Misunderstanding of the function of the plateau pika (Ochotona curzoniae) results in diminishing the diversity of both fauna and flora species and collapse of the the food on the Qinghai-Tibetan plateau. We used data obtained during an 11-year period to observe evolutionary habitat selection by the plateau pika in relation to an irrelevant phylogeny agent of livestock management. We hypothesized that local nomads are the irrelevant phylogeny agent in the Kobresia ecosystem of the Qinghai-Tibetan plateau. In order to verify the above hypothesis, distance to nearest yak-bedding areas and dung management are the variables that most strongly explains variation in pika occupancy probability and probability of occupancy detection based on free-ranging livestock. Both occupancy and detection probability of pikas decrease sharply with increasing distance to nearest yak-bedding area, strongly suggesting that pika population densities are highest closest to yak-bedding areas. There is a strong correlation between dung cover and occupancy of the plateau pika—namely, the more dung drying on the ground; the more plateau pikas occupy the area. After the dung has damaged the grass, plateau pikas are apparently detected there. Thus, rangeland dominated by sedges of the genus Kobresia on the Qinghai-Tibetan Plateau is modified by livestock grazing and management, especially dung management. This is the first reported evidence that local nomads may cause expansion of the habitat of the plateau pika and its occupancy.

Followed by developing modern medicine, leeches did not have extensive use as before, however, in the late 19th century, they were still used in most countries all over the world. Thus far, leeches were utilized in treating various diseases like skin disorders, arthritis, and cancer. In Egypt, using leeches for treatment dates back to early 1500 BC. A medical leech’s salivary glands involve over 100 bioactive materials and the salivary gland secretion contains bacteriostatic, analgesic, and anti-coagulation influences; with resolving activity, it causes microcirculation disorders elimination, restoring the hurt vascular permeability of organs and tissues, removing hypoxia, decreasing blood pressure, increasing immune system activity, and detoxifying the organism by antioxidant paths. The current work reviews the innovative treatment with medical leech especially proteins in leech saliva with high potential in medicine. The results showed that by the virtue of salivary gland secretions which are proteinaceous enzymes, leech acts on various diseases such as venous congestion in reconstructive and plastic surgery, osteoarthritis, cardiovascular diseases caused by blood coagulation disorders, skin disorders, migraine headache, diabetic foot ulcers, priapism, macroglossia, cancer complications, wounds and many other. To confirm the potential therapeutic impacts of leech treatment, more studies are required in more extensive areas with more exact methodologies.

Tubulin beta 8 class VII (TUBB8), a primate oocyte/embryo-specific β-tubulin isotype, is a preferentially analyzed gene in the genetic diagnosis of infertile women. Studies have currently identified 47 variants of this gene. However, the evaluation of its pathogenicity and the resulting phenotypes vary, and this gene requires further study in order to be included in genetic counseling analyses. We have performed a whole exome sequencing (WES) screening of 385 infertile female subjects and 400 controls, identifying 29 TUBB8 variants (of which 23 were novel). These variants may be responsible for female infertility, especially in the case of embryonic arrest, and their identification further expands the variant spectrum of TUBB8. Our findings are the first to report a new phenotype of large polar body in TUBB8 variant patients and determine some recurrent variants that were specific for complete cleavage failure. We have also illustrated some phenotypes of TUBB8 variant patients and recommended using computational modeling approach to assess the pathogenicity of novel TUBB8 variants, particularly for maternally inherited variants. Our studies will contribute in laying the foundation for the genetic counseling of infertile women in the future.

The pump-and-treat methodology represents a common remediation approach to mitigate hydrocarbon contaminations. In a well-studied site contaminated by large volume of jet fuel, continuous monitoring of the water table and floating phase thickness at a widely studied site contaminated by a large volume of jet fuel revealed the phenomenological process governing the effectiveness of the site's active remediation system. The floating phase thickness recorded in the monitored wells broadly varied and was negatively correlated with the water table level. Although the dependency of LNAPL thickness on water table fluctuations is widely recognized, the LNAPL recovery, which is governed by alternating cycles of release and entrapment of LNAPL in pore spaces, has been poorly described. Thus, we present a peculiar case in which the LNAPL recovery is expected only episodically, when water table falls sufficiently. In the period spanning from 2006 to 2008, LNAPL remediation recovered nearly 180 m3 of oil. In later years, the volume of recovered LNAPL declined and ceased between 2010 and 2014, when the water table rose. The conditions observed at the study site are likely common and may have important implications in the management of contaminated sites.

