bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneously hypertensive and Wistar Kyoto rats differ in delayed matching‐to‐place performance and response to dietary long‐chain polyunsaturated fatty acids
Authors: Clements Koreen M. , Girard Todd A. , Xing Hua‐Cheng , Wainwright Patricia E.
Published: June 2003

Spontaneously hypertensive rats (SHR) were used as an animal model of attention deficit hyperactivity disorder (ADHD). This study investigated whether, in comparison with its progenitor strain, Wistar‐Kyoto rats (WKY), SHR would show deficits in spatial short‐term memory in the delayed‐matching‐to‐place (DMP) version of the Morris water maze and be more distracted by exposure to a novel stimulus during recall trials. It also addressed whether dietary supplementation with long‐chain polyunsaturated fatty acids (LCPUFA) during development would increase brain docosahexaenoic acid (DHA) and improve SHR behavioral performance. Beginning at weaning (21 days), male SHR and WKY were fed either a control or LCPUFA supplemented diet [0.5% arachidonic acid (AA) and 0.9% DHA], and behavioral testing began at 8 weeks. The first three tasks comprised a series of problems, each consisting of an initial search trial and subsequent recall trials. The intertrial interval (ITI) between the search and recall trial was either 60 s or 60 min. Surprisingly, in contrast to SHR, WKY did not appear to use a spatial short‐term memory strategy to solve the problem. Notwithstanding, the performance of both strains was affected by the delay, such that they showed longer path lengths at the long compared with the short ITI. There was no effect of dietary supplementation on DMP performance. SHR fed the control diet were less responsive to a novel stimulus introduced on the first recall trial than WKY, and this tended to increase with supplementation. Analysis of brain fatty acid composition indicated that supplementation did increase DHA in the phosphatidylethanolamine fraction in WKY; however, in SHR, there was either no change (phosphatidylethanolamine) or paradoxical decreases (phosphatidylcholine and phosphatidyserine/phosphatidylinositol). Further research is needed to determine whether SHR are an appropriate model for studying a possible relationship between dietary LCPUFA and the behavioral symptoms of ADHD. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 57–69, 2003.
Comparative performance evaluations of IGBTs and MCT incorporated into voltage‐source‐type single‐ended quasi‐resonant zero‐voltage soft switching inverter
Authors: Terai Haruo , Hirota Izuo , Miyauchi Takahiro , Omori Hideki , Ogura Koki , Nakaoka Mutsuo
Published: May 2003

A cost‐effective high‐efficiency, simple, low‐noise voltage‐source‐type single‐ended quasi‐resonant high‐frequency inverter using a single power semiconductor switching device and its modified circuit topologies are commonly applied to consumer induction‐heated rice cookers with a warmer function, cooking heaters, and microwave ovens. This paper presents some comparative performance evaluations of several generations of IGBTs and MCT (MOS Controlled Thyristor) incorporated into the typical voltage‐source quasi‐resonant inverter operating in zero‐voltage soft switching transition mode. The latest generation of IGBT upgraded by lowering the saturation voltage characteristics was designed for consumer power applications in order to reduce conduction losses. The comparative steady‐state characteristics of some simple power semiconductor switching devices of several generations of IGBTs are examined on the basis of the simplest single‐ended quasi‐resonant inverter circuit operating under the zero‐voltage soft switching commutating principle. In addition, the power losses and temperature performance analysis of the latest IGBT are discussed and evaluated relative to previously developed IGBTs. Finally, the further reduced saturation voltage and conduction loss characteristics of MCT which are more suitable for consumer utilizations are presented in comparison with the conventional IGBT. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 58–68, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10151
A damping of rotor natural vibration in three‐phase hybrid stepping motors
Authors: Ogasawara Satoshi
Published: May 2003

This paper proposes a damping method of rotor natural vibration in three‐phase hybrid stepping motors, in which optimal commutation signals are calculated from the period of the natural vibration measured by detecting the motor voltages. Moreover, an acceleration and deceleration pattern is derived from a simple model of the rotor vibration, to suppress undesirable transient oscillation in acceleration, deceleration, and positioning operations. An experimental drive system has been implemented and tested to confirm the effectiveness and versatility of the proposed method. Some experimental results show that the experimental system can damp the rotor natural vibration even if the rotor inertia varies. Compared with the conventional pattern, it is confirmed that the proposed pattern makes a great contribution to damping the undesirable transient oscillations. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 69–77, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10153
High‐efficiency and low‐acoustic‐noise drive system using an open‐winding AC motor and two space vector modulated inverters
Authors: Kawabata Yoshitaka , Nasu Motoshi , Kawabata Takao
Published: May 2003

The combining of the outputs of two inverters using interphase reactors is a widely used method for supplying large AC drives rated at more than several thousand kilowatts. Certain drawbacks are associated with this method, such as high acoustic noise and high losses due to the interphase reactors. To overcome this problem, in this paper a new low‐acoustic‐noise and high‐efficiency drive system using an open‐winding AC motor and two space vector modulated inverters is proposed. This configuration consists of a three‐level inverter with switching once per cycle and a two‐level inverter of about 1 kHz switching frequency, connected to the opposite terminals of the open‐winding motor. With the proposed configuration, good current waveforms and high efficiency can be obtained. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 46–57, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10157
Photo‐excited photonic characteristics of ZnO thin films deposited by laser ablation method
Authors: Ohshima Tamiko , Ikegami Tomoaki , Ebihara Kenji , Thareja Raj Kumar
Published: May 2003

