gebhart/patrepeval huggingface dataset:
Strategies in Designing Multigene Expression Units to Downregulate HIV-1 (2010)

The treatment of viral diseases such as HIV and HCV is limited by the genetic diversity of the viruses, especially when they are under the selective pressure of drugs. This problem holds true for gene-based therapies using RNAi in which there is evolution of drug-resistant strains under the discriminating pressure of treatment (1, 2). In a gene therapy setting for treatment of HIV, the incorporation of multiple effector molecules, targeting different viral and cellular sequences, can improve viral inhibition by substantially delaying the emergence of escape mutants (3-8). However, for short hairpin RNA triggers of RNAi, high levels of expression by strong Pol III promoters has led to cell toxicity, and even death in experimental animals (9, 10). Here, we describe a new combinatorial anti-HIV gene expression system allowing simultaneous expression of multiple RNAi effector units from a single Pol II polycistronic transcript. Our platform is suitable for the inclusion of any shRNA sequence and can be combined with other types of small RNA antiviral inhibitors.
Permanent genetic memory with >1-byte capacity. (2014)

Genetic memory enables the recording of information in the DNA of living cells. Memory can record a transient environmental signal or cell state that is then recalled at a later time. Permanent memory is implemented using irreversible recombinases that invert the orientation of a unit of DNA, corresponding to the [0,1] state of a bit. To expand the memory capacity, we have applied bioinformatics to identify 34 phage integrases (and their cognate attB and attP recognition sites), from which we build 11 memory switches that are perfectly orthogonal to each other and the FimE and HbiF bacterial invertases. Using these switches, a memory array is constructed in Escherichia coli that can record 1.375 bytes of information. It is demonstrated that the recombinases can be layered and used to permanently record the transient state of a transcriptional logic gate.
Synthesis, characterization, and crosslinking of novel stars comprising eight poly(isobutylene‐azeotropic‐styrene) copolymer arms with allyl or hydroxyl termini. I. Living azeotropic copolymerization of isobutylene and styrene (2001)

Abstract The overall objective of this research is the creation of novel star polymers consisting of well‐defined stable cores out of which radiate multiple poly(isobutylene‐ co ‐styrene) [P(IB‐ co ‐St)] arms whose glass‐transition temperature ( T g ) can be controlled over a wide range (−73 to +100 °C) and whose arm termini are fitted with multipurpose (e.g., crosslinkable) functionalities. The first article of this series relates the synthesis and characterization of azeotropic IB/St copolymers [P(IB‐ aze ‐St)], which are to be subsequently used as end‐functional arms of the target stars. The P(IB‐ aze ‐St)s are models for statistical IB/St copolymers. The azeotropic composition is 21/79 (mol/mol) IB/St, and NMR, Fourier transform infrared, and gel permeation chromatography techniques demonstrate copolymer compositional homogeneity over the 12–96% conversion range. Conditions were developed for living azeotropic IB/St copolymerization. The livingness of the azeotropic copolymerization was proven by kinetic investigations. P(IB‐ aze ‐St)s with number‐average molecular weights of up to 24,000 g/mol and polydispersity indices (weight‐average molecular weight/number‐average molecular weight) less than 1.5 were prepared. The copolymerization reactivity ratios were determined: r IB = 3.41 ± 0.23 and r St = 1.40 ± 0.26. The effect of the P(IB‐ aze ‐St) molecular weight on T g was studied by DSC. T g increases linearly with the number‐average molecular weight and reaches a plateau at 62 °C at 24,000 g/mol. The heat stability of P(IB‐ aze ‐St) was investigated by thermogravimetric analysis, and a 5% weight loss was found at 250 °C in air. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci A: Polym Chem 39: 1515–1524, 2001
Targeting human langerin promotes HIV-1 specific humoral immune responses (2021)

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.
A Simple Correlation-Based Model Of Intelligibility For Nonlinear Speech Enhancement And Separation (2009)

Publication in the conference proceedings of EUSIPCO, Glasgow, Scotland, 2009
Scalable Synthesis of Porous Silicon by Acid Etching of Atomized Al–Si Alloy Powder for Lithium-Ion Batteries (2023)

