Lower Flank Research Articles

Maternal Mediterranean Diet During Lactation and Infant Growth.

Background: Human milk is considered the optimal source of nutrition for infants. Maternal diet is associated with the composition of human milk. The Mediterranean diet (MedDiet) has been studied in pregnancy and during lactation, and it has been associated with changes in milk composition, yet there is a lack of research on MedDiet during lactation and infant outcomes. Methods: Mother-infant dyads (n = 167) from ABC Baby, a prospective observational study, were included in this analysis. Maternal diet was obtained using an adapted version of the National Cancer Institute Diet History Questionnaire II, at 2 weeks or 2 months postpartum. Maternal MedDiet score was calculated using servings of vegetables, fruits, whole grains, nuts and seeds, legumes, fish, monounsaturated-to-saturated fatty acid ratio, red and processed meats, and added sugar. Infants' length, weight, and flank skinfold thickness were measured at 6 months. Using World Health Organization standards, weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) Z-scores were calculated. Multiple linear regression models were adjusted for potential confounders. Results: Higher maternal MedDiet score and intake of fruit and fish were associated with lower flank skinfold thickness (β = -0.33, -0.52, and -1.26, respectively). Intake of nuts and seeds was associated with higher WLZ (β = 0.29). Intake of red and processed meats was associated with lower WAZ (β = -0.18) and LAZ (β = -0.18). Energy-adjusted added sugar intake was associated with lower WLZ (β = -0.02). Conclusions: The maternal MedDiet score was associated with lower skinfold thickness, while its components were associated with differences in anthropometric Z-scores. Further research on the maternal MedDiet and corresponding human milk composition is needed to explore this relationship.

Geomorphology of subaerial mud volcanoes in Azerbaijan: Issues about edifice construction and degradation

Mud volcanoes in Azerbaijan present some of the largest and most well-preserved edifices among all the onshore examples. We examined their morphology based on remote sensing and field observations. We classify the general shapes of the edifices into Type 1 (conical edifice), Type 2 (shield-like edifice), Type 3 (domed edifice) and Irregular (or compound). The associated landforms of the examined mud volcanoes are wide-ranging: mud flows, summit mud pies, summit craters/areas, gryphons and mud cones (small- and medium-scale vent structures), and salses (ponds of watery mud). The variety of such constructional landforms testify to the complex processes of mud emplacement modulated by the presence of fluids such as saline/connate waters and hydrocarbons. Degradation features include gullies, aeolian forms, steep slopes at lower flanks and reduced edifice sections due to human exploitation. The steep slopes at lower flanks are interesting since they may represent evidence for wave-cut erosion. The complex interplay of edifice construction and degradation is an important area of future study.

Effects of starting one lung ventilation and applying individualized PEEP right after patients are placed in lateral decubitus position on intraoperative oxygenation for patients undergoing thoracoscopic pulmonary lobectomy: study protocol for a randomized controlled trial

BackgroundFor patients receiving one lung ventilation in thoracic surgery, numerous studies have proved the superiority of lung protective ventilation of low tidal volume combined with recruitment maneuvers (RM) and individualized PEEP. However, RM may lead to overinflation which aggravates lung injury and intrapulmonary shunt. According to CT results, atelectasis usually forms in gravity dependent lung regions, regardless of body position. So, during anesthesia induction in supine position, atelectasis usually forms in the dorsal parts of lungs, however, when patients are turned into lateral decubitus position, collapsed lung tissue in the dorsal parts would reexpand, while atelectasis would slowly reappear in the lower flank of the lung. We hypothesize that applying sufficient PEEP without RM before the formation of atelectasis in the lower flank of the lung may beas effective to prevent atelectasis and thus improve oxygenation as applying PEEP with RM.MethodsA total of 84 patients scheduled for elective pulmonary lobe resection necessitating one lung ventilation will be recruited and randomized totwo parallel groups. For all patients, one lung ventilation is initiated the right after patients are turned into lateral decubitus position. For patients in the study group, individualized PEEP titration is started the moment one lung ventilation is started, while patients in the control group will receive a recruitment maneuver followed by individualized PEEP titration after initiation of one lung ventilation. The primary endpoint will be oxygenation index measured at T4. Secondary endpoints will include intrapulmonary shunt, respiratory mechanics, PPCs, and hemodynamic indicators.DiscussionNumerous previous studies compared the effects of individualized PEEP applied alone with that applied in combination with RM on oxygenation index, PPCs, intrapulmonary shunt and respiratory mechanics after atelectasis was formed in patients receiving one lung ventilation during thoracoscopic surgery. In this study, we will apply individualized PEEP before the formation of atelectasis while not performing RM in patients allocated to the study group, and then we’re going to observe its effects on the aspects mentioned above. The results of this trial will provide a ventilation strategy that may be conductive to improving intraoperative oxygenation and avoiding the detrimental effects of RM for patients receiving one lung ventilation.Trial registrationwww.Chictr.org.cn ChiCTR2400080682. Registered on February 5, 2024.

