Retrograde regulation by the viral protein kinase epigenetically sustains the EBV latency-to-lytic switch to augment virus production [Virus-Cell Interactions]

Herpesviruses are ubiquitous and infection by some, like Epstein-Barr virus (EBV), is nearly universal. To persist, EBV must periodically switch from a latent to a replicative/lytic phase. This productive phase is responsible for most herpesvirus-associated diseases. EBV encodes a latency-to-lytic switch protein which upon activation sets off a vectorially-constrained cascade of gene expression that results in production of infectious virus. While triggering expression of the switch protein ZEBRA is essential to lytic cycle entry, sustaining its expression is equally important to avoid premature termination of the lytic cascade. We report that the viral protein kinase (vPK), encoded by a gene that is kinetically downstream of the lytic switch, sustains expression of ZEBRA, amplifies the lytic cascade increasing virus production, and importantly, prevents abortive lytic cycle. We find that vPK, through a non-canonical site phosphorylation, activates the cellular PI3-kinase-related kinase ATM to cause phosphorylation of the heterochromatin enforcer KAP1/TRIM28 even in the absence of EBV genomes or other EBV proteins. Phosphorylation of KAP1 renders it unable to restrain ZEBRA, thereby further derepressing and sustaining its expression to culminate in virus production. This partnership with a host kinase and a transcriptional corepressor enables retrograde regulation by vPK of ZEBRA – an observation that is counter to the unidirectional regulation of gene expression reminiscent of most DNA viruses.


Herpesviruses infect nearly all humans and persist quiescently for the life of the host. These viruses intermittently activate into the lytic phase to produce infectious virus, thereby causing disease. To ensure that lytic activation is not prematurely terminated, expression of the virally-encoded lytic switch protein needs to be sustained. In studying Epstein-Barr virus, one of the most prevalent human herpesviruses that also causes cancer, we have discovered that a viral kinase activated by the viral lytic switch protein partners with a cellular kinase to deactivate a silencer of the lytic switch protein, thereby providing a positive feedback loop to ensure successful completion of the viral productive phase. Our findings highlight key nodes of interaction between the host and virus that could be exploited to treat lytic phase-associated diseases by terminating the lytic phase or kill cancer cells harboring herpesviruses by accelerating the completion of the lytic cascade.

US & Japan: Stars Aligned for 3D Printing

Japanese Prime Minister Abe (left) and U.S. President Trump (right) [Source: Flickr]

Charles Goulding and Liam Nixon of R&D Tax Savers look at the relationship between the U.S. and Japan as it relates to 3D printing.

Collaborative Agreement between Trump and Abe

The U.S. and Japan have agreed to work together in the realm of space travel. As recently announced on May 27 during U.S. President Donald Trump’s visit to Japan at a press conference with Japanese Prime Minister Shinzo Abe, the U.S. and Japan have committed to venture beyond Planet Earth with each other’s assistance. Future trips to the Moon and eventually Mars are notable goals that the U.S. and Japan will strive to achieve in conjunction with one another. This agreement obviously has large implications for the space agencies of both nations, the U.S.’ NASA and Japan’s JAXA. Given that both of these agencies have utilized 3D printing technology in their development of space programs, there are now scintillating opportunities for 3D printing collaboration in the area of space travel.

NASA and JAXA 3D Printing Development

Both NASA and JAXA have utilized 3D printing in their respective approaches towards developing spacecrafts and equipment. NASA has utilized 3D printing technology to create and/or implement numerous materials for space travel. These have included a rocket engine combustion chamber, the thermal protection system of its Space Launch System rocket, a sensor platform to monitor astronauts or assist planetary rovers, and a 3D printer with plastic recycling capabilities for use in space. NASA’s website documents these and numerous other 3D printing projects.

JAXA has also taken a liking to the use of 3D printing technology. They have worked on and with various 3D printing projects such as carbon fiber composites, a 3D printed space drone, the ARTSAT 3D printed satellite, and transmission of solar power to eventually create power stations in space.

