gebhart/patrepeval huggingface dataset:
Functional Analysis of Paralogous Thiol-disulfide Oxidoreductases in Streptococcus gordonii (2013)

Disulfide bonds are important for the stability of many extracellular proteins, including bacterial virulence factors. Formation of these bonds is catalyzed by thiol-disulfide oxidoreductases (TDORs). Little is known about their formation in Gram-positive bacteria, particularly among facultative anaerobic Firmicutes, such as streptococci. To investigate disulfide bond formation in Streptococcus gordonii, we identified five putative TDORs from the sequenced genome. Each of the putative TDOR genes was insertionally inactivated with an erythromycin resistance cassette, and the mutants were analyzed for autolysis, extracellular DNA release, biofilm formation, bacteriocin production, and genetic competence. This analysis revealed a single TDOR, SdbA, which exhibited a pleiotropic mutant phenotype. Using an in silico analysis approach, we identified the major autolysin AtlS as a natural substrate of SdbA and showed that SdbA is critical to the formation of a disulfide bond that is required for autolytic activity. Analysis by BLAST search revealed homologs to SdbA in other Gram-positive species. This study provides the first in vivo evidence of an oxidoreductase, SdbA, that affects multiple phenotypes in a Gram-positive bacterium. SdbA shows low sequence homology to previously identified oxidoreductases, suggesting that it may belong to a different class of enzymes. Our results demonstrate that SdbA is required for disulfide bond formation in S. gordonii and indicate that this enzyme may represent a novel type of oxidoreductase in Gram-positive bacteria.
Automating CapCom Using Mobile Agents and Robotic Assistants (2005)

Mobile Agents (MA) is an advanced Extra-Vehicular Activity (EVA) communications and computing system to increase astronaut self-reliance and safety, reducing dependence on continuous monitoring and advising from mission control on Earth. MA is voice controlled and provides information verbally to the astronauts through programs called "personal agents." The system partly automates the role of CapCom in Apollo-including monitoring and managing navigation, scheduling, equipment deployment, telemetry, health tracking, and scientific data collection. Data are stored automatically in a shared database in the habitat/vehicle and mirrored to a site accessible by a remote science team. The program has been developed iteratively in authentic work contexts, including six years of ethnographic observation of field geology. Analog field experiments in Utah enabled empirically discovering requirements and testing alternative technologies and protocols. We report on the 2004 system configuration, experiments, and results, in which an EVA robotic assistant (ERA) followed geologists approximately 150 m through a winding, narrow canyon. On voice command, the ERA took photographs and panoramas and was directed to serve as a relay on the wireless network.
Quantitative visualization of synchronized insulin secretion from 3D-cultured cells (2017)

Quantitative visualization of synchronized insulin secretion was performed in an isolated rat pancreatic islet and a spheroid of rat pancreatic beta cell line using a method of video-rate bioluminescence imaging. Video-rate images of insulin secretion from 3D-cultured cells were obtained by expressing the fusion protein of insulin and Gaussia luciferase (Insulin-GLase). A subclonal rat INS-1E cell line stably expressing Insulin-GLase, named iGL, was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose. Furthermore, we demonstrated the effect of an antidiabetic drug, glibenclamide, on synchronized insulin secretion from 2D- and 3D-cultured iGL cells. The amount of secreted Insulin-GLase from iGL cells was also determined by a luminometer. Thus, our bioluminescence imaging method could generally be used for investigating protein secretion from living 3D-cultured cells. In addition, iGL cell line would be valuable for evaluating antidiabetic drugs.
CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation (2020)

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.
A wireless robotic video laparo-endoscope for minimal invasive surgery (2013)

