gebhart/patrepeval huggingface dataset:
Characterization of the Lipid Binding Properties of Otoferlin Reveals Specific Interactions between PI(4,5)P2 and the C2C and C2F Domains (2014)

Otoferlin is a transmembrane protein consisting of six C2 domains, proposed to act as a calcium sensor for exocytosis. Although otoferlin is believed to bind calcium and lipids, the lipid specificity and identity of the calcium binding domains are controversial. Further, it is currently unclear whether the calcium binding affinity of otoferlin quantitatively matches the maximal intracellular presynaptic calcium concentrations of ∼30-50 μM known to elicit exocytosis. To characterize the calcium and lipid binding properties of otoferlin, we used isothermal titration calorimetry (ITC), liposome sedimentation assays, and fluorescence spectroscopy. Analysis of ITC data indicates that with the exception of the C2A domain, the C2 domains of otoferlin bind multiple calcium ions with moderate (Kd = 25-95 μM) and low affinities (Kd = 400-700 μM) in solution. However, in the presence of liposomes, the calcium sensitivity of the domains increased by up to 10-fold. It was also determined that calcium enhanced liposome binding for domains C2B-C2E, whereas the C2F domain bound liposomes in a calcium-independent manner. Mutations that abrogate calcium binding in C2F do not disrupt liposome binding, supporting the conclusion that the interaction of the C2F domain with phosphatidylserine is calcium-independent. Further, domains C2C and C2F, not domains C2A, C2B, C2D, and C2E, bound phosphatidylinositol 4,5-bisphosphate 1,2-dioleoyl-sn-glycero-3-phospho(1'-myoinositol-4',5'-bisphosphate) [PI(4,5)P2], which preferentially steered them toward liposomes harboring PI(4,5)P2. Remarkably, lysine mutations L478A and L480A in C2C selectively weaken the PI(4,5)P2 interaction while leaving phosphatidylserine binding unaffected. Finally, shifts in the emission spectra of an environmentally sensitive fluorescent unnatural amino acid indicate that the calcium binding loops of the C2F domain directly interact with the lipid bilayer of negatively charged liposomes in a calcium-independent manner. On the basis of these results, we propose that the C2F and C2C domains of otoferlin preferentially bind PI(4,5)P2 and that PI(4,5)P2 may serve to target otoferlin to the presynapse in a calcium-independent manner. This positioning would facilitate fast calcium-dependent exocytosis at the hair cell synapse.
Mapping of POP1-binding Site on Pyrin Domain of ASC (2008)

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an essential adaptor protein in the formation of a multiprotein complex that activates procaspase-1. ASC is also known as a modulator of NF-kappaB activation pathways. ASC has a bipartite domain structure, consisting of an N-terminal pyrin domain (PYD) and a C-terminal caspase-recruitment domain. The PYD of ASC (ASC_PYD) is known to interact with various PYD-containing intracellular danger signal sensors and PYD-only proteins. Using purified proteins, we characterized the in vitro interaction of ASC_PYD with PYD-only protein 1 (POP1). POP1 specifically interacts with ASC_PYD with a dissociation constant of 4.08 +/- 0.52 microm but does not interact with Cryopyrin. NMR and mutagenesis experiments show that a negative electrostatic potential surface patch (EPSP) on ASC_PYD, consisting of the first (H1) and fourth (H4) helices, is essential in the interaction with POP1. A positive EPSP on POP1, consisting of the second (H2) and third (H3) helices, is a counterpart of this interaction. The interaction between ASC_PYD and POP1 is similar to the interaction between caspase recruitment domains of Apaf-1 and procaspase-9. In addition, we present evidence that conformational changes at the long loop of ASC_PYD between the H2 and H3 helices can affect its interaction with POP1. Based on our observations, we propose that the positive EPSP of ASC_PYD, including the H2 and H3 helices, may be the binding site for Cryopyrin, and the interaction with Cryopyrin may induce the dissociation of POP1 from ASC_PYD.
The role of protein kinase Cα in U‐87 glioma invasion (1999)

