Allometric Method Research Articles

Multi-spatial Resolution Imagery to Estimate Above-Ground Carbon Stocks in Mangrove Forests

Mangroves are a type of vegetation that can absorb carbon and have an essential role in controlling CO2 levels in the atmosphere. Mangroves can absorb carbon better than terrestrial ecosystems because of their ability to bury carbon in sediment. This research aims to compare and measure the carbon stock content above the surface of mangroves in the field using multi-spatial resolution imagery, namely, Landsat 8 OLI, Sentinel 2A, and Planetscope. Field carbon calculations were carried out using the allometric method based on mangrove species. The calculation results are then linked through regression analysis with the vegetation index Difference Vegetation Index (DVI) results. The total carbon obtained from PlanetScope imagery was 535.27 tons, Sentinel 2A imagery was 549.23 tons, and Landsat 8 OLI imagery was 533.57 tons. Among the three images used, based on Sentinel 2A statistical analysis reflects the possibility of overfitting or the best with higher r and R2 values in the calculations. However, based on SE accuracy tests, PlanetScope has better accuracy than the other two images. Apart from that, the accuracy test results using a 1:1 goodness of fit plot for each image, the distribution pattern of mangrove carbon stock estimates shows that the entire model in mapping mangrove carbon stocks is over-estimated. The overestimated results are possible because more objects around the mangrove, especially canopy density, are recorded by remote sensing sensors compared to tree diameter as input for field carbon results.

A comparison and development of methods for estimating shrub volume using drone‐imagery‐derived point clouds

AbstractShrub volume is used to calculate numerous, essential ecological indicators in rangeland ecosystems such as biomass, fuel loading, wildlife habitat, site productivity, and ecosystem structure. Field techniques for biomass estimation, including destructive sampling, ocular estimates, and allometric techniques, use shrub height and canopy widths to estimate volume and translate it to biomass with species‐specific allometric equations. These techniques are time‐consuming and pose challenges, including removal of plant material and training of observers. We compared canopy volume estimates from field‐based measurements with drone‐collected canopy volume estimates for seven dominant shrub species within mountain big sagebrush (Artemisia tridentata subsp. vaseyana) plant communities in southern Idaho, USA. Canopy height and two perpendicular width measurements were taken from 103 shrubs of varying sizes, and volume was estimated using a traditional allometric equation. Overlapping aerial images captured with a DJI Mavic 2 Professional drone were used to create a 3D representation of the study area using structure‐from‐motion photogrammetry. Each shrub was extracted from the point cloud, and volume was estimated using allometric and volumetric methods. The volumetric method, which involved converting point clouds to raster canopy height models with 2.5‐ and 5‐cm grid cells, outperformed the allometric method (R2 > 0.7) and was more reproducible and robust to user‐related variability. Drone‐estimated volume best‐matched field‐estimated volume (R2 > 0.9) for three larger species: A. tridentata subsp. tridentata, A. tridentata subsp. vaseyana, and Purshia tridentata. The volume of smaller shrubs (canopy widths <1 m) was slightly overestimated from drone‐based models. We argue that drone‐based models provide a suitable alternative to field methods, while having the added benefit of being less time‐consuming, with fewer limitations, and more easily scaled to larger study areas than traditional field techniques. Finally, we demonstrate a proof of concept for automating canopy volume estimates using point‐cloud‐based automatic shrub detection algorithms. These findings demonstrate that drone‐collected images can be used to assess shrub canopy volume for at least five upland sagebrush steppe shrub species and support the integration of drone data collection into rangeland vegetation monitoring.

