Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of the Hedgehog pathway downregulates estrogen receptor alpha signaling in breast cancer cells

Anti-estrogen treatment, exemplified by tamoxifen, is a well-established adjuvant therapy for estrogen receptor alpha (ERα)-positive breast cancer. However, the effectiveness of this drug is limited due to the development of resistance. The Hedgehog (HH) signaling pathway is critical in embryonic development, and aberrant activation of this transduction cascade is linked to various malignancies. However, it remains unclear whether HH signaling is activated in human breast cancer and related to tamoxifen resistance. Deciphering how this pathway may be involved in breast cancer is a crucial step towards the establishment of targeted combinatorial treatments for this disease. Here, we show that the expression of the HH signaling effector protein GLI1 is higher in tamoxifen resistant compared to sensitive cells. Tamoxifen resistant cells have stronger ERα transcriptional activity relative to sensitive cells, even though the ERα expression is similar in both cell types. Knockdown of GLI1 attenuates cell proliferation and reduces ERα transcriptional activity in both sensitive and resistant cells, irrespective of estrogen stimulation. Combinatorial treatment of tamoxifen and the GLI antagonist GANT61 further suppresses the growth of sensitive and resistant cells relative to administration of only tamoxifen, and this was irrespective of estrogen stimulation. Moreover, a positive correlation between GLI1 and ERα expression was identified in breast cancer samples. Additionally, high GLI1 expression predicted worse distant metastasis-free survival in breast cancer patients. These data suggest that the HH pathway may be a new candidate for therapeutic targeting and prognosis in ERα-positive breast cancer.
Molecular Xenomonitoring Using Mosquitoes to Map Lymphatic Filariasis after Mass Drug Administration in American Samoa

Background Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA. Methodology/Principle Findings Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20–0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp. Conclusions/Significance Our results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and transmission rates in humans.
Prediction of solidification behaviour of weld pool through modelling of heat transfer and fluid flow during gas tungsten arc welding of commercial pure aluminium

Abstract A mathematical model is developed to assess the solidification behaviour of the weld pools. To do so, during gas tungsten arc welding of commercial pure aluminium, equations of conversation of mass, energy and momentum are numerically solved considering three-dimensional steady state heat transfer and fluid flow conditions. The weld pool geometry, weld thermal cycles and various solidification parameters are calculated using temperature and velocity fields acquiring from the utilised model. The solidification behaviour of the weld pool at the weld centreline and the fusion line is then studied using the solidification parameters including temperature gradient G, solidification rate R and the combined forms G/R and GR. In order to verify the predictions, welding experiments are performed and geometry of the weld fusion zone is measured. The calculated geometry of the weld fusion zone is found to be in good agreement with the corresponding experimental result. The predictions show that the cooling rate GR increases toward the centreline while the other solidification parameter G/R shows a different behaviour. In addition, it is found that under the employed welding conditions, as the welding speed increases temperature gradients both at the weld centreline and at the fusion line are reduced.
Can biosecurity and local network properties predict pathogen species richness in the salmonid industry?

Salmonid farming in Ireland is mostly organic, which implies limited disease treatment options. This highlights the importance of biosecurity for preventing the introduction and spread of infectious agents. Similarly, the effect of local network properties on infection spread processes has rarely been evaluated. In this paper, we characterized the biosecurity of salmonid farms in Ireland using a survey, and then developed a score for benchmarking the disease risk of salmonid farms. The usefulness and validity of this score, together with farm indegree (dichotomized as ≤ 1 or > 1), were assessed through generalized Poisson regression models, in which the modeled outcome was pathogen richness, defined here as the number of different diseases affecting a farm during a year. Seawater salmon (SW salmon) farms had the highest biosecurity scores with a median (interquartile range) of 82.3 (5.4), followed by freshwater salmon (FW salmon) with 75.2 (8.2), and freshwater trout (FW trout) farms with 74.8 (4.5). For FW salmon and trout farms, the top ranked model (in terms of leave-one-out information criteria, looic) was the null model (looic = 46.1). For SW salmon farms, the best ranking model was the full model with both predictors and their interaction (looic = 33.3). Farms with a higher biosecurity score were associated with lower pathogen richness, and farms with indegree > 1 (i.e. more than one fish supplier) were associated with increased pathogen richness. The effect of the interaction between these variables was also important, showing an antagonistic effect. This would indicate that biosecurity effectiveness is achieved through a broader perspective on the subject, which includes a minimization in the number of suppliers and hence in the possibilities for infection to enter a farm. The work presented here could be used to elaborate indicators of a farm’s disease risk based on its biosecurity score and indegree, to inform risk-based disease surveillance and control strategies for private and public stakeholders.
Evaluation of United States Department of Agriculture—Sponsored Consumer Materials Addressing Food Security

