bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term results of reirradiation for patients with recurrent rectal carcinoma
Authors: Mohiuddin Mohammed , Marks Gerald , Marks John
Published: October 2002

BACKGROUND

The current study was conducted to assess the long‐term results of reirradiation in patients with recurrent rectal carcinoma.

METHODS

One hundred and three patients with recurrent adenocarcinoma of the rectum underwent reirradiation with concurrent 5‐fluorouracil–based chemotherapy. The initial radiation dose to the pelvis ranged from 3000 to 7400 centigrays (cGy) with a median dose of 5040 cGy. The median time from initial treatment to recurrence was 19 months. Irradiation techniques consisted of two lateral fields with/without a posterior pelvic field to include recurrent tumor with a margin of 2–4 cm only. The reirradiation doses ranged from 1500 to 4920 cGy with a median dose of 3480 cGy. Total cumulative doses ranged from 7060 to 1080 cGy with a median total dose of 8580 cGy. After the reirradiation, 34 patients also underwent surgical resection for residual disease. Fourteen patients underwent pelvic exenteration, 11 patients underwent abdominoperineal resection, 4 patients underwent transanal transabdominal proctosigmoidectomy, 2 patients underwent full thickness local excision, and 3 patients underwent a Hartmann resection.

RESULTS

Follow‐up ranged from 3 84 months with a median follow‐up of 2 years. The median survival for the whole group was 26 months and the 5‐year actuarial survival rate was 19%. The median interval and 5‐year survival rate of patients undergoing surgical resection after reirradiation was 44 months and 22% compared with 14 months and 15% for patients treated with reirradiation only (P = 0.001). Treatment was generally well tolerated. Fifteen patients required a treatment break and early termination of treatment for Grade 3 and higher diarrhea, moist desquamation, or mucositis. Late complications were seen in 22 patients, including persistent severe diarrhea in 18 patients with 10 patients requiring long‐term parental support, small bowel obstruction was seen in 15 patients, fistula formation in 4 patients, and coloanal stricture in 2 patients. There was no difference in incidence of acute or long‐term complications by the total radiation dose delivered.

CONCLUSIONS

In patients with recurrent rectal carcinoma, high doses of reirradiation can be delivered with acceptable risks without prohibitive long‐term side effects. Surgical salvage and long‐term survival of patients are possible. Cancer 2002;95:1144–50. © 2002 American Cancer Society.

DOI 10.1002/cncr.10799
Hantaviruses in Estonia
Authors: Golovljova Irina , Brus Sjölander Katarina , Lindegren Gunnel , Vene Sirkka , Vasilenko Veera , Plyusnin Alexander , Lundkvist Åke
Published: October 2002

Human serum samples collected from healthy individuals in 14 counties were screened by ELISA in order to investigate the presence of hantavirus infections in Estonia. Out of 1,234 serum samples, 124 were found positive for hantavirus‐specific IgG and were subsequently serotyped by a focus reduction neutralization test. A total of 112 samples neutralized at least one of the examined hantaviruses—Puumala (PUUV), Saaremaa (SAAV), Dobrava (DOBV), Hantaan, and Seoul viruses—and thereby, the focus reduction neutralization test confirmed the overall hantavirus seroprevalence rate in Estonia to be 9.1%. Most of the sera showed a specific reaction (at least 4‐fold higher endpoint titer) of neutralizing antibodies to PUUV (5.1%), while 3.4% showed a SAAV‐ or SAAV/DOBV‐specific reaction. The fact that seven sera (0.6%) could not be serotyped may indicate the presence of an unknown hantavirus serotype. Hantavirus infections were confirmed in 13 of 14 investigated counties, with highly varying seroprevalence rates (1.0–28.4%). The sex ratio was 1.8:1.0 (M:F), and the antibody prevalence peaked in the age group 45–54 years. A total of 513 rodents of seven species trapped in seven counties were examined for the presence of hantavirus antigen, in order to study the distribution of hantavirus natural carriers. Two species, Clethrionomys glareolus and Apodemus agrarius, were found positive for hantaviral antigen in 13.7% and 4.5% of the investigated rodents, respectively. Analyses of viral sequences recovered from infected C. glareolus tissue samples showed that the infecting virus belonged to the PUUV genotype, confirming that PUUV circulates in mainland Estonia. The Estonian PUUV strains were placed in the closest proximity to Russian PUUV strains in phylogenetic trees, suggesting a common evolutionary history. Together with earlier data on SAAV in A. agrarius, the results revealed that two hantaviruses, PUUV and SAAV, are common in Estonia and that the incidence of human infection is high in both cases. J. Med. Virol. 68:589–598, 2002. © 2002 Wiley‐Liss, Inc.
Complete nucleotide sequence of a Coxsackievirus B‐4 strain capable of establishing persistent infection in human pancreatic islet cells: Effects on insulin release, proinsulin synthesis, and cell morphology
Authors: Yin Hong , Berg Anna‐Karin , Westman Jan , Hellerström Claes , Frisk Gun
Published: October 2002

