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Unmet needs in the treatment of chronic otitis media and Eustachian tube dysfunction (ETD) triggered the development of stents for the Eustachian tube (ET). In this study, for the first time, stents were placed in an artificially blocked ET to evaluate stent function. Eight adult female sheep were injected with stabilized hyaluronic acid (HA) on both sides to induce ETD. Subsequently, a tapered nitinol ET stent was inserted on one side, and animals were examined bilaterally by endoscopy, tympanometry, cone beam computed tomography, and final histology. Seven of the stents were placed in the desired cartilaginous portion of the ET. At the end of the study, one stented side appeared slightly open; all other ET orifices were closed. Tympanometry revealed re-ventilation of the middle ear in four out of seven correctly stented animals within 3 to 6 weeks after stent insertion. The major amount of HA was found at the pharyngeal orifice of the ET anterior to the stent. Thus, the stent position did not completely align with the HA position. While a functional analysis will require refinement of the experimental setup, this study provides first promising results for stent insertion in a sheep model of ETD.

The Eustachian tube (ET) is a bottleneck when it comes to middle ear (ME) health. If its function is impaired, this can lead to serious consequences for the patient, such as hearing problems or deafness. Therefore, this study investigated a tapered nitinol stent (3–5 mm × 14 mm) for the human ET as a potential new permanent treatment for chronic Eustachian tube dysfunction (ETD) and thus ME ventilation disorders. The self-expanding stent was inserted unilaterally into the ET of 24 sheep with observation periods of 3, 6, and 12 months. Local tissue effects and the safety of the stent insertion were analyzed based on regular endoscopic checks, weekly tympanometry measurements, final imaging, and histological examinations. The animals showed no stent-related health restrictions. However, the individual anatomy and stenting procedure had an influence on the results. The tissue reaction in the endoscopic examinations was mild even though no concomitant antibiotics were administered. After all three monitoring periods, stented ETs had a significantly larger ET lumen than the non-stented contralateral ETs. However, tissue growth was detected in the stent. Overall, the first long-term study on an ET stent showed that the tapered ET stent could be a promising treatment option for ETD.

Chronic otitis media is often connected to Eustachian tube dysfunction. As successful treatment cannot be guaranteed with the currently available options, the aim is to develop a stent for the Eustachian tube (ET). Over the course of this development, different prototypes were generated and tested in ex vivo experiments. Four different prototypes of an ET stent and one commercially available coronary stent were implanted in the ET of seven human donor bodies. The position of the stents was verified by cone beam CT. The implanted ETs were harvested, embedded in resin and ground at 200 µm steps. Resulting images of the single steps were used to generate 3D models. The 3D models were then evaluated regarding position of the stent in the ET, its diameters, amount of squeezing, orientation of the axes and other parameters. Virtual reconstruction of the implanted ET was successful in all cases and revealed one incorrect stent placement. The cross-section increased for all metal stents in direction from the isthmus towards the pharyngeal orifice of the ET. Depending on the individual design of the metal stents (open or closed design), the shape varied also between different positions along a single stent. In contrast, the cross-section area and shape remained constant along the polymeric prototype. With the current investigation, insight into the behavior of different prototypes of ET stents was gained, which can help in defining the specifications for the intended ET stent.

Otitis media is often connected to Eustachian tube dysfunction (ETD). Until now, there was no large animal model available for the examination of new treatment methods such as stents for the Eustachian tube (ET). Thus, the aim of the study was to develop a method to reproducibly induce ETD by injection of fillers and without permanent closure of the ET. Tools for safe injection of hyaluronic acid (HA) in the surrounding of the ET were developed. In ex vivo experiments, HA mixed with Imeron® was injected close to the nasopharyngeal orifice of the ET of blackface sheep. The established depot was visualized using cone beam computer tomography and magnetic resonance imaging, and stents could be placed into the ET. A reliable position of the HA depot was achieved. This method was transferred to in vivo, and middle ear ventilation was investigated by tympanometry. ETD was achieved with amounts of 2.5 mL HA or higher. None of the animals showed any sign of discomfort or complications. The induced ETD lasted for 3 to 13 (maximum observation period) weeks and was also combined with middle ear effusion. A model of ETD based on injection of HA next to the ET was successfully established and is now available to test novel treatment options for ET functionality.

