gebhart/patrepeval huggingface dataset:
The angiogenic response is dictated by β3 integrin on bone marrow–derived cells (2008)

Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the alpha(v)beta(3) integrin. Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted beta(3) integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that alpha(v)beta(3) integrin enhances BMDC recruitment and retention at angiogenic sites by mediating cellular adhesion and transmigration of BMDCs through the endothelial monolayer but not their release from the bone niche. Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.
Enantioselective Reduction of meso-Cyclic-1,2-dicarboxylic Anhydrides and 1,2-Dicarboximides: Asymmetric Synthesis of Bicyclic Lactones and Hydroxylactams. (1994)

Chiral bicyclic lactones (3, 8, 9) and bicyclic hydroxylactams (10-13) were synthesized by highly enantioselective reduction of meso-cyclic-1, 2-dicarboxylic anhydrides (1, 4) and meso-cyclic-1, 2-dicarboximides (2) with lithium aluminum hydride (LiAlH4)-alcohol(ROH)-(R)- or (S)-1, 1'-bi-2-naphthol complex [(R)- or (S)-BINAL-H(ROH)]. Treatment of the hydroxylactams (10-13) with triethylsilane (Et3SiH) and trifluoroacetic acid (CF3CO2H) gave chiral bicyclic lactams (14, 15) in quantitative yields. Removal of the N-4-methoxyphenyl group of the lactams (14, 15) with cerium(IV) ammonium nitrate (CAN) proceeded smoothly to give the corresponding N-unsubstituted lactams (16, 17) in high optical purity.
New insights into 2-methoxyestradiol, a promising antiangiogenic and antitumor agent (2003)

In summary, preclinical studies continue to provide enthusiasm for 2ME2 as a broad-spectrum agent. New data help resolve the roles of the diverse cellular effects of 2ME2 including microtubule disruption, initiation of signal transduction pathways, and generation of reactive oxygen species, which culminate in induction of apoptosis. 2ME2 analogues with superior properties have been identified and may provide opportunities for second-generation drugs.
Hybridization Kinetics Explains CRISPR-Cas Off-Targeting Rules (2018)

Due to their specificity, efficiency, and ease of programming, CRISPR-associated nucleases are popular tools for genome editing. On the genomic scale, these nucleases still show considerable off-target activity though, posing a serious obstacle to the development of therapies. Off targeting is often minimized by choosing especially high-specificity guide sequences, based on algorithms that codify empirically determined off-targeting rules. A lack of mechanistic understanding of these rules has so far necessitated their ad hoc implementation, likely contributing to the limited precision of present algorithms. To understand the targeting rules, we kinetically model the physics of guide-target hybrid formation. Using only four parameters, our model elucidates the kinetic origin of the experimentally observed off-targeting rules, thereby rationalizing the results from both binding and cleavage assays. We favorably compare our model to published data from CRISPR-Cas9, CRISPR-Cpf1, CRISPR-Cascade, as well as the human Argonaute 2 system.
Intrathecal Methylprednisolone for Intractable Postherpetic Neuralgia (2000)

The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.
Unraveling Natural Killer T-Cells Development (2018)

Natural killer T-cells are a subset of innate-like T-cells with the ability to bridge innate and adaptive immunity. There is great interest in harnessing these cells to improve tumor therapy; however, greater understanding of invariant NKT (iNKT) cell biology is needed. The first step is to learn more about NKT development within the thymus. Recent studies suggest lineage separation of murine iNKT cells into iNKT1, iNKT2, and iNKT17 cells instead of shared developmental stages. This review will focus on these new studies and will discuss the evidence for lineage separation in contrast to shared developmental stages. The author will also highlight the classifications of murine iNKT cells according to identified transcription factors and cytokine production, and will discuss transcriptional and posttranscriptional regulations, and the role of mammalian target of rapamycin. Finally, the importance of these findings for human cancer therapy will be briefly discussed.
Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats (2015)

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.
Perspectives of Gene Therapy in Stem Cell Tissue Engineering (2006)

