bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategy, uncertainty and the focused factory in international process manufacturing
Authors: Ketokivi Mikko , Jokinen Mikko 
Published: February 2005

AbstractThe extant literature on the focused factory has not explored the contingencies associated with the de facto adoption and use of focused factory principles: Why are some plants focused while others are not? Is focus—or unfocus—a strategic choice, best practice or perhaps a reflection of an environmental constraint? In his pioneering work, Skinner [W. Skinner, 1974. The focused factory. Harvard Business Review 52 (3), 113–121] prescribes companies to ensure that the manufacturing task of their manufacturing units is simple and focused, for instance, by assigning a narrow product mix for each factory or concentrating on a narrow mix of production technologies. Especially in the absence of compelling empirical evidence on the effectiveness of the focused factory approach, we argue that we still do not understand why some plants may remain unfocused.We observe that in the international process industry case examined in this paper, some factories are unfocused and their manufacturing tasks are all but simple. Yet, some of them appear to be high performers. This presents an opportunity to seek empirical insight on the questions raised above. Specifically, we examine why manufacturing companies in the process industries may or may not follow the focused factory strategy. Our results suggest that in certain operating environments and with certain competitive strategies, choosing not to focus the manufacturing task should be viewed as a viable alternative manufacturing strategy, perhaps even a constraint imposed by the operating environment. We develop four contingency propositions to explain why focused manufacturing strategy may not be desirable or even possible.
Cardiovascular reactivity and family history of hypertension: A meta‐analysis
Authors: Pierce Thomas W. , Grim Rodney D. , King Joseph S. 
Published: February 2005

AbstractA regression‐based meta‐analysis examined the degree to which the effects of a family history of hypertension on cardiovascular reactivity are moderated by the magnitude of cardiovascular responses elicited in challenge/task conditions. Mean change scores for negative family history groups were regressed on mean change scores for positive family history groups. The slopes of separate regression lines obtained for systolic and diastolic blood pressure and heart rate were significantly less than 1.0 and the y‐intercepts for these regression lines were significantly greater than zero. This pattern indicates that family history differences in cardiovascular reactivity to stress are greatest in situations that elicit the smallest baseline‐stressor change scores in non‐family‐history groups.
Gene expression profile identifies a rare epithelioid variant case of pleomorphic liposarcoma carrying FUS‐CHOP transcript
Authors: De Cecco L , Gariboldi M , Reid J F , Lagonigro M S , Tamborini E , Albertini V , Staurengo S , Pilotti S , Pierotti M A 
Published: February 2005

Aims : To describe a tumour with morphological and immunophenotypic characteristics of epithelioid variant of pleomorphic liposarcoma. Pleomorphic liposarcoma is a very rare variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts showing peculiar epithelial‐like features that can be confused with primary or metastatic carcinoma.Methods and results : Molecular analysis demonstrated for the first time the presence of FUS‐CHOP transcript in this liposarcoma variant. Microarray analysis revealed a gene expression profile related to a more aggressive tumour type when compared with other myxoid/round cell liposarcomas.Conclusions : The present data show that the epithelioid variant of pleomorphic liposarcoma represents a further variant of myxoid liposarcoma sharing the FUS‐CHOP fusion transcript but carrying a distinct expression profile, in keeping with its aggressive clinical course.
Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast
Authors: Carder P J , Garvican J , Haigh I , Liston J C 
Published: February 2005

Aims : To review 21 screen‐detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non‐malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain.Methods and results : Forty‐seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, ‘papillomatosis’ or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either ‘B2’, benign, ‘B3’, of uncertain malignant potential, or ‘B4’, suspicious of malignancy. All of the 19 ‘B3’ or ‘B4’ cases and one of the two ‘B2’ lesions had undergone open surgical biopsy. All cases with a previous ‘B4’ were malignant on subsequent excision. All excised cases with a previous ‘B3’ or ‘B2’ were found benign, although four of the ‘B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size.Conclusion : Our results confirm the accuracy of NCB in the diagnosis of screen‐detected papillary lesions of the breast. Surgical excision may not always be necessary following a ‘B3’ core biopsy.
Association between cyclooxygenase‐2‐expressing macrophages, ulceration and microvessel density in colorectal cancer
Authors: Sheehan K M , Steele C , Sheahan K , O'Grady A , Leader M B , Murray F E , Kay E W 
Published: February 2005

