Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of extracellular acid–base disturbances on the intracellular pH of neurones cultured from rat medullary raphe or hippocampus

Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady‐state intracellular pH in response to a change in extracellular pH (ΔpHi/ΔpHo). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non‐chemosensitive region), we used BCECF to monitor pHi in cultured neurones subjected to extracellular acid–base disturbances. In medullary raphe neurones, respiratory acidosis (5%→ 9% CO2) caused a rapid fall in pHi (ΔpHi∼0.2) with no recovery and a large ΔpHi/ΔpHo of 0.71. Hippocampal neurones had a similar response, but with a slightly lower ΔpHi/ΔpHo (0.59). We further investigated a possible link between pHi regulation and chemosensitivity by following the pHi measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergic neurones). We found that the ΔpHi/ΔpHo of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the ΔpHi/ΔpHo of 0.75 for non‐serotonergic neurones (most of which are not chemosensitive), or from the ΔpHi/ΔpHo of hippocampal neurones. For both respiratory alkalosis (5%→ 3% CO2) and metabolic alkalosis (22 mm→ 35 mm HCO3−), ΔpHi/ΔpHo was 0.42–0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mm→ 14 mm HCO3−), which caused a large pHi decrease in ∼80% of medullary raphe neurones (ΔpHi/ΔpHo= 0.71), but relatively little pHi decrease in 70% of the hippocampal neurones (ΔpHi/ΔpHo= 0.09). Our comparison of medullary raphe and hippocampal neurones indicates that, except in response to metabolic acidosis, the neurones from the chemosensitive region do not have a uniquely high ΔpHi/ΔpHo. Moreover, regardless of whether neurones were cultured from the chemosensitive or the non‐chemosensitive region, pHi did not recover during any of the acid–base stresses.
Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability

Blockade of the programmed death 1 (PD-1) pathway has emerged as a novel therapy for cancer. Therefore, development of biomarkers for response prediction, such as PD-ligand 1 (PD-L1) expression by immunohistochemistry, may help to stratify patients. Solid tumors with CD8 T-cell rich tumor microenvironment have been implicated to be associated with increased PD-L1 expression. We hypothesized that gastric cancers associated with Epstein-Barr virus infection (EBV+) or microsatellite instability (MSI), both of which are known to harbor such tumor microenvironment, are associated with increased PD-L1 expression. Forty-four resected gastric cancers including 7 EBV+, 16 MSI, and 21 microsatellite stable cancers without EBV (EBV−/MSS) were studied for PD-L1 expression and T-cell subpopulations by immunohistochemistry. Positive PD-L1 expression (PD-L1+), defined as membranous staining in either tumor cells or tumor immune infiltrates, was seen in 32 (72%) gastric cancers. EBV+ or MSI cancers showed significantly higher rates of PD-L1+ compared with EBV−/MSS cancers (7/7, 100%; 14/16, 87%; 11/21, 52%; P=0.013). PD-L1+/EBV+ and PD-L1+/MSI cancers had significantly more CD8 T cells at tumor invasive front than PD-L1+/EBV−/MSS cancers (P<0.001). PD-L1+ was not associated with the depth of invasion or nodal metastasis (P=0.534, 0.288). Multivariate analysis showed PD-L1+ was not an independent predictor of disease-free survival while MSI was (P=0.548, 0.043). In summary, EBV+ or MSI gastric cancers are more likely to express PD-L1 and have increased CD8 T cells at tumor invasive front than EBV−/MSS cancers. Our results suggest EBV infection and MSI should be investigated for predicting response to PD-1 blockade.
Associations of stream geomorphic conditions and prevalence of alternative reproductive tactics among sockeye salmon populations

