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An extraordinarily rich debut novel set in India in 1947 at the time of the Partition, when India and Pakistan were split into separate countries. Bilal is determined to protect his dying father from the news of the Partition of his country – news that he knows will break his father's heart. With spirit, determination and the help of his good friends, Bilal persuades those around him to collude in a great deception, even printing false pages of the local newspaper to hide the ravages of unrest from his father. All he wants is for his father to die in peace. But how long will Bilal be able to keep up his well-meaning, beautiful lie?
This book was interesting as I wanted to see how far Bilal would go in his determination to hide the truth from his father. A good read.
I like the look of it, but i don't know if it would suit what i like.


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TVN'S OTT NEWS SUMMIT 2020
For News Streaming, Election Is Proving Ground
Executives from CNN, ABC News, E.W. Scripps, Gray and Yahoo say the 2020 election provides them an opportunity to build on the audiences surges they've seen on their streaming platforms since the pandemic.
By Michael Stahl | September 24, 2020 | 5:30 a.m. ET.
News organizations say the COVID-19 outbreak helped speed up the already growing viewership trend toward their OTT platforms. But the impending election presents them a watershed moment to retain and build on the large swaths of the audience they gained.
OTT's digital delivery may inherently be an advantageous means in which to effectively produce news in this tumultuous year, filled with ever-changing health and safety concerns — and now all the pinball-like dynamics of a presidential campaign season.
Socrates Lozano
"One of the things that the pandemic just does is it makes our group have to be a lot more flexible and adjust to whatever our audiences need and want," said Socrates Lozano, senior director of OTT content at the E.W. Scripps Co.
Speaking on a panel about the 2020 election's OTT programming opportunities, part of TVNewsCheck's OTT News Summit, Lozano said that his station group was already working to get OTT channels up in each of its markets, in what he called an "aggressive plan" that was in place before the pandemic.
Initially, the company rolled out OTT programming with a focus on just primetime news. "But once the pandemic hit and suddenly audiences started coming into the stream, wanting answers, we ended up expanding to a very aggressive 24/7 strategy plan overnight," Lozano said, "which was definitely a huge pivot."
Gray Television had also spun up OTT channels across its stations, going "all in" on the platform about a month prior to the pandemic landing stateside, said Glen Hale, the station group's VP of digital content and audience development. Gray had installed OTT "desks" in each of the newsrooms in its 93 markets and made sure that they could be manned by a lone individual.
A few months later, when Hurricane Laura struck Lake Charles, La., Gray was able to use those desks "in a way that we had not even fathomed before we had installed them," Hale said. After KPLC, its Lake Charles station, was evacuated, the group was able to send its crew from there to its WAFB in Baton Rouge, "and route things through as though they were at the originating station," Hale said.
"Those types of things were eye opening," he said. "We knew that there would be a lot of flexibility in that type of thing already, but to be able to put it in action [that quickly] it was pretty amazing how it evolved."
Related Story Actress Naya Rivera Missing In SoCal Lake
Even a relatively new brand in the space, such as Yahoo Finance, is embracing this chance to build its audience in OTT.
"We're just pivoting every second of the day; that's the nature of the beast when you're OTT, and that's a luxury," said Andy Serwer, the platform's editor in chief, who admitted that Yahoo Finance doesn't have the name recognition or reputation of CNN or ABC News, for example, but has been able to significantly build an audience during the pandemic.
"I told my team we were at 100, and we went to 200; we're probably not going to keep 200, but let's not go below 150," Serwer said, offering hypothetical numbers that hinted at a doubling up of viewership since the pandemic began. "Getting the word out and understanding that you have to use off-network and social, of course, business development, audience development, to get new people to come to your platform is hugely important."
Once a publisher has attracted viewer eyes, quality keeps them coming back around. Serwer said Yahoo Finance has been able to leverage its partnerships with HuffPost and Yahoo News to show viewers it means business, sure to serve them well as they cover the upcoming election.
"Lazy reporting cannot happen," Serwer said. "We need to prove ourselves, and so I think that's a challenge that our team tries to accept."
Even the offshoot OTT teams of legacy news brands feel the same drive.
Katie den Daas
In late February, the brass at ABC News directed Katie den Daas, executive producer of ABC News Live, to construct a daily show focusing on the coronavirus. The result was a 30-minute program with Dr. Jennifer Ashton and whatever health experts the team could book.
"About a week into that they called and said: 'Can you guys turn your 30-minute, digital-only show into a one-hour network show that goes onto both platforms?' " den Daas recalled. "That was Friday night at 7 o'clock, and by Tuesday we were on the air."
Her team's flexibility made that pivot possible, and den Daas said to be able to deliver on that request felt validating to the digital squad.
Related Story Dow Finishes Down 85, Nasdaq Drops 64
"Usually it's a one-way street where the network produces content and then we piggyback off of it," den Daas said. (After a presidential debate, for example, ABC News Live often offered contextual commentary after the fact.) "So, for us to get to produce that content and share it back down that lane, that was great for us."
Building on such momentum, den Daas added that the election provides "an opportunity for us to really double down on what ABC News does really well and bring it to a new audience, and really grow the future of ABC News, not just ABC News Live."
Coming off of the surprise results in 2016's presidential election, she said it feels incumbent upon ABC News and the group's OTT offering to "continue hitting the issues really hard that our viewers want to hear about versus following the horse race. This is an opportunity for us to actually serve our viewers better, in a more meaningful way," she said.
Michael Depp, TVNewsCheck editor and panel moderator, asked Mike Toppo, VP of global video programming at CNN Digital, what CNN's OTT offering can provide viewers that's so essential when the CNN network already broadcasts 24 hours a day, with a heavy election bend.
Toppo said his team's job is partially to "fill in gaps," with "more explainers, more commentary that we can use complimentary really only on OTT."
When Chris Cuomo came down with COVID-19, CNN's OTT team developed a series following his journey through recovery.
"Really all we did was package his TV segments in a way that made it look like a series, and we saw that people were going back and watching segments from his show two or three days later," Toppo said. "So with OTT you have this opportunity to do a lot of incredible packaging that you're not necessarily able to do on desktop web and mobile apps."
Such an approach can easily be applied to any element of campaign coverage, and be just one of the ways OTT, a growing resource, can help keep a news organization's audience engaged.
Find more OTT News Summit coverage here.
Executives from CNN, ABC News, E.W. Scripps, Gray and Yahoo say the 2020 election provides them an opportunity to build on the audiences surges they've seen on their streaming platforms since the pandemic. Click To Tweet
Tags: ABC, CNN, Gray, OTT News Summit, OTT News Summit 2020, political coverage, Scripps, Yahoo

