gebhart/patrepeval huggingface dataset:
Polyacrylic acid pore-filled microporous membranes and their use in membrane-mediated synthesis of nanocrystalline ferrihydrite (1998)

A series of cation-exchange membranes were obtained by photoinitiated grafting of acrylic acid onto a polypropylene microporous support having 0.2 µm diameter pores. The poly(acrylic acid) was shown to be contained within the pores of the membrane. The ion-exchange capacities of these "pore-filled" membranes ranged from 65 to 80% of the theoretical values calculated on the basis of their measured graft yields, with water contents ranging from 72 to 77%. The membranes exhibited a chemical valve effect of flux as a function of pH. Treatment of a poly(acrylic acid) grafted membrane with a solution containing ferrous ions resulted in a large uptake of iron (>24% by weight of iron with a membrane containing 152% graft yield of poly(acrylic acid)). Subsequent alkaline (pH 14) oxidation at 70°C with either oxygen or hydrogen peroxide led to the formation of a superparamagnetic nanocrystalline form of ferrihydrite, 5Fe2O3 ·9H2O. The oxide was identified by temperature-dependent Mössbauer spectroscopy recorded from 300 K to 4.2 K. TEM micrographs of sectioned membranes that were treated with H2O2 revealed the presence of two iron oxide morphologies, disk-shaped particles 3-4 nm in diameter and needle-like particles about 4 nm wide and 50 nm long. Only disk-shaped particles were observed in membranes treated with O2. Magnetization measurements indicate that the membranes are superparamagnetic above 50 K with a room temperature magnetization of 3.3 emu g-1 at 20 kOe.Key words: membrane, poly(acrylic acid); iron oxide, magnetic, Mössbauer spectroscopy; magnetization, photografting.
Abstract B126: Potent antigen-specific anti-tumor activity observed with antibody-drug conjugates (ADCs) made using a new class of DNA-crosslinking agents (2009)

Abstract The clinical support for ADC therapeutics has expanded as more highly-engineered ADCs advance in human clinical testing. Most of the ADCs now in clinical testing contain a tubulin-acting compound (a maytansine or dolastatin derivative) as the cytotoxic agent. While tubulin-acting agents can be effective against many different types of cancers, some cancers are more responsive to DNA-acting agents. To expand the therapeutic potential for ADCs, we sought to develop a new class of cytotoxic agents with a novel, DNA-acting mechanism of action for use with tumor-targeting antibodies. Herein, we report the development of our IGN family of cytotoxic agents. These IGN agents comprise indolino-benzodiazepine dimers that are highly potent by virtue of their ability to alkylate and crosslink DNA. This novel class of compounds demonstrated sequence-selective DNA adduct formation in vitro and cytotoxicity in the picomolar range towards cultured human cancer cells. The intense potency of these compounds, along with their desired aqueous solubility and stability, make them ideally suited for use in ADCs. A lead compound from this class was conjugated to an EpCAM-binding antibody, B38.1, and to a CD33-binding antibody, huMy9-6, through amide bonds. The B38.1-IGN conjugate was highly potent against three different EpCAM-expressing cell lines - COLO 205, LoVo and OVCAR-3 - with IC50 values of 1 pM, 5 pM and 18 pM, respectively. The addition of excess unconjugated B38.1 antibody abolished this cytotoxic effect, demonstrating that the activity of the conjugate is antigen specific. The B38.1-IGN conjugate was considerably less potent towards the antigen-negative Namalwa cell line, with an IC50 value of &amp;gt;1 nM, further demonstrating antigen specificity. Similar potent cytotoxicity was seen with a huMy9-6-IGN conjugate targeting the CD33-positive human promyelocytic leukemia cell line, NB4 (IC50 ∼4pM), in spite of the low antigen expression level (∼10,000 molecules/cell) in this cell line. Of particular interest, the B38.1-IGN conjugate also was potent towards multidrug resistant cancer cells. B38.1-IGN had a IC50 value of 14 pM for COLO 205MDR, a COLO 205 clone engineered to overexpress MDR1 transporter, and 7 pM for HCT-15, an EpCAM-expressing cell line that naturally expresses MDR1. Antibody-IGN conjugates demonstrated dose-dependent activity in multiple human tumor xenograft models in mice, with anti-tumor activity observed at non-toxic doses. The unique mechanism of action of the IGN class of compounds, and the high antigen-specific potency of antibody-IGN conjugates seen in vitro and in vivo, provides a promising new cytotoxic agent for use in the development of new ADCs. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B126.
PML-controlled responses in severe congenital neutropenia withELANE-misfolding mutations (2021)

