gebhart/patrepeval huggingface dataset:
A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies (2023)

HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. <b>IMPORTANCE</b> An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.
High-power AlGaN UVC LEDs using PhC reflector p-contact layers (2021)

We demonstrated an enhancement of light-extraction efficiency (LEE) in an AlGaN UVC light-emitting diode (LED) using photonic-crystal (PhC)-reflector fabricated on a p-GaN contact layer, which was introduced to realize both of low resistivity and high-reflectivity in p-contact layer. We fabricated an AlGaN UVC-LED with PhC-reflector on p-GaN contact layer, and confirmed that the external quantum efficiency (EQE) was increased by 1.7 times by introducing PhC-reflector. We also fabricated flip-chip UVC LED with PhC-reflector on p-contact layer and obtained more than 50 mW output power.
WARP, a Unified Wireless Network Testbed for Education and Research (2007)

In this paper, we introduce the wireless open-access research platform (WARP) developed at CMC lab, Rice University. WARP provides a scalable and configurable platform mainly designed to prototype wireless communication algorithms for educational and research oriented applications. Its programmability and flexibility makes it easy to implement various physical and network layer protocols and standards. Moreover, the online open-access WARP repository is used to document and share different wireless architectures and cross-layer designs developed at educational and research centers. This repository is a fast and easy solution for students and researchers with a wide range of backgrounds in hardware implementation and algorithm development to collaborate and initiate multi-disciplinary system designs.
Variant in the X-chromosome spliceosomal gene GPKOW causes male-lethal microcephaly with intrauterine growth restriction (2017)

Congenital microcephaly, with or without additional developmental defects, is a heterogeneous disorder resulting from impaired brain development during early fetal life. The majority of causative genetic variants identified thus far are inherited in an autosomal recessive manner and impact key cellular pathways such as mitosis, DNA damage response and repair, apoptosis and splicing. Here, we report a novel donor splice site variant in the G-patch domain and KOW motifs (GPKOW) gene (NG_021310.2:g.6126G>A, NM_015698.4:c.331+5G>A) that segregates with affected and carrier status in a multigenerational family with an X-linked perinatal lethal condition characterized by severe microcephaly and intrauterine growth restriction (IUGR). GPKOW is a core member of the spliceosome that has been shown in numerous model organisms and in human cells to be essential for survival. By investigating GPKOW transcripts in lymphoblastoid cell lines (LCLs) of three carrier females, we show that the GPKOW c.331+5G>A variant disrupts normal splicing of its pre-mRNAs. In a clonal culture expressing only the c.331+5G>A allele isolated from one carrier female LCL, we observed an 80% reduction in wild type GPKOW mRNA, 70% reduction in the full length GPKOW protein and the presence of a truncated GPKOW protein with possible dominant negative effect. Based on our and published data we propose that the GPKOW gene is essential for fetal development and when disrupted, leads to a severe, male-lethal phenotype characterised by microcephaly and IUGR.
In vivo fluorescence enhanced optical tomography reconstruction of lung cancer of non immersed small animals (2007)

Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.
Supplementary Methods from BGC 945, a Novel Tumor-Selective Thymidylate Synthase Inhibitor Targeted to α-Folate Receptor–Overexpressing Tumors (2023)

Supplementary Methods from BGC 945, a Novel Tumor-Selective Thymidylate Synthase Inhibitor Targeted to α-Folate Receptor–Overexpressing Tumors
TWIST, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage (1999)

