bluuebunny/crossref_metadata_2025 huggingface dataset:
Shape optimization for viscous flows by reduced basis methods and free‐form deformation
Authors: Manzoni Andrea , Quarteroni Alfio , Rozza Gianluigi
Published: November 2011

In this paper, we further develop an approach previously introduced in Lassila and Rozza, 2010, for shape optimization that combines a suitable low‐dimensional parametrization of the geometry (yielding a geometrical reduction) with reduced basis methods (yielding a reduction of computational complexity). More precisely, free‐form deformation techniques are considered for the geometry description and its parametrization, whereas reduced basis methods are used upon a FE discretization to solve systems of parametrized partial differential equations. This allows an efficient flow field computation and cost functional evaluation during the iterative optimization procedure, resulting in effective computational savings with respect to usual shape optimization strategies. This approach is very general and can be applied to a broad variety of problems. In this paper, we apply it to find the optimal shape of aorto‐coronaric bypass anastomoses based on vorticity minimization in the down‐field region. Blood flows in the coronary arteries are modeled using Stokes equations; afterwards, results have been verified in feedback using Navier–Stokes equations. Copyright © 2011 John Wiley & Sons, Ltd.
Numerical study of Prandtl effect on MHD flow at a lid‐driven porous cavity
Authors: Hasanpour A. , Farhadi M. , Sedighi K. , Ashorynejad H.R.
Published: November 2011

In this paper, the lattice Boltzmann method is used to study the Prandtl number effect on flow structure and heat transfer rates in a magnetohydrodynamic flow mixed convection in a lid‐driven cavity filled with a porous medium. The right and left walls are at constant but different temperatures (θh and θc), while the other walls are adiabatic. Gallium and salt water (0.02 < Pr < 13.4) are used as samples of the electroconducting fluids in the cavity. Typical sets of streamlines and isotherms are presented to analyze the flow patterns set up by the competition among the forced flow created by the lid‐driven wall, the buoyancy force of the fluid and the magnetic force of the applied magnetic field. Mathematical formulations in the porous media were constructed based on the Brinkman–Forchheimer model, while the multidistribution‐function model was used for the magnetic field effect. Numerical results were obtained and the effects of the Prandtl number and the other effective parameters such as Richardson, Hartman, and Darcy numbers were investigated. It was found that the fluid fluctuations within the cavity were reduced by increasing the Hartman number. A similar pattern was observed for the Darcy number reduction. Heat transfer was essentially dominated by the conduction for the low Prandtl number and forced convection dominated as the Prandtl number increased. Also, the average Nusselt number was raised by increasing the Prandtl number. It was discovered that a remarkable heat transfer enhancement of up to 28% could be reached by increasing the Prandtl number (from 0.02 to 13.4) at constant Richardson and Darcy numbers. Copyright © 2011 John Wiley & Sons, Ltd.
Silurian to Early Devonian organic‐walled phytoplankton and miospores from Argentina: biostratigraphy and diversity trends
Authors: Rubinstein Claudia V. , García Muro Victoria J.
Published: November 2011

The distribution and diversity of marine palynomorphs, such as acritarchs and chlorophytes, and terrestrial palynomorphs, such as miospores, are controlled mainly by palaeoenvironmental and palaeogeographical conditions. Recently, global patterns of organic‐walled phytoplankton were illustrated for the Late Silurian to earliest Devonian based on data from different stratigraphic sections and palaeocontinents. Here, we analyze the Silurian and the Early Devonian diversity in the Argentinean Precordillera, Central Andean, and Chacoparanense basins. The evolution of the diversity is evaluated in a well‐constrained biostratigraphic framework, bearing in mind local palaeoenvironmental conditions and changes within each basin. Taking into account recently published and unpublished data from well‐dated sections, the biodiversity of Silurian phytoplankton seemingly increases upwards, reaching its maximum peak during the Ludlovian. However, palynomorphs are rarely recorded in Wenlockian strata, and the supposed Pridolian layers are not confidently well constrained. The first record of trilete spores in Argentina is Ludlovian, approximately 30 million years after their first appearance in the Late Ordovician. Palynomorph diversity increases in the Early Devonian, with a higher diversity of miospores than that of the marine phytoplankton. We interpret possible discrepancies in biodiversity trends of organic‐walled phytoplankton between Argentina and other regions, as related to the quantitatively and qualitatively disparity of data, as well as the lack of rigorous biostratigraphic and palaeoenvironmental assessments of the Argentinean basins. Copyright © 2011 John Wiley & Sons, Ltd.
Prevention of radiation‐induced xerostomia by submandibular gland transfer
Authors: Zhang Ye , Guo Chuan‐Bin , Zhang Lei , Wang Yang , Peng Xin , Mao Chi , Yu Guang‐Yan
Published: November 2011

Background

This study was carried out for the purpose of evaluating the efficacy of submandibular gland transfer to prevent radiation‐induced xerostomia.

