gebhart/patrepeval huggingface dataset:
Three dimensional single-particle tracking with nanometer resolution (1998)

We have developed a method for three dimensional (3D) tracking of polystyrene spheres with nanometer resolution. The detection technique is based on measuring the displacement of a polystyrene sphere positioned in the center of a laser beam just behind the focus. A change in the lateral position of the sphere causes a deflection of the beam which can be measured using a position sensitive detector. A change in the axial position of the sphere causes a shift in the axial position of the focus behind another lens, which can be measured using an overfilled photodiode. A feedback system is used to keep the sphere in the center of the laser beam to avoid the influence of lateral displacements on the detection of the axial position. Spatial resolution for a 0.92 μm polystyrene sphere was better than 1 nm in three dimensions using a sampling rate of 1 kHz. This method was applied to track spheres bound to adhesion molecules LFA-1 expressed at the surface of living cells. It turned out to be a useful method to accurately measure the 3D trajectory of biological molecules on cells in real time.
2-Chlorodeoxyadenosine: hairy cell leukemia takes a surprising turn. (1993)

2-Chlorodeoxyadenosine (2CdA; Cladribine; Leustatin) was developed as a result of the discovery that the death of lymphocytes in hereditary adenosine deaminase deficiency was the result of the accumulation of deoxynucleotides, specifically in lymphocytes, because of their unique enzymatic profile. This deoxyadenosine analog was selected from 25 candidate compounds because it was resistant to deamination by ADA and because it had a favorable therapeutic index. The lymphoid specific action of this drug is a function of the high deoxycytidine kinase and low 5' nucleotidase activity of lymphocytes. The drug appears to trigger apoptosis, very likely by preventing the repair of nicks in double-stranded DNA. Accordingly, 2-CdA has been found effective against a variety of lymphoid neoplasms. Hairy cell leukemia has proved to be most sensitive to its action, with approximately 80% of patients achieving a complete, long-lasting remission after a single five- or seven-day infusion. 2-CdA also shows promise in the treatment of autoimmune disorders.
Functional characterization of the 5'-regulatory region of human factor IX gene. (1990)

Functional characterization of the 5'-regulatory region of the human factor IX gene was carried out by a series of gene dissection analyses. The region extending from -175 to -274 of the 5' end flanking sequence is required for the expression of this gene. Within this region, sequence elements AGCCACT at -238 and TCAAAT at -187 were assigned as the functional CAAT box and TATA box, respectively. The transcription initiation site was found to be at -150 for the factor IX chloramphenicol acetyltransferase chimeric gene. A negative regulatory (silencer) activity was located in the region spanning from 1.4 to 1.7 kilobases upstream of the promoter region. This region contains a short sequence element (ATCCTCTCC) known to have such activity. A strong promoter on the opposite strand was also located about 500 base pairs upstream of the promoter. The expression of factor IX gene was highly liver specific, as assessed by Northern blot analysis. Short sequence elements (TGGACC and CTTTGGACT) homologous to the known liver-specific elements were located in the vicinity of the defined promoter region.
Organic field-effect inversion-mode transistors and single-component complementary inverters on charged electrets (2006)

We demonstrate that the electrostatic polarization of an organic semiconductor (OSC) by a gate dielectric with stored charges and electric fields enables the realization of both threshold voltage tuning and inversion process control of OSC thin-film field-effect transistors (OFETs). As a result, OFETs based on typically unipolar n-channel copper hexadecafluorophthalocyanine semiconductor thin films, deposited on a silicon dioxide quasipermanent charged electret as a gate insulator, show unipolar p-channel “inversion” operation in ambient air and form complementary monolithic, single-semiconductor inverter circuits. The field produced by patterned, grid-controlled negative corona charging and subsequent thermal annealing (before semiconductor deposition) electrostatically induces sufficient positive charges to provide significant hole mobility, ca. 0.011cm2V−1s−1, in response to moderate additional negative gate voltages.
Nanofibrous solid dosage form of living bacteria prepared by electrospinning (2014)

The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses). Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at -20, 7 and 25C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below) 7C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.
Closed headpiece of integrin αIIbβ3 and its complex with an αIIbβ3-specific antagonist that does not induce opening (2010)

