Miracle-dz/UniFAR-FTUs huggingface dataset:
Beneficial Effects of Combination Therapy with Olmesartan and Azelnidipine in Murine Polycystic Kidneys

Background: Some reports have discussed the synergic effects of angiotensin II receptor blockers and calcium channel blockers on vascular injury or microalbuminuria. The present study examined the effects of combination treatment with olmesartan and azelnidipine on polycystic kidney disease in a mouse model (DBA/2-FG pcy mouse) and its mechanisms. Methods: The mice were divided into the following groups: combination treatment (n = 21), olmesartan treatment alone (n = 23), azelnidipine treatment alone (n = 29) or untreated (n = 26). Mean blood pressure and kidney weight were measured at 4 and 8 weeks after the treatment. Renal expression of angiotensin II, gp91, nitrotyrosine and endothelial NO synthase (eNOS) were examined by immunostaining. In addition, extracellular signal-regulated kinase activation was evaluated by Western blotting. Results: Olmesartan decreased the numbers of angiotensin II and gp91-positive cells, mainly macrophages, and cyst size at 4 weeks. However, only combination treatment suppressed cell infiltration, extracellular signal-regulated kinase activation and interstitial fibrosis with a significant change in the kidney weight/body weight ratio. The azelnidipine and combination treatment increased the numbers of interstitial eNOS-positive cells. Conclusion: The combination treatment protects against cyst enlargement in polycystic kidney disease by suppressing interstitial inflammation, fibrosis and oxidative stress by upregulating eNOS expression during disease course.
Cancer incidence among patients with ankylosing spondylitis in Sweden 1965–95: a population based cohort study

Background: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease which may lead to extra-articular complications. The disease associated cancer risk has been poorly explored. Recently, tumour necrosis factor α blockers have been found to be efficacious in AS, but their long term risk is unknown. Objective: To analyse a large national cohort of patients with AS to determine the overall cancer risk in AS as a background to the future introduction of new treatments. Methods: All patients with AS admitted to Swedish hospitals 1965–95 were linked through individual national registration numbers to the Swedish Cancer Register and National Death Register. Standardised incidence ratio (SIR) of cancer risk was calculated in 6621 people, monitored during 67 885 person-years. Results: No overall increase in cancer risk was found (SIR 1.05, 95% CI 0.94 to 1.17). Rectal cancer was less common (SIR 0.41, 95% CI 0.15 to 0.89) while unspecified kidney cancer was more common (SIR 5.90, 95% CI 1.61 to 15.1). Risks for colon, renal parenchymal, and renal pelvic cancer were not significantly increased. Laryngeal cancer was more common than expected, while lung cancer was not. Risks of haematopoietic malignancies were not increased. Conclusions: No overall increase in cancer risk was found. The decreased risk of rectal cancer might be due to local application of NSAIDs, and the increased risk of unspecified kidney cancer to frequent radiological pelvic examinations. If information on disease characteristics, including HLA-B27, was available for individual patients with cancer, risk-benefit analysis of long term effects of new immunomodulation treatment might be improved.
Characterization of a Two-Component High-Affinity Nitrate Uptake System in Arabidopsis. Physiology and Protein-Protein Interaction1[W]

The identification of a family of NAR2-type genes in higher plants showed that there was a homolog in Arabidopsis (Arabidopsis thaliana), AtNAR2.1. These genes encode part of a two-component nitrate high-affinity transport system (HATS). As the Arabidopsis NRT2 gene family of nitrate transporters has been characterized, we tested the idea that AtNAR2.1 and AtNRT2.1 are partners in a two-component HATS. Results using the yeast split-ubiquitin system and Xenopus oocyte expression showed that the two proteins interacted to give a functional HATS. The growth and nitrogen (N) physiology of two Arabidopsis gene knockout mutants, atnrt2.1-1 and atnar2.1-1, one for each partner protein, were compared. Both types of plants had lost HATS activity at 0.2 mm nitrate, but the effect was more severe in atnar2.1-1 plants. The relationship between plant N status and nitrate transporter expression revealed a pattern that was characteristic of N deficiency that was again stronger in atnar2.1-1. Plants resulting from a cross between both mutants (atnrt2.1-1 × atnar2.1-1) showed a phenotype like that of the atnar2.1-1 mutant when grown in 0.5 mm nitrate. Lateral root assays also revealed growth differences between the two mutants, confirming that atnar2.1-1 had a stronger phenotype. To show that the impaired HATS did not result from the decreased expression of AtNRT2.1, we tested if constitutive root expression of a tobacco (Nicotiana plumbaginifolia) gene, NpNRT2.1, previously been shown to complement atnrt2.1-1, can restore HATS to the atnar2.1-1 mutant. These plants did not recover wild-type nitrate HATS. Taken together, these results show that AtNAR2.1 is essential for HATS of nitrate in Arabidopsis.
HPV16 genotype, p16/Ki‐67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low‐grade squamous intraepithelial lesions

