Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140

1 In a previous investigation, Hoe 140, a specific and potent bradykinin B2 receptor antagonist, prevented the pancreatic oedema and the hypotension observed during acute experimental pancreatitis; however, it augmented the associated rises in the serum activities of pancreatic enzymes. Therefore, we have now investigated the consequences of the pancreatic oedema for the fate of activated enzymes released into the tissue during the course of acute pancreatitis. 2 Acute oedematous pancreatitis was induced in rats, pretreated with captopril (50 μmol kg−1, i.p.), by hyperstimulation of the exocrine function of the pancreas with the cholecystokinin analogue, caerulein (4 nmol kg−1 h−1, i.v.), for up to 120 min. 3 Pancreatic oedema began to develop 10 min after the start of the caerulein infusion, reached a maximum within about 45 min, and then declined slightly. The development of the oedema parallelled the second phase of the caerulein‐induced fall in blood pressure found in earlier experiments. No further extravasation of plasma proteins occurred during the 2nd hour of the caerulein infusion. The oedema formation was completely blocked in animals pretreated with the bradykinin receptor antagonist, Hoe 140 (100 nmol kg−1, s.c.). Pretreatment with aprotinin or soy bean trypsin inhibitor did not result in a significant inhibition of the oedema. 4 The haematocrit of animals with experimental pancreatitis showed a pronounced increase which started 10 min after the start of the caerulein infusion and reached maximal values at 60 min. The changes in haematocrit showed a reduction in total blood volume of 28% due to a 48% loss of plasma. This effect was completely blocked by Hoe 140. 5 In rats with caerulein‐induced pancreatitis, there was a time‐dependent increase in the activities of amylase and lipase in blood serum as well as in the pancreas. Pretreatment with Hoe 140 greatly augmented the caerulein‐induced rise in enzyme activities in blood serum but potently attenuated it in the pancreas. The activities of trypsin in both the blood serum and the pancreas were below or near the limit of detection in all experimental groups. 6 It is concluded that the second phase of hypotension in this model of acute pancreatitis is due to the liberation of kinins which cause a massive loss of blood plasma into the pancreas and into the retroperitoneal space. Activated enzymes are trapped in the pancreas, at least in part, by the oedema of the gland. Treatment with Hoe 140 prevents the oedema formation and greatly facilitates the egress of activated enzymes from the pancreas.
Genetic determinants of plasma triglycerides

Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies.
Forward-flyback resonant converter for high-efficient medium-power photovoltaic applications

In this paper, a quasi-resonant forward-flyback converter is proposed for photovoltaic power system. Since the output of forward-flyback converter is connected in series, the proposed circuit offers high-step up conversion. The quasi-resonant forward circuit that consists of a transformer leakage inductance and a resonant capacitor generates almost sinusoidal currents during the switch on-time so the primary switching stress has been significantly reduced. The flyback circuit transfers the energy stored in the magnetizing inductance to the load during the switch off-time. Design guidelines of the circuit parameters are presented. To verify the proposed circuit design, a 400-W experimental prototype has been designed, fabricated, and tested. Simulation and experimental results verify the effectiveness of the proposed circuit design.
Notch signaling controls the balance of ciliated and secretory cell fates in developing airways

Although there is accumulated evidence of a role for Notch in the developing lung, it is still unclear how disruption of Notch signaling affects lung progenitor cell fate and differentiation events in the airway epithelium. To address this issue, we inactivated Notch signaling conditionally in the endoderm using a Shh-Cre deleter mouse line and mice carrying floxed alleles of the Pofut1 gene, which encodes an O-fucosyltransferase essential for Notch-ligand binding. We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling. Strikingly, these mutants showed an almost identical lung phenotype characterized by an absence of secretory Clara cells without evidence of cell death, and showed airways populated essentially by ciliated cells, with an increase in neuroendocrine cells. This phenotype could be further replicated in cultured wild-type lungs by disrupting Notch signaling with a gamma-secretase inhibitor. Our data suggest that Notch acts when commitment to a ciliated or non-ciliated cell fate occurs in proximal progenitors, silencing the ciliated program in the cells that will continue to expand and differentiate into secretory cells. This mechanism may be crucial to define the balance of differentiated cell profiles in different generations of the developing airways. It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease.
Survival Rate and Risk Factors of Mortality Among HIV/Tuberculosis-Coinfected Patients With and Without Antiretroviral Therapy

