bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon‐γ Expression in Periventricular Leukomalacia in the Human Brain
Authors: Folkerth Rebecca D. , Keefe Rachael J. , Haynes Robin L. , Trachtenberg Felicia L. , Volpe Joseph J. , Kinney Hannah C.
Published: July 2010

Periventricular leukomalacia (PVL), the major lesion underlying cerebral palsy in survivors of prematurity, is characterized by focal periventricular necrosis and diffuse gliosis of immature cerebral white matter. Causal roles have been ascribed to hypoxiaischemia and maternal‐fetal infection, leading to cytokine responses, inflammation, and oligodendrocyte cell death. Because interferon‐γ (IFN‐γ) is directly toxic to immature oligodendrocytes, we tested the hypothesis that it is expressed in PVL (N=13) compared to age‐adjusted controls (N=31) using immunocytochemistry. In PVL, IFN‐γ immunopositive macrophages were clustered in necrotic foci, and IFN‐γ immunopositive reactive astrocytes were present throughout the surrounding white matter (WM). The difference in the number of IFN‐y immunopositive glial cells/high power field (IFN‐γ score, Grades 0–3) between PVL cases (age‐adjusted mean 2.59 ±0.25) and controls (age‐adjusted mean 1.39±0.16) was significant (p<0.001). In the gliotic WM, the IFN‐γ score correlated with markers for lipid peroxidation, but not nitrative stress. A subset of premyelinating (O4+) oligodendrocytes expressed IFN‐γ receptors in PVL and control cases, indicating that these cells are vulnerable to IFN‐γ toxicity via receptor‐mediated interactions. In PVL, IFN‐γ produced by macrophages and reactive astrocytes may play a role in cytokine‐induced toxicity to premyelinating oligodendrocytes as part of a cytokine response stimulated by ischemia and/or infection.
Genetic and Expression Profiles of Cerebellar Liponeurocytomas
Authors: Horstmann Sonja , Perry Arie , Reifenberger Guido , Giangaspero Felice , Huang Herve , Hara Akira , Masuoka Jun , Rainov Nikolai G. , Bergmann Markus , Heppner Frank L. , Brandner Sebastian , Chimelli Leila , Montagna Nádia , Jackson Thad , Davis Daron G. , Markesbery William R. , Ellison David W. , Weller Roy O. , Taddei Gian L. , Conti Renato , Del Bigio Marc R. , González‐Cámpora Ricardo , Radhakrishnan V.V. , Söylemezoglu Figen , Uro‐Coste Emmanuelle , Qian Jiang , Kleihues Paul , Ohgaki Hiroko
Published: July 2010

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or β‐catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.
Chronic Hydrocephalus in Adults
Authors: Edwards Richard J , Dombrowski Stephen M. , Luciano Mark G. , Pople Ian K
Published: July 2010

Chronic hydrocephalus is a complex condition, the incidence of which increases with increasing age. It is characterised by the presence of ventricular enlargement in the absence of significant elevations of intracranial pressure. The clinical syndrome may develop either as a result of decompensation of a “compensated” congenital hydrocephalus, or it may arise de novo in adult life secondary to a known acquired disturbance of normal CSF dynamics. The latter may be due to late onset acqueductal stenosis or disruption of normal CSF absorptive pathways following subarachnoid hemorrhage or meningitis (“secondary” normal pressure hydrocephalus (NPH)). In some cases the cause of the hydrocephalus remains obscure (“idiopathic” NPH). In all forms of chronic hydrocephalus the clinical course of the disease is heavily influenced by changes in the brain associated with aging, in particular cerebrovascular disease. Recent research has challenged previously held tenets regarding the CSF circulatory system and this in turn has led to a radical rethinking of the pathophysiological basis of chronic hydrocephalus.
Hippocampal Pathology in the Human Neuronal Ceroid‐Lipofuscinoses: Distinct Patterns of Storage Deposition, Neurodegeneration and Glial Activation
Authors: Tyynelä Jaana , Cooper Jonathan D , Khan M Nadeem , Shemilt Stephen JA , Haltia Matti
Published: July 2010

The neuronal ceroid‐lipofuscinoses (NCLs) are recessively inherited lysosomal storage diseases, currently classified into 8 forms (CLN1‐CLN8). Collectively, the NCLs constitute the most common group of progressive encephalopathies of childhood, and present with visual impairment, psychomotor deterioration and severe seizures. Despite recent identification of the underlying disease genes, the mechanisms leading to neurodegeneration and epilepsy in the NCLs remain poorly understood. To investigate these events, we examined the patterns of storage deposition, neurodegeneration, and glial activation in the hippocampus of patients with CLN1, CLN2, CLN3, CLN5 and CLN8 using histochemistry and immunohistochemistry. These different forms of NCL shared distinct patterns of neuronal degeneration in the hippocampus, with heavy involvement of sectors CA2‐CA4 but relative sparing of CA1. This selective pattern of degeneration was also observed in immunohistochemically identified interneurons, which exhibited a graded severity of loss according to phenotype, with calretinin‐positive interneurons relatively spared. Furthermore, glial activation was also regionally specific, with microglial activation most pronounced in areas of greatest neuronal loss, and astrocyte activation prominent in areas where neuronal loss was less evident. In conclusion, the NCLs share a common pattern of selective hippocampal pathology, distinct from that seen in the majority of temporal lobe epilepsies.
Ischemia Leads to Apoptosis—and Necrosis‐like Neuron Death in the Ischemic Rat Hippocampus
Authors: Müller Georg Johannes , Stadelmann Christine , Bastholm Lone , Elling Folmer , Lassmann Hans , Johansen Flemming Fryd
Published: July 2010