JAXA's 3D printing drone [Source: JAXA ]

JAXA’s 3D printing drone [Source: JAXA]

Looking towards the Future of NASA and JAXA

The recent announcement of collaboration between NASA and JAXA is a huge event for the 3D printing landscape. These two major space agencies can now begin to share information and technology in the 3D printing sector and partner to develop cutting-edge 3D printing projects to use in space travel. NASA has been unfortunately faced with both the threat of competition from private space exploration companies and decreased financial allocation from the U.S. government. This collaboration with JAXA can definitely accelerate NASA’s technological advancement in the realm of 3D printing. This work can lend itself to qualification for the R&D Tax Credit.



The Research & Development Tax Credit

Enacted in 1981, the now permanent Federal Research and Development (R&D) Tax Credit allows a credit that typically ranges from 4%-7% of eligible spending for new and improved products and processes. Qualified research must meet the following four criteria:

  • Must be technological in nature

  • Must be a component of the taxpayer’s business

  • Must represent R&D in the experimental sense and generally includes all such costs related to the development or improvement of a product or process

  • Must eliminate uncertainty through a process of experimentation that considers one or more alternatives

Eligible costs include U.S. employee wages, cost of supplies consumed in the R&D process, cost of pre-production testing, U.S. contract research expenses, and certain costs associated with developing a patent.

On December 18, 2015, President Obama signed the PATH Act, making the R&D Tax Credit permanent. Since 2016, the R&D credit has been used to offset Alternative Minimum Tax (AMT) for companies with revenue below $50MM and, startup businesses can obtain up to $250,000 per year in payroll tax cash rebates.

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Validity and Reliability of a Wearable Inertial Sensor to Measure Velocity and Power in the Back Squat and Bench Press

Orange, ST, Metcalfe, JW, Liefeith, A, Marshall, P, Madden, LA, Fewster, CR, and Vince, RV. Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press. J Strength Cond Res XX(X): 000–000, 2018—This study examined the validity and reliability of a wearable inertial sensor to measure velocity and power in the free-weight back squat and bench press. Twenty-nine youth rugby league players (18 ± 1 years) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. Repetitions were performed at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM) with mean velocity, peak velocity, mean power (MP), and peak power (PP) simultaneously measured using an inertial sensor (PUSH) and a linear position transducer (GymAware PowerTool). The PUSH demonstrated good validity (Pearson’s product-moment correlation coefficient [r]) and reliability (intraclass correlation coefficient [ICC]) only for measurements of MP (r = 0.91; ICC = 0.83) and PP (r = 0.90; ICC = 0.80) at 20% of 1RM in the back squat. However, it may be more appropriate for athletes to jump off the ground with this load to optimize power output. Further research should therefore evaluate the usability of inertial sensors in the jump squat exercise. In the bench press, good validity and reliability were evident only for the measurement of MP at 40% of 1RM (r = 0.89; ICC = 0.83). The PUSH was unable to provide a valid and reliable estimate of any other criterion variable in either exercise. Practitioners must be cognizant of the measurement error when using inertial sensor technology to quantify velocity and power during resistance training, particularly with loads other than 20% of 1RM in the back squat and 40% of 1RM in the bench press.
Address correspondence to Samuel T. Orange,
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (
Copyright © 2019 by the National Strength & Conditioning Association.

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Initial Impressions: HP 3D Printing And Digital Manufacturing Center Of Excellence

Christoph Schell and Ramon Pastor cut the ribbon [Image: Fabbaloo]

The new HP 3D Printing and Digital Manufacturing Center of Excellence is, well, excellent.

This week, I was in Barcelona for the opening of the new Center. It’s impressive.

HP says it’s the largest 3D printing R&D center in the world; that may well be the case. At 152,000 square feet, it’s certainly among the largest, at least. An undisclosed number of engineers (“hundreds”) are based here, in Building 10 of HP’s Barcelona campus — where the company’s 3D printing business has its deepest roots. The Center is, of course, not just for them: it’s a collaborative center, meant for close work with partners and customers.

