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The adoption of innovation is essential to the evolution of patient care. Breast surgical oncology advances through incorporating new techniques, devices, and procedures. Historical changes in practice standards from radical to modified radical mastectomy or axillary node dissection to sentinel node biopsy reduced morbidity without sacrifice in oncologic outcome. Contemporary oncoplastic techniques afford broader consideration for breast conservation and the potential for improved cosmetic outcomes. At present, many breast surgeons face the decision of which wireless device to use for localization of nonpalpable lesions. Consideration for future changes, such as robotic mastectomy, are on the horizon. No guideline exists to assist breast surgeons in the adoption of innovation into practice. The Ethics Committee of the American Society of Breast Surgeons acknowledges that breast surgeons confront many questions associated with onboarding innovation. This paper aims to provide a framework for asking relevant questions along with the ethical principles to consider when integrating an innovation into practice.

The COVID-19 pandemic has had widespread impact on healthcare, resulting in modifications to how we perform cancer research, including clinical trials for cancer. The impact of some healthcare workers and study coordinators working remotely and patients minimizing visits to medical facilities impacted clinical trial participation. Clinical trial accrual dropped at the onset of the pandemic, with improvement over time. Adjustments were made to some trial protocols, allowing telephone or video-enabled consent. Certain study activities were permitted to be performed by local healthcare providers or at local laboratories to maximize patients' ability to continue on study during these challenging times. We discuss the impact of COVID-19 on cancer clinical trials and changes at the local, cooperative group, and national level.

In this paper, we derive sharp bounds on the semigroup of the linearized incompressible Navier-Stokes equations near a stationary shear layer in the half plane and in the half space ($\mathbb{R}_+^2$ or $\mathbb{R}_+^3$), with Dirichlet boundary conditions, assuming that this shear layer in spectrally unstable for Euler equations. In the inviscid limit, due to the prescribed no-slip boundary conditions, vorticity becomes unbounded near the boundary. The novelty of this paper is to introduce boundary layer norms that capture the unbounded vorticity and to derive sharp estimates on this vorticity that are uniform in the inviscid limit., Comment: this greatly revised and shortened the previous version

SummaryBackgroundNanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. In a Phase 1 and 2 studies, (NCT04683484) the vaccine was found to be safe and induce a robust immune response in healthy adult participants.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and protective efficacy of the Nanocovax vaccine against Covid-19 in approximately 13,007 volunteers aged 18 years and over. The immunogenicity was assessed based on Anti-S IgG antibody response, surrogate virus neutralization, wild-type SARS-CoV-2 neutralization and the types of helper T-cell response by intracellular staining (ICS) for interferon gamma (IFNg) and interleukin-4 (IL-4). The vaccine efficacy (VE) was calculated basing on serologically confirmed cases of Covid-19.FindingsUp to day 180, incidences of solicited and unsolicited adverse events (AE) were similar between vaccine and placebo groups. 100 serious adverse events (SAE) were observed in both vaccine and placebo groups (out of total 13007 participants). 96 out of these 100 SAEs were determined to be unrelated to the investigational products. 4 SAEs were possibly related, as determined by the Data and Safety Monitoring Board (DSMB) and investigators. Reactogenicity was absent or mild in the majority of participants and of short duration. These findings highlight the excellent safety profile of Nanocovax.Regarding immunogenicity, Nanocovax induced robust IgG and neutralizing antibody responses. Importantly, Anti S-IgG levels and neutralizing antibody titers on day 42 were higher than those of natural infected cases. Nanocovax was found to induce Th2 polarization rather than Th1.Post-hoc analysis showed that the VE against symptomatic disease was 51.5% (95% confidence interval [CI] was [34.4%-64.1%]. VE against severe illness and death were 93.3% [62.2-98.1]. Notably, the dominant strain during the period of this study was Delta variant.InterpretationNanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%.FundingResearch was funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam; ClinicalTrials.gov number, NCT04922788.