Zinc oxide (ZnO), having a wide direct band gap of 3.37 eV at room temperature, may be a new potential candidate for optoelectronic devices such as ultraviolet (UV) laser, blue light‐emitting diode, and phosphorescent display. We have studied the ZnO thin films deposited by the pulsed laser ablation (PLA) method. In order to prepare high‐quality ZnO thin films, the spectroscopic properties of the plasma plume produced during film deposition were investigated to correlate the properties of the deposited film with plasma characteristics. Furthermore, we have deposited the ZnO thin films at various deposition conditions such as ambient oxygen gas pressure, substrate material, and substrate temperature. We have investigated the effect of deposition conditions on structural and optical properties of the ZnO thin films. X‐ray diffraction, atomic force microscopy, UV–visible photometry, and photoluminescence measurements were used to characterize the grown films. The ZnO thin films deposited at ambient oxygen gas pressure of 5 mTorr and substrate temperature of 550 °C showed strong c‐axis (002) orientation. The ZnO thin film deposited on Al2O3 (0001) at these deposition conditions provided the UV‐stimulated emission around 395 nm. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 1–7, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10177
Contributions of generators for power flow and loads in a power system
Authors: Inuzuka Toshiyasu , Uriu Yoshihisa , Koyanagi Fumiko
Published: May 2003

Because of the introduction of deregulation and competition in the electricity supply industry, large numbers of IPPs (Independent Power Producers) will get into the market. It has become much more important to be able to determine which generators are supplying a particular load, which generator is responsible for transmission line congestion, and what is each generator's contribution to the system losses. In this paper, we propose a way to calculate these contributions automatically. The applicability of the proposed technique is demonstrated using the EAST 10 47‐bus power system. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 28–35, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10181
A study of a unit commitment problem with transmission constraints
Authors: Sasaki Hiroshi , Yamamoto Tomoki , Kubokawa Junji , Nagata Takeshi , Fujita Hideki
Published: May 2003

Unit commitment problem is an optimization problem to determine the start‐up and shut‐down schedule of thermal units while satisfying various constraints, for example, generation‐demand balance, unit minimum up/down time, system reserve, and so on. Since this problem involves a large number of 0–1 type variables that represent up/down status of the unit and continuous variables expressing generation output, it is a difficult combinatorial optimization problem to solve. The study at present concerns the method for requiring the suboptimum solution efficiently.

Unit commitment method widely used solves the problem without consideration of voltage, reactive power, and transmission constraints. In this paper, we will propose a solution of unit commitment with voltage and transmission constraints, based on the unit decommitment procedure (UDP) method, heuristic method, and optimal power flow (OPF). In this method, initial unit status will be determined from random numbers and the feasibility will be checked for minimum start‐up/shut‐down time and demand‐generation balance. If the solution is infeasible, the initial solution will be regenerated until a feasible solution can be found. Next, OPF is applied for each time period with the temporary unit status. Then, the units that have less contribution to the cost are detected and will be shut down based on the unit decommitment rules. This process will be repeated until suboptimal solution is obtained.

The proposed method has been applied to the IEEE 118‐bus test system with 36 generating units with successful result. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 36–45, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10187
A model for numerical evaluation of the global stability region in power systems determined by a nonlinear limit cycle
Authors: Watanabe Masayuki , Miao Peiyun , Mitani Yasunori , Tsuji Kiichiro
Published: May 2003

A power system is a large dynamic system, which includes many nonlinear elements. According to the nonlinear analyses using Hopf bifurcation theory, it can be detected that a limit cycle exists around an operating point, which may affect the global stability of a power system significantly. The authors have presented a numerical method to analyze the nonlinear characteristics in power systems by observing the power swing after some perturbation where the coefficients of nonlinear terms are determined by the least squares method. In this paper the method is modified for the application to a longitudinally interconnected power system including an excitation system, and the influence of the excitation voltage limiter on the nonlinear phenomena of the whole power system can be detected by some numerical analyses. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 17–27, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10193
Internal voltage gradient and behavior of column on long‐gap DC free arc
Authors: Tanaka Shin‐Ichi , Sunabe Kin‐Ya , Goda Yutaka
Published: May 2003

The internal voltage gradient and behavior of column on long‐gap DC free arcs were analyzed quantitatively. In the analysis, an image processing technique developed by us was applied to the images shot from two orthogonal views by two high‐speed video cameras to estimate the three‐dimensional arc column paths. Objective free arcs were ignited between the rod electrodes with the current in the range of 100 to 2000A and the gap in the range of 1.6 to 3.2 m. In addition, some of the objective free arcs were placed in the external magnetic field brought about by a large coil. As a result, macroscopic changes with time in terms of the arc voltage gradient along the column path, the ratio of the arc column length to the gap length, and the distance from the center axis between the electrodes to the farthest point were derived. All average characteristics were shown as the experimental equations. In addition, the effect of the external magnetic field on the macroscopic velocity of the expansion was studied. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(3): 8–16, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10198
The indications and outcomes in the use of osteocutaneous radial forearm free flap
Authors: Villaret Douglas B. , Futran Neal A.
Published: May 2003

Introduction.

Whether secondary to cancer surgery ablation or trauma, surgeons are faced with defects of the mandible or maxilla that would be best reconstructed with a thin, pliable soft tissue component and vascularized bone. A subset of these challenging wounds do not require the bicortical bone necessary to reestablish structural integrity or to retain a dental prosthesis, because the soft tissue needs are more critical than the bony needs. It is this niche that the radial forearm osteofaciocutaneous free flap (RFOFF) fulfills well. In the past, potential and real donor site morbidity has precluded the routine use of this flap. New methods to reduce this morbidity have rekindled our use of this flap.

