Frag 176-191 Peptide Therapy | A-Z Guide

This in-depth guide on Frag 176-191 peptide therapy was crafted by the research team at Peptides.org – the premier source for all information about research peptides, SARMs, and more.

Human growth hormone fragment 176-191 – aka frag 176-191 – is a synthetic peptide that is identical to the final 16 amino acids of human growth hormone (hGH). As a result, this fragment retains a subset of hGH’s well-established effects on fat loss, without the additional unwanted effects linked to the full hGH protein. 

Based on the finding that a small fragment of the hGH protein can selectively drive fat loss without the risks that come along with increased IGF-1 levels, a considerable amount of research and development has gone into synthetic peptides that mimic the activity of this small fragment of hGH. 

Another hGH fragment named AOD9604 has received the most attention, and is nearly identical to frag 176-191, as both peptides share the same amino acid sequence from positions 177 to 191. Given the high degree of similarity, many experts consider the extensive clinical research performed for AOD9604 to be relevant for frag 176-191.

In this article, we will provide a thorough overview of the relevant research associated with frag 176-191, as well as reference guidelines for dosing and administration.

Our recommended source for purchasing research-grade frag 176-191 peptide is Peptide Sciences.

What is Frag 176-191?

Human growth hormone fragment 176-191 (frag 176-191) was discovered to be responsible for the fat-burning effects of the full human growth hormone (hGH) protein by Dr. Frank Ng in the 1990s at Monash University [1, 2]. 

Similar to the derivative peptide AOD9604, which will be explained below, several early studies used the nearly identical peptide named frag 177-191 (also referred to as AOD9601). Given the sequence similarity and overlap in receptor binding, the literature for these derivative peptides is relevant for the consideration of frag 176-191 and will be referred to interchangeably throughout this article.

The progenitor protein of frag 176-191, hGH, is a 191 amino acid protein that controls a complex interplay of diverse physiological processes, from cellular and tissue growth to fat loss and glucose metabolism [3]. 

Similar to many other multifunctional proteins, different processes are controlled by different regions of the hGH protein [4]. For instance, roughly the first 45 amino acids are responsible for promoting insulin synthesis, whereas the final 16 amino acids are responsible for fat loss [5]. 

Due to the modular nature of hGH, it is possible to use specific fragments of the protein to selectively control the functions associated with that part of the protein. 

Accordingly, the discovery that the final 16 amino acids confer the fat-burning effects of hGH led researchers to separately synthesize frag 176-191 as a standalone peptide. As predicted, frag 176-191 was indeed capable of inducing fat loss without the other effects associated with the full hGH protein [6]. 

Due to the severity of the obesity epidemic, this has been a landmark discovery, as doctors still face a very limited pharmacological toolset to help patients lose weight, with the full hGH protein causing too many side effects for long-term use. 

In an attempt to improve stability of the peptide, researchers changed the first amino acid in the frag 176-191 peptide from a-phenylalanine to a-tyrosine, resulting in a new peptide named anti-obesity drug 9604, or AOD9604 [5, 7]. 

AOD9604 is the most widely studied lipolytic hGH fragment to date and has been evaluated in six clinical trials [5]. Due to the nearly identical sequence similarity, and more importantly, 100% conservation of the region of the peptide needed to induce lipolysis, many researchers consider the literature on AOD9604 to be relevant for frag 176-191 [8].

What Does Frag 176-191 Do?

Although the precise mechanism of action is not clear, frag 176-191 peptide is thought to mimic the lipolytic activity of hGH while leaving other processes normally impacted by hGH unaffected [7, 8]. To gain a better understanding of how frag 176-191 works, one must begin by understanding the function of the parent protein, hGH.

hGH is a 191 amino acid protein that influences a complex series of physiological processes, with both anabolic and catabolic actions on different tissues in the body [3, 4 ,9]. For instance, hGH has a causal role in growth during puberty and can cause overgrowth of adult tissues in disorders such as acromegaly, but also plays an important role in promoting fat loss [10, 11, 12].

The diverse functional nature of hGH is related to its multifunctional protein domain structure, with different protein domains being responsible for different biochemical actions [13]. 

