Additional Contact Points Research Articles

Application and mechanistic insights of a washing/microwave/ultrasonic ternary pretreatment for enhancing barite flotation in waste drilling fluids

A quantity of recoverable barite exists in high-density waste drilling fluid. Based on the inefficiencies and complexities of existing recycling methods, a novel pre-treatment approach which includes clean-breaking, high-speed washing, ultrasonic dispersion, and microwave heating and a new depressant (Gellan Gum) was proposed. The floatability, separation efficiency and mechanism were discussed by SEM, adsorption capacity, zeta potential measurements and contact angle tests. The results of reverse flotation experiments results indicated that secondary water washing proves highly effective in enriching a significant quantity of barite solid phase. Subsequent microwave-ultrasonic and flotation can obtain barite of high quality with recovery and density reaching 81.5% and 4.238 g/cm3, respectively. It can be utilized directly in the preparation of drilling fluid. Mechanism studies shown that the per-treatments substantially enhances the barite grade while effectively eliminating low-density solid phases adhering to the barite surface, thus exposing additional contact points between the constituents so as to improve flotation separation. This new recovery scheme has environmental advantages and great reference value for the separation of barite within high-density waste drilling fluids.

Hybrid nanofluids flow over a Riga plate surrounded by a variable porous medium for heat transfer optimization

Enhancing the heat transfer rate in hybrid nanofluids is significantly aided by a porous medium. The nanofluid’s heat transfer to the surrounding medium is more efficient due to the presence of a porous medium. The porous space also provides additional surface contact points for heat exchange and an intricate network of interconnected pores. This article elaborates on the incorporation of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) into water to perform hybrid nanofluids. The flow is considered over a Riga plate surrounded by a variable porous space. Various applications, including thermal management systems, microelectronics cooling, and energy conversion devices, benefit greatly from the study of hybrid nanofluid flow on a Riga plate. The similarity equations of the flow problem are easily tackled with the homotopy analysis method (HAM) built on fundamental homotopy mapping. Furthermore, with the increments in paramount parameters, the skin friction coefficient and heat transfer rate are remarkably meliorated under a higher modified Hartmann number. All reverberations are illustrated in graphs and Tables. From the obtained results it is observed that flow control capabilities are enabled by the variations in permeability in the case of hybrid nanofluids. It is also observed that hybrid nanofluids are more capable to enhance the thermal capabilities of the traditional fluids as compared to the mano nanofluids.

Shish‐kebab structure evolution of HDPE/UHMWPE during hot drawing

AbstractUsing a solution‐mixing method, this research aimed to fabricate high‐density polyethylene (HDPE)/ultra‐high molecular weight polyethylene (UHMWPE) composite materials with uniform dispersion. By incorporating a small quantity of UHMWPE as a nucleating agent, additional contact points were introduced to enhance the crystallization rate of the HDPE matrix. Thermal stretching experiments were conducted on composite systems with varying UHMWPE contents and molecular weight additions at different temperatures. Elevating the stretching temperature was found to decrease the yield strain and yield strength, extend the stage of tensile plastic deformation, and diminish the overall mechanical properties of the composite material. Notably, stretching at temperatures ranging from 90 to 110°C accentuated the development of internal crystal orientation structures. Under low strain conditions, crystal slip was observed to be concentrated, with single crystals undergoing continuous stretching and breaking, resulting in a decrease in the long period. Conversely, at high strains, the induced formation of oriented lamellar structures was observed.Highlights Prepared HDPE/UHMWPE blends by UHMWPE with varying molecular weights. Analyzed the alterations in the HDPE/UHMWPE blends' internal crystal structure. Influence of UHMWPE addition, temperature on the evolution of crystal structure.

Pasos Hacia La Salud II: A Superiority RCT Utilizing Technology to Promote Physical Activity in Latinas

