gebhart/patrepeval huggingface dataset:
Liposomes for Gene Transfer and Expressionin vivo (1984)

A recombinant plasmid encoding rat preproinsulin I was encapsulated in large liposomes and injected intravenously into rats. Glycaemia and blood, splenic and hepatic insulin were assayed from 6 h after inoculation. Control animals received (i) empty liposomes, (ii) liposomes carrying the Escherichia coli pBR 322 plasmid, (iii) the free rat insulin I gene, or (iv) no injection. All controls showed unchanged glucose and insulin levels. Six hours after inoculation the treated rats had 72 +/- 5 mg glucose/100 ml of blood, compared with 107 +/- 2 mg/ml for controls. Radioimmunoassay of blood insulin gave 61 +/- 8 microunits/ml (43 +/- 5 microunits/ml for controls). Spleen and liver values were 242 +/- 22 and 204 +/- 20 microunits/g of tissue, respectively (112 +/- 20 and 87 +/- 15 microunits/g in controls). The kinetics and extent of uptake of liposomes by spleen and liver were studied by external gamma-camera imaging after injection of 111In-labelled liposomes. The results paralleled insulin synthesis in the two organs. The insulin gene was localized in liver cells after injection of liposomes containing the plasmid encoding the gene. Livers were processed 4 h after inoculation for isolation of hepatocytes, Kupffer cells and endothelial cells. DNA was purified and exogenous DNA detected by Southern blotting. Kupffer cells were the primary target for gene incorporation with liposomes consisting of phospholipids and cholesterol. Targeting of liposomes to other liver cells was attempted by including lactosylceramide in the liposomes. This increased the amount of the exogenous gene in hepatocytes and particularly in endothelial cells. The efficiency of liposome-mediated gene transfer in vivo is high, since a few per cent of the transferred DNA is taken up by the liver cells and detected.
Dexpanthenol (Ro 01-4709) in the treatment of constipation. (1982)

Functional constipation is not a life-threatening disease, but as a chronic state it worries the patient and causes him discomfort and often leads him to self-medication with potentially dangerous drugs. Ro 01-4709 contains as active substance dexpanthenol, which is the alcohol of pantothenic acid, a vitamin of the B-complex. In the cells, dexpanthenol is readily oxidized to pantothenic acid, which stimulates peristalsis when administered in therapeutically effective doses. Ro 01-4709 has already proven its efficacy in the prevention and treatment of adynamic ileus. Recently, several open and two double-blind studies have been carried out, investigating the efficacy of oral Ro 01-4709 in the treatment of chronic functional constipation. The two double-blind studies showed Ro 01-4709 to be superior to placebo in all parameters measured. The studies with an open design also demonstrated a favourable effect of Ro 01-4709 in the treatment of chronic functional constipation. Owing to its physiological action-which is in a favourable contrast to that of normal laxatives. Ro 01-4709 can be recommended for the treatment of functional constipation in pregnant women, children and the elderly.
The Seven Deadly Virtues (2004)

The university stifles most creative writers except the most intrepid—even reckless, the good along with the bad—in the process of teaching them to write according to the conventions of the academy in general, and their specific disciplines in particular.
Regulatory Network of Escherichia coli: Consistency Between Literature Knowledge and Microarray Profiles (2003)

The transcriptional network of Escherichia coli may well be the most complete experimentally characterized network of a single cell. A rule-based approach was built to assess the degree of consistency between whole-genome microarray experiments in different experimental conditions and the accumulated knowledge in the literature compiled in RegulonDB, a data base of transcriptional regulation and operon organization in E. coli. We observed a high and statistical significant level of consistency, ranging from 70%-87%. When effector metabolites of regulatory proteins are not considered in the prediction of the active or inactive state of the regulators, consistency falls by up to 40%. Similarly, consistency decreases when rules for multiple regulatory interactions are altered or when "on" and "off" entries were assigned randomly. We modified the initial state of regulators and evaluated the propagation of errors in the network that do not correlate linearly with the connectivity of regulators. We interpret this deviation mainly as a result of the existence of redundant regulatory interactions. Consistency evaluation opens a new space of dialogue between theory and experiment, as the consequences of different assumptions can be evaluated and compared.
Which Is the Actual Catalyst: Chiral Phosphoric Acid or Chiral Calcium Phosphate? (2010)

