Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneous Binding and Central Nervous System Distribution of the Multitargeted Kinase Inhibitor Ponatinib Restrict Orthotopic Efficacy in a Patient-Derived Xenograft Model of Glioblastoma

This study investigated how differences in drug distribution and free fraction at different tumor and tissue sites influence the efficacy of the multikinase inhibitor ponatinib in a patient-derived xenograft model of glioblastoma (GBM). Efficacy studies in GBM6 flank (heterotopic) and intracranial (orthotopic) models showed that ponatinib is effective in the flank but not in the intracranial model, despite a relatively high brain-to-plasma ratio. In vitro binding studies indicated that flank tumor had a higher free (unbound) drug fraction than normal brain. The total and free drug concentrations, along with the tissue-to-plasma ratio (Kp) and its unbound derivative (Kp,uu), were consistently higher in the flank tumor than the normal brain at 1 and 6 hours after a single dose in GBM6 flank xenografts. In the orthotopic xenografts, the intracranial tumor core displayed higher Kp and Kp,uu values compared with the brain-around-tumor (BAT). The free fractions and the total drug concentrations, hence free drug concentrations, were consistently higher in the core than in the BAT at 1 and 6 hours postdose. The delivery disadvantages in the brain and BAT were further evidenced by the low total drug concentrations in these areas that did not consistently exceed the in vitro cytotoxic concentration (IC50). Taken together, the regional differences in free drug exposure across the intracranial tumor may be responsible for compromising efficacy of ponatinib in orthotopic GBM6.
Alcohol consumption increases basal extracellular glutamate in the nucleus accumbens core of Sprague–Dawley rats without increasing spontaneous glutamate release

Glutamate neurotransmission in the nucleus accumbens core (NAc) mediates ethanol consumption. Previous studies using non‐contingent and voluntary alcohol administration in inbred rodents have reported increased basal extracellular glutamate levels in the NAc. Here, we assessed basal glutamate levels in the NAc following intermittent alcohol consumption in male Sprague‐Dawley rats that had access to ethanol for 7 weeks on alternating days. We found increased basal NAc glutamate at 24 h withdrawal from ethanol and thus sought to identify the source of this glutamate. To do so, we employed a combination of microdialysis, slice electrophysiology and western blotting. Reverse dialysis of the voltage‐gated sodium channel blocker tetrodotoxin did not affect glutamate levels in either group. Electrophysiological recordings in slices made after 24 h withdrawal revealed a decrease in spontaneous excitatory postsynaptic current (sEPSC) frequency relative to controls, with no change in sEPSC amplitude. No change in metabotropic glutamate receptor 2/3 (mGlu2/3) function was detected as bath application of the mGlu2/3 agonist LY379268 decreased spontaneous and miniature EPSC frequency in slices from both control and ethanol‐consuming rats. The increase in basal glutamate was not associated with changes in the surface expression of GLT‐1, however, a decrease in slope of the no‐net‐flux dialysis function was observed following ethanol consumption, indicating a potential decrease in glutamate reuptake. Taken together, these findings indicate that the increase in basal extracellular glutamate occurring after chronic ethanol consumption is not mediated by an increase in action potential‐dependent glutamate release or a failure of mGlu2/3 autoreceptors to regulate such release.
Accuracy of forced oscillation technique to assess lung function in geriatric COPD population

Introduction Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population. Aims To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients. Study design A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812. Methods Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. “Resistance” and “reactance” FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation. Results In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4–0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07–0.49 vs 0.61–0.67), small airway (r=0.05–0.48 vs 0.56–0.65), and lung volume (r=0.12–0.29 vs 0.43–0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not. Conclusion FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance parameters were better than resistance parameters in correlation with air trapping.
Microfluidic surface-enhanced Raman scattering sensor with monolithically integrated nanoporous gold disk arrays for rapid and label-free biomolecular detection

Abstract. We present a microfluidic surface-enhanced Raman scattering (SERS) sensor for rapid and label-free biomolecular detection. Our sensor design mitigates a common limiting factor in microfluidic SERS sensors that utilize integrated nanostructures: low-efficiency transport of biomolecules to nanostructured surface which adversely impacts sensitivity. Our strategy is to increase the total usable nanostructured surface area, which provides more adsorption sites for biomolecules. Specifically, a nanoporous gold disk (NPGD) array, a highly effective SERS substrate, has been monolithically integrated inside a microfluidic chip. Individual NPGD is known to feature an order of magnitude larger surface area than its projected disk area. The increased surface area arises from nanoscale pores and ligaments three-dimensionally distributed in the NPGD, which manifest themselves as high-density SERS hot-spots. High-density NPGD arrays further guarantee large coverage of these hot-spots on the microchannel floor. The sensor performance has been demonstrated using Rhodamine 6G to quantify spatial uniformity and determine the shortest detection time. Next, the sensor is applied to detect two biomolecules, dopamine and urea, with unprecedented detection limit and speed compared to other existing microfluidic SERS sensors. The sensor holds great promise in point-of-care applications for various biomolecular detections.
Profile of Secondary Glaucoma in A Semi Urban Tertiary Health Care Hospital In Nigeria

