Single Ab Research Articles

Potential Dependence of Electrochemical Barriers from ab Initio Calculations.

We present a simple and computationally efficient method to determine the potential dependence of the activation energies for proton-electron transfer from a single ab initio barrier calculation. We show that the potential dependence of the activation energy is given by the partial charge transferred at the transition state. The method is evaluated against the potential dependence determined explicitly through multiple calculations at varying potential. We show that the transfer coefficient is given by the charge transferred from the initial to transition state, which has significant implications for electrochemical kinetics.

The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths.

The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted.

A G-pentaplex-based assay for Cs(+) ions in aqueous solution using a luminescent Ir(III) complex.

A series of 5 randomly designed in-house cyclometalated Ir(III) complexes were examined for their application in G-pentaplex probes and the "proof-of-principle" concept in G-pentaplex-based Cs(+) ions detection. The G-pentaplex-forming sequence (DNA1, 5'-T(iG)4T-3', where iG=isoguanine) is present in single strand DNA form ab initio, however, the addition of Cs(+) ions lead to formation of the intermolecular G-pentaplex structure which is identified by the novel Ir(III) complex 1 afterward and produce an enhanced luminescence signal for Cs(+) ions monitoring. To the best of our knowledge, this is the first G-pentaplex probe and also the first G-pentaplex-based label-free detection platform for Cs(+) ions reported in the literature. The monitoring of spiked Cs(+) ions in natural water samples demonstrates the potential application and technical sound of this "proof-of-principle" concept sensing platform.

DeepCNF-D: Predicting Protein Order/Disorder Regions by Weighted Deep Convolutional Neural Fields.

Intrinsically disordered proteins or protein regions are involved in key biological processes including regulation of transcription, signal transduction, and alternative splicing. Accurately predicting order/disorder regions ab initio from the protein sequence is a prerequisite step for further analysis of functions and mechanisms for these disordered regions. This work presents a learning method, weighted DeepCNF (Deep Convolutional Neural Fields), to improve the accuracy of order/disorder prediction by exploiting the long-range sequential information and the interdependency between adjacent order/disorder labels and by assigning different weights for each label during training and prediction to solve the label imbalance issue. Evaluated by the CASP9 and CASP10 targets, our method obtains 0.855 and 0.898 AUC values, which are higher than the state-of-the-art single ab initio predictors.

Abstract P5-02-13: Triple negative breast cancer, the impact of isotype-specific progesterone receptor antibodies on the diagnosis results

Abstract Background: Given the poor therapeutic outcomes for triple negative breast cancer (TNBC), diagnostic accuracy is vital. In routine IHC testing, the progesterone receptor (PR) is determined using bispecific antibodies (Ab) that recognize epitopes common to PRA and PRB. PRA and PRB expression can be imbalanced in BC. Relative expression of the PR isotypes appears to be prognostic in BC evaluated with a bispecific Ab (Hopp 2004). Tumors can express PRA or PRB on different cells in the same tumor (Mote 2008), which differs from those expressing ERα (Zukiwski 2013). A true TN phenotype might escape detection with the use of one single Ab to detect both PRA and B epitopes, depending on sensitivity/specificity. This study evaluated the use of two isotype-specific PR Abs to fully characterize the PR status. Methods: 83 dual ERα and HER2 negative archived BC specimens with clinical data were obtained from the Oscar Lambret Cancer Center, Lille, FR. IHC was performed using anti-PRA, anti-PRB, and the bispecific anti-PR Pg636 antibodies. PR tumor positivity was explored using 2 cut-offs, ≥ 1% or ≥ 5% stained tumor cells. PR positive tumors were defined as either PRA or PRB positive. Results: For PR positive tumors with ≥ 1% positive cells, average PRA positivity was 41%, PRB was 38% (PRA vs PRB p = NS), and PRAB 3% (PRA vs PRAB = 0.001, PRB vs PR AB p = 0.0001). Using 1% as positivity cut off PRA and PRB were discordant in 14% of the cases, PRA and PR AB in 12%. PR B and PR AB were discordant in 2%. Discordance between PR positivity (either A or B) and PRAB positivity was 7% with no PR negative PRAB positive tumors i.e. no positivity was missed using two PR A and B antibodies while all 7% cases were missed by the PRAB antibody. Using 5% as a cut off, the discordance rate was 8% between PRA and PRB, 25% between PRA and PRAB and no PRA negative and PRAB positive case were found, and 26% between PRB and PRAB with no PRB negative PRAB positive cases either. PR positivity (A or B) was missed in 30% of the cases with a PRAB. Patients with tumors identified as PR positive (≥ 5%) using the isotype specific antibodies and PR negative with the PRAB antibody have a better prognosis (DFS). Conclusion: In TNBC, there is a different staining pattern when using isotype-specific vs bispecific anti-PR anti-bodies. The average percent of positive tumors cells is substantially reduced when using a bispecific Ab as compared to isotype-specific AB. This translates into potential false negative PRAB testing which varies from 7% to 30% depending of the cut off criteria. TNBC reclassified by the use of isotype-specific anti-PR antibodies may be appropriate for investigation with anti-progestins. Citation Format: Jacques Bonneterre, Jacques Bosq, Charline Alleaume, Erard Gilles, Philippe Jamme, Alexander Zukiwski. Triple negative breast cancer, the impact of isotype-specific progesterone receptor antibodies on the diagnosis results [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-13.