Soil amendment is one of the most effective method to improve saline-alkali soil. In this paper, we verify the effect of 13 kinds of amendments and its combination on soil pH、metal cations content、exchangeable Na+、exchangeable sodium percentage (ESP)in the lab, and then choose the most 5 effective amendments both applying in both dry and paddy field to evaluate their improvement on soda saline-alkali soil and crop yield. The results showed that AL, AL + Z and AL + ZH treatments could significantly reduce the pH in soil solution and increase the content of metal cations. Z and ZH treatments could adsorb metal cations in soil. Whether in dry or paddy fields, all treatments could reduce the content of exchangeable Na+ in soil, and decrease by 38.62% - 61.33% and 25.24% -71.53%, respectively; All treatments could reduce soil exchangeable sodium percentage, and decrease by 0.14 - 0.22 and 0.14 - 0.41, respectively; AL, AL+Z and AL+ZH treatments could improve soil organic matter content; All treatments could effectively improve the yield of crops, and increase 23.98% - 60.75% and 52.51% - 260.21%, respectively. The effect of AL treatment was the best in dry field and AL + ZH treatment was the best in paddy field of soda saline-alkali soil.

Controversial hypotheses to explain consciousness exist in many fields of science, psychology and philosophy. Recent experimental findings in quantum cognition and magnetic resonance imaging have added new controversies to the field, suggesting that the mind may be based on quantum computing. Quantum computers process information in quantum bits (qubits) using quantum gates. At a first glance, it seems unrealistic or impossible that the brain can meet the challenges to provide either of these. Nevertheless, we show here why the brain has the incredible ability to perform quantum computing and how that may be realized. 

Gli odori rappresentano uno degli elementi di disturbo maggiormente avvertito dalla popolazione e risultano essere la causa predominante dei conflitti nei confronti delle aziende che li diffondo. Nonostante la maggioranza delle sostanze odoranti non abbia effetti tossici, tali condizioni generano una serie di impatti negativi comportando una modifica dell’equilibrio psicofisico di una persona e influire negativamente sui suoi comportamenti che si concludono con una diminuzione dei valori degli immobili, e della qualità di vita nelle aree interessate.Tale sintomologia prende il nome della sindrome NIMBY (Not In My Back Yard, “non nel mio giardino”) e BANANA (Build Absolutely Nothing Anywhere Near Anything, “non costruire assolutamente nulla in alcun luogo vicino a qualunque cosa”). Facendo riferimento sempre alle emissioni in atmosfera, la normativa italiana ha emanato una direttiva (UE) 2015/2193 del Parlamento europeo e del consiglio tramite il Dgls 183/2017, limitando le emissioni di questi inquinanti originati da impianti di combustione medi (in special modo combustibili). Tale normativa ha avuto come conseguenza la necessità di agire in merito al problema delle emissioni odorigene da parte degli impianti industriali.La sfida attuale è la definizione di sistemi di monitoraggio degli odori strumentali (IOMS) che consentono la caratterizzazione continua degli odori. Attualmente non esistono regolamenti o procedure standardizzate, e in letteratura sono disponibili dati limitati con riferimento alle caratteristiche e alla procedura operativa di questi sistemi per il monitoraggio degli odori ambientali. I risultati evidenziano l'importanza e la flessibilità degli IOM proposti nel monitoraggio degli odori, fornendo informazioni accurate e in tempo reale sulla fonte e sulla concentrazione delle emissioni di odori.

