bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and complete assignment of the 1H and 13C NMR signals of new acetamido and aminoflavonoid derivatives
Authors: Casano Gilles , Robin Maxime , Barbier Pascale , Peyrot Vincent , Faure Robert
Published: June 2010

The complete 1H and 13C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamidoflavonols and 9 aminoflavonols has been performed using one‐ and two‐dimensional NMR techniques including COSY, HMQC and HMBC experiments. Copyright © 2010 John Wiley & Sons, Ltd.
Corticospinal tract dysfunction and development of amyotrophic lateral sclerosis following electrical injury
Authors: Huynh William , Lam Amanda , Vucic Steve , Cheah Benjamin C. , Clouston Paul , Kiernan Matthew C.
Published: June 2010

The causal relationship between electrical injury and development of amyotrophic lateral sclerosis (ALS) remains controversial. We describe the case of a 25‐year‐old man who developed ALS after a severe electrical injury. Cerebral magnetic resonance imaging (MRI) demonstrated hyperintensities involving the corticospinal tract. Functional testing with transcranial magnetic stimulation established that the motor cortex was relatively inexcitable. In addition, there were features of denervation on electromyography and muscle biopsy that supported concomitant lower motor neuron findings and the diagnosis of ALS. Muscle Nerve, 2010
Increased voluntary drive is associated with changes in common oscillations from 13 to 60 Hz of interference but not rectified electromyography
Authors: Neto Osmar P. , Baweja Harsimran S. , Christou Evangelos A.
Published: June 2010

The purpose of this study was to compare the capability of interference and rectified electromyography (EMG) to detect changes in the beta (13–30‐HZ) and Piper (30–60‐HZ) bands when voluntary force is increased. Twenty adults exerted a constant force abduction of the index finger at 15% and 50% of maximum. The common oscillations at various frequency bands (0–500 HZ) were estimated from the first dorsal interosseous muscle using cross wavelets of interference and rectified EMG. For the interference EMG signals, normalized power significantly (P < 0.01) increased with force in the beta (9.0 ± 0.9 vs. 15.5 ± 2.1%) and Piper (13.6 ± 0.9 vs. 21 ± 1.7%) bands. For rectified EMG signals, however, the beta and Piper bands remained unchanged (P > 0.4). Although rectified EMG is used in many clinical studies to identify changes in the oscillatory drive to the muscle, our findings suggest that only interference EMG can accurately capture the increase in oscillatory drive from 13 to 60 HZ with voluntary force. Muscle Nerve, 2010
Timeline of cardiac dystrophy in 3–18‐month‐old MDX mice
Authors: Van Erp Christel , Loch David , Laws Nicola , Trebbin Andrea , Hoey Andrew J.
Published: June 2010

The dystrophin‐deficient (mdx) mouse remains the most commonly used model for Duchenne muscular dystrophy (DMD). Mdx mice show a predominantly covert cardiomyopathy, the hallmark of which is fibrosis. We compared mdx and normal mice at six ages (3, 6, 9, 12, 15, and 18 months) using in vivo assessment of cardiac function, selective collagen staining, and measures of TGF‐β mRNA, Evans blue dye infiltration, macrophage infiltration, and aortic wall thickness. Clear temporal progression was demonstrated, including early fragility of cardiomyocyte membranes, which has an unrelated impact on cardiac function but is associated with macrophage infiltration and fibrosis. Aortic wall thickness is less in older mdx mice. Mdx mice display impaired responses to inotropic challenge from a young age; this is indicative of altered adrenoreceptor function. We draw attention to the paradox of ongoing fibrosis in mdx hearts without a strong molecular signature (in the form of TGF‐β mRNA expression). Muscle Nerve, 2010
Effect of electromyostimulation on apoptosis‐related factors in denervation and reinnervation of rat skeletal muscles
Authors: Lim Jae‐Young , Han Tai Ryoon
Published: June 2010

Electromyostimulation (EMS) has been utilized to reduce muscle atrophy, but its effect on denervated muscles is controversial. This study was performed to determine the effect of EMS on intramuscular changes and apoptosis during denervation and reinnervation following nerve damage. Rat sciatic nerves were denervated completely (CD) or partially (PD), and EMS was applied for 2 weeks. The same numbers of cases were followed without EMS. Nerve conduction studies, muscle weights, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measure apoptotic changes, and Western blot were done 4, 8, and 12 weeks after injury. TUNEL‐positive nuclei of CD muscles (18.6 ± 5.5%) were more prevalent than those of PD muscles (7.5 ± 3.3%). The EMS group showed greater muscle weight, fewer positive nuclei (4.7 ± 1.9%), and lower BAX and Bcl‐2 expression levels compared with the non‐EMS group at 4 weeks after PD but not after CD. Denervated muscle atrophy delayed by EMS may be linked with enhanced anti‐apoptosis under the control of apoptosis‐related factors. Muscle Nerve, 2010
New strategies of pelvic nerves stimulation for recovery of pelvic visceral functions and locomotion in paraplegics
Authors: Possover Marc , Schurch B , Henle KP
Published: June 2010

Aims

To present new strategies of pelvic nerves stimulation to enhance micturition, to control spasticity, and to recover locomotion in paraplegics.

Methods

Three consecutive patients—Th5, Th7, and Th10 spinal cord injured—underwent laparoscopic transperitoneal implantation of octipolar electrodes to the sciatic and the pudendal nerves and one double extradural Brindley–Finetech electrode bilaterally to the sacral nerve roots S3 and S4. The two octipolar electrodes were connected to an implanted rechargeable generator, while the double Brindley electrode was connected to an implanted Brindley–Finetech receiver block.