And so the opening festivities weren’t HP’s alone; executives from Siemens, Materialise, ZiggZagg, Avid Product Development, GKN Powder Metallurgy, and Volkswagen Group were on-site to share their experiences in working with Multi Jet Fusion and Metal Jet 3D printing technologies. Several other customers, partners, and potentially deepening relationships were also at the Center this week; we’ll likely hear more about just who they are and what will come of these relationships closer to formnext season. If at least one of my suspicions is correct about a partnership to come, there will be a good deal more to hear by then.

Labs at the Center are dedicated to MJF and Metal Jet, with various activities centered within each individual lab space. Walkthroughs of these labs afforded my first opportunities to watch the new Jet Fusion 5200 Series and the yet-to-be released Metal Jet systems in action.

We also saw an applications showcase, highlighting real-world use cases in automotive and transportation; medical; consumer goods; industrial; and inside-HP 3D printing. Among the products were familiar uses, like Wiivv’s partially 3D printed personalized flip flops (I have to confess I love my pair), and newer ones, like HP’s recently announced partnership with Smile Direct Club to 3D print molds for thermoformed dental aligners at volume.

A full MJF tray of Smile Direct Club molds [Image: Fabbaloo]

A full MJF tray of Smile Direct Club molds [Image: Fabbaloo]

The Center itself also houses significant workspace, and is very open concept. Conference rooms (all named for accomplished scientists who all happen to be women) dot the floor plan, and comfortable booths, tables, and sitting areas provide ample spaces to join colleagues and visitors in conversation. For a facility so focused on collaboration, the plans make a great deal of sense.

[Image: Fabbaloo]

[Image: Fabbaloo]

The building itself is also a testament to the future of architecture. Not in the 3D printed building sense (it’s not), but in a sustainable, customizable way. Formats can be maneuvered to best fit collaborative conversations, and a major focus on environmental friendliness is obvious. This was further underscored by both the obvious (a large photovoltaic roof over an outdoor patio area) and the stated (as Director of Product Stewardship John Ortiz noted an overarching focus on sustainability and the circular economy).

Photovoltaic roof soaking up the Barcelona sunshine [Image: Fabbaloo]

Photovoltaic roof soaking up the Barcelona sunshine [Image: Fabbaloo]

HP hosted a full program spread over a day and a half of meetings, and I also appreciated the chance to sit down for an interview with President of HP 3D Printing and Digital Manufacturing Christoph Schell as well as more casual chats with many of the execs and engineers from HP and its partners.

There’s much more to come so far as details and insights go — but for a first impression, it’s very clear: HP is in this game not just to play, and not (just) to win, but to captain.

Via HP 3D Printing and Digital Manufacturing

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The effect of ibuprofen on muscle, hematological and renal function, hydric balance, pain, and performance during intense long-distance running

Copyright © 2019.
The purpose of this study was to research the effect of prophylactic use of antipsychotic anti inflammatory medication (NSAID, i.e. Ibuprofen) on physical operation, vertical jump, muscle biomarkers, liver, kidney, intense pain along with hydration status of participants in the 42 km Course Running Challenge, a long-distance race incorporated over mountain paths. The sample consisted of 20 men randomly divided in to two classes: a control group (CG) and an experimental group (EG) using 12 completing the race (41.1±8.8 y; 75.7±12.1 kilogram ) and within the last analysis. Even the EG were administered with an ibuprofen capsule (400 milligrams ) fifteen minutes ahead of the start of the race, and again after 5 hours of rushing if the road was not yet complete. There were significant time main effects for creatine kinase (CK) (p=0.001; f2 Cohen=0.25), lactate dehydrogenase (LDH) (p<0.001; f-2 Cohen=2.05), aspartate aminotransferase (AST) (p=0.002; f 2 Cohen=1.53), creatinine (p=0.002; f-2 Cohen=2.24), urea (p=0.001; f-2 Cohen=2.25), heart rate (HR) (p<0.001; f 2 Cohen=4.88) and pain scores (p<0.001; f2 Cohen=1.93) which increased throughout the race. There has been a group × period discussion for squat jump (SJ) which somewhat decreased in only the CG (p= 0.045; f 2 Cohen=2.17). This might have been linked to greater frequency of pain mentioned following the race at the gastrocnemius of the C G in comparison with the EG (p<0.05). It was concluded that ibuprofen intake didn't reduce muscle damage during the contest however maintained leg muscular power performance (i.e. vertical jump), maybe by lowering gastrocnemius muscle pain.
Raphael Fabrício p Souza Cidade Universitária Prof. José Aloísio de Campos Av. Marechal Rondon, s/n Jardim Rosa Elze CEP 49100-000 São Cristóvão/SE -LRB-79-RRB- 2105-6600, -LRB-79-RRB- 2105-6537