Mutations in ELANE cause severe congenital neutropenia (SCN), but how they affect neutrophil production and contribute to leukemia predisposition is unknown. Neutropenia is alleviated by CSF3 (granulocyte colony-stimulating factor) therapy in most cases, but dose requirements vary between patients. Here, we show that CD34+CD45+ hematopoietic progenitor cells (HPCs) derived from induced pluripotent stem cell lines from patients with SCN that have mutations in ELANE (n = 2) or HAX1 (n = 1) display elevated levels of reactive oxygen species (ROS) relative to normal iPSC-derived HPCs. In patients with ELANE mutations causing misfolding of the neutrophil elastase (NE) protein, HPCs contained elevated numbers of promyelocyte leukemia protein nuclear bodies, a hallmark of acute oxidative stress. This was confirmed in primary bone marrow cells from 3 additional patients with ELANE-mutant SCN. Apart from responding to elevated ROS levels, PML controlled the metabolic state of these ELANE-mutant HPCs as well as the expression of ELANE, suggestive of a feed-forward mechanism of disease development. Both PML deletion and correction of the ELANE mutation restored CSF3 responses of these ELANE-mutant HPCs. These findings suggest that PML plays a crucial role in the disease course of ELANE-SCN characterized by NE misfolding, with potential implications for CSF3 therapy.
Blocking Periostin Prevented Development of Inflammation in Rhabdomyolysis-Induced Acute Kidney Injury Mice Model (2022)

POSTN was highly expressed in the kidney through rhabdomyolysis and was a positive regulator of AKI. Targeting POSTN might propose a new therapeutic strategy against the development of acute renal failure.
Different Permeability of Potassium Salts across the Blood-Brain Barrier Follows the Hofmeister Series (2013)

The passage of ions across biological membranes is regulated by passive and active mechanisms. Passive ion diffusion into organs depends on the ion-pairing properties of salts present in the serum. Potassium ions could affect brain activity by crossing the blood-brain barrier (BBB) and its accumulation in the extracellular cerebral space could precipitate seizures. In the present study, we analyze passive diffusion of a series of potassium salts in the in vitro isolated guinea pig brain preparation. Different potassium counter-anions confer ion-pairing and lipophilicity properties that modulate membrane diffusion of the salt. Extracellular recordings in different cortical areas demonstrated the presence of epileptiform activities that strongly relate to anion identity, following the qualitative order of the Hofmeister series. Indeed, highly lipophilic salts that easily cross the BBB enhanced extracellular potassium concentration measured by ion-selective electrodes and were the most effective pro-epileptic species. This study constitutes a novel contribution for the understanding of the potential epileptogenicity of potassium salts and, more generally, of the role of counter-anions in the passive passage of salts through biological membranes.
Benzene-crosslinked hexaphyrin: Molecules of benzene in hexaphyrin (2023)

Two blueish materials were obtained in the acid-catalyzed condensation of 5-pentafluorophenyldipyrromethane-1,9-bis{(petafluorophenyl)-methanol} with 4,8-dihydro-4,8-ethanopyrrol[3,4-[Formula: see text]]isoindole followed by oxidation, although the yields were low. Their structures were unambiguously determined by the X-ray analysis. One was ethylene-connected bisdipyrromethene and another was bicyclo[2.2.2]octene-crosslinked dihydrohexaphyrin, which was gradually transformed to benzene-crosslinked hexaphyrin under air in solution via bicyclo[2.2.2]octadiene-crosslinked hexaphyrin. The benzene-crosslinked hexaphyrin was directly obtained in the similar acid-catalyzed condensation procedure of the dipyrromethane with 4,8-dihydropyrrol[3,4-[Formula: see text]]isoindole, although the yield was also low.
Microwave-Induced Desalination via Direct Contact Membrane Distillation (2017)

