Here are Some Hints for Ensuing Business Owners about How to Choose the Most High-quality Virtual Storage for their Business

Keeping and sharing of the confidential files in a virtual space prove to be an inevitable requirement of the modern deal-making realm. Various providers offer deal-makers highly protected online venues which must bring the ease to the whole course of the transaction execution – so-called virtual platforms. Their main task is to guarantee protection to digital versions of documents. A virtual platform may be utilized not only as a repository for sensitive information but also as space where multiple stakeholders have a chance to exchange and have a conversation about information, transactions, and deals. That is how, virtual rooms eliminated the need to complete the whole transaction exclusively during face-to-face negotiations. In the event that you wish to know more about online data services, please, pay your attention to the reference – https://datarooms.org. As virtual rooms are becoming more and more popular, more and more providers offer their services on the VDR market. However, not each platform that exists is trustworthy and decent enough to entrust them confidential corporate information. To find a trustworthy room, the potential user is supposed to take into account the following nuances.

1. Reputation and experience intrinsic to the virtual room

Be attentive to the reputation of the vendor. Mainly, it might be evaluated according to the comments available on the Internet. Both – the opinions of lay public and the analysis by experts – proved to be relevant when it comes to choosing a data room vendor. Moreover, it is informative to check the peculiarities of the deals which were finished with the assistance of the provider and, possibly, even to talk to the deal-makers from a firm which has already utilized software developed by the provider. Moreover, the experienced vendor will capable of providing specific functions to a room user.

2. The functions the virtual platform will offer you

When searching out a data room, a particular set of important instrument is supposed to be considered. Eventually, a good virtual room focuses on document and access safety. The virtual platform is supposed to have all the security certificates (ISO 27001 and SSAE 16), provide data encryption, firewalls, two-step user authentication system, watermarks, etc. In addition, the virtual room administrator must be provided with all the rights to manage access to the repository in general and to certain documents, folders. Regular audit reports help to monitor all the actions that take place in the platform. Together with being safe, the repository is supposed to be convenient in exploitation. Thus, intuitive interface that enhances work in the data room is thought to be important. Numerous search and upload functions also simplify and accelerate the work in the room. The named features do not constitute an exhaustive list of the features that the customer have to look for in the room: the requirements will depend on the customer’s demands.

3. Price

Considering the fact that there are a lot of provides on VDR market, the potential clients may choose among VDRs that differ in price: the exploitation cost varies generally on the vendor, on the expected time needed for execution of the deal, on the particular tools expected, etc. Therefore, the deal-maker has to be pragmatic and to realize how much he is willing to pay for the virtual room.

4. The benefits you and your business partners will have an opportunity to experience

A virtual platform must be not only affordable and convenient for the owner but also fulfill the requirements of the owner’s present or potential business partners. Sometimes it is better to subscribe for the more luxurious room if it is equipped with certain options demanded by the other participants of the deal.

5. Adequate level of functionality

Before selecting a virtual room, an accurate investigation of the requirements and expectations is expected to take place: not a single deal-maker wants to pay for an extremely expensive virtual room provided with a wide range of excessive services. The potential client should make sure he is about to pay for the set of tools he actually needs and expects – not for trendy and fashionable tools which have nothing in common with information protection and storage.

If staying stick to these simple tips in mind, the one might have fewer difficulties when choosing a data room. Although the selection process can take a considerable amount of time, it is better to waste a bit more time and to check demo versions of several data rooms than to select the very first virtual platform which was available at adequate price. You are supposed to keep in mind the fact that you are paying for your protection and convenience and the data rooms are definitely not the ones to save money on.

Androgen Receptors Downregulate Don’t They? Part 2

In part 1 of this article we discussed the mistake of thinking about androgen receptors (testosterone receptors) in the same way we think of other receptors such as beta-receptors. Beta-receptors down regulate in response to beta-adrenergic stimulation whereas there is good evidence that androgen receptors increase in numbers in response to androgens. We also discussed the various affects of testosterone on muscle growth. Testosterone does far more than simply increase the rate of protein synthesis!