Si anodes have attracted considerable attention for their potential application in next-generation lithium-ion batteries because of their high specific capacity (Li<sub>15</sub>Si<sub>4</sub>, 3579 mAh g<sup>-1</sup>) and elemental abundance. However, Si anodes have not yet been practically applied in lithium-ion batteries because the volume change associated with lithiation and delithiation degrades their capacity during cycling. Instead of considering the active material, we focused on the structural design and developed a scalable process for producing Si anodes with excellent cycle characteristics while precisely controlling the morphology. Al-Si alloy powders were prepared by gas atomization, and porous Si with a skeletal structure was prepared by leaching Al using HCl. Porous Si (p-Si<sub>12</sub>, p-Si<sub>19</sub>) prepared from Al<sub>88</sub>Si<sub>12</sub> and Al<sub>81</sub>Si<sub>19</sub> comprised resinous eutectic Si, and porous Si (p-Si<sub>25</sub>) prepared from Al<sub>75</sub>Si<sub>25</sub> comprised lumpy primary Si and resinous eutectic Si. The porosity of the Si anodes varied from 63% to 76%, depending on the Si composition. The p-Si<sub>19</sub> anode displayed the finest pore distribution (20-200 nm), excellent rate characteristics, a reversible discharge capacity of 1607 mAh g<sup>-1</sup> after 200 cycles at a rate of 0.1 C with a Coulombic efficiency of over 97%, and high stability. The performances of the p-Si<sub>25</sub> and p-Si<sub>19</sub> electrodes began to decrease after 250 and 850 cycles, respectively, with a constant-charge capacity of 1000 mAh g<sup>-1</sup> and at a rate of 0.2 C. In contrast, the p-Si<sub>12</sub> anode maintained its discharge capacity at 1000 mAh g<sup>-1</sup> for up to 1000 cycles without degradation. Therefore, the developed manufacturing process is expected to produce porous Si as an active material in lithium-ion batteries for high capacity and long life at an industrial scale.
Dual-scale topology optoelectronic processor (1990)

D-STOP is a parallel, scalable, fully connected optoelectronic computing architecture suitable for applications in interconnection networks, numerical processing, neural networks, and artificial intelligence. The architecture consists of an array of N optoelectronic processing elements arranged in a 2-D topology. Each processing element consists of N electronic processing sub-units having detectors. These detector sub-units are electronically connected by an H-tree interconnection. At each node of the H-tree are additional fan-in processing sub-units. At the center of the H-tree is a single processing sub-unit having an optical modulator. Fully connected interprocessor communication is achieved through space-invariant optical interconnections, leading to a scalable architecture. The architecture can be used to perform outer product and inner product operations. Since all mathematical operations are performed electronically, the products can be generalized. Additional processing is available during fan-in, generalizing the conventional summation of inner products. This feature is particularly useful in neural network applications, including backpropagation networks. The key to the architecture is the dual scale of processing: detector and fan-in sub-units at the lower level and composite processing elements at the higher level. We will present the architecture, its functionality, applications, and optoelectronic design considerations.
Origin of light emission from silicon nanoparticles (2002)

Light emission characteristics from silicon nanoparticles consisting of a crystalline core encased in an amorphous oxide shell are reported. The particles were thermally oxidized to further reduce the silicon core dimensions. Photoluminescence measurements reveal substantial difference in emission intensities and peak wavelengths under low and high excitation levels. The results indicate that at least two mechanisms contribute to the light emission from Si nanoparticles, one associated with quantum size effects, and another possibly related to surface defects.
Passive, intermittent cryocooler for vibration-free and load-leveling space applications (2002)

This paper describes the use of passive adsorption/phase change subsystems for use in nonvibration cryocooling modes of operation in space applications. The specific focus here is the optimization and identification of working fluids and adsorbents for use in these systems. The authors' previous research (1995) has demonstrated specific power densities capable of 1-6 W/kg of total weight for a 60 minute operation, exceeding conventional mechanical cryocooler systems (0.1-1 W/kg). For much shorter online passive cooling operations (e.g., 10 minutes), the cooling capacity will be in the range of 5-36 W/kg. Fluids and adsorbents suitable for the range of 30 K up to 200 K in space and biomedical applications are also detailed in this paper, and implications for use in hybrid mechanical cryocoolers are discussed.
Biotransformation of (–)-Caryophyllene Oxide by Cell Suspension Culture of Catharanthus roseus (2006)