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain or improve tissue function. It is hoped that forming tissue de novo will overcome many problems in plastic surgery associated with such areas as wound healing and the immunogenicity of transplanted tissue that lead to dysfunctional repair. Gene therapy is the science of the transfer of genetic material into individuals for therapeutic purposes by altering cellular function or structure at the molecular level. Recently, tissue engineering has been used in conjunction with gene therapy as a hybrid approach. This combination of stem-cell-based tissue engineering with gene therapy has the potential to provide regenerative tissue cells within an environment of optimal regulatory protein expression and would have many benefits in various areas such as the transplantation of skin, cartilage or bone. The aim of this review is to outline tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery.
Recognition of IgG by Fcγ Receptor (2001)

Recently determined crystal structures of the complex between immunoglobulin constant regions (Fc) and their Fc-respective receptors (FcR) have revealed the detailed molecular interactions of this receptor-ligand pair. Of particular interest is the contribution of a glycosylation at Asn(297) of the C(H)2 domain of IgG to receptor recognition. The carbohydrate moieties are found outside the receptor.Fc interface in all receptor.Fc complex structures. To understand the role of glycosylation in FcR recognition, the receptor affinities of a deglycosylated IgG1 and its Fc fragment were determined by solution binding studies using surface plasmon resonance. The removal of carbohydrates resulted in a non-detectable receptor binding to the Fc alone and a 15- to 20-fold reduction of the receptor binding to IgG1, suggesting that the carbohydrates are important in the function of the FcgammaRIII. Structurally, the carbohydrates attached to Asn(297) fill the cavity between the C(H)2 domains of Fc functioning equivalently as a hydrophobic core. This may stabilize a favorable lower hinge conformation for the receptor binding. The structure of the complex also revealed the dominance of the lower hinge region in receptor.Fc recognition. To evaluate the potential of designing small molecular ligands to inhibit the receptor function, four lower hinge peptides were investigated for their ability to bind to the receptor FcgammaRIII. These peptides bind specifically to FcgammaRIII with affinities 20- to 100-fold lower than IgG1 and are able to compete with Fc in receptor binding. The results of peptide binding illustrate new ways of designing therapeutic compounds to block Fc receptor activation.
A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery (1998)

A family of N-substituted glycine oligomers (peptoids) of defined length and sequence are shown to condense plasmid DNA into small particles, protect it from nuclease degradation, and efficiently mediate the transfection of several cell lines. The oligomers were discovered by screening a combinatorial library of cationic peptoids that varied in length, density of charge, side-chain shape, and hydrophobicity. Transfection activity and peptoid-DNA complex formation are shown to be highly dependent on the peptoid structure. The most active peptoid is a 36-mer that contains 12 cationic aminoethyl side chains. This molecule can be synthesized efficiently from readily available building blocks. The peptoid condenses plasmid DNA into uniform particles 50-100 nm in diameter and mediates the transfection of a number of cell lines with efficiencies greater than or comparable to DMRIE-C, Lipofectin, and Lipofectamine. Unlike many cationic lipids, peptoids are capable of working in the presence of serum.
Injury‐Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms (2019)

Upon injury, psychotropic psilocybin-producing mushrooms instantly develop an intense blue color, the chemical basis and mode of formation of which has remained elusive. We report two enzymes from Psilocybe cubensis that carry out a two-step cascade to prepare psilocybin for oxidative oligomerization that leads to blue products. The phosphatase PsiP removes the 4-O-phosphate group to yield psilocin, while PsiL oxidizes its 4-hydroxy group. The PsiL reaction was monitored by in situ <sup>13</sup> C NMR spectroscopy, which indicated that oxidative coupling of psilocyl residues occurs primarily via C-5. MS and IR spectroscopy indicated the formation of a heterogeneous mixture of preferentially psilocyl 3- to 13-mers and suggest multiple oligomerization routes, depending on oxidative power and substrate concentration. The results also imply that phosphate ester of psilocybin serves a reversible protective function.
Fungal Biofilms and Drug Resistance (2004)

Candida species, including the novel opportunistic pathogen Candida dubliniensis, are now emerging as major agents of nosocomial infections. Many such manifestations of infections associated with the formation of Candida biofilms include those occurring on devices such as indwelling intravascular catheters. Fungal biofilm-associated infections are frequently refractory to conventional therapy because of resistance to antimicrobial agents. This resistance could be in part due to the surface-induced upregulation of drug efflux pumps. Biofilm-associated Candida show uniform resistance to a wide spectrum of the currently available conventional antifungal agents, which implies that antimicrobial drugs that specifically target biofilm-associated infections are needed. The novel classes of antifungal agents, the lipid formulation of amphotericins, and the echinocandins have demonstrated unique antifungal activity against the resistant Candida biofilms, providing a breakthrough in the treatment of life-threatening invasive systemic mycoses. The use of drugs effective in combating biofilm-associated infections could lead to major developments in the treatment of fungal implant infections.
Characterization and biological properties of chemically deglycosylated human chorionic gonadotropin. Role of carbohydrate moieties in adenylate cyclase activation. (1982)

