bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Alzheimer's Disease and Other Neurodegenerative Conditions by Shifting the Balance from Neurodegeneration to Neural Regeneration
Authors:   Phanes Biotech Inc., Malvern, PA, Iqbal Khalid ,   Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
Published: January 2024

Alzheimer’s disease (AD) is characterized histopathologically by neurodegeneration associated with numerous extracellular Abeta plaques and intraneuronal neurofibrillary tangles of hyperphosphorylated tau. Although studies have implicated both Aβ and tau pathologies in causing cognitive impairment, neurodegeneration, which accounts for the loss of brain mass to the tune of 200-300 g over the average disease progression of 7-10 years, is the most proximal pathology to the development of dementia in AD patients. Substantial evidence suggests that the Aβ and hyperphosphorylated tau (ptau) oligomers, rather than Aβ plaques and tau neurofibrillary tangles (NFTs), are the primary cause of neurodegeneration and dementia.
Human Factors Usability Analysis of the ArthroFree Wireless Surgical Camera
Authors: Griffin Pearl , Polito Patrick , Brownlee Leah , Ustin Jeff , Lee Kipum , Conner Craig
Published: January 2024

Conventional arthroscopy is performed with a narrow tube, the arthroscope, attached to a camera and two cables - one for power and one for fiber-optic light. The cables can be cumbersome, routed across or around the patient, and risk bridging the sterile and nonsterile fields. ArthroFree®, a wireless surgical camera for arthroscopy, features wireless communication and battery power and was designed to eliminate cable-associated burdens. An iterative product development process established the usability of ArthroFree. Feedback on ArthroFree’s design was received from 88 participants (82 surgeons and 6 other medical professionals) on ergonomics, ease of use, image quality, and patient experience following design validation testing (pre-FDA clearance; 76 participants) or clinical evaluation (post-FDA clearance; 12 participants). Participants were trained on the use of ArthroFree and then used the device in a surgical procedure performed on a cadaver, simulated model, or patient. Their experience was evaluated in a 13-statement human factors survey scored using a 5-point Likert scale. ArthroFree scored well in all survey statements, scoring “good” or “excellent” (4.5 mean score), suggesting users’ needs were satisfied in 91.30% of participants. Additionally, one-on-one interviews with surgeons gathered qualitative feedback on their independent experience with the ArthroFree device, providing key support for its introduction to the operating room.
Mechanisms of Haptotherapy, specific- and nonspecific therapy factors
Authors: Klabbers Gert A. , Boot Bob , Dekker Marjolein , Hagg Jan Willem
Published: January 2024

In addition to the insightful conversations, the experiential skill exercises and the affective contact-oriented therapeutic touch, the therapist-patient relationship in HT can also be seen as a specific therapy factor. While this article does not yet provide a conclusive rationale for the efficacy of haptotherapy, it offers a good overview of the specific and nonspecific therapy factors in haptotherapy and the presumed mechanisms of haptotherapy. Looking forward, the authors recommend e.g. demonstrating the importance of the body-subject experience. The authors’ aim with this article is to contribute to clear communication regarding the presumed mechanisms of haptotherapy, as well as their hope of contributing to future scientific research.
Patients Perceived Autonomy Support Affecting Treatment Motivation, Depression, Anxiety and Stress in CHD and Diabetes Mellitus
Authors: Idrees Saba , Hafeez Shazia , Azam Muhammad , Bhatti Sarfraz Hader
Published: January 2024

The study was aimed to investigate the impact of perceived autonomy support on treatment motivation, depression, anxiety and stress among patients of coronary heart disease and diabetes mellitus. Study was completed through correlational research design and 310 patients were selected as sample of study by applying convenient sampling technique. Three questionnaires were utilized as research instruments to measure variables; Health Care Climate Questionnaire (Ryan, 1995), Treatment Motivation Questionnaire (Ryan, 1995), and DASS (Lovibond, 1995). Findings revealed that treatment motivation was positively correlated with perceived autonomy support. Results suggest that there was negative correlation among depression, anxiety, stress and perceived autonomy support. Perceived autonomy support is significant positive predictor of treatment motivation. In addition no difference was investigated between gender on PAS and TM.  Level of depression anxiety and stress was reported higher among female as compared to male patients of CHD and DM. It was suggested that treatment motivation must be explored as mediator between PAS and DAS among patients in future.
Perinatal Outcome and Preventable Causes of Morbidity and Mortality in Eclampsia: A Cross-Sectional Observational Study in a Tertiary Hospital in Bangladesh
Authors: Sheuly Begum
Published: January 2024