redpajama_set_name: RedPajamaCommonCrawl


A most basic description of Ectoplasm if there ever was one, but past research has shown that this was a joking name for Ectoplasm until more of its properties were discovered.
Ectoplasm comes from ghosts when they take on a material form in the realm of the living. They draw energy from the realm of the dead to create their bodies, but when the spirit goes back the beyond, that body dissolves into a puddle of goo that we call Ectoplasm. When the energy from the ghost is gone the goo will evaporate within a few minutes, leaving only a stain on some surfaces that is easily washed away.
However, if acted upon with the proper magic within a few moments the Ectoplasm can be preserved and thereafter used for many useful things, not the least of which is creating potions and certain items. Once that process was discovered it was soon refined and a booming business sprouted up in which spirits were summoned and made to form physical bodies after which they would be banished from them and the Ectoplasm collected. This worked for a time until the spirits became restless by constant summoning and banishment and started to haunt those living beings that had been harassing them.
Now, willing spirits that are more than happy to help are used for the collection of Ectoplasm, and with certain mages being able to cross the plains of Life and Death they to have started to collect Ectoplasm for sale. Prices are still steep for Ectoplasm, however, and its uses are still being discovered. Below is a list of known items that Ectoplasm helps in the creation of, in no particular order.
This article was last modified: July 15, 2018, 2:08 p.m.


Mehra S currently working at Department of Cardiovascular sciences, Brody School of Medicine, Greenville, NC, USA. His international experience includes various programs, contributions and participation in different countries for diverse fields of study. His research interests reflect in wide range of publications in various national and international journals.


text:
«Антисемитизм — это социализм дураков» () является заявлением, опровергающим идею о том, что еврейское богатство и власть являются источником социальной несправедливости. По словам британского историка Ричарда Эванса, вероятно, он был изобретен австрийским демократом Фердинандом Кронаветером, но обычно приписывается немецкому социал-демократу Августу Бебелю, а иногда и Карлу Марксу. К 1890-м годам это выражение было широко распространено среди немецких социал-демократов.

Лео Штраус утверждал, что советский лидер Иосиф Сталин намеренно импортировал нацистские идеи о евреях, считая, что «социализм дураков» — это хорошо, потому что дураки — обычное дело.

Рекомендации

Дальнейшее чтение

Антисемитизм в Германии

redpajama_set_name: RedPajamaWikipedia


Proclivity is all about allowing you to create people power that matches your vision. The possibilities are limitless; our products and services overview will will get you started.
Every Procliviity assessment, development, selection product has two parts: scienfific perfiomance validation and customization to your specific needs. Our appoach is taking "off the shelve" validated cores to keep prices low, yet cutomize them to your specific performance requirements. Over 500 CEO's and senior managers have found value in our approach.