Basic helix-loop-helix (bHLH) transcription factors have been shown to play an important role in controlling cell type determination and differentiation. TWIST, a member of the bHLH transcription factor family, is involved in the development of mesodermally derived tissue, including the skeleton. We examined the role of human TWIST in osteoblast metabolism using stable expression of sense and antisense TWIST in human osteoblast HSaOS-2 cells. Changes in morphology and osteogenic phenotype characterized these stable clones. Cells that overexpressed TWIST exhibited a spindle shaped morphology, reduced levels of alkaline phosphatase, a reduced proliferation rate, and failed to respond to basic fibroblast growth factor (bFGF). In contrast, those that underexpressed TWIST demonstrated a cuboidal epithelial-like morphology characteristic of differentiated osteoblasts. TWIST antisense cells exhibited increased levels of alkaline phosphatase and type I collagen mRNA, initiated osteopontin mRNA expression, and had a reduced proliferation rate. These results indicate that TWIST overexpressing cells may de-differentiate and remain in an osteoprogenitor-like state, and antisense TWIST cells progress to a more differentiated mature osteoblast-like state. Therefore, the level of TWIST can influence osteogenic gene expression and may act as a master switch in initiating bone cell differentiation by regulating the osteogenic cell lineage.
Fast HIP Host Mobility (2020)

This document describes mobility scenarios and how to aggressively
support them in HIP. The goal is minimum lag in the mobility event.
Thiophene-Phenylene and Thiophene-Thiazole Oligomeric Semiconductors with High Field-Effect Transistor On/Off Ratios (2001)

A series of thiophene-containing oligomers that are less electron rich than alpha-6T were synthesized, and the thin film morphologies and field-effect transistor characteristics of the oligomers were evaluated. Phenyl and thiazole rings were included in many of the oligomers, and a new synthesis of perfluoroalkylmethyl-terminated oligomers was developed. Desirably low off currents were associated with calculated highest occupied molecular orbital energies above ca. 5.0 eV relative to vacuum. Some of the oligomers displayed mobilities above 0.01 cm2 (Vs)-1, but there was no correlation of mobility with calculated orbital energies and some compounds with seemingly continuous morphologies had low mobilities nonetheless. One compound, 1,4-bis(5‘-hexyl-2,2‘-bithiophen-5-yl)benzene, showed promising behavior as a solution-deposited semiconductor, with mobility up to 0.02 cm2 (Vs)-1 and an on/off ratio up to 20 000.
ATP-citrate lyase multimerization is required for coenzyme-A substrate binding and catalysis (2019)

ATP-citrate lyase (ACLY) is a major source of nucleocytosolic acetyl-CoA, a fundamental building block of carbon metabolism in eukaryotes. ACLY is aberrantly regulated in many cancers, cardiovascular disease, and metabolic disorders. However, the molecular mechanisms determining ACLY activity and function are unclear. To this end, we investigated the role of the uncharacterized ACLY C-terminal citrate synthase homology domain in the mechanism of acetyl-CoA formation. Using recombinant, purified ACLY and a suite of biochemical and biophysical approaches, including analytical ultracentrifugation, dynamic light scattering, and thermal stability assays, we demonstrated that the C terminus maintains ACLY tetramerization, a conserved and essential quaternary structure <i>in vitro</i> and likely also <i>in vivo</i> Furthermore, we show that the C terminus, only in the context of the full-length enzyme, is necessary for full ACLY binding to CoA. Together, we demonstrate that ACLY forms a homotetramer through the C terminus to facilitate CoA binding and acetyl-CoA production. Our findings highlight a novel and unique role of the C-terminal citrate synthase homology domain in ACLY function and catalysis, adding to the understanding of the molecular basis for acetyl-CoA synthesis by ACLY. This newly discovered means of ACLY regulation has implications for the development of novel ACLY modulators to target acetyl-CoA-dependent cellular processes for potential therapeutic use.
Facile Preparation of Aryl Sulfides Using Palladium Catalysis under Mild Conditions (2010)

A convenient method for C-S cross-coupling of aryl bromides with various thiols has been developed that involves the use of a 1,1′-bis(diphenylphosphino)ferrocene (DPPF)-ligated palladium complex with N,N-diisopropylethylamine (DIPEA) as the base. This coupling is tolerant of a wide range of functional groups, including hydroxy, amino, cyano, nitro, formyl, and carboxyl groups.
An Allosteric Ribozyme Regulated by Doxycyline This work was supported by Aventis Gencell and by a grant from the Volkswagen Foundation (Priority program “conformational control”) to M.F. We thank M. Blind, G. Mayer, D. Proske, and G. Sengle (Universität Bonn) for helpful discussions as well as J. Crouzet, J. F. Mayaux, and M. Finer (Aventis Gencell) for support. (2001)