Now in part 2 we will finish our discussion of androgen receptor regulation as it pertains to the way muscle cells grow. The very mechanism of real muscle growth opens the door for increased androgen receptor number in response to testosterone treatment.

Don’t forget Satellite cells!

Satellite cells are myogenic stem cells, or pre-muscle cells, that serve to assist regeneration of adult skeletal muscle. Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing the number of myonuclei for fiber growth and repair. Proliferation of satellite cells is necessary in order to meet the needs of thousands of muscle cells all potentially requiring additional nuclei. Differentiation is necessary in order for the new nucleus to behave as a nucleus of muscle origin. The number of myonuclei directly determines the capacity of a muscle cell to manufacture proteins, including androgen receptors.

In order to better understand what is physically happening between satellite cells and muscle cells, try to picture 2 oil droplets floating on water. The two droplets represent a muscle cell and a satellite cell. Because the lipid bilayer of cells are hydrophobic just like common oil droplets, when brought into proximity to one another in an aqueous environment, they will come into contact for a moment and then fuse together to form one larger oil droplet. Now whatever was dissolved within one droplet (i.e. nuclei) will then mix with the contents of the other droplet. This is a simplified model of how satellite cells donate nuclei, and thus protein-synthesizing capacity, to existing muscle cells.

Enhanced activation of satellite cells by testosterone requires IGF-1. Those androgens that aromatize are effective at not only increasing IGF-1 levels but also the sensitivity of satellite cells to growth factors.3 This action has no direct effect on protein synthesis, but it does lead to a greater capacity for protein synthesis by increasing fusion of satellite cells to existing fibers. This increases the number of myonuclei and therefore the capacity of the cell to produce proteins. That is why large bodybuilders will benefit significantly more from high levels of androgens compared to a relatively new user.

Testosterone would be much less effective if it were not able to increase myonucleation. There is finite limit placed on the cytoplasmic/nuclear ratio, or the size of a muscle cell in relation to the number of nuclei it contains.4 Whenever a muscle grows in response to training there is a coordinated increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating viable nuclei, overloaded muscle will not grow.5,6 Clearly, satellite cell activity is a required step, or prerequisite, in compensatory muscle hypertrophy, for without it, a muscle simply cannot significantly increase total protein content or CSA.

More myonuclei mean more receptors

So it is not only true that testosterone increases protein synthesis by activating genetic expression, it also increases the capacity of the muscle to grow in the future by leading to the accumulation of myonuclei which are required for protein synthesis. There is good reason to believe that testosterone in high enough doses may even encourage new fiber formation. To quote the authors of a recent study on the effects of steroids on muscle cells:

“Intake of anabolic steroids and strength-training induce an increase in muscle size by both hypertrophy and the formation of new muscle fibers. We propose that activation of satellite cells is a key process and is enhanced by the steroid use.”7

Simply stated, supraphysiological levels of testosterone give rise to increased numbers of myonuclei and thereby an increase in the number of total androgen receptors per muscle fiber. Keep in mind that I am referring to testosterone and testosterone esters. Not the neutered designer androgens that people take to avoid side effects.

Another group of researchers are quoted as saying:

“…it is intriguing to speculate that the upregulation of AR levels via the administration of pharmacological amounts of androgens might convert some muscles that normally have a minor or no response to muscles with enhanced androgen responsiveness”(8)

This is not an argument to rapidly increase the dosages you use. It takes time for these changes to occur and the benefits of higher testosterone levels will not be immediately realized. It does shed some light however on the proportional differences between natural and androgen assisted bodybuilders physiques.