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Ying-Yong Zhao
Northwest University, China
Berenice Gitomer
University of Colorado Anschutz Medical Campus, United States
ZHIGUO MAO
Department of Nephrology, Shanghai Changzheng Hospital, China
Pharmalogical Effect of Herbal Medicine on ADPKD
Front. Pharmacol., 27 April 2021
Sec. Renal Pharmacology
Volume 12 - 2021 | https://doi.org/10.3389/fphar.2021.629848
Applications of Herbal Medicine to Treat Autosomal Dominant Polycystic Kidney Disease
Guangying Shao1, Shuai Zhu1 and Baoxue Yang1,2*
1State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China
2Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary kidney disease, which is featured by progressively enlarged bilateral fluid-filled cysts. Enlarging cysts destroy the structure of nephrons, ultimately resulting in the loss of renal function. Eventually, ADPKD develops into end-stage renal disease (ESRD). Currently, there is no effective drug therapy that can be safely used clinically. Patients progressed into ESRD usually require hemodialysis and kidney transplant, which is a heavy burden on both patients and society. Therefore, looking for effective therapeutic drugs is important for treating ADPKD. In previous studies, herbal medicines showed their great effects in multiple diseases, such as cancer, diabetes and mental disorders, which also might play a role in ADPKD treatment. Currently, several studies have reported that the compounds from herbal medicines, such as triptolide, curcumin, ginkolide B, steviol, G. lucidum triterpenoids, Celastrol, saikosaponin-d, Sparganum stoloniferum Buch.-Ham and Cordyceps sinensis, contribute to the inhibition of the development of renal cysts and the progression of ADPKD, which function by similar or different mechanisms. These studies suggest that herbal medicines could be a promising type of drugs and can provide new inspiration for clinical therapeutic strategy for ADPKD. This review summarizes the pharmacological effects of the herbal medicines on ADPKD progression and their underlying mechanisms in both in vivo and in vitro ADPKD models.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with the current incidence of 1/1,000–1/400 worldwide. The course of the disease is characterized by multiple growing cysts in bilateral kidneys. The cysts are derived mainly from renal tubular epithelium. As the cyst getting larger, the cysts compress the normal renal parenchyma, thus resulting in the destruction of the normal renal structure and function (Bergmann et al., 2018).
Pkd1 and Pkd2 are two main genes participating in the pathogenesis of ADPKD, which encode protein polycystin 1 (PC1) and polycystin 2 (PC2), respectively (Cornec-Le Gall et al., 2019). Pkd1 gene mutation accounts for approximately 85–90% of total ADPKD patients, and 10–15% ADPKD patients are caused by Pkd2 gene mutation. PC1 localizes to the primary cilia, plasma membrane and adhesion complex in polarized epithelial cells. PC2 is a six-transmembrane protein and functions as a Ca2+-responsive cation channel of the transient receptor potential family, and co-localizes with PC1 to the cilium and plasma membrane. Proteins PC1 and PC2 work together to form the PC1-PC2 complex, which is activated in reaction to ciliary bending and then leads to the release of Ca2+ from the intracellular store, thus inducing signal transduction. The disruption of the functional PC1/PC2 complex abolishes normal cellular Ca2+ signaling, which subsequently increases intracellular cAMP and activates PKA signaling pathway, then activating downstream proliferative signalings (Yamaguchi et al., 2006). During the progression of ADPKD, some signaling pathways are activated, which are related to hyperproliferation, fluid secretion and fibrosis, such as mTOR, JAK, Wnt and MAPK signaling pathways. And some other pathways are suppressed, for example, AMPK pathway, which participates in intracellular energy generation.
However, existing drugs have their own limitations in ADPKD therapy. At present, tolvaptan, the first FDA-approved drug, is available clinically for ADPKD patients. Tolvaptan acts as a V2R antagonist, and functions by downregulating intracellular cAMP level to inhibit the abnormal proliferation in ADPKD kidneys. However, a signal of liver toxicity risk emerged with tolvaptan application, which is marked by extremely elevated ALT level and needs to be carefully monitored during the therapy. Another drug of vaptans, Lixivaptan, which is a newer, nonpeptide, oral V2R-specific antagonist, exhibits relatively preserved renal function (stage 1 and 2) and moderately impaired renal function (stage 3). Another family of drugs are the analogs of somatostatin, lanreotide and octreotide, which slow the progression of ADPKD by inhibiting the chlorine channel. However, they did not show significant effect on the renal function in clinical trials.
In addition, interventions to the abnormal signaling pathways, metabolic and dietetic approach are also regarded as possible strategies for ADPKD drug development. For example, mTOR inhibitors (everolimus and sirolimus), metformin (an agonist of AMPK), 2-deoxy glucose (2DG) (a glucose analog that can paralyze the glycolytic pathway), tyrosine kinase inhibitors (bosutinib and tesevatinib) and caloric restriction diet are all reported to retard cyst growth in ADPKD patients to different extent (Testa and Magistroni, 2020). But none of these drugs mentioned above is considered as satisfactory therapeutic agents for ADPKD for their drawbacks, such as unstable effects on slowing the progression of the disease, restricted applications of the aquaretic type drugs and little effect on the loss of renal function. Therefore, there still remains an urgent demand for alternative effective drugs.
The therapeutic properties of plants have long been recognized to treat various diseases for centuries. At present, a number of plant natural products have either been clinically used to treat a variety of human diseases, or have shown particularly interesting biological activities that are worth further exploration (Li and Weng, 2017), such as artemisinin from artemisia annua, which has great anti-malaria effect and won the Nobel prize in 2015. Recently, some studies have found that herbal medicines play different pharmacological roles in renal diseases including ADPKD (Wang et al., 2019). Several natural herbal medicines have been reported to restrain cystogenesis and improve renal function in animal models of ADPKD (Yuajit and Chatsudthipong, 2016). In this article, we summarized the pharmacological effects of several herbal medicines on ADPKD and the underlying mechanisms (Figure 1), expecting to provide new prospectives for ADPKD treatment.
FIGURE 1. Schematic illustration of the key mechanisms of ADPKD pathogenesis and targets of potential treatments of herbal medicines. PC1 and PC2 express in different subcellular locations and aberrant function of PC1 and PC2 results to decreased intracellular Ca2+ and subsequent activation of cAMP via AC6. Abnormally increased cAMP leads to the activation of PKA, activating Ras/B-Raf/MEK/ERK and mTOR signaling pathways through inhibiting TSC1 and TSC2, which drive cell proliferation. Moreover, the activated PKA can also promote the transport of Cl− into the cyst cavity via CFTR, thus causing increased cyst fluid secretion. Autophagy can also be induced by Ca2+-mobilizing agents by activating the CaMKKβ-AMPK-mTOR signaling cascades. In addition, EGF activates Ras and promotes cell proliferation by binding to the corresponding receptor. The targets of candidate drugs are depicted as red boxes. Abbreviations: PC1, polycystin-1; PC2, polycystin-2; AC6, adenylyl cyclase six; V2R, vasopressin type 2 receptor; SSTR, somatostatin receptor; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; CFTR, cystic fibrosis transmembrane conductance regulator; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; MEK, mitogen activated protein kinase; ERK, extracellular-signal regulated kinase; TSC, tuberous sclerosis; mTOR, the mammalian target of rapamycin; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+ atpase; CaMKKβ, Ca2+/CaM-dependent protein kinase β; AMPK, AMP-activated protein kinase; GA-A, ganoderic acid A; SBH, Sparganum stoloniferum Buch.-Ham.
Triptolide
Triptolide is a diterpene triepoxide that was first isolated from the medicinal plant Tripterygium wilfordii Hook F (TWHF) and its structure was characterized in 1972. Its molecular formula is C20H24O6 and the molecular mass is 360 (Wei et al., 2019). Clinical and experimental studies have shown that triptolide has anti-inflammatory and immunosuppressive activities in bone marrow, heart, kidney and skin transplantation, and can effectively prolong the survival time of the graft. Therefore triptolide has been widely used in inflammatory and autoimmune diseases (Yuan et al., 2019), including rheumatoid arthritis (RA), immune-complex nephritis, systemic lupus erythematosus (SLE), and organ transplantation (Liu, 2011).
It was found that triptolide could bind to PC2 based on extensive chromatographic protein fractionation, MALDI-MS analysis, and Western blot results. As a PC2 agonist, triptolide could restore cytosolic Ca2+ release. In Pkd2+/− mouse renal epithelial cells, triptolide increased intracellular Ca2+. When the cell line re-expressed Pkd2, the intracellular Ca2+ level was elevated and apoptosis was increased with triptolide's incubation (Leuenroth et al., 2007). Therefore, triptolide might inhibit cyst development by activating PC2, thus increasing intracellular Ca2+ and inducing caspase pathway. According to some other studies, induction of expression of p53 protein, activation of MAPK pathway and inhibition of NF-κB signaling pathway may also play roles in the progress of apoptosis, which needs to be further explored (Kim et al., 2010; Tai et al., 2010).
Rapamycin, an inhibitor of mTOR, could inhibit the cystic progress of ADPKD kidneys by downregulating cyclin A, cyclin B, cyclin 1D and cyclin E, which are associated with cell cycle, thereby preventing abnormal proliferation of renal epithelial cells (Li A. et al., 2017). Roscovitine, a cycle-dependent kinase inhibitor, has been shown to inhibit the formation of renal cysts in animal models (Billot et al., 2018), further illustrating that cell cycle may be one of targets in inhibiting ADPKD. Considering the cell cycle arrest effect of triptolide in colon cancer, the regulation of cell cycle may be involved in the inhibition of triptolide on the renal cyst formation in animal models. Triptolide arrested cell growth in Pkd1−/− mouse renal epithelial cell line. The up-regulated expression of cyclin p21 was detected (Leuenroth et al., 2007). Furthermore, inhibitory effect of triptolide on cell cycle was also demonstrated in the smooth muscle cells induced by platelet-derived growth factor (PDGF) (He et al., 2020) and renal cell carcinoma cells (Li et al., 2011) through G0/G1 cell cycle arrest, which supports that triptolide may induce cell cycle arrest in ADPKD model.
Curcumin, a polyphenol diferuloylmethane extracted from the rhizome of Curcuma longa plant, has been reported to have multiple effects including anti-oxidation, anti-inflammation and anti-proliferation. Curcumin has shown potential therapeutic effects on various diseases such as neurodegenerative disorders, inflammation-related diseases, fibrosis and cancers via regulating NF-κB, Wnt/β-catenin, MAPK and mTOR signaling pathways (Iqbal et al., 2009), which also are involved in the pathogenesis of ADPKD. Previous studies have demonstrated the inhibitory effect of curcumin on cyst growth by inhibiting cell proliferation and promoting epithelial cell differentiation in Pkd1 deletion mouse models, suggesting its potential to be a natural candidate drug for ADPKD.