In the communication by V. Thuillier, M. Famulok, and co-workers (Angew. Chem. Int. Ed. 2000, 39, 4369–4373), a correction is necessary in Figure 3: The authors noticed that clone D16-05 contains an additional C residue in position 42 between G41 and G43 (5′-end of the sequence region shown in orange). This mutation slightly alters the computer-generated secondary structure of the point mutant D16-05 to the folding shown in Figure 3 b. The RNA decoys incubated with D16-05 (Figure 3 a, lanes 7, 8, 10, and 11) did not contain C42 because they were transcribed from a template DNA that was obtained by means of PCR with a 5′ primer that lacks C42. The authors therefore repeated the analysis represented in Figure 3 with the correct primers. The analysis revealed that constructs 10 and 11 in Figure 3 a can effectively restore the cleavage activity. As a consequence, the previous statement that helix I (red) plays an important structural role in doxycycline binding is still valid but it now appears that the effect of helix I can be exerted in a sequence-independent manner. All other conclusions of this communication remain unaffected.3 Determination of the minimal sequence of clone D16-05. a) Relative activity kobs(norm) of the cleavage reaction under various conditions (always in the presence of 1 μM tRNA as an unspecific competitor). 1: Cleavage activity of D16-05 (1 nM). 2: Same in the presence of 200 nM 1. 3: Same as in 2 in the presence of 2.0 μM unselected pool as an unspecific competitor. 4–8: Same as in 2 in the presence of 2.0 μM cleavage inactive point mutant M16-05 (4), construct T16-05.4 (5), construct T16-05.9 (6), construct T16-05.13 (7), construct T16-05.1 (8). 9–11: Same as in 2 in the presence of 2.0 μM T16-05.9 with the depicted variations in helix I. b) Computer-generated secondary structure of the point mutant D16-05. The various marker symbols flank the sequences of the truncated versions tested. To enable T7-transcription two guanosine residues, which are not shown here, were inserted into the 5′-position of the truncated constructs. Orange: The original randomized region; red: constant region from the HHR (helix I); green: catalytic core. The guanosine residue shaded in black shows the point-mutation C−G. The numbers in parentheses refer to the numbering in (a).
Efficient real-time face tracking in wavelet subspace (2002)

We present a new method for visual face tracking that is carried out in wavelet subspace. First, a wavelet representation for the face template is created, which spans a low-dimensional subspace of the image space. The video sequence frames where the face is tracked are then orthogonally projected into this low-dimensional subspace. This can be done efficiently through a small number of applications of the wavelet filters. All further computations are performed in wavelet subspace, which is isomorphic to the image subspace spanned by the sets of wavelets in the representation. Robustness with respect to facial expression and affine deformations, as well as the efficiency of our method, are demonstrated in various experiments.
Bottom-up Growth of Graphene Nanospears and Nanoribbons (2022)

Graphene nanoribbons (GNRs) are considered one of the most promising materials for next generation electronics, however a reliable and controllable synthesis method is still lacking. Here, we report the CVD growth of GNRs on a copper surface and the corresponding mechanisms of growth. One-dimensional GNR growth is enabled by a vapor-liquid-solid (VLS) graphene growth guided by on-surface propagation of a liquid catalyst particle. Controlling the suppression of vapor-solid-solid (VSS) graphene growth along the width direction of the GNR by tuning the flow of H2 during growth gives rise to a spear head-shaped graphene that we term graphene nanospears (GNSs). The real-time visual and spatially resolved observations confirm the VSS growth of graphene can be fully suppressed and lead to GNR formation on Cu surface. These findings reveal key insight into the growth mechanism of graphene and open a door for achieving a facile and scalable method of synthesizing free standing GNRs.
Synthesis of α-Amidoketones from Vinyl Esters via a Catalytic/Thermal Cascade Reaction (2016)

