Born Method Research Articles

Study on the Interaction between Deuterium Clopidogrel and Omeprazole

Introduction: Dual antiplatelet therapy with aspirin in combination with a P2Y₁₂ receptor antagonist is a cornerstone for treating patients with acute coronary syndrome and in percutaneous coronary intervention. However, as this combination of antiplatelet therapy increases the risk of bleeding, proton pump inhibitors (PPIs) are currently recommended to prevent gastrointestinal ulcers and bleeding. The cytochrome P450 (CYP450) isoenzyme system metabolizes both clopidogrel (CLP) and PPIs. Unfortunately, omeprazole (OM) reduce the antiplatelet activity of CLP and increases the probability of recurrence of cardiovascular events by competitively inhibiting the CYP450 isoenzyme CYP2C19. Methods: To address these abovementioned problems, we designed and synthesized deuterium CLP (D-CL) using selective deuterium technology. Our previous research results showed that D-CL had better pharmacokinetic and pharmacodynamic properties. Thus, the HPLC-MS/MS method, cocktail method, Born method, electro-stimulated thrombus generation, and thrombus elastography were used to detect the production of thiol active metabolites (AM), CYP450 enzyme activities, platelet aggregation, time and length of thrombus formation, and the maximum clot strength after combination therapy. We investigated the pharmacokinetics and pharmacodynamics properties of D-CL combined with OM. Results: As compared to CLP, D-CL was less affected when combined with OM, which was reflected in lower inhibitory effects of CYP450 enzyme activities, a greater area under the curve of AM, and better antiplatelet and antithrombotic effects. Conclusion: D-CL may reduce drug-drug interactions and address the clinical disadvantages of CLP.

Importance of Three-Body Problems and Protein–Protein Interactions in Proteolysis-Targeting Chimera Modeling: Insights from Molecular Dynamics Simulations

Proteolysis-targeting chimeras (PROTACs) are a class of bifunctional molecules that can induce the ubiquitin degradation of its target protein by hijacking the E3 ligase to form a target protein-PROTAC-E3 ligase ternary complex. Its underlying principle has inspired the development of a wide range of protein degraders that are similar to or beyond PROTACs in recent years. The formation of the ternary complexes is the key to the success of PROTAC-induced protein degradation. Nevertheless, the lack of effective ternary complex modeling techniques has limited the application of computer-aided drug discovery tools to this emerging and fast developing new land in drug industry. Thus, in this study, we explored the application of the more physically sound molecular dynamics simulation and the molecular mechanics combined with the generalized Born and surface area continuum solvation (MM/GBSA) method to solve the underlying three-body problem in PROTAC modeling. We first verified the accuracy of our approach using a series of known Brd4 BD2 degraders. The calculated binding energy showed a good correlation with the experimental Kd values. The modeling of a unique property, namely, the α value, for PROTACs was also first and accurately performed to our best knowledge. The results also demonstrated the importance of PROTAC-induced protein-protein interactions in its modeling, either qualitatively or quantitatively. Finally, by standing on the success of earlier docking-based approaches, our protocol was also applied as a rescoring function in pose prediction. The results showed a notable improvement in reranking the initial poses generated from a modified Rosetta method, which was reportedly one of the best among a handful of PROTAC modeling approaches available in this field. We hope this work could provide a practical protocol and more insights to study the binding and the design of PROTACs and other protein degraders.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies.

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient’s age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

Monitoring of Aspirin Therapy in Patients with Cerebrovascular Pathology

Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM).Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer.Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p <0.05). In the group of patients with T2DM, the median ASA concentration was 0.01 [0; 0.32] μg/ml, and salicylic acid (SA)– 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025).Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.