Both catalysts work: A highly enantioselective direct Mannich-type reaction of N-Boc-protected aldimines with 1,3-dicarbonyl compounds has been developed with the use of a chiral phosphoric acid in the presence or absence of CaII. The absolute stereoselectivity of the phosphoric acid catalysis was found to be opposite to that of the calcium phosphate catalysis (see scheme; Boc=tert-butoxycarbonyl).
Minimum Mean-Square Error Equalization for Second-Order Volterra Systems (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <?Pub Dtl=""?>In this paper, a novel nonlinear Volterra equalizer is presented. We define a framework for nonlinear second-order Volterra models, which is applicable to different applications in engineering. We use this framework to define the channel and to model the equalizer. We then solve the minimum mean-square error (MMSE) problem explicitly for the tandem connection of the two second-order Volterra systems. Optimal solutions for a simplified, linear version of the MMSE equalizer are also presented. The novel equalizer was tested when applied to a nonlinear ultra-wideband transmitted reference receiver front end. As a comparison, a least mean squares (LMS) equalizer with a training sequence has been used to verify the performance of the newly proposed equalizer. The simulation results show that the LMS equalizer is only able to attain the proposed MMSE equalizer after very long training, which might not be desirable in a communication system. </para>
New synthetic cluster ligands for galactose/N-acetylgalactosamine-specific lectin of mammalian liver (1984)

Synthetic ligands containing up to six residues of nonreducing terminal galactose were prepared. The synthesis involved coupling of carboxyl groups of N-benzyloxy-carbonylaspartic acid or of N-benzyloxycarbonyltyrosyl-gamma-glutamylglutamic acid to the omega-amino group of the aglycon of a glycoside that contained up to three lactosyl residues. The benzyloxycarbonyl group was removed by hydrogenolysis before these ligands were tested as inhibitors to the binding of 125I-asialoorosomucoid to the galactose/N-acetylgalactosamine lectin, both soluble and on the surface of freshly isolated mammalian hepatocytes. Each addition of a galactosyl residue to an existing ligand structure invariably increased the binding affinity of such a ligand. However, at each level of galactose valency, the binding constant varied as much as 1000-fold depending on the structure of the ligand. At a given level of valency, the binding strength of a cluster ligand depended mainly on two factors: (1) the maximum spatial inter-galactose distances and (2) the flexibility of the arm connecting galactosyl residues and the branch points. It has been postulated that the three galactose-combining sites of the lectin are arranged in space at the vertexes of a triangle whose sides are 15, 22, and 25 A [Lee, Y. C., Townsend, R. R., Hardy, M. R., Lönngren, J., & Bock, K. (1984) in Biochemical and Biophysical Studies of Proteins and Nucleic Acids (Lo, T. B., Liu, T. Y., & Li, C. H., Eds.) pp 349-360, Elsevier, New York]. Ligands having inter-galactose distances shorter than these lengths were invariably poor ligands at their respective level of valency.(ABSTRACT TRUNCATED AT 250 WORDS)
Growth and Differentiation of Human Embryonic Stem Cells for Cardiac Cell Replacement Therapy (2006)

Due to the limited proliferation capacity of cardiac cells, cell replacement therapy has been proposed to restore cardiac function in patients suffering from ischemic heart disease and congestive heart failure. However, this approach is challenged by an insufficient supply of appropriate cells. Because of their apparent indefinite replicative capacity and their cardiac differentiation potential, human embryonic stem cells (hESCs) are potential candidates as sources of cells for cell replacement therapy. Significant progress has been made in improving culture conditions of undifferentiated hESCs, and using various methods, several laboratories have reported the generation of contracting cardiomyocytes from hESCs in vitro. Application of these cardiomyocytes to the clinic, however, still requires substantial experimentation to show that 1) they are functional in vitro; 2) they are efficacious in animal models of cardiac injury and disease; 3) they are safe and effective in human conditions, and 4) a sufficient amount of cardiomyocytes with expected characteristics can be generated in a reproducible manner. Here we review and discuss current findings on growth and differentiation of hESCs, and on characterization, enrichment and transplantation of hESC-derived cardiomyocytes.
Rokitamycin uptake by alveolar macrophages. (1988)

