gebhart/patrepeval huggingface dataset:
Kurt Semm and the fight against skepticism: endoscopic hemostasis, laparoscopic appendectomy, and Semm's impact on the "laparoscopic revolution". (1999)

In the 1970s, Semm developed thermocoagulation, adapted the Roeder Loop, and further invented extra- and intracoporeal endoscopic knotting to achieve endoscopic hemostasis. His numerous technical inventions, especially the electronic insufflator, allowed more complex operations to be performed laparoscopically. His technique, however, was not quickly adopted by the surgical community. When the first fully laparoscopic appendectomy was carried out by Semm in 1980, a veritable storm broke loose. In the opinion of many prominent surgeons, Semm exaggerated the problem of adhesions, and laparoscopic technique itself was regarded as very dangerous. Misunderstood by medical scientists, Semm displayed an ability to force his ideas through despite skepticism and suspicion. He realized that endoscopic surgery had tremendous potential, and promoted laparoscopic technique not only in his field of gynecology but among general surgeons as well. In 1985, Muhe, of Boblingen, Germany, used Semm's technique to remove the first gallbladder in the world laparoscopically. Three years later when Semm presented a videotape of his laparoscopic appendectomy in Baltimore, he gave impetus to McKernan and Save of Marietta. Georgia, to carry out the first laparoscopic cholecystectomy in the United States.
Targeting Hyaluronidase for Cancer Therapy: Antitumor Activity of Sulfated Hyaluronic Acid in Prostate Cancer Cells (2011)

The tumor cell-derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor. In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8-dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression. These effects were traced to a blockade in complex formation between phosphoinositide 3-kinase (PI3K) and HA receptors and to a transcriptional downregulation of HA receptors, CD44, and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA-HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression.
Optimal Microgrid Control and Power-Flow Study With Different Bidding Policies by Using PowerWorld Simulator (2013)

For a microgrid (MG) to participate in a real-time and demand-side bidding market, high-level control strategies aiming at optimizing the operation of the MG are necessary. One of the difficulties for research of a competitive MG power market is the absence of efficient computational tools. Although many commercial power system simulators are available, these power system simulators are usually not directly applicable to solve the optimal power dispatch problem for an MG power market and to perform MG power-flow study. This paper analyzes the typical MG market policies and investigates how these policies can be converted in such a way that one can use commercial power system software for MG power market study. The paper also develops a mechanism suitable for the power-flow study of an MG containing inverter-interfaced distributed energy sources. The extensive simulation analyses are conducted for grid-tied and islanded operations of a benchmark MG network.
Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice (2012)

Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.
Toward Selective Histone Deacetylase Inhibitor Design:  Homology Modeling, Docking Studies, and Molecular Dynamics Simulations of Human Class I Histone Deacetylases (2005)

Histone deacetylases (HDACs) play an important role in gene transcription. Inhibitors of HDACs induce cell differentiation and suppress cell proliferation in tumor cells. Although many HDAC inhibitors have been designed and synthesized, selective inhibition for class I HDAC isoforms is a goal that has yet to be achieved. To understand the difference between class I HDAC isoforms that could be exploited for the design of isoform-specific HDAC inhibitors, we have built three-dimensional models of four class I histone deacetylases, HDAC1, HDAC2, HDAC3, and HDAC8. Comparison of the homology model of HDAC8 with the recently published X-ray structure shows excellent agreement and validates the approach. A series of HDAC inhibitors were docked to the homology models to understand the similarities and differences between the binding modes. Molecular dynamic simulations of these HDAC-inhibitor complexes indicate that the interaction between the protein surface and inhibitor is playing an important role; also some active site residues show some flexibility, which is usually not included in routine docking protocols. The implications of these results for the design of isoform-selective HDAC inhibitors are discussed.
Tight junctions: Closing in on the seal (1999)

The claudins have recently been identified as a large family of transmembrane proteins located at tight junctions between epithelial cells; they create the paracellular diffusion barrier and, surprisingly, may also confer channel-like selectivity for passage of solutes through the tissue barrier.
siRNA and isRNA: two edges of one sword (2006)

