The filters in KPT 5 are not merely upgrades to the filters in KPT 3, they are totally new and original filters. That said, KPT 5 comes with all of the filters from KPT 3 so you won't have to miss out on all those tasty old effects. Now let's take a closer look at each of the new filters in KPT 5. I will be mentioning the speed of the filters from time to time as well. As a frame of reference, I tested KPT 5 on a 400 Mhz Pentium II (100 MB bus), 256 MB RAM, running Windows 98.
No, we didn't fall asleep on the "r" key, that's how MetaCreations spelled it. KPT Blurrrr adds a range of new blurring tools to your arsenal. Some of the blur effects are new and original such as the Hi-Speed Blur option (a fast Blur that leaves more of the original image intact), the Kraussian Blur option (an augmented Gaussian Blur), and Gaussian Weave Blur (a Gaussian Blur that is applied horizontally and vertically to create a burlap-style "weave" effect). Other Blur effects include Camera Optics (which simulates optical blur effects similar to those created with a camera), Zoom Blur, Spiral Blur, Spiral Weave Blur, and Motion Blur.
I found the Motion Blur to be particularly handy because it lacks the shortcomings of Photoshop's own Motion Blur. KPT's Motion Blur filter blurs the image or selection beyond the boundaries making the effect more realistic and less troublesome (with Photoshop's Motion Blur you must expand the image canvas or selection in order to achieve the same effect). Almost all of the effects were reasonably quick on a 640 x 480, 72 ppi image. Global applications took no more than 10 seconds, and many were applied instantaneously.
KPT FiberOptix applies various "fiber"-like looks to your images. That's right folks, it's the digital Chia Pet coming at you live in all it's psychedelic glory! Actually the effect can either be very dimensional or it can be flat to to generate a somewhat painterly look on global images. As Figure 3 shows, you can apply the filter to masked areas to localize the effect (although this is a bit confusing since you must apply this with the "Noise" setting). The "Noise" setting provides for a dramatic range of possible effects with the FiberOptix filter, many of which are far removed from its namesake effect. However, most of these are very wild and it can take a lot of time and experimentation to find something useful.
FraxFlame is yet another open ended filter. This one generates an infinite variety of patterns using fractals. FraxFlame does not generate the classic fractal pattern. Instead these patterns resemble ethereal phenomena such as galaxies, nebulas, and lightening. The results of this filter are nothing short of beautiful and they are perhaps a tad more usable in a general professional setting than effects created with the FraxPlorer filter.
With all of the filters from KPT 3, KPT 5 is simply the best plug-in value on the market at this time. The new filters in KPT 5 are a powerful blend of effects. The raw range possibilities in plug-ins such as FraxPlorer and KPT Noize make it possible to get a unique fractal or texture. What KPT 5 has lost in its sort of arcade game-like interfaces, it has gained in sheer depth of capability.
The activities of SINEs were scrutinized in chronic lymphoid leukemia (CLL) in a preclinical study . SINEs curbed cell growth by forcing the nuclear retention of major TSPs like p53, IkB and FOXO. KPT-185 resulted in the down regulation of MCL-1 expression in CLL cells. KPT-185 and KPT-251 were also examined in stromal cells such as HS-5 . SINEs increased overall survival rate in the Emu-TCL1-SCID mouse model of CLL with minimal toxicities. Therefore, CRM1/XPO1 is a valid target in CLL with minimal effects on normal cells. This favors further development of SINEs in CLL and related hematologic malignancies .
CRM1 is highly expressed and negatively correlates to survival in MM. In a preclinical study, CRM1 inhibition by SINE was explored in MM cells and in SCID mice. Higher levels of CRM1 were associated with bortezomib resistance, lytic bone disease and shorter survival. Blocking CRM1 activity by SINEs induced apoptosis in isolated MM cells and in those cultured in a simulated bone marrow microenvironment . KPT-330 and KPT-185 were found to directly block osteoclastogenesis and bone resorption without adverse effects on osteoblastogenesis. This study also defined the role of CRM1 in osteoclast formation. Both KPT-185 and KPT-330 inhibited NF-ĸB and NFATc1, thus preventing the formation of a functional osteoclast . This study also noted a synergistic effect when SINEs were combined with bortezomib .