In many species, males may exhibit alternative life histories to circumvent the costs of intrasexual competition and female courtship. While the evolution and underlying genetic and physiological mechanisms behind alternative reproductive tactics are well studied, there has been less consideration of the ecological factors that regulate their prevalence. Here, we examine six decades of age composition records from thirty‐six populations of sockeye salmon (Oncorhynchus nerka) to quantify associations between spawning habitat characteristics and the prevalence of precocious sneakers known as ‘jacks’. Jack prevalence was independent of neutral genetic structure among stream populations, but varied among habitat types and as a function of continuous geomorphic characteristics. Jacks were more common in streams relative to beaches and rivers, and their prevalence was negatively associated with stream width, depth, elevation, slope and area, but positively related to bank cover. Behavioural observations showed that jacks made greater use of banks, wood and shallows than guard males, indicating that their reproductive success depends on the availability of such refuges. Our results emphasize the role of the physical habitat in shaping reproductive tactic frequencies among populations, likely through local adaptation in response to variable fitness expectations under different geomorphic conditions.
Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss.

BACKGROUND A successful outcome of pregnancy depends on proper placental formation. In the very beginning of this process, trophoblast invasion and fibrin deposition into the wall of the decidual veins play an important part. Two polymorphisms, coagulation factor XIII (FXIII) Val34Leu and plasminogen activator inhibitor 1 (PAI-1) 4G/5G, interfere with fibrin cross-linking and regulation of fibrinolysis and may therefore contribute to early pregnancy loss. METHODS We enrolled 49 unrelated Caucasian women with a history of two consecutive or three to six nonconsecutive early pregnancy losses and 48 unrelated parous healthy controls without a history of pregnancy loss and evaluated them for the following genetic variants: the factor V Leiden and prothrombin G20210A gene mutations, the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and the PAI-1 4G/5G and FXIII Val34Leu polymorphisms. RESULTS For the isolated occurrence of PAI-1 4G/5G or FXIII Val34Leu, we found no statistically significant difference between cases and controls. For homozygosity of either or compound carrier status of both mutations, the overall relative risk for early pregnancy loss was significantly increased (odds ratio = 2.4; 95% confidence interval, 1.1-5.5; P = 0.032). We observed no statistically relevant association of any of the other tested mutations with early pregnancy loss. CONCLUSION Homozygosity for PAI-1 4G or FXIII 34Leu polymorphisms as well as compound carrier status is associated with early pregnancy loss.
Effects of Methiothepin and Lysergic Acid Diethylamide on Serotonin Release In Vitro and Serotonin Synthesis In Vivo: Possible Relation to Serotonin Autoreceptor Function

Abstract: An in vitro system characterizing the presyn‐ aptic serotonin (5‐HT) autoreceptor which controls the release of 5‐HT from rat brain slices is described. Using this system, methiothepin (1–10 μM) demonstrated 5‐HT autoreceptor antagonist activity ‐by enhancing 5‐HT release, while several recognized postsynaptic 5‐HT receptor antagonists were inactive: mianserin, cinanserin, cyproheptadine, methysergide. The activity of methiothepin was highest in hypothalamic slices and lowest in striatal slices and was inhibited by the autoreceptor agonists lysergic acid diethylamide (LSD) and 5‐methoxy‐ tryptamine (5‐MT). The reversal of the methiothepin‐enhanced 5‐HT release from hypothalamic slices by LSD was not influenced by 0.3 μM tetrodotoxin. The peripheral administration of LSD to rats has been shown to reduce 5‐HT synthesis and release by a mechanism thought to involve, in part, an autoreceptor‐mediated reduction in impulse flow of 5‐HT neurons. In the present experiments, intraperitoneal injection of methiothepin antagonized the LSD‐induced reduction in hypothalamic 5‐HT synthesis (5‐hydroxytryptophan accumulation) while exerting no influence by itself. Conversely, compounds which were not active as 5‐HT autoreceptor antagonists in vitro (i.e., cyproheptadine, methysergide, cinanserin) did not influence the effect of LSD on 5‐HT synthesis. Further, the reduction in 5‐hydroxytryptophan (5‐HTP) accumulation by LSD showed regional differences in inhibition by methiothepin (hypothalamus > cortex > striatum) which paralleled the autoreceptor antagonist activity of methiothepin in vitro. These data suggest that similar autoreceptor mechanisms control 5‐HT release and synthesis in terminal 5‐HT projection areas and that the reduction in 5‐HT accumulation by LSD and the antagonism by methiothepin may represent a useful biochemical measure of 5‐HT autoreceptor activity in vivo.
Diagnosis and Treatment of Intestinal Malabsorption in Cystic Fibrosis