Trace gas analysis is a key tool for the investigation of man-made environmental pollution as well as for early detection of respiratory diseases. To detect tiny concentrations, sensitive methods such as cavity ring down spectroscopy or plasmonic sensors have been used. Here, we demonstrate the combination of the photoacoustic effect in a classical cell with a novel, rapidly tunable, narrowband fiber-feedback optical parametric oscillator. The high sensitivity of photoacoustic cells and the extremely narrow linewidth as well as the wide and rapid tunability of the fiber-feedback optical parametric oscillator enable a high resolution of the rotational and vibrational bands of molecules in the near-infrared region. Photoacoustic spectra of methane, carbon dioxide, and water at ambient pressure are obtained in a broad spectral range and compared to high-resolution transmission molecular absorption database. In particular, scanning the entire carbon dioxide overtone around 4965 cm−1 at 2000 ppm takes 185 s with a signal-to-noise ratio of 31. This approach enables a wide tunability in the entire near- and mid-infrared spectral region suitable for many environmental and medical applications.

The evaluation of the analytical capabilities of a novel disposable flow cell for spectroscopic bioprocess monitoring is presented. The flow cell is presterilized and can be connected to any kind of bioreactor by weldable tube connections. It is clamped into a reusable holder, which is equipped with SMA-terminated optical fibers or an integrated light source and detection unit. This modular construction enables spectroscopic techniques like UV-Vis spectroscopy or turbidity measurements by scattered light for modern disposable bioreactors. A NIR scattering module was used for biomass monitoring in different cultivations. A high-cell-density fed-batch cultivation with Komagataella phaffii and a continuous perfusion cultivation with a CHO DG44 cell line were conducted. A high correlation between the sensor signal and biomass or viable cell count was observed. Furthermore, the sensor shows high sensitivity during low turbidity states, as well as a high dynamic range to monitor high turbidity values without saturation effects. In addition to upstream processing, the sensor system was used to monitor the purification process of a monoclonal antibody. The absorption module enables simple and cost-efficient monitoring of downstream processing and quality control measurements. Recorded absorption spectra can be used for antibody aggregate detection, due to an increase in overall optical density.

ABSTRACT: Extensive mechanistic evidence to support the beneficial function of dietary phytobiotic applications for broiler performance, gut function and health is highly warranted. In particular, for isoquinoline alkaloids (IQ) the underlying mechanisms related to critical gut homeostasis components such as cytoprotection and gut barrier are scarce, especially for young broilers at the starter growth stage (d1–10). The aim of this study was to investigate the effect of a standardized blend of IQs on the relative gene expression of critical biomarkers relevant for antioxidant response and barrier function along the intestine of young broilers at the end of starter growth phase. For this purpose, 182 one-day-old Ross 308 broilers were allocated in 2 treatments with 7 replicates of 13 broilers each: control diet-no other additions (NC), and control diet containing a standardized blend of IQs at 200 mg/kg of diet (M) for the starter growth period (1–10d). The results revealed that the IQs blend significantly upregulated (P < 0.05) the expression of genes related to antioxidant response in all intestinal segments. Moreover, the IQs blend enhanced (P < 0.05) gut barrier components primarily at duodenal level. In conclusion, the blend of IQs beneficially affected critical pathway components relevant for the gut antioxidant capacity and barrier along the intestine of young broilers.

The field of oceanography is transitioning from data-poor to data-rich, thanks in part to increased deployment of in-situ platforms and sensors, such as those that instrument the US-funded Ocean Observatories Initiative (OOI). However, generating science-ready data products from these sensors, particularly those making biogeochemical measurements, often requires extensive end-user calibration and validation procedures, which can present a significant barrier. Openly available community-developed and -vetted Best Practices contribute to overcoming such barriers, but collaboratively developing user-friendly Best Practices can be challenging. Here we describe the process undertaken by the NSF-funded OOI Biogeochemical Sensor Data Working Group to develop Best Practices for creating science-ready biogeochemical data products from OOI data, culminating in the publication of the GOOS-endorsed OOI Biogeochemical Sensor Data Best Practices and User Guide. For Best Practices related to ocean observatories, engaging observatory staff is crucial, but having a “user-defined” process ensures the final product addresses user needs. Our process prioritized bringing together a diverse team and creating an inclusive environment where all participants could effectively contribute. Incorporating the perspectives of a wide range of experts and prospective end users through an iterative review process that included “Beta Testers’’ enabled us to produce a final product that combines technical information with a user-friendly structure that illustrates data analysis pipelines via flowcharts and worked examples accompanied by pseudo-code. Our process and its impact on improving the accessibility and utility of the end product provides a roadmap for other groups undertaking similar community-driven activities to develop and disseminate new Ocean Best Practices.

