Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor stroma is the predominant uPA-, uPAR-, PAI-1-expressing tissue in human breast cancer: prognostic impact.

UNLABELLED Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor PAI-1, play a key role in tumor invasion and metastasis. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. Their antigens are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA- and PAI-1 in their primary tumor tissue have significantly better survival than patients with high levels of either factor. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is most relevant to patient outcome. This missing knowledge leads to an uncertainty concerning the management of breast cancer tissue specimens. It is unclear how much tumor stroma is allowed in one tumor tissue specimen for an adequate assessment of the patients' outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas (n=60) were separated by laser capture microdissection followed by ELISA-based determination of the uPA-, uPAR- and PAI-1-levels. In addition, we have assessed uPA-, uPAR- and PAI-1 distribution in formalin-fixed, paraffin-embedded breast cancer specimens (n=60) by immunohistochemistry. The uPA-, uPAR- and PAI-1 in tumor stroma only, tumor cells only and not separated tumor tissue did not show any significant differences in protein-levels determined by ELISA. Cox regression analysis showed that patients with high uPA-, high uPAR-, and/or high PAI-1-levels, as compared to patients with low levels of either factor, showed a significantly shorter relapse-free survival and overall survival (p=0.000001). These results suggest that a strong expression of uPA, uPAR and PAI-1 in the tumor stroma, as well as in tumor cells, have the same impact on the clinical behaviour of breast cancer. CONCLUSION When using uPA- and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for the assessment of the patients' outcome.
Phosphodiesterase Activity of Alkaline Phosphatase in ATP-initiated Ca2+ and Phosphate Deposition in Isolated Chicken Matrix Vesicles*

Inorganic pyrophosphate is a potent inhibitor of bone mineralization by preventing the seeding of calcium-phosphate complexes. Plasma cell membrane glycoprotein-1 and tissue nonspecific alkaline phosphatase were reported to be antagonistic regulators of mineralization toward inorganic pyrophosphate formation (by plasma cell membrane glycoprotein-1) and degradation (by tissue nonspecific alkaline phosphatase) under physiological conditions. In addition, they possess broad overlapping enzymatic functions. Therefore, we examined the roles of tissue nonspecific alkaline phosphatase within matrix vesicles isolated from femurs of 17-day-old chick embryos, under conditions where these both antagonistic and overlapping functions could be evidenced. Addition of 25 μm ATP significantly increased duration of mineralization process mediated by matrix vesicles, while supplementation of mineralization medium with levamisole, an alkaline phosphatase inhibitor, reduces the ATP-induced retardation of mineral formation. Phosphodiesterase activity of tissue nonspecific alkaline phosphatase for bis-p-nitrophenyl phosphate was confirmed, the rate of this phosphodiesterase activity is in the same range as that of phosphomonoesterase activity for p-nitrophenyl phosphate under physiological pH. In addition, tissue nonspecific alkaline phosphatase at pH 7.4 can hydrolyze ADPR. On the basis of these observations, it can be concluded that tissue nonspecific alkaline phosphatase, acting as a phosphomonoesterase, could hydrolyze free phosphate esters such as pyrophosphate and ATP, while as phosphodiesterase could contribute, together with plasma cell membrane glycoprotein-1, in the production of pyrophosphate from ATP.
US Special Forces: an other within the self

ABSTRACT In the post-9/11 era the United States’ (US) Special Operations Forces have become an increasingly prominent feature amongst the country’s vast military options. This article is the first to examine US Special Forces through a critical discursive lens. The article examines the conditions of possibility that US security discourse constructs for its Special Forces, who use some methods of warfare which are more commonly associated with US enemies in constructed notions of US warfare. The article argues that the Special Forces’ representation as an ‘elite’ fighting force in popular US discourse acts to stabilize the Special Forces within the wider discursive structures of US security. This is supplemented by a narrative of mystique and the willingness of the Special Forces to ‘fight fire with fire’ against imagined radical threats. In doing this it is possible to highlight the damaging effect of the Special Forces on understandings of the US Self, which constructs its identity in part through how the US ‘should’ fight wars. Despite the difficulty in articulating the Special Forces as part of the ‘American way of war’, US security discourse has proved remarkably flexible in reconciling the Special Forces within its existing structures.
Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models[S]