Morphological evidence of apoptosis in transient forebrain ischemia is controversial. We therefore investigated the time sequence of apoptosis‐related antigens by immunohistochemistry and correlated it with emerging nuclear patterns of cell death in a model of transient forebrain ischemia in CA1 pyramidal cells of the rat hippocampus. The earliest ischemic changes were found on day 2 and 3, reflected by an upregulation of phospho‐c‐Jun in a proportion of morphologically intact CA1 neurons, which matched the number of neurons that succumbed to ischemia at later time points. At day 3 and later 3 ischemic cell death morphologies became apparent: pyknosis, apoptosis‐like cell death and necrosis‐like cell death, which were confirmed by electron microscopy. Activated caspase‐3 was present in the vast majority of cells with apoptosis‐like morphology as well as in a small subset of cells undergoing necrosis; its expression peaked on days 3 to 4. Silver staining for nucleoli, which are a substrate for caspase‐3, revealed a profound loss of nucleoli in cells with apoptosis‐like morphology, whereas cells with necrosis‐like morphology showed intact nucleoli. Overall, cells with apoptosis‐like morphology and/or caspase‐3 expression represented a minor fraction (<10%) of ischemic neurons, while the vast majority followed a necrosis‐like pathway. Our studies suggest that CA1 pyramidal cell death following transient forebrain ischemia may be initiated through c‐Jun N‐terminal kinase (JNK) pathway activation, which then either follows an apoptosis‐like cell death pathway or leads to secondary necrosis.
JUNE 2004: A MALE IN HIS LATE 60s WITH RECURRENT EXTRA‐CEREBRAL TUMOR
Authors: Mawrin Christian , Hahne Rainer , Scherlach Cordula , Kirches Elmar , Dietzmann Knut
Published: July 2010

June 2004: Over the past year, this man in late‐60s had complained about progressive weakness of concentration and memory disturbances, associated with word finding difficulties. MRI examination revealed an extra‐axial, parasagittal tumor 3 cm in diameter located in the left frontoparietal region. Five years ago, a meningioma in the same region, with radiographic appearance comparable to the present tumor had been totally removed. The histological picture of the current tumor was dominated by sheets of large rounded pleomorphic tumor cells with abundant eosinophilic cytoplasm and eccentric nuclei (rhabdoid cells). Cytoplasmic inclusions were frequent; occasionally, multinucleated tumor cells were seen. Mitotic figures were absent and the MIB was 3%. Meningothelial lobules were scarce, and regions with fibroblastic appearance were absent. There were no psammoma bodies, necrosis or brain invasion. Moderate immunoreactivity for EMA was found. Additionally, strong cytoplasmic immunoreaction for vimentin within the rhabdoid cells was observed. Review of the previous material showed small islets of rhabdoid cells. Rhabdoid meningioma is an uncommon meningioma variant. It has been suggested that rhabdoid meningiomas are highly aggressive tumors (WHO grade III)and that the rhabdoid phenotype represents a marker of malignant transformation in meningiomas. Histologically, rhabdoid meningiomas usually exhibit signs of anaplasia, a high mitotic activity, and a markedly increased MIB‐1 labeling index. Extracranial metastases may occur in the course of the disease. However, not all rhabdoid tumors appear to have anaplastic features (as this case illustrates). Another interesting feature of rhabdoid meningiomas is that in a significant number of cases, the rhabdoid cells appear only at the time of recurrence. Alternatively, as seen in this case, the rhabdoid cells may be already present in the primary meningioma, but not as the predominating histological feature.
Neuropathology and Pathogenesis of Encephalitis following Amyloid β Immunization in Alzheimer's Disease
Authors: Ferrer Isidre , Rovira Mercé Boada , Guerra María Luisa Sánchez , Rey María Jesús , Costa‐Jussá Frederic
Published: July 2010

Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop β‐amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non treated transgenic animals im‐munization with amyloid β peptide has been initiated in a randomised pilot study in AD. Yet a minority of patients developed a neurological complication consistent with meningoencephalitis and one patient died; the trial has been stopped. Neuropathological examination in that patient showed meningoencephalitis and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid nor regression of tau pathology in neurofibrillary tangles and neuropil threads. The present neuropathological study reports the second case of menigoencephalitis following immunization with amyloid‐β peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation‐ with amyliod deposit regression, and possible molecular bases involved in the inflammatory response following immunization. Inflammatory infiltrates were composed of CD8+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. Characteristic neuropathological findings were focal depletion of diffuse and neuritic plaques, but not of amyloid angiopathy, and the presence of small numbers of extremely dense(collapsed) plaques surrounded by active microglia, and multinucleated giant cells filled with dense Aβ42and Aβ40, in addition to severe small cerebral blood Reduced amyloid burden was accompanied by low amyloid‐associated oxidative stress responses (reduced superoxide dismutase‐1:SOD‐1 expression) and by local inhibition of the stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau in neurofibrillary tangles and β‐amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. Furthermore, amyloid reduction was accompanied by increased expression of the PA28α/β inductor, and of LMP7, LMP2 and MECL1 subunits of the immunopro‐teasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells.Immunoproteasome subunit expression was accompanied by local presentation of MHC class molecules. Release of antigenic peptides derived from β‐amyloid processing may enhance T‐cell inflammatory responses accounting for the meningoencephalitis following amyloid‐β peptide immunization
The Intracellular Location and Function Of Proteins Of Neuronal Ceroid Lipofuscinoses
Authors: Ezaki Junji , Kominami Eiki
Published: July 2010

Neuronal ceroid lipofuscinoses are a group of diseases characterized by accumulation of hydrophobic proteins in lysosomes of neurons and other types of cells. NCLs are caused by at least 8 mutant genes (CLN1 CLN8), though CLN4 and CLN7 have not yet been identified. Except for Cln1p, the protein encoded by CLN1, the defective proteins are associated with lysosomal accumulation of mitochondrial ATP synthase subunit c Cln1p and Cln2p are soluble lysosomal enzymes, targeted to lysosomes in a mannose 6‐phosphate dependent manner. Mutations in the lysosomal protease cathepsin D cause another NCL. Cln3p, Cln5p, Cln6p and Cln8p are thought to be transmembrane proteins. Cln3p and Cln5p are localized in the endosome‐lysosomal compartment. Deficiency of endosomal membrane protein CLC‐3, a member of the chloride channel family, causes NCL‐like phenotype and lysosomal storage of subunit c. Herein, we review the features of NCL and NCL‐related proteins and discuss the involvement of the proteins in lysosomal degradation of subunit c.
Injections of Blood, Thrombin, and Plasminogen More Severely Damage Neonatal Mouse Brain Than Mature Mouse Brain
Authors: Xue Mengzhou , Del Bigio Marc R.
Published: July 2010

The mechanism of brain cell injury associated with intracerebral hemorrhage may be in part related to proteolytic enzymes in blood, some of which are also functional in the developing brain. We hypothesized that there would be an age‐dependent brain response following intracerebral injection of blood, thrombin, and plasminogen. Mice at 3 ages (neonatal, 10‐day‐old, and young adult) received autologous blood (15, 25, and 50 μl respectively), thrombin (3, 5, and 10 units respectively), plasminogen (0.03, 0.05, and 0.1 units respectively) (the doses expected in same volume blood), or saline injection into lateral striatum. Forty‐eight hours later they were perfusion fixed. Hematoxylin and eosin, lectin histochemistry, Fluoro‐Jade, and TUNEL staining were used to quantify changes related to the hemorrhagic lesion. Damage volume, dying neurons, neutrophils, and microglial reaction were significantly greater following injections of blood, plasminogen, and thrombin compared to saline in all three ages of mice. Plasminogen and thrombin associated brain damage was greatest in neonatal mice and, in that group unlike the other 2, greater than the damage caused by whole blood. These results suggest that the neonatal brain is relatively more sensitive to proteolytic plasma enzymes than the mature brain.
Angiocentric Neuroepithelial Tumor (ANET): A New Epilepsy‐Related Clinicopathological Entity with Distinctive MRI
Authors: Lellouch‐Tubiana Arielle , Boddaert Nathalie , Bourgeois Marie , Fohlen Martine , Jouvet Anne , Delalande Olivier , Seidenwurm David , Brunelle Françis , Sainte‐Rose Christian
Published: July 2010

Several types of glioneuronal tumors are known to induce intractable partial seizures in children and adults. The most frequent are dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. We report here a new clinicopathological entity within the spectrum of glioneuronal tumors observed in 10 children who underwent surgery for refractory epilepsy. These tumors demonstrate a unique, pathognomonic histological pattern and a specific appearance at magnetic resonance imaging (MRI). The most striking neuropathological feature is an angiocentric polarity of the tumor with gliofibrillary acidic protein (GFAP) positive fusiform and bipolar astrocytic cells arranged around blood vessels (perivascular cuffing with tumoral astrocytes). Characteristic MRI findings include involvement of cortical gray and white matter, intrinsically high signal on T1‐weighted images, as well as a stalk like extension to the ventricle. Immunohistochemical neuronal markers (neurofilament protein, synaptophysin and chromogranin) confirm the presence of a neuronal cell component. Therefore, the term angiocentric neuroepithelial tumor (ANET) is proposed.
Failure of Remyelination in the Nonhuman Primate Optic Nerve
Authors: Lachapelle François , Bachelin Corinne , Moissonnier Pierre , Nait‐Oumesmar Brahim , Hidalgo Antoine , Fontaine Denys , Evercooren Anne Baron‐Van
Published: July 2010

