Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new methodological developments and applications

In vivo electrotransfer is a physical method of gene delivery in various tissues and organs, relying on the injection of a plasmid DNA followed by electric pulse delivery. The importance of the association between cell permeabilization and DNA electrophoresis for electrotransfer efficiency has been highlighted. In vivo electrotransfer is of special interest since it is the most efficient non‐viral strategy of gene delivery and also because of its low cost, easiness of realization and safety. The potentiality of this technique can be further improved by optimizing plasmid biodistribution in the targeted organ, plasmid structure, and the design of the encoded protein. In particular, we found that plasmids of smaller size were electrotransferred more efficiently than large plasmids. It is also of importance to study and understand kinetic expression of the transgene, which can be very variable, depending on many factors including cellular localization of the protein, physiological activity and regulation. The most widely targeted tissue is skeletal muscle, because this strategy is not only promising for the treatment of muscle disorders, but also for the systemic secretion of therapeutic proteins. Vaccination and oncology gene therapy are also major fields of application of electrotransfer, whereas application to other organs such as liver, brain and cornea are expanding. Many published studies have shown that plasmid electrotransfer can lead to long‐lasting therapeutic effects in various pathologies such as cancer, blood disorders, rheumatoid arthritis or muscle ischemia. DNA electrotransfer is also a powerful laboratory tool to study gene function in a given tissue. Copyright © 2004 John Wiley & Sons, Ltd.
Can Computational Thinking help me? A quantitative study of its effects on education

Some researchers consider that the benefits of Computational Thinking (CT) in education are unclear, and therefore a quantitative study to understand the effects of CT skills in the basic levels of formal education is needed. The present study aims to analyze the effects of CT on the academic performance of students in high school. We seek to answer the following research questions: (RQ1) Can CT increase the problem-solving skills of students in high school? (RQ2) Is CT related to the performance of students in high school? (RQ3) Can CT improve the performance of students in high school? We conducted an analysis between two groups of students with similar profiles belonging to the same population, where the factor CT proficiency is the only feature that distinguishes both groups. The results show that there is a moderate correlation between the performance of evaluated students and their skills of CT developed by computer programming. In addition, we found that students proficient in computer programming have superior performance up to 10.2% in ENEM (National Exam of High School) assessment compared to those with little or no experience level and even better performance 21% in the WASI test problem-solving in students on attending high school.
Concurrent Directional Adaptation of Reactive Saccades and Hand Movements to Target Displacements of Different Size

ABSTRACT When eye and hand movements are concurrently aimed at double-step targets that call for equal and opposite changes of response direction (–10° for the eyes, +10° for the hand), adaptive recalibration of both motor systems is strongly attenuated; instead, hand but not eye movements are changed by corrective strategies (V. Grigorova et al., 2013a). The authors introduce a complementary paradigm, where double-step targets call for a –10° change of eye and a −30° change for hand movements. If compared to control subjects adapting only the eyes or only the hand, adaptive improvements were comparable for the eyes but were twice as large for the hand; in contrast, eye and hand aftereffects were comparable to those in control subjects. The authors concluded that concurrent exposure of eyes and hand to steps of the same direction but different size facilitated hand strategies, but didn't affect recalibration. This finding together with previous one (V. Grigorova et al., 2013a), suggests that concurrent adaptation of eyes and hand reveals different mechanisms of recalibration for step sign and step size, which are shared by reactive saccades and hand movements. However, hand mostly benefits from strategies provoked by the difference in target step sign and size.
A quantitative assessment of the depth sensitivity of an optical topography system using a solid dynamic tissue-phantom

A solid dynamic phantom with tissue-like optical properties is presented, which contains seven discrete targets impregnated with thermochromic pigment located at different depths from the surface. Changes in absorption are obtained in response to localized heating of the targets, simulating haemodynamic changes occurring in the brain and other tissues. The depth sensitivity of a continuous wave optical topography system was assessed successfully using the phantom. Images of the targets have been reconstructed using a spatially variant regularization, and the determined spatial localization in the depth direction is shown to be accurate within an uncertainty of about 3 mm down to a depth of about 30 mm.
Cerebrospinal fluid otorhinorrhoea due to inner-ear malformations: clinical presentation and new perspectives in management.

