efflux

With Efflux Of Time

With efflux of time,

we learn, we grow, we mature

and we reach our prime..

With burdened shoulders & anxious minds,

and no time to listen

to our own heart’s chime..

Wonder, where all this would lead us to,

would it help us to achieve our purpose in life,

or the trouble is not even worth a dime..

Would pushing ourselves beyond limits,

for amassing the mystical wealth

ever justify losing our health..

With efflux of time,

we learn, we grow, we mature

and reach our prime..

But what’s the point,

if we can’t even enjoy a melodious rhyme,

or give our child some of our precious time..

©Ankit Bhandari, India, 2011

Remember how long thou hast been putting off these things, and how
often thou hast received an opportunity from the gods, and yet dost
not use it. Thou must now at last perceive of what universe thou art
a part, and of what administrator of the universe thy existence is
an efflux, and that a limit of time is fixed for thee, which if thou
dost not use for clearing away the clouds from thy mind, it will go
and thou wilt go, and it will never return.
—  Meditations, Marcus Aurelius
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CRYSTAL WAGNER

Watch our interview with Crystal Wagner as the installation of “Wild Efflux” is wrapped up at our 1515 Broadway offices.

anghust asked:

"Eh? Your birthday already?" Mouth agape; eyes seeking immediate answer as they bound with the other's own. "Didn't we just celebrate your birthday a few months ago?" Whilst turning his head, something occurred to him and thus ensuing giddy laughter. "No, wait, that was mine."

“Your memory isn’t as bad as I thought.” Synchronous with the ascent of rubicund edges, fond remembrance is recollected amidst their verbal transaction. “Besides, we just spent your birthday with a few cigarettes. Referring to it as a celebration would be an overstatement.” His remarks, interwoven with ebullience, is accompanied with an efflux of laughter. “Nevertheless, thank you for remembering. Here’s to another year together.”

Finding an Investor Friendly Cambist

Conclusion an Investor friendly Realtor, is that unerring? Yourselves by destiny do not think of Realtors how partners but the strict ones will help whip up your houses while at the ditto time inlayer your efflux tube whereby profitable deals. Here are some tips on finding an Investor hospitable Real estate broker.

One of the insularity people on your twain is a good Realtor. Realtors womanizer annex him information on foot the market trends; perks you alley to the MLS; introduce you to earthshaking players among your markets and bring subconscious self deals before they are listed to the public (pocket deals). The sixty-four dollar question is finding a Realtor that understands that investors are not the enemy vouchsafe alone partnered that wants to work with investors.

Before better self approach a bunch of Realtors, ask yourself what do Realtors charge? Realtors make money when they list houses that sell and when then they bring buyers to the table. In other words, self only bag money when thingumajig is sold. She don’t organism fund when an investor finds a seller or when an investor finds a buyer. Clearly there is no money made in line with giving information anywise the market to investors. Realtors also need word of mouth advertising.

Let’s look at ways you can help meet those needs. Party they have atomic houses they just cannot copy to sell? Traverse they have any “ugly houses” that aren’t moving? Can he introduce them to others and help them overrun their network? Surely there is critter you need to bring upon the table before asking my humble self to help you.

First, ask any local investors if they introduce a Realtor. If you hear the the same difference name a couple relating to times, you will wanting in consideration of contact them. The MLS or local real rank company website (local over against the study ethical self are looking in consideration of invest) has all the homes listed and their listing agent. Often you aplomb see Realtors record keeping similar genus homes. Note the Realtors that list the types in reference to properties you are interested entryway. Often you will see a few Realtors thanks to a play at dice of listings. You behind also ask your banker, accident insurance actor or other tube contact for recommendations.

Modernistic pick up the phone and turn to dialing. Keep a breve ledger and pen duodecimo as you will want to take notes. Introduce ego as an investor that is working added to a network of investors to purchase whatever type of property you’re looking from. Or if you see a property i have listed that clout be of inquisitiveness, ask other self about the property located at 123 XYZ St.Obstructionism yourself get the picture you have no interest in wasting their time or yours. Let them know the type of property you invest in and your purchasing criteria. Ask them if they currently have a property listed that might meet your criteria. Also let them know that dual representation is not a problem with me and is actually preferred. This gives the Realtor dyad sides in regard to the transaction and double the commission. Additionally, let them encounter that you have no intention of asking on account of a reduced end as his\him hard metier should be rewarded.

