gebhart/patrepeval huggingface dataset:
Nurr1 Is Required for Maintenance of Maturing and Adult Midbrain Dopamine Neurons (2009)

Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in the Nurr1 gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of the Nurr1 gene was generated, and Nurr1 was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors. Nurr1 deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area when Nurr1 was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease.
The effects of daily exercise on susceptibility to sudden cardiac death. (1984)

The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)
VASCULAR SMOOTH MUSCLE CELLS AND NEOINTIMAL HYPERPLASIA IN CHRONIC TRANSPLANT REJECTION (1996)

Intimal hyperplasia is the characteristic pathological hallmark in the arterial tree of chronically rejecting solid organ grafts. Mechanisms underlying the development of this lesion are poorly understood. One strongly held hypothesis is that vascular smooth muscle cells (vs.mcs) migrate from the medial layer of arteries contained within the graft into the intima forming the "neointima" characteristic of intimal hyperplasia. This study investigated this theory in a rat aortic allograft model of intimal hyperplasia. It also examined the possibility, using a combination of immunocytochemistry and electron microscopy, that aortic vs.mcs may undergo a phenotypic change during this process. Intimal area in syngeneic grafts was 3509 +/- 4325 pixels (n = 5) compared with 240,896 +/- 87,042 in allogenic grafts (n = 9, P < 0.001) 12 weeks after transplantation. At that time medial nuclear density was markedly reduced in the same allografts compared with corresponding syngeneic grafts (0.83 +/- 0.14 versus 2.64 +/- 0.60, P < 0.001, respectively). The most striking finding was that there was strongly positive staining for alpha-actin cells in the neointima in association with an almost acellular medial layer. Immunocytochemical staining also demonstrated the presence of beta-actin cells in the neointima of allografts while electron microscopy showed these cells to be secretory in phenotype. These results support the hypothesis that vs.mcs form an important component of the lesion of intimal hyperplasia and also propose that a phenotypic change may occur in these cells once they are present in the neointima.
Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. (2002)

Overexpression of the epidermal growth factor receptor (EGFR) has been shown previously to correlate with enhanced malignant potential of many human tumor types, including glioblastoma multiforme (GBM). Anti-EGFR targeting has been demonstrated to enhance apoptosis and reduce both cellular invasion and angiogenic potential. It remains unclear whether absolute EGFR expression levels are sufficient to predict which tumors will respond best to anti-EGFR therapy. We have identified two primary GBM cell lines with equivalent EGFR expression levels with very different sensitivities to the EGFR receptor tyrosine kinase inhibitor, AG1478. This was apparent despite similar reductions in EGFR signaling in both cell lines, as measured by phospho-EGFR levels. AG1478 enhanced both spontaneous and radiation-induced apoptosis and reduced invasive potential in the GBM(S), but not in the GBM(R), cell line. The resistant GBM(R) cell line demonstrated an up-regulation of insulin-like growth factor receptor I (IGFR-I) levels on AG1478 administration. This resulted in sustained signaling through the phosphoinositide 3-kinase pathway, resulting in potent antiapoptotic and proinvasion effects. Cotargeting IGFR-I with EGFR greatly enhanced both spontaneous and radiation-induced apoptosis of the GBM(R) cells and reduced their invasive potential. Akt1 and p70(s6k) appeared to be important downstream targets of IGFR-I-mediated resistance to anti-EGFR targeting. These findings suggest that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy.
Human mulipotential mesenchymal/stromal stem cells are derived from a discrete subpopulation of STRO-1bright/CD34 /CD45 /glycophorin-A-bone marrow cells (2007)

Magnetic and flow cytometry-based methods were used to characterize clonogenic stromal cells in human bone marrow. STRO-1(bright) stromal cells were found to lack expression of CD34, CD45 and glycophorin-A markers associated with hematopoietic progenitor cells. These studies support the view that these are two distinct stem cell compartments in adult bone marrow.
Synthesis of New C2- Symmetric Fluoren-9-ylidene Malonate Derived Bis(oxazoline) Ligands and Their Application in Friedel-Crafts Reactions (2010)

