Miracle-dz/UniFAR-FTUs huggingface dataset:
Information-Centric Networking

Information-centric networking is an emerging networking paradigm that envisages to solve the shortcomings of the host-centric internet. The usage of internet has moved away from the initial host-centric remote access one to predominantly an information serving one. In the new paradigm, information rather than the host takes the central place in serving the users. Hence, the users will search for information and download it from the nearest device holding it. In order to serve the customers better while optimizing the use of network resources, in-network caching is enabled in ICN. In ICN, the intermediate routers will serve as cache repositories in addition to acting as data forwarding devices. There are several ICN architectures proposed in the literature, each having its own merits and demerits. This chapter has taken an in-depth look at the design principles of ICN along with future open research areas that need the immediate attention of the researchers.
Nonequilibrium Reactivation of Na+ Current Drives Early Afterdepolarizations in Mouse Ventricle

Background—Early afterdepolarizations (EADs) are triggers of cardiac arrhythmia driven by L-type Ca2+ current (ICaL) reactivation or sarcoplasmic reticulum Ca2+ release and Na+/Ca2+ exchange. In large mammals the positive action potential plateau promotes ICaL reactivation, and the current paradigm holds that cardiac EAD dynamics are dominated by interaction between ICaL and the repolarizing K+ currents. However, EADs are also frequent in the rapidly repolarizing mouse action potential, which should not readily permit ICaL reactivation. This suggests that murine EADs exhibit unique dynamics, which are key for interpreting arrhythmia mechanisms in this ubiquitous model organism. We investigated these dynamics in myocytes from arrhythmia-susceptible calcium calmodulin-dependent protein kinase II delta C (CaMKII&dgr;C)-overexpressing mice (Tg), and via computational simulations. Methods and Results—In Tg myocytes, &bgr;-adrenergic challenge slowed late repolarization, potentiated sarcoplasmic reticulum Ca2+ release, and initiated EADs below the ICaL activation range (–47±0.7 mV). These EADs were abolished by caffeine and tetrodotoxin (but not ranolazine), suggesting that sarcoplasmic reticulum Ca2+ release and Na+ current (INa), but not late INa, are required for EAD initiation. Simulations suggest that potentiated sarcoplasmic reticulum Ca2+ release and Na+/Ca2+ exchange shape late action potential repolarization to favor nonequilibrium reactivation of INa and thereby drive the EAD upstroke. Action potential clamp experiments suggest that lidocaine eliminates virtually all inward current elicited by EADs, and that this effect occurs at concentrations (40–60 &mgr;mol/L) for which lidocaine remains specific for inactivated Na+ channels. This strongly suggests that previously inactive channels are recruited during the EAD upstroke, and that nonequilibrium INa dynamics underlie murine EADs. Conclusions—Nonequilibrium reactivation of INa drives murine EADs.
Anti-FGF 2 approaches as a strategy to compensate resistance to anti-VEGF therapy : long-pentraxin 3 as a novel antiangiogenic FGF 2-antagonist

Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, plays a pivotal role in tumor growth, progression and metastasis. Over the last 30 years, numerous proand antiangiogenic molecules, their ligands, and intracellular signaling pathways have been identified, and significant efforts have been undertaken to develop antiangiogenic strategies for cancer therapy. Agents that selectively target vascular endothelial growth factor (VEGF) and its receptors have shown promising activity in clinical trials and have been approved for use in selected cancer indications. However, patients may ultimately develop resistance to these drugs. One proposed mechanism of tumor escape from anti-VEGF therapy is the up-regulation of fibroblast growth factor-2 (FGF2). FGF2 is a pleiotropic, angiogenesis inducer belonging to the family of the heparin-binding FGF growth factors. FGF2 is expressed by numerous tumor types and exerts its proangiogenic activity by interacting with tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins expressed on the endothelial cell surface. Experimental evidence suggests that targeting FGF2, in addition to VEGF, might provide synergistic effects in the treatment of angiogenesis-related diseases, including cancer. Several FGF2 inhibitors, with different chemical structure and mechanism of action, have been identified. Recent observations have shown the ability of the soluble pattern recognition receptor long-pentraxin-3 (PTX3) to bind FGF2, thus acting as a FGF2 antagonist. PTX3 binds FGF2 with high affinity and specificity. This interaction prevents the binding of FGF2 to its cognate tyrosine kinase receptors, leading to inhibition of the angiogenic activity of the growth factor. Further, preliminary observations support the hypothesis that PTX3 may inhibit FGF2-mediated tumor angiogenesis and growth. The identification of the FGF2-binding domain in the unique N-terminal extension of PTX3 has allowed the design of PTX3-derived synthetic peptides endowed with significant antiangiogenic activity in vitro and in vivo. These findings may provide the basis for the development of novel antiangiogenic FGF2 antagonists, with potential implications for cancer therapy.
Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability after intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.
Acetaminophen Toxicity Results in Site-specific Mitochondrial Damage in Isolated Mouse Hepatocytes