Abstract Catharanthus roseus cell suspension cultures were employed for the biotransformation of (-)-caryophyllene oxide (1), and four metabolites, 15-hydroxycaryophyllene oxide (2), 4β ,5α- dihydroxycaryophyll-8(13)-ene (3), 2β -hydroxycaryophyllene oxide (4), and 2-hydroxy-4,5- epoxycaryophyllan-13-ol (5) were obtained. Metabolites 4 and 5 were found to be new compounds, and their structures were deduced by different spectroscopic techniques.
Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents (2006)

One of the few books to cover all aspects of cyclin-dependent kinases (CDKs), Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents provides an overview of CDKs as molecular and functional entities, their involvement in different disease processes, and their potential for pharmacological modulation. With contributions from the top inte
Homeobox genes in mouse development. (1991)

Following the discovery of the homeobox as a conserved sequence in developmentally important genes of Drosophila, a plethora of such sequences have been identified in evolutionarily distant organisms. Among mammals, the mouse homeobox genes have been studied most intensively with a hope of deciphering basic mechanisms of embryonic development. The genomic arrangement of many mouse homeobox genes is similar to the organization of the Drosophila genes, suggesting that they arose as a consequence of gene duplication and divergence from a primordial cluster during evolution. Homeobox genes encode proteins that may form a part of the autoregulatory and transregulatory network specifying positional value in the embryo. Supporting this view, the more diverged members of this growing family function as transcription factors, some of which regulate the expression of tissue-specific genes. Mouse homeobox genes are expressed during embryonic development in a spatially restricted manner and alterations in their expression pattern can disrupt embryonic development. The implications of these findings will be discussed in the context of the role of homeobox genes in the embryonic development of Drosophila and other organisms.
Characterization of the canine type C enterotoxin produced by Staphylococcus intermedius pyoderma isolates (1997)

The type C staphylococcal enterotoxins (SECs) are a group of highly conserved proteins with substantial antigenic cross-reactivity. Although Staphylococcus intermedius and coagulase-positive species of staphylococci are reported to produce SEC and other SEs, toxins produced by species other than Staphylococcus aureus have not been previously characterized. In this study we report the molecular, biological, and immunological properties of the canine SEC (SECcanine) expressed by pathogenic isolates of S. intermedius. The mature form of SECcanine has 239 amino acid residues and a pI of 7.0. Typical of the SEs, purified SECcanine induces an emetic response in monkeys and the proliferation of T cells in a Vbeta-dependent manner. Although SECcanine has >95% sequence identity to previously described SEC variants, its sequence is most related to SEC2 and SEC3. In contrast to the sequence similarity, the Vbeta profile induced by SECcanine is typical of that induced by SEC1. This result is likely explained by the conservation of a cysteine residue at position 26 in SECcanine; residues at this position have been previously shown to determine subtype-dependent differences in T-cell receptor interactions of other SEs. Overall, these results show that superantigen toxins produced by the multiple members of the genus Staphylococcus are highly conserved in respect to biological and structural properties. Further, the frequent association of SECcanine with pyoderma in dogs supports the notion that the toxins are important for staphylococcal survival and pathogenesis.
Biostable conductive nanocomposite for implantable subdermal antenna (2020)

Current antennas used for communication with implantable medical devices are connected directly to the titanium device enclosure, but these enclosures are shrinking as batteries and circuits become smaller. Due to shrinking device size, a new approach is needed that allows the antenna to extend beyond the battery pack, or to be entirely separate from it. Softer properties are needed for antennas in direct contact with body tissues. This must be achieved without compromising the high electrical conductivities and stabilities required for acceptable performance. Here, a nanocomposite based approach was taken to create soft, biocompatible antennas that can be embedded in the fat layer as an alternative to the metallic antennas used today. The nanocomposite films combine the exceptional electrical conductivity, biocompatibility, and biostability of Au nanoparticles with the mechanical compliance, biocompatibility, and low water permeability of polyurethane. Nanocomposite film synthesis utilized flocculation and vacuum assisted filtration methods. The soft antenna films display high conductivities (∼103 S/m–105 S/m), reduced Young’s moduli (∼102 MPa–103 MPa), exceptional biocompatibilities characterized by in vivo and in vitro work, and notable biostabilities characterized by accelerated degradation studies. Consequently, the nanocomposite antennas are promising for chronic in vivo performance when the conductivity is above 103 S/m.
How well does molecular simulation reproduce environment-specific conformations of the intrinsically disordered peptides PLP, TP2 and ONEG? (2022)