The SARS-CoV-2 main protease (Mpro) plays an important role in the viral transcription and replication of the SARS-CoV-2 virus that is causing the Covid-19 pandemic worldwide. Therefore, it represents a very attractive target for drug development for treatment of this disease. It is a cysteine protease because it has in the active site the catalytic dyad composed of cysteine (C145) and histidine (H41). The catalytic site represents the binding site for inhibitors, many of them bind to Mpro with a covalent bond. In this research, structural and physiochemical characteristics of the Mpro binding site are investigated when the ligand 11a is covalently and non-covalently bound. All-atom molecular dynamics (MD) simulations were run for 500 ns at physiological temperature (310 K). It is found that conformations of both the Mpro protein and the ligand are stable during the simulation with covalently bound complex showing stronger stability. When the ligand is covalently bound (its final state), residues that stably interact with the ligand are H41, C145, H163, H164 and E166. The optimal conformation of these residues is stabilized also via the Hbond interactions with the catalytic water present in the Mpro binding site. In the case of the non-covalently bound ligand (state before the covalent bond is formed), the binding site residues retain their conformations similar to the covalent binding site, and they still form Hbonds with the catalytic water, except H41. This residue, instead, adopts a different conformation and looses the Hbond with the catalytic water, leaving more freedom to move to the ligand. We hypothesize that H41 could play a role in guiding the ligand to the optimal position for final covalent bonding. Further analyses are in process to check this hypothesis. These results represent an important basis for studying drug candidates against SARS-CoV-2 by means of computer aided drug design.

The pandemic of COVID-19 severe acute respiratory syndrome, which was fatal for millions of people worldwide, triggered the race to understand in detail the molecular mechanisms of this disease. In this work, the differences of interactions between the SARS-CoV/SARS-CoV-2 Receptor binding domain (RBD) and the human Angiotensin Converting Enzyme 2 (ACE2) receptor were studied using in silico tools. Our results show that SARS-CoV-2 RBD is more stable and forms more interactions with ACE2 than SARS-CoV. At its interface, three stable binding patterns are observed and named red-K31, green-K353 and blue-M82 according to the central ACE2 binding residue. In SARS-CoV instead, only the first two binding patches are persistently formed during the MD simulation. Our MM/GBSA calculations indicate the binding free energy difference of about 2.5 kcal/mol between SARS-CoV-2 and SARS-CoV which is compatible with the experiments. The binding free energy decomposition points out that SARS-CoV-2 RBD–ACE2 interactions of the red-K31 ($$-23.5~\pm ~0.2~kcal/mol$$ - 23.5 ± 0.2 k c a l / m o l ) and blue-M82 ($$-9.1~\pm ~0.1~kcal/mol$$ - 9.1 ± 0.1 k c a l / m o l ) patterns contribute more to the binding affinity than in SARS-CoV ($$-1.8~\pm ~0.02~kcal/mol$$ - 1.8 ± 0.02 k c a l / m o l for red-K31), while the contribution of the green-K353 pattern is very similar in the two strains ($$-17.8~\pm ~0.2~kcal/mol$$ - 17.8 ± 0.2 k c a l / m o l and $$-22.7~\pm ~0.1~kcal/mol$$ - 22.7 ± 0.1 k c a l / m o l for SARS-CoV-2 and SARS-CoV, respectively). Five groups of mutations draw our attention at the RBD–ACE2 binding interface, among them, the mutation –PPA469-471/GVEG482-485 has the most important and favorable impact on SARS-CoV-2 binding to the ACE2 receptor. These results, highlighting the molecular differences in the binding between the two viruses, contribute to the common knowledge about the new corona virus and to the development of appropriate antiviral treatments, addressing the necessity of ongoing pandemics.

Microlasers based on biomaterials have attracted enormous interest because of their promising potential for future applications in medical treatments, bio-tracking, and biosensing. In this work, we demonstrate chicken albumen as a novel and excellent low-cost biomaterial for a laser cavity. By using a simple but effective emulsion process, rhodamine B-doped chicken albumen microspheres with various diameters ranging from 20 μm to 100 μm can be fabricated. Under optical pulse excitation, these microspheres emit lasing emission. The lasing mechanism is investigated and ascribed to the whispering gallery mode (WGM). A threshold of 23.2 μJ mm-2 and a high Q-factor of approximately 2400 are obtained from an 82 μm-diameter microsphere. Size-dependent lasing characteristics are also examined, and the result shows good agreement with the WGM theory. Interestingly, these microsphere biolasers can operate in aqueous and biological environments such as water and human blood serum, which makes them a promising candidate for laser-based biosensing and biological applications.