The mechanisms limiting myelin repair in human central nervous system (CNS) remain unknown. Models of induced‐demyelination in the nonhuman primate CNS may provide the necessary grounds to unravel these mechanisms and to investigate the development of strategies to promote myelin repair. To address this issue, we developed a model of focal demyelination in the adult Macaca fascicularis CNS. Lesions were induced by microinjection of lysolecithin in the optic nerve and the profile of remyelination was compared to that of lysolecithin‐induced lesions of the spinal cord. In both structures, the time‐course of demyelination as well as the onset of remyelination were found to be similar to that in the rodent CNS. While spinal cord lesions were remyelinated within 6 weeks, optic nerve lesions remained demyelinated for up to 3 months post‐injection. The failure of remyelination in the optic nerve correlated with a reduced density of NG2′ oligodendrocyte progenitor cells, the presence of oligodendrocytes that fail to ensheath naked axons in the lesion and the absence of astrocyte recruitment in the lesion compared with spinal cord lesions. Our present data suggest that the reduced oligodendrocyte progenitor population, the improper activation of oligodendrocytes at the onset of remyelination in the optic nerve, and possibly, the involvement of astrocytes contribute to the chronicity of the optic nerve lesion. This model of chronic demyelination in the macaque optic nerve stress its pertinence to unravel the mechanisms limiting remyelination in multiple sclerosis.
ES Cell‐Derived Glial Precursors Contribute to Remyelination in Acutely Demyelinated Spinal Cord Lesions
Authors: Perez‐Bouza Alberto , Glaser Tamara , Brüstle Oliver
Published: July 2010

Pluripotent embryonic stem (ES) cells have emerged as a powerful tool for disease modeling and neural regeneration. Transplantation studies in rodents indicate that ES cell‐derived glial precursors (ESGPs) efficiently restore myelin in dysmyelinating mutants and chemically induced foci of myelin loss. Here we explore the myelination potential of ESGPs in an antibody/complement‐induced demyelination model. Microinjection of an antibody to myelin oligodendrocyte glycoprotein (MOG) and complement was employed to generate circumscribed areas of demyelination in the adult rat spinal cord. ESGPs transplanted into 2‐day‐old lesions were found to survive and differentiate into both oligodendrocytes and astrocytes. The engrafted cells remained largely confined to the lesion site and showed no evidence of tumor formation up until 4 weeks after transplantation. Within areas of pronounced microglial activation and macrophage extravasation, engrafted ES cell‐derived oligodendrocytes contacted and enwrapped host axons and alongside endogenous glia, contributed to the formation of new myelin sheaths. These findings demonstrate that ESGPs transplanted into acutely demyelinated lesions can contribute to myelin repair.
Oxidative and Nitrative Injury in Periventricular Leukomalacia: A Review
Authors: Haynes R. L. , Baud O. , Li J. , Kinney H. C. , Volpe J. J. , Folkerth R. D.
Published: July 2010

Periventricular leukomalacia (PVL) is the major substrate of cerebral palsy in survivors of prematurity. Its pathogenesis is complex and likely involves ischemia/reperfusion in the critically ill premature infant, with impaired regulation of cerebral blood flow, as well as inflammatory mechanisms associated with maternal and/or fetal infection. During the peak period of vulnerability for PVL, developing oligodendrocytes (OLs) predominate in the white matter. We hypothesize that free radical injury to the developing OLs underlies, in part, the pathogenesis of PVL and the hypomyelination seen in long‐term survivors. In human PVL, free radical injury is supported by evidence of oxidative and nitrative stress with markers to lipid peroxidation and nitrotyrosine, respectively. Evidence in normal human cerebral white matter suggests an underlying vulnerability of the premature infant to free radical injury resulting from a developmental mismatch of antioxidant enzymes (AOE) and subsequent imbalance in oxidant metabolism. In vitro studies using rodent OLs suggest that maturational susceptibility to reactive oxygen species is dependent, not only on levels of individual AOE, but also on specific interactions between these enzymes. Rodent in vitro data further suggest 2 mechanisms of nitric oxide damage: one involving the direct effect of nitric oxide on OL mitochondrial integrity and function, and the other involving an activation of microglia and subsequent release of reactive nitrogen species. The latter mechanism, while important in rodent studies, remains to be determined in the pathogenesis of human PVL. These observations together expand our knowledge of the role that free radical injury plays in the pathogenesis of PVL, and may contribute to the eventual development of therapeutic strategies to alleviate the burden of oxidative and nitrative injury in the premature infant at risk for PVL.
Excitotoxicity in Perinatal Brain Injury
Authors: Johnston Michael V.
Published: July 2010