Targeting SARS-CoV-2 Receptor Binding Domain with Stapled Peptides: An In Silico Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a pandemic of unprecedented scale. This coronavirus enters cells by the interaction of the receptor binding domain (RBD) with the human angiotensin-converting enzyme 2 receptor (hACE2). In this study, we employed a rational structure-based design to propose 22-mer stapled peptides using the structure of the hACE2 α1 helix as a template. These peptides were designed to retain the α-helical character of the natural structure, to enhance binding affinity, and to display a better solubility profile compared to other designed peptides available in the literature. We employed different docking strategies (PATCHDOCK and ZDOCK) followed by a double-step refinement process (FIBERDOCK) to rank our peptides, followed by stability analysis/evaluation of the interaction profile of the best docking predictions using a 500 ns molecular dynamics (MD) simulation, and a further binding affinity analysis by molecular mechanics with generalized Born and surface area (MM/GBSA) method. Our most promising stapled peptides presented a stable profile and could retain important interactions with the RBD in the presence of the E484K RBD mutation. We predict that these peptides can bind to the viral RBD with similar potency to the control NYBSP-4 (a 30-mer experimentally proven peptide inhibitor). Furthermore, our study provides valuable information for the rational design of double-stapled peptide as inhibitors of SARS-CoV-2 infection.

Use of increased concentrations of adenosinediphosphate for high residual platelet reactivity in patients with coronary heart disease

Detection of a tendency to increased thrombosis in patients with coronary heart disease (CHD) is of important prognostic value in the selection of drugs aimed at achieving a persistent antithrombotic effect. The aim of the study was to evaluate the use of elevated ADP inducer concentrations to improve the accuracy of ADP-induced platelet aggregation in patients with coronary heart disease. Material and method. Material and method. We studied 48 patients with CHD who were on continuous double antiplatelet therapy for 6 months (aspirin 75mg and clopidogrel 75mg per day). The aggregation activity of the platelet suspension was studied using the Born method G. in the modification of Gabbasov Z. A. Platelet activity was evaluated by the degree of aggregation of platelet-rich plasma along the light transmission curve under the influence of the inducer adenosine diphosphate (ADP) at a concentration of 2 mmol/l and by its own patented method against the background of additional ADP application. Results. In patients, platelet aggregation decreased to 5-35% (p<0.005) compared to the standard values, which are 50-60%. The values of platelet aggregation with the additional introduction of the inducer of aggregation ADP in a ratio of 2:1 to 2 µmol/l for 1, 2, 3, and 4-minute registration of platelet aggregation, resulted in increased aggregation from 55% to 75% (p<0.001), indicating high residual platelet reactivity on the background of double antiplatelet therapy. Correlations of the degree of aggregation for elevated ADP concentrations with multivessel arterial lesion and dyslipidemia were also found, r=0.86 and r=0.92, respectively. Conclusion. The use of elevated concentrations of adenosine diphosphate in platelet aggregation in patients with ischemic heart disease increases the accuracy of assessing ADP-induced platelet aggregation against the background of dual antiplatelet therapy and contributes to the detection of high residual platelet reactivity.

Druggability assessment of precursor membrane protein as a target for inhibiting the Zika virus

The Zika virus (ZIKV), a significant zoonotic flavivirus, was neglected as a human pathogen until the recent epidemic. The rapid geographic spread of the virus and association with neurological disorders has created a global public health concern pressing the need for anti-ZIKV drugs. Previous ZIKV drug discovery research has focused on three primary targets, RNA-dependent RNA polymerase, envelope protein, and viral proteases, and none has yet resulted in a commercially viable inhibitor. In the quest for finding effective inhibitors, it is important to expand the number of targets available for drug discovery research. To this end, the ZIKV precursor membrane protein (prM) comes to the forefront as a potential target due to its critical role in virus infectivity and pathogenicity. prM acts as a chaperone for envelope protein folding and prevents premature fusion of virions to the host membrane and has not been attempted as a drug target before. One critical requirement for a protein to be an effective target is the ability of the protein to be druggable, i.e. having active sites that can bind to specific ligands. In this work, the druggability of prM was assessed via molecular docking combined molecular dynamics simulations followed binding affinity kinetics studies. Compounds that had a high affinity to the prM protein were screened in silico and ligand-binding free energies were computed using molecular mechanics with generalized Born and surface area continuum solvation (MM-GBSA) method. In vitro binding kinetics via biolayer interferometry (BLI) and interaction analysis confirmed that prM could be targeted for drug discovery to combat ZIKV infection. Communicated by Ramaswamy H. Sarma