In this paper we give a proof of an Onsager type conjecture on conservation of energy and entropies of weak solutions to the relativistic Vlasov--Maxwell equations. As concerns the regularity of weak solutions, say in Sobolev spaces $W^{\alpha,p}$, we determine Onsager type exponents $\alpha$ that guarantee the conservation of all entropies. In particular, the Onsager exponent $\alpha$ is smaller than $\alpha = 1/3$ established for fluid models. Entropies conservation is equivalent to the renormalization property, which have been introduced by DiPerna--Lions for studying well-posedness of passive transport equations and collisionless kinetic equations. For smooth solutions renormalization property or entropies conservation are simply the consequence of the chain rule. For weak solutions the use of the chain rule is not always justified. Then arises the question about the minimal regularity needed for weak solutions to guarantee such properties. In the DiPerna--Lions and Bouchut--Ambrosio theories, renormalization property holds under sufficient conditions in terms of the regularity of the advection field, which are roughly speaking an entire derivative in some Lebesgue spaces (DiPerna--Lions) or an entire derivative in the space of measures with finite total variation (Bouchut--Ambrosio). In return there is no smoothness requirement for the advected density, except some natural a priori bounds. Here we show that the renormalization property holds for an electromagnetic field with only a fractional space derivative in some Lebesgue spaces. To compensate this loss of derivative for the electromagnetic field, the distribution function requires an additional smoothness, typically fractional Sobolev differentiability in phase-space. As concerns the conservation of total energy, if the macroscopic kinetic energy is in $L^2$, then total energy is preserved.

In recent years, whispering gallery mode microlasers have attracted tremendous interest in sensing due to their ultra-high sensitivity at atomic levels. However, due to the non-magnetic properties, it is difficult to locate the microlasers at hard-to-reach positions, thus, limiting their sensing potential in many in-vitro and in-vivo applications. In this work, we report magnetic microlasers fabricated by encapsulating Ni0.2Zn0.8Fe2O4 magnetic nanoparticles (MNPs) within their cavity made of bovine serum albumin. The presence of MNPs allows the transportable actuation of the magnetic microlasers while maintaining lasing emission characteristics. Microlasers with various concentrations of MNPs are investigated to identify the optimum concentration that can balance a good magnetization, a low lasing threshold, and a high quality (Q) factor. These magnetic microlasers can be employed for sensing applications where sensors need to be navigated through different sensing media. As a proof of concept, we observed a clear shift of lasing wavelength of a magnetic microlaser while dragging it through different adjacent media by magnetic navigation. This result demonstrates the potential applications of magnetic microlasers for future biological and chemical applications.

BackgroundNanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant.MethodsWe conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 microgram (mcg), 50 mcg, and 75 mcg doses, aluminum hydroxide adjuvanted). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2 which involved in 560 healthy adults, the primary outcomes are vaccine safety; and anti-S IgG antibody response. Secondary outcomes were surrogate virus neutralization, wild-type SARS-CoV-2 neutralization, and T-cell responses by intracellular staining (ICS) for interferon gamma (IFNg). We performed primary analyses at day 35 and day 42.ResultsFor phase 1 study, no serious adverse events (SAE) were observed for all 60 participants. Most adverse events (AE) were grade 1 and disappeared shortly after injection. For phase 2 study, after randomization, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive placebo. Reactogenicity was absent or mild in the majority of participants and of short duration (mean, ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. There was no statistical difference in antibody responses among dose strengths on Day 42, in terms of anti S-IgG level and neutralizing antibody titer.ConclusionsUp to 42 days, Nanocovax vaccine was safe, well tolerated and induced robust immune responses. We propose using Nanocovax 25 mcg for Phase 3 to evaluate the vaccine efficacy. (Research funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam;ClinicalTrials.govnumber,NCT04683484.)

