Minimal Penetration Research Articles

Chemical Solution Mitigates Stuck Inflow Control Devices in Horizontal Completion

Summary Horizontal open holes covering long reservoir sections can be benefitted by installing inflow control devices (ICDs) along the lateral to even the production contribution from the entire heterogeneous permeability profile. During the drilling and completion process, the well can be shut in for prolonged periods of time. Though the ICDs are designed to withstand the buildup of debris, they are still subjected to the accumulation of weighting and bridging materials existing in the drilling fluid, such as calcium carbonate (CaCO3). This debris deposits on the internal diameter of the valves or the flow control device, preventing proper shifting against the seats, or blocking the flow path of the devices. Recovering the function of the ICDs requires a chemical treatment. In high-permeability formations, it is undesirable to have acid contact the rock since this may compromise the mechanical integrity of the formation or trigger further solids buildup in the ICDs. Therefore, an acid designed to dissolve the solid deposits on ICDs but not penetrating the formation is required. In this study, a modified coreflood setup was designed and an acid-based chemical treatment was formulated to remove solid deposition on the ICD. The goal was to dissolve the CaCO3 scale on the ICD with minimal penetration into the formation to avoid formation softening. The core assembly simulates the geometry of the ICD completion system with a core matrix behind the ICD operating space. Calcite marble was used to represent the scale deposited on the ICDs, while Indiana limestone was used to represent the reservoir rock. Several acid formulations were tested using the custom-designed coreflood setup. One acid blend composed of a strong organic acid [methane sulfonic acid (MSA)] mixed with hydrochloric acid (HCl) and a second blend of HCl and mutual solvent (glycol-based solvent) showed the desirable effect of dissolving the scale deposits (calcite marble in this case) with minimum to no penetration into the formation matrix. The success of the two acid systems in dissolving CaCO3 deposits on the ICDs was confirmed by analyzing the pressure data during the coreflooding experiment, as well as from analyzing the post-treated core samples using computed tomography (CT) scan. Simulation of completion design in the laboratory is a key factor in testing and designing acid treatments to overcome scale problems in the field. Single-phase acid systems containing no gelling or emulsifying agents were tested and proved capable of dissolving the solids deposited on the ICDs with minimum to no formation contact. This will result in an economical and easier one-step treatment in the field, avoiding the complexity encountered with pulling the whole completion string out of the wellbore to be treated with acid on the surface and then reinstalling it back into the well.

Synthesis and characterization of Cobalt-chromium based alloys via spark plasma sintering for biomedical applications

The present study investigates the impact of Mo and Nb on the characteristics of CoCr sintered alloys, with a specific focus on their potential for biomedical applications. Cobalt-chromium-based alloys (namely, Co-Cr-2.5Mo-2.5 Nb, Co-Cr-3Mo-3 Nb, and Co-Cr-3.5Mo-3.5 Nb) were fabricated using sintering conditions comprising a heating rate of 200 °C/min, pressure of 50 MPa, temperature of 1100 °C, and a dwell period of 15 minutes. The findings indicated that the CoCr alloy, when supplemented with Mo and Nb, exhibited a singular-phase composition consisting mostly of a face-centered cubic (FCC) core comprised of gamma-Co, accompanied by a minor proportion of a hexagonal close-packed (HCP) solid solution matrix known as epsilon-Co, and interspersed with precipitates. The inclusion of Co-Cr-3Mo-3 Nb alloy composition resulted in the highest relative density of 97.56 % compared to other alloy compositions, indicating its optimum alloying properties. The Co-Cr-3Mo-3 Nb alloy had the maximum polarization resistance of 522.52 Ω, indicating a strong resistance to corrosion. Additionally, it displayed the least corrosion rate of 1.5904 mm/year. The ternary alloy consisting of Co-Cr-3.5Mo-3.5 Nb demonstrated superior resistance to the applied indentation stress, as shown by its minimal maximum penetration depth of 372.23 nm and the lowest average coefficient of friction (COF) values.

