The Effect Of Knowledge Management Systems On Absorptive Capacity: Findings From International Law Firms

This case study is engaged in examining the effects of knowledge management systems (KMS) on absorptive capacity (ACAP). Often regarded as the major source of innovation and firm competitive advantage, ACAP raises questions of how to value, assimilate and apply new knowledge. Based on a multiple case study design we specifically investigate KMS as antecedent of ACAP. We interviewed six experts employed in knowledge management functions at two different international law firms operating in the Asian-Pacific, American, and European legal market. The findings from our case study analysis demonstrate that KMS have a positive effect on ACAP, especially on knowledge acquisition and assimilation

Impact of peatlands on carbon dioxide (CO2) emissions from the Rajang River and Estuary, Malaysia

Tropical peat-draining rivers are known as potentially large sources of carbon dioxide (CO2) to the atmosphere due to the high loads of carbon they receive from surrounding soils. However, not many seasonally resolved data are available, limiting our understanding of these systems. We report the first measurements of carbon dioxide partial pressure (pCO2) in the Rajang River and Estuary, the longest river in Malaysia. The Rajang River catchment is characterized by extensive peat deposits found in the delta region, and by human impact such as logging, land use and river damming. pCO2 averaged 2540±189 µatm during the wet season and 2350±301 µatm during the dry season. Using three different parameterizations for the gas transfer velocity, calculated CO2 fluxes to the atmosphere were 1.5 (0.5–2.0) g C m−2 d−1 (mean, minimum – maximum) during the wet season and 1.7 (0.6–2.6) g C m−2 d−1 during the dry season. This is at the low end of reported values for Southeast Asian peat-draining rivers, but similar to values reported for Southeast Asian rivers that do not flow through peat deposits. In the Rajang River, peatlands probably do not contribute much to the CO2 flux due to the proximity of the peatlands to the coast, which limits the opportunity for degradation of organic C during transport. Thus, we suggest that peat coverage is, by itself, insufficient as the sole predictor of CO2 emissions from peat-draining rivers, and that other factors, like the spatial distribution of peat in the catchment and pH, also need to be considered

Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer

Background!#!Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.!##!Methods!#!A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2.!##!Results!#!Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features.!##!Conclusions!#!Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application

Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence

Syndecan-1 (CD138) is a transmembrane proteoglycan expressed in various normal and malignant tissues. It is of interest due to a possible prognostic effect in tumors and its role as a target for the antibody-drug conjugate indatuximab ravtansine. Here, we analyzed 17,747 prostate cancers by immunohistochemistry. Membranous and cytoplasmic CD138 staining was separately recorded. In normal prostate glands, CD138 staining was limited to basal cells. In cancers, membranous CD138 positivity was seen in 19.6% and cytoplasmic CD138 staining in 11.2% of 12,851 interpretable cases. A comparison with clinico-pathological features showed that cytoplasmic CD138 staining was more linked to unfavorable tumor features than membranous staining. Cytoplasmic CD138 immunostaining was associated with high tumor stage (p<0.0001), high Gleason grade (p<0.0001), nodal metastases (p<0.0001), positive surgical margin (p<0.0001), and biochemical recurrence (p<0.0001). This also holds true for both V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion positive and ERG fusion negative tumors although the cytoplasmic CD138 expression was markedly more frequent in ERG positive than in ERG negative tumors (p<0.0001). Comparison with 11 previously analyzed chromosomal deletions identified a conspicuous association between cytoplasmic CD138 expression and 8p deletions (p<0.0001) suggesting a possible functional interaction of CD138 with one or several 8p genes. Multivariate analysis revealed the cytoplasmic CD138 expression as an independent prognostic parameter in all cancers and in the ERG positive subgroup. In summary, our study indicates the cytoplasmic CD138 expression as a strong and independent predictor of poor prognosis in prostate cancer. Immunohistochemical measurement of CD138 protein may thus—perhaps in combination with other parameters—become clinically useful in the future

Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer

Protein phosphatase 1 nuclear-targeting subunit (PNUTS) is ubiquitously expressed and associates with PTEN and protein phosphatase 1 (PP1) to control its activity. The role of PNUTS overexpression has hardly been studied in cancer. In this study, we used immunohistochemistry to quantitate PNUTS expression on a tissue microarray containing 17,747 clinical prostate cancer specimens. As compared to normal prostate epithelium, PNUTS expression was often higher in cancer. Among 12,235 interpretable tumors, PNUTS staining was negative in 21%, weak in 34%, moderate in 35%, and strong in 10% of cases. High PNUTS expression was associated with higher tumor stage, classical and quantitative Gleason grade, nodal stage, surgical margin, Ki67 labeling index, and early biochemical recurrence (p<0.0001 each). PNUTS expression proved to be a moderate prognostic parameter with a maximal univariable Cox proportional hazard for PSA recurrence-free survival of 2.21 compared with 5.91 for Gleason grading. It was independent from established prognostic parameters in multivariable analysis. Comparison with molecular data available from earlier studies using the same TMA identified associations between high PNUTS expression and elevated androgen receptor expression (p<0.0001), presence of TMPRSS2:ERG fusion (p<0.0001), and 8 of 11 chromosomal deletions (3p13, 5q21, 8p21, 10q23, 12p13, 13q14, 16q24, and 17p13; p<0.05 each). Particularly strong associations with PTEN and 12p13 deletions (p<0.0001 each) may indicate a functional relationship, which has already been established for PNUTS and PTEN. PNUTS had no additional role on outcome in PTEN-deleted cancers. In conclusion, the results of our study identify high PNUTS protein levels as a predictor of poor prognosis possibly linked to increased levels of genomic instability. PNUTS measurement, either alone or in combination, might be of clinical utility in prostate cancers