Stock solution EtOH A Stock solution was prepared by dissolving accurately weighed portions of about 666 mg of tobramycin in portions of the mobile phase and diluted to produce 100 ml solution. An appropriate portion of the stock solution was spiked into a blank placebo matrix to produce concentrations of 80, 100, and 120 of the target level. Mean recovery of spiked samples was 99.45 % for tobramycin [Table 2]. Table 2 Accuracy data (analyte recovery): Tobramycin Precision Instrumental precision was determined by six replicate determinations of standard solution and the relative standard deviation was 0.29 for tobramycin. Method precision or intra-assay precision was performed by preparing six different samples involving different weighing.

Each solution was injected in triplicate under same conditions and the mean value of peak area response for each solution was taken. Corrections in area were made for each weight that had been taken to prepare six sample solutions and relative standard deviation of the contents of tobramycin the six sample solutions was calculated. Relative standard deviation was 0.29 for tobramycin. Intermediate precision was performed by analyzing the samples by two different analysts employing different instruments. The standard solution and six different samples at 100% target level were prepared by each analyst. The relative standard deviation obtained from 12 assay results by two analysts was 0.42 for tobramycin. Robustness Robustness of the proposed method was performed by keeping chromatographic conditions constant with the following deliberate variations: (i) change in the column oven temperature (ii) change in flow rate from 1.

0 ml/min to 1.2 ml/min. The standard solution was injected six times in replicate for each minor change. System suitability parameters like peak asymmetry, theoretical plates, capacity factor, and relative standard deviation were recorded for each peak and found to be within acceptable limits. Six test samples at the target concentration level were prepared and analyzed for each change. The percentage difference in assay and relative standard deviations was calculated during each change and found to be �� 0.5% and less than 1.0, respectively. It was noted that slight addition of solvents in the mobile phase affects the method and does not produce results of similar system suitability, as in the proposed method it resulted in poor peak response or no elution of tobramycin peak.

System suitability System suitability tests were performed to chromatograms obtained from standard and test solutions to check parameters such as column efficiency, peak asymmetry, and capacity factor of tobramycin peaks. Results obtained from six replicate injections of standard solution as per the proposed method are summarized in AV-951 Table 3.

More recently, high throughput selleckchem Cabozantinib genome sequencing and mass spectrometric analyses of bacteria have given unprecedented access to a wealth of genetic and proteomic information [3]. As a consequence, we propose to use a polyphasic approach [4] to describe new bacterial taxa that includes their genome sequence, MALDI-TOF spectrum and major phenotypic characteristics (habitat, Gram staining, culture and metabolic characteristics, and when applicable, pathogenicity). Here we present a summary classification and a set of features for A. senegalensis sp. nov. strain JC50T together with the description of the complete genomic sequencing and annotation. These characteristics support the creation of the A. senegalensis species. The genus Alistipes (Rautio et al.

2003) was created in 2003 [5] and is composed of strictly anaerobic Gram-negative rods that resemble the Bacteroides fragilis group in that most species are bile-resistant and indole-positive; however, they are only weakly saccharolytic and most species produce light brown pigment only on laked rabbit blood agar [6]. The genus Alistipes contains five species namely A. finegoldii, A. putredinis [5], A. indistinctus [7], A. onderdonkii and A. shahii [8]. The natural habitat of the genus Alistipes is unknown but most of the species have mostly been isolated from blood samples, appendiceal tissue samples, perirectal and brain abscess material [9,10]. Predisposing factors to Alistipes sp. bacteremia include malignant neoplasms, recent gastrointestinal or obstetric-gynecologic surgery, intestinal obstruction, and use of cytotoxic agents or corticosteroids [9].

A 16S rRNA phylogenetic analysis revealed that A. senegalensis is closely related to A. shahii. To the best of our knowledge, our report is the first to report the isolation of Alistipes sp. from the normal fecal flora. Classification and features A stool sample was collected from a healthy 16-year-old male Senegalese volunteer patient living in Dielmo (rural villages in the Guinean-Sudanian zone in Senegal), who was included in a research protocol. The patient gave an informed and signed consent, and the agreement of the National Ethics Committee of Senegal and the local ethics committee of the IFR48 (Marseille, France) (agreement 09-022), were obtained. The fecal specimen was preserved at -80��C after collection and sent to Marseille.

