Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Virtual reality for acute pain in outpatient hysteroscopy: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of virtual reality as a distraction technique in the management of acute pain and anxiety during outpatient hysteroscopy. DESIGN: Parallel group, prospective randomised controlled trial. SETTING: UK University Hospital. METHODS: Forty consenting, eligible women were randomised to virtual reality intervention (immersive video content as a distraction method) or standard care during outpatient hysteroscopy from August to October 2018. MAIN OUTCOME MEASURES: Pain and anxiety outcomes were measured as a numeric rating score (scale 0-10). RESULTS: Compared with standard care, women with virtual reality intervention experienced less average pain (score 6.0 versus 3.7, mean difference 2.3, 95% CI 0.61-3.99, P = 0.009) and anxiety (score 5.45 versus 3.3, mean difference 2.15, 95% CI 0.38-3.92, P = 0.02). CONCLUSION: Virtual reality was effective in reducing pain and anxiety during outpatient hysteroscopy in a mixed-methods randomised control trial. Its wide potential role in ambulatory gynaecological procedures needs further evaluation. TWEETABLE ABSTRACT: Virtual reality can be used as a part of a multimodal strategy to reduce acute pain and anxiety in patients undergoing outpatient hysteroscopy.

Association between Hashimoto's thyroiditis and melanoma: a retrospective matched cohort study.

An inflammatory microenvironment has been shown to increase risk for malignant melanoma, suggesting that melanoma may be related to a pro-inflammatory state. Though Hashimoto's thyroiditis is one of the most common autoimmune diseases, there are no investigations of its relationship with melanoma. We aim to determine if Hashimoto's increases risk of developing melanoma. A retrospective, validated cohort of patients with a diagnosis of Hashimoto's between 2005 and 2020 were identified using the Olmsted County database. Patients were age and sex matched to controls without a Hashimoto's diagnosis. The primary outcomes were development of melanoma and time to first melanoma diagnosis. 4805 patients were included in the study, with 1726 (36%) having a diagnosis of Hashimoto's. Hashimoto's patients had no significant difference in risk of melanoma (relative risk 0.96, 95% CI 0.78-1.17) or nonmelanoma skin cancer (relative risk 0.95, 95% CI 0.86-1.06) compared with matched controls. This suggests that the local proinflammatory environment present in Hashimoto's does not contribute significantly to melanoma risk. Larger studies may be needed to further characterize the relationship between these diseases.

Effect of gas flow on electronic transport in a DNA-decorated carbon nanotube.

We calculate the two-time current correlation function using the experimental data of the current-time characteristics of the Gas-DNA-decorated carbon nanotube field effect transistor. The pattern of the correlation function is a measure of the sensitivity and selectivity of the sensors and suggest that these gas flow sensors may also be used as DNA sequence detectors. The system is modelled by a one-dimensional tight-binding Hamiltonian and we present analytical calculations of quantum electronic transport for the system using the time-dependent nonequilibrium Green's function formalism and the adiabatic expansion. The zeroth and first order contributions to the current I(0)(t) and I(1)(t) are calculated, where I(0)(t) is the Landauer formula. The formula for the time-dependent current is then used to compare the theoretical results with the experiment.

Synthesis, Anticancer, and Antibacterial Studies of Benzylidene Bearing 5-substituted and 3,5-disubstituted-2,4-Thiazolidinedione Derivatives.