This paper describes the design, prototype and deployment of a network of wireless Miniature Anchored Robotic Videoscopes for Expedited Laparoscopy (MARVEL). The MARVEL robotic Camera Modules (CMs) remove the need for a dedicated trocar port for an external laparoscope, additional incisions for surgical instrumentation, camera cabling for power, video and xenon light, and an assistant in the operating room to hold and position the laparoscope. The system includes: (1) Multiple MARVEL CMs that feature a wireless controlled pan/tilt camera platform, which provides a full hemisphere field of view inside the abdominal cavity from different angles, wirelessly controlled focus and a wireless illumination control system, (2) a Master Control Module (MCM) that provides a near-zero latency video wireless communications link, independent wireless control for multiple MARVEL CMs, digital zoom, manual focus, and a wireless Human-Machine Interface (HMI) that provides the surgeon with full control over all the functions of the CMs. In-vivo experiments on a porcine subject were carried out to test the performance of the system.
Correction for Chakrabarti et al., Robust Neutralizing Antibodies Elicited by HIV-1 JRFL Envelope Glycoprotein Trimers in Nonhuman Primates (2014)

Bimal K. Chakrabarti, Yu Feng, Shailendra Kumar Sharma, Krisha McKee, Gunilla B. Karlsson Hedestam, Celia C. LaBranche, David C. Montefiori, John R. Mascola, Richard T. Wyatt IAVI Neutralizing Antibody Center at The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, California, USA; The Vaccine Research Center, NIH, Bethesda, Maryland, USA; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA; The Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA
Binding of Different Divalent Cations to the Active Site of Avian Sarcoma Virus Integrase and Their Effects on Enzymatic Activity (1997)

Retroviral integrases (INs) contain two known metal binding domains. The N-terminal domain includes a zinc finger motif and has been shown to bind Zn2+, whereas the central catalytic core domain includes a triad of acidic amino acids that bind Mn2+ or Mg2+, the metal cofactors required for enzymatic activity. The integration reaction occurs in two distinct steps; the first is a specific endonucleolytic cleavage step called "processing," and the second is a polynucleotide transfer or "joining" step. Our previous results showed that the metal preference for in vitro activity of avian sarcoma virus IN is Mn2+ > Mg2+ and that a single cation of either metal is coordinated by two of the three critical active site residues (Asp-64 and Asp-121) in crystals of the isolated catalytic domain. Here, we report that Ca2+, Zn2+, and Cd2+ can also bind in the active site of the catalytic domain. Furthermore, two zinc and cadmium cations are bound at the active site, with all three residues of the active site triad (Asp-64, Asp-121, and Glu-157) contributing to their coordination. These results are consistent with a two-metal mechanism for catalysis by retroviral integrases. We also show that Zn2+ can serve as a cofactor for the endonucleolytic reactions catalyzed by either the full-length protein, a derivative lacking the N-terminal domain, or the isolated catalytic domain of avian sarcoma virus IN. However, polynucleotidyl transferase activities are severely impaired or undetectable in the presence of Zn2+. Thus, although the processing and joining steps of integrase employ a similar mechanism and the same active site triad, they can be clearly distinguished by their metal preferences.
Diode proximity-coupled Nd:GdVO<inf>4</inf> planar waveguide laser (2006)

We demonstrated a compact linear-polarized planer waveguide laser with diode proximity-coupling pump geometry, and uniaxial laser material of Nd:GdVO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</inf> The laser cavity size is as small as 4-mm x 1mm including the 5-stripe pumping diode, The total output power of 1.7-W for five independent nearly diffraction- limited beams was obtained at the pumping diode output power of 5.7-W.
Low-power high-tuning range CMOS ring oscillator VCOs (2008)

This paper presents the design of two new ring oscillators based on differential and single-ended topologies using a 0.13 mum 1P8M CMOS technology. The differential oscillator utilizes feed-forward technique and a new composite load with inductive impedance, reducing the delay per stage and widening the tuning range. The output frequency ranges from 0.5 to 9.5 GHz and the circuit consumes only 9 mW. The simulation result of phase noise is -85.3 dBc/Hz @ 1 MHz offset from centre frequency. The single-ended ring oscillator with inductive composite load oscillates from 6.3 to 13.9 GHz and consumes only 5.1 mW with phase noise of -81.5 dBc/Hz @ 1 MHz offset from centre frequency.
Synthesis technique for direct-coupled-resonators bandpass filters (2001)