The aim of the present investigation was to study the effect of infection of human pancreatic islet cells with a strain (VD2921) of Coxsackie B virus serotype 4 capable of establishing persistent infection in these cells, as well as to sequence the strain, to study the determinants of virulence and persistence. Groups of islets were infected and assessments of proinsulin, insulin content, and virus replication were made. Insulin release in response to high glucose was measured. Infected and control islets displayed a strong insulin response to high glucose 3–4 days as well as 7–8 days post‐infection (dpi). At 11–17 dpi, the infected islets did not respond at all to high glucose, and the response of the control islets was at this late time point somewhat reduced. The insulin and proinsulin content of the infected islets did not differ significantly from that of the control islets. TCID50 titrations showed that the VD2921 strain replicated in the islet cells during the whole study. Electron microscopic examination of infected islets did not reveal any virus‐induced changes of cell morphology compared with the controls, although higher magnifications of the infected β‐cells showed virus‐like particles in the cytoplasm. These results show that certain strains of Coxsackievirus B‐4 in vitro can establish a persistent infection that might mimic, the more gradual loss of β‐cell function seen during the clinical course of autoimmune diabetes. The ability of this Coxsackievirus B‐4 strain to establish a persistent infection might be due to substitution of 11 amino acids located at the surface of the structural protein VP1, adjacent to the predicted receptor binding canyon of the virus. J. Med. Virol. 68:544–557, 2002. © 2002 Wiley‐Liss, Inc.
Recombinant hepatitis C virus‐like particles expressed by baculovirus: Utility in cell‐binding and antibody detection assays
Authors: Xiang Jinhua , Wünschmann Sabina , George Sarah L. , Klinzman Donna , Schmidt Warren N. , LaBrecque Douglas R. , Stapleton Jack T.
Published: October 2002

Hepatitis C virus (HCV) is difficult to study due to the lack of an efficient cell culture system or small animal model. As a result, HCV–cell interactions are not well‐defined. In addition, several studies have identified a subset of patients in whom HCV RNA is present, but HCV antibody is not detected. We produced recombinant baculoviruses that expressed HCV structural proteins (core, E1 and E2, nt 342–2651) or control proteins. The HCV structural protein precursor was processed into immunoreactive proteins of appropriate size, and sucrose density sedimentation and electron microscopy of infected cell lysates demonstrated particle formation. To evaluate HCV antigenicity, particularly in patients who tested negative for HCV antibody in commercial HCV immunoassays but had persistent viremia, we evaluated the virus‐like particles (VLPs) in solid‐phase immunoassays. VLPs reacted with sera from HCV antibody positive subjects in these solid phase immunoassays, but not with control sera. Plasma samples from 19% (5/26) of HCV antibody negative subjects who were persistently HCV RNA positive also reacted with the HCV VLPs. When incubated with MOLT‐4 cells at 4°C, HCV VLPs demonstrated cell binding, and behaved similar to plasma‐derived HCV preparations in a flow cytometry‐based cell binding assay. These data suggest that recombinant HCV VLPs may allow identification of HCV antibody in patients, including some patients with persistent viremia and who are seronegative with current assays. In addition, HCV VLPs seem useful for evaluating HCV–cell interactions. J. Med. Virol. 68:537–543, 2002. © 2002 Wiley‐Liss, Inc.
Disialoganglioside GD2 and a novel tumor antigen: Potential targets for immunotherapy of desmoplastic small round cell tumor
Authors: Modak Shakeel , Gerald William , Cheung Nai‐Kong V.
Published: October 2002

Background

Desmoplastic small round cell tumor (DSRCT) is an aggressive and often misdiagnosed neoplasm of children and young adults. It is chemotherapy‐sensitive, yet patients often relapse off therapy because of residual microscopic disease at distant sites: peritoneum, liver, lymph node, and lung. Strategies directed at minimal residual disease (MRD) may be necessary for cure. Monoclonal antibodies selective for cell surface tumor‐associated antigens may have utility for diagnosis and therapy of MRD, as recently demonstrated in advanced‐stage neuroblastoma (JCO 16: 3053, 1998). We examined DSRCT samples for the expression of two tumor antigens that could serve as possible targets for antibody‐based immunotherapeutic approaches.

Procedures

Using immunohistochemistry, we studied the expression of two antigens: (1) GD2 using antibody 3F8 and (2) a novel antigen using antibody 8H9 in a panel of 46 freshly frozen DSRCT. GD2 is a disialoganglioside, which is widely expressed among neuroectodermal tumors as well as adult sarcomas. 8H9 recognizes a 58 kDa surface antigen expressed among neuroectodermal, mesenchymal, and epithelial tumors with restricted expression on normal tissues.

Results

Thirty‐two of 46 (70%) tumors were reactive with 3F8, and 44 of 46 (96%) with 8H9. Both GD2 and the 58 kDa antigen were localized to tumor cell membrane and stroma. In general, immunoreactivity was stronger and more homogeneous with 8H9 than with 3F8. There was no correlation between expression of either antigen or clinical outcome.

