gebhart/patrepeval huggingface dataset:
Segmental Versican Expression in the Trabecular Meshwork and Involvement in Outflow Facility (2011)

Versican appears to be a central component of the outflow resistance, where it may organize GAGs and other ECM components to facilitate and control open flow channels in the TM. However, the exact molecular organization of this resistance appears to differ between human and porcine eyes.
In vivo antitumor activity of multiple injections of recombinant interleukin 2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors. (1988)

We have used several transplantable experimental murine tumors to evaluate the potentiation of antitumor activity by a combination of human recombinant interleukin 2 (rHIL2) and recombinant interferons (rIFNs). The combination of rHIL2 and either human hybrid recombinant alpha-interferon A/D (rIFN-alpha A/D) or mouse recombinant beta-interferon (rIFN-beta) induced the s.c. adenocarcinoma 755, which had been established for 8 days, to regress, although rHIL2 or the rIFNs alone hardly inhibited the tumor's growth. Eight injections of the rHIL2-rIFN-alpha A/D combination cured 38% of the tumor-bearing mice. The rHIL2-rIFN-beta combination achieved a complete cure only when given in more than 13 injections. The administration of rHIL2 and mouse recombinant gamma-interferon (rIFN-gamma) markedly inhibited tumor growth of the s.c. established adenocarcinoma 755, but did not cure any of the mice. Other tumors, B16-F10 melanoma, and colon tumors 38 and 26 responded almost as well to a rHIL2-rIFN-alpha A/D or -beta combination, but not to a rHIL2-rIFN-gamma combination. The growth of Lewis lung carcinoma was inhibited to a lesser extent by all combinations, for which there were no long-term survivors. The combination therapy of rHIL2 and rIFN-beta produced a marked regression of the tumor in beige mice which have low natural killer activity, suggesting the activated natural killer cells not to be responsible for the therapeutic effect. And T-cell immunity may be important in the regression of s.c. established tumors, because of the lesser potentiation of antitumor activity in athymic mice. These results demonstrate that combination therapies of rHIL2 and rIFN-alpha A/D or -beta can function synergistically in the various s.c. established murine tumor systems and give further evidence in support of their clinical potential.
Phenethylthiazolethiourea (PETT) Compounds, a New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogs (1995)

A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 microM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM. The 50% cytotoxic dose in cell culture is > 380 microM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2-pyridyl)-thiourea (62; LY300046.HCl) as a candidate for clinical evaluation. LY300046.HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.
Direct Electrophilic Silylation of Terminal Alkynes (2004)

[reaction: see text] A variety of alkynylsilanes were efficiently prepared via direct silylation of terminal alkynes with aminosilanes in the presence of zinc halides. Base- and nucleophile-sensitive functionalities were perfectly tolerated under the above reaction conditions. Initial mechanistic studies support the electrophilic character of this transformation.
Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4‐reductase (2001)

Many plant species exhibit a reduced range of flower colors due to the lack of an essential gene or to the substrate specificity of a biosynthetic enzyme. Petunia does not produce orange flowers because dihydroflavonol 4-reductase (DFR) from this species, an enzyme involved in anthocyanin biosynthesis, inefficiently reduces dihydrokaempferol, the precursor to orange pelargonidin-type anthocyanins. The substrate specificity of DFR, however, has not been investigated at the molecular level. By analyzing chimeric DFRs of Petunia and Gerbera, we identified a region that determines the substrate specificity of DFR. Furthermore, by changing a single amino acid in this presumed substrate-binding region, we developed a DFR enzyme that preferentially reduces dihydrokaempferol. Our results imply that the substrate specificity of DFR can be altered by minor changes in DFR.
Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines. (1993)

