A Note on Solid-State Maxwell Demon

Starting from 2002, at least two kinds of laboratory-testable, solid-state Maxwell demons have been proposed that utilize the electric field energy of an open-gap n-p junction and that seem to challenge the validity of the Second Law of Thermodynamics. In the present paper we present some arguments against the alleged functioning of such devices.Comment: 9 pages, 4 figures. Foundations of Physics, forthcoming. arXiv admin note: substantial text overlap with arXiv:1101.505

Evolutionary modes in protein observable space: the case of Thioredoxins

In this article, we investigated the structural and dynamical evolutionary behaviour of a set of ten thioredoxin proteins as formed by three extant forms and seven resurrected ones in laboratory. Starting from the crystallographic structures, we performed all-atom molecular dynamics simulations and compare the trajectories in terms of structural and dynamical properties. Interestingly, the structural properties related to the protein density (i.e. the number of residues divided by the excluded molecular volume) well describe the protein evolutionary behaviour. Our results also suggest that the changes in sequence as occurred during the evolution have affected the protein essential motions, allowing us to discriminate between ancient and extant proteins in terms of their dynamical behaviour. Such results are yet more evident when the bacterial, archaeal and eukaryotic thioredoxins are separately analysed

Efficient and Accurate Modeling of Conformational Transitions in Proteins: The Case of c-Src Kinase

The theoretical computational modeling of large conformational transitions occurring in biomolecules still represents a challenge. Here, we present an accurate "in silico" description of the activation and deactivation mechanisms of human c-Src kinases, a fundamental process regulating several crucial cell functions. Our results clearly show that by applying an efficient and automated algorithm able to drive the molecular dynamics (MD) sampling along the pathway between the two c-Src conformational states - the active state and the inactive state - it is possible to accurately describe, at reduced computational costs, the molecular mechanism underlying these large conformational rearrangements. This procedure, combining the MD simulations with the sampling along the well-defined principal motions connecting the two conformational states, allows to provide a description well beyond the present computational limits, and it is easily applicable to different systems where the structures of both the initial and final states are known

Small Molecule Inhibitors of Human Papillomavirus Protein - Protein Interactions

Human papillomaviruses (HPV) have now been identified as a necessary cause of benign and malignant lesions of the differentiating epithelium, particularly cervical cancer, the second most prevalent cancer in women worldwide. While two prophylactic HPV vaccines and screening programs are available, there is currently no antiviral drug for the treatment of HPV infections and associated diseases. The recent progress toward the identification and characterization of specific molecular targets for small molecule-based approaches provides prospect for the development of effective HPV antiviral compounds. Traditionally, antiviral therapies target viral enzymes. HPV encode for few proteins, however, and rely extensively on the infected cell for completion of their life cycle. This article will review the functions of the viral E1 helicase, which encodes the only enzymatic function of the virus, of the E2 regulatory protein, and of the viral E6 and E7 oncogenes in viral replication and pathogenesis. Particular emphasis will be placed on the recent progress made towards the development of novel small molecule inhibitors that specifically target and inhibit the functions of these viral proteins, as well as their interactions with other viral and/or cellular proteins

a review of empirical data and ethical analysis

Background Appropriate information and consent has been one of the most intensely discussed topics within the context of biobank research. In parallel to the normative debate, many socio-empirical studies have been conducted to gather experiences, preferences and views of patients, healthy research participants and further stakeholders. However, there is scarcity of literature which connects the normative debate about justifications for different consent models with findings gained in empirical research. In this paper we discuss findings of a limited review of socio-empirical research on patients’ and healthy research participants’ experiences and views regarding consent to biobank research in light of ethical principles for appropriate information and consent. Methods Review question: Which empirical data are available on research participants’ perceptions and views regarding information and elicitation of consent for biobank research? Search of articles published till March 1st 2014 in Pubmed. Review of abstracts and potentially relevant full text articles by two authors independently. As categories for content analysis we defined (i) understanding or recall of information, (ii) preferences regarding information or consent, and (iii) research participants’ concerns. Results The search in Pubmed yielded 337 abstracts of which 10 articles were included in this study. Approaches to information and consent varied considerably across the selected studies. The majority of research participants opted for some version of limited consent when being informed about such possibility. Among the factors influencing the type of preferred consent were information about sponsoring of biobank research by pharmaceutical industry and participants’ trade-off between privacy and perceived utility. Studies investigating research participants’ understanding and recall regarding the consent procedure indicated considerable lack of both aspects. Research participants’ perceptions of benefits and harms differ across those studies. Conclusion The knowledge, perceptions and views of research participants who have undergone a consent procedure within the context of biobank research raise several questions on the issue of how to inform and elicit consent in an ethically acceptable way. In our empirical-ethical analysis we develop suggestions on how the practice of eliciting consent in the biobank context should be improved

