Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina.

Progerin, the protein that causes Hutchinson-Gilford progeria syndrome, triggers nuclear membrane (NM) ruptures and blebs, but the mechanisms are unclear. We suspected that the expression of progerin changes the overall structure of the nuclear lamina. High-resolution microscopy of smooth muscle cells (SMCs) revealed that lamin A and lamin B1 form independent meshworks with uniformly spaced openings (~0.085 µm2). The expression of progerin in SMCs resulted in the formation of an irregular meshwork with clusters of large openings (up to 1.4 µm2). The expression of progerin acted in a dominant-negative fashion to disrupt the morphology of the endogenous lamin B1 meshwork, triggering irregularities and large openings that closely resembled the irregularities and openings in the progerin meshwork. These abnormal meshworks were strongly associated with NM ruptures and blebs. Of note, the progerin meshwork was markedly abnormal in nuclear blebs that were deficient in lamin B1 (~50% of all blebs). That observation suggested that higher levels of lamin B1 expression might normalize the progerin meshwork and prevent NM ruptures and blebs. Indeed, increased lamin B1 expression reversed the morphological abnormalities in the progerin meshwork and markedly reduced the frequency of NM ruptures and blebs. Thus, progerin expression disrupts the overall structure of the nuclear lamina, but that effect-along with NM ruptures and blebs-can be abrogated by increased lamin B1 expression.

Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures.

Lipoprotein lipase (LPL) is secreted into the interstitial spaces by parenchymal cells and then transported into capillaries by GPIHBP1. LPL carries out the lipolytic processing of triglyceride (TG)-rich lipoproteins (TRLs), but the tissue-specific regulation of LPL is incompletely understood. Plasma levels of TG hydrolase activity after heparin injection are often used to draw inferences about intravascular LPL levels, but the validity of these inferences is unclear. Moreover, plasma TG hydrolase activity levels are not helpful for understanding LPL regulation in specific tissues. Here, we sought to elucidate LPL regulation under thermoneutral conditions (30 °C). To pursue this objective, we developed an antibody-based method to quantify (in a direct fashion) LPL levels inside capillaries. At 30 °C, intracapillary LPL levels fell sharply in brown adipose tissue (BAT) but not heart. The reduced intracapillary LPL levels were accompanied by reduced margination of TRLs along capillaries. ANGPTL4 expression in BAT increased fourfold at 30 °C, suggesting a potential explanation for the lower intracapillary LPL levels. Consistent with that idea, Angptl4 deficiency normalized both LPL levels and TRL margination in BAT at 30 °C. In Gpihbp1-/- mice housed at 30 °C, we observed an ANGPTL4-dependent decrease in LPL levels within the interstitial spaces of BAT, providing in vivo proof that ANGPTL4 regulates LPL levels before LPL transport into capillaries. In conclusion, our studies have illuminated intracapillary LPL regulation under thermoneutral conditions. Our approaches will be useful for defining the impact of genetic variation and metabolic disease on intracapillary LPL levels and TRL processing.

The discovery and evaluation of [18F]BMS-986229, a novel macrocyclic peptide PET radioligand for the measurement of PD-L1 expression and in-vivo PD-L1 target engagement.

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Randomized comparison of in vivo performance of TearLab® and I-PEN® osmometry in normal dogs.

OBJECTIVE: To compare tear film (TF) osmolarity measured using TearLab® and I-PEN® osmometers in the same dogs without any ocular surface disease. ANIMAL STUDIED: Fifty-two dogs (98 eyes) of different breeds were evaluated. PROCEDURES: Tear film (TF) osmolarity was evaluated at 2-min intervals. The test was randomly determined, and single measurements were performed using each osmometer. Subsequently, complete ophthalmologic examinations were performed based on Schirmer tear test-1 (STT-1) analysis, tear film breakup time (TFBUT), and slit-lamp biomicroscopy. For each osmometer, the mean ± standard deviation of the TF osmolarity was calculated, and a paired Student's t-test was used to compare the values obtained. Pearson correlation analysis was performed to assess the association between osmolarity and other values such as STT-1, TFBUT, and age. RESULTS: Tear film osmolarity determined using TearLab® (340.42 ± 15.87 mOsm/L) and I-PEN® (321.58 ± 17.39 mOsm/L) were significantly different (p < .001). However, statistical significance could not be confirmed between osmolarity and other values, such as STT-1, TFBUT, and age. CONCLUSIONS: In dogs, the TF osmolarity values obtained using TearLab® tend to be higher than those obtained using I-PEN®, contrary to that observed in humans. These findings can serve as a reference for establishing normal values for each osmometer for clinical use in measuring TF osmolarity in dogs.

