A parallel algorithm to produce long polymer chains in molecular dynamics.

Generating initial configurations of polymer melts above the entanglement molecular weight is a challenge in molecular dynamics and Monte Carlo simulations. In this work, we adapt an algorithm mimicking a chemical polymerization to all-atom force fields. The principle of this algorithm is to start from a bath of monomers between which bonds are created and relaxed sequentially. Our implementation is parallel and efficient. The parallelization is that of a classical molecular dynamics code and enables the user to generate large systems, up to 7 × 106 atoms. The efficiency of the algorithm comes from the linear scaling between the simulation time and the chain length in the limit of very long chains. The implementation is able to produce long polymer chains, up to ∼2000 carbon atoms, with thermodynamic and local structural properties in good agreement with their experimental and numerical counterparts. Moreover, the chain conformations are close to being equilibrated right after the end of the polymerization process, corresponding to only a few hundred of picoseconds of simulation, despite a systematical drift from Gaussian-like behavior when the density of reactively available monomers decreases. Finally, the algorithm proposed in this work is versatile in nature because the bond creation can be easily modified to create copolymers, block copolymers, and mixtures of polymer melts with other material.

Multiscale Modeling Approach toward the Prediction of Viscoelastic Properties of Polymers.

We report a multiscale modeling approach to study static and dynamical properties of polymer melts at large time and length scales. We use a bottom-up approach consisting of deriving coarse-grained models from an atomistic description of the polymer melt. We use the iterative Boltzmann inversion (IBI) procedure and a pressure-correction function to map the thermodynamic conditions of the atomistic configurations. The coarse-grained models are incorporated in the dissipative particle dynamics (DPD) method. The thermodynamic, structural, and dynamical properties of the cis-1,4-polybutadiene melt are very well reproduced by the coarse-grained DPD models with a significative computational gain. We complete this study by addressing the challenging question of the investigation of the shear modulus evolution. As expected from experiments, the stress correlation functions show behaviors that are dependent on the molecular weights defining unentangled and weakly entangled polymer melts.

Simulated glass-forming polymer melts: glass transition temperature and elastic constants of the glassy state.

By means of molecular-dynamics simulation we study a flexible and a semiflexible bead-spring model for a polymer melt on cooling through the glass transition. Results for the glass transition temperature T(g) and for the elastic properties of the glassy state are presented. We find that T(g) increases with chain length N and is for all N larger for the semiflexible model. The N dependence of T(g) is compared to experimental results from the literature. Furthermore, we characterize the polymer glass below T(g) via its elastic properties, i.e., via the Lamé coefficients λ and µ. The Lamé coefficients are determined from the fluctuation formalism which allows to split λ and µ into affine (Born term) and nonaffine (fluctuation term) contributions. We find that the fluctuation term represents a substantial correction to the Born term. Since the Born terms for λ and µ are identical, the fluctuation terms are responsible for the different temperature dependence of the Lamé coefficients. While λ decreases linearly on approaching T(g) from below, the shear modulus µ displays a much stronger decrease near T(g). From the present simulation data it is not possible to decide whether µ takes a finite value at T(g), as would be expected from mode-coupling theory, or vanishes continuously, as suggested by recent work from replica theory.

Processing of horizontal optic flow in three visual interneurons of the Drosophila brain.

Motion vision is essential for navigating through the environment. Due to its genetic amenability, the fruit fly Drosophila has been serving for a lengthy period as a model organism for studying optomotor behavior as elicited by large-field horizontal motion. However, the neurons underlying the control of this behavior have not been studied in Drosophila so far. Here we report the first whole cell recordings from three cells of the horizontal system (HSN, HSE, and HSS) in the lobula plate of Drosophila. All three HS cells are tuned to large-field horizontal motion in a direction-selective way; they become excited by front-to-back motion and inhibited by back-to-front motion in the ipsilateral field of view. The response properties of HS cells such as contrast and velocity dependence are in accordance with the correlation-type model of motion detection. Neurobiotin injection suggests extensive coupling among ipsilateral HS cells and additional coupling to tangential cells that have their dendrites in the contralateral hemisphere of the brain. This connectivity scheme accounts for the complex layout of their receptive fields and explains their sensitivity both to ipsilateral and to contralateral motion. Thus the main response properties of Drosophila HS cells are strikingly similar to the responses of their counterparts in the blowfly Calliphora, although we found substantial differences with respect to their dendritic structure and connectivity. This long-awaited functional characterization of HS cells in Drosophila provides the basis for the future dissection of optomotor behavior and the underlying neural circuitry by combining genetics, physiology, and behavior.

