Miracle-dz/UniFAR-FTUs huggingface dataset:
What is Systems Biology?

Systems biology is increasingly popular, but to many biologists it remains unclear what this new discipline actually encompasses. This brief personal perspective starts by outlining the asthetic qualities that motivate systems biologists, discusses which activities do not belong to the core of systems biology, and finally explores the crucial link with synthetic biology. It concludes by attempting to define systems biology as the research endeavor that aims at providing the scientific foundation for successful synthetic biology.
Whole-Exome Sequencing Identifies a Novel Genotype-Phenotype Correlation in the Entactin Domain of the Known Deafness Gene TECTA

Postlingual progressive hearing loss, affecting primarily the high frequencies, is the clinical finding in most cases of autosomal dominant nonsyndromic hearing loss (ADNSHL). The molecular genetic etiology of ADNSHL is extremely heterogeneous. We applied whole-exome sequencing to reveal the genetic etiology of high-frequency hearing loss in a mid-sized Korean family without any prior linkage data. Whole-exome sequencing of four family members (two affected and two unaffected), together with our filtering strategy based on comprehensive bioinformatics analyses, identified 21 potential pathogenic candidates. Sanger validation of an additional five family members excluded 20 variants, leaving only one novel variant, TECTA c.710C>T (p.T237I), as the strongest candidate. This variant resides in the entactin (ENT) domain and co-segregated perfectly with non-progressive high-frequency hearing loss in the family. It was absent among 700 ethnically matched control chromosomes, and the T237 residue is conserved among species, which supports its pathogenicity. Interestingly, this finding contrasted with a previously proposed genotype-phenotype correlation in which variants of the ENT domain of TECTA were associated with mid-frequency hearing loss. Based upon what we observed, we propose a novel “genotype to phenotype” correlation in the ENT domain of TECTA. Our results shed light on another important application of whole-exome sequencing: the establishment of a novel genotype-phenotype in the molecular genetic diagnosis of autosomal dominant hearing loss.
Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

Background and Purpose— Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke. Methods— Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation. Results— Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice. Conclusions— MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion.
Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.

PURPOSE Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.
System Interactive Cyber Presence for E learning to Break Down Learner Isolation

he development of technologies of multimedia, linked to that of Internet and democratization of high speed, has made henceforth E-learning possible for learners being in virtual classes and geographically distributed. One benefit to taking course online is that the online course structure is typically more student focused than teacher centered and encouraging more active participation by students in collaborative learning activities. The quality and quantity of asynchronous and synchronous communications are the key elements for E- learning success. A potential problem that has received little exploration is student's feeling of isolation. It is important to have a propitious supervision to breaking down learner feeling isolation in E-learning environment. This feeling of isolation is among the main causes of loss and high rates of dropout in E-learning. It impacts on their levels of participation, satisfaction and learning. To overcome this feeling of isolation, we aim, by this research, to provide the trainer and each learner with an environment allowing them to behave as if being face to face; in other words, to approach the pedagogy of classroom teaching. Our contribution to reduce the feeling of isolation is to ensure the presence of the teacher in the educational tools. These tools aim to establish a real dialogue with the learner, forcing him to take an active part in their learning. Among the tools we offer, video conference Openmeeting integrated in Moodle providing the possibility of using the notion of class and whiteboard, the indicator of motivation quantification tool based hand gesture that we developed and finally social networks web 2.0 like Facebook, youtube, twitter… to promote collaboration, sharing and communication of the learner with his peers.
CTLA-4 gene polymorphism is associated with predisposition to coeliac disease

Background—Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. Aims—To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. Patients—101 patients with coeliac disease and 130 healthy controls. Methods—Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. Results—The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p<0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p=0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p=0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer. Conclusion—The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.
Ligand-insensitive State of Cardiac ATP-sensitive K+ Channels

The mechanism by which ATP-sensitive K+ (KATP) channels open in the presence of inhibitory concentrations of ATP remains unknown. Herein, using a four-state kinetic model, we found that the nucleotide diphosphate UDP directed cardiac KATP channels to operate within intraburst transitions. These transitions are not targeted by ATP, nor the structurally unrelated sulfonylurea glyburide, which inhibit channel opening by acting on interburst transitions. Therefore, the channel remained insensitive to ATP and glyburide in the presence of UDP. “Rundown” of channel activity decreased the efficacy with which UDP could direct and maintain the channel to operate within intraburst transitions. Under this condition, the channel was sensitive to inhibition by ATP and glyburide despite the presence of UDP. This behavior of the KATP channel could be accounted for by an allosteric model of ligand-channel interaction. Thus, the response of cardiac KATP channels towards inhibitory ligands is determined by the relative lifetime the channel spends in a ligand-sensitive versus -insensitive state. Interconversion between these two conformational states represents a novel basis for KATP channel opening in the presence of inhibitory concentrations of ATP in a cardiac cell.
Analysis of the humoral response to the flagellin protein of Borrelia burgdorferi