Mineralogy of Lateritic Weathering Profiles Developed on the Rocks under a Sub-equatorial Monsoon Climate: Case of the Bambouto Mountains

ABSTRACT The main objective of this work is to make a comparative assessment of the mineralogy on weathering profiles resulting from the alteration of the different rocks in an equatorial microclimate of altitude. This was carried out in the lower flank of the southern slope of the Bambouto Mountains. Mineralogical analysis and normative restructuring have given very interesting results on the profiles, between the basement rocks and the surface/cover rocks. Given that the alteration pathways of the basement rocks are different, they are similar within the zone of containment and potential leaching. Meanwhile, the cover rocks vary from one domain to another: virtual weathering, potential confinement, potential and virtual weathering, and induration. The alterological activity is very intense in the profile on trachybasalt. The predominant weathering processes in all cases are allitization and monosialitization, which are marked by a singular phenomenon of ferrolysis. The characteristic minerals of this profile are kaolinite and diopside. The weathering profile on biotite and hornblende granitoid is not very differentiated and is particularly rich in quartz (max: 40 weight-%) and microcline (max: 40 weight-%). The soils developed on granitoid, adopt elastic-fragile deformation to elastoplastics with sharp break in relation to the load applied. The alteration profile on orthogneiss is poorly differentiated, and thin, with a low degree of alteration. Hydrolytic alteration by monosiallitization marked this profile. This is particularly rich in quartz (max: 100 weight-%) and kaolinite (max: 57 weight-%). The profile on anatexite is particularly rich in quartz (max: 66 weight-%) and kaolinite (max: 40 weight-%). The normative restructuring confirmed over 98 weight-% of the various minerals obtained and thus made it possible to better characterize the alteration and its application in geotechnics. These soils constitute potential deposits of chromatogenic minerals: kaolinite, hematite, goethite, gibbsite, magnetite, biotite.

Comparing Bio-Ester and Mineral-Oil Emulsions on Tool Wear and Surface Integrity in Finish Turning a Ni-Based Superalloy

The paper compares the performance of two bio-ester and two mineral-oil emulsion metalworking fluids (MWFs) in finish turning an Inconel 718 alloy bar with a high hardness (HB 397 – 418). In this study, a coolant with a lean concentrate diluted at 6.5% to create an emulsion with stabilised water hardness was used to prepare each MWF. The finish-turning method used a small tool nose radius (0.4 mm) and small depth of cut (0.25 mm) to turn down 52.2 mm diameter bars in multiple passes to reach a maximum tool flank wear of 200 µm. In each MWF turning test, the tool flank wear, cutting forces, and surface roughness were measured against cut time. Chips from each MWF turning test were also collected at the same cut time instances. The surface and subsurface integrity on a workpiece obtained from each MWF turning test were compared by using a new unworn tool. Overall, for the machining parameters studied, the findings suggest the bio-esters were capable of equivalent machining performance as the mineral-oil emulsions, apart from one bio-ester that displayed improved surface roughness. Common to all MWF turning tests was a change in the chip form at low flank wear, which is discussed. Further findings discussed include the sensitivity of the concentration of the MWF diluted in the emulsion and the effect of the workpiece hardness within the batch used, with useful recommendations to improve the finish-turning method for the assessment of MWFs.

Tool wear and surface roughness characteristics in sustainable machining of additively manufactured titanium alloys

Titanium is widely acknowledged as a challenging metal due to its inherent characteristics. Manufacturers often encounter challenges such as tool wear, reduced tool lifecycle, and increased cutting heat when working with Ti64. This research investigates the cutting characteristics of additively manufactured (AMed) Ti64 under dry cutting, Minimum Quantity Lubrication (MQL), Cryogenic Carbon dioxide (CO2), and a hybrid approach combining MQL and CO2 conditions. Surface roughness, flank wear, temperature, chip morphology, and microhardness were analyzed to assess the impact of cooling strategies. Results indicate that the hybrid approach outperforms individual methods, showing superior surface finish and reduced tool wear. Machined Surface roughness (Ra) measurements reveal a substantial improvement in the hybrid condition, reducing Ra values by 62.44–67.02%, 35.65–41.38%, and 18.68–27.59% compared to dry, MQL, and CO2. Tool wear assessments exhibit significantly lower flank wear values in the hybrid condition, emphasizing the synergistic benefits of lubrication and cryogenic cooling. This research provides valuable insights into tailoring cooling strategies for optimal precision in machining AMed-Ti64 material, which is crucial for achieving high-quality manufacturing outcomes.

