Epigenetics is the study of heritable alterations in gene expression that are not accompanied by the corresponding change in DNA sequence. Three interlinked epigenetic processes regulate gene ...expression at the level of chromatin, namely DNA methylation, nucleosomal remodeling and histone covalent modifications. Post-translational modifications that occur on certain amino acid residues of the tails of histone proteins modify chromatin structure and form the basis for "histone code". The enzymes Histone Acetyl Transferase (HAT) and Histone Deacetylase (HDAC) control the level of acetylation of histones and thereby alter gene expression. In many cancers, the balance between HAT and HDAC is altered. HDAC enzymes are grouped into four different classes namely Class I (HDAC1, HDAC2, HDAC3, and HDAC8), Class II (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10), Class III HDAC and Class IV (HDAC11). Histone Deacetylase Inhibitors (HDACI) exert anticancer activity by promoting acetylation of histones as well as by promoting acetylation of non-histone protein substrates. The effects of HDACI on gene transcription are complex. They cause cell cycle arrest, inhibit DNA repair, induce apoptosis and acetylate non histone proteins causing downstream alterations in gene expression. HDACI are a diverse group of compounds, which vary in structure, biological activity, and specificity. In general, HDACIs contain a zinc-binding domain, a capping group, and a straight chain linker connecting the two. They are classified into four classes namely short chain fatty acids, hydroxamic acids, cyclic peptides and synthetic benzamides. This review describes the clinical utility of HDACI as monotherapy as well as combination therapy with other treatment modalities such as chemotherapy and radiotherapy. Adverse effects and shortcomings of treatment with HDACI are also discussed in detail.
Facility location decisions play a critical role in the strategic design of supply chain networks. In this paper, a literature review of facility location models in the context of supply chain ...management is given. We identify basic features that such models must capture to support decision-making involved in strategic supply chain planning. In particular, the integration of location decisions with other decisions relevant to the design of a supply chain network is discussed. Furthermore, aspects related to the structure of the supply chain network, including those specific to reverse logistics, are also addressed. Significant contributions to the current state-of-the-art are surveyed taking into account numerous factors. Supply chain performance measures and optimization techniques are also reviewed. Applications of facility location models to supply chain network design ranging across various industries are presented. Finally, a list of issues requiring further research are highlighted.
The support of stringent requirements such as ultra-low latency and ultra-reliability of the forthcoming 5G services poses several challenges to telecommunications infrastructure providers. Network ...Function Virtualization, multi-access edge computing (MEC), and network slicing capabilities can help the support of such requirements. However, a trade-off between the cost of resource deployment and the support of service requirements needs to be taken into account in the design of NFV-based 5G networks. In this paper, we investigate the MEC location problem, which aims at selecting locations to place MECs hosting protected slices. We propose a MEC location problem enhanced with 1: 1 and <inline-formula> <tex-math notation="LaTeX">1:N </tex-math></inline-formula> protection schemes for the provisioning of protected slices. In the 1: 1 scheme, protection is assured by reserving a backup slice for each tenant, whereas in the <inline-formula> <tex-math notation="LaTeX">1:N </tex-math></inline-formula> scheme, a backup slice is shared among <inline-formula> <tex-math notation="LaTeX">N </tex-math></inline-formula> tenants. The problem is modeled as a multi-criteria optimization problem and solved by the employment of a multi-objective evolutionary non-dominated sorting genetic algorithm. A comparison between the 1: 1 and <inline-formula> <tex-math notation="LaTeX">1:N </tex-math></inline-formula> protection schemes is carried out in the context of 5G network slicing. Results show that the protection scheme 1: 1 can reduce the response time, at a higher deployment cost when compared to the <inline-formula> <tex-math notation="LaTeX">1:N </tex-math></inline-formula> scheme.
The World Health Organization (WHO) has articulated a priority pathogens list (PPL) to provide strategic direction to research and develop new antimicrobials. Antimicrobial resistance (AMR) patterns ...of WHO PPL in a tertiary health care facility in Southern India were explored to understand the local priority pathogens. Culture reports of laboratory specimens collected between 1st January 2014 and 31st October 2019 from paediatric patients were extracted. The antimicrobial susceptibility patterns for selected antimicrobials on the WHO PPL were analysed and reported. Of 12,256 culture specimens screened, 2335 (19%) showed culture positivity, of which 1556 (66.6%) were organisms from the WHO-PPL. E. coli was the most common organism isolated (37%), followed by Staphylococcus aureus (16%). Total of 72% of E. coli were extended-spectrum beta-lactamases (ESBL) producers, 55% of Enterobacteriaceae were resistant to 3rd generation cephalosporins due to ESBL, and 53% of Staph. aureus were Methicillin-resistant. The analysis showed AMR trends and prevalence patterns in the study setting and the WHO-PPL document are not fully comparable. This kind of local priority difference needs to be recognised in local policies and practices.