Results

Continuous stimulation of the sciatic and pudendal nerves at a frequency of 20 Hz in all three patients permits complete control of the spasticity of the lower extremities and of reflex incontinence. Bladder emptying is obtained by sacral nerve roots stimulation alone in the first patient, by simple interruption of pudendal stimulation in the second (“pudendal‐deblockade”) and by simultaneous sacral nerve roots stimulation with high‐frequency pudendal nerve blockade in the third patient. Functional electrical stimulation of the femoral nerves enables the Th4 paraplegics lower‐limb cycling and the two further patients standing and alternative locomotion.

Conclusion

This short series indicated that laparoscopic implantation of neuroprothesis to the pelvic nerves offers absolutely new strategies based on new combinations of various reported methods to enhance bladder functions and to recover some locomotion in paraplegics. Neurourol. Urodynam. 29:1433–1438, 2010. © 2010 Wiley‐Liss, Inc.
Development of bladder dysfunction in a rat model of dopaminergic brain lesion
Authors: Soler Roberto , Füllhase Claudius , Santos Cesar , Andersson Karl‐Erik
Published: June 2010

Aims

Parkinson's disease (PD) is one of the most common neurological disorders causing lower urinary tract dysfunction. We evaluated the temporal development of bladder dysfunction in rat PD model where urodynamic changes were induced by unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB).

Methods

Female Sprague–Dawley rats underwent a unilateral stereotaxic injection of 6‐OHDA or vehicle (sham group) into the MFB. Cystometry was performed in conscious animals at 3, 14, and 28 days after the injury. Aged‐matched unlesioned rats were used as healthy controls.

Results

Three days after lesion 6‐OHDA rats showed higher threshold (TP), maximum pressures (MP), and spontaneous activity (SA) compared to healthy controls. Sham animals exhibited higher TP. After 14 days 6‐OHDA rats had also higher micturition frequency, decreased bladder capacity, micturition volume and bladder compliance (Bcom) compared to sham and healthy controls. Sham animals showed lower Bcom and higher MP and SA. After 28 days, 6‐OHDA rats exhibited the same changes as those in 14 days, while sham‐operated animals showed parameters similar to those in healthy controls.

Conclusions

These findings suggest that 6‐OHDA lesion of the MFB causes bladder dysfunction already after 3 days. A pattern of detrusor overactivity was more clearly defined 14 days after the injection and persisted for 28 days. Cystometry may be a useful tool to study the pathophysiology of bladder dysfunction in PD, and urodynamic parameters may possibly be used to evaluate the effects of therapeutic interventions. Neurourol. Urodyn. 30:188–193, 2011. © 2010 Wiley‐Liss, Inc.
A pilot study of botulinum toxin for interstitial cystitis/painful bladder syndrome
Authors: Gottsch Henry P. , Miller Jane L. , Yang Claire C. , Berger Richard E.
Published: June 2010

Objectives

Preliminary studies using botulinum toxin (BTX) have demonstrated some benefits in treating interstitial cystitis (IC)/painful bladder syndrome (PBS) pain. The purpose of this study was to investigate the efficacy of a periurethral injection of BTX to block urethral visceral and somatic afferent fibers, for the treatment of IC/PBS.

Methods

Twenty adult women with IC/PBS were identified from the Female Urology Clinic at our hospital. Symptom evaluation was performed using a female modification of the Chronic Prostatitis Symptom Index (CPSI), AUA Symptom Index, Graded Chronic Pain Scale, Perceived Stress Scale, and symptom improvement Visual Analog Scale (VAS). All patients were randomized to receive either botulinum toxin A (BTX‐A) or placebo (normal saline). Patients randomized to BTX‐A received 50 U diluted in 2 cm3 normal saline injected periurethrally. The physician and patient were blinded to the treatment.

Results

BTX was administered to nine women. There were no complications or side effects reported. There was no improvement between placebo and BTX‐A groups in the CPSI score at 3‐month follow‐up (P = 0.97). Additionally, there were no improvements in the other symptom indices. At follow‐up, the mean VAS for the BTX group was −0.3, indicating the subjects' symptoms were the same as at the start of the study.

Conclusions

Periurethral injection of botulinum toxin in women did not effectively treat the pain of IC/PBS. While the results from this study are negative, there is still a valid rationale for further investigations of novel injection protocols given the dearth of current effective treatments. Neurourol. Urodyn. 30:93–96, 2011. © 2010 Wiley‐Liss, Inc.
Effects of thoracic epidural analgesia on lower urinary tract function in women
Authors: Wuethrich Patrick Y. , Burkhard Fiona C. , Panicker Jalesh N. , Kessler Thomas M.
Published: June 2010

Aims: The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4–T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies. Methods: In 13 women with no preoperative lower urinary tract symptoms undergoing open kidney surgery by lumbotomy under TEA, we prospectively assessed changes in urodynamic parameters the day before and 2–3 days after surgery with the patients under TEA. Results: Before versus during TEA, there was a significant increase in postvoid residual (median, 5 ml vs. 220 ml, P < 0.001) and a significant decrease in maximum detrusor pressure (median, 23 cmH2O vs. 5 cmH2O, P = 0.001), detrusor pressure at maximum flow rate (median, 18 cmH2O vs. 5 cmH2O, P = 0.001), maximum flow rate (median, 12 ml/sec vs. 3 ml/sec, P < 0.001), and voided volume (median, 250 ml vs. 40 ml, P < 0.001). In addition, maximum urethral closure pressure at rest decreased significantly under TEA from median 75 cmH2O to 56 cmH2O (P = 0.002). Bladder sensation, maximum cystometric capacity, compliance, and functional profile length at rest were not influenced by TEA. Conclusions: TEA has a significant effect on bladder emptying with clinically relevant postvoid residual (PVR) necessitating (indwelling or intermittent) catheterization or monitoring of PVR. Neurourol. Urodyn. 30:121–125, 2011. © 2010 Wiley‐Liss, Inc.
Independent spanning trees on folded hyper‐stars
Authors: Yang Jinn‐Shyong , Chang Jou‐Ming
Published: June 2010