ESTIMATIONS OF CARBON STORAGE AND ECONOMIC VALUE OF MANGROVE FOREST ON THE NORTH COAST OF CAWAN ISLAND, INDRAGIRI HILIR

Mangrove forests are important for human life and the surrounding environment, one of which is as a CO2 absorber and carbon storage. The North Coast of Cawan Island in Indragiri Hilir has a relatively good mangrove forest that is estimated to absorb and store more carbon. This study aims to (1) estimate the value of carbon storage in stands (stems), below-ground carbon (roots), litter, and sediment of mangrove forests, (2) estimate the CO2 absorption capacity of mangrove forests, and (3) estimate the economic value of absorption CO2 by mangrove forest on the North Coast of Cawan Island. The station determination method uses purposive sampling of five stations, each consisting of a transect with three plots measuring 10x10 m2. Measurement of stem and root biomass using the allometric method. Litter biomass measurement used the dry weight weighing method, and sediment carbon measurement used the Loss on Ignition (LOI) method. The result showed that average carbon storage in stems was 34.56 tons/ha, roots were 16.41 tons/ha, litter was 0.10 tons/ha, and sediment was 32.91 tons/ha. The estimated ability of mangrove forests to absorb CO2 is an average of 187.10 tons/ha or 636,450.59 tonnes for the entire North Coast of Cawan Island. The estimated economic value of mangrove forest carbon is an average of IDR 149,809,099 /ha or IDR 509,599,619,024 for the entire North Coast of Cawan Island.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

ESTIMATION OF WOODY CARBON DENSITY BY ALLOMETRIC METHOD IN THE SELECTED SAL FORESTS OF BANGLADESH

Estimation of Carbon (C) density in different Sal forests of Bangladesh has not yet been done for exploring their potentials in storing C. The present study compared the woody C density among three selected Sal forests located in Madhupur, Lalmai and Singra of Bangladesh in order to examine the effects of management intensities on C stocks. A total of 19 plots (each with 10 m × 10 m in size), 9 from Madhupur forest and each 5 from other two forests were placed to collect data on vegetation structure, plant diameter and woody C density. Allometric method was used to estimate C density for both aboveground and belowground parts of juvenile and adult tree plants of the selected plots. Woody biomass was converted into C content by multiplying the value with van Bemmelen factor (1.724). Results showed that woody C density was significantly (p = 0.0156) higher in Lalmai (552.46±64.09 ton/ha) and Singra forests (547.13±62.43 ton/ha) than the Madhupur Sal forest (354.03±38.43 ton/ha). Mean diameter of Sal tree plant at breast height was significantly (p = 0.022) higher in Lalmai (38.84±2.12cm) and Singra (37.36±1.97 cm) forests than Madhupur forest (30.72±1.93 cm). Results clearly demonstrated that forest trees with high average diameter had the high woody biomass content. This study thus suggested that long term forest conservation could be an effective approach to increase C stock in the forest ecosystems.

Abstract A139: Preclinical characterization and prediction of human pharmacokinetics and efficacious dose for VIP236, a novel alpha V beta 3 binding small molecule-drug conjugate (SMDC)

Abstract VIP236 is a small molecule drug conjugate (SMDC) consisting of an alpha v beta 3 (αvβ3) integrin binder linked to an optimized camptothecin (optCPT) payload via a protease sensitive peptide sequence. The overall drug design strategy for VIP236 is targeted delivery to the tumor microenvironment (TME) with extracellular release of the opCPT by neutrophil elastase (NE) present in the TME. VIP236 is anticipated to kill tumor cells while reducing effects to normal tissue. VIP236 was characterized in preclinical pharmacokinetic (PK) and efficacy studies to predict its human PK and efficacious dose. Briefly, VIP236 was administered intravenously (IV) to mice, rats, and dogs to characterize both its in vivo PK (1-2 mg/kg) and its routes of excretion (bile-duct cannulated [BDC] rat at 10 mg/kg). VIP236 was evaluated in vitro for its protein binding characteristics and as a substrate of human drug transporters. In addition, VIP236 was dosed to MX-1 (breast cancer) xenografted mice at doses ranging from 26-40 mg/kg IV on a 3 days on/4 days off regimen to characterize its antitumor activity. VIP236 had low plasma clearance in mice, rats, and dogs (CL=2.7-4.4 mL/min/kg) and low volume of distribution (Vss = 0.11 to 0.25 L/kg). Terminal half-life ranged from 0.93 hour in mice to 3.07 hours in dogs. In BDC rats, VIP236 was primarily excreted in bile with biliary clearance accounting for essentially all the total body CL. There was minimal to no metabolites in rat bile and urine. In vitro VIP236 exhibited low permeability in MDCKII cell monolayers and was identified as a substrate of BSEP and MRP2. VIP236 was highly protein bound to plasma protein with fraction unbound being <5% in all species tested. VIP236 showed robust tumor regression in MX-1 xenografted mice at all doses tested. Allometric methods were used to predict a low human VIP236 CL (0.87-2.68 mL/min/kg) and Vss (0.10 L/kg). Translational pharmacokinetic/pharmacodynamic modeling was used to predict human efficacious doses and exposures by benchmarking VIP236 against irinotecan antitumor activity in MX-1 xenograft mice after 5 cycles of dosing. Based on this analysis, predicted human doses ranged from 1-5 mg/kg IV on a 2 days on/5 days off regimen. VIP236 is currently being evaluated in a first-in-human study in patients with advanced or metastatic solid tumors (NCT05712889). Citation Format: Harvey Wong, Beatrix Stelte-Ludwig, Hans-Georg Lerchen, Amy J Johnson, Melanie M Frigault, Raquel Izumi, Ahmed Hamdy. Preclinical characterization and prediction of human pharmacokinetics and efficacious dose for VIP236, a novel alpha V beta 3 binding small molecule-drug conjugate (SMDC) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A139.