OBJECTIVE In children cerebrospinal fluid (CSF) otorhinorrhoea can be due to congenital inner-ear malformations. Cochlear dysplasia associated with a defect in the stapes footplate is usually the cause of the CSF leak. Repair of the CSF leak in these cases is usually done by packing the vestibule with muscle or fascia. This traditional method of repair has a 30 to 60 per cent failure rate. MATERIAL AND METHODS CSF otorhinorrhoea due to congenital inner-ear anomalies in four patients was repaired using multiple-layer packing of the vestibule with glue, muscle and fascia, reinforced by a pedicle temporalis muscle graft. Intra-operatively, continous lumbar drainage was performed. RESULTS Repair of the CSF leak was successful in four cases and no recurrence was noticed. Inner-ear magnetic resonance imaging (MRI) using three-dimensional fast-spin echo (3D FSE) T2-weighted imaging (T2WI) and 3D steady-state free precession (FIESTA) sequences was found to be a very helpful, noninvasive investigation to localize the site and route of the CSF leak. CONCLUSIONS Children presenting with recurrent meningitis and CSF rhinorrhoea should be investigated for congenital inner-ear anomalies. In these cases CSF fistulae should be repaired using fibrin or cyanoacrylate glue and intra-operative continuous lumbar drainage; 3D FSE T2WI and 3D FIESTA MRI sequences of the inner ear are helpful.
Colonic Wall Thickening on Computed Tomography Scan and Clinical Correlation. Does it Suggest the Presence of an Underlying Neoplasia?

The widespread use of computed tomography (CT) scanning technology frequently leads to the incidental discovery of thickened bowel wall. The clinical significance of such a CT scan finding is largely under-investigated. The purpose of our study was to determine the incidence of significant clinical pathology and, particularly, neoplasia in patients with abnormally thickened bowel on CT scan examination. This is a single institution retrospective analysis of patients that underwent CT scanning of their abdomen. The radiological picture was correlated with colonoscopic findings. A total of 40 consecutive patients with thickened bowel on CT scan that also underwent colonoscopy were identified and their records were reviewed. Thirty-five patients had no history of previous gastrointestinal disorder and form our study group. The median age of the patients was 69 years (range, 24–97 years). There were 26 female and 9 male patients. The incidental CT finding of bowel wall thickening was the only reason for the colonoscopy in 14 (35%) out of the 40 patients. Eight (23%) patients with thick bowel had colonic neoplasia based on pathology. Five (14%) patients had invasive adenocarcinoma of the colon. Four (11%) of the 5 patients with colon adenocarcinoma did not have any associated gastrointestinal symptoms or signs. One (3%) patient had lymphoma of the colon and two (6%) had benign polyps. Colonoscopy was unremarkable in 10 (28%) patients. The incidental finding of colonic thickening on CT imaging could be associated with underlying colonic malignancy and, more importantly, represent the initial disease presentation. Therefore, we propose that these patients should undergo colonoscopy.
DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma

DEP domain containing 1 (DEPDC1) is a newly identified cancer-related and cell cycle related gene and has been demonstrated as a novel therapeutic target for bladder cancer. However, the functional involvement and therapeutic potential of DEPDC1 in nasopharyngeal carcinoma (NPC) remains unclear. Our results showed that DEPDC1 was overexpressed at both mRNA and protein levels in NPC tissues compared with normal or non-tumor tissues. The siRNA-mediated DEPDC1 depletion resulted in significant inhibition of proliferation and delay in cell cycle progression in both NPC cell lines, CNE-1 and HNE-1. Detailed analysis with indirect immunofluorescence assays revealed that DEPDC1 depletion caused significant mitotic arrest accompanied with mitotic defects such as multipolar spindles and multiple nuclei followed by apoptotic cell death. Notably, DEPDC1 depletion also reduces migration and invasion ability in both cell lines. Consistent with its regulatory role in NF-κB pathway, knockdown of DEPDC1 caused significant upregulation of A20 and downregulation of mutiple NF-κB downstream target genes implicated in proliferation and tumorigenesis (c-Myc, BCL2, CCND1, CCNB1 and CCNB2), and metastasis (MMP2, MMP9, ICAM1, vimentin, Twist1). Moreover, in vivo study demonstrated that DEPDC1 knockdown also caused significant inhibition of tumor growth in the NPC xenograft nude mouse model. Taken together, our present study demonstrated that DEPDC1 is essentially required for the accelerated cell cycle progression and motility in NPC cells, and strongly suggested that DEPDC1 may serve as a novel therapeutic target in NPC.
Relay Assignment in Multiple Source-Destination Cooperative Networks With Limited Feedback