For this reason, frag 176-191 is capable of selectively inducing fat loss similar to hGH but without the unwanted additional effects such as tissue growth, hypertension, and edema [5, 14].

The selective activity profile of frag 176-191 compared with hGH, largely informed by the literature on AOD9604, is enabled by the fact that 176-191 cannot bind to the growth hormone receptor [7, 15]. Consequently, all processes downstream of growth hormone receptor signaling, including upregulation of IGF-1 production, are unaffected by the frag 176-191 peptide.

Although the molecular interactions mediating the fat loss effects of frag 176-191 are unknown, hGH is known to induce fat loss by increasing circulating levels of free fatty acids (FFAs) by increasing lipolysis and through inhibition of FFA uptake into fat cells [4, 9]. 

Finally, there is evidence that frag 176-191 may positively affect cartilage regeneration through a similar mechanism to hGH, once again without the negative effects around impaired glucose metabolism [16].

Frag 176-191 Clinical Trials and Research

No clinical trials have been performed using human growth hormone fragment 176-191 (frag 176-191), as researchers instead have chosen to use the nearly identical derivative peptide, AOD9604 [5]. 

As described above, the literature on AOD9604 is considered by experts to be relevant for understanding the biology of frag 176-191 and will be referenced in this section. 

Preclinical animal studies

In obese Zucker rats administered a daily, 500mcg oral dose of AOD9604, body weight gains were significantly decreased compared with controls [17]. Note that the orally treated mice did not lose weight, but instead gained weight at a slower rate compared with controls. 

Importantly, mice treated with injectable AOD9604 in earlier studies actually lost weight from baseline, which will be a relevant distinction in discussion of human clinical trials [18]. 

To understand the mechanism of action of the lipolytic fragment of hGH, researchers used genetically engineered mice lacking the beta-3 adrenergic receptor (β3-AR) to understand whether the lipolytic effects of AOD9604 are mediated by β3-AR [7]. 

Interestingly, study authors found that both hGH and its lipolytic fragment did in part exert their lipolytic effects by modulating expression of the β3-AR receptor. However, β3-AR knock-out mice were found to acutely respond to AOD9604 in demonstrating that there is a β3-AR-independent lipolytic effect of AOD9604.

Finally, a study in rabbits found that AOD9604 could promote cartilage regeneration when administered directly into the knee joint, suggesting another promising application for the hGH fragment [16].

Clinical trials in humans

A total of six clinical trials were performed in humans between 2001 and 2006 evaluating safety, tolerability, and efficacy of AOD9604 [5]. 

In the first two studies, safety of AOD9604 was evaluated via intravenous (IV) infusion, which is unique from most clinical trials of peptides, which are usually administered via subcutaneous or intramuscular injection. Across both studies, AOD9604 was well tolerated with no observable trends in adverse events between treatment and control groups [5]. 

Importantly, no changes in IGF-1 levels were observed, confirming the hypothesis that the lipolytic fragment of hGH operates independent of the growth-promoting pathways of hGH [5]. Despite the acceptable safety profile, researchers decided to pursue an oral formulation.

An additional four clinical trials were performed evaluating AOD9604 but using an oral formation. The orally-administered AOD9604 was similarly found to be well-tolerated, reaching the end point in each of the safety studies [5]. 

However, clinical trials ultimately did not find that oral AOD9604 was effective as an anti-obesity drug and ceased clinical trials following completion of a phase IIb trial [5]. 

Some experts attribute the disappointing clinical results to the decision to pursue an oral formulation, as most peptides have minimal bioavailability when taken orally. AOD9604 was subsequently licensed by another pharmaceutical company pursuing a different route of administration in acknowledgment of the problems of oral administration [19].

Frag 176-191 Safety and Side Effects 

As highlighted above, researchers have not undertaken human studies with frag 176-191 peptide, instead using the nearly identical peptide AOD9604 due to a hypothesized increase in stability. Accordingly, an assessment of the safety of frag 176-191 must be extrapolated based on data from AOD9604, which is only different by one amino acid.

