Miracle-dz/UniFAR-FTUs huggingface dataset:
A longitudinal diffusion tensor imaging study in symptomatic Huntington's disease

Objective The striatum and its projections are thought to be the earliest sites of Huntington's disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging. Method Diffusion weighted images were acquired in 18 HD patients and in 17 healthy controls twice, 1 year apart. Mean diffusivity (MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures. Results MD was significantly higher in the caudate and putamen bilaterally for patients compared with controls at both time points although there were no significant MD differences in the thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year 1. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini-Mental State Examination scores and caudate MD and putamen MD at both time points in HD. Conclusions It appears that microstructural changes influence cognitive status in HD. Although MD was significantly higher in HD compared with controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.
Cytogenetic and molecular study of 32 Down syndrome families: potential leukaemia predisposing role of the most proximal segment of chromosome 21q

Down syndrome (DS) children have a 10–20‐fold increased risk of developing ALL or AML compared to non‐DS children. An increased disomic homozygosity of the polymorphic DNA markers in the pericentromeric region of chromosome 21q (21q11) has repeatedly been found in DS patients with ANLL‐M7 and DS‐specific transient abnormal myelopoiesis (TAM), compared to the majority of DS subjects without leukaemia. Analysis of cytogenetic heteromorphisms and 26 polymorphic DNA markers from chromosome 21q showed an increased number of pericentromeric crossovers between the non‐disjoined chromosomes in DS‐ANLL cases (3/11), compared to DS‐ALL (0/9) and DS‐non‐leukaemic cases (0/12). These findings are compatible with the model of disomic homozygosity of the predisposing allele of a putative pericentromeric gene, as an explanation for the high prevalence of ANLL in DS.
Assessing the utility and limitations of high throughput virtual screening

Due to low cost, speed, and unmatched ability to explore large numbers of compounds, high throughput virtual screening and molecular docking engines have become widely utilized by computational scientists. It is generally accepted that docking engines, such as AutoDock, produce reliable qualitative results for ligand-macromolecular receptor binding, and molecular docking results are commonly reported in literature in the absence of complementary wet lab experimental data. In this investigation, three variants of the sixteen amino acid peptide, α-conotoxin MII, were docked to a homology model of the a 3 β 2 -nicotinic acetylcholine receptor. DockoMatic version 2.0 was used to perform a virtual screen of each peptide ligand to the receptor for ten docking trials consisting of 100 AutoDock cycles per trial. The results were analyzed for both variation in the calculated binding energy obtained from AutoDock, and the orientation of bound peptide within the receptor. The results show that, while no clear correlation exists between consistent ligand binding pose and the calculated binding energy, AutoDock is able to determine a consistent positioning of bound peptide in the majority of trials when at least ten trials were evaluated.
Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland

The tear-producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. The lacrimal gland possesses many features that make it an excellent model in which to investigate tubulogenesis, but the cell types and lineage relationships that drive lacrimal gland formation are unclear. Using single-cell sequencing and other molecular tools, we reveal novel cell identities and epithelial lineage dynamics that underlie lacrimal gland development. We show that the lacrimal gland from its earliest developmental stages is composed of multiple subpopulations of immune, epithelial and mesenchymal cell lineages. The epithelial lineage exhibits the most substantial cellular changes, transitioning through a series of unique transcriptional states to become terminally differentiated acinar, ductal and myoepithelial cells. Furthermore, lineage tracing in postnatal and adult glands provides the first direct evidence of unipotent KRT5+ epithelial cells in the lacrimal gland. Finally, we show conservation of developmental markers between the developing mouse and human lacrimal gland, supporting the use of mice to understand human development. Together, our data reveal crucial features of lacrimal gland development that have broad implications for understanding epithelial organogenesis. Summary: Single-cell sequencing combined with a battery of molecular tools reveals novel features of cellular dynamics and differentiation during lacrimal gland development in mice.
Spatiotemporal trajectory models for metalevel target tracking