Biocatalytic approaches for the quantitative production of single stereoisomers from racemates.

Strategies for the chemoenzymatic transformation of a racemate into a single stereoisomeric product in quantitative yield have been developed. A range of industrially relevant alpha-hydroxycarboxylic acids was deracemized in a stepwise fashion via lipase-catalysed enantioselective O-acylation, followed by mandelate racemase-catalysed racemization of the remaining non-reacted substrate enantiomer. Alternatively, aliphatic alpha-hydroxycarboxylic acids were enzymatically isomerized using whole resting cells of Lactobacillus spp. Enantioselective hydrolysis of rac-sec-alkyl sulphate esters was accomplished using novel alkyl sulphatases of microbial origin. The stereochemical path of catalysis could be controlled by choice of the biocatalyst. Whereas Rhodococcus ruber DSM 44541 and Sulfolobus acidocaldarius DSM 639 act through inversion of configuration, stereo-complementary retaining sulphatase activity was detected in the marine planctomycete Rhodopirellula baltica DSM 10527.

The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial.

BACKGROUND: Recent studies of antidandruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit. OBJECTIVES: The purpose of this 6-month, 200-patient, randomized, investigator-blinded, parallel-group clinical study was to assess the hair growth benefits of a 1% pyrithione zinc shampoo. The efficacy of a 1% pyrithione zinc shampoo (used daily), was compared with that of a 5% minoxidil topical solution (applied twice daily), a placebo shampoo and a combination of the 1% pyrithione zinc shampoo and the 5% minoxidil topical solution. METHODS: Two hundred healthy men between the ages of 18 and 49 years (inclusive) exhibiting Hamilton-Norwood type III vertex or type IV baldness were enrolled. Total hair counts, the primary efficacy measure, were obtained using fibre-optic microscopy and a computer-assisted, manual hair count method. Secondary measures of efficacy included assessments of hair diameter, as well as patient and investigator global assessments of improvement in hair growth. These were based on photographs of the scalp using both midline and vertex views. RESULTS: Hair count results showed a significant (P < 0.05) net increase in total visible hair counts for the 1% pyrithione zinc shampoo, the 5% minoxidil topical solution, and the combination treatment groups relative to the placebo shampoo after 9 weeks of treatment. The relative increase in hair count for the 1% pyrithione zinc shampoo was slightly less than half that for the minoxidil topical solution and was essentially maintained throughout the 26-week treatment period. No advantage was seen in using both the 5% minoxidil topical solution and the 1% pyrithione zinc shampoo. A small increase in hair diameter was observed for the minoxidil-containing treatment groups at week 17. Assessments of global improvements by the patients and investigator generally showed the benefit of 5% minoxidil. The benefit of the 1% pyrithione zinc shampoo used alone tended (P < 0.1) to be apparent only to the investigator. CONCLUSIONS: Hair count results show a modest and sustained improvement in hair growth with daily use of a 1% pyrithione zinc shampoo over a 26-week treatment period.

Quantitative evaluation of skin condition in an epidemiological survey of females living in northern versus southern Japan.