Charge Density Analysis of 2,6-Dinitrophenol

The charge density of 2,6-dinitrophenol has been carefully determined from low temperature (20 K) single crystal X-ray diffraction data and periodic ab initio theoretical calculations. The topological analysis performed on the refined densities within the framework of the Quantum Theory of Atoms in Molecules (QTAIM), allowed us to characterize, both qualitatively and quantitatively, the various intra- and intermolecular interactions existing in the crystal structure of this compound. Notably two strong intramolecular noncovalent interactions have been characterized (O···H, De > 60 kJ/mol; O···O, De ∼ 19 kJ/mol). In addition, a series of weaker intermolecular interactions (O···N, O···O, O···C, and C···C) with estimated dissociation energies of 1–9 kJ/mol have been identified.

Linear free-energy relationships between a single gas-phase ab initio equilibrium bond length and experimental pKa values in aqueous solution.

Remarkably simple yet effective linear free energy relationships were discovered between a single ab initio computed bond length in the gas phase and experimental pKa values in aqueous solution. The formation of these relationships is driven by chemical features such as functional groups, meta/para substitution and tautomerism. The high structural content of the ab initio bond length makes a given data set essentially divide itself into high correlation subsets (HCSs). Surprisingly, all molecules in a given high correlation subset share the same conformation in the gas phase. Here we show that accurate pKa values can be predicted from such HCSs. This is achieved within an accuracy of 0.2 pKa units for 5 drug molecules.

MENINGKATKAN KEMAMPUAN MENARI TARI BALANSE MADAM MELALUI METODE SAS UNTUK ANAK TUNARUNGU (Single Subject Research Kelas II SMP di SLB Bundo Kanduang Padang)

Abstrack: This study aims to test the effectiveness of the use of SAS methods in studyng dancing skills for children of dance of balanse madam in SLB Bundo Kanduang Padang. This research was using Single Subject Research approach wit AB design . Subjects were a deaf children in class II SMPLB . To measure the research variables, the percentage of the techniques applied. Based on the results of data analysis, it was found that the use of SAS method effective to improve dancing skills of balanse madam in class II SMP SLB Bundo Kanduang Padang. Kata-kata kunci: Metode SAS; Menari; Tari Balanse Madam; Tunarungu

Abstract 5567: Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC)

Abstract Background: Given the poor therapeutic outcomes for triple negative BC, diagnostic accuracy is vital. In routine IHC, PR is measured using bispecific antibodies (Ab) that recognize epitopes common to PRA and PRB. PR A and B expression is imbalanced in BC. Relative expression of the PR isotypes appears to be prognostic in tumors evaluated with a bispecific Ab (Hopp 2004). Tumors can express PRA or PRB on different cells in the same tumor (Mote 2008), which differ from those expressing ERα (Zukiwski 2013). A true triple negative phenotype might escape detection with the use of one single Ab to detect both PR A and B epitopes, depending on its sensitivity/specificity. This study evaluated the use of two isotype-specific PR Abs to fully characterize PR status. Methods: 312 archived BC specimens with clinical data came from Oscar Lambret Cancer Center, Lille. HER2 status was previously determined. IHC was performed using anti-ERα, anti-PRA and PRB Abs. ERα and PR tumor positivity was defined as ≥ 1% stained tumor cells. Results: 276 cases had complete data. Table 1 shows ERα, PRA and PRB status. 38/276 cases (14%) were ERα and HER2 negative: 22 were PR A or B negative, 9 were PR A and B positive, 2 were positive only for PRA and 5 only for PRB. Discussion: Bispecific PR Abs rarely report PRA and PRB similarly (Mote 2001). PR Phosphorylation and activation may vary across tumors. Potentially only one PR isotype may drive BC tumor growth. Triple-negative BC status determination could be PR Ab-dependent. These cases are currently being tested with a standard bispecific PR Ab to understand which would be considered triple-negative with routine IHC. Conclusion: Further evaluation of IHC with specific PRA and PRB Abs is warranted to determine if certain patients, currently classified as having triple-negative BC, could respond to antiprogestins, which have shown activity in BC. Table 1% of276 casesPR (PRA or PRB)PRAPRBERαNegativePositiveTotalNegativePositiveTotalNegativePositiveTotalNegative148221742115722Positive77178146579106868Total217910031691002575100 Citation Format: Erard Gilles, Jacques Bosq, Laura Caplier, Alice Bexon, Alexander Zukiwski, Jacques Bonneterre. Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5567. doi:10.1158/1538-7445.AM2014-5567

