bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and isolation of embryonic stem cells in reproductive endocrinology: theoretical protocols for conservation of human embryos derived from in vitro fertilization
Authors: Sills Eric Scott , Takeuchi Takumi , Tanaka Noriko , Neri Queenie V , Palermo Gianpiero D 
Published: July 2005

Abstract

Background
Embryonic stem cells (ESC) are pluripotent cells obtained from the inner cell mass (ICM) of blastocysts derived from in vitro culture associated with reproductive endocrinology therapy. Human ESCs are regarded as highly significant since they retain the capacity to differentiate into any of approximately 200 unique cell types. Human ESC research is controversial because to acquire such cells, the ICM of human blastocysts must be manipulated in a way that renders embryos nonviable and unsuitable for transfer in utero. Techniques to yield competent ESCs with conservation of source blastocysts would satisfy many objections against ESC research, but at present such approaches remain largely untested.

Results and discussion
We contrast experimental culture of single blastomeres obtained by 1) non-destructive biopsy of embryos destined for transfer, and 2) isolation of karyotypically normal blastomeres from disaggregated ("dead") embryos considered unsuitable for transfer, and evaluate these approaches with regard to production of ESCs. Pluripotency was confirmed by morphological criteria and by quantification of divergent homeodomain proteins specific to undifferentiated cell development. Following ESC isolation and identification, assessment was conducted according to a novel ESC grading system, also proposed here.

Conclusion
The role of reproductive endocrinology in ESC research remains paramount. In this report, we hypothesize new and expand on existing strategies having the potential to enhance human ESC isolation, identification and in vitro maintenance.
Re-evaluating the role of natural killer cells in innate resistance to herpes simplex virus type 1
Authors: Halford William P , Maender Jennifer L , Gebhardt Bryan M 
Published: July 2005

AbstractBackgroundInterferon-γ acts to multiply the potency with which innate interferons (α/β) suppress herpes simplex virus type 1 (HSV-1) replication. Recent evidence suggests that this interaction is functionally relevant in host defense against HSV-1. However, it is not clear which WBCs of the innate immune system, if any, limit HSV-1 spread in an IFN-γ dependent manner. The current study was initiated to determine if natural killer (NK) cells provide innate resistance to HSV-1 infection, and if so to determine if this resistance is IFN-γ-dependent.ResultsLymphocyte-deficientscidorrag2-/-mice were used to test four predictions of the central hypothesis, and thus determine if innate resistance to HSV-1 is dependent on1.NK cell cytotoxicity,2.NK cells,3.WBCs, or4.the IFN-activated transcription factor, Stat 1. Loss of NK cell cytotoxic function or depletion of NK cells had no effect on the progression of HSV-1 infection inscidmice. In contrast, viral spread and pathogenesis developed much more rapidly inscidmice depleted of WBCs. Likewise, loss of Stat 1 function profoundly impaired the innate resistance ofrag2-/-mice to HSV-1.ConclusionLymphocyte-deficient mice possess a very tangible innate resistance to HSV-1 infection, but this resistance is not dependent upon NK cells.
Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein
Authors: Bossart Katharine N , Mungall Bruce A , Crameri Gary , Wang Lin-Fa , Eaton Bryan T , Broder Christopher C 
Published: July 2005

Abstract

Background
The recent emergence of four new members of the paramyxovirus family has heightened the awareness of and re-energized research on new and emerging diseases. In particular, the high mortality and person to person transmission associated with the most recent Nipah virus outbreaks, as well as the very recent re-emergence of Hendra virus, has confirmed the importance of developing effective therapeutic interventions. We have previously shown that peptides corresponding to the C-terminal heptad repeat (HR-2) of the fusion envelope glycoprotein of Hendra virus and Nipah virus were potent inhibitors of both Hendra virus and Nipah virus-mediated membrane fusion using recombinant expression systems. In the current study, we have developed shorter, second generation HR-2 peptides which include a capped peptide via amidation and acetylation and two poly(ethylene glycol)-linked (PEGylated) peptides, one with the PEG moity at the C-terminus and the other at the N-terminus. Here, we have evaluated these peptides as well as the corresponding scrambled peptide controls in Nipah virus and Hendra virus-mediated membrane fusion and against infection by live virus in vitro.