Image analysis and biophysical methods were used to compare the skin condition of a group of females ranging in age from 5 to 65 years who had lived all of their lives in either Kagoshima (n=300), located in southern Japan, or Akita (n=302), located in northern Japan. Kagoshima annually receives approximately 1.5 times more solar UVB radiation than Akita. The methods used and corresponding skin parameters reported in this survey were: high resolution digital imaging followed by computer analysis of facial images for facial skin wrinkling and hyperpigmentation; silicone skin replicas followed by Moiré interferometry for facial skin surface roughness (texture); the Minolta Chromameter for skin color (L*a*b*) on sun-exposed (forehead) and sun-protected (upper inner arm) skin sites; the Corneometer for skin capacitance (hydration) on the cheek and ventral forearm; the Sebumeter for sebum excretion rate on the forehead; and the Minolta Spot Thermometer for skin temperature on the upper cheek. Compared with Japanese women living in Akita, Japanese women living in Kagoshima had significantly longer facial wrinkles, higher number of wrinkles, larger hyperpigmented spots, higher number of spots, rougher facial skin texture, more yellow foreheads and upper inner arms, darker foreheads, and less stratum corneum hydration in the cheeks and arms. When compared on an age-for-age basis, the average 40-year-old Kagoshima women has the same level of facial wrinkling as a 48-year-old Akita women, a delay of 8 years for living in the northern latitude. For facial hyperpigmentation, the delay is 16 years; the average 40-year-old Kagoshima women has the same level of facial hyperpigmentation as a 56-year-old Akita women. The results further testify to the skin damaging effects of sun exposure and may be useful in public health education to promote everyday sun protection.

Safety of deferring angioplasty in patients with normal coronary flow velocity reserve.

BACKGROUND: In the catheter laboratory there is a need for functional tests validating the hemodynamic significance of coronary artery stenosis. OBJECTIVES: It was the objective of our study to compare the long-term cardiac event rate and the clinical symptoms in patients with reduced coronary flow velocity reserve (CFVR) and standard PTCA with patients with normal CFVR and deferred angioplasty. METHODS: Our study included 70 patients with intermediate coronary artery stenoses (13 f, 57 m; diameter stenosis >50%, <90%) and an indication for PTCA due to stable angina pectoris and/or signs of ischemia in noninvasive stress tests. CFVR was measured distal to the lesion after intracoronary administration of adenosine using 0.014 inch Doppler-tipped guide wires. RESULTS: In 22 patients (31%), PTCA was deferred due to a CFVR > or = 2.0 (non-PTCA group). In the remaining 48 patients (69%) mean CFVR of 1.4+/-0.23 (p < 0.001) was measured (PTCA group). CFVR increased to 2.0+/-0.51 after angioplasty. During follow-up (average 15+/-6.0 months), the following major adverse cardiac events (MACE) occurred: in the PTCA group re-PTCA was performed in nine patients (18.8%) because of unstable angina, five patients (10.4%) suffered an acute myocardial infarction (MI) (two infarctions occurred during the angioplasty, three patients suffered an infarction during follow-up), two patients (4.2%) needed blood transfusions due to severe bleedings, two patients (4.2%) underwent bypass surgery and one patient (2.1%) died. In the non-PTCA group, angioplasty was necessary only in two cases (9.1%) during follow-up. We did not observe any MI in the non-PTCA group. The overall rate of MACE was significantly lower in the non-PTCA group compared to the PTCA group (9.1% vs. 33.3%, p < 0.01). However, only 40% of the patients of the non-PTCA group were free of angina pectoris at stress. In the PTCA group, 63% did not complain of any symptoms at follow-up (p < 0.05). CONCLUSIONS: We conclude that determination of the CFVR is a valuable parameter for stratifying the hemodynamic significance of coronary artery stenosis. PTCA can safely be deferred in patients with significant coronary stenosis but a CFVR > or = 2.0. The total rate of MACE at follow-up was below 10% among these patients. However, if PTCA was deferred the number of patients who are free of angina is lower compared to those patients who underwent angioplasty.

A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen in Drosophila.

Dorsoventral axis formation in the Drosophila embryo is established by a signal transduction pathway that comprises the products of at least 12 maternal genes. Two of these genes, dorsal and cactus, show homology to the mammalian transcription factor NF-kappa B and its inhibitor I kappa B, respectively. As in the case for I kappa B and NF-kappa B, Cactus inhibits Dorsal by retaining it in the cytoplasm. In response to the signal produced and transmitted by the products of the other genes, Dorsal translocates to the nucleus preferentially on the ventral side of the embryo. Here, we show that Cactus forms a cytoplasmic concentration gradient inversely correlated to the nuclear translocation gradient of Dorsal. Deletions of the N-terminus and C-terminus of Cactus reveal that two modes of degradation control cactus activity: signal-induced degradation and signal-independent degradation, respectively. Genetic evidence indicates that degradation of Cactus is required, but not sufficient to translocates Dorsal completely into the nucleus.

