gebhart/patrepeval huggingface dataset:
Role of theHaemophilus ducreyiTon System in Internalization of Heme from Hemoglobin (1998)

By cloning into Escherichia coli and construction of isogenic mutants of Haemophilus ducreyi, we showed that the hemoglobin receptor (HgbA) is TonB dependent. An E. coli hemA tonB mutant expressing H. ducreyi hgbA grew on low levels of hemoglobin as a source of heme only when an intact H. ducreyi Ton system plasmid was present. In contrast, growth on heme by the E. coli hemA tonB mutant expressing hgbA was observed only at high concentrations of heme, was TonB independent, and demonstrated that H. ducreyi HgbA was not sufficient to function as a typical TonB-dependent heme receptor in E. coli. Allelic replacement of the wild-type H. ducreyi exbB, exbD, and tonB loci with the exbB, exbD, and tonB deletion resulted in an H. ducreyi isogenic mutant unable to utilize hemoglobin but able to utilize hemin at the same levels as the parent strain to fulfill its heme requirement. This finding confirms the TonB dependence of HgbA-mediated hemoglobin utilization and suggests that uptake of hemin in H. ducreyi is TonB independent. Additionally, the H. ducreyi Ton system mutant synthesized increased amounts of HgbA and other heme-regulated outer membrane proteins, consistent with derepression of these proteins due to lower intracellular heme and/or iron concentrations in the mutant. Sequencing of the Ton system genes revealed that the arrangement of the genes was exbB exbD tonB. The proximity and structure of these genes suggested that they are transcribed as an operon. This arrangement, as well as the DNA and deduced amino acid sequences of these H. ducreyi genes, was most similar to those from other pasteurellae.
Bacterial Extracellular Polysaccharides Involved in Biofilm Formation (2009)

Extracellular polymeric substances (EPS) produced by microorganisms are a complex mixture of biopolymers primarily consisting of polysaccharides, as well as proteins, nucleic acids, lipids and humic substances. EPS make up the intercellular space of microbial aggregates and form the structure and architecture of the biofilm matrix. The key functions of EPS comprise the mediation of the initial attachment of cells to different substrata and protection against environmental stress and dehydration. The aim of this review is to present a summary of the current status of the research into the role of EPS in bacterial attachment followed by biofilm formation. The latter has a profound impact on an array of biomedical, biotechnology and industrial fields including pharmaceutical and surgical applications, food engineering, bioremediation and biohydrometallurgy. The diverse structural variations of EPS produced by bacteria of different taxonomic lineages, together with examples of biotechnological applications, are discussed. Finally, a range of novel techniques that can be used in studies involving biofilm-specific polysaccharides is discussed.
Chymase Is Upregulated in Diabetic Nephropathy (2003)

Angiotensin II (AngII) has been shown to play a critical role in diabetic nephropathy and vasculopathy. Although it is well recognized that an angiotensin-converting enzyme (ACE)-dependent AngII-generating system is a major source of intrarenal AngII production, it is here reported that the chymase-dependent AngII-generating system is upregulated in the human diabetic kidney. This becomes particularly strong in those with hypertension. In the normal kidney, while ACE was constitutively expressed by most kidney cells, chymase was weakly expressed by mesangial cells (MC) and vascular smooth muscle cells (VSMC) only. In the diabetic kidney, while ACE expression was significantly upregulated (1 to 3-fold) by tubular epithelial cells (TEC) and infiltrating mononuclear cells, there was also markedly increased chymase expression (10 to 15-fold) by both MC and VSMC, with strong deposition in the collagen-rich extracellular matrix including both diffuse and nodular glomerulosclerosis, tubulointerstitial fibrosis, and vascular sclerosis. Interestingly, while ACE expression showed no difference in patients with or without hypertension, upregulation of chymase in hypertensive patients was much stronger than that seen in those without hypertension (4 to 7-fold, P < 0.001). Correlation analysis showed that, in contrast to the ACE expression, upregulation of chymase correlated significantly with the increase in BP and the severity of collagen matrix deposition within the glomerulus, tubulointerstitium, and arterial walls (all with P < 0.001). In conclusion, the present study demonstrates that chymase, as an alternative AngII-generating enzyme, is markedly upregulated in the diabetic kidney and may be associated with the development of diabetic/hypertensive nephropathy. In addition, differential expression of ACE and chymase in the diabetic kidney indicates that both ACE and chymase may be of equal importance for AngII-mediated diabetic nephropathy and vascular disease. Results from this study suggest that blockade of both AngII-generating pathways may provide additional beneficial effect on diabetic nephropathy.
Use of molecular modelling to probe the mechanism of the nucleoside transporter NupG (2012)