Exposure of isolated mouse hepatocytes to a toxic concentration of acetaminophen (5 mM) resulted in damage to the mitochondrial respiratory apparatus. The nature of this damage was investigated by measuring respiration stimulated by site-specific substrates in digitonin-permeabilized hepatocytes after acetaminophen exposure. Respiration stimulated by succinate at energy-coupling site 2 was most sensitive to inhibition and was decreased by 47% after 1 h. Respiration supported by NADH-linked substrates (site 1) was also decreased but to a lesser extent, while there was no decrease in the rate of ascorbate + N,N,N’,N’tetramethyl-p-phenylenediamine (TMPD)-supported respiration (site 3). The loss of mitochondrial respiratory function was accompanied by a decrease in ATP levels and ATP/ADP ratios in the cytosolic compartment and was preceded by a loss of reduced glutathione in both the cytosol and mitochondria. All these effects occurred well before the loss of cell membrane integrity. The putative toxic metabolite of acetaminophen, N-acetyl-p-benzoquinonimine (NAPQI), produced a similar pattern of respiratory dysfunction in isolated hepatic mitochondria. Respiration stimulated by succinateand NADH-linked substrates was very sensitive to 50 PM NAPQI, while ascorbate + TMPD-supported respiration was unaffected. The interaction between NAPQI and the respiratory chain was further investigated using submitochondrial particles. Succinate dehydrogenase (associated with respiratory complex 11) was found to be very sensitive to NAPQI, while NADH dehydrogenase (respiratory complex I) was inhibited to a lesser extent. Our results indicate that a loss of the ability to utilize succinateand NADHlinked substrates due to attack of the respiratory chain by NAPQI causes a disruption of energy homeostasis in acetaminophen hepatotoxicity.
Reactive changes of retinal astrocytes and Müller glial cells in kainate‐induced neuroexcitotoxicity

The aim of this study was to investigate reactive changes of astrocytes and Müller glial cells in rats subjected to kainate treatment, which leads to neuronal degeneration in the ganglion cell layer and the inner border of the inner nuclear layer as confirmed by labelling with Fluoro‐Jade B, a marker for degenerating neurons and fibres. Both the astrocytes and the Müller glial cells reacted vigorously to kainate injection as shown by their up‐regulated expression of nestin, glial fibrillary acidic protein and glutamine synthetase. A major finding was the induced expression of nestin together with glial fibrillary acidic protein beginning at 1 day post‐injection of kainate. The marked nestin expression appeared to be most intense at 1 day and was sustained till 2 weeks as compared with the untreated/normal retina. Western blotting analysis confirmed a marked increase in expression of nestin, glial fibrillary acidic protein and glutamine synthetase as compared with untreated/normal retina. Double labelling study revealed that astrocytes and Müller glial cells expressed the radial glia marker nestin, and incorporated bromodeoxyuridine to re‐enter into their cell cycle. The induced expression of these proteins in astrocytes and Müller glial cells indicated an induction of gliotic responses and de‐differentiation that may be associated with regenerative efforts after kainate‐induced injury. Indeed, with the acquisition of an immature molecular profile as manifested by the induced expression of brain lipid‐binding protein and doublecortin in astrocytes and Müller glial cells, the potential of these cells to de‐differentiate in retinal neurodegeneration is greatly amplified.
[The expression and significance of the Notch signaling pathway molecules in tongue squamous cell carcinoma].

OBJECTIVE To explore the expression of Notch signaling receptors Notchl, Notch3 and its ligand Jaggedl, Jagged2 in tongue squamous cell carcinoma (TSCC). METHODS mRNA and protein expression levels of tissue samples from 74 cases of tongue cancer patients and human tongue cell line Cal-27 were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot. Its relationship with cell proliferation and clinical pathology was analyzed. RESULTS mRNA and protein expression were detected in tongue cancer tissues, adjacent tissues and cell lines. Notchl and Notch3 protein expression in tongue cancer was higher than the adjacent tissues. Jaggedl and Jagged2 protein expression in tongue cancer and adjacent tissues had no difference. Notchl and Notch3 protein had correlation with tongue cancer clinical staging. Pathway protein expression had no correlation with pathological grade, age, gender. Notchl protein expression in lymph node metastasis-positive cases was higher than in lymph node metastasis-negative cases. The expression of Notch3 and Jagged2 had correlation. Jaggedl expression grade in metastasis-positive cases was higher than in negative cases. CONCLUSION Notch signaling molecules have active expression in TSCC and may play important roles in tongue cancer development.
Early cognitive impairment in multiple sclerosis predicts disability outcome several years later

Cognition is frequently impaired in the early stages of multiple sclerosis (MS). The predictive value of cognitive impairment on disability is unknown. The objective of this study was to correlate cognitive impairment and the progression of disability over 7 years. Forty-five patients, recruited after MS diagnosis, were followed for 7 years by yearly Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) evaluations and were classified as cognitively impaired (CI) or unimpaired (CU) according to neuropsychological testing at baseline. At baseline, 47.8% of patients were CI, with deficits in mainly memory and information processing speed (IPS). The baseline EDSS correlated significantly with one IPS test. The EDSS, but not the MSFC, deteriorated significantly over the 7 years in the whole group and the CI group, but not the CU group. A multivariate analysis showed correlations between the EDSS change over 5 and 7 years and two baseline tests evaluating IPS and verbal memory. The deterioration of the EDSS after 7 years was significantly correlated with verbal memory testing at baseline after adjustment for age and baseline EDSS. In conclusion, in this sample of MS patients early in the disease, the baseline IPS and verbal memory impairments predict the EDSS score 5 and 7 years later.
Fundamental data on the desorption of pure interstellar ices