Excitotoxicity is an important mechanism involved in perinatal brain injuries. Glutamate is the major excitatory neurotransmitter, and most neurons as well as many oligodendrocytes and astrocytes possess receptors for glutamate. Perinatal insults such as hypoxia‐ischemia, stroke, hypoglycemia, kernicterus, and trauma can disrupt synaptic function leading to accumulation of extracellular glutamate and excessive stimulation of these receptors. The activities of certain glutamate receptor/channel complexes are enhanced in the immature brain to promote activity‐dependent plasticity. Excessive stimulation of glutamate receptor/ion channel complexes triggers calcium flooding and a cascade of intracellular events that results in apoptosis and/or necrosis. Recent research suggests that some of these intracellular pathways are sexually dimorphic. Age dependent expression of different glutamate receptor subtypes with varying abilities to flux calcium has been associated with special patterns of selective vulnerability at different gestational ages. For example, selective injury to the putamen, thalamus and cerebral cortex from near total asphyxia in term infants may be related to excessive activation of neuronal NMDA and AMPA type glutamate receptors, while brain‐stem injury may be related primarily to stimulation of neuronal AMPA/kainate receptors. In contrast, periventricular leukomalacia in premature infants has been linked to expression of AMPA/kainate receptors on immature oligodendrocytes. Insight into the molecular pathways that mediate perinatal brain injuries could lead to therapeutic interventions.
Does Thrombin Play a Role in the Pathogenesis of Brain Damage After Periventricular Hemorrhage?
Authors: Xue Mengzhou , Balasubramaniam Janani , Parsons Kari A. L. , McIntyre Ian W. , Peeling James , Del Bigio Marc R.
Published: July 2010

Neonatal periventricular hemorrhage (PVH) is a devastating complication of prematurity in the human infant. Based upon observations made primarily in adult rodents and the fact that the immature brain uses proteolytic systems for cell migration and growth, we hypothesized that thrombin and plasmin enzyme activities contribute to the brain damage after PVH. The viability of mixed brain cells derived from newborn rat periventricular region was suppressed by whole blood and thrombin, but not plasmin. Following injection of autologous blood into the periventricular region of newborn rat brain, proteolytic activity was detected in a halo around the hematoma using membrane overlays impregnated with thrombin and plasmin fluorogenic substrates. Two‐day old rats received periventricular injection of blood, thrombin, and plasminogen. After 2 days, thrombin and blood were associated with significantly greater damage than saline or plasminogen. Two‐day old mice received intracerebral injections of blood in combination with saline or the proteolytic inhibitors hirudin, α2macroglobulin, or plasminogen activator inhibitor‐1. After 2 days, hirudin significantly reduced brain cell death and inflammation. Two‐day‐old mice then received low and high doses of hirudin mixed with blood after which behavioral testing was conducted repeatedly. At 10 weeks there was no statistically significant evidence for behavioral or structural brain protection. These results indicate that thrombin likely plays a role in neonatal periventricular brain damage following PVH. However, additional factors are likely important in the recovery from this result.
Ability of Selected Lactic Acid Bacteria to Ferment a Pearl Millet–Soybean Slurry to Produce Gruels for Complementary Foods for Young Children
Authors: Songré‐Ouattara Laurencia T. , Mouquet‐Rivier Claire , Humblot Christèle , Rochette Isabelle , Diawara Bréhima , Guyot Jean‐Pierre
Published: July 2010

Abstract:  To assess the ability of lactic acid bacteria to improve some nutritional characteristics of the pearl millet–soybean slurry to prepare complementary foods for young children in African countries, inoculation was performed using strains previously selected for their ability to hydrolyse starch, phytate, or α‐galactooligosaccharides (α‐GOS). For the sake of comparison with the action of a natural microflora, fermentation was also performed by back slopping inoculation, that is, with a sample obtained from spontaneously fermented traditional pearl millet slurry obtained from a small scale processing unit in Burkina Faso (Ouagadougou). Starter cultures thrived on the slurry as shown by counts on MRS agar, TTGE fingerprints, and fermentation patterns. The fermentation of precooked slurries inoculated by back slopping or with mixed cultures containing the amylolytic strain Lb. plantarum A6 enabled partial starch hydrolysis. Corresponding gruels had a suitable consistency for young child feeding at high dry matter content, and a high energy density: 88.7 ± 4.2 and 75.8 ± 5.1 kcal/100 g of sweetened gruel, for the gruels inoculated by back slopping or with Lb. plantarum A6, respectively. Unexpectedly, no decrease in phytates was observed in any of the experiments, suggesting the presence of one or more inhibitory compounds in soybean. Furthermore, preprocessing conditions before fermentation affect the carbohydrate composition of slurry and have a more profound effect than fermentation on the reduction of the α‐GOS content.