Long-term evaluation of the effects of vitreous degeneration on cataracts and retinal detachment in dogs.

OBJECTIVE: We aimed to track and evaluate the association between vitreous degeneration and the development of cataracts or retinal detachments in dogs over a long period. ANIMAL STUDIED: Data on vitreous degeneration, cataracts, and retinal detachment in 102 eyes were collected from 68 dogs who underwent ocular ultrasonography at least twice between March 2017 and November 2021 at the Veterinary Medical Teaching Hospital, Konkuk University. The mean follow-up time was 515 ± 256 (mean ± standard deviation; range: 81-1196) days. PROCEDURE: Development of cataracts and retinal detachment, according to the severity of vitreous degeneration grade (VDG), was evaluated during long-term follow-up. RESULTS: In the cataract study (87 eyes, 61 dogs), the number of cataracts developed according to VDG (grade: 0-3) were as follows: VDG 0: 1 in 10 (10%) eyes, VDG 1: 15 in 35 (43%) eyes, VDG 2: 15 in 30 (50%) eyes, and VDG 3: 10 in 12 (83%) eyes. It was significantly different among grades (p = .026). In the retinal detachment study (95 eyes, 64 dogs), the number of retinal detachments developed according to each VDG were as follows: VDG 0: 0 in 11 (0%) eyes, VDG 1: 1 in 36 (3%) eyes, VDG 2: 5 in 35 (14%) eyes, and VDG 3: 4 in 13 (30%) eyes. It was also significantly different among grades (p = .019). CONCLUSIONS: During long-term follow-up, dogs with severe vitreous degeneration had an increased risk of cataract and retinal detachment development than those without or with mild vitreous degeneration.

Artistic Robotic Arm: Drawing Portraits on Physical Canvas under 80 Seconds.

In recent years, the field of robotic portrait drawing has garnered considerable interest, as evidenced by the growing number of researchers focusing on either the speed or quality of the output drawing. However, the pursuit of either speed or quality alone has resulted in a trade-off between the two objectives. Therefore, in this paper, we propose a new approach that combines both objectives by leveraging advanced machine learning techniques and a variable line width Chinese calligraphy pen. Our proposed system emulates the human drawing process, which entails planning the sketch and creating it on the canvas, thus providing a realistic and high-quality output. One of the main challenges in portrait drawing is preserving the facial features, such as the eyes, mouth, nose, and hair, which are crucial for capturing the essence of a person. To overcome this challenge, we employ CycleGAN, a powerful technique that retains important facial details while transferring the visualized sketch onto the canvas. Moreover, we introduce the Drawing Motion Generation and Robot Motion Control Modules to transfer the visualized sketch onto a physical canvas. These modules enable our system to create high-quality portraits within seconds, surpassing existing methods in terms of both time efficiency and detail quality. Our proposed system was evaluated through extensive real-life experiments and showcased at the RoboWorld 2022 exhibition. During the exhibition, our system drew portraits of more than 40 visitors, yielding a survey outcome with a satisfaction rate of 95%. This result indicates the effectiveness of our approach in creating high-quality portraits that are not only visually pleasing but also accurate.

RoF-based indoor distributed antenna system that can simultaneously support 5G mmWave and 6G terahertz services.

The telecommunication society is paving the way toward ultra-high frequency regions, including the millimeter wave (mmWave) and sub-terahertz (sub-THz) bands. Such high-frequency electromagnetic waves induce a variety of physical constraints when they are used in wireless communications. Inevitably, the fiber-optic network is deeply embedded in the mobile network to resolve such challenges. In particular, the radio-over-fiber (RoF)-based distributed antenna system (DAS) can enhance the accessibility of next-generation mobile networks. The inherent benefits of RoF technology enhance the DAS network in terms of practicality and transmission performance by enabling it to support the 5G mmWave and 6G THz services simultaneously in a single optical transport link. Furthermore, the RoF allows the indoor network to be built based on the cascade architecture; thus, a service zone can be easily added on request. This study presents an RoF-based multi-service DAS network and experimentally investigates the feasibility of the proposed system.

NRG1 functions downstream of EDS1 to regulate TIR-NLR-mediated plant immunity in Nicotiana benthamiana.