Enriched gradient recovery for interface solutions of the Poisson-Boltzmann equation

Accurate calculation of electrostatic potential and gradient on the molecular surface is highly desirable for the continuum and hybrid modeling of large scale deformation of biomolecules in solvent. In this article a new numerical method is proposed to calculate these quantities on the dielectric interface from the numerical solutions of the Poisson-Boltzmann equation. Our method reconstructs a potential field locally in the least square sense on the polynomial basis enriched with Green's functions, the latter characterize the Coulomb potential induced by charges near the position of reconstruction. This enrichment resembles the decomposition of electrostatic potential into singular Coulomb component and the regular reaction field in the Generalized Born methods. Numerical experiments demonstrate that the enrichment recovery produces drastically more accurate and stable potential gradients on molecular surfaces compared to classical recovery techniques.

Structural and functional insights of STAT2-NS5 interaction for the identification of NS5 antagonist – An approach for restoring interferon signaling

Dengue is a mosquito-borne viral infection caused by Dengue virus (DENV) and is an emerging concern in public health affecting billions of people worldwide annually with no effective drugs available till now. Immunogenic and highly conserved properties of Non-Structural Protein 5(NS5) in DENV makes it a potent marker to identify DENV infection. DENV interfere in the innate immune signaling and thereby decreases antiviral responses and favors viral replication. Viral recognition by host pathogen recognition receptors facilitates binding of interferon (IFN) to the interferon receptors that further activates both the Signal Transducer and Activator of Transcription-2 (STAT-2) a factor producing an antiviral response. The most debilitating factor of DENV infection is emaciation of human immune system by DENV- NS5. NS5 counters the antiviral response by STAT2 degradation impeding the transcriptional activation of interferon stimulated genes through interferon stimulated response elements. The present study aims to identify inhibitors for NS5 Methyl Transferase (MTase) domain and to provide an insight into the mechanism of STAT2 degradation in the host infected with DENV. Virtual screening and molecular docking studies identified five potential inhibitors ZINC84154300, ZINC08762321, ZINC08762323, ZINC12659408 and ZINC12285470 with docking scores of -10.55, -10.53, -10.78, -11.28 and -10.78 kcal/mol respectively. To further investigate the stability of the complexes, we have used Molecular Dynamics Simulations (MD). Besides, the binding free energy of top 5 docked ligands were estimated through Molecular Mechanics Generalized Born and Surface Area Solvation (MM/GBSA) methods. This study also provides an insight on the mechanism of immunological processes involved in alleviating the antiviral immune response and computational identification of potent inhibitors for viral NS5 protein.

Дифференциальные сечения рассеяния частиц плотной квазиклассической плазмы на основе метода Борна

Дифференциальные сечения рассеяния частиц плотной квазиклассической плазмы на основе метода Борна

Keluarga Dan Nilai Budaya Masyarakat Sunda Pada Perawatan Ibu Nifas Dan Bayi Baru Lahir

