Miracle-dz/UniFAR-FTUs huggingface dataset:
Hsp 90 inhibition by WK 881 potently suppresses the growth of gefitinib-resistant H 1975 cells harboring the T 790 M mutation in EGFR

Heat shock protein 90 (Hsp90) is a molecular chaperone for numerous client proteins, many of which are crucial for the pathogenesis of non-small cell lung cancers (NSCLCs). To date, therapeutic approaches using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib for the treatment of NSCLCs have been limited due to the emergence of acquired drug resistance mainly mediated by a secondary T790M mutation in EGFR. Considering this, Hsp90 inhibition seems promising as it leads to overall degradation of the oncogenic EGFR family proteins. In this regard, the present study provides the preclinical basis for a new Hsp90 inhibitor, WK88-1, for the treatment of NSCLCs harboring the T790M mutation in EGFR. Our data revealed that inhibition of Hsp90 by WK88-1 induced overall degradation of multiple oncogenic signaling molecules including EGFR, ErbB2 and ErbB3, leading to subsequent growth arrest and apoptosis in the gefitinib-resistant H1975 cell line. In addition, treatment with WK88-1 markedly inhibited proliferation, migration and invasion in H1975 cells. Moreover, an in vivo xenograft assay indicated that WK88-1 markedly suppressed tumor growth in the H1975 xenografts, highlighting the potential efficacy of WK88-1 for overcoming gefitinib resistance in NSCLCs harboring the T790M mutation in EGFR.
Structure-Based Design of Ricin Inhibitors

Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. Development of these lead compounds into potent drug candidates is a challenging prospect for numerous reasons, including poor solubility of pterins, the large and highly polar secondary binding pocket of RTA, as well as the enzyme’s near perfect catalytic efficiency and tight binding affinity for its natural substrate, the eukaryotic ribosome. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10−4 M range, leaving significant room for improvement. This review highlights the variety of techniques routinely employed in structure-based drug design projects, as well as the challenges faced in the design of RTA inhibitors.
A Keypoint-Based Approach toward Scenery Character Detection

This paper proposes a new approach toward scenery character detection. This is a key point-based approach where local features and a saliency map are fully utilized. Local features, such as SIFT and SURF, have been commonly used for computer vision and object pattern recognition problems, however, they have been rarely employed in character recognition and detection problems. Local feature, however, is similar to directional features, which have been employed in character recognition applications. In addition, local feature can detect corners and thus it is suitable for detecting characters, which are generally comprised of many corners. For evaluating the performance of the local feature, an experimental result was done and its results showed that SURF, i.e., a simple gradient feature, can detect about 70% of characters in scenery images. Then the saliency map was employed as an additional feature to the local feature. This trial is based on the expectation that scenery characters are generally printed to be salient and thus higher salient area will have a higher probability to be a character area. An experimental result showed that this expectation was reasonable and we can have better discrimination accuracy with the saliency map.
HomeMesh: a low-cost indoor wireless mesh for home networking

Wi-Fi access technology has become popular in recent years. Many users nowadays use Wi-Fi to gain wireless access to the Internet from offices, public libraries, shopping malls, homes, and other places. However, current Wi-Fi deployment is limited to areas where wired LAN is available. Due to its relatively short transmission range in indoor environments (typically several tens of meters), Wi-Fi coverage needs to be extended significantly to full coverage of a certain area. The wireless mesh network (WMN) is a practical and effective solution. In this article we present HomeMesh, an off-the-shelf, simple, and cost-effective WMN for the indoor home environment. HomeMesh is based on simple protocols, implementable in normal notebooks or PCs, and is compatible with existing Wi-Fi APs and clients (i.e., no AP and client modifications). To achieve better end-to-end delay and throughput, HomeMesh dynamically selects its access path based on the ETX metric. We have implemented HomeMesh and conducted proofof- concept experiments in an indoor environment. Our mesh solution is shown to be effective in improving Wi-Fi services.
A 5-Day High-Fat, High-Calorie Diet Impairs Insulin Sensitivity in Healthy, Young South Asian Men but Not in Caucasian Men