Intestinal malabsorption is severe and of early onset in virtually all people who have cystic fibrosis. The main cause is deficiency of pancreatic enzymes. Bicarbonate deficiency, abnormal bile salts, mucosal transport problems, motility differences, and anatomical structural changes are other contributory factors. Effective treatment should allow a normal to high‐fat diet to be taken, control symptoms, correct malabsorption, and achieve a normal nutritional state and growth. Appropriate pancreatic enzyme replacement therapy will achieve normal or near‐normal absorption in most people with cystic fibrosis. Early identification and treatment of intestinal malabsorption is critical to achieving optimal nutritional status. The occurrence of fibrosing colonopathy in a few patients on very high doses of those enzymes which have the copolymer Eudragit L30 D55 in their covering resulted in guidelines in the UK to avoid doses equivalent to more than 10,000 IU lipase per kg per day, and also to avoid preparations containing this copolymer in children and adolescents. For patients not responding to 10,000 IU lipase per kg per day review of adherence to treatment, change of enzyme preparation, variation in time of administration, and reduction in gastric acid may improve absorption. The importance of early investigation to exclude other gastrointestinal disorders as a cause of the patient's symptoms, rather than merely increasing the dose of enzymes, is stressed. With modern pancreatic enzymes in doses up to or only slightly in excess of 10,000 IU lipase per kg per day, adequate control of gastrointestinal symptoms and absorption can be achieved, and a normal nutritional state and growth rate maintained in most people with cystic fibrosis. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
Does the Cognitive Reflection Test actually capture heuristic versus analytic reasoning styles in older adults?

ABSTRACT Background/Study Context: This study evaluated adult age differences in the original three-item Cognitive Reflection Test (CRT; Frederick, 2005, The Journal of Economic Perspectives, 19, 25–42) and an expanded seven-item version of that test (Toplak et al., 2013, Thinking and Reasoning, 20, 147–168). The CRT is a numerical problem-solving test thought to capture a disposition towards either rapid, intuition-based problem solving (Type I reasoning) or a more thoughtful, analytical problem-solving approach (Type II reasoning). Test items are designed to induce heuristically guided errors that can be avoided if using an appropriate numerical representation of the test problems. Methods: We evaluated differences between young adults and old adults in CRT performance and correlates of CRT performance. Older adults (ages 60 to 80) were paid volunteers who participated in experiments assessing age differences in self-regulated learning. Young adults (ages 17 to 35) were students participating for pay as part of a project assessing measures of critical thinking skills or as a young comparison group in the self-regulated learning study. Results: There were age differences in the number of CRT correct responses in two independent samples. Results with the original three-item CRT found older adults to have a greater relative proportion of errors based on providing the intuitive lure. However, younger adults actually had a greater proportion of intuitive errors on the long version of the CRT, relative to older adults. Item analysis indicated a much lower internal consistency of CRT items for older adults. Conclusion: These outcomes do not offer full support for the argument that older adults are higher in the use of a “Type I” cognitive style. The evidence was also consistent with an alternative hypothesis that age differences were due to lower levels of numeracy in the older samples. Alternative process-oriented evaluations of how older adults solve CRT items will probably be needed to determine conditions under which older adults manifest an increase in the Type I dispositional tendency to opt for superficial, heuristically guided problem representations in numerical problem-solving tasks.
Use of Pioglitazone in Patients with Lichen Planopilaris