To evaluate the association of human papillomavirus (HPV) 16 and non‐16 genotype, p16/Ki‐67 dual staining and koilocytosis and their role in the prediction of the clinical outcome of low‐grade squamous intraepithelial lesion (LSIL) cytology.
When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment

Abstract Measurement of stress hormone metabolites in fecal samples has become a common method to assess physiological stress in wildlife populations. Glucocorticoid metabolite (GCM) measurements can be collected noninvasively, and studies relating this stress metric to anthropogenic disturbance are increasing. However, environmental characteristics (e.g., temperature) can alter measured GCM concentration when fecal samples cannot be collected immediately after defecation. This effect can confound efforts to separate environmental factors causing predeposition physiological stress in an individual from those acting on a fecal sample postdeposition. We used fecal samples from American pikas (Ochotona princeps) to examine the influence of environmental conditions on GCM concentration by (1) comparing GCM concentration measured in freshly collected control samples to those placed in natural habitats for timed exposure, and (2) relating GCM concentration in samples collected noninvasively throughout the western United States to local environmental characteristics measured before and after deposition. Our timed‐exposure trials clarified the spatial scale at which exposure to environmental factors postdeposition influences GCM concentration in pika feces. Also, fecal samples collected from occupied pika habitats throughout the species' range revealed significant relationships between GCM and metrics of climate during the postdeposition period (maximum temperature, minimum temperature, and precipitation during the month of sample collection). Conversely, we found no such relationships between GCM and metrics of climate during the predeposition period (prior to the month of sample collection). Together, these results indicate that noninvasive measurement of physiological stress in pikas across the western US may be confounded by climatic conditions in the postdeposition environment when samples cannot be collected immediately after defecation. Our results reiterate the importance of considering postdeposition environmental influences on this stress metric, especially in multiregional comparisons. However, measurements of fecal GCM concentration should prove useful for population monitoring within an eco‐region or when postdeposition exposure can be minimized.
Clinical and Sonographic Patterns of Tandem Internal Carotid Artery/Middle Cerebral Artery Occlusion in Tissue Plasminogen Activator–Treated Patients

Background and Purpose— The National Institutes of Health Stroke Scale (NIHSS) is predictive of thrombus presence but has limited ability to identify occlusion location in the anterior circulation. We describe clinical and sonographic patterns that are associated with tandem internal carotid artery (ICA) and middle cerebral artery (MCA) occlusions. Methods— Consecutive acute ischemic stroke patients receiving intravenous tissue plasminogen activator (TPA) were studied. Pretreatment NIHSS scores and bedside transcranial Doppler (TCD) were obtained for all patients. Results— A total of 95 patients treated with intravenous TPA at 132±60 minutes from stroke onset were studied. On TCD, 48 had isolated MCA occlusion (mean NIHSS 16.8±5.8, median 17, range 5 to 28); and 16 had tandem ICA/MCA occlusion (mean NIHSS 18.8±5.8, median 22, range 8 to 29;P =NS). In the MCA occlusion and tandem ICA/MCA occlusion groups, 19% and 11%, respectively, had NIHSS scores <12 points. Compared with the NIHSS scores in patients with hemiplegia, forced gaze deviation, and complete neglect, the lower NIHSS scores were attributable to partial arm and/or leg paresis, gaze preference, and partial neglect. In those patients, TCD showed ≥2 major collateral channels and low-resistance flow at the M1 origin, suggesting perfusion of perforating arteries. Although TCD cannot differentiate between high-grade ICA stenosis or occlusion, collateral flow patterns and stenotic signals at the terminal ICA differentiated tandem lesions from isolated MCA occlusion (P <0.01). Conclusions— Tandem ICA/MCA occlusion was found on TCD in 17% of TPA-treated patients. NIHSS scores were similar in patients with isolated MCA and tandem occlusions. Lower NIHSS scores were seen in patients with a higher number of major collateral flow channels and higher Thrombolysis in Brain Ischemia (TIBI) flow grades at the MCA origin.
RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components

Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S‐i, Ito K, Kameyama K, Kobayashi M & Katoh R (2010) Histopathology 57, 444–450 RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components
Modeling sensitization to stimulants in humans: an [11C]raclopride/positron emission tomography study in healthy men.

