gebhart/patrepeval huggingface dataset:
Mesopore-Free Hollow Silica Particles with Controllable Diameter and Shell Thickness via Additive-Free Synthesis (2012)

Mesopore-free hollow silica particles with a spherical shape, smooth surface, and controllable diameter (from 80 to 300 nm) and shell thickness (from 2 to 25 nm) were successfully prepared using an additive-free synthesis method. Different from other hollow particle developments, a mesopore-free shell was produced because of the absence of additive. Although common reports pointed out the importance of the additional additive in pasting and growing silica on the surface of a template, here we preferred to exploit the effect of the template charge in gaining the silica coating process. To form the silica, basic amino acid (i.e., lysine) was used as a catalyst to replace ammonia or hydrazine, which is harmless and able to control the silica growth and produce hollow particles with smooth surfaces. Control of the particle diameter was drastically achieved by altering the size of the template. The flexibility of the process in controlling the shell thickness was predominantly attained by varying the compositions of the reactants (i.e., silica source and catalyst). The present mesopore-free hollow particles could be efficiently used for various applications, especially for thermal insulator and optical devices because of their tendency not to adsorb large molecules, as confirmed by adsorption analysis.
INHIBITION OF CARBONIC ANHYDRASE ISOZYMES I, II AND IV WITH ARSANILIC ACID DERIVATIVES (1998)

Reaction of arsanilic acid with sulfonyl halides, sulfeny.l halides, acyl chlorides, isocyanates, isothiocyanates and cyanamide afforded a series of derivatives possessing the general formula RNH-C 6 H 4 -AsOiH,, which were characterized by standard physico-chemical procedures. The new derivatives showed good inhibitory activity against three isozymes of carbonic anhydrase (CA), i.e., CA I, II and IV. Structureactivity correlations in the series of prepared enzyme inhibitors are discussed too.
Solvent regulation of oxygen affinity in hemoglobin. Sensitivity of bovine hemoglobin to chloride ions. (1984)

Under physiological conditions of pH (7.4) and chloride concentration (0.15 M), the oxygen affinity of bovine hemoglobin is substantially lower than that of human hemoglobin. Also, the Bohr effect is much more pronounced in bovine hemoglobin. Numerical simulations indicate that both phenomena can be explained by a larger preferential binding of chloride ions to deoxyhemoglobin in the bovine system. Also, they show that the larger preferential binding may be produced by a decreased affinity of the anions for oxyhemoglobin, thereby stressing the potential relevance of the oxy conformation in regulating the functional properties of the protein. The conformation of the amino-terminal end of the beta subunits appears to regulate the interaction of hemoglobin with solvent components. The pronounced sensitivity of the oxygen affinity of bovine hemoglobin to chloride concentration and to pH suggests that in bovine species these are the modulators of oxygen transport in vivo.
Noradrenergic innervation of serotoninergic neurons in the myenteric plexus (1987)

The monoaminergic innervation of the guinea pig small intestine was investigated to determine if there is an anatomical basis for the hypothesis that serotoninergic and noradrenergic neurons physiologically interact in the enteric nervous system. Initial rates of uptake of tritiated 5-hydroxytryptamine (3H-5-HT) or norepinephrine (3H-NE) by segments of guinea pig small intestine were measured in order to estimate the regional density of the serotoninergic and noradrenergic innervation. No change was found in the uptake of 3H-5-HT as a function of distance between duodenum and ileum, whereas the relative uptake of 3H-NE declined. The pattern of serotoninergic elements demonstrated radioautographically was compared with that obtained by visualizing 5-HT immunoreactivity. Both methods revealed that a small number of serotoninergic neurons, located in 35.3% +/- 1.5% of myenteric ganglia, give rise to many fibers that form thick bundles in interganglionic connectives. Moreover, there was a pronounced heterogeneity in the serotoninergic innervation of individual myenteric neurons and ganglia. In material fixed with aldehydes and postfixed with NaMnO4, noradrenergic axon terminals were identified by their characteristic small dense-cored vesicles. Following incubation with 3H-NE only terminals with small dense-cored vesicles were radioautographically labeled, confirming that these terminals are noradrenergic. When 3H-5-HT was substituted for 3H-NE, noradrenergic terminals were not labeled, showing that nonspecific uptake of 3H-5-HT into noradrenergic axons did not occur in the presence of 5-hydroxydopamine. The combination of aldehyde-NaMnO4 fixation with the radioautographic localization of 3H-5-HT thus permitted the simultaneous identification of serotoninergic and noradrenergic neural elements. Serotoninergic varicosities were found to differ from noradrenergic varicosities in the size, appearance, and packing density of their synaptic vesicles. In addition, recognizable but rudimentary pre- and postsynaptic membrane specializations were associated with serotoninergic but not noradrenergic varicosities. Most serotoninergic neuronal cell bodies were contacted both by serotoninergic synapses and noradrenergic varicosities. Similar appositions of noradrenergic varicosities with nonserotoninergic neurons appeared to be rare. In view of earlier observations that sympathetic nerves affect the release of 5-HT from stimulated enteric serotoninergic neurons, it seems likely that the noradrenergic appositions with serotoninergic neurons are the anatomical substrate for this effect.(ABSTRACT TRUNCATED AT 400 WORDS)
Ubiquitin Binding Site of the Ubiquitin E2 Variant (UEV) Protein Mms2 Is Required for DNA Damage Tolerance in the Yeast RAD6 Pathway (2005)