Nucleosides play key roles in biology as precursors for salvage pathways of nucleotide synthesis. Prokaryotes import nucleosides across the cytoplasmic membrane by proton- or sodium-driven transporters belonging to the Concentrative Nucleoside Transporter (CNT) family or the Nucleoside:H(+) Symporter (NHS) family of the Major Facilitator Superfamily. The high resolution structure of a CNT from Vibrio cholerae has recently been determined, but no similar structural information is available for the NHS family. To gain a better understanding of the molecular mechanism of nucleoside transport, in the present study the structures of two conformations of the archetypical NHS transporter NupG from Escherichia coli were modelled on the inward- and outward-facing conformations of the lactose transporter LacY from E. coli, a member of the Oligosaccharide:H(+) Symporter (OHS) family. Sequence alignment of these distantly related proteins (∼ 10% sequence identity), was facilitated by comparison of the patterns of residue conservation within the NHS and OHS families. Despite the low sequence similarity, the accessibilities of endogenous and introduced cysteine residues to thiol reagents were found to be consistent with the predictions of the models, supporting their validity. For example C358, located within the predicted nucleoside binding site, was shown to be responsible for the sensitivity of NupG to inhibition by p-chloromercuribenzene sulphonate. Functional analysis of mutants in residues predicted by the models to be involved in the translocation mechanism, including Q261, E264 and N228, supported the hypothesis that they play important roles, and suggested that the transport mechanisms of NupG and LacY, while different, share common features.
Cycle-accurate energy measurement and characterization with a case study of the ARM7TDMI [microprocessors] (2002)

Energy characterization is the basis for high-level energy reduction. Measurement-based characterization is accurate and independent of model availability and is thus suitable for commercial off-the-shelf (COTS) components, but conventional measurement equipment has serious limitations in this context. We introduce a new technique for the energy characterization of a microprocessor using a cycle-accurate energy measurement system based on charge transfer which is robust to spiky noise and is able to collect a range of energy consumption profiles in real time. It measures the energy variation of the CPU core by changing the instruction-level energy-sensitive factors such as opcodes (operations), instruction fetch addresses, register numbers, register values, data fetch addresses and immediate operand values at each pipeline stage. Using the ARM7TDMI RISC processor as a case study, we observe that the energy contributions of most instruction-level energy-sensitive factors are orthogonal to the operations. We are able to characterize the energy variation, preserving all the effects of the energy-sensitive factors for various software methods of energy reduction. We also demonstrate applications of our measurement and characterization techniques.
Development and application of non-integrating lentiviral vectors for gene therapy (2009)

Lentiviruses stably integrate their genome into the host genome. Although this feature can be advantageous for long term transgene expression, it also has the potential to cause mutagenesis and cell transformation. To address this problem, thereby improving the safety of lentiviral gene therapy, non-integrating lentiviral vectors (NILVs) were developed.&#13;\nNILVs were generated by mutating the cis-acting sequences that interact with integrase (att sites) or by mutating specific residues in integrase in different domains (catalysis - D64V, strand transfer – Q148A, K264R, K266R, K273R, DNA or chromatin binding - N120L, W235E). Relevant mutations were then combined in order to improve the safety of these vectors.&#13;\nIt was shown that all mutant vectors were efficiently produced and mutations did not affect infectivity. In contrast to dividing cells, differentiated muscle cells infected with NILVs show stable transgene expression over time without degradation of episomal viral DNA. The vectors were also tested in vivo by intramuscular injection in neonate mice. Transgene expression from muscle cells was maintained for 8 months using both integrating and NILVs.&#13;\nThe vectors were then tested in a haemophilia B disease model. It was shown that plasma levels of FIX produced by muscle cells infected with integrating lentiviral vectors were above the therapeutic threshold. However, expression from NILVs was lower. This was studied in detail and it was found that integrating lentiviral vectors are transcriptionally more active than NILVs. A comparison of expression levels revealed that integrated lentivectors express more transgene protein per vector copy than NILVs and AAV vectors, but both episomal vectors display similar levels of transgene expression per vector copy.&#13;\nIn conclusion, NILVs have the potential to be used as tools for prolonged transgene expression in non-dividing muscle cells or transient expression in dividing cells. However, vectors may need to be optimised if high expression levels are required.
Biosynthesis of the beta-lactam antibiotic, thienamycin, by Streptomyces cattleya. (1985)

Radioactive- and stable isotope-containing substrates were used to identify the biosynthetic precursors of the beta-lactam antibiotic, thienamycin, in Streptomyces cattleya. Acetate is utilized by the organism to form C(6) and C(7) of the beta-lactam ring. The two carbons of the hydroxyethyl group attached to C(6) are both derived from the methyl of methionine. The cysteaminyl side chain attached to C(2) is derived from cysteine. Selective inhibition of thienamycin and cephamycin C biosynthesis has been achieved either through the addition of metabolic inhibitors or through manipulation of the growth medium. These results suggest that the two beta-lactam antibiotics, thienamycin and cephamycin C, are formed by different biosynthetic pathways.
Ultra-thin, planar, Babinet-inverted plasmonic metalenses (2013)