Procedures Used.

A retrospective review of patients with defects of the mandible or maxilla treated with the RFOFF from July 1, 1997, to December 31, 2000, was performed. After flap harvest, the donor site was rigidly fixated. A skin graft was placed, and a volar splint was applied for 7 days. The arm was then fully mobilized. Parameters examined were defect location, donor site complications, flap survival, fistula occurrence, plate fracture, and/or extrusion.

Results.

Thirty‐four patients were reconstructed with the RFOFF with a follow‐up of 10–54 months. Seven patients had an anterior maxillectomy defect, and 27 patients had a lateral mandibulectomy defect with associated tongue/tonsillar fossa and/or palate defect. There were no cases of flap failure or donor site radius fracture. During the follow‐up period, there were no plate fractures or intraoral exposures as evidenced by clinical and radiographic evaluation. Fistulas occurred in five patients; all healed without surgical intervention.

Conclusion.

With rigid fixation of the residual radius, donor site morbidity has been minimized, and indications for this flap have expanded. Specifically the anterior maxillary arch and the ascending ramus, angle, and posterior body of the mandible (nontooth‐bearing areas) are the sites most amenable to the thin bony stock of the harvested radius. The pliable forearm skin is ideal for the soft tissue defects. We believe that the RFOFF with bone has a definite role in the reconstruction of select head and neck defects. © 2003 Wiley Periodicals, Inc. Head Neck 25: 475–481, 2003
Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: The significance of extracapsular spread and soft tissue deposits
Authors: Jose Jemy , Coatesworth Andrew P. , Johnston Colin , MacLennan Ken
Published: May 2003

Background.

Literature regarding the prognostic significance of extracapsular spread and soft tissue deposits in cervical lymph node metastases of squamous cell carcinoma of the upper aerodigestive tract shows variable results.

Methods.

We analyzed 215 prospectively collected neck dissections from 155 patients with upper aerodigestive tract squamous cell carcinoma to assess the prevalence of extracapsular spread and soft tissue deposits and to assess their effect on survival.

Results.

Both extracapsular spread and soft tissue deposits significantly reduced survival (actuarial and recurrence free) compared with pN0 necks (p < .001) and pN+ve necks without extracapsular spread (p < .0025). There was no statistically significant difference between pN+ve necks without soft tissue deposits or extracapsular spread compared with those with pN0 necks (p = .24). Multivariate analysis revealed comparable results.

Conclusions.

Microscopic and macroscopic extracapsular spread and soft tissue deposits are of prognostic significance for survival and recurrence‐free survival in patients with upper aerodigestive tract squamous cell carcinoma. © 2003 Wiley Periodicals, Inc. Head Neck 25: 451–456, 2003
Effect of irradiation on vestibular evoked myogenic potentials in nasopharyngeal carcinoma survivors
Authors: Wu Chen‐Chi , Young Yi‐Ho , Ko Jenq‐Yuh
Published: May 2003

Background.

This study aims to investigate the effect of irradiation on vestibular evoked myogenic potentials (VEMPs) in nasopharyngeal carcinoma (NPC) survivors, because radiotherapy to NPC covers a column from the basal skull to the clavicle level.

Methods.

Twenty‐two irradiated NPC survivors and five fresh NPC patients were subjected to VEMP testing, which is evoked by short‐tone burst (95 dBHL, 500 Hz) stimulation. Interactions among VEMPs and radiation effects, such as radiation dosage, postirradiation interval, radiation‐induced otitis media, sensorineural hearing loss, or canal paresis, were then explored.

Results.

The mean latencies of p13 and n23 in irradiated ears were significantly delayed compared with either pr‐irradiated ears or normal control ears. Delayed VEMPs represented 50% in ears with a mean radiation dosage of 71 Gy, whereas it represented 100% in those with a mean radiation dosage of 123 Gy. Ears with radiation otitis media revealed higher occurrence (65%) of delayed VEMPs than those without radiation otitis media (29%, p < .05), possibly because of radiation sequela affecting the brainstem and neck. However, delayed VEMPs were unrelated to sensorineural hearing loss or canal paresis caused by irradiation.

Conclusions.

Delayed VEMPs in NPC survivors are possibly due to radiation‐induced otitis media, a brainstem lesion, or neck fibrosis. Hence, VEMP testing may expand the test battery for clinicians to explore balance problems in NPC survivors after irradiation. © 2003 Wiley Periodicals, Inc. Head Neck 25: 482–487, 2003
Identification of NY‐ESO‐1, MAGE‐1, and MAGE‐3 in head and neck squamous cell carcinoma
Authors: Kienstra Matthew A. , Neel H. Bryan , Strome Scott E. , Roche Patrick
Published: May 2003

Background.

Certain tumor antigens have been identified that stimulate an immune response, thus making them targets for immunotherapy. NY‐ESO‐1, MAGE‐1, and MAGE‐3 are such antigens. This study was undertaken to determine their presence or absence in head and neck squamous cell cancers and to correlate this with patient characteristics.

Methods.

Reverse transcriptase polymerase chain reaction (RT‐PCR) and immunohistochemistry (IH) were used to identify NY‐ESO‐1, MAGE‐1, and MAGE‐3 in surgical specimens. Patient data (previous treatment, gender, age, primary site, metastasis, tumor grade, tumor stage, smoking history, and alcohol history) were collected by chart review and examined for correlation with presence or absence of antigen.

Results.