Abstract A neuron’s regenerative capacity is governed by its intrinsic and extrinsic environment. Both peripheral and central neurons exhibit cell-type-dependent axon regeneration, but the underlying mechanism is unclear. Glia provide a milieu essential for regeneration. However, the routes of glia-neuron signaling remain underexplored. Here, we show that regeneration specificity is determined by the axotomy-induced Ca2+ transients only in the fly regenerative neurons, which is mediated by L-type calcium channels, constituting the core intrinsic machinery. Peripheral glia regulate axon regeneration via a three-layered and balanced modulation. Glia-derived tumor necrosis factor acts through its neuronal receptor to maintain calcium channel expression after injury. Glia sustain calcium channel opening by enhancing membrane hyperpolarization via the inwardly-rectifying potassium channel (Irk1). Glia also release adenosine which signals through neuronal adenosine receptor (AdoR) to activate HCN channels (Ih) and dampen Ca2+ transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair.

Der vorliegende Beitrag beleuchtet den Ansatz des scholar-led publishing und zeigt auf, welche Zusammenhänge zwischen scholar-led Initiativen und der 'klassischen' Open Access-Bewegung bestehen. Nach einer kurzen Diskurseinordnung leitet der Beitrag diachron ab, wie scholar-led Initiativen aus den Geistes- und Sozialwissenschaften schon früh und parallel zu den weithin rezipierten Entwicklungen aus dem medizinisch-naturwissenschaftlichen Bereich der 1990er Jahre auf eigene Weise wichtige Impulse zur Öffnung von Publikationskulturen setzten. Dazu werden exemplarisch eine Vielzahl von medien- und kulturwissenschaftlichen scholar-led Journals, Buchverlagen sowie weiterreichenden Netzwerk- und Infrastruktur-Initiativen entlang der größeren Entwicklungen der letzten vier Jahrzehnte hin zur Digitalisierung von wissenschaftlichen Publikationspraktiken und dem sich daraus ergebenden Potential eines alternativen Publikationssystems, welches gemeinschaftliche Kollaboration unter den Vorzeichen von Gemeinnützigkeit über kommerzorientierten Wettbewerb stellt.

In this paper we propose a new method for symmetry calculation in wearable devices. The problem in this domain is that only discrete features such as stride length, stride duration, or duration of gait phases are used for the symmetry calculation. However, this can lead to failures, since the use of features can result in partial loss of information from the time series. From this we present a possibility to calculate the symmetry by using Dynamic Time Warping (DTW). DTW uses the complete time series for the analysis and is therefore independent of certain features.

IntroductionThe video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.Purpose (Aim)To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.MethodsWe enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.ResultsPooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.ConclusionOur study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes.

Bradyzoites are a quiescent form of Toxoplasma gondii enclosed in cysts during chronic infections. Here, Christiansen et al. develop a human myotube-based in vitro culture model of cysts that are infectious to mice and characterize their metabolism in comparison to fast replicating tachyzoites.

Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B.

Diffraction imaging offers high spatiotemporal resolution, but fitting complex molecular structure data is expensive. Here, the authors use a machine learning algorithm with a convolutional neural network to retrieve a complex and large molecule, fenchone (C10H16O), from laser-induced electron diffraction data without the need for fitting or ab initio calculations.

Toxoplasma gondii virulence in wild-derived mice is restricted by Immunity-Related GTPases (IRG). Here, the authors show specific binding of the IRG tandem protein Irgb2-b1 with the virulence effector ROP5, and provide insights into how different ROP5 isoforms and IRG alleles shape virulence among T. gondii strains.