To investigate the hypothesis that protein kinase Calpha (PKCalpha) is functional glial tumor cell invasion, stable PKCalpha sense and antisense transfected U-87 cell lines were established and PKCalpha expression characterized by Western blot and PKC activity assays. Invasion assays including barrier migration (Koochekpour et al., Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in human glioma lines. Eur. J. Cancer, 1995, 31, 375-380; Merzak et al., CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res., 1994, 54, 3988-3992; Merzak et al., Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro. Neurosci. Lett., 1994, 177, 11-16), and spheroid confrontation were used to study the relationship between PKCalpha expression and invasiveness. PKCalpha overexpressing clones show increased barrier migration (1.5x) relative to the control transfected clones. PKCalpha inhibited clones exhibited reduced invasiveness, to < 50%. In coculture with PKCalpha overexpressing clones, the remaining normal fetal rat brain aggregate volume was significantly decreased (up to 200%) but 90% of the initial brain volume was left in PKCalpha inhibited clone in the rat brain aggregate tumor spheroid confrontation. This effect was not associated with significant growth inhibition. We conclude that expression of PKCalpha in glioma-derived cell lines appears to be central to glioma invasion in vitro.
A Missense Mutation in γ-Glutamyl Carboxylase Gene Causes Combined Deficiency of All Vitamin K-Dependent Blood Coagulation Factors (1998)

To identify potential mutations in the gamma-glutamyl carboxylase gene, the sequence of all exons and intron/exon borders was determined in 4 patients from a consanguineous kindred with combined deficiency of all vitamin K-dependent procoagulants and anticoagulants and results were compared with normal genomic sequence. All 4 patients were homozygous for a point mutation in exon 9 that resulted in the conversion of an arginine codon (CTG) to leucine codon (CGG) at residue 394. Screening of this mutation based on introduction of Alu I site in amplified fragment from normal allele but not from the mutated allele showed that 13 asymptomatic members of the kindred were heterozygous for the mutation. The mutation was not found in 340 unrelated normal chromosomes. The segregation pattern of the mutation which is the first reported in the gamma-glutamyl carboxylase gene fits perfectly with phenotype of the disorder and confirms the suggested autosomal recessive pattern of inheritance of combined deficiency of all vitamin K-dependent procoagulants and anticoagulants in this kindred. The mutated carboxylase protein expressed in Drosophila cells was stable but demonstrated threefold reduced activity compared with WT carboxylase, confirming that the L394R mutation results in a defective carboxylase.
A magnetoresistive gradiometer (1988)

A novel magnetoresistive transducer, sensitive to magnetic field gradients, has been analyzed for use as a read transducer in magnetic recording systems. The device uses two thin-film magnetoresistive elements separated by a thin, nonmagnetic insulating layer. A theoretical analysis shows that the magnetoresistive elements can be biased and sensed to reduce common-mode noise while maintaining sensitivity to magnetic field gradients. An experimental transducer was fabricated, showing nonmultidomain elements that eliminated Barkhausen noise. Effects due to thermal drift were reduced by more than 10 dB, stress effects were undetectable, and uniform field rejection was almost 20 dB. Gradiometer operation of the device was confirmed using a magnetic recorded transition.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Origami-inspired active graphene-based paper for programmable instant self-folding walking devices (2015)

Origami-inspired active graphene-based paper with programmed gradients in vertical and lateral directions is developed to address many of the limitations of polymer active materials including slow response and violent operation methods. Specifically, we used function-designed graphene oxide as nanoscale building blocks to fabricate an all-graphene self-folding paper that has a single-component gradient structure. A functional device composed of this graphene paper can (i) adopt predesigned shapes, (ii) walk, and (iii) turn a corner. These processes can be remote-controlled by gentle light or heating. We believe that this self-folding material holds potential for a wide range of applications such as sensing, artificial muscles, and robotics.
Growth characteristics of a mouse plasma cell tumor. (1968)