A Study on the Oil Film Thickness Between the Lower Rail of Oil Control Ring and Lower Flank of Oil Control Ring Groove of an Engine

Abstract Lubricating oil consumption (LOC) of engines causes particulate matter in exhaust gas and abnormal combustion like pre-ignition which becomes a serious problem in hydrogen engines. Lubricating oil transports upward into the combustion chamber of an engine via the sliding surface, the gap, and the side and back of a piston ring. The target of this study was to clarify the mechanism of oil flowing between an oil control ring lower flank and the groove which was the first entrance of lubricating oil supplied from the crankshaft. Oil film thickness at the lower flank of the oil control ring was measured by laser-induced fluorescence method using optical fibers embedded in the lower flank of the ring groove. The measured oil film thickness was compared with forces acting on the lower rail of three-piece type oil control ring. The oil film thickness change was well explained using those forces and it was found that friction force at the sliding surface and pressure in the ring groove were dominant on the oil film thickness under all operating conditions tested in this study.

Abstract A016: NXP800, a novel, small molecule GCN2 kinase activator, demonstrates potent single-agent activity in ARID1A and ARID1B-deficient endometrial cancer xenograft models

Abstract Background: NXP800 is a clinical stage, antineoplastic, oral, small molecule GCN2 kinase activator that was discovered in a phenotypic screen for inhibitors of the heat shock factor 1-regulated stress response. In a panel of human carcinoma cell lines NXP800 induced the expression of genes associated with activation of the integrated stress response and demonstrated robust antiproliferative activity, particularly in ARID1a-mutated ovarian carcinoma cells lines. In ARID1a-mutated ovarian carcinoma xenografts, treatment with NXP800 resulted in substantial tumor growth inhibition and tumor regression. NXP800 is currently being investigated in a Phase 1b clinical trial in patients with ARID1a-mutated ovarian carcinoma. Here we describe an in vivo study of NXP800 in ARID1a/ARID1b-deficient endometrial cancer xenografts, supporting the clinical development of NXP800 in this indication. Methods: Animal strain: CD1 Nude mice (nu/nu, Charles River). Human endometrial cancer cell lines: RL95-2 (ARID1a mutated, ATCC) and KLE (ARID1a wildtype, ARID1b mutated, ATCC), SNG-M (ARID1a mutated, Creative Bioarray). Xenograft tumors were generated by subcutaneous implantation on the right lower flank of the thigh at a cell density of 2 × 106 cells/mouse, at 0.1 ml Matrigel dilution volume/injection. Experiment groups: Vehicle, NXP800 (35 mg/kg); treatment: QD on days 0-4, 7-11, 14-18, 21-25, 28-30. Loss of ARID1A protein expression was confirmed by western blots. Results: In the SNG-M model, baseline tumor volume for the vehicle and NXP800 groups were 130.2, and 139.7 mm3, respectively, and on Day 32, average tumor volumes were 420.4, and 85.4 mm3, respectively, representing TGI of 81%. In the RL-95 model, baseline tumor volume for the vehicle and NXP800 groups were 124.5, and 129.9 mm3, respectively, and on Day 32, average tumor volumes were 773.8, and 190.3 mm3, respectively, representing TGI of 76%. In the KLE model, baseline tumor volume for both the vehicle and NXP800 groups were 88.1 mm3, respectively, and on Day 32, average tumor volumes were 216.4, and 18.9 mm3, for the vehicle and NXP800 groups, respectively, representing TGI of 91.3%. Conclusions: ARID1A and ARID1B genes encode the alternate, but obligatory, DNA-targeting subunit of the switch/sucrose non-fermentable (SWI/SNF) complex. ARID1A is the most frequently mutated SWI/SNF subunit across cancer types and is mutated in approximately 35% of endometrial carcinomas. NXP800 demonstrated robust antitumor activity in xenografts of endometrial carcinoma, a serious condition for which new treatment options are needed, including sustained tumor growth inhibition both in ARID1A and ARID1B mutated models, supporting the clinical development of NXP800 in endometrial cancer. Citation Format: Ramez N. Eskander, Bradley J. Monk, Brian M. Slomovitz, Enrique Poradosu, Allison Woods, Shay Shemesh, Paul Clarke, Robert Te Poele, Marissa Powers, Paul Workman, Shannon N. Westin. NXP800, a novel, small molecule GCN2 kinase activator, demonstrates potent single-agent activity in ARID1A and ARID1B-deficient endometrial cancer xenograft models [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A016.