The platelet integrin α(IIb)β(3) is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the α(IIb)β(3) headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the α(IIb)β(3) headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the α(IIb) subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, α(IIb) Y190 and α(IIb) D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce α(IIb)β(3) to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.
Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma (2012)

TROP2 can be used as an independent prognostic indicator for laryngeal SCC.
Value of nocturnal oxygen saturation as a screening test for sleep apnoea. (1991)

The sensitivity and specificity of overnight recording of arterial oxygen saturation (SaO2) in routine clinical practice was evaluated in 41 subjects who were being investigated for possible sleep apnoea-hypopnoea syndrome. SaO2 was measured with an ear probe oximeter (Biox IIa) and chart recorder during an "acclimatisation" night immediately before a detailed polysomnographic study. The recordings were classified by two observers as positive, negative, or uninterpretable. Twelve of the 41 patients had the obstructive sleep apnoea syndrome when defined in terms of an apnoea-hypopnoea index greater than 15 events an hour on the second night. The sensitivity of nocturnal SaO2 on the acclimatisation night when the diagnostic criterion was an apnoea-hypopnoea index of greater than 5, greater than 15, and greater than 25/h was 60%, 75%, and 100% respectively. Corresponding values for specificity were 95%, 86%, and 80%. Oximetry alone therefore allowed recognition of a moderate or severe sleep apnoea syndrome. In routine practice an appreciable number of equivocal results is likely and repeat oximetry or more detailed polysomnography will then be required if clinical suspicion is high.
Demonstration of two-pump fibre optical parametricamplification (1997)

The authors demonstrate a two-pump fibre optical parametric amplifier. The pumps were pulsed, each with 2.3 W peak power. A gain of ~8 dB was observed between the pumps near 1550 nm in a 200 m long fibre, agreeing well with theory.
A recombinant, fully human, bispecific antibody neutralizes the biological activities mediated by both vascular endothelial growth factor receptors 2 and 3 (2005)

Vascular endothelial growth factors (VEGF) and their receptors (VEGFR) have been implicated to play important roles in tumor-associated angiogenesis and lymphangiogenesis, and hence in tumor growth and metastasis. We previously produced a number of fully human antibodies directed against VEGF receptor 2 (VEGFR2) and VEGF receptor 3 (VEGFR3) and showed that these antibodies are capable of inhibiting growth factor (VEGF and VEGF-C)-induced receptor activation, migration, and proliferation of human endothelial cells. In this report, we constructed and produced a bispecific antibody, a diabody, using the variable domain genes of two neutralizing antibodies, IMC-1121 to VEGFR2 and hF4-3C5 to VEGFR3. The diabody binds to both VEGFR2 and VEGFR3 in a dose-dependent manner, and blocks interaction between VEGF/VEGFR2, VEGF-C/VEGFR2, and VEGF-C/VEGFR3. In cell-based assays, the diabody neutralized both VEGF and VEGF-C-stimulated activation of VEGFR2, VEGFR3, and p44/p42 mitogen-activated protein kinase in endothelial cells. Furthermore, the diabody was able to inhibit both VEGF and VEGF-C-induced migration of endothelial cells. Taken together, our results suggest that a dual blockade of both VEGFR2 and VEGFR3 simultaneously may represent a more potent approach to effective cancer therapy.
In situ PCR: protocols and applications. (1995)

Since the discovery of the structure of DNA in 1953, a great deal of effort has been devoted to detecting specific target sequences. The first commonly used technique, filter hybridization, offered an excellent sensitivity of one copy per 100 cells. Restriction endonuclease digestion in conjunction with electrophoresis and varying stringencies (Southern blot hybridization) allowed 9 for high specificity; however, the prerequisite nucleic acid extraction precluded localization of the target to its specific cell of origin. In many instances, this is critical information. For example, although HIV-1 DNA can be routinely detected from lymph nodes in seropositive, asymptomatic patients, it is very important to note which of the many different cell types that reside in this site are reservoirs of the virus prior to the development of AIDS. Furthermore, simple, although important, data such as the percentage of a given cell type that contains the target of interest cannot be obtained by Southern blot hybridization because of the obligatory destruction of tissue.
Molecular Testing in the Diagnosis and Management of Hepatitis C Virus Infection (2002)