The COVID-19 pandemic has had widespread impact on healthcare, resulting in modifications to how we perform cancer research, including clinical trials for cancer. The impact of some healthcare workers and study coordinators working remotely and patients minimizing visits to medical facilities impacted clinical trial participation. Clinical trial accrual dropped at the onset of the pandemic, with improvement over time. Adjustments were made to some trial protocols, allowing telephone or video-enabled consent. Certain study activities were permitted to be performed by local healthcare providers or at local laboratories to maximize patients’ ability to continue on study during these challenging times. We discuss the impact of COVID-19 on cancer clinical trials and changes at the local, cooperative group, and national level.

The COVID-19 pandemic has had widespread impact on healthcare, resulting in modifications to how we perform cancer research, including clinical trials for cancer. The impact of some healthcare workers and study coordinators working remotely and patients minimizing visits to medical facilities impacted clinical trial participation. Clinical trial accrual dropped at the onset of the pandemic, with improvement over time. Adjustments were made to some trial protocols, allowing telephone or video-enabled consent. Certain study activities were permitted to be performed by local healthcare providers or at local laboratories to maximize patients' ability to continue on study during these challenging times. We discuss the impact of COVID-19 on cancer clinical trials and changes at the local, cooperative group, and national level.

In this study, we demonstrate a simple approach to fabricate a high-performance random laser (RL) from the natural inverse photonic glass structure of Artemia eggshells. Herein, the three-dimensional structures of Artemia eggshells provide an ideal scattering medium with a significantly high-reflectance stopband which facilitates resonance feedback for random lasing action. By doping organic dye molecules into the Artemia eggshells, RLs are realized by optical pumping with a threshold of 79 μJ mm−2, and a quality (Q) factor of 2328. In comparison with other works on RLs from natural photonic crystals such as butterfly wings, our RLs demonstrate a significantly lower lasing threshold and a comparable Q factor. Our results indicate that the natural inverse photonic glass structure is not only served as an effective scattering medium for random lasing but also paves a novel approach in designing and fabricating bio-controlled photonic devices.

Allopurinol (ALP), a xanthine oxidase inhibitor, is an FDA-approved urate-lowering medication used to treat Gout, prevent tumor lysis syndrome, and prevent recurrent calcium nephrolithiasis in hyperuricosuria patients. However, it has been known as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS), especially in patients carrying the Human Leukocyte Antigens allele HLA-B*58:01, which is more prevalent in Asian population. However, although patients do not carry the HLA-B*58:01 allele, they still exhibit allopurinol-induced SCAR. Surprisingly, a large number of these patients have the HLA-A*33:03 allele. In this research, we investigated the binding of ALP to the HLA-A*33:03 structure using Molecular Dynamics (MD) simulation. Our results showed that the complex of HLA-A*33:03 and ALP was stable after 100000 ps simulation time. ALP had strong interactions with three important residues locating in the active site of HLA-A*33:03, which include the seven amino acid residues Val 76, Asp 77, Leu 81, Ile 95, Gln 96, Asp 116, and Tyr 123. This data suggests that ALP has strong binding affinity for this allele. Thus, in addition to HLA-B*58:01, HLA-A*33:03 may be a potential screening marker before prescribing Allopurinol for Gout treatment.