Relationship between autoantibodies combination, metabolic syndrome components and diabetic complications in autoimmune diabetes in adults.

The aim of our study was to establish the possible association between double or triple antibody positivity and latent autoimmune diabetes (LADA) phenotype in the context of metabolic syndrome (MS) prevalence and its individual components. This cross-sectional study population comprised 69 islet cell antibody-positive patients coming for their comprehensive annual review. They were divided into three groups according to antibody positivity. Twenty-five (36.2 %) were male, mean age of 51 years with disease duration of 8 years. Twenty-eight (40.58 %) were positive only for GAD Abs, 26 (37.68 %) were positive for ICA and GAD Abs and 15 (21.74 %) were positive for GAD, ICA, and IA2 Abs. The lowest value of waist circumference, MS, and artherial hypertension prevalence was found in the group positive for all three antibodies. In the multinomial multivariate logistic regression model, MS was negatively associated with triple Abs positivity compared to single Ab positivity and double Abs positivity. Our results highlight the importance of inverse association between simultaneous Abs positivity for ICA, GAD, and IA2 with the MS and its components present in LADA patients. This inverse relationship might implicate that LADA patients are phenotypically closer to T1DM. The contribution of IA2 Ab positivity merits is to be considered in the determination of LADA phenotypes, while its diagnostic value needs to be clarified in future follow-up studies.

Orthographically sensitive treatment for dysprosody in children with Childhood Apraxia of Speech using ReST intervention

Objective: Impaired prosody is a core diagnostic feature of Childhood Apraxia of Speech (CAS) but there is limited evidence of effective prosodic intervention. This study reports the efficacy of the ReST intervention used in conjunction with bisyllabic pseudo word stimuli containing orthographic cues that are strongly associated with either strong-weak or weak-strong patterns of lexical stress. Methods: Using a single case AB design with one follow-up and replication, four children with CAS received treatment of four one-hour sessions per week for three weeks. Sessions contained 100 randomized trials of pseudo word treatment stimuli. Baseline measures were taken of treated and untreated behaviors; retention was measured at one day and four weeks post-treatment. Results: Children’s production of lexical stress improved from pre to post-treatment. Treatment effects and maintenance varied among participants. Conclusions: This study provides support for the treatment of prosodic deficits in CAS.

Influence of computerized sounding out on spelling performance for children who do and do not rely on AAC

Purpose: Spelling is an important skill for individuals who rely on augmentative and alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Methods: Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. Results: The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. Conclusion: The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed.Implications for RehabilitationWe investigated how computerized sounding out influenced spelling accuracy of pseudowords for children with complex communication needs who did and did not use augmentative and alternative communication (AAC).Results indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words by participants, suggesting that computerized sounding out might assist in more accurate spelling for children who use AAC.Future research is needed to determine how language and reading abilities influence the use of computerized sounding out with children who have a range of speech intelligibilityabilities and do and do not use AAC.

Signature of bulk longitudinal plasmon-polaritons in the transmission/reflection spectra of one-dimensional metamaterial heterostructures

A systematic theoretical study of the transmission and reflection spectra of a 1D metamaterial heterostructure consisting of the finite repetition of a double layer of two different building blocks A (normal non-dispersive layer) and B (dispersive metamaterial) is presented, with the multi-layered system sandwiched between two semi-infinite layers of the A material. For the metamaterial slabs B we have studied two different dielectric/magnetic responses: a first one with both the electric permittivity and magnetic permeability given by a Drude-like metamaterial dispersion response, and a second one with the electric permittivity still given by a Drude-like response, whereas the magnetic permeability is given by a more realistic split-ring resonator metamaterial response. Theoretical calculations are performed within the transfer-matrix formalism, and transmission and reflection coefficients of the metamaterial heterostructure are straightforwardly evaluated. For oblique incidence, a finite projection along the growth direction of the electric or magnetic field of the incident wave associated with the TM or TE modes, respectively, leads to a coupling in each layer of the metamaterial heterostructure of the photon modes with the bulk electric or magnetic metamaterial plasmons, respectively. Such photon–plasmon coupling results in the formation of plasmon-polariton modes and gives rise to signatures of the electric or magnetic longitudinal bulk-plasmon polariton modes in the transmission and reflection spectra of the metamaterial heterostructure. Such features survive even in the case of a single AB double-layer metamaterial heterostructure, and experimental observation should be, therefore, easily achieved.