Objective: to identify the Sundanese cultural value for family in mother’s postpartum care and new born baby Methods: Qualitative method was used in this study along with descriptive techniques to analyzed the data. Data mining is done using profound interview with four respondents who originally from the Sundanese tribe and live in Cipagalo village. Respondents are mothers who have two to six months old child.. Furthermore, the interview was also conducted with paraji as person who are still active giving services in the area. All data was collected by recording the conversations and based on the respondents’ consent. Next, the data were interpreted, reduced, and coded for final result. Analytical descriptive analysis was next conducted to this research findings using journals assessment. All findings were divided into three categories; useful findings, harmful findings, and insignificant findings. Useful findings are results that have scientific evidence and can be recommended to do. Harmful ones are things that are scientifically proofed to have harmful effect, whereas insignificant findings are results with unknown scientific proofs whether its harmful or not.Results: Results in this study showed various Sundanese cultural habits in Cipagalo village:(1) There are some forbidden food and beverages during the postpartum phase, including spicy, sour, and cold ones.(2) Suggestion to consume apple during the postpartum phase.(3) Herbs or traditional potion for postpartum. Herbs can be consumed in various ways like (a) boiling and drinking it, (b) grating and squeezing it, (c) boiling and using it to wash the private area (smeared).(4) Rest and sleep pattern. There is tradition which done by the mothers; they should not take a nap in the afternoon, afraid that the white blood cells would go up the eyes, or they could take a nap in a seated position with both toes tied together in hope it would help to tighten mom’s private area.(5) Clothes and mother’s care. There is a habit of using corset (stagen) or what they called bebengkung, soaking feet in warm water, and massaging mom’s body.(6) Massaging mom’s body. Not only massaging body parts, there is also massaging the uterus (disangsurkeun).(7) Baby care culture and traditional ceremonies. This includes placenta burial using spices or what the sundanese called as bali, baby girls circumcision and ear piercing.Conclusion: The habit of consuming apple, body massage, feet massage in warm water, the use of binahong leaves and ginger, handeuleum, and baby massage showed benefits not only for moms, but also babies during postpartum phase.

Structure-based drug design of peroxisome proliferator-activated receptor gamma inhibitors: ferulic acid and derivatives

Peroxisome proliferator-activated receptor gamma (PPARγ), ligand-activated transcription factor, is a key modulator of genes considered in diabetes development as well as treatment. Adipogenesis differentiation through PPARγ, CCAAT-enhancer protein alpha (C/EBPα) is identified as a critical mechanism in fat accumulation and weight gain. Polyphenols studied against adipocyte differentiation is taken up for consistent support and drug discovery. Structure-based drug design found useful to distinguish the underlying mechanism of receptor–ligand interaction and function. In this work, phenolic acids, ferulic acid and its derivatives are used as ligands. Molecular parameters have been set to filter and sort the 34 derivatives from ZINC and PubChem databases. Besides, for affinity and activity identification, troglitazone and resveratrol co-crystallized ligands have been studied. Absorption, distribution, metabolism, elimination and toxicity, density functional theory, highest occupied molecular orbital–lowest unoccupied molecular orbital values and docking scores define the drug candidate as a potential inhibitor. Residues Ser 342 and Arg 280 bind with the ligands by forming hydrogen bonds and hydrophobic contacts. Based on the docking score, pharmacophore properties and functional energy values of the top six compounds are chosen for molecular dynamics and simulation. Consistency and stability maintained throughout the simulation up to 50 ns were observed. Free binding energy values and standard deviation of receptor and ligand calculated using molecular mechanics–generalized Born and surface area solvation method (MM_GBSA) is found significant. Therefore, ferulic acid derivatives and phenolic acids could be a potential inhibitor for adipocyte differentiation and lipid accumulation. Communicated by Ramaswamy H. Sarma

Factors associated with platelet reactivity during dual antiplatelet therapy in patients with diabetes after acute coronary syndrome

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478–10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073–1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097–0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.