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Comprehensive characterization of the HERV-K(HML-6): overview of their structure, phylogeny and contribution to the human genome [Genetic Diversity and Evolution]

The 8% human genome is composed of Human Endogenous Retroviruses (HERVs), remnants of ancestral germline infections by exogenous retroviruses, which have been vertically transmitted as Mendelian characters. The HML-6 group, a member of the class II Betaretrovirus-like, includes several proviral loci with an increased transcriptional activity in cancer, and at least two elements that are known for retaining an intact open reading frame (ORF) and for encoding small proteins such as ERVK3-1, that is expressed in various healthy tissues, and HERV-K-MEL, a small Env peptide expressed in samples of cutaneous and ocular melanoma, but not in normal tissues.

Importance: We reported the distribution and genetic composition of 66 HML-6 elements. We analyzed the phylogeny of the HML-6 sequences and identified two main clusters. We provided the first description of a Rec domain within the env sequence of 23 HML-6 elements. A Rec domain was also predicted within the ERVK3-1 transcript sequence, revealing its expression in various healthy tissues. Evidence about the context of insertion and co-localization of 19 HML-6 elements with functional human genes are also reported, including the sequence 16p11.2, whose 5’LTR overlapped the exon of one transcript variant of a cellular Zinc-finger up-regulated and involved in hepatocellular carcinoma. The present work provides the first complete overview of the HML-6 elements in GRCh37(hg19), describing the structure, phylogeny and genomic context of insertion of each locus. This information allows a better understanding of the genetics of one of the most expressed HERV groups in the human genome.

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Assessment of loaded squat jump height with a free-weight barbell and Smith machine: comparison of the take-off velocity and flight time procedures

The aims of this study were to compare the reliability and magnitude of jump height between the two standard procedures of analysing force platform data to estimate jump height (take-off velocity [TOV] and flight time [FT]) in the loaded squat jump (SJ) exercise performed with a free-weight barbell and in a Smith machine. Twenty-three collegiate men (age 23.1 ± 3.2 years, body mass 74.7 ± 7.3 kg, height 177.1 ± 7.0 cm) were tested twice for each SJ type (free-weight barbell and Smith machine) with 17, 30, 45, 60, and 75 kg loads. No substantial differences in reliability were observed between the TOV (Coefficient of variation [CV]: 9.88%; Intraclass correlation coefficient [ICC]: 0.82) and FT (CV: 8.68%; ICC: 0.88) procedures (CV ratio: 1.14), while the Smith SJ (CV: 7.74%; ICC: 0.87) revealed a higher reliability than the free-weight SJ (CV: 9.88%; ICC: 0.81) (CV ratio: 1.28). The TOV procedure provided higher magnitudes of jump height than the FT procedure for the loaded Smith machine SJ (systematic bias: 2.64 cm; P0.05). Heteroscedasticity of the errors was observed for the Smith machine SJ (r2: 0.177) with increasing differences in favour of the TOV procedure for the trials with lower jump height (i.e. higher external loads). Based on these results the use of a Smith machine in conjunction with the FT more accurately determine jump height during the loaded SJ.
Corresponding author: Amador García-Ramos, Faculty of Sport Sciences, University of Granada, Ctra. Alfacar, s/n, 18011, Granada (Spain), Phone: (+34) 677815348, Fax: (+34) 958244369, E-mail:
Copyright © 2019 by the National Strength & Conditioning Association.