We have identified a messenger RNA coding for a variant estrogen receptor jointly expressed with the normal mRNA in the estrogen receptor-positive, -responsive mammary carcinoma cell lines MCF-7 and ZR 75-1 by means of reverse transcription polymerase chain reaction. This variant mRNA was not observed in estrogen receptor-negative, -unresponsive MDA-MB 231 cells. Partial sequence analysis of the variant complementary DNA revealed identity to sequences of the estrogen receptor exons 3, 5, and 6, but the absence of the entire exon 4. We suggest that this variant receptor messenger is created by alternative splicing. The variant protein is expected to lack most of the hinge domain and part of the hormone binding domain, and it might have a cellular distribution and estrogen-binding affinity different from that of the normal receptor protein.
Antibacterial activity in bovine lactoferrin-derived peptides (1997)

Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two peptides were copurified, one identical to Lf-cin B and another differing from Lf-cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other peptides were copurified from chymosin-hydrolyzed Lf, one differing from Lf-cin B by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer linked by a disulfide bond. These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC). They were characterized by N-terminal Edman sequencing, mass spectrometry, and antibacterial activity determination. Pure lactoferricin, prepared from pepsin-hydrolyzed Lf, was purified by standard chromatography techniques. This peptide was analyzed against a number of gram-positive and gram-negative bacteria before and after reduction of its disulfide bond or cleavage after its single methionine residue and was found to inhibit the growth of all the test bacteria at a concentration of 8 microM or less. Subfragments of lactoferricin were isolated from reduced and cleaved peptide by reverse-phase HPLC. Subfragment 1 (residues 1 to 10) was active against most of the test microorganisms at concentrations of 10 to 50 microM. Subfragment 2 (residues 11 to 26) was active against only a few microorganisms at concentrations up to 100 microM. These antibacterial studies indicate that the activity of lactoferricin is mainly, but not wholly, due to its N-terminal region.
Thermally-actuated, phase change flow control for microfluidic systems (2005)

An easy to implement, thermally-actuated, noninvasive method for flow control in microfluidic devices is described. This technique takes advantage of the phase change of the working liquid itself-the freezing and melting of a portion of a liquid slug-to noninvasively close and open flow passages (referred to as a phase change valve). The valve was designed for use in a miniature diagnostic system for detecting pathogens in oral fluids at the point of care. The paper describes the modeling, construction, and characteristics of the valve. The experimental results favorably agree with theoretical predictions. In addition, the paper demonstrates the use of the phase change valves for flow control, sample metering and distribution into multiple analysis paths, sealing of a polymerase chain reaction (PCR) chamber, and sample introduction into and withdrawal from a closed loop. The phase change valve is electronically addressable, does not require any moving parts, introduces only minimal dead volume, is leakage and contamination free, and is biocompatible.
An Essential Role of Sialylated O-Linked Sugar Chains in the Recognition of Mouse CD99 by Paired Ig-Like Type 2 Receptor (PILR) (2008)

The paired Ig-like type 2 receptor (PILR), which comprises both inhibitory and activating isoforms, is well conserved among most mammalians. The inhibitory PILRalpha possesses an ITIM in its cytoplasmic domain, whereas the activating PILRbeta does not have an ITIM but transduces activating signals by associating with the ITAM-bearing DAP12 adapter molecule. Both mouse PILRalpha and PILRbeta recognize mouse CD99, which is broadly expressed on various cells, including lymphocytes, and is involved in the regulation of immune responses. We herein report that sialylated O-linked sugar chains on CD99 are essential for the recognition by PILR. Mutations of one of two O-glycosylation sites on CD99 significantly reduced recognition of CD99 by the activating PILRbeta, whereas recognition by the inhibitory PILRalpha was not affected. In contrast, mutations of both O-glycosylation sites on CD99 completely abrogated the recognition by both PILRalpha and PILRbeta. PILR did not recognize CD99 treated with neuraminidase, and CD99 expressed on cells transfected with core 2 beta-1,6-N-acetylglucosaminyltransferase was not recognized by PILR. NK cells expressing endogenous activating PILRbeta receptors mediated cytotoxicity against cells expressing wild-type CD99 but not cells expressing mutant CD99 that lacked O-glycosylation sites. These findings indicate that sialylated O-linked sugar structures on CD99 play an important role in the recognition of PILR.
An apparatus for the determination of ion drift in MIS structures (1984)