Membrane distillation (MD) is emerging as an important desalination technology that can operate at relatively low temperatures and can handle high salt concentrations. In this Article, we present microwave-induced membrane distillation (MIMD) where microwave radiation is used to heat the saline water for MD. Pure water vapor flux from MIMD was compared to that generated by conventional heating, and the enhancement reached as high as 52%. Because of the higher dielectric constants, flux enhancement was more significant at high salinity, and the mass transfer coefficient at 150 000 ppm was found to be nearly 99% higher than what was observed under conventional heating. Performance enhancement in MIMD was attributed to nonthermal effects such as the generation of nanobubbles, localized superheating, and breaking down of the hydrogen-bonded salt–water clusters. These effects were investigated using FTIR, ion mobility measurements, and dynamic light scattering. In addition, microwave heating consumed nearly 20% less energy to heat water to the same temperature. The combination of energy savings and higher flux represents a significant advancement over the state of the art for MD.
An Unusual Salt Effect in an Interfacial Nucleophilic Substitution Reaction (2018)

This paper reports a kinetic characterization of the interfacial reaction of N-methylpyrrolidine with a self-assembled monolayer presenting an iodoalkyl group. SAMDI (self-assembled monolayers for matrix-assisted laser desorption/ionization) mass spectrometry was used to determine the extent of reaction for monolayers that were treated with a range of concentrations of the nucleophile for a range of times. These data revealed a second-order rate constant for the reaction that was approximately 100-fold greater than that for the analogous solution-phase reaction. However, addition of sodium iodide to the reaction mixture resulted in a 7-fold decrease in the reaction rate. Addition of bromide and chloride salts also gave slower rate constants for the reaction, but only at 100- and 1000-fold higher concentrations than was observed with iodide, respectively. The corresponding solution-phase reactions, by contrast, had rate constants that were unaffected by the concentration of halide salts. This work provides a well-characterized example illustrating the extent to which the kinetics and properties of an interfacial reaction can depart substantially from their better-understood solution-phase counterparts.
Contribution of Antibody Hydrodynamic Size to Vitreal Clearance Revealed through Rabbit Studies Using a Species-Matched Fab (2016)

We have developed a tool Fab fragment of a rabbit monoclonal antibody that is useful for early evaluation in rabbit models of technologies for long acting delivery (LAD) of proteins to the eye. Using this Fab we show that vitreal clearance can be slowed through increased hydrodynamic size. Fab (G10rabFab) and Fab' (G10rabFab') fragments of a rabbit monoclonal antibody (G10rabIgG) were expressed in Chinese hamster ovary (CHO) cells and purified using antigen-based affinity chromatography. G10rabFab retains antigen-binding upon thermal stress (37 °C) for 8 weeks in phosphate-buffered saline (PBS) and can be detected in rabbit tissues using an antigen-based ELISA. Hydrodynamic radius, measured using quasi-elastic light scattering (QELS), was increased through site-specific modification of the G10rabFab' free cysteine with linear methoxy-polyethylene glycol(PEG)-maleimide of 20000 or 40000 molecular weight. Pharmacokinetic studies upon intravitreal dosing in New Zealand white rabbits were conducted on the G10rabFab and PEGylated G10rabFab'. Results of single and multidose pharmacokinetic experiments yield reproducible results and a vitreal half-life for G10rabFab of 3.2 days. Clearance from the eye is slowed through increased hydrodynamic size, with vitreal half-life showing a linear dependence on hydrodynamic radius (RH). A linear dependence of vitreal half-life on RH suggests that molecule diffusivity makes an important contribution to vitreal clearance. A method for prediction of vitreal half-life from RH measurements is proposed.
Improvement of 3D current mapping by coupling magnetic microscopy and X-Ray computed tomography (2014)