Background: Eclampsia poses a substantial threat to perinatal health in developing countries, with Bangladesh experiencing a notable impact on infant well-being. This cross-sectional observational study, conducted at Enam Medical College Hospital, Savar, Dhaka, aimed to investigate perinatal outcomes in eclampsia patients and identify preventable causes of perinatal mortality and morbidity associated with this condition. The study period spanned from June 2015 to July 2017, with a focus on understanding the specific factors contributing to adverse perinatal events in this population. Methods: A total of 155 eclampsia patients were enrolled in the study, resulting in the delivery of 161 babies, including six sets of twins. The study employed a comprehensive observational approach, assessing maternal and fetal conditions to analyze their correlation with perinatal outcomes. Data collection and analysis were conducted in the Department of Obstetrics and Gynaecology at the tertiary hospital, employing standard protocols and statistical methods to derive meaningful insights. Results: The study revealed a perinatal death rate of 27.32%, with stillbirth accounting for 15.52% and early neonatal death for 11.80%. In contrast, 84.47% of babies were born healthy. Among live-born neonates, 27.94% experienced jaundice, while 30.88% had no complications. Prematurity emerged as a significant contributor to perinatal loss in eclampsia cases. The findings underscore the critical role of early referral of eclampsia patients, the implementation of timely resuscitative measures, and improved neonatal care as potential avenues to enhance perinatal outcomes. Conclusion: In conclusion, this study highlights the importance of addressing stillbirth as a predominant component of perinatal death in eclampsia cases. Prematurity was identified as a key factor contributing to adverse perinatal outcomes. Early referral of eclampsia patients and the implementation of resuscitative measures, coupled with enhanced neonatal care, are crucial interventions that can potentially mitigate perinatal morbidity and mortality associated with eclampsia in the context of a tertiary hospital setting in Bangladesh. These findings provide valuable insights for healthcare practitioners and policymakers to guide strategies aimed at improving perinatal outcomes in similar healthcare settings.
Dynamics of the polynomial differential systems
Authors: Fatima Feneniche , Salem Rezaoui Med
Published: January 2024

In general, there are several free parameters. By using a method introduced in a previous paper,  we obtain a sequence of algebraic a proximations to the bifurcationsets,in the parameter space
Socio-demographic characteristics associated with prevention practices of cervical cancer among women of reproductive age in internally displaced persons’ camps in Federal Capital Territory, Abuja.
Authors:   Department of Public Health, Babcock University., Jo-Amadi Harmony , Ogunsanmi Ololade ,   Department of Public Health, Babcock University., Johnson Faith
Published: January 2024

Cervical cancer is a public health menace affecting Nigerian women especially in the north-east. Insurgency in the northeast has displaced millions of women and girls to environments that increase their risks to cervical cancer. The persistent high mortality rates due to cervical cancer in Nigeria despite being a preventable disease are reasons to explore cervical cancer research among the vulnerable groups of women in IDP camps. Hence, this study aimed to assess socio-demographic characteristics associated with prevention practices of cervical cancer among women of reproductive age in IDP camps in Abuja. This was a cross-sectional descriptive study. The population was women of reproductive age (15-49) years in IDP camps in FCT, who consented through a validated interviewer administered questionnaire. The results showed the mean age of participants was 27.66 years and majority (43.1%) had at least secondary school education with 21.6% reporting non-formal education. The assessed preventive practices of cervical cancer showed a mean (SD) of 5.123 (3.323) which translates to 34.2% prevention level. Findings also reported a statistically significant relationship between age and cervical screening practices [OR=1.19; p = 0.37; 95% CI: (101-1.41)]. In addition, a statistically significant relationship was reported between marital status and cervical cancer screening [p = 0.36; OR = 2.01; 95% CI (1.04 – 3.877)] and getting information from clinic [ p = 0.01; OR = 2.55; 95% CI (1.17-5.59)]. Findings from this study revealed poor cervical cancer screening practices and recommends free periodic cervical cancer screening services for women and girls in IDP camps. Keywords: Attitudinal Disposition, Cervical Cancer, Prevention Practice, Socio-demographic characteristics, Reproductive age women.
Phytochemical Analysis and Antimicrobial Activity of Pongamia Pinnata: A Comprehensive Study
Authors: Sattar Aamir , Raza Syed Muhammad Fakhar , Sarfraz Sharmeen , Shahzad Muhammad , Farooq Muhammad Umar , Shabbir Asad
Published: January 2024

Background: Antimicrobial resistance (AMR) poses a significant global health challenge, exacerbated by the misuse of antimicrobial agents. With the rising prevalence of AMR in various plant and animal pathogens, there is an urgent need to explore alternative therapeutic options. Plant extracts, historically utilized for disease treatment, offer a promising avenue. Pongamia pinnata, also known as Indian Karanja, is notable for its rich phytochemical content and has been the subject of recent scientific interest.
Objective: The primary aim of this study is to investigate the antimicrobial efficacy of P. pinnata extracts, prepared using the Ultrasonic Assisted Extraction (UAE) method, against a range of bacterial and fungal species known to exhibit AMR.
Methods: In this study, an experimental laboratory design was utilized to evaluate the antimicrobial properties of Pongamia pinnata. Aqueous and alcoholic extracts of P. pinnata were prepared and subjected to biochemical analysis to identify the spectrum of phytochemicals present. The antimicrobial activity of these extracts was then assessed using the well-diffusion method against selected bacterial and fungal pathogens.
Results: Both aqueous and alcoholic extracts of P. pinnata demonstrated significant antimicrobial effects against the tested microbial species. The study highlights the potent antimicrobial properties of P. pinnata, attributed to its diverse phytochemical composition.
Conclusion: The findings of this study underscore P. pinnata as a valuable source of natural antimicrobial agents. Its efficacy against AMR pathogens suggests its potential application in the development of new treatments for infectious diseases. P. pinnata holds promise for medicinal use, particularly in contexts where conventional antibiotics are ineffective.
Using Deep Neural Networks to Improve the Precision of Fast-Sampled Particle Timing Detectors
Authors: Kocot Mateusz , Misan Krzysztof , Grzanka Leszek , Avati Valentina , Bossini Edoardo , Minafra Nicola
Published: January 2024

