bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of estrogen receptors, progesterone receptors and c‐erbB2 oncogene protein expression in ductal carcinomas of the breast
Authors: Hussein Mahmoud R. , Abd‐Elwahed Saad R.A.H. , Abdulwahed Ahmad Rezk 
Published: January 2008

AbstractEstrogens are important for stimulating the growth of a large proportion of breast cancers. Progesterone plays critical roles in breast development and tumorigenesis. The c‐erbB2 gene (HER‐2/neu) is a proto‐oncogene expressed in 10–34% of breast cancers. Its expression is associated with poor clinical outcome. The hypothesis that the progression of in situ ductal carcinoma of breast to invasive ductal carcinoma is associated with alterations of ER, PgR and HER‐2/neu protein expression was tested. Of 100 mastectomy specimens examined, all contained both ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) not otherwise specified (NOS). The status of ER, PgR and HER‐2/neu proteins was examined by immunochemistry. ER and PgR protein expression was scored as the mean value of positively stained cells. HER‐2/neu protein expression was evaluated on ts staining pattern (0, 1+, 2+ and 3+). We found variations between DCIS and IDC with significant decrease of the mean values of ER and PgR positively stained cells in high‐grade (Grade 3) IDC (ER: 49.2 ± 10.3 vs. 30.8 ± 5.5 and PgR: 40.0 ± 10.0 vs. 22.3 ± 5.1 in DCIS and IDC, respectively, P < 0.05). Invasive carcinomas with lymph node metastases or lymphovascular invasion or both had lower mean values of ER and PgR positively stained cells compared to those without these features. In IDC (Grade 3), HER‐2/neu protein expression values (1.2 ± 0.2) were significantly high compared to DCIS (0.7 ± 0.3, P < 0.05). In addition, HER‐2/neu protein expression values were significantly higher (P < 0.05) in IDC with lymph node metastases or lymphovascular invasion (1.5 ± 0.3) than those without these features (0.8 ± 0.2). A significantly high mean (P < 0.05) of ER and PgR positively stained cells was observed in postmenopausal females compared to premenopausal women. In contrast, high HER‐2/neu expression values were seen only in premenopausal females. A significant positive correlation was observed between ER and PgR receptor expression (r = 0.81). A low degree inverse correlation (r = −0.24, P < 0.012) was found between ER+/PgR+ tumors and HER‐2/neu expression. These findings substantiate the notion that breast cancer progression is often associated with alterations of ER, PgR and HER‐2/neu expression. The underlying mechanisms of these alterations are open for further investigation.
Piezoelectricity and prostate cancer: Proposed interaction between electromagnetic field and prostatic crystalloids
Authors: Ghabili Kamyar , Shoja Mohammadali M. , Agutter Paul S. 
Published: January 2008

AbstractThere is evidence that electromagnetic fields (EMF) play some part in the pathogenesis of prostate cancer, but the pathogenic mechanism remains unknown. The normal prostate gland and both benign and malignant prostate lesions contain abundant calcium/phosphorus crystalloids with various morphologies, which seem to be heterogeneously and diffusely distributed within the gland. We hypothesize that an environmental EMF may result in simultaneous, multidirectional and diffuse compression or expansion of these crystalloids (a piezoelectric effect). This would result in a slight mechanical distortion of the prostate, potentially altering cell behavior and enhancing the expression of specific genes, particularly those involved in suppressing apoptosis. A mathematical model of the cell mechanical effect is presented, and the hypothesis is related to current clinical evidence and to potential validation by critical laboratory tests.
Magnetosonic solitons in a dusty plasma slab
Authors: MARKLUND M. , STENFLO L. , SHUKLA P. K. 
Published: January 2008

AbstractThe existence of magnetosonic solitons in dusty plasmas is investigated. The nonlinear magnetohydrodynamic equations for a warm dusty magnetoplasma are thus derived. A solution of the nonlinear equations is presented. It is shown that, owing to the presence of dust, static structures are allowed. This is in sharp contrast to the formation of the so-called shocklets in usual magnetoplasmas. A comparatively small number of dust particles can thus drastically alter the behavior of the nonlinear structures in magnetized plasmas.
Honoré Fabri and the Trojan Horse of Inertia
Authors: Elazar Michael 
Published: January 2008