Physiologically based mechanistic insight into differential risk of valproate hepatotoxicity between children and adults: A focus on ontogeny impact.

The anticonvulsant valproic acid (VPA) despite complex pharmacokinetics has been in clinical use for nearly 6 decades. Previous reports indicated neonates, infants, and toddlers/preschoolers had higher risk of valproate hepatotoxicity than adults. However, dosing recommendations for those less than 10 years of age are lacking. To decipher clinical puzzles, physiologically-based pharmacokinetic (PBPK) models of VPA and its hepatotoxic metabolite 4-ene-VPA were constructed and simulated with particularly integrated information of drug-metabolizing enzyme ontogeny. Adult and pediatric PK data of VPA (n = 143 subjects) and 4-ene-VPA (n = 8 subjects) collected from previous reports were used for model development and validation. Sensitivity analyses were performed to characterize ontogeny impacts of CYP2C9 and UGT2B7 on dispositions of VPA and 4-ene-VPA across age groups. Optimal VPA dosing for each pediatric age group was also predicted and objectively judged by ensuring VPA efficacy and avoiding 4-ene-VPA hepatotoxicity. The study revealed UGT2B7 ontogeny was quite influential on VPA clearance even in neonates and small children. Intrinsic clearance of CYP2C9 was the most prominent determinant for areas under the concentration-time curve of VPA and 4-ene-VPA in infants, and toddlers/preschoolers, reflecting higher hepatotoxicity risk due to noxious 4-ene-VPA accumulation in these groups. The ontogeny-based PBPK approach complements conventional allometric methods in dosing estimation for the young by providing more mechanistic insight of the processes changing with age. The established ontogeny-based PBPK approach for VPA therapy deserves further corroboration by real-world therapeutic data to affirm its clinical applicability.

Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2

IntroductionM8891 is a selective and reversible inhibitor of methionine aminopeptidase 2 (MetAP2). We describe translational research to define the target pharmacokinetics (PK) of M8891 and associated pharmacodynamic (PD) levels, which were used to support efficacious dose selection in humans.MethodsIn vitro and in vivo PK characteristics were investigated in animal species, and data integrated using in vitro–in vivo correlation and allometric methods to predict the clearance, volume of distribution, and absorption parameters of M8891 in humans. In parallel, inhibition of MetAP2 activity by M8891 was studied in renal cancer xenografts in mice by measuring accumulation of Met-EF1α, a substrate of MetAP2. The corresponding PD effect was described by a turnover and effect compartment model. This model was used to simulate PD at the M8891 dose showing in vivo efficacy, i.e. significant tumor growth inhibition. Simulations of M8891 PK and associated PD in humans were conducted by integrating predicted human PK parameters into the preclinical PK/PD model.ResultsThe target minimum PD level associated with efficacy was determined to be 125 µg Met-EF1α per mg protein. Integrating predicted human PK parameters into the preclinical PK/PD model defined a minimal M8891 concentration at steady-state (Ctrough) of 1500 ng/mL (3.9 µM) in humans as being required to produce the corresponding minimum target Met-EF1a level (125 µg per mg protein).ConclusionThe defined target PK and PD levels supported the design of the clinical Phase Ia dose escalation study of M8891 (NCT03138538) and selection of the recommended Phase II dose.

