1,721,118 research outputs found
Protein, peptide and non-peptide drug PEGylation for therapeutical application: a review
No full textFor many years proteins have been investigated as therapeutic agents, but unfortunately their potential advantages could not be exploited completely. The main drawbacks regard the intrinsic short life in the body, the immunological adverse reaction and the proteolytic digestion. Among all the approaches studied for overcoming these problems, PEGylation (the modification of molecules with polyethylene-glycol, PEG) achieved the most interesting results leading to a novel series of products that reached already the market and, furthermore, promising others will be available soon. Since the first studies in this field, the conjugation of PEG to a protein showed the possibility to improve the pharmacokinetics profile of linked drug. In the last years this technology, firstly developed for proteins, has been transferred to non-peptide drugs, opening a new area of investigation that is now receiving increasing interest. This leads to new opportunities for many therapeutic treatments since it is possible to use molecules that could not be used before for limitations such as inadequate water solubility, high non-specific toxicity and poor pharmacokinetic profiles. In this review the recent achievements in PEGylation of protein, peptide and non-peptide drugs were described for what the chemistry of binding is concerned, and many examples from literature are reported both in the field of protein therapeutic as well as non-peptide drugs
Relationship between sagittal plane kinematics, foot morphology and vertical forces applied to three regions of the foot
Full text linkKinetic analysis of human motion with a multi-segment musculoskeletal foot model requires the distribution of loading applied to the modeled foot segments to be determined. This work thus examines the existence of any correlation between intersegmental foot kinematics, foot morphology, and the distribution of vertical loading in a multi-segment foot model. Gait analysis trials were performed by 20 healthy subjects at a self-selected speed with intersegmental foot joint angles and the distribution of vertical loading measured for a multi-segment foot model. A statistical relationship between the sagittal plane foot kinematics and loads applied to each foot sub-area was sought using multiple regression analyses. The sub-segmental loading of the normal and abnormal morphological groups was also compared. No meaningful relationships between sagittal plane foot kinematics and sub-segment foot loading were found (max. R2 = 0.36). Statistically significant relationships between foot morphology classification and sub-area foot loading were however identified, particularly for feet exhibiting hallux valgus. Significant variation in inter-subject foot sub-segmental loading indicates that an appropriate technique for determining this load distribution must be determined before effective kinetic analyses are performed with multi-segment musculoskeletal foot models. The results of this study suggest that foot morphology is a better indicator of sub-area loading than sagittal plane kinematics and warrants further investigation
O 065 - The impact of dynamic simulation on diabetic foot prevention: Two different approaches combining gait analysis and finite element modelling
No full textVerify the benefit of adopting a dynamic FEM approach versus a quasi-static one in identifying diabetic subjects at risk of ulceration
ARPHA: a software prototype for fault detection, identification and recovery in autonomous spacecrafts
No full textThis paper introduces a software
prototype called ARPHA for on-board diagnosis,
prognosis and recovery. e goal is to allow
the design of an innovative on-board FDIR (Fault
Detection, Identification and Recovery) process
for autonomous systems, able to deal with uncertain
system/environment interactions, uncertain
dynamic system evolution, partial observability and
detection of recovery policies taking into account
imminent failures. We propose to base the inference
engine of ARPHA on Dynamic Probabilistic
Graphical Models suitable to reason about system
evolution with control actions, over a finite time
horizon. e model needed by ARPHA is derived
from standard dependability modeling, exploiting
an extension of the Dynamic Fault Tree language,
called EDFT. We finally discuss the software architecture
of ARPHA, where on-board FDIR is
implemented and we provide some preliminary results
on simulation scenarios for Mars rover activities
Evidences of altered Redox Homeostasis in Trichothiodystrophy
No full textTrichothiodystrophy (TTD) is a rare hereditary disease whose prominent feature is brittle hair. Additional clinical signs are physical and neurodevelopmental abnormalities and in about half of the cases hypersensitivity to UV radiation. Although the mutations involved in this condition have been characterized, the correlation between the molecular defects and the plethora of clinical symptoms is not well understood. Recently, the presence of a redox imbalance in TTD has been suggested although no clear evidence has been reported on this aspect