ArgumentThis paper discusses the theory of motion of the philosopher Honoré Fabri (1608–1688), a senior representative of early modern Jesuit scientists. It argues that the consensus prevailing among historians – according to which Fabri's theory of impetus is diametrically opposed to Galileo's or Descartes' concept of inertia – is false. It shows: that Fabri carefully constructed his concept of impetus in order to easily incorporate the principle of linear conservation of motion (designated here as “limited inertia”), by adopting formal (rather than efficient) causality between impetus and motion and by allowing impetus to act only along straight lines; that he explicitly deemed Aristotle's famous “inertial paradox” not as a paradox at all; and that linear conservation of motion was not limited to “counterfactual” circumstances but played a significant part in his discrete theory of free fall and constituted an integral component of his general physical (and even mathematical) philosophy. However, the paper also shows that Fabri's notion of inertia was restricted to one dimension only, and therefore should indeed be considered “limited.” In his analysis of horizontal projectiles, Fabri explicitly rejected Galileo's important principle of superposition, and thus revealed significant constraints to his “inertial” thinking.
Writing “The Case of Ellen West”: Clinical Knowledge and Historical Representation
Authors: Akavia Naamah 
Published: January 2008

Argument“The Case of Ellen West” was published by the Swiss psychiatrist, Ludwig Binswanger, in 1944–1945. The case-history depicts the illness and suicide of a young woman who was his patient twenty years earlier. It came to be considered one of the paradigmatic studies of the newly established discipline ofDaseinsanalyse, an attempt to synthesize existential philosophy and therapeutic practice. This paper analyzes the case-study, employing newly uncovered archival material to expose important details regarding the treatment of Ellen West (a pseudonym) and the posthumous writing of her case-history. The richness of the archival sources and the various historiographical characteristics they exhibit raise methodological questions about the potentialities and limitations of historical representation. The new data will thus serve as a platform from which to explore and discuss more generally the problems involved in historical reconstruction – of both subjective experience and clinical knowledge – and the questions of authorship and intertextuality in the genre of the case-history.
Combining inhaled glucocorticoids and long acting β2‐adrenoceptor agonists in asthma and COPD
Authors: Knox A J , Mortimer K 
Published: January 2008

Inhaled long‐acting β2‐adrenoceptor agonists and glucocorticoids form the mainstay of maintenance treatment of asthma and chronic obstructive pulmonary disease (COPD), usually given as a combination inhaler. Most patients will have good asthma control if they comply with this therapy, although it is generally less effective in COPD. The traditional dogma has been that these agents act on distinct components of disease pathophysiology with β2 agonists acting on the bronchospastic component and glucocorticoids acting on the inflammatory component. Considerable evidence has emerged recently, however, to suggest that these two classes of agents interact at a molecular level. Understanding the mechanisms of these interactions may enable the development of new therapies for asthma and COPD.British Journal of Pharmacology (2008) 153, 1085–1086; doi:10.1038/bjp.2008.4; published online 28 January 2008
Formulation and in vitro Evaluation of Eudragit L100 piroxicam
Authors: Saffari Mostafa , Shahbazi Malihe , Shafiee Ardestani Mehdi 
Published: January 2008

AbstractThe aim of this study was to formulate and evaluate controlled release preparations of a water-insoluble drug using Copolymers synthesized from acrylic and methacrylic acidesters (Eudragit L 100) as the retardant material. Microspheres were prepared by solvent evaporation method using an alcohol / liquid paraffin system. Span60 was used as the droplet stabilizer. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well as by differential scanning calorimetry. The in vitro release studies were performed first in pH1.2 and then pH 6.8, phosphate buffer. The prepared microspheres were yellow, and spherical in shape. The drugloaded microspheres showed 71-85% of entrapment and release was extended up to 7 h. The differential scanning calorimetry thermographs showed stable character of drug in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. The best-fit release kinetics was achieved with Higuchi plot. The release of drug was influenced by the drug to polymer ratio and particle size that was found to be diffusion controlled.
Neuroprotective effect of hydrogen peroxide on an in vitro model of brain ischaemia
Authors: Nisticò R , Piccirilli S , Cucchiaroni M L , Armogida M , Guatteo E , Giampà C , Fusco F R , Bernardi G , Nisticò G , Mercuri N B 
Published: January 2008