Fault‐tolerant broadcasting and secure message distribution are important issues for numerous applications in networks. It is a common idea to design multiple independent spanning trees (ISTs) as a broadcasting scheme or a distribution protocol for receiving high levels of fault‐tolerance and security. Recently, hyper‐stars were introduced as a competitive model of interconnection network for both hypercubes and star graphs. The class of folded hyper‐stars is a strengthened variation of hyper‐stars obtained by adding additional links to connect complemented nodes. Both hyper‐stars and folded hyper‐stars have been shown to have lower network cost (measured by the product of degree and diameter) than hypercubes, folded hypercubes, and other variants. In this article, we propose an algorithm to construct k + 1 ISTs on a regular folded hyper‐star FHS (2k,k), where the number of ISTs matches the connectivity of FHS(2k,k). In particular, for k > 4, the constructed k ISTs have height 2 k − 2, and the other one has height k + 1. © 2010 Wiley Periodicals, Inc. NETWORKS, 2010
Increased prevalence of risk factors for cardiovascular disease in long‐term survivors of acute lymphoblastic leukemia and Wilms tumor treated with radiotherapy
Authors: Geenen M.M. , Bakker P.J.M. , Kremer L.C.M. , Kastelein J.J.P. , Leeuwen F.E. van
Published: June 2010

Background

Only a few studies have assessed cardiovascular risk factors (CRFs) in childhood cancer survivors. We determined the prevalence of CRFs in long‐term survivors of acute lymphoblastic leukemia (ALL) and Wilms tumor.

Procedure

Adult survivors of ALL and Wilms tumor treated with radiotherapy and chemotherapy (RT + CT) or treated with chemotherapy alone (CT) were compared with sibling controls. CRFs (hypertension, diabetes mellitus, hypercholesterolemia, obesity, renal insufficiency) and hormonal deficiencies were assessed in each participant. Multivariate logistic regression analysis was used to evaluate the association between CRFs and treatment.

Results

Seventy‐nine ALL, 62 Wilms tumor survivors, and 69 control subjects (mean ages 24.5, 25.9, and 26 years, respectively) were enrolled. Mean follow‐up time since cancer treatment was 20.8 years. In the Wilms RT + CT group significantly more survivors had hypertension (21.6% vs. 1.4%, P < 0.001) and renal insufficiency (8.1% vs. 0%, P = 0.016) compared to controls. There were also more patients with multiple CRFs in the Wilms RT + CT group (16.2% vs. 2.9% in controls, P = 0.019). Almost 15% of ALL RT + CT survivors had growth hormone deficiency. Hypogonadism was seen in 18.9% of survivors in the Wilms RT + CT group. We observed no significant differences between CT‐treated survivors of both malignancies and controls. The adjusted odds ratio for the occurrence of at least one CRF was 2.6 increased for survivors following abdominal radiotherapy. Treatment with CT alone was not associated with the occurrence of multiple CRFs.

Conclusions

Long‐term survivors of ALL and Wilms tumor have unfavorable CRFs due to previous RT not CT. Pediatr Blood Cancer. 2010;55:690–697. © 2010 Wiley‐Liss, Inc.
Refractory dilated cardiomyopathy associated with metastatic neuroblastoma
Authors: Carlson Peter , Jefferies John L. , Kearney Debra , Russell Heidi
Published: June 2010

A 2‐year‐old African American male presented with heart failure and an abdominal mass. Computerized tomography (CT) scan revealed a 7 cm adrenal lesion, confirmed as poorly differentiated neuroblastoma (NB). CT and meta‐iodobenzoguanidine (MIBG) scans identified multiple metastases, but cardiac MIBG imaging was absent. Cardiac ejection fraction (EF) was 8% with 7% shortening fraction. The patient underwent six cycles of chemotherapy and investigational immunotherapy. Cardiac function improved to 26% EF. However, the tumor proved unresponsive to treatment. The patient died from stage IV congestive heart failure (CHF) and progressive NB. Autopsy confirmed dilated cardiomyopathy with endocardial fibroelastosis. Pediatr Blood Cancer. 2010;55:736–738. © 2010 Wiley‐Liss, Inc.
Development of secondary T‐cell acute lymphoblastic leukemia in a child with hemophagocytic lymphohistiocytosis
Authors: Shamsian Bibi Shahin , Gharib Atoosa , Rezaei Nima , Esfahani Shadi Abdar , Alavi Samin , Goudarzipour Kourosh , Arzanian Mohammad Taghi
Published: June 2010

Hemophagocytic lymphohistiocytosis (HLH) is a severe life‐threatening disorder, characterized by hyperactivation of macrophages. A 12‐year‐old female was referred to our center; the diagnosis of HLH was made for the patient and immunosuppressive regimen was started. After a 2‐year follow‐up, the patient developed secondary T‐cell acute lymphoblastic leukemia (T‐ALL), confirmed by flow cytometric studies. Treatment was started based on T‐ALL protocol, but the patient died because of relapse and sepsis. This case highlights the issue of secondary malignancy following HLH and demonstrates the need for continued follow‐up in such patients. Pediatr Blood Cancer. 2010;55:725–726. © 2010 Wiley‐Liss, Inc.
Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: A children's oncology group study
Authors: George Rani E. , Lahti Jill M. , Adamson Peter C. , Zhu Kejin , Finkelstein David , Ingle A. Mark , Reid Joel M. , Krailo Mark , Neuberg Donna , Blaney Susan M. , Diller Lisa
Published: June 2010

Background

Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors.