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Zika virus production is resistant to RNase L antiviral activity [Virus-Cell Interactions]

There is currently no knowledge of how the emerging human pathogen Zika virus (ZIKV) interacts with the antiviral endoribonuclease L (RNase L) pathway during infection. Since activation of RNase L during infection typically limits virus production dramatically, we used CRISPR-Cas9 gene editing technology to knockout (KO) targeted host genes involved in the RNase L pathway to evaluate the effects of RNase L on ZIKV infection in human A549 cells. RNase L was activated in response to ZIKV infection, which degraded ZIKV genomic RNA. Surprisingly, despite viral genome reduction, RNase L activity did not reduce ZIKV infectious titers. In contrast, both the flavivirus dengue virus as well as the alphavirus Sindbis virus replicated to significantly higher titers in RNase L KO cells compared to wild-type (WT) cells. Using MAVS/RNase L double KO cells, we demonstrated that the absence of increased ZIKV production in RNase L KO cells was not due to compensation by enhanced type I IFN transcripts to thus inhibit virus production. Finally, when synthetic dsRNA was used to activate OAS3 and induce RNase L antiviral activity prior to ZIKV infection, we observed reduced ZIKV replication factory (RF) formation as well as a 42-fold reduction in virus yield in WT but not RNase L KO cells. This study proposes that ZIKV evades RNase L antiviral activity by generating a viral genome reservoir protected from RNase L cleavage during early infection, allowing for sufficient virus production before RNase L activation is detectable.


With the onset of the 2015 ZIKV outbreak, ZIKV pathogenesis has been of extreme global public health interest, and a better understanding of interactions with the host would provide insight into molecular mechanisms driving the severe neurological outcomes of ZIKV disease. Herein is the initial report on the relationship between ZIKV and the host oligoadenylate synthetase-RNase L (OAS-RNase L) system, a potent antiviral pathway effective at restricting replication of diverse viruses. Our study elucidated a unique mechanism whereby ZIKV production is impervious to antiviral RNase L activity, through a mechanism of viral RNA protection that is not mimicked during infection with numerous other RNase L-activating viruses, thus identifying a distinct replication strategy potentially important for ZIKV pathogenesis.

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Artec Releases Powerful New 3D Scanning Software

Artec Studio 14 includes powerful 3D scanning features [Source: Artec]

Artec released Artec Studio 14, their latest and most powerful version of their 3D scanning management software.

Artec offers a line of multiple types of 3D scanning instruments; some are handheld, others tripod-mounted, and one is even fully portable with onboard processing. They’ve also experimented with an automation system for 3D scanning by using a robotic setup. Their product line seems to cover a huge scope of 3D scanning possibilities, ranging from the ability to capture high-resolution scans of tiny objects, all the way to 3D scans of entire rooms and large buildings.

All of these devices are controlled through the Artec Studio software, which can also process the received scan data and produce useful 3D models. Of course, these scans can be used for reverse engineering or direct 3D printing in some cases.

The latest release, Artec Studio 14, includes a few very interesting features that we haven’t seen in other scanning tools.

Artec has improved their large-scale 3D scanning solution by automating some of the manual work required in setting up their tripod-mounted Ray system. Instead of requiring stationing targets in the scene to assist in calibrating the 3D scene, the software now can take on some or all of this work itself. This should greatly speed up the effort required to capture large scenes, and in some cases enable capture of scenes not previously possible.