Conclusions

GD2 and the novel tumor antigen recognized by 8H9 are potential targets for immunodiagnosis and antibody‐based therapy of DSRCT. Med Pediatr Oncol 2002;39:547–551. © 2002 Wiley‐Liss, Inc.
Response to initial treatment of multisystem langerhans cell histiocytosis: An important prognostic indicator
Authors: Minkov Milen , Grois Nicole , Heitger Andreas , Pötschger Ulrike , Westermeier T. , Gadner Helmut ,   for the DAL‐HX Study Group
Published: October 2002

Background

Reliable prediction of prognosis allowing risk‐adapted therapy remains a major issue in the management of multisystem Langerhans cell histiocytosis (LCH). In a recent publication of the International LCH Study Group, response to initial therapy appears to be a reliable outcome predictor. The aim of this study is to test this observation in a cohort of patients treated with more intensive initial therapy. Furthermore, we compare the predictive value of response to initial therapy to some other well‐established stratification systems.

Procedure

Response to initial combination chemotherapy (prednisolone, vinblastine, and etoposide) at 6 weeks and its prognostic value was evaluated retrospectively in 63 patients with multisystem LCH from the DAL‐HX 83 and 90 Studies, and correlated to some established scoring systems from the literature.

Results

After 6 weeks of therapy, 50/63 (79%) patients qualified as responders, 4/63 (7%) patients showed intermediate response, and 9/63 (14%) patients did not respond. Probability of survival at 5 years was 0.94 ± 0.03 for responders, 0.75 ± 0.22 for patients with intermediate response, and only 0.11 ± 0.10 for non‐responders.

Conclusions

Response to initial therapy appears to be a reliable prognostic predictor. Compared to the published international LCH‐I Study, our results suggest that more intensive initial treatment allows a better discrimination between responders and non‐responders. This allows to identify a subgroup of patients with extremely poor prognosis (mortality rate 90%) relatively early in the disease course. Med Pediatr Oncol 2002;39:581–585. © 2002 Wiley‐Liss, Inc.
Four case studies of prospective science teachers' beliefs concerning constructivist teaching practices
Authors: Haney Jodi J. , McArthur Julia
Published: October 2002

To gain a better understanding of the emerging constructivist beliefs and classroom practices, case studies were constructed for four prospective teachers who were purposely selected as a result of their scores on the Classroom Learning Environment Survey (CLES) (Taylor, Fraser, & White, A classroom environment questionnaire for science educators interested in the constructivist reform of school science. Paper presented at the annual meeting of the National Association for Research in Science Teaching, Anaheim, CA, 1994). The case studies provided insight into two primary questions (1) what are the beliefs of the prospective science teacher regarding constructivist teaching practices and (2) are these beliefs consistent with subsequent classroom practice? The components of constructivist teaching by Taylor, Fraser, and White (1994) were used as a theoretical framework in conjunction with Ajzen and Fishbein's components of the Theory of Planned Behavior (Ajzen, 1985). Data collection consisted of document analysis, classroom observation, and interviews. Data were analyzed using the constant comparative method. Findings from the case studies suggest that at least two kinds of beliefs were in operation: central beliefs and peripheral beliefs. The central beliefs were defined as those dictating subsequent teaching behaviors; whereas the peripheral beliefs were those that were stated but not operationalized. © 2002 Wiley Periodicals, Inc. Sci Ed 86:783–802, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10038
Research in Operations Management
Authors: Buffa Elwood S.
Published: October 2002

The field of Operations Management has evolved from a purely descriptive origin through the Management Science/Operations Research phase, and is now in the process of finding itself as a functional field of management. Emerging with this identity and at last founding the Journal of Operations Management, researchers need to give careful thought concerning the future directions of research. Research during the MS/OR phase made great progress, but is characterized by the development of models of problems of restricted scope, the results of which could be evaluated by a single valued criterion. The most promising future research is felt to be embodied in projects that are of broader managerial scope, reflecting relationships between subsystems and interfunctional effects. Evaluative criteria should reflect the multiple criteria realities of the managerial world. Types of research that appear to be in keeping with the new thrust of Operations Management are suggested.
Some problems with transient phenomena when simulating unpaced lines
Authors: Kottas John F. , Lau Hon‐Shiang
Published: October 2002

Unlike earlier simulation studies of unpaced production lines which generally concentrated on steady‐state behavior, we are concerned with their transient characteristics. This paper (1) presents an approach for studying and monitoring transient behavior, (2) reports some important transient operating characteristics previously overlooked, and (3) demonstrates that the conflicting results reported in some of the earlier simulation studies are due to an inadequate accounting for transient behavior. Thus, this paper illustrates the importance of having a better understanding of transient behavior in unpaced lines, and presents our initial steps towards dealing with it.
The service sector: Challenges and imperatives for research in operations management
Authors: Sullivan Robert S.
Published: October 2002

The United States has undergone a transformation from an industrial society to the first postindustrial society. Consequently, the service sector has outstripped manufacturing in its contribution to the GNP and in employment. This paper discusses the challenges and imperatives for research in service operations management (SOM). Service operations have unique characteristics that must be considered in developing research strategies. Recent attempts at evolving a general theory of service organizations are reviewed, and it is suggested that these conceptual models provide a unifying framework for the study of SOM. Research in SOM requires a broad perspective that includes the customer and the interactions with other functional areas. It requires an integration of conventional production concepts with behavioral and marketing considerations.
An experimental comparison of human schedulers and heuristic algorithms for the traveling salesman problem
Authors: Hill Arthur V.
Published: October 2002

