Accelerating the search for global minima on potential energy surfaces using machine learning.

Controlling molecule-surface interactions is key for chemical applications ranging from catalysis to gas sensing. We present a framework for accelerating the search for the global minimum on potential surfaces, corresponding to stable adsorbate-surface structures. We present a technique using Bayesian inference that enables us to predict converged density functional theory potential energies with fewer self-consistent field iterations. We then discuss how this technique fits in with the Bayesian Active Site Calculator, which applies Bayesian optimization to the problem. We demonstrate the performance of our framework using a hematite (Fe2O3) surface and present the adsorption sites found by our global optimization method for various simple hydrocarbons on the rutile TiO2 (110) surface.

Unilateral segmentally arranged basaloid follicular hamartomas with osteoma cutis and hypodontia: a case of Happle-Tinschert syndrome.

Happle-Tinschert syndrome (HTS) is a rare syndrome characterized by segmentally arranged basaloid follicular hamartomas (BFH) associated with ipsilateral osseous, dental and cerebral abnormalities. Happle and Tinschert first reported this disorder in 2008, and three cases with similar presentations have since been reported. We report another case, that of a 40-year-old man, presenting with the characteristic clinical features of HTS.

Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.

AIMS/HYPOTHESIS: We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita mouse model of type 1 diabetes. METHODS: Adult male Akita mice (12 weeks old) were treated with insulin implants and killed at week 16. Untreated non-Akita littermates served as controls. The effects of insulin on blood glucose, systolic BP (SBP), renal proximal tubular cell (RPTC) gene expression and interstitial fibrosis were studied. We also examined immortalised rat RPTCs stably transfected with control plasmid or with plasmid containing rat Agt promoter in vitro. RESULTS: Insulin treatment normalised blood glucose levels and SBP, inhibited renal AGT expression but enhanced hnRNP F, hnRNP K and angiotensin-converting enzyme-2 expression, attenuated renal hypertrophy and glomerular hyperfiltration and decreased urinary albumin/creatinine ratio, as well as AGT and angiotensin II levels, in Akita mice. In vitro, insulin inhibited Agt but stimulated Hnrnpf and Hnrnpk expression in high-glucose media via p44/42 mitogen-activated protein kinase signalling in RPTCs. Transfection with Hnrnpf or Hnrnpk small interfering RNAs prevented insulin inhibition of Agt expression in RPTCs. CONCLUSIONS/INTERPRETATION: These data indicate that insulin prevents hypertension and attenuates kidney injury, at least in part, through suppressing renal Agt transcription via upregulation of hnRNP F and hnRNP K expression in diabetic Akita mice. HnRNP F and hnRNP K may be potential targets in the treatment of hypertension and kidney injury in diabetes.

Body composition changes following laparoscopic gastric banding for morbid obesity.

Most reports of outcome following obesity surgery report weight and co-morbidity changes only. We studied body composition changes in 17 adult patients (15 F, 2 M, age 43+/-2 years, range 28-58 years), with morbid obesity (initial BMI 40.4+/-4.9 kg/m(2), range 34.7-48.8) who were managed surgically by laparoscopically inserting an adjustable gastric band. Body composition was studied before and after surgery (mean interval of 909+/-51 days, range 441-1155 days) using anthropometry (abdominal circumference, AC, sum of four skinfold thicknesses, SFSUM), whole-body potassium counting (TBK), in vivo neutron activation analysis total body nitrogen (TBProtein) and whole-body dual-energy ray absorptiometry (total body percent fat TBF%, and total body bone mineral density TBBMD). Weight loss over the study period was 23.4+/-2.5 kg. ( p<0.0003) with an AC reduction of 20.0+/-4.5 cm ( p<0.008). Both SFSUM and TBF% were significantly reduced ( p<0.02 and p<0.0005 respectively). Both TBK and TBProtein after normalization for sex and height, were significantly ( p<0.0054 and p<0.001 respectively) reduced, but the ratio of loss of fat mass to fat-free mass, at 4.4:1 was usual for weight loss, and there was no significant changes in the ratio of potassium to protein. TBBMD, after normalization relative to a young same sex adult, was not significantly changed. In this group of patients, most of the substantial weight loss over a 2- to 3-year period was due to loss of fat mass, with relatively less reduction in the components of fat-free mass. Adjustable laparoscopic gastric banding induces fat loss without significant other deleterious effects on body composition.