An effective technique for the synthesis of selective filters for D-WDM systems realized by cascaded Bragg-gratings, direct-coupled ring resonators or cascaded PBG resonators is presented. The devices are very compact and have a high out-of-band rejection.
A radiologic approach to paediatric skull swellings. (2018)

Poster: ECR 2018 / C-2171 / A radiologic approach to paediatric skull swellings. by: M. M. M. Ashour 1, A. Mugahid2, R. A. M. A. Helal3, A. H. A. H. Ibrahim2, M. A. M. Ayoub2, S. Mohamed2, P. M. A. D. Mohamed Abouelhoda2, A. M. A. Farag2, M. A. Abo El Ela2; 1Cairo, New Cairo/EG, 2Cairo/EG, 3Cairo- Egypt/EG
Stereochemical Elucidation of Neohomohalichondrin B (aka Halistatin 3) (2023)

Halistatin 3 and neohomohalichondrin B are members of the halichondrin class of natural products, isolated and characterized independently, albeit without full stereochemical assignment. Here, we determine the absolute stereochemistry of these compounds, confirming they are structurally identical. This study involved the initial preparation of a series of stereoisomeric models for comparison with the left half of these natural products, leading to a proposed assignment of 50S,51R,54R for their left half side chain. Next, we prepared a synthetic compound incorporating this revised stereochemistry. Finally, we present two strands of evidence that this compound was structurally identical to the natural products: (i) NMR comparison showed excellent agreement with the reported data for both halistatin 3 and neohomohalichondrin B, and (ii) HPLC comparison confirmed that our revised stereochemistry was identical to an authentic sample of isolated halistatin 3.
Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1 (2011)

Assessment of genetic associations can be strengthened using a genetic/genomic approach. This approach identified several candidate genes, including Acvr1, associated with increased susceptibility to acute lung injury in mice.
Constrained Corticotropin-Releasing Factor Antagonists withi-(i+ 3) Glu−Lys Bridges (1997)

Hypothesis driven and systematic structure-activity relationship (SAR) investigations have resulted in the development of effective central nervous system (CNS) antagonists of corticotropin (ACTH)-releasing factor (CRF) such as alpha-helical CRF(9-41) and analogues of our assay standard [DPhe12,Nle21,38]hCRF(12-41). On the other hand, equally potent CRF antagonists that block the hypothalamic/pituitary/adrenal (HPA) axis had not been described until recently. Predictive methods, physicochemical measurements (nuclear magnetic resonance spectrometry and circular dichroism spectroscopy), and SAR studies suggest that CRF and its family members (urotensins and sauvagine) assume an alpha-helical conformation when interacting with CRF receptors. To further test this hypothesis, we have systematically scanned the hCRF(9-41) or hCRF(12-41) sequences with an i-(i + 3) bridge consisting of the Glu-Xaa-Xbb-Lys scaffold which we and others had shown could maintain or enhance alpha-helical structure. From this series we have identified seven analogues that are either equipotent to, or 3 times more potent than, the assay standard; in addition, as presented earlier cyclo(30-33)[DPhe12,-Nle21,38,Glu30, Lys33]hCRF(12-41) (astressin) is 32 times more potent than the assay standard in blocking ACTH secretion in vitro (rat pituitary cell culture assay). In vivo, astressin is also significantly more potent than earlier antagonists at reducing hypophysial ACTH secretion in intact stressed or adrenalectomized rats. Since the corresponding linear analogues that were tested are significantly less potent, our interpretation of the increased potency of the cyclic analogues is that the introduction of the side chain to side chain bridging element (Glu30-Lys33, and to a lesser extent that of Glu14-Lys17, Glu20-Lys23, Glu23-Lys26, Glu26-Lys29, Glu28-Lys31, Glu29-Lys32, and Glu33-Lys36) induces and stabilizes in the receptor environment a putative alpha-helical bioactive conformation of the fragment that is not otherwise heavily represented. The effect of the introduction of two favored substitutions [(cyclo(20-23) and cyclo(30-33)] yielded 37 with a potency 8 times that of the assay standard but actually 12 times less than expected if the effect of the two cycles had been multiplicative. These results suggest that the pituitary CRF receptor can discriminate between slightly different identifiable conformations, dramatically illustrating the role that secondary and tertiary structures play in modulating biological signaling through specific protein-ligand interactions.
Electrocatalytic Site Activity Enhancement via Orbital Overlap in A2MnRuO7 (A = Dy3+, Ho3+, and Er3+) Pyrochlore Nanostructures (2021)