Strain JC50T (Table 1) was isolated in March 2011 by anaerobic cultivation on Schaedler agar with kanamycin and vancomycin (Becton Dickinson, Heidelberg, Germany). Anacetrapib Table 1 Classification and general features of Alistipes senegalensis strain JC50T The strain exhibited 97.0%, 16S rRNA nucleotide sequence similarity with A. shahii, the phylogenetically-closest validly published Alistipes species.(Figure 1). Although the level of sequence similarity of the 16S rRNA gene sequence is not uniform across taxa, this value was lower than the 98.

The method was validated as per the guidelines laid by ICH. The results of the validation tests were found to be satisfactory and therefore this method can be applied successfully to analyze drug formulations. ACKNOWLEDGMENT We would like to thank Macleods Pharmaceuticals add to favorites Ltd, Mumbai, India, for providing pure drug samples for this study and the Amrutvahini Sheti and Shikshan Vikas Sanstha, Sangamner, M.S., India, for providing us the research facility. Footnotes Source of Support: Nil Conflict of Interest: None declared.
Cefdinir is an advanced generation, broad / extended-spectrum oral semisynthetic cephalosporin.[1] The drug is an oral aminothiazolyl hydroxyimino cephalosporin. Cefdinir a broad spectrum cephalosporin is effective against enteric gram-positive and gram-negative bacteria.

Cefdinir is stable in the presence of some, but not all, ��-lactamase enzymes. As a result, many organisms are resistant to penicillins and some cephalosporins are susceptible to cefdinir.[2] It has been proven to be effective for common bacterial infections of the ear, sinus, throat, and skin.[3] Chemically, cefdinir [Figure 1] is [6R-[6��,7��(Z)]]-7-[[(2-amino-4-thiazolyl) (hydroxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. [4] Cefdinir is structurally similar to other oral (cefpodoxime proxetil, ceftibuten) or parenteral (cefepime, cefotaxime, ceftazidime, ceftriaxone) cephalosporins that contain an aminothiazolyl side chain at position 7 of the cephalosporin nucleus; however, cefdinir contains an unsubstituted oxime group rather than the methoxyimino group contained in many aminothiazolyl cephalosporins.

The oxime group may contribute to the improved activity against gram-positive bacteria. Similar to cefixime, cefdinir contains a vinyl moiety at position 3 of the cephalosporin nucleus, which makes the drug suitable for oral administration.[5�C6] The antibiotic has been approved for the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis, treatment of respiratory and urinary tract infections, and for uncomplicated skin and skin structure infections. Thus, the third generation of cephalosporin is of great value in medical treatment due to its broad spectrum bactericidal effect.

Figure 1 Chemical structure of cefdinir A literature survey revealed that few analytical methods are available for the estimation of cefdinir from bulk drugs / dosage forms[7�C16] and from human plasma.[17] Anacetrapib The reported method for the estimation of cefdinir includes HPLC,[7�C11] the ultraviolet (UV) spectroscopic and colorimetric method,[12�C13] and the spectroflourimetric method of analysis.[14] There is also a liquid chromatography-tandem mass spectrometry (LCMS-MS) method reported for the estimation of cefdinir from human plasma.

Compared with other members of the Cryomorphaceae, the strain most similar to strain UST20020801T with respect to the content of straight-chain fatty acids and branched-chain hydroxy fatty acids is Cryomorpha ignava 1-22T [1]. In addition to phosphatidylethanolamine third as major polar lipid, six unidentified lipids, one unidentified aminolipid, one unidentified aminophospholipid and one unidentified glycolipid were found in strain UST20020801T [15]. MK-6 was detected as a major respiratory quinone in strain UST20020801T [1]. Genome sequencing and annotation Genome project history This organism was selected for sequencing on the basis of its phylogenetic position [41], and is part of the Genomic Encyclopedia of Bacteria and Archaea project [42].

The genome project is deposited in the Genomes On Line Database [27] and the complete genome sequence is deposited in GenBank. Sequencing, finishing and annotation were performed by the DOE Joint Genome Institute (JGI). A summary of the project information is shown in Table 2. Table 2 Genome sequencing project information Growth conditions and DNA isolation O. hongkongensis strain UST20020801T, DSM 17368, was grown in DSMZ medium 1168 (YPS medium) [43] at 30��C. DNA was isolated from 0.5-1 g of cell paste using Jetflex Genomic DNA Purification kit (GENOMED 600100) following the standard protocol as recommended by the manufacturer with an extended cell-lysis procedure, i.e. incubation with additional 80 ��l protease K for one hour at 58��C. DNA is available through the DNA Bank Network [44].