Molecular tests are valuable tools for use in the diagnosis and treatment of patients infected with HCV.
Synthesis and Characterization of Injectable Poly(N-isopropylacrylamide-co-acrylic acid) Hydrogels with Proteolytically Degradable Cross-Links (2003)

Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with peptide cross-linkers to create an artificial extracellular matrix (ECM) amenable for testing hypotheses regarding cell proliferation and migration in three dimensions. Peptide degradable cross-linkers were synthesized by the acrylation of the amine groups of glutamine and lysine residues within peptide sequences potentially cleavable by matrix metalloproteinases synthesized by mammalian cells (e.g., osteoblasts). With the peptide cross-linker, loosely cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, and enzymatic degradation properties were investigated. The peptide-cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and fluidlike at room temperature and could be injected through a small-diameter aperture. The LCST of peptide-cross-linked hydrogel was influenced by the monomer ratio of NIPAAm/AAc but not by cross-linking density within the polymer network. A peptide-cross-linked hydrogel with a 97/3 molar ratio of NIPAAm/AAc exhibited a LCST of approximately 34.5 degrees C. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, and swelling media; however, all hydrogels maintained more than 90% water even at 37 degrees C. In enzymatic degradation studies, breakdown of the peptide-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on both the concentration of collagenase and the cross-linking density. These results suggest that peptide-cross-linked P(NIPAAm-co-AAc) hydrogels can be tailored to create environmentally-responsive artificial extracellular matrixes that are degraded by proteases.
Enantioselective de Novo Synthesis of 4-Deoxy-d-hexopyranoses via Hetero-Diels–Alder Cycloadditions: Total Synthesis of Ezoaminuroic Acid and Neosidomycin (2011)

The de novo synthesis of carbohydrates constitutes an important aspect of organic chemistry, and its application toward deoxy sugars is particularly noteworthy in targeting biologically active compounds. The enantioselective preparation of 4-deoxy-D-ribo-, 4-deoxy-D-lyxo-, and 4-deoxy-D-xylo-hexopyranosides, along with their uronate counterparts has been successfully accomplished using hetero-Diels-Alder reactions as the key step. Jacobsen chromium(III) catalyst and a titanium-binaphthol complex have been used to successfully catalyze diene and aldehyde cycloadditions, leading to optically active dihydropyran templates. 6-Hydroxydesosamine, orthogonally protected ezoaminuroic acid, and neosidomycin were synthesized using a comparative study. Also, a novel chiron approach to 4-deoxy-lyxo-hexopyranosiduronic acid methyl ester derivatives was efficiently accomplished starting from readily accessible starting materials. This work represents a systematic and comprehensive study toward a de novo synthesis of 4-deoxy-hexopyranoses via enantioselective hetero-Diels-Alder reactions.
The human papillomavirus E7 oncoprotein and the cellular transcription factor E2F bind to separate sites on the retinoblastoma tumor suppressor protein (1993)

The ability of the high-risk and low-risk human papillomavirus E7 oncoproteins to disrupt complexes of the retinoblastoma tumor suppressor protein pRB and the cellular transcription factor E2F was studied. The ability of E7 to disrupt this transcription factor complex correlated with the different pRB binding efficiencies of the high-risk and low-risk human papillomavirus-encoded E7 proteins. The pRB binding site was the sole determinant for these observed differences. The phosphorylation status of the casein kinase II site that is immediately adjacent to the pRB binding site in E7 had no marked effect on this biochemical property of E7. Peptides consisting of the pRB binding site of E7, however, were not able to disrupt the pRB/E2F complex. These data suggest that additional carboxy-terminal sequences in E7 are also required for the efficient disruption of the pRB/E2F complex and that E7 and E2F may interact with nonidentical sites of pRB.
Potential antitumor agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo (1989)

In a search for compounds related to flavoneacetic acid with activity against solid tumors, a series of methyl-, methoxy-, chloro-, nitro-, and hydroxy-substituted xanthenone-4-acetic acids have been synthesized and evaluated against subcutaneously implanted colon adenocarcinoma 38 in vivo, using a short-term histology assay as a primary screening system. A major goal of this work was to identify compounds with similar profiles of activity to that of flavoneacetic acid but of higher potency. The level of activity of the compounds appeared to depend more on the nature of the substituent than its positioning, in the order Cl greater than Me, OMe greater than NO2, OH. However, the potency of the compounds was related much more to the position rather than the nature of the substitution, with 5-substituted compounds being clearly the most dose potent. 5-Methylxanthenone-4-acetic acid has a similar level of activity to that of flavoneacetic acid in the test systems employed but is more than 7-fold as dose potent.
Seamless Staircase Electrical Contact to Semiconducting Graphene Nanoribbons (2017)