Vehicle routing and scheduling for laundry, courier, mail, and other service operations is a significant service industry problem. Several computer‐based heuristic algorithms have been developed to assist schedulers in developing efficient delivery (and pick up) vehicle routes. This paper reports the results of an experiment that compared the performance of inexperienced human schedulers and seven heuristic vehicle routing algorithms. A large set of traveling salesman test problems ranging in size from 10 to 80 customers was used in the experiment. The results of the experiment suggest that inexperienced, untrained human schedulers can consistently find traveling salesman solutions as good as or better than all but one of the seven heuristic algorithms tested (including the widely used ClarkeWright distance saved heuristic and the recently published largest‐angle insertion heuristic). The human schedulers found traveling salesman routes as good as the best heuristic tested (Lin's 3‐optimal) in 29 percent of the test problems. On average, the human schedulers' solution distances were only 2.8 percent above the 3‐optimal heuristic solution distances.
Currently practiced formulations for the assembly line balance problem
Authors: Gunther Richard E , Johnson Gordon D , Peterson Roger S
Published: October 2002

New formulations for the assembly line balance problem are proposed based on interviews and surveys of practicing engineers. These formulations are the basis for a model in goal programming form. A branch‐and‐bound algorithm is developed which can solve the model for an optimum solution. Computational studies show that computer run time is very modest for moderate size problems.

Interviews and a survey of practicing engineers were used to develop a list of goals or constraints germane to the assembly line balance problem. These included minimizing working areas or employees, making sure tasks assigned to a station do not exceed the cycle time, and adhering to sequence constraints. These constraints are included in most traditional models. However, additional goals were mentioned. These included avoiding changes in workload assigned to a work area, adhering to layout requirements of the plant, making combinations of tasks interesting, avoiding the combination of physiologically demanding tasks, etc.

The additional goals above are incorporated in a new formulation for the assembly line balance problem. This formulation is in goal programming form. The goal programming model attempts to minimize deviations from goals. If deviations are necessary, lowest ranked goals are violated first. The objective function of the model is based on an ordinal ranking of goals only. The survey mentioned above showed that engineers did not find it difficult to rank the importance of goals.

The proposed goal programming model is a mixed integer linear program. Previous studies have shown that cutting plane and implicit enumeration techniques are inferior to branch‐and‐bound algorithms. A branch‐and‐bound method, called GoalOriented Algorithm for Line Balance (GOAL), is developed to solve the formulations proposed in the paper.

GOAL was computationally tested with 50 problems. These problems varied in size from 4 to 35 tasks. One of the problems was an engine cradle assembly problem encountered by an automobile manufacturer. Computer run times appeared reasonable. For example, the engine cradle problem 35 tasks) required only 16.3 seconds CPU on the DEC PDF 11/70 at California State University, Northridge. GOAL's execution time appeared linearly proportional to the number of tasks required for most problems.
A simulation analysis of due date assignment rules
Authors: Ragatz Gary L. , Mabert Vincent A.
Published: October 2002

In the job shop scheduling literature, due dates, when considered, are treated in one of two ways: 1) externally imposed or 2) internally set. Externally imposed due dates are outside the control of the scheduler and are assumed to be set by an order entry or marketing department in agreement with the customer. In this situation, current shop status information is not normally considered in setting the date. Research in this setting has focused on the identification of those priority (dispatching) rules which yield good “due date performance.” Due date performance is usually measured by job lateness, job tardiness, and/or proportion of jobs tardy.

Internally set due dates are established by the scheduler as each job arrives. Using job characteristics and/or shop status information, the scheduler estimates the job flow time for each job and sets the due date accordingly. The early research in this setting did not focus explicitly on predicting individual job flow times, but rather on identifying simple due date assignment heuristics which provide good due date performance in concert with a variety of priority rules. More recent researchers have included shop status information in setting due dates.

This article reports on a study of eight different rules for specifying due dates in a job shop and the evaluation of their performance. A series of tests is conducted with a computer simulation model utilizing three different dispatching rules to control the sequencing of work. Mean tardiness, mean absolute missed due dates, and standard deviation of lateness data are collected to measure each rule's performance. This study reports the first comparative analysis of various due date assignment rules that have been mentioned in the literature by different authors.