This study evaluated the effects of antimicrobial addition on the shelf-life of rendered chicken fat. Sodium bisulfate (SBS) and lactic acid (LA), were each added at 0.5% to chicken fat and incubated for 6 weeks at 40°C. Peroxide value (PV), p-anisidine value (AV) and free fatty acid (FFA) levels were measured at day 0 (D0), 1(D1), 3 (D3), 5 (D5), and 7 (D7), and week 2 (W2), 3 (W3), 4 (W4), 5 (W5), and 6 (W6). The FFA level of untreated-control fat was ~7% and remained consistent throughout the incubation until W6 (~8.5%; (P<0.05). The FFA values in SBS treated fat were constant (range 7.25-8.30%) throughout the incubation; whereas, the LA treated fat peaked at W5 (9.3%, P<0.05). For the control fat, PVs were between 0.56-0.67 meqv/100gm until W1 then declined. For the SBS treated fat, the PVs remained low and like the control with the exception of a slight increase on W4 to 0.38 meqv/100gm, P<0.05). In the LA treated fat PV was greater than the control from W1 and increased to a peak on W5 (2.52 meqv/100gm). The AV of control fat averaged 2.12 at D0 and increased through W2. In control and LA treated fat, the AV values declined slightly thereafter; whereas, SBS treated fat increased (P<0.05) to 10.28 on W5.This study indicates that at antimicrobial effective doses the LA in rendered chicken fat may impact the shelf-life, but SBS had a minimal effect over a period of 6 weeks.

The simulation of nano-silver solder joints in flip-chips is performed by the finite element software ANSYS, and the stress-strain distribution results of the solder joints are displayed. In this simulation, the solder joints use Anand viscoplastic constitutive model, which can reasonably simulate the stress and strain of solder joints under thermal cycling load. At the same time this model has been embedded in ANSYS software, so it is more convenient to use. The final simulation results show that the areas where the maximum stresses and strains occur at the solder joints are mostly distributed in the contact areas between the solder joints and the copper pillars and at the solder joints. During the entire thermal cycling load process, the area where the maximum change in stress and strain occurs is always at the solder joint, and when the temperature changes, the temperature at the solder joint changes significantly. Based on comprehensive analysis, the relevant empirical correction calculation equation is used to calculate and predict the thermal fatigue life of nano-silver solder joints. The analysis results provide a reference for the application of nano-silver solder in the electronic packaging industry.

The represented multi-material design contains an aluminium EN AW-6016 and a high strength steel CR330Y590T-DP. This dissimilar combination is an example for affordable lightweight design solutions, but it requires an adapted joining technology. Hybrid joining technologies such as self-piercing riveting (SPR) in combination with a structural adhesive enable an assembly of such dissimilar material combinations. Besides higher manufacturing costs for mechanical joining the design process still requires a great amount of effort. This study provides a simple approach to assess hybrid joined multi-material connections. Therefore, tests on several combinations of the most relevant parameters on the fatigue life (material properties, sheet thicknesses, load cases) were performed under quasi-static and cyclic loads. Based on the data acquired, it is shown that the fatigue life of the hybrid joined connections can be estimated by superposing the contributing fatigue lives of the purely SPR and purely adhesive joints.

There are widespread distributions and seepage of groundwater in rock fractures. Seepage conditions in the fractures can be affected by stress conditions. Theoretical model is suggested based on rock fracture seepage problem in two dimensional space. Combined with the mass conversion equation, Euler fluid flow equation and rock deformation equation the functions of seepage pressure have been deduced. The functions of seepage pressure with the surrounding rock are nonlinear second order partial differential equations of space-time. It is analyzed by differential simulation and parameters effects on seepage are presented. As the elastic modulus of rock increases, the deformation of surrounding rock becomes smaller, which indicates that the seepage in soft rock is greatly affected by the deformation of surrounding rock. The deformation of surrounding rock becomes larger with the increase of crack analysis length, which indicates that the deformation of surrounding rock has more effect in long crack seepage than in short crack seepage. With the increase of the rock width, the effect of the surrounding rock deformation on the seepage becomes smaller, which indicates that the shallower the buried depth, the greater the effect. For the initial crack scale of different scales, the smaller the initial crack, the more obvious the effect of surrounding rock deformation on seepage.

In this paper, by means of p-adic Volkenborn integrals we introduce and study two different degenerate versions of the Bernoulli polynomials of second kind, namely the partially and fully degenerate Bernoulli polynomials of the second kind and also their higher-order versions. We derive several explicit expressions of those polynomials and various identities involving them.