Replicate plating: does it increase reliability?

As a part of a clinical study to evaluate the antibacterial effect of a topically applied erythromycin gel, microbiological specimens were taken from two groups of patients: one group using 2% erythromycin gel and the other group using a placebo gel. These specimens were plated in triplicate using a common source on bacteriological media using standard procedures. After the appropriate incubation times, the numbers of aerobic and anaerobic organisms were counted separately from each of three plates. A comparison of the bacterial colony counts from the replicate plates showed a high degree of similarity for each type of organism. Tests for treatment differences in organism counts were performed based on single, double and triplicate plating. The results obtained were almost identical, suggesting that replicate plating from a common source is no more accurate than single plating. The only apparent advantage of this type of replicate plating is heightened confidence in the reliability of bacterial counts from single plates.

[Preliminary comments on a "History of German medical literature of the middle ages" exemplified by the 12th century]. / Vorüberlegungen zu einer "Geschichte der deutschen Medizinliteratur des Mittelalters" am Beispiel des 12. Jahrhunderts.

My long-term goal is to prepare a study leading to a history of medieval German medical literature, from the beginnings to about 1500. This literature is largely missing from the standard histories of medicine, and it also seldom appears in histories of German literature. After reviewing the "überlieferungsgeschichtliche Ansatz", the method of examining texts in the historical and codicological contexts in which they are transmitted, I review the six German medical texts attested in twelfth century manuscripts (not counting individual recipes). These are: the, Prüller Kräuterbuch', the, Prüller Steinbuch', the 'Arzneibuch Ipocratis', the 'Capsula Eburnea', the 'Innsbrucker Arzneibuch', and the 'Frauengeheimnisse', all printed in Friedrich Wilhelm's collection of twelfth century texts. These texts are all from the second half of the century and from the Upper German language area, with Regensburg as the particular focus, and they are transmitted along with important theological and philosophical texts of the time.

Evaluating the effects of tubal sterilization on menstrual function: selected issues in data analysis.

We examined selected issues in data analysis in the Collaborative Review of Sterilization (CREST). CREST is a multicentre, prospective, observational study of women undergoing tubal sterilization. We analysed menstrual function after sterilization in over 5000 women who were enrolled in the period 1978-1983 and followed for 5 years with yearly follow-up interviews. To take into account the dependency among repeated responses from the same individuals, we used the generalized estimating equations (GEE) approach to longitudinal data analysis. Marginal modelling resulted in a statistically significant increase in the odds of menstrual dysfunction at 5 years after tubal sterilization. Transitional modelling produced rates of menstrual dysfunction given a woman's menstrual function at baseline, after adjusting for other baseline characteristics such as method of contraception before sterilization. To examine the direction of the bias that could result from non-random missing data, we refitted our models using imputed values. The models with imputed values showed the same trends as the original models.

Mn-DPDP enhancement patterns of hepatocellular lesions on MR images.

The recently developed paramagnetic hepatobiliary contrast agent manganese dipyridoxyl diphosphate (DPDP) was evaluated in eight patients. Pathologic diagnoses included five hepatocellular carcinomas, two cirrhoses, and one focal nodular hyperplasia. T1-weighted spin-echo and gradient-echo images were obtained after intravenous injection of 5 or 10 mumol/kg Mn-DPDP; these were compared with unenhanced T1-weighted spin-echo and gradient-echo images and T2-weighted spin-echo images. In all patients with lesions of hepatocellular origin, focal areas of increased enhancement were seen in the lesions after administration of Mn-DPDP. In the cirrhotic livers, these areas corresponded to foci of hepatic regeneration. In all patients, the signal-to-noise ratio in normal liver tissue increased significantly after injection of Mn-DPDP. Signal intensity in the six primary liver tumors was further increased, so that they appeared hyperintense relative to surrounding liver tissue on all T1-weighted images. Conspicuity and demarcation of all lesions were improved on Mn-DPDP-enhanced images.

[Magnetic resonance tomography of the hepatobiliary system: indications, limitations and outlook]. / Magnet-Resonanz-Tomographie des hepatobiliären Systems: Indikation, Limitationen und Ausblick.