Measurements from particle timing detectors are often affected by the time walk effect caused by statistical fluctuations in the charge deposited by passing particles. The constant fraction discriminator (CFD) algorithm is frequently used to mitigate this effect both in test setups and in running experiments, such as the CMS-PPS system at the CERN’s LHC. The CFD is simple and effective but does not leverage all voltage samples in a time series. Its performance could be enhanced with deep neural networks, which are commonly used for time series analysis, including computing the particle arrival time. We evaluated various neural network architectures using data acquired at the test beam facility in the DESY-II synchrotron, where a precise MCP (MicroChannel Plate) detector was installed in addition to PPS diamond timing detectors. MCP measurements were used as a reference to train the networks and compare the results with the standard CFD method. Ultimately, we improved the timing precision by 8% to 23%, depending on the detector's readout channel. The best results were obtained using a UNet-based model, which outperformed classical convolutional networks and the multilayer perceptron.
Building a customer satisfaction system: Effective listening when the customer speaks
Authors: Stein Martin M. , Bowen Maurice
Published: May 2003

In the automobile and related industries, customer satisfaction has become a point of competitive
differentiation, thanks to J.D. Powers & Associates and other highly publicized surveyors. It can, however,
be more than a marketing tool. Customer needs can become the appropriate focus for organizational change
efforts. The more an organization understands its customers and aligns business processes with meeting
customers' needs, the more customers it can get. © 2003 Wiley Periodicals, Inc.
Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas
Authors: Vermi William , Bonecchi Raffaella , Facchetti Fabio , Bianchi Denise , Sozzani Silvano , Festa Silvana , Berenzi Angiola , Cella Marina , Colonna Marco
Published: May 2003

The present study has analysed the distribution and phenotype of dendritic cells (DCs) in primary cutaneous melanomas and sentinel lymph nodes by immunohistochemistry. In primary melanomas, an increase of DCs was found in the epidermis and the peritumoural area. Intraepidermal DCs were mostly CD1a+/Langerin+ Langerhans cells. Peritumoural DCs included a large population of DC‐SIGN+/mannose‐receptor+/CD1a− DCs, a small subset of CD1a+ DCs, and, remarkably, plasmacytoid monocytes/plasmacytoid DCs (PM/PDCs). The PM/PDCs, most likely recruited by SDF‐1 secreted by melanoma cells, produced type I interferon (IFN‐I), but the expression of the IFN‐α inducible protein MxA was extremely variable and very limited in the majority of cases. All DC subsets were predominantly immature. The peritumoural area also contained a minor subset of mature CD1a+ DCs. However, the small amount of local interleukin (IL)‐12 p40 mRNA and the naïve phenotype of 20–50% of peritumoural T‐lymphocytes are consistent with poor T‐cell stimulation or erroneous recruitment. In sentinel lymph nodes, notable expansion of mature CD1a+/Langerin+ DCs was observed. The paucity of intratumoural DCs and the predominant immature phenotype of peritumoural dermal DCs indicate defective maturation of primary cutaneous melanoma‐associated DCs, resulting in lack of T‐cell priming. These results may explain why melanoma cells grow despite the presence of infiltrating immune cells. Copyright © 2003 John Wiley & Sons, Ltd.
Surgical Influence on Th1/Th2 Balance and Monocyte Surface Antigen Expression and Its Relation to Infectious Complications
Authors: Tatsumi Hiroomi , Ura Hideki , Ikeda Shinichiro , Yamaguchi Koji , Katsuramaki Tadashi , Asai Yasufumi , Hirata Koichi
Published: May 2003

Abstract

Malignancy and operation for it cause several alterations in immune function that are considered to be concerned with the development of infectious complications. Forty‐three patients who underwent curative surgery for gastrointestinal malignancies were entered into this study and were divided into two groups, those with and those without postoperative infection. Changes in the proportion of Th1/Th2 subsets in CD4+ T cells and the expression of human leukocyte antigen (HLA)‐DR and CD16a molecules on monocytes were measured by flow cytometry before and after surgery. We performed intracellular cytokine stainings to exactly detect Th1/Th2 subsets. The proportions of interferon‐γ‐producing CD4+ T (Th1) cells in the preoperative state were almost equal in the two groups, and the proportion decreased on postoperative day (POD) 1 in both groups. On POD 7, the proportion of Th1 cells recovered to the preoperative level in the noninfection group, while the suppression was further reinforced in the infection group (26.8% versus 18.3%, p < 0.005). In contrast, the proportion of interleukin‐4‐producing CD4+ T (Th2) cells in the infection group (11.3%) was already suppressed in the preoperative state when compared with the noninfection group (17.3%, p < 0.005). Changes in HLA‐DR and CD16a expression on monocytes were similar to the changes in the proportion of Th1 cells. These results indicate that the suppression of Th1 cell and monocyte functions during the early phase of the postoperative course was directly related to the occurrence of infectious complications and that several immunological impairments have already occurred in the preoperative state in cancer patients.
Ceramide inhibits pancreatic β‐cell insulin production and mitogenesis and mimics the actions of interleukin‐1β
Authors: Sjöholm Åke
Published: May 2003

