gebhart/patrepeval huggingface dataset:
The Features and Shortcomings for Gene Delivery of Current Non-Viral Carriers (2006)

Since the viral vector for gene therapy has serious problems, including oncogenesity and other adverse effects, non-viral carriers have attracted a great deal of attention. Non-viral carriers are expected to achieve gene therapy without serious side effects. However, the most critical issue of gene delivery by non-viral carriers is the low-expression efficiencies of the desired gene. In order to apply non-viral carriers for gene therapy in practical clinical usage, further understanding of the cellular barriers against gene delivery is a prerequisite. Moreover, additional intelligent concepts for gene delivery are also needed. We will summarize the features and shortcomings of currently developed non-viral delivery systems. Especially, we will address the current progress of cationic lipids (lipoplex) and cationic polymers (polyplex) in terms of transfection efficiency. Furthermore, our group has developed a system that responds to the particular intracellular signals of target disease cells. We have named this gene delivery system a drug delivery system based on responses cellular signal (D-RECS). We will introduce this new concept of intelligent non-viral delivery system that our group recently developed.
Temporal origin of viral phospholipids of the enveloped bacteriophage ϕ6 (1976)

The enveloped bacteriophage phi 6 contains a higher relative level of the negatively charged phospholipid phosphatidylglycerol than is found in the membranes of the host bacterium. During infection of Pseudomonas phaseolicola with phi 6, the level of phosphatidylglycerol synthesis increases significantly. The lipid used to form the viral envelope consists almost entirely of cellular phospholipids synthesized before infection and phosphatidylglycerol synthesized after infection. Based on these and previously published results, a speculative model for this viral envelope formation process is presented.
Indications for pneumonectomy. Pneumonectomy for malignant disease. (1999)

The anatomic extent of a pulmonary malignancy usually dictates the need for pneumonectomy to achieve a complete resection. The requirement for a pneumonectomy can frequently be predicted by accurate clinical staging, but may also be required due to intraoperative findings relating to tumor invasion or nodal spread. Completion pneumonectomy is usually reserved for locally recurrent lung cancer or early to late complications following pulmonary resection. Malignant involvement of the carina frequently requires sleeve pneumonectomy.
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants (2020)

Manipulation of DNA by CRISPR-Cas enzymes requires the recognition of a protospacer-adjacent motif (PAM), limiting target site recognition to a subset of sequences. To remove this constraint, we engineered variants of <i>Streptococcus pyogenes</i> Cas9 (SpCas9) to eliminate the NGG PAM requirement. We developed a variant named SpG that is capable of targeting an expanded set of NGN PAMs, and we further optimized this enzyme to develop a near-PAMless SpCas9 variant named SpRY (NRN and to a lesser extent NYN PAMs). SpRY nuclease and base-editor variants can target almost all PAMs, exhibiting robust activities on a wide range of sites with NRN PAMs in human cells and lower but substantial activity on those with NYN PAMs. Using SpG and SpRY, we generated previously inaccessible disease-relevant genetic variants, supporting the utility of high-resolution targeting across genome editing applications.
Direct Writing on Paper of Foldable Capacitive Touch Pads with Silver Nanowire Inks (2014)

Paper-based capacitive touch pads can be fabricated utilizing high-concentration silver nanowire inks needle-printed directly onto paper substrates through a 2D programmable platform. Post deposition, silver nanowire tracks can be photonically sintered using a camera flash to reduce sheet resistance similar to thermal sintering approaches. Touch pad sensors on a variety of paper substrates can be achieved with optimized silver nanowire tracks. Rolling and folding trials, which yielded only modest changes in capacitance and no loss of function, coupled with touch pad functionality on curved surfaces, suggest sufficient flexibility and durability for paper substrate touch pads to be used in diverse applications. A simplified model to predict touch pad capacitance variation ranges with differing touch conditions was developed, with good agreement against experimental results. Such paper-based touch pads have the advantage of simple structure, easy fabrication, and fast sintering, which holds promise for numerous commercial applications including low-cost portable devices where ultrathin and lightweight features, coupled with reliable bending stability are desirable.
Chemo- and Diastereoselectivity in the Dimethyldioxirane Oxidation of 2,3-Dihydro-4H-1-benzothiopyran-4-ones and 4H-1-Benzothiopyran-4-ones. Unusual Reactivity of 4H-1-Benzothiopyran-4-one 1-Oxides1 (2001)