The effects of SINEs on mantle cell lymphoma (MCL) were also studied [29,30]. Compared with normal cells, MCL cells had higher XPO1 expression . KPT-185 was found to enhance apoptosis of MCL cells through increased nuclear p53 levels . Oral administration of KPT-276 significantly inhibited MCL growth in a mouse model without severe toxicity . KPT-276 increased nuclear retention of CRM1.
A phase I trial of KPT-335 was done in 17 dogs with lymphoma, mast cell tumor or osteosarcoma. KPT-335 was administered at an oral dose of 1.75 mg/kg twice weekly. The common side effects of anorexia, weight loss, vomiting and diarrhea were manageable with supportive care .
Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC.
We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer.
We found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo.
In this study, we investigated the biological function of XPO1 in GBC and the anti-cancer effects of the XPO1 inhibitor, KPT-330. Our study is the first to demonstrate the significant association between overexpression of XPO1, and poor clinical characteristics and prognosis in GBC patients. It was found that XPO1 inhibitor KPT-330 inhibited proliferation and colony formation of GBC cells. XPO1 inhibitor KPT-330 also induced mitochondria-dependent apoptosis and autophagy of GBC cells. Furthermore, KPT-330 activated the p53/mTOR pathway to induce autophagy-dependent apoptosis. In a nude mouse model of GBC, KPT-330 inhibited tumor growth without causing obvious toxic effects. Overall, XPO1 is a promising prognostic indicator for GBC, and KPT-330, a specific inhibitor of this transporter, might be a more effective and less cytotoxic chemotherapeutic agent for the treatment of GBC.
The in vivo experiment showed that the XPO1 inhibitor, KPT-330, had potent anti-GBC activity. Administration of 20 mg/kg of KPT-330 significantly inhibited the growth of GBC cells in a nude mouse xenograft model without any significant toxic effects. However, some clinical studies with KPT-330 have revealed adverse effects such as decreased appetite, vomiting, and decreased weight, but without significant effects on vital organs . Further studies are needed to investigate in vivo effects of KPT-330 treatment.
The authors gratefully acknowledge the patients and the volunteers for providing their bone marrow cells in this study. This work was supported by grants from the Natural Science Foundation of Guangdong Province, China (D.N. 2016A030313360, J.X. 2017A030310017), and the Foundation of Guangdong Provincial Department of Science and Technology, China (Y.L. 2016A020215062).
Although there have been studies investigating the relationship between abnormal head posture and pain, studies on the relationship between forward head posture and respiratory function are inadequate. Moreover, while the McKenzie exercise has been demonstrated to be effective in decreasing pain and improving posture, there are insufficient studies on the effects of this exercise program on respiratory function. Based on past results that demonstrated the negative impact of musculoskeletal issues on respiratory function, the authors deem the McKenzie exercise to be an appropriate intervention. Therefore, the purpose of the present study was to investigate the effects of McKenzie exercise on forward head posture and respiratory function.
In order to determine the effects of the McKenzie exercise on forward head posture and respiratory function, the randomized trial selected subjects whose craniovertebral angle (CVA) was less than 49° as a reference.23 The subjects in the experimental group underwent McKenzie exercise, whereas the control group received no intervention. This was done to measure changes in CVA and respiratory function from pre-intervention to post-intervention (after four weeks of exercise) in the experimental group. Furthermore, changes in CVA and respiratory function from pre-intervention to post-intervention between the two groups were analyzed. This study was approved by the Bioethics Committee of the Catholic University of Pusan (CUPIRB-2013-015). 2b1af7f3a8