gebhart/patrepeval huggingface dataset:
An 18 ns 56-bit multiply-adder circuit (1990)

A multiply-adder that achieves a 56-b X*X+Z function with cycle time of 18 ns in a 1- mu m CMOS technology is discussed. The organization requires only two pipeline stages, ensuring quick recovery from branch instructions. The design is for the fraction part of a 64-b multiply-adder and is itself 56 b wide at input and output. To achieve high performance and reasonable density, it uses Booth encoding and a Wallace tree array. Data are captured at the input latches and routed immediately to the Booth encoders, which, in addition to encoding the X input, also provide driven Y and Y-bar signals for the array. The Z input is also captured and routed to the Z shifter. Encoded X, Y-bar, and Z and shifted Z signals are all routed to the partial product array. Booth encoding for 56 b produces 29 partial products; the Z input raises the number of terms to be added to 30. The partial product array reduces this to three, at which point a second latch captures the reduced result. After the latch, the three terms are reduced to two in a full adder, and the resulting two terms added and renormalized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of toxA and regA by the Escherichia coli fur gene and identification of a Fur homologue in Pseudomonas aeruginosa PA103 and PA01 (1991)

A multicopy plasmid containing the Escherichia coli fur gene was introduced into Pseudomonas aeruginosa strain PA103C. This strain contains a toxA-lacZ fusion integrated into its chromosome at the toxA locus. Beta-galactosidase synthesis in this strain is regulated by iron, as is seen for exotoxin A production. Beta-galactosidase synthesis and exotoxin A production in PA103C containing multiple copies of E. coli fur was still repressed in low iron conditions. The transcription of regA, a positive regulator of toxA, was also found to be inhibited by multiple copies of the E. coli fur gene. In addition, the ability of PA103C containing multiple copies of E. coli fur to produce protease was greatly reduced relative to PA103C containing a vector control. A polyclonal rabbit serum containing antibodies that recognize E. coli Fur was used to screen whole-cell extracts from Vibrio cholerae, Shigella flexneri, Salmonella typhimurium and Pseudomonas aeruginosa. All strains tested expressed a protein that was specifically recognized by the anti-Fur serum. These results and those described above suggest that Fur structure and function are conserved in a variety of distinct bacterial genera and that at least some of these different genera use this regulatory protein to control genes encoding virulence factors.
Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis (2011)

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.
Use of Caveolin‐1, Thyroid Transcription Factor‐1, and Cytokeratins 7 and 20 in Discriminating Between Primary and Secondary Pulmonary Adenocarcinoma from Breast or Colonic Origin (2007)

The objectives of this study were firstly to compare the immunostaining patterns of antibodies against caveolin-1, thyroid transcription factor-1 (TTF-1), cytokeratin 7 (CK7) and cytokeratin 20 (CK20) in primary and secondary pulmonary adenocarcinomas of breast or colonic origin, and secondly, to investigate their use alone and in combination, in distinguishing between primary and secondary lung adenocarcinomas from breast or colonic origin. Of the 49 lung adenocarcinoma specimens that were enrolled in this study, 30 were primary pulmonary adenocarcinomas, and 19 (9, breast origin; 10, colonic origin) were metastatic pulmonary carcinomas. Immunohistochemical staining was used to detect the expression of caveolin-1, TTF-1, CK7, and CK20. Primary pulmonary adenocarcinoma most often had the CK7-positive/CK20-negative immunohistochemical phenotype and was either TTF-1 positive or caveolin-1 negative. Secondary pulmonary adenocarcinoma of breast origin most often had the CK7-positive/CK20-negative immunohistochemical phenotype and was either TTF-1 negative or caveolin-1 positive, while secondary pulmonary adenocarcinoma of colonic origin most often had the CK20-positive/CK7-negative immunohistochemical phenotype and was either TTF-1 negative or caveolin-1 positive. The results suggest that caveolin-1, TTF-1, or CK7/CK20 alone did not distinguish reliably between primary and secondary pulmonary adenocarcinomas originating from breast or colon. The use of a panel of antibodies that includes TTF-1, caveolin-1, and CK7/CK20 may have higher sensitivity in discriminating between primary adenocarcinomas and metastatic lung adenocarcinomas from breast or colonic origin.
A Novel Role of the Mammalian GSPT/eRF3 Associating with Poly(A)-binding Protein in Cap/Poly(A)-dependent Translation (2002)