The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis. Recent developments in MALDI mass spectrometry imaging (MSI) enable rapid and specific detection of lipids directly from thin tissue sections. In this study, we performed multimodal imaging of acylcarnitines, phosphatidylcholines (PC), a lysophosphatidylcholine (LPC), and a sphingomyelin (SM) from different microenvironments of breast tumor xenograft models, which carried tdTomato red fluorescent protein as a hypoxia-response element-driven reporter gene. The MSI molecular lipid images revealed spatially heterogeneous lipid distributions within tumor tissue. Four of the most-abundant lipid species, namely PC(16:0/16:0), PC(16:0/18:1), PC(18:1/18:1), and PC(18:0/18:1), were localized in viable tumor regions, whereas LPC(16:0/0:0) was detected in necrotic tumor regions. We identified a heterogeneous distribution of palmitoylcarnitine, stearoylcarnitine, PC(16:0/22:1), and SM(d18:1/16:0) sodium adduct, which colocalized primarily with hypoxic tumor regions. For the first time, we have applied a multimodal imaging approach that has combined optical imaging and MALDI-MSI with ion mobility separation to spatially localize and structurally identify acylcarnitines and a variety of lipid species present in breast tumor xenograft models
Three-dimensional image contribution for evaluation of operative procedural errors in endodontic therapy and dental implants.

Acceptable therapeutic protocol in dentistry depends on the outcomes obtained with follow up. Operative procedural errors (OPE) may occur and they represent risk factors able to compromise a tooth or a dental implant. The aim of this study was to detect the OPE in endodontically treated teeth and dental implants, using cone beam computed tomography (CBCT). Eight hundred and sixteen CBCT exams were performed between January 2009 and October 2010, and only those which presented endodontically treated teeth and/or dental implants were selected. The sample was as follows: 195 CBCT exams (n=200 teeth and 200 dental implants), 72 male, 123 female, with mean age of 51 years.In endodontically treated teeth, OPE included underfilling, overfilling, and root perforation; OPEin dental implants were thread exposures, contact with anatomical structures, and contact with adjacent teeth. Kolmogorov-Smirnov test was used for statistical analysis, with significance level set at α=0.05. Underfilling, overfilling, and root perforations were detected in 33.5%, 8% and 4.5% of the teeth, respectively. Dental implants with thread exposures, contact with important anatomical structures and contact with adjacent teeth were seen in 37.5%, 13% and 6.5% of the cases, respectively. OPE were detected in endodontically treated teeth and dental implants, and underfilling and thread exposures were the most frequent occurrences, respectively.
Childhood vulvovaginitis and vaginal discharge in general practice.

OBJECTIVE This study aims to examine the aetiology, clinical features and response to treatment of childhood vulvovaginitis in general practice. METHOD A longitudinal survey of consecutive premenarchal patients presenting with vulvovaginitis and/or vaginal discharge in the course of normal consultations with a general practitioner was conducted in a semi-rural, group general practice with 11,000 patients in Plymouth, UK. Forty-two premenarchal girls with vaginal inflammation or discharge were surveyed, with main outcome measures being clinical evaluation, microbiological assessment of urine and vaginal swabs, and patients' and parents' assessments of resolution and relapse of symptoms. RESULTS Non-specific vulvovaginitis with mixed bacterial flora, associated with poor hygiene and atrophic vaginal mucosa, was the commonest cause; specific bacteria were found in 10 out of 42 cases, including six of Streptococcus pyogenes. No candida was isolated. Treatment with topical oestrogen cream was effective only with mixed infection, oral antibiotics were effective in both mixed and single organisms. No evidence of sexual abuse nor foreign body was found. CONCLUSION Childhood vulvovaginitis is not uncommon in general practice, is usually associated with mixed growth of faecal organisms, and is seldom due to serious causes such as sexual abuse or foreign body.
Lansoprazole in Adolescents with Gastroesophageal Reflux Disease: Pharmacokinetics, Pharmacodynamics, Symptom Relief Efficacy, and Tolerability