The light pulse technique has been used to create an apparatus for the determination of the drift of impurity ions in the insulator of metal-insulator-semiconductor structures. It is demonstrated that by using very simple circuits for signal processing, the same information is obtained from this apparatus as when using traditional, more complicated measurement methods.
Mode of Functional Connectivity in Amygdala Pathways Dissociates Level of Awareness for Signals of Fear (2006)

Many of the same regions of the human brain are activated during conscious attention to signals of fear and in the absence of awareness for these signals. The neural mechanisms that dissociate level of awareness from activation in these regions remain unknown. Using functional magnetic resonance imaging with connectivity analysis in healthy human subjects, we demonstrate that level of awareness for signals of fear depends on mode of functional connectivity in amygdala pathways rather than discrete patterns of activation in these pathways. Awareness for fear relied on negative connectivity within both cortical and subcortical pathways to the amygdala, suggesting that reentrant feedback may be necessary to afford such awareness. In contrast, responses to fear in the absence of awareness were supported by positive connections in a direct subcortical pathway to the amygdala, consistent with the view that excitatory feedforward connections along this pathway may be sufficient for automatic responses to "unseen" fear.
The trihelix DNA-binding motif in higher plants is not restricted to the transcription factors GT-1 and GT-2 (1998)

GT-2 is a plant transcriptional activator that contains two separate, but similar, trihelix DNA-binding domains. GT-1 is similar to GT-2, although it contains only one of such domains. cDNAs that encode GT-2 were isolated from rice (OS-GT2) and Arabidopsis (AT-GT2). Evidence is presented for the existence of an Arabidopsis gene family that is structurally related to AT-GT2. Two members of this GT2-like family, AT-GTL1 and AT-GTL2, have been isolated and characterized. Their sequences suggest that they evolved by a recent gene duplication event. Both AT-GT2 and AT-GTL genes contain an intron in the amino-terminal trihelix motif, indicating that this DNA-binding domain resulted from exon shuffling. RNA gel blot analysis using AT-GTL1 as a probe revealed four transcripts in the aerial part of the plant. All mRNA levels were significantly higher in siliques, suggesting that this gene family may function in fruit and/or seed development. To date, DNA-binding proteins characterized by the trihelix motif have been described only in plants, and may therefore be involved in plant-specific processes. Our results show that in Arabidopsis thaliana, the trihelix motif is not restricted to the GT-1 and GT-2 DNA-binding proteins.
Mechanism of Membrane Binding of the Phospholipase D1 PX Domain (2004)

Mammalian phospholipases D (PLD), which catalyze the hydrolysis of phosphatidylcholine to phosphatidic acid (PA), have been implicated in various cell signaling and vesicle trafficking processes. Mammalian PLD1 contains two different membrane-targeting domains, pleckstrin homology and Phox homology (PX) domains, but the precise roles of these domains in the membrane binding and activation of PLD1 are still unclear. To elucidate the role of the PX domain in PLD1 activation, we constructed a structural model of the PX domain by homology modeling and measured the membrane binding of this domain and selected mutants by surface plasmon resonance analysis. The PLD1 PX domain was found to have high phosphoinositide specificity, i.e. phosphatidylinositol 3,4,5-trisphosphate (PtdIns-(3,4,5)P(3)) >> phosphatidylinositol 3-phosphate > phosphatidylinositol 5-phosphate >> other phosphoinositides. The PtdIns(3,4,5)P(3) binding was facilitated by the cationic residues (Lys(119), Lys(121), and Arg(179)) in the putative binding pocket. Consistent with the model structure that suggests the presence of a second lipid-binding pocket, vesicle binding studies indicated that the PLD1 PX domain could also bind with moderate affinity to PA, phosphatidylserine, and other anionic lipids, which were mediated by a cluster of cationic residues in the secondary binding site. Simultaneous occupancy of both binding pockets synergistically increases membrane affinity of the PX domain. Electrostatic potential calculations suggest that a highly positive potential near the secondary binding site may facilitate the initial adsorption of the domain to the anionic membrane, which is followed by the binding of PtdIns(3,4,5)P(3) to its binding pocket. Collectively, our results suggest that the interaction of the PLD1 PX domain with PtdIns(3,4,5)P(3) and/or PA (or phosphatidylserine) may be an important factor in the spatiotemporal regulation and activation of PLD1.
NOD2/CARD15 gene polymorphisms in idiopathic pulmonary fibrosis. (2005)