Since the discovery of the role of NLRP3 in microbial infection in 2001, many studies have shown that NLRP3 play a key role in causing many mammal acute and chronic diseases. However, a full understanding of the mechanism of NLRP3 activation is still lacking. Our previous theoretical work and experimental evidence show the role of ATP in interacting with and activating the NATCH region of NLRP3. In this study, we continue to use bioinformatics and molecular dynamic (MD) simulation to evaluate the competitive impact of the interaction the ligand ATP and colchicine (COL) with this NACHT protein. The later ligand is a medication to treat gout attacks. Our results show that COL bind stably to the ATP binding pocket of mice NACHT domain with high numbers of hydrophobic and van der Waals interactions, while hydrogen bond and electrostatic interactions are important types of contact for keeping ATP at its NACHT pocket. Our results assist in building in-silico screening model for natural compounds with pharmacological effects to NLRP3 similar to colchicine with few side effects. In addition, this work helps to better understand the balance between this inflammasome activation and inhibition, which will help in the improvement and development of new therapies for related diseases.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in rapid and regionally different approaches to breast cancer care.In order to evaluate these changes, a COVID-19-specific registry was developed within the American Society of Breast Surgeons (ASBrS) Mastery that tracked whether decisions were usual or modified for COVID-19. Data on patient care entered into the COVID-19-specific registry and the ASBrS Mastery registry from 1 March 2020 to 15 March 2021 were reviewed.Overall, 177 surgeons entered demographic and treatment data on 2791 patients. Mean patient age was 62.7 years and 9.0% (252) were of African American race. Initial consultation occurred via telehealth in 6.2% (173) of patients and 1.4% (40) developed COVID-19. Mean invasive tumor size was 2.1 cm and 17.8% (411) were node-positive. In estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) disease, neoadjuvant endocrine therapy (NET) was used as the usual approach in 6.9% (119) of patients and due to COVID-19 in an additional 31% (542) of patients. Patients were more likely to receive NET due to COVID-19 with increasing age and if they lived in the Northeast or Southeast (odds ratio [OR] 1.1, 2.3, and 1.7, respectively; p 0.05). Genomic testing was performed on 51.5% (781) of estrogen-positive patients, of whom 20.7% (162) had testing on the core due to COVID-19. Patients were less likely to have core biopsy genomic testing due to COVID-19 if they were older (OR 0.89; p = 0.01) and more likely if they were node-positive (OR 4.0; p 0.05). A change in surgical approach due to COVID-19 was reported for 5.4% (151) of patients.The ASBrS COVID-19 registry provided a platform for monitoring treatment changes due to the pandemic, highlighting the increased use of NET.

The structure and stability of ternary systems prepared with polysorbate 60 and various combinations of cetyl (C16) and stearyl (C18) alcohols (fatty alcohol 16g, polysorbate 4g, water 180g) were examined as they aged over 3 months at 25oC. Rheological results showed that the consistency of these systems increased initially during roughly the first week of aging, which was succeeded by little changes in consistency (systems containing from 30% to 70% C18, with the 50% C18 system showing the highest consistencies in viscosity and elasticity) or significant breakdown of structure (remaining systems). The formation and/or disintegration of all ternary systems were also detected by microscopy and differential scanning calorimetry experiments. This study emphasizes the fact that the structure and consistency of ternary systems are dominantly controlled by the swelling capacity of the lamellar $\alpha-$crystalline gel phase. When the conversion of this gel phase into non-swollen $\beta$- or $\gamma$-crystals occurs, systems change from semisolids to fluids. Molecular dynamics simulations were performed to provide important details on the molecular mechanism of our ternary systems. Computational results supported the hypothesis experimentally proposed for the stability of the mixed system being due to an increase in the flexibility, hence an increase in the configurational entropy of the chain tip of the alcohol with a longer hydrocarbon chain (with the highest flexibility observed in the 50:50 C18:C16 system). This finding is in excellent agreement with experimental conclusions. Additionally, simulation data show that in the mixed system, the alcohol with shorter hydrocarbon chain becomes more rigid. These molecular details could not be available in experimental measurements, Comment: 19 ages, 10 figures, 4 tables

We study the linearized Vlasov–Poisson system around suitably stable homogeneous equilibria on $${\mathbb {R}}^d\times {\mathbb {R}}^d$$ (for any $$d \ge 1$$ ) and establish dispersive $$L^\infty $$ decay estimates in the physical space.

The translocator protein (TSPO) is a 18kDa transmembrane protein, ubiquitously present in human mitochondria. It is overexpressed in tumor cells and at the sites of neuroinflammation, thus representing an important biomarker, as well as a promising drug target. In mammalian TSPO, there are cholesterol–binding motifs, as well as a binding cavity able to accommodate different chemical compounds. Given the lack of structural information for the human protein, we built a model of human (h) TSPO in the apo state and in complex with PK11195, a molecule routinely used in positron emission tomography (PET) for imaging of neuroinflammatory sites. To better understand the interactions of PK11195 and cholesterol with this pharmacologically relevant protein, we ran molecular dynamics simulations of the apo and holo proteins embedded in a model membrane. We found that: (i) PK11195 stabilizes hTSPO structural fold; (ii) PK11195 might enter in the binding site through transmembrane helices I and II of hTSPO; (iii) PK11195 reduces the frequency of cholesterol binding to the lower, N–terminal part of hTSPO in the inner membrane leaflet, while this impact is less pronounced for the upper, C–terminal part in the outer membrane leaflet, where the ligand binding site is located; (iv) very interestingly, cholesterol most frequently binds simultaneously to the so-called CRAC and CARC regions in TM V in the free form (residues L150–X–Y152–X(3)–R156 and R135–X(2)–Y138–X(2)–L141, respectively). However, when the protein is in complex with PK11195, cholesterol binds equally frequently to the CRAC–resembling motif that we observed in TM I (residues L17–X(2)–F20–X(3)–R24) and to CRAC in TM V. We expect that the CRAC–like motif in TM I will be of interest in future experimental investigations. Thus, our MD simulations provide insight into the structural features of hTSPO and the previously unknown interplay between PK11195 and cholesterol interactions with this pharmacologically relevant protein.