Selection of the Process of Arc Welding of Sealing Surfaces of Power Valves with a Consumable Electrode in the Shielding Gas

Introduction. One of the main requirements to the methods of weld overlay of sealing surfaces of power valve trim parts is to obtain a high-quality wear-resistant pad with minimal penetration and optimal process performance. Currently, arc, electroslag, plasma, beam, induction and other surfacing techniques have been developed and introduced into production. However, the influence of various arc welding processes with a consumable electrode in shielding gas on the geometric parameters of weld beads and metal hardness of sealing surfaces is understudied. The presented research is intended to fill this gap. The objective of its authors is to select such a process of arc welding of beads on parts of the power valve trim with a consumable electrode in shielding gases, which would provide the best workability of the deposited metal.Materials and Methods. Arc surfacing with a consumable electrode in a mixture of gases was performed on steel plates. The welding torch was moved in a straight line, without transverse oscillations, using the FRC-9 mechanism (Fronius). A microprocessor-controlled inverter-type digital current source TransPulsSynergic 3200 CMT (Fronius) was used as the power supply. The following welding processes were analyzed: MIG/MAG process with self-regulation (Standard mode), synergic process of MIG/MAG method (Synergic mode), short arc process with mechanical separation of electrode metal droplets (CMT-ColdMetalTransfer), and synergic pulse-arc process (PulseSynergic). The short-cut process of bead surfacing was evaluated by the stability of the values of the energy parameters of the bead surfacing mode in time at the same electrode wire feed rates, which were recorded by oscilloscopes, as well as by comparing the geometric characteristics of the deposited beads and the hardness of the deposited metal.Results. The analysis of experimental data of the geometrics of the weld beads and their complex dimensional characteristics made it possible to establish that the welding engineering requirements for the welded beads are most fully met by long-arc surfacing by the PulseSynergic pulse-arc process.Discussion and Conclusion. The study and the resulting data make a certain contribution to solving the problem of the influence of arc welding processes on the parameters of weld beads and on the hardness of the metal of sealing surfaces. A detailed analysis of the modes of arc surfacing of beads with a consumable electrode in shielding gases on the trim parts of power valves can be used in further research on this topic. The conclusions of the authors will not only provide considerable theoretical assistance to scientists, but will also make adjustments to the activities of practitioners.

Abstract PR001: Discovery of Etrumadenant, a first-in-class dual A2a and A2b adenosine receptor antagonist for cancer immunotherapy

Abstract High levels of adenosine are generated in the tumor microenvironment (TME) by sequential hydrolysis of extracellular ATP by the ecto-nucleotidases CD39 (ATP→AMP) and CD73 (AMP→adenosine). Adenosine activates A2a and A2b adenosine receptors on immune cells, resulting in immunosuppression. Since A2aR is expressed by a variety of lymphocytes, the suppressive effects of adenosine on this cell type can be potentially reversed by blocking the A2aR. In contrast, myeloid cells that have comparable expression of A2aR and A2bR require dual A2a/bR blockade for full reversal of the immunosuppressive effects of adenosine. The first generation of adenosine antagonists deployed in oncology were repurposed CNS drug candidates with properties that were deemed less than optimal for anti-tumor efficacy (e.g., A2aR-selective, good BBB permeability, not optimized for minimal plasma protein binding, etc.). We sought to design a potent and selective dual antagonist of A2aR and A2bR to effectively block the high concentrations of adenosine found in tumors, with diminished brain penetration, and minimal non-specific binding to plasma proteins. Using a pharmacophore mapping approach, we discovered potent A2aR antagonists with favorable PK profile in rats, good selectivity, and moderate potency against A2bR. Systematic SAR studies led to improvement in A2bR potency, which ultimately resulted in Etrumadenant (AB928). Etrumadenant inhibits both A2aR and A2bR with similar potencies (KB: 1.4 nM and 2 nM, respectively), and is highly selective against other targets in the adenosine pathway with minimal penetration across the blood brain barrier. Etrumadenant provides superior dendritic cell activity compared to A2aR antagonist alone. Its combination with immunogenic chemotherapy enhances immune activity and suppresses tumor growth and metastasis in vivo. These data support our rational design of a dual A2a and A2b adenosine receptor antagonist to impact adenosine biology on multiple cell types within the TME. Etrumadenant is currently undergoing phase 2 clinical trials in colorectal and lung cancer patients. Citation Format: Ehesan U. Sharif, Dillon H. Miles, Brandon R. Rosen, Joel Beatty, Jenna L. Jeffrey, Laurent P. P. Debien, Rhiannon Thomas-Tran, Debashis Mandal, Dan Direnzo, Sachie Marubayashi, Kristen Zhang, Ferdie Soriano, Elaine Ginn, Divyank Soni, Pei-Yu Chen, Lixia Jin, Steve W. Young, Matt J. Walters, Manmohan R. Leleti, Jay P. Powers. Discovery of Etrumadenant, a first-in-class dual A2a and A2b adenosine receptor antagonist for cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr PR001