RNA interference mediated by small interfering RNAs (siRNA) has emerged as a powerful tool to target specific knockdown of gene expression in cell culture. siRNA is now the gold standard technique to study gene function, and expectations for the development of new target-specific drugs are high. In addition to the gene-silencing activity of siRNA, a number of recent studies have pointed to immunological effects of siRNAs, including the induction of proinflammatory cytokines and type I interferon. There is good evidence that gene silencing and immunostimulation are two independent functional characteristics of RNA oligonucleotides. Immunorecognition of RNA depends on certain molecular features such as length, double- versus single-strand configuration, sequence motifs, and nucleoside modifications such as triphosphate residues. RNA-sensing immunoreceptors include three members of the Toll-like receptor (TLR) family (TLR3, TLR7, TLR8) and cytosolic RNA-binding proteins like PKR and the helicases RIG-I and Mda5. Detection of RNA molecules occurs during viral infection and triggers antiviral innate defense mechanisms including the induction of type I interferons (IFN-alpha, IFN-beta) and downregulation of gene expression. Type I interferon induction by synthetic siRNAs requires TLR7 and is sequence dependent, similar to the detection of CpG motifs in DNA by TLR9. Identification of the exact molecular mechanisms of immunorecognition of RNA will allow the development of methods to avoid immunostimulation of siRNA and the design of potent immunostimulatory RNA (isRNA) oligonucleotides, depending on the aim. Furthermore, the combination of both gene-silencing and immunostimulation in one RNA molecule may lead to novel drugs that use both functional activities of RNA as two edges of one sword for effective treatment of viral infection and cancer.
Metal-Free Sequential [3 + 2]-Dipolar Cycloadditions using Cyclooctynes and 1,3-Dipoles of Different Reactivity (2010)

Although metal-free cycloadditions of cyclooctynes and azides to give stable 1,2,3-triazoles have found wide utility in chemical biology and material sciences, there is an urgent need for faster and more versatile bioorthogonal reactions. We have found that nitrile oxides and diazocarbonyl derivatives undergo facile 1,3-dipolar cycloadditions with cyclooctynes. Cycloadditions with diazocarbonyl derivatives exhibited similar kinetics as compared to azides, whereas the reaction rates of cycloadditions with nitrile oxides were much faster. Nitrile oxides could conveniently be prepared by direct oxidation of the corresponding oximes with BAIB, and these conditions made it possible to perform oxime formation, oxidation, and cycloaddition as a one-pot procedure. The methodology was employed to functionalize the anomeric center of carbohydrates with various tags. Furthermore, oximes and azides provide an orthogonal pair of functional groups for sequential metal-free click reactions, and this feature makes it possible to multifunctionalize biomolecules and materials by a simple synthetic procedure that does not require toxic metal catalysts.
A monoclonal antibody against human colonic adenoma recognizes difucosylated Type-2-blood-group chains (1983)

A monoclonal antibody C14/1/46/10 showing preferential binding to membranes of human colorectal carcinomas over normal colon mucosae was obtained by immunization of mice with extra-nuclear membranes of a human colonic adenoma. Binding and inhibition of binding assays using blood cells or glycoproteins with known blood-group activities indicated that the antibody recognizes a carbohydrate antigen co-existing with the blood-group-H determinant: Fuc alpha 1 leads to 2 Gal. Inhibition assays with structurally defined oligosaccharides showed that the antigenic determinant involves difucosylated Type-2-blood-group chains with the structure: (formula; see text)
Therapeutic Benefit (1999)

Based on the available evidence, aspirin is preferred for the majority of stroke or myocardial infarction patients at risk of recurrent atherothrombotic events. Clopidogrel may, however, provide valuable therapeutic benefit over aspirin in patients with peripheral arterial disease and in stroke or myocardial infarction patients for whom aspirin treatment is contraindicated or for whom aspirin fails to achieve the desired therapeutic effect.
Silica Nanoparticles Suppress Fibronectin-Mediated Adhesion and Migration in Normal Human Keratinocytes (2012)

Nanotechnology has been increasingly applied to various fields, such as biology, chemistry, physics, medicine and engineering. However, a major concern that has been the topic in nanoscience is whether exposure of humans to engineered nanoparticles might cause toxic effects. In the present in vitro study, the influence of silica nanoparticles on fibronectin-mediated cellular response was assessed in normal human keratinocytes. Our results demonstrated that silica nanoparticles but not silica microparticles significantly suppressed cell adhesion and migration to fibronectin. This phenomenon was not observed in cell response to Poly-L-Lysine, which mediates cell adhesion and migration in a way different from that of fibronectin. Moreover, it seemed that this suppression was not due to cytotoxic effects induced by silica nanoparticles. Subsequently, we also showed that silica nanoparticles impaired the fibronectin-induced activation of FAK and its downstream PI3K, AKT and Src. Taken together, our data suggests that silica nanoparticles may negatively modulate cell response to fibronectin.
Improved anticoagulation management after palmaz schatz coronary stent implantation by sealing the arterial puncture site with a vascular hemostasis device (1993)