Across six clinical trials of AOD9604 that included a total of 893 subjects, zero safety issues attributable to the peptide were noted, with AOD9604 displaying an excellent safety profile [5]. Importantly, AOD9604 did not cause any of the undesirable effects of hGH treatment including increased IGF-1 or impaired glucose metabolism. 

In the first clinical trial, 15 subjects received three different doses of AOD9604 (25mcg/kg to 400mcg/kg) and one dose of placebo, given via IV injection, separated by seven days. Over the course of the study, a total of 29 adverse events were recorded, though the incidences were all mild and evenly distributed between treatment and placebo groups, suggesting no causal role of the peptide [5].

A second study in 23 subjects evaluating a smaller dose range (25, 50, and 100mcg/kg) came away with a similar set of conclusions, as there was no trend in the incidence of adverse events between placebo and control groups and AOD9604 was well-tolerated. However, in this study, there were three adverse events considered to be of severe intensity, with one in the AOD9604 group and two in the placebo. The adverse event in the AOD9604 group (chest tightness) was notable only because it could not be ruled out as related to AOD9604 treatment [5].

Despite the overall acceptable safety profile that was found across both safety studies, clinical development shifted to an oral formulation of AOD9604. Across the remaining four clinical trials for AOD9604, no serious safety concerns were raised. The only finding of note is the increased frequency of mild gastrointestinal side effects observed in the highest dose (54mg) oral AOD9604 group [5].

Similar to IV AOD9604, no increase in serum IGF-1 was observed when AOD9604 was administered orally, nor were there impairments in glucose metabolism [5]. 

In summary, AOD9604 was found to be safe and well-tolerated, regardless of the route of administration. This is reflected by the fact that AOD9604 has been classified by a panel of experts to be “Generally Recognized as Safe” (GRAS), an uncommon classification for synthetic peptides [5].

Is Frag 176-191 Legal?

Similar to other research peptides, frag 176-191 is legal for purchase, sale, and handling for research purposes only. Frag 176-191 is not available as a medical product as it is not FDA approved for any use at this time. 

As a result, frag 176-191 cannot be marketed in the United States for human consumption nor for the treatment of medical conditions. Similar laws apply in the European Union and in the United Kingdom. 

The gap in regulatory coverage over peptides like frag 176-191 has led to a largely unregulated peptide market in which unqualified vendors inappropriately market products with unsupported medical claims. These vendors are subject to legal penalties in many countries, including the US and UK, while consumers are subject to the risks of administering adulterated compounds. 

Researchers are accordingly advised to exercise caution and ensure purchasing materials from qualified vendors with long-track records of delivering high-quality, research-grade peptides. 

Frag 176-191 for Competitive Athletics

For researchers with the intention of applying their work towards competitive athletics, it is important to note that frag 176-191 is classified as a banned substance by multiple doping agencies, due to its potential for enhancing athletic performance. 

Frag 176-191 is specifically classified as an S2 non-specified substance by the World Anti-Doping Agency (WAD), which has also been adopted by the United States Anti-Doping Agency (USADA) [20, 21].

Frag 176-191 Dosage and Cycle

The limited efficacy of orally-administered human growth hormone fragment 176-191 (frag 176-191) has informed our position that frag 176-191 would be best administered via subcutaneous injection, similar to hGH.

Since frag 176-191 peptide’s discontinuation for clinical evaluation, expert opinion has shifted such that an appropriate dosing range for subcutaneously injected frag 176-191 would be approximately 200-500mcg per day, for purposes of inducing weight loss in subjects. 

Although frag 176-191’s equivalent AOD9604 was demonstrated to have an excellent safety profile, tolerance of subcutaneous injections should still be initially assessed using conservative doses [5]. 