Investigation of sub-nm binary oxidic surface modifications on mixed ionic electronic conductors with ToF-SIMS: Oxidic overlayer stability and ionic interdiffusion behavior

Modifications of mixed ionic electronic conductor (MIEC) surfaces are a promising approach to improve oxygen exchange reaction (OER) kinetics and can have a tremendous impact on surface charges and secondary ion yields. Utilizing time-of-flight secondary ion mass spectrometry (ToF-SIMS), we examined degradation, segregation, and cation interdiffusion behaviors on La0.6Sr0.4CoO3-δ (LSC) and Pr0.2Ce0.8O2-δ (PCO) thin films modified with ∼0.5 nm CaO, TiO2, and SnO2 overlayers after annealing at 700 °C and 800 °C, respectively. Surface profiles (AFM; ToF-SIMS) and depth profiles (ToF-SIMS) revealed structural and chemical transformations, including particle formation and surface roughening. The overlayer stability varied significantly for different overlayers on the same material and for the same overlayer on LSC and PCO. All oxidic overlayers were more stable on PCO than LSC. Depth profiling indicated that 40Ca+ ions penetrated the entire LSC and PCO layers (30 nm). 48Ti+ aligns more accurately with a typical analytical solution to Fick’s diffusion equation for finite systems, showing higher diffusion coefficients in LSC than PCO. 120Sn+ exhibited minimal penetration, indicating high stability on the surface and less intermixing with either MIEC. These results hint at the need to differentiate between the stability of the binary oxides on the surface and the bulk diffusivity.

Curation and reporting of pathogenic genome-wide copy-number variants in a prenatal cell-free DNA screen.

Advances in fetal fraction amplification in prenatal cell-free DNA screening now allow for high-resolution detection of copy-number variants (CNVs). However, approaches to interpreting CNVs as part of a primary screen are still evolving and require consensus. Here, we present a conservative, patient-centered framework for reporting fetal CNVs. Syndromes described in the literature were evaluated for inclusion based on a definable minimal critical region, disease severity, penetrance, and age of onset. The reporting framework required that a CNV overlap a defined minimal critical region and/or that it be ≥5 Mb and contain at least 1 OMIM disease-associated gene. This framework was then applied to CNVs identified from a cohort of 313,544 prenatal cfDNA screening patient samples. Patient-friendly terminology describing syndrome phenotypes was developed by scientists with training in genetic counseling. 65 syndromes met criteria for inclusion and represented the second most common class of CNVs in a retrospective cohort, more so than an established panel of microdeletions (1p36, 4p, 5p, 15q11.2-q13, and 22q11.2). Frequencies were concordant with reported syndrome incidence rates. The most common CNVs were those ≥5 Mb encompassing an OMIM disease gene(s). This framework for genome-wide fetal-CNV reporting carefully prioritizes findings with the potential to affect reproductive decision making.

Ambient light spectrum affects larval Mexican jumping bean moth (Cydia saltitans) behavior despite light obstruction from host seed

Spectral differences in ambient light can affect animal behavior and convey crucial information about an individual’s environment. The ability to perceive and respond to differences in ambient light varies widely by taxa and is shaped by a species’ ecology. Mexican jumping bean moths, Cydia saltitans, spend their entire larval period encased in fallen host seeds and contend with potentially lethal environmental temperatures when host seeds are in direct sunlight. We investigate if and how C. saltitans larvae in host seeds respond to lighting conditions associated with these thermal risks. In a temperature-controlled experiment, we identified that larvae demonstrated distinct behavioral (“jumping”) responses corresponding to four lighting treatments (white, red, green, and purple), despite extremely minimal light penetration through host seed walls. Red light induced the greatest larval activity (measured by probability of movement and by displacement from origin), suggesting that larvae have mechanisms to perceive low levels of red light and/or to detect subtle increases in heat produced by red/near infrared-biased light spectra, possibly providing them with an early-warning mechanism against thermal stress. Our findings highlight the interplay of environmental lighting, behavior, and potential thermosensory adaptations in a species with a visually constrained environment.

