Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.

1,1,1-Trichloro-2,2-bis(4-ethoxyphenyl)ethane

In the title compound, C18H19Cl3O2, which is the 4-ethoxyphenyl analogue of the insecticidally active 4-methoxyphenyl compound methoxychlor, the dihedral angle between the two benzene rings is 60.38(13)deg. An intramolecular aromatic C-H...Cl interaction is present.

Isopropyl 2,2-bis(4-bromophenyl)-2-hydroxyacetate

In the structure of the title compound C17H16Br2O3, which is a restricted commercial acaricide (common name bromopropylate), has two independent and conformationally similar molecules in the asymmetric unit [dihedral angle between the planes of the two phenyl rings in each, 68.7(4) and 77.4(5)deg]. The C-atoms of the isopropyl group of one of the molecules are disordered over two sites with occupancies of 0.638 and 0.362. Minor non-merohedral twinning was also present in the crystal. Intermolecular hydrogen-bonding interactions involving the hydroxy groups and carboxyl O-atom acceptors give separate centrosymmetric homodimers through cyclic hydrogen-bonding motifs [graph set R2/2(10)].

Promotion and succession management and associated retention issues in Australian law firms

The focus of this research was promotion and succession management in Australian law firms. Two staff retention issues currently faced by the Australian legal industry were identified as suggesting possible failures in this area: 1) Practitioners are leaving law firms early in their careers, 2) Female representation is disproportionally low at partnership level. The research described current Australian law firm promotion and succession practices and then explained their possible relevance to the two retention issues. The overall aim of the research was to uncover key findings and present practical recommendations to law firm managers and partners ready for incorporation into their future promotion and succession planning practice. In so doing the research aimed to benefit the Australian legal community as a whole. Four areas of literature relevant to the topic were reviewed, 1) law firm governance concluding that the fundamental values of the P²-Form remained constant (Cooper, Hinings, Greenwood & Brown, 1996; Morris & Pinnington, 1998) with ownership and strategic control of law firms remaining in the hands of partners; 2) the importance of individual practitioners to law firms concluding that the actual and opportunity costs relating to practitioner turnover were significant due to the transient nature of knowledge as a key asset of law firms (Gottschalk & Khandelwal, 2004; Rebitzer & Taylor, 2007); 3) generational differences concluding with support for the work of Finegold, Mohrman and Spreitzer (2002), Davis, Pawlowski and Houston (2006), Kuhnreuther (2003), and Avery, McKay, and Wilson (2007) which indicated that generational cohort differences were of little utility in human resources management practice; and 4) previous research relating to law firm promotion and succession practices indicating that five practices were relevant in law firm promotion outcomes; 1) firm billing requirements (Gorman & Kmec, 2009; Phillips, 2001; Noonan & Corcoran, 2004; Webley & Duff, 2007); 2) mentoring programs (Phillips, 2001; Noonan & Corcoran, 2004); 3) the existence of female partners (Gorman & Kmec, 2009; Beckman & Phillips, 2005); 4) non-partner career paths (Phillips, 2001; Corcoran & Noonan, 2004); and 5) the existence of family friendly policies (Gorman & Kmec, 2009; Phillips, 2001; Noonan & Corcoran, 2004; Webley & Duff, 2007.) The research was carried out via a sequential mixed method approach. The initial quantitative study was based upon a theoretical framework grounded in the literature and provided baseline information describing Australian law firm promotion and succession practices. The study was carried out via an on-line survey of Australian law firm practitioners. The results of the study provided the basis for the second qualitative study. The qualitative study further explained the statistically generated results and focused specifically on the two identified retention issues. The study was conducted via one-on-one interviews with Australian law firm partners and experienced law firm managers. The results of both studies were combined within the context of relevant literature resulting in eight key findings: Key findings 1) Organisational commitment levels across generational cohorts are more homogenous than different. 2) Law firm practitioners are leaving law firms early in their careers due to the heavy time commitment behaviour demanded of them, particularly by clients. 3) Law firm promotion and succession practices reinforce practitioner time commitment behaviour marking it as an indicator of practitioner success. 4) Law firm practitioners believe that they have many career options outside law firms and are considering these options. 5) Female practitioners are considering opting out of law firms due to time commitment demands related to partnership conflicting with family commitment demands. 6) A masculine, high time commitment culture in law firms is related to the decision by female practitioners to leave law firms. 7) The uptake of alternative work arrangements by female practitioners is not fatal to their partnership prospects particularly in firms with supportive policies, processes and organisational culture. 8) Female practitioners are less inclined than their male counterparts to seek partnership as an ultimate goal and are more likely to opt out of law firms exhibiting highly competitive, masculine cultures. Practical recommendations Further review of the data collected in relation to the key findings provided the basis for nine practical recommendations specifically geared towards implementation by law firm managers and partners. The first recommendation relates to the use of generational differences in practitioner management. The next six relate to recommended actions to reduce the time commitment demands on practitioners. The final two recommendations relate to the practical implementation of these actions both at an individual and organisational level. The recommendations are as follows: 1) "Generationally driven," age based generalisations should not be utilised in law firm promotion and succession management practice. 2) Expected levels of client access to practitioners be negotiated on a client by client basis and be included in client retention agreements. 3) Appropriate alternative working arrangements such as working off-site, flexible working hours or part-time work be offered to practitioners in situations where doing so will not compromise client serviceability. 4) The copying of long working hour behaviours of senior practitioners should be discouraged particularly where information technology can facilitate remote client serviceability. 5) Refocus the use of timesheets from an employer monitoring tool to an employee empowerment tool. 6) Policies and processes relating to the offer of alternative working arrangements be supported and reinforced by law firm organisational culture. 7) Requests for alternative working arrangements be determined without regard to gender. 8) Incentives and employment conditions offered to practitioners to be individualised based on the subjective need of the individual and negotiated as a part of the current employee performance review process. 9) Individually negotiated employment conditions be negotiated within the context of the firm’s overall strategic planning process. Through the conduct of the descripto-explanatory study, a detailed discussion of current law firm promotion and succession practices was enabled. From this discussion, 7 eight key findings and nine associated recommendations were generated as well as an insight into the future of the profession being given. The key findings and recommendations provide practical advice to law firm managers and partners in relation to their everyday promotion and succession practice. The need to negotiate individual employee workplace conditions and their integration into overall law firm business planning was put forward. By doing so, it was suggested that both the individual employee and the employing law firm would mutually benefit from the arrangement. The study therefore broadened its practical contribution from human resources management to a contribution to the overall management practice of Australian law firms. In so doing, the research has provided an encompassing contribution to the Australian legal industry both in terms of employee welfare as well as firm and industry level success.

