Miracle-dz/UniFAR-FTUs huggingface dataset:
The Discovery of SB-435495: A Potent, Orally Active Inhibitor of Lipoprotein-Associated Phospholipase A2 for Evaluation in Man.

A significant problem in cancer treatment is the development of tumor resistance to chemotherapeutic agents. Acquired drug resistance is often mediated through overexpression of drug efflux proteins especially P-glycoprotein (Pgp) and MRP1. In our search for improved Pgp antagonists, we have identified families of substituted azabicyclo[3.2. 1]octanes that selectively antagonizes Pgp over MRP1. N-substituted-8-azabicyclo[3.2. 1]octanes were synthesized. These compounds were evaluated for their toxicity towards drug-sensitive MCF-7 breast carcinoma cells, and for their abilities to antagonize Pgp and MRP1 in drug-resistant cell lines (NCI/ADR and MCF-7/VP, respectively). 171. MULTIPHOTON ACTIVATION OF EFFECTOR MOLECULES FOR SPATIALTEMPORAL CONTROL OF DRUG ACTIVITY. Eric J Jervis , Basil Perdicakis , Heather J. Montgomery , Dan Fishlock , J. Guy Guillemette , and Gilles A. Lajoie . (1) Department of Chemical Engineering, University of Waterloo, 200 University Ave. West, Waterloo, ON N2L3G1, Canada, Fax: 519-746-4979, ericjj@cape.uwaterloo. ca, bperdica@engmail.uwaterloo. ca, (2) Department of Chemistry, University of Waterloo Nitric oxide (NO) is involved in a number of physiological processes and is produced in mammalian cells by nitric oxide synthase (NOS) isoenzymes. Due to the diverse functions of NO, pharmaceutical interventions which seek to abrogate adverse effects of excess NOS activity must not interfere with the normal regulation of NO levels in the body. A caged isoform-specific NOS inhibitor has been synthesized, the near infrared multiphoton (NIR-MP) activation characterized in vitro, and uncaging evaluated in acute murine neural tissue slice cultures. NIR-MP activation of pharmaceuticals may confer significant advantages over other methods of drug delivery including minimisation of drug side effects in non-target tissue and real time control of active drug concentration. This technology could potentially be used to reduce NO related tissue damage inflicted during ischemia or reperfusion following engraftment by selectively inhibiting NO production in localized tissue volumes. 172. PREPARATION OF WATER-IN-OIL-IN-WATER DOUBLE EMULSION FOR DRUG RELEASE APPLICATIONS. Weihong Guo , Valerie Gunn , Yvon G. Durant , and Robert Gyurik . (1) Materials Science, University of New Hampshire, G101 Parsons Hall, Durham, NH 03824, Fax: 603 862 4892, wguo@cisunix.unh.edu, yvon.durant@unh.edu, (2) Bently Pharmaceutical Inc Stable water-in-oil-in-water double emulsions were prepared. The inner aqueous phase contained insulin and the oil phase was composed mostly of cyclo pentadecanolide. Insulin was tagged with fluorescein-5-isthiocyanate to enhance fluorescence detection. The structures and release characteristics of insulin from WOW were studied. The particle size of WOWs are in an average diameter of 40 micrometer, the inside water droplets have an average diameter of 3micrometer. WOW double emulsions remained structurally stable for over 3 months when MEDI
Lecture 27 & 28 : 2 D Directional Wavelet Frames

Let us now return to the analysis of pointwise singularities of signals f via the decay of Wf(u, s) as s ! 0. Let be a real valued wavelet, and recall that a wavelet modulus maxima is defined as a point (u0, s0) such that |Wf(u, s0)| is locally maximum at u = u0. All of the results regarding wavelet coefficient decay and the pointwise regularity of f(t) (including, in particular, Theorems 5.5, 5.7, and 5.8) hold for dyadic wavelet semi-discrete frames by restricting s = 2 for j 2 Z. Let (u0, j) be a modulus maxima point of Wf(u, j), meaning that @Wf @u (u0, j) = 0 (81)
EFFECT OF AUDITOR'S EXPERIENCE AND ETHICS ON AUDIT QUALITY IN PUBLIC ACCOUNTANT OFFICES IN BANDUNG CITY