An Investigation of Residual Stresses after the Turning of High-Tempered Bearing Steel

This study is focused on analysing residual stresses (RSs) after turning high-tempered bearing steel through the use of the X-ray diffraction (XRD) technique. Phase transformations expressed in terms of the near-surface white layer (WL) and the corresponding microhardness profiles are correlated with the RSs as well as the depth of the RS profiles. Normal and shear components of RS and FWHM (full width at half maximum) of the diffraction peaks are analysed as a function of cutting insert flank wear as well as the cutting speed. It was found that the influence of tool wear prevails over cutting speed, RSs tend to shift into the compressive region with increasing tool flank wear, and the valuable shear components of RSs can be found in the near-surface region when the cutting inserts of lower flank wear are employed. The increasing flank wear also increases the depth in which the compressive RSs can be found. Furthermore, surface RSs are affected by the phase transformation process (formation of re-hardened WL) as well as the superimposing mechanical and thermal load.

Influence of V concentration in TiAlSiVN coating on self-lubrication, friction and tool wear during two-pass dry turning of austenitic steel 316 L

The present work investigates the performance of TiAlSiVN coating with 5 and 11 at% of V concentration deposited on the Al2O3/SiC cutting tools during dry turning of austenitic 316 L stainless steel. The maximum flank wear reduction compared to the uncoated tool for coated tools with 11% and 5% V concentration was 85% and 67%, respectively. The Raman analysis indicated the formation of V2O5 in the cutting zone, which helps to reduce friction and machining forces for the coated tools. Overall, the presence of higher V content (11 at%) enhances the self-lubrication behaviour of the TiAlSiVN coating, accounting to lower fluctuations in cutting forces, superior surface finish, and lower flank wear when compared to the TiAlSiV5N coated and uncoated cutting tools.

Abstract LB_C04: Novel orally bioavailable macrocycles that target cyclin A and B elicit antitumor activity in breast cancer patient-derived xenograft models

Abstract Background: Cyclin/cyclin-dependent kinase (CDK) complexes regulate the activity of RB1 and E2F to drive cell cycle progression while ensuring fidelity of DNA replication. The interaction between cyclins and a critical subset of their substrates, including RB1 and E2F, is mediated by a conserved short linear RxL motif. RxL peptides have been shown to inhibit substrate phosphorylation by CDK2/cyclin A (AACR 2022 poster #5379). Previously, we have shown that macrocycles that selectively inhibit RxL-mediated binding to cyclins A and B (RxL inhibitors) lead to growth inhibitory activity in multiple cancer cell lines, and result in tumor regression in small cell lung cancer (SCLC) and ovarian cancer xenograft models (AACR 2023 poster #1560). Here, we test the antitumor activity of CID-016 in patient-derived xenograft (PDX) models from breast cancer. Methods: Bioinformatic analyses using RNA sequencing (RNAseq) and whole exome sequencing (WES) data from 39 breast cancer cell lines was employed to identify biomarker profiles that associate with sensitivity to CID-016. The antiproliferative activity of CID-016 was assessed by GI50 after 4-8 days of treatment. Hallmark pathway scores were calculated by Gene Set Variation Analysis (GSVA) method using MSigDb Hallmark collection from cell lines and existing PDX models. Based on the calculated hallmark pathway score, triple negative breast cancer (TNBC) PDX models were selected to test the anti-tumor activity of CID-016. In vivo, NMRI-Foxn1nu/nu mice were implanted with tumor fragments in the lower flank and treated with vehicle or CID-016 oral formulation of 50-100 mg/kg BID or 100 mg/kg QD, respectively for at least 28 days. Tumor volume and body weight were measured biweekly. Pharmacodynamic (PD) analyses will be conducted after treatment with CID-016. Results: Treatment of the breast cancer cell line panel with CID-016 demonstrated greater potency by GI50 in TNBC compared to other breast cancer cell lines (p=0.009). Gene expression levels of CCNB1, CCNA2, CCNE1 as well as target hallmark scores for “E2F targets”, “G2M checkpoint” and “Mitotic spindle” were significantly higher in TNBC vs other breast cancer cell lines. Oral treatment with CID-016 resulted in tumor regression in at least one triple-negative breast cancer PDX model and was well tolerated with no significant body weight changes. In vivo PD analyses will be assessed after 5 days of treatment with CID-016. Conclusions: The selective cyclin A/B RxL inhibitor CID-016 exhibits potent antitumor activity in TNBC preclinical models, consistent with the proposed mechanism of RB1/E2F pathway dysregulation. Given their compelling characteristics, orally bioavailable RxL inhibitors are advancing as the only first-in-class orally bioavailable dual inhibitors of cyclins A and B into clinical development. Citation Format: Mariana Paes Dias, Li-Fen Liu, Bernard Levin, Cristina Molina, Marta Guzmán, Olga Rodríguez, Evelyn W. Wang, Violeta Serra. Novel orally bioavailable macrocycles that target cyclin A and B elicit antitumor activity in breast cancer patient-derived xenograft models [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 LB_C04.