Results
Unlike their predecessors, the second generation HR-2 peptides exhibited high solubility and improved synthesis yields. Importantly, both Nipah virus and Hendra virus-mediated fusion as well as live virus infection were potently inhibited by both capped and PEGylated peptides with IC50 concentrations similar to the original HR-2 peptides, whereas the scrambled modified peptides had no inhibitory effect. These data also indicate that these chemical modifications did not alter the functional properties of the peptides as inhibitors.

Conclusion
Nipah virus and Hendra virus infection in vitro can be potently blocked by specific HR-2 peptides. The improved synthesis and solubility characteristics of the second generation HR-2 peptides will facilitate peptide synthesis for pre-clinical trial application in an animal model of Henipavirus infection. The applied chemical modifications are also predicted to increase the serum half-life in vivo and should increase the chance of success in the development of an effective antiviral therapy.
The expression of the ubiquitin ligase subunit Cks1 in human breast cancer
Authors: Slotky Merav , Shapira Ma'anit , Ben-Izhak Ofer , Linn Shai , Futerman Boris , Tsalic Medy , Hershko Dan D 
Published: July 2005

Abstract
Introduction
Loss of the cell-cycle inhibitory protein p27Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27Kip1 and Skp2 expression and to tumor aggressiveness.

Methods
The expressions of Cks1, Skp2, and p27Kip1 were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan–Meier method.

Results
The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27Kip1 (r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen.

Conclusion
These results suggest that Cks1 is involved in p27Kip1 down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer.
Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1
Authors: Zhuang Dazhong , Qiu Yaling , Haque S Jaharul , Dong Fan 
Published: July 2005

AbstractMutations in the granulocyte-colony stimulating factor receptor (G-CSF-R) gene resulting in carboxy terminal truncation have been associated with acute myeloid leukemia (AML). The truncated G-CSF-R from AML patients mediate enhanced and prolonged activation of signal transducer and activator of transcription 5 (Stat5). It has been shown that Src homology-2 (SH2)-containng tyrosine phosphatase-1 attenuates the intensity of G-CSF-induced Stat5 activation through interacting with the carboxy terminus of the G-CSF-R. Using a series of tyrosine-to-phenylalanine substitution mutants, we show here that tyrosine (Tyr) 729, located in the carboxy terminus of the G-CSF-R, controls the duration of G-CSF-stimulated activation of Stat5, Akt, and extracellular signal-regulated kinase 1/2. It is interesting that activation of these signaling molecules by G-CSF was prolonged by pretreating cells with actinomycin D or cyclohexamide, suggesting that de novo protein synthesis is required for appropriate termination of G-CSF-R signaling. The transcripts for suppressor of cytokine signaling 3 (SOCS3) and SOCS1 were up-regulated rapidly upon G-CSF stimulation. Expression of SOCS3 or SOCS1, but not SOCS2 and cytokine-inducible SH2 domain-containing protein, completely suppressed G-CSF-induced Stat5 activation but had only a weak effect on Stat5 activation mediated by the receptor mutant lacking Tyr 729. SOCS1 and SOCS3 also inhibited G-CSF-dependent cell proliferation, but the inhibitory effect of the two SOCS proteins on cell proliferation was diminished when Tyr 729 of the G-CSF-R was mutated. These data indicate that Tyr 729 of the G-CSF-R is required for SOCS1- and SOCS3-mediated negative regulation of G-CSF-R signaling and that the duration and intensity of G-CSF-induced Stat5 activation are regulated by two distinct mechanisms.
Flagellin enhances NK cell proliferation and activation directly and through dendritic cell-NK cell interactions
Authors: Tsujimoto Hironori , Uchida Takefumi , Efron Philip A , Scumpia Philip O , Verma Amrisha , Matsumoto Tadashi , Tschoeke Sven K , Ungaro Ricardo F , Ono Satoshi , Seki Shuhji , Clare-Salzler Michael J , Baker Henry V , Mochizuki Hidetaka , Ramphal Reuben , Moldawer Lyle L 
Published: July 2005