Chemical deglycosylation of purified human chorionic gonadotropin (hCG) was performed by treatment with anhydrous HF in the presence of anisole at 0 "C for 1 h.Gel chromatography of the product on Sephadex G-100 revealed a single peak with Kav = 0.28, as compared to the Kav = 0.21 of intact hCG.Subunit dissociation by the HF treatment was less than 5%. Sodium dodecylsulfate-gel electrophoresis of the pooled peak, denoted as HF-hCG, showed two bands with molecular sizes 30% lower than the native a and P subunits.No change in amino acid composition was detected, but carbohydrate analysis showed that the HF treatment removed 76-87% of sialic acid, galactose, mannose, and fucose, 52% of N-acetyl-D-glucosamine, and 14% of N-acetyl-D-galactosamine.These findings indicate that HF cleavages occurred predominantly at the mannose residues of the asparagine-linked moiety and the galactose residues of the serine-linked moiety.Deglycosylated hCG did not bind to concanavalin A, and was inert to the fuchsin-sulfite reagent after periodate oxidation.When analyzed for binding to hCG and P-subunit antisera, HF-hCG cross-reacted equally with hCG in the anti-hCG system, but was less potent in anti-hCGP and anti-hCGP-COOH-peptide systems.In the rat testis luteinizing hormone receptor assay, HF-hCG displayed 2.5 times higher binding activity than intact hCG.In contrast, the in vitro biological activities of HF-hCG upon stimulation of testosterone and cAMP production in Leydig cells and the activation of adenylate cyclase in interstitial membranes were at least 100-fold less active than hCG.No in vivo biological activity of HF-hCG was detectable in the rat uterine weight assay at 2.5 pg/rat, whereas 12.5 ng of hCG doubled the uterine weight.Activation of cAMP production by 1 ng/ml of hCG was completely antagonized by 0.1 pg/ml of HF-hCG.Similarly, activation of adenylcyclase in interstitial membranes by 1 pg/ml of hCG was inhibited to the basal level by 2 pg/ml of HF-hCG.HF-hCG was rapidly cleared in rats as evidenced by the fact that the maximal serum content of HF-hCG measured at 30 min after intraperitoneal injection was less than 10% of that reached by hCG after 3 h of injection.These results indicate the importance of the carbohydrate moieties of hCG in activation of Leydig cell responses following hormone binding to the luteinizing hormone receptors, and demonstrate the antagonist properties of deglycosylated hCG upon adenylate cyclase in the rat testis.
Tabhu: tools for antibody humanization (2014)

Supplementary data are available at Bioinformatics online.
Optimizing the migration of virtual computers (2002)

This paper shows how to quickly move the state of a running computer across a network, including the state in its disks, memory, CPU registers, and I/O devices. We call this state a capsule . Capsule state is hardware state, so it includes the entire operating system as well as applications and running processes.We have chosen to move x 86 computer states because x 86 computers are common, cheap, run the software we use, and have tools for migration. Unfortunately, x 86 capsules can be large, containing hundreds of megabytes of memory and gigabytes of disk data. We have developed techniques to reduce the amount of data sent over the network: copy-on-write disks track just the updates to capsule disks, "ballooning" zeros unused memory, demand paging fetches only needed blocks, and hashing avoids sending blocks that already exist at the remote end. We demonstrate these optimizations in a prototype system that uses VMware GSX Server virtual, machine monitor to create and run x 86 capsules. The system targets networks as slow as 384 kbps.Our experimental results suggest that efficient capsule migration can improve user mobility and system management. Software updates or installations on a set of machines can be accomplished simply by distributing a capsule with the new changes. Assuming the presence of a prior capsule, the amount of traffic incurred is commensurate with the size of the update or installation package itself. Capsule migration makes it possible for machines to start running an application within 20 minutes on a 384 kbps link, without having to first install the application or even the underlying operating system. Furthermore, users' capsules can be migrated during a commute between home and work in even less time.
Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. (1994)