Background and purpose:Reactive oxygen species (ROS) have been postulated to play a crucial role in the pathogenesis of ischaemia‐reperfusion injury. Among these, hydrogen peroxide (H2O2) is known to be a toxic compound responsible for free‐radical‐dependent neuronal damage. In recent years, however, the ‘bad reputation’ of H2O2 and other ROS molecules has changed. The aim of this study was to assess the protective role of H2O2 and modification in its endogenous production on the electrophysiological and morphological changes induced by oxygen/glucose deprivation (OGD) on CA1 hippocampal neurons.Experimental approach:Neuroprotective effects of exogenous and endogenous H2O2 were determined using extracellular electrophysiological recordings of field excitatory post synaptic potentials (fEPSPs) and morphological studies in a hippocampal slice preparation. In vitro OGD was delivered by switching to an artificial cerebrospinal fluid solution with no glucose and with oxygen replaced by nitrogen.Key results:Neuroprotection against in vitro OGD was observed in slices treated with H2O2 (3 mM). The rescuing action of H2O2 was mediated by catalase as pre‐treatment with the catalase inhibitor 3‐amino‐1,2,4‐triazole blocked this effect. More interestingly, we showed that an increase of the endogenous levels of H2O2, due to a combination of an inhibitor of the glutathione peroxidase enzyme and addition of Cu,Zn‐superoxide dismutase in the tissue bath, prevented the OGD‐induced irreversible depression of fEPSPs.Conclusions and implications:Taken together, our results suggest new possible strategies to lessen the damage produced by a transient brain ischaemia by increasing the endogenous tissue level of H2O2.British Journal of Pharmacology (2008) 153, 1022–1029; doi:10.1038/sj.bjp.0707587; published online 28 January 2008
Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator
Authors: Schmidt A , Hughes L K , Cai Z , Mendes F , Li H , Sheppard D N , Amaral M D 
Published: January 2008

Background and purpose:Cystic fibrosis (CF) is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. In the search for new CF therapies, small molecules have been identified that rescue the defective channel gating of CF mutants (termed CFTR potentiators). Here, we investigate the long‐term effects of genistein, the best‐studied CFTR potentiator, on the expression and function of CFTR.Experimental approach:We pre‐treated baby hamster kidney (BHK) cells expressing wild‐type or F508del‐CFTR (the most common CF mutant) with concentrations of genistein that potentiate (30 μM) or inhibit (100 μM) CFTR function for 2 or 24 h at 37 °C before examining CFTR maturation, expression and single‐channel activity.Key results:Using the iodide efflux technique, we found that genistein pre‐treatment failed to restore function to F508del‐CFTR, but altered that of wild‐type CFTR. Pre‐treatment of cells with genistein for 2 h had little effect on CFTR processing, whereas pre‐treatment for 24 h either augmented (30 μM genistein) or impaired (100 μM genistein) CFTR maturation. Using immunocytochemistry, we found that all genistein pre‐treatments increased the localization of CFTR protein to the cell surface. However, following the incubation of cells with genistein (100 μM) for 2 h, individual CFTR Cl− channels exhibited characteristics of channel block upon channel activation.Conclusions and implications:Genistein pre‐treatment alters the maturation, cell surface expression and single‐channel function of CFTR in ways distinct from its acute effects. Thus, CFTR potentiators have the potential to influence CFTR by mechanisms distinct from their effects on channel gating.British Journal of Pharmacology (2008) 153, 1311–1323; doi:10.1038/sj.bjp.0707663; published online 28 January 2008
The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high‐fat diet
Authors: Di Marzo V , Capasso R , Matias I , Aviello G , Petrosino S , Borrelli F , Romano B , Orlando P , Capasso F , Izzo A A 
Published: January 2008

