gebhart/patrepeval huggingface dataset:
Anchimeric assistance in the specific acid-catalysed hydration of benzonitriles (1993)

2-(Acylamido)benzonitriles react to give exclusively the corresponding 2-(acylamido)benzamides under relatively mild aqueous acid conditions. The kinetics for hydration at 50 °C in aqueous HCI with ionic strength kept at 1 mol dm–3 with KCl obey the equation rate =kH×[H+][nitrile] at low acid concentrations: at higher concentrations of acid the pseudo first order rate constants show a positive deviation from linearity. The rate constants (kH) for the substituted benzamido-benzonitriles fit a Hammett relationship. log kH=–0.36 ± 0.04σ– 3.49 ± 0.01 (r= 0.963)The reactivity due to the ortho amido group is more than 25 000 that of the unsubstituted benzonitrile under the same conditions. The mechanism is considered to involve protonation of the nitrile followed by rate limiting intramolecular attack of the amido oxygen to form an intermediate which rapidly breaks down to the acylamidobenzamide.
Synthesis of 11C-amides using [11C]carbon monoxide and in situ activated amines with 1,2,2,6,6-pentamethylpiperidine in palladium mediated carboxamination (2003)

Synthesis of 11C-amides using [11C]carbon monoxide and in situ activated amines with 1,2,2,6,6-pentamethylpiperidine in palladium mediated carboxamination
A Novel Method for Growing Human Breast Epithelium in Vivo Using Mouse and Human Mammary Fibroblasts (2002)

A novel system is described for studying the growth of normal human mammary epithelium in vivo as grafts in athymic nude mice. The key feature of this model is reconstitution of the epithelial-stromal interactions required for normal growth and differentiation of the human mammary epithelium, which produces ducts that are comparable to those in the normal human mammary gland. Human breast epithelial organoids were combined with mammary fibroblasts from mouse or human origin in collagen gels, which were subsequently transplanted under the renal capsule of female nude mice hosts. The resulting grafts showed an increase in the ductal density compared with that observed previously. These ducts expressed appropriate markers for luminal and myoepithelial cells and steroid receptors. Treatment of the host with diethylstilbestrol or estradiol and progesterone significantly increased the number of ducts observed and increased cell proliferation. The grafts also displayed production of beta-casein and milk fat globule membrane protein when the hosts were allowed to become pregnant. This model allows for a variety of epithelial and stromal cells to be used in combination, which would aid in understanding key factors that regulate normal human mammary gland development.
Plant Biology in 2010 (2000)

The completion of the Arabidopsis sequence will be followed by a new ten-year project that will determine the function of all angiosperm genes. Funding for the U.S. component of this multinational project will originate from a new initiative from the U.S. National Science Foundation called the 2010 Project. Progress toward completion of this ambitious project will necessitate significant changes in how the plant biology community selects and approaches research objectives. The plan envisions that the project will facilitate the development of a computational model of a virtual plant that will allow predictive queries about basic mechanisms underlying plant growth and development.
Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficientop/op mouse: Evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma (1996)

Macrophages have been suggested to play a major role in the immune response to cancer. They have also been suggested to stimulate the formation of tumor stroma and to promote tumor vascularization. The availability of the op/op mouse, which has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a profound macrophage deficiency, provides a new model to verify these notions. Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/op mice with human recombinant CSF-1 corrects this impairment. Histological analysis of tumors grown in op/op and normal mice revealed marked differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteries and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent macrophage subpopulation missing in op/op mice plays a primary role in supporting tumor stroma formation and tumor vascularization in murine LLC tumors.
Editorial Comment (1991)

RUBASH, HARRY E. M.D.; BERMAN, ARNOLD T. M.D.; GLICKMAN, MURRAY M.D. Author Information
CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion. (1992)

The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggests a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta 1 integrins, particularly very late antigen-4, more efficiently than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells.
Safety and Immunogenicity of Recombinant Human Immunodeficiency Virus-Like Particles in Rodents and Rhesus Macaques (1996)