The mammalian GSPT, which consists of amino-terminal (N) and carboxyl-terminal (C) domains, functions as the eukaryotic releasing factor 3 (eRF3) by interacting with eRF1 in translation termination. This function requires only the C-domain that is homologous to the elongation factor (EF) 1alpha, while the N-domain interacts with polyadenylate-binding protein (PABP), which binds the poly(A) tail of mRNA and associates with the eukaryotic initiation factor (eIF) 4G. Here we describe a novel role of GSPT in translation. We first determined an amino acid sequence required for the PABP interaction in the N-domain. Inhibition of this interaction significantly attenuated translation of capped/poly(A)-tailed mRNA not only in an in vitro translation system but also in living cells. There was a PABP-dependent linkage between the termination factor complex eRF1-GSPT and the initiation factor eIF4G associating with 5' cap through eIF4E. Although the inhibition of the GSPT-PABP interaction did not affect the de novo formation of an 80 S ribosomal initiation complex, it appears to suppress the subsequent recycle of ribosome. These results indicate that GSPT/eRF3 plays an important role in translation cycle through the interaction with PABP, in addition to mediating the termination with eRF1.
Hereditary Late-Onset Lymphedema (1978)

Two different types of hereditary late-onset lymphedema are presented. In one family the father and one son had recurrent streptococcal lymphangitis beginning in childhood. In the son there was lymphatic hypoplasia in both legs with the infection having only occurred in one. Prophylaxis with penicillin prevented the recurrent lymphangitis. Because of 30 years of untreated lymphangitis, the father has chronic severe lymphedema. The second type, lymphedema associated with extra eyelashes (distichiasis) and a wide spinal canal, occurred in a woman whose lymphedema began at age 12 but in whom the hereditary nature of the disorder was not recognized until she was 29. Both of these types of late-onset lymphedema, lymphedema with lymphangitis and lymphedema with distichiasis, are due to autosomal dominant genes. Both families would have benefited from early diagnosis of the cause of the lymphedema.
Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution (2015)

Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs’ joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing.
New Recombinant Serotypes of AAV Vectors (2005)

AAV based vectors can achieve stable gene transfer with minimal vector related toxicities. AAV serotype 2 (AAV2) is the first AAV that was vectored for gene transfer applications. However, the restricted tissue tropism of AAV and its low transduction efficiency have limited its further development as vector. Recent studies using vectors derived from alternative AAV serotypes such as AAV1, 4, 5 and 6 have shown improved potency and broadened tropism of the AAV vector by packaging the same vector genome with different AAV capsids. In an attempt to search for potent AAV vectors with enhanced performance profiles, molecular techniques were employed for the detection and isolation of endogenous AAVs from a variety of human and non-human primate (NHP) tissues. A family of novel primate AAVs consisting of 110 non-redundant species of proviral sequences was discovered and turned to be prevalent in 18-19% of the tissues evaluated. Phylogenetic and functional analyses revealed that primate AAVs are segregated into clades based on phylogenetic relatedness. The members within a clade share functional and serological properties. Initial evaluation in mouse models of vectors based on these novel AAVs for tissue tropism and gene transfer potency led to the identification of some vector with improved gene transfer to different target tissues. Gene therapy treatment of several mouse and canine models with novel AAV vectors achieved long term phenotypic corrections. Vectors based on new primate AAVs could become the next generation of efficient gene transfer vehicles for various gene therapy applications.
Long-term follow-up of idiopathic ventricular fibrillation ablation: a multi-centre study (2009)

info:eu-repo/semantics/published
Molecular Determinants of Nuclear Protein Phosphatase-1 Regulation by NIPP-1 (1999)

NIPP-1 is a subunit of the major nuclear protein phosphatase-1 (PP-1) in mammalian cells and potently inhibits PP-1 activity in vitro. Using yeast two-hybrid and co-sedimentation assays, we mapped a PP-1-binding site and the inhibition function to the central one-third domain of NIPP-1. Full-length NIPP-1 (351 residues) and the central domain, NIPP-1(143-217), were equally potent PP-1 inhibitors (IC50 = 0.3 nM). Synthetic peptides spanning the central domain of NIPP-1 further narrowed the PP-1 inhibitory function to residues 191-200. A second, noninhibitory PP-1-binding site was identified by far-Western assays with digoxygenin-conjugated catalytic subunit (PP-1C) and included a consensus RVXF motif (residues 200-203) found in many other PP-1-binding proteins. The substitutions, V201A and/or F203A, in the RVXF motif, or phosphorylation of Ser199 or Ser204, which are established phosphorylation sites for protein kinase A and protein kinase CK2, respectively, prevented PP-1C-binding by NIPP-1(191-210) in the far-Western assay. NIPP-1(191-210) competed for PP-1 inhibition by full-length NIPP-1(1-351), inhibitor-1 and inhibitor-2, and dissociated PP-1C from inhibitor-1- and NIPP-1(143-217)-Sepharose but not from full-length NIPP-1(1-351)-Sepharose. Together, these data identified some of the key elements in the central domain of NIPP-1 that regulate PP-1 activity and suggested that the flanking sequences stabilize the association of NIPP-1 with PP-1C.
Bioactive Compound Synthetic Capacity and Ecological Significance of Marine Bacterial Genus Pseudoalteromonas (2007)