Aim : In colorectal carcinomas, cyclooxygenase‐2 (COX‐2) is expressed predominantly by epithelial cells and is implicated in tumour progression. Tumour‐associated macrophages may influence tumour growth, proliferative rate and angiogenesis and also express COX‐2 when activated. Thus they may play an important stromal‐epithelial role in carcinogenesis. Τhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX‐2 and macrophage COX‐2 expression.Methods and results : Sixty‐five cases of formalin‐fixed paraffin‐embedded colorectal cancer were included in the study. Tissues were immunostained for COX‐2, CD68 (macrophage marker) and CD34 (endothelial marker to assess MVD). Thirty‐six cases were grossly ulcerated cancers and 29 cases showed focal/microscopic ulceration. Macrophages were in high concentration at the base of ulcerated areas, and were also diffusely dispersed within tumoral stroma. However, the pattern of macrophage COX‐2 expression revealed two populations of macrophages—those deep within the tumour (negative for COX‐2) and those at the base of ulcers (positive for COX‐2). In all cases, the tumour epithelial cells expressed COX‐2. MVD was higher at the base of ulcers, adjacent to COX‐2+ macrophages, and was lower deep within the tumour.Conclusions : In colorectal cancers, macrophages may have a dual role. Those concentrated at the base of the ulcers, where there is an associated high MVD, may induce angiogenesis, but their function may be in a healing/repair process. The lack of COX‐2+ macrophages and lower MVD deep within the tumour suggests that it may be the epithelial COX‐2 component that is important in tumour progression.
CD10 and Bcl‐2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large‐cell lymphoma with very good or very poor prognoses
Authors: Biasoli I , Morais J C , Scheliga A , Milito C B , Romano S , Land M , Pulcheri W , Spector N 
Published: February 2005

Aims : Diffuse large B‐cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk‐adaptive strategies.Methods and results : Bcl‐2 and CD10 expression was determined by immunohistochemistry. The impact of the positivity on survival was evaluated in combination with the IPI in 86 patients with a confirmed diagnosis of DLBCL. Patients were divided according to the IPI into low‐risk (no to two factors) or high‐risk (three to five factors) groups. Positivity rates were 25% for CD10 and 42% for Bcl‐2. In a Cox analysis, the high‐risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl‐2 expression (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the low‐risk IPI group, CD10 positivity was associated with an excellent 8‐year overall survival (92% versus 45%, P = 0.06). In the high‐risk IPI group, Bcl‐2 positivity identified a subgroup with invariably fatal disease.Conclusions : The expression of CD10 in the low‐risk IPI group, and the expression of Bcl‐2 in the high‐risk IPI group can identify two subgroups of patients who might benefit from new risk‐adaptive treatment approaches.
Natural killer T‐cell populations in C57BL/6 and NK1.1 congenic BALB.NK mice—a novel thymic subset defined in BALB.NK mice
Authors: Stenström Martin , Sköld Markus , Andersson Åsa , Cardell Susanna L. 
Published: February 2005

SummaryNatural killer (NK) T lymphocytes are a subpopulation of T lymphocytes regarded as early regulators of immune responses. The majority of NKT cells are restricted by the CD1d molecule. NKT cells have mostly been studied in one single mouse strain, C57BL/6 (B6), because of the absence of NK1.1 in other common mouse strains, and the lack of other reliable surface markers for CD1d‐restricted cells. To investigate NKT cell subsets in a mouse strain of a genetic background different from B6, we have back‐crossed the NKT cell marker NK1.1 from the B6 mouse to the BALB/c mouse strain. We show that NKT cells in the congenic BALB.B6‐NK1.1b mouse share many characteristics with their B6 counterparts, but seem to be deficient in the functional NKT cell subtype characterized by low interleukin‐4 and high interferon‐γ production, and surface expression of CD49b but not CD69. Moreover, in the thymus but not the spleen of BALB.B6‐NK1.1b mice we find a novel Vα14‐Jα18 invariant NKT cell subset which is devoid of a set of NK markers, suggesting that these cells represent a less differentiated NKT cell stage, and carries high levels of the T‐cell receptor and uses a skewed T‐cell receptor Vβ‐repertoire.
Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV
Authors: Kumar Sanjeev , Bunting Karen A. , Kalsi Jatinderpal , Hinks John A. , Latchman David S. , Pearl Laurence H. , Isenberg David A. 
Published: February 2005