In the forskolin-induced MDCK model, which is an in vitro cyst model with MDCK cells cultured in 3D collagen gel, the cell proliferation was significantly inhibited by curcumin incubation and the inhibitory effect may be reversible. The Western blot results revealed that in MDCK cells, curcumin could downregulate B-Raf, upregulate Raf-1 and inhibit ERK signalings, indicating that curcumin inhibits cyst development via suppressing Ras/B-Raf/MEK/ERK signaling pathway (Gao et al., 2011).
Another crucial modulator of cell proliferation activated in ADPKD is STAT3. An inducible kidney-specific Pkd1-deletion mouse model was designed to investigate whether STAT3 signaling was involved in the inhibition of cystogenesis by curcumin. Experimental analysis reflected that activated STAT3 was significantly reduced by curcumin. Therefore, STAT3 inhibition might be a possible mechanism in the curcumin-mediated inhibition on cystogenesis (Leonhard et al., 2011).
MDCK tubule model, in which MDCK cells were incubated in 3T3 conditioned medium, was used to investigate the effect of chemicals on the differentiation of MDCK cells/cysts. Treated with curcumin (at 0.4, 2 or 10 μM) for 12 days, the number of tubule-like structures increased in a dose-dependent manner, and the average length of the longest tubules derived from each MDCK cyst treated by curcumin was longer than those in control group. Consequently, curcumin can promote MDCK cell differentiation, subsequnently inhibiting cyst development (Gao et al., 2011).
Ginkolide B
Ginkgolide B, a major terpene lactone, is an active component of Ginkgo biloba. Ginkgolide B is used as a traditional medicine due to its pharmacological properties such as anti-inflammatory, anti-oxidant, anti-tumor and anti-apoptotic activity (Zhou et al., 2016). Ginkgolide B was also found to inhibit cyst growth in MDCK cyst model and in Pkd1 knockout mice. Experimental results showed that ginkgolide B inhibited cyst formation and growth in a dose-dependent manner through downregulating Ras/MAPK pathway and the inhibitory effect was reversible (Zhou et al., 2012).
Stevioside and Its Derivative
Stevioside is a high-sweet, low-calorie sweetener extracted from the leaves and stems of Stevia Rebuadiana plant, which is a herbaceous plant of the composite family. It is degraded by intestinal microflora to its aglycone, steviol, then taken up into the blood circulation. Stevioside has been reported to have properties including anti-hypertension, anti-hyperglycemia, anti-inflammation, anti-tumor, anti-diarrhea and immunity regulation (Chatsudthipong and Muanprasat, 2009). At present, the pharmacological effect and possible mechanisms of stevioside and its derivative steviol in ADPKD have been investigated, and the possible mechanisms in suppressing cyst progression include restraining the cyst fluid secretion and inhibiting tubule cell proliferation.
ADPKD progression contains two key processes, cell proliferation and fluid secretion, involving multiple signaling pathways. The fluid secretion is driven by cAMP-activated transepithelial chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel located at apical membrane of the ADPKD epithelial cells lining the cyst (Li and Sheppard, 2009). CFTR chloride channel has been proposed as a potential target for PKD intervention. Steviol and its derivatives (isosteviol, dihydroisosteviol and 16-oxime isosteviol) inhibited the formation and growth of cysts in the MDCK cyst model, and the inhibitory effect of steviol was the greatest. Furthermore, the underlying mechanisms of the inhibition of steviol on the forskolin-stimulated apical chloride current included direct inhibition of CFTR chloride channel activity and reduction of CFTR expression via activating proteasome degradation pathway (Yuajit et al., 2013). In addition to proteasome degradation, an ADPKD mouse model showed that steviol also activated adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which could subsequently decrease CFTR chloride channel expression. Accordingly, steviol can retard cyst expansion in part by reducing CFTR expression via promoting AMPK activity or proteasome-mediated CFTR degradation (Yuajit et al., 2014).
It has been demonstrated that cyst expansion is induced by the excessive secretion of Cl− and water into the cyst lumen through CFTR and aquaporins (AQPs) respectively. Aquaporin 2 (AQP2) is involved in fluid secretion in ADPKD and promotes cyst enlargement. Steviol was found to significantly inhibit the growth of cysts in vitro by reducing AQP2 expression in mouse renal cyst epithelial cells. In addition, steviol treatment could increase the expression of enzyme marker of lysosomes, LAMP2, whch also might play a role in AQP2 degradation. Thus, steviol reduced AQP2 expression by reducing AQP2 transcription and promoting proteasome and lysosome-mediated AQP2 degradation, sequentially slowing cyst growth (Noitem et al., 2018).
Stevioside is metabolized into steviol by gut bacteria, which is easily absorbed by the gut and can also reach the kidney (Cosola et al., 2018). In Pkd1flox/flox: Pkhd1-Cre mice, high dose of stevioside could decrease kidney weight and cystic index similar to steviol, but could not improve renal function as steviol. In an orthologous mouse model of human ADPKD (Pkd1flox/flox;Pkhd1-Cre), stevioside and steviol inhibited the CFTR expression and mTOR/S6K proteins by activating AMP-activated protein kinase, thereby delaying the cyst development through inhibiting proliferation of renal epithelial cells (Yuajit et al., 2014). Moreover, Steviol enhanced the expression of lysosomal enzyme marker LAMP2, indicating the increase of lysosomal degradation of β-catenin, which involves in cell proliferation (Yuajit et al., 2017). In general, stevioside and its derivative, steviol, could regulate pathways of cell proliferation to slow down progression of cysts.
G. lucidum Triterpenoids
Ganoderma lucidum is a Chinese traditional medicine. It has been widely used as a dietary supplement or medicine to enhance immunity and therefore improve health for more than 2,000 years in Asia region (Hsu and Yen, 2014). Previous studies have confirmed that Ganoderma lucidum consists of a large number of bioactive components, including terpenoids, proteins, polysaccharides, amino acids, flavonoids, alkaloids and steroids (Geng et al., 2020). Pharmacological and clinical studies showed a variety of pharmacological effects of G. lucidum including anti-oxidation, anti-inflammation (Zhang et al., 2018), anti-liver disorder (Zhong et al., 2018) and anti-tumor (Chen S. et al., 2017), which were mainly attributed to two major active components: G. lucidum polysaccharides and G. lucidum triterpenoids (GTs) (Wu et al., 2001; Liang et al., 2019). GTs can also target NF-κB, Ras/MAPK, PI3K/Akt/mTOR and other signalings through G protein-coupled receptor or RTK membrane receptor signal transduction pathways, causing stagnation of cell cycle and inducing tumor cell apoptosis (Gao et al., 2002). Based on the fact that the activated signaling pathways in the pathogenesis of ADPKD are highly similar to that in solid tumor, drugs inhibiting tumor proliferation may have similar effects in the treatment of ADPKD.
To investigate whether GTs have the potential in inhibiting the progression of ADPKD, MDCK cyst model was performed, and GTs were shown to inhibit the formation and growth of cysts (Su et al., 2017). Meanwhile, the embryonic renal cyst model and two rapidly advancing ADPKD mouse models were employed to confirm the inhibitory effect of GTs on renal cysts at organ level and in internal environment. In vitro experiments also showed that the GTs could down-regulate the expression of H-ras, B-Raf, p-MEK, p-ERK, Egr-1 and c-fos, and up-regulate the expression of Raf-1, suggesting that GTs suppressed cell proliferation by down-regulating intracellular excessive accumulation of cAMP and the Ras/MAPK signaling pathway. Meanwhile, GTs promoted epithelial tubule formation in MDCK cells, which also contributes to alleviate the development of cysts by promoting epithelial cell differentiation (Su et al., 2017).
Due to the complexity and structural diversity of triterpene components of G. lucidum, screening and identifying the effective monomer components is of great significance for the development of drugs for ADPKD treatment with G. lucidum extract. 12 monomer components, including ganoderic acid A, ganoderic acid B, ganoderic acid C2 and ganoderic acid D, were isolated and extracted from GTs. The pharmacodynamic study was carried out in the in vitro MDCK cyst model and found that compared with other monomers, ganoderic acid A (GA-A) has a superior inhibitory effect on the development of ADPKD renal cysts, as shown in Figure 2 (Meng et al., 2020). Results showed that GA-A could inhibit the expression of B-Raf, p-ERK and c-fos in a dose-dependent manner, with no significant effect on normal cells and the kidney tissue of wild-type mice, indicating that GA-A could inhibit the development of ADPKD cysts by down-regulating the Ras/MAPK signaling pathway. The in vitro activities of GA-A and other GT compounds were compared via MDCK cyst model and embryonic kidney cyst model, and it was found that the inhibitory effect on cyst of GA-A was better than other compounds (Meng et al., 2020). Therefore, GA-A may be the main effective component in retarding the development of ADPKD cysts, and has the potential to be developed as a therapeutic drug for the treatment of ADPKD.
FIGURE 2. Inhibition of GA-A on the growth of cysts in ADPKD. (A) Representative light micrographs of MDCK cysts in collagen gel from 4th to 12th day that were untreated or treated with GA-A at different concentrations. The first row, as the control group, was given only FSK stimulation for 12 days; the second, third, and fourth rows were given FSK and 6.25, 25, 100 μM GA-A co-stimulation from the 5th to 12th day, respectively. In the fifth row, FSK and 25 μM GA-A were co-stimulated from the fifth to eighth day, and the GA-A was washed out from the 9th to 12th day with only FSK. The thick black lines indicate the culture time with GA-A. Scale bar = 500 μm. As the concentration of GA-A increases, the inhibitory effect on cyst growth was more obvious. The cyst growth could be restored after removal of GA-A, indicating that the inhibitory effect of GA-A on cyst growth is reversible. (B) Representative graphs of inhibitory effect of different doses of GA-A on mouse embryonic kidney cysts on day 0 and day 6. Embryonic kidneys were cultivated as the negative control (Ctrl) without 100 μM 8-Br-cAMP or exposed to different GA-A concentrations in the presence of 100 μM 8-Br-cAMP. Scale bar = 500 μm. Results showed that GA-A also inhibited the cyst development at the organ level and the inhibitory effect showed a certain dose-effect relationship. (C) Mouse kidneys from wild-type (WT) mice and kPKD mice on postnatal day 4 were treated with vehicle or 50 mg/kg/d GA-A for 4 days. Scale bar = 5 mm. Compared with WT mice, the kidney volumes of kPKD mice were significantly increased, and GA-A effectively inhibited the kidney volumes of kPKD mice with no obvious effect on the kidney volume of WT mice. (D) Hematoxylin and eosin staining of kidneys in vehicle- or GA-A-treated kPKD mice. Scale bar = 1 mm. The kidney of kPKD mice had obvious cystic structure, and normal tissue structure of the kidney was destroyed. The cyst growth in the kidney of kPKD mice treated with GA-A was effectively slowed. (E) Representative Western blotting of signaling proteins in MDCK cells treated with 10 μM FSK and without or with GA-A at different concentrations for 30 min. Results demonstrated that GA-A downregulating the Ras/MAPK signaling pathway in the FSK-treated MDCK cells. (F) Representative Western blotting of signaling proteins in mouse kidneys without or with GA-A treatment.