Orthogonal subspace projection-based approaches to classification of MR image sequences.

Orthogonal subspace projection (OSP) approach has shown success in hyperspectral image classification. Recently, the feasibility of applying OSP to multispectral image classification was also demonstrated via SPOT (Satellite Pour 1'Observation de la Terra) and Landsat (Land Satellite) images. Since an MR (magnetic resonance) image sequence is also acquired by multiple spectral channels (bands), this paper presents a new application of OSP in MR image classification. The idea is to model an MR image pixel in the sequence as a linear mixture of substances (such as white matter, gray matter, cerebral spinal fluid) of interest from which each of these substances can be classified by a specific subspace projection operator followed by a desired matched filter. The experimental results show that OSP provides a promising alternative to existing MR image classification techniques.

PDGF-BB and IGF-I use different signaling pathways to induce fibronectin synthesis in cultured rat thoracic aortic smooth muscle cells.

Fibronectin, an extracellular matrix protein, acts as an early signal in initiating cell proliferation. Results have indicated that platelet-derived growth factor BB (PDGF-BB) and insulin-like growth factor-I (IGF-I) both enhance fibronectin gene expression. Genistein inhibits PDGF-BB-induced fibronectin levels without inhibiting IGF-I-induced fibronectin levels. It indicates that PDGF-BB and IGF-I utilize separate signaling pathways to induce the synthesis of fibronectin.

PDGF-BB and IGF-I use different signaling pathways to induce NaK-ATPase subunits in cultured rat thoracic aortic smooth muscle cells.

(Na(+)+K(+))-adenosine triphosphatase (NaK-ATPase), an ubiquitous membrane transport protein consisting of alpha and beta subunits, regulates Na(+)/K(+)fluxes and maintains many vital physiological functions, including cell growth. Results have indicated that platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) both enhance NaK-ATPase subunits. Genistein, an inhibitor of tyrosine phosphorylation, inhibits serum- and PDGF-BB-induced NaK-ATPase alpha(1)subunit protein levels without inhibiting IGF-I-induced NaK-ATPase alpha(1)subunit protein levels. These results indicate that PDGF-BB and IGF-I utilize separate signaling pathways to induce the synthesis of NaK-ATPase alpha(1)subunits. In addition, genistein failed to inhibit PDGF-BB-stimulated NaK-ATPase beta(1)subunit levels, suggesting that two separate pathways are involved to induce the synthesis of the NaK-ATPase alpha(1)and beta(1)subunits, respectively.

Identification and characterization of a protease from Streptococcus oralis C104.

Streptococcus oralis is among the earliest colonizers of the tooth surface during plaque formation. As such, its enzymatic activities may influence ecologic succession on the tooth surface. In the current study, we use zymograms and preparative polyacrylamide gel electrophoresis to identify and purify a protease from S. oralis (sanguis) C104. Proteases from S. oralis C104 were detected in cell pellets at 133, 146 and 176 kDa as clear proteolytic bands on gelatin-substrate zymograms. Preparation of the major (146 kDa) protease were obtained by continuous-elution electrophoresis. The protease was active over the pH range of 7 to 9 with optimum activity between pH 8 and 9. Protease activity was inhibited by several serine protease inhibitors including phenylmethylsulfonyl fluoride, di-isopropyl-phosphofluoridate and aprotinin. The protease showed highest hydrolytic activity against azoalbumin and Bz-Pro-Phe-Arg-NA. Immunofluorescence studies with a polyclonal antiserum to the 146-kDa protease suggest it is present on the cell surface of S. oralis C104. Zymograms of cell pellets from other S. oralis strains as well as S. sanguis and Streptococcus mitis suggest that functionally similar proteases are elaborated by many early colonizers of the tooth surface.

Regulation of NaK-ATPase by Platelet-Derived Growth Factors in Cultured Rat Thoracic Aortic Smooth Muscle Cells.