A hypothetical Frag 176-191 dosing protocol to help researchers understand potential study design is as follows:

• Initial dose: To assess tolerance, begin with a frag 176-191 dose of 100mcg injected subcutaneously. Note that 1mg is equal to 1000mcg, and 100mcg is equal to 1/10th of a milligram.
• Subsequent doses: If the initial dose is well tolerated, escalate dosing to between 200-500mcg per injection, depending on the goals of the study. 
• Administration timing and frequency: Based on what is understood about hGH pharmacokinetics and pharmacodynamics, frag 176-191 is likely best administered on an empty stomach, approximately 30 minutes to 1 hour prior to exercise. Note that the total daily dosage can be split between a morning and evening injection.

For intranasal formulations of frag 176-191, bioavailability will be lower due to reduced absorption of the peptide solution through the nasal membrane, compared with injection [22]. To compensate for reduced systemic absorption, researchers could consider using the same protocol listed above, but with doses increased at each step by up to 50%.

Frag 176-191 | Injectable vs. Nasal Spray 

Since the discovery of frag 176-191 and its derivative AOD9604, clinical trials have evaluated safety and efficacy using either injection or oral administration of pills and capsules [5]. Given the poor efficacy of oral administration, as well as the long history of using injectable hGH, administration of frag 176-191 via subcutaneous injection is the best option for maximizing bioavailability. 

Another commonly used route of administration for peptides like frag 176-191 is via nasal spray, which is used in multiple FDA-approved peptide therapies, as well as FDA-compliant clinical trials [23]. 

The nasal membrane is capable of rapidly absorbing peptides and small proteins and has been of interest for researchers and pharmaceutical companies looking to avoid injections, which are often less desirable and lead to poor patient compliance [22]. As a result, a significant amount of clinical development has gone into validating the compatibility of peptides and small proteins with nasal spray administration [23].

To ensure that frag 176-191 peptide is delivered with maximal bioavailability via nasal spray, researchers can keep the following factors and guidelines in mind when thinking about hypothetical clinical protocols:

• To maximize absorption, allow at least one minute between sprays in the same nostril to avoid oversaturation of the nasal membrane and subsequent loss of the peptide to swallowing.
• Administer to subjects in a tilted head position to avoid loss from the bottom of the nose.
• Clear any nasal congestion prior to administration to minimize blockage of the nasal membrane and ensure maximum absorption.
• Ensure that the spray pump is kept clean and is refrigerated at all times when not in use to minimize contamination and degradation of the peptide.

Whether qualified researchers choose to use an injectable or nasal spray format of frag 176-191 will depend on the nature of the trial design. If maximum bioavailability is important, injectable frag 176-191 will be best. However, if poor subject compliance with injections is a concern, then the nasal spray format of frag 176-191 may be worth considering. 

Where to Buy Frag 176-191 Online?

Qualified researchers interested in studying the peptide in preclinical laboratory testing may be interested to find out the best place to buy Frag 176-191 online. 

The review team at Peptides.org has experience with several online vendors, and we are confident that the best sources for frag 176-191 are:

Injectable Frag 176-191: Peptide Sciences  

Nasal spray Frag 176-191: PureRawz

We selected both vendors based on several key criteria that allow us to recommend the highest-quality research-grade frag 176-191 peptide:

• Quality and Purity. Both Peptide Sciences and PureRawz produce research-grade frag 176-191 peptide and adhere to rigorous quality control standards, ensuring that researchers can purchase unadulterated peptides.
• Excellent Pricing. Both of our recommended vendors offer competitive pricing alongside top-notch quality and customer service.
• Multiple Payment Methods. Peptide Sciences accepts CashApp, Zelle, Bitcoin, Ether, as well as e-checks. PureRawz accepts major credit cards, Bitcoin, PayPal, and checks.
• Customer Service. Peptide Sciences and PureRawz both have reputable customer service departments with dedicated teams that can handle questions or concerns.

Qualified buyers interested in getting started with pre-clinical laboratory research on frag 176-191 should not hesitate to check out either vendor.

How to Reconstitute Frag 176-191

Your injectable frag 176-191 peptide will usually arrive as a lyophilized powder in a glass vial. Lyophilization preserves the biological activity of the peptide in a temperature-stable format, allowing shipment and extended shelf-life. 

To prepare frag 176-191 for injection, researchers will need to reconstitute the lyophilized peptide with bacteriostatic water. This will dissolve the powder into a clear liquid that can be drawn up into a syringe.