Objectives: To evaluate the pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability of lansoprazole in adolescents between 12 and 17 years of age with gastroesophageal reflux disease (GERD). Methods: Adolescents with symptomatic, endoscopically and/or histologically proven GERD were enrolled in this multicenter, double‐blind trial and randomized to lansoprazole 15 mg or 30 mg once daily for 5 days. Results: Sixty‐three adolescents were enrolled in the study. After lansoprazole administration, Tmax occurred at 1.6 hours in those treated with lansoprazole 15 mg and at 1.7 hours in those treated with lansoprazole 30 mg. Dose‐proportional increases in lansoprazole Cmax and AUC were observed in the treatment groups. Age, weight, and gender had no significant effect on Tmax, Cmax, or AUC. Lansoprazole produced significant increases (P ≤ 0.05) in mean 24‐hour intragastric pH and the percentages of time intragastric pH was above 3 and 4. The majority of adolescents treated with lansoprazole 15 mg (69%, 22/32) or lansoprazole 30 mg (74%, 23/31) demonstrated improvement in their reflux symptoms after 5 days of treatment. Adolescents in both dosage groups exhibited reductions from baseline in the percentage of days and nights with heartburn (or other predominant symptom of GERD), the severity of heartburn, the percentage of days antacids were used, and the number of antacid tablets used per day. Pharyngitis and headache were the most commonly reported side effects among adolescents treated with lansoprazole 15 mg and 30 mg, respectively. Five patients experienced adverse events considered to be possibly treatment‐related. One patient with a history of environmental allergies experienced a mild allergic reaction after 3 days of treatment with lansoprazole 15 mg. Among those treated with lansoprazole 30 mg, 4 patients each reported one occurrence of pain (toothache), diarrhea, dizziness, and rash. Conclusion: The pharmacokinetic parameters of lansoprazole observed in this study of adolescents are similar to those observed in studies of healthy adults. Lansoprazole 15 mg or 30 mg once daily for 5 days produces significant increases in intragastric pH, effectively relieves symptoms of reflux disease, and is well tolerated in adolescents with GERD.
Acute tryptophan depletion selectively attenuates cardiac slowing in an Eriksen flanker task

In the present study, the effects of transiently lowering central serotonin levels by means of acute tryptophan depletion on measures of cognitive flexibility were examined. Flexible behaviour was measured in an Eriksen flanker task, and cardiac and electro-cortical responses to errors and congruent and incongruent stimuli were measured. The depletion was successful in lowering tryptophan levels and, as expected, it did not affect subjective mood. Depletion did not affect performance and electro-cortical measures and selectively affected cardiac measures. Depletion attenuated cardiac slowing to incongruent flanker stimuli but did not affect cardiac responses to congruent stimuli and errors. The selective effect on cardiac responses as compared to performance and electro-cortical measures was in accordance with earlier findings, as well as the attenuation of cardiac slowing. The selective effect on the cardiac response to incongruent stimuli was unexpected. Detailed analyses showed a close connection to the earlier reported attenuation of the cardiac response to negative feedback, and the effect is explained in terms of reduced anticipation of the feedback stimulus due to enhanced punishment prediction.
Safety, Tolerability, and Pharmacokinetics of Eliglustat Tartrate (Genz‐112638) After Single Doses, Multiple Doses, and Food in Healthy Volunteers