The ability of antibiotics to enter cells, especially phagocytic cells, may be an important factor affecting therapy for infections caused by organisms which survive and proliferate intracellularly. It is well known that macrolides and clindamycin have high intracellular penetration ability. We studied the uptake of rokitamycin (RKM), a new oral macrolide, using rabbit alveolar macrophages and 2 other macrolides for comparison. Intracellular concentrations of erythromycin and josamycin were, respectively, approximately 20 and 40 times higher than extracellular concentrations when they were incubated at an initial extracellular concentration of 5 micrograms/ml (I/E = 20.1 +/- 2.6, 40.8 +/- 7.4). In comparison to these 2 macrolides, the uptake of RKM was massive and very rapid. The cellular concentration of RKM was approximately 120 times higher than the extracellular concentration. Uptake of the 3 macrolides by rabbit alveolar macrophages at 4 degrees C was approximately 10% of that at 37 degrees C. This study demonstrated that RKM was rapidly and massively accumulated by alveolar macrophages, and that the drug accumulation depends on temperature. These observations suggest that RKM therapy may be very effective for the treatment of some infectious diseases.
Peroxisomal trans‐2‐enoyl‐CoA reductase is involved in phytol degradation (2006)

Phytol is a naturally occurring precursor of phytanic acid. The last step in the conversion of phytol to phytanoyl-CoA is the reduction of phytenoyl-CoA mediated by an, as yet, unidentified enzyme. A candidate for this reaction is a previously described peroxisomal trans-2-enoyl-CoA reductase (TER). To investigate this, human TER was expressed in E. coli as an MBP-fusion protein. The purified recombinant protein was shown to have high reductase activity towards trans-phytenoyl-CoA, but not towards the peroxisomal beta-oxidation intermediates C24:1-CoA and pristenoyl-CoA. In conclusion, our results show that human TER is responsible for the reduction of phytenoyl-CoA to phytanoyl-CoA in peroxisomes.
Library construction for next-generation sequencing: Overviews and challenges (2014)

High-throughput sequencing, also known as next-generation sequencing (NGS), has revolutionized genomic research. In recent years, NGS technology has steadily improved, with costs dropping and the number and range of sequencing applications increasing exponentially. Here, we examine the critical role of sequencing library quality and consider important challenges when preparing NGS libraries from DNA and RNA sources. Factors such as the quantity and physical characteristics of the RNA or DNA source material as well as the desired application (i.e., genome sequencing, targeted sequencing, RNA-seq, ChIP-seq, RIP-seq, and methylation) are addressed in the context of preparing high quality sequencing libraries. In addition, the current methods for preparing NGS libraries from single cells are also discussed.
Immunohistochemical identification of tissue factor in solid tumors (1992)

Patients with cancer experience a much higher than expected incidence of thromboembolic disorders, commonly referred as Trousseau syndrome. Although this association has been well documented, the etiology of the hypercoagulable state is not known. The expression on tumor cells of tissue factor (TF), a membrane-bound lipoprotein that functions as a cofactor to factor VIIa in the initiation of the extrinsic pathway of blood coagulation, has been postulated as a possible mechanism. Whereas the distribution of TF in normal tissues is known, no large survey of TF expression in malignant tissues has been reported. In this study a polyclonal, monospecific rabbit anti-human TF IgG was used for immunohistochemical localization of TF antigen in 85 different tumor specimens. In general, cell types which normally express TF continued to do so after malignant transformation (41 of 60 epithelial tumor specimens were positive for TF). Tumors of nonepithelial origin frequently lacked TF, with only 3 of 19 specimens containing evidence of TF antigen. In addition five of six benign tumors did not express TF. Many tumor types commonly associated with Trousseau syndrome, for example lung, pancreatic, breast, colon and gastric carcinomas, stained positively for TF. Based on this survey, it appears that TF expression by tumors may be an important factor in the pathogenesis of a hypercoagulable state in some patients with cancer.
Analysis of current density and related parameters in spinal cord stimulation (1998)