Unveiling the potential of phytochemicals to inhibit nuclear receptor binding SET domain protein 2 for cancer: Pharmacophore screening, molecular docking, ADME properties, and molecular dynamics simulation investigations.

Nuclear receptor binding SET domain protein 2 (NSD2) significantly contributes to the development of cancer, making it a promising target for cancer drug discovery. This research explores natural compounds as potential selective inhibitors for NSD2 in cancer treatment. Employing a comprehensive in silico approach, the study utilized pharmacophore modeling, molecular docking, pharmacokinetic profiling, and molecular dynamics simulations. An e-pharmacophore model-based screening using the first selective and potent ligand bound to NSD2 identified 49,248 natural compounds from the SuperNatural 3.0 database (containing 449,008 molecules) with acceptable alignment with the developed pharmacophore hypotheses. Subsequently, molecular docking was executed to assess the standout compounds which led to the selection of ten candidates that surpassed the reference inhibitor in accordance w the binding affinity expressed as a G score. Ligand-residue interaction analyses of the top three hits (SN0450102, SN0410255, and SN0142336) revealed diverse crucial interactions with the NSD2 active site, including hydrogen bonds, pi-pi stacking, and hydrophobic contacts with key amino acid residues in the NSD2-PWWP1 domain. Pharmacokinetic profiling confirmed the drug-likability for the refined hits, indicating good cellular permeability and minimal blood-brain barrier penetration. Molecular dynamics simulations for 200 nanoseconds affirmed the stability of protein-ligand complexes, with minimal fluctuations in root mean square deviation and root mean square fluctuation analyses. Overall, this study identified promising natural compounds as potential pharmaceutical agents in the treatment of NSD2-associated cancers.

Microleakage Assessment of Modified Resin Infiltration With Zinc Oxide (ZnO) and Magnesium Oxide (MgO) Nanoparticles on Artificial Enamel Caries Lesion: An In Vitro Study.

Background Incorporating nanoparticles into resin infiltrant (RI) can alter its physical properties, including microleakage. This study aimed to examine the microleakage properties of RI modified with 2.5% and 5% zinc oxide (ZnO) and magnesium oxide (MgO) nanoparticles on artificially induced carious lesions (ACLs) in bovine teeth. Materials and methods Modified RIs were applied to five sound and 30 ACLs on bovine incisors. They were divided into seven groups based on the procedure (Group 1: sound enamel (SE), Group 2: artificial caries lesion only (ACL), Group 3: RI, Group 4: RI+ 2.5% ZnO, Group 5: RI + 5% ZnO, Group 6: RI + 2.5% MgO, Group 7: RI + 5% MgO). The samples were subjected to 5000 thermal cycles and then exposed to methylene blue solution for 24 hours in an incubator. The teeth were sectioned and examined with a stereomicroscope to assess the depth of methylene blue penetration (MBP), quantifying microleakage according to the following scoring: 0 = no penetration, 1 = outer half of enamel, 2 = inner half of enamel, 3 = outer half of dentin, and 4 = inner half of dentin. An ANOVA test was conducted to assess the significance of differences among the groups. Post-hoc tests, including Tukey's HSD (honestly significant difference) test, were performed to identify specific group differences and determine which differences were statistically significant. Results SE samples (Group 1) showed minimal penetration, with 100% scoring 1, indicating high resistance to MBP. The ACL group had significant penetration, with 77.78% scoring 3 and 22.22% scoring 2. The RI group completely prevented MBP, with all samples scoring 0. Both RI+2.5% ZnO (Group 4) and RI+2.5% MgO (Group 6) were highly effective, with 88.89% scoring 0 and 11.11% scoring 1. RI+5% ZnO (Group 5) and RI+5% MgO (Group 7) also prevented MBP but had slightly higher minimal penetration, with 77.78% scoring 0 and 22.22% scoring 1. Significant differences were observed between the ACL group and all other groups, underscoring the effectiveness of RI treatments. No significant differences were found between RI+ZnO and RI+MgO at both concentrations, indicating similar effectiveness. Conclusions The study demonstrated that RI modified with 2.5% and 5% ZnO and MgO nanoparticles effectively reduced microleakage in ACLs on bovine teeth compared to untreated lesions. These modifications significantly inhibited MBP, particularly in enamel and dentin, indicating their potential to enhance the durability and effectiveness in clinical applications. This research emphasizes the promising role of nanoparticle-modified RI in minimizing microleakage and optimizing treatment outcomes. Further research is needed to confirm these findings and refine protocols.