Abstract B162: NXP900, a novel YES1/SRC kinase inhibitor demonstrates inhibition of YAP1 nuclear localization and potent single agent anti-tumor activity in esophageal squamous cancer models

Abstract Background: NXP900 (eCF506) is a novel potent and selective SRC family kinase (SFK) inhibitor, (IC50 of 0.47 nM against YES1). NXP900 locks its target into its native “closed” conformation (type 1.5 inhibitor), thereby inhibiting both kinase activity and complex formation with protein partners (Temps et al. Cancer Res. 2021, 81, 5438-5450). In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active “open” conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Cell Rep 2021, 34, 108876). Crosstalk between YES1 and the Hippo pathway suggests that NXP900 may have therapeutic potential in cancers with Hippo pathway alterations. YES1 and Hippo pathway alterations are prevalent in several squamous cancers including esophageal (ESCC), lung, head and neck, and cervical. Methods: Animal strain: CD1 Nude mice (Charles River). Human ESCC cancer cell lines: KYSE70, OE21, KYSE410, KYSE30 and OE19 cells (Sigma), KYSE140 (DSMZ), TE5, and TE14 (Riken). Xenograft tumors were generated by subcutaneous implantation on the right lower flank of the thigh at a cell density of 2x106 to 1x107 cells/mouse. Experiment groups: Vehicle, NXP900 (40 mg/kg); treatment: QD for 28 days, oral gavage. Colony formation assay: 500 (KYSE70, OE21, KYSE410, KYSE30) or 1500 cells (OE19, TE5, TE14) were seeded in 24 well plates in triplicates and treated with NXP900 for 14 days followed by staining with crystal violet. KYSE70 and KYSE140 cells were treated with NXP900 for 24 hours before fixation and labelling with anti-YAP, phalloidin and hoechst. Images were analyzed using IN Carta® software. Expression and mutation status of hippo pathway modulators was determined by analysis of Dependency Map (DepMap) data. Results: NXP900 strongly inhibited cell proliferation of KYSE70, KYSE410, KYSE30, OE21, OE19, TE5 and TE14 in a colony formation assay. NXP900 significantly inhibited the activating phosphorylation of SRC in KYSE70 cells at 10 nM. Potent dose-dependent reduction in YAP1 nuclear localization was observed in ESCC lines. Oral administration of NXP900 in a KYSE70 xenograft mouse model with YES1 gene amplification, resulted in an average decrease of tumor volume of 71% while in the vehicle control group tumor volume increased by 472% (p ≤ 0.001), demonstrating significant tumor regression. Body weight measurements indicate good tolerability. Bioinformatics analysis demonstrate elevated expression and mutation of several hippo pathway modulators in ESCC cells responding to NXP900 in this study. Conclusions: NXP900 is a novel potent and selective YES1/SRC kinase inhibitor with subnanomolar IC50 against YES1. NXP900 potently inhibits YAP1 nuclear localization and cell proliferation in a panel of ESCC cell lines and induces tumor regressions in a KYSE70 xenograft model providing substantial proof of concept for targeting solid tumors with YES1 and Hippo pathway alterations. An IND for NXP900 has been cleared by the FDA and the start of the phase 1 study is pending. Citation Format: Neil O Carragher, Sweta Dash, Katherine Nyswaner, Mungo J B Harvey, Ben King, Allison Woods, Asier Unciti-Broceta, Enrique Poradosu, John Brognard. NXP900, a novel YES1/SRC kinase inhibitor demonstrates inhibition of YAP1 nuclear localization and potent single agent anti-tumor activity in esophageal squamous cancer models [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 B162.