Experimental Fock-State Superradiance Ortiz-Gutiérrez, L; Muñoz-Martínez, L F; Barros, D F ...
Physical review letters,
02/2018, Letnik:
120, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Superradiance in an ensemble of atoms leads to the collective enhancement of radiation in a particular mode shared by the atoms in their spontaneous decay from an excited state. The quantum aspects ...of this phenomenon are highlighted when such collective enhancement is observed in the emission of a single quantum of light. Here we report a further step in exploring experimentally the nonclassical features of superradiance by implementing the process not only with single excitations, but also in a two-excitation state. Particularly, we measure and theoretically model the wave packets corresponding to superradiance in both the single-photon and two-photon regimes. Such progress opens the way to the study and future control of the interaction of nonclassical light modes with collective quantum memories at higher photon numbers.
Lipoabdominoplasty Saldanha, Osvaldo R; Federico, Rodrigo; Daher, Presper F ...
Plastic and reconstructive surgery (1963)
124, Številka:
3
Journal Article
Recenzirano
Abdominoplasty is one of the most common aesthetic operations. Wide bibliographic research has revealed that there is a safe method whereby two techniques--liposuction and abdominoplasty--can be ...associated in the same procedure. The authors present a new abdominoplasty technique combining a selective undermining with complete abdominal liposuction.
The authors standardized steps with which to perform a safe association of traditional abdominoplasty with liposuction of the entire abdomen and infracostal areas. Using selective undermining, it is possible to preserve at least 80 percent of the blood supply in the abdominal wall, causing little nervous trauma, preserving the great majority of the lymphatic vessels, and resulting in few complications compared with traditional abdominoplasty, including post-bariatric surgery procedures. In this study, lipoabdominoplasty was performed on 445 patients: eight male patients and 437 female patients, from 2000 to 2007.
The authors consider the results good and excellent, especially regarding patient evaluation, better body contour, abdominal rejuvenation, shorter scars, the form of the umbilicus, and a decrease in the abdominal measures.
With a progressive adaptation of this technique, it is possible to achieve a harmonious body contour using a safe liposuction method on the abdominal and costal areas, with fast recovery and good to excellent results.
Lipoabdominoplasty: the Saldanha technique Saldanha, Osvaldo R; Azevedo, Sérgio F D; Delboni, Pablo S F ...
Clinics in plastic surgery,
07/2010, Letnik:
37, Številka:
3
Journal Article
Recenzirano
Traditional abdominal plastic surgery results in a high rate of morbidity because of the necessity for a large undermining of the flap. In 2001, Saldanha, using the term "lipoabdominoplasty" for the ...first time, standardized a selective undermining, corresponding to 30% of the traditional undermining, between the medial borders of the rectus abdominal muscles. This procedure combines 2 traditional techniques, abdominoplasty and liposuction.
A
bstract
The very low radioactive background of the Borexino detector, its large size, and the well proved capability to detect both low energy electron neutrinos and antineutrinos make an ideal ...case for the study of short distance neutrino oscillations with artificial sources at Gran Sasso.
This paper describes the possible layouts of
51
Cr (
ν
e
) and
144
Ce-
144
Pr
source experiments in Borexino and shows the expected sensitivity to eV mass sterile neutrinos for three possible different phases of the experiment. Expected results on neutrino magnetic moment, electroweak mixing angle, and couplings to axial and vector currents are shown too.
Protein homeostasis (proteostasis) is essential for cellular and organismal health. Stress, aging and the chronic expression of misfolded proteins, however, challenge the proteostasis machinery and ...the vitality of the cell. Enhanced expression of molecular chaperones, regulated by heat shock transcription factor-1 (HSF-1), has been shown to restore proteostasis in a variety of conformational disease models, suggesting this mechanism as a promising therapeutic approach. We describe the results of a screen comprised of ∼900,000 small molecules that identified new classes of small-molecule proteostasis regulators that induce HSF-1-dependent chaperone expression and restore protein folding in multiple conformational disease models. These beneficial effects to proteome stability are mediated by HSF-1, FOXO, Nrf-2 and the chaperone machinery through mechanisms that are distinct from current known small-molecule activators of the heat shock response. We suggest that modulation of the proteostasis network by proteostasis regulators may be a promising therapeutic approach for the treatment of a variety of protein conformational diseases.
PDF