Effector-triggered immunity (ETI) in plants involves a large family of nucleotide-binding leucine-rich repeat (NLR) immune receptors, including Toll/IL-1 receptor-NLRs (TNLs) and coiled-coil NLRs (CNLs). Although various NLR immune receptors are known, a mechanistic understanding of NLR function in ETI remains unclear. The TNL Recognition of XopQ 1 (Roq1) recognizes the effectors XopQ and HopQ1 from Xanthomonas and Pseudomonas, respectively, which activates resistance to Xanthomonas euvesicatoria and Xanthomonas gardneri in an Enhanced Disease Susceptibility 1 (EDS1)-dependent way in Nicotiana benthamiana In this study, we found that the N. benthamiana N requirement gene 1 (NRG1), a CNL protein required for the tobacco TNL protein N-mediated resistance to tobacco mosaic virus, is also essential for immune signaling [including hypersensitive response (HR)] triggered by the TNLs Roq1 and Recognition of Peronospora parasitica 1 (RPP1), but not by the CNLs Bs2 and Rps2, suggesting that NRG1 may be a conserved key component in TNL signaling pathways. Besides EDS1, Roq1 and NRG1 are necessary for resistance to Xanthomonas and Pseudomonas in N. benthamiana NRG1 functions downstream of Roq1 and EDS1 and physically associates with EDS1 in mediating XopQ-Roq1-triggered immunity. Moreover, RNA sequencing analysis showed that XopQ-triggered gene-expression profile changes in N. benthamiana were almost entirely mediated by Roq1 and EDS1 and were largely regulated by NRG1. Overall, our study demonstrates that NRG1 is a key component that acts downstream of EDS1 to mediate various TNL signaling pathways, including Roq1 and RPP1-mediated HR, resistance to Xanthomonas and Pseudomonas, and XopQ-regulated transcriptional changes in N. benthamiana.

Efficacy of biodegradable collagen matrix (Ologen® CM) in augmenting the success rate of Ahmed glaucoma valve implantation in canine glaucoma.

OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.

16 Ch × 200 GHz DWDM-Passive Optical Fiber Sensor Network Based on a Power Measurement Method for Water-Level Monitoring of the Spent Fuel Pool in a Nuclear Power Plant.

This paper presents a remote 16 Ch × 200 GHz dense wavelength division multiplexing (DWDM)-passive optical fiber sensor (OFS) network. We particularly investigate the remote water-level monitoring capability of the OFS network based on an optical power measurement that features simplicity and a fast processing speed. The OFS network utilizes a seeded amplified spontaneous emission (ASE) light that is spectrum-sliced and distributed by an arrayed waveguide grating (AWG) towards multiple sensing units (SU), where each SU is installed at a different height in the water pool. Then, each SU reflects either of the two different optical powers according to the medium (air vs. water) back to the monitoring station. Therefore, the total received optical power at the monitoring station linearly changes according to the water level. We can simply recognize the water level by utilizing the optical power meter (OPM) at the monitoring station rather than the optical spectrum analyzer (OSA), which is bulky and expensive and requires a relatively long processing time. Consequently, we can reduce the system complexity, processing time, and cost (both installation and maintenance). However, the OPM-based OFS network requires a new methodology to derive the water level from the measured optical power. Thus, we come up with the reference-to-power ratio (RPR) analysis, which can be used for the maximum distance analysis as well as water level recognition. Based on the new reception architecture supported by the new post-processing scheme, the OFS network can distinguish 17 different water levels of the SFP at the monitoring station, which is >40 km away from the SFP, without using any active devices (such as optical amplifiers) at the remote places.

Effect of gintonin on matrix metalloproteinase-9 concentration in tears during corneal wound healing in rabbits.

It has been shown that gintonin, isolated from Panax ginseng, can promote rapid corneal wound healing. We aimed to elucidate the underlying mechanism and investigated whether gintonin affects the concentration of the extracellular matrix remodelling factor matrix metalloproteinase-9 (MMP-9) in tears during rabbit corneal wound healing in vivo. Twelve eyes (six rabbits) were divided equally into three groups. All eyes underwent corneal de-epithelialisation. The control group received Tearin Free sodium hyaluronate 0.1%, the solcoseryl group received solcoseryl-120 concentrate, and the gintonin group received 2.5 mg gintonin in sodium hyaluronate 0.1%. All preparations were administered for 5 days and the concentration of MMP-9 was measured in tears via ELISA on days 0, 1, and 5. MMP-9 concentrations in all groups were increased at day 1 and reduced at day 5. Of note, we found a significant change over the time frame for the gintonin group (P < 0.05) but not for the control or solcoseryl groups (P > 0.05) Moreover, increased MMP-9 levels between days 0 and 1, and their reduction between days 1 and 5, were significant in the gintonin group compared to those in the other groups (P < 0.05); however, and once more, these changes were not significant between the control and solcoseryl groups (P > 0.05). In conclusion, gintonin increases the concentration of MMP-9 rapidly within a day of injury, and decreasing it thereafter.