The microscopic mechanism of the H2 adsorption of two Mg-MOF-74 isoreticular frameworks, one with a benzenedicarboxylate (BDC) linker and the other with a dihydroxyfumarate (DHF) linker, were studied on the basis of density functional theory (DFT) method. Possible adsorption sites on the internal surface of the two MOFs were detected using ab initio molecular dynamics (AIMD) annealing simulations. The simulations were able to reproduce all adsorption sites which have been experimentally observed for the BDC-based M-MOF-74 frameworks with M = Ni and Zn. In descending order of binding strengths, they are the adsorption sites primarily induced by the open metal sites P1, the oxygen atoms of the oxido groups P2 and the aromatic rings P3. The H2–framework binding strengths were properly evaluated by taking into account the vibrational zero-point energy (ZPE) contribution. An additional type of adsorption sites induced by the oxygen atoms of the carboxyl groups P4 is predicted for the Mg-MOF-74 framework. Two types of adsorption sites primarily induced by the open metal sites P1 and oxygen atoms of the carboxyl groups P2 were predicted for the DHF-based Mg-MOF-74 framework. Detailed analysis of the electron density showed that the electrostatic interaction of the H2 molecule with the charge distribution of the local framework environment within a radius of ∼3.5 A is a key factor to define adsorption positions and binding strength. The absence of the P4 sites in the BDC-based Zn-MOF-74 framework is caused by the lower charge density at the oxygen atoms induced by less electro-positive metal. The substitution of the nonaromatic DHF linker for the aromatic BDC linker reduces the binding strength at the metal induced adsorption sites by 1.45 kJ mol−1 due to the absence of the aromatic ring.

The brain is strictly protected by the blood brain barrier preventing the crossing of therapeutics to treat brain diseases. The high and low intensity focused ultrasound methods have been used to temporarily open the blood brain barrier, facilitating the transport of drugs. The methods are very promising because the opening is transient, localized, and noninvasive. However, the molecular mechanism of the opening is unknown, and this limits the development and application of these methods. With this in mind, we carry out a molecular dynamics simulation study to understand the interaction of ultrasound with the cell membrane and the tight junction. Our minimal blood brain barrier model is composed of two lipid bilayers, mimicking two portions of neighboring cells, connected together by a tight junction formed by a pair of two cis-dimers of the claudin-5 protein. Using an experimental ultrasound frequency of 50 MHz, simulations show that at low intensities, ultrasound does not impact the structure of the cell membranes and tight junction, implying that the direct interaction of ultrasound with the blood brain barrier is not responsible for the experimentally observed opening. At high intensities, the ultrasound pulls the monolayers of individual cell membrane lipid bilayers apart, creating air compartments inside the bilayers. This reduces the free energy barrier for the translocation of drugs across the lipid bilayer and enhances drug permeability. At very high intensities, the two monolayers are largely separated, resulting in cell damage and implying that the blood brain barrier is primarily opened at the experimentally observed damaged areas.

The classical Orr--Sommerfeld equations are the resolvent equations of the linearized Navier--Stokes equations around a stationary shear layer profile in the half plane. In this paper, we derive po...

