurements and Main Results Shortening fraction, cardiac index (CI), end-systolic wall stress (ESWS), and corrected velocity of circumferential shortening (Vcfc) were measured in each patient. Data points were plotted as a stress-velocity relationship, compared with published normal values, then correlated with changes in vital signs and pharmacologic interventions. Fourteen of 16 patients who were enrolled completed the study. A strong negative correlation between ESWS and Vcfc was confirmed (p < .001). As an internal measure of validity, Vcfc had a strong positive correlation with CI measurements (p = .012). An increase in dopamine infusion was associated with a fall in ESWS (p = .02), an increase in Vcfc (p = .03), and an increase in the CI as measured by Doppler (p = .035). The infusion of dopamine above renal perfusion levels moved patients from zones of normal or compensated contractility for afterload on a modified stress-velocity relationship to a zone of high contractility for afterload. Urine output was the only clinical index of cardiac function that had a significant correlation with the echocardiographic indices. Hemodynamically unstable patients followed similar patterns of deterioration and recovery on the modified stress-velocity graph. All surviving patients returned to a normal or compensated zone. ConclusionsWall-stress analysis of cardiac function is easily and safely performed on mechanically ventilated pediatric patients with the production of consistently high-quality data. For internal validity, Vcfc and CI measurements were correlated and were strongly positive. Wall-stress indices reliably detected patient deterioration, recovery, and response to changes in dopamine infusion. Patients who failed to return to areas of normal or compensated levels of contractility and afterload did poorly in this study. Noninvasive measures of afterload and contractility appear useful for monitoring cardiac function of critically ill children in an intensive care setting.
Using Markov Chains to Exploit Word Relationships in Information Retrieval

Document expansion and query expansion aim to add related terms into document and query representations in order to make them more complete. However, most previous studies are limited in two respects: They use either query expansion or document expansion, but not both; expansion has been limited to directly related words. In this paper, we propose a more general approach: both document and query representations are expanded, and the expansion process also exploits indirect term relationships. The whole process is implemented through Markov chains. Our experiments show that each of these extensions brings additional improvements.
Expression of the LIM‐homeobox gene LH2 generates immortalized Steel factor‐dependent multipotent hematopoietic precursors

The genes controlling self‐renewal and differentiation in the hematopoietic system are largely unknown. The LIM‐homeobox genes are known to be important for asymmetric cell divisions and differentiation of specific cell types and organs. One member of this family, LH2, is expressed in fetal liver at the time of active hematopoiesis. Therefore, we have assessed the function of LH2 during the formation and initial expansion of the hematopoietic system by differentiating LH2‐transduced embryonic stem (ES) cells in vitro. This procedure generated multipotent hematopoietic precursor cell (HPC) lines that required Steel factor for growth. HPC lines have been maintained in an undifferentiated state in culture for >7 months. Other growth factors tested efficiently induce terminal differentiation of HPCs into various mature myeloid lineages. Steel factor is also required and acts synergistically with the other growth factors to generate multilineage colonies from the HPCs. These HPC lines express transcription factors that are consistent with an immature progenitor, and the pattern of cell surface marker expression is similar to that of early fetal multipotent hematopoietic progenitors. Collectively, these data suggest that the HPC lines represent an early fetal multipotent hematopoietic progenitor, and suggest a role for LH2 in the control of cell fate decision and/or proliferation in the hematopoietic system.
Valsartan Protects Pancreatic Islets and Adipose Tissue From the Inflammatory and Metabolic Consequences of a High-Fat Diet in Mice

Obesity, hypertension, cardiovascular disease, and inflammation are closely associated with the rising incidence of diabetes mellitus. One pharmacological target that may have significant potential to lower the risk of obesity-related diseases is the angiotensin type 1 receptor (AT1R). We examined the hypothesis that the AT1R blocker valsartan reduces the metabolic consequences and inflammatory effects of a high-fat (Western) diet in mice. C57BL/6J mice were treated by oral gavage with 10 mg/kg per day of valsartan or vehicle and placed on either a standard chow or Western diet for 12 weeks. Western diet-fed mice given valsartan had improved glucose tolerance, reduced fasting blood glucose levels, and reduced serum insulin levels compared with mice fed a Western diet alone. Valsartan treatment also blocked Western diet–induced increases in serum levels of the proinflammatory cytokines interferon-&ggr; and monocyte chemotactic protein 1. In the pancreatic islets, valsartan enhanced mitochondrial function and prevented Western diet–induced decreases in glucose-stimulated insulin secretion. In adipose tissue, valsartan reduced Western diet–induced macrophage infiltration and expression of macrophage-derived monocyte chemotactic protein 1. In isolated adipocytes, valsartan treatment blocked or attenuated Western diet–induced changes in expression of several key inflammatory signals: interleukin 12p40, interleukin 12p35, tumor necrosis factor-&agr;, interferon-&ggr;, adiponectin, platelet 12-lipoxygenase, collagen 6, inducible NO synthase, and AT1R. Our findings indicate that AT1R blockade with valsartan attenuated several deleterious effects of the Western diet at the systemic and local levels in islets and adipose tissue. This study suggests that AT1R blockers provide additional therapeutic benefits in the metabolic syndrome and other obesity-related disorders beyond lowering blood pressure.
Review of Treatment and Prognosis of Stage IVB Cervical Carcinoma

Objectives In most patients, stage IVB cervical cancer is incurable, and the outcomes are poor. There is significant individual variation in patients with stage IVB cervical cancer, in whom standard treatment has not been well defined. This study aims to review the outcomes and discuss treatment strategies in patients with stage IVB cervical cancer. Methods From January 1, 1992, to December 31, 2011, we retrospectively reviewed the data of patients with stage IVB cervical cancer who were given a diagnosis at the Department of Gynecology of the Cancer Institute Hospital. Results A total of 111 patients were enrolled. At the time of analysis, the median overall survival (OS) was 16.6 months (range, 0.2–120.9 months), and the 5-year OS rate was 20.2%. The 5-year OS rate was 59.4% for those with only para-aortic lymph node metastases; 24.8% for those with lymphogenous metastases, excluding those with only para-aortic lymph node metastases; 6.1% for those with hematogenous metastases; and 0% for those with disseminated metastases. The OS in patients with lymphogenous metastases was better compared with that of those with either hematogenous or disseminated metastases (P < 0.0001). In multivariate analysis, the performance status, site of metastases (only lymph node or other metastases), and local stage were all independent prognostic factors. Conclusions We determined performance status, site of metastases (only lymph node or other metastases), and local stage as independent prognostic factors in patients with stage IVB cervical cancer. Regarding treatment, we confirmed that the effectiveness of chemotherapy was also of significance.