A series of new C(2)-symmetric fluoren-9-ylidene malonate-derived bis(oxazoline) ligands were synthesized from fluoren-9-ylidene malonate and enantiomerically pure amino alcohols via a convenient route. Their asymmetric catalytic properties in the Friedel-Crafts reactions of indoles with arylidene malonates were evaluated, and the Cu(OTf)2 complex of a fluoren-9-ylidene malonate-derived bis(oxazoline) bearing a phenyl group showed moderate to good enantioselectivity (up to 88% ee).
What Did Sudan Vote For (2010)

Sudan held national elections in April 2010 for the first time in many years. The elections were part of the peace process which began in 2005. This paper discusses the context of the elections and the multiple problems which affected them, and at how the events of the election will affect the final stages of the peace process.&#13;\n&#13;\nThe national elections held in Sudan in April 2010 involved multiple levels of government: candidates stood for the position of national president; for the presidency of the autonomous Government of Southern Sudan; for the position of governor in each of Sudan’s 25 states; for the National Assembly; for the assembly for the autonomous Government of Southern Sudan; and for legislatures in each of the states. This was, apparently, a feast of democracy, but the elections proved to be profoundly problematic. Media reports on the elections spoke of ‘chaos’ in the first day or two, as the complex demands of these multiple ballots stretched resources and organisational capacity to the limit. Once the ballots had been cast, the process of counting came close to complete collapse. When results were finally, belatedly, declared, they showed an overwhelming victory for the two parties which rule northern and southern Sudan respectively. Other parties rejected the results entirely and observers announced that the elections did not meet international standards for freedom and fairness. The people of Sudan were supposed to be voting for a national democratic transition; instead the election entrenched the division of the country between two authoritarian regimes, and it is now widely expected that the referendum due to be held in January 2011 will –if it goes ahead– result in a vote for southern secession.
The gut microbiota and its relationship to diet and obesity (2012)

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.
Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins (2000)

Spinal muscular atrophy (SMA) is a neurodegenerative disease of motor neurons caused by reduced levels of functional survival of motor neurons (SMN) protein. Cytoplasmic SMN directly interacts with spliceosomal Sm proteins and facilitates their assembly onto U snRNAs. Nuclear SMN, in contrast, mediates recycling of pre-mRNA splicing factors. In this study, we have addressed the function of SMN in the nucleus. We show that a monoclonal antibody directed against SMN inhibits pre-mRNA splicing. Interestingly, the mode of inhibition suggests a novel role for SMN in splicing that occurs prior to, or in addition to, its role in recycling. Using biochemical fractionation and anti-SMN immunoaffinity chromatography, we identified two distinct nuclear SMN complexes termed NSC1 and NSC2. The biochemical properties and protein composition of NSC1 were determined in detail. NSC1 migrates in sucrose gradients as a U snRNA-free 20S complex containing at least 10 proteins. In addition to SMN, these include the SMN-interacting protein 1 (SIP-1), the putative helicase dp103/Gemin3, the novel dp103/Gemin3-interacting protein GIP1/Gemin4 and three additional proteins with apparent masses of 43, 33 and 18 kDa, respectively. Most surprisingly, NSC1 also contains a specific subset of spliceosomal Sm proteins. This shows that the SMN-Sm protein interaction is not restricted to the cytoplasm. Our data imply that nuclear SMN affects splicing by modulating the Sm protein composition of U snRNPs.
Characteristics of an Induced Variant of Bacterionema matruchotii (1973)

Bacterionema matruchotii, a calcifiable filamentous organism, was treatetl ultrasonically. The disrupted cells produced typical colonies that developed macroscopic globular structures. A nonfilamentous, pleomorphic variant was derived from the globules. The variant retained the calcification potential of the filament, as well as fermentation and ultrastructural similarities.
Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours (1993)