Methods

Thirty‐eight patients with oropharyngeal carcinoma were recruited. Twenty‐six submandibular glands were transferred into the submental space to elude radiotherapy in 24 patients (transfer group); the submandibular gland was not disturbed in the control group (n = 14). The salivary flow rate, xerostomia, and quality of life (QOL) were assessed preoperatively, postoperatively, and after radiotherapy. The swallowing function was then evaluated after radiotherapy.

Results

All the transferred glands survived and functioned after radiotherapy. The submandibular salivary flow rate recovered by 6 months after radiotherapy in the transfer group, whereas the flow rate declined drastically after radiotherapy and remained at a low level in the longer term in the control group. Two years after radiotherapy, 92.3% of patients in the transfer group had no or minimal xerostomia. QOL in the transfer group was better than that in the control group from 3 months after radiotherapy. Histologically, the majority of the transferred glands had normal glandular acini and ducts. There was no significant difference in dysphagia between the groups.

Conclusions

The submandibular gland can be successfully transferred to the submental space, thus preserving salivary function and preventing radiation‐induced xerostomia. The transfer of the submandibular gland can improve the QOL by alleviating xerostomia, although it did not relieve dysphagia in this study. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Indications for pedicled pectoralis major flap in a free tissue transfer practice
Authors: Schneider Daniel S. , Wu Vivian , Wax Mark K.
Published: November 2011

Background

The pedicled pectoralis major myocutaneous flap (PMMF) was highly used over the last 3 decades. The current era of free tissue transfer has gradually relegated the PMMF to a secondary role.

Methods

In a retrospective review of all patients undergoing pedicled PMMF from 2002 to now, we sought to determine the current role and assess the outcomes of the PMMF in a primary microvascular head and neck reconstructive center.

Results

Fifty‐five PMMFs were performed in 53 patients (24 myocutaneous and 31 myofascial); group 1 consisted of 20 patients (38%) who underwent a secondary PMMF after a free flap complication (flap failure 9/20, fistula 5/20, wound breakdown with great vessel exposure 3/20, loss of soft tissue skin paddle 2/20, and delayed hematoma in 1/20); group 2 included 18 patients (33%) who had a simultaneous free flap with a PMMF for dead space filler or cervical skin/great vessel coverage reconstruction, whereas the remaining 15 patients (29%) in group 3 underwent primary PMMF for reconstruction of cervical skin defect, great vessel coverage, pharyngocutaneous fistula, infection, and dead space filler. Complications of PMMF included 3 hematomas, 2 partial dehiscences, 1 chest wall abscess, and 1 case of mastitis. Because of cervical tethering, 14 of 53 patients underwent secondary pectoralis myectomy with cervical contracture release at a mean of 10.3 months after initial surgery.

Conclusion

The pedicled PMMF continues to serve an important role in head and neck reconstruction in the microvascular era with notable uses for free flap rescue, with simultaneous free flap reconstruction and for primary reconstruction in select circumstances with an overall acceptable short‐ and long‐term morbidity profile. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas
Authors: Cabanillas Rubén , Astudillo Aurora , Valle Miguel , de la Rosa Jorge , Álvarez Rebeca , Durán Noelia S. , Cadiñanos Juan
Published: November 2011

Background

The ability to identify individuals at increased risk of cancer is of immediate clinical relevance. Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported in families with genetic susceptibility to head and neck squamous cell carcinomas (HNSCC).

Methods

We report the pedigree of a patient with an unusually high incidence of HNSCC and melanomas. CDKN2A mutation analysis was performed with standard capillary sequencing and multiplex ligation‐dependent probe amplification.

Results

A previously unreported germline CDKN2A mutation affecting only the p16/INK4A open reading frame, c.106delG (p.Ala36ArgfsX17), was detected in the proband. This mutation causes a premature termination codon.

Conclusions

Our report emphasizes the need to consider germinal CDKN2A mutations in the differential diagnosis of familial HNSCC and the importance of awareness of these tumors in carriers of CDKN2A mutations. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Longitudinal analysis of voice quality in patients with early glottic cancer after transoral laser microsurgery
Authors: Chu Pen‐Yuan , Hsu Yen‐Bin , Lee Tsung‐Lun , Fu Sherry , Wang Li‐Mei , Kao Ya‐Chung
Published: November 2011

Background

We conducted longitudinal voice evaluations in patients with early glottic cancer who underwent transoral laser microsurgery (TLM) to determine the time to stability.

Methods

Twenty‐five patients underwent TLM, including 13 limited cordectomies (type I and type II) and 12 extended cordectomies (type III to type IV). Multidimensional voice evaluations were performed before treatment and at 1, 3, 6, and 12 months after treatment.

Results

Voice parameters of asthenicity, strain, mean airflow rate (MFR), voice handicap index (VHI)–functional, VHI–physical, and VHI–total scores improved in all patients. Most patients had improved 6 months after TLM. Patients with extended cordectomy showed higher breathiness, MFR, VHI–functional, and VHI–total scores. Healing was complete in all cases by 6 months and in a majority of cases (76%) by 3 months.