Celastrol is another main active ingredient of Tripterygium wilfordii in addition to triptolide (Salminen et al., 2010). Previous in vitro studies have proved that celastrol has a significant inhibitory effect on the angiogenesis of vascular endothelial cells and the proliferation of endothelial cells. And celastrol showed anti-inflammatory, anti-tumor, anti-obesity properties and the application in autoimmune diseases (Lee et al., 2014; Liu et al., 2015; Shaker et al., 2014; Yu et al., 2018). Celastrol also played a part in regulating autophagy and apoptosis (Liu et al., 2019) and inhibiting cell proliferation in tumor cells (Liu et al., 2019), suggesting that celastrol could possibly possess the therapeutic potential for ADPKD.
Celastrol was identified as a potent inhibitor of cyst growth in both in vitro 3D cell model and a Pkd1-deficient mouse model (Booij et al., 2019). Considering the anti-inflammatory effect of celastrol in other diseases, the effect of celastrol on pro-inflammatory factors and signaling pathways in ADPKD was investigated. The experimental results indicated that celastrol could suppress the expression of proinflammatory cytokines and macrophage infiltration, and had a tendency to decrease NF-κB with no statistical difference (Chang et al., 2018). According to the knowledge that AMPK activation retards renal cystogenesis via inhibiting mTOR-mediated cell proliferation, the level of AMPK phosphorylation was measured with celastrol treatment in the cystic kidneys. The results displayed that celastrol considerably increased AMPK activation. Thus, celastrol exerts a more powerful role in anti-inflammatory effect than in inhibiting cell proliferation. However, 2 mg/kg/d dosage of celastrol may be toxic in female Pkd1 miR TG mice, and the potential complications should be monitored and paid extra attention to (Chang et al., 2018).
Saikosaponin-d
Saikosaponin-d, one of the major triterpenoid saponins derived from Bupleurum falcatum L (Umbelliferae), has strong pharmacological activities, such as antipyretic, sedative, anti-inflammatory, antibacterial, liver protection, anti-nephritis and immune regulation effects (Cheng et al., 2006; Li C. et al., 2017). Based on previous studies that saikosaponin-d inhibited cell proliferation in three human anaplastic thyroid cancer cell lines and induced G1-phase cell cycle arrest in different cancer cell lines (Liu and Li, 2014), saikosaponin-d can be presumed to be developed as an alternative herbal medicine for ADPKD.
In terms of the pathogenesis of ADPKD, autophagy plays a crucial role in the cystogenesis (Zhu et al., 2017), which is supported by the fact that autophagy activators can slow down the formation and growth of renal cysts, thereby preserving renal function in a Pkd1 mutant zebrafish model.
In the MDCK cell cyst model, MDCK cells were cultivated for 7 days with forskolin stimulation and formed cysts. With saikosaponin-d treatment, cyst diameters were significantly reduced. The induction of cell cycle arrest of saikosaponin-d was also confirmed in ADPKD cells by accumulation of P27 (Shi et al., 2018). In addition, saikosaponin-d increased autophagy by increasing autophagosome formation and promoted autophagic flux in ADPKD cells. Furthermore, previous experimental results (Wong et al., 2013) showed that saikosaponin-d increased cytosolic Ca2+ level and activated autophagy via CaMKK β-MPK-mTOR kinase cascade, which may explain the role of saikosaponin-d in the inhibition of cyst growth in ADPKD (Shi et al., 2018).
Sparganum stoloniferum Buch.-Ham
The Chinese herb Sparganum stoloniferum Buch.-Ham (SBH), also called common burred rhizome, consists of several active ingredients including volatile oils and flavonoids, saponins, organic acids, phenylpropanoids and alkaloids (Wang et al., 2015). Recent evidence proved that SBH exerts anticoagulant, antithrombotic, analgesic, anti-inflammatory, antitumor and other pharmacological effects (Sun et al., 2011). The effect of SBH on ADPKD has also drawn the attention.
The direct activation of epithelial growth factor receptor (EGFR) by its ligands is associated with hyperactivated proliferation (Melenhorst et al., 2008), migration, inflammation and fibrosis (Rayego-Mateos et al., 2018) of renal tubular cells. Downregulation of this pathway has been suggested to be involved in the pathogenesis of ADPKD (Torres and Harris, 2006). Based on previous researches, SBH could regulate EGFR activation, therefore explaining the therapeutic potential for ADPKD. In ADPKD cyst-lining epithelial cells, compared with untreated group, SBH could significantly inhibit cell proliferation stimulated by epithelial growth factor (EGF). Moreover, SBH could also repress the phosphorylation of EGFR in cyst-lining epithelial cells stimulated by EGF. Therefore, SBH may inhibit PKD cyst growth by inhibiting phosphorylation of EGFR (Chenggang et al., 2002) and decreasing the proliferation of the cyst-lining epithelial cells.
Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao), a herbal medicine also known as Chinese caterpillar fungus, is one of widely accepted ingredients in traditional Chinese medicine (Zhang et al., 2014). Laboratory and clinical studies have demonstrated that Cordyceps sinensis could improve a wide range of disorders, including respiratory, kidney, liver and cardiovascular diseases and hyperlipidemia (Chen Y. C. et al., 2017). Cordyceps sinensis also showed therapeutic effects on CKD (Deng et al., 2001) by inhibiting mesangial proliferation (Yang et al., 2003) and reducing the accumulation of extracellular matrix in the renal cortex and renal interstitial fibrosis (Dong et al., 2019) with its anti-oxidant (Yamaguchi et al., 2000) and anti-inflammatory properties.
The extract of Cordyceps sinensis, FTY720 (fingolimod), acts as a potent inhibitor of the S1P receptor (S1PR) due to the similar chemical structure to sphingosine-1-phosphate (S1P). In Cy/+ Han:SPRD rat, which is a non-orthologous rat model of ADPKD, FTY720 downregulated the expression of proinflammatory cytokines including IL-6 and TNFα, and attenuated the activation of inflammatory pathways such as the STAT and NF-κB pathways, leading to the inhibition of renal cyst growth and improvement of renal function. As the only clinical drug derived from Cordyceps sinensis, FTY720 may delay the progression in ADPKD through inhibition inflammation via reducing the accumulation of S1P (Li et al., 2020).
Autosomal dominant polycystic kidney disease is a common hereditary kidney disease, which is characterized by progressively enlarged cysts and may eventually develop into end-stage renal failure. Based on the pathogenesis of ADPKD, several drugs are currently under investigation, including vasopressin antagonists, somatostatin analogs and mTOR inhibitors. However, these drugs have some limitations, such as severe liver toxicity and unstable activities. Therefore, searching for effective, stable and safe medicines for ADPKD is imperative. Natural products extracted from herbal medicines, have been drawing extensive attention due to their good efficacy against ADPKD progression and safety in vivo studies, such as triptolide, curcumin, ginkolide B, steviol, G. lucidum triterpenoids, celastrol, saikosaponin-d, Sparganum stoloniferum Buch.-Ham and cordyceps sinensis, as shown in Table 1.
TABLE 1. Underlying possible mechanisms of herbal medicine in ADPKD.
However, the use of herbal medicines still requires careness, since some herbal medicines have a narrow therapeutic window, bringing restrictions to clinical application. Meanwhile, although herbal medicines are realtively safe, they may also exhibit a potential toxic effect at a relatively high dose. For example, the main adverse reactions of triptolide include liver and kidney injuries, and the loss of functions of reproductive system and hematopoietic system. Furthermore, some herbal medicines with complex components lack proper standards to evaluate their pharmacological effects, which limits the clinical use and requires further research to clarify the main ingredients with effectiveness or toxicity.
To sum up, herbal medicines exhibit great therapeutic effects on ADPKD in both in vivo and in vitro experiments. To develop herbal medicines into effective therapeutic drugs for ADPKD, further studies are required.
GS completed the collection and analysis of relevant literature data and the writing of the first draft of the review; SZ assisted with analysis and sorting of literature data; BY supervised and administrated the project, and guided the writing of review. All authors have read and agreed to the final text.
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Keywords: chronic kidney disease (CKD), autosomal dominant polycystic kidney disease (ADPKD), herbal medicine, therapy, pathogenesis
Citation: Shao G, Zhu S and Yang B (2021) Applications of Herbal Medicine to Treat Autosomal Dominant Polycystic Kidney Disease. Front. Pharmacol. 12:629848. doi: 10.3389/fphar.2021.629848
Received: 16 November 2020; Accepted: 08 March 2021;
Published: 27 April 2021.
Ying-Yong Zhao, Northwest University, China
Berenice Gitomer, University of Colorado Anschutz Medical Campus, United States
Zhiguo Mao, Shanghai Changzheng Hospital, China
Copyright © 2021 Shao, Zhu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Baoxue Yang, baoxue@bjmu.edu.cn
Applications of Herbal Medicine to Control Chronic Kidney Disease
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With 25 individually-designed, en suite bedrooms the Brook Hall is an ideal base for visiting the attractions around Cheshire, Liverpool, North Wales and interesting towns such as Port Sunlight.
Brook (Meadow) Hall Hotel offers a unique manor house style hotel with 25 bedrooms, the homely feel of the hotel will entice you to stay again and again.
Nestled in the beautiful countryside of Childer Thornton, with over three acres of stunning landscaped gardens.
Locally sourced seasonal food, served with a passion and love for the ingredients - Come and try us!
Our resident Chef creates a delicious menu based on seasonal produce. Our menu's are changed daily by our Chef who serves up a mouth watering meal made from only the best and freshest local produce.
Brook (Meadow) Hall Hotel offers a range of menu's, the evening dinner menu changes on a daily basis so that our Chef can produce the freshest meals for our diners.
The hotel also offers a Sunday lunch menu served from 12pm – 3pm, the menu's are created based on seasonal ingredients and is cooked to perfection.
Finding your perfect Wedding venue is a large part of planning your dream Wedding. Imagine becoming Lord and Lady of the manor for a day to enjoy your celebrations with your guests.
Brook (Meadow) Hall is fully licensed to perform ceremonies either in the Buckingham suite, the old chapel from when the original house was owned by Monks or the Garden Pavilion that is situated at the bottom of the gardens, surrounded by the tranquil Brook and is the perfect setting for any intimate ceremony.
The Kensington suite is our large ballroom that can seat up to 150 guests and is ideal for a Wedding breakfast and a Wedding reception, with a resident DJ and an on site venue dresser, we offer a Wedding service like no other. Leave all of the planning to our Wedding co-ordinator, giving you an enjoyable and stress free Wedding planning experience.
Delightful place/food and great character building.
Would recommend to all looking for a comfy stay in the countryside.
The team at Brook Hall were incredible. Took all the worries away from our big day.
I'd like to thank them on behalf of myself and my new wife. The food was great and what a beautiful location to have our big day.
What a great find! Beautifully secluded location and very relaxing.
Stayed here for a long weekend celebrating my husbands birthday. Loved every minute.