Prior to reconstitution, ensure that a sufficient amount of bacteriostatic water is available. Note that bacteriostatic water is recommended for reconstitution, as it will protect the peptide against contamination for at least one month due to the presence of 0.9% benzyl alcohol.

Bacteriostatic water, along with other supplies needed for injection of frag 176-191, can be purchased from BacteriostaticWater.org . 

Once bacteriostatic water is on hand, determine the volume needed to dilute the peptide to the desired concentration. Refer to the following protocol on how to complete reconstitution:

• Clean hands and swab the rubber stopper on the frag 176-191 vial, as well as that of the bacteriostatic water vial.
• Insert the needle into the bacteriostatic water vial and draw up the required volume of water.
• Remove the syringe and insert it into the frag 176-191 vial, ensuring that the full volume of bacteriostatic water is dispensed prior to removal.
• Gently rotate the frag 176-191 vial until the lyophilized powder is completely dissolved. 

Once the peptide is reconstituted, keep the vial refrigerated.

Frag 176-191 FAQ 

How to Take Frag 176-191

Frag 176-191 is usually administered in the morning, 30 minutes to 1 hour prior to activity, and ideally on an empty stomach. Doses can also be split into morning and evening doses.

How is Frag 176-191 Delivered?

Frag 176-191 can be delivered via injection or nasal spray, with each format having distinct advantages and disadvantages, as outlined in the above section comparing the two formats.

Is Frag 176-191 Dangerous?

Across six clinical trials, the frag 176-191 derivative AOD9604 was found to be safe and well-tolerated. Notably, AOD9604 has been classified by a panel of experts to be “Generally Recognized as Safe” (GRAS).

Is Frag 176-191 a Steroid?

No, frag 176-191 is a peptide, not a steroid. It has no affinity for the androgen receptor and will not impact endogenous steroid production. 

Does Frag 176-191 Increase Testosterone?

There is no data to suggest that frag 176-191 or its derivatives increase testosterone. Based on the current mechanistic understanding of hgh fragments, frag 176-191 would not be expected to impact testosterone production.  

Does Frag 176-191 Build Muscle?

Neither Frag 176-191 nor its derivative AOD9604 have been shown to build muscle. Unlike hGH itself, these fragments do not increase IGF-1 production, which is the mechanism that drives muscle-building. 

Does Frag 176-191 Cause Weight Gain?

Neither Frag 176-191 nor its derivative AOD9604 have been shown to cause weight gain, and would instead be hypothesized to lead to overall weight loss due to reductions in fat mass. 

Frag 176-191 Peptide Therapy | Review

Human growth hormone fragment 176-191 (frag 176-191) is thought to be the lipolytic fragment of hGH, designed to confer the fat-burning effects of hGH without unwanted effects like tissue growth, hypertension, and impaired glucose regulation. 

The fragment’s potential to yield the fat loss benefits of hGH is incredibly compelling for obesity researchers, who still have a limited pharmacological tool set.

Additionally, frag 176-191 and derivatives like AOD9604 appear to have potential in driving cartilage regeneration similar to hGH, again without the unwanted side effects associated with long-term usage. 

To source research-grade frag 176-191, qualified researchers can trust Peptide Sciences for injectable frag 176-191, and PureRawz for a nasal spray version of the peptide.

References

Wu, Z., & Ng, F. M. (1993). Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochemistry and molecular biology international, 30(1), 187–196.

Natera, S. H., Jiang, W. J., & Ng, F. M. (1994). Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Biochemistry and molecular biology international, 33(5), 1011–1021.

Strobl, J. S., & Thomas, M. J. (1994). Human growth hormone. Pharmacological reviews, 46(1), 1–34.

Vijayakumar, A., Novosyadlyy, R., Wu, Y., Yakar, S., & LeRoith, D. (2010). Biological effects of growth hormone on carbohydrate and lipid metabolism. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 20(1), 1–7. https://doi.org/10.1016/j.ghir.2009.09.002 

Stier, H., Vos, E., & Kenley, D. (2013). Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal Of Endocrinology And Metabolism, 3(1-2), 7-15.