Procedure

Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1‐hr decitabine infusion for 7 days, followed by doxorubicin (45 mg/m2) and cyclophosphamide (1 g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase‐8, MAGE‐1 and fetal hemoglobin (HbF), and expression profiling of pre‐ and post‐treatment peripheral blood and bone marrow cells.

Results

The maximum‐tolerated dose of decitabine was 5 mg/m2/day for 7 days. Dose‐limiting toxicities at 10 mg/m2/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ≥4 months. Sustained MAGE‐1 demethylation and increased HbF expression were observed in the majority of patients post‐treatment (12/20 and 14/16, respectively). Caspase‐8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis.

Conclusion

Low‐dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non‐cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored. Pediatr Blood Cancer. 2010;55:629–638. © 2010 Wiley‐Liss, Inc.
Matched unrelated umbilical cord blood transplantation for a patient with chemotherapy resistant Wilms tumor
Authors: Lucas Kenneth G. , Shapiro Terry , Freiberg Andrew , Frauenhoffer Elizabeth
Published: June 2010

We report a patient with chemotherapy refractory Wilms tumor who underwent an unrelated donor cord blood transplant for chemotherapy refractory disease. The preparative regimen consisted of busulfan, melphalan, and anti‐thymocyte globulin, and was well tolerated. This patient did not experience significant toxicity related to the chemotherapy regimen and did not develop any graft versus host disease from his HLA (A, B, DR) 6/6 matched cord blood transplant. Follow‐up CT scans 2 years post‐transplant have shown no evidence of disease progression, with only a few pulmonary nodules remaining, which are unchanged in size from his pre‐transplant CT scan. It is possible that high‐dose chemotherapy and stem cell transplantation can be curative in patients with tumors that are non‐responsive to conventional chemotherapy. Pediatr Blood Cancer. 2010;55:763–765. © 2010 Wiley‐Liss, Inc.
Traditional laboratory measures of cardiovascular risk in hereditary spherocytosis
Authors: Crary Shelley E. , Troendle Sarah , Ahmad Naveed , Buchanan George R.
Published: June 2010

Background

Individuals who have undergone splenectomy may be at an increased risk of arterial and venous thrombosis. We sought to determine if splenectomy affects surrogate laboratory measures of cardiovascular risk in persons with hereditary spherocytosis (HS).

Procedure

We conducted a prospective cross‐sectional study of 21 children and 36 adults with HS. Fasting blood samples were collected for complete blood count and plasma lipid panel, homocysteine, lipoprotein (a), C‐reactive protein, and fibrinogen. The variables were compared between the groups with and without prior splenectomy by Mann–Whitney tests.

Results

Subjects with prior splenectomy had higher hemoglobin, white blood cell and platelet counts and lower reticulocyte counts and total serum bilirubin concentrations (P < 0.001). Subjects not having had splenectomy had lower than normal levels of total and LDL‐cholesterol (LDL‐C). Total and LDL‐C values were significantly higher, as were fibrinogen and homocysteine concentrations, in the post‐splenectomy subjects than in individuals with intact spleen.

Conclusion

Various lipid levels and other measures of cardiovascular risk are affected by splenectomy in persons with HS. Further investigations are indicated to more clearly define the balance of the potential benefits of hemolysis and anemia versus the deleterious effects of splenectomy in HS. Pediatr Blood Cancer. 2010;55:684–689. © 2010 Wiley‐Liss, Inc.
Acquired hemophilia in pediatrics: A systematic review
Authors: Franchini Massimo , Zaffanello Marco , Lippi Giuseppe
Published: June 2010

Acquired hemophilia A is a rare but potentially life‐threatening hemorrhagic disorder caused by the development of autoantibodies directed mostly against coagulation factor VIII. Acquired hemophilia is frequently associated with several underlying conditions such as malignancy, autoimmune disorders, drug reactions, and pregnancy, although the pathogenesis remains undetermined (idiopathic) in up to 50% of reported cases. The disorder occurs most commonly in the elderly and only rarely affects pediatric patients, who might however experience severe, and sometimes life‐threatening, hemorrhage. The maternal transplacental transfer of the autoantibody to the neonate occurs very rarely and also in this circumstance it may be associated with clinically significant bleeding. The management of acute bleeding and the inhibitor eradication are the mainstay of the treatment. The outcome in pediatric patients seems more favorable than in adults because the inhibitors usually resolve more quickly and in a higher rate of patients. The epidemiology, diagnosis, clinical course, and management of this hemorrhagic disorder in children will be addressed in this systematic review. Pediatr Blood Cancer. 2010;55:606–611. © 2010 Wiley‐Liss, Inc.
Spielerisches Bimetall. Spielwiese
Authors: Ucke Christian , Schlichting Hans Joachim
Published: June 2010

