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Messages - Big Chicken
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« on: Today at 05:02:27 pm »
I bought a Dewalt 20 V Vauumc cordless handheld. As usual I was pulled into secondary once I enter the Airport. This time they brought my luggage to the room. My abroad runner forgot to question how to transport the Dewalt 20 V Lithium Max XR battery. The battery reads Dewalt XR 20 V 5 AH. Customs did take the two batteries I had. Which I had no problem with. Their doing here job. I'm pulled in so much. I know them all by name and have written them diets. But sometimes new guys are working that I do not know.
My wife ordered a 20 V XR 8 AH battery. My question. Will this fit and is the (8AH) just a longer lasting battery as far as use before battery dies? The battery that came with it is a 20 V 5ah battery.
I tried canceling but it appears when ordering online. The charger and battery comes from different locations?
The product is Dewalt 20 V Vacuum Cordless hand Held vacuum (battery DCV501HB) Also thinking should I order 2-3vbatteries. Want to use to clean boats and the family's SUV
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« on: Today at 01:34:52 pm »
Can you Mail Drugs Through the USPS Without Getting Caught?
Table of Contents
How to Mail Drugs Through the USPS?
Mailing Drugs (such as Marijuana) Through the United States Postal Service
Drug Trafficking Already Occurs Through the Mail
Drug Mailing Methodology
Staying Anonymous
Shipping Non-Obscure Parcels
Hiding the Drugs: Incognito Shipments
Vacuum Sealing and Zip-Loc Baggies
Drop Shipping To Another Location
Mailing Drugs Through UPS, FedEx, DHL or Other Postal Services
Risks of Getting Caught Trying to Ship Drugs in the Mail
How to Mail Drugs Through the USPS?
Mailing Drugs (such as Marijuana) Through the United States Postal Service
The United States Postal Service was created almost two and a half centuries ago offering the government a supreme earning opportunity on what feels like a monopoly on shipping. That in mind, is it smart to ship drugs through the USPS? Can it be done successfully (without being caught)? Analyzing the shipping process and establishment’s implemented procedures towards protecting against shipments of drugs moving through the nation’s biggest shipping operation can help identify and even circumvent the risks. That is going to help answer the biggest question: what are the risks of mailing or shipping cannabis or other drugs through the U.S. mail? And are people getting away with mailing marijuana?
One of the most profound defenses (if not the biggest defense) the USPS has in place to eliminate the shipping of illegal drugs is the postal inspector. Although they hold many responsibilities, postal inspectors were basically created to specifically identify and intercept drugs in the mail. Having an entire team of specially trained and operating “postal soldiers” helps eliminate most of the drug trafficking, both: domestic packages, as well as international imports entering the U.S. from abroad. Regardless of the postal inspector, some people still attempt to get away with mailing their marijuana or other drugs and think they will get away with it. Many drug traffickers still believe it is worth the risk, despite how many billions of packages containing cannabis are confiscated.
Taking a chance of mailing weed in the USPS has proven for many to have its upsides. For one, it can seem safer than purchasing marijuana (or other drugs) off the street from unknown persons. For two, it can become a somewhat “anonymous” process, especially with the uprising of the automated shipping clerk machines popping up in 24/7 access USPS lobbies. And in some states, the possession of marijuana has been decriminalized, and thus the risks of being caught with the substance even at the post office seems less severe. However, whether cannabis is legal or not, it is still illegal to ship cannabis…forcing traffickers to maintain elastic creativity when bringing their bud to the shipping counter. And everyone knows it’s no secret: the Mexican Cartel has been using the United States Postal Service as a drug mule for decades; and most cannabis in the United States, still comes from Mexico. Point being: it works for someone!
Drug Trafficking Already Occurs Through the Mail
Although people have been shipping drugs in the mail for decades, in recent times the internet shined light on a rather dark place: the silk road. Media absolutely engulfed this idea and the idea of the “Dark Net”. Unfortunately, this led the FBI to bust the silk road and shut it down, only to bring it back up again with their informants scattered all throughout the network…in short: the silk road is now the farthest thing from a “safe way to buy drugs on the internet”. In fact, it seems much more like a “sure way to get caught buying drugs on the internet”. Regardless of how the deal went down (or goes down), people still looked to ship the drugs using the Postal Service (even when they were purchased on the Silk Road, there was no secret delivery system available, the drugs were usually still shipped using the normal USPS).