The desorption of molecular ices from grain surfaces is important in a number of astrophysical environments including dense molecular clouds, cometary nuclei and the surfaces and atmospheres of some planets. With this in mind, we have performed a detailed investigation of the desorption of pure water, pure methanol and pure ammonia ices from a model dust-grain surface. We have used these results to determine the desorption energy, order of desorption and the pre-exponential factor for the desorption of these molecular ices from our model surface. We find good agreement between our desorption energies and those determined previously; however, our values for the desorption orders, and hence also the pre-exponential factors, are different to those reported previously. The kinetic parameters derived from our data have been used to model desorption on time-scales relevant to astrophysical processes and to calculate molecular residence times, given in terms of population half-life as a function of temperature. These results show the importance of laboratory data for the understanding of astronomical situations whereby icy mantles are warmed by nearby stars and by other dynamical events.
Inverse Relationship of Serum Hepcidin Levels with CD4 Cell Counts in HIV-Infected Patients Selected from an Indonesian Prospective Cohort Study

Background Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB. Methods Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm3 (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin. Results A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection. Conclusion Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.
Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study

Objective To determine whether combinations of metabolic risk factors (obesity, diabetes and hypercholesterolemia) influence the magnitude of left ventricular (LV) mass and prevalence of LV hypertrophy. Design Cross-sectional, relational. Methods A total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African Americans) and 342 normotensive (180 women, 183 African Americans) participants in the Hyper tension G enetic E pidemiology N etwork (HyperGEN) Study, without prevalent cardiovascular disease, were studied. Echocardiographic LV mass, normalized by height2.7 or fat-free mass or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude estimate of arterial compliance) were analyzed in relation to obesity [by body mass index (BMI)], central fat distribution (by waist circumference), diabetes (by ADA criteria) and hypercholesterolemia. Results Obesity, hypercholesterolemia, and diabetes were more frequent among hypertensives than normotensives (all P < 0.001). After controlling for age, sex, race and type and combination of antihypertensive medication, LV mass/height2.7, but not LV mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk factors, both in normotensive and hypertensive participants, also after further adjustment for blood pressure (all P < 0.001). Stroke volume/pulse pressure also decreased in hypertensive, but much less in normotensive subjects, with increasing number of metabolic risk factors, independently of relevant confounders (P < 0.0001). Prevalence of LV hypertrophy was predicted by older age, hypertension, central fat distribution, black race and independently increased with the number of associated metabolic risk factors (P < 0.0001). Conclusions The progressive addition of metabolic risk factors including central obesity, diabetes and hypercholesterolemia is associated with higher LV mass normalized by height2.7, independently of hypertension and other important biological covariates. Obesity played a major role in this association. This finding indicates that LV mass is a potentially useful bioassay of strategies of global cardiovascular prevention.
Preprocessing and Meta-Classification for Brain-Computer Interfaces

A brain-computer interface (BCI) is a system which allows direct translation of brain states into actions, bypassing the usual muscular pathways. A BCI system works by extracting user brain signals, applying machine learning algorithms to classify the user's brain state, and performing a computer-controlled action. Our goal is to improve brain state classification. Perhaps the most obvious way to improve classification performance is the selection of an advanced learning algorithm. However, it is now well known in the BCI community that careful selection of preprocessing steps is crucial to the success of any classification scheme. Furthermore, recent work indicates that combining the output of multiple classifiers (meta-classification) leads to improved classification rates relative to single classifiers (Dornhege , 2004). In this paper, we develop an automated approach which systematically analyzes the relative contributions of different preprocessing and meta-classification approaches. We apply this procedure to three data sets drawn from BCI Competition 2003 (Blankertz , 2004) and BCI Competition III (Blankertz , 2006), each of which exhibit very different characteristics. Our final classification results compare favorably with those from past BCI competitions. Additionally, we analyze the relative contributions of individual preprocessing and meta-classification choices and discuss which types of BCI data benefit most from specific algorithms
Validation of a heterogeneous elastic-biphasic model for the numerical simulation of the PDL

An elastic-biphasic model for the simulation of the periodontal ligament (PDL) and the adjacent tooth is presented and investigated. The PDL is modelled as a biphasic material following the work of Ehlers and Markert (2001), whereas the tooth is modelled as a linear elastic body. A spatial discretisation scheme is proposed based on mixed finite elements for the spatial discretisation. Due to nonlinearity in the model, a predictor–corrector scheme is employed as a temporal discretisation scheme. In order to validate the PDL model, in vitro measurements are compared with numerical simulations. The numerical simulations are performed using geometries resulting from micro-CT scanner of the same porcine tooth, which was employed for the invitro measurements.