In order to evaluate the significance of adhesion molecules expressed on melanocytic tumours for progression and prognosis in vivo, we studied integrin expression (VLA-1 to VLA-6, CD18, CD51, CD61) on 10 naevi, 40 primary malignant melanomas, and 11 metastases by immunohistology using the APAAP technique. Evaluation was done by grouping the percentage of positive tumour cells in six categories. Statistical analysis (Wilcoxon rank test, Scheffe test) revealed significant differences in the expression of VLA-1 (P < 0.0001), VLA-2 (P = 0.0001), VLA-5 (P = 0.0093), VLA-6 (P = 0.0232), and CD61 (P = 0.0002) between naevi and primary melanomas. Comparing primary melanomas with metastases, a statistically significant decrease in the expression of VLA-1, VLA-2, and VLA-6 was detectable, as well as a significant increase in VLA-4 and VLA-5. There was no correlation between integrin expression and tumour type (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma), regression and ulceration. Changes of VLA-1, VLA-4, and VLA-6 expression correlated with the tumour thickness of the primary melanoma, but only VLA-4 and VLA-6 expression on primary melanomas correlated significantly with the development of metastases (P = 0.024 and P = 0.001). These changes of integrin expression during tumour progression particularly, the data showing an increase of VLA-4, and a decrease of VLA-6 expression support the concept that integrins are a new additional set of prognostic markers which indicate predisposition to the development of metastases.
The Role of Thymic Stromal Lymphopoietin in CD8+ T Cell Homeostasis (2008)

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by stromal cells, epithelial cells, and basophils that acts on dendritic cells, mast cells, and CD4(+) T cells. The receptor for TSLP contains a TSLP-specific receptor chain (TSLPR) and the IL-7R alpha-chain. Although IL-7 critically controls the expansion and survival of naive and memory CD8(+) T cells, an action for TSLP on CD8(+) T cells has not been reported. We now demonstrate that CD8(+) T cells express TSLPR and that TSLP activates both STAT5 and Akt and induces Bcl-2 in these cells. Correspondingly, TSLP increases CD8(+) T cell survival in vitro as well as in wild-type and T-depleted mice in vivo, without altering the homeostatic proliferation of these cells. Moreover, TSLP can maintain CD8(+) T cells even in the absence of IL-7. Thus, our data reveal that TSLP contributes to CD8(+) T cell homeostasis in both normal and lymphopenic conditions.
True (2000)

We previously reported that exposure of DiFi human colon cancer cells to the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 resulted in apoptosis, but the mechanisms remain to be elucidated. In the present study, we investigated the effects of a panel of four anti-EGF receptor mAbs, each of which binds to different epitopes of the EGF receptor in DiFi cells, on the induction of apoptosis. We found that each of these mAbs induced apoptosis in DiFi cells. Exposure of DiFi cells to mAb 225 activated the initiation caspase-8, which was detectable between 8 and 16 h after exposure of the cells to the antibody. There was also an activation of the initiation caspase-9, which lagged a few hours behind the activation of caspase-8. Exposure of DiFi cells to mAb 225 also activated the execution caspase-3, which was accompanied temporally by evidence of cleavage of a well-characterized caspase-3 substrate, poly(ADP)ribosepolymerase (PARP). Pre-exposure of the cells to the caspase-3-specific inhibitor DEVD-CHO partially reduced the mAb 225-induced PARP cleavage and apoptosis, whereas pre-exposure of the cells to the caspase pan-inhibitor z-VAD-fmk completely inhibited mAb 225-induced apoptosis. Caspases-3, -8 and -9 were not activated in the cell lines in which mAb 225 only induced G1 phase arrest of the cell cycle. In contrast to the apoptosis of DiFi cells induced by ultraviolet irradiation, which strongly activated the c-jun N-terminal kinase-1 (JNK1) and the caspase cascade, mAb 225-induced apoptosis and activation of the caspase cascade in DiFi cells were not associated with activation of JNK1.
Long‐Lifetime Polymer Light‐Emitting Electrochemical Cells (2007)

Polymer light-emitting electrochemical cells with long operating lifetimes (see figure) are reported. The ions inside the luminescent semiconducting polymer are spatially redistributed by applying a voltage at a temperature above the melting point of the ionic liquid. These ionic-liquid-based light-emitting electrochemical cells also exhibit excellent current-rectification diode properties, a single-phase active layer, and short response times.
Monoclonal antibodies IPO-3 and IPO-10 against human B cell differentiation antigens. (1989)