Figure 1. Louisiana per student expenditures since enactment of the No Child Left Behind law. Data from the Louisiana Department of Education annual financial and statistical reports.
Figure 2. Louisiana schools failing to make annual yearly progress. Data from the Louisiana Department of Education state progress reports.
Figure 3. Annual number of new charter schools in Louisiana. Data from theLouisiana Department of Education.
The No Child Left Behind Act of 2001 (NCLB) changed the way schools and state and district education offices organized and carried out their tasks. This paper describes some of these changes, paying special attention to addressing funding changes to meet requirements of NCLB and whether NCLB contributed to bureaucratic expansion and organizational restructuring.
NCLB was put into place in 2002. It strived to improve student outcomes by instituting rigorous academic standards that every child in America would receive an adequate education, especially those children who have been historically disadvantaged. Over the past 10 years, NCLB has resulted in increased educational spending and extensive organizational restructuring.
NCLB affected both administrative and adequacy costs. Administrative costs refer to testing implementation, accountability systems, highly qualified teacher systems and progress monitoring. Adequacy costs refer to the money spent on additional programs, including tutoring, summer school and supplementary services, as well as restructuring costs such as reducing student-teacher ratios. Most scholars agree that NCLB increased the expenditures for both administrative and adequacy costs. Debate continues over who should pay for these additional costs – states or the federal government. Federal politicians typically claim that NCLB is fully funded because the federal education budget was increased to fund NCLB, but states and local school districts often claim the federal increase was insufficient.
Louisiana already had an accountability system that included many of the NCLB elements in 2001; therefore, program costs were not very high at the outset. However, once it became clear that more than 75 percent of Louisiana's schools would be classified as needing improvement, the program costs began to increase dramatically. More specifically, Louisiana spent most of its money trying to bring the lowest 5 percent of students up to proficiency through lower teacher-student ratios, tutoring and summer school.
Figure 1 compares per-student expenditures to student enrollment from 2001 to 2009. Student enrollment declined significantly, mostly due to Hurricane Katrina in 2005. At the same time per-student expenditures increased 65 percent from about $6,700 to $11,100.
Spending has also shifted. Budgets for subjects that are not tested, such as art, music and physical education, have been cut so that schools can focus on improving student test scores. Because Louisiana's commitment to school accountability predated NCLB, it is difficult to distinguish whether costs associated with NCLB would have happened anyway under Louisiana's accountability program.
Under NCLB, the administrative responsibilities of state departments of education expanded. States were responsible for identifying schools needing improvement and developing plans (jointly with local school districts) to turn these schools around or shut them down. Plans for turning failing schools around in Louisiana involved allowing failing schools to reopen as a charter school or turn over operations to the state or a private company. As Figure 2 suggests, the sheer numbers of failing schools (with an average of about 100 schools per year failing to meet adequate progress from 2002 to 2009) resulted in both an expansion of charter schools and an increase in state control of schools.
Charter schools are operated by a private nonprofit or for-profit organization under a five-year contract or "charter" that is overseen by the Board of Elementary and Secondary Education. In order to keep the charter, schools must participate in the state accountability program and meet achievement results. Charter schools are far more popular than state takeovers because they are intended to empower local communities to loosen bureaucratic regulations by allowing schools to be innovative in hiring, budgeting and instruction. Charters existed beforehand, but under NCLB they have proliferated across the United States; Louisiana is no exception.
Figure 3 shows the growth of charter schools in Louisiana from 1996 to 2010. In 2004, New Orleans became the first majority-charter schools city in the United States.
Louisiana's Recovery School District is a new organizational entity created to deal with clusters of failing schools in the state, with a strong emphasis on New Orleans. It was created in 2002 to oversee academically unacceptable schools that have been removed from the jurisdiction of the local school board. Its jurisdiction was expanded during the period where New Orleans and Louisiana were recovering from hurricanes Katrina and Rita in 2005-2006, so many more public schools in New Orleans qualified to be controlled by the new district.
Nelson Smith, an education policy consultant, claims that the Recovery School District in New Orleans led to significant educational gains, including a 63 percent reduction in the number of schools classified as "academically unacceptable" and a graduation rate increase of 19.5 percent from 2009 to 2010. The RSD was initially given five years to accomplish its mission; however, the goal was extended in 2010 so that schools that show strong results for two consecutive years can now choose to remain in the RSD or return to a local governing authority.
Some NCLB-motivated changes will soon fade away, while other state-led initiatives will further change the structure of the Louisiana education system. First, Louisiana was granted an exemption by the U.S. Department of Education from the swiftly approaching 2014 NCLB goals. The waiver allows funding flexibilities. For example, districts will no longer be required to spend as much on supplemental education services or professional development programs as outlined in NCLB. In addition, districts will no longer be required to submit federal reports such as the School Improvement Plan or Highly Qualified Teacher Target Improvement Plan.
In 2012, Gov. Bobby Jindal proposed a vast overhaul of Louisiana's education system, promising additional financial and organizational change. First, teachers will now be compensated and "tenured" on basis of effectiveness rather than years of service. This new system has the potential to create additional costs related to the hiring and retaining of highly qualified teachers and related to organizational restructuring aimed at supporting efforts to switch from the old, seniority-based to the new, merit-based tenure system. Second, the Jindal plan works to restructure the charter application process, creates new types of charter schools, provides vouchers for low-income students to attend private schools, creates greater course choice and allows students to vote failing schools into the Recovery School District. All these aspects of the new system have potential significant implications for the way schools are financed and organized. And that is partially the point of the new law – to force real changes.
NCLB had the admirable goal of improving the education system and leveling the playing field for students. It also forced substantial financial and administrative restructuring. Louisiana was unable to reach the goals of NCLB and many schools deemed "in need of improvement" remain in the public school system, resulting in more expenditure and further restructuring. As new legislation becomes effective, the education system will continue to change as the academic goals, measurement of progress, and reporting systems are once again altered.
Mark J. Schafer is an associate professor in the Department of Agricultural Economics & Agribusiness, and Amanda D. Cowley is a former graduate student in the Department of Sociology.