South Asians (SAs) develop type 2 diabetes at a younger age and lower BMI compared with Caucasians (Cs). The underlying cause is still poorly understood but might result from an innate inability to adapt to the Westernized diet. This study aimed to compare the metabolic adaptation to a high-fat, high-calorie (HFHC) diet between both ethnicities. Twelve healthy, young lean male SAs and 12 matched Cs underwent a two-step hyperinsulinemic-euglycemic clamp with skeletal muscle biopsies and indirect calorimetry before and after a 5-day HFHC diet. Hepatic triglyceride content (HTG) and abdominal fat distribution were assessed using magnetic resonance imaging and spectroscopy. At baseline, SAs had higher insulin clamp levels than Cs, indicating reduced insulin clearance rate. Despite the higher insulin levels, endogenous glucose production was comparable between groups, suggesting lower hepatic insulin sensitivity in SAs. Furthermore, a 5-day HFHC diet decreased the insulin-stimulated (nonoxidative) glucose disposal rate only in SA. In skeletal muscle, no significant differences were found between groups in insulin/mammalian target of rapamycin signaling, metabolic gene expression, and mitochondrial respiratory chain content. Furthermore, no differences in (mobilization of) HTG and abdominal fat were detected. We conclude that HFHC feeding rapidly induces insulin resistance only in SAs. Thus, distinct adaptation to Western food may partly explain their propensity to develop type 2 diabetes.
Dose-response relationship between moderate-intensity exercise duration and coronary heart disease risk factors in postmenopausal women.

PURPOSE This study was designed to investigate whether, in a dose-response manner, there would be greater health benefits in a group of postmenopausal women completing 45 minute- vs. 30 minutes of moderate intensity (50% maximal oxygen uptake reserve, VO2R) exercise 5 days . wk(-1). METHODS Apparently healthy but sedentary postmenopausal women (n = 33) were randomized to a nonexercise control group, a 30-minute exercise duration group, or a 45-minute exercise duration group. Exercise training was performed 5 days . wk(-1) for 12 weeks at 50% VO2R. Participants were instructed to not change their usual diet throughout the study. RESULTS Twenty-six women completed the study. After 12 weeks, VO2max increased significantly (p < 0.05) in both 30-minute (0.20 +/- 0.21 L . min(-1)) and 45-minute (0.41 +/- 0.10 L . min(-1)) groups. Repeated measures ANOVA identified a significant interaction between exercise duration and VO2max values (F = 4.72, p < 0.05), indicating that VO2max responded differently to 30-minute and 45-minute exercise durations. Trend analysis showed that body mass, body composition, waist circumference, and high-density lipoprotein cholesterol (HDL-C) changed favorably (p < 0.05) across control, 30-minute, and 45-minute groups. CONCLUSIONS Although most health organizations agree that 150 min . wk(-1) of physical activity will reduce the risk of all-cause and cardiovascular mortality, few randomized, controlled studies have examined whether completing more physical activity than the recommended amount will yield additional benefits. Findings from the present study suggest that there is a dose-response relationship between exercise duration and numerous health outcomes in postmenopausal women, including cardiorespiratory fitness, body mass, body composition, waist circumference, and HDL-C.
Pregnancy decisions of married women living with HIV during wide access to antiretroviral therapy in southern Malawi

Availability of antiretroviral therapy and prevention of mother to child transmission of HIV programmes have increased childbearing decisions in people living with HIV. However, pregnancy decisions of married women living with HIV have not been adequately reported in Malawi. In order to provide information to inform the development of antiretroviral and family planning services targeted to the unique needs of women living with HIV, this study explored pregnancy decisions of women living with HIV in rural southern Malawi. Twenty in-depth interviews on married women living with HIV selected purposively were conducted in two antiretroviral clinics of patrilineal Chikhwawa and matrilineal Chiradzulu districts in 2010. With their pregnancy and child rearing experiences, the women who got pregnant after a positive HIV diagnosis decided to never get pregnant again. Their lived experiences of motherhood when living with HIV play a major role in their pregnancy decisions despite free access to antiretroviral therapy, which has improved the quality of their life’s and survival. Societies in Malawi must accept this behavioural change by married women living with HIV and their needs for family planning. Health care workers must be knowledgeable and sensitive about it and assist women living with HIV who are willing to adapt their pregnant decisions based on living experiences.
Improved algorithm for pattern matching with independent wildcard gaps

Pattern matching is critical in some applications such as biological sequence analysis and text filtering. A wildcard gap matches any subsequence with a length in a specified interval, and introduces much adaptability to patterns. However, most existing works require that gaps in a pattern be identical. In this paper, we define a new pattern matching problem where gaps are independently specified. We develop an efficient algorithm to compute the number of all matches based on pattern decomposed. Experimental results show that our algorithm has better performance in the aspects of time complexity and space complexity.
Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation

AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3′ untranslated regions (3′UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor–α (TNFα) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation–related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs—Let-7 and the synthetic microRNA miRcxcr4—likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
Three-Step Semi-Empirical Radiometric Terrain Correction Approach for PolSAR Data Applied to Forested Areas