Human Kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

Effect of bone morphogenetic protein-4 (BMP-4) on the expression of Sox2, Oct-4 and c-Myc in human periodontal ligament cells during long-term culture

Recent studies demonstrated endogenous expression level of Sox2, Oct-4 and c-Myc is correlated with the pluripotency and successful induction of induced pluripotent stem cells (iPSCs). Periondontal ligament cells (PDLCs)have multi-lineage diferentiation capability and ability to maintain undifferentiated stage, which makes PDLCs a suitable cell source for tissue repair and regeneration. To elucidate the effect of in vitro culture condition on the stemness potential of PDLCs, we explored the cell growth, proliferation, cell cycle, and the expression of Sox2, Oct-4 and c-Myc in PDLCs from passage 1 to 7 with or without the addition of recombinant human BMP4(rhBMP4). Our results revealed that BMP-4 promoted cell growth and proliferation, arrested PDLCs in S phase of cell cycle and upregulated PI value. It was revealed that without the addition of rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs only maintained nucleus location until passage 3, then lost nucleus location subsequently. The mRNA expression in PDLCs further confirmed that the level of Sox2 and Oct-4 peaked at passage 3, then decreased afterwards, whereas c-Myc maintained consistently upregulation along passages. after the treatment with rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs maintained nucleus location even at passage 7 and the mRNA expression of Sox2 and Oct-4 significantly upregulated at passage 5 and 7. These results demonstrated that addition of rhBMP-4 in the culture media could improve the current culture condition for PDLCs to maintain in an undifferentiated stage.