Targeted drugs and Psycho-oncological intervention for breast cancer patients

Personalized medicine is a new field based on molecular biology and genomics in which targeted tumor therapies are administered to patients. Psycho- oncology is a complementary approach that considers social and psychological aspects of patients as part of the treatments for cancer patients. The aim of this mini-review is to weigh clinical benefits for breast cancer patients of both treatments and possibily enhance benefits by modulating the use of both interventions. We have compared and evaluated on the one hand the use of anti Vascular Endothelial Growth Factor and, on the other hand, psycho-oncological interventions in metastatic and non-metastatic breast cancer patients. Both treatments did not increase survival of metastatic breast cancer patients, while in a selected study psycho-oncological interventions extended lifespan of non-metastatic breast cancer patients and ameliorate psychological and social factors of metastatic breast cancer patients. Because the two approaches address completely different aspects of cancer patients, if the comparison is limited to the extension of survival, the value of these two treatments cannot be assessed and compared. It is likely that by comparing patients reported outcomes, possibly by using standardized Quality of Life questionnaires, both patients and health care providers can weigh the benefits of the two treatments. It is therefore important to evaluate the use of cancer patients’ quality of life measures as a mean to improve their experiences about life and treatment, and possibly to extend their survival

Left atrial anomalous muscular band as incidental finding during video-assisted mitral surgery

Congenital fibromuscular bands have been described inleft ventricle or right atrium and have been diagnosed by echocardiography and CT scan. The first report of anomalous band in the left atrium was described in 1897 by Rollestone (1). We hereby present a case of a patient with an incidental finding of left atrial band during a minimally invasive mitral surgery procedure

Surgical embolectomy for acute massive pulmonary embolism: state of the art

Massive pulmonary embolism (PE) is a severe condition that can potentially lead to death caused by right ventricular (RV) failure and the consequent cardiogenic shock. Despite the fact thrombolysis is often administrated to critical patients to increase pulmonary perfusion and to reduce RV afterload, surgical treatment represents another valid option in case of failure or contraindications to thrombolytic therapy. Correct risk stratification and multidisciplinary proactive teams are critical factors to dramatically decrease the mortality of this global health burden. In fact, the worldwide incidence of PE is 60–70 per 100,000, with a mortality ranging from 1% for small PE to 65% for massive PE. This review provides an overview of the diagnosis and management of this highly lethal pathology, with a focus on the surgical approaches at the state of the art

Extraction of Zero-Point Energy from the Vacuum: Assessment of Stochastic Electrodynamics-Based Approach as Compared to Other Methods

In research articles and patents several methods have been proposed for the extraction of zero-point energy from the vacuum. None of the proposals have been reliably demonstrated, yet they remain largely unchallenged. In this paper the underlying thermodynamics principles of equilibrium, detailed balance, and conservation laws are presented for zero-point energy extraction. The proposed methods are separated into three classes: nonlinear processing of the zero-point field, mechanical extraction using Casimir cavities, and the pumping of atoms through Casimir cavities. The first two approaches are shown to violate thermodynamics principles, and therefore appear not to be feasible, no matter how innovative their execution. The third approach, based upon stochastic electrodynamics, does not appear to violate these principles, but may face other obstacles. Initial experimental results are tantalizing but, given the lower than expected power output, inconclusive.Comment: 18 pages including 12 figure

Cerebrovascular complications and infective endocarditis. impact of available evidence on clinical outcome

Infective endocarditis (IE) is a life-threatening disease. Its epidemiological profile has substantially changed in recent years although 1-year mortality is still high. Despite advances in medical therapy and surgical technique, there is still uncertainty on the best management and on the timing of surgical intervention. The objective of this review is to produce further insight intothe short- and long-term outcomes of patients with IE, with a focus on those presenting cerebrovascular complications