Genome sequencing and assembly The genome was sequenced using a combination of Illumina and 454 sequencing platforms. All general aspects of library construction and sequencing can be found at the JGI website [45]. Pyrosequencing reads were assembled using the Newbler assembler (Roche). The initial Newbler assembly, consisting of 39 contigs in one scaffold, was converted into a phrap [46] assembly by making fake reads from the consensus to collect the read pairs in the 454 paired end library. Illumina GAii sequencing data (5,738.3 Mb) was assembled with Velvet [47] and the consensus sequences were shredded into 1.5 kb overlapped fake reads and assembled together with the 454 data. The 454 draft assembly was based on 81.1 Mb 454 draft data and all of the 454 paired end data. Newbler parameters are -consed -a 50 -l 350 -g -m -ml 20.

The Phred/Phrap/Consed software package [46] was used for sequence assembly and quality assessment in the subsequent finishing process. After the shotgun stage, reads were assembled with parallel phrap (High Performance Software, LLC). Possible mis-assemblies were corrected with gapResolution [45], Dupfinisher [48], or sequencing cloned bridging PCR fragments with Drug_discovery subcloning. Gaps between contigs were closed by editing in Consed, by PCR and by Bubble PCR primer walks (J.-F. Chang, unpublished).

maris Coryn-1T [8], C. marinum 7015T [9] and C. humireducens MFC-5T [10] as well as C. diphtheriae NCTC 11397T [11] indicates that http://www.selleckchem.com/products/Vandetanib.html C. halotolerans YIM 70093T, together with C. maris, C. marinum, and C. humireducens, form a distinct subclade within the genus Corynebacterium. Interestingly, C. xerosis and C. freneyi do not group closely with this subclade when C. diphtheriae is added to the comparison. Figure 1 shows the phylogenetic neighborhood of C. halotolerans in a 16S rRNA based tree. The sequences of the four identical 16S rRNA gene copies in the genome differ by eight nucleotides from the previously published 16S rRNA sequence (“type”:”entrez-nucleotide”,”attrs”:”text”:”AY226509″,”term_id”:”29372859″,”term_text”:”AY226509″AY226509), which contains two ambiguous bases.

Figure 1 Phylogenetic tree highlighting the position of C. halotolerans relative to type strains of other species within the genus Corynebacterium as selected by Chen et al. [1]. In addition, the recently described C. maris, C. marinum, and C. humireducens were … C. halotolerans YIM 70093T is Gram-positive and cells are rod-shaped, 0.5-1 ��m long and 0.25-0.5 ��m wide (Table 1 and Figure 2). It is described to be non-motile [1], which coincides with a complete lack of genes associated with ��cell motility�� (functional category N). Optimal growth of YIM 70093T was shown to occur at 28��C, pH 7.2 and 100 g/l KCl, albeit the strain tolerates a wide range of salinity, between 0-250 g/l, NaCl, and MgCl2 [1].

Carbon sources utilized by strain YIM 70093T include glucose, galactose, sucrose, arabinose, mannose, mannitol, maltose, xylose, ribose, salicin, dextrin, and starch [1], although the latter is doubtful as C. halotolerans cannot hydrolize starch [1]. Table 1 Classification and general features of C. halotolerans YIM 70093T according to the MIGS recommendations [14]. Figure 2 Scanning electron micrograph of C. halotolerans YIM 70093T. Chemotaxonomy The peptidoglycan of strain YIM 70093T contains meso-diaminopimelic acid, galactose, and arabinose [1], therefore it belongs to cell wall type IV, sugar type A. The menaquinones detected in the cell membrane of YIM 70093T are MK-8(H2) (35.5%) and MK-9(H2) (64.5%) [1]. Cellular fatty acids are predominantly saturated straight chain acids, C16:0 (42.1%), C14:0 (7.3%); and C18:0 (4.5%), and unsaturated acids, cis-9-C18:1 (28.