The genus Pseudoalteromonas is a marine group of bacteria belonging to the class Gammaproteobacteria that has come to attention in the natural product and microbial ecology science fields in the last decade. Pigmented species of the genus have been shown to produce an array of low and high molecular weight compounds with antimicrobial, anti-fouling, algicidal and various pharmaceutically-relevant activities. Compounds formed include toxic proteins, polyanionic exopolymers, substituted phenolic and pyrolle-containing alkaloids, cyclic peptides and a range of bromine-substituted compounds. Ecologically, Pseudoalteromonas appears significant and to date has been shown to influence biofilm formation in various marine econiches; involved in predator-like interactions within the microbial loop; influence settlement, germination and metamorphosis of various invertebrate and algal species; and may also be adopted by marine flora and fauna as defensive agents. Studies have been so far limited to a relatively small subset of strains compared to the known diversity of the genus suggesting that many more discoveries of novel natural products as well as ecological connections these may have in the marine ecosystem remain to be made.
Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer (2008)

A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.
Identification of amino acid residues in the ligand binding repeats of LDL receptor important for PCSK9 binding (2019)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDL receptor (LDLR) degradation, increasing plasma levels of LDL cholesterol and the risk of cardiovascular disease. We have previously shown that, in addition to the epidermal growth factor precursor homology repeat-A of LDLR, at least three ligand-binding repeats (LRs) of LDLR are required for PCSK9-promoted LDLR degradation. However, how exactly the LRs contribute to PCSK9's action on the receptor is not completely understood. Here, we found that substitution of Asp at position 172 in the linker between the LR4 and LR5 of full-length LDLR with Asn (D172N) reduced PCSK9 binding at pH 7.4 (mimic cell surface), but not at pH 6.0 (mimic endosomal environment). On the other hand, mutation of Asp at position 203 in the LR5 of full-length LDLR to Asn (D203N) significantly reduced PCSK9 binding at both pH 7.4 and pH 6.0. D203N also significantly reduced the ability of LDLR to mediate cellular LDL uptake, whereas D172N had no detectable effect. These findings indicate that amino acid residues in the LRs of LDLR play an important role in PCSK9 binding to the receptor.
Polarized resonant Raman study of isolated single-wall carbon nanotubes: Symmetry selection rules, dipolar and multipolar antenna effects (2002)

We studied the polarization dependence of the resonance Raman spectra for several different isolated single-wall carbon nanotubes (SWNTs). One isolated SWNT acts as a dipolar antenna, polarized along the tube axis. For light polarized parallel to the tube axis, the strong resonance-effect breaks the symmetry-selection rules, and symmetry-forbidden modes appear in the Raman spectrum. When the light is not polarized parallel to the tube axis, G-band mode symmetries can be identified. Unusual G-mode intensity behavior is observed when the Raman signal is obtained from more than one SWNT, suggesting a complex multipolar antenna pattern.
Alterations in the Equine Herpesvirus Type-1 (EHV-1) Strain RacH During Attenuation (1996)

The equine herpesvirus type-1 modified live-vaccine strain RacH (256th passage on porcine embryonic kidney cells) was investigated by restriction-enzyme analysis and compared to representative plaque isolates of the 12th passage (RacL11, RacL22) and 185th passage (RacM24, RacM36). The restriction patterns of all Rac plaque isolates differed compared with reference strain Ab4. The left UL terminus was shortened by 0.1 kbp and a missing BamHI site led to the fusion of the f and t fragments. In some Rac derivatives, losses of restriction sites without deletions were observed: 1. One BamHI site located in the ribosyl reductase gene was missing in RacH, RacM24, RacM36, and RacL22; and 2. An SalI site mapping to the gp14 (gB) gene was absent in RacM24, RacM36 and RacH. An identical deletion of 0.85 kbp in size was found in both copies of the inverted repeat (IR) regions of RacH. The deletion was present only in the terminal IR of the medium-passage derivative RacM36. By contrast, in the genomes of the apathogenic RacM24, as well as the pathogenic plaque isolates RacL11 and RacL22, no deletions in the IRs were detectable. Nucleotide-sequence and Northern-blot analyses revealed that the deletions led to the elimination of one or both copies of the gene 67 (IR6) open-reading frame in RacM36 and RacH and affected the gene 68 (EUS1) in RacH.
Potent anti-murine cytomegalovirus activity and reduced nephrotoxicity of ganciclovir cyclic phosphonate (1996)