CONTEXT In animals, repeated exposure to stimulant drugs leads to an enhanced drug-induced psychomotor response and increased dopamine release. This phenomenon, known as sensitization, may confer vulnerability to drug addiction or drug-induced psychosis in humans. A similar phenomenon, referred to as endogenous sensitization, is also believed to play a role in the emergence of positive symptoms in patients with schizophrenia. OBJECTIVE To determine whether behavioral and neurochemical sensitization occur in healthy individuals after limited exposure to amphetamine in the laboratory. DESIGN Open-label, 1-year follow-up of repeated amphetamine administration in healthy volunteers. SETTING Department of Psychiatry, McGill University, and McConnell Brain Imaging Center, Montreal Neurological Institute. PARTICIPANTS Ten healthy men (mean +/- SD age, 25.8 +/- 1.8 years). INTERVENTION Three single doses of amphetamine (dextroamphetamine sulfate, 0.3 mg/kg by mouth) were administered on days 1, 3, and 5. MAIN OUTCOME MEASURES Using positron emission tomography and [11C]raclopride, we measured dopamine release in response to amphetamine on the first exposure (day 1) and 14 days and 1 year after the third exposure. RESULTS The initial dose of amphetamine caused dopamine release in the ventral striatum (a reduction in [11C]raclopride binding). Consistent with a sensitization-like phenomenon, 14 and 365 days after the third dose of amphetamine there was a greater psychomotor response and increased dopamine release (a greater reduction in [11C]raclopride binding), relative to the initial dose, in the ventral striatum, progressively extending to the dorsal caudate and putamen. A high novelty-seeking personality trait and self-rating assessments indicating impulsivity predicted proneness to sensitization. CONCLUSIONS Sensitization to stimulants can be achieved in healthy men in the laboratory. This phenomenon is associated with increased dopamine release and persists for at least 1 year.
Daxx functions as a scaffold of a protein assembly constituted by GLUT4, JNK1 and KIF5B

We have previously reported the physical interaction between Daxx, the adaptor protein that mediates activation of the Jun amino‐terminal kinase (JNK), and GLUT4, the insulin‐dependent glucose transporter, interaction that involves their C‐domains. Co‐immunoprecipitation and two‐hybrid‐based protein–protein interaction studies show now that Daxx and GLUT4 interact with JNK1 through D‐sites in their NH2‐(aa 1‐501) and large endofacial loop, respectively. Serum deprivation strongly enhances the association of JNK1 with Daxx and dissociates the kinase from GLUT4. SP600125, a potent JNK1 inhibitor, reduces the JNK1 activity associated with GLUT4 and the phosphorylation of two minor GLUT4 species in serum‐starved 3T3‐L1 adipocytes. In addition, Daxx interacts with kinesin KIF5B through the 6xTPR domain of the kinesin light chain, a domain engaged in the grab hold of protein cargo by kinesin motors that codistribute with JNK. Depletion of Daxx in 3T3‐L1 adipocytes provokes the partial translocation of the GLUT4 retained in the GLUT4 storage compartment to endosomes. J. Cell. Physiol. 218: 416–426, 2009. © 2008 Wiley‐Liss, Inc.
Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group.