AIM: To develop novel compounds having potent anticancer and antibacterial activities. BACKGROUND: Several studies have proved that benzylidene analogues of clinical 2,4-TZDs, such as troglitazone and ciglitazone, have more potent antiproliferative activity than their parent compounds. Literature studies also revealed that the attachment of more heterocyclic rings, containing nitrogen on 5th position of 2,4-TZD, can enhance the antimicrobial activity. Hence, attachment of various moieties on the benzylidene ring may produce safe and effective compounds in the future. OBJECTIVE: The objective of the present study was to synthesize a set of novel benzylidene ring containing 5- and 3-substituted-2,4-thiazolidinedione derivatives and evaluate them for their anticancer and antibacterial activity. METHODS: The synthesized compounds were characterized by IR, NMR, mass, and elemental studies. The in vitro cytotoxicity studies were performed for human breast cancer (MCF-7) and human lung cancer (A549) cells and HepG2 cell-line and compared to standard drug doxorubicin by MTT assay. Antimicrobial activity of the synthesized 2,4-thiazolidinediones derivatives was carried out using the cup plate method with slight modification. RESULTS: The results obtained showed that TZ-5 and TZ-13 exhibited good antiproliferative activity against A549 cancer cell-line, whereas TZ-10 exhibited moderate antiproliferative activity against HepG2 cell-line when compared to standard drug doxorubicin. TZ-5 also exhibited reasonable activity against the MCF-7 cell-line with doxorubicin as standard. TZ-4, TZ-5, TZ-6, TZ-7, and TZ- 16 exhibited remarkable antibacterial activity against Gram positive and moderate activity against Gram negative bacteria with the standard drug ciprofloxacin. CONCLUSION: Attachment of heterocyclic rings containing nitrogen as the hetero atom improves the anticancer and antimicrobial potential. Attachment of electronegative elements like halogens can also enhance the antimicrobial activity. Further structure modifications may lead to the development of more potent 2,4-TZD leads that can be evaluated for further advanced studies.

Structural and thermodynamic properties of a linearly perturbed matrix model for RNA folding.

The structural and thermodynamic properties of a matrix model of homo-RNA folding with linear external interaction are studied. The interaction distinguishes paired bases of the homo-RNA chain from the unpaired bases hence dividing the possible RNA structures given by the linear model into two structural regimes. The genus distribution functions show that the total number of structures for any given length of the chain are reduced for the simple linear interaction considered. The partition function of the model exhibits a scaling relation with the matrix model in which the base pairing strength parameter is re-scaled (G. Vernizzi, H. Orland, A. Zee, Phys. Rev. Lett. 94, 168103 (2005)). The thermodynamics of the model are computed for i) largely secondary structures, (with tertiary structures suppressed by a factor 10(-4)) and ii) secondary plus tertiary structures. A structural change for large even lengths is observed in the free energy and specific heat. This change with largely secondary structures appears much before (with respect to length of the chain) than when all the structures (secondary and pseudoknots) are considered. The appearance of different structures which dominate the ensemble with varying temperatures is also found as a function of the interaction parameter for different types of structures (given by different numbers of pairings).

Synthesis and In Silico Molecular Docking Studies on Substituted Piperic Acid Derivatives as Inhibitors of Bacterial DNA Gyrase.

BACKGROUND: Piperine or piperic acid was isolated from fruits of Piper nigrum and had been reported as pharmacological valuable bioactive constituents. Keeping in view, a series of piperic acid-based N heterocyclic's derivatives were synthesized and evaluated for antibacterial activity. All these prepared ligands were docked to study the molecular interactions and binding affinities against the protein PDB ID: 5 CDP. OBJECTIVE: To meet the real need of newer antibacterials, we designed and synthesized scaffolds with good antibacterial activity. The obtained antibacterials have been validated in terms of ligand-protein interaction and thus prove to build up as good drug candidates. METHODS: Antibacterial activity of the compounds were carried out against bacterial strains; three Grampositive and three Gram-negative bacterial strains using agar well diffusion method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0. RESULTS: Compounds BC 28, BC 32, and BC 33 exhibits antibacterial activity along with Glide docking score of -8.580, -9.753 kcal/mol, and -8.813 kcal/mol, respectively. Docking studies explained hydrogen bonding, pi-pi, and hydrophobic interactions with amino acid residues which explain the binding affinity of the most docked ligand with protein. CONCLUSION: In the present study, substituted piperic acid was synthesized and evaluated as antibacterial compared with standard drug ciprofloxacin and results interpret that having nitrogen as heteroatom in the heterocyclic nucleus found to be more potent than the standard drug ciprofloxacin. On comparing, substitution with electron-donating groups generates excellent antibacterial potential against the bacterial strains. It was also proved that having substitution with electron-donating groups on meta and para position with triazoline ring system exhibits greater potential while compounds which have a meta- electron-donating substituent showed lesser activity with thiazole nucleus. In addition, structure-based activities of the prepared analogs were discussed under Structure-Activity Relationship (SAR) section.