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Image courtesy of University of Saskatchewan Archives.
Remembering Douglas A. Schmeiser (BA'54, LLB'56)
The College of Law is sad to share the passing of Professor and Dean Emeritus Douglas A. Schmeiser, SOM, QC.
30-Apr-2018 11:27 AM
Schmeiser was a student of the University of Saskatchewan (U of S), receiving his Bachelor of Arts from St Thomas More College in 1954 and his Bachelor of Laws from the College of Law in 1956. He also received both a Master of Laws and a Doctor of Juridical Science from the University of Michigan, in 1958 and 1963 respectively.
In 1956, Schmeiser was hired as a special lecturer by the U of S and secured a full-time teaching position at the College of Law in 1961, which led to a full professorship in 1968. He served the college as director of graduate legal studies from 1964 to 1974 and as dean from 1974 to 1977.
A generous supporter of both the College of Law and St Thomas More College, Schmeiser's philanthropy reflected his belief in giving students a solid educational foundation and his gratitude for his own memorable experience at the U of S. He endowed two scholarships to the College of Law, the Douglas A. Schmeiser Prize in Criminal Procedure and the Douglas A. Schmeiser Prize in Constitutional Law.
He was author of numerous books and served his community in leadership positions on many boards and councils. In 2010, Schmeiser was given the Saskatchewan Order of Merit, the highest honour the province bestows.