The findings reported here provide some useful insight into past and future research. First, both job characteristic and shop status information should be used to develop due date assignment rules. Second, the dispatching rule used to sequence jobs at work centers influences shop performance. Third, information about work center congestion along a job's routing is more useful information than general shop conditions. And fourth, the use of more detailed information in predicting flow time provides only marginal improvement in performance over other rules that use more aggregate information.
A dispute on James R. Evans' “an efficient implementation of the Wagner Whitin algorithm for dynamic lot‐sizing,” journal of operations management, vol. 5, no. 2, February 1985
Authors: Chong Philip S.
Published: October 2002

This note disputes several observations made by James R. Evans' article, “An Efficient Implementation of the Wagner‐Whitin (WW) Algorithm for Dynamic Lot‐Sizing,” Journal of Operations Management, Vol. 5, No. 2, February 1985. By testing the algorithm within a micro‐based manufacturing resource planning (MRP) system, the writer of this note shows that WW is still computationally burdensome compared to heuristic methods, particularly within the context of a micro‐based MRP system implementation.
Sequencing rules and due date setting procedures in flow line cells with family setups
Authors: Russell Gregory R. , Philipoom Patrick R.
Published: October 2002

The purpose of this study is to investigate due date setting procedures and dispatching decisions in a flow line cell with family setups. In this environment, setups are not required when switching from a job in a given family to a job in the same family. However, switching from a job in one family to a job in another family requires a setup. Family setups in this shop are sequence independent. The dispatching decisions in this shop are threefold: (1) when should the decision to switch from one part family to another be made; (2) once the decision to switch families is made, how should the next part family be chosen (next family decision); and (3) how should the jobs within a family be prioritized (next job decision)? If the decision to switch classes can only be made after the current family is exhausted, the rule is called a class exhaustion rule. Otherwise the rule is a truncated rule. The results indicate that the due date setting procedure has a major impact on how dispatching should be performed in the shop. The family exhaustion procedure using the APT next family rule and the SPT next job rule is the best performer for mean flow time. When setup times are long, the SEQ due date rule using the family exhaustion procedure with the FCFS next family and the EDD next job rules performed well for due date criteria. When setup times are short, the EDD/T, Sawicki truncation rule and the family exhaustion rules performed well for due date criteria.
A comparative evaluation of nine well‐known algorithms for solving the cell formation problem in group technology
Authors: Miltenburg John , Zhang Wenjiang
Published: October 2002

Nine algorithms, developed to solve the cell formation problem, are evaluated and compared for their ability to produce good solutions to large problems. A primary performance measure and two secondary performance measures are presented for gauging the quality of a solution to the cell formation problem. Eight problems from the open literature and 60 randomly generated, large problems are analyzed. The analysis shows that there is no solution algorithm that performs better on all performance measures for problems from both the literature and the randomly generated data sets. One algorithm, called the ISNC algorithm and based on clustering around seeds, performs significantly better than all other algorithms on the primary performance measure (and performs well on the secondary measures) for the randomly generated data set, and performs well for the problems from the literature. Therefore this algorithm appears to the most appropriate algorithm to use as a general purpose solution algorithm for CF problems having between 25 and 50 machines, 35 and 50 parts, and densities between 10 and 20%. (It may not be appropriate for larger problems, since its computational and space requirements appear to be high.) After the ISNC algorithm, there is no significant difference between most of the other algorithms. However. different kinds of solutions are developed by some of these other algorithms. The well‐known SC/ROC and ROC/ROC algorithms develop solutions which consist of a small number of relatively large cells. The BEA algorithm develops solutions which consist of relatively small cells (where each machine in the cell is visited by most of the parts assigned to that cell) and one large cell for those parts not assigned to the small cells.
A tool cluster based strategy for the management of cutting tools in flexible manufacturing systems
Authors: De Souza R.B.R. , Bell R.
Published: October 2002

The management of tooling systems in cell‐based flexible manufacturing systems is described. The use of cluster analysis in the management of cutting tools is presented. The role and functioning of a cluster based tool management strategy is described with respect to the management of the cutting tools, scheduling of the work flow and the number of captive tools. The research findings are described and supported by an example. A Rank Order Clustering (ROC) algorithm was used, selected for its simplicity and rapid implementation, to cluster tools. The ROC algorithm is applied to cluster tools. These clusters are scheduled on work stations based on part (the primary priority) and cluster (secondary) priority management rules. This provides the dynamics of managing the change of tool clusters as well as providing for the case where resident tool clusters are desired. A spreadsheet‐based computer assisted tool clustering model, intended for industrial usage, is described. The clustering model reduces the requirement for robust advance schedule generation and encourages the adoption of smaller tool magazine capacities. The cluster based model advances beyond just tool kitting to provide rapid on‐line generation of tooling configurations where part mix and production ratios may be varied almost instantaneously on a spreadsheet and where rigidity in scheduling may be relaxed by allowing a tool cluster to attract any part in the cluster set. The paper concludes with a brief description of on‐going research effort in applying cluster analysis to cell tool management.
A thermosensitive mutant of HRV2 2A proteinase: evidence for direct cleavage of eIF4GI and eIF4GII
Authors: Liebig Hans-Dieter , Seipelt Joachim , Vassilieva Elena , Gradi Alessandra , Kuechler Ernst
Published: October 2002