RNA matrix models with external interactions and their asymptotic behavior.

We study a matrix model of RNA in which an external perturbation on n nucleotides is introduced in the action of the partition function of the polymer chain. The effect of the perturbation appears in the exponential generating function of the partition function as a factor exp(1-nalpha/L) (where alpha is the ratio of strengths of the original to the perturbed term and L is the length of the chain). The asymptotic behavior of the genus distribution functions as a function of length for the matrix model with interaction is analyzed numerically for all n

Practical consensus recommendations regarding the management of sentinel lymph node issues in early breast cancer.

Axillary lymph node involvement is a very important poor prognostic factor in the clinical staging and management of breast cancer patients. Traditionally, axillary lymph node dissection (ALND) has been used for determining the status of the axillary lymph nodes. More recently the sentinel lymph node biopsy (SLNB) procedure has gained wider acceptance as the standard of care, having the advantage of being less invasivewhile providing good accuracy. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of the two different procedures and other issues in patients with early breast cancer for the benefit of community oncologists.

Therapeutic Potential of N-heterocyclic Analogs as Anti-inflammatory Agents.

BACKGROUND: Various mediators and anti-inflammatory drugs were used since from a long time but it is still a challenge for the medicinal chemists to treat or reduce the symptoms of inflammatory diseases. Most of the clinically used anti-inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable toxicity. OBJECTIVE: The search of novel anti-inflammatory agent is not an ending process. Although the drug treatment has been improved steadily but yet, it is still there is a need to develop more potent therapeutic agents. METHOD: Reported literature survey has been studied to summarize the nitrogen containing moieties which were utilized as potential therapeutic agents. RESULTS: A variety of N-heterocyclic analogs are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal and anti-HIV. However, numerous approaches were used to overcome the toxicity level such as co-administration with suitable agent/substance which provides protection against toxicity as well to synthesise new potent and safe anti-inflammatory drug. CONCLUSION: The present review summarizes the synthetic methodology and therapeutic potential of some N-heterocyclic analogs as potent anti-inflammatory agents.

Adsorption and dissolution behavior of human plasma fibronectin on thermally and chemically modified titanium dioxide particles.

Titanium is known for its biocompatibility and is widely used in dental and orthopedic reconstructive surgery. There are reports that osteointegration of these implants is not optimal. The objective of this study was to modify titanium dioxide particles and examine the resultant effects on protein adsorption to these altered surfaces using a model cell binding protein, human plasma fibronectin (HPF). HPF is an important matrix glycoprotein that plays a major role in cell and protein attachment, Titanium dioxide surfaces were modified by heating the titanium dioxide powder at 800 degrees C for 1 h or treating with an oxidizing agent: peroxide in ammonium hydroxide followed by peroxide in hydrochloric acid. Oxidized and control samples were further treated with 9:1 butanol:water for 30 min. Brunauer-Emmett-Teller showed no change in particle surface area as a result of thermal or chemical treatment. Hydrophobicity increased with butanol treatment of titanium dioxide. Diffuse reflectance Fourier transform infrared spectroscopy showed the presence of -CH2 and -CH3 vibrations in the region of 2850-3000 cm(-1) for both the heated, butanol and peroxide/butanol-treated samples. The absence of increased C-O and O-C=O features as determined by electron spectroscopy for chemical analysis indicates that butanol adsorption is not occurring via an esterification mechanism. The interaction between butanol and pre-heated or peroxide-treated titanium dioxide may be one of association (weak electrostatic and/or Van der Waals forces) rather than direct ionic bonding. Maximum HPF adsorption on modified or unmodified titanium dioxide occurred within 30 min, with greater protein adsorption occurring on butanol-treated samples. Desorption was minimal with all modifications. Zeta potential measurements showed that HPF adsorption caused an increase in the negative zeta potential with the greatest change noted for the butanol-treated samples. These findings suggest that wettability and surface charge both play an important role in protein adsorption to titanium dioxide. Thus, by modifying the physico-chemical properties of titanium dioxide surfaces, it may be possible to alter protein adsorption and hence optimize cell attachment.