We conclude that the NOD2/CARD15 gene is not likely to be involved in susceptibility to IPF in Italians.
Fundamentals of structural geology (2005)

1. Motivations and opportunities 2. Structural mapping techniques and tools 3. Characterizing structures using differential geometry 4. Physical quantities, fields, dimensions and scaling 5. Deformation and flow 6. Force, traction and stress 7. Conservation of mass and momentum 8. Elastic deformation 9. Brittle behavior 10. Viscous flow 11. Rheological behavior 12. Model development and methodology Index.
Blue Laser Inhibits Bacterial Growth of Staphylococcus aureus , Escherichia coli, and Pseudomonas aeruginosa (2015)

Blue laser light was capable of inhibiting bacterial growth at low fluences over time, thus presenting no time-dependent effect.
Plasma Gelsolin Depletion and Circulating Actin in Sepsis—A Pilot Study (2008)

We conclude that circulating actin and pGSN deficiency are associated with early sepsis. The degree of pGSN deficiency correlates with sepsis mortality. Reversing pGSN deficiency may be an effective treatment for sepsis.
Robotic-assisted micro-surgery of the throat: The trans-nasal approach (2013)

Minimally Invasive Surgery of the throat is predominantly performed trans-orally. Although trans-oral (TO) access provides a scarless access into the airways, its outcomes are affected by complications, high cost, and long setup time. This paper investigates the clinical motivation for trans-nasal (TN) access to the throat and presents the design and hybrid position/compliant motion control of a rapidly deployable endo-nasal telerobotic system. The system exploits a unique Ø5 mm surgical slave with force sensing capabilities used to enable semi-automating the insertion process. Working channels allow the deployment of surgical tools such as a fiberscope, positioning sensors, grippers, suction tubes, cautery, and laser fibers. The treatment of vocal fold paralysis is chosen as a benchmark application and a feasibility study for collagen injection is conducted. Experiments on a realistic human intubation trainer demonstrated successful and safe TN deployment of the end-effector and the feasibility of robotic-assisted treatment of vocal nerve paralysis. We believe this system constitutes a first step toward low-cost office-based head and neck surgical procedures.
Leflunomide, a new disease-modifying anti-rheumatic drug and the never ending rheumatoid arthritis story (2000)

Leflunomide, a new disease-modifying anti-rheumatic drug and the never ending rheumatoid arthritis story
Alterations in Lactoferrin in Salivary Gland Disease (1978)

During the active phase of chronic recurrent parotitis there is a marked elevation in the parotid concentration of lactoferrin (Lf), and iron-binding glycoprotein with antibacterial properties. The Lf concentration decreases during the recovery period, but still remains above normal levels. The changes of Lf in parotitis parallel recent findings in mastitis and pancreatitis. Elevations in Lf were also noted in five of six subjects with Sjögren's disease, but not in subjects with sarcoidosis, diabetes or "dry mouth" without sialographic changes. The source of the Lf has not been determined; it could arise in part from disrupting polymorphonuclear leucocytes and in part from epithelial cells that synthesize Lf in the salivary glands. Inflammatory stimulation of Lf synthesis would suggest a basic protective mechanism in exocrine glands and should be fully explored.
Abstract 5346: A novel immunotoxin comprising quadruple RNase tethered to an internalizing anti-TROP-2 humanized MAb shows potent cytotoxicity against diverse solid tumors in vitro (2010)