Abstract - The purpose of this research was to know the effect of the Auditor Experience and the Auditor Ethics toward Audit Quality. The study was conducted using a survey method towards forty-five auditor who worked on thirteen public accountant firm in the city of Bandung. Data analysis was performed by multiple linear regression models. Hypothesis testing was done to determine whether there is any influence on the Auditor Experience and the Auditor Ethics towards the Audit Quality either simultaneously or partially. The test result indicates that simultaneously, the Auditor Experience and the Auditor Ethics are significantly affecting the Audit Quality. The test result also indicates that partially, either the Auditor Experience or the Auditor Ethics are significantly affecting the Audit Quality.Keywords: Auditor Experience, Auditor Ethics, Audit Quality.
Immunostimulatory activity of aqueous leaf extract of Cassia occidentalis on human neutrophils

The use of herbal extract in the treatment of infectious disease has been a regular practice in Nigeria and other developing countries. The study aim was to evaluate the immunostimulatory effect of aqueous leaf extract of Cassia occidentalis on human neutrophils. Thirty (30) healthy volunteers were recruited into this study, consisting of 15 male and 15 female. Blood sample collected was used to isolate the Neutrophils. Different concentrations (25 µg/ml 50 µg/ml, 100 µg/ml and 1mg/ml) of the plant extract were prepared. Giemsa stain was used to determine the neutrophils phagocytic function while methylene blue was used to carryout micro bicidal capacity analysis. There was significant increase in phagocytic index and micro bicidal capacity of neutrophils with increase in the plant extract concentration (p
Coordination abilities of mono and multi-histidinic and glutamate peptide fragments towards manganese(II) and cobalt(II)

It is known that rich repeat domains in peptides can be of interest as the models for the study of molecular phenomena related to metal ion binding in proteins involved in neurodegenerative disorders. Imbalances in transition metal ions are assumed to contribute to the conversion of the multi-histidinic amyloid β-peptide (Aβ) from its soluble form to an amyloidogenic form, and to Aβ deposition. Of these ions, it has been reported that manganese binding to PrP is detrimental and causes a conformational change in the protein, suggesting that manganese binding could potentially play a role in prion disease progression in vivo. It appears that PrP is less stable on binding manganese and quickly converts to a misfolded form. The binding of manganese to PrP potentially results in the conversion of the protein to an abnormal isoform with properties reminiscent of Pr Psc . In particular, although PrP can bind the same number of manganese atoms as of copper atoms, the resulting protein becomes proteinase resistant, forms fibrils and loses function. [1,2] Regarding cobalt, a novel low-affinity binding site for Co(II) was discovered between PrP residues 104 and 114, with residue His111 being the key amino acid for coordinating Co(II). [3] Thus, despite the interest in manganese and cobalt binding to PrP, a thorough analysis of the interaction of both metals with proteins related to brain pathies has not yet been reported. The (T 1 R 2 S 3 R 4 S 5 H 6 T 7 S 8 E 9 G 10 ) 3 fragment from Cap43 protein, which is induced by metal ions, is characterized by a decarepeat domain comprising three decapeptide units with one histidine and one glutamate residue in each repeat. Therefore the study of the interaction of the 30-aminoacid peptide from Cap43 protein with metal ions can contribute to the understanding of the crucial role of multi-imidazol and glutamate sites in the protein coordination processes and the possible role of divalent metal ions in the pathogenesis of prion disease and other related protein pathies. [4-8] Here we present our recent results on the Cobalt(II) and Manganese(II) complexes of terminally protected mono- and multi-histidine-glutamate peptides studied by combination of potentiometric measurements and spectroscopic techniques (NMR, UV-Vis and EPR). Metal complexation induces important structural changes with the C-terminal portion of the ligand, constraining it to leave its disordered conformation and promoting side chain orientation. Our results give rise to a molecular model of the induced structure for the peptides complexed with cobalt and manganese.
CHRONISCHE RHINOSINUSITIS MIT NASENPOLYPEN