Background and purpose:Endocannabinoids (via cannabinoid CB1 receptor activation) are physiological regulators of intestinal motility and food intake. However, their role in the regulation of gastric emptying is largely unexplored. The purpose of the present study was to investigate the involvement of the endocannabinoid system in the regulation of gastric emptying in mice fed either a standard diet (STD) or a high‐fat diet (HFD) for 14 weeks.Experimental approach:Gastric emptying was evaluated by measuring the amount of phenol red recovered in the stomach after oral challenge; CB1 expression was analysed by quantitative reverse transcription‐PCR; endocannabinoid (anandamide and 2‐arachidonoyl glycerol) levels were measured by liquid chromatography‐mass spectrometry.Key results:Gastric emptying was reduced by anandamide, an effect counteracted by the CB1 receptor antagonist rimonabant, but not by the CB2 receptor antagonist SR144528 or by the transient receptor potential vanilloid type 1 (TRPV1) antagonist 5′‐iodoresiniferatoxin. The fatty acid amide hydrolase (FAAH) inhibitor N‐arachidonoyl‐5‐hydroxytryptamine (but not the anandamide uptake inhibitor OMDM‐2) reduced gastric emptying in a way partly reduced by rimonabant. Compared to STD mice, HFD mice exhibited significantly higher body weight and fasting glucose levels, delayed gastric emptying and lower anandamide and CB1 mRNA levels. N‐arachidonoylserotonin (but not rimonabant) affected gastric emptying more efficaciously in HFD than STD mice.Conclusions and implications:Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight.British Journal of Pharmacology (2008) 153, 1272–1280; doi:10.1038/sj.bjp.0707682; published online 28 January 2008
Best uniform rational approximation of 𝑥^{𝛼} on [0,1]
Authors: Stahl Herbert 
Published: January 2008

A strong error estimate for the uniform rational approximation of

x

α

{x^{\alpha }}

on [0, 1] is given, and its proof is sketched. Let

E

n
n

(

x
α

,
[
0
,
1
]
)

{E_{nn}}({x^\alpha },[0,1])

denote the minimal approximation error in the uniform norm. Then it is shown that
\[

lim

x
→
∞

e

2
π

α
n

E

n
n

(

x
α

,
[
0
,
1
]
)
=

4

1
+
α

|

sin
⁡
π
α

|

\lim \limits _{x \to \infty } {e^{2\pi \sqrt {\alpha n} }}{E_{nn}}({x^\alpha },[0,1]) = {4^{1 + \alpha }}|\sin \pi \alpha |

\]
holds true for each

α
>
0

{\alpha > 0}

.
Electrostatic effects in unfolded staphylococcal nuclease
Authors: Fitzkee Nicholas C. , García‐Moreno E Bertrand 
Published: January 2008

AbstractStructure‐based calculations of pK a values and electrostatic free energies of proteins assume that electrostatic effects in the unfolded state are negligible. In light of experimental evidence showing that this assumption is invalid for many proteins, and with increasing awareness that the unfolded state is more structured and compact than previously thought, a detailed examination of electrostatic effects in unfolded proteins is warranted. Here we address this issue with structure‐based calculations of electrostatic interactions in unfolded staphylococcal nuclease. The approach involves the generation of ensembles of structures representing the unfolded state, and calculation of Coulomb energies to Boltzmann weight the unfolded state ensembles. Four different structural models of the unfolded state were tested. Experimental proton binding data measured with a variant of nuclease that is unfolded under native conditions were used to establish the validity of the calculations. These calculations suggest that weak Coulomb interactions are an unavoidable property of unfolded proteins. At neutral pH, the interactions are too weak to organize the unfolded state; however, at extreme pH values, where the protein has a significant net charge, the combined action of a large number of weak repulsive interactions can lead to the expansion of the unfolded state. The calculated pK a values of ionizable groups in the unfolded state are similar but not identical to the values in small peptides in water. These studies suggest that the accuracy of structure‐based calculations of electrostatic contributions to stability cannot be improved unless electrostatic effects in the unfolded state are calculated explicitly.
Critical contribution of VH–VL interaction to reshaping of an antibody: The case of humanization of anti‐lysozyme antibody, HyHEL‐10
Authors: Nakanishi Takeshi , Tsumoto Kouhei , Yokota Akiko , Kondo Hidemasa , Kumagai Izumi 
Published: January 2008