SummaryWhile immunoglobulin G (IgG) antibodies to double‐stranded (ds)DNA are serological markers of systemic lupus erythematosus (SLE), not all antibodies to DNA (anti‐DNA) are able to cause tissue damage to a similar extent. It has been proposed that anti‐DNA‐induced renal damage could be linked to differences in the fine specificity of the antibodies. In an attempt to gain insight into their fine binding properties, we investigated the cross‐reactivity of two human lupus monoclonal IgG anti‐dsDNA (B3 and RH14) to a recently described Escherichia coli PolIV (a DNA polymerase). These autoantibodies possess distinct pathogenic properties in severe combined immunodeficient (SCID) mice. Although both antibodies cause proteinuria, only RH14 induces early histological features of lupus nephritis. Both RH14 and B3 bound PolIV; however, they exhibited a marked difference in their reactivity to the PolIV–dsDNA complex. Alhough RH14 exhibited significant activity to the complex, the binding of B3 to PolIV complexed with dsDNA was almost abolished. Furthermore, there was a significant difference in the way the lupus sera recognized naked dsDNA and that presented on PolIV. Although 67% of lupus sera bound naked dsDNA, ≈ 90% of these sera (93% calf thymus DNA; 90% synthetic oligonucleotide) reacted to the complex when dsDNA was presented on PolIV. Thus, the IgG anti‐dsDNA likely to exist in lupus patients may be distinguished into those that recognize dsDNA in the context of PolIV and those which do not. This difference in binding ability may help to distinguish those dsDNA antibodies that are more pathogenic.
Haemopoietic mechanisms in murine allergic upper and lower airway inflammation
Authors: Li Jing , Saito Hiroko , Crawford Lynn , Inman Mark D. , Cyr Michael M. , Denburg Judah A. 
Published: February 2005

SummaryEosinophil recruitment to the airways, including involvement of haemopoietic eosinophil–basophil progenitors (Eo/B‐CFU), is primarily regulated by interleukin‐5 (IL‐5) and eotaxin. In this study, we investigated the haemopoietic mechanisms in upper and lower airway eosinophilic inflammation. Ovalbumin (OVA) sensitized and challenged BALB/c mice were used to establish isolated upper (UAC), isolated lower (LAC), or combined upper and lower airway (ULAC) inflammation. Airway, blood and bone marrow responses were evaluated in each model. Numbers of airway eosinophils and CD4+ cells were increased significantly in the nasal mucosa in UAC and ULAC mice, and in the lung tissue in LAC and ULAC groups. Levels of IL‐5 and eotaxin were increased significantly in the nasal lavage fluid (NL) in UAC and ULAC mice, and in the bronchoalveolar lavage fluid (BAL) in LAC and ULAC groups. The proportion of IL‐5‐responsive bone marrow Eo/B‐CFU was significantly higher than the control in all treatment groups, but peaked much earlier in the ULAC group. Kinetic studies revealed that IL‐5 and eotaxin in NL, BAL and serum peaked between 2 and 12 hr after OVA challenge in ULAC mice, and at 24 hr in UAC mice, related to the timing of maximal progenitor responses. These data support the concept that the systemic mechanisms linking rhinitis to asthma depend on the location and extent of airway allergen exposure.
Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC)
Authors: Choe Hyeryun , Moore Michael J. , Owens Christopher M. , Wright Paulette L. , Vasilieva Natalya , Li Wenhui , Singh Agam P. , Shakri Rushdi , Chitnis Chetan E. , Farzan Michael 
Published: February 2005

Summary Plasmodium vivax is one of four Plasmodium species that cause human malaria. P. vivax and a related simian malaria parasite, Plasmodium knowlesi, invade erythrocytes by binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy binding proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy binding proteins of P. vivax (PvDBP) and P. knowlesi (PkDaBP) with DARC‐expressing cells. These sulphated tyrosines also participate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP‐1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to phenylalanine interferes with the association of IL8 with DARC. A soluble sulphated amino‐terminal domain of DARC, but not one modified to phenylalanine at residue 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of many or most chemokines with their receptors, and identify a key molecular determinant of erythrocyte invasion by P. vivax.
Two substrate‐targeting sites in the Yersinia protein tyrosine phosphatase co‐operate to promote bacterial virulence
Authors: Ivanov Maya I. , Stuckey Jeanne A. , Schubert Heidi L. , Saper Mark A. , Bliska James B. 
Published: February 2005

SummaryYopH is a protein tyrosine phosphatase and an essential virulence determinant of the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host cells using a type III secretion mechanism. YopH dephosphorylates several focal adhesion proteins including p130Cas in human epithelial cells, resulting in disruption of focal adhesions and cell detachment from the extracellular matrix. How the C‐terminal protein tyrosine phosphatase domain of YopH targets specific substrates such as p130Cas in the complex milieu of the host cell has not been fully elucidated. An N‐terminal non‐catalytic domain of YopH binds p130Cas in a phosphotyrosine‐dependent manner and functions as a novel substrate‐targeting site. The structure of the YopH protein tyrosine phosphatase domain bound to a model phosphopeptide substrate was solved and the resulting structure revealed a second substrate‐targeting site (‘site 2’) within the catalytic domain. Site 2 binds to p130Cas in a phosphotyrosine‐dependent manner, and co‐operates with the N‐terminal domain (‘site 1’) to promote efficient recognition of p130Cas by YopH in epithelial cells. The identification of two substrate‐targeting sites in YopH that co‐operate to promote epithelial cell detachment and bacterial virulence reinforces the importance of protein–protein interactions for determining protein tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature of microbial pathogenicity factors.
Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5
Authors: Wieland Hagen , Ullrich Susanne , Lang Florian , Neumeister Birgid 
Published: February 2005