Bimetalle sind technisch weit verbreitet und finden in Thermometern und als Schalter vielfältig Verwendung. Bei der Klickscheibe und der Lichtwippe wird ein Bimetall in spielerischer Form eingesetzt. Ein Klangobjekt mit Bimetallantrieb ist ein eher künstlerisches Beispiel.
Auftrieb durch Wasser und Wind. Physik des Segelns
Authors: Scheer Elke
Published: June 2010

Physikalisch gesehen ist Segeln ein dynamisches Zusammenspiel verschiedener Kräfte. Entscheidend sind die Auftriebskräfte über und unter Wasser. Über Wasser gibt die anströmende Luft dem Segel ein Profil, das daraufhin wie ein Flügel wirkt. Unter Wasser sorgt das um das Profil der Kielflosse strömende Wasser für eine Gegenkraft. Da mit Luft und Wasser zwei hydrodynamisch sehr verschiedene Fluide das Segeln bestimmen, ist das Zusammenspiel beider Kräfte physikalisch komplex. Es erlaubt Segeln in einem großen Winkelbereich relativ zum Wind – außer direkt gegen ihn.
Turbulenz verbessert Quantenkommunikation
Authors: Semenov Andrew A. , Vogel Werner
Published: June 2010

Einer Forschungsgruppe um Anton Zeilinger in Wien gelang es im letzten Jahr, verschränkte Photonen über eine Distanz von 144 km durch die turbulente Atmosphäre zu übertragen. In einer theoretischen Arbeit konnten wir jetzt zeigen, dass Turbulenz in der Atmosphäre die Transmission sogar verbessert. Dies ist für Anwendungen in der Quantenkommunikation von Bedeutung.
Präzisionsmessung der Gravitations‐Rotverschiebung
Authors: Müller Holger , Peters Achim
Published: June 2010

Nach der Allgemeinen Relativitätstheorie verlangsamt die Schwerkraft den Ablauf der Zeit. Diese Vorhersage konnten Wissenschaftler aus Berkeley, Berlin und Washington, D.C. mit einem Atominterferometer an der Stanford University bis auf 7 · 10–9 bestätigen. Es ist damit der bislang genaueste Test der Gravitations‐Rotverschiebung.
Von der Hydro‐ zur Aerodynamik
Authors: Junk Andreas
Published: June 2010

Einer der Pioniere bei der Visualisierung von Turbulenzen in laminaren Strömungsgebieten war der Göttinger Forscher Ludwig Prandtl, dessen Wirken in der Hydro‐ und Aerodynamik sich auf mehr als ein halbes Jahrhundert erstreckt. Er legte mit seinen Forschungsmethoden und ‐resultaten Grundlagen, in deren Tradition sich die Hydro‐ und Aerodynamiker bei der Modellierung moderner Tragflächen oder Schiffsrümpfe bis heute bewegen.
Warum können große Vögel nicht fliegen?
Authors: Rolfs Claus
Published: June 2010

Ein Mathematiker hat angeblich einmal bewiesen, dass Hummeln nicht fliegen können. Doch aller Theorie zum Trotz tun sie es. Aber sehr schwere Vögel wie Truthähne oder Strauße können sich wirklich nicht in die Lüfte erheben. Der Grund ist letztlich eine nicht ausreichende Energieproduktion der Körper.
Der Salonphysiker
Authors: Loos Andreas
Published: June 2010

Eigentlich wollte er Chirurg werden. Wäre da nicht das viele Blut gewesen. So verlegt er sich auf die Physik, die er allerdings anfangs eher als Hobby betreibt. Ein Freund sagt über ihn: “Er führt sozusagen das Leben einer dieser Katzen aus gutem Hause, die sich auf dem besten Platz im Schlafzimmer oder im Salon niederlassen. Wenn Besuch kommt, der ihm nicht behagt, zieht er sich in seinen Winkel zurück, mit seinem Notizbuch und seinem Bleistift, den er immer bei sich hat.” Doch dieser Salonphysiker soll in die Geschichte eingehen.
Kalte Baisers – Schäume unter Temperaturschock
Authors: Vilgis Thomas
Published: June 2010

Süße Schäume aus Eiklar, Baisers, gehören zu den beliebtesten Kindheitserinnerungen aller Naschkatzen. Das Trocknen dieser Gebilde aus schaumig geschlagenem Eiklar mit Zucker bei 100 °C führt auf die brüchig staubigen und süßen, im Mund zergehenden Knusprigkeiten. Baisers kann man aber auch – eines Physikers würdig – in flüssigem Stickstoff bei – 196°C herstellen. Nur die Physik der Schäume lässt das Arbeiten in diesen riesigen Temperaturbereichen zu.
New perspectives on polyhedral molecules and their crystal structures
Authors: Alvarez Santiago , Echeverría Jorge
Published: June 2010

Relevant families of ideal polyhedra (Platonic, Archimedean, prisms, Johnson, and Fullerenes) are briefly summarized, and an overview of polyhedral alkanes and alkenes, existing or hypothetical, is presented. The assignment of a polyhedral shape to a specific compound with the help of continuous shape measures and derived tools is also briefly discussed, and application of shape analysis to cyclic molecules such as cyclobutane, cyclohexane, and cyclooctatetraene is presented to illustrate the usefulness of ideal polyhedra in the stereochemical description of non‐polyhedral molecules. Finally, the presence of latent octahedral symmetry in icosahedral polyhedra is used to design new molecules with nested shells of the two supposedly incompatible symmetries, and to explain the cubic crystal structures of icosahedral molecules such as dodecahedrane and Buckminsterfullerene. Copyright © 2010 John Wiley & Sons, Ltd.
Spontaneous oscillatory in vitro chiral conversion of simple carboxylic acids and its possible mechanism
Authors: Sajewicz Mieczysław , Matlengiewicz Marek , Leda Marcin , Gontarska Monika , Kronenbach Dorota , Kowalska Teresa , Epstein Irving R.
Published: June 2010