Center of mass-based posturography for free living environment applications
Full text linkBackground: Postural assessment is crucial as risk of falling is a major health problem for the elderly. The most widely used devices are force and balance plates, while center of pressure is the most studied parameter as measure of neuromuscular imbalances of the body sway. In out-of-laboratory conditions, where the use of plates is unattainable, the center of mass can serve as an alternative. This work proposes a center of mass-based pos-turographic measurement for free living applications. Methods: Ten healthy and ten Parkinson's disease individuals (age = 26.1 +/- 1.5, 70.4 +/- 6.2 years, body mass index = 21.7 +/- 2.2, 27.6 +/- 2.8 kg/m2, respectively) participated in the study. A stereophotogrammetric system and a force plate were used to acquire the center of pressure and the 5th lumbar vertebra displacements during the Romberg test. The center of mass was estimated using anthropometric measures. Posturographic parameters were extracted from center of pressure, center of mass and 5th lumbar vertebra trajectories. Normalized root mean squared difference was used as metric to compare the trajectories; Spearman's correlation coefficient was computed among the posturographic parameters. Findings: Low values of the metric indicated a good agreement between 5th lumbar vertebra trajectory and both center of pressure and center of mass trajectories. Statistically significant correlations were found among the postural variables. Interpretation: A method to perform posturography tracking the movement of the 5th lumbar vertebra as an approximation of center of mass has been presented and validated. The method requires the solely kinematic tracking of one anatomical landmark with no need of plates for free living applications
Circadian Clock and OxInflammation: Functional Crosstalk in Cutaneous Homeostasis
No full textCircadian rhythms are biological oscillations that occur with an approximately 24 h period and optimize cellular homeostasis and responses to environmental stimuli. A growing collection of data suggests that chronic circadian disruption caused by novel lifestyle risk factors such as shift work, travel across time zones, or irregular sleep-wake cycles has long-term consequences for human health. Among the multiplicity of physiological systems hypothesized to have a role in the onset of pathologies in case of circadian disruption, there are redox-sensitive defensive pathways and inflammatory machinery. Due to its location and barrier physiological role, the skin is a prototypical tissue to study the influence of environmental insults induced OxInflammation disturbance and circadian system alteration. To better investigate the link among outdoor stressors, OxInflammation, and circadian system, we tested the differential responses of keratinocytes clock synchronized or desynchronized, in an in vitro inflammatory model exposed to O3. Being both NRF2 and NF-κB two key redox-sensitive transcription factors involved in cellular redox homeostasis and inflammation, we analyzed their activation and expression in challenged keratinocytes by O3. Our results suggest that a synchronized circadian clock not only facilitates the protective role of NRF2 in terms of a faster and more efficient defensive response against environmental insults but also moderates the cellular damage resulting from a condition of chronic inflammation. Our results bring new insights on the role of circadian clock in regulating the redox-inflammatory crosstalk influenced by O3 and possibly can be extrapolated to other pollutants able to affect the oxinflammatory cellular processes
Evaluation of anomaly and failure scenarios involving an exploration rover: a Bayesian network approach
No full textRecent studies focused on the achievement of autonomy
by spacecrafts, with the aim of avoiding the intervention
of the ground control. In this sense, the ARPHA software
prototype has been developed for the automatic failure
detection, identification and recovery (FDIR), and is
based on the on-board analysis of a Dynamic Bayesian
Network (DBN) representing the system behaviour conditioned
by the conditions of components and environment.
In this paper, we describe the main functionalities
of ARPHA, and we apply its FDIR capabilities to
the power supply subsystem of an exploring rover, taking
into account four scenarios leading to anomalies or failures.
The DBN model of the system is described. Then,
we test the execution of ARPHA, together with a rover
simulator providing sensor data and plan data. In particular,
we show the results of diagnosis, prognosis and
recovery, returned by ARPHA when the scenarios occur
ARPHA: an innovative on-board FDIR reasoning engine for autonomous systems to perform diagnosis, prognosis and recovery
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