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Studies in History and Philosophy of... Oct 2020We examine the interrelationships between analog computational modelling and analogue (physical) modelling. To this end, we attempt a regimentation of the informal...
We examine the interrelationships between analog computational modelling and analogue (physical) modelling. To this end, we attempt a regimentation of the informal distinction between analog and digital, which turns on the consideration of computing in a broader context. We argue that in doing so, one comes to see that (scientific) computation is better conceptualised as an epistemic process relative to agents, wherein representations play a key role. We distinguish between two, conceptually distinct, kinds of representation that, we argue, are both involved in each case of computing. Based on the semantic and syntactic properties of each of these representations, we put forward a new account of the distinction between analog and digital computing. We discuss how the developed account is able to explain various properties of different models of computation, and we conceptually compare analog computational modelling to analogue (scale) modelling. It is concluded that, contrary to the standard view, the two practices are orthogonal, differing both in their foundations and in the epistemic functions they fulfil.
Topics: Computer Simulation; Semantics
PubMed: 32958274
DOI: 10.1016/j.shpsa.2020.05.001 -
Nanomaterials (Basel, Switzerland) Dec 2022The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in...
The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in its response spectrum. The implementation of EIT requires highly demanding laboratory conditions, which greatly limits its acceptance and application. In this paper, an improved harmonic spring oscillation (HSO) model with four oscillators is proposed as a classical analog for the tunable triple-band EIT effect. A more general HSO model including more oscillators is also given, and the analyses of the power absorption in the HSO model conclude a formula, which is more innovative and useful for the study of the multiple-band EIT effect. To further inspect the analogizing ability of the HSO model, a hybrid unit cell containing an electric dipole and toroidal dipoles in the metamaterials is proposed. The highly comparable transmission spectra based on the HSO model and metamaterials indicate the validity of the classical analog in illustrating the formation process of the multiple-band EIT effect in metamaterials. Hence, the HSO model, as a classical analog, is a valid and powerful theoretical tool that can mimic the multiple-band EIT effect in metamaterials.
PubMed: 36558255
DOI: 10.3390/nano12244405 -
Cancer Letters Jul 2006Natural somatostatin is characterized as an inhibitory peptide and had anti-neoplastic actions. The effect of somatostatin is mediated via specific somatostatin... (Review)
Review
Natural somatostatin is characterized as an inhibitory peptide and had anti-neoplastic actions. The effect of somatostatin is mediated via specific somatostatin receptors (SSTRs). Clinical trials have demonstrated therapeutic applications of radionuclide labeled somatostatin analogues in many tumors bearing the receptors. In prostate cancer, significance of neuroendocrine cells remains unclear, there were conflicting data about occurrence and localization of SSTRs. Therefore, radionuclide labeled somatostatin analog therapy is not applied to prostate cancer clinically, experimental trials with non-radioactive analogues have been disappointing. More efforts need to be made for evaluation of potential applications of somatostatin analog therapy in prostate cancer, for example, transfection of the receptor gene to increase binding of analogues to the tumor cells, improvement of radionuclide delivery and combinations of different therapeutic modalities.
Topics: Animals; Humans; Indium Radioisotopes; Male; Prostatic Neoplasms; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin
PubMed: 16126334
DOI: 10.1016/j.canlet.2005.07.020 -
Endocrinology, Diabetes & Metabolism... Nov 2019ACTH-secreting pheochromocytoma is a very rare cause of Cushing's syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We...
SUMMARY
ACTH-secreting pheochromocytoma is a very rare cause of Cushing's syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We report the case of a 45-year-old female patient with a 3 cm, high-density, left adrenal mass, diagnosed as an ACTH-secreting pheochromocytoma. The biochemical sensitivity of the tumor to somatostatin analogues was tested by a 100 μg s.c. octreotide administration, which led to an ACTH and cortisol reduction of 50 and 25% respectively. In addition to alpha and beta blockers, preoperative approach to laparoscopic adrenalectomy included octreotide, a somatostatin analogue, together with ketoconazole, in order to achieve an adequate pre-surgical control of cortisol release. Histopathological assessment confirmed an ACTH-secreting pheochromocytoma expressing type 2 and 5 somatostatin receptors (SSTR-2 and -5).
LEARNING POINTS
ACTH-secreting pheochromocytomas represent a rare and severe condition, characterized by high morbidity and mortality risk. Surgical removal of the adrenal mass is the gold standard treatment, but adequate medical therapy is required preoperatively to improve the surgical outcome and to avoid major complications. Somatostatin analogs, in addition to other medications, may represent a useful therapeutic option for the presurgical management of selected patients. In this sense, the octreotide challenge test is a useful tool to predict favorable therapeutic response to the treatment.
PubMed: 31765327
DOI: 10.1530/EDM-19-0123 -
Journal of Bioenergetics and... Dec 2023Obesity, which is already pervasive throughout the world, endangers public health by raising the prevalence of metabolic disorders and making their treatment more...