Picking up the pieces: Assessing alternative methods for reconstructing whole red abalone (Haliotis rufescens) shell size from fragments

Dense layers of red abalone shells (“red abalone middens”) have been heavily studied along the California coast for their implications for pre-contact subsistence, paleo-sea surface temperatures, and nearshore ecology. However, shells in these deposits are typically broken which lessens their scientific value. To compensate for this problem, we evaluate four alternative methods for predicting the size of whole abalone shells from fragments. The first was a template made up of the outlines of complete modern and archaeological shells. The others were based on regression formulas that rely on measurements of shell features that potentially track with shell growth: (1) maximum diameter of the last developed aperture, (2) distance between the last two developed apertures, (3) maximum diameter of the muscle scar. We conducted a blind study with archaeological laboratory volunteers to evaluate the accuracy of these methods, and found that the template outperformed the allometric methods, and, of the latter, the muscle scar measurement was the most accurate. Our results provide a framework for future studies to assess variation in abalone size from fragmented shells as a proxy for past climate change and harvesting pressure. They also provide a methodological approach for reconstructing sizes of other shell species found in midden deposits elsewhere.

Morphometric Differentiation of the Swimming Crab Portunus sanguinolentus (Herbst, 1783) Populations in East Asia: Implications for Stock Identification and Management

Morphometric disparities were employed to characterize the geographical variations in and elucidate the phylogeography of Portunus sanguinolentus in East Asia. In this study, a comprehensive assessment was undertaken based on measurements from 833 individual crabs. These crabs were sampled from eight distinct locations, namely Kyushu (KS), Fuzhou (FZ), Yilan (YL), Xiamen (XM), Tainan (TN), Hong Kong (HK), Vietnam (VN), and Singapore (SG). Twelve morphometric measurements were standardized based on size using the allometric method. A cluster analysis and a canonical variate analysis (CVA) were then conducted for a data analysis. Randomization tests were subsequently performed to validate the morphometric differences observed among the groups. The analytical results classified the eight sampled populations into at least two distinct clusters. The first cluster included three samples from China (specifically FZ, XM, and HK), while the second cluster consisted of samples from East Asia (including KS, YL, TN, VN, and SG). The CVA revealed a tripartite division into three groups: the mainland China group (FZ, XM, and HK), the Kuroshio group (KS, YL, and TN), and the Southeast Asia group (VN and SG). The observed morphometric variations between these broad groups were statistically significant for both genders. These differences may be attributed to evolutionary origins, geographical events, or environmental adaptations. This study highlights the effectiveness of morphometric techniques in providing comprehensive insights into species delimitation and philogeographic relationships.

Analyze the Relationship Between Aboveground Biomass and NDVI Values Derived from UAV Multispectral Imagery

Aboveground biomass is usually estimated using an allometric method. Diameter at breast height (DBH) is one of the important variables that is used in estimating aboveground biomass. There is a relationship between aboveground biomass values with size of trees, DBH, tree height, crown diameter and greenness of trees. In remote sensing, the tree biophysical parameters can be derived from digital image processing and greenness of the trees can be assessed using normalized difference vegetation index (NDVI). Thus, the aim of this study is to analyze the relationship between aboveground biomass and NDVI values using UAV-based multispectral imagery. Three developed allometric equations were used to analyse the relationship between aboveground biomass and NDVI values. The results show that there is a moderate relationship between the NDVI values derived from multispectral imagery and estimated aboveground biomass with average R2 is 0.55. Altogether, 347 samples of data have been successfully collected at the study in Seksyen U11, Bukit Bandaraya, Shah Alam with the average diameter at breast height (DBH) is 29.457cm.

The Potential of Bekasi “Eduforest” urban forest in cultural environmental services

Setu Subdistrict, Bekasi Regency is an area designated as urban forest development for providers of cultural environmental services. The purpose is to identify the community's perceptions, motivations, and preferences around the urban forest. Primary data collection by questionnaire to 31 people was determined purposively and analyzed quantitatively using a 4-point Likert Scale. Calculation of air temperature and humidity, thermal comfort, biomass with allometric methods, and CO2 absorption to support recommendations for attractions. The results show that community knowledge, benefits, and functions of urban forests are well known. People visit urban forests because they provide comfort and good air quality so that they are physically and mentally healthy. Community preferences are in the form of harvesting honey and developing urban forests together so that they can participate further. The potential of the urban forest in cultural environmental services can be developed through the provision of massive information and counseling, the development of tourist attractions in the form of forest healing, educational, and culinary tourism, also panoramic and landscape attractions. With the relative humidity of 60% and the thermal comfort of 25.2 oC, categorized as quite comfortable, the development of health therapy tourism can be considered.