Different ubiquitin modifications to proliferating cell nuclear antigen (PCNA) signal distinct modes of lesion bypass in the RAD6 pathway of DNA damage tolerance. The modification of PCNA with monoubiquitin signals an error-prone bypass, whereas the extension of this modification into a Lys-63-linked polyubiquitin chain promotes error-free bypass. Chain formation is catalyzed by the Mms2/Ubc13 conjugating enzyme variant/conjugating enzyme (UEV.E2) complex together with the Rad5 ubiquitin ligase. In vitro studies of this UEV.E2 complex have identified a ubiquitin binding site that is mainly localized on Mms2. However, the role of this site in DNA damage tolerance and the molecular features of the ubiquitin/Mms2 interaction are poorly understood. Here we identify two molecular determinants, the side chains of Mms2-Ile-57 and ubiquitin-Ile-44, that are required for chain assembly in vitro and error-free lesion bypass in vivo. Mutating either of these side chains to alanine elicits a severe 10-20-fold inhibition of chain synthesis that is caused by compromised binding of the acceptor ubiquitin to Mms2. These results suggest that the ubiquitin binding site of Mms2 is necessary for error-free lesion bypass in the RAD6 pathway and provide new insights into ubiquitin recognition by UEV proteins.
Human Embryonic Stem Cell Lines Derived from Single Blastomeres (2006)

At present it is necessary to destroy embryos ex utero to obtain human embryonic stem (hES) cells, but a study in mice suggests that ES cells might be generated using a single-cell biopsy technique similar to that used for preimplantation genetic diagnosis (PGD). This will not interfere with the developmental potential of the embryo. Overnight growth of a single blastomere could yield cells that may be used for both genetic testing and stem cell production without altering the clinical outcome. The investigators carried out ten experiments which, collectively, showed that hES cells can be derived from single blastomeres. Starting with unused embryos produced by in vitro fertilization, 19 ES-cell-like outgrowths and two stable hES cell lines were obtained. A majority of isolated blastomeres divided at least once, and about half formed vesicles or clumps that produced outgrowths within 2 days. The cells remained able to form derivatives of all three embryonic germ layers (primitive endoderm, mesoderm, ectoderm) in vitro and also in teratomas. Among the outcomes observed over several days were three that are typical when ES cells are derived from human embryos. Cells resembling trophectoderm dominated some cultures. Secondly, cells that initially resembled ES cells differentiated within cultures. Finally, ES-cell-like cells continued to proliferate without differentiating. Some hES cell lines proliferated without differentiating for longer than 8 months. Both karyotypes and the expression of markers of pluripotency were normal. The ability to create new stem cell lines without destroying embryos addresses the ethical concerns shared by many interested individuals. Potentially, matched tissues can be generated for children and siblings born from transferred PGD embryos. Further studies will be needed to learn whether blastomere-derived hES cell lines resemble conventional hES cell lines in their ability to form functional differentiated cell types. The investigators recommend that, until safety issues are resolved, this procedure be used only in the context of PGD.
SkewTune (2012)