Ceramide, generated during sphingomyelinase‐induced sphingolipid cleavage, is considered an important mediator in cytokine signaling. The effects of endogenously generated and exogenously delivered ceramide on long‐term insulin secretion and replication by pancreatic β‐cells were investigated, and compared to the effects of interleukin 1β (ILI‐1β). Generation of β‐cell ceramide by exogenous sphingomyelinase, or addition of cell‐permeant ceramide analogs C2‐ceramide and C6‐ceramide, caused inhibitory effects on β‐cell insulin production and mitogenesis mimicing those evoked by IL‐1β. Hence, ceramide may be involved in transducing the cytostatic and cytotoxic actions of IL‐1β in the β‐cell.
Atomic structure at 2.5 Å resolution of uridine phosphorylase from E. coli as refined in the monoclinic crystal lattice
Authors: Morgunova E.Yu. , Mikhailov A.M. , Popov A.N. , Blagova E.V. , Smirnova E.A. , Vainshtein B.K. , Mao Ch. , Armstrong Sh.R. , Ealick S.E. , Komissarov A.A. , Linkova E.V. , Burlakova A.A. , Mironov A.S. , Debabov V.G.
Published: May 2003

Uridine phosphorylase from E. coli (Upase) has been crystallized using vapor diffusion technique in a new monoclinic crystal form. The structure was determined by the molecular replacement method at 2.5 Å resolution. The coordinates of the trigonal crystal form were used as a starting model and the refinement by the program XPLOR led to the R‐factor of 18.6%. The amino acid fold of the protein was found to be the same as that in the trigonal crystals. The positions of flexible regions were refined. The conclusion about the involvement in the active site is in good agreement with the results of the biochemical experiments.
Complete separation of the β,ε‐ and β,β‐carotenoid biosynthetic pathways by a unique mutation of the lycopene cyclase in the green alga, Scenedesmus obliquus
Authors: Bishop Norman I. , Urbig Thomas , Senger Horst
Published: May 2003

The mutant, C‐2A′‐34, lacks the β, ϵ‐carotenoids, α‐carotene, lutein and loroxanthin. When grown under heterotrophic or mixotropic conditions this strain develops significantly higher levels of β‐carotene and violaxanthin than does the original developmental mutant of Scenedesmus, C‐2A′. The decrease in chlorophyll a and chlorophyll b observed in C‐2A′‐34 is accompanied by the near absence of the LHC. The light intensity dependence of greening of this strain is comparable to that of C‐2A′; the loss of the β,ϵ‐carotenoids and modification of the pool of β,β‐carotenoids neither prevent the proximal pigment‐protein complexes of photosystems I and II from developing nor cause any short term photosensitivity. The increase in the β,β‐carotenoids in C‐2A′‐34 apparently compensates for the loss of the β,ε‐carotenoids required in formation of the proximal and distal antennae systems but not in the LHCs.
Localization of a sequential B‐epitope in the VP2 protein of hepatitis A virus
Authors: Kulik Liudmila N. , Ivanov Vadim S. , Tchikin Leonid D. , Ostrovsky Andrey G. , Ivanov Vadim T.
Published: May 2003

A set of synthetic peptides derived from the capsid proteins of hepatitis A virus was used to search for B‐epitopes. Peptides from the 115–139 region of the VP1 protein, from the 69–99 region of the VP2 protein and peptide 137–150 from the VP3 protein were found to react with monoclonal and polyclonal anti‐HAV antibodies. MAPs based on 64–80 and 66–80 fragments of VP3 were reactive as well. Peptides, their conjugates with protein carriers and MAPs were used for antipeptide antibody production. Only free peptide 69–99 from the VP2 protein caused formation of HAV binding antibodies.
Copper chloride, an inhibitor of protein import into chloroplasts
Authors: Seedorf Matthias , Soll Jürgen
Published: May 2003

We have used the oxidant CuCl2 to study its effect on precursor protein import into chloroplasts and on the components involved. CuCl2 reversibly oxidizes thiol groups, which in turn, can form disulfide bridges. Concentrations of 40 μM CuCl2 almost completely inhibit precursor protein binding and subsequent translocation into chloroplasts. This inhibitory effect is reversible by a dithiothreitol treatment. Disulfide bridges, which form upon oxidation by CuCl2, are build up intramolecular and intermolecular, if the thiol groups are in close vicinity to each other. CuCl2 can thus be used as a thiol cleavable crosslinker without an additional spacer distance between the two targets. When purified outer envelope membranes were treated with CuCl2, a hetero oligomeric complex is detected, consisting of OEP86, OEP75 and OEP34, indicating the close vicinity and protein‐protein interaction between polypeptides in situ, which are involved in protein translocation into chloroplasts.
A novel mechanism of glutamine synthetase inactivation by ammonium in the cyanobacterium Synechocystis sp. PCC 6803. Involvement of an inactivating protein
Authors: Reyes J.C. , Florencio F.J.
Published: May 2003

The glutamine synthetase of the cyanobacterium Synechocystis sp. PCC 6803 can be inactivated in vivo by ammonium addition by a new mechanism that involves the binding to the enzyme of an inactivating factor. This binding provokes a different mobility of the inactive enzyme with respect to the active form in non‐denaturing PAGE, but not in SDS‐PAGE. This modification of glutamine synthetase is for the first time visualized by Western blot analysis of the active and inactive forms. Cross‐linking experiments using 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC) demonstrate the existence of two main complexes of 56 kDa and 67 kDa between the inactivating factor and the glutamine synthetase subunit (53 kDa) in the inactive but not in the active form of glutamine synthetase.
Identification of a mitochondrial form of kynurenine aminotransferase/glutamine transaminase K from rat brain
Authors: Malherbe Pari , Alberati-Giani Daniela , Köhler Christer , Cesura Andrea M.
Published: May 2003

