Miracle-dz/UniFAR-FTUs huggingface dataset:
Heregulin inhibits proliferation via ERKs and phosphatidyl‐inositol 3‐kinase activation but regulates urokinase plasminogen activator independently of these pathways in metastatic mammary tumor cells

Heregulin (HRG) and type I receptor tyrosine kinase (RTK) expression was investigated in the highly invasive and metastatic LM3 cell line, our previously described model of metastasis for mammary cancer (Bal de Kier Joffe et al. [1986] Invasion Metastasis 6:302–12; Urtreger et al. [1997] Int J Oncol 11:489–96). Although LM3 cells do not express HRG, they exhibit high levels of ErbB‐2 and ErbB‐3 as well as moderate expression of ErbB‐4. Addition of exogenous HRGβ1 resulted in inhibition of both proliferation and migration of LM3 cells. HRGβ1 was also able to decrease the activity of urokinase‐type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP‐9), 2 key enzymes in the invasion and metastatic cascade. HRGβ1 treatment of LM3 cells induced tyrosine phosphorylation of ErbB‐2, ErbB‐3 and ErbB‐4 as well as the formation of ErbB‐2/ErbB‐3 and ErbB‐2/ErbB‐4 heterodimers. Assessment of the signaling pathways involved in HRGβ1 action indicated that the addition of HRGβ1 to LM3 cells resulted in activation of phosphatidylinositol 3‐ kinase (PI‐3K) and in strong induction of the association of the p85 subunit of PI‐3K with ErbB‐3. HRGβ1 also caused the rapid activation of ERK1/ERK2 and Stat3 and Stat5 (signal transducers and activators of transcription [STAT]). This is the first demonstration of the ability of HRGβ1 to activate STATs in mammary tumor cells. Blockage of PI‐3K activity with its chemical inhibitor wortmannin, or of MEK1/ERKs activity with PD98059, resulted in suppression of the ability of HRGβ1 to inhibit LM3 cell growth. Notwithstanding the suppression of these 2 signaling pathways, HRGβ1 still proved capable of inhibiting uPA activity. Therefore, our results provide evidence that signaling pathways involved in HRGβ1‐induced proliferation appear to be distinct from those involved in HRGβ1 regulation of uPA, a protease that plays a pivotal role in invasion and metastasis. © 2002 Wiley‐Liss, Inc.
On the status of subject markers in African languages

Ethelbert Emmanuel Kari (2017), On the Status of Subject Markers in African Languages. Studies in Linguistics 44, 99-134. This paper discusses subject markers in African languages, noting that whereas the grammatical functions of these morphemes are fairly clear; their status as affixes or clitics is not. The unclear status of subject markers has led to their analysis as affixes in some languages or as clitics in others. It has been suggested recently that African subject markers, which have been traditionally regarded as affixes, can be reanalyzed as clitics. The paper highlights the fact that in some African languages, subject markers that were previously analyzed as affixes have now been analyzed as clitics, suggesting that there is an on-going process of grammaticalization of African subject markers. On the basis of a variety of data and characteristic phonological and syntactic behaviour, this paper successfully and consistently shows that subject markers in some African
Role for Thymic and Splenic Regulatory CD4+ T Cells Induced by Donor Dendritic Cells in Allograft Tolerance by LF15-0195 Treatment1

A 20-day treatment with LF15-0195, a deoxyspergualine analogue, induced allograft tolerance in a fully MHC-mismatched heart allograft model in the rat. Long-term allografts displayed minimal cell infiltration with no signs of chronic rejection. CD4+ spleen T cells from tolerant LF15-0195-treated recipients were able to suppress in vitro proliferation of allogeneic CD4+ T cells and to transfer tolerance to second syngeneic recipients, demonstrating dominant suppression by regulatory cells. A significant increase in the percentage of CD4+CD25+ T cells was observed in the thymus and spleen from tolerant LF15-0195-treated recipient. In vitro direct stimulation with donor APCs demonstrated that CD4+ regulatory T cells proliferated weakly and expressed low levels of IFN-γ, IL-10, and IL-2. CD4+CD25+ cell depletion increased IL-2 production by CD4+CD25− thymic cells, but not splenic cells. Moreover, tolerance was transferable with splenic and thymic CD4+CD25+ cells, but also in 50% of cases with splenic CD4+CD25− cells, demonstrating that CD25 can be a marker for regulatory cells in the thymus, but not in the periphery. In addition, we presented evidences that donor APCs were required to induce tolerance and to expand regulatory CD4+ T cells. This study demonstrates that LF15-0195 treatment induces donor APCs to expand powerful regulatory CD4+CD25+/− T cells present in both the central and peripheral compartments.
Isotropic and Homogeneous Behavior of Chiral Media Based on Periodical Inclusions of Cranks