We consider in this paper relay assignment for cooperative systems with mutiple source-destination pairs. The objective here is to assign relays to the source-destination pairs in such a way that all pairs achieve the maximum diversity. In networks with mutiple source-destination pairs, it is normally difficult for destinations to acquire the channel state information (CSI) of the entire network without feedback. To this end, we design a practical limited feedback strategy in conjunction with two relay assignment schemes, i.e., fullset selection and subset selection, which are based on maximizing the minimum end-to-end (E2E) signal to noise ratio (SNR) among all pairs. In this strategy, each destination acquires its SNR, quantizes it, and feeds it back to the relays. The relays then construct the E2E SNR table and select the relay assignment permutation from all possible relay assignment permutations or only a subset of these permutations. We analyze the performance of these schemes over independent Rayleigh fading channels in terms of the worst E2E SNR. We derive closed-form expressions for the E2E bit error rate (BER) and investigate the asymptotic performance at high SNR. We show that relay assignment with quantized CSI can achieve the same first-order diversity as that of the full CSI case, but there is a second-order diversity loss. We also demonstrate that increasing the quantization levels yields performance that is close to that of having full knowledge of the CSI.
Value of laparoscopy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis

The outcome of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on the extent of peritoneal carcinomatosis. The role of laparoscopy in the preoperative assessment of extent of peritoneal carcinomatosis in potential candidates for cytoreductive surgery and HIPEC was evaluated in a consecutive series.
Trypsinogen Activation Peptide Induces HMGB1 Release from Rat Pancreatic Acinar Cells

Abstract Background The development of acute pancreatitis (AP) is associated with intracellular events in pancreatic cells, as well as with early and late inflammatory responses; however, their underlying mechanisms remain unclear. This study investigated trypsinogen activation peptide (TAP)-induced release of high mobility group box-l (HMGB1) from pancreatic acinar cells and how ethyl pyruvate (EP) affects this release. Methodology Pancreatic acinar cells from Sprague Dawley rats were divided into control, TAP (administered TAP), and EP (administered TAP and EP) groups. Cells were collected at 3, 6, 12, and 24 hours after TAP administration to detect HMGB1 mRNA and protein levels using quantitative PCR (qPCR) and Western blotting, respectively. Results The TAP and EP groups exhibited higher levels of HMGB1 mRNA and protein expression (P<0.05) than the control group. The HMGB1 mRNA and protein expression levels also increased with prolonged TAP activity (P<0.05)–especially at 12 and 24 hours (P<0.01)–and showed positive correlations with TAP activity duration (3, 6, 12, and 24 hours) (r=0.971, P<0.01; r=0.966, P<0.01, respectively). Conclusion TAP induces HMGB1 release from pancreatic acinar cells. A positive temporal link exists between early TAP activity and late HMGB1 expression in AP, and EP inhibits HMGB1 release.
Rat Membrane Cofactor Protein (MCP; CD46) Is Expressed Only in the Acrosome of Developing and Mature Spermatozoa and Mediates Binding to Immobilized Activated C31