A soluble aminotransferase with kynurenine aminotransferase (KAT) activity has been recently isolated from rat brain. This enzyme corresponds to a cytosolic form of glutamine transaminase K (GTK). In addition to the cytosolic enzyme, a mitochondrial‐associated form of this KAT/GTK also exists. In the present work we have isolated a rat brain cDNA clone encoding a KAT/GTK enzyme identical to the soluble form but carrying an additional stretch of 32 amino acids at its NH2‐terminus. Several structural features of this sequence resemble those of leader peptides for mitochondrial import. Evidence that the isolated cDNA encoded for mitochondrial KAT/GTK was obtained after transfection of HEK‐293 cells with the cDNA coding for this new KAT/GTK isoenzyme. In fact, a significant enrichment of both KAT and GTK enzymatic activities was found in the crude mitochondrial fraction of the transfected cells.
Green‐fluorescent protein mutants with altered fluorescence excitation spectra
Authors: Ehrig Torsten , O'Kane Dennis J. , Prendergast Franklyn G.
Published: May 2003

Using random mutagenesis and visual selection of fluorescent clones, we have isolated a T2031 and a E222G mutant of the Aequorea green‐fluorescent protein. Each mutant has one of the two fluorescence excitation bands of the wild type deleted and retains the other without a wavelength shift. This finding is consistent with each excitation band corresponding to a distinct spectroscopic state of the chromophore. Both mutations are single amino acid exchanges which in the linear sequence are located remotely from the chromophore but in the folded protein may be situated in its vicinity. We conclude that the mutations influence the fluorescence properties by changing the interactions between the chromophore and its protein environment.
Effect of the Ca2+ channel activator CGP 28392 on reactivation of oxygen evolution of Ca2+‐depleted photosystem II
Authors: Krieger Anja
Published: May 2003

The effect of the Calcium channel activator, CGP 28392, on the reactivation of oxygen evolution in Ca2+‐depleted Photosystem II (PS II) particles has been investigated. Ca2+‐binding is associated with a functional water splitting complex of PS II. In the presence of the activator, a low affinity site of Ca2+‐binding is converted into a high affinity binding site. Following removal of the extrinsic proteins (17 and 23 kDa), any effect of the activator is no longer observed. Ca2+ channel inhibitors can inhibit the Ca2+‐dependent reactivation of oxygen evolution. The activator partially protects against this type of inhibition. It is suggested that the extrinsic proteins form a Ca2+ channel‐like structure at the donor side of PS II.
Inhibition of U‐937 membrane‐associated cathepsin G by GP 120 (IIIB) and V3 loop‐derived peptides from several strains of HIV‐1
Authors: Avril Laurence-Emmanuelle , di Martino-Ferrer Michèle , Brillard-Bourdet Michèle , Gauthier Francis
Published: May 2003

A cell surface‐associated cathepsin G has been reported to be a possible complementary factor for HIV‐1 infection of U‐937 cells. The effect of recombinant gp120 (IIIB) and a series of V3 loop peptides derived from the sequence of different strains of HIV on the activity of U‐937 cathepsin G was assayed. The sequence on the N‐terminal side of the highly conserved GPGRAF V3 loop segment was required for interaction with cathepsin G. The inhibition was stable for several hours and there was no cleavage of the peptides derived from the HIV‐1(IIIB) strain. Recombinant gp120 (IIIB) also remained uncleaved after incubation with cathepsin G for 3 h, but some cleavage occurred, generating 2 fragments (50 kDa and 70 kDa), after 16 h. Linear peptides derived from HIV‐1 Mal, ELI, MN, CDC4 and SF162 strains, and consensus V3 peptides all had inhibitory properties towards cathepsin G, although they were significantly cleaved after one hour. The cleavage site was at the carboxy‐terminus of Tyr323 which is conserved in all these HIV‐1 strains but not in HIV‐1(IIIB). There was no cleavage at the Arg residue of the GPGRAF sequence, whatever the V3 peptide sequence, the amount of proteinase, or the incubation time. We conclude that the inhibition of membrane‐associated cathepsin G of U‐937 cells by the gp120 V3 loop of HIV‐1 does not occur via a Kunitz‐type mechanism, and that the proteinase‐V3 loop interaction does not result in a significant cleavage of the V3 loop, though it has been suggested that this event is required for the entry phase of the virus.
Pseudomonas aeruginosa aliphatic amidase is related to the nitrilase/cyanide hydratase enzyme family and Cys166 is predicted to be the active site nucleophile of the catalytic mechanism
Authors: Novo Carkos , Tata Renée , Clemente Alda , Brown Paul R.
Published: May 2003

A database search indicated homology between some members of the nitrilase/cyanide hydratase family, Pseudomonas aeruginosa and Rhodococcus erythropolis amidases and several other proteins, some of unknown function. BLOCK and PROFILE searches confirmed these relationships and showed that four regions of the P. aeruginosa amidase had significant homology with corresponding regions of nitrilases. A phylogenetic tree placed the P. aeruginosa and R. erythropolis amidases in a group with nitrilases but separated other amidases into three groups. The active site cysteine in nitrilases is conserved in the P. aeruginosa amidase indicating that Cys166 is the active site nucleophile.
Altered P450 activity associated with direct selection for fungal azole resistance
Authors: Joseph-Horne T. , Hollomon D. , Loeffler R.S.T. , Kelly S.L.
Published: May 2003