Blow-up phenomena of solutions of a class of parabolic equations for porous media with nonlocal source terms cross-coupled under Dirichlet and Neumann boundary conditions. The differential inequality technique is used to obtain the lower bounds on the blow up time of the equation set under two different boundary conditions.

Based on the multi-quadrics (MQ) radial basis function, the two-step discretization method will be used to solve Allen-Cahn (AC) equation in this paper. In the first step, we will use the Backward Euler Formula to solve the AC equation with Newton iterative, and then apply the global RBF method to solve the Semi discrete linearized problem on a small number of collocation points or on a coarse mesh. In the second step, finite difference (FD) and radial basis function-finite difference (RBF-FD) methods will be used to solve the problem on a fine mesh or on a large number of collocation points, respectively. The two-step method will be proved to be more feasible and efficient by some numerical examples. In addition, compared with FD method, the application of RBF-FD method will improve the accuracy of the numerical solution in the second step.

Background: Prostate cancer early detection (PCa-ED) trough prostatic specific antigen (PSA) and digital rectal examination (DRE) has proved to lower mortality rates and should be carry out by primary care physicians (PCP). In Mexico, 80% of prostate cancers are detected in advanced-stages but PCP trends on PCa-ED remain unknown. Aim: To assess PCP knowledge and skills regarding PCaED. Materials and Methods: A self-administrating survey about the knowledge and skills of PCa-ED was created and delivered to PCP. Logistic regression analysis was conducted for the propensity of PCP to test prostatic specific antigen (PSA) on asymptomatic men. Results: The survey was completed by 170 PCP. The 13.5% answered being “not-well trained”. Score on risk factors knowledge was 51.5±15.7% but a score above the mean was not associated with testing PSA on asymptomatic men (p=0.674). The 40.6% answered having an institutional program on PCa-ED and 86% having access to PSA testing. Testing PSA on asymptomatic men was found in 40%. Moreover, 61.2% do not perform any digital rectal examination for PCa-ED, and this was not associated with preventing factors like lack of space, time, and assistance (p>0.05). Fewer years in practice and being a family medicine resident was associated with a less likelihood of testing PSA in asymptomatic men whereas having access to PSA testing and an institutional program on PCa-ED, increased the probability. The only significantly associated factor in the multivariable model was to have access to PSA testing [OR: 3.36 (CI 95% 1.54-7.30) p=0.002]. Conclusions: A low proportion of PCP in southeast Mexico performs PCa-ED and uses concepts outside evidence-based recommendations. A national program on PCa-ED and continuing medical education for PCP is a promising strategy to improve PCa-ED.

OBJECTIVES: To summarize ultrasonographic features of rare primary and common cervical cancer and the association of these cancers with HPV infection so as to diagnose rare primary cervical cancer. METHODS: Sixty-five cases with cervical cancer suspected by ultrasonography and three cases with clinical symptoms treated at our department underwent cervical biopsy. Sixty-four diagnosed cases were retrospectively analyzed and divided into common-type (CTCC) and rare-type (RTCC) cervical cancers. RESULTS: Sixty-one cases were diagnosed, four misdiagnosed, three missed the diagnosis by ultrasonography, the sensitivity of which was 95.31% (61/64). The common-type cervical cancer had 43 cases of squamous cell carcinoma. The rare-type cervical cancer had 15 cases of adenocarcinoma, four of small-cell carcinoma, and two of adenosquamous carcinoma. The demographic characteristics of the two groups were not significantly different (P > 0.2). The tumor size in RTCC were smaller than those in CTCC (P < 0.05). Hypoechoic lesions in CTCC and isoechoic lesions in RTCC composed 74.42% (32/43) and 61.90% (13/21), respectively (P < 0.001). Exophytic in CTCC and endophytic in RTCC composed 67.44% (29/43) and 66.67% (14/21), respectively (P = 0.01). HPV infection composed 83.72% (36/43) in CTCC and 47.62% (10/21) in RTCC, respectively (P = 0.003). Color Doppler blood signals were found in all cases, as compared with normal cervical tissue. The consistency between ultrasonography and pathology staging diagnosis of RTCC was good (Weighted kappa (95%CI) = 0.87). CONCLUSION: Ultrasonography can distinguish RTCC from CTCC. There is a very good consistency between ultrasonography and pathology staging diagnosis of RTCC.