IntroductionLatinas face increased risk for chronic diseases associated with insufficient physical activity (PA). The researchers previously showed that a website-based intervention could increase PA among insufficiently active Latinas, yet rates of meeting national PA guidelines were low. The original intervention was enhanced by adding additional features, content, and points of contact, including via text messaging. This study tests the efficacy of the enhanced intervention compared with the original, aimed at maximizing and sustaining PA gains across 24 months. It also examines if increases in PA differed by baseline PA. Study designThe researchers conducted a superiority randomized controlled trial (data collected 2018-2022, analyzed 2023). Setting/participantsParticipants were 195 Spanish-speaking Latinas ages 18-65 in the Providence, RI area. InterventionThe original intervention is an empirically supported Spanish-language, individually-tailored, website-delivered PA intervention. The enhanced intervention includes text messaging and additional data-driven content and interactive features. Main outcome measuresTotal weekly minutes of moderate to vigorous PA (MVPA) was measured via accelerometry and self-report at 6, 12, 18, and 24 months. ResultsParticipants in both groups increased their MVPA over 24 months. There were no significant between-group differences at 6 or 12 months; at 18 months the enhanced intervention group had higher levels of self-reported (mean (sd): 90.35 (43.55) vs. 70.18 (9.99)) and accelerometer-measured (66.21 (18.26) vs. 60.27 (16.00)) MVPA compared to the original intervention group. They also had higher levels of self-reported (111.17 (23.35) vs. 81.44 (1.82)) and accelerometer-measured (63.76 (15.12) vs. 54.86 (14.59)) MVPA at 24 months. Baseline PA moderated the intervention effect. ConclusionsThis study demonstrates the potential to enhance the efficacy of website-based PA interventions by utilizing text messaging, and adding more interactive features, content, and phone support. These enhancements may be particularly beneficial in supporting long-term PA maintenance. Trial registrationThis study is registered at www.clinicaltrial.gov (NCT03491592).

A West Coast Straussian Appreciation of The Classical and Christian Origins of American Politics

Cooper and Dyer’s outstanding book deserves praise for its thorough investigation of the ideas of the American Founders, bringing us back to the common sense of the subject. Just as the main stream of American political thinking argued at the outset, natural rights and natural theology were important to the ideas, institutions, and culture of the Founders. Looking beyond their project, there are additional points of contact with other scholarship that can be drawn out—which I shall endeavor to do here.

The main directions of development and measures to support public-private partnership in the context of new economic sanctions

The article highlights the main directions of development and measures to support public-private partnership in the context of the introduction of new anti-Russian sanctions. In the context of economic turmoil, the need to optimize and search for additional points of contact between the state and business is increasing, which can serve as a catalyst for restoring the economic balance. The article assigns the leading role to the state in partnership with business as a guarantor of state and economic security. It was noted that in the current economic situation, PPP projects for the development of the social sphere, infrastructure, IT-sphere, and tourism acquire particular relevance.

Application of a technique for reducing supersonic starting loads on internal wind tunnel balances

Higher than anticipated supersonic starting loads in the VTI T-38 wind tunnel were a consequence of higher than designed minimum start pressures. Initially, high starting loads limited the usefulness of the facility at high supersonic Mach numbers. Over time, it was established that several procedures and techniques had to be used cooperatively to diminish the problem. One of the techniques is the establishment of additional points of contact of the model and the support sting for the duration of the starting loads, so that a part of the aerodynamic loads is transferred to the sting through the added path, relieving the sensitive force balance. Some applications of this technique require dedicated mechanisms to operate, which was impractical for the VTI T-38 wind tunnel. To the contrary, the implementation of the idea in the VTI T-38 wind tunnel relies on using suitable inserts to make the clearance between the model and the sting such that model-sting contact is forced to occur during the start and stop phenomena, but not during the measurement phase of the test. For typical model configurations, transient starting and stopping loads can be reduced by more than 50%.

Healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy.

ObjectivesOur primary aim was to evaluate the healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy. Second, we aim to assess the effect of the number of diagnostic tests and clinical contact points on the total time and costs between symptom onset and diagnosis defining a quantitative hypothetical optimized diagnostic pathway.SettingClinical and cost data were collected from patients presenting between 2010 and 2018 in a tertiary referral institution in South London involving two participating hospitals.ParticipantsThirty‐eight adult patients with a definite diagnosis of transthyretin amyloidosis cardiomyopathy were included, mostly male (n = 28, 74%) and of African‐Caribbean descent (n = 23, 64%). We excluded patients without a confirmed transthyretin amyloidosis cardiomyopathy or those on inotersen, patisiran, or diflunisal at point of referral.Primary and secondary outcome measuresThe average time between first presentation and final diagnosis, and the cost per patient per month. By comparing to a more optimal clinical pathway towards diagnosis, we considered what could be the theoretical gain in terms of time to diagnosis and financial savings.ResultsThe average time between first presentation and final diagnosis was 2.74 years. The average cost per patient per month was higher with progressive heart failure symptoms. A hypothetical optimal pathway reduces time to diagnosis of 1.65 to 1.74 years per patient. The potential financial savings are estimated within the range of £3000 to £4800 per patient.ConclusionsPatients diagnosed with transthyretin amyloidosis cardiomyopathy have substantial healthcare resource utilization and costs starting from symptom onset. Higher costs were observed with progression in symptoms and appear linked to a delayed diagnosis. The number of additional diagnostic tests and clinical contact points may contribute to this and could represent a path to explore further for important health and cost savings, with more efficient pathways for these patients to be managed.