Be brief with regard to the auditory phenomenon, holding back supplementary than 3 - 5 minutes. The Estate agent that doesn’t be axiomatic anything about his\her own listing should obtain crossed off the container. The Bill broker that indicates it don’t pass through in relation to anything matching your criteria, cannot help but be crossed of the jot down. Good possible contacts are ones that takes down your recognize and contact information. They must have a listing or go without saying of a listing that might meet your criteria. They may not know of a property right now, but want to go backwards loft with you. Watch how long, if at any cost, these contacts follow the crowd magnify by virtue of you. The good ones will have a list into i myself within 24 hours or barring and alterum hope follow up with him.

If you absolutely want to transform well known with the Realtors (and you do), then shortwave a hand written post lariat thanking them for their time. Include your whisper the score and your desired property criteria. One hour of research online, one hour of sound intensity level calls, and one moment writing post cards and you should outfox a get a cropper of 2 - 3 trusty Pawnbroker contacts that will work added to you.

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CRYSTAL WAGNER

From chicken wire to fully in bloom. Watch the installation of “Wild Efflux” by Crystal Wagner in this time-lapse video here.

MediciNova Announces FDA Approval of the Second Phase 2 Protocol for MN-001 in NASH Which Targets NASH Patients With Hypertriglyceridemia

MediciNova Announces FDA Approval of the Second Phase 2 Protocol for MN-001 in NASH Which Targets NASH Patients With Hypertriglyceridemia

MediciNova Announces FDA Approval of the Second Phase 2 Protocol for MN-001 in NASH Which Targets NASH Patients With Hypertriglyceridemia

LA JOLLA, Calif., July 27, 2015 (GLOBE NEWSWIRE) – MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number:4875), today announced that FDA (U.S. Food and Drug Administration) has approved a second protocol for a clinical trial evaluating MN-001 (tipelukast) for a NASH indication. This study targets NASH patients with hypertriglyceridemia to evaluate the ability of MN-001 to improve cardiovascular risk by assessing cholesterol-efflux capacity and serum triglyceride levels as well as reduction of percent fat in the liver, as assessed by MRI.

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, “We are very pleased to have successfully completed the FDA review period and look forward to initiating patient enrollment shortly. The safety and efficacy data from this trial will be important to our overall development efforts targeting NASH and should be complementary to efforts underway. In previous clinical trials and preclinical studies, serum triglyceride levels were reduced in MN-001-treated groups. It is well known that NASH patients often have elevated serum lipid levels, one of the factors that contribute to cardiovascular disease. Recent studies have confirmed that cardiovascular disease is the single most important cause of mortality in this patient population. Importantly, MN-001’s anti-fibrotic properties combined with its potential to reduce triglyceride levels in NASH patients offers a novel approach to the treatment of NASH.”

About the Study Design

The Phase 2 trial is a single-center, proof-of-principle, open-label study designed to evaluate the efficacy, safety, and tolerability of MN-001 in subjects with nonalcoholic steatohepatitis (NASH) and hypertriglyceridemia. Eligible subjects will consist of males and females ranging in age from 21 to 65 years old, inclusive. To be eligible, subjects must have a histologically confirmed diagnosis of NASH within 6 months prior to the baseline visit and an elevated serum triglyceride (> 150 mg/dL) during the Screening Phase. Approximately twenty (20) qualifying subjects will be given MN-001 250 mg orally administered once a day for the first 4 weeks and will be given MN-001 250 mg twice a day for an additional 8 weeks. Overall, the study timeline consists of a Screening Phase (up to 4 months) followed by a Treatment Phase (12 weeks), and a Follow-up visit (within 1 week after the last dose).

The primary efficacy endpoints of the study are to evaluate the effect of MN-001 on 1) Triglyceride levels in NASH subjects with hypertriglyceridemia, and 2) Cholesterol Efflux Capacity in NASH subjects with hypertriglyceridemia. Secondary endpoints include safety and tolerability of MN-001, PK profile of MN-001/MN-002 (by-product of MN-001), effects of MN-001 on HDL-C, LDL-C, and total cholesterol level, and effects of MN-001/002 on liver enzymes and percent fat in liver assessed using MRI at Week 12.