Physical sensor-based target tracking is a classical problem that has been studied in great detail [1], [2]. This article presents metalevel tracking middleware algorithms to help human radar operators interpret tracks in order to detect and visualize suspicious spatiotemporal target trajectories. While state space models are ideal for target tracking, the main idea in this article is that stochastic context-free grammar (SCFG) models are also useful for modeling and interpreting trajectories.
Corporate social responsibility in the mining industry: an exploration of host-communities’ perceptions and expectations in a developing-country

Purpose The purpose of this paper is to explore how and what drives corporate social responsibility (CSR) in host communities of mining companies in developing countries. Design/methodology/approach To address this knowledge gap, this paper used Ghana as a test case and conducted 24 in-depth interviews with participants drawn from mining host communities. Findings The paper discovered that while CSR is broadly understood and encompasses six thematic categories in the mining host communities, there are emphases on philanthropic and environmental responsibilities. Contrary to the evidence found in other studies, this paper discovered that CSR rhetoric plays a more positive/significant role than so far explored in CSR research, as it incentivizes the host communities to push for the fulfilment of their CSR expectations and/or CSR initiatives proposed by mining companies. Research limitations/implications Quantitative studies are needed to strengthen the findings from the present paper. Practical implications Because developing countries share similar socio-economic and geo-political realities, the findings of this paper may be applicable not only for CSR advocates, but also for policy-makers in developing countries. Originality/value The paper provides new inputs from a developing country perspective to the current debate about the CSR performance of the extractive industry.
Physicochemical and Biological Characterization of Pep‐1/Elastin Complexes

Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell‐penetrating peptides have been studied to increase the penetration of therapeutic proteins into and through the skin. Cell‐penetrating peptides facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a cell‐penetrating peptide called Pep‐1. As the biophysical characteristics of cell‐penetrating peptide/protein complexes have been linked with their biological responses, in this study, we investigated biophysical properties of Pep‐1/elastin complexes (ratio 10:1) stored in three temperatures (−20 °C, 4 °C and 25 °C) by photon correlation spectroscopy, circular dichroism and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In‐Vivo FX Pro Imaging System.
Major ocular glands (Harderian gland and lacrimal gland) of the musk shrew (Suncus murinus) with a review on the comparative anatomy and histology of the mammalian lacrimal glands

The Harderian gland of the musk shrew Suncus murinus is elongated anteroposteriorly from in front of the eye to behind the ear. The gland is divided into two portions: an anterior portion (A portion) and a posterior portion (P portion). The single secretory duct of the gland emerges from the anterior end of the P portion, receives several secretory ducts of the A portion during the course along it, runs around the ventral aspect of the eyeball, and finally opens into the anterior corner of conjunctival sacs. The two portions of the gland show a fundamentally similar histological structure, having a poorly developed intraglandular duct system and wide tubular alveoli. The quantity of lipid vacuoles and stromal connective tissue in the A portion is greater than in the P portion. The lipid vacuoles in both portions are surrounded by unit membranes, but their contents appear different.
Examining the determinants of import demand in Tanzania: An ARDL approach

The study investigates the determinants of aggregate and disaggregated import demand for Tanzania, over the period 1985 to 2015. The study employed the autoregressive distributed lag (ARDL) bounds testing approach. The empirical results confirm that aggregate import demand is positively determined by investment spending and export of goods and services, both in the long run and short run, but negatively determined by trade liberalisation policy only in the short run. The long-run results confirm that import demand for consumer goods is positively determined by gross national income, but negatively determined by trade liberalisation policy. The import demand for intermediate goods is found to be positively determined by exports of goods and services and gross national income, but negatively determined by trade liberalisation policy. The results further show that exports of goods and services and relative import price are positive determinants of import demand for capital goods. In the short run, the results confirm that import demand for consumer goods is positively determined by export of goods and services, gross national income and import demand for consumer goods in the previous period, but negatively determined by gross national income in the previous period and trade liberalisation policy. The results further confirm that the import demand for intermediate goods is positively determined by exports of goods and services, but negatively determined by gross national income. Lastly, import demand for capital goods is found to be positively determined by import demand for capital goods in the previous period, exports of goods and services, and relative import price.
Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants

Obesity is a multifactorial disorder with high heritability (50–75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.
Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that occurs upon mutation of either the TSC1 or TSC2 genes, which encode the protein products hamartin and tuberin, respectively. Here, we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). First, coexpression of hamartin and tuberin repressed phosphorylation of 4E-BP1, resulting in increased association of 4E-BP1 with eIF4E; importantly, a mutant of TSC2 derived from TSC patients was defective in repressing phosphorylation of 4E-BP1. Second, the activity of S6K1 was repressed by coexpression of hamartin and tuberin, but the activity of rapamycin-resistant mutants of S6K1 were not affected, implicating mTOR in the TSC-mediated inhibitory effect on S6K1. Third, hamartin and tuberin blocked the ability of amino acids to activate S6K1 within nutrient-deprived cells, a process that is dependent on mTOR. These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mTOR and suggest that the formation of tumors within TSC patients may result from aberrantly high levels of mTOR-mediated signaling to downstream targets.
Nanoporous alumina membrane and nanoparticle based microfluidic sensing platform for direct DNA detection

Nucleic acids based detection has become increasingly important for biomedical diagnostics, environmental monitoring and food screening. In this paper, a nanoporous alumina membrane and nanoparticles based sensing platform has been developed for direct DNA detection. Single stranded DNA (ssDNA) was first covalently immobilized on the nanopore walls via (3-glycidoxypropyl) trimethoxysilane (GPMS). Double strand DNA (dsDNA) hybridization in the nanopores induced blockage in the nanopores, which could be detected by electrochemical impedance spectroscopy (EIS). The blockage signal was then amplified by DNA with gold nanoparticles (AuNPs) and silver catalytic deposition method. This platform is promising for simple, rapid and sensitive DNA detection.
Evaluation of percutaneously adjustable hydraulic urethral sphincters with and without induced mechanical failure.

OBJECTIVE To describe (1) the radiographic appearance of intact hydraulic urethral sphincters (HUS) and (2) the success of leak detection using clinically feasible methods. STUDY DESIGN Prospective, blinded in vitro study. SAMPLE POPULATION Thirty HUS devices (10 each of 8, 10, and 12 mm diameter sizes). MATERIALS AND METHODS All devices were inflated with saline (0.9% NaCl) solution to complete occlusion, inspected, and weighed over a 24-hour period for manufacturing defects. HUS phantoms were created to mimic surrounding soft tissues. One randomly selected HUS of each size was evaluated radiographically at different inflation volumes and angles. All HUS systems were then evaluated in random order before and after puncture with volumetry, manometry, radiography, and contrast fluoroscopy. Volumetry was the total volume (mL) retrieved from each HUS system. Manometry was the pressure (cm H2 O) within each HUS system. The HUS devices were filled to a known volume before each measurement. RESULTS When all HUS sizes were considered, volumetry did not reveal significant differences before and after puncture, but manometry was significantly different (P < .001). Radiography was 63.8% sensitive and 88.3% specific for puncture diagnosis, with inter-observer agreement of 0.58. Contrast fluoroscopy was 78.4% sensitive and 100% specific, with inter-observer agreement of 0.97. CONCLUSIONS Of those methods tested, contrast fluoroscopy was the most sensitive, specific, and consistent method of leak detection. Manometry was also helpful, but may be difficult to use clinically. Volumetry and radiography were relatively poor indicators of leakage in this model.
Inaccuracy of peranesthetic gastric intubation for emptying liquid stomach contents

To assess the accuracy of the method of peranesthetic gastric intubation for emptying the liquid stomach contents, this procedure was tried on 80 patients undergoing general anesthesia. Half of the patients had a double‐barrelled 16F‐Argyle Salem sump tube, length 120 cm, size 16 CH, and the other half had a singlebarrelled stomach tube, length 80 cm, size 25 CH. After emptying the stomach with the tubes 25 ml of glucose was given through the gastric tube to half of the Salem tube group and half of the stomach tube group. Similarly 100 ml of glucose was given to half of the Salem tube group and half of the stomach tube group. After instillation of glucose 25 ml or 100 ml, the Salem tube recovered 21.0 9.1 ml (mean s. d.), median 24 ml, range 6–36 ml or 86.8 26.9 ml, median 92 ml, range 18–136 ml, respectively, and the stomach tube 17.1 10.8 ml, median 18 ml, range 2–34 ml or 54.0 28.5 ml, median 50 ml, range 14–104 ml, respectively. This indicates that the method of gastric intubation for emptying the liquid stomach contents is inaccurate.
Expression of antigens in Immunocytochemical images utilizing an image analysis method