Point Mutations at a Key Site Alter the Cytochrome P450 OleP Structural Dynamics.

Substrate binding to the cytochrome P450 OleP is coupled to a large open-to-closed transition that remodels the active site, minimizing its exposure to the external solvent. When the aglycone substrate binds, a small empty cavity is formed between the I and G helices, the BC loop, and the substrate itself, where solvent molecules accumulate mediating substrate-enzyme interactions. Herein, we analyzed the role of this cavity in substrate binding to OleP by producing three mutants (E89Y, G92W, and S240Y) to decrease its volume. The crystal structures of the OleP mutants in the closed state bound to the aglycone 6DEB showed that G92W and S240Y occupied the cavity, providing additional contact points with the substrate. Conversely, mutation E89Y induces a flipped-out conformation of this amino acid side chain, that points towards the bulk, increasing the empty volume. Equilibrium titrations and molecular dynamic simulations indicate that the presence of a bulky residue within the cavity impacts the binding properties of the enzyme, perturbing the conformational space explored by the complexes. Our data highlight the relevance of this region in OleP substrate binding and suggest that it represents a key substrate-protein contact site to consider in the perspective of redirecting its activity towards alternative compounds.

Abstract 2444: Do all 4 NCL RNA Binding Domains play a role in mRNA target specificity? An in silico study to decipher NCL-mRNA interactions

Abstract RNA binding proteins (RBPs) are post-transcriptional regulators that associate with RNA molecules through one or more of their RNA-binding domains (RBDs). The dysregulation of RBPs, and the RNA metabolism pathways they intersect, are known drivers of tumorigenesis. Nucleolin (NCL) is a stress responsive RBP with four RBDs that directly impacts gene expression by altering rRNA processing, RNA localization, miRNA biogenesis, mRNA decay, and translation. NCL is known to interact with both the 3' and 5' untranslated regions (UTR) and coding regions of target mRNAs to either modulate their stability or translation via recognition of AU-rich or G-rich elements in the RNA. However, the consequences of NCL-mRNA interactions are target-specific as well as context and location dependent. While NCL interacts with both 3' and 5' UTR of TP53 mRNA and suppresses its translation, interactions of NCL with 5' UTR of an anti-apoptotic gene, BCL2, stabilizes this transcript. NCL-mediated enhanced biogenesis of tumorigenic mir-15a and mir-16, on the other hand, results in the translational repression of BCL2. Because NCL exerts its functions in such a complex manner, elucidation of its roles in tumorigenic pathways is paramount in the development of therapeutical applications targeting NCL-RNA interactions. Mechanisms driving NCL-mRNA interactions are currently unknown and this knowledge gap is further compounded by the incomplete nature of the current structural information for NCL and its mRNA targets. In this study, we aim to elucidate NCL RBD-mRNA interactions using computational tools. We investigated interactions of NCL with a specific subset of mRNAs that are implicated in breast cancer progression. We have previously generated and validated in silico models for all the four NCL-RBDs (1-4) in various combinations. Using several secondary and tertiary structure prediction programs along with structure refinement programs, we have generated 3D models of TP53, BCL2, CSF-1, and GADD45α mRNA UTR molecules. Our docking analyses suggests that RBD1-2 and RBD3-4 collaborate in most NCL-mRNA interactions using RNA binding motifs (RNP1 & RNP2) on NCL. We further identify additional contact points in the bridging linker regions between the RBDs that might be crucial for the structural stability of these complexes. This study provides details previously not reported in the literature and provides a comprehensive map of NCL RBD-mRNA interactions that have direct pathophysiological relevance in breast cancer. Altered levels of NCL expression are linked with poor prognosis in breast cancers and targeting NCL results in a better survival outcome. Understanding how NCL associates with its mRNA targets will reveal binding pockets and hence potential sites for drug interventions in addition to characterizing the complex nature of NCL-mRNA interactions/specificity in multiple cancer types. Citation Format: Avdar San, Anjana Saxena, Shaneen Singh. Do all 4 NCL RNA Binding Domains play a role in mRNA target specificity? An in silico study to decipher NCL-mRNA interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2444.