Diagnostik Die Diagnostik der PN basiert auf einer endoskopischen Untersuchung der vorderen und hinteren Nasenabschnitte mittels starrer (seltener flexibler) Optiken (3). In der bildgebenden Diagnostik zur Darstellung des Nebenhöhlensystems haben sich die hochauflösende Computertomografie (CT) und die digitale Volumentomografie (DVT) (oder „cone beam computed tomography“, CB-CT) etabliert (3). DVT und CT sind hinsichtlich der räumlichen Auflösung im Hochkontrastbereich (Knochendarstellung) wie auch in der Strahlenexposition vergleichbar. Ein MRT ist bei Verdacht auf entzündliche intrakranielle oder orbitale Komplikationen oder in der Differenzialdiagnostik der Tumoren der Nasennebenhöhlen empfehlenswert, aufgrund der schlechteren Darstellung der knöchernen Strukturen jedoch nicht für die Planung chirurgischer Maßnahmen. Bei Patienten Ausgeprägte eosinophile Zell infiltrationen sind typisch für eine chronische Sinusitis vom Th2-dominierten Endotyp.
STANDARISASI PARAMETER SPESIFIK EKSTRAK METANOL BIJI KEBIUL (Caesalpinia Bonduc L.) SEBAGAI BAHAN BAKU OBAT HERBAL TERSTANDAR

The determination of specific parameters standardization of knicker nut (Caesalpinia BonducL.) methanol extract as the standardized herbal medicine raw materials has been carried out to ensure the quality improvement of traditional medicines and the efficacy of the plant. The purpose of this research is to determine the specific parameters of knicker nut extract so that it can be consumed as herbal medicines that have been scientifically tested. The knicker nut extract was obtained from the extraction employing the maceration method with methanol as the solvent. Specific parameters testing included extract identity, extract organoleptic, dissolved compound in certain solvents, along with extract chemical test. The results of extract identity testing show that the Latin name is CaesalpiniaBonducL. with the nut as the used part of the plant. The organoleptic test reveals that the plant is in the form of thick extract, blackish-brown in color, bitter, has pungent smell/typical smell of knicker nut, contains water-soluble compound of 10.33% with the standard deviation ±1.154707755, N-hexane-soluble compound of 3.33% with the standard deviation ±1.154707755, and methanol-soluble compound of 17.33% with the standard deviation ±3.511886957. Moreover, the flavonoids wavelengths are 382 nm (band I) and 262 nm (band II).
Caractérisation par micro-faisceau d'ions des réactions physico-chimiques induites in vitro par des verres bioactifs nanostructurés élaborés par la méthode sol-gel

Les verres bioactifs permettent de combler les defauts osseux lors d'applications cliniques. Nous avons elabore par sol-gel plusieurs verres bioactifs, parmi lesquels des verres dopes en Sr. La bioactivite des verres est averee : au contact d'un milieu biologique, une couche Ca-P se forme rapidement en surface de nos materiaux. La caracterisation de l'interface verre/ milieu biologique par faisceau d'ions demontre que le verre binaire est le plus rapide en ce qui concerne la dissolution de la matrice et l'apparition de la couche Ca-P. Pour les verres contenant du P, ces phenomenes sont retardes, mais la couche Ca-P-Mg se developpe vite en une couche apatitique. Pour les verres dopees en Sr, la couche Ca-P-Mg se forme sur une profondeur reduite. Neanmoins elle evolue plus vite en apatite. De plus la presence de Sr a l'interface verre/ liquide et dans le milieu biologique pourrait resulter, grâce aux effets benefiques du Sr sur l'activite cellulaire, en une bioactivite amelioree in vivo
The Augmentation of Retinogeniculate Communication during Thalamic Burst Mode

Retinal signals are transmitted to cortex via neurons in the lateral geniculate nucleus (LGN), where they are processed in burst or tonic response mode. Burst mode occurs when LGN neurons are sufficiently hyperpolarized for T-type Ca2+ channels to deinactivate, allowing them to open in response to depolarization, which can trigger a high-frequency sequence of Na+-based spikes (i.e., burst). In contrast, T-type channels are inactivated during tonic mode and do not contribute to spiking. Although burst mode is commonly associated with sleep and the disruption of retinogeniculate communication, bursts can also be triggered by visual stimulation, thereby transforming the retinal signals relayed to the cortex. To determine how burst mode affects retinogeniculate communication, we made recordings from monosynaptically connected retinal ganglion cells and LGN neurons in male/female cats during visual stimulation. Our results reveal a robust augmentation of retinal signals within the LGN during burst mode. Specifically, retinal spikes were more effective and often triggered multiple LGN spikes during periods likely to have increased T-type Ca2+ channel activity. Consistent with the biophysical properties of T-type Ca2+ channels, analysis revealed that effect magnitude was correlated with the duration of the preceding thalamic interspike interval and occurred even in the absence of classically defined bursts. Importantly, the augmentation of geniculate responses to retinal input was not associated with a degradation of visual signals. Together, these results indicate a graded nature of response mode and suggest that, under certain conditions, bursts facilitate the transmission of visual information to the cortex by amplifying retinal signals. SIGNIFICANCE STATEMENT The thalamus is the gateway for retinal information traveling to the cortex. The lateral geniculate nucleus, like all thalamic nuclei, has two classically defined categories of spikes—tonic and burst—that differ in their underlying cellular mechanisms. Here we compare retinogeniculate communication during burst and tonic response modes. Our results show that retinogeniculate communication is enhanced during burst mode and visually evoked thalamic bursts, thereby augmenting retinal signals transmitted to cortex. Further, our results demonstrate that the influence of burst mode on retinogeniculate communication is graded and can be measured even in the absence of classically defined thalamic bursts.
Angiotensin II Receptor Type 1 Blockade Prevents Arterial Remodeling and Stiffness in Iron Overloaded Rats