Thermal and chemical modification of titanium-aluminum-vanadium implant materials: effects on surface properties, glycoprotein adsorption, and MG63 cell attachment.

The microstructure, chemical composition and wettability of thermally and chemically modified Ti-6Al-4V alloy disks were characterized and correlated with the degree of radiolabeled fibronectin-alloy surface adsorption and subsequent adhesion of osteoblast-like cells. Heating either in pure oxygen or atmosphere (atm) resulted in an enrichment of Al and V within the surface oxide. Heating (oxygen/atm) and peroxide treatment both followed by butanol treatment resulted in a reduction in content of V, but not in Al. Heating (oxygen/atm) or peroxide treatment resulted in a thicker oxide layer and a more hydrophilic surface when compared with passivated controls. Post-treatment with butanol, however, resulted in less hydrophilic surfaces than heating or peroxide treatment alone. The greatest increases in the adsorption of radiolabeled fibronectin following treatment were observed with peroxide/butanol-treated samples followed by peroxide/butanol and heat/butanol, although binding was only increased by 20-40% compared to untreated controls. These experiments with radiolabeled fibronectin indicate that enhanced adsorption of the glycoprotein was more highly correlated with changes in chemical composition, reflected in a reduction in V content and decrease in the V/Al ratio, than with changes in wettability. Despite promoting only a modest elevation in fibronectin adsorption, the treatment of disks with heat or heat/butanol induced a several-fold increase in the attachment of MG63 cells promoted by a nonadhesive concentration of fibronectin that was used to coat the pretreated disks compared to uncoated disks. Therefore, results obtained with these modifications of surface properties indicate that an increase in the absolute content of Al and/or V (heat), and/or in the Al/V ratio (with little change in hydrophilicity; heat+butanol) is correlated with an increase in the fibronectin-promoted adhesion of an osteoblast-like cell line. It would also appear that the thermal treatment-induced enhancement of cell adhesion in the presence of this integrin-binding protein is due to its increased biological activity, rather than a mass effect alone, that appear to be associated with changes in chemical composition of the metallic surface. Future studies will investigate the influence of the surface chemical composition of various implantable alloys on protein adsorption and receptor-mediated cell adhesion. In addition, by altering the properties of bound osteogenic protein enhancing exposure to cell integrin binding domains, it may be possible to develop implant surfaces which enhance the attachment, adhesion and developmental response of osteoblast precursors leading to accelerated osseointegration.

Minor alkaloids of tobacco release [3H]dopamine from superfused rat striatal slices.

In addition to S(-)-nicotine, several minor tobacco alkaloids ((+/-)-nornicotine, anabaseine, S(-)-anabasine, and S(-)-N-methylanabasine) are present in tobacco smoke. This study demonstrates that these alkaloids increase fractional 3H release in a concentration-dependent manner from rat striatal slices preloaded with [3H]dopamine, with desensitization of this response. The rank order of EC50 values was S(-)-nicotine (3.0 +/- 2.2 microM) > (+/-)-nornicotine (6.7 +/- 2.1 microM) > anabaseine (15.4 +/- 6.1 microM) = S(-)-N-methylanabasine (16.3 +/- 4.7 microM) = S(-)-anabasine (19.3 +/- 3.2 microM). The alkaloids did not modulate fractional 3H release evoked by electrical-field depolarization. Thus, minor tobacco alkaloids may contribute to the apparent neuroprotective effects of smoking in neurodegenerative diseases.