Optimized binding of substituted quinoline ALLINIs within the HIV-1 integrase oligomer

During the integration step, human immunodeficiency virus type 1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Allosteric human immunodeficiency virus type 1 integrase inhibitors (ALLINIs) are a new class of antiviral agents that bind at the dimer interface of the IN catalytic core domain and occupy the binding site of LEDGF/p75. While originally designed to block IN-LEDGF/p75 interactions during viral integration, several of these compounds have been shown to also severely impact viral maturation through an IN multimerization mechanism. In this study, we tested the hypothesis that these dual properties of ALLINIs could be decoupled toward late stage viral replication effects by generating additional contact points between the bound ALLINI and a third subunit of IN. By sequential derivatization at position 7 of a quinoline-based ALLINI scaffold, we show that IN multimerization properties are enhanced by optimizing hydrophobic interactions between the compound and the C-terminal domain of the third IN subunit. These features not only improve the overall antiviral potencies of these compounds but also significantly shift the ALLINIs selectivity toward the viral maturation stage. Thus, we demonstrate that to fully maximize the potency of ALLINIs, the interactions between the inhibitor and all three IN subunits need to be simultaneously optimized.

Effect of Filler Synergy and Cast Film Extrusion Parameters on Extrudability and Direction-Dependent Conductivity of PVDF/Carbon Nanotube/Carbon Black Composites.

In the present study, melt-mixed composites based of poly (vinylidene fluoride) (PVDF) and fillers with different aspect ratios (carbon nanotubes (CNTs), carbon black (CB)) and their mixtures in composites were investigated whereby compression-molded plates were compared with melt-extruded films. The processing-related orientation of CNTs with a high aspect ratio leads to direction-dependent electrical and mechanical properties, which can be reduced by using mixed filler systems with the low aspect ratio CB. An upscaling of melt mixing from small scale to laboratory scale was carried out. From extruded materials, films were prepared down to a thickness of 50 µm by cast film extrusion under variation of the processing parameters. By combining CB and CNTs in PVDF, especially the electrical conductivity through the film could be increased compared to PVDF/CNT composites due to additional contact points in the sample thickness. The alignment of the fillers in the two directions within the films was deduced from the differences in electrical and mechanical film properties, which showed higher values in the extrusion direction than perpendicular to it.

Strontium hexaaluminate formation in alumina and alumina–zirconia matrixes

In this study, the formation mechanism of strontium hexaaluminate (SrAl12O19) in Al2O3–SrO and Al2O3–SrO–ZrO2 composites was investigated. Strontium oxide (SrO) powder was added to initial suspensions in various quantities. High-purity submicron powders were used during the experiments. Powder compositions were thermally treated in the temperature range of 900°С–1500°С for 5 h. The stepwise character of SrAl12O19 formation was established by X-ray phase analysis. The SrAl2O4 intermediate compound formed in the temperature range of 900°С–1200°С. The onset of SrAl12O19 formation corresponded to 1200 °C. Formation of SrAl12O19 was completed in the temperature range of 1400°C-1500°С. After sintering at 1300°С–1500°С for 1 h, the samples were analysed. The density of materials indicated a decreasing trend with an increase in the amount of SrO. The density of alumina ceramics sintered at 1500 °C was 3.65 ± 0.2 g/cm3. However, alumina ceramics comprised 15 wt% SrAl12O19 and their density was 3.35 ± 0.4 g/cm3. A decrease in the density level is explained by the platelet shape of SrAl12O19 grains, which prevented additional contact points from generating between the matrix grains and led to porosity formation in the materials. The effect of a reduction in the alumina grain size was established with an increase in the content of the initial SrO and SrAl12O19 powders. Scanning electron microscopy found that the SrAl12O19 platelets comprised one to three layers fused together along the basal planes. Zirconia grains inhibited the lateral growth of the SrAl12O19 platelets.

Crystal structure, Hirshfeld surface analysis and computational study of the 1:2 co-crystal formed between N,N'-bis-[(pyridin-4-yl)meth-yl]ethanedi-amide and 3-chloro-benzoic acid.

