supernova - Stellar mass limits for Neutron Star and Black Holes

A succinct summary of supernova types is given in the following image based on Heger et al. (2003):

^{Image courtesy of Wikipedia user Fulvio 314 under the Creative Commons Attribution-Share Alike 3.0 Unported license. The graph is based on the graph in Fig. 1 of the linked paper.}

The pair instability realm is upwards of ~100 solar masses, though it is metallicity-dependent (Question 3). As Figure 1 (below) shows, neutron stars form in the mass range of >9 solar masses - again, this is metallicity-dependent (Question 1a). Starting at around 25 solar masses, black holes will form (Question 1b).

I'm not aware of ways to form an astronomical black hole or neutron star not involving a Type I or Type II supernova without resorting to speculative possibilities like primordial black holes, but that doesn't make it entirely out of the question.

resource - A good website for laymen to share their discoveries?

This is a wonderful Q&A forum, but I'm wondering if anybody knows of a good website where someone can let other people interested in astronomy know about new things that they have become aware of:

For instance: Someone could inform others about what they have found out about the latest news event (ie: gravitational waves, the "megastructure" (probably not) found by Hubble, the possible new planet discovery, etc.) Another person could inform everybody about cool websites for people interested in astronomy (ie. ADS, SIMBAD, NASA's Kepler Datapage, Astrobiology On-Line Magazine, and countless others)

I just found out that there is a series of 40 full articles in "ADS" submitted from 2007 to the present titled "The HARPS search for southern extra-solar planets". If you read them in chronological order they are not only very informative, but you can see the history and evolution of the project.

I know there are numerous websites, but I am looking for one that is serious and not just an astronomy chat room.

bioinformatics - Introductory literature for synthetic / systems biology?

I'm a computer engineer (MsC Computer Engineering) who's looking to switch into the field of synthetic / systems biology.

I've got a comprehensive layman's understanding of evolution, genetics, transcription, etc, but my academic studies have been in the areas Informatics/Comp Sci/Comp Eng/Math.

Does anyone have a good recommendation for standard literature in the field, to get me up to speed?

human biology - How do the pharmacodynamics of the NSAIDs differ and are there "resistant" COX phenotypes?

This is a draft.

How do the pharmacodynamics of the NSAIDs differ - -?

Merck's manual ch. 36 to start little bit at an introductory level:

The anti-inflammatory activity of the NSAIDs is mediated chiefly
through inhibition of biosynthesis of prostaglandins (Figure 36–2).
Various NSAIDs have additional possible mechanisms of action,
including inhibition of chemotaxis, down-regulation of interleukin-1
production, decreased production of free radicals and superoxide,
and interference with calcium-mediated intracellular events. Aspirin
irreversibly acetylates and blocks platelet cyclooxygenase, while most
non-COX-selective NSAIDs are reversible inhibitors.

and see the coming answer below.
These questions should be answered together.
To split them can be confusing.

Is there any difference in the degree to which these drugs manipulate/inhibit the enzymes (I assume their affinities for COX-1 and COX-2 are at least somewhat different)?

Please, see ch 1.03.3 in Comprehensive Natural Products II: Chemistry and Biology: 10 Volume Set:

and their conclusions about the structure

and please, see the whole chapter of the book, since its about the topic - and I think good one.

From Katzung et al.

Selectivity for COX-1 versus COX-2 is variable and incomplete for
the older NSAIDs, but many selective COX-2 inhibitors have been
synthesized. The selective COX-2 inhibitors do not affect platelet
function at their usual doses.

On the other hand, selective COX-2 inhibitors may increase the
incidence of edema and hypertension.

To varying degrees, all newer NSAIDs are analgesic, anti-inflammatory, and antipyretic, and all (except the COX-2- selective
agents and the nonacetylated salicylates) inhibit platelet
aggregation. NSAIDs are all gastric irritants and can be associated
with gastrointestinal ulcers and bleeds as well, although as a group
the newer agents tend to cause less gas- trointestinal irritation than
aspirin.