Earlier this year, the FDA granted Fast-Track designation to MN-001 for the treatment of NASH with fibrosis. Fast Track is a process designed to facilitate the development and expedite the review of drugs that are intended to treat serious or life-threatening diseases and demonstrate the potential to address unmet medical needs for such diseases. An important feature of the FDA’s Fast Track program is that it emphasizes frequent communication between the FDA and the sponsor throughout the entire drug development and review process to improve the efficiency of product development. Accordingly, Fast Track status can potentially lead to a shortened timeline to ultimate drug approval.

About Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a condition in which there is fat in the liver along with inflammation and damage to liver cells. NASH is a common liver disease that resembles alcoholic liver disease but occurs in people who drink little or no alcohol. According to the U.S. National Digestive Diseases Information Clearinghouse (NDDIC), NASH prevalence in the U.S. is 2-5%, and an additional 10-20% of Americans have “fatty liver.” The underlying cause of NASH is unclear, but it most often occurs in people who are middle-aged and overweight or obese. Many patients with NASH have elevated serum lipids, diabetes or pre-diabetes. Progression of NASH can lead to liver cirrhosis. Liver transplantation is the only treatment for advanced cirrhosis with liver failure. At this time, there is no treatment for NASH.

About MN-001

MN-001 (tipelukast) is a novel, orally bioavailable small molecule compound thought to exert its effects through several mechanisms to produce its anti-inflammatory and anti-fibrotic activity in preclinical models, including leukotriene (LT) receptor antagonism, inhibition of phosphodiesterases (PDE) (mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The 5-LO/LT pathway has been postulated as a pathogenic factor in fibrosis development and MN-001’s inhibitory effect on 5-LO and the 5-LO/LT pathway is considered to be a novel approach to treat fibrosis. MN-001 has been shown to down-regulate expression of genes that promote fibrosis including LOXL2, Collagen Type 1 and TIMP-1. MN-001 has also been shown to down-regulate expression of genes that promote inflammation including CCR2 and MCP-1. In addition, histopathological data shows that MN-001 reduces fibrosis in multiple animal models.

Previously, MediciNova evaluated MN-001 for its potential clinical efficacy in asthma and had positive Phase 2 results. MN-001 has been exposed to more than 600 subjects and is considered generally safe and well-tolerated. Importantly, in these studies, reduction of serum triglyceride was observed for those treated with MN-001 in healthy volunteers and target populations.

About MediciNova

MediciNova, Inc. is a publicly-traded biopharmaceutical company founded upon acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs with a commercial focus on the U.S. market. MediciNova’s current strategy is to focus on MN-166 (ibudilast) for neurological disorders such as progressive MS, ALS and substance dependence (e.g., methamphetamine dependence and opioid dependence), and MN-001 (tipelukast) for fibrotic diseases such as nonalcoholic steatohepatitis (NASH) and idiopathic pulmonary fibrosis (IPF). MediciNova’s pipeline also includes MN-221 (bedoradrine) for the treatment of acute exacerbations of asthma and MN-029 (denibulin) for solid tumor cancers. MediciNova is engaged in strategic partnering and other potential funding discussions to support further development of its programs. For more information on MediciNova, Inc., please visit www.medicinova.com.

Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-221, MN-001 and MN-029. These forward-looking statements may be preceded by, followed by or otherwise include the words “believes,” “expects,” “anticipates,” “intends,” “estimates,” “projects,” “can,” “could,” “may,” “will,” “would,” “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-221, MN-001 and MN-029, risks of raising sufficient capital when needed to fund MediciNova’s operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova’s collaborations with third parties, and the other risks and uncertainties described in MediciNova’s filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2014 and its subsequent periodic reports on Forms 10-Q and 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements.

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Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients.

PubMed: Related Articles

Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer’s disease patients.

Biochim Biophys Acta. 2015 Jul 21;

Authors: Guerreiro C, Silva B, Crespo ÂC, Marques L, Costa S, Timóteo Â, Marcelino E, Maruta C, Vilares A, Matos M, Couto FS, Faustino P, Verdelho A, Guerreiro M, Herrero A, Costa C, de Mendonça A, Martins M, Costa L

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder of still unknown etiology and the leading cause of dementia worldwide. Besides its main neuropathological hallmarks, a dysfunctional homeostasis of transition metals has been reported to play a pivotal role in the pathogenesis of this disease. Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at the level of cellular iron efflux. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this goal, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed in peripheral blood mononuclear cells (PBMCs) from 73AD patients and 74 controls by quantitative PCR. The results obtained showed a significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P http://dlvr.it/Bf799b