Understanding the conformational ensembles of intrinsically disordered proteins and peptides (IDPs) in their various biological environments is essential for understanding their mechanisms and functional roles in the proteome, leading to a greater knowledge of, and potential treatments for, a broad range of diseases. To determine whether molecular simulation is able to generate accurate conformational ensembles of IDPs, we explore the structural landscape of the PLP peptide (an intrinsically disordered region of the proteolipid membrane protein) in aqueous and membrane-mimicking solvents, using replica exchange with solute scaling (REST2), and examine the ability of four force fields (ff14SB, ff14IDPSFF, CHARMM36 and CHARMM36m) to reproduce literature circular dichroism (CD) data. Results from variable temperature (VT) <sup>1</sup>H and Rotating frame Overhauser Effect SpectroscopY (ROESY) nuclear magnetic resonance (NMR) experiments are also presented and are consistent with the structural observations obtained from the simulations and CD. We also apply the optimum simulation protocol to TP2 and ONEG (a cell-penetrating peptide (CPP) and a negative control peptide, respectively) to gain insight into the structural differences that may account for the observed difference in their membrane-penetrating abilities. Of the tested force fields, we find that CHARMM36 and CHARMM36m are best suited to the study of IDPs, and accurately predict a disordered to helical conformational transition of the PLP peptide accompanying the change from aqueous to membrane-mimicking solvents. We also identify an α-helical structure of TP2 in the membrane-mimicking solvents and provide a discussion of the mechanistic implications of this observation with reference to the previous literature on the peptide. From these results, we recommend the use of CHARMM36m with the REST2 protocol for the study of environment-specific IDP conformations. We believe that the simulation protocol will allow the study of a broad range of IDPs that undergo conformational transitions in different biological environments.
Scene flow constrained multi-prior patch-sweeping for real-time upper body 3D reconstruction (2013)

We present a high performance real-time approach for robust 3D structure estimation of human bodies. Our idea extends state of the art high precision patch-sweep techniques by exploiting temporal information. By parameterizing 3D patches in the spatio-temporal domain we gain increased quality and robustness, while the computational complexity decreases drastically. The key to these improvements is the utilization of a global scene flow like prior called spatio-temporal object (STO). The target application of our method reaches from video communication and virtual eye contact scenarios till future digital cinema 3D post-production and real-time person modelling and modification. The result of this work extends a novel 3D scene representation developed in the EC research project SCENE.
Risk factors of local recurrence after surgery in extraabdominal desmoid‐type fibromatosis: A multicenter study in Japan (2020)

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.
Vertical and lateral heterogeneous integration (2002)

The wafer-scale integration of advanced optical, electrical, and micromechanical semiconductor devices on a single chip requires techniques for combining differing semiconductor structures in the plane of the wafer. We have developed a technique for achieving large-scale monolithic integration of lattice-mismatched materials in the vertical direction and the lateral integration of dissimilar lattice-matched structures. The technique uses a single nonplanar wafer-bonding step to transform epitaxial structures into lateral epitaxial variation across the surface of a wafer.
Comprehensive catalog of dendritically localized mRNA isoforms from sub-cellular sequencing of single mouse neurons (2019)

We integrate our list of localized RNAs with the literature to provide a comprehensive list of known dendritically localized RNAs as a resource. This catalog of transcripts, including differentially localized isoforms and computationally hypothesized localization motifs, will help investigators further dissect the genome-scale mechanism of RNA localization.
Polymerizing Base Sensitive Cyclic Carbonates Using Acid Catalysis (2013)

Organic acids were explored as a means to expand the library of cyclic carbonate monomers capable of undergoing controlled ring-opening polymerization. Various nitrogenous bases have proven incredibly adept at polymerizing cyclic carbonates; however, their use has largely precluded monomers with an acidic proton. Molecular modeling of acid catalysis provided new mechanistic insight, wherein a bifunctional activation pathway was calculated. Depending on acid structure, modeling experiments showed both monomer carbonyls and propagating hydroxyl groups undergo hydrogen bonding activation. The dual activation mechanism suggests acid strength, as well as conjugate base effects, play vital roles in catalyzing cyclic carbonate polymerizations. Moreover, the use of acid catalysis was shown to be compatible with amide-containing monomers while promoting controlled polymerizations.