Conclusions

Voice quality achieved stability 6 months after TLM. Comparing treatment outcomes and surgical intervention are not recommended within 6 months of surgery. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Surgical management of T1 oropharyngeal carcinoma
Authors: Karatzanis Alexander D. , Psychogios Georgios , Waldfahrer Frank , Zenk Johannes , Velegrakis George A. , Iro Heinrich
Published: November 2011

Background

The purpose of this study was to assess the efficacy of primary transoral surgery in the management of T1 oropharyngeal carcinoma.

Methods

A retrospective evaluation was conducted on the files of all patients treated with primary surgery for pT1 oropharyngeal carcinoma at a tertiary referral center between 1976 and 2005.

Results

A total of 223 cases were assessed. Disease‐specific survival was 88% and local control 93%. Transoral surgery with the use of CO2 laser or electrocautery was adopted in every case. Positive surgical margins and regional disease were found to significantly worsen prognosis. A low rate of complications and satisfactory retention of pharyngeal function were noted.

Conclusions

Primary transoral surgical treatment is very effective against T1 oropharyngeal carcinoma. A low rate of complications should be expected. However, in every case complete excision of the tumor must be accomplished and the neck included in the primary treatment plan. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Comprehensive approach to restoration of function in patients with radiation‐induced pharyngoesophageal stenosis: Report of 31 patients and proposal of new classification scheme
Authors: Urken Mark L. , Jacobson Adam S. , Lazarus Cathy L.
Published: November 2011

Background

The treatment for upper aerodigestive tract malignancy with external beam radiation therapy and chemotherapy can result in a “cure,” yet result in pharyngoesophageal (PE) stenosis. To improve communication, compare therapeutic results, and assist in treatment planning, we developed a new classification system to describe PE stenoses. Additionally, we analyzed our 6‐year experience.

Methods

The new classification system was defined and used to assess patient management.

Results

Thirty‐one patients underwent treatment for PE stenoses using: 4 rendezvous dilations, 3 regional, and 24 free tissue transfers. Overall success was based on airway status, speech, and swallowing outcomes.

Conclusion

Classification of posttreatment stenoses has been applied to this patient group. It is effective in defining the problem and considerations related to treatment planning and surgical access when augmentation pharyngoplasty is required. Patients with an intact larynx have many issues that make recovery of function less consistent, despite segment restoration. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Rosai–dorfman disease: Presentation, diagnosis, and treatment
Authors: Lai Kwong Lun , Abdullah Victor , Ng Kwan Shun , Fung Ngai Sheung , van Hasselt C. Andrew
Published: November 2011

Background

Sinus histiocytosis with massive lymphadenopathy or Rosai–Dorfman disease (RDD) is a rare benign disease with nodal and extranodal involvement.

Methods and Results

Herein, we report 3 cases in which the patients presented with nasal masses. In addition, 2 of the 3 patients had subglottic lesions. Only 2 of the 3 patients had cervical lymphadenopathy, which is the commonest presentation of RDD. Histopathology via fine‐needle aspiration cytology (FNAC) or open biopsy is required for diagnosis. Emperipolesis with S‐100 immunohistochemical staining is characteristic. The disease runs a benign course and the literature reports that treatment can vary from steroids, to cytotoxic chemotherapy to radiotherapy with variable outcomes. Surgical intervention may be necessary for airway protection.

Conclusion

RDD is self‐limiting, but can sometimes be a life‐threatening condition. Treatment should be tailored to the individual patient. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Murine model of neuromuscular electrical stimulation on squamous cell carcinoma: Potential implications for dysphagia therapy
Authors: Linkov Gary , Branski Ryan C. , Amin Milan , Chernichenko Natalya , Chen Chun‐Hao , Alon Gad , Langmore Susan , Wong Richard J. , Kraus Dennis H.
Published: November 2011

Background

Dysphagia is a potential consequence of treatment for head and neck cancer. Neuromuscular electrical stimulation (NMES) has evolved as a treatment option, with the goal of improved swallow function in patients with chronic dysphagia. However, the effects of NMES on tumorigenicity are unknown and often confound the initiation of this therapy, potentially limiting its efficacy in treating patients with head and neck cancer.

Methods

Squamous cell carcinoma was grown in the flank of athymic, nude mice. Mice were randomized into treatment and control groups; the experimental group received daily NMES directly to the flank for 8 days.

Results

Tumor volumes, recorded on days 0, 3, 7, and 10, demonstrated no significant differences between groups on each day of measurement. Immunohistochemical analysis of apoptosis, proliferation, and vascularization also failed to demonstrate statistically significant differences between treated and untreated groups.

Conclusions

NMES does not promote the growth of underlying tumor in our model. These data may provide preliminary evidence that applying electrical stimulation over the muscles of the anterior neck does not increase the risk of tumorigenicity. Early initiation of NMES in this challenging population may be feasible from an oncologic standpoint. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Successful treatment of anaplastic meningioma metastatic to cervical lymph nodes
Authors: Moubayed Sami P. , Guertin Louis , Lambert Carole , Desrochers Pascal , Nehmé Jade , Coulombe Geneviève
Published: November 2011

Background

Cervical lymph node metastases of meningioma represent an important diagnostic and treatment challenge. Not only has this entity been rarely described, but successful treatment has never been reported in the literature.