Immunocytochemistry is a common laboratory technique in which the quality of interaction between antibody antigen is evaluated on a cell surface. The amount of binding between antibodies and cancerous cells in Immunocytochemical images indicates how much the antibody is effective for treating the cancerous cell. In this paper, an automated system has been proposed for the first time, to measure such binding, utilizing well-known image processing methods. The experiments are simulated using the collected reference images in this research which can be used as a benchmark in the future researches. Proposing this method leads to an accurate and fast evaluation of the antigens' expression along with more reduced human-error factors.
Analysing activities in the Portuguese secondary schools’ Science Learning Studios

Supervisor: Doctor Vitor Duarte Teodoro, Assistant Professor (Professor Auxiliar com nomeação definitiva), Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa Jury: President: Doctor Maria Paula Pires dos Santos Diogo, Full Professor (Professora Catedrática), School of Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa External examiner: Doctor Teresa Frederica Tojal de Valsassina Heitor, Full Professor (Professora Catedrática), Instituto Superior Técnico, Universidade de Lisboa External examiner: Doctor Pedro Guilherme Rocha dos Reis, Associate Professor (Professor Associado), Instituto de Educação, Universidade de Lisboa Internal examiner: Doctor Carlos Francisco Mafra Ceia, Full Professor (Professor Catedrático), Faculdade de Ciências Sociais e Humanas, Universidade Nova de Lisboa Internal examiner: Doctor Mariana Teresa Gaio Alves, Assistant Professor (Professora Auxiliar com Agregação), Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa Internal examiner: Doctor Francisco José Brito Peixoto, Assistant Professor (Professor Auxiliar), Instituto Universitário de Ciências Psicológicas, Sociais e da Vida
Destabilization of the human epigenome: consequences of foreign DNA insertions.

AIM We previously reported changes of DNA methylation and transcription patterns in mammalian cells that carry integrated foreign DNA. Experiments were now designed to assess the epigenetic consequences of inserting a 5.6 kbp plasmid into the human genome. METHODS Differential transcription and CpG methylation patterns were compared between transgenomic and nontransgenomic cell clones by using gene chip microarray systems. RESULTS In 4.7% of the 28.869 gene segments analyzed, transcriptional activities were up- or downregulated in the transgenomic cell clones. Genome-wide profiling revealed differential methylation in 3791 of > 480,000 CpG's examined in transgenomic versus nontransgenomic clones. CONCLUSION The data document genome-wide effects of foreign DNA insertions on the epigenetic stability of human cells. Many fields in experimental biology and medicine employ transgenomic or otherwise genome-manipulated cells or organisms without considering the epigenetic consequences for the recipient genomes.
Evaluation of anticonvulsant activity of Artocarpus heterophyllus Lam. leaves (Jackfruit) in mice

Artocarpus heterophyllus Lam. (Jackfruit) is traditionally used as anticonvulsant. The aqueous and methanol extracts of leaves of Artocarpus heterophyllus Lam. was evaluated for anticonvulsant activity by using Maximal electroshock (MES) and Strychnine induced convulsions models on Swiss albino mice. The methanol extracts of leaves of Artocarpus heterophyllus Lam. were found to be more significant, while aqueous extract were found to be less significant with regards to anticonvulsant activity. The plant extract exhibited a dose dependent significant (P<0.01) reduction in various phases of epileptic seizure on comparison with the reference standard Diazepam 5mg/kg, p.o. The results indicate the potential of Artocarpus heterophyllus Lam. as an anticonvulsant agent.