In recent decades, most methods proposed for radiometric slope correction involved the backscattering intensity values in synthetic aperture radar (SAR) data. However, these methods are not fully applicable to quad-polarimetric SAR (PolSAR) matrix data. In this paper, we propose a three-step semi-empirical radiometric terrain correction approach for PolSAR forest area data. The three steps of terrain effects correction are: polarisation orientation angle (POA), effective scattering area (ESA), and angular variation effect (AVE) corrections. We propose a novel method to determine adaptively the “n” value in the third step by minimising the correlation coefficient between corrected backscattering coefficients and the local incidence angle; we then constructed the correction coefficients matrix and used it to correct PolSAR matrix data. PALSAR-2 HBQ (L-band, quad-polarisation) data were used to verify the proposed method. After three-step correction, differences between front and back slopes were significantly reduced. Our results indicate that POA, ESA, and AVE corrections are indispensable steps to producing PolSAR data. In the POA correction step, horizontal–vertical (HV) polarisation was maximally influenced by the POA shift. The max deviation of the POA correction was greater than 1 dB for HV polarisation and approximately 0.5 dB for HH/VV polarisation at an intermediate shift angle (±20°). Based on Light Detection and Ranging (LiDAR)-derived forest aboveground biomass (AGB) data, we analysed the relationship between forest AGB and backscattering coefficient; the correlation was improved following the terrain correction. HV polarisation had the best correlation with forest AGB (R = 0.81) and the correlation improved by approximately 0.3 compared to the uncorrected data.
C-NAIL® - a new implant for minimally-invasive treatment of intraarticular calcaneal fractures

The treatment of dislocated intra-articular fractures of calcaneus gives a lot of debates between the orthopaedic surgeons. Minimally-invasive techniques beside offering good reduction of the fracture have lesser complications and for this reason tend to replace the open procedures. In this paper, we want to describe a new method of minimally-invasive technique used in the treatment of intra-articular calcaneal fractures and internal fixation with C-NAIL®. The nail offers the possibility to insert up to seven screws into the calcaneus: two sustentacular screws, three latero-medial screws into the tuberosity and anterior process and 2 supero-inferior into the tuberosity. The first step of the procedure is the closed reduction of the calcaneal tuberosity to the sustentacular fragment and open reduction and internal fixation of the posterior facet through a 3-cm long incision made below the apex of the lateral malleolus. Second step in the insertion of the nail via a minimal incision just below the insertion of the Achille tendon. The nail and the screws creates an angularly stable fixation; the main stability is obtained by inserting the two screws into the sustentaculum.
Determinants of functional outcome in hip fracture patients: the role of specific neuropsychiatric symptoms

Abstract Background: The correlation between single neuropsychiatric symptoms and functional outcome in hip fracture patients is little investigated in the literature, and it is not yet established which neuropsychiatric symptoms are the most important determinants of functional outcome. Aim: To determine which neuropsychiatric symptoms are the most important determinants of functional outcome. Methods: This prospective study was carried out in 204 consecutive patients with primary diagnosis of hip fracture admitted to our Rehabilitation Unit for a course of rehabilitation. Neuropsychiatric symptoms were assessed at admission with the Neuropsychiatric Inventory (NPI). Outcome measures of rehabilitation were: final score, efficiency and effectiveness in motor-Functional Independence Measure (motor-FIM), and discharge destination. Pearson's correlation coefficients were used to assess the relationship between NPI variables and the outcome measures, while backward stepwise regression was used to identify determinants of the outcome measures. Results: Pearson's correlation showed that night-time behavior disturbances were related to all outcome measures, while agitation, depression, elation, apathy, disinhibition and irritability were significantly related to motor-FIM outcomes. At multivariate regression analysis agitation was the only determinant of final motor-FIM score, while irritability was the only determinant of efficiency and effectiveness in motor-FIM score. No neuropsychiatric symptom was a determinant of discharge destination. Conclusions: This study highlights that in hip fracture patients there are relationships between specific neuropsychiatric symptoms and functional outcome. Among the neuropsychiatric symptoms, irritability and agitation are the most important. They are associated to poor functional outcome and are the only determinants of motor-FIM outcome measures. Implications for Rehabilitation Relationships between specific neuropsychiatric symptoms and functional outcome have not been clearly described in hip fracture patients. Irritability and agitation have been shown to have the strongest relationship with poor functional outcomes. Appropriate identification, assessment and treatment of neuropsychiatric symptoms may be useful to physicians for the management of hip fracture patients.
Characterization of Apoptosis Induced by Fucoxanthin in Human Promyelocytic Leukemia Cells