Methods and Results

This case report was conducted using reviews of the literature. A 58‐year‐old man with a history of resected anaplastic meningioma was referred for a right neck mass. Excisional biopsy revealed metastatic meningioma, and a metastatic workup was negative. Modified radical neck dissection showed positivity in 5 lymph nodes. The patient received adjuvant intensity‐modulated radiation therapy (IMRT), for a mean target dose of 60 Gray (Gy). Two years after treatment, the patient was disease free. Eleven cases of cervical lymph node metastasis of meningioma were identified in our literature search, and none described successful treatment of this entity.

Conclusion

Cervical lymph node metastasis of anaplastic meningioma is potentially treatable with surgical resection and IMRT, although further studies with long‐term follow‐up are necessary. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Metastases to the oral region from pleural mesothelioma: Clinicopathologic review
Authors: Sinon Suraya H. , Rich Alison M. , Hussaini Haizal M. , Yoon Han‐Seung , Firth Norman A. , Seymour Gregory J.
Published: November 2011

Background

Malignant mesothelioma is a rare neoplasm that usually develops after exposure to asbestos and particularly involves the pleural cavity. It has a poor prognosis with aggressive local invasion and metastatic spread.

Methods

The literature relating to malignant mesothelioma metastatic to the oral region was reviewed.

Results

In all, 14 cases of malignant mesothelioma metastatic to the oral cavity were found. All were from pleural mesotheliomas, the tongue was the most common site of metastasis (8/14), and most metastases (9/13) were of the epithelioid type. The newly reported case is only the second report of a mesothelioma metastasizing to the buccal mucosa. It showed strong immunopositivity for keratin markers, vimentin, calretinin, and Wilms tumor product‐1.

Conclusions

The incidence of mesothelioma is predicted to continue to increase for at least another decade. Clinicians and pathologists should be aware of this lesion and its propensity to metastasize to the oral cavity. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Label‐free identification and characterization of human pluripotent stem cell‐derived cardiomyocytes using second harmonic generation (SHG) microscopy
Authors: Awasthi Samir , Matthews Dennis L. , Li Ronald A. , Chiamvimonvat Nipavan , Lieu Deborah K. , Chan James W.
Published: November 2011

Pluripotent stem cell‐derived cardiomyocytes (PSC‐CMs) are a potentially unlimited source of cardiomyocytes (CMs) for cardiac transplantation therapies. The establishment of pure PSC‐CM populations is important for this application, but is hampered by a lack of CM‐specific surface markers suitable for their identification and sorting. Contemporary purification techniques are either non‐specific or require genetic modification. We report a second harmonic generation (SHG) signal detectable in PSC‐CMs that is attributable to sarcomeric myosin, dependent on PSC‐CM maturity, and retained while PSC‐CMs are in suspension. Our study demonstrates the feasibility of developing a SHG‐activated flow cytometer for the non‐invasive purification of PSC‐CMs. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The influence of movement on the localization precision of sub‐resolution particles in fluorescence microscopy
Authors: Deschout Hendrik , Neyts Kristiaan , Braeckmans Kevin
Published: November 2011

Obtaining sub‐resolution particle positions in fluorescence microscopy images is essential for single particle tracking and high‐resolution localization microscopy. While the localization precision of stationary single molecules or particles is well understood, the influence of particle motion during image acquisition has been largely neglected. Here, we address this issue and provide a theoretical description on how particle motion influences the centroid localization precision, both in case of 2‐D and 3‐D diffusion. In addition, a novel method is proposed, based on dual‐channel imaging, for the experimental determination of the localization precision of moving particles. For typical single particle tracking experiments, we show that the localization precision is approximately two‐fold worse than expected from the stationary theory. Strikingly, we find that the most popular localization method, based on the fitting of a Gaussian distribution, breaks down for lateral diffusion. Instead, the centroid localization method is found to perform well under all conditions. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optimal apheresis treatment volume for the efficacy and safety of leukocytapheresis with cellsorba in patients with active ulcerative colitis
Authors: Fukunaga Ken , Kamikozuru Koji , Yokoyama Yoko , Hida Nobuyuki , Ohda Yoshio , Takeda Naohisa , Yoshida Koji , Iimuro Masaki , Kikuyama Risa , Kato Kyoichi , Nagase Kazuko , Nakamura Shiro , Miwa Hiroto , Matsumoto Takayuki
Published: November 2011