Three tumors were found to be positive for NY‐ESO‐1 by RT‐PCR. All of these tumors were also positive for MAGE‐1 and MAGE‐3. IH was only positive for NY‐ESO‐1 in one patient. Eighteen of the 45 tumors (40%) were positive for MAGE‐1 by RT‐PCR. By IH, only six tumors were positive for MAGE‐1. Five (83.3%) of those that were positive by IH were positive by RT‐PCR. Twenty of the 45 tumors (44.4%) were positive for MAGE‐3 by RT‐PCR. By IH, 12 tumors were positive for MAGE‐3. Nine (75%) of those positive by IH were also positive by RT‐PCR. Overall, of the 45 tumors, 27 (60%) were positive by RT‐PCR for at least one of the antigens. None of the patient characteristics correlated with the presence or absence of antigen.

Conclusions.

There is high expression of MAGE‐1 and MAGE‐3 antigens in head and neck squamous cell carcinomas, whereas NY‐ESO‐1 is not significantly expressed. IH correlates but is not as sensitive as RT‐PCR for detection of these antigens. There is no correlation between antigen expression and patient data. On the basis of the high levels of MAGE‐1 and MAGE‐3 expression, use of these antigens may serve as a potential approach to immunotherapy for squamous cell carcinoma from head and neck sources. © 2003 Wiley Periodicals, Inc. Head Neck 25: 457–463, 2003
Outpatient weekly 24‐hour infusional adjuvant chemotherapy of cisplatin, 5‐fluorouracil, and leucovorin for high‐risk nasopharyngeal carcinoma
Authors: Lin Jin‐Ching , Jan Jian‐Sheng , Chen Kuang Y. , Hsu Chen‐Yi , Liang Wen‐Miin , Wang Wen‐Yi
Published: May 2003

Background.

Distant metastasis rather than locoregional recurrence is the major site of failure after adequate radiotherapy in nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the toxicity and survival of outpatient weekly 24‐hour infusion adjuvant chemotherapy for NPC patients with high‐risk of distant failure.

Methods.

Our definition of high‐risk NPC included patients with (1) 1992 AJCC staging system of N3, T4N2, or N2 with one of nodal size > 4 cm; (2) supraclavicular node metastasis; and (3) residual disease after radiotherapy or neck relapse. From August 1994 to August 1997, 41 NPC patients matching the preceding criteria agreed to receive weekly PFL (cisplatin 25 mg/m2, 5‐fluorouracil 1250 mg/m2, and leucovorin 120 mg/m2) adjuvant chemotherapy for a total of 18 weeks. Clinical data of another 88 patients with similar disease status who did not receive adjuvant chemotherapy during the same period were collected and analyzed for comparison. Survival analysis was investigated by the Kaplan‐Meier method and the Cox proportional hazards model.

Results.

A total of 700 weekly chemotherapy doses was delivered to 41 patients. The ratio of actual/planned dose delivery was 94.9%. Grade 3–4 toxicity of adjuvant chemotherapy included leucopenia (7.3%), anemia (2.4%), thrombocytopenia (2.4%), and nausea/vomiting (2.4%). After a median follow‐up of 70 months, 26.8% (11 of 41) and 47.7% (42 of 88) of patients in PFL and no adjuvant chemotherapy groups had distant metastasis (p = .0247). The 5‐year metastasis‐free survival rates were 71.9% for the PFL group compared with 48.4% for no adjuvant chemotherapy patients (p = .0187). The 5‐year overall survival rates were 53.7% (PFL group) and 38.3% (no adjuvant chemotherapy group), respectively (p = .0666). Multivariate Cox analysis showed PFL adjuvant chemotherapy was the independent factor that predicted metastasis‐free survival after adjustment for other variables.

Conclusions.

Outpatient weekly 24‐hour continuous infusion PFL adjuvant chemotherapy is a well‐tolerated regimen with promising results in high‐risk NPC patients and merits investigation in phase III studies. © 2003 Wiley Periodicals, Inc. Head Neck 25: 438–450, 2003
Xerostomia: 12‐Month changes in saliva production and its relationship to perception and performance of swallow function, oral intake, and diet after chemoradiation
Authors: Logemann Jeri A. , Pauloski Barbara Roa , Rademaker Alfred W. , Lazarus Cathy L. , Mittal Bharat , Gaziano Joy , Stachowiak Linda , MacCracken Ellen , Newman Lisa A.
Published: May 2003

Background.

Previous investigators have found permanent changes in saliva production after chemoradiation but have not examined these in relation to swallowing measures, diet changes, and patient comfort over time.

Methods.

Thirty patients with advanced stage cancer of the oropharynx treated with chemoradiation were followed with videofluoroscopic swallow studies, a measure of stimulated total saliva production, a questionnaire of their perception of dry mouth, and a questionnaire on the nature of their oral intake at pretreatment until 12 months after treatment.

Results.

Saliva declined significantly from pretreatment to 12 months. Swallowing‐related complaints increased significantly over the 12 months, especially in patients with lower saliva weights. Diet choices increased over time after treatment, except crunchy foods. Swallow measures did not relate to saliva weight.

Conclusions.

Reduced saliva weight does not correlate with slowed or inefficient swallow. Instead, reduced saliva weight seems to change patients' perceptions of their swallowing ability and, on that basis, their diet choices. © 2003 Wiley Periodicals, Inc. Head Neck 25: 432–437, 2003
Malignant peripheral primitive neuroectodermal tumor‐peripheral neuroepithelioma of the head and neck: A clinicopathologic study of five cases and review of the literature
Authors: Nikitakis Nikolaos G. , Salama Andrew R. , O'Malley Bert W. , Ord Robert A. , Papadimitriou John C.
Published: May 2003

Background.