Practical Application:  This research aims to investigate the capacity of selected lactic acid bacteria to produce in a bioprocess high energy density and nutritious gruels for complementary feeding of young children from an African cereal (pearl millet) mixed with soybean.
Development of Associations and Kinetic Models for Microbiological Data to Be Used in Comprehensive Food Safety Prediction Software
Authors: Halder Amit , Black D. Glenn , Davidson P. Michael , Datta Ashim
Published: July 2010

Abstract:  The objective of this study was to use an existing database of food products and their associated processes, link it with a list of the foodborne pathogenic microorganisms associated with those products and finally identify growth and inactivation kinetic parameters associated with those pathogens. The database was to be used as a part of the development of comprehensive software which could predict food safety and quality for any food product. The main issues in building such a predictive system included selection of predictive models, associations of different food types with pathogens (as determined from outbreak histories), and variability in data from different experiments. More than 1000 data sets from published literature were analyzed and grouped according to microorganisms and food types. Final grouping of data consisted of the 8 most prevalent pathogens for 14 different food groups, covering all of the foods (>7000) listed in the USDA Natl. Nutrient Database. Data for each group were analyzed in terms of 1st‐order inactivation, 1st‐order growth, and sigmoidal growth models, and their kinetic response for growth and inactivation as a function of temperature were reported. Means and 95% confidence intervals were calculated for prediction equations. The primary advantage in obtaining group‐specific kinetic data is the ability to extend microbiological growth and death simulation to a large array of product and process possibilities, while still being reasonably accurate. Such simulation capability could provide vital ‘‘what if’’ scenarios for industry, Extension, and academia in food safety.
Addition of Soluble Soybean Polysaccharides to Dairy Products as a Source of Dietary Fiber
Authors: Chen Wenpu , Duizer Lisa , Corredig Milena , Goff H. Douglas
Published: July 2010

Abstract:  Increasing consumption of dietary fiber in food leads to many important health benefits: for example, reduction in blood cholesterol, reduced risk of diabetes, and improved laxation. Water soluble soybean polysaccharide (SSPS) is a dietary fiber extracted and refined from okara, a byproduct of soy manufacturing. It was incorporated into 3 categories of dairy‐based products, thickened milkshake‐style beverages, puddings, and low‐fat ice cream, to the maximum amount without over‐texturing the food. Rheological measurements and sensory tests were used to develop desirable SSPS‐fortified products. From the rheological data, 4% SSPS‐fortified dairy beverages and 4% SSPS ‐fortified puddings were in the range of commercial products. From sensory analyses, 4% SSPS‐fortified dairy beverage with 0.015%κ−carrageenan, 4% SSPS‐fortified pudding with 0.1%κ−carrageenan, and 2% SSPS‐fortified low‐fat ice cream gained the highest scores in consumer hedonic rating. Panelists also indicated their willingness to consume those products if they were available commercially.

Practical Application:  Since the dietary fiber intake of many people is below their suggested adequate intake values, strategies to successfully fortify foods with fiber may help alleviate this gap. We have developed 3 dairy products, a beverage, a pudding, and a low‐fat ice cream, that have been fortified with soluble soybean polysaccharide at levels of 4%, 4%, and 2%, respectively. These products were within acceptable ranges of rheological parameters and other physical stability measurements and were judged to be acceptable by sensory analyses.
Small‐molecule elicitation of microbial secondary metabolites
Authors: Pettit Robin K.
Published: July 2010

Microbial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the biosynthetic potential of many strains is much greater than that observed by fermentation. Prodding the expression of such silent (cryptic) pathways will allow us to maximize the chemical diversity available from microorganisms. Cryptic metabolic pathways can be accessed in the laboratory using molecular or cultivation‐based approaches. A targeted approach related to cultivation‐based methods is the application of small‐molecule elicitors to specifically affect transcription of secondary metabolite gene clusters. With the isolation of the novel secondary metabolites lunalides A and B, oxylipins, cladochromes F and G, nygerone A, chaetoglobosin‐542, ‐540 and ‐510, sphaerolone, dihydrosphaerolone, mutolide and pestalone, and the enhanced production of known secondary metabolites like penicillin and bacitracin, chemical elicitation is proving to be an effective way to augment natural product libraries.
DEMAND MANAGEMENT‐TODAY'S CHALLENGE FOR SERVICE INDUSTRIES
Authors: Crandall Richard E. , Markland Robert E.
Published: July 2010

This study examines the issue of demand management in service industries, proposes an expanded description of the term, presents evidence of the importance of demand /capacity management, provides a classification of demand management strategies, and identifies some of the factors that may influence the choice of demand management strategies. The results indicate that industries have different resources, demand patterns, and strategic objectives; this suggests that these differences should influence the choice of demand management strategies. However, the industries studied were less different in their choice of demand management strategies than in the differences indicated by the independent variables. This may result from the. fact that most companies, except utilities, indicated that their demand management programs were largely informal in practice. Most companies use demand management strategies that emphasize customer service‐the provide and match strategies. However, almost without exception, all industries indicated a desire to shift their focus toward the resource utilization side of the range‐the influence and control strategies. In this exploratory study, the findings suggest that there is a need for companies to spend more time in evaluating and planning their demand management strategies.
EVALUATING THE TRADE‐OFFS BETWEEN IDLING AND SHUTTING DOWN PRODUCTION LINES IN PROCESS INDUSTRIES
Authors: DeMatta Renato , Miller Tan
Published: July 2010