Abstract The rat analogue of the complement regulator membrane cofactor protein (MCP; CD46) was recently cloned and analysis at the mRNA level suggested that expression was restricted to testis. In light of the proposed roles of human MCP in sperm-egg interaction, we undertook to analyze rat MCP expression at the protein level in order better to address its putative role in fertilization. Recombinant fusion proteins comprising antibody Fc and specific domains of rat MCP were generated and used to develop a monoclonal antibody, MM.1, specific for rat MCP. Immunohistochemistry using these reagents confirmed the reported testis-specific expression of MCP in sexually mature rats and demonstrated that MCP was expressed only by spermatozoa and their immediate precursors in spermiogenesis, spermatids. Prepubertal male rats did not express MCP, and there was no evidence of MCP expression at any site in the embryo. Spermatozoal MCP expression was restricted to the inner acrosomal membrane, exposed only after fixation or induction of the acrosome reaction. Acrosome-reacted but not unreacted spermatozoa bound methylamine-activated C3 immobilized on plastic. The retention of MCP at this subcellular site, which is probably crucial to sperm-egg interaction, and the functional demonstration of binding to activated C3 strengthen suggestions from human studies that MCP may play an important role in fertilization. The reagents and results described here will enable studies of the role of spermatozoal MCP in sperm-egg interaction using a relevant animal model system.
Mortalité différentielle en Suisse 1900-2005

La presente etude traite principalement deux questions fondamentales. Quels facteurs exercent l’influence la plus determinante sur l’esperance de vie ? Comment tenir compte concretement de ces facteurs dans le cadre de la reforme du systeme de retraite ? Les premieres analyses portant sur l’influence de la nationalite et du niveau de revenu n’ont pas donne de resultats. En revanche, il ressort que les professions du secteur tertiaire connaissent un risque de deces plus faible que les professions du secteur secondaire. Il est cependant impossible d’etablir une classification plus fine par branche economique, dans la mesure ou l’esperance de vie depend fortement de la fonction exercee. Pour les auteurs de l’etude, les differences les plus marquees dans le risque de mortalite apres le depart a la retraite sont liees au niveau de formation. Plus le niveau de formation est eleve, plus le risque de mortalite apres 65 ans est faible. Ce lien confirme pour la Suisse les resultats observes a l’echelle de l’ensemble des pays industrialises. Se basant sur l’indicateur du niveau de formation, les auteurs ont elabore divers modeles de differenciation de l’âge de la retraite. Ces modeles doivent montrer qu’il est theoriquement possible de differencier l’âge ordinaire de la retraite en tenant compte des differences de mortalite selon le niveau de formation. Contrairement a d’autres variables categorisant la position sociale (par ex. la branche d’activite ou le revenu), le niveau de formation est relativement aise a utiliser du fait que la formation acquise n’a pas tendance a fluctuer dans le temps. Les resultats des modeles developpes dans l’etude suggerent qu’une differenciation de la retraite de l’ordre de 2 a 4 ans entre les differents niveaux de formation permettrait de reduire les ecarts de la duree moyenne de retraite en fonction du groupe d’appartenance. Les modeles integrent en outre un second indicateur de nature biologique, la difference d’esperance de vie entre hommes et femmes. Si on en tient compte, il faudrait rajouter au moins deux ans de differenciation supplementaires pour garantir une parfaite equite a l’echelle des sexes. L’etude montre clairement que l’âge de la retraite pourrait etre differencie en fonction de certains facteurs. Des analyses plus poussees sont encore necessaires pour evaluer les consequences individuelles et financieres ainsi que les effets sur les assurances sociales ne relevant pas de la prevoyance vieillesse. (Werner Gredig)
Hepatic extraction, metabolism, and biliary excretion of irinotecan in the isolated perfused rat liver.

Irinotecan (CPT-11) is a semisynthetic derivative of camptothecine that has proved activity in the treatment of colorectal carcinoma. The metabolites identified in humans include SN-38, SN-38 glucuronide, and several CYP3A-derived metabolites. We have studied the hepatic extraction, metabolism, and biliary excretion of irinotecan in the isolated perfused rat liver. After injection of a bolus dose of 5 micromol in the reservoir, irinotecan lactone disappeared from the perfusate following a two-exponential decay with half-lives of 3.5 and 120 min and a total clearance of 1.54 +/- 0.07 mL/min per gram of liver. The area under the curve (AUC) ratio lactone/total drug was 0.212 +/- 0.098 and the half-life of interconversion was 5.02 +/- 0.10 min. Bolus administrations of 2.5, 5, and 25 micromol of irinotecan gave AUCs proportional to the doses administered, indicating that no saturation occurred during dose increase. However, the relative formation of SN-38 and SN-38 glucuronide decreased at the high dose. This result was not the case for the CYP3A metabolites, which had identical metabolic ratios at all three doses. Infusions of 30 and 90 min of a dose of 5 micromol led to the same AUCs and metabolic ratios as a bolus of the same dose. Biliary elimination of irinotecan and metabolites represented 18-22% of the dose administered at 2.5 and 5 micromol but only 7-9% at 25 micromol, suggesting a saturation of this process. These data indicate that the hepatic disposition of irinotecan may vary at high dose, both at the level of biliary excretion and of activation to SN-38.
Interleukin‐4‐ and interleukin‐13‐mediated host protection against intestinal nematode parasites