Magnetic Microscopy has demonstrated all its functionality for 2D component thanks to its ability to image current density distribution from magnetic field. At the “More than Moore” age, we need to improve our capabilities to detect and localize failure in 3D components. Unfortunately, it is not possible to directly image 3D current density from a magnetic field scan. 3D conductive path information, that could come from design, and failure assumptions are also needed. In this paper, a new approach based on X-Ray Computed Tomography that bypasses the need of design information and failure site assumptions is presented and its results are discussed.
Phase Ib study of anti-mesothelin antibody drug conjugate anetumab ravtansine in combination with pegylated liposomal doxorubicin in platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. (2018)

5571 Background: Anetumab ravtansine (AR) comprises a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. A phase Ib dose escalation was conducted in patients with platinum-resistant ovarian cancer to assess overall safety, pharmacokinetics (PK) and clinical activity. Methods: Eligible pts with histologically confirmed, locally invasive or metastatic platinum-resistant ovarian cancer, and ECOG performance status ≤1 were enrolled. Pegylated liposomal doxorubicin (PLD) at 30 mg/m2IV every 21 days (q3w) was administered with AR in two IV dosing schedules: 5.5 or 6.5 mg/kg q3w in 9 pts (Part I dose escalation) and at 6.5 mg/kg q3w in 12 patients (Part II expansion cohort). Tumor response was assessed based on RECIST v1.1 q6w C1-C9 and q12w thereafter. Determination of mesothelin expression in archival or fresh biopsy tumor samples by IHC (SP74, Ventana) was highly encouraged. PK of AR and PLD was performed. Results: A total of 21 pts were evaluable in Part I and II: mean age 61.5 yrs (range 42-77), PS 0/1 66.7%/33.3%, median prior lines of therapy 3 (range 1-10). The maximally tolerated dose (MTD) in combination was AR at 6.5 mg/kg and PLD at 30 mg/m2 q3w. Adverse events (AEs) were similar to previously reported AEs for of each agent as monotherapy, including reversible corneal disorders, neutropenia, liver function test increases and gastrointestinal disorders. Drug-related (DR) serious AEs were low (2 pts, 9.5%). Most common grade 3-4 AEs were neutrophil count decreased (5, 23.8%) and platelet count decreased (2, 9.5%). A total of 11 pts (52%) had confirmed partial responses (PR) and 7 (33%) had stable disease for a disease control rate of 86%. Six pts (29%) had a durable PR ( > 250 days). No PK interaction was observed. Conclusions: AR in combination with PLD showed preliminary efficacy with durable PRs in pts with platinum-resistant ovarian cancer. The safety profile was manageable. Further study of this combination is warranted. Clinical trial information: NCT02751918.
Performance evaluation between CDMA systems by mobile system interference simulator (2003)

In this paper, we optimize the frequency coordination between CDMA systems by mobile interference simulator, which is based on the Monte-Carlo methodology. We develop the simulator to analyze the radio interference between CDMA systems. It can calculate or estimate the probability density function of interference from an adjacent frequency band, which is also power controlled. We simulate the interference effects between two CDMA systems, which is based on IS-2000 (usually called cdma2000), by using this simulator. We present the required guard band and zone for two operators to meet the required coverage efficiency and outage probability of signal to interference plus noise ratio (SINR).
Cyclic Loading of Rotator Cuff Repairs: An In Vitro Biomechanical Comparison of Bioabsorbable Tacks With Transosseous Sutures (2005)

This study demonstrates the biomechanical advantages of a sutureless tack device for rotator cuff repair compared with a traditional augmented suture repair technique.
High‐Density Mapping of Spontaneous Pulmonary Vein Activity Initiating Atrial Fibrillation in Humans (2006)

Arrhythmogenic activity from PVs in humans is predominantly due to discrete focal activity.
Structural symmetry ofYD3epitaxial thin films (2000)