Summary A quantitative spleen-colony assay was developed and used to evaluate the growth characteristics of the Adj. PC-5 colony-forming units (CFU). There was a positive correlation between the number of colonies per spleen and the number of tumor cells injected, which is compatible with the assumption that each colony arises from one malignant cell. At 21 days, each colony contains 8.4 ± 2.1 × 107 cells, but less than 4.4% of these are tumor stem cells with the proliferative capacity to form a colony. The growth rate of tumor CFU was estimated in the spleen (CFU TD = 20 ± 4 hours) and femoral marrow (CFU TD = 29 ± 5 hours). A survival TD of 36 ± 2 hours was estimated from the survival of mice injected with graded numbers of tumor cells as an indication of the growth rate of the total tumor. The proliferative capacity of the tumor CFU was completely suppressed during a 10-hour exposure to vinblastine in vivo. This result suggests that the majority of tumor CFU have a TG of less than 10 hours. All of the tumor CFU appear to be in cell cycle, for no detectable tumor CFU survived a 10-hour exposure to vinblastine, and 70% of these cells were killed by a 20-minute exposure to tritiated thymidine in vitro. Based on these findings, a model is proposed for the growth kinetics of this tumor. The model states that a small fraction of the tumor population is composed of cells in a short generation cycle with unlimited proliferative capacity (i.e., tumor stem cells). The remaining tumor cells lack the proliferative capacity to form a colony. This model for the Adj. PC-5 tumor is compared with that of a transplantable AKR lymphoma, and the chemotherapeutic implications are discussed.
A low molecular weight copper chelator crosses the blood–brain barrier and attenuates experimental autoimmune encephalomyelitis (2004)

Abstract Increasing evidence suggests that enhanced production of reactive oxygen species (ROS) activates the MAP kinases, c‐Jun N‐terminal protein kinase (JNK) and mitogen‐activated protein kinase MAPK (p38). These phosphorylated intermediates at the stress‐activated pathway induce expression of matrix metalloproteinases (MMPs), leading to inflammatory responses and pathological damages involved in the etiology of multiple sclerosis (MS). Here we report that N ‐acetylcysteine amide (AD4) crosses the blood–brain barrier (BBB), chelates Cu 2+ , which catalyzes free radical formation, and prevents ROS‐induced activation of JNK, p38 and MMP‐9. In the myelin oligodendrocyte glycoprotein (MOG)‐induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, oral administration of AD4 drastically reduced the clinical signs, inflammation, MMP‐9 activity, and protected axons from demylination damages. In agreement with the in vitro studies, we propose that ROS scavenging by AD4 in MOG‐treated animals prevented MMP's induction and subsequent damages through inhibition of MAPK pathway. The low toxicity of AD4 coupled with BBB penetration makes this compound an excellent potential candidate for the therapy of MS and other neurodegenerative disorders.
Ferulic acid esterase from Aspergillus niger: purification and partial characterization of two forms from a commercial source of pectinase (1993)

Two forms of ferulic acid esterase from Aspergillus niger have been isolated from a commercial source of pectinase. One, designated I, has a M(r) of 132,000, is probably dimeric, and has a pI of 3.0. The second, designated II, was partially purified and is monomeric (M(r) 29,000), with a pI of 3.6. Both enzymes were free of pectinase and xylanase activity and released ferulic acid from methyl ferulate. In association with a xylanase, they also released ferulic acid from destarched wheat bran. Ferulic acid esterase II released a small amount of ferulic acid (0.09 unit/mg of protein) in the absence of xylanase. The enzymes had different specificities for a range of methyl ester derivatives of cinnamoyl and benzoyl acids, acetylated xylan and p-nitrophenyl acetate.
Phenylalanine ammonia-lyase activity in soybean hypocotyls and leaves following infection with Phytophthora megasperma f.sp. glycinea (1988)

Phenylalanine ammonia-lyase activity increased rapidly beginning 2 h after inoculation with Phytophthora megasperma (Drechs.) f.sp. glycinea (Hildeb.) Kuan &amp; Erwin race 1 in unwounded hypocotyls of soybean cv. Harosoy 63 (resistant) but did not change significantly in cv. Harosoy (susceptible). Small increases in phenylalanine ammonia-lyase activity also were caused by wounding. Activity increased more slowly in hypocotyls (cv. Harosoy 63) wounded just before inoculation than in intact inoculated hypocotyls, but most activity developed in hypocotyls wounded 12 h before inoculation. There were comparable effects of wounding on symptom development. Trifoliolate leaves of 14-day-old cv. Harosoy 63 plants are resistant, but trifoliolate leaves of 12-day-old cv. Harosoy 63 plants and of 14-day-old cv. Harosoy plants are susceptible to race 1. Increases in phenylalanine ammonia-lyase activity following inoculation were demonstrated only in 14-day-old Harosoy 63 plants but not until 24–36 h after the inoculation. Significant accumulation of glyceollin occurred by 24 h. Susceptible trifoliolate leaves of 12-day-old cv. Harosoy 63 plants produced only low levels of glyceollin following either infection or treatment with the abiotic elicitor AgNO 3 , whereas trifoliolate leaves of 14-day-old cv. Harosoy plants produced high levels of glyceollin in response to AgNO 3 . It is concluded that trifoliolate leaves of 12-day-old, as opposed to 14-day-old, cv. Harosoy 63 plants have not developed mechanisms that trigger responses to either infection or the abiotic elicitor or they are deficient in metabolic processes that support glyceollin biosynthesis or other defense-related responses.
The use of whole organ decellularization for the generation of a vascularized liver organoid (2010)