Ng, F., Natera, S., Jiang, W.-J. US Patent No. 5,869,452 (1999).

Heffernan, M., Summers, R. J., Thorburn, A., Ogru, E., Gianello, R., Jiang, W. J., & Ng, F. M. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology, 142(12), 5182–5189. https://doi.org/10.1210/endo.142.12.8522 

Ogru, E., Wilson, J. C., Heffernan, M., Jiang, W. J., Chalmers, D. K., Libinaki, R., & Ng, F. (2000). The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone. The journal of peptide research : official journal of the American Peptide Society, 56(6), 388–397. https://doi.org/10.1034/j.1399-3011.2000.00771.x 

Berneis, K., & Keller, U. (1996). Metabolic actions of growth hormone: direct and indirect. Bailliere's clinical endocrinology and metabolism, 10(3), 337–352. https://doi.org/10.1016/s0950-351x(96)80470-8 

Cara J. F. (1993). Growth hormone in adolescence. Normal and abnormal. Endocrinology and metabolism clinics of North America, 22(3), 533–552. 

Barkan, A. L., Stred, S. E., Reno, K., Markovs, M., Hopwood, N. J., Kelch, R. P., & Beitins, I. Z. (1989). Increased growth hormone pulse frequency in acromegaly. The Journal of clinical endocrinology and metabolism, 69(6), 1225–1233. https://doi.org/10.1210/jcem-69-6-1225 

Sharma, R., Luong, Q., Sharma, V. M., Harberson, M., Harper, B., Colborn, A., Berryman, D. E., Jessen, N., Jørgensen, J. O. L., Kopchick, J. J., Puri, V., & Lee, K. Y. (2018). Growth hormone controls lipolysis by regulation of FSP27 expression. The Journal of endocrinology, 239(3), 289–301. https://doi.org/10.1530/JOE-18-0282 

Ng, F. M., Jiang, W. J., Gianello, R., Pitt, S., & Roupas, P. (2000). Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Journal of molecular endocrinology, 25(3), 287–298. https://doi.org/10.1677/jme.0.0250287 

Reed, M. L., Merriam, G. R., & Kargi, A. Y. (2013). Adult growth hormone deficiency - benefits, side effects, and risks of growth hormone replacement. Frontiers in endocrinology, 4, 64. https://doi.org/10.3389/fendo.2013.00064 

Heffernan, M. A., Thorburn, A. W., Fam, B., Summers, R., Conway-Campbell, B., Waters, M. J., & Ng, F. M. (2001). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 25(10), 1442–1449. https://doi.org/10.1038/sj.ijo.0801740 

Kwon, D. R., & Park, G. Y. (2015). Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of clinical and laboratory science, 45(4), 426–432. 

Ng, F. M., Sun, J., Sharma, L., Libinaka, R., Jiang, W. J., & Gianello, R. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone research, 53(6), 274–278. https://doi.org/10.1159/000053183

Ng, F., Jiang, W.-J. International Patent No. WO 99/12969 (1999).

Valentino, M. A., Lin, J. E., & Waldman, S. A. (2010). Central and peripheral molecular targets for antiobesity pharmacotherapy. Clinical pharmacology and therapeutics, 87(6), 652–662. https://doi.org/10.1038/clpt.2010.57 

The prohibited list [Internet]. World Anti Doping Agency. 2023 [cited 2023Feb8]. Available from: https://www.wada-ama.org/en/prohibited-list?q=ipamorelin 

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Costantino, H. R., Illum, L., Brandt, G., Johnson, P. H., & Quay, S. C. (2007). Intranasal delivery: physicochemical and therapeutic aspects. International journal of pharmaceutics, 337(1-2), 1–24. https://doi.org/10.1016/j.ijpharm.2007.03.025 

Alabsi, W., Eedara, B. B., Encinas-Basurto, D., Polt, R., & Mansour, H. M. (2022). Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols. Pharmaceutics, 14(9), 1870. https://doi.org/10.3390/pharmaceutics14091870 

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