Background: Recent basic science research has revealed a decreased tissue expression of peroxisome proliferator-activated receptor (PPAR) γ in lichen planopilaris (LPP). Therefore, thiazolidinediones, being PPARγ agonists, could be used to treat LPP. Methods: We followed 24 patients with LPP who were treated with oral pioglitazone hydrochloride. Improvement in LPP was defined as a decrease in or disappearance of symptoms and perifollicular erythema in the context of halted spread of old patches. Results: Twenty of 24 patients were females. The average age was 52.5 years, and ages ranged from 22 to 70 years. Five of 24 patients have achieved remission; improvement was noted in half of the patients; there was no change in 3 patients; and 4 patients discontinued treatment due to side effects. Side effects were mild and included left calf pain, lightheadedness and nausea, dizziness, and hives. Conclusion: Use of thiazolidinediones might be a new promising venue of LPP treatment.
Management of Design as a Translation Process

This dissertation proposes a new perspective on management of design by regarding it as a translation process, using a framework based on ActorNetwork Theory. Within the field of management of design, design has been defined as a problem-solving activity, a tool for either improving the decisionmaking process or for fostering radical innovation by making sense of things. Designers have generally been considered individuals with a different sensibility, able to make a difference by producing interesting and intriguing products which can deliver value to the customers and create value for the firm. Actor-Network Theory is a methodology for the socio-technical analysis that treats the actors as enacted and relational, and explores the network creation through an analysis based on a flat ontology, in which there is symmetry between humanand non-human actors. There is no a priori size, power or complexity of the actors, as these elements are built through the relations and understood by following them. The study is based on an ethnographic investigation of three design objects: the Serie7, the Egg (designed respectively in 1955 and 1958) and the Ice (designed in 2002), manufactured by Fritz Hansen. Based on the analysis, a new interpretation of the design, the design process, the role of the managers and designers, the value creation process, and the role of technologies of managing is presented. Design is defined as an outcome of the construction process of things made by mobilising and enrolling actors through the translations of goals. The design process is the process of enrolling, mobilising, and translating goals, creating the design in a heterogeneous network of allies. It is a chaotic practice, muddled and contingent, with the inevitable risk of unintended consequences. This process is guided by the managers, who act as spokespersons, while the designers are macro-actors, representing all the actors involved in the creation process, in the multitude making or agreeing on the final decisions concerning the design and its development during the life cycle of the object. The individual qualities of insight, intuition, vision, and creativity are reinterpreted and assembled in the language of the design. These qualities are no longer the properties of an individual, but collective virtues in relation
Intraosseous access in the setting of pediatric critical care transport

Objective: To demonstrate safety and efficacy of intraosseous needle placement among health care provider groups in the setting of pediatric critical care transport. Design: Retrospective chart review. Setting: Pediatric critical care transports to a pediatric intensive care unit. Patients: Children undergoing pediatric critical care transport between January 1, 2000, and March 31, 2002, requiring intraosseous access before arrival to the pediatric intensive care unit. Interventions: Intraosseous access placed for emergent vascular access. Measurements and Main Results: During the study period, the transport team performed 1,792 transports and identified 47 patients requiring 58 intraosseous placements. These were placed by emergency medical technician-paramedics (18%), referring emergency medicine physicians (42%), and the transport team members (40%). The intraosseous needles were placed with a mean of 1.2 attempts per placement and a first attempt success rate of 78%. Main site of placement was the proximal anterior tibia (95%). Access was maintained for a mean of 5.2 hrs. The intraosseous needle was used for fluids, medications, and laboratory studies. Admitting diagnoses included respiratory distress (28%), cardiopulmonary arrest (26%), neurologic insults (17%), dehydration (15%), sepsis (11%), and other (3%). Ages ranged from 3 wks to 14 yrs (mean 2.2 yrs) and weights from 2.1 to 60 kg (mean 12.3 kg). Complications were noted in seven of 58 (12%), all limited to local edema or infiltration. Conclusions: Intraosseous placement is frequently needed in the care of critically ill pediatric patients before they reach the pediatric intensive care unit. We have demonstrated that intraosseous needles can be placed safely with similar rates of success when comparing different provider groups. Emergency medical technician-paramedics, emergency medicine physicians, and pediatric critical care transport teams should be familiar with intraosseous placement.
KENYAN CIVIC EDUCATION: A SOURCE OF EMPOWERMENT?