On exploiting nonparametric kernel-based probabilistic machine learning over the large compositional space of high entropy alloys for optimal nanoscale ballistics

The large compositional space of high entropy alloys (HEA) often presents significant challenges in comprehensively deducing the critical influence of atomic composition on their mechanical responses. We propose an efficient nonparametric kernel-based probabilistic computational mapping to obtain the optimal composition of HEAs under ballistic conditions by exploiting the emerging capabilities of machine learning (ML) coupled with molecular-level simulations. Compared to conventional ML models, the present Gaussian approach is a Bayesian paradigm that can have several advantages, including small training datasets concerning computationally intensive simulations and the ability to provide uncertainty measurements of molecular dynamics simulations therein. The data-driven analysis reveals that a lower concentration of Ni with a higher concentration of Al leads to higher dissipation of kinetic energy and lower residual velocity, but with higher penetration depth of the projectile. To deal with such conflicting computationally intensive functional objectives, the ML-based simulation framework is further extended in conjunction with multi-objective genetic algorithm for identifying the critical elemental compositions to enhance kinetic energy dissipation with minimal penetration depth and residual velocity of the projectile simultaneously. The computational framework proposed here is generic in nature, and it can be extended to other HEAs with a range of non-aligned multi-physical property demands.

Effects on cerebral blood flow after single doses of the β2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, β-adrenoceptor (β-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant β2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, β2-AR agonist clenbuterol (20-160 μg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5mg), a β-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral β2-AR responses. Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3h after 20, 40, 80 and 160 μg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 μg clenbuterol were observed both without and with 5mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of β2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful β2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Without mandated demand for greenhouse gas removal – High integrity GtCO2-scale global deployment will be jeopardized: Insight from US economic policy 2020–23

Greenhouse gas removals (GGRs) will be essential at GtCO2-scale to offset residual emissions and achieve global net zero by 2050. Engineered GGRs have the greatest long-term, large-scale CO2 storage potential and, therefore, offer opportunities to realize high-integrity removals. However, the most prominent engineered solutions are capital-intensive, generate expensive offset credits, and have achieved minimal market penetration. The United States has established policies subsidizing GGR deployment value chains which generate high-integrity removals to bring down engineered GGR costs. The US regime has the potential to result in substantial GGR cost reductions which will likely have implications on the policy frameworks for global GGR technology deployment. To date, research addressing the impact of US policies on the commercial imperatives and investment uncertainties for the global GGR sector is limited. Using a mixed methods approach, this contribution unpacked the motivations of early private sector actors. It did this by identifying characteristics of the most investable GGR business models and policy implementation requirements to establish the nascent sector, which will be critical to the GGR sector becoming a global multi-trillion-dollar, self-sustaining market. The analysis reveals that cost reduction alone will be insufficient to establish a high-integrity global GtCO2-scale sector. Systemic market risks, especially certainty of offtake through demand-side incentives, need to be `addressed. Therefore, the development of a stable and sustainable GGR sector, both in the US and globally, will remain problematic due to the inability to attract large-scale private capital investment.