Azole antifungals inhibit CYP51A1‐mediated sterol 14α‐demethylation and the mechanism(s) of resistance to such compounds in Ustilago maydis were examined. The inhibition of growth was correlated with the accumulation of the substrate, 24‐methylene‐24,25‐dihydrolanosterol (eburicol), and depletion of ergosterol. Mutants overcoming the effect of azole antifungal treatment exhibited a unique phenotype with leaky CYP51A1 activity which was resistant to inhibition. The results demonstrate that alterations at the level of inhibitor binding to the target site can produce azole resistance. Similar changes may account for fungal azole resistance phenomena in agriculture, and also in medicine where resistance has become a problem in immuno‐compromised patients suffering from AIDS.
Evidence for specific, high‐affinity binding sites for a proteinaceous elicitor in tobacco plasma membrane
Authors: Wendehenne David , Binet Marie-Noëlle , Blein Jean-Pierre , Ricci Pierre , Pugin Alain
Published: May 2003

Binding of cryptogein, a proteinaceous elicitor, was studied on tobacco plasma membrane. The binding of the [125I]cryptogein was saturable, reversible and specific with an apparentKdof 2 nM. A single class of cryptogein binding sites was found with a sharp optimum pH for binding at about pH 7.0. The high‐affinity correlates with cryptogein concentrations required for biological activity in vivo.
Expression of cytochrome P450 CYP1B1 in breast cancer
Authors: McKay Judith A. , Melvin William T. , Ah-See A.K. , Ewen Stanley W.B. , Greenlee William F. , Marcus Craig B. , Burke M.Danny , Murray Graeme I.
Published: May 2003

The expression of CYP1B1 has been identified in breast cancer using the reverse transcriptase‐polymerase chain reaction and immunoblotting. CYP1B1 mRNA was expressed in the majority of breast tumours and immunoblotting of breast tumours identified a single protein band of molecular weight 60 kDa corresponding to the predicted molecular weight of human CYP1B1. This is the first study to identify CYP1B1 expression in a tumour where it may represent a previously unknown pathway for the metabolism of oestradiol and chemotherapeutic drugs.
The effect of heparin on Cu2+‐mediated oxidation of human low‐density lipoproteins
Authors: Albertini Riccardo , Rindi Simonetta , Passi Alberto , Palladini Giuseppina , Pallavicini Giosue , De Luca Giancarlo
Published: May 2003

The effect of heparin (HE) on the susceptibility of human low‐density lipoprotein (LDL) to Cu2+‐induced oxidation was investigated by monitoring conjugated diene formation. HE did not modify the maximum formation of conjugated diene, but increased markedly the lag phase. The plot of change in oxidation rate vs. time showed that the absolute value of V
max was dependent on Cu2+ concentration and that HE increased the time necessary to reach V
max. The value of constant K (the Cu2+ concentration producing a t
lag of twice the minimum value) increased in the presence of HE, whereas the value of t
min (the time theoretically required for LDL oxidation at an infinite Cu2+ concentration) was not substantially affected. These results indicate that HE might play a protective antioxidant effect on LDL, probably affecting both the structural properties of the particle and the amount of Cu2+ available for the oxidation.
Precise mapping of the tms1 binding site on p53
Authors: Wagner Peter , Fuchs Annette , Prowald Alexandra , Montenarh Mathias , Nastainczyk Wolfgang
Published: May 2003

Originally identified as multicopy suppressor of a lethal growth arrest caused by expression of a tumour mutant cDNA of p53 in fission yeast the tms1 gene product was found to form stable complexes with p53 in yeast. By using purified recombinant proteins multimeric complexes of tms1 and p53 could be demonstrated and recently the p53 binding site on the tms1 protein was established to the sequence YYITTEDFCT (aa 116–125) in the vicinity of a well conserved cell division motif. Here we report the precise mapping of the tms1 binding site on the p53 protein to the sequence LQIRGRERFE (aa 330–339) which defines a new functional domain on the p53 protein.
Crystal structure of an uncleaved α1‐antitrypsin reveals the conformation of its inhibitory reactive loop
Authors: Hyun Kyu Song  , Kee Nyung Lee  , Ki-Sun Kwon  , Myeong-Hee Yu  , Se Won Suh
Published: May 2003

The crystal structure of a recombinant human α
1‐antitrypsin, in the uncleaved and uncomplexed state, has been determined by X‐ray crystallographic methods and refined to an R‐factor of 18.4% for 8.0–3.46 Å data with good stereochemistry. This structure provides the first view at the inhibitory loop and the central β‐sheet A of the uncleaved α
1‐antitrypsin. The reactive loop takes a distorted helical conformation and no pre‐insertion of two residues in the reactive loop into the β‐sheet A is observed. The present structure is largely in agreement with the model predicted by Engh, Wright, and Huber [Prot. Eng. 3 (1990) 469–477].
Purification and reconstitution of activity of Saccharomyces cerevisiae P450 61, a sterol Δ22‐desaturase
Authors: Kelly Steven L. , Lamb David C. , Corran Andrew J. , Baldwin Brian C. , Parks Leo W. , Kelly Diane E.
Published: May 2003

P450 was purified from microsomal fractions of a strain of Saccharomyces cerevisiae which contained detectable P450 despite the disruption of CYP51A1. The P450 had a molecular mass of 58 kDa, similar to P450 51A1, and in a reconstituted assay with rabbit NADPH‐P450 reductase and dilauryl phosphotidylcholine exhibited activity for conversion of ergosta‐5,7‐dienol into ergosterol. N‐Terminal amino acid sequencing of the purified protein corresponded to the translated sequence of P450 61 which was recently identified during sequencing of chromosome XIII. This allowed the function of this family of P450 to be identified as sterol Δ
22‐desaturation in the pathway of ergosterol biosynthesis.
Immunological evidence that HMG‐CoA reductase kinase‐A is the cauliflower homologue of the RKIN1 subfamily of plant protein kinases
Authors: Ball Kathryn L. , Barker Jacqueline , Halford Nigel G. , Hardie D.Grahame
Published: May 2003