Data from long-term non-progressing human immunodeficiency virus (HIV)-infected individuals and populations at high risk suggest that an early cytolytic T cell response rather than the humoral immune response might be involved in controlling disease progression. These observations may be used as a guide to the type of response that a vaccine should induce. To clarify the role of different arms of the immune system in conferring protection, the candidate vaccine should allow a regulated, selective induction of different immune responses. Based on a better understanding of the molecular mechanisms regulating the morphogenesis of HIV, we developed an autologous, non-replicating and safe antigen delivery system. This system takes advantage of molecular characteristics of the HIV group-specific antigens (gag) to self-assemble to highly immunogenic virus-like particles (VLP). The immunogenicity of the gag-derived VLP was expanded either by replacing defined domains by selected HIV-1 cytotoxic T lymphocyte (CTL) epitopes (type 1 VLP) or by stable anchoring derivatives of the HIV-1 envelope protein on the surface of the VLP (type 2 VLP). In complete absence of adjuvants, type 1 and type 2 VLP stimulated CD8+ CTL in BALB/c mice, which specifically recognised HIV sequences. In contrast to type 1 VLP, generating an HIV-specific CTL response in the absence of env-specific antibodies, type 2 VLP induced both arms of the immune system including reasonable levels of neutralising antibodies. Initial studies performed in rhesus macaques confirmed these results. Thus, depending on the type and formulation of the VLP, the proposed antigen delivery system allows either the induction of a CTL response (1) in the absence and (2) the presence of an envelope-specific antibody response. A comparison of these approaches in appropriate animal models might contribute to further define the correlates of protection.
A diversity oriented synthesis of natural product inspired molecular libraries (2017)

Natural products are the source of innumerable pharmaceutical drug candidates and also form an important aspect of herbal remedies. They are also a source of various bioactive compounds. Herein we have leveraged the structural attributes of several natural products in building a library of architecturally diverse chiral molecules by harnessing R-tryptophan as the chiral auxiliary. It is converted to its corresponding methyl ester 1 which in turn provided a bevy of 1-aryl-tetrahydro-β-carbolines 2a-d, which were then converted to chiral compounds via a diversity oriented synthetic strategy (DOS). In general, intermolecular and intramolecular ring rearrangements facilitated the formation of the final compounds. Four different classes of molecules with distinct architectures were generated, adding up to nearly twenty-two individual molecules. Phenotypic screening of a representative section of the library revealed two molecules that selectively inhibit MCF7 breast cancer cells with IC<sub>50</sub> of ∼5 μg mL<sup>-1</sup> potency.
Decoding of Quasi-cyclic LDPC Codes Using an On-the-Fly Computation (2006)

The implementation complexity of the decoder for low-density parity-check codes (LDPC) is dictated by memory and interconnect requirements. We propose new LDPC decoder architectures that reduce the need of message passing memory by 80% (for standard message passing)-55%(for layered decoding) and the router requirements by more than 50%. These novel architectures are based on scheduling of computation that results in "on the fly computation" of variable node and check node reliability messages. These architectures are targeted for quasi- cyclic LDPC codes such as array LDPC codes (regular QC-LDPC) and block LDPC codes (irregular QC-LDPC). FPGA and ASIC implementation results show substantial gains when compared to the existing work in the literature.
3-Substituted GABA analogs with central nervous system activity: A review (1999)

Gabapentin and Pregabalin are both 3-alkylated gamma-amino butyric acid (GABA) analogs. Gabapentin was designed as a lipophilic GABA analog and was first synthesized as a potential anticonvulsant and was launched in 1994 as add-on therapy for the treatment of epilepsy. In this review the discovery and development of gabapentin as an anticonvulsant are discussed. During human trials and while in clinical use, it became apparent that gabapentin induced some other potentially useful therapeutic effects in chronic pain states and behavioral disorders. A review of animal and clinical data relating to these other potential therapeutic utilities is presented. Pregabalin was identified after an investigation into other 3-substituted GABA analogs. It has since been shown to have a similar pharmacological profile to gabapentin with greater potency in preclinical models of pain and epilepsy. Studies of the mechanism(s) of action of these compounds are discussed. Work towards identifying new analogs of both gabapentin and pregabalin is also reviewed.
Speech Understanding with the CIS and the n-of-m Strategy in the MED-EL COMBI 40+ System (2000)