Maintenance of the kind of muscle mass seen in top-level bodybuilders today requires a given level of androgens in the body. That level will vary from individual to individual depending on their genetics. Nevertheless, if the androgen level drops, or if they were to “cycle off” the absolute level of lean mass will also drop. Likewise, as the level of androgens goes up, so will the level of lean mass that individual will be able to maintain. All of this happens without any evidence of AR down regulation. More accurately it demonstrates a relationship between the amount of androgens in the blood stream and the amount of lean mass that you can maintain. This does not mean that all you need is massive doses to get huge. Recruitment of satellite cells and increased myonucleation requires consistent “effective” training, massive amounts of food, and most importantly, time. Start out with reasonable doses. Then, as you get bigger you can adjust your doses upwards.

References:

1. Kemppainen JA, Lane MV, Sar M, Wilson EM. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. J Biol Chem 1992 Jan 15;267(2):968-74

2. Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol. Metab. 82(11):3710-37-19, 1997

3. Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I. Endocrinology. 124:2110-2117, 1989

4. Rosenblatt JD, Yong D, Parry DJ., Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17:608-613, 1994

5. Rosenblatt JD, Parry DJ., Gamma irradiation prevents compensatory hypertrophy of overloaded extensor digitorum longus muscle. J. Appl. Physiol. 73:2538-2543, 1992

6. Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat. Rec. 247:179-188, 1997

7. Kadi F, Eriksson A, Holmner S, Thornell LE. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc 1999 Nov;31(11):1528-34

8. Antonio J, Wilson JD, George FW. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol. 1999 Dec;87(6):2016-9.

Androgen Receptors Downregulate Don’t They? Part 1

There is as much misinformation about steroids as there is good information had among bodybuilding enthusiasts. Go to any gym and you will hear some kid spouting off to his buddies about how steroids do this, or how they do that, or whatever. This soon starts somewhat of a pissing contest (excuse the expression) as to who knows more about steroids. It’s the same kind of titillating and infectious banter that adolescent boys get into about girls and sex. With steroid banter you hear all the popular terms like Deca, Test, GH, gyno, zits, raisins, “h-u-u-u-ge”, roid, freak, monster, roid-rage, “I knew this guy once”, etc., etc.. If by some rare chance they are smart and have been reading this or some other high quality bodybuilding site on the net, they may actually get a few details right. More often than not they know just enough to be dangerous. Fortunately steroids haven’t proven to be all that dangerous. Not only that, but most of these guys who are infatuated with steroids won’t ever use or even see them except in magazines.

This kind of ego driven gym talk doesn’t really bother me until they begin giving advice to other clueless people who actually have access to them. Spewing out steroid lingo gives other less experienced kids the impression that these kids actually know what they are talking about. That’s how all of the psuedo-science folklore about steroids perpetuates. This is also why most people who actually use steroids know little about them. This last fact should bother anyone who cares about bodybuilding and/or bodybuilders.

I started out with this article planning on giving some textbook style explanation as to why using steroids doesn’t down regulate androgen receptors (AR). Then after considering some of my critics views that I tend to write articles that hardly anyone can read, I decided to write an easy to read, yet informative explanation about what androgens actually do and how this precludes androgen receptor down regulation. I still have a few references but not so many that it looks like a review paper.

Androgen receptors down-regulate….Don’t they?

One misunderstood principle of steroid physiology is the concept of androgen receptors (AR), sometimes called “steroid receptors”, and the effects of steroid use on their regulation. It is commonly believed that taking androgens for extended periods of time will lead to what is called AR “down regulation”. The premise for this argument is; when using steroids during an extended cycle, you eventually stop growing even though the dose has not decreased. This belief has persisted despite the fact that there is no scientific evidence to date that shows that increased levels of androgens down regulates the androgen receptor in muscle tissue.

The argument for AR down-regulation sounds pretty straightforward on the surface. After all, we know that receptor down-regulation happens with other messenger-mediated systems in the body such as adrenergic receptors. It has been shown that when taking a beta agonist such as Clenbuterol, the number of beta-receptors on target cells begins to decrease. (This is due to a decrease in the half-life of receptor proteins without a decrease in the rate that the cell is making new receptors.) This leads to a decrease in the potency of a given dose. Subsequently, with fewer receptors you get a smaller, or diminished, physiological response. This is a natural way for your body to maintain equilibrium in the face of an unusually high level of beta-agonism.