Glucagon-like peptide-1 (GLP-1) is promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may be involved in the early phase of meal-induced GLP-1 secretion, various intestinal regulatory peptides and neurotransmitters of the gut were administered intraarterially in the isolated vascularly perfused rat colon preparation. The release of GLP-1 in the portal effluent was measured by a specific RIA. Intraarterial infusion of glucose-dependent insulinotropic peptide (GIP) over the concentration range 0.25-1 nM evoked a dose-dependent release of GLP-1, with a maximal response of 350% of the basal value. Tetrodotoxin did not modify the GIP-induced release of GLP-1. Secretin or cholecystokinin did not stimulate the secretion of GLP-1. Bombesin (10(-9)-10(-7) M) provoked a dose-dependent release of GLP-1, consisting of an early peak, followed by a sustained response. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise of GLP-1 immunoreactivity in the portal effluent (peak at 800% of the basal value 10 min after the start of infusion). Similarly, the beta-adrenergic agonist isoproterenol at concentrations of 10(-7) and 10(-6) M provoked a pronounced release of GLP-1 (peak at 500% of the basal value with 10(-6) M isoproterenol). Finally, the muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M evoked a gradual increase in GLP-1 immunoreactivity, which reached a maximal value (900% over basal) at the end of the 30-min infusion period. The lowest concentration of bethanechol used in the present study (10(-5) M) did not increase portal GLP-1 immunoreactivity over the basal value. Tetrodotoxin did not modify the bethanechol-, isoproterenol-, calcitonin gene-related peptide-, or bombesin-induced GLP-1 release. In conclusion, the present study conducted with the isolated vascularly perfused rat colon shows that there are interactions between the two most potent incretins, GIP and GLP-1, probably through an enteroendocrine pathway. Additionally, several transmitters of the gut are potent stimulants of GLP-1 release and, therefore, represent potential tools in the treatment of the noninsulin-dependent diabetes mellitus.
The Solubility of Amorphous Silica at High Temperatures and High Pressures (1976)

The solubility of amorphous silica in water at high temperatures and high pressures was investigated using commercial silica gel and fused quartz as starting materials. The experiments were carried out in a stainless steel bomb with an internal capacity of 89 cc. The weight of the silica starting material varied from 35 to 57 gm. Periodically, small amounts of solution (0.5 to 1.0 gm) were withdrawn in triplicate from the bottom of the bomb through a high pressure stainless steel capillary tube. Pressure was maintained almost constant by pumping water into the top of the bomb during sampling. The solutions were withdrawn through a filter (20 micron mean pore opening) inside the bomb, quenched in an ice bath before exiting from the capillary, and immediately diluted with previously weighted silica-free water. The diluted samples were analyzed for colorimetrically-reactive and total silica. The fused quartz usually gave similar amounts of colorimetric and total silica. The silica gel gave the same colorimetric silica as did the fused quartz, but higher and erratic amounts of total silica. The erratically-high total silica values probably were due to small amounts of very fine-grained solid particles of silica that disaggregated from the coarse-grained gelatinous starting material.
Applying SPHINX-II to the DARPA Wall Street Journal CSR task (1992)

This paper reports recent efforts to apply the speaker-independent SPHINX-II system to the DARPA Wall Street Journal continuous speech recognition task. In SPHINX-II, we incorporated additional dynamic and speaker-normalized features, replaced discrete models with sex-dependent semi-continuous hidden Markov models, augmented within-word triphones with between-word triphones, and extended generalized triphone models to shared-distribution models. The configuration of SPHINX-II being used for this task includes sex-dependent, semi-continuous, shared-distribution hidden Markov models and left context dependent between-word triphones. In applying our technology to this task we addressed issues that were not previously of concern owing to the (relatively) small size of the Resource Management task.
A Survey of Real‐time Soft Shadows Algorithms (2003)

Abstract ACM CSS: I.3.3 Computer Graphics Picture/Image Generation— Bitmap and framebuffer operations
Oxo‐ and imino‐functionalized 1,2‐oxazetidines. An overview (1993)

Abstract This review article describes syntheses and reactions of 1,2‐oxazetidines that have an oxo or (substituted) imino group attached to either C‐3 or C‐4. The rare case of a bifunctional derivative is also treated. In a final chapter, spectroscopic properties are surveyed.