Over recent decades, observations based on merchant vessels (Ships of Opportunity—SOOP) equipped with sensors measuring the CO2 partial pressure (pCO2) in the surface seawater formed the backbone of the global ocean carbon observation system. However, the restriction to pCO2 measurements alone is one severe shortcoming of the current SOOP observatory. Full insight into the marine inorganic carbon system requires the measurement of at least two of the four measurable variables which are pCO2, total alkalinity (TA), dissolved inorganic carbon (DIC), and pH. One workaround is to estimate TA values based on established temperature-salinity parameterizations, but this leads to higher uncertainties and the possibility of regional and/or seasonal biases. Therefore, autonomous SOOP-based TA measurements are of great interest. Our study describes the implementation of a novel autonomous analyzer for seawater TA, the CONTROS HydroFIAⓇ TA system (-4H-JENA engineering GmbH, Germany) for unattended routine TA measurements on a SOOP line operating in the North Atlantic. We present the installation in detail and address major issues encountered with autonomous measurements using this analyzer, e.g., automated cleaning and stabilization routines, and waste handling. Another issue during long-term deployments is the provision of reference seawater in large-volume containers for quality assurance measurements and drift correction. Hence, a stable large-volume seawater storage had to be found. We tested several container types with respect to their suitability to store seawater over a time period of 30 days without significant changes in TA. Only one gas sampling bag made of polyvinylidene fluoride (PVDF) satisfied the high stability requirement. In order to prove the performance of the entire setup, we compared the autonomous TA measurements with TA from discrete samples taken during the first two trans-Atlantic crossings. Although the measurement accuracy in unattended mode (about ± 5 μmol kg^-1) slightly deteriorated compared to our previous system characterization, its overall uncertainty fulfilled requirements for autonomous TA measurements on SOOP lines. A comparison with predicted TA values based on an established and often used parameterization pointed at regional and seasonal limitations of such TA predictions. Consequently, TA observations with better coverage of spatiotemporal variability are needed, which is now possible with the method described here.

An enormous wealth of digital tools now exists for collaborating on scholarly research projects. In particular, it is now possible to collaboratively author research articles in an openly participatory and dynamic format. Here we describe and provide recommendations for a more open process of digital collaboration, and discuss the potential issues and pitfalls that come with managing large and diverse authoring communities. We summarize our personal experiences in a form of ‘ten simple recommendations’. Typically, these collaborative, online projects lead to the production of what we here introduce as Massively Open Online Papers (MOOPs). We consider a MOOP to be distinct from a ‘traditional’ collaborative article in that it is defined by an openly participatory process, not bound within the constraints of a predefined contributors list. This is a method of organised creativity designed for the efficient generation and capture of ideas in order to produce new knowledge. Given the diversity of potential authors and projects that can be brought into this process, we do not expect that these tips will address every possible project. Rather, these tips are based on our own experiences and will be useful when different groups and communities can uptake different elements into their own workflows. We believe that creating inclusive, interdisciplinary, and dynamic environments is ultimately good for science, providing a way to exchange knowledge and ideas as a community. We hope that these Recommendations will prove useful for others who might wish to explore this space.

The European Research Infrastructure Consortium “Integrated Carbon Observation System” (ICOS) aims at delivering high quality greenhouse gas (GHG) observations and derived data products (e.g., regional GHG-flux maps) for constraining the GHG balance on a European level, on a sustained long-term basis. The marine domain (ICOS-Oceans) currently consists of 11 Ship of Opportunity lines (SOOP – Ship of Opportunity Program) and 10 Fixed Ocean Stations (FOSs) spread across European waters, including the North Atlantic and Arctic Oceans and the Barents, North, Baltic, and Mediterranean Seas. The stations operate in a harmonized and standardized way based on community-proven protocols and methods for ocean GHG observations, improving operational conformity as well as quality control and assurance of the data. This enables the network to focus on long term research into the marine carbon cycle and the anthropogenic carbon sink, while preparing the network to include other GHG fluxes. ICOS data are processed on a near real-time basis and will be published on the ICOS Carbon Portal (CP), allowing monthly estimates of CO2 air-sea exchange to be quantified for European waters. ICOS establishes transparent operational data management routines following the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principles allowing amongst others reproducibility, interoperability, and traceability. The ICOS-Oceans network is actively integrating with the atmospheric (e.g., improved atmospheric measurements onboard SOOP lines) and ecosystem (e.g., oceanic direct gas flux measurements) domains of ICOS, and utilizes techniques developed by the ICOS Central Facilities and the CP. There is a strong interaction with the international ocean carbon cycle community to enhance interoperability and harmonize data flow. The future vision of ICOS-Oceans includes ship-based ocean survey sections to obtain a three-dimensional understanding of marine carbon cycle processes and optimize the existing network design.

The Surface Ocean CO2 NETwork (SOCONET) and atmospheric Marine Boundary Layer (MBL) CO2 measurements from ships and buoys focus on the operational aspects of measurements of CO2 in both the ocean surface and atmospheric MBLs. The goal is to provide accurate pCO2 data to within 2 micro atmosphere (μatm) for surface ocean and 0.2 parts per million (ppm) for MBL measurements following rigorous best practices, calibration and intercomparison procedures. Platforms and data will be tracked in near real-time and final quality-controlled data will be provided to the community within a year. The network, involving partners worldwide, will aid in production of important products such as maps of monthly resolved surface ocean CO2 and air-sea CO2 flux measurements. These products and other derivatives using surface ocean and MBL CO2 data, such as surface ocean pH maps and MBL CO2 maps, will be of high value for policy assessments and socio-economic decisions regarding the role of the ocean in sequestering anthropogenic CO2 and how this uptake is impacting ocean health by ocean acidification. SOCONET has an open ocean emphasis but will work with regional (coastal) networks. It will liaise with intergovernmental science organizations such as Global Atmosphere Watch (GAW), and the joint committee for and ocean and marine meteorology (JCOMM). Here we describe the details of this emerging network and its proposed operations and practices.