LGG-43. LASER-ASSISTED ENDOSCOPIC RESECTION OF TECTAL GLIOMA IN A 3-YEAR-OLD CHILD

Abstract BACKGROUND Pediatric tectal gliomas generally have a benign clinical course. However, some patients may present with non-communicating hydrocephalus needing endoscopic procedures. Historically, lasers have been used in neurosurgical procedures including neuroendoscopy, but their adoption was limited by a significant rate of complication due to their inappropriate wavelength and uncontrollable tissue interaction. Recently, a 2-micron near-infrared laser with adequate wavelength and minimal tissue penetration became available. CASE-REPORT We describe the case of a 3-year-old child who presented with gait ataxia, papilloedema and headache. Magnetic Resonance (MR) was performed and he was diagnosed with obstructive hydrocephalus due to tectal glioma. Endoscopic third ventriculostomy (ETV) and simultaneous endoscopic biopsy were performed during the same surgery using a single burr hole with a rigid endoscope, a 2-micron continuous-wave thulium laser and the aid of neuronavigation. After tumoral sample removal, the laser was used for hemostasis and to evaporate tissue near the tumour without mechanical stress to the brain tissue. The final histological analysis identified a non-otherwise specified (NOS) low-grade glioma. The hospitalization was uneventful and the boy was discharged home after 4 days. No new cognitive impairment was reported secondary to this procedure and the symptoms present in the preoperative period completely improved. At 1-year follow-up, neurological examination findings were unremarkable, and there was no radiographic evidence of tumour progression. CONCLUSIONS The use of the neuroendoscopic laser permits cutting and coagulating simultaneously, avoiding multiple instruments’ use (forceps and coagulation). It therefore makes neuroendoscopic procedures more straightforward with a minimum need to change tools, and particularly suitable also in a pediatric setting.

Response to Feldman: Minimal Penetration of Practice Relevant Research—Challenge Remains

The social work profession has enhanced its research capabilities since the 1991 Task Force on Social Work Research. However, these impressive changes have not closed the research-practice gap or made substantial contributions to empirically supported social work practice knowledge. Modified challenges as presented by Feldman are offered along with suggested recommendations.

A Summarized Review of Formulation, in Vitro Evaluation of Sunscreen

The efficacy and safety of sunscreens are diminished when their agents permeate the skin, resulting in systemic circulation and unidentified negative effects. The filters in sunscreens muster main on the skin's surface with minimal penetration through the dermis in order to preserve their safety and efficacy. Sunscreen should always be worn, even in the event that filters manage get through. Damage like as erythema, the production of free radicals, aging of the skin, and skin cancer brought on by UV radiation. Research is being done to limit skin penetration, assess sun protection factor (SPF), and improve formulation properties and stability in order to target potential negative effects caused by topical absorption of sunscreens. In vitro or in vivo investigations are used in current assays to determine sunscreen penetration since they mimic the physiological conditions of use. This review objectives are to reexamine data on sunscreen skin penetration over the last ten years and identify variables that may increase skin penetration or boost sunscreen efficacy. Sunburn is caused by ultraviolet B radiation, but ultraviolet A may be more damaging to the skin. Sunscreens should ideally block both wavebands. A sunscreen sun protection factor is mostly determined by how well it blocks ultraviolet B. The efficiency of preventing ultraviolet A is not measured. Sunscreens may be organic or inorganic chemicals. If metal oxide sunscreens are made into nanoparticles, their cosmetic acceptance might increase. It doesn’t seem that absorbing organic sunscreens and nanoparticles has any appreciable systemic effects. Frequent use of sunscreen prevents melanoma, squamous cell carcinoma, and actinic keratosis from developing.

Study on LBE corrosion failure of FeAl/Al2O3 coatings after ion irradiation

FeAl/Al2O3 coatings, candidate coating materials for lead-cooled fast reactors, are first irradiated to produce pre-defects and then subjected to lead-bismuth eutectic corrosion to simulate the performance in the coupled field of irradiation and corrosion. Irradiation causes voids in the outer Al2O3 layer resulting in irradiation swelling and causes lattice distortion and dislocations in the inner FeAl layer resulting in compressive strain and intercrystalline void expansion. The weakened coatings crack during corrosion and suffer from Pb, Bi, and O penetration, causing internal corrosion and oxidation. Beyond the cracked areas, the coatings demonstrate commendable corrosion resistance with minimal penetration. The irradiation-induced structural evolution and the subsequent lead-bismuth eutectic corrosion failure of the coatings are elucidated in detail.

Abstract PO3-18-07: Therapeutic Potential of Combining Eltanexor with Tamoxifen to Treat Primary and Metastatic Estrogen Receptor Positive (ER+) Breast Cancers