Obesity, which is already pervasive throughout the world, endangers public health by raising the prevalence of metabolic disorders and making their treatment more difficult. The development of drugs to treat obesity is a focus of effort. Melanin concentrated hormone receptor 1 (MCHR1) is the target of some of these therapeutic possibilities since as increased levels of melanin concentrated hormone have been found in obesity models. Known MCHR1 antagonists include BMS-830216, GW-856464, NGD-4715, ALB-127158, and AMG 076, but many have failed phase-I clinical studies. As a potential treatment for cardiotoxicity, KRX-104130 has only recently been identified. As MCH system is potentially effective target for treatment of obesity, in silico research into interaction between MCHR1 and its antagonists at molecular level was the primary goal of this study. Analogues ALB-127158 and KRX-104130 were screened among the RealEnamine library. The complexes obtained by molecular docking were embedded in mimics brain-cell membrane and simulated for 540 ns, and then MM-GBSA were calculated with MMPBSA.py. With all these computational studies, similar or different aspects of selected analogous compounds to ALB-127158 and KRX-104130 were investigated. The specificity of this study was that it analyzed MCHR1 protein as embedded in membrane. It was concluded that KRX-104130's analogue Z1922310273 and ALB-127158's analogue PV-002757495233 did not cause a difference in terms of phospholipid membrane properties. In addition, all ligands remained stable in putative binding site. It has been suggested that PV-002757495233 and Z1922310273 compounds can be evaluated as MCHR1 antagonists when all these outputs are considered in melting pots.
Topics: Humans; Melanins; Membrane Proteins; Molecular Docking Simulation; Obesity; Hormones; Receptors, Somatostatin
PubMed: 37940722
DOI: 10.1007/s10863-023-09993-4 -
Frontiers in Behavioral Neuroscience 2014Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested...
Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible) and a past subliminal (invisible) situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation ("analog") or not ("broken analog"). Words in analogs versus broken analogs were judged closer semantically, which indicates unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network.
PubMed: 24478656
DOI: 10.3389/fnbeh.2014.00009 -
Current Topics in Medicinal Chemistry 2009Oligosaccharides in glycoconjugates such as glycoproteins and glycolipids play important roles in a variety of biological functions. Since glycosyltransferases are... (Review)
Review
Oligosaccharides in glycoconjugates such as glycoproteins and glycolipids play important roles in a variety of biological functions. Since glycosyltransferases are responsible for the biosynthesis of these oligosaccharides, inhibitors of glycosyltransferases are targets for drug discovery. Bisubstrate analogues, in which donor and acceptor analogue are covalently attached to each other, offer donor's high affinity and acceptor's high selectivity. In this review, we describe the design and synthesis of bisubstrate analogues of glycosyltransferases as well as their inhibitory potency hoping to inform the development of potent and selective inhibitors.
Topics: Carbohydrate Sequence; Enzyme Inhibitors; Fucosyltransferases; Galactosyltransferases; Glycosyltransferases; Molecular Sequence Data; Structure-Activity Relationship; Tunicamycin
PubMed: 19199998
DOI: 10.2174/156802609787354351 -
Drug and Therapeutics Bulletin Oct 2004Four recombinant human insulin analogues are currently available in the UK. In reviewingthefirst of these, insulin lispro, in 1997, we concluded that "it has a more... (Review)
Review
Four recombinant human insulin analogues are currently available in the UK. In reviewingthefirst of these, insulin lispro, in 1997, we concluded that "it has a more rapid onset, time to peak and shorter duration of action than soluble human insulin" but "does not appear to alter overall control (haemoglobin A1c levels) and it is not clear whether it reduces the occurrence of hypoglycaemia compared with soluble human insulin". Recombinant analogues marketed in the UK since then include another short-acting analogue, [symbol: see text]insulin aspart (NovoRapid--Novo Nordisk), and two longer-acting analogues, [symbol: see text]insulin glargine (Lantus--Aventis Pharma) and [symbol: see text]insulin detemir (Levemir--Novo Nordisk). In addition, there are two biphasic formulations that contain both a short-acting analogue and a longer-acting protamine suspension of that analogue: biphasic insulin lispro (Humalog Mix25, Humalog Mix50--Lilly) and biphasic [symbol: see text]insulin aspart (NovoMix 30--Novo Nordisk). Here we review insulin analogues and consider what advantages, if any, they offer over conventional human insulin preparations.
Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15491022
DOI: 10.1136/dtb.2004.421077 -
Bioorganic & Medicinal Chemistry Letters Jan 2014We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was...
We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors.
Topics: Animals; Dose-Response Relationship, Drug; Microwaves; Molecular Structure; Rats; Receptors, Somatostatin; Somatostatin; Structure-Activity Relationship
PubMed: 24342240
DOI: 10.1016/j.bmcl.2013.11.065 -
European Journal of Gastroenterology &... Dec 2001Hepatitis B virus replicates inside the hepatocyte through an intermediate step of reverse transcription mediated by the viral polymerase. We describe five... (Review)
Review
Hepatitis B virus replicates inside the hepatocyte through an intermediate step of reverse transcription mediated by the viral polymerase. We describe five nucleoside/nucleotide analogues that interfere with the replication mechanisms of the hepatitis B virus. The resemblance of nucleoside analogues to natural nucleosides may lead to direct cytotoxicity. Therefore, antiviral activity should always be interpreted in the light of cellular toxicity. In addition, prolonged therapy with a nucleoside analogue may induce mutations in the viral polymerase, causing structural and configurational changes of the polymerase resulting in a decreased affinity for the nucleoside analogue. Subsequently, the mutated virus is capable of renewed replication during continued antiviral pressure of the nucleoside analogue. The best antiviral strategy in the future is probably combination therapy, either with several nucleoside analogues or with a nucleoside analogue and interferon.
Topics: 2-Aminopurine; Adenine; Antiviral Agents; Famciclovir; Ganciclovir; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Organophosphonates; Reverse Transcriptase Inhibitors
PubMed: 11742201
DOI: 10.1097/00042737-200112000-00016