A thin-film laminated structure comprised of Pd(5 nm)/Nb(5 nm)/Y(500 nm)/Nb(5 nm) on $\ensuremath{\alpha}{\ensuremath{-}\mathrm{A}\mathrm{l}}_{2}{\mathrm{O}}_{3}(110)$ was synthesized by molecular beam epitaxy to yield a crystalline Y layer with the c axis oriented perpendicular to the growth plane. Neutron diffraction and topographical measurements of the epitaxial ${\mathrm{YD}}_{3}$ layer formed after deuteriding the Y metal layer were consistent with a twinlike structure possessing ${P6}_{3}\mathrm{cm}$ and/or $P3\ifmmode\bar\else\textasciimacron\fi{}c1$ symmetry.
Fibronectin is a survival factor for differentiated osteoblasts (1998)

The skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.
Quantized conductance of one-dimensional strongly correlated electrons in an oxide heterostructure (2019)

Oxide heterostructures are versatile platforms with which to research and create novel functional nanostructures. We successfully develop one-dimensional (1D) quantum-wire devices using quantum point contacts on MgZnO/ZnO heterostructures and observe ballistic electron transport with conductance quantized in units of $2{e}^{2}/h$. Using dc-bias and in-plane field measurements, we find that the $g$ factor is enhanced to around 6.8, more than three times the value in bulk ZnO. We show that the effective mass ${m}^{*}$ increases as the electron density decreases, resulting from the strong electron-electron interactions. In this strongly interacting 1D system we study features matching the ``0.7'' conductance anomalies up to the fifth subband. This Rapid Communication demonstrates that high-mobility oxide heterostructures such as this can provide good alternatives to conventional III-V semiconductors in spintronics and quantum computing as they do not have their unavoidable dephasing from nuclear spins. This paves a way for the development of qubits benefiting from the low defects of an undoped heterostructure together with the long spin lifetimes achievable in silicon.
Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development. (2002)

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.
The synthesis of deuteriated tri‐tert‐butyl phosphine (2022)

The synthesis of deuteriated tri-tert-butyl phosphine is reported. This synthesis is an adaptation of the known procedure for tri-tert-butyl phosphine via a Grignard intermediate.
Regiosymmetric Poly(dialkylphenylenedioxythiophene)s: Electron‐Rich, Stackable π‐Conjugated Nanoribbons (2006)

Farbige Bänder: Das lösliche, elektronenreiche konjugierte Titelpolymer (Alkyl=Dodecyl) mit regiosymmetrischer Struktur wurde durch Grignard-Metathese erhalten. Das Polymer ist in Lösung ausgeprägt thermochrom. Die AFM-Untersuchung schleuderbeschichteter Filme ergibt die Bildung von Nanobändern, und nach einer 2D-WAXS-Analyse liegt eine 2D-Ordnung im Material vor (siehe Bild). Das Polymer sollte sich daher für den Bau von Funktionseinheiten eignen.
Interaction of Antimicrobial Peptides with Lipopolysaccharides (2003)

We study the interaction of antimicrobial peptides with lipopolysaccharide (LPS) bilayers to understand how antimicrobial peptides interact with the LPS monolayer on the outer membrane of Gram-negative bacteria. LPS in water spontaneously forms a multilamellar structure composed of symmetric bilayers. We performed X-ray lamellar diffraction and wide-angle in-plane scattering to study the physical characteristics of LPS multilayers. The multilayer alignment of LPS is comparable to phospholipids. Thus, it is suitable for the application of oriented circular dichroism (OCD) to study the state of peptides in LPS bilayers. At high hydration levels, the chain melting temperature in multilamella detected by X-ray diffraction is the same as that of LPS aqueous dispersions, as measured by calorimetry. LPS has a strong CD, but with a careful subtraction of the lipid background, the OCD of peptides in LPS is measurable. The method was tested successfully with melittin. It was then applied to two representative antimicrobial peptides, magainin and protegrin. At peptide concentrations comparable to the physiological conditions, both peptides penetrate transmembrane in LPS bilayers. The results imply that antimicrobial peptides readily penetrate the LPS monolayer of the outer membrane.