Background: The impact of antiretroviral therapy (ART) on survival among patients coinfected with HIV and tuberculosis (TB) has not been well established. Methods: A retrospective cohort study was conducted among HIV-infected patients with TB between January 2000 and December 2004. Patients were categorized into ART+ group (received ART) and ART− group (did not receive ART) and were followed until April 2005. Results: A total of 1003 patients were identified; 411 in ART+ group and 592 in ART− group. Median (interquartile range) CD4 count was 53 (20-129) cells/mm3. Survival rates at 1, 2, and 3 years after TB diagnosis were 96.1%, 94.0%, and 87.7% for ART+ group and 44.4%, 19.2%, and 9.3% for ART− group (log-rank test, P < 0.001). Cox proportional hazard model showed that ART was associated with lower mortality rate; gastrointestinal TB and multidrug resistant TB were associated with higher mortality rate (P < 0.05). Among patients in ART+ group, the patients who delayed ART ≥6 months after TB diagnosis had a higher mortality rate than those who initiated ART <6 months after TB diagnosis (P 0.018, hazard ratio = 2.651, 95% confidence interval = 1.152-6.102). Conclusions: Antiretroviral therapy substantially reduces mortality rate among HIV/TB-coinfected patients. Initiation of ART within 6 months of TB diagnosis is associated with greater survival.
Pressure Receptors in the Fins of the Dogfish Scylliorhinus Canicula

1. The presence of so-called terminal corpuscles in the connective tissues of the fins of Scylliorhinuis canicula , first described by Wunderer in 1908, is confirmed. 2. It is demonstrated that they are pressure receptors with a slow rate of adaptation. 3. From their topographic distribution and from their mode of response to mechanical stimulation, it is postulated that the terminal corpuscles serve as proprioceptors in the widest sense of the term by signalling the spatio-temporal patterns of active or passive deformation of the fin. 4. Their topographic distribution makes it possible to distinguish their responses from those of sense endings associated with the muscles or tendons of the fin.
Production , Manufacturing and Logistics An approach for integrated scheduling and lot-sizing

In this paper a non time discrete approach is developed for an integrated planning procedure, applied to a multi-item capacitated production system with dynamic demand. The objective is to minimize the total costs, which consist of holding and setup costs for one period. The model does not allow backlog. Furthermore, a production rate of zero or full capacity is the only possibility. The result is a schedule, lot-sizes and the sequences for all lots. The approach is based on a specific property of the setup cost function, which allows for replacement of the integer formulation for the number of setup activities in the model. In a situation where the requirements for the multi-item continuous rate economic order quantity, the so-called economic production lot (EPL) formula, are fulfilled, both the EPL as well as the presented model results are identical for the instances dealt with. Moreover, with the new model problems with an arbitrary demand can be solved. 2004 Elsevier B.V. All rights reserved.
Effects of Protein Kinase CK2, Extracellular Signal-regulated Kinase 2, and Protein Phosphatase 2A on a Phosphatidic Acid-preferring Phospholipase A1*

A soluble, phosphatidic acid-preferring phospholipase A1, expressed in mature bovine testes but not in newborn calf testes, may contribute to the formation or function of sperm. Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importancein vivo. Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730; 5) CK2α formed a stable, MgATP/MgGTP-dependent complex with the phospholipase by a novel mechanism; and 6) the complex showed reduced phospholipase activity and resembled a complex identified in homogenates of macaque testis. These results provide the first available information about the effects of reactions of phosphorylation and dephosphorylation on the behavior of the phospholipase, shed light on properties of CK2α that may be required for the formation of complexes with its substrates, and raise the possibility that a complex containing CK2α and the phospholipase may play a special biological role in the testis.
Loss of the cellular prion protein affects the Ca2+ homeostasis in hippocampal CA1 neurons

Previous neurophysiological studies on prion protein deficient (Prnp–/–) mice have revealed a significant reduction of slow afterhyperpolarization currents (sIAHP) in hippocampal CA1 pyramidal cells. Here we aim to determine whether loss of PrPC. directly affects the potassium channels underlying sIAHP or if sIAHP is indirectly disturbed by altered intracellular Ca2+ fluxes. Patch‐clamp measurements and confocal Ca2+ imaging in acute hippocampal slice preparations of Prnp–/– mice compared to littermate control mice revealed a reduced Ca2+ rise in CA1 neurons lacking PrPC following a depolarization protocol known to induce sIAHP. Moreover, we observed a reduced Ca2+ influx via l‐type voltage gated calcium channels (VGCCs). No differences were observed in the protein expression of the pore forming α1 subunit of VGCCs Prnp–/– mice. Surprisingly, the β2 subunit, critically involved in the transport of the α1 subunit to the plasma membrane, was found to be up‐regulated in knock out hippocampal tissue. On mRNA level however, no differences could be detected for the α1C, D and β2–4 subunits. In conclusion our data support the notion that lack of PrPC. does not directly affect the potassium channels underlying sIAHP, but modulates these channels due to its effect on the intracellular free Ca2+ concentration via a reduced Ca2+ influx through l‐type VGCCs.
That's Not How I see It: How Trust in the Organization, Leadership, Process, and Outcome Influence Individual Responses to Organizational Change