The oxidation of the 1-thiochromanones 1-3 by dimethyldioxirane (DMD) produced the corresponding sulfoxides 4-6 or sulfones 7-9; their relative amounts depended on the amount of oxidant used. A low diastereoselectivity was observed in the sulfoxidation of the 2-substituted 1-thiochromanones 2 and 3, due to the small steric differentiation during the DMD attack. An unusual reactivity pattern was found in the DMD oxidation of the 1-thiochromones 10-12, in that the sulfoxides 13-15 were more reactive toward the electrophilic oxidizing agent than the corresponding sulfides. The observed anomaly may be explained in terms of transannular stabilization of the transition structure (TS) for the sulfone formation, promoted through favorable conformational effects in the sulfoxide. Higher sulfoxide/sulfone ratios were found in solvents of greater hydrogen bond donor capacity, which is in accordance with the postulated stabilizing effect.
Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans (2013)

New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, isolated from an African donor, neutralize ∼70% of circulating isolates with a median IC50 less than 0.05 µg ml(-1). Here, we show that three family members, PGT121, PGT122 and PGT123, have very similar crystal structures. A long 24-residue HCDR3 divides the antibody binding site into two functional surfaces, consisting of an open face, formed by the heavy chain CDRs, and an elongated face, formed by LCDR1, LCDR3 and the tip of the HCDR3. Alanine scanning mutagenesis of the antibody paratope reveals a crucial role in neutralization for residues on the elongated face, whereas the open face, which accommodates a complex biantennary glycan in the PGT121 structure, appears to play a more secondary role. Negative-stain EM reconstructions of an engineered recombinant Env gp140 trimer (SOSIP.664) reveal that PGT122 interacts with the gp120 outer domain at a more vertical angle with respect to the top surface of the spike than the previously characterized antibody PGT128, which is also dependent on the N332 glycan. We then used ITC and FACS to demonstrate that the PGT121 antibodies inhibit CD4 binding to gp120 despite the epitope being distal from the CD4 binding site. Together, these structural, functional and biophysical results suggest that the PGT121 antibodies may interfere with Env receptor engagement by an allosteric mechanism in which key structural elements, such as the V3 base, the N332 oligomannose glycan and surrounding glycans, including a putative V1/V2 complex biantennary glycan, are conformationally constrained.
New technique for culturing corneal epithelial cells of normal mice. (2009)

Cultured MCECs maintain their proliferation and differentiation capabilities as well as their corneal epithelial cell characteristics. These results suggest that MCECs produced by this culturing method provide a useful experimental model which can enable further development of research of the corneal epithelium.
Forward-imaging instruments for optical coherence tomography (1997)

We discuss the design and implementation of forward-imaging instruments for optical coherence tomography (OCT), which require the delivery, scanning, and collection of single-spatial-mode optical radiation. A hand-held surgical probe for use in open surgery can provide cross-sectional images of subsurface tissue before surgical incisions are made. A rigid laparoscope for minimally invasive surgical OCT imaging provides a simultaneous enface view of the area being imaged. OCT imaging is demonstrated on in vitro human specimens.
Vasodepressor Actions of Angiotensin-(1–7) Unmasked During Combined Treatment With Lisinopril and Losartan (1998)

Blockade of angiotensin II (Ang II) function during 8 days of oral therapy with lisinopril (20 mg/kg) and losartan (10 mg/kg) normalized the arterial pressure (112+/-3/70+/-3 mm Hg) and raised the plasma concentrations of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] of 21 male spontaneously hypertensive rats (SHR). Treated animals were then given a 15-minute infusion of either mouse immunoglobulin G1 or a specific monoclonal Ang-(1-7) antibody while their blood pressure and heart rate were recorded continuously in the awake state. The concentrations of Ang II and Ang-(1-7) in arterial blood were determined by radioimmunoassay. Infusion of the Ang-(1-7) antibody caused significant elevations in mean arterial pressure that were sustained for the duration of the infusion and were accompanied by transient bradycardia. Although the hemodynamic effects produced by infusion of the Ang-(1-7) antibody had no effect on plasma levels of Ang II, they caused a twofold rise in the plasma concentrations of Ang-(1-7). A pressor response of similar magnitude and characteristics was obtained in a separate group of SHR treated with the combination of lisinopril and losartan for 8 days during an infusion of [Sar1-Thr8]Ang II. The pressor response induced by the administration of this competitive, non-subtype-selective Ang II receptor blocker was not modified by pretreatment of the rats with an angiotensin type-2 (AT2) receptor blocker (PD123319). Plasma concentrations of Ang II and Ang-(1-7) were not changed by the administration of [Sar1-Thr8]Ang II either in the absence or in the presence of PD123319 pretreatment. These results are the first to indicate an important contribution of Ang-(1-7) in mediating the vasodilator effects caused by combined inhibition of angiotensin-converting enzyme and AT1 receptors. The comparable results obtained by administration of [Sar1-Thr8]Ang II suggest that the vasodepressor effects of Ang-(1-7) during the combined treatment is modulated by a non-AT1/AT2 angiotensin subtype receptor.
Spontaneous Polarization-Induced Nanohelixes, Nanosprings, and Nanorings of Piezoelectric Nanobelts (2003)