AbstractFlagellin, the principal component of bacterial flagella, is a ligand for Toll-like receptor 5 (TLR5) or TLR11 and contributes to systemic inflammation during sepsis through activation of dendritic cells (DCs) and other cells of the innate immune system. Here, we report that flagellin and the TLR4 ligand, lipopolysaccharide (LPS), induced phenotypic and functional maturation of murine bone marrow-derived DCs and enhanced DC accumulation in the draining popliteal lymph node following their footpad injection. It is interesting that flagellin injection enhanced myeloid (CD8α−1) and plasmacytoid (plasmacytoid DC antigen+ B220+) DC subsets, whereas LPS only increased myeloid DCs in the draining lymph node. In addition, the footpad injection of flagellin or LPS induced significant CD4+ T cell activation in the draining popliteal lymph node, as judged by increased CD69 or CD25 expression. We illustrate, for the first time, that flagellin also increases natural killer (NK) cell number and activation status in the draining lymph node after footpad injection. Using coculture with enriched carboxy-fluorescein diacetate succinimidyl ester-labeled NK cells, flagellin-treated DCs induce significant NK cell proliferation and activation. In fact, direct treatment of NK cells with flagellin induces a greater increase in cell proliferation than treatment with LPS. In contrast, flagellin treatment of NK cells was not a strong inducer of interferon-γ (IFN-γ) production, indicating that NK cell proliferation and IFN-γ production may be regulated differentially. These data suggest that flagellin is a capable maturation agent for murine myeloid-derived DCs, and flagellin-activated DCs and flagellin itself are potent inducers of NK cell proliferation.
The kringle domain of urokinase-type plasminogen activator potentiates LPS-induced neutrophil activation through interaction with αVβ3 integrins
Authors: Kwak Sang-Hyun , Mitra Sanchayita , Bdeir Khalil , Strassheim Derek , Park Jong Sung , Kim Jael Yeol , Idell Steven , Cines Douglas , Abraham Edward 
Published: July 2005

AbstractUrokinase plasminogen activator (uPA) is a serine protease that catalyzes the conversion of plasminogen to plasmin. In addition, uPA has been shown to have proinflammatory properties, particularly in potentiating lipopolysaccharide (LPS)-induced neutrophil responses. To explore the mechanisms by which uPA exerts these effects, we examined the ability of specific uPA domains to increase cytokine expression in murine and human neutrophils stimulated with LPS. Whereas the addition of intact uPA to neutrophils cultured with LPS increased mRNA and protein levels of interleukin-1β, macrophage-inflammatory protein-2, and tumor necrosis factor α, deletion of the kringle domain (KD) from uPA resulted in loss of these potentiating effects. Addition of purified uPA KD to LPS-stimulated neutrophils increased cytokine expression to a degree comparable with that produced by single-chain uPA. Inclusion of the arginine-glycine-aspartic but not the arginine-glycine-glutamic peptide to neutrophil cultures blocked uPA kringle-induced potentiation of proinflammatory responses, demonstrating that interactions between the KD and integrins were involved. Antibodies to αV or β3 integrins or to the combination of αVβ3 prevented uPA kringle-induced enhancement of expression of proinflammatory cytokines and also of adhesion of neutrophils to the uPA KD. These results demonstrate that the KD of uPA, through interaction with αVβ3 integrins, potentiates neutrophil activation.
Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells
Authors: Titos Esther , Clària Joan , Planagumà Anna , López-Parra Marta , González-Périz Ana , Gaya Joan , Miquel Rosa , Arroyo Vicente , Rodés Joan 
Published: July 2005