Counting multiple solutions in glassy random matrix models.

This is a first step in counting the number of multiple solutions in certain glassy random matrix models introduced by N. Deo [Phys. Rev. E 65, 056115 (2002)]. We are able to do this by reducing the problem of counting the multiple solutions to that of a moment problem. More precisely, we count the number of different moments when we introduce an asymmetry (tapping) in the random matrix model and then take it to vanish. It is shown here that the number of moments grows exponentially with respect to N, the size of the matrix. As these models map onto models of structural glasses in the high temperature phase (liquid), this may have interesting implications for the supercooled liquid phase in these spin glass models. Further, it is shown that the nature of the asymmetry (tapping) is crucial in finding the multiple solutions. This also clarifies some of the puzzles raised by E. Brézin and N. Deo [Phys. Rev. E 59, 3901 (1999)].

Glassy random matrix models.

This paper discusses random matrix models that exhibit the unusual phenomena of having multiple solutions at the same point in phase space. These matrix models have gaps in their spectrum or density of eigenvalues. The free energy and certain correlation functions of these models show differences for the different solutions. This study presents evidence for the presence of multiple solutions both analytically and numerically. As an example this paper discusses the double-well matrix model with potential V(M)=-(mu/2)M(2)+(g/4)M(4), where M is a random N x N matrix (the M(4) matrix model) as well as the Gaussian Penner model with V(M)=(mu/2)M(2)-t ln M. First this paper studies what these multiple solutions are in the large N limit using the recurrence coefficient of the orthogonal polynomials. Second it discusses these solutions at the nonperturbative level to bring out some differences between the multiple solutions. Also presented are the two-point density-density correlation functions, which further characterize these models in a different universality class. A motivation for this work is that variants of these models have been conjectured to be models of certain structural glasses in the high temperature phase.

Spectral statistics of instantaneous normal modes in liquids and random matrices.

We study the statistical properties of eigenvalues of the Hessian matrix H (matrix of second derivatives of the potential energy) for a classical atomic liquid, and compare these properties with predictions for random matrix models. The eigenvalue spectra (the instantaneous normal mode or INM spectra) are evaluated numerically for configurations generated by molecular dynamics simulations. We find that distribution of spacings between nearest-neighbor eigenvalues, s, obeys quite well the Wigner prediction s exp(-s(2)), with the agreement being better for higher densities at fixed temperature. The deviations display a correlation with the number of localized eigenstates (normal modes) in the liquid; there are fewer localized states at higher densities that we quantify by calculating the participation ratios of the normal modes. We confirm this observation by calculating the spacing distribution for parts of the INM spectra with high participation ratios, obtaining greater conformity with the Wigner form. We also calculate the spectral rigidity and find a substantial dependence on the density of the liquid.

A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis.