The asymmetric unit of the title 1:2 co-crystal, C14H14N4O2·2C7H5ClO2, comprises a half-mol-ecule of oxalamide (4 LH2), being located about a centre of inversion, and a mol-ecule of3-chloro-benzoic acid (3-ClBA) in a general position. From symmetry, the 4 LH2 mol-ecule has a (+)anti-periplanar conformation with the 4-pyridyl residues lying to either side of the central, planar C2N2O2 chromophore with the dihedral angle between the core and pyridyl ring being 74.69 (11)°; intra-molecular amide-N-H⋯O(amide) hydrogen bonds are noted. The 3-ClBA mol-ecule exhibits a small twist as seen in the C6/CO2 dihedral angle of 8.731 (12)°. In the mol-ecular packing, three-mol-ecule aggregates are formed via carb-oxy-lic acid-O-H⋯N(pyrid-yl) hydrogen bonding. These are connected into a supra-molecular tape along [111] through amide-N-H⋯O(carbon-yl) hydrogen bonding. Additional points of contact between mol-ecules include pyridyl and benzoic acid-C-H⋯O(amide), methyl-ene-C-H⋯O(carbon-yl) and C-Cl⋯π(pyrid-yl) inter-actions so a three-dimensional architecture results. The contributions to the calculated Hirshfeld surface are dominated by H⋯H (28.5%), H⋯O/O⋯H (23.2%), H⋯C/C⋯H (23.3%), H⋯Cl/Cl⋯H (10.0%) and C⋯Cl/C⋯Cl (6.2%) contacts. Computational chemistry confirms the C-Cl⋯π inter-action is weak, and the importance of both electrostatic and dispersion terms in sustaining the mol-ecular packing despite the strong electrostatic term provided by the carb-oxy-lic acid-O-H⋯N(pyrid-yl) hydrogen bonds.

The Structural Interface between HIV-1 Vif and Human APOBEC3H

Human APOBEC3H (A3H) is a cytidine deaminase that inhibits HIV-1 replication. To evade this restriction, the HIV-1 Vif protein binds A3H and mediates its proteasomal degradation. To date, little information on the Vif-A3H interface has been available. To decipher how both proteins interact, we first mapped the Vif-binding site on A3H by functionally testing a large set of A3H mutants in single-cycle infectivity and replication assays. Our data show that the two A3H α-helixes α3 and α4 represent the Vif-binding site of A3H. We next used viral adaptation and a set of Vif mutants to identify novel, reciprocal Vif variants that rescued viral infectivity in the presence of two Vif-resistant A3H mutants. These A3H-Vif interaction points were used to generate the first A3H-Vif structure model, which revealed that the A3H helixes α3 and α4 interact with the Vif β-sheet (β2-β5). This model is in good agreement with previously reported Vif and A3H amino acids important for interaction. Based on the predicted A3H-Vif interface, we tested additional points of contact, which validated our model. Moreover, these experiments showed that the A3H and A3G binding sites on HIV-1 Vif are largely distinct, with both host proteins interacting with Vif β-strand 2. Taken together, this virus-host interface model explains previously reported data and will help to identify novel drug targets to combat HIV-1 infection.IMPORTANCE HIV-1 needs to overcome several intracellular restriction factors in order to replicate efficiently. The human APOBEC3 locus encodes seven proteins, of which A3D, A3F, A3G, and A3H restrict HIV-1. HIV encodes the Vif protein, which binds to the APOBEC3 proteins and leads to their proteasomal degradation. No HIV-1 Vif-APOBEC3 costructure exists to date despite extensive research. We and others previously generated HIV-1 Vif costructure models with A3G and A3F by mapping specific contact points between both proteins. Here, we applied a similar approach to HIV-1 Vif and A3H and successfully generated a Vif-A3H interaction model. Importantly, we find that the HIV-1 Vif-A3H interface is distinct from the Vif-A3G and Vif-A3F interfaces, with a small Vif region being important for recognition of both A3G and A3H. Our Vif-A3H structure model informs on how both proteins interact and could guide toward approaches to block the Vif-A3H interface to target HIV replication.

Semitic Loan Words in the Gospel of John: Elements of Antilanguage or Points of Contact?

This article analyzes sociolinguistic as pects of three Semitic words used in the Gospel of John. Since all these words had wellestablished Hellenistic equivalents in the time of John's writing, their use may be interpreted as a deliberate attempt to establish additional points of contact with nonbelieving Jewish readers. In that case, the use of the convergent forms [~abbi,], [Messi,aj], and [~Wsanna,] in the Fourth Gos pel does not support the hypothesis of “antilanguage” in John and makes one reconsider the results of the research based on that concept.