The term primitive neuroectodermal tumor (PNET) encompasses a number of neoplasms of common neuroectodermal origin, but of variable clinical, histopathologic, ultrastructural, and molecular characteristics. Here, we focus on one particular member of the PNET family, the malignant peripheral PNET (pPNET) or peripheral neuroepithelioma of head and neck.

Methods.

Five patients diagnosed with malignant pPNET–peripheral neuroepithelioma of head and neck were included in the study. All existing literature was reviewed.

Results.

The diagnosis of malignant pPNET–peripheral neuroepithelioma of the head and neck was confirmed in all five cases. All patients are alive after treatment with a combination of therapeutic modalities; only one patient had metastatic disease develop. A literature review revealed another 38 reported cases.

Conclusions.

Malignant pPNET–peripheral neuroepithelioma should be included in the differential diagnosis of small, round, blue cell tumors of head and neck. A combination of multiple diagnostic modalities is essential for correct diagnosis, and multimodality treatment offers the best outcome. © 2003 Wiley Periodicals, Inc. Head Neck 25: 488–498, 2003
Efficacy of radiation therapy in the local control of desmoplastic malignant melanoma
Authors: Vongtama Roy , Safa Afshin , Gallardo David , Calcaterra Thomas , Juillard Guy
Published: May 2003

Background.

Desmoplastic malignant melanoma (DMM) is a rare variant of malignant melanoma with high local recurrence rate after surgical excision. We performed a retrospective review to address the role of radiation therapy in local control of this tumor.

Methods.

Between 1976 and 1997, 44 patients with the pathologic diagnosis of DMM were registered at our tumor registry. Fourteen patients received postoperative RT, and one patient received preoperative RT. Three of the irradiated lesions had gross residual or positive surgical margins. Doses ranged from 44 to 66 Gy.

Results.

Sixty‐eight percent of DMM lesions occurred in the head and neck region. Forty‐eight percent (21 of 44) of patients experienced a local recurrence after initial excision (mean time to recurrence, 12 months). Local failure in head and neck was 46% (14 of 30). Clark level, primary site, and neurotropism did not predict local recurrence; the Clark level predicted distant metastasis. No viable tumor was found in the surgical specimen of the patient who received preoperative RT. None of 15 patients who received adjuvant irradiation had any additional recurrences (mean follow‐up, 64.7 months). By contrast, four of seven patients with history of recurrence who did not receive RT had local relapse (p = .005). The incidence of distant metastasis did not reach statistical significance between the irradiated and nonirradiated groups.

Conclusions.

The high rate of local recurrence of DMM after surgical resection is dramatically reduced by adjuvant radiation therapy. We recommend adjuvant postoperative radiation therapy as a part of treatment of DMM. © 2003 Wiley Periodicals, Inc. Head Neck 25: 423–428, 2003
Pentopyranosyl Oligonucleotide Systems. Communication No. 13
Authors: Jungmann Oliver , Beier Markus , Luther Anatol , Huynh Hoan K. , Ebert Marc‐Olivier , Jaun Bernhard , Krishnamurthy Ramanarayanan , Eschenmoser Albert
Published: June 2003

Among the members of a family of diastereoisomeric pentopyranosyl‐(4′→2′)‐oligonucleotide systems derived from D‐ribose, D‐xylose, L‐lyxose, and L‐arabinose, the α‐arabinopyranosyl system shows by far the strongest WatsonCrick base pairing. The system is, in fact, one of the strongest oligonucleotide‐type base‐pairing systems known. It undergoes efficient cross‐pairing with all the other members of the pentopyranosyl family, but not with RNA and DNA. The paper describes the synthesis and pairing of the properties of α‐L‐arabinopyranosyl‐(4′→2′)‐oligonucleotides.
Copper‐Binding Motifs: Structural and Theoretical Aspects
Authors: Kaufman Katz Amy , Shimoni‐Livny Liat , Navon Oshrit , Navon Nadav , Bock Charles W. , Glusker Jenny P.
Published: June 2003

In this paper, we report the results of a study involving the coordination geometries of CuI, CuII, and CuIII crystal structures in the Cambridge Structural Database, and on Cu binding sites in proteins taken from the Protein Data Bank. The motifs used to bind two bridged Cu ions are also described. In addition, we report the results of ab initio molecular‐orbital calculations performed on a variety of model CuI/CuII complexes (CuI/CuII⋅XnYm (X, Y=NH3, SH2); n+m=4; n=0–4) to provide data on the structural and energetic changes that occur in isolated complexes when the oxidation state of the Cu ion is changed from II to I while the coordination number is conserved. The use of such simple ligands in these calculations eliminates constraints on the geometric changes that may be imposed by more‐complicated ligands.
Dilemmas in Crystallization. The ‘Unusual' Behavior of trans‐1,5‐Dichloro‐9,10‐diethynyl‐9,10‐dihydroanthracene‐9,10‐diol and the More ‘Normal' Behavior of Its Pseudopolymorphs with Dipolar Aprotic Solvents
Authors: Banerjee Rahul , Desiraju Gautam R. , Mondal Raju , Batsanov Andrei S. , Broder Charlotte K. , Howard Judith A. K.
Published: June 2003