Abstract Estrogen receptors are key pathway initiators in the aggressive development of more than two-thirds of all breast cancers. Tamoxifen (TAM) is a selective estrogen receptor modulator that disables the ER pathway and inhibits the progression of ER+ breast cancer. Unfortunately, 10-40% of patients with ER+ breast cancer who were treated with TAM experience recurrence and metastasis within 10 years. We have previously identified exportin 1 (XPO1) to be more highly expressed in breast cancers with acquired TAM resistance compared to TAM-sensitive counterparts and showed that a combination treatment of TAM with an XPO1 inhibitor, selinexor, is an effective method of tumor suppression in preclinical models. In this study we investigated the activity of eltanexor, an investigational second generation XPO1 inhibitor with minimal penetration of the blood-brain barrier, to inhibit cancer growth without leading to weight loss. Our results show that mice harboring MCF7-ESR1Y537Sxenograft tumors had significantly less (P < .05) flank tumor growth when administered a treatment regimen of TAM and eltanexor compared to control mice. In metastatic tumor models, we observed decreased metastatic burden in mice harboring MCF7-ESR1 D538G and MCF7-ESR1Y537S tumors when co-administered TAM and eltanexor. We did not observe weight changes in either model. Our findings suggest that eltanexor may be a relevant treatment for further exploration in the context of a TAM combination therapy for treatment of ER+ breast cancer. Citation Format: Vedant Jain, Myra Kamdar, Hannah McGee, Qianying Zuo, Jin Young Yoo, Yosef Landesman, Christopher Walker, Zeynep Madak-Erdogan. Therapeutic Potential of Combining Eltanexor with Tamoxifen to Treat Primary and Metastatic Estrogen Receptor Positive (ER+) Breast Cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-07.

Intrinsic free carrier absorption limited THz generation from Bi2Te3 and Bi2Se3 topological insulators

We investigate the influence of intrinsic free charge carriers on the ultrashort THz pulse generation efficiency of three-dimensional topological insulators (3dTIs). Wavelength dependence of the optical penetration depth of the femtosecond excitation pulses is exploited to vary the excitation volume within Bi2Te3 and Bi2Se3 crystals and accordingly, the free carrier population, to contribute to THz attenuation. The standard free carrier absorption (FCA) formalism is inadequate to explain wavelength-dependent enhancement in the THz emission as observed in the experiments. Within a modified framework, the THz attenuation by FCA is accounted for accurately, which consistently explains the experimental results for samples having different carrier density and mobility. We conclude that the THz generation efficiency of 3dTIs can be enhanced by engineering samples with high carrier mobility and low intrinsic carrier density and by using excitation wavelengths of minimal penetration depth.

Phase 1 Healthy Volunteer Study of AL01211, an Oral, Non-brain Penetrant Glucosylceramide Synthase Inhibitor, to Treat Fabry Disease and Type 1 Gaucher Disease.

Glycosphingolipid (GSL) storage diseases are caused by deficiencies in the enzymes that metabolize different GSLs in the lysosome. Glucosylceramide synthase (GCS) inhibitors reduce GSL production and have potential to treat multiple GSL storage diseases. AL01211 is a potent, oral GCS inhibitor being developed for the treatment of Type 1 Gaucher disease and Fabry disease. AL01211 has minimal central nervous system penetration, allowing for treatment of peripheral organs without risking CNS-associated adverse effects. AL01211 was evaluated in a Phase 1 healthy volunteer study with single ascending dose (SAD) and multiple ascending dose (MAD) arms, to determine safety, pharmacokinetics including food effect, and pharmacodynamic effects on associated GSLs. In the SAD arm, AL01211 showed a Tmaxof approximately 3.5 hours, mean clearance (CL/F) of 130.1 L/h, and t1/2of 39.3 hours. Consuming a high-fat meal prior to dose administration reduced exposures 3.5-5.5-fold, indicating a food effect. In the MAD arm, AL01211 had an approximately 2-fold accumulation, reaching steady-state levels by 10 days. Increasing exposure inversely correlated with a decrease in GSL with plasma glucosylceramide and globotriacylceramide reduction from baseline levels, reaching 78% and 52% by day 14, respectively. AL01211 was generally well-tolerated with no AL01211 associated serious adverse events, thus supporting its further clinical development.

Study of composite coatings based on nickel alloy

A composite coating Inconel-625/WC on a VT6 nickel alloy is obtained by laser cladding. Studies of laser tracks of composite composition in a wide range of concentrations of the carbide phase and at different values of technological para meters of the process are carried out. Based on the results of quantitative metallographic analysis, optimal coating compositions are selected and intervals of technological parameters are established, allowing to obtain nonporous coatings with minimal penetration of the substrate and a given geometry of the cross-section of the laser track.