BACKGROUND: Congenital tibial dysplasia is a severe pediatric condition that classically results in a persistent pseudarthrosis. A majority of these cases are associated with neurofibromatosis type I (NF1), a genetic disorder in which inactivation of the NF1 gene leads to overactivity of the Ras-MEK-MAPK (mitogen-activated protein kinase) signaling pathway. We therefore hypothesized that pharmaceutical inhibition of MEK-MAPK may be a beneficial therapeutic strategy. METHODS: In vitro methods were used to demonstrate a role for the MEK inhibitor PD0325901 in promoting osteogenic differentiation in Nf1-/- calvarial osteoblasts. Local applications of rhBMP-2 and/or PD0325901 were then tested in a mouse model of NF1 tibial pseudarthrosis featuring localized double inactivation of the Nf1 gene in a fracture. Mice received no treatment, PD0325901 (10 mg/kg/day from two days before fracture to ten days after fracture), rhBMP-2 (10 µg), or a combination of rhBMP-2 and PD0325901. RESULTS: Animals treated with the delivery vehicle alone, PD0325901, rhBMP-2, or the PD0325901 + rhBMP-2 combination showed union rates of 0%, 8%, 69% (p < 0.01), or 80% (p < 0.01), respectively, at twenty-one days after fracture. Mice treated with the rhBMP-2 + PD0325901 combination displayed a callus volume sixfold greater than the vehicle controls and twofold greater than the group receiving rhBMP-2 alone. Although MEK inhibition combined with rhBMP-2 led to increases in bone formation and union, the proportion of fibrous tissue in the callus was not significantly reduced. CONCLUSIONS: The data suggest that MEK inhibition can promote bone formation in combination with rhBMP-2 in the context of an NF1 pseudarthrosis. However, PD0325901 did not promote substantive bone anabolism in the absence of an exogenous anabolic stimulus and did not suppress fibrosis. CLINICAL RELEVANCE: This study examines a signaling pathway-based approach to treating poor bone healing in a model of NF1 pseudarthrosis.

Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib).

MEK inhibitors (MEKi) PD0325901 and AZD6244 (Selumetinib) are drugs currently under clinical investigation for cancer treatment, however the Ras-MAPK pathway is also an important mediator of normal bone cell differentiation and function. In this study we examined the effects of these compounds on endochondral processes using both in vitro and in vivo models. Treatment with PD0325901 or AZD6244 significantly increased Runx2 and Alkaline phosphate gene expression in calvarial osteoblasts and decreased TRAP+ cells in induced osteoclast cultures. To test the effects of these drugs on bone healing, C57/Bl6 mice underwent a closed tibial fracture and were treated with PD0325901 or AZD6244 at 10mg/kg/day. Animals were culled at day 10 and at day 21 post-fracture for analysis of the fracture callus and the femoral growth plate in the contralateral leg. MEKi treatment markedly increased cartilage volume in the soft callus at day 10 post-fracture (+60% PD0325901, +20% AZD6244) and continued treatment led to a delay in cartilage remodeling. At the growth plate, we observed an increase in the height of the hypertrophic zone relative to the proliferative zone of +78% in PD0325901 treated mice. Osteoclast surface was significantly decreased both at the terminal end of the growth plate and within the fracture calluses of MEKi treated animals. The mechanistic effects of MEKi on genes encoding cartilage matrix proteins and catabolic enzymes were examined in articular chondrocyte cultures. PD0325901 or AZD6244 led to increased matrix protein expression (Col2a1 and Acan) and decreased expression of catabolic factors (Mmp13 and Adamts-5). Taken together, these data support the hypothesis that MEKi treatment can impact chondrocyte hypertrophy, matrix resorption, and fracture healing. These compounds can also affect bone architecture by expanding the hypertrophic zone of the growth plate and reducing osteoclast surface systemically.

Genus distribution and thermodynamics of a random matrix model of RNA with Penner interaction.

The nonlinear Penner external interaction is introduced and studied in the random matrix model of homo RNA. A numerical technique is developed to study the partition function, and a general formula is obtained for all lengths. The genus distribution function for the system is obtained, plotted, and compared with the genus distribution for the real RNA structures found from the protein databank. The genus distribution shows that the nonlinear interaction favors the formation of low genus structures and matches the result for real RNA structures. The distribution of structure with temperature suggests that nonlinear interaction is biased toward the planar structures. The variation of chemical potential with temperature and interaction strength indicates the presence of additional molecules in the system other than the magnesium ions and possibly represents a phase transition. The specific heat has a bump and its derivatives shows a double-peak behavior at a particular temperature. On analyzing the specific heat and derivatives for each genus separately, the planar structure (genus zero) is shown to contribute the most to the bump and double peak. This observation in the nonlinear model is similar to that observed in the unfolding experiments on RNA.