In short, there must be differences to which these drugs manipulate/inhibit the enzymes.
Please, see

• Selinsky BS, Gupta K, Sharkey CT, Loll PJ. Structural analysis of
  NSAID binding by prostaglandin H2 synthase: time-dependent and time
  independent inhibitors elicit identical enzyme conformations. Biochemistry 40, 5172–5180 (2001).

Defining the COX Inhibitor Selectivity of NSAIDs: Implications for Understanding Toxicity. Expert Rev Clin Pharmacol. 2010;3(6):769-776. And see the chapter Expert Commentary which locates at the end of the publication there:

Not withstanding the caveats on the merit of IC50 values, in vitro
analyses of COX-1 and COX-2 selectivity of NSAIDs has driven the
concept that inhibition of COX-1 explains the predominant reduction in
synthesis of mucosal protective PGs and hence gastrointestinal
toxicity of NSAIDs relative to COX-2 inhibition, which plays a role in
ulcer healin

Merck's manual chapter 36

The discovery of two cyclooxygenase isoforms (COX-1 and COX-2) led to
the concept that the constitutive COX-1 isoform tends to be
homeostatic in function, while COX-2 is induced during inflammation
and tends to facilitate the inflammatory response. On this basis,
highly selective COX-2 inhibitors have been developed and marketed on
the assumption that such selective inhibitors would be safer than
nonselective COX-1 inhibitors but without loss of efficacy.

Inflammatory processes are expressed by both COX-1 and COX-2 differently.
This means that a change in the cell membrane expresses lysosomal enzymes differently:

The cell damage associated with inflammation acts on cell membranes to
cause leukocytes to release lysosomal enzymes; arachidonic acid is
then liberated from precursor compounds, and various eicosanoids are
synthesized.

Also, the cyclooxygenase (COX) pathway of arachidonate metabolism produces prostaglandins, which have a variety of effects on blood vessels, on nerve endings, and on cells involved in inflammation. (See Merck, ch. 18)

I like the Figure 36.2 in Merck's manual.
To better answer your question, one could label the arrows there with relevant enzymes in each processes and compare those between COX-1 and COX-2 and relate to corresponding publications (only few existing!).

Adrenaline and other compounds activate the cyclooxygenase pathway, COX-1 pathway for instance, and the conversion of arachidonate to PGs and TXs. [2, p. 67]
The classic law of mass action allows to describe the reversible binding:

begin{equation}
[Protein] + [L] rightleftharpoons^{k_{1}}_{k_{-1}} [Protein-L]
end{equation}

where $L$ is ligand, Protein-L the protein-ligand complex, $k_1$ the rate constant of the forward reaction, while $K_{-1}$ the rate constant of the reverse reaction.
This fine regulation differs between COX-1 and COX-2 at enzymatic level regulated by cytokines.

COX-1 becomes only little activated in inflammation, in comparison to COX-2.
COX-2 is present in macrophages (chronic inflammation! - cytokines), fibroblasts, endothelial cells, synovial fluids, and chondriocytes.

[A]re there “resistant” COX phenotypes?

I have not heard about this that there would not be.
There are so many components in PGHSs which can develop resistances.

[A]re there any known phenotypes of COX-1 and COX-2 enzymes that are present in the general population that affect the ability of these drugs to act?

Please, see for the phenotypes of COX-1 here, while about COX-2 much less has been research, see here - no known phenotypes, see this.
Please, note also that COX has at least two isoforms: COX-1 (PGHS-1) and COX-2 (PGHS-2).

COX-1 phenotypes

Is there any evidence as to whether the the NSAIDs collect in certain areas of the body in a compartmental fashion?

No.