Electrical contact to low-dimensional (low-D) materials is a key to their electronic applications. Traditional metal contacts to low-D semiconductors typically create gap states that can pin the Fermi level (E<sub>F</sub>). However, low-D metals possessing a limited density of states at E<sub>F</sub> can enable gate-tunable work functions and contact barriers. Moreover, a seamless contact with native bonds at the interface, without localized interfacial states, can serve as an optimal electrode. To realize such a seamless contact, one needs to develop atomically precise heterojunctions from the atom up. Here, we demonstrate an all-carbon staircase contact to ultranarrow armchair graphene nanoribbons (aGNRs). The coherent heterostructures of width-variable aGNRs, consisting of 7, 14, 21, and up to 56 carbon atoms across the width, are synthesized by a surface-assisted self-assembly process with a single molecular precursor. The aGNRs exhibit characteristic vibrational modes in Raman spectroscopy. A combined scanning tunneling microscopy and density functional theory study reveals the native covalent-bond nature and quasi-metallic contact characteristics of the interfaces. Our electronic measurements of such seamless GNR staircase constitute a promising first step toward making low resistance contacts.
Essential involvement of interleukin-8 (IL-8) in acute inflammation (1994)

Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as neutrophil infiltration in these conditions. These results suggest that IL-8 plays a causative role in acute inflammation by recruiting and activating neutrophils.
A Review of Metalorganic Chemical Vapor Deposition of High-Temperature Superconducting Thin Films (1990)

A status report is given on the metalorganic chemical vapor deposition (MOCVD) of high-temperature superconducting thin films. The advantages of MOCVD processing manifest themselves in the quality of the films produced, and in the economy of the process. Metalorganic precursor requirements, deposition parameters and film properties are discussed. Also difficulties have been identified in making MOCVD a manufacturing technology. To solve these problems, future research directions are proposed.
Mutational Analysis of the Substrate Binding Site of Human Complement Factor D (1994)

Complement factor D is a serine protease with a single natural substrate, C3b-complexed factor B, and very low catalytic activity against synthetic esters. The recently solved X-ray crystal structure of factor D has demonstrated certain key differences from other serine protease in the conformation of residues of the catalytic triad and the substrate-binding regions. To investigate possible contributions of unique amino acid substitutions to these distinct structural and functional features of factor D, we constructed a series of mutants by substituting trypsin substrate-binding residues for the corresponding factor D residues. Wild-type and seven mutant factor D cDNAs were expressed stably in Chinese hamster ovary cells, and the recombinant proteins were purified from culture supernatants and assayed by hemolytic, proteolytic, and esterolytic assays. The combined results indicate that residues Thr-198, Ser-199, Arg-202, and perhaps also Val-203 provide determinants for substrate binding and catalysis. The data also provide additional support for the hypothesis that the proteolytically active conformation of the active center of factor D is induced by its substrate, C3bB.
Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat. (2001)

Immunoconjugates effectively inhibited progression of CNV in this model. The results suggest that mAb-mediated drug targeting may be beneficial in the treatment of CNV.
The Role of Corticotropin-Releasing Factor and Corticosterone in Stress- and Cocaine-Induced Relapse to Cocaine Seeking in Rats (1998)

We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain corticotropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rats. The ability of footshock stress and priming injections of cocaine to induce relapse to cocaine seeking was studied after intracerebroventricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for reinstatement were given after intermittent footshock (10 min; 0.5 mA) and after priming injections of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced reinstatement at all doses tested in both intact animals and animals with corticosterone replacement. Reinstatement by priming injections of cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D-Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress-induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine seeking. Furthermore, the data show that although reinstatement of cocaine seeking by footshock stress requires minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.
Trends in Prevalence and Control of Diabetes in the United States, 1988–1994 and 1999–2010 (2014)

National Institutes of Health.