A straightforward, modular, and atom-efficient method is reported for the synthesis of α-amidoketones from vinyl esters via a cascade reaction including hydroformylation, condensation with a primary amine, and a rearrangement step giving water as the only byproduct. The reaction sequence can be performed in one pot or as a three-step procedure. The synthetic applicability is demonstrated by the preparation of different α-amidoketones in moderate to good yields.
Single Residue Substitutions That Confer Voltage-Gated Sodium Ion Channel Subtype Selectivity in the NaV1.7 Inhibitory Peptide GpTx-1 (2016)

There is interest in the identification and optimization of new molecular entities selectively targeting ion channels of therapeutic relevance. Peptide toxins represent a rich source of pharmacology for ion channels, and we recently reported GpTx-1 analogs that inhibit NaV1.7, a voltage-gated sodium ion channel that is a compelling target for improved treatment of pain. Here we utilize multi-attribute positional scan (MAPS) analoging, combining high-throughput synthesis and electrophysiology, to interrogate the interaction of GpTx-1 with NaV1.7 and related NaV subtypes. After one round of MAPS analoging, we found novel substitutions at multiple residue positions not previously identified, specifically glutamic acid at positions 10 or 11 or lysine at position 18, that produce peptides with single digit nanomolar potency on NaV1.7 and 500-fold selectivity against off-target sodium channels. Docking studies with a NaV1.7 homology model and peptide NMR structure generated a model consistent with the key potency and selectivity modifications mapped in this work.
New dual function resin with initiator and acrylate functionality for low migration applications (2014)

A dual function UV curable resin, which contains both initiation and polymerization functional groups, was developed for applications where low migration is required. This low extractable resin was specifically designed for: 1) ease of use, 2) high compatibility, 3) photo activation under UVA excitation, and most importantly 4) negligible migration.
Reassortants of H5N1 Influenza Viruses Recently Isolated from Aquatic Poultry in Hong Kong SAR (2003)

The H5N1 virus (H5N1/97) that caused the bird flu incident in Hong Kong in 1997 has not been isolated since the poultry slaughter in late 1997. But the donor of its H5 hemagglutinin gene, Goose/Guangdong/1/96-like (Gs/Gd/96-like) virus, established a distinct lineage and continued to circulate in geese in the area. In 2000, a virus from the Goose/Guangdong/1/96 lineage was isolated for the first time from domestic ducks. Subsequently, it has undergone reassortment, and these novel reassortants now appear to have replaced Gs/Gd/96-like viruses from its reservoir in geese and from ducks. The internal gene constellation is also different from H5N1/97, but these variants have the potential for further reassortment events that may allow the interspecies transmission of the virus.
Multi-Language Neural Network Language Models (2016)

Recently there has been a lot of interest in neural network based language models. These models typically consist of vocabulary dependent input and output layers and one or more vocabulary independent hidden layers. One standard issue with these approaches is that large quantities of training data are needed to ensure robust parameter estimates. This poses a significant problem when only limited data is available. One possible way to address this issue is augmentation: model-based, in the form of language model interpolation, and data-based, in the form of data augmentation. However, these approaches may not always be possible to use due to vocabulary dependent input and output layers. This seriously restricts the nature of the data possible to use in augmentation. This paper describes a general solution whereby only one or more vocabulary independent hidden layers are augmented. Such approach makes it possible to examine augmentation from previously impossible domains. Moreover, this approach paves a direct way for multi-task learning with these models. As a proof of the concept this paper examines the use of multilingual data for augmenting hidden layers of recurrent neural network language models. Experiments are conducted using a set of language packs released within IARPA Babel program.
Successful Treatment of Estrogen Excess in Primary Bilateral Macronodular Adrenocortical Hyperplasia with Leuprolide Acetate (2017)

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient's right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic <i>PDE11A</i> mutation, as well as variants in the <i>ARMC5</i> and <i>INHA</i> genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the <i>PDE11A</i> locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction.
Phase-dependent electrocatalytic activity of colloidally synthesized WP and α-WP2 electrocatalysts for hydrogen evolution reaction (2021)

Transition metal phosphides (TMPs) have emerged as efficient non-noble electrocatalysts for hydrogen evolution reaction (HER).