9%) and cis-9-C16:1 (9.8%), in addition to 10-methyl C18:0 (7.4%) [1]. Like many, but not Entinostat all corynebacteria, C. halotolerans also contains mycolic acids, predominantly of the short chain type (C32-C36): C32:0 (36.0%), C34:0 (20.8%), C34:1 (25.1%), C36:0 (3.6%), C36:1 (8.4%), and C36:2 (5.1%) [1]. The reported major polar lipids consist of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylinositol (PI), glycolipid and phosphatidylinositol mannosides (PIM) [1]. Genome sequencing and annotation Genome project history C.

Genome sequencing information Genome project history Strain BD11-00177 was sequenced because of its relevance to biodefense. The draft genome sequence was finished in August 2012. The GenBank accession number for the project is 177784. The genome project selleckchem is listed in the Genome OnLine Database (GOLD) [22] as project Gi21611. Sequencing was carried out at the Dutch Organization for Applied Scientific Research (TNO) and the Swedish Defense Research Agency (FOI). Initial automatic annotation was performed using the DOE-JGI Microbial Annotation Pipeline (DOE-JGI MAP). Table 2 shows the project information and its association with MIGS 2.0 compliance. Table 2 Project information Growth conditions and DNA isolation For DNA preparation, strain BD11-00177 was grown on 5% sheep blood agar plates for 72 h at 35��C in the presence of 5% CO2.

DNA was extracted using the Qiamp DNA Micro Kit according manufacturers guidelines (Qiagen, Westburg b.v., Leusden, The Netherlands). Genome sequencing and assembly Sequencing was performed by the Microbiology and Systems Biology group at TNO and the Division for CBRN Defence and Security at FOI using 454 Roche GS Junior and the Illumina MiSeq platforms. The initial draft assembly yielded 95 large (>1,000 bp) and 86 small (<1,000 bp), non-redundant contigs of 1,813,372 bp by combing 75,245 Roche/454 reads at 23�� coverage and 8,289,332 Illumina reads at 690�� coverage by hybrid assembly through the Ray Assembler V2.1 [24].

Genome annotation Open Reading Frames (ORFs) were predicted using the Prodigal gene prediction algorithm [23] as part of the DOE-JGI Microbial Annotation Pipeline (DOE-JGI MAP) using default parameters, followed by a round of manual curation. CRISPR elements were predicted using CRT and PILERCR [25]. Predictions from both methods were concatenated. Identification of tRNAs was performed using tRNAScan. Ribosomal RNA genes (5S, 16S, 23S) are predicted using the program RNAmmer [26]. With the exception of tRNA and rRNA, all models from Rfam [27] are used to search the genome sequence. For faster detection, sequences are first compared to a database containing all the ncRNA genes in the Rfam database using BLAST, with a very loose cutoff. Subsequently, sequences that have hits to any genes belonging to an Rfam model are searched using the program INFERNAL Entinostat [27]. Protein coding genes were compared to protein families (e.g., COGs, Pfam, KEGG) and the proteome of selected ��core�� genomes, which are publicly available, and the product names were assigned based on the results of these comparisons. Genome properties The genome was assembled into 95 large (>1,000 bp) contigs and includes one circular chromosome with a total size of 11,813,372 bp (32.23% GC content).

Another clinical study found that a gel containing 10% L. sidoides essential oil was not a good antiplaque agent.22. This study used a 21-day partial-mouth experimental model of gingivitis, in which the test gel was placed undiluted on a toothshield. It is possible that solubilization in saliva or Volasertib buy the mechanical action of a toothbrush may be necessary for an antibacterial effect to occur,13,22 which could explain the difference between this and the present study. We might also infer that, in our trial, tooth brushing released the volatile active components from the test gel, thus enabling these compounds to exert their biological actions. This study did not test the bioavailability or half-life of L. sidoides essential oil in the formulated gel.

By inference, a study showed that, after a single oral dose, thymol can be detected for 24 h in urine and 41 h in plasma, which shows its high systemic availability in humans.30 Moreover, use of L. sidoides essential oil did not induce any significant acute toxicological changes as evaluated by biochemical or hematological parameters, and this product is considered safe for use in vivo.19 The composition of L. sidoides essential oil was similar to that reported in other studies, with the phenolic compounds thymol and carvacrol being the major constituents.18,19 These volatile oils constitute a group of plant secondary metabolites that are best obtained through hydrodistillation and have potent antimicrobial activity, as has been well documented in the literature.