Background: Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume. Methods: In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA‐LCAP) was evaluated in 14 patients with active UC. Fourteen demography matched UC patients who had been treated with the routine 3,000 mL LCAP were randomly sampled from our database as a control group. All patients were given 10 weekly LCAP sessions. In the BWA‐LCAP group, the processed blood volume (PBV) was set at 30 mL/kg × BW/session. Baseline demographic measures were not significantly different between the two groups. Results: The average PBV in the BWA‐LCAP group was 1971.0 ± 330.0 mL, range 1,020–2,460. In both groups, the average UC clinical disease activity index, the endoscopic index, and the concomitant prednisolone dosage were significantly and equally reduced during the course of 10 LCAP. Accordingly, at the end of the trial, no significant difference was seen in any outcome measure between the two groups. However, a significantly higher incidence of adverse event (AE) was observed in the routine 3,000 mL LCAP group as compared with the BWA‐LCAP group (P < 0.01). Conclusions: The outcomes of this investigation showed that the therapeutic efficacy of LCAP based on 30 mL/kg × BW is similar to the routine 3,000 mL per session LCAP. However, BWA‐LCAP should be favored if one is to see the full potential of LCAP without AE. © 2011 Wiley Periodicals, Inc.
A review of the world's active seabird restoration projects
Authors: Jones Holly P. , Kress Stephen W.
Published: November 2011

Within the past several decades, seabird populations have been actively restored in locales where they were reduced or extirpated. Chick translocation, acoustic vocalization playbacks, and decoys are now used widely to lure breeding seabirds to restoration sites. In this first worldwide review of seabird restoration projects we evaluate the factors affecting project success or failure and recommend future directions for management. We identified 128 active restoration projects that were implemented to protect 47 seabird species in 100 locales spanning 14 countries since active restoration methods were pioneered in 1973. Active seabird restoration can achieve conservation goals for threatened and endangered species, and for species affected by anthropogenic impacts (e.g., oil spills, invasive species, fisheries). It also can be used to relocate populations from undesired breeding locales to more favorable locations, and to establish multiple breeding locations to reduce risks posed by catastrophic events. Active restoration can help to restore ecological processes, as large seabird colonies function to cycle marine nutrients to terrestrial ecosystems and create habitats for commensal species. Active restoration is especially appropriate where the original causes of decline are no longer working to suppress colony establishment and growth. Successful restoration efforts require careful planning and long‐term commitments. We introduce the different forms of active seabird restoration techniques, review their utility for different seabird species, and use case studies to suggest how to optimize this technique to restore seabird species globally. Wildlife managers can use this review to guide their seabird restoration projects in the planning, implementation, and monitoring stages; tailor their restoration to seabird‐specific life histories; and identify areas for further research to improve restoration utility in the future. © 2011 The Wildlife Society.
hp‐adaptive extended finite element method
Authors: Byfut A. , Schröder A.
Published: November 2011

This paper discusses higher‐order extended finite element methods (XFEMs) obtained from the combination of the standard XFEM with higher‐order FEMs. Here, the focus is on the embedding of the latter into the partition of unity method, which is the basis of the XFEM. A priori error estimates are discussed, and numerical verification is given for three benchmark problems. Moreover, methodological aspects, which are necessary for hp‐adaptivity in XFEM and allow for exponential convergence rates, are summarized. In particular, the handling of hanging nodes via constrained approximation and an hp‐adaptive strategy are presented. Copyright © 2011 John Wiley & Sons, Ltd.
A new particle method for simulation of incompressible free surface flow problems
Authors: Koh C. G. , Gao M. , Luo C.
Published: November 2011

A new Lagrangian particle method called the consistent particle method (CPM), which solves the Navier–Stokes equations in a semi‐implicit time stepping scheme, is proposed in this paper. Instead of using kernel function as in some particle methods, partial differential operators are approximated in a way consistent with Taylor series expansion. A boundary particle recognition method is applied to help define the changing liquid domain. The incompressibility condition of free surface particles is enforced by an adjustment scheme. With these improvements, the CPM is shown to be robust and accurate in long time simulation of free surface flow particularly for smooth pressure solution. Two types of free surface flow problems are presented to verify the CPM, that is, two‐dimensional dam break and liquid sloshing in a rectangular tank. In the dam break example, the CPM solutions of pressure and wave elevation are in good agreement with published experimental results. In addition, an experimental study of water sloshing in tank on a shake table was conducted to verify the CPM solutions. Copyright © 2011 John Wiley & Sons, Ltd.
Precorrected FFT accelerated BEM for large‐scale transient elastodynamic analysis using frequency‐domain approach
Authors: Xiao Jinyou , Ye Wenjing , Cai Yaxiong , Zhang Jun
Published: November 2011

A precorrected fast Fourier transform (pFFT) accelerated boundary element method (BEM) for large‐scale transient elastodynamic analysis is developed and described in this paper. The frequency‐domain approach is used. To overcome the ‘wrap‐around’ problem associated with the discrete Fourier transform, the exponential window method (EWM) is employed and incorporated in the frequency‐domain BEM. An improved implementation scheme of the pFFT method based on polynomial interpolation technique is developed and applied to accelerate the elastodynamic BEM. This new scheme reduces the memory required to save the convolution matrix by a factor of 8. To further improve the efficiency of the code, a newly developed linear system solver based on the induced dimension reduction method is employed. Its performance is investigated and compared with that of the well‐known GMRES. The accuracy and computational efficiency of the method are evaluated and demonstrated by three examples: a classical benchmark, a plate subject to an impact loading and a porous cube with nearly half million DOFs subject to a step traction loading. Both analytical and experimental results are employed to validate the method. It has been found that the EWM can effectively resolve the wrap‐around problem and accurate time responses for an arbitrarily chosen time period can be obtained. Copyright © 2011 John Wiley & Sons, Ltd.
Von der Schrecksekunde zum Drug Design
Authors: Helmstädter Axel
Published: November 2011