Speech tests have been performed on 6 subjects for comparing the standard 12-channel continuous interleaved sampling (CIS) strategy (CIS12), the 7-channel CIS strategy (CIS7) and the 7-of-12 strategy in the MED-EL COMBI 40+ system. An ABAB experimental design was used whereby each strategy was reversed and replicated. Speech tests were performed in quiet (vowels, consonants, monosyllables, sentences) and noise (sentences). Results showed that for vowels, CIS12 is significantly superior to CIS7, for consonants and sentences CIS12, CIS7 and 7-of-12 performed equally well, and that for monosyllables 7-of-12 is significantly superior to both CIS12 and CIS7. In addition, 7-of-12 is superior to CIS7 by almost the same amount as CIS12, but in this case the difference is not significant. Further, all strategies have been found to be equally robust in noise with respect to sentence understanding. The differences between CIS12 and 7-of-12 on the one hand and CIS7 on the other hand may be attributed to decreased spectral resolution of the latter. The fact that - in contrast to what has been reported for the SPEAK strategy - 7-of-12 is equally robust in noise as the CIS strategies is explained by the use of higher stimulation rates, wider frequency bands and a higher percentage of channels stimulated in each cycle.
Equilibrium dialysis studies of polyamine binding to DNA (1982)

Abstract Binding constants and binding site sizes for the interactions of the polyamines spermine (+4), spermidine (+3), and putrecine (+2) with helical DNA have been determined as a function of ionic conditions and temperature by equilibrium dialysis using 14 C‐labeled polyamines. In addition, competition equilibrium dialysis has been used to determine binding parameters for the divalent cations putrescine and Mg 2+ from the competitive effect of these ions on the binding of spermine or spermidine. In all cases, the logarithm of the binding constant (log K obs ) varies linearly with the logarithm of the monovalent salt concentration; the slopes d log K obs / d log[NaCl] are proportional to the valence of the ligand, and values of the extrapolated binding constants at 1 M NaCl obtained from the intercepts are small (of order 1–10 M −1 ). In those cases examined, K obs is insensitive to temperature; the free energy of binding is predominantly entropic. Consequently, polymines as DNA‐binding ligands behave analogously to the oligolysìnes investigated previously [cf. Record, Lohman &amp; de Haseth (1976) J. Mol. Biol. 107 , 145–158; Lohman, de Haseth &amp; Record (1980) Biochemistry 19 , 3522–3530]. The interactions of these oligocations with DNA are predominantly electrostatic and are driven by the release of thermodynamically bound electrolyte ions from the vicinity of the DNA. The extent to which these oligocations are localized at individual phosphate binding sites or delocalized on the DNA molecule is currently not known.
Removal of Thiazolidinethione Auxiliaries with Benzyl Alcohol Mediated by DMAP (2004)

In the presence of DMAP, a range of N-acylthiazaolidinethiones carrying different substituents were smoothly converted into the corresponding benzyl esters.
Packet Forwarding with Multiprotocol Label Switching (2005)

Abstract—MultiProtocol Label Switching (MPLS) is an emerging technology that aims to address many of the existing issues associated with packet forwarding in today’s Internetworking environment. It provides a method of forwarding packets at a high rate of speed by combining the speed and performance of Layer 2 with the scalability and IP intelligence of Layer 3. In a traditional IP (Internet Protocol) routing network, a router analyzes the destination IP address contained in the packet header. The router independently determines the next hop for the packet using the destination IP address and the interior gateway protocol. This process is repeated at each hop to deliver the packet to its final destination. In contrast, in the MPLS forwarding paradigm routers on the edge of the network (label edge routers) attach labels to packets based on the forwarding Equivalence class (FEC). Packets are then forwarded through the MPLS domain, based on their associated FECs, through swapping
Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation (2009)

Pasteurella multocida toxin is a major virulence factor of Pasteurella multocida, which causes pasteurellosis in men and animals and atrophic rhinitis in rabbits and pigs. The approximately 145 kDa protein toxin stimulates various signal transduction pathways by activating heterotrimeric G proteins of the Galpha(q), Galpha(i), and Galpha(12/13) families by using an as yet unknown mechanism. Here, we show that Pasteurella multocida toxin deamidates glutamine-205 of Galpha(i2) to glutamic acid. Therefore, the toxin inhibits the intrinsic GTPase activity of Galpha(i) and causes persistent activation of the G protein. A similar modification is also evident for Galpha(q), but not for the closely related Galpha(11), which is not a substrate of Pasteurella multocida toxin. Our data identify the alpha-subunits of heterotrimeric G proteins as the direct molecular target of Pasteurella multocida toxin and indicate that the toxin does not act like a protease, which was suggested from its thiol protease-like catalytic triad, but instead causes constitutive activation of G proteins by deamidase activity.
Universal noninvasive detection of solid organ transplant rejection (2011)