AbstractActivation of Kupffer cells is a prominent feature of necro-inflammatory liver injury. We have recently demonstrated that 5-lipoxygenase (5-LO) and its accessory protein, 5-LO-activating protein (FLAP), are essential for the survival of Kupffer cells in culture, as their inhibition drives these liver resident macrophages to programmed cell death. In the current study, we explored whether the potent FLAP inhibitor, Bay-X-1005, reduces the number of Kupffer cells in vivo and whether this pharmacological intervention protects the liver from carbon tetrachloride (CCl4)-induced damage. Rats treated with CCl4 showed an increased number of Kupffer cells, an effect that was abrogated by the administration of Bay-X-1005 (100 mg/Kg body weight, per oral, daily). Consistent with a role for Kupffer cells in necro-inflammatory liver injury, partial depletion of Kupffer cells following FLAP inhibition was associated with a remarkable hepatoprotective action. Indeed, Bay-X-1005 significantly reduced the intense hepatocyte degeneration and large bridging necrosis induced by CCl4 treatment. Moreover, Bay-X-1005 induced a reduction in the gelatinolytic activity of matrix metalloproteinase-2 (MMP-2) and a decrease in mRNA expression of tissue inhibitor of MMP-2. The FLAP inhibitor reduced leukotriene (LT)B4 and cysteinyl LT levels and down-regulated 5-LO and FLAP protein expression in the liver. It is interesting that a significant increase in the hepatic formation of lipoxin A4, an endogenous, anti-inflammatory lipid mediator involved in the resolution of inflammation, was observed after the administration of Bay-X-1005. These findings support the concept that modulation of the 5-LO pathway by FLAP inhibition may be useful in the prevention of hepatotoxin-induced necro-inflammatory injury.
Examination of urinary mercury levels in dentists in Turkey
Authors: Karahalil B , Rahravi H , Ertas N 
Published: July 2005

Mercury (Hg) is a naturally occurring element and its toxicity, especially in certain forms, has been known for many years. Exposure to Hg can occur in occupational and environmental settings. The toxicity of Hg compounds in dentistry has been an issue of increasing concern. Dental personnel are occupationally exposed to Hg vapor in their working environment and this exposure constitutes a potential risk to people in the dental surgery, mainly from the inhalation of Hg vapor and fine particles of amalgam. In this study, the urinary Hg excretion levels of 20 dentists and nine control subjects, matched for age, were determined by cold-vapor atomic absorption spectrometer (CV-AAS). The levels of Hg in the urine samples of the dentists was about three times higher than the control subjects (6.29±3.5 and 1.979±0.9 μg/L, respectively) (P B < 0.001). Some 90% of dentists wore both gloves and masks. Standards of hygiene (use of mask, glove and gown) may contribute to the degree of exposure. Attention to important hygiene measures, such as the avoidance of spills of Hg, cleaning of floors after such spills, ventilation and the installation of ventilation, depending on technology, should be taken into consideration. Age and smoking habits did not influence the urinary Hg excretion. Our results showed that dentists had significant exposure to Hg vapor compared to control subjects and therefore might be subject to possible adverse effects due to Hg toxicity.
Development of a STEP-compliant inspection framework for discrete components
Authors: Ali L , Newman S T , Petzing J 
Published: July 2005

The measurement and inspection of manufactured parts play a vital role in manufacturing industry and is considered an integral part of the quality control. Though this is recognized, the state of the art in measurement and inspection of components is still recognized as a separate island of automation with no formal overall integration of standards and specifications. Although the introduction of probing has enabled automated inspection processes to become commonplace, the solutions for the in-process gauging at CNC machine tools and the programming of coordinate measuring machines is still vendor specific. The introduction of new standards for data exchange, such as STEP, AP219, and STEP-NC, has influenced the future direction of the inspection process. In light of current research in this field, a STEP compliant inspection framework for a component is presented. This framework aims to provide a capability to establish standardized measuring and inspection across the total CAx chain. It will facilitate the use of information downstream in the chain, such as an inspection workplan, workingsteps, and a mechanism to close the loop and feedback of inspection results to component model design. In order to achieve this integration STEP-NC (ISO14649) along with AP219 has been used in this research to provide the basis of a STEP-compliant inspection framework.
The polishing process of advanced ceramic balls using a novel eccentric lapping machine
Authors: Kang J , Hadfield M 
Published: July 2005