A new snake of the genus Dendrelaphis Boulenger, 1890 (Squamata: Colubridae) from the coastal area of southern Vietnam.

We describe a new species of Dendrelaphis from the coastal area in southern Vietnam based on morphological data and nucleotide sequences from one partial mitochondrial gene (Cytb). Dendrelaphis binhi sp. nov. is diagnosed by the following morphological characters: body scale rows 13 at neck and midbody, 9-11 before vent; vertebral scale row feebly enlarged; ventrals 154-158 in males and 161-170 in females; subcaudals 95-106 in males and 95-102 in females; one supralabial touching the eye; 18 or 19 maxillary teeth; hemipenis spinose, reaching 10th or 11th SC, with a slender papilla; cloacal plate divided; dorsum dark brown; and a white stripe along the lower flank. The new species differs from its congeners by an uncorrected p-distance in Cytb sequences of at least 8.1%.

Dystocia in Miniature Horses and Shetland ponies: assisted vaginal delivery, fetotomy and field Caesarean section

Dystocia in the horse is a life-threatening emergency. Prompt and effective intervention is essential to improve the outcome for both mare and foal. Resolution is possible via assisted vaginal delivery, controlled vaginal delivery, fetotomy or Caesarean section. Guidelines exist but the final choice is influenced by several factors including fetal viability, duration of dystocia, availability of obstetric assistance and financial considerations. The purpose of this study was to report our experience in the management of dystocia in Miniature horses and Shetland ponies. Data were collected from the records of 17 mares treated between 2020 and 2022. According to the clinic's protocol, correction was first attempted by assisted vaginal delivery; in case of failure, fetotomy or Caesarean section was performed. All mares were referred to the clinic after prolonged labor and only 2 (12%) were presented with their foal still alive. In 8/17 mares, the foal was delivered via assisted vaginal delivery. In 6/17 mares, a partial fetotomy was performed. In the 3 remaining cases, a conventional Caesarean section was proposed but not considered due to its financial cost; a field Caesarean section was therefore performed. General anesthesia was maintained using a continuous rate infusion of triple drip consisting of a combination of 250 ml sodium chloride (0.9%), 250 ml guaifenesin (10%), 20 ml ketamine (10%) and 1 ml detomidine (1%).After local anesthesia, a low left flank celiotomy in lateral recumbency was performed. Overall survival rate of the presented mares was 59% (10/17). Mares’ survival rates following assisted vaginal delivery, fetotomy and field Caesarean section were respectively 63% (5/8), 33% (2/6) and 100% (3/3). Both foals alive at arrival survived delivery and one (6%) survived to discharge. While in warmblood horses, fetotomy has been proven rapid and safe (Norton et al. Equine Vet J 2007;39:37-41), in small breeds the feasibility of fetotomy is largely hampered by their body size and is deemed too stressful for the exhausted mares. In addition, complications after dystocia are aggravated in small breeds due to the high risk of hypertriglyceridemia and consequently hyperlipemia. Hypertriglyceridemia was determined in 35% (6/17) of the mares and hyperlipemia was the cause of death in 3 out of these 6 mares. Caesarean section is associated with several complications, such as retained placenta, metritis, laminitis and uterine hemorrhage. Due to a lack of asepsis in a non-optimal setting, peritoneal or incisional infections could be a weak point of the field Caesarean section. Our results, supported by those of others (Gandini et al. Reprod Dom Anim 2013;48:49-51), are promising for considering field Caesarean section as a preferable resolution to dystocia in Miniature horses and Shetland ponies.

Preclinical efficacy of NXP900, a YES1/SRC kinase inhibitor in esophageal squamous cancer models.