Introduction : Iron is an essential metal for cellular homeostasis participating in important physiological processes. Concentrations of this metal in the organism need to be rigorously regulated, because the deficiency and excess of this metal cause serious damage to health. Regarding iron overload, it has been suggested that the vasculature is damaged human and animal models, characterized by endothelial dysfunction and reduced compliance. Objective : To prove that angiotensin II receptor type 1 blockade prevent arterial remodeling and stiffness in iron overloades rats. Material and Methods: We previously demonstrated that in vitro blockade of the angiotensin II type 1 receptor (AT1R) reversed functional vascular changes induced by chronic iron overload. In this study the effect of chronic AT1R blocker on aorta stiffening was test in iron overloaded rats. Aortic mechanics, geometry, and composition was assessed in Wistar rats treated for 15 days with saline as control group, iron-dextran 200 mg/kg/day five days a week (iron overload group), losartan (20 mg/kg/day in drinking water), and iron-dextran plus losartan. Results: There were no differences in aortic hemodynamics and vascular tone due to iron overload, but thoracoabdominal aortic pulse-wave velocity (PWV) increased significantly indicating a decrease in aortic compliance. Co-treatment with losartan prevented changes on PWV, β-index and elastic modulus from iron overloaded rats. This iron-related increase in PWV was not related to changes in aortic geometry and wall stress but increased elastic modulus/wall stress ratio suggesting that a change in the composition of the wall was responsible for the stiffness. Confirming, despite not changing circulating iron or vascular deposits, losartan also ameliorated the increase in aorta collagen content of the iron overload group. Conclusions: Taking together, losartan prevented the structural and functional indices of aortic stiffness in the iron loading rats, suggesting a capacity for renin-angiotensin system inhibition to limit the vascular remodeling in chronic iron overload.
ANTICOCCIDIAL EFFICACY OF METRONIDAZOLE

This study was carried out to study the efficacy of metronidazole as anticoccidial drug at two levels of doses (25 and 50 mg / kg B.W) for 5 consecutive days via drinking water. one hundred and fifty mixed sex one day old Arbor Acres F.s. chicks were divided into six equal main groups. All were fed on ordinary ration free from any anticoccidial agents allover the experiment (41 days). -The first group was non infected non treated (negative control). the second group was treated without infection with 25 mg / kg of metronidazole (flagyl susp Alex co) ,the third group was treated with 50 mg/kg B.W of metronidazole without infection The fourth group was infected non treated group (positive control) . The fifth and sixth groups were infected with E. tenella (50.000 oocysts / bird) at 18 days of age and treated with( 25 and 50mg /kg B.W) of metronidazole respectively after symptoms appeared for 5 consecutive days . The evaluation was based on clinical signs, lesion scores, oocyst counts, and histopathological findings of treated and infected non treated group. The results showed that the infected non treated group (positive control) showed the typical signs of coccidiosis including depression, loss of appetite and bloody droppings one week post infection. Variable degrees of illness were recorded until the end of experiment. Medication of metronidazole after infection at both dose levels improved the clinical signs, oocyst counts and Lesion score,The mortality rate as well as the epithelial lining of the intestinal gland of infected treated group than that of the infected non treated group, in addition to the degeneration of most of the developmental stages of E tenella in treated Groups. Anticoccidial Efficacy Of Metronidazole. M.A. Aziz et al.,
Vasoactive Potential of the B1 Bradykinin Receptor in Normotension and Hypertension