Three phase 1 studies of eliglustat tartrate (Genz‐112638), an oral inhibitor of glucosylceramide synthase under development for treating Gaucher disease type 1 (GD1), evaluated the safety, tolerability, and pharmacokinetics in healthy volunteers after escalating single doses (n = 99), escalating multiple doses (n = 36), and food (n = 24). Eliglustat tartrate was well tolerated at single doses ≤20 mg/kg and multiple doses ≤200 mg bid, with 50 mg bid producing plasma concentrations in the predicted therapeutic range. No serious adverse events occurred. Mild to moderate events of nausea, dizziness, and vomiting increased in frequency with escalating single and multiple doses. Single doses ≥10 mg/kg caused mild increases in electrocardiogram PR, QRS, and QT/QTc intervals. Single‐dose pharmacokinetics showed dose linearity but not proportionality. Maximum plasma concentrations occurred at ∼2 hours, followed by a monophasic decline with a ∼6‐hour terminal half‐life. Unchanged drug in 8‐hour urine collections was <1.5% of administered doses. Food did not significantly affect the rate or extent of absorption. Multiple‐dose pharmacokinetics was nonlinear, showing higher than expected plasma drug concentrations. Steady state was reached ∼60 hours after bid dosing. Higher drug exposure occurred in slower CYP2D6 metabolizers. Based on favorable results in healthy participants, a phase 2 trial of eliglustat tartrate was initiated in GD1 patients.
Print versus digital preferences of university students in Australia

This paper presents findings of a survey that investigated the reading preferences of university students at Edith Cowan University (ECU) in Perth, Australia. This survey is being undertaken as part of the Academic Reading Format International Study (ARFIS), which is investigating print versus digital reading preferences in 31 countries. A total of 582 students completed the survey. Results from the survey indicate a strong preference for reading in print because of issues such as eyestrain, tactile features, better focus, and ability to highlight and take notes. Issues such as cost, usability and accessibility also impacted on students’ reading decisions. First published 1 February 2018 This work is licensed under a Creative Commons Attribution-NonCommercial License
Volume Surface Integral Equation Method Based on Higher Order Hierarchical Vector Basis Functions for EM Scattering and Radiation From Composite Metallic and Dielectric Structures

This paper presents a novel Galerkin-type method of moments solution of the volume surface integral equation (VSIE), which is developed for the analysis of electromagnetic scattering and radiation from composite metallic and dielectric structures. Our new scheme utilizes curved tetrahedral elements and curved triangular patches for geometric modeling, and the associated higher order hierarchical vector (HOHV) basis functions for volume/surface current modeling. In contrast to the previous studies on higher order VSIE, our scheme, which is reported for the first time in VSIE, is much more flexible. In comparison with the conventional low-order scheme, our scheme requires much less memory and computational time for the same accuracy level. Numerical results are provided to demonstrate the accuracy, efficiency, and flexibility of our scheme.
Are CFOs Effective Operators? An Empirical Analysis of CFO/COO Duality

While the popular press has documented Chief Financial Officer (CFO) role expansion into traditional operations functions, recent research suggests that time spent on non-core CFO activities harms financial reporting quality. We examine the operational acumen of CFOs and potential negative reporting consequences stemming from one person simultaneously holding the role of CFO and Chief Operations Officer (COO) (CFO/COO duality). Empirically, CFO/COO duality occurs with increasing frequency during our sample period (2000–2016); duality is not uncommon (among firms with a COO, over 10 percent have a unified CFO/COO executive). We find no evidence that combining the CFO and COO positions adversely affects operations. Regarding financial reporting quality, we find some evidence that CFO/COO duality firms have relatively more volatile discretionary accruals; however, these accruals are also relatively more predictive of future cash flows. Collectively, our results suggest that unifying control of operations and reporting can be an effective corporate reconfiguration.
A cytosolic tRNA with an unmodified adenosine in the wobble position reads a codon ending with the non-complementary nucleoside cytidine.