In reality this example using Clenbuterol is not an appropriate one. Androgen receptors and adrenergic receptors are quite different. Nevertheless, this is the argument for androgen receptor down-regulation and the reasoning behind it. The differences in the regulation of ARs and adrenergic receptors in part show the error in the view that AR down-regulate when you take steroids. Where adrenergic receptor half-life is decreased in most target cells with increased catecholamines, AR receptors half-live’s are actually increased in many tissues in the presence of androgens.1

Let me present a different argument against AR down-regulation in muscle tissue. I feel that once you consider all of the effects of testosterone on muscle cells you come to realize that when you eventually stop growing (or grow more slowly) it is not because there is a reduction in the number of androgen receptors.

Testosterone: A multifaceted anabolic

Consider the question, “How do anabolic steroids produce muscle growth?” If you were to ask the average bodybuilding enthusiast I think you would hear, “steroids increase protein synthesis.” This is true, however there is more to it than simple increases in protein synthesis. In fact, the answer to the question of how steroids work must include virtually every mechanism involved in skeletal muscle hypertrophy. These mechanisms include:

  • · Enhanced protein synthesis
  • · Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
  • · Enhanced activation of myogenic stem cells (i.e. satellite cells)
  • · Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)
  • · New myofiber formation

Starting with enhanced growth factor activity, we know that testosterone increases GH and IGF-1 levels. In a study by Fryburg the effects of testosterone and stanozolol were compared for their effects on stimulating GH release.2 Testosterone enanthate (only 3 mg per kg per week) increased GH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol (0.1mg per kg per day) had no effect whatsoever on GH or IGF-1 levels. This study was only 2-3 weeks long, and although stanozolol did not effect GH or IGF-1 levels, it had a similar effect on urinary nitrogen levels.

What does this difference in the effects of testosterone and stanozolol mean? It means that stanozolol may increase protein synthesis by binding to AR receptors in existing myonuclei, however, because it does not increase growth factor levels it is much less effective at activating satellite cells and therefore may not increase satellite cell activity nor myonuclear number directly when compared to testosterone esters. I will explain the importance of increasing myonuclear number in a moment, first lets look at how increases in GH and IGF-1 subsequent to testosterone use effects satellite cells…

In part 2 we will discuss the role of satellite cells and myonuclei and how testosterone (androgens) activates these systems to create muscle growth far beyond what simple activation of the androgen receptor can produce.

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Testosterone – The Good, the Bad, the Ugly

One of the most infamous hormones around is Testosterone. You hear Clueless news anchors about it on the evening news. You hear about it in the gym. You even read about it in the “growing older with style” magazines. Depending on who you talk to, it is both the good, the bad, and the ugly of hormones.

In bodybuilding it is hailed as the king of muscle builders. Among forward-thinking baby boomers it is considered the fountain of youth. In other circles it is pointed to as the cause of all men’s shortcomings including violence and sexual promiscuity. Finally, it has even been associated with potentially lethal diseases that threaten the lives of thousands of men each year. So how can one hormone be so many different things to so many different people? Taking a closer look at this complex hormone may shed some light on this question.

First, what exactly is testosterone? Testosterone is the principle male hormone and belongs to a class of steroid chemicals called androgens (andro = man, gen = to make). It is produced primarily in the testes but can also be made by enzymatically converting other androgens (e.g. androstenediol) secreted from the adrenal gland into testosterone. Testosterone plays a role in everything from growth and maintenance of the male sexual organs during puberty, to male pattern baldness in the later years. It also plays an important role in bone growth, sexual behavior, male fertility, muscle protein synthesis, as well as inducing the appearance of secondary male sexual characteristics such as facial hair, body hair, and deepening of the voice.