Microtubule-regulating kinesins

Microtubule-regulating kinesins

The Influence of 150-Cavity Binders on the Dynamics of Influenza A Neuraminidases as Revealed by Molecular Dynamics Simulations and Combined Clustering

Neuraminidase inhibitors are the main pharmaceutical agents employed for treatments of influenza infections. The neuraminidase structures typically exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site. This site offers promising additional contact points for improving potency of existing pharmaceuticals, as well as generating entirely new candidate inhibitors. Several inhibitors based on known compounds and designed to interact with 150-cavity residues have been reported. However, the dynamics of any of these inhibitors remains unstudied and their viability remains unknown. This work reports the outcome of long-term, all-atom molecular dynamics simulations of four such inhibitors, along with three standard inhibitors for comparison. Each is studied in complex with four representative neuraminidase structures, which are also simulated in the absence of ligands for comparison, resulting in a total simulation time of 9.6µs. Our results demonstrate that standard inhibitors characteristically reduce the mobility of these dynamic proteins, while the 150-binders do not, instead giving rise to many unique conformations. We further describe an improved RMSD-based clustering technique that isolates these conformations – the structures of which are provided to facilitate future molecular docking studies – and reveals their interdependence. We find that this approach confers many advantages over previously described techniques, and the implications for rational drug design are discussed.

Influence of the middle ear anatomy on the performance of a membrane sensor in the incudostapedial joint gap

There is a great demand for implantable microphones for future generations of implantable hearing aids, especially Cochlea Implants.An implantable middle ear microphone based on a piezoelectric membrane sensor for insertion into the incudostapedial gap is investigated. The sensor is designed to measure the sound-induced forces acting on the center of the membrane. The sensor mechanically couples to the adjacent ossicles via two contact areas, the sensor membrane and the sensor housing. The sensing element is a piezoelectric single crystal bonded on a titanium membrane. The sensor allows a minimally invasive and reversible implantation without removal of ossicles and without additional sensor fixation in the tympanic cavity.This study investigates the implantable microphone sensor and its implantation concept. It intends to quantify the influence of the sensor's insertion position on the achievable microphone sensitivity. The investigation considers anatomical and pathological variations of the middle ear geometry and its space limitations.Temporal bone experiments on a laboratory model show that anatomical and pathological variations of the middle ear geometry can prevent the sensor from being placed optimally within the incudostapedial joint. Beyond scattering of transfer functions due to anatomic variations of individual middle ears there is the impact of variations in the sensor position within the ossicular chain that has a considerable effect on the transfer characteristics of the middle ear microphone. The centering of the sensor between incus and stapes, the direction of insertion (membrane to stapes or to incus) and the effect of additional contact points with surrounding anatomic structures affect the signal yield of the implanted sensor. The presence of additional contact points has a considerably impact on the sensitivity, yet the microphone sensitivity is quite robust against small changes in the positioning of the incus on the sensor. Signal losses can be avoided by adjusting the position of the sensor within the joint.The findings allow the development of an improved surgical insertion technique to ensure maximally achievable signal yield of the membrane sensor in the ISJ and provides valuable knowledge for a future design considerations including sensor miniaturization and geometry.Measurements of the implanted sensor in temporal bone specimens showed a microphone sensitivity in the order of 1 mV/Pa.This article is part of a Special Issue entitled “MEMRO 2012”.

HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods.

The binding between the HIV-1 trans-activator of transcription (Tat) and p300/(CREB-binding protein)-associated factor (PCAF) bromodomain is a crucial step in the HIV-1 life cycle. However, the structure of the full length acetylated Tat bound to PCAF has not been yet determined experimentally. Acetylation of Tat residues can play a critical role in enhancing HIV-1 transcriptional activation. Here, we have combined a fully flexible protein-protein docking approach with molecular dynamics simulations to predict the structural determinants of the complex for the common HIV-1BRU variant. This model reproduces all the crucial contacts between the Tat peptide 46SYGR(AcK)KRRQRC56 and the PCAF bromodomain previously reported by NMR spectroscopy. Additionally, inclusion of the entire Tat protein results in additional contact points at the protein-protein interface. The model is consistent with the available experimental data reported and adds novel information to our previous structural predictions of the PCAF bromodomain in complex with the rare HIVZ2 variant, which was obtained with a less accurate computational method. This improved characterization of Tat.PCAF bromodomain binding may help in defining the structural determinants of other protein interactions involving lysine acetylation.