This package contains Kryptel compressors, i.e. low-level components compressing a data block or an arbitrary length data stream. The included compressors are ZIP and NullCompressor.
Null compressor is a special 'compressor' component sending the input data to output 'as is', that is, performing no compression at all. It can be used for debugging, or when no compression is required. For example, high-level components such as Silver Key engine require a compressor component. There are two ways to turn compression off – either to set the compression level to CT_NO_COMPRESSION (see Constants class), or to pass NullCompressor. The former is not reliable as some compressing libraries (BZIP, for instance) do not support a no compression mode. Providing the NullCompressor component is a more reliable way (also NullCompressor will likely work faster).
A static compressor component's structure describing allowed compressor parameters.
A helper structure, used to pack compressor parameters in order to return them in a single function call.
Main compressor interface for compressing or decompressing data blocks of arbitrary size.
Gets or sets the compressor parameters.
Compresses or decompresses in-memory data.
Improves File Encryption example by adding a compression step.


text:
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Gwen Davis
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NASA should not have to resort to circus acts as the price for doing science. It's in such circumstances that violence is done to process, to rigor, to integrity.
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Windows Phone 7 Goes on Sale at AT&T and T-Mobile
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Michael Douglas' 'Blatant Honesty' Could Stone Wall Street 2
Simply put: Michael Douglas can't stop talking. None of this is good for the sleep of Oliver Stone, a wayward director who needs Wall Street: Money Never Sleeps to be a mega-hit to stay on top.
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