Infection of mammalian cells with picornaviruses like entero‐, rhino‐, and aphthoviruses leads to an inhibition of cap‐dependent cellular protein synthesis by the cleavage of both translation initiation factors, eIF4GI and eIF4GII. In entero‐ and rhinovirus infection this cleavage process is mediated by the viral 2A proteinase (2Apro). In order to discriminate between a direct mode of eIF4G cleavage and an indirect cleavage via activation of a cellular proteinase, a thermosensitive 2Apro mutant (ts‐2Apro) of human rhinovirus 2 was employed. Temperature shift experiments of cytoplasmic HeLa cell extracts incubated with ts‐2Apro strongly support a direct mode of cleavage of eIF4GI and eIF4GII by the viral 2Apro.
Mutation of the RGD sequence does not affect plasma membrane association and growth inhibitory effects of elevated IGFBP‐2 in vivo
Authors: Hoeflich A. , Reisinger R. , Vargas G.A. , Elmlinger M.W. , Schuett B. , Jehle P.M. , Renner-Müller I. , Lahm H. , Russo V.C. , Wolf E.
Published: October 2002

Using insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) transgenic mice (D mice) as a model of elevated IGFBP‐2 expression, which is often found in unphysiological conditions, we found association of IGFBP‐2 to purified plasma membranes of many organs. To determine whether the RGD (Arg‐Gly‐Asp) motif of IGFBP‐2 mediates cell surface binding in vivo, we mutated the RGD motif of IGFBP‐2 into an RGE (Arg‐Gly‐Glu) sequence and produced transgenic mice (E mice) which express elevated amounts of mutated IGFBP‐2. Our data demonstrate that in vivo IGFBP‐2 cell surface association is not dependent on the RGD motif and that mutation of this sequence does not alter growth inhibitory effects of IGFBP‐2.
Interaction of hnRNP‐C1/C2 proteins with RNA: analysis using the yeast three‐hybrid system
Authors: Koloteva-Levine Nadejda , Amichay Maya , Elroy-Stein Orna
Published: October 2002

Three‐hybrid assays for the analysis of RNA–protein interactions in vivo are usually used, due to technical limitations, only for RNA baits that do not contain runs of four or more consecutive uridines. The present study provides the first example of a three‐hybrid analysis of synthetic and natural uridine‐rich RNA sequences. The use of the three‐hybrid assay enabled us to demonstrate a functional difference between two closely related proteins, heterogeneous nuclear ribonucleoprotein C1 (hnRNP‐C1) and hnRNP‐C2. The hnRNP‐C2 protein, an alternatively spliced variant of hnRNP‐C1, contains an additional 13 amino acids between an RNA binding domain (RBD) and a basic leucine zipper‐like motif (bZLM), also implied in RNA binding. This study shows that (i) for efficient binding of hnRNP‐C1/C2 to RNA, the context of the U‐stretch is more important than the stretch itself; (ii) both the RBD and the bZLM bind RNA independently; and (iii) the C2‐related 13‐amino acid insert enhances the specificity of either the RBD, the bZLM, or the full‐length protein towards its ligand, allowing it to bind only the most high‐affinity sequences while discriminating against those that do not perfectly match this category. The three‐hybrid system is a powerful tool to work out the functional significance of peptide ‘modules’ within RNA binding proteins generated by alternative splicing.
The 1.62 Å structure of Thermoascus aurantiacus endoglucanase: completing the structural picture of subfamilies in glycoside hydrolase family 5
Authors: Lo Leggio Leila , Larsen Sine
Published: October 2002

The crystal structure of Thermoascus aurantiacus endoglucanase (Cel5A), a family 5 glycoside hydrolase, has been determined to 1.62 Å resolution by multiple isomorphous replacement with anomalous scattering. It is the first report of a structure in the subfamily to which Cel5A belongs. Cel5A consists solely of a catalytic module with compact eight‐fold β/α barrel architecture. The length of the tryptophan‐rich substrate binding groove suggests the presence of substrate binding subsites −4 to +3. Structural comparison shows that two glycines are completely conserved in the family, in addition to the two catalytic glutamates and six other conserved residues previously identified. Gly 44 in particular is part of a type IV C‐terminal helix capping motif, whose disruption is likely to affect the position of an essential conserved arginine. One aromatic residue (Trp 170 in Cel5A), not conserved in term of sequence, is nonetheless spatially conserved in the substrate binding groove. Its role might be to force the bend that occurs in the polysaccharide chain on binding, thus favoring substrate distortion at subsite −1.
Functional selectivity for glycerol of the nodulin 26 subfamily of plant membrane intrinsic proteins
Authors: Wallace Ian S , Wills David M , Guenther James F , Roberts Daniel M
Published: October 2002

The nodulin‐like intrinsic protein (NIP) subfamily of water and solute channels in plants is named for nodulin 26 of legume nodules. Two NIPs, soybean nodulin 26 and Lotus japonicus LIMP2, show a distinct functional profile with a low intrinsic osmotic water permeability (P
f) and the ability to flux uncharged polyols such as glycerol. NIPs have a conserved signature sequence within the ‘aromatic/arginine’ region that forms the selectivity filter for major intrinsic proteins. This sequence is a hybrid of glyceroporin and aquaporin residues as well as exhibiting substitutions unique to the NIP subfamily. Site‐directed mutagenesis of a conserved tryptophan in helix 2 of LIMP2 shows that this is a major determinant of glycerol selectivity.
Autocatalytic processing of recombinant human procathepsin B is a bimolecular process
Authors: Rozman Jerica , Stojan Jure , Kuhelj Robert , Turk Vito , Turk Boris
Published: October 2002