PURPOSE To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma. PATIENTS AND METHODS Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival. RESULTS In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96). CONCLUSION The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.
The job strain model is enough for managers: No augmentation needed

This paper reports on the results of a study aimed at identifying the relative influence of generic and job‐specific stressors experienced by a cohort of Australian managers. The results of a regression analysis revealed that both the generic components of the job strain model (JSM) and job‐specific stressors were predictive of the strain experienced by participants. However, when looking at the total amount of variance that is explained by the predictor variables, the combined influence of job demand, job control and social support contributed 98 per cent of the explained variance in job satisfaction and 90 per cent of the variance in psychological health. The large amount of variance explained by the JSM suggests that this model provides an accurate account of the work characteristics that contribute to the strain experienced by managers and no augmentation is needed.
Campus, city, networks and nation : student-migrant activism as socio-spatial experience in Melbourne, Australia

'Education-migration nexus' policies in Australia between 1998 and 2010 linked international education with different forms of temporary and permanent migration. This resulted in a blurring of boundaries around student, worker, consumer, migrant and ethnic identities. While the exploitation, marginalization and vulnerability of international students in Australia has gained a great deal of media and scholarly attention, less consideration has been given to the varied forms of subsequent protest undertaken by student migrants in Australian cities. This article analyses three case studies of protests involving student migrants in Melbourne: a protest against unfair assessment; a fight for a campus prayer room; and labour protests within the retail service and taxi industries. It draws on theoretical work on new social movements and social transformation in urban spaces to find ways to conceptualize this activism in relation to the scales of campus, city and nation. In doing so, it argues primarily that these sites of protest are socio-spatial experiences that encompass shifting and socially produced spatial scales, as well as complex networks of association across different communities, which in turn reflect different student-migrant identities.
The Laboratory for Ubiquitous Computing and Interaction Department of Informatics

Conceptual metaphors are pivotal to human cognition, but most previous computational linguistics treatments of metaphor focus on discerning a metaphor's literal meaning. Instead, this article presents computational metaphor identification (CMI), a technique for identifying potential conceptual metaphors in written text. This technique draws on and extends previous related work in cognitive linguistics and computational linguistics. CMI hinges on mapping selectional preferences from a source corpus to a target corpus in order to identify metaphorical mappings. Example results are presented and then evaluated via two methods: comparison with expert linguistic analysis, and assessment by non-expert human subjects. The results show that CMI is an effective means for identifying conceptual metaphors; computationally identified metaphors are shown to be conceptually similar to those identified in previous expert linguistic analysis, and confidence scores assigned by the system to identified metaphors correlate significantly with non-expert subjects' assessments. This work represents a novel direction, both for computational linguistics research on metaphor, and for artificial intelligence research more broadly.
Effect of ethanol on plasma corticosterone levels.

Following interperitoneal administration fo ethanom to rats, the effect of this alcohol on pituitary-adrenal function has been studied by measuring changes in plasma corticosterone concentration. Doses of ethanol ranging from 0.5 to 4.0 g/kg increased plasma steroid levels in a roughly parallel relationship to the size of the dose. After 2 g/kg of ethanol, the duration of the adrenocortical response was approximately 6 hr, which corresponded to the period of detectable blood alcohol concentration. When ethanol was given to hypophysectomized animals. no elevation of corticosterone concentration was observed. Pretreatment of intact animals with pentobarbital and morphine produced a complete blockade of the steroid response to ethanol. Pentobarbital alone reduced the response to about 50% of the usual ethanol effect. Since the intraperitoneal injection of a local anesthetic prior to ethanol administration failed to alter the action of ethanol, it is assumed that peritoneal irritation could not have been a part of the involved mechanism of action. Repeated daily injections of ethanol for 1 wk did not result in pituitary-adrenal adaptation and decreased steroid response to a subsequent injection as has been demonstrated for certain other centrally acting depressant drugs. These observations suggest that ethanol induces hypersecretion of corticotropin by acting through an unexplained central nervous system mechanism.
Melan-A–specific Cytotoxic T Cells Are Associated with Tumor Regression and Autoimmunity Following Treatment with Anti-CTLA-4

Purpose: Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known. Experimental Design: We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated. Results: Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A–specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A–specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A–expressing tumor cells. Conclusions: Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.
A Re-ranking Model for Dependency Parser with Recursive Convolutional Neural Network

In this work, we address the problem to model all the nodes (words or phrases) in a dependency tree with the dense representations. We propose a recursive convolutional neural network (RCNN) architecture to capture syntactic and compositional-semantic representations of phrases and words in a dependency tree. Different with the original recursive neural network, we introduce the convolution and pooling layers, which can model a variety of compositions by the feature maps and choose the most informative compositions by the pooling layers. Based on RCNN, we use a discriminative model to re-rank a $k$-best list of candidate dependency parsing trees. The experiments show that RCNN is very effective to improve the state-of-the-art dependency parsing on both English and Chinese datasets.