10,18,19,28 Thymol and carvacrol have a similar molecular formula (C10H14O), with only a minor structural difference in the position of the hydroxyl group.18 The antimicrobial action of these compounds is attributed to their phenolic character and is similar to that of eugenol. Its antimicrobial action occurs at the cell membrane level and is attributed to cellular lipid changes, loss of intracellular material, and inhibition of nucleic acid synthesis.31 These data support the antiplaque effect of L. sidoides found in the present trial and are in agreement with other studies that investigated agents with similar compounds.10,18,20,28 The test groups showed significant reductions on gingivitis at the end of the trial (LS, 40%; CLX, 52%); this is consistent with previous studies.

10,21 Nevertheless, this percent difference was Carfilzomib not significant, showing that LS had a potential similar to chlorhexidine as an antigingivitis agent. In spite of insufficient data in the literature about the anti-inflammatory action of L. sidoides preparations, this property has been reported previously. 10,21,22 This anti-inflammatory action could be due an indirect action on plaque reduction or to a direct effect on the cyclooxygenase cycle (COX-2).22 Similarly to those found in other herbal products, the flavonoids contained in L.

Tumor progression model for PC in which the pancreatic ductal epithelium progresses from normal to increased grades of pancreatic intraepithelial neoplasia (PanINs) merely to invasive cancer. Multiple alterations in genes that are important in PC progression have been identified, for example K-ras, INK4A, p53, and SMAD4/DPC4 [4], [5]. PC is characterized by near-universal mutations in K-ras and frequent deregulation of crucial embryonic signalling pathways, including the Hedgehog (HH) signaling pathway [6], [7]. A better understanding of the mechanisms underlying the development of PC might help to improve early diagnosis and potentially identify molecular therapeutic targets. The hedgehog (HH) signaling pathway was first identified in the embryonic development of Drosophila [8] and has been shown to be crucial for growth and patterning in the pancreas during embryonic development.

HH signaling regulates cell differentiation and organ formation during embryonic development , and is expressed in pancreatic epithelial cells [9], [10]. Constitutive activation of HH signaling is detected in a variety of human cancers, including pancreatic cancer [9]�C[13]. Given its misexpression in both metastatic pancreatic cancer cell lines and in precursor lesions (PanIN) [14], HH signal activation may be involved in both early and late pancreatic tumorigenesis. Of the three mammalian ligands in the HH family, Sonic (SHH), Desert (DHH), and Indian (IHH) Hedgehog [15], the former has been associated with both pancreatic organogenesis and pancreatic cancer.

HH signals are transmitted and modified by two transmembrane proteins, patched (PTCH) and smoothened (SMO), and by downstream transcription factors that are members of the glioma-associated oncogene (GLI) family (GLI1, 2, and 3). GLI2 and GLI3 have transactivation and repressive domains, whereas GLI1 likely functions only as a transactivator and transcriptional target of the HH pathway itself [16]�C[19]. The regenerating gene (Reg) family, a group of small secretory proteins, is involved in cell proliferation or differentiation in digestive organs [20], is upregulated in several gastrointestinal cancers, and functions as trophic or antiapoptotic factors [21]�C[23]. RegIV, a member of the regenerating gene family, is involved in digestive tract malignancies, including the stomach [24], colorectum [25], [26], and pancreas [27], [28], as well as in benign diseases such as ulcerative colitis [29].

RegIV overexpression in tumor cells has been associated with cell growth, survival, adhesion, and resistance to apoptosis. Recently, RegIV overexpression Drug_discovery was reported to be associated with the initiation and progression of pancreatic cancer, and was suggested as a promising tumor marker to screen early stage PC and target for adjuvant therapy in PC [28], [30].

Traditionally, the response to cancer treatment in solid tumors is evaluated by subsequent clinical or radiological assessments, and is defined as a significant etc decrease in the measurable tumor dimensions. A reduction in the viable tumor cell fraction, however, does not always result in a volume reduction, since tumor tissue can be replaced by necrotic or fibrotic tissue, and morphological images are often unable to differentiate between these different tissue types. In recent years, metabolic imaging with positron emission tomography (PET) has become increasingly important in cancer management. Although the performances of PET and CT are comparable in terms of the process of staging before the initiation of imatinib therapy, PET can evaluate the tumor response as early as 1 week after the start of treatment, preceding the CT response by several weeks (14).