We present an automatic skew mitigation approach for user-defined MapReduce programs and present SkewTune, a system that implements this approach as a drop-in replacement for an existing MapReduce implementation. There are three key challenges: (a) require no extra input from the user yet work for all MapReduce applications, (b) be completely transparent, and (c) impose minimal overhead if there is no skew. The SkewTune approach addresses these challenges and works as follows: When a node in the cluster becomes idle, SkewTune identifies the task with the greatest expected remaining processing time. The unprocessed input data of this straggling task is then proactively repartitioned in a way that fully utilizes the nodes in the cluster and preserves the ordering of the input data so that the original output can be reconstructed by concatenation. We implement SkewTune as an extension to Hadoop and evaluate its effectiveness using several real applications. The results show that SkewTune can significantly reduce job runtime in the presence of skew and adds little to no overhead in the absence of skew.
Structure of the KvAP voltage-dependent K + channel and its dependence on the lipid membrane (2005)

Voltage-dependent ion channels gate open in response to changes in cell membrane voltage. This form of gating permits the propagation of action potentials. We present two structures of the voltage-dependent K(+) channel KvAP, in complex with monoclonal Fv fragments (3.9 A) and without antibody fragments (8 A). We also studied KvAP with disulfide cross-bridges in lipid membranes. Analyzing these data in the context of the crystal structure of Kv1.2 and EPR data on KvAP we reach the following conclusions: (i) KvAP is similar in structure to Kv1.2 with a very modest difference in the orientation of its voltage sensor; (ii) mAb fragments are not the source of non-native conformations of KvAP in crystal structures; (iii) because KvAP contains separate loosely adherent domains, a lipid membrane is required to maintain their correct relative orientations, and (iv) the model of KvAP is consistent with the proposal of voltage sensing through the movement of an arginine-containing helix-turn-helix element at the protein-lipid interface.
Effects of chemical modification on the potency, serum stability, and immunostimulatory properties of short shRNAs (2009)

Small hairpin RNAs (shRNAs) with 19-base-pair, or shorter, stems (short shRNAs [sshRNAs]) have been found to constitute a class whose mechanism of action appears to be distinct from that of small interfering RNAs (siRNAs) or longer shRNAs. These sshRNAs can be as active as canonical siRNAs or longer shRNAs. Their activity is affected by whether the antisense strand is positioned 5' or 3' to the loop (L or R sshRNAs, respectively). Dicer seems not to be involved in the processing of sshRNAs, although the mechanism of target gene suppression by these hairpins is through Ago2-mediated mRNA cleavage. In this study, the effects of chemical modifications on the potency, serum stability, and innate immune response of sshRNAs were investigated. Deoxynucleotide substitution and 2'-O-methyl (2'-OMe) modification in the sense strand and loop did not affect silencing activity, but, unlike with siRNAs, when placed in the antisense strand these modifications were detrimental. Conjugation with bulky groups at the 5'-end of L sshRNAs or 3'-end of R sshRNAs had a negative impact on the potency. Unmodified sshRNAs in dimer form or with blunt ends were immunostimulatory. Some modifications such as 3'-end conjugation and phosphorothioate linkages on the backbone of the sshRNAs could also induce inflammatory cytokine production. However, 2'-OMe substitution of sshRNAs abrogated the innate immune response and improved the serum stability of the hairpins.
Treatment of autoimmune hemolytic anemias (2001)

Treatment of autoimmune hemolytic anemias varies depending on whether the patient has autoimmune hemolytic anemia of warm antibody type, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, or autoimmune hemolytic anemia secondary to an underlying disorder. Initial therapy for warm antibody autoimmune hemolytic anemia should be corticosteroids, such as prednisone at conventional doses of 1 to 1.5 mg/kg/d orally. Criteria must be established to determine whether the therapeutic response is adequate, because long-term therapy may lead to significant detrimental side effects. Splenectomy has the advantage over therapeutic options in that it has the potential for complete and long-term remission. The major adverse effect is the syndrome of overwhelming postsplenectomy infection. Other therapeutic options, which are less likely to have long-term benefit, are immunosuppressive drugs, danazol, intravenous immunoglobulin, and plasma exchange. Therapy of cold agglutinin syndrome often is unsatisfactory. All patients should avoid exposure to cold, and if additional therapy is necessary, the therapies used for warm antibody autoimmune hemolytic anemia may be tried with less likelihood of response. Paroxysmal cold hemoglobinuria requires aggressive supportive therapy, generally supplemented by corticosteroids. Hemolysis usually terminates spontaneously. Patients with secondary autoimmune hemolytic anemia may be treated similarly to those with idiopathic autoimmune hemolytic anemia, and additional therapy for the underlying disorder also may result in remission of the hemolysis.
Insulin Stimulates PKCζ-mediated Phosphorylation of Insulin Receptor Substrate-1 (IRS-1) (2001)