We read with interest the article by Robinson et al. reporting cross-reacting and specific epitopes on the flagellar protein of Borrelia burgdorferi (5). The authors have overlooked previous findings, including our own study, which precisely characterized the common and specific epitopes of the flagellar protein by using overlapping decapeptides (6) and which have been confirmed since by others using recombinant fragments (1, 3). This is especially unfortunate because the authors thus did not realize that they interrupted the integrity of the Nand C-terminal cross-reacting epitopes (6) by their choice of fragments (5). In addition, by sera being preabsorbed with Escherichia coli cell sonicate (5), which is not done in routine diagnostic studies, potential crossreacting antibodies were excluded from their study, despite known sequence homologies between the flagellin of E. coli and that of B. burgdorfeni (2). Furthermore, the unspecific binding of immunoglobulins to a region between amino acids (aa) 49 and 68 is already known (6) and can be blocked by preincubation with ovalbumin (4, 6). The question posed by Robinson et al. regarding the regions recognized preferentially from sera from patients at different stages of Lyme disease has also been answered in our previous study: sera from stage I and II patients recognize the epitope within aa 151 to 166 but not the epitope within aa 205 to 226, which is the preferential epitope recognized by sera of patients at stage III and the Borrelia-specific monoclonal antibody H9724 (1, 6). We hope that Table 1, summarizing what is known, will enable future investigators to extend the current knowledge on B. burgdorferi epitopes. Nonetheless, we agree with Robinson et al. that an enzyme-linked immunosorbent assay based on the central region of the B. burgdorferi flagellin would substantially improve the serodiagnosis of Lyme disease; however, we suggest excluding aa 121 to 148 and 255 to 280, because the main cross-reacting epitopes of sera from healthy controls and patients with syphilis are located in these regions.
Essential Role for Neutrophils in Pathogenesis and Adaptive Immunity in Chlamydia caviae Ocular Infections

ABSTRACT Trachoma, the world's leading cause of preventable blindness, is produced by chronic ocular infection with Chlamydia trachomatis, an obligate intracellular bacterium. While many studies have focused on immune mechanisms for trachoma during chronic stages of infection, less research has targeted immune mechanisms in primary ocular infections, events that could impact chronic responses. The goal of this study was to investigate the function of neutrophils during primary chlamydial ocular infection by using the guinea pig model of Chlamydia caviae inclusion conjunctivitis. We hypothesized that neutrophils help modulate the adaptive response and promote host tissue damage. To test these hypotheses, guinea pigs with primary C. caviae ocular infections were depleted of neutrophils by using rabbit antineutrophil antiserum, and immune responses and immunopathology were evaluated during the first 7 days of infection. Results showed that neutrophil depletion dramatically decreased ocular pathology, both clinically and histologically. The adaptive response was also altered, with increased C. caviae-specific IgA titers in tears and serum and decreased numbers of CD4+ and CD8+ T cells in infected conjunctivae. Additionally, there were changes in conjunctival chemokines and cytokines, such as increased expression of IgA-promoting interleukin-5 and anti-inflammatory transforming growth factor β, along with decreased expression of T cell-recruiting CCL5 (RANTES). This study, the first to investigate the role of neutrophils in primary chlamydial ocular infection, indicates a previously unappreciated role for neutrophils in modulating the adaptive response and suggests a prominent role for neutrophils in chlamydia-associated ocular pathology.
Lossless layout compression for maskless lithography systems

Future lithography systems must produce more dense chips with smaller feature sizes, while maintaining throughput comparable to today's optical lithography systems. This places stringent data-handling requirements on the design of any maskless lithography system. Today's optical lithography systems transfer one layer of data from the mask to the entire wafer in about sixty seconds. To achieve a similar throughput for a direct-write maskless lithography system with a pixel size of 25 nm, data rates of about 10 Tb/s are required. In this paper, we propose an architecture for delivering such a data rate to a parallel array of writers. In arriving at this architecture, we conclude that pixel domain compression schemes ar essential for delivering these high data rates. To achieve the desired compression ratios, we explore a number of binary lossless compression algorithms, and apply them to a variety of layers of typical circuits such as memory and control. The algorithms explored include the Joint Bi-Level Image Processing Group (JBIG), Ziv-Lempel (LZ77) as implemented by ZIP, as well as our own extension of Ziv-Lempel to two-dimensions. For all the layouts we tested, at least one of the above schemes achieves a compression ratio of 20 or larger, demonstrating the feasibility of the proposed system architecture.
Chronic care management of globesity: promoting healthier lifestyles in traditional and mHealth based settings

Obesity and being overweight could be real chronic conditions above all if there are other complications such as type 2 diabetes, cardiovascular diseases, hypertension, dyslipidemia, hypercholesterolemia, cancer, and various psychosocial and psychopathological disorders. Due to the multifactorial etiology of obesity, evidence-based interventions to improve weight loss, maintain a healthy weight, and reduce related comorbidities combine different treatment approaches: dietetic, nutritional, physical, behavioral, psychological, and, in some situations, pharmacological and surgical. There are significant limitations in this multidisciplinary chronic care management of obesity, most notably those regarding costs and long-term adherence and efficacy. Programs including eHealth platforms and new technologies could overcome limitations connected to the traditional in-patient chronic care management of obesity, thus providing promising opportunities in enhancing weight reduction and reducing complications in terms of long-term efficacy and effectiveness across clinical, organizational, and economic perspectives.
Joint minimization of congestion and hop distance in design of optical networks

The design of a virtual topology of optical networks optimizes a performance measurement: maximum congestion, average hop distance, number of transceivers, etc. The virtual topology design (VTD) is typically obtained as solution to a mixed integer linear program (MILP) that optimizes any of the above performance measures. In this paper, we investigate a multicriteria formulation to compute the set of solutions from static VTD of the optical networks with two objective functions to: 1) minimize the maximum congestion and 2) minimize the average hop distance. The approach permits the decision maker to have a better perception of the gain and the loss of choosing any given solution. We present the method applied to obtain the set of solutions. We report some computational results which fully justify the interest of carrying out a multicriteria study.
Changes in c-Fos Expression in the Forced Swimming Test: Common and Distinct Modulation in Rat Brain by Desipramine and Citalopram

Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST.
Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference

Abstract Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.