A volume conductor model of the spinal cord and surrounding anatomical structures is used to calculate current (and current density) charge per pulse, and maximum charge density per pulse at the contact surface of the electrode in the dorsal epidural space, in the dorsal columns of the spinal cord and in the dorsal roots. The effects of various contact configurations (mono-, bi-, and tripole), contact area and spacing, pulsewidth and distance between contacts and spinal cord on these electrical parameters were investigated under conditions similar to those in clinical spinal cord stimulation. At the threshold stimulus of a large dorsal column fiber, current density and charge density per pulse at the contact surface were found to be highest (1.9.10(5) microA/cm2 and 39.1 microC/cm2.p, respectively) when the contact surface was only 0.7 mm2. When stimulating with a pulse of 500 microseconds, highest charge per pulse (0.92 microC/p), and the largest charge density per pulse in the dorsal columns (1.59 microC/cm2. p) occurred. It is concluded that of all stimulation parameters that can be selected freely, only pulsewidth affects the charge and charge density per pulse in the nervous tissue, whereas both pulsewidth and contact area strongly affect these parameters in the nonnervous tissue neighboring the electrode contacts.
Monomeric Recombinant TCR Ligand Reduces Relapse Rate and Severity of Experimental Autoimmune Encephalomyelitis in SJL/J Mice through Cytokine Switch (2004)

Our previous studies demonstrated that oligomeric recombinant TCR ligands (RTL) can treat clinical signs of experimental autoimmune encephalomyelitis (EAE) and induce long-term T cell tolerance against encephalitogenic peptides. In the current study, we produced a monomeric I-A(s)/PLP 139-151 peptide construct (RTL401) suitable for use in SJL/J mice that develop relapsing disease after injection of PLP 139-151 peptide in CFA. RTL401 given i.v. or s.c. but not empty RTL400 or free PLP 139-151 peptide prevented relapses and significantly reduced clinical severity of EAE induced by PLP 139-151 peptide in SJL/J or (C57BL/6 x SJL)F(1) mice, but did not inhibit EAE induced by PLP 178-191 or MBP 84-104 peptides in SJL/J mice, or MOG 35-55 peptide in (C57BL/6 x SJL/J)F(1) mice. RTL treatment of EAE caused stable or enhanced T cell proliferation and secretion of IL-10 in the periphery, but reduced secretion of inflammatory cytokines and chemokines. In CNS, there was a modest reduction of inflammatory cells, reduced expression of very late activation Ag-4, lymphocyte function-associated Ag-1, and inflammatory cytokines, chemokines, and chemokine receptors, but enhanced expression of Th2-related factors, IL-10, TGF-beta3, and CCR3. These results suggest that monomeric RTL therapy induces a cytokine switch that curbs the encephalitogenic potential of PLP 139-151-specific T cells without fully preventing their entry into CNS, wherein they reduce the severity of inflammation. This mechanism differs from that observed using oligomeric RTL therapy in other EAE models. These results strongly support the clinical application of this novel class of peptide/MHC class II constructs in patients with multiple sclerosis who have focused T cell responses to known encephalitogenic myelin peptides.
CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis (2003)

tions In addition, NK cell-dependent tumor rejection is favored in the absence of CD69 (13). However, the functional role of CD69 expressed by T cells and macrophages at inflammatory sites and in autoimmune processes has not been explored.
Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice (2019)

Secreted Wnt proteins regulate development and adult tissue homeostasis by binding and activating cell-surface Frizzled receptors and co-receptors including LRP5/6. The hydrophobicity of Wnt proteins has complicated their purification and limited their use in basic research and as therapeutics. We describe modular tetravalent antibodies that can recruit Frizzled and LRP5/6 in a manner that phenocopies the activities of Wnts both in vitro and in vivo. The modular nature of these synthetic Frizzled and LRP5/6 Agonists, called FLAgs, enables tailored engineering of specificity for one, two or multiple members of the Frizzled family. We show that FLAgs underlie differentiation of pluripotent stem cells, sustain organoid growth, and activate stem cells in vivo. Activation of Wnt signaling circuits with tailored FLAgs will enable precise delineation of functional outcomes directed by distinct receptor combinations and could provide a new class of therapeutics to unlock the promise of regenerative medicine.
Atomic layer deposition of lithium containing thin films (2009)