Regulation of (Na(+) + K(+))-adenosine triphosphatase (NaK-ATPase) by platelet-derived growth factor (PDGF) in cultured rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances SMC proliferation and NaK-ATPase activity. Ouabain, an inhibitor of NaK-ATPase activity, prevents PDGF-BB-induced SMC proliferation. As shown by Western blot and immunochemiluminescence analysis, PDGF-BB also enhances alpha(1), truncated alpha(1), and beta(1) NaK-ATPase subunit levels. PDGF-AA and PDGF-AB show no effect on alpha(1) and truncated alpha(1) levels in slot blot analysis. Induction of NaK-ATPase subunit levels by PDGF-BB could be one of the initial events in vascular SMC proliferation. Copyright 1996 S. Karger AG, Basel

Determination of retinoic acid and retinol at physiological concentration by HPLC in Caucasians and Japanese women.

A sensitive, specific and simple method for simultaneous determination of retinoic acid and retinol in human serum by reverse phase HPLC with UV detector has been developed. Retinoic acid is measurable at physiological concentration in human serum by this method. There is no significant difference in serum retinoic acid level between Caucasian and Japanese subjects. However, the serum retinol level in Japanese women is significantly lower than that in Caucasian women.

In vitro shear strength of bonded amalgam cores with and without pins.

This study compared the shear bond strength of resin-bonded amalgam with and without pins. The coronal third of 240 embedded posterior teeth was removed to expose a flat, nonretentive surface. Three Minikin pins were placed in the dentin in a triangular pattern 1 mm apart. Amalgam was condensed into a Delrin mold (4.2 mm in diameter and 3 mm in height) positioned over each tooth. The adhesives Amalgam-bond, All-bond, Amalgambond with high-performance additive, Panavia EX, and Panavia with Photobond were the materials used to bond the amalgam to the dentin. Half of the samples were immersed in normal saline solution for 7 days and the others for 30 days. Shear bond strengths were recorded as the maximum load per cross-sectional area of the bonded surface with a testing machine with 1 kN load cell and crosshead speed of 0.5 mm/min. A three-factor analysis of variance and Student-Newman-Keuls test (p = 0.05) identified Amalgambond with high-performance additive as the strongest adhesive in this study. The use of pins with or without adhesives increased the shear strength of amalgam samples significantly more than samples that used adhesives alone.

Regulation of Fibronectin by Platelet-Derived Growth Factors in Cultured Rat Thoracic Aortic Smooth Muscle Cells.

Induction of fibronectin (FN) gene expression by platelet-derived growth factor (PDGF) isoforms in rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances FN levels in SMC cultures in a time- and concentration-response fashion. PDGF-AA and PDGF-AB show no effect on FN levels. The effects of insulin and insulin-like growth factor-I (IGF-I) on PDGF-BB-induced FN levels were examined. No additivity of FN levels is observed between PDGF-BB and insulin and/or IGF-I. Experiments also show that PDGF-BB enhances FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. Induction of FN and FN mRNA levels by PDGF-BB could be one of the initial events in vascular SMC proliferation and extracellular matrix expansion, leading to atherosclerosis and hypertension. Copyright 1995 S. Karger AG, Basel

Regulation of fibronectin by insulin-like growth factor-I in cultured rat thoracic aortic smooth muscle cells and glomerular mesangial cells.

We examined the regulation of fibronectin (FN) levels by insulin-like growth factor-I (IGF-I) in rat thoracic aortic smooth muscle cell (SMC) and glomerular mesangial cell cultures. IGF-I enhances FN levels in the culture media of the SMC and in the cell samples of the mesangial cells. It shows no effect on FN levels in the cell samples of the SMC and in the culture media of the mesangial cells. Modulation of IGF-I-induced FN levels by insulin was also examined. Insulin enhances FN levels in the culture media of the SMC but not in the cell samples. Insulin did not induce an increase in FN levels in either the mesangial cell samples or the culture media. No additive effect of FN levels was observed when the SMC were treated with insulin and IGF-I together. The effect of IGF-I on FN mRNA levels was assessed. IGF-I enhances SMC and FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. The effects of actinomycin D and cycloheximide on IGF-I-induced FN mRNA levels were also examined. Inhibition of the IGF-I-induced FN mRNA levels by actinomycin D and an increase of FN mRNA levels by cycloheximide suggest that IGF-I regulates FN mRNA synthesis at the transcriptional level.

Preferred meal patterns in non-insulin-dependent diabetes.