In earlier studies, we have collected experimental evidence (mostly from thin‐layer chromatography and polarimetry) on the spontaneous oscillatory in vitro chiral conversion of simple carboxylic acids dissolved in 70% aqueous ethanol. To elucidate this phenomenon, we developed a simple theoretical model of two linked Templators. Recently, we have obtained additional experimental evidence of the spontaneous condensation of chiral carboxylic acids, based on the biuret test (amino acids), high performance liquid chromatography, and 13C NMR spectroscopy (profens and hydroxy acids). We briefly describe our experimental results in the context of the existing literature and outline an improved theoretical model for these phenomena. Our system resembles in some respects the reported oscillatory condensation of organic silanols. Here, the key reaction is the formation of carboxylic acid‐derived enols. Finally, we discuss the importance of the oscillatory chiral conversion of simple carboxylic acids for biochemistry, pharmacology, and related life sciences. Copyright © 2010 John Wiley & Sons, Ltd.
Redox, kinetics, and complexation chemistry of the CrVI/CrV/CrIV ‐D‐glycero‐D‐gulo‐heptono‐1,4‐lactone System
Authors: Mangiameli María F. , González Juan C. , García Silvia , Bellú Sebastián , Santoro Mabel , Caffaratti Evangelina , Frascaroli María I. , Peregrín Juan Manuel Salas , Atria Ana M. , Sala Luis F.
Published: June 2010

When a 60‐times or higher excess of D‐glycero‐D‐gulo‐heptono‐1,4‐lactone (GHL) over CrVI is used, reaction yields D‐gluconic acid, formic acid and CrIII as final products. The redox reaction involves formation of intermediates, CrIV and CrV species, reacting with GHL at comparable rates. CrIV is a very reactive intermediate and does not accumulate during this reaction; its rate of disappearance is 2.0 × 104 and 4.0 × 103 times higher than CrVI or CrV reaction with GHL, respectively. Kinetic studies show that the redox reaction proceeds through a mechanism combining CrVI → CrIV → CrII and CrVI → CrIV → CrIII pathways. This mechanism is supported by the observation of free radicals, superoxoCrIII (CrO) and oxo‐CrV as intermediates species. Complete rate laws for the GHL/chromium redox reaction are described in the present work. EPR spectra show that five‐coordinate oxo‐CrV bischelates (giso1 = 1.9802; giso2 = 1.9803) are formed at pH ≤ 4 where the OH and O‐ring groups of GHL participate in the bonding to oxo‐CrV. Penta‐coordinated oxo‐CrV monochelates are observed as minor species (giso3 = 1.9866; giso4 = 1.9879) in addition to the major penta‐coordinated oxo‐CrV bischelates. Copyright © 2010 John Wiley & Sons, Ltd.
On the synthesis and optical properties of sulfur‐bridged analogues of triangulenium cations and their precursors
Authors: Nicolas Cyril , Bernardinelli Gérald , Lacour Jérôme
Published: June 2010

Several sulfur‐bridged heterocyclic carbocations of the acridinium and triangulenium family were prepared using 9‐(2,6‐dimethoxyphenyl)‐1,8‐dimethoxy‐thioxanthenium tetrafluoroborate [7][BF4] as key synthetic intermediate. Thanks to simple yet not so facile aromatic nucleophilic substitution reactions, thiachromenoacridinium, azaoxa‐ and dioxathiotriangulenium salts (e.g., [8][BF4], [9][BF4], and [10][BF4], respectively) were obtained in moderate to good yields. Importantly, from the crystal structural analysis of 9‐(2,6‐dimethoxyphenyl)‐1,8‐dimethoxy‐9H‐thioxanthen‐9‐ol 16, bond lengths between sulfur and carbon atoms were confirmed to be much longer than that of classical CO or CN in analogous frameworks. This clearly triggers a distortion of the sulfur‐containing six‐membered ring which can be invoked to explain the relative lack of stabilization of the resulting carbenium ions. The increased electrophilicity of the central carbon set off a strongly reduced reactivity towards SNAr reactions. A comparison between electronic absorption spectra of the sulfur‐bridged dyes and their aza analogues was also carried out. A ca. 50 nm shift towards the low energy region was found to occur upon the insertion of the sulfur atom. Copyright © 2010 John Wiley & Sons, Ltd.
Hyperconjugation in β,β′‐silyl substituted vinyl cations – indications from IR spectroscopy
Authors: Klaer Andrea , Müller Thomas
Published: June 2010

Alkyl substituted vinyl cations 1a–c have been synthesized in the form of their [B(C6F5)4]− salts and have been characterized by NMR and IR spectroscopy. The IR absorption bands detected for the νas(CC+) vibrations in vinyl cations are of great diagnostic value, due to their high intensity and relative isolated position in the IR spectra ($\tilde {\nu }$ = 1930–2020 cm−1). DFT calculations of the harmonic force constants at the B3LYP/cc‐pvtz level of theory allowed for an unequivocal assignment of the band after scaling of the theoretical values to account for the anharmonicity of the experimental vibrational potential. A study on the energy of the νas(CC+) of alkyl (1) and aryl substituted vinyl cations (2) revealed a systematic trend, which indicates a decreasing stabilization of the vinyl cations by β‐SiC hyperconjugation when the electron donating ability of the substituent R2 next to the positively charged carbon atom is increased. Copyright © 2010 John Wiley & Sons, Ltd.
Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping
Authors: Lee Hsiau‐Wei , Wylie Greg , Bansal Sonal , Wang Xu , Barb Adam W. , Macnaughtan Megan A. , Ertekin Asli , Montelione Gaetano T. , Prestegard James H.
Published: June 2010