Incubation of rat hepatoma Fao cells with insulin leads to a transient rise in Tyr phosphorylation of insulin receptor substrate (IRS) proteins. This is followed by elevation in their P-Ser/Thr content, and their dissociation from the insulin receptor (IR). Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, abolished the increase in the P-Ser/Thr content of IRS-1, its dissociation from the IR, and the decrease in its P-Tyr content following 60 min of insulin treatment, indicating that the Ser kinases that negatively regulate IRS-1 function are downstream effectors of PI3K. PKCzeta fulfills this criterion, being an insulin-activated downstream effector of PI3K. Overexpression of PKCzeta in Fao cells, by infection of the cells with adenovirus-based PKCzeta construct, had no effect on its own, but it accelerated the rate of insulin-stimulated dissociation of IR.IRS-1 complexes and the rate of Tyr dephosphorylation of IRS-1. The insulin-stimulated negative regulatory role of PKCzeta was specific and could not be mimic by infecting Fao cells with adenoviral constructs encoding for PKC alpha, delta, or eta. Because the reduction in P-Tyr content of IRS-1 was accompanied by a reduced association of IRS-1 with p85, the regulatory subunit of PI3K, it suggests that this negative regulatory process induced by PKCzeta, has a built-in attenuation signal. Hence, insulin triggers a sequential cascade in which PI3K-mediated activation of PKCzeta inhibits IRS-1 functions, reduces complex formation between IRS-1 and PI3K, and inhibits further activation of PKCzeta itself. These findings implicate PKCzeta as a key element in a multistep negative feedback control mechanism of IRS-1 functions.
A pore-level scenario for the development of mixed-wettability in oil reservoirs (1992)

Understanding the role of thin films in porous media is vital if wettability is to be elucidated at the pore level. The type and thickness of films coating pore walls determines reservoir wettability and whether or not reservoir rock can be altered from its initial state of wettability. Pore shape, especially pore wall curvature, is an important factor in determining wetting-film thicknesses. Yet, pore shape and the physics of thin wetting films are generally neglected in models of flow in porous rocks. This paper incorporates thin-film forces into a collection of star-shaped capillary tubes model to describe the geological development of mixed-wettability in reservoir rock. Here, mixed-wettability refers to continuous and distinct oil and water-wetting surfaces coexisting in the porous medium. The proposed model emphasizes the remarkable role of thin films. New pore-level fluid configurations arise that are quite unexpected. For example, efficient water displacement of oil (i.e, low residual oil saturation) characteristic of mixed-wettability porous media is ascribed to interconnected oil lenses or rivulets which bridge the walls adjacent to a pore corner. Predicted residual oil saturations are approximately 35 % less in mixed-wet rock compared to completely water-wet rock. Calculated capillary pressure curves mimic those of mixed-wet porous media in the primary drainage of water, imbibition of water, and secondary drainage modes. Amott-Harvey indices range from {minus}0.18 to 0.36 also in good agreement with experimental values. (Morrow et al, 1986; Judhunandan and Morrow, 1991).
Functional Interrogation of Primary Human T Cells via CRISPR Genetic Editing (2018)