Unbewusst verwendet gehörten sympathomimetische und parasympatholytische Agenzien bereits lange zum tradierten Arzneischatz, bevor Adrenalin um 1900 als Reinsubstanz verfügbar wurde. Das Hormon wurde ebenso wie Ephedrin bereits früh inhalativ gegen asthmatische Beschwerden eingesetzt. Ein gewisser Fortschritt war das seit Ende der 1930er‐Jahre eingeführte Isoprenalin (Isoproterenol), das bereits eine gewisse Selektivität zeigte. Die heute noch verwendeten antiasthmatischen Betasympathomimetika wie beispielsweise Salbutamol wurden in den 1960er‐Jahren systematisch entwickelt, nachdem kurz zuvor die Differenzierung adrenerger Rezeptoren gelungen war. Mit den etwa zeitgleich entwickelten druckgasbetriebenen Dosieraerosolen standen praktische und handliche Applikationsgeräte zur Verfügung, die den Erfolg der Substanzklasse mit begründeten.
Mit gentechnisch veränderten Mücken gegen Malaria kämpfen
Authors: Winckler Thomas
Published: November 2011

Möglichkeiten zur Eradikation von Infektionskrankheiten durch genetische Manipulation der Erreger‐übertragenden Insekten werden in Fachkreisen schon länger diskutiert. Ein Forscherteam präsentiert nun einen gentechnischen Ansatz, der die Verbreitung des Malaria‐Erregers durch Anopheles‐Mücken stoppen soll.
Kampf gegen Humane Papillomviren – impfen oder eincremen?
Authors: Zündorf Ilse , Dingermann Theo
Published: November 2011

2008 gab es für die Identifizierung der Humanen Papillomviren (HPV) als Auslöser des Gebärmutterhalskrebses den halben Nobelpreis für Physiologie und Medizin. Bereits zwei Jahre vorher war der erste Impfstoff gegen eine HPV‐Infektion in Deutschland erhältlich, und obwohl die Ständige Impfkommission (STIKO) am Robert‐Koch‐Institut die Impfung 2007 in ihre jährlichen Empfehlungen mit aufgenommen hat, sind die Ressentiments gegen den HPV‐Impfstoff nach wie vor groß.
Interference of low‐molecular substances with the thioflavin‐T fluorescence assay of amyloid fibrils
Authors: Noormägi Andra , Primar Kateryna , Tõugu Vello , Palumaa Peep
Published: November 2011

Abnormal fibrillization of amyloidogenic peptides/proteins has been linked to various neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as with type‐II diabetes mellitus. The kinetics of protein fibrillization is commonly studied by using a fluorescent dye Thioflavin T (ThT) that binds to protein fibrils and exerts increased fluorescence intensity in bound state. Recently, it has been demonstrated that several low‐molecular weight compounds like Basic Blue 41, Basic Blue 12, Azure C, and Tannic acid interfere with the fluorescence of ThT bound to Alzheimers' amyloid‐β fibrils and cause false positive results during the screening of fibrillization inhibitors. In the current study, we demonstrated that the same selected substances also decrease the fluorescence signal of ThT bound to insulin fibrils already at submicromolar or micromolar concentrations. Kinetic experiments show that unlike to true inhibitors, these compounds did neither decrease the fibrillization rate nor increase the lag‐period. Absence of soluble insulin in the end of the experiment confirmed that these compounds do not disaggregate the insulin fibrils and, thus, are not fibrillization inhibitors at concentrations studied. Our results show that interference with ThT test is a general phenomenon and more attention has to be paid to interpretation of kinetic results of protein fibrillization obtained by using fluorescent dyes. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Antinociceptive effect of [Met5]enkephalin semicarbazide is not affected by dipeptidyl carboxypeptidase‐I
Authors: Rezaee Zahra , Arabanian Seyed Abbas , Balalaie Saeed , Ahmadiani Abolhassan , Khalaj Leila , Nasoohi Sanaz
Published: November 2011

Dipeptidyl carboxypeptidase‐I is an enzyme involved in the biological degradation of enkephalins. It has been suggested that C‐terminal amidation of enkephalins enhances their resistance to dipeptidyl carboxypeptidase‐I‐mediated biodegradation. In this study, a novel [Met5]enkephalin amide (MEA) analogue [Met5]enkephalin (ME)‐semicarbazide synthesized by another laboratory in our group was assessed for its antinociceptive effects compared with ME‐ethylamide, MEA and ME, using tail flick test. To protect the administered drugs from biodegradation, rats were pretreated with peptidase inhibitors including amastatin, phosphoramidon and captopril. Then captopril (dipeptidyl carboxypeptidase‐I inhibitor) was deleted from the peptidase inhibitors' combination for evaluating in vivo resistance of the synthetic drugs to dipeptidyl carboxypeptidase‐I.

