Knowledge management (KM) is about enhancing the use of organizational knowledge through sound practices of information management and organizational learning. The study emphasizes on information technology, organizational learning, and knowledge management in higher education institutes of Pakistan. The impact of knowledge management components and practices are empirically tested through econometric techniques. The study uses a sample of 26 universities of Khyber Pakhtoonkhawa (KPK) province of Pakistan, both in the public and private sectors.The results indicate that knowledge management practices measured through information technology, organization, and knowledge significantly affect organizational performance of the universities.

Fluid shear stress maintains vascular homeostasis by influencing endothelial gene expression. One mechanism by which shear stress achieves this is through the induction of transcription factors including Krü ppel-like factor 2 (KLF2). We have previously reported that a 62-bp region of the KLF2 promoter is responsible for its shear stressinduced expression via the binding of nuclear factors. In this study, we find that the 62-bp shear stress response region contains a 30-bp tripartite palindrome motif. Electrophoretic mobility supershift and chromatin immunoprecipitation assays demonstrate that PCAF (P-300/ cAMP-response element-binding protein-binding protein-associated factor)) and heterogeneous nuclear ribonucleoprotein D bind this region as components of the shear stress regulatory complex. We have also characterized a PI3K-dependent/Akt-independent pathway responsible for shear stress-induced KLF2 nuclear binding, promoter activation, and mRNA expression. Furthermore, the shear stress response region of the KLF2 promoter was specifically immunoprecipitated by antibodies against acetylated histones H3 and H4 in shear-stressed but not static hemangioendothelioma cells. The acetylation of these histones was blocked by PI3K inhibition. Finally, we have found that KLF2 increases endothelial nitric-oxide synthase expression in murine endothelial cultures, an effect that is also blocked by PI3K inhibition. These results define the DNA regulatory element, signal transduction pathway, and molecular mechanism activating the flow-dependent expression of a vital endothelial transcription factor.Mechanical forces influence endothelial phenotypes through signal transduction and gene activation. Hemodynamic shear stress, the frictional force that results from viscous blood flow (1), is of primary importance to the endothelium. It stimulates an adaptive response to generate antioxidant, anti-proliferative, anti-apoptotic, and anti-atherosclerotic patterns of gene expression (2, 3).One of the most important factors in this response is the level of nitric oxide (NO) 1 production. In addition to being a potent vasodilator (4), NO inhibits inflammation (5), smooth muscle cell proliferation (6), platelet aggregation (7), and endothelial cell apoptosis (8). NO levels are increased, in part, through the activation of endothelial nitric-oxide synthase (eNOS) by phosphorylation on Ser 1177 via the pro-survival phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which plays an integral role in the response to fluid shear stress (9 -11). It is also responsible for the induction of eNOS mRNA by shear stress (12). Although Akt is the canonical immediate target of PI3K activation, PI3K-dependent/Akt-independent shear stress signal transduction pathways have been reported (13,14). However, little is known regarding the effectors of the PI3K mechanotransduction pathway or the molecular mechanisms underlying the signaling events from shear stress to gene expression in endothelial cells.The application of shear stress up-regulates mRNA levels ...

Purpose The purpose of this paper is to examine the reasons behind low penetration of Islamic banking in Pakistan. Specifically, the study investigates the differentiation of Islamic banks (IBs) from conventional banks, the role of religion in choosing Islamic banking and the perception of IBs amongst the consumers. Design/methodology/approach The study uses a mixed-method approach, qualitative research along with a survey of users of conventional and Islamic banking. Factor analysis identified underlying dimensions and cluster analysis ascertained the differences between users and non-users of Islamic banking. Inferential statistics were used to test purported hypotheses. Findings The study finds that the users and non-users both perceive that Islamic banking is not completely interest-free. Furthermore, consumers presume that IBs are more of eyewash and are not truly practicing Islamic banking. Moreover, religion is not a major factor that attracts new users but there are also other important factors in marketing Islamic banking, such as service quality, convenience, branch network, etc. Originality/value This is one of the sparse studies in the field of Islamic banking consumer behaviour, which uses focus groups of users and non-users, and in-depth interviews of experts, to identify the issues and factors considered relevant and important by the users rather than relying only on literature review. Furthermore, it also provides a profile of users versus non-users of Islamic banking which is very useful for segmentation and targeting of customers.