e15133 Background: NXP900 (eCF506) is a novel potent and selective SRC family kinase (SFK) inhibitor, (IC50 of 0.47 nM against YES1). NXP900 locks its target into its native “closed” conformation (type 1.5 inhibitor), thereby inhibiting both kinase activity and complex formation with protein partners (Temps et al. Cancer Res. 2021, 81, 5438-5450). In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active “open” conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation of conformational protein activation (Higuchi et al. Cell Rep 2021, 34, 108876). YES1 gene amplification is prevalent in several squamous cancers including esophageal squamous cell carcinoma (ESCC), lung SCC, head and neck SCC, and bladder cancer, indicating that YES1 would be an attractive target in these cancer types. Moreover, crosstalk between YES1 and the Hippo pathway suggests that NXP900 may have a therapeutic potential in squamous cancers with Hippo pathway alterations. Methods: Animal strain: CD1 Nude mice (Charles River). Human ESCC cancer cell lines: KYSE70, OE21, KYSE410, KYSE30 and OE19 cells (Sigma), TE5, and TE14 (Riken). Xenograft tumors were generated by subcutaneous implantation on the right lower flank of the thigh at a cell density of 2x106 to 1x107 cells/mouse at 0.1 mL Matrigel/cell dilution volume per injection. Experiment groups: Vehicle, NXP900 (40 mg/kg); treatment: QD for 28 days, oral gavage. Colony formation assay: 500 cells of 4 cell lines (KYSE70, OE21, KYSE410 and KYSE30) and 1500 cells of 3 cell lines (OE19, TE5 and TE14) were seeded in 24 well plates in triplicates; and treated with NXP900 for 14 days followed by staining with crystal violet. Results: NXP900 strongly inhibited cell proliferation of KYSE70, KYSE410, KYSE30, OE21, OE19, TE5 and TE14 in a colony formation assay. NXP900 significantly inhibited the activating phosphorylation of SRC in KYSE70 cells at 10 nM, while no effect was observed on the inhibitory tyrosine residues on YES1/FYN at 250 nM. Oral administration of NXP900 in a KYSE70 xenograft mouse model with YES1 gene amplification, resulted in an average decrease of tumor volume of 71% while in the vehicle control group tumor volume increased by 472% (p ≤ 0.001), demonstrating significant tumor regression. On Day 27, a mean increase from baseline in body weight of 2.0% and 3.5% was seen in the NXP900 and control groups respectively, indicating good tolerability. Conclusions: NXP900 is a novel potent and selective YES1/SRC kinase inhibitor with subnanomolar IC50 against YES1. NXP900 has marked antitumor efficacy in esophageal carcinoma models in vitro and in vivo providing substantial proof of concept for targeting solid tumors with YES1 and Hippo pathway alterations. IND enabling studies for NXP900 have been completed.

STUDY THE EFFECTS OF THE MULTINITE COAT OF THE HIGH SPEED STEEL DRILL BIT IN DRILLING

Drilling is an important metal manufacturing processes. Drill bits are used in drilling to create holes. Wear of drill bits can have an adverse effect on the quality of the drilling hole. To increase the wear resistance of drill bits, surface modifications have been introduced and studied their effectiveness. Multinite coating is a candidate for surface modification techniques to increase wear resistance of the drill bits. In this study, the effect of multinite coating on the wear resistance of drill bits has been investigated. Two types of 6 mm diameters drill bits, the uncoated high speed steel, and the multinite coated high speed steel drill bits, were used to create the hole with 30 mm in depth on ASTM A36 steel. The drilling parameters were 1,100 rpm of rotation speed and 135 mm/min of the feed rate. The thrust force and the cutting torque during drilling were measured by a force sensor. Flank wear on the drill bits were measured by overlap image technique. Also, the roughness of hole surfaces were investigated. Results showed that the higher surface hardness of multinite coated high speed steel drill bit led to a lower flank wear rate at the beginning of drilling. Consequently, built-up of chip on the multinite coated high speed steel drill bit was less compared to the uncoated one. We conclude that the higher surface hardness of multinite coated high speed steel drill bit improves the wear resistance of drill bit by a decrease of wear rate at the beginning of drilling and a lesser amount of chip built-up on the cutting edge and the surface quality of hole after drilling.

Deep‐water sedimentary systems and tectono–sedimentary interactions on the oblique convergent margin in Antarctica

ABSTRACTActive continental margins are tectonic sites with complex sedimentary processes. Tectono–sedimentary interactions occur over geological time and determine the modern morphology of the margin. However, such interactions have been poorly documented in high‐latitude regions. This study focuses on deep‐water sedimentary systems on the South Shetland convergent margin, which is the only remaining active continental margin in Antarctica. Numerous gullies, 20 canyons and three contourite drifts are identified by interpreting bathymetry, oceanography and reflection seismic data. Heavy mineral contents of a gravity core, located at a downslope elongated mounded drift, show the asynchronous interplay of downslope and alongslope processes. The rest of the margin is dominated by turbidity currents. Variations in the slope gradient control thalweg profiles and sinuosity of canyons. Tectonic‐related morphology restricts the distribution of contourite drifts. Earthquakes triggered by underplating and tectonic compression may induce slope instability at the lower flank of the plastered drift. Tectonic uplift influences the amount of sediments transported by ice sheets and controls the shelf stacking pattern. The mixed turbidite–contourite system transitions to separated canyon and drift systems from passive to active continental margins under the influence of the tectonic‐related morphology. A systematic comparison has been made among several convergent margins with similar tectonic settings. Results suggest that submarine canyons on these shelf‐slope systems have similar morphological features and are comparable in size. Coarse sediment input and steep continental slopes (mean slope 7 to 10°) control the canyon morphology on these margins. Therefore, this research has important implications for furthering the current understanding of sedimentary systems on high‐latitude convergent margins and tectono–sedimentary interactions.