Research has shown that resistance exercise can significantly raise testosterone levels. (1) This is good news if you’re looking to build a more muscular body. When in comes to muscle growth, testosterone production is the key to success. Testosterone literally turns on the genetic machinery leading to bigger and stronger muscles. It works like this. Testosterone binds to receptors inside your muscle cells. These receptors then transport the testosterone molecule to the nucleus. The nucleus is where your DNA is located. Your DNA contains blue prints for every protein found in your body. This androgen receptor, once bound to testosterone, acts as a messenger that tells the DNA which proteins to make from the blue prints. In muscle tissue the whole process results in the production of contractile proteins, which are used to make your muscle contract more forcefully, as well as structural proteins that are used to make the cell larger to accommodate the new contractile proteins. In plain and simple terms, testosterone is a messenger that tells your muscles to grow! Still, this barely touches the surface of the many secondary roles testosterone plays in muscle tissue as well as in the brain.

Clearly, testosterone is important to both mind and body. Among the anti-aging crowd, testosterone stands as a symbol of youth and vitality. One of the signs of aging is a reduction in the circulating levels of testosterone. This in turn has been associated with a decrease in muscle mass and strength as the years go by. Doctors are now calling this “andropause”. (2) Through testosterone replacement therapy, many older patients express a sense of psychological well-being and vitality they haven’t experienced since they were 30 years younger. (3,4) If men desire it, in the near future hormone replacement for men will be just as common as it is for women today.

Unfortunately, testosterone is not free from negative effects on the body. One common undesirable effect of testosterone, which could be considered minor, is alopecia or male pattern baldness. The drug Propecia, a 5-alpha reductase inhibitor, prevents the conversion of testosterone into a more potent androgen called dihydrotestosterone (DHT). DHT, and a set of your parent’s genes, is responsible for male pattern baldness. In many men Propecia is effective at preventing further hair loss and even allowing some to grow back. (5) On a more serious note, DHT may also be a serious risk factor for some cancers such as prostate cancer. (6) Treatment of prostate cancer often involves a total elimination of circulating testosterone. Although this helps to reduce the growth rate of tumors, removing a man’s testosterone leaves him feeling emotionally disoriented, there is a complete loss of sex drive and sexual function, muscle is lost and fat patterning takes on a feminine characteristic, even hot flashes, usually associated with female menopause, are experienced.

All in all testosterone plays a very important role in a man’s sense of health and well-being. It is the major muscle-building hormone; it increases the strength of both muscles and bones, and even affects our brains. Certainly a man’s interest in keeping his testosterone levels optimized is justified despite the unavoidable risks and negative effects it may impart. A healthy lifestyle including proper diet and regular resistance exercise will ensure that you are getting all the benefits testosterone has to offer.

Don’t think for a minute that testosterone is only important for men. For more information on how testosterone effects women, check out Contrarian Endocrinology Part I: Testosterone for Women by Karlis Ullis and Josh Shackman .

References:

1) Kremer WJ., Marchitelli L., Gordon SE., et al: Hormonal and growth factor responses to heavy resistance exercise. J Appl Physiol 69(4): 1442-1450, 1990

2) Tserotas K, Merino G. Andropause and the aging male. Arch Androl 1998 Mar-Apr;40(2):87-93

3) Lund BC, Bever-Stille KA, Perry PJ. Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men. Pharmacotherapy 1999 Aug;19(8):951-6

4) Tenover JL. Male hormone replacement therapy including “andropause”. Endocrinol Metab Clin North Am 1998 Dec;27(4):969-87

5) Baumann LS, Kelso EB. Selections from current literature: androgenetic alopecia: the science behind a new oral treatment. Fam Pract 1998 Oct;15(5):493-6

6) Sandow J, von Rechenberg W, Engelbart K. Pharmacological studies on androgen suppression in therapy of prostate carcinoma. Am J Clin Oncol 1988;11 Suppl 1:S6-10