Sealing the arterial puncture site with a vascular hemostasis device has the potential to maintain optimal anticoagulation after stent implantation. The level of heparinization during the first 3 days after successful stent implantation was retrospectively compared between 2 groups of medically treated patients with (group A; n = 18) and without (group B; n = 17) a Vasoseal after sheath removal. The number of APTTs sampled in group A and B was 233 and 168, respectively. Respective mean values of APTT (seconds) in group A and B were 180 +/- 79 and 172 +/- 91 at day 1 (p = NS), 132 +/- 43 and 125 +/- 61 at day 2 (p = NS) and 123 +/- 36 and 116 +/- 48 at day 3 (p = NS). More APTTs were suboptimal (< 80 secs) in group B (34/168; 20%) compared to group A (17/233; 7%) [p < 0.001]. More patients in group B compared to group A had 1 or more (14/17; 82% vs. 8/18; 44%; p = 0.04), 2 or more (10/17; 59% versus 3/18; 17%; p = 0.02) and 3 or more (8/17; 47% vs. 2/18; 11%; p = 0.03) suboptimal APTTs. Bleeding complications were seen in 4 patients without and in 3 patients with a Vasoseal. Thus application of a vascular hemostasis device results in a less variable anticoagulation after coronary stenting, but it does not abolish entry site-related bleeding complications.
Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss (2010)

These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake.
Stability and Properties of Double and Triple Helices: Dramatic Effects of RNA or DNA Backbone Composition (1992)

Studies of a series of short oligonucleotide double and triple helices containing either all RNA, all DNA, or a mixture of the two show strand-dependent variation in their stability and structure. The variation in stability for both groups falls over a range of greater than 10 kilocalories per mole. In forming the triple helix, RNA is favored on both pyrimidine strands, whereas DNA is favored on the purine strand. In general, relatively unstable duplexes form particularly stable triplexes and vice versa. Structural data indicate that the strands in hybrid helices adopt a conformation that is intermediate between molecules containing all DNA and all RNA. Thus, RNA-DNA hybrids were not forced into the conformation of the RNA (A-form). The provocative stability of the triplex with an RNA third strand+DNA duplex points to novel antisense strategies and opens the possibility of an in vivo role of these structures. Overall, the data emphasize the fundamental role of sugars in determining the properties of nucleic acid complexes.
Sub-10 nm Nano-Organization in AB2- and AB3-Type Miktoarm Star Copolymers Consisting of Maltoheptaose and Polycaprolactone (2013)

The AB2- and AB3-type miktoarm star copolymers consisting of maltoheptaose (MH, as A block) and poly(ε-caprolactone) (PCL, as B block), namely MH-b-(PCL)2 and MH-b-(PCL)3, were synthesized, and their nano-organization was characterized. The syntheses of MH-b-(PCL)2 and MH-b-(PCL)3 were carried out through two reaction steps: (1) preparation of linear and three-branched PCLs bearing an azido group on the chain center (N3-(PCL)2 and N3-(PCL)3) by the diphenyl phosphate-catalyzed ring-opening polymerization of ε-caprolactone (ε-CL) using azido-functionalized di- and triols (N3-(OH)2 and N3-(OH)3) as the initiators and (2) the copper-catalyzed azide–alkyne cycloaddition of N3-(PCL)2 and N3-(PCL)3 with the ethynyl-functionalized MH. The miktoarm star copolymers having Mn for the PCL block of ca. 5000 (MH-b-(PCL2.5k)2 and MH-b-(PCL1.7k)3) and 10 000 (MH-b-(PCL5k)2 and MH-b-(PCL3.3k)3) were obtained with a very narrow polydispersity index of less than 1.05. Bulk samples of the four types of miktoarm star copolymers exhibited body-centered cubic phases, as determined by small-angle X-ray diffraction experiments. The domain-spacing were determined to be 9.8 nm for MH-b-(PCL2.5k)2, 8.8 nm for MH-b-(PCL1.7k)3, 10.5 nm for MH-b-(PCL5k)2, and 9.8 nm for MH-b-(PCL3.3k)3, which were smaller than those of the corresponding linear diblock copolymers.
Enoxaparin ameliorates post–traumatic brain injury edema and neurologic recovery, reducing cerebral leukocyte endothelial interactions and vessel permeability in vivo (2015)

ENX reduces LEU recruitment to injured brain, diminishing visible microvascular permeability and edema. ENX may also accelerate neurologic recovery without increasing cerebral contusion size. Further study in humans is necessary to determine safety, appropriate dosage, and timing of ENX administration early after TBI.
Programmable Oligomers for Minor Groove DNA Recognition (2006)

The four Watson-Crick base pairs of DNA can be distinguished in the minor groove by pairing side-by-side three five-membered aromatic carboxamides, imidazole (Im), pyrrole (Py), and hydroxypyrrole (Hp), four different ways. On the basis of the paradigm of unsymmetrical paired edges of aromatic rings for minor groove recognition, a second generation set of heterocycle pairs, imidazopyridine/pyrrole (Ip/Py) and hydroxybenzimidazole/pyrrole (Hz/Py), revealed that recognition elements not based on analogues of distamycin could be realized. A new set of end-cap heterocycle dimers, oxazole-hydroxybenzimidazole (No-Hz) and chlorothiophene-hydroxybenzimidazole (Ct-Hz), paired with Py-Py are shown to bind contiguous base pairs of DNA in the minor groove, specifically 5'-GT-3' and 5'-TT-3', with high affinity and selectivity. Utilizing this technology, we have developed a new class of oligomers for sequence-specific DNA minor groove recognition no longer based on the N-methyl pyrrole carboxamides of distamycin.
Defective Epithelial Chloride Transport in a Gene-Targeted Mouse Model of Cystic Fibrosis (1992)