Ganciclovir cyclic phosphonate (SR3775) is a derivative of the R enantiomer (SR3773) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine), both of which are potent inhibitors of human ctyomegalovirus and murine cytomegalovirus (MCMV). Against wild-type and four drug-resistant strains of MCMV, SR3773 was 2.3- to 3-fold more potent than SR3775. SR3775 was about half as active as SR3773 against MCMV infections in severe combined immunodeficient mice. However, whereas SR3773 caused 20 to 30% destruction of renal tubules at 50 mg/kg of body weight per day (but exerted no toxicity at 25 mg/kg/day), SR3775 showed no deleterious renal effects at 600 mg/kg/day over 14 days. SR3775 has a therapeutic index at least 12 times higher than SR3773 in mice, making it a candidate for the treatment of human cytomegalovirus disease.
Leucocyte typing IV : white cell differentiation antigens (1989)

What next?, C.Milstein statistical analysis, W.Gilks et al. Part 1 B-cells: B-cell section report, B.Dorken et al cluster reports and B-cell papers. Part 2 T-cells: T-cell section report, P.Rieber et al cluster reports and T-cell papers. Part 3 Activation antigens: Activation antigens section report, H.Stein and R.Schwarting cluster reports and activation papers. Part 4 NK-and non-lineage antigens: NK- and non-lineage antigens section report, R.E.Schmidt et al cluster reports and NK- and non-lineage papers. Part 5 Myeloid cells: Myeloid cells section report, W.Knapp et al cluster reports and myeloid papers. Part 6 Platelets: Platelets section report, AEG Kr von dem Borne et al cluster reports and platelet papers. Part 7 Plenary papers.
Sonication-Assisted Functionalization and Solubilization of Carbon Nanotubes (2002)

Carbon nanotubes were solubilized via functionalization with poly(propionylethylenimine-co-ethylenimine). The diimide-activated amidation reaction for the functionalization was found to be significantly improved in both efficiency and yield by sonication under ambient conditions. It was also found that depending on the duration of sonication the nanotubes were shortened to different lengths in the functionalization reactions. The method allows relatively efficient preparation of solubilized carbon nanotubes of potentially a selectable average length.
Structural and Dynamic Requirements for Optimal Activity of the Essential Bacterial Enzyme Dihydrodipicolinate Synthase (2012)

Dihydrodipicolinate synthase (DHDPS) is an essential enzyme involved in the lysine biosynthesis pathway. DHDPS from E. coli is a homotetramer consisting of a 'dimer of dimers', with the catalytic residues found at the tight-dimer interface. Crystallographic and biophysical evidence suggest that the dimers associate to stabilise the active site configuration, and mutation of a central dimer-dimer interface residue destabilises the tetramer, thus increasing the flexibility and reducing catalytic efficiency and substrate specificity. This has led to the hypothesis that the tetramer evolved to optimise the dynamics within the tight-dimer. In order to gain insights into DHDPS flexibility and its relationship to quaternary structure and function, we performed comparative Molecular Dynamics simulation studies of native tetrameric and dimeric forms of DHDPS from E. coli and also the native dimeric form from methicillin-resistant Staphylococcus aureus (MRSA). These reveal a striking contrast between the dynamics of tetrameric and dimeric forms. Whereas the E. coli DHDPS tetramer is relatively rigid, both the E. coli and MRSA DHDPS dimers display high flexibility, resulting in monomer reorientation within the dimer and increased flexibility at the tight-dimer interface. The mutant E. coli DHDPS dimer exhibits disorder within its active site with deformation of critical catalytic residues and removal of key hydrogen bonds that render it inactive, whereas the similarly flexible MRSA DHDPS dimer maintains its catalytic geometry and is thus fully functional. Our data support the hypothesis that in both bacterial species optimal activity is achieved by fine tuning protein dynamics in different ways: E. coli DHDPS buttresses together two dimers, whereas MRSA dampens the motion using an extended tight-dimer interface.
Glycemic Control and Sliding Scale Insulin Use in Medical Inpatients With Diabetes Mellitus (1997)

Suboptimal glycemic control is common in medical inpatients with diabetes mellitus. The risk of suboptimal control is associated with selected demographic and clinical characteristics, which can be ascertained at hospital admission. Although sliding scale insulin regimens are prescribed for the majority of inpatients with diabetes, they appear to provide no benefit; in fact, when used without a standing dose of intermediate-acting insulin, they are associated with an increased rate of hyperglycemic episodes.