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Space--time fractional forms of the modified Korteweg-de Vries equation, the modified Equal Width equation and Benney-Luke equations are solved by using simple hyperbolic tangent ansatz approach. A simple compatible wave transformation in one dimension is employed to reduce the governing equations to integer--ordered ODEs. Then, the hyperbolic tangent ansatz is used to derive exact solutions. Some illustrative examples are presented for some particular choices of parameters and derivative orders.

Introduction: Uterine leiomyoma is one of the most common benign tumors in women. Severe bleeding and unstable hemodynamics might occur in patients undergoing hysteroscopic myomectomy due to excessive irrigation fluid absorption.The aim of this study was to evaluate the effect of Intraoperative oxytocin infusion on the absorption of irrigation fluid in patients undergoing hysteroscopic myomectomy. Methods: In a randomized double-blind clinical trial, 50 patients aged 25-45 years with American Society of Anesthesiologists (ASA) class I or II undergoing hysteroscopic myomectomy were studied. In the study group (Group O), 250 mL ringer solution containing 15 units of oxytocin was infused at rate of 125 mL/h; while, the placebo group (Group P) received 250 mL ringer solution containing 1.5 ml of normal saline was infused at rate of 125 mL/h.Intraoperative hemodynamic alterations, fluid deficit, declined hemoglobin, hematocrit, sodium and albumin levels from baseline, complications and incidence of toxicity with the administered solutions were evaluated at both intraoperative and 24 hours postoperative phases. Results: The volume of irrigation fluid (P=0.032) and volume deficit (P=0.034) were significantly lower in the Group O. The incidence of intraoperative hypotension was significantly lower in Group O compared to Group P (P=0.019). Serum hematocrit (P=0.043) and sodium (P=0.026) levels were significantly lower in Group O. Conclusion: Intraoperative infusion of oxytocin during hysteroscopic myomectomy might be associated with decreased irrigation fluid absorption and its associated complications. Therefore, this method could be used to reduce the complications caused by the absorption of large volumes of irrigation fluid during hysteroscopic myomectomy

Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine crystal structures obtained to date. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for physiological function of these important drug targets. Here, we determine whether the presence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay. Upon ligand binding, the A1Δ291R or A2AΔ316R variants were unable to couple to human-yeast chimeric G-protein chimeras to generate a downstream signal in yeast, though full-length receptors showed native-like G-protein coupling. Further, constructs transfected into mammalian cells (HEK-293) showed similar behavior – i.e. the variants with C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptors. Although the C-terminus was essential for Gα protein- associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e. Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in signaling, but not specificity, for the interaction with Gα protein. This result has further implications in drug discovery both in enabling the experimental use of chimeras for ligand design, and in cautious interpretation of structure-based drug design based on truncated receptors.

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor-stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three-dimensional, in vitro, vascularized, IBC platform to quantify the spatial and temporal dynamics of tumor-vasculature and tumor-ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA-IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non-IBC cells, MDA-MB-231 (triple negative). An acellular collagen platform with an endothelial blood vessel served as control. SUM149 and MDA-MB-231 platforms exhibited a significantly (p<0.05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA-IBC3 and SUM149, expressed higher levels of VEGF (p<0.05) and increased collagen ECM porosity compared to non-IBC MDA-MB-231 (p<0.05) and control (p<0.01) platforms. Additionally, unique to the MDA-IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA-IBC3 cells replicating a feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well-described in vivo and clinical IBC phenotypes and provide an adaptable, high throughout tool for systematically and quantitatively investigating tumor-stromal mechanisms and dynamics of tumor progression.