Purpose. Food insecurity in the United States is a major public health issue. The main objective of this study was to evaluate the availability and quality of printed materials addressing food security targeted to special populations by the United States Department of Agriculture (USDA). Design. Nutrition education resources addressing food security available from USDA websites were selected for analysis. Setting. Not applicable. Participants. The review team consisted of project staff (n = 6), two of who were fluent in Spanish. Method. Selection criteria were established to identify the food-security materials, and a group of reviewers assessed the quality of each publication both quantitatively and qualitatively. A consensus meeting among the reviewers was held to make final determinations of the quality of the materials. The quantitative data analysis consisted of basic descriptive statistics. Results. Among the 27 materials initially identified, 20 were either irrelevant or of low relevance to food security. Moreover, very few of them were intended for minority populations. The quality of most of the materials ranged from “average” to “good. ” Some of the major weaknesses include readability level, lack of cultural relevance, and inadequate coverage of food insecurity. Conclusion. Very few materials on food insecurity are of high quality. In the development of such materials, emphasis should be given to the readability level, content, and cultural relevance.
Roles of Fas/FasL‐mediated apoptosis and inhibin B in the testicular dysfunction of rats with left‐side varicocele

We investigated the role of the Fas/FasL signalling pathway and inhibin B expression in rats with an experimentally induced left‐side varicocele. Forty‐five Sprague Dawley (SD) male rats were randomly divided into three groups in average: control group, sham group and experimental group. The expression of inhibin B in the rat left testis was analysed at the mRNA and protein levels by reverse transcription–polymerase chain reaction (RT‐PCR) and Western blotting respectively. The expressions of Fas, FasL and caspase‐3 in the left testis were measured by RT‐PCR and immunofluorescence. The apoptosis index (AI) was measured by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Both the mRNA and protein of inhibin B were significantly reduced in the experimental group compared with that in the control group or the sham group. The expression of Fas, FasL and caspase‐3 in the experimental group was significantly increased compared to that in the control group or the sham group. The concentration of serum inhibin B was also inversely related to circulating FSH concentrations and positively correlated with sperm count. It is concluded that Fas/FasL system may play an important role in apoptosis of rats with experimental varicocele and inhibin B could reflect spermatogenesis function.
Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

BACKGROUND The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined. PATIENTS AND METHODS 29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14. RESULTS An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.
Evaluation of consistency in quantification of gene copy number by real‐time reverse transcription quantitative polymerase chain reaction and virus titer by plaque‐forming assay for human respiratory syncytial virus

The plaque‐forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque‐forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT‐qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque‐forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT‐qPCR. Two real‐time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque‐forming units. In conclusion, RT‐qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque‐forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.
Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES‐M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential.
The Impact of Consumers’ Beliefs on Attitudes and Patronage Intention Toward Green Restaurant in Taiwan

Since 1990, the Green Restaurant Association (GRA), a United States based national non-profit organization, has led the green restaurant movement by providing certification for restaurants to become more environmentally responsible. Certification services include rating existing restaurants and food service operations with points in seven environmental categories. The present study intended to employ Fishbein and Ajzen’s Theory of Reasoned Action (TRA) to examine and understand the impact of consumers’ beliefs on attitudes and patronage intention toward green restaurant in Taiwan. A total of 389 respondents completed a survey conducted at the downtown hectic transit station of Taipei’s Metro system. The results of a structural equation analysis revealed that consumers’ beliefs of green restaurant positively affected their attitudes and patronage intentions toward green restaurant. Implications and suggestions for future research are discussed.
Drug repurposing: In-vitro anti-glycation properties of 18 common drugs

Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover “new targets” for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout. This study was carried out by using two in-vitro protein anti-glycation assay models. Results revealed that nimesulide (3), a non-steroidal anti-inflammatory drug, possesses a good anti-glycation activity in in-vitro BSA-MG and BSA-glucose glycation models with IC50 values of 330.56 ± 2.90, and 145.46 ± 16.35 μM, respectively. Phloroglucinol dihydrate (11), a drug used for the treatment of gastrointestinal diseases, showed a weak activity in BSA-MG glycation model (IC50 = 654.89 ± 2.50 μM), while it showed a good activity in BSA-glucose assay (IC50 = 148.23 ± 0.15 μM). Trimethylphloroglucinol (9), a drug used for the treatment of pain related to functional disorders of the digestive and biliary tracts, also showed a good antiglycation activity in BSA-MG model (IC50 = 321.15 ± 1.26 μM), while it was found to be inactive in in-vitro BSA-glucose assay (IC50 = 12.95% inhibition). These activities of drugs were compared with the anti-glycation activity of the standard, rutin (IC50 = 294.5 ± 1.50 μM in BSA-MG glycation model, and IC50 = 86.94 ± 0.24 μM in BSA- glucose model). Rest of the drugs exhibited a relatively weak antiglycation activity. This study identifies nimesulide (3), and phloroglucinol dihydrate (11) as new inhibitors of in-vitro protein glycation for further investigations as potential anti-diabetic agents.
Abnormalities on Brain Susceptibility-weighted Imaging in Neuro-Sweet Disease