Summary: Intestinal worm infections characteristically induce T‐helper 2 cell (Th2) cytokine production. We reviewed studies performed with mice infected with either of two intestinal nematode parasites, Nippostrongylus brasiliensis or Trichinella spiralis, that evaluate the importance of the Th2 cytokine interleukin‐4 (IL‐4) and IL‐13 in protection against these parasites. These studies demonstrate that while IL‐4/IL‐13 protect against both parasites by activating signal transducer and activator of transcription 6 (Stat6) through IL‐4 receptor α (IL‐4Rα) ligation, Stat6 activation protects against these parasites through different mechanisms. Stat6‐dependent gene transcription promotes expulsion of N. brasiliensis solely through effects on non‐bone marrow‐derived cells that may include enhancement of intestinal smooth muscle contractility, changes in intestinal epithelial cell function, and increased intestinal mucus secretion. In contrast, Stat6 signaling promotes immunity to T. spiralis both through effects on bone marrow‐derived cells that can be reproduced by treating mice with IL‐4 or IL‐13 and through effects on non‐bone marrow‐derived cells. The former effects appear to include T‐cell‐dependent induction of intestinal mastocytosis, while the latter sensitize non‐bone marrow‐derived cells to mast cell‐produced mediators. We argue that a limited ability of the host immune system to distinguish among different nematode parasites has led to the evolution of a stereotyped Th2 response that activates a set of effector mechanisms that protects against most intestinal nematode parasites.
Which Requirements Artifact Quality Defects are Automatically Detectable? A Case Study

[Context:] The quality of requirements engineering artifacts, e.g. requirements specifications, is acknowledged to be an important success factor for projects. Therefore, many companies spend significant amounts of money to control the quality of their RE artifacts. To reduce spending and improve the RE artifact quality, methods were proposed that combine manual quality control, i.e. reviews, with automated approaches. [Problem:] So far, we have seen various approaches to automatically detect certain aspects in RE artifacts. However, we still lack an overview what can and cannot be automatically detected. [Approach:] Starting from an industry guideline for RE artifacts, we classify 166 existing rules for RE artifacts along various categories to discuss the share and the characteristics of those rules that can be automated. For those rules, that cannot be automated, we discuss the main reasons. [Contribution:] We estimate that 53% of the 166 rules can be checked automatically either perfectly or with a good heuristic. Most rules need only simple techniques for checking. The main reason why some rules resist automation is due to imprecise definition. [Impact:] By giving first estimates and analyses of automatically detectable and not automatically detectable rule violations, we aim to provide an overview of the potential of automated methods in requirements quality control.
Structural features and restricted expression of a human alpha-tubulin gene

The nucleotide sequence of a human alpha-tubulin gene (b alpha 1) is described. This gene is extensively homologous to a rat alpha-tubulin gene in its coding regions, 3'-untranslated region and, indeed, in segments of its largest intron. However, with the exception of three short conserved blocks of homology, the 5' flanking regions of the rat and human genes are unrelated. Hence, these genes each encoding an identical protein are transcribed under the influence of divergent promoters. Blot analyses using RNA from a variety of transformed cells derived from different tissues indicate that expression of the human alpha-tubulin gene is restricted to cells of neurological origin. Among neurological cell types b alpha 1 expression is further restricted to adherent cells that are morphologically differentiated. The data presented suggest that the b alpha 1 gene encodes a prominent neuronal and glial alpha-tubulin and that b alpha 1 expression is a function of the differentiated state of these cells.