Performance of the EOMIP-CCSD(2) Method for Determining the Structure and Properties of Doublet Radicals: A Benchmark Investigation.

We present a benchmark study on the performance of the EOMIP-CCSD(2) method for computation of structure and properties of doublet radicals. The EOMIP-CCSD(2) method is a second-order approximation to the standard EOMIP-CCSD method. By retaining the black box nature of the standard EOMIP-CCSD method and adding favorable N(5) scaling, the EOMIP-CCSD(2) method can become the method of choice for predicting the structure and spectroscopic properties of large doublet radicals. The EOMIP-CCSD(2) method overcomes the typical problems associated with the standard single reference ab initio treatment of doublet radicals. We compare our results for geometries and harmonic vibrational frequencies with those obtained using the standard EOMIP-CCSD method, as well as unrestricted Hartree-Fock (UHF)- and restricted open-shell Hartree-Fock (ROHF)-based single-reference coupled-cluster and second order many-body perturbation theory (MBPT(2)) methods. The effect of the basis set on the quality of the results has been studied using a hierarchy of Dunning's correlation-consistent aug-cc-pVXZ (X = D, T, Q) basis sets. Numerical results show that the EOMIP-CCSD(2) method, despite its N(5) scaling, gives better agreement with experimental results, compared to the UHF- and ROHF-based MBPT(2), as well as the single-reference coupled-cluster methods.

CAN THE SOCIAL ROBOT PROBO HELP CHILDREN WITH AUTISM TO IDENTIFY SITUATION-BASED EMOTIONS? A SERIES OF SINGLE CASE EXPERIMENTS

Children with autism spectrum disorders have difficulties in identifying situation-based emotions, which is a fundamental ability for mind reading. Social robots received increased attention as assisting tools for improving the social and emotional skills of children with autism. This study investigates whether the social robot Probo can help children with autism spectrum disorders to enhance their performance in identifying situation-based emotions. Three participants (age between 5 and 6) diagnozed with autism spectrum disorders were included in a single case AB experimental design, with intersubjects replications. The results show that children's performance improved with moderate to large effect sizes in identifying both sadness and happiness. Based on these results, we intend to perform more extensive investigations regarding the effectiveness of robot assisted therapy in improving social-emotional abilities for children with autism spectrum disorders.

Modified ab externo method for introducing 2 polypropylene loops for scleral suture fixation of intraocular lenses

We describe a method that enables the introduction of 2 suture loops for scleral fixation of an intraocular lens (IOL) by a single ab externo procedure. A long needle carrying a polypropylene suture loop is inserted through the scleral fixation site and docked with a hollow needle inserted through the opposite fixation site. The hollow needle pulls the suture needle out, but the suture loop end is left external. Another polypropylene suture loop is placed through the first loop. As the first (leading) suture is pulled, the second (trailing) suture is drawn into the eye. The suture loops are retrieved through the main incision. The IOL haptics are secured with a polypropylene loop by cow hitches. After the IOL is placed in the eye, the sutures are fixated to the sclera. This technique enhances efficiency and control during the introduction of suture loops for scleral fixation of IOLs.

Disease-Enhancing Antibodies Improve the Efficacy of Bacterial Toxin-Neutralizing Antibodies

During infection, humoral immunity produces a polyclonal response with various immunoglobulins recognizing different epitopes within the microbe or toxin. Despite this diverse response, the biological activity of an antibody (Ab) is usually assessed by the action of a monoclonal population. We demonstrate that a combination of monoclonal antibodies (mAbs) that are individually disease enhancing or neutralizing to Bacillus anthracis protective antigen (PA), a component of anthrax toxin, results in significantly augmented protection against the toxin. This boosted protection is Fc gamma receptor (FcγR) dependent and involves the formation of stoichiometrically defined mAb-PA complexes that requires immunoglobulin bivalence and simultaneous interaction between PA and the two mAbs. The formation of these mAb-PA complexes inhibits PA oligomerization, resulting in protection. These data suggest that functional assessments of single Abs may inaccurately predict how the same Abs will operate in polyclonal preparations and imply that potentially therapeutic mAbs may be overlooked in single Ab screens.