The compound trans‐1,5‐dichloro‐9,10‐diethynyl‐9,10‐dihydroanthracene‐9,10‐diol (DDDA) has an inversion center as the only molecular symmetry element and yet does not occupy an inversion center in the centrosymmetric space group that it adopts in the crystal structure. The reason for this very unusual occurrence is the crowded environment of the H‐bond donors and acceptors that leads to less than optimal H‐bonding. A centrosymmetric supramolecular synthon constituted with four Cl‐atoms in a planar array occupies an i site in the crystal, and this appears to provide a satisfactory alternative packing. Based on the hypothesis that H‐bonding is less than optimal in the crystal structure of DDDA, pseudopolymorphs were prepared with strongly H‐bond‐accepting solvents. The crystal structures of five of these solvates are described, wherein the DDDA molecule is able to occupy an i site and form strong and linear OH ⋅⋅⋅O H‐bonds with the solvent molecules. Competition experiments show that a smaller solvent molecule with a greater H‐bond‐accepting ability is included more readily and that the H‐bonds formed are correspondingly better.
Crystalline‐State Photoreaction of 1‐Azido‐2‐nitrobenzene – Direct Observation of Heterocycle Formation by X‐Ray Crystallography
Authors: Takayama Terufumi , Kawano Masaki , Uekusa Hidehiro , Ohashi Yuji , Sugawara Tadashi
Published: June 2003

The crystalline‐state photoreaction of 1‐azido‐2‐nitrobenzene (1) was investigated by a combination of X‐ray crystallography, IR spectroscopy, electron‐spin resonance (ESR), and by means of theoretical calculations. Upon low‐temperature (80 K) photolysis of 1, the formation of benzofuroxan (2) was directly observed by X‐ray single‐crystal analysis. ESR Measurements at 5 K suggested the presence of a triplet nitrene as an intermediate in the formation of the heterocycle. Temperature‐dependent IR spectroscopy also revealed that another intermediate, trans,trans‐1,2‐dinitrosobenzene, was produced at temperatures below 80 K.
Chiral Heterospirocyclic 2H‐Azirin‐3‐amines as Synthons for 3‐Amino‐2,3,4,5‐tetrahydrofuran‐3‐carboxylic Acid and Their Use in Peptide Synthesis
Authors: Stamm Simon , Linden Anthony , Heimgartner Heinz
Published: June 2003

The heterospirocyclic N‐methyl‐N‐phenyl‐5‐oxa‐1‐azaspiro[2.4]hept‐1‐e n‐2‐amine (6) and N‐(5‐oxa‐1‐azaspiro[2.4]hept‐1‐en‐2‐yl)‐(S)‐proline methyl ester (7) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10, respectively, by consecutive treatment with COCl2, 1,4‐diazabicyclo[2.2.2]octane, and NaN3 (Schemes 1 and 2). The reaction of these 2H‐azirin‐3‐amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14, and the diastereoisomeric mixtures of the N‐benzoyl dipeptides 15 and 16, respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid‐state conformations of all six benzamides were determined by X‐ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis, the reactions of 7 with Z‐Leu‐Aib‐OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z‐Ala‐OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H‐bond in 17. The dipeptides (S,R)‐18 and (S,S)‐18 were deprotected at the N‐terminus and were converted to the crystalline derivatives (S,R)‐19 and (S,S)‐19, respectively, by reaction with 4‐bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (S,R)‐18 and (S,S)‐18 gave the dipeptide acids (R,S)‐20 and (S,S)‐20, respectively. Coupling of a diastereoisomeric mixture of 20 with H‐Phe‐OtBu led to the tripeptides 21 (Scheme 5). X‐Ray crystal‐structure determinations of (S,R)‐19 and (S,S)‐19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series.
Enantioselective Synthesis of Key Intermediates in a Novel Approach towards the Iboga‐Alkaloid Family
Authors: Höck Stefan , Borschberg Hans‐Jürg
Published: June 2003

Significant improvements in the realm of a recently disclosed, novel synthetic concept towards the Iboga alkaloid family are presented. The key step for the construction of the bicyclic aliphatic core consists of an intramolecular nitroneolefin 1,3‐dipolar cycloaddition reaction of a 1 : 1 mixture 15/16 yielding the two diastereoisomeric tricyclic isoxazolidine derivatives 17 and 18. The required nitrones were prepared from the readily available (S)‐hydroxylactone 6 in twelve steps with an overall yield of 15% (average: 83.5% per step). The relative configuration of the minor isomer was deduced unambiguously by single‐crystal X‐ray analysis of the derived tricyclic carbamate 21. As four out of five asymmetric centers in the pair 17/18 have opposite configuration, destruction of the one possessing the same absolute configuration transforms the original set of diastereoisomers into a pair of enantiomers. We verified this contention by oxidizing the two alcohols 20 and 22 to yield the two antipodal forms of ketone 23. The absence of significant amounts of by‐product and the high reproducibility of the crucial cycloaddition reaction represent marked improvements over our earlier attempts. In addition, the new route, which starts from L‐glutamate, should provide access to both naturally occurring antipodal series of the targeted alkaloid class.
The Yellow Polymorphs of Mercuric Iodide (HgI2)
Authors: Hostettler Marc , Birkedal Henrik , Schwarzenbach Dieter
Published: June 2003