Evaluation of renal dysfunction includes estimation of glomerular filtration rate (eGFR) as the initial step and subsequent laboratory testing. We hypothesized that combined analysis of serum creatinine, myo-inositol, dimethyl sulfone, and valine would allow both assessment of renal dysfunction and precise GFR estimation. Bio-banked sera were analyzed using nuclear magnetic resonance spectroscopy (NMR). The metabolites were combined into a metabolite constellation (GFRNMR) using n = 95 training samples and tested in n = 189 independent samples. Tracer-measured GFR (mGFR) served as a reference. GFRNMR was compared to eGFR based on serum creatinine (eGFRCrea and eGFREKFC), cystatin C (eGFRCys-C), and their combination (eGFRCrea-Cys-C) when available. The renal biomarkers provided insights into individual renal and metabolic dysfunction profiles in selected mGFR-matched patients with otherwise homogenous clinical etiology. GFRNMR correlated better with mGFR (Pearson correlation coefficient r = 0.84 vs. 0.79 and 0.80). Overall percentages of eGFR values within 30% of mGFR for GFRNMR matched or exceeded those for eGFRCrea and eGFREKFC (81% vs. 64% and 74%), eGFRCys-C (81% vs. 72%), and eGFRCrea-Cys-C (81% vs. 81%). GFRNMR was independent of patients’ age and sex. The metabolite-based NMR approach combined metabolic characterization of renal dysfunction with precise GFR estimation in pediatric and adult patients in a single analytical step.

Identical glass spheres of 434 ± 17 μ m diameter are charged in collisions among each other. At slow speed some form dimers under microgravity and oscillate within the electrical field of a capacitor. The dipole moments deduced from these oscillations are large. They cannot be explained by the net charges measured for each grain (up to ±3 × 10 ^5 e ) and show no significant dependence on the net charge in the given range. This requires a highly non-homogeneous charge distribution on the grain surface. We simulate heterogeneous charging with a Q-patch charging model in agreement to the experimental data.

This work presents two new methods to estimate oceanic alkalinity (AT), dissolved inorganic carbon (CT), pH, and pCO2 from temperature, salinity, oxygen, and geolocation data. “CANYON-B” is a Bayesian neural network mapping that accurately reproduces GLODAPv2 bottle data and the biogeochemical relations contained therein. “CONTENT” combines and refines the four carbonate system variables to be consistent with carbonate chemistry. Both methods come with a robust uncertainty estimate that incorporates information from the local conditions. They are validated against independent GO-SHIP bottle and sensor data, and compare favorably to other state-of-the-art mapping methods. As “dynamic climatologies” they show comparable performance to classical climatologies on large scales but a much better representation on smaller scales (40–120 d, 500–1,500 km) compared to in situ data. The limits of these mappings are explored with pCO2 estimation in surface waters, i.e., at the edge of the domain with high intrinsic variability. In highly productive areas, there is a tendency for pCO2 overestimation due to decoupling of the O2 and C cycles by air-sea gas exchange, but global surface pCO2 estimates are unbiased compared to a monthly climatology. CANYON-B and CONTENT are highly useful as transfer functions between components of the ocean observing system (GO-SHIP repeat hydrography, BGC-Argo, underway observations) and permit the synergistic use of these highly complementary systems, both in spatial/temporal coverage and number of observations. Through easily and robotically-accessible observations they allow densification of more difficult-to-observe variables (e.g., 15 times denser AT and CT compared to direct measurements). At the same time, they give access to the complete carbonate system. This potential is demonstrated by an observation-based global analysis of the Revelle buffer factor, which shows a significant, high latitude-intensified increase between +0.1 and +0.4 units per decade. This shows the utility that such transfer functions with realistic uncertainty estimates provide to ocean biogeochemistry and global climate change research. In addition, CANYON-B provides robust and accurate estimates of nitrate, phosphate, and silicate. Matlab and R code are available at https://github.com/HCBScienceProducts/.