Application of Allometric Methods for Indexation of Left Ventricular End-Diastolic Volume to Normal Echocardiographic Data and Assessing Gender and Racial Differences

Gender and racial differences in cardiac chamber size are vital to establish normal ranges of cardiac chamber size in healthy subjects. Many studies report either non-indexed raw measurements or indexation to isometric body surface area (BSA) when establishing normal reference values. Other studies advocate allometric indexation for standardization of heart size. We compared several allometric methods on gender and racial differences in left ventricular end-diastolic volume (LVEDV) measured by three-dimensional echocardiography (3DE). 3DE LVEDV data from the World Alliance Societies of Echocardiography (WASE) normal values study were indexed to isometric BSA, BSA1.5, BSA1.8, isometric height, height2.3, height2.9, and estimated lean body mass (ELBM). Gender, racial, national, and regional differences in indexed and non-indexed LVEDV were assessed using Cohen's d or Cohen's f statistics, according to the number of groups being compared. Cohen's d < 0.20 and Cohen's f < 0.10 were regarded as very small relative magnitude of differences. Differences in LVEDV among White, Black, and Asian races were smallest when BSA1.5 or BSA1.8 was used for indexation, followed by ELBM. LVEDV/BSA1.5 was nearly identical for males and females (very small, d = 0.05). However, both LVEDV/BSA1.5 and LVEDV/BSA1.8 still provided moderate relative magnitude of differences (f = 0.22 to 0.37) among geographic regions. Specifically, among Asians, Indians had the smallest LVEDV/BSA1.5 (1.8). Brazilians had the smallest LVEDV/BSA1.5 (1.8) among Whites. Gender and racial differences in LVEDV became smaller when LVEDV was indexed to BSA1.5 or BSA1.8. However, differences in LVEDV among nations remain even after applying allometric scaling. This finding suggests that differences in body composition and/or hemodynamics are potentially more important determinants of heart size than race or gender.

The potential of biomass and carbon storage of avicennia alba in the mangrove rehabilitation area of Kedaburapat village, Kepulauan Meranti district

This research was conducted from May – August 2023 in the rehabilitation mangrove area of Kedaburapat Village, Rangsang Pesisir Sub-District, Kepulauan Meranti Regency, Riau Province. This study aims to determine the average of tree diameter, potential biomass and carbon storage of each tree and the relationship between potential biomass and carbon storage with the diameter of the Avicennia alba rehabilitation mangrove trees in Kedaburapat Village. The method used in this study is a survey method and determination of sampling points by purposive sampling. The potential biomass and carbon storage of each tree were calculated using the allometric method. The relationship between average tree diameter and potential biomass and carbon storage was analyzed using simple linear regression. The average diameter at breast height (DBH) of A. alba per tree ranged from 2.81 – 4.03 cm, the average biomass per tree was 7.39 – 12.80 kg, the average carbon storage per tree was 3.47 – 5.00 kg C and tree carbon total per ha was 32.62 – 43.95 ton C/ha. The potential of biomass and carbon storage of each tree has a relatively strong positive relationship with the average tree diameter, with a correlation coefficient (r) of 0.9921. The quality of the waters measured in this study were temperatures ranging from 28-30°C, salinity 25-28‰, and pH 7.5-7.9. Environmental parameters indicate that the condition of the rehabilitation mangrove area in Kedaburapat Village is still good and can support the life of mangrove vegetation.

Using an animal model to predict the effective human dose for oral multiple sclerosis drugs.

The objective of this study was to determine the potential usefulness of an animal model to predict the appropriate dose of newly developed drugs for treating relapsing remitting multiple sclerosis (RRMS). Conversion of the lowest effective dose (LEffD) for mice and rats in the experimental autoimmune encephalomyelitis (EAE) model was used to predict the human effective dose utilizing the body surface area correction factor found in the 2005 US Food and Drug Administration (FDA) Guidance for Industry in selecting safe starting doses for clinical trials. Predictions were also tested by comparison with doses estimated by scaling up the LEffD in the model by the human to animal clearance ratio. Although initial proof-of-concept studies of oral fingolimod tested the efficacy and safety of 1.25 and 5mg in treating RRMS, the EAE animal model predicted the approved dose of this drug, 0.5mg daily. This approach would have also provided useful predictions of the approved human oral doses for cladribine, dimethyl fumarate, ozanimod, ponesimod, siponimod, and teriflunomide, drugs developed with more than one supposed mechanism of action. The procedure was not useful for i.v. dosed drugs, including monoclonal antibodies. We maintain that drug development scientists should always examine a simple allometric method to predict the therapeutic effective dose in humans. Then, following clinical studies, we believe that the animal model might be expected to yield useful predictions of other drugs developed to treat the same condition. The methodology may not always be predictive, but the approach is so simple it should be investigated.