Three different antibodies against theRKIN1andBKIN12gene products from rye and barley recognized the 58 kDa subunit of HMG‐CoA reductase kinase‐A (HRK‐A) fromBrassica oleraceaon Western blots. HRK‐A was also detected by an antipeptide antibody in enzyme‐linked immunoassays, and this was competed by the peptide antigen. HRK‐A was not recognized by antibodies against plant, mammalian andSaccharomyces cereviseaerelatives of RKIN1, i.e. wheat PKABA1, rat AMP‐activated protein kinase andS. cerevisiaeSnf1p. RKIN1/HMG‐CoA reductase kinase‐A are now among the first protein kinases in plants to be well characterized at both the molecular and biochemical levels.
Co‐selection of cognate antibody‐antigen pairs by selectively‐infective phages
Authors: Krebber Claus , Spada Stefania , Desplancq Dominique , Plückthun Andreas
Published: May 2003

We have developed a chloramphenicol resistant derivative of fd phage with which cognate pairs of antibodies and antigens can be selected. The phage genome encodes a fusion of single‐chain antibody to the C‐terminal domain of gIIIp, rendering the phage non‐infective. The antigen fused to the N‐terminal domains of gIIIp is encoded in the same phage genome. Antigen and antibody fusion interact with each other in the periplasm of the phage‐producing cell, restoring infectivity. This system has a very low background and will allow simultaneous randomisation of antibody and antigen.
Differential regulation of cardiac heme oxygenase‐1 and vascular endothelial growth factor mRNA expressions by hemin, heavy metals, heat shock and anoxia
Authors: Eyssen-Hernandez Rodrigo , Ladoux Annie , Frelin Christian
Published: May 2003

Increasing attention has been paid to the effects of hypoxia, heavy metals and heat shocks on gene expression and to the similarities in their actions. This paper compares mRNA levels of two putative hypoxia, heavy metal and heat shock sensitive genes: heme oxygenase‐1 (HO‐1) and vascular endothelial growth factor (VEGF) in myocyte‐enriched cultures of neonatal rat heart cells. HO‐1 mRNA expression is stimulated by hemin, Cd2+, Co2+ and heat shocks but not by Ni2+ or Mn2+. It is stimulated by long (13 h) but not by short (4 h) periods of anoxia. Conversely, VEGF mRNA expression is stimulated by short as well as long periods of anoxia, by Cd2+, Co2+, Ni2+ and Mn2+ but not by hemin or heat shocks. The results suggest that heavy metals, anoxia and heat shocks exert their effects on VEGF and HO‐1 mRNA expression through separate though potentially overlapping mechanisms. Increased expressions of HO‐1 and VEGF may be both cardioprotective under hypoxic/ischemic conditions.
Dynamics of the cytosolic chelatable iron pool of K562 cells
Authors: Breuer William , Epsztejn Silvina , Ioav Cabantchik Z.
Published: May 2003

The labile iron pool of cells (LIP) constitutes the primary source of metabolic and catalytically reactive iron in the cytosol. We studied LIP homeostasis in K562 cells using the fluorescent metal‐sensitive probe calcein. Following brief exposure to iron(II) salts or to oxidative or reductive stress, LIP rose by up to 120% relative to the normal level of 350 nM. However, the rate of recovery to normal LIP level differed markedly with each treatment (respectiveof 27, 65–88 and ≤17 min). We show that the capacity of K562 cells to adjust LIP levels is highly dependent on the origin of the LIP increase and on the pre‐existing cellular iron status.
Using production and transfer batches in flowshops under MRP control
Authors: Veral Emre
Published: May 2003

This study investigates the impact of using material flow control and order release throttling mechanisms on shop floor effectiveness in MRP based order release environments. The research methodology involves simulation experiments conducted using a flow shop model of a manufacturing and assembly setting. Specifically addressed issue is the decoupling of shop floor control decisions from MRP release schedules. This decoupling effect is implemented through the use of smaller production batch sizes, staggering the release of the production quantities to initial work stations, and using transfer batches.

In a 14 parts/9 processes simulation environment, the effects of shop floor control decisions are evaluated based on average hours of work in process inventory and average number of tardy units for the simulated planning horizon. Experimental results suggest that increasing material flow frequency through smaller process and transfer batch sizes have significant consequences on inventory and service levels. By separating work in process inventories into two components, it is shown that reducing batch sizes may not affect inventory levels of asynchronized assembly units (i.e. component delay). The results also indicate the presence of a possible threshold effect for throttling and staggering work order releases where service levels are compromised and marginal gain on inventory reduction diminishes.
Forecasting system parent group formation: An empirical application of cluster analysis
Authors: Fliedner Eugene B. , Lawrence Barry
Published: May 2003

The focus of this empirical investigation is twofold. First, an examination of formal hierarchical forecasting system structural parameters is reported. Four formal experimental factors used to define the hierarchical forecasting system are examined. These factors are evaluated in a controlled comparison by means of parametric statistical analysis. Second, a comparative analysis of formal hierarchical forecasting system performance with (1) an informal hierarchical strategy, and (2) a traditional forecasting approach is presented. The best performing combination of factor level settings identified in the examination of formal hierarchical forecast strategies is subsequently evaluated in the second part of this analysis by means of paired difference comparisons with (1) a randomized, informal approach, and (2) a common forecast strategy over the same time series data. Traditional measures of forecast accuracy are used as dependent performance criteria.
Comparing the effects of cellular and functional manufacturing on employees' perceptions and attitudes
Authors: Shafer Scott M. , Tepper Bennett J. , Meredith Jack R. , Marsh Robert
Published: May 2003