Monoclonal antibodies (mAbs) IPO-3 and IPO-10 were generated following immunization of a BALB/c mice with human cell lines RPMI-1788 and Daudi respectively. The reactivity of these mAbs was studied by indirect immunofluorescence technique with 10 human cell lines, blood cells of healthy persons and patients with the malignant lymphoproliferative diseases. Studies of normal and neoplastic B cells suggest that mAbs IPO-3 and IPO-10 which recognize antigens are B lineage restricted. The presence of an antigen defined by the mAb IPO-10 appears to include most but not all the stages of B cell differentiation, whereas IPO-3 detected antigen is not represented on resting B cells and has a very limited expression on activated B lymphocytes. The results obtained with mAbs IPO-3 and IPO-10 are discussed in relation to other known B cell surface markers.
A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition (2008)

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110alpha inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110beta-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G(1) phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.
Long-Term Results of the Gamma-Irradiation-Preserved Homograft Monocusp for Transannular Reconstruction of the Right-Ventricular Outflow Tract in Tetralogy of Fallot (1994)

The long-term results of a consecutive series of transannular gamma-irradiated homograft monocusp patches in tetralogy of Fallot were studied. Seven survivors out of 8 patients are doing clinically well after a mean of 22.4 years of follow-up, 5 of them being in New York Heart Association class I and 2 in class II. In one patient the completely calcified gamma-irradiated homograft monocusp patch was replaced 15 years after intracardiac repair. Echocardiographic investigation at the end of follow-up of the remaining 6 patients with a gamma-irradiated homograft monocusp patch in situ showed mild pulmonary regurgitation in 1, moderate regurgitation in 3, and severe regurgitation in 2. Residual pulmonary stenosis was present in 4 patients (gradients ranging from 10 to 40 mmHg). Right-ventricular dilatation was present in all patients. In the long-term the gamma-irradiated transannular homograft monocusp patch behaves like a simple transannular patch.
Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. (1987)

Thyrotropin (TSH) concentrations were measured in 1580 hospitalized patients and 109 normal persons. Using the mean +/- 3 SD limits of the log values for the controls (0.35-6.7 milli-int. units/L), the proportion of abnormal TSH results in the hospitalized patients was 17.2%. TSH was undetectable (less than 0.1 milli-int. unit/L) in 3.1% of patients, suggesting hyperthyroidism, and high (greater than 20 milli-int. units/L) in 1.6%, suggesting hypothyroidism. On follow-up of 329 patients, 62% with abnormal TSH (less than 0.35 or greater than 6.7 milli-int. units/L) and 38% with normal TSH concentrations, only 24% of those with undetectable TSH had thyroid disease: 36% of them were being treated with glucocorticoids and 40% had nonthyroidal illness (NTI). Although half the patients with TSH greater than 20 milli-int. units/L had thyroid disease, 45% of patients had high TSH values associated with NTI. TSH concentrations usually returned towards normal when patients' therapy with glucocorticoids was discontinued or they recovered from NTI. TSH test sensitivity appeared good when the mean +/- 3 SD limits of the reference population were used, i.e., no cases of hyper- or hypothyroidism, as identified by free thyroxin index (FT4I), were missed. However, TSH test specificity was inferior to that of the FT4I test (90.7% vs 92.3%), although specificity could be improved to 97.0% if the wider TSH reference limits of 0.1 to 20 milli-int. units/L were used--limits considered pathological if applied to outpatients. Evidently, different reference intervals for TSH are needed for hospitalized and nonhospitalized patients. We conclude that a "sensitive TSH assay" is not a cost-effective thyroid screening test for hospitalized patients as compared with the FT4I.
Total Synthesis of (−)‐ and (+)‐Decarbamoyloxysaxitoxin and (+)‐Saxitoxin (2008)

Playing the sax: The enantioselective total syntheses of (-)- and (+)-decarbamoyloxysaxitoxin (doSTX) and (+)-saxitoxin (STX) are reported. A new methodology was developed for the synthesis of STXs, featuring discriminative reduction of the nitro group and N-O bond in nitroisoxazolidine. Enantioselective total syntheses of (-)- and (+)-decarbamoyloxysaxitoxin (doSTX) and (+)-saxitoxin (STX) were achieved. The characteristic spiro-fused cyclic guanidine structure of STX was constructed by oxidation at the C4 position with IBX via an alpha-iminium carbonyl intermediate and acid-promoted cyclization of guanidine at the C5 position. A second-generation methodology was developed for the synthesis of STX, featuring discriminative reduction of the nitro group and N-O bond in nitroisoxazolidine. This approach provides efficient access to the key diamine intermediate for STXs.