Potential Carbon Storage In The Forest Area Of Mount Merbabu National Park (MMbNP) Resort Selo Central Java

Forests play a very large function in the solution of climate problems. Trees are capable of absorbing carbon dioxide (CO2) in the photosynthesis process and store it in the form of biomass, thereby reducing the concentration of carbon in the atmosphere. The forest area of Mount Merbabu National Park (MMbNP) has great potential to absorb carbon emissions and mitigate climate. The purpose of this study was to determine the potential for carbon storage in MMbNP. The research method used is quantitative descriptive and analyzed by allometric method adapted to tree species at low, medium, and high densities. The estimated carbon storage refers to the Indonesian National Standard (SNI) 7724 of 2011. The potential for total carbon storage in the forest area is 129.357,71 tons. In detail, the total carbon storage in low density land cover types is 10.201,87 tons, medium density is 23.729.66 tons, and high density is 95.426,18 tons. This type of land cover with high density has the highest carbon absorption capacity; this is relevant to the presence of the number of trees that are able to absorb more carbon and have a larger area than other types of land cover.

КОМПЛЕКСНЫЙ ПОДХОД В ПАЛЕОРЕКОНСТРУКЦИЯХ ХАЗАРСКИХ ТРАНСГРЕССИЙ КАСПИЯ

Along with the malacofaunistic method, which is the main one for studying the paleo events of the Pleistocene, on which the system for diagnosing transgressions and their correlation on different coasts of the Caspian Sea is based, geomorphological and allometric methods were used in the work. Small rivers are very sensitive to small and short-term changes in sea level, which makes it possible to apply the geomorphological method for paleoreconstruction. An integrated approach makes it possible to diagnose a number of paleogeographic changes: fluctuations in sea level, passage of cold or warm currents, straits, changes in sea water temperature. According to the studied fossil complex, it is possible to obtain information about the parameters of the habitat of didacn, when comparing it with previous and subsequent ones, it is possible to judge the direction of paleogeographic events. The alternation of different complexes of bivalves, the use of morphometric characteristics of mollusk shells as an indicator of the ecological situation in the Quaternary period help to stratify the deposits in detail. The change in temperature and salinity of Paleocaspian waters is evidenced by the occurrence in Pleistocene sediments of representatives of didacnas of one of three groups (catillus, crassa, trigonoides). We have correlated the sections of the Khazar deposits of the Dagestan region.

Integrated morphometric and molecular analyses indicate three male morphotypes in the freshwater prawn Macrobrachium olfersii (Decapoda, Palaemonidae) along the Brazilian neotropical region

AbstractMales of Macrobrachium olfersii have a large cheliped (second pereiopod) with individual variations in shape and ornamentation, and they vary in size within and between populations. Some misidentification or doubts about taxonomic validity occur due to this morphological variability throughout their geographic distribution. We carried out a morphometric analysis to detect specific patterns and the potential occurrence of morphotypes in M. olfersii from different populations. Our data set included 52 females and 109 males collected in the Neotropical region, between the north and south limits of Brazilian territory, in coastal rivers from the states of Rio Grande do Norte, Bahia, Espírito Santo, Rio de Janeiro, São Paulo, Paraná and Santa Catarina. Body measurements were size standardized by allometric methods and explored by the principal component analysis (PCA) and non‐hierarchical analysis of K‐means clustering and canonical variate analysis (CVA). Our results suggested three distinct morphological groups (morphotypes) only for males in M. olfersii. Furthermore, the confirmation of monophyly of the different populations of M. olfersii was accomplished by sequences of 16S rDNA. Additional studies about relative growth in other populations and the analysis of the entire ontogenetic development of males in the laboratory will be important to complement the knowledge about morphotypes in this species.