In a prospective study we examined the diagnostic value of MRI and MR cholangiography (MRC) in patients suffering from hepatobiliary disease. By using hepatobiliary contrast media (Mn-DPDP, Gd-BOPTA), sensitivity and specificity of MRI were significantly increased. In 65 patients we comparatively analyzed the diagnostic results of MRI and MRC versus ultrasound, CT and invasive techniques such as ERCP. We conclude that the use of MRI and MRC improves the diagnostic evaluation of patients with hepatobiliary disease.

[Magnetic resonance tomography and magnetic resonance angiography in lymphangiomatosis]. / Magnetresonanztomographie und Magnetresonanzangiographie der Lymphangiomatose.

Generalised lymphangiomatosis is a rare benign congenital abnormality of the lymphatic vessels with a complex pattern. 3 patients with different types of lymphangiomatosis were studied by MRT and MRA and histopathologically. All patients had multiple organ involvement in the abdomen, the skeleton and the skull. The basis in each case was lymphangiomatosis of capillary-cavernous, cystic or cavernous type. The results of MRT and MRA in diagnosing splenic, vascular and skeletal changes correlated accurately with operative findings and with the histopathological classification. In summary, MRT combined with MRA and using paramagnetic contrast media are the diagnostic methods of choice for the investigation of generalised lymphangiomatosis with multiple organ involvement.

Menstrual function after tubal sterilization.

More than 10 million women in the United States have undergone tubal sterilization. There has been concern that this procedure may increase the risk of later menstrual dysfunction. The Collaborative Review of Sterilization (CREST) is a large, multicenter, prospective study of tubal sterilization in the United States. This report describes CREST participants who were interviewed immediately before sterilization and again in annual poststerilization interviews for up to 5 years between 1978 and 1988. The authors analyzed reported changes in six menstrual cycle characteristics for 5,070 women undergoing interval sterilizations. Longitudinal, multivariate regression was used to adjust for baseline menstrual function and other potential confounders. Five years after sterilization, 35% of the CREST participants reported high levels of menstrual pain, 49% reported heavy or very heavy menstrual flow, and 10% reported spotting between periods. In contrast to the fifth year, the first year of follow-up was similar to presterilization menstrual function; in the first year, 27% of participants reported high menstrual pain, 41% reported heavy menstrual flow, and 7% reported spotting. These findings may be affected by aging of the cohort and other study limitations, but they suggest that if tubal sterilization leads to changes in menstrual function, such changes may take some time to develop.

PIP: Over 100 Million women worldwide have undergone tubal sterilization. The Collaborative Review of Sterilization (CREST) study at 12 medical centers in the US between 1978-83 examined 5070 women at 4 periodic intervals up to 5 years after the procedure. The purpose was to ascertain whether there were any changes in 6 menstrual cycle characteristics. Several different sterilization methods were examined: unipolar coagulation, bipolar coagulation, silastic band application, spring clips application, partial salpingectomy, and thermocoagulation. Other baseline characteristics which might affect changes in menstrual function over time were examined, i.e., race, body mass index, education, age, gravidity, history of pelvic pathology and pelvic surgery, method contraception immediately preceding sterilization, and incidental pelvic pathology during the sterilization. The presurgery interview included information on baseline menstrual function. The findings from multivariate analysis with unadjusted data showed changes at 5 years but not 2, including increases in menstrual pain, amount of bleeding, and intermenstrual spotting in an amount 1.3-1.8 times greater than those reporting in year 2. There were significant decreases in days/cycle and days of bleeding/cycle for the most women reporting changes. Sterilization method analysis revealed differences between methods for days/cycle, amount of bleeding, menstrual pain, irregularity, and spotting. 33% of women with the spring clip procedure reported increases in menstrual pain. The adjusted model, showed statistically significant differences in cycle length in the 5th year vs. the 1st year, as well as increases in menstrual pain, amount of bleeding, and spotting. Women with the longest cycle lengths in the adjusted analysis used the unipolar coagulation method, and the shortest cycle lengths, the spring clip. Those with the spring clip were also more likely to have menstrual pain and greater bleeding. Black women reported less irregularity and spotting and fewer days of bleeding. Older age at sterilization was related to less pain and greater regularity. The changes in bleeding pattern and menstrual pain are of greatest concern and the most frequently reported in other studies of effects of sterilization. Tissue destruction was found not to be related. Caution is urged in the interpretation of findings. Future research should focus on follow up after 5 years and comparisons with nonsterilized women.