Demonstration of photonics-aided terahertz wireless transmission system with using silicon photonics circuit: erratum.

We present an erratum for our recent paper [Opt. Express 28, 23397 (2020)] to include funding information in the funding section.

Demonstration of photonics-aided terahertz wireless transmission system with using silicon photonics circuit.

We experimentally demonstrate the use of silicon photonics circuit (SPC) in the simple and cost-effective photonics-aided Terahertz (THz) wireless transmission system. We perform theoretical investigation (with experimental confirmation) to understand that the system performance is more sensitive to the free space path loss (FSPL) at the THz wireless link than the SPC's insertion loss. The SPC, we design and fabricate, combines two incident optical carriers at different wavelengths and modulates one of two optical carriers with data to transfer, consequently reducing the system footprint that is indeed one of the key challenges that must be tackled for better practicability of the THz communication system. We perform experimental verification to show the feasibility of 40 Gb/s non-return-to-zero (NRZ) on-off-keying (OOK) signal transmission over 1.4 m wireless link for possibly its application in short-reach indoor wireless communication systems utilizing (sub-)THz frequency band such as, e.g., indoor WiFi, distributed antenna/radio systems, rack-to-rack data delivery, etc. The SPC could be further integrated with various photonic elements such as semiconductor optical amplifiers, laser diodes, and photo-mixers, which will enable the path towards all-photonic THz-wave synthesizers.

Multiplexed Passive Optical Fiber Sensor Networks for Water Level Monitoring: A Review.

Water management is a critical mission required to protect the water resources that is essential in diverse industrial applications. Amongst a variety of parameters such as level (or depth), temperature, conductivity, turbidity, and pH, the water level is the most fundamental one that needs to be monitored on a real-time basis for securing the water management system. This paper presents an overview of water level monitoring technologies based on optical fiber sensor (OFS) networks. Firstly, we introduce and compare the passive distributed and quasi-distributed (discrete) sensor networks with the recent achievements summarized. The performance (i.e., sensing range and resolution) of the OFS networks can be enhanced through diverse multiplexing techniques based on wavelength, time, coherence, space, etc. Especially, the dense wavelength division multiplexing (DWDM)-based sensor network provides remote sensing (where its reach can be extended to >40 km) with high scalability in terms of the channel number that determines the spatial resolution. We review the operation principle and characteristics of the DWDM-based OFS network with full theoretical and experimental analysis being provided. Furthermore, the key system functions and considerations (such as the link protection from physical damages, self-referencing, management of sensing units, and so on) are discussed that could be a guideline on the design process of the passive OFS network.

Long-Reach DWDM-Passive Optical Fiber Sensor Network for Water Level Monitoring of Spent Fuel Pool in Nuclear Power Plant.

This paper presents a passive optical fiber sensor network based on the dense wavelength division multiplexing (DWDM) to remotely monitor the water level of the spent fuel pool in nuclear power plants. In states of emergency, such as a tsunami, safety information must be secured for rapid response, in spite of all power losses in the plant. We consider the proposed passive sensor network to be one of the best solutions that is able to provide the remote (more than tens of kilometers) monitoring station with the highly reliable on-site information. The principle of water level measurement is based on the change of Fresnel reflection power coefficient at sensing units, which are installed according to the water levels in a row. The sensing units that play the role of reflector and modulator at the same time are connected to an arrayed waveguide grating (AWG) for DWDM. By measuring the spectrum of the optical signal transferred from the sensing units, the water level can be determined in real-time. However, in the remote sensing, the system performance can be seriously degraded due to the Rayleigh Back-Scattering (RBS) of the seeded amplified spontaneous emission (ASE) light that is induced at the fiber-optic link. As such, we investigate the effect of RBS on the remote (more than tens of kilometers) sensing performance of the proposed network. Following the theoretical analysis, we propose a simple network configuration to overcome the RBS issue by utilizing two different transmission paths: one for downstream of the ASE seed light, and the other for upstream of the optical signals coming from the sensing units. Based on the proposed configuration, the maximum sensing distance can be increased up to 42.5 km without the support of any optical amplifier.