It is challenging to monitor the health of transplanted organs, particularly with respect to rejection by the host immune system. Because transplanted organs have genomes that are distinct from the recipient's genome, we used high throughput shotgun sequencing to develop a universal noninvasive approach to monitoring organ health. We analyzed cell-free DNA circulating in the blood of heart transplant recipients and observed significantly increased levels of cell-free DNA from the donor genome at times when an endomyocardial biopsy independently established the presence of acute cellular rejection in these heart transplant recipients. Our results demonstrate that cell-free DNA can be used to detect an organ-specific signature that correlates with rejection, and this measurement can be made on any combination of donor and recipient. This noninvasive test holds promise for replacing the endomyocardial biopsy in heart transplant recipients and may be applicable to other solid organ transplants.
Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat (2008)

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.
Detection of circular arcs for content-based retrieval from an image database (1994)

Methods are discussed for producing a summary of geometric content for images from a specific geological application, which can be used for content-based retrieval of interesting images from a large database. Using a data set of 100 images, it is shown that a local are detection scheme provides a more concise and hence a better summary of image content than a conventional edge map, while giving a superior performance.
ChemInform Abstract: The Chiral Bilayer Effect Stabilizes Micellar Fibers. (1987)

Abstract Dihelical fibers several micrometers in length and gels are obtained by spontaneous aggregation of octyl‐L‐ (Ia) and ‐D‐gluconamides (II).
Structure-Function Analysis of the Adherence-Binding Domain on the Pilin of Pseudomonas aeruginosa Strains PAK and KB7 (1995)

The pili of Pseudomonas aeruginosa mediate bacterial binding to human epithelial cell surfaces. We have previously shown that a 17-residue synthetic peptide, KCTSDQDEQFIPKGCSK, corresponding to the C-terminal sequence of the PAK pilin protein (residues 128-144) contains the adherence binding domain. Another pilin strain, KB7, has been cloned and sequenced [Paranchych et al. (1990) in Pseudomonas Biotransformations, Pathogenesis and Evolving Biotechnology, pp 343-351, American Society for Microbiology, Washington, DC]. The C-terminal 17-residue sequence of the KB7 pilin is SCATTVDAKFRPNGCTD, which is semiconserved as compared to the PAK sequence. In this study, the interactions between the A549 human lung carcinoma cells and the two P. aeruginosa pilin strains were elucidated using a single alanine replacement analysis on the C-terminal 17-residue synthetic peptide of the pilins. The ability of these peptide analogs to inhibit the binding of the biotinylated PAK pili to A549 cells was assessed. Six PAK amino acid side chains (Ser131, Gln136, Ile138, Pro139, Gly141, and Lys144) and nine KB7 side chains (Ala130, Thr131, Thr132, Val133, Asp134, Ala135, Lys136, Arg138, and Pro139) were found to be important in mediating the pilus adhesin binding to A549 cells. In addition, a flexible peptide analog with both cysteine residues replaced by alanine failed to inhibit the binding of PAK pili to A549 cells. This suggests that the interactions between the pilin ligand and the A549 cell surface receptors are dependent on the conformation mediated by the disulfide bridge (Cys129 and Cys142). The residues considered to contribute to bacterial adherence are referred to as the "adhesintope". Four PAK and three KB7 side chains were located in a structurally more rigid region of the disulfide-bridged peptide as revealed by two-dimensional NMR studies [McInnes et al. (1993) Biochemistry 32, 13432-13440]. The structural aspects of the pilin-receptor interactions related to the mapped adhesintope sequences are discussed. The dissimilarities between the PAK and KB7 adhesintopes may suggest that compensatory mutations could occur among different pilin strains so as to allow the pilin adhesins to interact with the same receptor.
Results of Pediatric Cardiac Transplantation - Long-Term Results of a 15-Year Experience (2005)

Pediatric heart transplantation is a curative treatment for DCM and CHD with excellent clinical mid-term results. However, further follow-up is necessary to evaluate long-term side effects of immunosuppressants. Donor shortage remains a problem.