The traditional NMR‐based method for determining oligomeric protein structure usually involves distinguishing and assigning intra‐ and intersubunit NOEs. This task becomes challenging when determining symmetric homo‐dimer structures because NOE cross‐peaks from a given pair of protons occur at the same position whether intra‐ or intersubunit in origin. While there are isotope‐filtering strategies for distinguishing intra from intermolecular NOE interactions in these cases, they are laborious and often prove ineffectual in cases of weak dimers, where observation of intermolecular NOEs is rare. Here, we present an efficient procedure for weak dimer structure determination based on residual dipolar couplings (RDCs), chemical shift changes upon dilution, and paramagnetic surface perturbations. This procedure is applied to the Northeast Structural Genomics Consortium protein target, SeR13, a negatively charged Staphylococcus epidermidis dimeric protein (Kd 3.4 ± 1.4 mM) composed of 86 amino acids. A structure determination for the monomeric form using traditional NMR methods is presented, followed by a dimer structure determination using docking under orientation constraints from RDCs data, and scoring under residue pair potentials and shape‐based predictions of RDCs. Validation using paramagnetic surface perturbation and chemical shift perturbation data acquired on sample dilution is also presented. The general utility of the dimer structure determination procedure and the possible relevance of SeR13 dimer formation are discussed.
Structure and dynamics of the water around myoglobin
Authors: Phillips George N. , Montgomery Pettitt B.
Published: June 2010

The interplay between simulations at various levels of hydration and experimental observables has led to a picture of the role of solvent in thermodynamics and dynamics of protein systems. One of the most studied protein‐solvent systems is myoglobin, which serves as a paradigm for the development of structure‐function relationships in many biophysical studies. We review here some aspects of the solvation of myoglobin and the resulting implications. In particular, recent theoretical and simulation studies unify much of the diverse set of experimental results on water near proteins.
Early intermediates in the folding of dihydrofolate reductase from escherichia coli detected by hydrogen exchange and NMR
Authors: Jones Bryan E. , Robert Matthews C.
Published: June 2010

The kinetic folding mechanism for Escherichia coli dihydrofolate reductase postulates two distinct types of transient intermediates. The first forms within 5 ms and has substantial secondary structure but little stability. The second is a set of four species that appear over the course of several hundred milliseconds and have secondary structure, specific tertiary structure, and significant stability (Jennings PA, Finn BE, Jones BE, Matthews CR, 1993, Biochemistry 52:3783–3789). Pulse labeling hydrogen exchange experiments were performed to determine the specific amide hydrogens in α‐helices and β‐strands that become protected from exchange through the formation of stable hydrogen bonds during this time period. A significant degree of protection was observed for two subsets of the amide hydrogens within the dead time of this experiment (6 ms). The side chains of one subset form a continuous nonpolar strip linking six of the eight strands in the β‐sheet. The other subset corresponds to a non‐polar cluster on the opposite face of the sheet and links three of the strands and two α‐helices. Taken together, these data demonstrate that the complex strand topology of this eight‐stranded sheet can be formed correctly within 6 ms. Measurement of the protection factors at three different folding times (13 ms, 141 ms, and 500 ms) indicates that, of the 13 amide hydrogens displaying significant protection within 6 ms, 8 exhibit an increase in their protection factors from ∼5 to ∼50 over this time range; the remaining five exhibit protection factors >100 at 13 ms. Only approximately half of the population of molecules form this set of stable hydrogen bonds. Thirteen additional hydrogens in the β‐sheet become protected from exchange as the set of native conformers appear, suggesting that the stabilization of this network reflects the global cooperativity of the folding reaction.
Replacements in a conserved leucine cluster in the hydrophobic heme pocket of cytochrome c
Authors: Lo Terence P. , Murphy Michael E.P. , Guy Guillemette J. , Smith Michael , Brayer Gary D.
Published: June 2010

A cluster of highly conserved leucine side chains from residues 9, 68, 85, 94, and 98 is located in the hydrophobic heme pocket of cytochrome c. The contributions of two of these, Leu 85 and Leu 94, have been studied using a protein structure‐function‐mutagenesis approach to probe their roles in the maintenance of overall structural integrity and electron transfer activity. Structural studies of the L85C, L85F, L85M, and L94S mutant proteins show that, in each case, the overall fold of cytochrome c is retained, but that localized conformational shifts are required to accommodate the introduced side chains. In particular, the side chains of Cys 85 and Phe 85 form energetically favorable interactions with Phe 82, whereas Met 85 takes on a more remote conformation to prevent an unfavorable interaction with the phenyl ring of Phe 82. In the case of the L94S mutant protein, the new polar group introduced is found to form hydrogen bonds to nearby carbonyl groups. In all proteins with substitutions at Leu 85, the hydrophobic nature of the heme pocket is preserved and no significant decrease in heme reduction potential is observed. Despite earlier predictions that Leu 85 is an important determinant in cytochrome c electron transfer partner complexation, our studies show this is unlikely to be the case because the considerable surface contour perturbations made by substitutions at this residue do not correspondingly translate into significant changes in electron transfer rates. For the L94S mutant protein, the substitution of a polar hydroxyl group directly into the hydrophobic heme pocket has a larger effect on heme reduction potential, but this is mitigated by two factors. First, the side chain of Ser 94 is rotated away from the heme group and, second, the side chain of Leu 98 shifts into a portion of the new space available, partially shielding the heme group. The Leu 94 Ser substitution does not perturb the highly conserved interface formed by the nearly perpendicular packing of the N‐ and C‐terminal helices of cytochrome c, ruling this out as the cause of this mutant protein becoming thermally labile and having a lower functional activity. Our results show these effects are most likely attributable to disruption of the heme pocket region. Much of the ability of cytochrome c to absorb the introduction of mutations at Leu 85 and Leu 94 appears to be a consequence of the conformational flexibility afforded by the leucine cluster in this region as well as the presence of a nearby internal cavity. It is possible that these two structural features play a part in providing structural flexibility between oxidation states in the course of cytochrome c electron transfer.
Neural networks for secondary structure and structural class predictions
Authors: Chandonia John‐Marc , Karplus Martin
Published: June 2010