Poly[(mu6-4-amino-3,5,6-trichloropyridine-2-carboxylato)aquacaesium

In the structure of the title complex, [Cs(C6H2Cl3N2O2)(H2O)]n, the caesium salt of the commercial herbicide picloram, the Cs+ cation lies on a crystallographic mirror plane, which also contains the coordinating water molecule and all non-H atoms of the 4-amino-3,5,6-trichloropicolinate anion except the carboxylate O-atom donors. The irregular CsCl4O5 coordination polyhedron comprises chlorine donors from the ortho-related ring substituents of the picloramate ligand in a bidentate chelate mode, with a third chlorine bridging [Cs-Cl range 3.6052 (11)-3.7151 (11) Å] as well as a bidentate chelate carboxylate group giving sheets extending parallel to (010). A three-dimensional coordination polymer structure is generated through the carboxylate group, which also bridges the sheets down [010]. Within the structure, there are intra-unit water O-HOcarboxylate and amine N-HNpyridine hydrogen-bonding interactions.

4-(4-Nitrobenzyl)pyridinium 3-carboxy-4-hydroxybenzenesulfonate

In the title salt, C12H11N2O2+·C7H5O6S-, the dihedral angle between the benzene and pyridine rings in the 4-(4-nitrobenzyl)pyridinium cation is 82.7 (2)°. Within the anion there is an intramolecular hydroxy-O-HO(carboxylic acid) bond. In the crystal, the cation forms a single N+-HOsulfonate hydrogen bond with the anion. These cation-anion pairs interact through duplex anion carboxylic acid O-HOsulfonate hydrogen bonds, giving a centrosymmetric cyclic association [graph set R22(16)]. The crystals studied were non-merohedrally twinned.

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide--2-nitrobenzoic acid (1/1)

In the asymmetric unit of the title co-crystal, C12H14N4O2S·C7H5NO4, the sulfamethazine and 2-nitrobenzoic acid molecules form a heterodimer through intermolecular amide-carboxylic acid N-HO and carboxylic acid-pyrimidine O-HN hydrogen-bond pairs, giving a cyclic motif [graph set R22(8)]. The dihedral angle between the two aromatic ring systems in the sulfamethazine molecule is 88.96 (18)° and the nitro group of the acid is 50% rotationally disordered. Secondary aniline N-HOsulfone hydrogen-bonding associations give a two-dimensional structure lying parallel to the ab plane.

Changing learning to improve practice : hand hygiene education in Queensland medical schools

The aim of Queensland Health’s ‘Clean hands are life savers’ program is to change the culture and behaviour of healthcare workers related to hand hygiene. Hand hygiene is considered to be the most effective means of preventing pathogen cross-transmission and healthcare-associated infections. Most hospitals throughout Queensland as well as Australia now manage a hand hygiene program to increase the hand hygiene compliance of all healthcare workers. Reports taken from routine hand hygiene observations reveal that doctors are usually less compliant in their hand-washing practices than other healthcare worker groups. The Centre for Healthcare Related Infection Surveillance and Prevention (CHRISP) has attempted to have an impact on this challenging group through their Medical Leadership Initiative. With education as a core component of the program, efforts were made to ensure our future doctors were receiving information that aligned with Queensland Health standards during their formative years at medical school. CHRISP met with university instructors to understand what infection prevention education was currently included in the curriculum and support the introduction of new learning activities that specifically focused on hand hygiene. This prompted change to the existing curriculum and a range of interventions were employed with mixed success. Although met with challenges, methods to integrate more infection prevention teaching were found.

Silver Gelatin Print: A group exhibition curated by Karen Milder that investigates and captures the traditional processes using photograms, liquid emulsion, toning, hand-colouring and film. Part of the Queensland Festival of Photography 4 (QFP4).

Pillar of salt: (3 hand-applied silver gelatin photographs) Statement: For women moving into new experiences and spaces, loss and hardship is often a price to be paid. These courageous women look back to things they have overcome in order to continue to grow.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.