Abstract Ribonucleases (RNase) are potential anti-tumor agents, and their potency can be enhanced by recombinant fusion or chemical conjugation with tumor-targeting antibodies, as have been demonstrated for ranpirnase (Rap), an amphibian RNase, conjugated to LL2, a murine anti-CD22 MAb (Newton et al., Blood 2001; 97: 528-35) or fused to a humanized anti-CD74 MAb (Chang et al., Blood 2005; 106: 4308-14). We have now applied the Dock-and-Lock (DNL) method to link four copies of Rap site-specifically to the carboxyl termini of a panel of tumor-targeting humanized antibodies, in particular, hRS7, an internalizing, humanized, anti-TROP-2 MAb. We combined Rap-DDD2, a fusion protein comprising Rap and the dimerization and docking domain (DDD) of cAMP-dependent protein kinase (PKA), with hRS7-IgG-AD2, a fusion protein comprising two AD2 peptides derived from A-kinase anchoring proteins (AKAPs) having each AD2 appended to the carboxyl terminus of the heavy chain. Since Rap-DDD2 is isolated as a dimer, the resulting DNL complex, designated E1-Rap, contains four copies of Rap tethered to a bivalent hRS7 IgG. In the present study, we compared the in vitro growth inhibitory properties of E1-Rap against a variety of carcinoma cell lines. In breast (MDA-MB-468), cervical (ME-180), and pancreatic (BxPC-3 and Capan-1) tumor lines, all of which express high levels of TROP-2, E1-Rap was very potent, showing EC50 in the subnanomolar range (5 to 890 pM), which was 1,000- to 100,00-fold higher than untargeted Rap or the combination of Rap and hRS7. In cell lines expressing moderate levels of TROP-2, such as the three prostate cancer lines (PC-3, DU 145, and LNCaP), E1-Rap was less potent, but still showed EC50 in the nanomolar range (1 to 890 nM). The cell binding data obtained for these solid cancer cell lines suggest that the sensitivity of a cell line to E1-Rap appears to correlate with its TROP-2 expression on the cell surface. No toxicity was observed for E1-Rap in the prostate cancer line, 22Rv1, which fails to bind hRS7. Based on these results, further in vivo studies are warranted to better determine the efficacy of E1-Rap for future development as a new candidate therapeutic for TROP-2-positive solid tumors, including breast, cervical, pancreatic, and prostatic carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5346.
Sphingosine Kinase Inhibitors and Cancer: Seeking the Golden Sword of Hercules (2011)

There is considerable evidence that sphingosine kinases play a key role in cancer progression, which might involve positive selection of cancer cells that have been provided with a survival and growth advantage as a consequence of overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a novel class of compounds that have potential as anticancer agents. Poor inhibitor potency is a major issue that has precluded successful translation of these compounds into the clinic. However, recent discoveries have shown that sphingosine kinase 1 is an allosteric enzyme and that some inhibitors offer improved effectiveness by inducing proteasomal degradation of the enzyme or having nanomolar potency. Herein, we provide a perspective about these recent developments and highlight the importance of translating basic pharmacologic and biochemical findings on sphingosine kinase into new drug discovery programs for treatment of cancer.
Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF (2009)

www.clinicaltrials.gov (nCT00264992).
The Process of Physical Weakening and Dissolution of the HA-coated Implant in Bone and Soft Tissue (1998)

Hydroxyapatite (HA)-coated implants were developed to promote osseointegration of titanium implants and to overcome the mechanical drawbacks of solid HA implants. Although many clinical reports on the prognosis of HA-coated implants have reported high success rates, the risks of dissolution and weakening of the coating have been noted. We hypothesized that the chemical and mechanical stability of HA coating are affected by its microstructural characteristics. The present study investigates differences in the microstructures of available HA-coated implants, before and after implantation into the coxal bones of dogs for periods ranging from 3 weeks to 10 months and under the coxal periosteum of dogs for 10 months. The results of transmission electron microscopy and energy-dispersive x-ray analysis revealed that crystallization of super-fine HA crystals occurred in the amorphous phase of the HA coating and progressed over time. This crystallization weakens HA-coated implants by making the amorphous phase brittle, causing stress accumulation within the coating, and causing a decrease in the binding strength between the coating and the substrate. Furthermore, the HA coating dissolved in soft tissue. Dissolution started with the super-fine HA crystals in the crystallized portion that was originally part of the amorphous phase.