Fluid shear stress is crucial for maintenance of a properly functioning endothelium. In this study we demonstrate that the KLF2 transcription factor is greatly induced by pulsatile shear stress in murine microvascular endothelial cells. The promoter elements responsible for the induction were studied by transfection with luciferase-reporter plasmids including the 5' flanking region of the murine KLF2 gene. Deletion analysis reveals that the responses are regulated by a region from -157 to -95 bp from the start site of transcription. Furthermore, shear stress induces specific nuclear binding within this region. These results define a novel shear stress response region that is highly conserved between mouse and human homologs.

Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du Myé lome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezomib during induction, before and in consolidation after tandem melphalanbased transplantation; TT3A applied VTD (bortezomib, thalidomide, dexamethasone) in the first year of maintenance and TD for 2 more years, whereas TT3B used VRD (bortezomib, lenalidomide, dexamethasone) maintenance for 3 years. The cumulative incidence of SPMs did not differ significantly among the TT trial components when measured from enrollment (P ‫؍‬ .78) or from initiation of maintenance (P ‫؍‬ .82). However, a pairwise comparison of the TT2 arms suggested a lower incidence of hematologic SPMs in the thalidomide maintenance arm (hazard ratio ‫؍‬ 0.38; P ‫؍‬ .09). These trials are registered at www.clinicaltrials.gov as NCT00573391 (TT2), NCT00081939 (TT3A), and NCT00572169 (TT3B). (Blood. 2012; 120(8):1597-1600)

Theragnostics represent cutting-edge, multi-disciplinary strategies that combine diagnostics with therapeutics in order to generate personalized therapies that improve patient outcome. In oncology, the approach is aimed at more accurate diagnosis of cancer, optimization of patient selection to identify those most likely to benefit from a specific therapy and to generate effective therapeutics that enhance patient survival. MicroRNAs (miRNAs) are master regulators of the human genome that orchestrate myriad cellular pathways to control growth during physiologic and pathologic conditions. Compelling evidence shows that miRNA deregulation promotes events linked to tumor initiation, metastasis and drug resistance as seen in multiple myeloma (MM), an invariably fatal hematologic malignancy. miRNAs are readily detected in body fluids, for example, serum, plasma, urine, as well as circulating tumor cells to demonstrate their potential as readily accessible, non-invasive diagnostic and prognostic biomarkers and potential therapeutics. Specific miRNAs are aberrantly expressed early in myelomagenesis and may more readily detect high-risk disease than current methods. Although only recently discovered miRNAs have rapidly advanced from preclinical studies to evaluation in human clinical trials. The development of miRNA theragnostics should provide widely applicable tools for the targeted delivery of personalized medicines to improve the outcome of patients with MM.

No abstract

Change in gene functions (gene cooption) is one of the key mechanisms of molecular evolution. Genes can acquire new functions via alteration in properties of encoded proteins and/or via changes in temporal or spatial regulation of expression. Here we demonstrate radical changes in the functions of orthologous ATP1B4 genes during evolution of vertebrates. Expression of ATP1B4 genes is brain-specific in teleost fishes, whereas it is predominantly muscle-specific in tetrapods. The encoded ␤m-proteins in fish, amphibian, and avian species are ␤-subunits of Na,K-ATPase located in the plasma membrane. In placental mammals ␤m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). Through interaction with SKIP, eutherian ␤m acquired new functions as exemplified by regulation of TGF-␤-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-␤ signaling. Thus, orthologous vertebrate ATP1B4 genes represent an instance of gene cooption that created fundamental changes in the functional properties of the encoded proteins.ATP1B4 ͉ gene cooption ͉ skeletal muscle development ͉ TGF-␤ ͉ Smad7