Interestingly enough, cannabis confiscations are down in recent years…so the traffickers must be getting away with a lot more. And while it is much harder to believe they are trying less often, it must also be admitted that the USPS has been hurting for business for at least the last decade. In fact, total shipping volume of first class mail has declined by over 30 billion parcels in the last decade and total volume has declined more than 25 percent in the same time period. Still, more than a million pounds of illicit substances are confiscated each year through the United States Postal Service, some years exceeding multiple millions of pounds. And still, the battle to combat drug shipments in the US mail rages forward even receiving the full spot light of a former Attorney General, Eric Holder, who was famously quoted complaining about how frequently the mail system is used to ship drugs around. Marijuana remains the most common drug that postal inspectors come across.
The USPS takes a very vigilant, proactive stance on eliminating drug trafficking in the US mail system and guarantees the U.S. Postal Inspection Service’s primary focus is to identify and pursue traffickers of all types of illicit substances (which includes marijuana obviously). Anything that is illegal under the federal Controlled Substances Act is considered “unmailable”. A special “prohibited narcotics program” was created to disrupt and eliminate organized narcotics trafficking. The USPS maintains every possible effort within their budget to reduce the distribution of narcotics through their mail system.
Despite the fact that several states have legalized possession of marijuana, it still largely remains federally illegal to possess, and thus the U.S. Postal Inspection Service technically “employs” federal agents, mandated to protect and enforce federal law as it pertains to the U.S. mail. And given there are over 200 laws related to the U.S. mail and its parcels, these federal inspectors are given very powerful, elastic control over interpretation of risk and unmailable items. An average of one thousand suspects are detained and arrested each year by postal inspectors, specifically for trafficking drugs in the U.S. mail. Cash related to these operations are seized as a asset of criminal activity. Additionally, there are many accounts where postal inspectors have actually used federal forfeiture laws. This means postal inspectors have justified seizing homes, boats, vehicles, and all types of items “purchased using drug money”.
Drug Mailing Methodology
The below techniques and methods for mailing drugs are merely theory and for information and education purposes only.
Staying Anonymous
One huge attribute of most successful drug trafficking operations using the U.S. mail seems to be the availability of anonymity in shipments. In recent years many post offices have been making automated shipping stations available after hours in the lobbies. This allows for drug traffickers to send packages without genuine return address information, all anonymously from a self-serve kiosk in the dead of the night.
Shipping Non-Obscure Parcels
One technique very commonly implemented in drug trafficking through the mail system is blending in. It is much easier to get a package delivered if it looks like most other packages getting delivered. Sending obscure items and parcels leads to unwanted attention and getting caught. Shipping normal sized boxes and parcels, with normal labeling and weights does not draw any suspicion by any postal employees or inspectors handling the parcel.
Hiding the Drugs: Incognito Shipments
Most drug traffickers do not merely slip the marijuana (or Ketamine, cocaine, ecstacy or other drug) into a manila envelope and slap a stamp on the front. Instead, a common technique is to disguise the substance as best as possible. Some people use food (especially foods that high strong scents, which can also throw off any postal inspection canine units – yes, postal inspectors do employ the use of drug sniffing dogs in some instances and locations). One account reported Ketamine taped to the back of a pokemon card, located within a sealed pack of brand new pokemon cards, all shipped in a simple first class letter. The larger the quantity drug being shipped, the larger and more creative the package being shipped has to be. Child toys and games, as well as baby-related items and gifts are typically used because people believe they are much less likely to receive scrutiny from inspectors and postal workers.
Traffickers will apply drugs in layers to the backsides of framed photographs, collectable baseball cards, or other artworks. Depending upon the drug, some illicit substances can be dissolved into a spray bottle and “sprayed” onto gift cards, which then are consumed on the recipient end (paper and all), and in this method, the drug is even invisible! One case presented nearly 500 kilograms of cocaine stuffed in what appeared to be completely fresh, unpeeled bananas.