These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery.
Eliminating handoff latencies in 802.11 WLANs using multiple radios: applications, experience, and evaluation (2005)

Deployment of Voice-over IP (VoIP) and other real-time streaming applications has been somewhat limited in wireless LANs today, partially because of the high handoff latencies experienced by mobile users. Our goal in this work is to eliminate handoff latency by exploiting the potential of multiple radios in WLAN devices. Our proposed approach, called MultiScan, is implemented entirely on the client-side, and, unlike prior work, MultiScan requires neither changing the Access Points (APs), nor having knowledge of wireless network topology. MultiScan nodes rely on using their (potentially idle) second wireless interface to opportunistically scan and pre-associate with alternate APs and eventually seamlessly handoff ongoing connections. In this paper we describe our implementation of MultiScan, present detailed evaluations of its effect on handoff latency and evaluate performance gains for MultiScan-enhanced wireless clients running Skype, a popular commercial VoIP application.
Cross-Linked Hydroxy-Al-Montmorillonite as a Stationary Phase in Liquid Chromatography (1990)

Abstract Quasi-spherical particles (7- µ m mean diameter) were prepared from cross-linked hydroxy-Al-montmorillonite (basal spacing =15.3 and 18.6 Å) by spray-drying. These particles (SP-CLM) were used as a packing material for columns in high-pressure liquid chromatography (HPLC). Aromatic phosphate esters, chlorosubstituted phenyl-ureas, monosubstituted benzenes, and the o-, m-, and p-isomers of disubstituted benzenes were separated on the columns, using isopropanol and hexane. Alkyl and alkoxy groups in the solute molecules sterically hindered the interaction of these molecules with the solid phase. The retention of the isomers of disubstituted benzenes that possess one electronegative (or dipolar) and one nonpolar substituent increased in the order: o- &lt; m- &lt; p-. In contrast, for all investigated disubstituted benzenes containing two electronegative (or dipolar) substituents, the o-isomer was retained on the 18.6-Å SP-CLM more strongly than the m- and p-isomers. The chromatographic data suggest that the strength of the interaction of phenolic groups with the solid phase increased with the acidity of these groups. The o-isomers of phenols that contained an additional electronegative (or dipolar) substituent displayed an exceptionally strong adsorption. The capacity of the o-isomers of disubstituted benzenes containing two electronegative (or dipolar) substituents to form chelates with Al probably was responsible for the strong retention of such o-isomers compared with the retention of the corresponding m- and p-isomers. Cross-linked hydroxy-Al-montmorillonite acted as a strong and selective adsorbent for many families of organic compounds. It was used successfully as the solid phase in HPLC separations with eluents ranging from nonpolar (e.g., hexane) to highly polar (e.g., water).
Gender Differences in Personality across the Ten Aspects of the Big Five (2011)

This paper investigates gender differences in personality traits, both at the level of the Big Five and at the sublevel of two aspects within each Big Five domain. Replicating previous findings, women reported higher Big Five Extraversion, Agreeableness, and Neuroticism scores than men. However, more extensive gender differences were found at the level of the aspects, with significant gender differences appearing in both aspects of every Big Five trait. For Extraversion, Openness, and Conscientiousness, the gender differences were found to diverge at the aspect level, rendering them either small or undetectable at the Big Five level. These findings clarify the nature of gender differences in personality and highlight the utility of measuring personality at the aspect level.
Conjugates Bearing Multiple Formyl-Methionyl Peptides Display Enhanced Binding to but Not Activation of Phagocytic Cells (2002)