SummaryThe infectious agent of Legionnaires’ disease, Legionella (L) pneumophila, multiplies intracellularly in eukaryotic cells. This study has been performed to explore the nutrient requirements of L. pneumophila during intracellular replication. In human monocytes, bacterial replication rate was reduced by 76% in defined medium lacking l‐cysteine, l‐glutamine or l‐serine. SLC1A5 (hATB0,+), a neutral amino acid transporter, was upregulated in the host cells after infection with L. pneumophila. Inhibition of SLC1A5 by BCH, a competitive inhibitor of amino acid uptake as well as siRNA silencing of the slc1a5 gene blocked intracellular multiplication of L. pneumophila without compromising viability of host cells. These observations suggest that replication of L. pneumophila depends on the function of host cell SLC1A5.
Severing all ties between mother and daughter: cell separation in budding yeast
Authors: Yeong Foong May 
Published: February 2005

SummaryAt the end of nuclear division in the budding yeast, acto‐myosin ring contraction and cytokinesis occur between mother and daughter cells. This is followed by cell separation, after which mother and daughter cells go their separate ways. While cell separation may be the last event that takes place between the two cells, it is nonetheless under tight regulation which ensures that both cells are viable upon separation. It is becoming increasingly clear that the components of the cell separation machinery are controlled at various levels, including the temporal and spatial regulation of the genes encoding for the components and the specific localization of the components to the neck. In addition, these regulatory controls are co‐ordinated with exit from mitosis, thereby placing a mechanistic link between the end of mitosis and cell separation. More importantly, the success of the cell separation event is contingent upon the presence of a trilaminar septum, whose assembly is dependent on a host of proteins which localize to the neck over the span of one cell division cycle.
2004 ASM Conference on the New Phage Biology: the ‘Phage Summit’
Authors: Adhya Sankar , Black Lindsay , Friedman David , Hatfull Graham , Kreuzer Kenneth , Merril Carl , Oppenheim Amos , Rohwer Forest , Young Ry 
Published: February 2005

SummaryIn August, more than 350 conferees from 24 countries attended the ASM Conference on the New Phage Biology, in Key Biscayne, Florida. This meeting, also called the Phage Summit, was the first major international gathering in decades devoted exclusively to phage biology. What emerged from the 5 days of the Summit was a clear perspective on the explosive resurgence of interest in all aspects of bacteriophage biology. The classic phage systems like λ and T4, reinvigorated by structural biology, bioinformatics and new molecular and cell biology tools, remain model systems of unequalled power and facility for studying fundamental biological issues. In addition, the New Phage Biology is also populated by basic and applied scientists focused on ecology, evolution, nanotechnology, bacterial pathogenesis and phage‐based immunologics, therapeutics and diagnostics, resulting in a heightened interest in bacteriophages per se, rather than as a model system. Besides constituting another landmark in the long history of a field begun by d’Herelle and Twort during the early 20th century, the Summit provided a unique venue for establishment of new interactive networks for collaborative efforts between scientists of many different backgrounds, interests and expertise.
Getting down to malarial nuts and bolts: the interaction between Plasmodium vivax merozoites and their host erythrocytes
Authors: Rayner Julian 
Published: February 2005

SummaryOf the four Plasmodium species that routinely cause malaria in humans, Plasmodium falciparum is responsible for the majority of malaria mortality and consequently gets most of the headlines. Outside Africa, however, more malaria cases are caused by its distant cousin Plasmodium vivax, resulting in a daunting morbidity and economic burden for countries across Asia and the Americas. Plasmodium life cycles are complex, but the symptoms and pathology of malaria occur during the blood phase, when merozoites recognize and invade erythrocytes, initiating a developmental programme that culminates in lysis of the erythrocyte and release of multiple daughter merozoites. P. vivax merozoites are dependent on a single host cell receptor for erythrocyte invasion, the Duffy antigen receptor for chemokines, and humans that do not express this receptor on the surface of their erythrocytes are immune to P. vivax infection. This essential receptor–ligand interaction is addressed from both the host and parasite side in two papers in this issue of Molecular Microbiology, with important implications for plans to develop a P. vivax vaccine.