Focal liver lesions: MR imaging with Mn-DPDP--initial clinical results in 40 patients.

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) (DPDP) was evaluated as a contrast agent for magnetic resonance (MR) imaging (1.5 T) of focal liver lesions in 40 patients. Doses of 5 and 10 mumol/kg were administered intravenously. Mn-DPDP-enhanced T1-weighted images were compared quantitatively and subjectively with standard T1- and T2-weighted nonenhanced images. Use of Mn-DPDP resulted in a statistically significant increase in signal intensity of liver parenchyma in T1-weighted images at both doses. No enhancement was seen in metastases, cholangiocarcinomas, or lymphomas, while all hepatocellular carcinomas were enhanced. Enhancement was seen in focal nodular hyperplasia and in regenerative nodules. The lesion-to-liver contrast in Mn-DPDP-enhanced gradient-recalled-echo images was superior to that of all precontrast images (P less than .01). The number of nonenhancing malignant liver lesions detected in spin-echo (SE) images was increased (272 in T2-weighted SE images vs 390 in T1-weighted Mn-DPDP-enhanced SE images). Image interpretation (eg, visualization and demarcation of the lesions) was markedly better in Mn-DPDP-enhanced images than in all precontrast images (P less than .001).

[The clinical value of Mn-DPDP: a new paramagnetic hepatobiliary contrast medium for magnetic resonance tomography of the liver]. / Klinische Wertigkeit von Mn-DPDP: neues paramagnetisches hepatobiliäres Kontrastmittel für die Magnetresonanztomographie der Leber.

In an open prospective study the tolerance and diagnostic value of the new hepatobiliary contrast agent Mn-DPDP in MR imaging was evaluated in 20 patients suspected of having focal liver lesions. T1- and T2-weighted spin-echo sequences and T1-weighted gradient-echo sequences were obtained before and after intravenous application of Mn-DPDP. In all patients the signal to noise (S/N) values of normal liver tissue increased significantly after application of Mn-DPDP. All focal lesions could be better localized and differentiated due to increased contrast to noise ratios of lesion to liver. Pathological examination revealed in 14 patients malignant and in 5 patients benign liver lesions; one patient had no pathological findings. In metastatic disease of the liver 25-120% more lesions could be detected in MRI after Mn-DPDP-application, compared with the unenhanced images. In 5 patients the lesions showed significant enhancement of Mn-DPDP (2 cirrhotic nodules, 2 hepatocellular carcinomas, 1 focal nodular hyperplasia). Our preliminary results indicate that Mn-DPDP is a well-tolerated contrast agent useful for the detection and differentiation of liver lesions in MR imaging.

[The physician and author. On the participation of physicians in late middle age publishing]. / Arzt und Literat. Zum Anteil der Arzte am spätmittelalterlichen Literaturbetrieb.

During the 15th century a very great percentage (if not the major part) of German men of letters were physicians. This article concentrates on three of them, all of whom were born in Southern Germany, three of them studied in Italy, wrote during the second third of the century, and became widely renowned as physicians as well as poets or writers of prose. Johannes Hartlieb is well-known as author of a 'Kräuterbuch', but his fame is based mainly on his 'Alexanderroman'. The article tries to show a connection between the two aspects of Hartlieb's work, which have not been related to each other until now: the 'Alexanderroman' is, at least in its central theme, a novel that could only be written by a physician; the traces of the author's profession are obvious. The second part of the article deals with Hermann Schedel. It reconstructs his studies in Padua and then concentrates on five of his manuscripts, which reveal the names and professions of his patients. One may compare Hermann's cousin, Hartmann Schedel to Hartlieb. His 'Weltchronik', which is mainly famous for its illustrations, is the work of a physician, as was Hartlieb's 'Alexander'. Hartmann inserted biographical informations about 40 celebrities among his 'colleagues'. If the 15th century may rightly be called the 'century of the layman', it is because it was the 'century of the physician'.