Determination of the effect of EDTA and PCMB on purified bromelain activity from pineapple core and in vitro antiplatelet activity

Bromelain is an enzyme belongs to the cysteine protease. In this study, bromelain isolated from pineapple core (Ananascomosus [L.] Merr) was purified by fractionation using ammonium sulfate followed by dialysis and then ion exchange chromatography. The fraction of bromelain obtained from each purification step showed an increase in specific activity. The highest specific activity of protease was found in 20-50% ammonium sulfate fraction of 104.018 U/mg with a purity level 3.2-fold compared to crude extract. Further purification by ion exchange chromatography using DEAE-Cellulose, the fraction of bromelain showed an increase in specific activity to 278.333 U/mg with a purity level 8.8-fold compared to crude extract. The determination of kinetics parameter of purified bromelain using Lineweaver-Burk plot gives Km value of 0.15 % (w/v) and Vmax of 0.056 U/min. This bromelain can be strongly inhibited by EDTA and PCMB. The addition of EDTA and PCMB at a concentration of 0.5 mM can decrease the activity of the enzyme up to 88.50% by showing the competitive and mix-inhibition types of inhibition, respectively. The antiplatelet activity of the bromelain fraction was tested in-vitro based on the Born method, by using plasma (PRP), acetosal as a positive control and ADP as an aggregator. The purified bromelain showed the ability of an antiplatelet agent with percentage of aggregation 29.51% and percentage of inhibition 68.91%.

Design, synthesis, and biological evaluation of 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamide derivatives as potential antiplatelet agents.

A series of 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamides 6a-u were designed according to the splicing principle of structural design in the medicinal chemistry theory and were synthesized in five steps: nitration, acylation, ammoniation, reduction, and secondary ammoniation. The structures of the target compounds were characterized and verified by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and electron spray ionization spectroscopy. Their in vitro antiplatelet aggregation activities induced by adenosine diphosphate (ADP) or arachidonic acid (AA) were assessed by Born's method. The biological evaluation revealed that all compounds exhibited certain levels of activities in both of the antiplatelet aggregation assays; compounds 6c (IC50 = 3.84 μM) and 6f (IC50 = 3.12 μM) displayed the strongest antiplatelet aggregation activities in the ADP-induced and AA-induced assay, separately. Moreover, compounds that had stronger activities were chosen for cell toxicity testing via the cell counting kit-8 assay. The results indicated that none of the compounds had obvious cell toxicity against L929 cells at the doses of 10 and 20 μM. It is worth pointing out that compound 6c showed the highest antiplatelet activity and the lowest cell toxicity. In general, 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamides have the potential to become a kind of safer and more effective antiplatelet agents.

Default sequence of Mozart’s compositions during pregnancy gave higher dendritic density in the cerebrum and cerebellum of Rattus norvegicus offsprings compared with reversed sequence and control

Objectives: This study aim to determine sequence of Mozart songs in the analyzing differences in dendritic density of cerebellum and cerebellum of new born Rattus novergicusMaterials and Methods: Experimental study randomized post test only control group design using Rattus norvegicus. Animal subjects were divided into three groups which were control group, and the treatment group that were given exposure to default sequence and reversed sequence of Mozart's music from gestation day 10. We used a comparison test in the analysis expression of BDNF.Results: In the cerebrum there was a significant difference in the Mozart group in reverse rather than with Mozart standard sequence and in standard Mozart group with no exposure group, with p=0.003 and p=0.000. In the cerebellum there was a significant difference in the group in reverse rather than with standard Mozart and in the standard Mozart group with the control group, with p=0.000 and p=0.000. However, there was no significant difference between control group and Mozart group upside down in cerebrum and cerebellum with p=0.109 and p=0.077Conclusion: The density of dendrites in the cerebrum and cerebellum of Rattus norvegicus newborn exposed to Mozart's music during pregnancy with standard Mozart sequence was higher than that in those receiving reverse order and without exposure. There were no significant differences between the density of the cerebrum and cerebellum dendrites between groups exposed to reversed sequence of Mozart composition and those without exposure.