Cathepsin B and other lysosomal cysteine proteinases are synthesized as inactive zymogens, which are converted to their mature forms by other proteases or by autocatalytic processing. Procathepsin B autoactivation was shown in vitro at pH 4.5 to be a bimolecular process with K
s and k
cat values of 2.1±0.9 μM and 0.12±0.02 s−1, respectively. Autoactivation is substantially accelerated in the presence of active cathepsin B molecules, indicating that mature cathepsin B is the catalytic species in the process. Proenzyme is cleaved without significant conformational changes as judged by circular dichroism, suggesting that propeptide unfolding occurs only after the cleavage. Procathepsin B autoactivation is pH‐dependent with a pH optimum at 4.5 and with no processing observed at pH>6.0. However, in the presence of 0.5 μg/ml of dextran sulfate, relatively rapid processing is observed even at pH 6.5 (t
1/2∼90 min), suggesting that glycosaminoglycans are involved in in vivo processing of lysosomal cysteine proteases.
Propagation of a finite-amplitude potential
vorticity front along the wall of a stratified fluid
Authors: STERN MELVIN E. , HELFRICH KARL R.
Published: October 2002

A similarity solution to the long-wave shallow-water equations is obtained for a
density current (reduced gravity = g′, Coriolis parameter = f) propagating alongshore (y = 0). The potential vorticity q = f/H1 is uniform in
−∞ < x [les ] xnose(t),
0 < y [les ] L(x, t), and the nose of this advancing potential vorticity front displaces fluid
of greater q = f/H0, which is located at L < y < ∞. If L0 = L(−∞, t), the nose point
with L(xnose(t), t) = 0 moves with velocity Unose = √g′H0 φ, where φ is a function of
H1/H0, f2L20/g′H0. The assumptions made in the similarity theory are verified by an
initial value solution of the complete reduced-gravity shallow-water equations. The
latter also reveal the new effect of a Kelvin shock wave colliding with a potential
vorticity front, as is confirmed by a laboratory experiment. Also confirmed is the
expansion wave structure of the intrusion, but the observed values of Unose are only
in qualitative agreement; the difference is attributed to the presence of small-scale
(non-hydrostatic) turbulence in the laboratory experiment but not in the numerical
solutions.
Ecological groups of estuarine macrobenthic invertebrates in the Baie de Somme (France): changes in time and space
Authors: Ducrotoy J.-P. , Ibanez F.
Published: October 2002

This work is an interpretation of a chronological data set on abundances of estuarine soft substrate invertebrates using an ecological approach. The data were collected in the framework of the European programme COST 647 (Coopération Scientifique et Technique) on coastal benthic ecology which terminated in 1992. Species numbers and selected environmental factors were recorded at two stations in the Baie de Somme (France) from 1981 to 1992. Inter-annual and seasonal variations in benthos numbers were analysed using a plotting procedure based on a non-probabilistic approach, proposed by Andrews in 1972. Ecological groups of species were identified and succession in time described, coinciding with alterations in the landings of cockles Cerastoderma edule. The chronological data set was processed through the application of the cumulated function, giving directly intensity and duration of any changes in relation to the climate and water quality, especially potential eutrophication manifestations.
The match between ocean circulation and zoogeography of epipelagic siphonophores around southern Africa
Authors: Gibbons Mark J. , Thibault-Botha Delphine
Published: October 2002

Published and unpublished records of epipelagic calycophoran siphonophores from around southern Africa were examined for zoogeographic structure. There is a close match between prevailing patterns of surface ocean circulation and zoogeography, which while similar to previous studies of intertidal taxa and euphausiids, is different from them in some key details. Separate subtropical provinces are associated with both the Angola and Agulhas Currents, and the latter system has a marked influence on the composition of (warm-temperate) assemblages along the south coast of South Africa. The nearshore waters in the Benguela upwelling ecosystem (cold temperate) are distinct, but the Lüderitz upwelling cell does not appear to act as an internal boundary within the Benguela ecosystem, as has been previously noted for benthic communities. Species richness is greater in oceanic than coastal waters, and peaks in subtropical waters. High diversity is also noted offshore in the area between Capes Agulhas and Columbine, where water of Indian, Southern and Atlantic Ocean interact. Indicator species for each major water mass were tentatively identified.
Place-name evidence for an Anglo-Saxon
animal name: OE *pohha/*pocca fallow deer’
Authors: Hough Carole
Published: October 2002