Apoptosis induced by fucoxanthin in HL-60 cells was associated with a loss of mitochondrial membrane potential at an early stage, but not with an increase in reactive oxygen species. Fucoxanthin treatment caused cleavages of procaspase-3 and poly (ADP-ribose) polymerase without any effect on the protein level of Bcl-2, Bcl-XL, or Bax. Apoptosis induction by fucoxanthin may be mediated via mitochondrial membrane permeabilization and caspase-3 activation.
Multi-user Feedback for Large-scale Cross-lingual Ontology Matching

Automatic matching systems are introduced to reduce the manual workload of users that need to align two ontologies by finding potential mappings and determining which ones should be included in a final alignment. Mappings found by fully automatic matching systems are neither correct nor complete when compared to gold standards. In addition, automatic matching systems may not be able to decide which one, among a set of candidate target concepts, is the best match for a source concept based on the available evidence. To handle the above mentioned problems, we present an interactive mapping Web tool named ICLM (Interactive Cross-lingual Mapping), which aims to improve an alignment computed by an automatic matching system by incorporating the feedback of multiple users. Users are asked to validate mappings computed by the automatic matching system by selecting the best match among a set of candidates, i.e., by performing a mapping selection task. ICLM tries to reduce users’ effort required to validate mappings. ICLM distributes the mapping selection tasks to users based on the tasks’ difficulty, which is estimated by considering the lexical characterization of the ontology concepts, and the confidence of automatic matching algorithms. Accordingly, ICLM estimates the effort (number of users) needed to validate the mappings. An experiment with several users involved in the alignment of large lexical ontologies is discussed in the paper, where different strategies for distributing the workload among the users are evaluated. Experimental results show that ICLM significantly improves the accuracy of the final alignment using the strategies proposed to balance and reduce the user workload.
Impact of Domestic Care Environment on Trauma and Posttraumatic Stress Disorder among Orphans in Western Kenya

Objective The aim of this study was to determine the impact of the domestic care environment on the prevalence of potentially traumatic events (PTEs) and posttraumatic stress disorder (PTSD) among orphaned and separated children in Uasin Gishu County, western Kenya. Methods A total of 1565 (55.5% male) orphaned and separated adolescents aged 10–18 years (mean 13.8 years, sd 2.2), were assessed for PTSD and PTEs including bullying, physical abuse and sexual abuse. In this sample, 746 lived in extended family households, 746 in Charitable Children's Institutions (CCIs), and 73 on the street. Posttraumatic stress symptom (PTSS) scores and PTSD were assessed using the Child PTSD Checklist. Results Bullying was the commonest PTE in all domestic care environments, followed by physical and sexual abuse. All PTEs were commonest among the street youth followed by CCIs. However, sexual abuse was more prevalent in households than in CCIs. Prevalence of PTSD was highest among street youth (28.8%), then households (15.0%) and CCIs (11.5%). PTSS scores were also highest among street youth, followed by CCIs and households. Bullying was associated with higher PTSS scores and PTSD odds than either sexual or physical abuse. Conclusion This study demonstrated differences in distribution of trauma and PTSD among orphaned and separated children in different domestic care environments, with street youth suffering more than those in CCIs or households. Interventions are needed to address bullying and sexual abuse, especially in extended family households. Street youth, a heretofore neglected population, are urgently in need of dedicated mental health services and support.
Nonlinear Thrust Controller for Marine Propellers in Four-Quadrant Operations

In this paper a nonlinear thrust controller for a marine propeller in four-quadrant operations is presented. It is a shaft speed controller where the desired velocity is computed based on the desired propeller thrust and on the torque losses, estimated with a nonlinear observer. Experimental results are provided to demonstrate the effectiveness of the controller. The proposed scheme shows improved performance in thrust production when compared to traditional shaft speed and torque control.
An object-oriented design of a World Model for autonomous city vehicles

This paper presents an object-oriented world model for the road traffic environment of autonomous (driver-less) city vehicles. The developed World Model is a software component of the autonomous vehicle's control system, which represents the vehicle's view of its road environment. Regardless whether the information is a priori known, obtained through on-board sensors, or through communication, the World Model stores and updates information in real-time, notifies the decision making subsystem about relevant events, and provides access to its stored information. The design is based on software design patterns, and its application programming interface provides both asynchronous and synchronous access to its information. Experimental results of both a 3D simulation and real-world experiments show that the approach is applicable and real-time capable.