Current advice on the across-the-day distribution of energy and carbohydrate intakes in non-insulin-dependent diabetes (NIDD) is based on inadequate evidence. We have addressed this by a comparison of an even as opposed to a main evening meal pattern in 11 subjects with NIDD. Contributions of macronutrients to energy intake were fat 29%, protein 20% and carbohydrate 51% with each meal pattern. The peak glycaemic response in the morning was not as good as the response in the evening (P<0.01), where an even energy and carbohydrate spread was used; this contrasts with previous reports in healthy subjects where the morning response to glucose is better than that later in the day. This difference between peak morning and peak evening glycaemic response was not seen with a main evening meal. There was a lower overall glycaemic response with a main evening meal compared with an even meal pattern (P<0.01, by area comparison). The overall insulin response was not significantly different between the two meal patterns, although the sensitivity for insulin appeared better in the evening where there was an evening main meal.

Regulation of rat renal (Na(+) + K+)-adenosine triphosphatase mRNA levels by corticosterone.

We investigated the mechanisms for glucocorticoid regulation of rat renal NaK-ATPase activity. Our findings suggest that the magnitudes of corticosterone-induced increases in alpha 1 mRNA and beta 1 mRNA levels are similar in the kidney of the adult adrenalectomized rats. The results also suggest that corticosterone restores NaK-ATPase activity in adrenalectomized rats prior to any enhanced sodium delivery.

Determination of tocotrienol and tocopherol isomers at physiological concentration by HPLC in Caucasian and Japanese women.

A sensitive, specific and simple method for simultaneous evaluation of tocopherol and tocotrienol isomers in human serum by normal phase HPLC with a fluorescence detector has been developed. Tocopherol and tocotrienol isomers are measurable in physiological concentration in human serum by this method. There is no significant difference in serum alpha- and beta-tocopherols and alpha-, gamma-, and delta-tocotrienols between Caucasian and Japanese subjects. However, serum gamma- and delta-tocopherol concentrations in Japanese women are significantly higher than in Caucasian women.

Neomycin inhibits mastoparan-induced lactate dehydrogenase release, ethidium bromide accumulation, and intracellular fluorescein depletion in MDCK cells.

Mechanisms of cell death induced by toxins probably involve one or more processes such as inhibition of protein synthesis and impairment of plasma membrane integrity leading to an increase in membrane permeability. Since one of the possible actions of mastoparan, a cationic tetradecapeptide from wasp venom, is to perturb membrane phospholipids resulting in an increase in membrane permeability, we studied the effect of chemically synthesized mastoparan on lactate dehydrogenase release (LDH), ethidium bromide and fluorescein accumulation in Madin-Darby Canine Kidney (MDCK) cultured cells. Our results demonstrated that mastoparan induced cytosolic LDH release, ethidium bromide accumulation and intracellular fluorescein depletion in MDCK cells. Neomycin, a polycationic aminoglycoside, interacts with anionic polyphosphoinositides at the plasma membrane. Since both mastoparan and neomycin are cationic peptides and react with the negatively charged membrane phospholipids, we studied the interaction of these two peptides on membrane permeability. Our results demonstrated that neomycin inhibited mastoparan-induced LDH release, ethidium bromide accumulation and intracellular fluorescein depletion.

Inhibition of alpha-aminoisobutyric acid uptake by mastoparan in Madin-Darby Canine Kidney cells.

Mastoparan, a wasp venom, was found to inhibit Na(+)-dependent net alpha-aminoisobutyric acid (AIB) uptake in Madin Darby Canine Kidney (MDCK) cells. Mastoparan also produced a significant increase in AIB efflux when compared to controls. Pretreatment of MDCK cells with 2 mM neomycin attenuated mastoparan's inhibition of net AIB uptake and completely suppressed mastoparan-mediated increases in AIB efflux when compared to controls. These data suggest that mastoparan's inhibition of net AIB uptake involves more than a single basic mechanism.

Mastoparan increases membrane bound phosphatidylinositol kinase and phosphatidylinositol 4-monophosphate kinase activities in Madin-Darby canine kidney cells.

Synthetic wasp venom Mastoparan induced an increase of [3H] inositol phosphates levels and a corresponding decrease of [3H]inositol phospholipids levels in Madin-Darby canine kidney (MDCK) cells. The effect was dose (5-100 micrograms/ml) and time (1 to 15 min) dependent. Mastoparan also enhanced the endogenous activity of phosphatidylinositol kinase and phosphatidylinositol 4-monophosphate kinase. The effect was dose (25-75 micrograms/ml) and time dependent (1 to 15 min).