Background and Purpose. Despite widespread abuse of cocaine, there are no approved treatments for cocaine use disorder. Chronic cocaine use is associated with upregulated dopamine D3 receptor (D3R) expression in the brain, and therefore, most D3R-based medication development has focused on D3R antagonists. However, D3R antagonists do not attenuate cocaine intake under “easy” self-administration conditions when response requirements are low. Here we evaluated a novel, highly selective and metabolically stable D3R partial agonist, VK4-40, for its efficacy in reducing cocaine intake and relapse to drug seeking. Experimental Approach. The impact of VK4-40 on cocaine intake and relapse were evaluated using intravenous self-administration procedures under a fixed-ratio 2 reinforcement schedule and cocaine-primed reinstatement conditions in rats. Optogenetic brain-stimulation reward procedures were used to evaluate the interaction of VK4-40 and cocaine in the mesolimbic dopamine system. Sucrose self-administration and a conditioned place preference paradigm was used to evaluate the abuse potential of VK4-40 alone and other unwanted effects. Key Results. VK4-40 dose-dependently reduced cocaine self-administration and cocaine-primed reinstatement of drug-seeking behavior. In addition, VK4-40 inhibited cocaine-enhanced brain-stimulation reward caused by optogenetic stimulation of dopamine neurons in the ventral tegmental area. VK4-40 alone decreased brain-stimulation reward, and produced neither conditioned place preference nor place aversion. This new D3R partial agonist also failed to alter oral sucrose self-administration. Conclusions and Implications. The novel D3R partial agonist, VK4-40, attenuates cocaine reward and relapse in rodents, without significant unwanted effects. These findings support further investigation of D3R partial agonists as putative treatments for cocaine use disorder.

Widespread dispersal of progeny is expected to result in enough gene flow to maintain genetic homogeneity over large areas. Surveys of genetic markers in species with planktonic larvae have mostly confirmed this expectation. However, genetic structure has occasionally been found at small spatiotemporal scales and interpreted as evidence of restricted dispersal, natal homing, sweepstakes reproductive success, or natural selection. We investigated genetic population structure in blue crabs from the Atlantic and Gulf of Mexico coasts of North America. Sampling was most intensive from five estuaries along the coast of Louisiana, with megalopae, juveniles and adults sampled from 2010 to 2016. 1446 individuals were genotyped at 2486 SNPs in 1363 putative protein-coding loci. Levels of differentiation between locations were consistently low, but significant differentiation was found among locations and among years. No evidence was found for chaotic genetic patchiness or sweepstakes reproductive success: no genetic differentiation was detected among collections of megalopae and none of the sampled individuals were closely related. Our results indicate that gene flow in blue crabs maintains near genetic homogeneity from the northern Gulf of Mexico through the Atlantic coast of North America.

BACKGROUND AND PURPOSE: A single dose of JV-GL1 lowers intraocular pressure (IOP) for a week according to previous studies on non-human primates. This highly protracted effect did not correlate with its ocular bio-disposition, where the drug was undetectable inside the eye after only one day post-dosing. Our current studies were intended to determine the role of EP2 receptors in mediating the long-term ocular hypotensive activity of JV-GL1 and utilized mice deficient in EP2 receptors. EXPERIMENTAL APPROACH: The protracted intraocular pressure reduction produced by JV-GL1 was investigated in C57BL/6J and EP2 receptor knock-out mice (B6.129-Ptger2tm1Brey/J, EP2KO). Both ocular normotensive and steroid induced ocular hypertensive (SI-OHT) mice were studied. Intraocular pressure was measured tonometrically under general anesthesia. Aqueous humor outflow facility was measured ex vivo using the iPerfusion system in normotensive C57BL/6J mouse eyes perfused with 100 nM de-esterified JV-GL1 and in SI-OHT C57BL/6J mouse eyes that had received topical JV-GL1 (0.01%) 3 days prior. KEY RESULTS: In SI-OHT, JV-GL1 did not lower IOP in EP2 KO mice. However, in WT mice with SI-OHT, JV-GL1 lowered IOP for 4-6 days. JV-GL1 did not alter outflow facility in WT mice at 3 days after topical administration. CONCLUSIONS AND IMPLICATIONS: The long-term effect of JV-GL1 on IOP in the SI-OHT model of glaucoma is EP2 receptor dependent. Such protracted activity of a single dose of a small molecule (JV-GL1) is unprecedented. Future studies on JV-GL1 may eventually lead to “once-weekly” small molecules, with reduced drug prices and better disease control.