Vacuum Sealing and Zip-Loc Baggies
Creativity may be rampant in some drug shipments…but there are still some folks who just prefer to stuff their weed in a few zip lock bags and throw it in the mail. While this is obviously hugely primitive and the risk is likely much higher, lots of people still seem to get away with it. There are also some traffickers that use expensive vacuum sealing systems to eliminate nearly all smells…and some methods which combine vacuum sealing with incognito shipments. One example, would be a vacuum sealed ounce of marijuana, which is then stuffed into the bottom of a hollowed out can of shaving cream (that still expends shaving cream upon being tested by a postal inspected).
Drop Shipping To Another Location
One crude method for shipping drugs in the mail, is to ship them to someone else’s address. This person could know the actual recipient, or be blind to the fact mail is being shipped to their address altogether. Some people pick a neighbor who isn’t home in the daytime and simply watch for the delivery. Other people pick a neighbor or friend who is actually in on the shipment. This method is in fact crude, as it does not indemnify the recipient address or actual recipient by any means. It simply makes the recipient feel better about receiving drugs in the mail.
Remember: Besides the machines (which are not that sophisticated), it really comes down to parcels being able to “pass” human scrutiny. The Postal Inspectors are the most advanced form of defense the USPS employs, still relying upon human scrutiny.
Mailing Drugs Through UPS, FedEx, DHL or Other Postal Services
Since the USPS seems like a bad option, many people consider using private shipping entities. The biggest three private shipping companies outside of the United States Postal Service are UPS, FedEx, and DHL. Obviously marijuana (and other illicit substances) are going to be on the prohibited items list. But the question at hand is: Are any of these other options a safer alternative for shipping drugs in the mail? And additionally, many people falsely assume that these private companies are farther from the prying eyes and hands of the government, and government searches. In reality, these three companies all very specifically reserve their right to inspect any packages within their system for any reason at their total discretion; whereas the USPS is actually a much stronger advocate of the Fourth Amendment. In fact, postal inspectors are required to attain a search warrant before inspecting any mail or parcel, which includes obtaining probable cause. Although it is acceptable to single out and track a suspicious parcel, the USPS states very clearly that first class letters and parcels are protected from search and seizures without warrant. Additionally, the Supreme Court recently ruled that shipping packages with these private couriers removes all reasonable expectation of privacy; and ultimately this implied more liability for these companies, forcing greater parcel scrutiny.
Noteworthy: It is also worth mentioning that the USPS offers workers and/or the public a $50,000 reward to anyone providing information leading to an arrest and indictment (charges filed) of a drug trafficker.
Risks of Getting Caught Trying to Ship Drugs in the Mail
Obviously the postal service deals with so many packages every year, it cannot realistically inspect every single parcel…at least not without a super computer scanner capable of 100 percent contraband detection, which simply doesn’t seem to exist just yet. And it is highly doubtful the USPS is going to receive exorbitant budget increases any time soon…simply put: some packages containing drugs are going to slip through and get delivered. But just because one package gets delivered, doesn’t mean all future packages will be delivered, oftentimes leading a first-time successful delivery to lower a drug traffickers perception of shipment risks.
Although shipping drugs in the mail is easier (and probably safer) than the government would like, the USPS still partners with local law enforcement and other federal agencies to bring charges against thousands of traffickers every year. And thus shipping narcotics through the U.S. Postal Service is still a gamble, and one which could lead to forfeiture of one’s house! Remember, because the U.S. Postal Service is a government entity, it is a federal agency and federal law applies. Illicit use of the U.S. mail is a felony, and on top of that, the narcotics which would be mailed are scheduled, controlled substances. Shipping 50 grams or less of marijuana, for example, can come with a 5 year federal penitentiary price tag. And shipping more, means greater risk. There is also a common myth that only the sending party is at risk. The recipient is also at risk, as any knowledge or participation in the shipping of narcotics (and thus the abuse and use of the U.S. mail system to ship illicit substances), can land the recipient felonies too.
Disclaimer: Mr Hyde and Drugs and Bad Ideas do not suggest or condone mailing any type of drugs through the USPS or any other mail postal service. This guide is purely for educational purposes only.
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« on: Today at 01:11:17 pm »
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor[9] that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone,[10] in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.[11][12]
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression;[13] however, the androgen receptor has other functions as well.[14] Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype.
Function
Effect on development
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation.[15] Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles.[16] Testosterone is therefore responsible primarily for the development of male primary sexual characteristics, whilst dihydrotestosterone is responsible for secondary male characteristics.
Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.[17]
Knockout-mice studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.[18]
Maintenance of male skeletal integrity
Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes.[19]
Role in females
The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.
Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS). Complete (CAIS) and partial (PAIS) which are a result of mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported.[citation needed]
Mechanism of action
Genomic
The primary mechanism of action for androgen receptors is direct regulation of gene transcription. The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene transcription.[20] Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is the insulin-like growth factor 1 receptor (IGF-1R).[21] Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
One function of androgen receptor that is independent of direct binding to its target DNA sequence is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor, a protein that activates several genes that cause muscle growth.[22]
Androgen receptor is modified by post-translational modification through acetylation,[23] which directly promotes AR-mediated transactivation, apoptosis[24] and contact-independent growth of prostate cancer cells.[25] AR acetylation is induced by androgens[26] and determines recruitment into chromatin.[27] The AR acetylation site is a key target of NAD-dependent and TSA-dependent histone deacetylases[28] and long non-coding RNA.[29]
Non-genomic
More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA.[14][30] Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
Genetics
Gene
In humans, the androgen receptor is encoded by the AR gene located on the X chromosome at Xq11–12.[31][32]
Deficiencies
At least 165 disease-causing mutations in this gene have been discovered. [33] The androgen insensitivity syndrome, formerly known as testicular feminization, is caused by a mutation in the androgen receptor gene on the X chromosome (locus: Xq11–Xq12).[34] The androgen receptor seems to affect neuron physiology and is defective in Kennedy's disease.[35][36] In addition, point mutations and trinucleotide repeat polymorphisms have been linked to a number of additional disorders.[37]
CAG repeats
The AR gene contains CAG repeats that affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists,[38][39] with African-Americans having fewer repeats than non-Hispanic white Americans.[38] The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.
Mutations
The enhancer and the gene encoding for these receptors contain recurrent mutations, such as structural rearrangements and copy number changes, acquired in the progression of metastatic castration-resistant prostate cancer (mCRPC) treatment with therapy targeting these receptors (abiraterone, enzalutamide), make the disease progression determined by the androgen receptor genotype.[40]
Structure
Structural domains of the two isoforms (AR-A and AR-B) of the human androgen receptor. Numbers above the bars refer to the amino acid residues that separate the domains starting from the N-terminus (left) to C-terminus (right). NTD = N-terminal domain, DBD = DNA-binding domain, LBD = ligand-binding domain, AF = activation function.
Isoforms
Two isoforms of the androgen receptor (A and B) have been identified:[41]
AR-A – 87 kDa; N-terminus truncated (lacks the first 187 amino acids), which results from in vitro proteolysis.[42]
AR-B – 110 kDa; full length
Domains
Like other nuclear receptors, the androgen receptor is modular in structure and is composed of the following functional domains labeled A through F:[43]
A/B) – N-terminal regulatory domain contains:[44]
activation function 1 (AF-1) between residues 101 and 370 required for full ligand-activated transcriptional activity
activation function 5 (AF-5) between residues 360–485 is responsible for the constitutive activity (activity without bound ligand)
dimerization surface involving residues 1–36 (containing the FXXLF motif; where F = phenylalanine, L = leucine, and X = any amino acid residue) and 370–494, both of which interact with the ligand binding domain (LBD) in an intramolecular[45][46][47] head-to-tail interaction[48][49][50]
C) – DNA binding domain (DBD)
D) – Hinge region; flexible region that connects the DBD with the LBD; along with the DBD, contains a ligand dependent nuclear localization signal[51]
E) – Ligand binding domain (LBD) containing
activation function 2 (AF-2), responsible for agonist induced activity (activity in the presence of bound agonist)
AF-2 binds either the N-terminal FXXFL motif intramolecularly or coactivator proteins (containing the LXXLL or preferably FXXFL motifs)[50]
A ligand dependent nuclear export signal[52]
F) – C-terminal domain
Splice variants
AR-V7 is an androgen receptor splice variant that can be detected in circulating tumor cells of metastatic prostate cancer patients[53][54] and is predictive of resistance to some drugs.[55]
Clinical significance
High expression in androgen receptor has been linked to aggression and sex drive by affecting the HPA and HPG axis[56]
Aberrant androgen receptor coregulator activity may contribute to the progression of prostate cancer.[57][40]
Ligands
vte Affinities[a][58]
Compound RBA
Metribolone 100
Dihydrotestosterone 85
Cyproterone acetate 7.8
Bicalutamide 1.4
Nilutamide 0.9
Hydroxyflutamide 0.57
Flutamide <0.0057
Notes:
At androgen receptors; measured in human prostate tissue.