Guided primarily by critical constructivism as the theoretical framework, this dissertation examines the extent to which civic education in Kenya creates dialogic spaces where issues of social difference, peace and democracy are addressed. The participants of the study included four history and government teachers; four Form 1 classes; principals of the two high schools and one curriculum developer. History and government was selected because one of the course‟s objectives is to develop responsible and active citizens who would participate in fostering peace and democracy. In this study, peace is conceptualized as the absence of both direct and structural violence, and democracy is conceived, not merely as majority rule, but as exercising one‟s opinions where citizens‟ contributions influence decisions and have control over public policies that govern their lives. Using observations, interviews and document analysis, the study focuses on pedagogical practices, educators‟ and students‟ views about civic education in two public schools in Nairobi. The two sites were selected because the students came from diverse social and ethnic backgrounds and the schools offered co-education. Therefore, the schools‟ student demographics provided the kind of social differences that are the focus of this study. In the analysis, attention was paid to the official curriculum and the way teachers enacted the curriculum to foster peace and social justice. Findings indicate that although the official
The Major Murine Systemic Lupus Erythematosus Susceptibility Locus Sle1 Results in Abnormal Functions of Both B and T Cells1

Sle1 is a major susceptibility locus in the NZM2410 murine model of systemic lupus erythematosus. When isolated on a C57BL/6 background in the B6.Sle1 congenic strain, Sle1 results in the production of high levels of anti-chromatin IgG Abs, histone-specific T cells, and increased B and T cell activation. We have shown by mixed bone marrow chimeras with allotypic markers that Sle1 is expressed in B cells. Using the same technique, we now show that it is also expressed in T cells. To assess whether Sle1 results in intrinsic defects in B or T cells, we have bred the μMT and Tcrα−/− mutations onto B6.Sle1 resulting in the absence of circulating B cells and αβ T cells in B6.Sle1. μMT and B6.Sle1. Tcrα−/−, respectively. The immune phenotypes in these two strains were compared with that of B6.Sle1 and B6. μMT or B6. Tcrα−/−. Sle1-expressing B cells broke tolerance to chromatin in the absence of T cells, as shown by high levels of anti-ssDNA IgM Abs in B6.Sle1. Tcrα−/− mice, and had an increased expression of activation markers. Conversely, increased expression of activation markers and increased cytokine production were observed in Sle1-expressing T cells in the absence of B cells in B6.Sle1. μMT mice. However, the production of IgG antinuclear Abs required the presence of both T and B cells. These experiments showed that Sle1 expression results in both B and T cells intrinsic defects and demonstrate that the documented involvement of each cell compartment in the production of anti-chromatin Abs corresponds to genetic defects rather than bystander effects.
Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells

Naidu, Padma S. , Victoria Velarde, Christiana S. Kappler, Roger C. Young, Ronald K. Mayfield, and Ayad A. Jaffa. Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1061–H1068, 1999. —The vasoactive peptide bradykinin (BK) has been implicated in the pathophysiology of a number of vascular wall abnormalities, but the cellular mechanisms by which BK generates second messengers that alter vascular function are as yet undefined. Exposure of vascular smooth muscle cells (VSMC) to BK (1027 M) produced a rapid and transient rise in intracellular calcium, which preceded an increase in tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). MAPK activation by BK was observed as early as 1 min, peaked at 5 min, and returned to baseline by 20 min. Treatment of cells with the intracellular calcium chelator EGTA-acetoxymethyl ester inhibited BK-stimulated MAPK activation, suggesting that intracellular calcium mobilization contributes to the activation of MAPK. The calmodulin inhibitor W-7 also markedly inhibited BK-induced MAPK phosphorylation in the cytoplasm as well as in the nucleus. Moreover, the BK-induced increase in c-fos mRNA levels was significantly inhibited by the calmodulin inhibitor, indicating that calmodulin is required for BK signaling leading to c-fos induction. These results implicate the calcium-calmodulin pathway in the mechanisms for regulating MAPK activity and the resultant c-fos expression induced by BK in VSMC.