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Planet Estrogen Part 3: The Menstrual Cycle and Athletic Performance

While the participation of women in sports has increased significantly over the last several decades, research of women in sports has lagged behind that of men. This is particularly true in matters related to reproduction and menstruation. Up until even recent years, women were cautioned not to partake in sports while pregnant or during menstruation because exercise during these times was thought to be detrimental to a woman’s health. While there certainly are precautions recommended for pregnant women, recent studies show that modified participation in exercise and sports activities is beneficial. As well, menstruation has become less of a roadblock in achieving sports goals for women. Nevertheless, there is still much we do not understand regarding women and gynecological issues. [Read more…]

Planet Estrogen Part 2: Apples and Pears

“At the same time that hormones challenge the pubertal brain, they change the body. A girl’s high estrogen content helps in the deposition of body fat on the breasts, hips, thighs and buttocks, subcutaneously, everywhere. Because of estrogen and auxiliary hormones, women have more body fat than men…..We can look at the deposition of body fat that comes with womanhood and say it’s natural for girls to fatten up when they mature, but what ‘natural’ means is subject to cultural definition, and our culture still hasn’t figured out how to handle fat.” –Natalie Angier1 [Read more…]

Planet Estrogen: Hormone Therapy, Training and Diet

A common concern amongst many women is how their hormones affect their exercise training and diet. Women’s bodies are influenced by fluctuations in hormones not only throughout the normal monthly reproductive cycle, but also throughout their entire lives. Both men and women experience a significant change in hormones at the onset of puberty and sexual maturation. For the remainder of their lives, men normally have less significant fluctuations in their sex hormone levels until approaching middle age. Studies document a gradual decline in sex hormones past the age of 40 years. Women, however, may see great fluctuations in sex hormone levels throughout their adult lives depending on physiological state, contraceptive methods, and menopause. [Read more…]

Connective Tissue Part 4: Glycosaminoglycans

What are glycosaminoglycans?

Proteoglycans are very large molecules consisting of proteins with attached chains of polysaccharides called glycosaminoglycans (GAGs)(see Part 1). GAG chains contain repeating units of modified sugars: one of two amino sugars (glucosamine or galactosamine) and a uronic acid. Many of these chains attach to a protein core and are collectively referred to as a proteoglycan (PG) monomer. Imagine, if you will, a bottlebrush with the bristles as GAGs. The molecular weight of a PG monomer may be one million. In articular cartilage, up to a hundred of these monomers can link to a hyaluronic acid chain to form a PG aggregate. The molecular weight of the aggregate may be as much as 100,000,000. [Read more…]

Connective Tissue Part 3: The Good and the Bad Continued…

As was discussed in Part II of this series, the major impact of diet upon connective tissue integrity is a deficiency in energy intake, usually associated with inadequate protein and carbohydrates. Aside from its role in mediation of inflammation, there is little research in effects of dietary fats on connective tissue. Micronutrients (minerals and vitamins) have many documented roles in cellular function and thus are critical in the wound healing process. Of nearly any population, athletes generally maintain an adequate diet specifically designed to meet the demands of their sport. Most athletes eat a balanced diet that adequately supplies both macro and micronutrients. Therefore, defects in collagen, elastin and proteoglycan metabolism are generally only seen as a result of deficiencies or excess. As well, successful healing of connective tissue injuries will rely on the presence of adequate nutritional stores. The roles of micronutrients in connective tissue injury healing are discussed in Part III of this series. [Read more…]

Connective Tissue Part 2: The Good, The Bad and the Ugly

In Part I of this series, readers were introduced to basic histology and physiology of connective tissue. We learned that all connective tissue has similar components, although the proportions of these components vary. These variations impart the mechanical and biochemical attributes to specific connective tissue. To illustrate, mechanical properties of articular cartilage that allow it to absorb impact and resist wear are partially due to the large proteoglycan aggregates. [Read more…]