According to the results, ME‐semicarbazide and MEA were resistant enough to dipeptidyl carboxypeptidase‐I to exert their strong antinociception following intrathecal administration even in the absence of captopril, whereas the antinociceptive effects produced by ME‐ethylamide (10 nmol) were abolished in rats not pretreated with captopril, indicating that significant amounts of the ME‐ethylamide were degraded by dipeptidyl carboxypeptidase‐I. Replacement of the amide moiety of MEA with semicarbazide provides a new ME derivative, with high analgesic effects as well as more resistance to dipeptidyl carboxypeptidase‐I‐mediated biodegradation. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Antibacterial potential of hGlyrichin encoded by a human gene
Authors: Sha Jibin , Zhao Guang , Chen Xiaojuan , Guan Weiping , He Yanling , Wang Zhaoqing
Published: November 2011

Emerging multidrug‐resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero‐immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin‐resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42–60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero‐immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.
Authors: Tomasinsig Linda , Skerlavaj Barbara , Scarsini Michele , Guida Filomena , Piccinini Renata , Tossi Alessandro , Zanetti Margherita
Published: November 2011

The yeast‐like algae of the genus Prototheca are ubiquitous saprophytes causing infections in immunocompromised patients and granulomatous mastitis in cattle. Few available therapies and the rapid spread of resistant strains worldwide support the need for novel drugs against protothecosis. Host defence antimicrobial peptides inactivate a wide array of pathogens and are a rich source of leads, with the advantage of being largely unaffected by microbial resistance mechanisms. Three structurally diverse bovine peptides [BMAP‐28, Bac5 and lingual antimicrobial peptide (LAP)] have thus been tested for their capacity to inactivate Prototheca spp. In minimum inhibitory concentration (MIC) assays, they were all effective in the micromolar range against clinical mastitis isolates as well as a Prototheca wickerhamii reference strain. BMAP‐28 sterilized Prototheca cultures within 30–60 min at its MIC, induced cell permeabilization with near 100% release of cellular adenosine triphosphate and resulted in extensive surface blebbing and release of intracellular material as observed by scanning electron microscopy. Bac5 and LAP inactivated Prototheca following 3–6 h incubation at fourfold their MIC and did not result in detectable surface damage despite 70–90% killing, suggesting they act via non‐lytic mechanisms. In circular dichroism studies, the conformation of BMAP‐28, but not that of Bac5 or LAP, was affected by interaction with liposomes mimicking algal membranes. Our results indicate that BMAP‐28, Bac5 and LAP kill Prototheca with distinct potencies, killing kinetics, and modes of action and may be appropriate for protothecal mastitis treatment. In addition, the ability of Bac5 and LAP to act via non‐lytic mechanisms may be exploited for the development of target‐selective drugs. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Solution structure by nuclear magnetic resonance of the two lantibiotics 97518 and NAI‐107
Authors: Vasile Francesca , Potenza Donatella , Marsiglia Barbara , Maffioli Sonia , Donadio Stefano
Published: November 2011

Lantibiotics 97518 and NAI‐107, produced by the related genera Planomonospora and Microbispora respectively, are members of a family of nisin‐related compounds. They represent promising compounds to treat infections caused by multiresistant Gram‐positive pathogens. Despite their similar structure and a similar antibacterial spectrum, the two lantibiotics exhibit significant differences in their potency. To gain an insight into the structure–activity relationships, their conformational properties in solution are determined by NMR. After carrying out an NOE analysis of 2D 1H NMR spectra, high‐resolution 3D structures are determined using molecular dynamics simulations. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
In Vivo Fate Mapping Identifies Mesenchymal Progenitor Cells
Authors: Grcevic Danka , Pejda Slavica , Matthews Brya G. , Repic Dario , Wang Liping , Li Haitao , Kronenberg Mark S. , Jiang Xi , Maye Peter , Adams Douglas J. , Rowe David W. , Aguila Hector L. , Kalajzic Ivo
Published: November 2011

Adult mesenchymal progenitor cells have enormous potential for use in regenerative medicine. However, the true identity of the progenitors in vivo and their progeny has not been precisely defined. We hypothesize that cells expressing a smooth muscle α-actin promoter (αSMA)-directed Cre transgene represent mesenchymal progenitors of adult bone tissue. By combining complementary colors in combination with transgenes activating at mature stages of the lineage, we characterized the phenotype and confirmed the ability of isolated αSMA+ cells to progress from a progenitor to fully mature state. In vivo lineage tracing experiments using a new bone formation model confirmed the osteogenic phenotype of αSMA+ cells. In vitro analysis of the in vivo-labeled SMA9+ cells supported their differentiation potential into mesenchymal lineages. Using a fracture-healing model, αSMA9+ cells served as a pool of fibrocartilage and skeletal progenitors. Confirmation of the transition of αSMA9+ progenitor cells to mature osteoblasts during fracture healing was assessed by activation of bone-specific Col2.3emd transgene. Our findings provide a novel in vivo identification of defined population of mesenchymal progenitor cells with active role in bone remodeling and regeneration.