4 × 4 MIMO architecture supporting IFoF-based analog indoor distributed antenna system for 5G mobile communications.

We demonstrate the analog indoor distributed antenna system (DAS) for 5G mobile communications that supports 4 × 4 multiple-input multiple-output (MIMO) configuration. For this, we exploit a pair of intermediate frequency over fiber (IFoF)-based analog optical links, transporting 32 frequency allocation (FA) 5G mobile signals (effectively ~4 GHz bandwidth). The analog optical link manifests its high fidelity in the measured characteristics: small gain variation (< ± 1 dB for the entire transmission bandwidth), low noise (<-136 dBm/Hz), and large dynamic range (spurious free dynamic range of >106 dB∙Hz2/3), subsequently providing superior error vector magnitude (EVM) performance (~2%) for a wide range of ambient temperatures (-20 ~60°C). Consequently, the IFoF-based 4 × 4 MIMO supporting analog indoor DAS is capable of providing record high peak throughput of 5.3 Gb/s for millimeter wave based 5G mobile communication system.

Ahmed glaucoma valve implantation with Ologen® Collagen Matrix for the surgical treatment of feline glaucoma.

An Ahmed valve implantation with an Ologen® Collagen Matrix (Ologen® CM, Aeon Astron, Leiden, the Netherlands) was performed for the treatment of uncontrolled glaucoma in a cat. This cat was a 5-year-old castrated Russian Blue male with a 12-week history of conjunctival hyperemia and mydriasis of the left eye. During the ophthalmic examination, the intraocular pressure (IOP) oculus sinister (OS) was 52 mmHg, and a narrow iridocorneal angle (ICA) was detected by gonioscopy. Medical treatment with Cosopt® (2% dorzolamide and 0.5% timolol) failed to decrease the IOP. The left eye still had vision, and an Ahmed valve implantation was performed. During the gonioimplantation, Ologen® CM was used to inhibit scar formation around the valve. Following the operation, the IOP was stable at an approximate average of 15 mmHg during the 7-month follow-up period, and vision in the left eye was retained without medication. An adequate subconjunctival filtering bleb was formed after 140 days. This is the first case report in which an Ahmed valve gonioimplant with an Ologen® CM has been used for the surgical treatment of glaucoma in a cat.

Cavity-induced phase noise suppression in a Fabry-Perot modulator-based optical frequency comb.

We investigate for the first time, to the best of our knowledge, both theoretically and experimentally, how the phase noise of the radio frequency (RF) drive signal affects the phase noise of the individual tones of a Fabry-Perot (F-P) modulator-based optical frequency comb. We observe that the expected deleterious effect of the RF drive signal phase noise on the comb output is partially suppressed due to the filtering characteristics of the F-P cavity. We found that the cavity-induced phase noise suppression is strongest for high-order comb tones, e.g., reaching up to 40 dB for the 100th comb tone at high offset frequencies. The phase noise suppression becomes even stronger for low RF-drive powers, or when the seed laser does not resonate in the F-P cavity. For both cases, we observe up to a 10 dB increase in phase noise suppression. We also evaluate the timing jitter improvement obtained, thanks to the cavity-induced phase noise reduction. The timing jitter (integrated from 2.5 MHz to 2.5 GHz) decreased by a factor of 7 for the beat signal obtained between two comb tones that are 100 tones apart (in comparison with the timing jitter obtained in a cavity-less comb generator).

Radiosynthesis and preclinical PET evaluation of 89Zr-nivolumab (BMS-936558) in healthy non-human primates.

Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types. This study reports the preparation and in vivo evaluation of 89Zr labeled nivolumab in healthy non-human primates (NHP) as a preliminary study of biodistribution and clearance. The radiochemical and in vivo stabilities of the 89Zr complex were shown to be acceptable for imaging. Three naïve NHPs were intravenously injected with tracer only or tracer co-injected with nivolumab followed by co-registered by positron emission tomography (PET) and magnetic resonance imaging (MRI), acquired for eight days following injection. Image-derived standardized uptake values (SUV) were quantified by region of interest (ROI) analysis. Radioactivity in the spleen was significantly reduced by addition of excess nivolumab compared to the tracer only study at all imaging time points. Liver uptake of the radiotracer was consistent as a clearance organ with minimal signal from other tissues: lung, muscle, brain, heart, and kidney. The results indicate specific biodistribution to the spleen, which can be blocked by co-administration of excess nivolumab. Distribution to other organs is consistent with elimination pathways of antibodies, with primary clearance through the liver.