Growth of (0001) facet-dominated, free-standing, piezoelectric zinc oxide (ZnO) nanostructures is challenged by the divergence of the surface energy due to intrinsic polarization. By controlling growth kinetics, we show the success of growing nanobelt-based novel structures whose surfaces are dominated by the polarized ±(0001) facets. Owing to the positive and negative ionic charges on the zinc- and oxygen-terminated ±(0001) surfaces, respectively, a spontaneous polarization is induced across the nanobelt thickness. As a result, right-handed helical nanostructures and nanorings are formed by rolling up single-crystal nanobelts; this phenomenon is attributed to a consequence of minimizing the total energy contributed by spontaneous polarization and elasticity. The polar-surface-dominated ZnO nanobelts are likely to be an ideal system for understanding piezoelectricity and polarization-induced ferroelectricity at nanoscale; and they could have applications as one-dimensional nanoscale sensors, transducers, and resonators.
Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain (2006)

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer's disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders.
Immune response of BALB/c mice against an experimental vaccine of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with BCG or Mycobacterium vaccae. (2010)

Immune response in BALB/c mice immunized 3 times with different doses (50 μg or 200 μg of protein) of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with either BCG (1x10(7); CFU) or different doses of killed Mycobacterium vaccae (1x10(6), 1x10(7)) was assessed. Mice immunized with low dose of Alum-ALM mixed with either BCG or low M. vaccae showed a significantly higher IFN-gamma production and a lower IL-4 level and a significantly lower parasite burden compared to the control PBS injected group. It seems that immunization with a low dose of Alum-ALM mixed with an adjuvant induces a Th1 type of immune response in susceptible BALB/c mice.
Metrics for long wavelength asymmetries in inertial confinement fusion implosions on the National Ignition Facility (2014)

We investigate yield degradation due to applied low mode P2 and P4 asymmetries in layered inertial confinement fusion implosions. This study has been performed with a large database of &amp;gt;600 2D simulations. We show that low mode radiation induced drive asymmetries can result in significant deviation between the core hot spot shape and the fuel ρR shape at peak compression. In addition, we show that significant residual kinetic energy at peak compression can be induced by these low mode asymmetries. We have developed a metric, which is a function of the hot spot shape, fuel ρR shape, and residual kinetic energy at peak compression, that is well correlated to yield degradation due to low mode shape perturbations. It is shown that the ρR shape and residual kinetic energy cannot, in general, be recovered by inducing counter asymmetries to make the hot core emission symmetric. In addition, we show that the yield degradation due to low mode asymmetries is well correlated to measurements of time dependent shape throughout the entire implosion, including early time shock symmetry and inflight fuel symmetry.
Evaluation of the ability of canarypox-vectored equine influenza virus vaccines to induce humoral immune responses against canine influenza viruses in dogs (2007)

Canarypox-vectored EIV vaccines induce biologically important antibodies and may substantially impact CIV transmission within a community and be of great value in protecting dogs against CIV-induced disease.
Beyond disclosure: gambling research, political economy, and incremental reform (2015)

Gambling research is beset with vested interests, be they those of the state or the gambling industry. The effect of these on the quality and focus of research has been largely ignored. Full and transparent disclosure policies are a useful first step in identifying possible sources of conflict. Progress in public health tends to be achieved in small, incremental steps, as the experience in tobacco and alcohol research makes plain. The rest of the journey will involve the achievement of the level of independence in gambling research that has been modelled by the alcohol and tobacco research assemblages.
BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure (2002)

Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.
Phosphane‐Free Palladium‐Catalyzed Carbonylative Suzuki Coupling Reaction of Aryl and Heteroaryl Iodides (2009)

Abstract The carbonylative cross‐coupling reaction of an arylboronic acid with an aryl iodide and a heteroaryl iodide to give unsymmetrical biaryl ketones was carried out by using Pd(tmhd) 2 /Pd(OAc) 2 as a phosphane‐free catalyst. Various aryl and heteroaryl iodides with different arylboronic acid derivatives provided good to excellent yields of the desired products under optimized reaction conditions.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Prognostic Influence of Elevated Values of Cardiac Troponin I in Patients With Unstable Angina (1997)

These data indicate that cTnI is an important prognostic variable in patients with unstable angina. Elevations of cTnI predict an adverse short- and long-term prognosis.
OXIDATIVE COUPLING OF METHANE OVER Mn_2O_3-Na_2WO_4/SiO_2 CATALYST IN THE ABSENCE OF DILUTE GAS (1995)

The oxidative coupling of methane over catalyst has been investigated in the absence of dilute gas. 16.4% of C2 yield and 80.4% of the selectivity to C2 hydrocarbons were obtained at CH4/O2 = 8.5/1.5. The effect of flow rate on the selectivity to C2 hydrocarbons and CH4 conversion was different under the reaction condition of different ratio of CH4 to oxygen. The flow rate had a more remarkable effect on the selectivity at the lower ratio of methane to oxygen. The addition of steam into the reaction gas can increase C2 yield to some extent, but that of HC1 decrease the selectivity to C2 hydrocarbons.
Thrombopoietin expands hematopoietic stem cells after transplantation (2002)

Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of marrow-associated colony forming unit–culture (a surrogate measure of stem cell homing) were observed in each type of recipient 24 hours following transplantation, we found that a minimum of fourfold greater numbers of marrow cells were required to radioprotect Tpo-null mice than to radioprotect controls. To assess whether long-term repopulating (LTR) HSCs self-renew and expand in Tpo–/– recipients or controls, we performed limiting-dilution secondary transplants using donor cells from the Tpo–/– or Tpo+/+ recipients 5–7.5 weeks following primary transplantation. We found that LTR HSCs expand to levels 10–20 times greater within this time period in normal recipients than in Tpo-null mice and that physiologically relevant amounts of TPO administered to the Tpo–/– recipients could substantially correct this defect. Our results establish that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation.
IFN-γ and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy (2001)

Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8+ T cells, vascular injury, disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on CD8+ T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-γ–dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-γ production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of tumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-γ and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8+ T cell–mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response.
Recombinant Brassinosteroid Insensitive 1 Receptor-Like Kinase Autophosphorylates on Serine and Threonine Residues and Phosphorylates a Conserved Peptide Motif in Vitro (2000)

BRASSINOSTEROID-INSENSITIVE 1 (BRI1) encodes a putative Leucine-rich repeat receptor kinase in Arabidopsis that has been shown by genetic and molecular analysis to be a critical component of brassinosteroid signal transduction. In this study we examined some of the biochemical properties of the BRI1 kinase domain (BRI1-KD) in vitro, which might be important predictors of in vivo function. Recombinant BRI1-KD autophosphorylated on serine (Ser) and threonine (Thr) residues with p-Ser predominating. Matrix-assisted laser desorption/ionization mass spectrometry identified a minimum of 12 sites of autophosphorylation in the cytoplasmic domain of BRI1, including five in the juxtamembrane region (N-terminal to the catalytic KD), five in the KD (one each in sub-domains I and VIa and three in sub-domain VIII), and two in the carboxy terminal region. Five of the sites were uniquely identified (Ser-838, Thr-842, Thr-846, Ser-858, and Thr-872), whereas seven were localized on short peptides but remain ambiguous due to multiple Ser and/or Thr residues within these peptides. The inability of an active BRI1-KD to transphosphorylate an inactive mutant KD suggests that the mechanism of autophosphorylation is intramolecular. It is interesting that recombinant BRI1-KD was also found to phosphorylate certain synthetic peptides in vitro. To identify possible structural elements required for substrate recognition by BRI1-KD, a series of synthetic peptides were evaluated, indicating that optimum phosphorylation of the peptide required R or K residues at P - 3, P - 4, and P + 5 (relative to the phosphorylated Ser at P = 0).