Abstract 5457: QLH11811, a selective 4th-generation EGFR inhibitor for osimertinib-resistant EGFR-mutant NSCLC

Abstract Background: The 3rd-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), like osimertinib, provide marked clinical benefit for EGFR-mutant non-small cell lung cancer (NSCLC) patients with extended overall survival vs former EGFR TKIs (e.g., gefitinib). Approximate 10%-24% of NSCLC patients acquired C797S mutation when treated with osimertinib. Unfortunately, limited treatments are available for patients after osimertinib resistance. QLH11811 is a new generation EGFR TKI designed to target the EGFR with ex19del/L858R/T790M/C797S mutations. Here, we disclosed its preclinical data to support its clinical development in EGFR-mutant NSCLC. Methods: The inhibitory activity of QLH11811 on mutated and wild-type EGFR was tested in engineered cell lines and patient-derived organoid (PDO). The in vivo antitumor activity of QLH11811 was evaluated in the patient-derived xenograft (PDX) model with cis EGFR ex19del/T790M/C797S triple mutations, and the H1975 (cis EGFR L858R/T790M/C797S and cis EGFR ex19del/T790M/C797S), PC-9 (EGFR ex19del), and Ba/F3 (EGFR ex19del/C797S) cell line-derived xenograft (CDX) models. The pharmacokinetic (PK) profile was investigated in animals, and the human PK profile was projected using allometric scaling method. Results: QLH11811 displayed potent anti-proliferation activity against Ba/F3 (EGFR ex19del/T790M/C797S, L858R/T790M/C797S, ex19del/C797S, or L858R/C797S), PC-9 (EGFR ex19del/T790M/C797S), H1975 (EGFR L858R/T790M/C797S, L858R/T790M), H3255 (L858R) and HCC827 (ex19del) with IC50 of 2.6, 3.1, 2.4, 4.1, 51, 50, 27, 21, and 11 nM, respectively. QLH11811 also showed excellent selectivity when compared the above values with its IC50 against Ba/F3 (EGFR wild-type, 61 nM) and A431 (EGFR wild-type, 440nM). QLH11811 demonstrated excellent inhibitory activities against seven osimertinib-resistant PDO models. Daily oral QLH11811 significantly inhibited tumor growth at all doses tested (P &amp;lt;0.001) in the PDX model, the H1975, PC-9, and Ba/F3 CDX models. QLH11811 had good PK profile in mice, rats, dogs, and monkeys, with the absolute bioavailability at 71%, 29%, 80% and 42%. The human PK parameters were obtained by allometric scaling method, and the efficacious dose in human was projected to 103 mg, daily. Conclusion: The in vitro and in vivo preclinical data demonstrated QLH11811 is a highly potent and selective 4th-generation EGFR TKI with activity against the osimertinib-resistant NSCLC with EGFR C797S mutation. The preclinical PK data supported the efficacious dose of QLH11811 in human would be 103 mg. Citation Format: Shansong Zheng, Wei Deng, Qingmei Zheng, Yingying Yang, Na Li, Tan Pang, Xueying Feng, Simon Taylor, Lina Ma, Yaqiong Wu, Ziwei Zhao. QLH11811, a selective 4th-generation EGFR inhibitor for osimertinib-resistant EGFR-mutant NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5457.

Assessment of Carbon Stock and Carbon Sequestration Potential in three major density-based forest ecosystems of Tripura, North-East India

Forest ecosystems are playing major role in regulating the carbon cycle of the earth. We have investigated the vegetation carbon, below ground soil carbon, soil nutrient properties and carbon sequestration potential of three different density-based forest ecosystems viz ., Open forest (OP), very dense forests (VDF) and moderately dense forests (MDF) of Tripura, Northeast India. The tree biomass was analyzed by the allometric method of Nath et al. (2019) and IPCC (2019) default manual was chosen below-ground measurement. While the total biomass carbon was estimated with the manual of Brown et al. (1989) method. The SOC stock was analyzed by the formula of the Blanco-Canqui and Lal. (2008). It was observed that the three categories of forests have variation in carbon stock and carbon sequestration potential. The stand density recorded higher in OF , while the VDF recorded maximum basal area. The biomass-C and Sequestration potential were recorded higher in VDF and MDF respectively. The rate of the sequestration percentage was recorded highest in VDF and lowest in MDF. The SOC stock was observed maximum in MDF followed by OF and VDF. The Soil Physico-chemical properties have been showing variations along with the forest categories. However, these forests have been facing a greater number of anthropogenic disturbances, which decreases the species number and its richness to the wild day-by-day. We suggest more future studies on these forest types to explore ecosystem level carbon stock, and restored such systems for better understanding their role in carbon management.