Developing precise and efficient gene editing approaches using CRISPR in primary human T cell subsets would provide an effective tool in decoding their functions. Toward this goal, we used lentiviral CRISPR/Cas9 systems to transduce primary human T cells to stably express the Cas9 gene and guide RNAs that targeted either coding or noncoding regions of genes of interest. We showed that multiple genes (<i>CD4</i>, <i>CD45</i>, <i>CD95</i>) could be simultaneously and stably deleted in naive, memory, effector, or regulatory T cell (Treg) subsets at very high efficiency. Additionally, nuclease-deficient Cas9, associated with a transcriptional activator or repressor, can downregulate or increase expression of genes in T cells. For example, expression of glycoprotein A repetitions predominant (GARP), a gene that is normally and exclusively expressed on activated Tregs, could be induced on non-Treg effector T cells by nuclease-deficient Cas9 fused to transcriptional activators. Further analysis determined that this approach could be used in mapping promoter sequences involved in gene transcription. Through this CRISPR/Cas9-mediated genetic editing we also demonstrated the feasibility of human T cell functional analysis in several examples: 1) <i>CD95</i> deletion inhibited T cell apoptosis upon reactivation; 2) deletion of <i>ORAI1</i>, a Ca<sup>2+</sup> release-activated channel, abolished Ca<sup>2+</sup> influx and cytokine secretion, mimicking natural genetic mutations in immune-deficient patients; and 3) transcriptional activation of <i>CD25</i> or <i>CD127</i> expression enhanced cytokine signaling by IL-2 or IL-7, respectively. Taken together, application of the CRISPR toolbox to human T cell subsets has important implications for decoding the mechanisms of their functional outputs.
A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells (2002)

We report a photoactivatable variant of the Aequorea victoria green fluorescent protein (GFP) that, after intense irradiation with 413-nanometer light, increases fluorescence 100 times when excited by 488-nanometer light and remains stable for days under aerobic conditions. These characteristics offer a new tool for exploring intracellular protein dynamics by tracking photoactivated molecules that are the only visible GFPs in the cell. Here, we use the photoactivatable GFP both as a free protein to measure protein diffusion across the nuclear envelope and as a chimera with a lysosomal membrane protein to demonstrate rapid interlysosomal membrane exchange.
A Reconfigurable Architecture Using a Flexible LO Modulator to Unify High-Sensitivity Signal Reception and Compressed-Sampling Wideband Signal Detection (2018)

The direct RF-to-information converter unifies high-sensitivity signal reception and compressed-sampling (CS) wideband signal detection into a rapidly reconfigurable and easily scalable architecture occupying 0.56 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> in 65-nm CMOS. In reception mode, the DRF2IC RF frontend consumes 46.5 mW from 1.15 V and delivers 40-MHz RF bandwidth, 41.5-dB conversion gain, 3.6-dB noise figure, and -2 dBm B1dB. In CS wideband detection mode, 66-dB operational dynamic range, 40-dB instantaneous dynamic range, and 1.43-GHz instantaneous bandwidth are demonstrated, and six interferers each 10 MHz wide scattered over a 1.27-GHz span are detected in 1.2 μs consuming 58.5 mW.
Inhibition of nonspecific tumoricidal activity by activated macrophages with antiserum against a soluble cytotoxic factor (1981)

Mouse peritoneal macrophages activated for tumor cytotoxicity by any of several in vivo or in vitro treatments released a soluble cytotoxin into culture fluids only after exposure to small amounts of bacterial lipopolysaccharides. This cytotoxic factor was physicochemically similar to the cytotoxic factor (tumor necrosis factor) in sera of BCG-infected mice injected with lipopolysaccharide. A rabbit antiserum against partially purified serum cytotoxic factor also inhibited the activity of macrophage-derived cytotoxic factor. Of special interest was the observation that rabbit anti-cytotoxic factor inhibited the cytotoxic activity of macrophages both in the presence and in the absence of exogenously added lipopolysaccharide. Inhibition was not complete but was consistent in all experiments. Thus, cytotoxic factor was implicated as a possible effector molecule in the nonspecific tumoricidal activity of activated macrophages.
Primary structure of a cerulenin-binding beta-ketoacyl-[acyl carrier protein] synthase from barley chloroplasts. (1991)

The radioactively labeled beta-ketoacyl thioester synthase inhibitor [3H] cerulenin was used to tag three dimeric barely chloroplast proteins (alpha alpha, alpha beta, and beta beta) from the stromal fraction. Oligonucleotides corresponding to amino acid sequences obtained from the purified proteins were used to generate with the polymerase chain reaction a probe for cDNAs encoding the beta subunit. cDNA sequencing revealed an open reading frame for 462 residues comprising the mature protein and a 35-amino acid transit peptide. The deduced amino acid sequence of the mature protein is homologous to the beta-ketoacyl-[acyl carrier protein] (ACP) synthase I [3-oxoacyl-ACP synthase; acyl-ACP:malonyl-ACP C-acyltransferase (decarboxylating), EC 2.3.1.41] of Escherichia coli. Under analogous experimental conditions [3H]cerulenin tagged a single dimeric protein from spinach chloroplasts.