The finishing process of advanced ceramic balls can be divided into two steps. The first step is lapping in which most of the stock from the ball is removed at a higher material removal rate. The second step is polishing in which the required ball surface roughness, roundness, and dimensional and geometric accuracy are achieved. In polishing, the abrasive particle size is 1 μm, and the load and speed are lower than lapping. A novel eccentric lapping machine is used for polishing hot isostatically pressed (HIPed) silicon nitride balls. In the initial polishing stage, the polishing load is demonstrated as being most influential in the reduction of surface roughness value Ra. However, in the later polishing stages, the erosive process played a major role in the further reduction of Ra, although the high roughness peaks cannot be removed by erosive process alone. Experimental results also show that, in order to achieve desired surface roughness value, the initial surface quality of the upper plate should be reasonably high, and deep scratches on the ball surface from previous lapping processes should be avoided. The best polishing results achieved were surface roughness values of Ra of 0.003 μm and r.m.s. ( Rq) of 0.004 μm, ball roundness of 0.08–0.09 μm. This proves that the novel eccentric lapping machine is also suitable for polishing advanced ceramic balls.
Design of a pile-yarn-manipulating mechanism
Authors: Topalbekiroglu M , Kireçci A , Dülger Canan L 
Published: July 2005

A pile-yarn-manipulating mechanism for carpet weaving was designed and implemented. The pile-yarn-manipulating mechanism served to prepare the coloured pile yarn for a knotting mechanism according to a carpet pattern used as input. Such a mechanism required two auxiliary mechanisms (a holding mechanism and a cutting mechanism) to perform its function. A model for the pile yarn manipulating mechanism is presented herein. Important developments of weaving technology have been recorded. There are many carpet looms working at high speeds, but production methods of handmade carpets have not changed for several hundred years. The main difference between handmade and machine carpets is their texture type. The pile surface of machine carpets is produced by Jacquard's mechanism, but it is produced independently in handmade carpets by the weaver. There are basically two kinds of knot, namely the Turkish knot and the Persian knot.
Rapid prototyping methods of silicon carbide micro heat exchangers
Authors: Liu H-C , Tsuru H , Cooper A G , Prinz F B 
Published: July 2005

Conventional heat exchangers are mainly constructed of metal alloys. The manufacturing process of metal alloys usually requires assembling and joining techniques such as welding and diffusion bonding. In addition, the structures are limited to simple shapes due to the restrictions of the fabrication methods. This research focused on the manufacturing of compact heat exchangers made of high thermal-conductivity ceramic material, rather than on the performance of the devices. To achieve a high surface-volume ratio in heat exchangers, a strategy was adopted that fabricates miniaturized devices with a high shape complexity. This paper discusses an approach that uses a combination of mould shape deposition manufacturing (Mould SDM) and the gelcasting process to fabricate monolithic ceramic heat exchangers. This approach not only makes one-piece heat exchangers possible but introduces materials with superior thermal properties to the heat management applications. Silicon carbide is chosen for such applications because of its high thermal conductivity, thermal resistance, and corrosion resistance. The high chemical resistance of ceramic materials also extends the use of heat exchangers to chemical processing devices such as chemical reactors. The initial investigation of the process for micro reactors is also discussed.
A gear rattle model accounting for oil squeeze between the meshing gear teeth
Authors: Brancati R , Rocca E , Russo R 
Published: July 2005

In this paper a non-linear one-degree-of-freedom model for analysis of gear rattle vibrations in automotive manual transmissions is presented. In order to take into account the damping effects owing to the oil in the gap between two teeth of a meshing gear, a simple one-dimensional model for the oil-film squeeze effects is proposed. The squeeze model assumes that the damping force is proportional to the oil viscosity and to the extension of the oil film in the plane of curvature of the teeth, which may depend on the lubrication conditions (dry sump, splash, bath). The results provided from several numerical simulations, carried out with reference to helical involute tooth pairs, confirm the capability of oil in reducing the high-frequency vibrations subsequent to the impact between the teeth. In particular, the influence exerted by oil viscosity and gap extension on the rattle characteristics is investigated through the analysis of the transient response of the driven gear by imposing a harmonic motion to the driving gear.