Isotropic chiral materials at microwave frequency are usually obtained by distributing, as random as possible, elements of chiral symmetry in a host medium. Here we propose a new manufacturing technique based on the precise location of same handedness cranks in a periodical configuration. By this method electromagnetic active media are produced with homogeneous, isotropic and reciprocal behavior for the microwave frequency range. These materials also present some fabrication advantages and new parameters for material design.
TAVI-Mimic for testing of heart valve leaflet materials in physiological loading situations

Abstract The loading situation of the aortic valve is complex, complicating the identification of innovative approaches for heart valve leaflet materials, e.g. for transcatheter aortic valve implantation (TAVI). Materials engineering experiments allow for screening of materials but especially for durability testing, the consideration of physiological loads is vital/critical for the suitability-assessment of innovative leaflet materials. For this reason, a framework structure for the testing of leaflet materials in physiological loading (TAVI-Mimic) was developed. The exemplary use case for the TAVI-Mimic was a test for calcification propensity of pericardium during durability testing. The TAVI-Mimic was designed as a fourparted frame, based on previous work of our group. The leaflet material can be attached between inner and outer shells without sewing. In a second step, the TAVI-Mimic was optimized regarding radial load-deformation in comparison to a commercial TAVI by means of finite element analysis (FEA) and hydrodynamic characterization in a pulse duplicator system. Mechanical properties dependent on water uptake of different materials for 3D-printing of the TAVI-Mimic were investigated. After optimization, TAVI-Mimics were equipped with glutaraldehyde-fixated pericardial tissue and prototypes were calcified by using a heart valve durability tester and a metastable calcification-liquid, developed in earlier studies. The development of the TAVI-Mimic using FEA and experiments was successful, leading to a radial load dependent deformation of 0.6 mm which correlates with commercial TAVI. Two methacrylic photopolymers were identified for 3D-printing of the TAVI-Mimic and prototypes attached with pericardial tissue were manufactured. Pericardium TAVI-Mimics were calcified in vitro for one week and an average calciumphosphate precipitate of 0.34- 0.54 mg/cm² was measured. The optimization of the TAVR-Mimic led to an improved load-dependent behaviour compared to a commercial prosthesis while testing. The calcification method, combining the TAVI-Mimic, the metastable calcification solution and the durability tester enabled a successfully calcification of pericardial tissue, approaching the in vivo situation.
An FDTD method with FFT-accelerated exact absorbing boundary conditions

An accurate and efficient finite-difference time-domain (FDTD) method for analyzing axially symmetric structures is presented. The method achieves its accuracy and efficiency using exact absorbing conditions (EACs) for terminating the computation domain and a blocked-FFT based scheme for accelerating the computation of the temporal convolutions present in non-local EACs. The method is shown to be especially useful in characterization of long-duration resonant wave interactions.
Mode Combination in an Ideal Wireless OAM-MIMO Multiplexing System

In this letter, we present the mode combinations needed to achieve orthogonal sub-channels in an ideal wireless orbital angular momentum based multiple-input multiple-output (OAM-MIMO) multiplexing system with N OAM transmitters and M receive antennas. The results show that, orthogonality is achieved if the absolute difference between any two transmitted modes |vk| mod M ≠ 0. The modes are considered equivalent if their absolute difference is a multiple of M. Orthogonal OAM-MIMO multiplexing systems can be used to enhance spectral efficiency in wireless backhaul networks.
Genetic and Phenotypic Characteristics of Pleomorphic Lobular Carcinoma In Situ of the Breast

The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.
Quality of life in patients receiving telemedicine enhanced chronic heart failure disease management: A meta-analysis

Background Previous reviews have investigated the effectiveness of telemedicine in the treatment of heart failure (HF). Dependent variables have included hospitalisations, mortality rates, disease knowledge and health costs. Few reviews, however, have examined the variable of health-related quality of life (QoL). Methods Randomised controlled trials comparing the delivery methods of any form of telemedicine with usual care for the provision of HF disease-management were identified via searches of all relevant databases and reference lists. Studies had to report a quantitative measure for mental, physical or overall QoL in order to be included. Results A total of 33 studies were identified. However, poor reporting of data resulted in the exclusion of seven, leaving 26 studies with 7066 participants. Three separate, random effects meta-analyses were conducted for mental, physical and overall QoL. Telemedicine was not significantly more effective than usual care on mental and physical QoL (standardised mean difference (SMD) 0.03, (95% confidence interval (CI) −0.05–0.12), p = 0.45 and SMD 0.24, (95% CI −0.08–0.56), p = 0.14, respectively). However, when compared to usual care, telemedicine was associated with a small significant increase in overall QoL (SMD 0.23, (95% CI 0.09–0.37), p = 0.001). Moderator analyses indicated that telemedicine delivered over a long-duration (≥52 weeks) and via telemonitoring was most beneficial. Conclusion Compared to usual care, telemedicine significantly increases overall QoL in patients receiving HF disease management. Statistically non-significant but nonetheless positive trends were also observed for physical QoL. These findings provide preliminary support for the use of telemedicine in the management of heart failure without jeopardising patient well-being.
Mutations in penicillin-binding proteins 1, 2 and 3 are responsible for amoxicillin resistance in Helicobacter pylori.