HgI2 crystallizes under ambient conditions from various solvents and by sublimation into three concomitant polymorphs whose colors are red, orange, and yellow. The orange and yellow phases are metastable and transform into the red phase when touched. A phase transition from red to yellow occurs at 400 K. The reverse transition from yellow to red shows a huge hysteresis. We established that the structures of the metastable yellowM phase (determined by single‐crystal X‐ray diffraction) and the high‐temperature yellowHT phase (determined by powder synchrotron X‐ray diffraction and second‐harmonic generation) are different, albeit closely related. Both show analogous packings of IHgI molecules, which are straight in the first and bent with an angle of ca. 160° in the second. The red and orange phases are tetrahedral semiconductor structures that sublime even at room temperature. The growth of the yellowM phase from 2‐chloroethanol and the kinetics of the reconstructive phase transition red to yellowHT and back were studied by optical microscopy, Raman spectroscopy in solution, luminescence, and powder synchrotron X‐ray diffraction as a function of time at various temperatures. Both yellow phases grow by accretion of HgI2 molecules, present in the solution or liberated from the red crystals, on the surface of the crystal. In contrast, the reverse transformation from yellow to red occurs in the bulk of the crystal, presumably by migration of Hg in the packing of I and subsequent rearrangement of I. The displacement parameters of Hg in both structures are considerably larger than those of I and apparently not dominated by disorder effects.
Chiral Amplification of Oligopeptides in the Polymerization of α‐Amino Acid N‐Carboxyanhydrides in Water
Authors: Hitz Thomas , Luisi Pier Luigi
Published: June 2003

This article is concerned with the chiral amplification of oligopeptides formed in the polymerization of chiral, nonracemic mixtures of the N‐carboxyanhydride (NCA) of Leu and Glu in aqueous solution. Labeling (deuteration) of one enantiomer and reversed‐phase and normal‐phase high‐performance liquid chromatography mass spectrometry (RP‐ and NP‐HPLC/MS, respectively) were used to determine the product distribution, both with respect to oligopeptide chain length and stereoisomer distribution. Starting the polymerization with an enantiomeric excess (ee) of 20% of the L‐enantiomer (L‐amino acid/D‐amino acid 6 : 4) leads to an ee of 73% at the level of the homochiral enantiomeric (Leu)5, and of 71% at the level of the homochiral enantiomeric (Glu)7. For the Leu system and in the presence of a solid support (quartz), the ee reached values of up to 100%. We argue that such amplification processes could be relevant for the chemical evolution towards single‐handedness.
From Hit to Lead: De Novo Design Based on Virtual Screening Hits of Inhibitors of tRNA‐Guanine Transglycosylase, a Putative Target of Shigellosis Therapy
Authors: Brenk Ruth , Gerber Hans‐Dieter , Kittendorf Jeffrey D. , Garcia George A. , Reuter Klaus , Klebe Gerhard
Published: June 2003

Shigellosis, a bacterial disease, causes the death of more than one million people per year. Extensive studies of Shigella flexneri have recognized tRNA‐guanine transglycosylase (TGT, EC 2.4.2.29) as one of the key enzymes involved in the regulation of bacterial virulence. Based on the crystal structure of the Zymomonas mobilis enzyme, we have embarked on the rational design of TGT inhibitors. Herein, we describe the structure‐based optimization of hits previously found by virtual screening (see Tables 1–3). For the pteridines, the most potent compound class discovered in a previous virtual screening run, a versatile synthesis could be established giving access to a broad range of substituted derivatives (see Scheme 5). The best ligand in this series, 14, exhibits a Ki=0.45 μM.
Reduction‐Labile Organo‐cob(III)alamins via Cob(II)alamin: Efficient Synthesis and Solution and Crystal Structures of [(Methoxycarbonyl)methyl]cob(III)alamin
Authors: Puchberger Michael , Konrat Robert , Kräutler Bernhard , Wagner Ulrike , Kratky Christoph
Published: June 2003

An efficient synthesis of Coβ‐[(methoxycarbonyl)methyl]cob(III)alamin (6) is reported as an example of a new method for the preparation of some easily reducible organo‐cob(III)alamins via the alkylation of cob(II)alamin. The procedure represents a considerable improvement compared to earlier methods that were based on an alkylation of cob(I)alamin. Thus, aquacob(III)alamin chloride (5+⋅Cl) was reduced to cob(II)alamin (4), either by controlled potential electrolytic reduction or with an excess of sodium formate as reducing agent. The solution of 4 was then treated with an excess of methyl bromoacetate while being reductively poised potentiostatically or kept reduced by the formate, to give crystalline 6 in a yield of up to 91%. The structure of 6 in aqueous solution was mainly established by the completely assigned 1H‐ and 13CNMR spectra (Table 1). The NOE data (Table 2) were best rationalized by the presence of a single main conformation of the (methoxycarbonyl)methyl ligand. Single crystals of 6 were obtained by crystallization from an aqueous solution, and the crystal structure was determined by X‐ray analysis at cryotemperatures. The NMR and crystallographic data of 6 indicated similar structures in aqueous solution and in the crystal with the (methoxycarbonyl)methyl ligand preferring a ‘southern' orientation in each case.
Structural Aspects of the β‐Polymorph of (E)‐4‐Formylcinnamic Acid: Structure Determination Directly from Powder Diffraction Data and Elucidation of Structural Disorder from Solid‐State NMR
Authors: Meejoo Siwaporn , Kariuki Benson M. , Kitchin Simon J. , Cheung Eugene Y. , Albesa‐Jové David , Harris Kenneth D. M.
Published: June 2003

Among the derivatives of (E)‐cinnamic acid for which the solid‐state photochemical properties have been studied, (E)‐4‐formylcinnamic acid (1) has already received much attention. Given the inability to prepare single crystals of the β‐polymorph of 1 that are of suitable size and quality for structural characterization by single‐crystal X‐ray diffraction, the structure of this material was determined directly from powder X‐ray‐diffraction data by means of the genetic‐algorithm technique for structure solution, followed by Rietveld refinement. High‐resolution solid‐state 13CNMR was also applied to elucidate details of structural disorder concerning the orientation of the formyl group, and provided independent support for the disorder model established form the Rietveld refinement. The reported structure establishes that the β‐phase of 1 is not structurally anomalous among photoreactive (E)‐cinnamic acid crystals, and finally resolves a long‐standing controversy concerning the structural properties of this material.
Structures of Four Crystal Forms of Decaplanin
Authors: Lehmann Christopher , Debreczeni Judit É. , Bunkóczi Gábor , Dauter Miroslawa , Dauter Zbigniew , Vértesy László , Sheldrick George M.
Published: June 2003