It is well known that the extant corpus of Old English literature preserves only a
proportion of the vocabulary that once existed. In some instances, terms for
concepts that must have been familiar to the Anglo-Saxons have been lost
without trace; in others, they may be reconstructed from non-literary forms of
evidence such as the place-names coined by early settlers in the areas now
known as England and southern Scotland. The main dictionary of place-name
terminology, Smith's English Place-Name Elements of 1956, includes many
entries for words which are otherwise either unattested, or attested only with
other meanings. Animal names in particular constitute an area of vocabulary
which is under-represented in literary sources but common in place-names, and
for which toponymic evidence often proves crucial. Old English animal names
unattested in the extant literature but included in English Place-Name Elements
are *bagga ‘badger’, *bula ‘bull’, *ean ‘lamb’, *gæten ‘kid’, *galt ‘pig, boar’, *græg
‘badger’, *hyrse ‘mare’, *padde ‘toad’, *padduc ‘frog’, *pigga ‘young pig’, *stedda
‘horse’, *tacca and *tagga ‘teg, young sheep’, *tige ‘goat’, *todd ‘fox’ and *wiðer
‘ram, wether’. Those identied more recently include *brun ‘pig’ and *wearg
‘wolf ’. As the English Place-Name Survey progresses, providing detailed
coverage of the country's toponyms in a series of annual volumes inaugurated
in the 1920s, further examples may be expected to come to light. The aim of this
article is to offer a new addition to the corpus.
Initiation, changes in use and effectiveness of highly active anti-retroviral therapy in a cohort of injecting drug users
Authors: EGEA J. M. , MUGA R. , SIRERA G. , CLOTET B. , TOR J. , ARDÈVOL M. , REY-JOLY C. , MUÑOZ A.
Published: October 2002

The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992–6 and 1997–2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2–15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992–6 as the reference category the relative hazard of AIDS during 1997–2000 was 0.42 (95% CI, 0.1–1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58% reduction of the hazard of AIDS.
Impaired Collateral Artery Development in Spontaneously Hypertensive Rats
Authors: TUTTLE JAY L. , SANDERS BRIDGET M. , BURKHART HAROLD M. , FATH STEVEN W. , KERR KIMBERLY A. , WATSON WILLIAM C. , HERRING B. PAUL , DALSING MICHAEL C. , UNTHANK JOSEPH L.
Published: October 2002

Objective: To determine whether collateral artery development is impaired in spontaneously hypertensive (SHR) relative to normotensive (WKY) rats.

Methods: Sequential mesenteric arteries were ligated to create a collateral pathway responsible for the perfusion of approximately 50 first‐order arterioles. Collateral development was assessed by measurement of in vivo arterial diameter before and 1 week after ligation. Histological and morphometric measurements were made from cross‐sectional preparations of these arteries to evaluate intimal and medial cell numbers and medial area. eNOS expression was evaluated with Western blotting.

Results: One week after arterial ligation, collateral diameter was increased more in WKY than SHR both absolutely (137 ± 9.1 versus 99 ± 8.6 µm) and relative to same‐animal controls (38 ± 5.5% versus 13 ± 7.1%). At the time of model creation, blood flow was elevated to comparable levels in both WKY and SHR, and wall shear rate in the SHR collateral was greater than both the SHR control and WKY collateral arteries. Endothelial cell number in arterial cross‐section was increased in collaterals by 80% in WKY and only 22% in the SHR. eNOS expression was increased in the WKY (128%) but not in the SHR collateral.

Conclusions: For equivalent arterial occlusion, the data demonstrate that collateral development is suppressed in the SHR as indicated by luminal expansion. This impairment of luminal expansion is associated with a decreased endothelial proliferation and the lack of an increase in eNOS expression.
Arteriolar Occlusion Causes Independent Cellular Responses in Endothelium and Smooth Muscle
Authors: CHEN YIFAN , RIVERS RICHARD J.
Published: October 2002

Objectives: To test the hypothesis that arteriolar occlusion causes different cellular changes in endothelial and smooth muscle cells.

Methods: Cheek pouch arterioles (resting diameter 41 ± 2 µm) of anesthetized hamsters were occluded briefly (<60 seconds) either upstream or downstream from an observation site. Changes in membrane potential and intracellular calcium concentration ([Ca2+]i) of the endothelial or smooth muscle cells were determined by using fluorescence microscopy (ratiometric analysis).

Results: The pressure in the occluded segment decreased by 17.4 ± 2.6 cm H2O during upstream occlusion and increased by 16.8 ± 6 cm H2O during downstream occlusion (n= 5). Upstream occlusion caused vasoconstriction of the occluded segment by 2.4 ± 0.4 µm, whereas downstream occlusion produced brief vasodilatation by 1.1 ± 0.2 µm. The endothelial cells hyperpolarized during upstream or downstream occlusion (ratio change: 2.26 ± 0.24% and 2.39 ± 0.42%, respectively; p < 0.01, n= 5). There were no changes in endothelial [Ca2+]i. The smooth muscle cells depolarized (ratio change: −2.08 ± 0.14%, n= 5) with an increase in [Ca2+]i (ratio change: 2.92 ± 0.16%, n= 6) during downstream occlusion. However, there was no detectable change in membrane potential or [Ca2+]i of smooth muscle cells during upstream occlusion. All the changes rapidly recovered when occlusion was released. Responses of an in‐situ isolated segment on a side branch revealed conducted dilatory signals caused by the occlusions.

Conclusions: Our results show that the endothelial and smooth muscle cells respond independently to arteriolar occlusion. The endothelial and smooth muscle cells do not effectively communicate in [Ca2+]i or membrane potential during acute arteriolar occlusion. Hyperpolarizing signals in endothelium cause conducted dilation.