Out of more than 500 sequenced cytosolic tRNAs, there is only one with an unmodified adenosine in the wobble position (position 34). The reason for this rare occurrence of A34 is that it is mostly deaminated to inosine-34 (I34). I34 is a common constituent in the wobble position of tRNAs and has a decoding capacity different from that of A34. We have isolated a mutant (proL207) of Salmonella typhimurium, in which the wobble nucleoside G34 has been replaced by an unmodified A in tRNA(Pro)(GGG), which is the only tRNA that normally reads the CCC codon. Thus, this mutant apparently has no tRNA that is considered cognate for the codon CCC. Despite this, the mutant grows normally. As expected, Pro-tRNA selection at the CCC codon in the A-site in a mutant deleted for the proL gene, which encodes the tRNA(Pro)(GGG), was severely reduced. However, in comparison this rate of selection was only slightly reduced in the proL207 mutant with its A34 containing tRNA(Pro)(AGG) suggesting that this tRNA reads CCC. Moreover, measurements of the interference by a tRNA residing in the P-site on the apparent termination efficiency at the A-site indicated that indeed the A34 containing tRNA reads the CCC codon. We conclude that A34 in a cytosolic tRNA is not detrimental to the cell and that the mutant tRNA(Pro)(AGG) is able to read the CCC codon like its wild-type counterpart tRNA(Pro)(GGG). We suggest that the decoding of the CCC codon by a 5'-AGG-3' anticodon occurs by a wobble base-pair between a protonated A34 and a C in the mRNA.
Environmental decision-making: the influence of policy information

ABSTRACT The success of technological development depends on citizens’ social acceptance, whereas several challenges related to the understanding of citizens’ reactions to renewable energy and its policies are identifiable. Most importantly, the gap between general attitudes towards the environment and specific voting behaviour regarding environment-friendly policy proposals calls for an explanation of how a policy’s design causes citizens who might otherwise support environmental measures to express opposition in direct democratic votes. Therefore, how policy design and policy information impact opinion formation is investigated. Salient aspects are identified, and the different types of information or qualifications that may cause opposition are considered. This new approach reveals that citizens, in environmental decision-making, do indeed consider policy design and policy information, which they regard as conditions for support, and that the type of policy information matters since citizens do not consider all of the policy details when they make decisions.
Comparison of Initial Treatment Response to Two Enhanced-Viscosity Artificial Tears

Purpose. To compare the effectiveness of 1.0% carboxymethylcellulose (CMC) (Refresh Liquigel, Allergan, Inc., Irvine, CA) and propylene glycol/polyethylene glycol 400 (PG-HPG) (Systane, Alcon, Fort Worth, TX) in providing relief of dry eye symptoms and signs. Methods. To evaluate patient comfort and drop preference, patients were given CMC in one eye and PG-HPG in the other. Five minutes after the initial drop application, patients were questioned on overall preference and comfort, as measured by stickiness, blurring, and soothing. Patients were then randomized to receive CMC or PG-HPG in both eyes for 1 week. Fluorescein staining was evaluated at baseline and week 1. Results. Of patients with a preference, more patients preferred CMC than PG-HPG. Thirty-six percent preferred CMC, and 24% preferred PG-HPG. More (35%) patients found CMC to be more soothing than PG-HPG (22%). After 1 week of treatment, eyes treated with CMC consistently showed less ocular surface staining than did eyes treated with PG-HPG. Mean corneal staining score in the inferior region was significantly lower in the CMC group than in the PG-HPG group (P = 0.008) at week 1. CMC provided a statistically significant decrease in mean corneal inferior staining (P < 0.001), whereas the PG-HPG group (P = 0.185) had no significant change. In the temporal conjunctival region, CMC provided a significantly lower mean staining score than PG-HPG after 1 week of treatment (P = 0.005). Conclusions. Patients found CMC to be more comfortable than PG-HPG. After 1 week of use, CMC provided greater relief of dry eye signs and symptoms than PG-HPG.