The purpose of this study was to investigate whether or not CM represents a source of job enrichment that ultimately translates into positive outcomes for the individual and the organization. Two hypotheses were formulated and tested: (1) job characteristics mediate the effects of CM on employees' attitudes, and (2) growth need strength moderates the effects of job characteristics on attitudes. To test the hypotheses, data were collected at two manufacturing facilities in the midwest that produce generic clothing. At plant 1, 85% of the production employees worked in cellular configurations, while 100% of the production at plant 2 was performed in cells. Sixty‐eight workers (29 workers from functional departments and 39 cellular workers) completed surveys at plant 1, while eighty‐five cellular workers completed surveys at plant 2.

The results indicate that CM has both positive and negative effects on employees' attitudes. Consistent with the job characteristics model, job characteristics positively mediate the effects of CM on employees' attitudes. However, the findings indicate that CM has negative direct effects on employees' attitudes suggesting that unmeasured variables such as reliance on co‐workers mediate the negative effects of CM. There was no support for the prediction that growth need strength moderates the effects of CM on attitudes. Several complementary explanations for our findings are discussed.
Operating decisions, supplier availability and quality: An empirical study
Authors: Kekre Sunder , Murthi B.P.S. , Srinivasan Kannan
Published: May 2003

In the just‐in‐time (JIT) philosophy, purchasing strategies advocate the use of fewer sources of supply to enable a firm to improve the quality of its products. However, there is paucity of empirical evidence in support of the theory. We develop a model by integrating concepts from manufacturing, marketing, and business strategy to better understand the links between operating decisions of the firm, supplier availability, and product quality. We empirically test the hypotheses using cross‐sectional PIMS data. Our analysis shows that operating decisions and environmental factors such as wider product lines, lower levels of competition, and greater frequency of product changes increase the likelihood of a firms' reduction of supplier base, which in turn raises quality levels.
Plant objectives as revealed by shop floor activities
Authors: Miller Robert A. , Ramnath Prasad
Published: May 2003

One problem management scientists face in adapting heuristics to actual applications on the factory floor is eliciting preferences from plant managers about the importance of different jobs. Even when the goal of the firm is apparently as straightforward as profit maximization, reputation and goodwill can play such critical roles in affecting the revenue flow, that exclusively focusing on a few key variables (such as the price of individual items, their production times, and the raw material cost) may give a distorted picture about which jobs the firm values most highly. This paper offers a new way of eliciting preferences, utilizing high‐frequency data on plant operations that are routinely collected by many firms, in order to infer the direct and indirect cost of scheduling jobs, from actual job schedules that managers reveal by their choices. We then apply our method to a scheduling problem in a steel tube manufacturing plant. After estimating the preferences of the plant manager, we demonstrate how our estimates can be used to evaluate heuristics for hard scheduling problems, and to forecast the effects of structural change, such as expansion in plant capacity, or shifts in job order flow.
Thyroid hormone and uncoupling proteins
Authors: Lanni A. , Moreno M. , Lombardi A. , Goglia F.
Published: May 2003

Thyroid hormone (TH/T3) exerts many of its effects on energy metabolism by affecting gene transcription. However, although this is an important target for T3, only a limited number of T3‐responsive genes have been identified and studied. Among these, the genes for uncoupling proteins (UCPs) have attracted the interest of scientists. Although the role of UCP1 seems quite well established, uncertainty surrounds the physiological function of the recently discovered UCP1 analogs, UCP2 and UCP3. The literature suggests that T3 affects both the expression and the activity of each of these UCPs but further studies are needed to establish whether the mechanisms activated by the hormone are the same. Recently, because of their larger range of expression, much attention has been devoted to UCP2 and UCP3. Most detailed studies on the involvement of these proteins as mediators of the effects of T3 on metabolism have focused on UCP3 because of its expression in skeletal muscle. T3 seems to be unique in having the ability to stimulate the expression and activity of UCP3 and this may be related to the capacity of T3 to activate the integrated biochemical processes linked to UCP activity, such as those related to fatty acids, coenzyme Q and free radicals.
In vivo stabilization of nuclear retinoid X receptor α in the presence of peroxisome proliferator‐activated receptor α
Authors: Tanaka Naoki , Hora Kazuhiko , Makishima Hideki , Kamijo Yuji , Kiyosawa Kendo , Gonzalez Frank J. , Aoyama Toshifumi
Published: May 2003

Retinoid X receptor α (RXRα) can reveal diverse functions through forming a heterodimer with peroxisome proliferator‐activated receptor α (PPARα). However, the mechanism of regulation of the cellular RXRα level is unclear. Thus, quantitative change of RXRα was investigated in mouse liver. Nuclear RXRα level was constitutively lower in PPARα‐null mice than in wild‐type mice. The level was also increased by clofibrate treatment in wild‐type mice without a concomitant increase of RXRα mRNA, but not in PPARα‐null mice. Pulse chase experiments demonstrated that the presence of PPARα and its activation by ligands significantly affected the stability of nuclear RXRα. These findings suggest a novel regulatory mechanism of nuclear RXRα in vivo.