AbstractTo clarify the effects of humanizing a murine antibody on its specificity and affinity for its target, we examined the interaction between hen egg white lysozyme (HEL) and its antibody, HyHEL‐10 variable domain fragment (Fv). We selected a human antibody framework sequence with high homology, grafted sequences of six complementarity‐determining regions of murine HyHEL‐10 onto the framework, and investigated the interactions between the mutant Fvs and HEL. Isothermal titration calorimetry indicated that the humanization led to 10‐fold reduced affinity of the antibody for its target, due to an unfavorable entropy change. Two mutations together into the interface of the variable domains, however, led to complete recovery of antibody affinity and specificity for the target, due to reduction of the unfavorable entropy change. X‐ray crystallography of the complex of humanized antibodies, including two mutants, with HEL demonstrated that the complexes had almost identical structures and also paratope and epitope residues were almost conserved, except for complementary association of variable domains. We conclude that adjustment of the interfacial structures of variable domains can contribute to the reversal of losses of affinity or specificity caused by humanization of murine antibodies, suggesting that appropriate association of variable domains is critical for humanization of murine antibodies without loss of function.
Identification of phosphorylation sites in mammalian mitochondrial ribosomal protein DAP3
Authors: Miller Jennifer L. , Koc Hasan , Koc Emine C. 
Published: January 2008

AbstractMammalian mitochondrial ribosomes synthesize 13 proteins that are essential for oxidative phosphorylation. In addition to their role in protein synthesis, some of the mitochondrial ribosomal proteins have acquired functions in other cellular processes such as apoptosis. Death‐associated protein 3 (DAP3), also referred to as mitochondrial ribosomal protein S29 (MRP‐S29), is a GTP‐binding pro‐apoptotic protein located in the small subunit of the ribosome. Previous studies have shown that phosphorylation is one of the most likely regulatory mechanisms for DAP3 function in apoptosis and may be in protein synthesis; however, no phosphorylation sites were identified. In this study, we have investigated the phosphorylation status of ribosomal DAP3 and mapped the phosphorylation sites by tandem mass spectrometry. Mitochondrial ribosomal DAP3 is phosphorylated at Ser215 or Thr216, Ser220, Ser251 or Ser252, and Ser280. In addition, phosphorylation of recombinant DAP3 by Protein kinase A and Protein kinase Cδ at residues that are endogenously phosphorylated in ribosomal DAP3 suggests both of these kinases as potential candidates responsible for the in vivo phosphorylation of DAP3 in mammalian mitochondria. Interestingly, the majority of the phosphorylation sites detected in our study are clustered around the highly conserved GTP‐binding motifs, speculating on the significance of these residues on protein conformation and activity. Site‐directed mutagenesis studies on selected phosphorylation sites were performed to determine the effect of phosphorylation on cell proliferation and PARP cleavage as indication of caspase activation. Overall, our findings suggest DAP3, a mitochondrial ribosomal small subunit protein, is a novel phosphorylated target.
Structural characterization of partially folded intermediates of apomyoglobin H64F
Authors: Schwarzinger Stephan , Mohana‐Borges Ronaldo , Kroon Gerard J.A. , Dyson H. Jane , Wright Peter E. 
Published: January 2008

AbstractWe present a detailed investigation of unfolded and partially folded states of a mutant apomyoglobin (apoMb) where the distal histidine has been replaced by phenylalanine (H64F). Previous studies have shown that substitution of His64, located in the E helix of the native protein, stabilizes the equilibrium molten globule and native states and leads to an increase in folding rate and a change in the folding pathway. Analysis of changes in chemical shift and in backbone flexibility, detected via [1H]‐15N heteronuclear nuclear Overhauser effect measurements, indicates that the phenylalanine substitution has only minor effects on the conformational ensemble in the acid‐ and urea‐unfolded states, but has a substantial effect on the structure, dynamics, and stability of the equilibrium molten globule intermediate formed near pH 4. In H64F apomyoglobin, additional regions of the polypeptide chain are recruited into the compact core of the molten globule. Since the phenylalanine substitution has negligible effect on the unfolded ensemble, its influence on folding rate and stability comes entirely from interactions within the compact folded or partly folded states. Replacement of His64 with Phe leads to favorable hydrophobic packing between the helix E region and the molten globule core and leads to stabilization of helix E secondary structure and overall thermodynamic stabilization of the molten globule. The secondary structure of the equilibrium molten globule parallels that of the burst phase kinetic intermediate; both intermediates contain significant helical structure in regions of the polypeptide that comprise the A, B, E, G, and H helices of the fully folded protein.