Oxygen electrocatalysis at transition metal oxides is one of the key challenges underpinning electrochemical energy conversion systems, involving a delicate interplay of the bulk electronic structure and surface coordination of the active sites. In this work, we investigate for the first time the structure–activity relationship of A2RuMnO7 (A = Dy3+, Ho3+, and Er3+) nanoparticles, demonstrating how orbital mixing of Ru, Mn, and O promotes high density of states at the appropriate energy range for oxygen electrocatalysis. The bulk structure and surface composition of these multicomponent pyrochlores are investigated by high-resolution transmission electron microscopy, X-ray diffraction, X-ray absorption spectroscopy, X-ray emission spectroscopy (XES), and X-ray photoemission spectroscopy (XPS). The materials exhibit high phase purity (cubic fcc with a space group Fd3̅m) in which variations in M–O bonds length are less than 1% upon replacing the A-site lanthanide. XES and XPS show that the mean oxidation state at the Mn-site as well as the nanoparticle surface composition was slightly affected by the lanthanide. The pyrochlore nanoparticles are significantly more active than the binary RuO2 and MnO2 toward the 4-electron oxygen reduction reaction in alkaline solutions. Interestingly, normalization of kinetic parameters by the number density of electroactive sites concludes that Dy2RuMnO7 shows twice higher activity than benchmark materials such as LaMnO3. Analysis of the electrochemical profiles supported by density functional theory calculations reveals that the origin of the enhanced catalytic activity is linked to the mixing of Ru and Mn d-orbitals and O p-orbitals at the conduction band which strongly overlap with the formal redox energy of O2 in solution. The activity enhancement strongly manifests in the case of Dy2RuMnO7 where the Ru/Mn ratio is closer to 1 in comparison with the Ho3+ and Er3+ analogs. These electronic effects are discussed in the context of the Gerischer formalism for electron transfer at the semiconductor/electrolyte junctions.
Bortezomib Retreatment in Relapsed Multiple Mycelia - A Retrospective Multicenter Survey. (2007)