N-Formyl-methionyl peptides can specifically bind to surface receptors on phagocytic cells. A single copy of N-formyl-methionine-leucine-phenylalanine (fMLF) covalently linked to a poly(ethylene glycol)-based polymer displayed reduced binding avidity (Kd = 190 nM) for differentiated HL-60 cells relative to free fMLF (Kd = 28 nM). Increasing the number of fMLF residues (up to eight) attached to a single polymer results in enhanced avidity for these cells (Kd = 0.18 nM), which appears to be independent of whether the polymer backbone is linear or branched. However, no conjugate showed enhanced ability to activate phagocytic cells, relative to the free peptide (EC50 = 5 nM), as measured by transient stimulation of release of calcium ions from intracellular stores into the cytoplasm. A polymer bearing four fMLF and four digoxigenin residues showed specific enhancement in binding to differentiated HL-60 cells and mouse peritoneal macrophages in situ relative to a polymer lacking fMLF; no such enhancement was seen in binding to receptor-negative lymphocytic Jurkat cells. These results suggest that multiple fMLF residues linked to a drug-delivery polymer can be used to target appended drugs to phagocytic cells with relatively little toxicity due to cellular activation.
In Vivo and In Vitro Characterization of the ARR11 Response Regulator Implicated in the His-to-Asp Phosphorelay Signal Transduction in Arabidopsis thaliana (2003)

In Arabidopsis thaliana, Histidine-to-Aspartate (His--> Asp) phosphorelay is a paradigm of a signaling system that is considered to be involved in response to plant hormones, including ethylene and cytokinin. In the current framework of His-->Asp phosphorelay in this higher plant, the type-B ARR (response regulator) family members appear to act as DNA-binding transcriptional regulators. Although Arabidopsis thaliana has 11 type-B ARR family members, except for ARR1 and ARR2, no biological information is available with regard to others. As the main objective of this study, we characterized another example, ARR11, in terms of not only its in vitro biochemical properties, but also its biological activity in plants. In plants, the ARR11 gene was expressed predominantly in roots. In vitro, ARR11 showed the ability to acquire a phosphoryl group from a histidine-containing phosphotransfer intermediate (AHP), and also it showed the ability to recognize a specific nucleotide sequence, GGATT. These in vitro results supported the view that ARR11 is indeed a DNA-binding transcription factor, the ability of which is most likely modulated by phosphorylation in its receiver domain. In vivo, when a C-terminal DNA-binding domain lacking the N-terminal phospho-accepting (or receiver) domain was aberrantly expressed, the resulting transgenic plants showed characteristic anomalies during development of apical parts. The observed anomalies included "unusual proliferation of tissues in cotyledons" and "outgrowth of adventitious shoots near cotyledons". These results with regard to the functions of ARR11 are mainly discussed in comparison with those of the previously characterized type-B response regulators.
A Stereoselective Synthesis oftrans-1,2-Disubstituted Alkenes Based on the Condensation of Aldehydes with Metallated 1-Phenyl-1H-tetrazol-5-yl Sulfones (1998)

The reaction of metallated 1-phenyl-1H-tetrazol-5-yl sulfones and aldehydes gives good yields and stereoselectivity of trans-1,2-disubstituted alkenes when potassium or sodium hexamethyldisilazide is used as base and 1,2-dimethoxyethane is used as solvent.
Murine Monoclonal Antibodies Defining Neutralizing Epitopes on Tumor Necrosis Factor (1987)

A panel of four monoclonal antibodies (MAbs) was generated against recombinant human tumor necrosis factor-alpha (rTNF). These MAbs immunoprecipitate 125I-labeled rTNF, block binding of 125I-labeled rTNF to L929 mouse fibroblasts, and neutralize in vitro cytotoxicity of rTNF and native TNF (nTNF) in the L929 cytotoxicity assay. They define distinct epitopes closely associated with the receptor binding site of rTNF. In Western analysis they bind to both monomeric and dimeric rTNF. Two MAbs recognizing distinct epitopes were used to develop a 'sandwich' enzyme immunometric assay (EIMA) to measure rTNF levels in human serum and other fluids.
Observation of ferromagnetic resonance in a microscopic sample using magnetic resonance force microscopy (1996)

We report the observation of a ferromagnetic resonance signal arising from a microscopic (∼20 μm×40 μm) particle of thin (3μm) yttrium iron garnet film using magnetic resonance force microscopy (MRFM). The large signal intensity in the resonance spectra suggests that MRFM could become a powerful microscopic ferromagnetic resonance technique with a micron or sub-micron resolution. We also observe a very strong nonresonance signal which occurs in the field regime where the sample magnetization readily reorients in response to the modulation of the magnetic field. This signal will be the main noise source in applications where a magnet is mounted on the cantilever.