The outbreak of the 2019-nCoV coronavirus causing severe acute respiratory syndrome which can be fatal, especially in elderly population, has been declared a pandemic by the World Health Organization. Many biotechnology laboratories are rushing to develop therapeutic antibodies and antiviral drugs for treatment of this viral disease. The viral CoV spike (S) glycoprotein is one of the main targets for pharmacological intervention. Its receptor-binding domain (RBD) interacts with the human ACE2 receptor ensuring the entry of the viral genomes into the host cell. In this work, we report on the differences in the binding of the RBD of the previous coronavirus SARS-CoV and of the newer 2019-nCoV coronavirus to the human ACE2 receptor using atomistic molecular dynamics techniques. Our results show major mutations in the 2019-nCoV RBD with respect to the SARS-CoV RBD occurring at the interface of RBD-ACE2 complex. These mutations make the 2019-nCoV RBD protein backbone much more flexible, hydrophobic interactions are reduced and additional polar/charged residues appear at the interface. We observe that higher flexibility of the 2019-nCoV RBD with respect to the SARS-CoV RBD leads to a bigger binding interface between the 2019-nCoV RBD and ACE2 and to about 20% more contacts between them in comparison with SARS-CoV. Taken together, the 2019-nCoV RBD shows more stable binding interface and higher binding affinity for the ACE2 receptor. The mutations not only stabilize the binding interface, they also lead to overall more stable 2019-nCoV RBD protein structure, even far from the binding interface. Our results on the molecular differences in the binding between the two viruses can provide important inputs for development of appropriate antiviral treatments of the new viruses, addressing the necessity of ongoing pandemics.

In this paper we construct particular solutions to the classical Vlasov-Poisson system near stable Penrose initial data on $\mathbb{T} \times \mathbb{R}$ that are a combination of elementary waves with arbitrarily high frequencies. These waves mutually interact giving birth, eventually, to an infinite cascade of echoes of smaller and smaller amplitude. The echo solutions do not belong to the analytic or Gevrey classes studied by Mouhot and Villani, but do, nonetheless, exhibit damping phenomena for large times., 16 pages

The aim of this paper is to provide a justification of the Maxwell–Boltzmann approximation of electron density from kinetic models. First, under reasonable regularity assumption, we rigorously derive a reduced kinetic model for the dynamics of ions, while electrons satisfy the Maxwell–Boltzmann relation. Second, we prove that equilibria of the electrons distribution are local Maxwellians, and they can be uniquely determined from conserved mass and energy constants. Finally, we prove that the reduced kinetic model for ions is globally well-posed. The constructed weak solutions conserve energy.

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC. We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis. Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (± ALND) increased from 28% in 2009 to 86% in 2017 (p

In their classical work, Sammartino and Caflisch (Commun Math Phys 192(2):433–461, 1998a; Commun Math Phys 192(2):463–491, 1998b) proved the inviscid limit of the incompressible Navier–Stokes equations for well-prepared data with analytic regularity in the half-space. Their proof is based on the detailed construction of Prandtl’s boundary layer asymptotic expansions. In this paper, we give a direct proof of the inviscid limit for general analytic data without having to construct Prandtl’s boundary layer correctors. Our analysis makes use of the boundary vorticity formulation and the abstract Cauchy–Kovalevskaya theorem on analytic boundary layer function spaces that capture unbounded vorticity.

We prove the inviscid limit for the incompressible Navier-Stokes equations for data that are analytic only near the boundary in a general two-dimensional bounded domain. Our proof is direct, using the vorticity formulation with a nonlocal boundary condition, the explicit semigroup of the linear Stokes problem near the flatten boundary, and the standard wellposedness theory of Navier-Stokes equations in Sobolev spaces away from the boundary., 28 pages

Adjuvant hormonal therapy (HT) reduces breast cancer recurrence risk in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS). We assessed national practice patterns and influence of surgery and pathology on HT use in DCIS. Data on DCIS patients diagnosed from 2004 to 2014 were extracted from the National Cancer Database, and patients were classified according to ER status and whether HT was received. Factors associated with HT use were assessed using Chi square tests for univariate analysis and logistic regression for multivariate analysis. Overall, 207,738 patients were evaluable as follows: ER+ (69.3%), ER− (13.7%), and ER unknown (17.0%). Among ER+ DCIS patients, 46.5% received HT, and HT use increased over time (42.3% in 2004 to 50.6% in 2014; p