Relative to Metribolone, which is by definition 100%
Agonists
Endogenous androgens (e.g., testosterone, dihydrotestosterone, androstenedione, androstenediol, dehydroepiandrosterone)
Synthetic androgens (e.g., methyltestosterone, metandienone, nandrolone, trenbolone, oxandrolone, stanozolol)
Mixed
Selective androgen receptor modulators (e.g., andarine, enobosarm)
Antagonists
Steroidal antiandrogens (e.g., cyproterone acetate, chlormadinone acetate, spironolactone, oxendolone)
Nonsteroidal antiandrogens (e.g., flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, RU-58841)
N-Terminal domain antiandrogens (e.g., bisphenol A, EPI-001, ralaniten, JN compounds)[59]
As a drug target
The AR is an important therapeutic target in prostate cancer. Thus many different antiandrogens have been developed, primarily targeting the ligand-binding domain of the protein.[60] AR ligands can either be classified based on their structure (steroidal or nonsteroidal) or based on their ability to activate or inhibit transcription (agonists or antagonists).[61] Inhibitors that target alternative functional domains (N-terminal domain, DNA-binding domain) of the protein are still under development.[59]
Drug resistance
Alteration of ARs may lead to treatment resistance (castration resistance) in prostate cancer as there may be missense mutations of the ligand binding domain, amplifications of the gene coding for this receptor or in its enhancer, mostly, suggesting the presence of different subclones with different genotypes of these receptors.[40]
Interactions
Androgen receptor has been shown to interact with:
AKT1,[62]
BAG1,[63][64][65]
Beta-catenin,[66][67][68][69][70][71]
BRCA1,[72][73]
C-jun,[74]
Calmodulin 1,[75]
Caveolin 1,[76]
CDK9,[77]
COX5B,[78]
CREB-binding protein,[79][80][81][82]
Cyclin D1,[83][84][85][86]
Cyclin-dependent kinase 7,[87]
DACH1,[88]
Death associated protein 6,[89]
L-DOPA,[90]
EFCAB6,[91]
Epidermal growth factor receptor,[92][93]
FOXO1,[94]
GAPDH,[95]
Gelsolin,[96]
GNB2L1,[97]
GSK3B,[98]
HDAC1,[99]
HSP90AA1,[100][101]
HTATIP,[99]
MAGEA11,[102][103]
MED1,[104]
MYST2,[105]
NCOA1,[67][106][107]
NCOA2,[66][81][102][108][109]
NCOA3,[108][110][111]
NCOA4,[62][109][112][113][114][115][116][117][118]
NCOA6,[119]
NCOR2,[66][120][121]
NONO,[81]
p300,[122]
PA2G4,[123]
PAK6,[124][125]
PATZ1,[126]
PIAS2,[127][128]
PRPF6,[129]
PTEN,[130]
RAD9A,[131]
RANBP9,[132]
RCHY1,[133]
Retinoblastoma protein,[134][135]
RNF14,[109][112][136][137]
RNF4,[126][138][139]
SART3,[140]
SIRT1,[28]
SMAD3,[141][142][143]
Small heterodimer partner,[144]
Src,[130][145][146]
SRY,[147]
STAT3,[148][149]
SVIL,[150]
Testicular receptor 2,[151]
Testicular receptor 4,[152]
TGFB1I1,[112][153]
TMF1,[154]
TRIM68,[155]
UBE2I,[66][67][156][157][158][159]
UXT,[160] and
ZMIZ1.[161]
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« on: Today at 01:00:13 pm »
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« on: March 26, 2023, 03:01:25 pm »
biggerben692000
Founding Member
Today at 8:32 AM
#203
Just stopping in to thank EG for another pleasant experience. One of my guys wants as much Pharmacy grade gear as I can find him and I've found plenty with EG He is impressed all the way around. Thank you, EG
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