Abstract Bortezomib (Velcade) has demonstrated highest single agent response rates in anti-myeloma therapy. There is no data from preclinical studies to suggest that resistance develops from repeated treatment with bortezomib. It was therefore of interest to investigate, whether repeated bortezomib treatment is safe, feasible and efficient. Here, we have retrospectively collected data from multiple myeloma patients who had previously responded to bortezomib (previous bortezomib treatment), presented with relapsed disease and who received bortezomib for a second time (retreatment). Treatment and retreatment had been on discretion of the physician according to prescribing information, and no diagnostic or therapeutic instructions were given during the course of this multicenter non-interventional survey (26866138MMY4014). Data from from a total of 15 centers and 65 patients were obtained: these patients had all received bortezomib and were eligible for safety analyses. Sixteen patients had to be excluded due to major protocol violations, leaving 49 patients for the modified intention to treat population. Patients had a median age of 66 years and had been treated with a median of 4 prior therapies before receiving bortezomib for the first time. Median cycle number for previous bortezomib therapy and retreatment was 5 and 4, respectively. The majority of patients (85.7%) received doses of 1.3 mg/m2 body surface area. Concomitant dexamethasone was given in 38.8% of patients with previous bortezomib treatment, and in 62.2% with retreatment. Six patients (12.2%) received various anti-myeloma therapies between bortezomib treatment and retreatment. Efficacy data is summarized below, revealing very encouraging responses and similar response durations for previous bortezomib therapy and retreatment. Thirty-three (50.8%) patients experienced a total of 109 adverse drug reactions (ADRs). Three (4.6%) patients experienced a total of 12 life-threatening or disabling ADRs and six (9.2%) experienced 13 severe ADRs (related to bortezomib = 6 SADRs). By the end of the documentation period, 21 patients had died (32.8%). This retrospective survey suggests that the safety profile of bortezomib retreatment is in line with the current SmPC of Velcade and that high remission rates can be achieved. It remains to be shown if these bortezomib retreatment results can be repeated in prospective trials and larger patient cohorts. Previous bortezomib treatment Retreatment Overall response rate 100% (per protocol) 63.3% Complete remission rate 12.2% 10.2% Time to response (median) 3.2 months 3.0 months Duration of response (median) 6.3 months 4.5 months Treatment free interval (median) 6.6 months 4.1 months Time to progression (median) 10.9 months 6.7 months
Through Thick and Thin: Tuning the Threshold Voltage in Organic Field-Effect Transistors (2014)

Organic semiconductors (OSCs) constitute a class of organic materials containing densely packed, overlapping conjugated molecular moieties that enable charge carrier transport. Their unique optical, electrical, and magnetic properties have been investigated for use in next-generation electronic devices, from roll-up displays and radiofrequency identification (RFID) to biological sensors. The organic field-effect transistor (OFET) is the key active element for many of these applications, but the high values, poor definition, and long-term instability of the threshold voltage (V(T)) in OFETs remain barriers to realization of their full potential because the power and control circuitry necessary to compensate for overvoltages and drifting set points decrease OFET practicality. The drifting phenomenon has been widely observed and generally termed "bias stress." Research on the mechanisms responsible for this poor V(T) control has revealed a strong dependence on the physical order and chemical makeup of the interfaces between OSCs and adjacent materials in the OFET architecture. In this Account, we review the state of the art for tuning OFET performance via chemical designs and physical processes that manipulate V(T). This parameter gets to the heart of OFET operation, as it determines the voltage regimes where OFETs are either ON or OFF, the basis for the logical function of the devices. One obvious way to decrease the magnitude and variability of V(T) is to work with thinner and higher permittivity gate dielectrics. From the perspective of interfacial engineering, we evaluate various methods that we and others have developed, from electrostatic poling of gate dielectrics to molecular design of substituted alkyl chains. Corona charging of dielectric surfaces, a method for charging the surface of an insulating material using a constant high-voltage field, is a brute force means of shifting the effective gate voltage applied to a gate dielectric. A gentler and more direct method is to apply surface voltage to dielectric interfaces by direct contact or postprocess biasing; these methods could also be adapted for high throughput printing sequences. Dielectric hydrophobicity is an important chemical property determining the stability of the surface charges. Functional organic monolayers applied to dielectrics, using the surface attachment chemistry made available from "self-assembled" monolayer chemistry, provide local electric fields without any biasing process at all. To the extent that the monolayer molecules can be printed, these are also suitable for high throughput processes. Finally, we briefly consider V(T) control in the context of device integration and reliability, such as the role of contact resistance in affecting this parameter.
A low-leakage 2.5GHz skewed CMOS 32b adder for nanometer CMOS technologies (2005)

A 32b parallel prefix adder demonstrates leakage-current-reduction capabilities of skewed CMOS logic. Sub-100nA leakage currents and single-cycle activation from standby mode is achieved using multi-tox logic gates in 90nm CMOS technology. The data path contains improved sense amplifier-based flip-flops and skewed CMOS logic adapted latches.