The purpose of this research was to understand the sensemaking processes people use to determine their responses to organizational change initiatives as they unfold overtime. Based on a longitudinal comparative case study of five business units in a $900-million manufacturing organization in the United States, it shows that people continuously assess how the initiatives will enhance or diminish their individual and organizational identities using four kinds of trust: trust in the organization, trust in leadership, trust in the process, and trust in outcomes. The complex dynamics among these “four trusts” and their influence on responses to change are described. A four trusts model is proposed to help change leaders formulate specific trust-building strategies to increase the probability of success of organizational change initiatives. Implications for research and practice are discussed.
Effects of scopolamine on dopamine neurons in the substantia nigra: Role of the pedunculopontine tegmental nucleus

Previous neurochemical and behavioral studies suggest that muscarinic receptor antagonism has an excitatory effect on the nigrostriatal dopamine (DA) system. Using in vivo extracellular single unit recording, this study examined whether blockade of the muscarinic receptor by scopolamine alters the firing properties of DA neurons in the substantia nigra (SN). Scopolamine was administered either systemically or locally to DA neurons using microiontophoresis. Surprisingly, scopolamine did not cause any significant change in either the firing rate or pattern of the spontaneously active DA neurons. However, systemic injection of scopolamine significantly increased the number of active DA neurons in the SN. Local infusion of scopolamine into the pedunculopontine tegmental nucleus (PPT) mimicked the effect induced by systemically administered scopolamine, significantly increasing the number of active DA neurons without altering the firing rate and pattern. These results suggest that the reported increase in striatal DA release induced by scopolamine is in part mediated by activation of silent nigral DA neurons. The experiments with PPT local infusion further suggest that part of the effect of scopolamine may be due to its blockade of the inhibitory muscarinic autoreceptors on PPT cholinergic cells. The latter effect may lead to activation of quiescent DA neurons by increasing acetylcholine (ACh) release in the SN or in other brain areas providing inputs to DA neurons. Further understanding of the mechanism of action of scopolamine may help us further understand the role of ACh in both the pathophysiology and treatment of DA‐related disorders including schizophrenia and Parkinson's disease. Synapse 63:673–680, 2009. © 2009 Wiley‐Liss, Inc.
Immigrant Identity: Code Switchingamong Kenyans in Upstate New York

There are a substantial number of Kenyans in the US scattered across the many cities of the country although there are thought to be particular concentrations in Minnesota, Texas, New Jersey and Delaware. Many of these have come to the US as students, for business, as permanent residents and as employees of multinational companies (Kahura 2003). Entering the US is a big experience for many and part of their adaptation strategy to a new way of life in the US has been a tendency to stay close to other Kenyans hence the concentration in particular states and also the use of community networks like social gatherings, informal Kenyan clubs and fraternities, umbrella groups like the Kenyan Community Abroad (KCA) and internet websites set up by Kenyans for topical discussions among themselves. These forums seem to serve as a reification of common interests, heritage and identity. While it would appear, outwardly at least, that membership in these informal Kenyan groups and networks, indexes a Kenyan identity, my interest in this inquiry focuses on the role of language in this identification project. There are over forty languages in Kenya with Swahili and English being coofficial. As such, most of these first generation Kenyans in the US are trilingual in Swahili, English and some other Kenyan language. In addition, they come with a tradition of code switching that has been shown to be second nature to them in their home country (Myers-Scotton 1993, Ogechi 2001). Indeed, according to Mazrui (1995), code switching finds its most overt structure in Sheng, an urban vernacular in Kenya that Mazrui and others consider to be based on code switching. Outside of the home country, far away in America, is there code switching and how does it manifest itself? What role does it play in the new context of Kenyans living as a minority in a dominant US cultural setting?
Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation

Significance During pregnancy, nutrients are required for fetal growth and for the mother to maintain the pregnancy. The placenta is central to this tug-of-war over nutrients, as it is responsible for materno-fetal resource allocation. Failure to allocate resources appropriately can lead to pregnancy complications and abnormal fetal development, with long-term health consequences for both mother and baby. Here we use manipulation of a growth-regulatory protein, p110α, in mice to compare the importance of the maternal environment and genotype with fetal genotype in determining placental resource allocation. This study shows that the placenta fine-tunes the supply of maternal resources to the fetus via p110α in accordance with both the fetal drive for growth and the maternal ability to supply the required nutrients. Pregnancy success and life-long health depend on a cooperative interaction between the mother and the fetus in the allocation of resources. As the site of materno-fetal nutrient transfer, the placenta is central to this interplay; however, the relative importance of the maternal versus fetal genotypes in modifying the allocation of resources to the fetus is unknown. Using genetic inactivation of the growth and metabolism regulator, Pik3ca (encoding PIK3CA also known as p110α, α/+), we examined the interplay between the maternal genome and the fetal genome on placental phenotype in litters of mixed genotype generated through reciprocal crosses of WT and α/+ mice. We demonstrate that placental growth and structure were impaired and associated with reduced growth of α/+ fetuses. Despite its defective development, the α/+ placenta adapted functionally to increase the supply of maternal glucose and amino acid to the fetus. The specific nature of these changes, however, depended on whether the mother was α/+ or WT and related to alterations in endocrine and metabolic profile induced by maternal p110α deficiency. Our findings thus show that the maternal genotype and environment programs placental growth and function and identify the placenta as critical in integrating both intrinsic and extrinsic signals governing materno-fetal resource allocation.
Estimation of Integer Carrier Frequency Offset in OFDM Systems Based on the Maximum Likelihood Principle

An algorithm is derived for the estimation of the integer part of the carrier frequency offset in OFDM systems. The algorithm employs correlation of consecutive OFDM symbols in the frequency domain, is formulated for the general case of a system using data subcarriers and/or pilots and approximates the maximum likelihood (ML) correlation-based estimator for the AWGN channel. The cases of pseudo-pilots, boosted pilots and virtual subcarriers are also examined. It is shown that, compared to previous approaches based on symbol correlation, the algorithm makes better use of the information contained in the correlated symbols, leading to a more accurate, approximate ML estimate of the integer carrier frequency offset at operating signal-to-noise ratios. Simulations indicate that, even in the case of multipath channels, the proposed algorithm is very likely to outperform other techniques.
Ovarian cancer ascites enhance the migration of patient‐derived peritoneal mesothelial cells via cMet pathway through HGF‐dependent and ‐independent mechanisms

Ovarian cancer ascites consist of a proinflammatory environment that is characterized by the presence of abundant human peritoneal mesothelial cells (HPMCs). Cytokines and growth factors in ascites modulate cell activities of tumor cells. The expression of proinflammatory cytokines in ascites is associated with a more aggressive tumor phenotype. The effect of ascites on HPMCs is for the most part unknown but this interplay is thought to be important for epithelial ovarian cancer (EOC) progression. Here, we examine the components of ascites, which stimulate patient‐derived HPMC migration, from women with advanced EOC. We show that ovarian cancer ascites enhanced the migration of HPMCs. This effect was inhibited by heat treatment, hepatocyte growth factor (HGF) blocking antibodies and a HGF receptor (cMet) inhibitor. In ovarian cancer ascites, HGF is present at high concentration compared to benign fluids. Ascites‐mediated activation of cMet was associated with Akt and EKR1/2 phosphorylation. This response was partly inhibited by heat treatment and cMet inhibitor. Ascites‐induced migration and a cMet phosphorylation were strongly inhibited by epidermal growth factor receptor (EGFR) inhibitor PD153035, suggesting the transactivation of cMet by EGFR. Our study suggests that HGF and ligands of EGFR are factors that mediate ovarian cancer ascites‐mediated migration of HPMCs by activating cMet and possibly downstream ERK1/2 and Akt pathways. The study provides evidence for the first time that ascites not only support tumor growth but also enhance the migratory potential of cancer‐associated mesothelial cells, which in turn may support cancer progression.
Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy.

PURPOSE Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy. PATIENTS AND METHODS We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy. RESULTS Fifty-eight patients were assessable for second tumors. Nine (50%) of 18 patients who received radiotherapy after their OPGs developed 12 second tumors in 308 person-years of follow-up after radiotherapy. Eight (20%) of 40 patients who were not treated with radiotherapy developed nine tumors in 721 person-years of follow-up after diagnosis of their OPGs. The relative risk of second nervous system tumor after radiotherapy was 3.04 (95% CI, 1.29 to 7.15). CONCLUSION There is a significantly increased risk of second nervous system tumors in those NF1 patients who received radiotherapy for their OPGs, especially when treated in childhood. Thus radiotherapy should only be used if absolutely essential in children with NF1.