OBJECTIVES To elucidate the relationship between the mutations of penicillin-binding protein (PBP)1, PBP2 and PBP3 and amoxicillin resistance in Helicobacter pylori. METHODS The mutations detected only in clinical amoxicillin-resistant strains were determined by comparison of the deduced amino acid sequences of PBP1(HP0597), PBP2(HP1556) and PBP3(HP1565) encoded by the pbp1, ftsI and pbp2 genes, respectively, in 13 clinical H. pylori strains and three ATCC strains. The contribution of the mutations in PBPs was analysed by the natural transformation of the amoxicillin-susceptible strain ATCC 700392 with various combinations of the pbp1, ftsI and pbp2 genes from the amoxicillin-resistant strain TH743 (MIC of amoxicillin: 8 mg/L). RESULTS We initially identified six, four and two mutations of PBP1, PBP2 and PBP3, respectively, which were detected only in amoxicillin-resistant strains. By the natural transformation of an amoxicillin-susceptible strain ATCC 700392, we found that mutations in PBP1 and PBP3 conferred higher resistance to amoxicillin than mutations in PBP1 and PBP2, or mutations only in PBP1. Furthermore, mutations in PBP1, PBP2 and PBP3 conferred a 256-fold higher amoxicillin resistance when compared with ATCC 700392. CONCLUSIONS Multiple mutations in PBP2 and PBP3, in addition to mutations in PBP1, confer higher amoxicillin resistance in H. pylori.
Preferential Binding of Poly(A)-binding Protein 1 to an Inhibitory RNA Element in the Human Immunodeficiency Virus Type 1 gag mRNA*

Human immunodeficiency virus type 1 (HIV-1) mRNAs encoding structural proteins contain multiple inhibitory/instability elements (INS), which decrease the efficiency of viral protein expression. We have previously identified a strong INS element (INS-1) within the p17gag coding region. Here we show that poly(A)-binding protein 1 (PABP1) binds preferentially to INS-1 within the p17gag mRNA, but not to a mutated mRNA in which INS-1 function is eliminated. Competition experiments performed in the presence of different nucleic acids and homoribopolymers demonstrated preferential binding of PABP1 to the INS-1-containing RNA. In contrast to HeLa cells and several lymphoid cell lines, certain human glioma cell lines exhibit high levels of gag expression in the absence of Rev upon transient transfection with wild type gag expression vectors. We analyzed extracts of different cell lines and found that the binding of PABP1 to INS-1 RNA is significantly diminished in glial cell extracts. The expression levels of gag correlate with the absence of binding of PABP1 to the INS-1 RNA in cellular extracts. These results suggest a role for PABP1 in the inhibition of gag expression mediated through INS-1.
Interactive Surveillance Event Detection through Mid-level Discriminative Representation

Event detection from real surveillance videos with complicated background environment is always a very hard task. Different from the traditional retrospective and interactive systems designed on this task, which are mainly executed on video fragments located within the event-occurrence time, in this paper we propose a new interactive system constructed on the mid-level discriminative representations (patches/shots) which are closely related to the event (might occur beyond the event-occurrence period) and are easier to be detected than video fragments. By virtue of such easily-distinguished mid-level patterns, our framework realizes an effective labor division between computers and human participants. The task of computers is to train classifiers on a bunch of mid-level discriminative representations, and to sort all the possible mid-level representations in the evaluation sets based on the classifier scores. The task of human participants is then to readily search the events based on the clues offered by these sorted mid-level representations. For computers, such mid-level representations, with more concise and consistent patterns, can be more accurately detected than video fragments utilized in the conventional framework, and on the other hand, a human participant can always much more easily search the events of interest implicated by these location-anchored mid-level representations than conventional video fragments containing entire scenes. Both of these two properties facilitate the availability of our framework in real surveillance event detection applications.
A two-phase hybrid heuristic search approach to the location-routing problem