Evaluation of the Anti-Metastatic Effect of Foeniculum Vulgare on the Protein Expression of HSP 70 & 90 in Balb/c Mice with 4t1 Model of Breast Cancer.

Breast cancer is one of the important factors of cancer-related deaths. Considering the drug resistance, special attention has been paid to natural compounds. This study aimed at evaluating the anti-metastatic activity of fennel in a breast cancer mouse model. A total of 35 adult female BALB/C mice were used in this study. Breast cancer was induced by subcutaneous injection of 4T1 cells in the right lower flank. The mice received fennel extracts daily via intraperitoneal injection for two weeks. Meanwhile, tumor volume was measured every day using calipers. After two weeks, each animal was anesthetized. The protein expression of HSP 70 & 90 was measured in liver tissue and ovary. The expression of her2 was measured in tumor tissue. The activity of Glutathione peroxidase and reductase as anti-oxidant agents were measured in serum. Tumor size significantly decreased after nine days' treatment of the fennel. The expression of HER2 increased in the tumor tissue and decrease with different dose of fennel. Fennel treatment caused a decrease in the protein expression of HSP 70 & 90 in the liver tissues. Based on our findings, fennel has anti-tumor and anti-metastatic activities against aggressive cancers.

Detection of Copper by the ChemCam Instrument Along Curiosity's Traverse in Gale Crater, Mars: Elevated Abundances in Glen Torridon

AbstractLaser‐induced breakdown spectroscopy, as utilized by the ChemCam instrument onboard the Curiosity rover, detected enhanced abundances of the element copper. Since landing in Gale crater (6 August 2012), 10 enhancements in copper abundance were observed during 3007 Martian days (sols) of rover operations and 24 km of driving (as of 20 January 2021). The most prominent ones were found in the Kimberley area on the crater floor (Aeolis Palus) and in Glen Torridon (GT) on the lower flanks of Aeolis Mons (Mt. Sharp). Enhancements in copper record the former existence of modestly acidic and oxidizing fluids, which were more oxidizing in Kimberley than in GT. Of the two main types of bedrock in the lowest part of GT, Mg‐rich “coherent” and K‐rich “rubbly” (named based on their outcrop expression), copper was detected only in coherent, not in rubbly bedrock. The difference between these two types of bedrock may be due to difference in provenance. Alternatively, based on a recently developed lacustrine‐groundwater mixing model, we suggest that rubbly bedrock was altered by modestly acidic, shallow‐subsurface lake water that leached out both copper and manganese, while coherent bedrock was affected by dominantly alkaline fluids which would be consistent with its mineralogical composition (including siderite) as returned by the CheMin instrument onboard the rover. Higher up in GT, ChemCam data indicated significant gradients in the copper concentration in coherent bedrock on a local scale of only a few meters, which suggests a different alteration style and possibly different types of diagenetic fluids.

Study of Residual Stresses and Austenite Gradients in the Surface after Hard Turning as a Function of Flank Wear and Cutting Speed.

This paper investigates the influence of cutting speed and flank wear on the depth profile of residual stresses, as well as the fraction of retained austenite after hard turning of quenched bearing steel 100Cr6. Residual stress and retained austenite profiles were studied for the white layer, heat-affected zone thickness, and XRD sensing depth. It was found that the influence of flank wear on the white layer and heat-affected zone thickness predominates. On the other hand, residual stresses are affected the cutting speed and the superimposing contribution of flank wear. Moreover, these aspects also alter microhardness in the affected regions. The study also demonstrates that information concerning residual stresses and the austenite fraction is integrated into the white layer, and the heat-affected zone in the surface is produced by the insert of low flank wear since the XRD sensing depth is more than the thickness of the white layer. On the other hand, the pure contribution of the white layer or the heat-affected zone to residual stress and the austenite fraction can be investigated when the affected surface region is thick enough.