Each disease has its own characteristics.
Gout, for instance, has swelling of syvovial joints and usage of NSAIDs with COX-2.
My professor of abdominal surgery answered to this question directly - impossible to answer generally which I agree with her. (17.10.2014)

I think the OP has in mind some antibiotics which concentrate in some parts of the body (such as 1st generation quinolones concentrating in the renal tubules and bladder, thus exerting local antibacterial effect).
There is no similar effect with NSAIDs.

Instead, NSAIDs have local and systemic effects, not because they are concentrating in some parts of the body, but because they have several mechanisms itself.
Please, see this thread about Effect of NSAIDS on stomach.

Are there differences in fat solubility, etc., between the different drugs?

Fat burner - of course, there are differences in fat solubility between different NSAIDs.
Please, see this publication Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Aqueous Solutions of Non-ionic Surfactants.
I will update this part next week more.

Other sources

1. Basic and Clinical Pharmacology, 11th edition, 2009, Bertram Katzung.


2. My notes during Biochemistry classes in Tartu 2011-2013

neuroscience - Why do the brains of cocaine-users shrink faster than the brains of non-cocaine users?

The mechanism of action of cocaine is dependent on pre-existing dopamine production and secretion. Normally, secreted dopamine is cleared from the synapse via the dopamine transporter (DAT) located on presynaptic dopaminergic terminals. Cocaine inhibits
this reuptake of dopamine, increasing it's duration of action on post-synaptic dopamine receptors. Thus, cocaine's effect depends on neuronal dopamine production. Without intrinsic dopamine, cocaine would have no effect. This is actual not exactly true though because cocaine also inhibits serotonin and norepinepherine reuptake transporters as well but the same argument applies to those neurotransmitters as well.

The overall effect of cocaine on the nervous system is extremely complex as it prolongs the action of dopamine, serotonin and norepinephrine wherever those reuptake transporters are present. There is a particularly high density of DAT in the basal ganglia and nucleus accumbens. What these areas of the brain normally do is under intense study and debate. The accumbens may play a role in goal directed behavior and incentive salience, which is the attribution of value to various actions or objects in the environment. This is what naturally guides us to perform one action over another. The simplistic view is that cocaine "highjacks" this system such that cocaine itself acquires greater incentive salience than natural reinforcers such as food, sex, money etc.

Getting back to the original question regarding why cocaine causes brain atrophy. This appears to be a finding quoted from a paper by the original inquirer. It is not obvious to me what the mechanism of this atrophy would be. I suggest you look at the discussion section of the paper from which that abstract was quoted to see what the authors suggest. However, to my knowledge, such atrophy has not been widely discussed in the cocaine literature but I could be wrong.

For further information see Sulzer. 2011. How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission.

coordinate - Protocol for establishing longitudinal meridians on other heavenly bodies

When we first observe a new heavenly body (it could be a new star, asteroid, etc., but let's say a minor planet in our own solar system), are there any procedures set in place for establishing a system of longitudinal meridians? Being that a prime meridian is an arbitrary concept that you can pick and establish anywhere, is a location decided based on a physical feature, or perhaps from the first points of data we gather when making detailed observations of a heavenly body for the first time? What about heavenly bodies with no easily discernible or non-stationary features (Gas Giants)? Also does the IAU regulate this process? I have always wondered if the USSR and the US shared common reference points for locations such as on the moon.

evolution - What is the benefit for cells having the ATP production regulated in mitochondria compared to being from the nucleus?

For starters, see this thread.

My understanding is that the ancient predecessors of mitochondria were free-living unicellular organisms. Supposedly at one point, these mitochondria-like cells developed an endosymbiotic relationship with a larger cell. This relationship was advantageous for both cells: the smaller cell could focus on energy production, leaving tasks like homeostasis, nutrient collection, etc, to the larger cell. Over evolutionary time, this endosymbiosis caused the smaller cell to lose all functions unrelated to energy production, while the larger cell (as we now know it) came to rely heavily on the mitochondria for energy production.

So it's possible that at one time the nucleus encoded machinery for ATP production, but apparently the modularity and separation of function provided by this ancient symbiosis turned out to be successful.