Five different lithium containing compounds, all representing different chemical systems, were studied in order to deposit lithium containing films by atomic layer deposition ALD. The studied compounds were a lithium β-diketonate Li(thd) (thd = 2,2,6,6-tetramethyl-3,5-heptanedionate), a lithium alkoxide LiOtBu (OtBu = tert-butoxide), a lithium cyclopentadienyl LiCp (Cp = cyclopentadienyl), a lithium alkyl n-butyllithium, and a lithium amide lithium dicyclohexylamide. Films containing lithium carbonate (Li2CO3) were obtained from alternate pulsing of Li(thd) and ozone in a temperature range of 185–300 °C. The film composition was analyzed by time-of-flight elastic recoil detection analysis (TOF-ERDA). The films grown at 225 °C were polycrystalline lithium carbonate as analyzed by X-ray diffraction (XRD). A 120 nm thick lithium carbonate film grown at 225 °C had a surface roughness of 19 nm as analyzed by AFM. Lithium lanthanate thin films were grown by combining the Li(thd) process with a ALD process for lanthanum oxide from La(thd)3 and ozone. The film composition was varied by controlling the number of lithium carbonate and lanthanum oxide sub-cycles. Lithium containing films were also obtained from LiCp and water and from LiOtBu and water.
Tendon-to-Bone Pressure Distributions at a Repaired Rotator Cuff Footprint Using Transosseous Suture and Suture Anchor Fixation Techniques (2005)

Stronger and faster rotator cuff healing may be expected when beneficial pressure distributions exist between the repaired rotator cuff and its insertion footprint. Tendon-to-tuberosity pressure and contact characteristics should be considered in the development of improved open and arthroscopic rotator cuff repair techniques.
On-demand multicast in mobile wireless networks (2002)

We propose an "on-demand" multicast routing protocol for a wireless, mobile, multihop network. The proposed scheme has two key features: (a) it is based on the forwarding group concept (i.e., a subset of nodes is in charge of forwarding the multicast packets via scoped flooding) rather than on the conventional multicast tree scheme (b) it dynamically refreshes the forward group members using a procedure akin to on-demand routing (hence the name). "On-demand" multicast is well suited to operate in an on-demand routing environment where routes are selectively computed as needed between communicating node pairs instead of being maintained and updated globally by a routing "infrastructure" (like in distance vector or link state, for example). On-demand multicast is particularly attractive in mobile, rapidly changing networks, where the traffic overhead caused by routing updates and tree reconfigurations may become prohibitive beyond a critical speed; and in large network with sparse traffic requirements, where the traffic, processing and storage overhead of the routing infrastructure solution compromises scalability. Via simulation, we compare on-demand multicast with a traditional tree multicast scheme, DVMRP, and with a version of forwarding group multicast which uses conventional distance vector routing instead of on-demand routing. This allows us to assess the penalty of the tree and of the global routing infrastructure as a function of mobility and sparseness.
Mimotopes of polyreactive anti‐DNA antibodies identified using phage‐display peptide libraries (1997)

Three monoclonal IgG2a anti-DNA polyreactive autoantibodies, derived from lupus-prone mice (NZB x NZW)F1, were studied by surface plasmon resonance (BIAcore) analysis using three different synthetic double-stranded (ds) oligonucleotides of 25, 30, and 25 base pairs (bp). These monoclonal antibodies (mAb) exhibited dissociation rate constants (k(off)), ranging from 0.0001 (mAb F14.6 and F4.1) to 0.01/s (mAb J20.8) and k(on) ranging from 2 x 10(5) to 2 x 10(6) /M/s. The screening of a constrained random peptide library displayed on M13 bacteriophages on these mAb allowed the determination of the specific consensus motifs (mimotopes) for mAb F14.6 and J20.8, but not for mAb F4.1. No cross-reaction was observed between F14.6- and J20.8-specific peptides (and vice versa). Binding of all phages selected on F14.6 was inhibited with 700 ng/ml soluble DNA. The binding of one group of peptides selected on J20.8 was inhibited by 400 ng/ml soluble DNA, of a second group by 2500 ng/ml, while binding of a third group could not be inhibited. The determined consensus sequences do not match with known sequences. Peptides specific for F14.6 share negative charges and aromatic rings that may mimic a DNA backbone, while peptides selected with J20.8 do not bear any negative charge, implying a different kind of molecular recognition, for example hydrogen or salt bonds. The peptides selected on J20.8 also bind serum antibodies from human patients with systemic lupus erythematosus. In addition, BALB/c mice immunized with some of the selected phages exhibit high serum titers of IgG3 anti-dsDNA antibodies, further supporting the hypothesis that peptide epitopes may mimic an oligonucleotide structure.