The costs of starting‐up and shutting down production lines (and plants) in a process industry are often quite high. Therefore, when a plant's capacity significantly exceeds its forecast demand over an annual planning horizon, a manufacturer must either plan temporary production line shutdowns during the year, or plan to temporarily idle production lines without formally shutting line(s) down. The trade‐offs between these two strategies can be complex. In this paper, we propose a methodology to evaluate the impact of both strategies on a plant's production costs by developing an analytical model based on the authors' experience with several process industries.
A COMPARISON OF PRODUCTION SCHEDULING POLICIES ON COSTS, SERVICE LEVEL, AND SCHEDULE CHANGES
Authors: Metters Richard , Vargas Vicente
Published: July 2010

We consider a single product, single level, stochastic master production scheduling (Mps) model where decisions are made under rolling planning horizons. Outcomes of interest are cost, service level, and schedule stability. The subject of this research is the Mps control system: the method used in determining the amount of stock planned for production in each time period. Typically, Mps control systems utilize a single buffer stock. Here, two Mps dual‐buffer stock systems are developed and tested by simulation. We extend the data envelopment analysis (dea) methodology to aid in the evaluation of the simulation results, where Dea serves to increase the scope of the experimental design. Results indicate that the dual‐buffer control systems outperform existing policies.
TOWARD A “NEW ARCHITECTURE” FOR POM
Authors: Hayes Robert H.
Published: July 2010

The field of POM is steadily expanding its scope. This allows us to pursue interesting new fields of inquiry and makes us ever more relevant to the needs of practitioners. But it also increases the risk that over time our efforts will become fragmented and unfocused, causing us to slowly lose our sense of community and break up into separate camps. In this paper I ask, “What kind of new organizing framework, or ‘architecture,’ will allow us to maintain our sense of community as our interests diverge?” I describe the experience of one academic organization that faced a similar problem several years ago and how the situation was resolved. This experience leads us to propose a possible solution to Pom's emerging problem: engage with real operations managers and focus our efforts on helping them deal with the actual problems they are facing in today's complex and fast‐changing world.
LEAN AND GREEN? AN EMPIRICAL EXAMINATION OF THE RELATIONSHIP BETWEEN LEAN PRODUCTION AND ENVIRONMENTAL PERFORMANCE
Authors: KING ANDREW A. , LENOX MICHAEL J.
Published: July 2010

Lean production may have a significant public good spillover—improved environmental performance. However, empirical evidence of the link between lean production practices and environmental performance has not resolved the nature of the relationship. To explore this issue, we conduct an empirical analysis of the environmental performance of 17,499 U.S. manufacturing establishments during the time period 1991–1996. We find that those establishments that adopt the quality management standard ISO 9000 are more likely to adopt the environmental management standard ISO 14000. We also find strong evidence that lean production, as measured by ISO 9000 adoption and low chemical inventories, is complementary to waste reduction and pollution reduction.
A STUDY OF THE UTILIZATION OF CAPACITY CONSTRAINED RESOURCES IN DRUM‐BUFFER‐ROPE SYSTEMS*
Authors: ATWATER J. BRIAN , CHAKRAVORTY SATYA S.
Published: July 2010

Goldratt, the originator of the Theory of Constraints (TOC), maintains that only the system's primary resource constraint(s) should be scheduled at 100% of capacity. All other resources should have excess capacity. This paper presents the results of a simulation experiment that studies how changes in the capacity utilization of a systems two most heavily utilized resources affect the performance of a drum‐buffer‐rope (DBR)scheduling system. The research demonstrates that 100% utilization of the primary constraint is not optimal. It also shows that DBR responds well to relatively low levels of increased capacity at the operations second most heavily utilized resource. This research also highlights several other issues related to capacity utilization that need further investigation.
EMPLOYEE DEVELOPMENT: AN EXAMINATION OF SERVICE STRATEGY IN A HIGH‐CONTACT SERVICE ENVIRONMENT
Authors: GOLDSTEIN SUSAN MEYER
Published: July 2010

A critical component of service strategy in high‐contact environments is service encounter management. Effective service encounters are a result of the quality of employee development, including systems for work and job design, training and development, and attention to employee well being. Results of empirical analysis indicate that service strategies reflecting the dimensions of employee development drive employee outcomes such as productivity and satisfaction. Employee outcomes are significantly associated with customer satisfaction, but only some linkages to financial performance are significant. This study illustrates the importance of employee development in service strategy design for managing service encounters in high contact service environments.
The Effects of Severity of Failure and Customer Loyalty on Service Recovery Strategies
Authors: Craighead Christopher W. , Karwan Kirk R. , Miller Janis L.
Published: July 2010

Service failures do not need to result in permanent negative consequences as long as effective recovery activities are undertaken. Unfortunately, existing research has been limited in providing information to support prescriptive approaches for applying specific service recovery techniques. By using data from a large sample ( n = 861) of service failure incidents and employing the use of hierarchical and non‐hierarchical cluster analysis, this exploratory study creates and analyzes empirical types of service failures. The derived failure types, or common situations faced by service providers, focus on customer loyalty and the severity of the failure, and may be visualized in a two‐by‐two matrix. Regression analysis is then used to demonstrate how effective recovery strategies and supporting activities should vary, based on the location of the failure within the matrix. The approach and results offer important implications for strategy and service support activities as well as a foundation for systematizing service recovery efforts.
Incentive Schemes for Semiconductor Capacity Allocation: A Game Theoretic Analysis
Authors: Karabuk Suleyman , Wu S. David
Published: July 2010