A pair of neural network‐based algorithms is presented for predicting the tertiary structural class and the secondary structure of proteins. Each algorithm realizes improvements in accuracy based on information provided by the other. Structural class prediction of proteins nonhomologous to any in the training set is improved significantly, from 62.3% to 73.9%, and secondary structure prediction accuracy improves slightly, from 62.26% to 62.64%. A number of aspects of neural network optimization and testing are examined. They include network overtraining and an output filter based on a rolling average. Secondary structure prediction results vary greatly depending on the particular proteins chosen for the training and test sets; consequently, an appropriate measure of accuracy reflects the more unbiased approach of “jackknife” cross‐validation (testing each protein in the database individually).
Strategies and rationales for the de novo design of a helical hairpin peptide
Authors: Fezoui Youcef , Weaver David L. , Osterhout John J.
Published: June 2010

The de novo design of αtα, a helical hairpin peptide, is described. αtα (α‐helix/turn/α‐helix) was developed to provide a model system for protein folding at the level of secondary structure association and stabilization. According to the prevailing models of protein folding, the second step in the folding process is the association and stabilization of secondary structural elements or microdomains. A brief description of the design, along with CD and NMR evidence confirming the conformation of the peptide in solution, has been published (Fezoui Y, Weaver DL, Osterhout JJ, 1994, Proc Natl Acad Sci USA 91:3675–3679). The present work includes a full description of the design process, including the trade‐offs that were made during the development of the peptide, a discussion of recent experimental results that were not available at the time of the original design, indications of areas where, in retrospect, the design might have been done differently, and a discussion of how the present work fits into the field of de novo protein design.
Protein structure refinement based on paramagnetic NMR shifts: Applications to wild‐type and mutant forms of cytochromec
Authors: Gochin Miriam , Roder Heinrich
Published: June 2010

A new approach to NMR solution structure refinement is introduced that uses paramagnetic effects on nuclear chemical shifts as constraints in energy minimization or molecular dynamics calculations. Chemical shift differences between oxidized and reduced forms of horse cytochromecfor more than 300 protons were used as constraints to refine the structure of the wild‐type protein in solution and to define the structural changes induced by a Leu 94 to Val mutation. A single round of constrained minimization, using the crystal structure as the starting point, converged to a low‐energy structure with an RMS deviation between calculated and observed pseudo‐contact shifts of 0.045 ppm, 7.5‐fold lower than the starting structure. At the same time, the procedure provided stereospecific assignments for more than 45 pairs of methylene protons and methyl groups. Structural changes caused by the mutation were determined to a precision of better than 0.3 A. Structure determination based on dipolar paramagnetic (pseudocontact) shifts is applicable to molecules containing anisotropic paramagnetic centers with short electronic relaxation times, including numerous naturally occurring metalloproteins, as well as proteins or nucleic acids to which a paramagnetic metal ion or ligand may be attached. The long range of paramagnetic shift effects (up to 20 Å from the iron in the case of cytochrome c) provides global structural constraints, which, in conjunction with conventional NMR distance and dihedral angle constraints, will enhance the precision of NMR solution structure determination.
Binding of phosphorus‐containing inhibitors to thermolysin studied by the Poisson‐Boltzmann method
Authors: Shen Jian , Wendoloski John
Published: June 2010

Zinc endopeptidase thermolysin can be inhibited by a series of phosphorus‐containing peptide analogues, Cbz‐Gly‐ψ(PO2)‐X‐Leu‐Y‐R (ZGP(X)L(Y)R), where X = NH, O, or CH2; Y = NH or O; and R = Leu, Ala, Gly, Phe, H, or CH3. The affinity correlation as well as an X‐ray crystallography study suggest that these inhibitors bind to thermolysin in an identical mode. In this work, we calculate the electrostatic binding free energies for a series of 13 phosphorus‐containing inhibitors with modifications at X, Y, and R moieties using finite difference solution to the Poisson‐Boltzmann equation. A method has been developed to include the solvation entropy changes due to binding different ligands to a macromolecule. We demonstrate that the electrostatic energy and empirically derived solvation entropy can account for most of the binding energy differences in this series. By analyzing the binding contribution from individual residues, we show that the energy of a hydrogen bond is not confined to the donor and acceptor. In particular, the positive charges on Zn and Arg 203, which are not the acceptors, contribute significantly to the hydrogen bonds between two amides of ZGPLL and the thermolysin.