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an adenosine 3',5'-monophosphate (cyclic AMP)-activated chloride channel. In cystic fibrosis (CF) patients, loss of CFTR function because of a genetic mutation results in defective cyclic AMP-mediated chloride secretion across epithelia. Because of their potential role as an animal model for CF, mice with targeted disruption of the murine CFTR gene [CFTR(-/-)] were tested for abnormalities in epithelial chloride transport. In both freshly excised tissue from the intestine and in cultured epithelia from the proximal airways, the cyclic AMP-activated chloride secretory response was absent in CFTR(-/-) mice as compared to littermate controls. Thus, disruption of the murine CFTR gene results in the chloride transport abnormalities predicted from studies of human CF epithelia.
The Role of Antigenic Determinants in the Control of IgM and IgG Antibody Responses to Denatured DNA (1973)

Abstract Rabbits immunized with complexes of denatured calf thymus DNA and methylated bovine serum albumin (MBSA) produced only IgM antibodies to denatured DNA, confirming the results of previous studies. In contrast, both IgM and IgG antibodies were induced by MBSA complexes of T4 and T6 bacteriophage DNA, in which the normal base cytosine is replaced by glucosylated hydroxymethylcytosine. The glucose in not essential for this switch, since a preparation of modified T2 phage DNA, which contained nonglucosylated hydroxymethylcytosine, also induced the formation of both classes of antibodies. With or without glycosylation, the hydroxymethylcytosine served as a dominating determinant for specificity as well as a signal for 7S antibody production. The validity of complement fixation as an assay for these responses was confirmed by quantitative precipitation tests.
Trends in funding science education, 1994–2004* (2005)

This review looks at the changes over the last 10 years in priorities guiding funding decisions in science education. A general survey of trends in funding both graduate and undergraduate education are covered, followed by a description of specific National Science Foundation initiatives. Understanding these changes should help proposal writers put their current submissions into context and better reply to the call for proposals from various agencies.
Blanche-an experiment in guidance and navigation of an autonomous robot vehicle (1991)

The principal components and capabilities of Blanche, an autonomous robot vehicle, are described. Blanche is designed for use in structured office or factory environments rather than unstructured natural environments, and it is assumed that an offline path planner provides the vehicle with a series of collision-free maneuvers, consisting of line and arc segments, to move the vehicle to a desired position. These segments are sent to a low-level trajectory generator and closed-loop motion control. The controller assumes accurate knowledge of the vehicle's position. Blanche's position estimation system consists of a priori map of its environment and a robust matching algorithm. The matching algorithm also estimates the precision of the corresponding match/correction that is then optimally (in a maximum-likelihood sense) combined with the current odometric position to provide an improved estimate of the vehicle's position. The system does not use passive or active beacons. Experimental results are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Studies on the Phenylphenol Derivatives with Biological Activity (1968)

More than ninety phenylphenol derivatives were tested for fungistatic activity toward ten species of agriculturally important fungi. One of N-methylcarbamates and some nitro- or chloro-substituted derivatives were highly toxic against Piricularia oryzae. From the relationship between the chemical structure and the activity, it is supposed that the reactivity, the permeability, the steric effect and the metabolic activation of the compound are the responsible factors for the fungistatic activity.
Multi-tone transmission for asymmetric digital subscriber lines (ADSL) (2002)

Multi-tone transmission is a potentially viable technique for application on asymmetric digital subscriber lines (ADSLs). The results of a preliminary study on the performance of an ideal discrete multi-tone (DMT) signaling technique for a 1.6-Mb/s ASDL are presented. The performance margins using single-tone 16-point quadrature amplitude modulation (QAM) with ideal decision feedback equalization (DFE) are presented. The feedforward filter of the DFE is a quarter-baud spaced fractionally spaced equalizer (FSE). The interference is assumed to be the sum of far-end crosstalk (FEXT) and additive white Gaussian noise (AWGN). The subscriber loops are assumed to be in a plant environment where the maximum resistance does not exceed 1300 /spl Omega/. The projected performance of an ideal DMT with a sampling rate of 1.024 MHz and 256-subchannel segmentation offers potential margin enhancement up to 3 dB over a quarter baud-spaced FSE-based 16-QAM signaling.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>