Default sequence of Mozart’s compositions during pregnancy gave higher dendritic density in the cerebrum and cerebellum of Rattus norvegicus offsprings compared with reversed sequence and control

Objectives: This study aim to determine sequence of Mozart songs in the analyzing differences in dendritic density of cerebellum and cerebellum of new born Rattus novergicus Materials and Methods: Experimental study randomized post test only control group design using Rattus norvegicus . Animal subjects were divided into three groups which were control group, and the treatment group that were given exposure to default sequence and reversed sequence of Mozart's music from gestation day 10. We used a comparison test in the analysis expression of BDNF. Results: In the cerebrum there was a significant difference in the Mozart group in reverse rather than with Mozart standard sequence and in standard Mozart group with no exposure group, with p=0.003 and p=0.000. In the cerebellum there was a significant difference in the group in reverse rather than with standard Mozart and in the standard Mozart group with the control group, with p=0.000 and p=0.000. However, there was no significant difference between control group and Mozart group upside down in cerebrum and cerebellum with p=0.109 and p=0.077 Conclusion: The density of dendrites in the cerebrum and cerebellum of Rattus norvegicus newborn exposed to Mozart's music during pregnancy with standard Mozart sequence was higher than that in those receiving reverse order and without exposure. There were no significant differences between the density of the cerebrum and cerebellum dendrites between groups exposed to reversed sequence of Mozart composition and those without exposure.

Improving DOT reconstruction with a Born iterative method and US-guided sparse regularization.

Ultrasound (US)-guided diffuse optical tomography (DOT) is a promising low-cost imaging technique for diagnosis and assessment of breast cancer. US-guided DOT is best implemented in reflection geometry, which can be co-registered with US pulse-echo imaging and also minimizes the tissue depth for adequate light penetration. However, due to intense light scattering, the DOT reconstruction problem is ill-posed. In this communication, we describe a new non-linear Born iterative reconstruction method with US-guided depth-dependent sparse regularization for improving DOT reconstruction by incorporating a priori lesion depth and shape information from the co-registered US image. Our method iteratively solves the inverse problem by updating the photon-density wave using the finite difference method, computing the weight matrix based on Born approximation, and reconstructing the absorption map using the fast iterative shrinkage-thresholding optimization algorithm (FISTA). We validate our method using both phantom and patient data and compare the results with those using the first order linear Born method. Phantom experiments demonstrate that the non-linear Born method provides more accurate target absorption reconstruction and better resolution than the linear Born method. Clinical studies on 20 patients show that non-linear Born reconstructs more realistic tumor shapes than linear Born, and improves the malignant-to-benign lesion contrast ratio from to , which is a improvement. For lesions approximately more than cm in diameter, the average malignant-to-benign lesion contrast ratio is increased from to , which is a improvement.

Molecular modelling of fullerene C60 and its amino acid derivatives in aqueous medium

The hydration free energy ΔGs of fullerene C60 has been determined using the quantum mechanical methods and continuum solvent models, microscopic free energy molecular dynamics techniques, and compilation of known experimental data. Theoretical calculations using standard parameterization schemes of solvent models have predicted negative values of ΔGs(C60) whereas application of the revised parameters, that take into account special features of carbon structures, shifts the computed ΔGs(C60) to positive values. Reasonably accurate estimates of the hydration free energies of the neutral and anionic states of functionalized fullerenes were obtained from the generalized Born method. The described data have shown that the calculations of hydration thermodynamics of fullerenes apparently require separate parameterization for the carbon atoms met in these nanomolecules.

Scintillation index of flat-topped beam through non-Kolmogorov turbulence

The mathematical formula of off-axis scintillation for flat-topped beam through non-Kolmogorov atmospheric turbulence is derived using the generalized non-Kolmogorov spectrum model and the equivalent structure constant based on the Born and Rytov perturbation methods. The variations of the off-axis scintillation at the receiver plane is analyzed comprehensively versus the radial distance. The results can correctly reduce to the existing off-axis intensity fluctuations of Gaussian beams in non-Kolmogorov turbulence. It is indicated that flat-topped beams possess much smaller off-axis scintillation indexes than that of Gaussian beams at large radial distance and the scintillation of flat-topped beam will suffer invariability even descend before increasing with the increment of radial distance. These results can be applied to research of flat-topped laser communication.