Abstract—The B1 type receptor of bradykinin (Bk B1R) is believed to be physiologically inert but highly inducible by inflammatory mediators and tissue damage. To explore the potential participation of the Bk B1R in blood pressure (BP) regulation, we studied mice with deleted Bk B2R gene with induced experimental hypertension, either salt-dependent (subtotal nephrectomy with 0.5% NaCl as drinking water) or renin/angiotensin-dependent (renovascular 2-kidney–1-clip). Compared with the wild-type controls, the B2R gene knockout mice had a higher baseline BP (109.7±1.1 versus 101.1±1.3 mm Hg, P=0.002), developed salt-induced hypertension faster (in 19.3±2.3 versus 27.7±2.4 days, P=0.024), and had a more severe end point BP (148±3.7 versus 133±3.1 mm Hg, P<0.05). On the contrary, renovascular hypertension developed to the same extent (149.7±4.3 versus 148±3.6 mm Hg) and in the same time frame (14±2.2 versus 14±2.1 days). A bolus infusion of a selective B1R antagonist at baseline produced a significant hypertensi.
Relative worth of estrogen and progesterone receptors as indicators of prognosis in breast cancer

Breast cancer is one of the most common and most frequently diagnosed cancers in women both in the developed and less developed countries. Estrogens and progesterone play a leading role in regulating the normal growth and differentiation of cells, premalignant and malignant cell types, especially breast epithelial cells. Estrogen is targeted either directly by selective estrogen receptor modulators and pure antagonists or indirectly by aromatized inhibitors that block estrogen production. Estrogen receptor also serves as a prognostic marker for responsiveness to endocrine therapy through its receptors alpha and beta. Mammogram screening is used for the early detection of cancer. An ideal screening test for breast cancer must have a high sensitivity in order to correctly diagnose all women with the disease and a high specificity to avoid false positive results Progesterone is also an ovarian steroid hormone that is essential for normal breast development during puberty and in preparation for lactation and breastfeeding. The actions of progesterone are primarily mediated by its high-affinity receptors, which includes progesterone receptor-A and progesterone receptor-B located in diverse tissues, where progesterone controls development of breast and reproductive organs. There is also an important role of progesterone and progesterone receptors in breast carcinogenesis, including cancer progression to metastasis and of their clinical importance in the prevention, treatment and prognosis of the disease. The role of progesterone is not well known, although it causes the tumor development by regulating proliferative pathways in the cell.
Preparation of macroporous methacrylate-based monoliths for chromatographic applications

A strongly growing fraction of newly developed pharmaceuticals are based on proteins. During their production, 50-80% of the total manufacturing costs incur in downstream processing and purification. Most of these large-scale bioseparation processes are based on chromatography, since the choice of purification methods is strongly limited because the biomolecules have to be separated under conditions such that their biological activity is maintained. All this is the motivation for the development of new and more efficient stationary phases for biomolecule purification. A widely used packing material for chromatography are macroporous beaded polymer supports. The technology for the preparation of such macroporous beads is very well developed and an excellent control over bead size, porosity and surface chemistry can be achieved. But chromatographic columns packed with such beads show some important limitations. Especially in the case of purification of large molecules like proteins, monoliths have already shown a great potential as an alternative to conventional bead material as stationary phase. Monoliths are a single piece of a continuous porous material comprising a interconnected network of flow-through pores and sub-domains with a highly mesoand/or micro-porous structure. A rather new approach of preparing such macroporous monolith material based on organic polymers is the ‘Reactive Gelation’ process. It was developed by Marti et al. using polystyrene as the polymer matrix. This thesis studies the preparation of macroporous polymeric monoliths on the basis of polymethylmethacrylate (PMMA) by ‘Reactive Gelation’, the hydrodynamic behavior of this monoliths in chromatography and, functionalized with SO−3 , the application as a strong cation exchange medium for the separation of proteins. The methylmethacrylic monoliths obtained by this process can be operated at large surface velocities and high pressure drops and show excellent hydrodynamic properties. The most important result with respect to the hydrodynamic behavior is the exceptionally high column efficiency, which is not decreasing at higher flow rates as common for columns packed with beads. Besides the excellent hydrodynamic prop-