If you’re not familiar with the concept of targets in 3D scanning, they are still used with some processes. The idea is to create known fixed locations that can provide the software with a quick way to rapidly interpret the orientation of the received data. However, it requires manual effort to place the targets. This is a case of software ingenuity vs. manual labor, but it seems that Artec Studio 14 turns that equation upside down.

Artec Studio 14 identifies curves in 3D scanned geometry [Source: Artec]

Artec Studio 14 identifies curves in 3D scanned geometry [Source: Artec]

Reduce Glare In 3D Scans

One new feature focuses specifically on reverse engineering. Artec Studio 14 is able to identify some geometry in captured scans, and can also export these curves in CSV and DXF file format. These files can be directly imported into several CAD tools, including SOLIDWORKS or similar, and can greatly assist in reverse engineering work. Without these curves, they would have to be manually identified by the CAD operator, a tedious task indeed.

So tedious is that work that those performing reverse engineering often resort to intermediate systems that perform much of this scan interpretation before launching the CAD tool. The big idea here is that, in theory, you could eliminate the need for the intermediate system entirely and jump directly from Artec Studio 14 to CAD. Of course, the curves won’t nearly be as comprehensive an analysis as can be done by dedicated intermediate systems, but for many applications it might just be sufficient.

Artec Studio 14 can automatically fix glare spots in 3D scans [Source: Artec]

Artec Studio 14 can automatically fix glare spots in 3D scans [Source: Artec]

Another very intriguing feature is the glare removal function. Glare is often encountered during a 3D scan, as lighting may bounce off of reflective surfaces. These pollute the scan, mainly by messing with the surface texture, which can have an overblown glare spot. The new Artec Studio 14 can automatically eliminate these. They explain:

“With Studio 14, users can adjust the level of glare removal with a few clicks and watch as the vibrant color of an object is restored, saving hours of work for applications such as 3D printing or CGI. To further ensure a model represents true color, a new Dynamic Auto Brightness feature will automatically tailor the brightness to optimal levels during both the scan preview and the duration of the scanning process. The visual differentiation algorithms can set the correct levels of brightness for both dark and light objects – no matter the lighting conditions.”

Join Two 3D Scans

Artec Studio 14 can join two 3D scans together very easily [Source: Artec]

Artec Studio 14 can join two 3D scans together very easily [Source: Artec]

Sequence animation looks to be a powerful feature to allow two different scans of the same object to be properly joined together. This is an incredibly powerful feature that could make scanning workflows much easier.

It seems Artec Studio 14 just made all of Artec’s line of 3D scanners a lot more powerful, thus proving the critical importance of software for 3D scanning. The best solutions involve both good hardware and good software.

Via Artec

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Kaposi Sarcoma-associated Herpesvirus Glycoprotein H is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell Types [Virus-Cell Interactions]

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in vivo in diverse human cell types. The role of glycoprotein H (gH) in herpesvirus entry mechanisms remains largely unresolved. To characterize the requirement for KSHV gH in the viral life cycle and in determination of cell tropism, we generated and characterized a mutant KSHV in which expression of gH was abrogated. Using a bacterial artificial chromosome containing a complete recombinant KSHV genome and recombinant DNA technology, we inserted stop codons into the gH coding region. We used electron microscopy to reveal that the gH-null mutant virus assembled and exited from cells normally, compared to wild-type virus. Using purified virions, we assessed infectivity of the gH-null mutant in diverse mammalian cell types in vitro. Unlike wild-type virus or a gH-containing revertant, the gH-null mutant was unable to infect any of the epithelial, endothelial, or fibroblast cell types tested. However, its ability to infect B cells was equivocal, and remains to be investigated in vivo due to generally poor infectivity in vitro. Together, these results suggest that gH is critical for KSHV infection of highly permissive cell types including epithelial, endothelial, and fibroblasts.


All homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH was indispensable for KSHV infection of epithelial, endothelial, and fibroblast cells in vitro. This suggests that gH is an important target for the development of a KSHV prophylactic vaccine to prevent initial viral infection.

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