In many logistic environments, managers must make decisions such as facility location and distribution planning. Though this interdependence between the two decisions has been recognized and an extensive body of combined location-routing literature has developed in less than 30 years, simultaneous solution methods are limited to heuristics due to the problem complexity. This paper proposes a two-phase hybrid heuristic search approach, which decomposes the location-routing problem into a location-allocation problem and a vehicle routing problem. The two-phase approach aims to integrate two levels of decision making (location and routing) in a computationally efficient manner. In the location phase of the algorithm, a tabu search is performed on the location variables to determine a good configuration of facilities to be used in the distribution. For each of the location configurations, ant colony algorithm is run on the routing variables in order to obtain a good routing for the given configuration. In the routing phase of the algorithm, the large problem can be furthermore decomposed into the much smaller sub-problems. The approach does not only improve the efficiency, but also improves the effectiveness of the algorithm. The results indicate that this method performs well in terms of the solution quality and run time consumed.
Construct validity and reliability of the Handover Evaluation Scale.

AIMS AND OBJECTIVES To examine the psychometric properties of the Handover Evaluation Scale using exploratory and confirmatory factor analysis. BACKGROUND Handover is a fundamental component of clinical practice and is essential to ensure safe patient care. Research indicates a number of problems with this process, with high variability in the type of information provided. Despite the reported deficits with handover practices internationally, guidelines and standardised tools for its conduct and evaluation are scarce. Further work is required to develop an instrument that measures the effectiveness of handover in a valid and reliable way. DESIGN Secondary analysis of data collected between 2006-2008 from nurses working on 24 wards across a large Australian healthcare service. METHODS A sample of 299 nurses completed the survey that included 20 self-report items which evaluated the effectiveness of handover. Data were analysed using exploratory factor analysis and confirmatory factor analysis supported by structural equation modelling. RESULTS Analyses resulted in a 14-item Handover Evaluation Scale with three subscales: (1) quality of information (six items), (2) interaction and support (five items) and (3) efficiency (three items). A fourth subscale, patient involvement (three items), was removed from the scale as it was not a good measure of handover. CONCLUSIONS The scale is a self-report, valid and reliable measure of the handover process. It provides a useful tool for monitoring and evaluating handover processes in health organisations, and it is recommended for use and further development. RELEVANCE TO CLINICAL PRACTICE Monitoring handover is an important quality assurance process that is required to meet healthcare standards. This reliable and valid scale can be used in practice to monitor the quality of handover and provide information that can form the basis of education and training packages and guidelines to improve handover policies and processes.
Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness.

PURPOSE To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness. MATERIALS AND METHODS The requirement for institutional review board approval was waived. Intra- and interpatient variation of PZ ADCs was determined by means of repeated measurements of normal ADCs at three magnetic resonance (MR) examinations in a retrospective cohort of 10 consecutive patients who had high prostate-specific antigen levels and negative findings at transrectal ultrasonographically-guided biopsy. In these patients, no signs of PZ cancer were found at all three MR imaging sessions. The effect of interpatient variation on the assessment of prostate cancer aggressiveness was examined in a second retrospective cohort of 51 patients with PZ prostate cancer. Whole-mount step-section pathologic evaluation served as reference standard for placement of regions of interest on tumors and normal PZ. Repeated-measures analysis of variance was used to determine the significance of the interpatient variations in ADCs. Linear logistic regression was used to assess whether incorporating normal PZ ADCs improves the prediction of cancer aggressiveness. RESULTS Analysis of variance revealed that interpatient variability (1.2-2.0×10(-3) mm2/sec) was significantly larger than measurement variability (0.068×10(-3) mm2/sec±0.027 [standard deviation]) (P=.0058). Stand-alone tumor ADCs showed an area under the receiver operating characteristic curve (AUC) of 0.91 for discriminating low-grade versus high-grade tumors. Incorporating normal PZ ADC significantly improved the AUC to 0.96 (P=.0401). CONCLUSION PZ ADCs show significant interpatient variation, which has a substantial effect on the prediction of prostate cancer aggressiveness. Correcting this effect results in a significant increase in diagnostic accuracy.
"Birds in the Clouds": Adventures in Data Engineering

Leveraging their eBird crowdsourcing project, the Cornell Lab of Ornithology generates sophisticated Spatio-Temporal Exploratory Model (STEM) maps of bird migrations. Such maps are highly relevant for both scientific and educational purposes, but creating them requires advanced modeling techniques that rely on long and potentially expensive computations. In this paper, we share our experience porting the eBird STEM data pipeline from a physical cluster to the cloud, providing a seamless deployment at a lower cost. Using open source tools and cloud "marketplaces", we managed to divide the operating costs by a factor of 6, making it possible to scale our pipeline on a research budget.