We study incentive issues that arise in semiconductor capacity planning and allocation. Motivated by our experience at a major U. S. semiconductor manufacturer, we model the capacity‐allocation problem in a game‐theoretic setting as follows: each product manager (PM) is responsible for a certain product line, while privately owning demand information through regular interaction with the customers. Capacity‐allocation is carried out by the corporate headquarters (HQ), which allocates manufacturing capacity to product lines based on demand information reported by the PMs. We show that PMs have an incentive to manipulate demand information to increase their expected allocation, and that a carefully designed coordination mechanism is essential for HQ to implement the optimal allocation. To this end, we design an incentive scheme through bonus payments and participation charges that elicits private demand information from the PMs. We show that the mechanism achieves budget‐balance and voluntary‐participation requirements simultaneously. The results provide important insights into the treatment of misaligned incentives in the context of semiconductor capacity‐allocation.
The Impact of Product Lifecycle on Capacity Planning of Closed‐Loop Supply Chains with Remanufacturing
Authors: Georgiadis Patroklos , Vlachos Dimitrios , Tagaras George
Published: July 2010

Product recovery operations in reverse supply chains face rapidly changing demand due to the increasing number of product offerings with reduced lifecycles. Therefore, capacity planning becomes a strategic issue of major importance for the profitability of closed‐loop supply chains. This work studies a closed‐loop supply chain with remanufacturing and presents dynamic capacity planning policies developed through the methodology of System Dynamics. The key issue of the paper is how the lifecycles and return patterns of various products affect the optimal policies regarding expansion and contraction of collection and remanufacturing capacities. The model can be used to identify effective policies, to conduct various “what‐if” analyses, and to answer questions about the long‐term profitability of reverse supply chains with remanufacturing. The results of numerical examples with quite different lifecycle and return patterns show how the optimal collection expansion/contraction and remanufacturing contraction policies depend on the lifecycle type and the average usage time of the product, while the remanufacturing capacity expansion policy is not significantly affected by these factors. The results also show that the collection and remanufacturing capacity policies are insensitive to the total product demand. The insensitivity of the optimal policies to total demand is a particularly appealing feature of the proposed model, given the difficulty in obtaining accurate demand forecasts.
Inventory Record Inaccuracy, Double Marginalization, and RFID Adoption
Authors: Heese H. Sebastian
Published: July 2010

Most retailers suffer from substantial discrepancies between inventory quantities recorded in the system and stocks truly available to customers. Promising full inventory transparency, radio frequency identification (RFID) technology has often been suggested as a remedy to the problem. We consider inventory record inaccuracy in a supply chain model, where a Stackelberg manufacturer sets the wholesale price and a retailer determines how much to stock for sale to customers. We first analyze the impact of inventory record inaccuracy on optimal stocking decisions and profits. By contrasting optimal decisions in a decentralized supply chain with those in an integrated supply chain, we find that inventory record inaccuracy exacerbates the inefficiencies resulting from double marginalization in decentralized supply chains. Assuming RFID technology can eliminate the problem of inventory record inaccuracy, we determine the cost thresholds at which RFID adoption becomes profitable. We show that a decentralized supply chain benefits more from RFID technology, such that RFID adoption improves supply chain coordination.
In VivoEfficacy of Simulated Human Dosing Regimens of Prolonged-Infusion Doripenem against Carbapenemase- ProducingKlebsiella pneumoniae
Authors: Bulik Catharine C. , Nicolau David P.
Published: July 2010

Carbapenemase-producingKlebsiella pneumoniae(KPC) bacteria are rapidly becoming one of the most detrimental drug-resistant Gram-negative pathogens. Doripenem is the newest FDA-approved carbapenem that has the greatestin vitropotency against a wide range of Gram-negative organisms, including multidrug-resistant organisms. Previous work in an animal model has shown efficacy againstPseudomonas aeruginosawith MICs above the current breakpoints of susceptibility. The purpose of this study is to evaluate the efficacy of 1-g and 2-g dose prolonged infusions of doripenem against KPC isolates in both an immunocompetent and neutropenic murine thigh model. Seven clinical KPC isolates (broth microdilution [BMD] MIC range, 4 to 32 μg/ml; Etest MIC range, 3 to >32 μg/ml) were used. After infection, groups of mice were administered doripenem doses previously shown to simulate the exposures observed in humans after the administration of 1 or 2 g every 8 h as a 4-h infusion. In immunocompromised mice, 1- and 2-g doses of doripenem achieved bacteriostasis against isolates with MICs up to and including 8 μg/ml and 16 μg/ml, respectively. In immunocompetent animals, statistically significant reductions in the number of CFU were observed with overall decreases of approximately 1 log (P< 0.05). While carbapenemase-producingKlebsiella pneumoniaecontinues to decrease our meager supply of active agents, the ability of doripenem to produce CFU reductions in the presence of white blood cells (WBCs) using humanized exposures suggests the potential utility of this agent in combination against this increasingly problematic pathogen.