An 81-year-old woman presented with a one-week history of pyrexia (38.6°C), headache, acalculia, and hemianopia. Laboratory examinations revealed an elevated leukocyte count (10,000/mm), neutrophil count (8,200/mm), and erythrocyte sedimentation rate (43 mm/h). CSF study revealed pleocytosis (33/mm) and an elevated protein level (402 mg/dL). MRI showed leptomeningeal gadolinium enhancement (arrowheads) and multiple cortical-subcortical areas of dotted signal loss in the left parieto-occipital lobes on susceptibility-weighted imaging (SWI) (Picture 1). NeuroSweet disease (NSD) was diagnosed in accordance with the proposed diagnostic criteria based on the HLA type (B54 and Cw1), the presence of painful erythema nodosum (Picture 2), and the detection of neutrophilic infiltration on skin biopsy (1). Corticosteroid therapy led to the effective improvement of the clinical symptoms and a partial improvement in the MRI abnormalities. To the best of our knowledge, this is the first reported case of NSD in which marked leptomeningeal abnormalities were detected on SWI. The abnormalities were considered to consist of cerebral microbleeds and treatable congested veins, which were caused by the vasculopathy associated with Sweet disease. Actually, one autopsy case of NSD with microbleeds and congested veins has been reported (2). Because SWI abnormalities are likely to go undetected in an incomplete examination, a neuroradiological analysis based
Localization of Multiple Underwater Objects With Gravity Field and Gravity Gradient Tensor

We present a novel algorithm to locate multiple underwater objects in real time using gravity field vector and gravity gradient tensor signals. This algorithm formulates the task of localization of multiple underwater objects into a regularized nonlinear problem, which is solved with the standard Levenberg–Marquardt algorithm. The regularization parameters are estimated by cross validation. The initial coordinates and masses of these underwater objects are automatically determined by solving a single-object localization problem. A synthetic navigation model with two underwater objects was adopted to validate the proposed algorithm. The results show that it has good stability and antinoise ability for multiple underwater objects localizations.
Tailoring fabrication parameters of silver helical metamaterials for enhanced polarization properties in terahertz regime

Metallic helices have been extensively researched and demonstrated for their application as broadband circular polarizers in different frequency regimes. For making such 3D helices, two photon lithography (TPL) has been employed in conjunction with electroplating of metals. Recently, our group has demonstrated selective silver electroless plating of two photon fabricated polymer (SU-8) structures on silicon substrate. This procedure allows us to make metal-coated polymer helices. In this work, we examine how these fabrication process parameters could be tailored to obtain higher extinction ratios for circular polarizers in THz regime (or MIR regime). We further analyze the role of aspect-ratio of helices in their polarizing action. We will present both simulation and experimental results to show the improved performance of the polarizers.
Some experiments on artificial dielectrics at centimetre wavelengths

A parallel-plate transmission line has been developed for wavelengths between 8 and 11 cm and has been used for an examination of the properties of artificial dielectrics under conditions which approximate closely to those existing in free space. An experimental method by which the effective electrical length of dielectric samples can be determined has been shown to give reliable results. Particular attention has been paid to the occurrence of dispersion and a distinction is drawn between two forms of this. The first arises from the resonance of the elements from which the dielectric is constructed and is called “dipolar dispersion”because of the similarity to the corresponding behaviour of solid dielectrics. The second depends primarily on the spacings between the conducting elements and is referred to as “cavity dispersion. ” Experimental results are given for both types of dispersion.
Textile-specific Properties that Influence Plasma Treatment, Effect Creation and Effect Characterization

This paper discusses specific properties of textile products that influence plasma-textile interactions and impede both the fundamental understanding and the commercial application of plasma technology in the textile industry: (a) a large specific surface, (b) the three-dimensional porous structure and (c) the presence of impurities at the fiber surface, as well as in the fiber structure. The paper also clarifies the need for “plasma-for-textiles” i.e. a generic approach to the plasma treatment of textiles.