Anti‐CD2 producing pig xenografts effect localized depletion of human T cells in a huSCID model

We investigated whether graft produced anti-human CD2, mediated by adenovirus (Adv) transduction of pig neonatal islet cell clusters (pNICC), would protect xenografts in a humanized mouse model from immune attack and whether such immunosuppression would remain local. A mouse anti-human CD2 Ab (CD2hb11) previously generated by us was genetically engineered to produce chimeric and humanized versions. The three forms of CD2hb11 were named dilimomab (mouse), diliximab (chimeric) and dilizumab (humanized). All 3 forms of CD2hb11 Ab were tested for their ability to bind CD3(+) human T cells and to inhibit a human anti-pig xenogeneic mixed lymphocyte reaction (MLR). They were administered systemically in a humanized mouse model in order to test their ability to deplete human CD3(+) T cells and whether they induced a cytokine storm. An adenoviral vector expressing diliximab was generated for transduction of pNICC. Humanized mice were transplanted with either control-transduced pNICC or diliximab-transduced pNICC and human T cells within grafts and spleens were enumerated by flow cytometry. Dilimomab and diliximab inhibited a human anti-pig xenogeneic response but dilizumab did not. All 3 forms of CD2hb11 Ab bound human T cells in vitro though dilimomab and diliximab exhibited 300-fold higher avidity than dilizumab. All 3 anti-CD2 Abs could deplete human CD3(+) T cells in vivo in a humanized mouse model without inducing upregulation of activation markers or significant release of cytokines. Humanized mice transplanted with diliximab-transduced pNICC afforded depletion of CD3(+) T cells at the graft site leaving the peripheral immune system intact. Local production of a single Ab against T cells can reduce graft infiltration at the xenograft site and may reduce the need for conventional, systemic immunosuppression.

Free-energy based pair-additive potentials for bulk Ni-Al systems: Application to study Ni-Al reactive alloying

We present new numerical pair-additive Al, Ni, and Al-Ni potentials by force-matching (FM) ionic force and virial data from single (bulk liquid) phase ab initio molecular dynamics (MD) simulations using the Born-Oppenheimer method. The potentials are represented by piece-wise functions (splines) and, therefore, are not constrained to a particular choice of analytical functional form. The FM method with virial constraint naturally yields a potential which maps out the ionic free-energy surface of the reference ensemble. To further improve the free energetics of the FM ensemble, the FM procedure is modified to bias the potentials to reproduce the experimental melting temperatures of the reference (FCC-Al, FCC-Ni, B2-NiAl) phases, the only macroscopic data included in the fitting set. The performance of the resultant potentials in simulating bulk metallic phases is then evaluated. The new model is applied to perform MD simulations of self-propagating exothermic reaction in Ni-Al bilayers at P = 0-5 GPa initiated at T = 1300 K. Consistent with experimental observations, the new model describes realistically a sequence of peritectic phase transformations throughout the reaction and at a realistic rate. The reaction proceeds through interlayer diffusion of Al and Ni atoms at the interface with formation of B2-NiAl in the Al melt. Such material responses have, in the past, been proven to be difficult to observe with then-existing potentials.

Mechanism of densification in silica glass under pressure as revealed by a bottom-up pairwise effective interaction model

A new short-range pairwise numerical potential for silica is presented. The potential is derived from a single ab initio molecular dynamics (AIMD) simulation of molten silica using the force-matching method with the forces being represented numerically by piecewise functions (splines). The AIMD simulation is performed using the Born-Oppenheimer method with the generalized gradient approximation (BLYP) for the XC energy functional. The new effective potential includes a soft-repulsive shoulder to describe the interactions of oxygen ions at short separations. The new potential, despite being short-ranged and derived from single-phase data, exhibits a good transferability to silica crystalline polymorphs and amorphous silica. The importance of the O-O soft-repulsive shoulder interaction on glass densification under cold and shock compressions is assessed from MD simulations of silica glass under room and shock Hugoniot conditions, respectively. Results from these simulations indicate that the appearance of oxygen complexes (primarily pairs) interacting through soft-repulsive shoulder potential occurs at 8-10 GPa, and under cold compression conditions becomes notable at 40 GPa, essentially coinciding with the transition to a Si sixfold coordination state. An analysis of changes in system structure in compressed and shocked states reveals that the O ions interacting through the soft-repulsive shoulder potential in denser states of silica glass may create a mechanical multi-stability under elevated pressures and thus to contribute to the observed anomalous densification.