Glaucoma is the second-most-frequent cause of blindness in the world, with a total of 5.2 million blind people as a result of this disease; 80% live in developing countries [1]. Glaucoma is responsible for 16% of blindness in Nigerian adults and the foremost cause of irreversible blindness among Nigerian adults [2]. In a multicentre study involving 2 tertiary eye institutions, 7 secondary eye centres with eye care facilities in Lagos, a total of 6240 patients visited the outpatient department over the 4-week period, out of which 1577 (25.3%) were glaucoma patients [3]. Glaucoma visits constitute a significant proportion of eye clinic visits and substantial manpower, infrastructure, and equipments are usually mobilized for its optimal management [3]. Glaucoma can be primary or secondary. Secondary glaucoma is a form of glaucoma in which the aetiology is traceable to an ocular or systemic pathology. Secondary glaucoma refers to any form of glaucoma in which there is an identifiable cause of increased intraocular pressure (IOP) resulting in optic nerve damage with or without vision loss [4]. As with primary glaucoma, secondary glaucoma can be of open angle or angle closure type which can be unilateral or bilateral. Most primary glaucomas are managed by early diagnosis and treatment however secondary glaucomas differ from primary by the fact that, if the primary pathology is treated properly and the possibility of secondary glaucoma is kept in mind, glaucomatous damage can be easily prevented [4]. Early detection of the risk factors and aetiology of secondary glaucoma can help to avoid progression of this disease. Ocular trauma, cataract, diabetic, hypertension and infectious uveitis represent special risks for developing secondary glaucoma [1]. Abstract
Human Cortical Traveling Waves: Dynamical Properties and Correlations with Responses

The spatiotemporal behavior of human EEG oscillations is investigated. Traveling waves in the alpha and theta ranges are found to be common in both prestimulus and poststimulus EEG activity. The dynamical properties of these waves, including their speeds, directions, and durations, are systematically characterized for the first time, and the results show that there are significant changes of prestimulus spontaneous waves in the presence of an external stimulus. Furthermore, the functional relevance of these waves is examined by studying how they are correlated with reaction times on a single trial basis; prestimulus alpha waves traveling in the frontal-to-occipital direction are found to be most correlated to reaction speeds. These findings suggest that propagating waves of brain oscillations might be involved in mediating long-range interactions between widely distributed parts of human cortex.
The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs

Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I–III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.
Increasing the expressive power of gesture-based interaction on mobile devices. (Augmenter le pouvoir d'expression de l'interaction gestuelle sur les appareils mobiles)

Current mobile interfaces let users directly manipulate the objects displayed on the screen with simple stroke gestures, e.g. tap on soft buttons or menus or pinch to zoom. To access a larger command space, the users are often forced to go through long steps, making the interaction cumbersome and inefficient. More complex gestures offer a powerful way to access information quickly and to perform a command more efficiently [5]. However, they are more difficult to learn and control. Gesture typing [78] is an interesting alternative to input text: it lets users draw a gesture on soft keyboards to enter text, from the first until the final letter in a word. In this thesis, I increase the expressive power of mobile interaction by leveraging the gesture’s shape and dynamics and the screen space to produce rich output, to invoke commands, and to facilitate appropriation in different contexts of use. I design "Expressive Keyboard" that transforms the gesture variations into rich output, and demonstrate several applications in the context of textbased communication. As well, I propose "CommandBoard", a gesture keyboard that lets users efficiently select commands from a large command space while supporting the transition from novices to experts. I demonstrate different applications of "CommandBoard", each offers users a choice, based on their cognitive and motor skills, as well as the size and organization of the current command set. Altogether, these techniques give users more expressive power by leveraging human’s motor control and cognitive ability to learn, to control, and to appropriate.
A preliminary study of water quality index in Terengganu River Basin, Malaysia

The Malaysian Department of Environment-Water Quality Index (DOE-WQI) was determined for the Terengganu River basin which is located at the coastal water of the southern South China Sea between July and October 2008. Monthly samplings were carried out at ten sampling stations within the basin. Six parameters listed in DOE-WQI were measured based on standard methods: pH, dissolved oxygen (DO), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS) and ammonical nitrogen (AN). The results indicated the impact of various anthropogenic activities which contribute to high values of BOD, COD, TSS and AN at middle and downstream stations, as compared with the upstream of the basin. The reverses were true for the pH and DO values. The DOE-WQI ranged from 71.5-94.6% (mean 86.9%), which corresponded to a classification status range from slightly polluted to clean. With respect to the Malaysia National Water Quality Standards (NWQS), the level of most of the parameters measured remained at Class I which is suitable for the sustainable conservation of the natural environment, for water supply without treatment and as well as for very sensitive aquatic species. It is suggested that monitoring should be carried out continuously for proper management of this river basin.
Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect

Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS) in semi-field conditions and long lasting insecticidal nets (LLINs) in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46%) but high for other predominant species such as Mansonia africana (93% to 97%). There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001). Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible “Kisumu”, mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted.
Self-harm in first-episode psychosis

Background Little is known about self-harm occurring during the period of untreated first-episode psychosis. Aims To establish the prevalence, nature, motivation and risk factors for self-harm occurring during the untreated phase of first-episode psychosis. Method As part of the æSOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study, episodes of self-harm were identified among all incident cases of psychosis presenting to services in south-east London and Nottingham over a 2-year period. Results Of the 496 participants, 56 (11.3%) had engaged in self-harm between the onset of psychotic symptoms and first presentation to services. The independent correlates of self-harm were: male gender, belonging to social class I/II, depression and a prolonged period of untreated psychosis. Increased insight was also associated with risk of self-harm. Conclusions Self-harm is common during the pre-treatment phase of first-episode psychosis. A unique set of fixed and malleable risk factors appear to operate in those with first-episode psychosis. Reducing treatment delay and modifying disease attitudes may be key targets for suicide prevention.
Low-frequency dispersion and state dependency in modem microwave III-V HEMTs

An AlGaN/GaN HEMT- and an InAlAs/InGaAs mHEMT technology, both with a gate-length of 100 nm, are investigated w.r. t. low-frequency dispersion and state dependency vs. average gate and drain voltages. Based on a comprehensive DC-CW and pulsed-RF small-signal characterization, it is shown that the GaN HEMT shows both effects, while the mHEMT is nearly free of state dependency. A new formulation of the recently proposed integral transform large-signal FET model is capable of describing both effects in pulsed-RF and even in CW load-pull operation conditions.
Empirical Research on Corporate Social Responsibility and Financial Performance

this study is conducted for investigating the corporate social responsibility (CSR) disclosure practices of listed firms in the textile and apparel industry Vietnam and their determinants. A checklist of 20 attributes was developed to capture the social and environmental disclosures from the annual reports of 56 firms in textile and apparel industry on the Vietnam Stock Exchange over a two-year period from 2016 to 2017. The determinants of the disclosure are proxied by the firm, financial performance (profitability) and auditor type. The data obtained were analysed using descriptive statistics, correlation, and regression. The results show that the level of CSR is 38%, made up of social disclosure (63%) and environmental disclosure (6%). Findings also reveal that CSR is influenced by firm size, auditor type; and profitability. This paper recommends a mandatory CSR reporting framework in line with international practices for all listed firms in the textile and apparel industry Vietnam
Monozygotic Twins With Neurofibromatosis Type 1 (NF1) Display Differences in Methylation of NF1 Gene Promoter Elements, 5' Untranslated region, Exon and Intron 1

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by heterozygotic inactivation of the NF1 tumor suppressor gene at 17q11.2. The associated phenotypes are highly variable, and modifying genes have been proposed to explain at least in part the intriguing expressivity. Given that haploinsufficiency of the NF1 gene product neurofibromin is responsible for some of the clinical manifestations, variations in expression of the wildtype NF1 allele might modify the phenotype. We therefore investigated epigenetic molecular modifications that could result in variable expression of the normal NF1 allele. To exclude confounding by DNA sequence variations, we analyzed monozygotic twin pairs with NF1 who presented with several discordant features. We fine-mapped the methylation pattern of a nearly 1 kb NF1 promoter region in lymphocytes of 8 twin pairs. All twin pairs showed significant intra-pair differences in methylation, especially of specific promoter subregions such as 5'UTR, exon 1 and intron 1 (+7 to +622), transcription factor binding sites and promoter elements like NF1HCS. Furthermore, we detected significant intra-pair differences in cytosine methylation for the region from -249 to -234 with regard to discordance for optic glioma with a higher grade of methylation in glioma cases. In conclusion, our findings of epigenetic differences of the NF1 promoter in leukocytes within mono zygotic twin pairs may serve as a proof of principle for other tissues. The results point towards a role of methylation patterns of the normal NF1 allele for expression differences and for modification of the NF1 phenotype.
econstor Make Your Publications Visible . A Service of zbw

Identifying Sorting: In Theory We argue that using wage data alone, it is virtually impossible to identify whether Assortative Matching between worker and firm types is positive or negative. In standard competitive matching models the wages are determined by the marginal contribution of a worker, and the marginal contribution might be higher or lower for low productivity firms depending on the production function. For every production function that induces positive sorting we can find a production function that induces negative sorting but generates identical wages. This arises even when we allow for non-competitive mismatch, for example due to search frictions. Even though we cannot identify the sign of the sorting, we can identify the strength, i.e., the magnitude of the cross-partial, and the associated welfare loss. While we show analytically that standard fixed effects regressions are not suitable to recover the strength of sorting, we propose an alternative procedure that measures the strength of sorting in the presence of search frictions independent of the sign of the sorting. JEL Classification: J31, C78