Disclosure of potential conflicts of interest is found at the end of this article.
HOXB4 Can Enhance the Differentiation of Embryonic Stem Cells by Modulating the Hematopoietic Niche
Authors: Jackson Melany , Axton Richard A. , Taylor A. Helen , Wilson Julie A. , Gordon-Keylock Sabrina A.M. , Kokkaliaris Konstantinos D. , Brickman Joshua M. , Schulz Herbert , Hummel Oliver , Hubner Norbert , Forrester Lesley M.
Published: November 2011

Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells (HPCs) where it promotes self-renewal, but it is also expressed in the primitive streak of the gastrulating embryo. This led us to hypothesize that HOXB4 might modulate gene expression in prehematopoietic mesoderm and that this property might contribute to its prohematopoietic effect in differentiating ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ERT2) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an increase in the expression of genes associated with paraxial mesoderm that gives rise to the hematopoietic niche. Therefore, we considered that HOXB4 might modulate the formation of the hematopoietic niche as well as the production of hematopoietic cells per se. Cell mixing experiments supported this hypothesis demonstrating that HOXB4 activation can generate a paracrine as well as a cell autonomous effect on hematopoietic differentiation. We provide evidence to demonstrate that this activity is partly mediated by the secreted protein FRZB.

Disclosure of potential conflicts of interest is found at the end of this article.
Human Neural Stem Cell Tropism to Metastatic Breast Cancer
Authors: Zhao Donghong , Najbauer Joseph , Annala Alexander J. , Garcia Elizabeth , Metz Marianne Z. , Gutova Margarita , Polewski Monika D. , Gilchrist Megan , Glackin Carlotta A. , Kim Seung U. , Aboody Karen S.
Published: November 2011

Metastasis to multiple organs is the primary cause of mortality in breast cancer patients. The poor prognosis for patients with metastatic breast cancer and toxic side effects of currently available treatments necessitate the development of effective tumor-selective therapies. Neural stem cells (NSCs) possess inherent tumor tropic properties that enable them to overcome many obstacles of drug delivery that limit effective chemotherapy strategies for breast cancer. We report that increased NSC tropism to breast tumor cell lines is strongly correlated with the invasiveness of cancer cells. Interleukin 6 (IL-6) was identified as a major cytokine mediating NSC tropism to invasive breast cancer cells. We show for the first time in a preclinical mouse model of metastatic human breast cancer that NSCs preferentially target tumor metastases in multiple organs, including liver, lung, lymph nodes, and femur, versus the primary intramammary fat pad tumor. For proof-of-concept of stem cell-mediated breast cancer therapy, NSCs were genetically modified to secrete rabbit carboxylesterase (rCE), an enzyme that activates the CPT-11 prodrug to SN-38, a potent topoisomerase I inhibitor, to effect tumor-localized chemotherapy. In vitro data demonstrate that exposure of breast cancer cells to conditioned media from rCE-secreting NSCs (NSC.rCE) increased their sensitivity to CPT-11 by 200-fold. In vivo, treatment of tumor-bearing mice with NSC.rCE cells in combination with CPT-11 resulted in reduction of metastatic tumor burden in lung and lymph nodes. These data suggest that NSC-mediated enzyme/prodrug therapy may be more effective and less toxic than currently available chemotherapy strategies for breast cancer metastases.

Disclosure of potential conflicts of interest is found at the end of this article.
Assessment of smart traffic handling scheme in multimode multiband cellular network
Authors: Sheikh Muhammad Usman , Lempiäinen Jukka
Published: November 2011

The aim of this paper is to analyze the impact of smart traffic handling scheme in managing the radio resources among the different layers of multimode multiband radio network. The impact of two different traffic handling schemes on loading of GSM900/1800 layers along with Universal Mobile Telecommunications System (UMTS) 900/2100 layers was observed. Interference margin is introduced in the UMTS link budget as a system parameter that will account for systems degradation. One of the targets of this massive simulation campaign was to observe the impact of smart traffic handling scheme on interference margin. Network performance was analyzed with different interference factors. Results presented in this paper show that 1–2.5 dB of interference margin can be reduced for UMTS coverage layer and that 5–22% of UMTS capacity layer utilization can be improved. Significant improvement in speech blocking probability was observed because of optimized load balancing among the layers. UMTS base station power was effectively used by restraining the speech users from using the power resources of UMTS layers. Finally, the simulation results revealed the importance of deploying UMTS900 in a multilayer network. The suggested traffic handling scheme is compact and intelligent scheme, and it is based on distance of the user from the base station and required service type. Copyright © 2011 John Wiley & Sons, Ltd.