The glycopeptide antibiotic decaplanin (1; formerly known as MM 47761 and M86‐1410) crystallizes in two P21 and two P6122 crystal forms, each with four monomers in the asymmetric unit, with solvent contents varying from 48 to 69%. Although with ca. 600 unique atoms, the structures are larger than typical small molecules, one was solved by direct methods. The other three were solved by typical macromolecular methods: single‐wavelength anomalous diffraction (SAD) of the Cl‐atoms present naturally in the structure, multiple‐wavelength anomalous diffraction (MAD) at the Br absorption edge for a crystal soaked in NaBr solution, and molecular replacement. There is evidence of appreciable radiation damage with loss of 20–30% of the covalent and ionic halogens affecting the synchrotron datasets that may even have unintentionally facilitated the MAD structure solution. The structures contain the dimer units typical of antibiotics related to vancomycin, but, in addition, there are a variety of further intermolecular interactions responsible for the polymorphy leading to intertwined 61‐helices in two of the crystal forms. Except for the sugars and some sidechains, the conformations of the 16 independent monomers are very similar.
Glycosylidene Carbenes. Part 31
Authors: Bernet Bruno , Mangholz Sissi E. , Briner Karin , Vasella Andrea
Published: June 2003

The diastereoselectivity of the addition of NH3 and MeNH2 to glyconolactone oxime sulfonates and the structures of the resulting N‐unsubstituted and N‐methylated glycosylidene diaziridines were

The 15N‐labelled glucono‐ and galactono‐1,5‐lactone oxime mesylates 1* and 9* add NH3 mostly axially (>3 : 1; Scheme 4), while the 15N‐labelled mannono‐1,5‐lactone oxime sulfonate 19* adds NH3 mostly equatorially (9 : 1; Scheme 7). The 15N‐labelled mannono‐1,4‐lactone oxime sulfonate 30* adds NH3 mostly from the exo side (>4 : 1; Scheme 9). The configuration of the N‐methylated pyranosylidene diaziridines 17, 18, 28, and 29 suggests that MeNH2 adds to 1, 9, 19, and 23 mostly to exclusively from the equatorial direction (>7 : 3; Schemes 5 and 8). The mannono‐1,4‐lactone oxime sulfonate 30 adds MeNH2 mostly from the exo side (85 : 15; Scheme 10), while the ribo analogue 37 adds MeNH2 mostly from the endo side (4 : 1; Scheme 10). Analysis of the preferred and of the reactive conformers of the tetrahedral intermediates suggests that the addition of the amine to lactone oxime sulfonates is kinetically controlled. The diastereoselectivity of the diaziridine formation is rationalized as the result of the competing influences of intramolecular H‐bonding during addition of the amines, steric interactions (addition of MeNH2), and the kinetic anomeric effect.

The diaziridines obtained from 2,3,5‐tri‐O‐benzyl‐D‐ribono‐ and ‐D‐arabinono‐1,4‐lactone oxime methanesulfonate (42 and 48; Scheme 11) decomposed readily to mixtures of 1,4‐dihydro‐1,2,4,5‐tetrazines, pentono‐1,4‐lactones, and pentonamides.

The N‐unsubstituted gluco‐ and galactopyranosylidene diaziridines 2, 4, 6, 8, and 10 are mixtures of two trans‐substituted isomers (S/R ca. 19 : 1, Scheme 2). The main, (S,S)‐configured isomers S are stabilised by a weak intramolecular H‐bond from the pseudoaxial NH to ROC(2). The diaziridines 12, derived from GlcNAc, cannot form such a H‐bond; the (R,R)‐isomer dominates (R/S 85 : 15; Scheme 3). The 2,3‐di‐O‐benzyl‐D‐mannopyranosylidene diaziridines 20 and 22 adopt a 4C1 conformation, which does not allow an intramolecular H‐bond; they are nearly 1 : 1 mixtures of R and S diastereoisomers, whereas the OH5 conformation of the 2,3:5,6‐di‐O‐isopropylidene‐D‐mannopyranosylidene diaziridines 24 is compatible with a weak H‐bond from the equatorial NH to OC(2); the (R,R)‐isomer is favoured (R/S ≥7 : 3; Scheme 6). The mannofuranosylidene diaziridine 31 completely prefers the (R,R)‐configuration (Scheme 9).
Crystals and Life
Authors: Arrhenius Gustaf O.
Published: June 2003

The record of life's emergence on Earth has been thoroughly obliterated by the remelting and turnover of the crust, soggy and pliable from the water, retained by the planet's gravitational field. Provided that life existed on a smaller body such as Mars with an arrested crustal evolution, a protected sedimentary record there may give clues to the decisive events in the first 500 million years in the history of our solar system. Until such records become available, we have in our guesswork to rely on laboratory constructions that need to satisfy the demands both of chemical feasibility and environmental boundary conditions. The combination leaves few survivors among competing hypotheses.
As life entails a decrease in entropy and creation of order, the origin and propagation of crystalline order has become a guiding theoretical concept. Recognizing Jack Dunitz's fundamental contribution to this field of knowledge, I wish to dedicate my modest discourse to this great scientist upon his scoring of the fourth significant time mark on the staff of life.