Treatment-induced changes resulting in tumor cell death or growth arrest should therefore result in a subsequent reduction in glucose uptake, making this technique a sensitive and early marker for response evaluation. There are several limitations to this study. First, this was a retrospective review of cases collected over a number of years for which CT scans were performed irregularly, depending on the condition of the patients. Second, unenhanced images were not obtained in all patients, and it is unclear whether or not any subtle enhancement changes are present in the metastatic lesions. Third, we did not provide any pathologic correlation in any of the cases.

Pathologic correlation with the radiologic findings for metastatic lesions is helpful for clinicians as well as for radiologists. In conclusion, after treatment with imatinib, responsive intra-abdominal extra-hepatic metastases of gastrointestinal stromal tumors appear as well-defined cystic lesions on contrast-enhanced CT. These metastases become smaller and resemble ascites, but may be detected for a long time on the follow-up CT scans. Footnotes This study was supported in part by the 2003 BK21 Project for Medicine, Dentistry and Pharmacy.
Chronic hepatitis C infection affects nearly 170 million people worldwide, and it is the most common indication for liver transplantation.1-3 Between 20 and 30% of infected individuals will eventually go on to develop cirrhosis and its sequelae.

1-3 Unfortunately, even in developed countries, deaths due to hepatitis C are increasing because of inadequate detection and treatment.4-6 In a high endemic area of HBV infection, chronic hepatitis C may be overlooked until the disease has progressed significantly. In Korea, which is a high endemic area of HBV infection, about 50-90 thousand people are chronically infected with HCV, and at least 10-17% of hepatocellular carcinoma (HCC) cases are probably attributable Batimastat to HCV infection.

2002). The completed recipient blocks were sectioned at 4 ��m and transferred to silanized glass slides. A total of five recipient blocks were made. Histological Evaluation The whole section slides that were used for selecting representative TMA cores were used for histological evaluation of morphologic characteristics. Sunitinib purchase Mitotic figures were counted in 50 consecutive high-power fields (HPFs). Additional variables recorded included the presence of spindled and/or epithelioid cell morphology. Focal or diffuse atypia was defined according to Miettinen et al. (2006). Other variables such as necrosis, ulceration, and hemorrhage were also assessed. Immunohistochemical Staining and Scoring Sections from the arrays were stained with H&E to confirm the presence of representative tumor in each core.

Further sections were stained using a Ventana (Tucson, AZ) automated immunohistochemical stainer according to manufacturer’s guidelines. The antibody used for detecting KIT-positive cases was c-KIT (polyclonal, dilution 1:200; Dako, Carpinteria, CA). The immunostaining was performed with an avidin-biotin detection system. Diaminobenzidine hydrochloride solution with hydrogen peroxide (Ventana Gen II, Dab basic) was the chromogen. Morphometric Scoring Digital images of sections from the TMA stained with H&E were used for morphometric analyses, captured using a BLISS scanner (Bacus Laboratories; Lombard, IL). The slides were scanned at ��40 objective magnifications. A plug in for the open source program ImageJ (http://rsb.info.nih.

gov/ij/) was created to combine the separate images stored by BLISS scanner and form the individual images of the tissue cores (http://rsb.info.nih.gov/ij/plugins/stitch-bliss.html). The resulting pixel dimensions of the individual core images were 3760 �� 3360. A separate Nuclear Stain Analyzer plug in was created for assessment of morphometric parameters of the tumor nuclei (Figure 1). The following characteristics/dimensions of the nuclei were thereby quantified: area, intensity, optical density, perimeter, width and height of bounding rectangle, ellipse major and minor, ellipse ratio, ellipse angle, circularity, Feret diameter, and roundness. In addition, number of nuclei in each core was registered. The formula used for roundness was 4 �� area/�� �� square(major axis).

Ellipse major and minor were the primary and secondary axes of best-fitting ellipse, and the ratio between shortest and longest axis was used to evaluate the ratio between the two (SL ratio). Figure 1 Core with outlined nuclei. All the images are publicly available at the companion site: www.gpecimage.ubc.ca/tma/web/viewer.php. The site was constructed at Genetic Carfilzomib Pathology Evaluation Centre (GPEC) (Vancouver, Canada) using a GPEC database and a Java applet provided by Bacus Laboratories.