We experimentally demonstrate the focusing of visible light with ultra-thin, planar metasurfaces made of concentrically perforated, 30-nm-thick gold films. The perforated nano-voids—Babinet-inverted (complementary) nano-antennas—create discrete phase shifts and form a desired wavefront of cross-polarized, scattered light. The signal-to-noise ratio in our complementary nano-antenna design is at least one order of magnitude higher than in previous metallic nano-antenna designs. We first study our proof-of-concept ‘metalens’ with extremely strong focusing ability: focusing at a distance of only 2.5 μm is achieved experimentally with a 4-μm-diameter lens for light at a wavelength of 676 nm. We then extend our work with one of these ‘metalenses’ and achieve a wavelength-controllable focal length. Optical characterization of the lens confirms that switching the incident wavelength from 676 to 476 nm changes the focal length from 7 to 10 µm, which opens up new opportunities for tuning and spatially separating light at different wavelengths within small, micrometer-scale areas. All the proposed designs can be embedded on-chip or at the end of an optical fiber. The designs also all work for two orthogonal, linear polarizations of incident light. Scientists in the USA have developed powerful ultrathin planar lenses made from 30-nm-thick perforated gold films. These plasmonic metalenses, created by Xingjie Ni and co-workers at Purdue University, focus a beam of visible light into a spot measuring only slight larger than the wavelength of operation. The devices rely on a concentric pattern of Babinet-inverted nano-antennas (nano-avoids) in a metal film that manipulate the phase of the incident light. For example, a 4-μm-diameter lens provides a focal length of 2.5 μm at a wavelength of 676 nm. The lenses are designed to work at two orthogonal linear polarizations and in future could be suitable for use as miniature couplers or light concentrators in on-chip optical devices.
Monoclonal antibodies against brain acetycholinesterases which recognize the subunits bearing the hydrophobic anchor (1993)

Monoclonal antibodies were raised against amphiphilic detergent-soluble (DS) acetylcholinesterase (AChE) from human brain caudate nucleus. Three mAb, 132-4 (IgG1), 132-5 (IgG1) and 132-6 (IgG3), specific for brain DS-AChE were selected and subcloned. These mAb reacted with native as well as heat-denatured and SDS-denatured DS-AChE, indicating that the epitopes to which mAb bound are continuous determinants. The mAb cross-reacted with DS-AChE from bovine and mouse brain and with brain DS-AChE from river trout (Salmo trutta forma fario) and lake trout (Salmo trutta forma lacustris). No cross-reaction was detected with the following antigens: salt-soluble (SS) AChE from bovine brain, glycophospholipid-anchored AChE from human and bovine erythrocytes, DS-butyrylcholinesterase and SS-butyrylcholinesterase (BtChE) from the brains of human and bovine, DS-BtChE from chicken and BtChE from human serum. Deglycosylation of brain DS-AChE with N-glycosidase F did not abolish the binding of mAb to DS-AChE. After reduction of brain DS-AChE by dithiothreitol, the mAb no longer reacted with the antigen, indicating that a disulfide bridge is important for the epitope. Monomerization of brain DS-AChE by trypsin and limited proteinase K treatment also abolished the binding of mAb to DS-AChE. Sucrose-density-gradient centrifugation showed that mAb reacted only with native tetrameric forms, but not with dimeric and monomeric forms. Western blot, after SDS/PAGE under non-reducing conditions, showed that mAb reacted with those subunits carrying the hydrophobic anchor (i.e. tetramers, trimers and heavy dimers) but not with those devoid of it (light dimers or monomers). Since mAb 132-4, 132-5 and 132-6 recognized DS-AChE from fish up to mammalian brain in the evolutionary tree, it is concluded that the epitope to which these mAb bind, is conserved in nature.
PDT-related photophysical properties of conformationally distorted palladium(II) porphyrins (2001)

The photodynamic therapy (PDT) related photophysical properties of five palladium(II) porphyrins with increasing steric demand of the meso-substituents were investigated by steady state and time-resolved absorption and luminescence spectroscopy. The steric strain of the meso-substituents is reflected in a bathochromic shift of the B-band in the absorption spectra. In contrast to free-base porphyrins, the palladium(II) complexes exhibit only a very weak fluorescence with Φ Fl ~ 10 -4 . Instead, the corresponding triplet states of the porphyrins are formed via inter system crossing (ISC) with a quantum yield Φ ISC of nearly unity. A phosphorescence quantum yield Φ ISC of 10 -4 was determined assuming dynamic quenching. The triplet state of all compounds is efficiently quenched by molecular oxygen, generating singlet molecular oxygen with a quantum yield of Φ Δ ~ 0.85. The various substitution patterns exerted no significant influence on the ISC rates or singlet oxygen quantum yields. Significant differences, on the other hand, were observed with respect to the triplet lifetimes, with a tendency of longer lifetimes for the porphyrins with sterically more demanding substituents (in air-saturated solution). All porphyrins were successfully incorporated into liposomes. The phototoxic activity of three compounds was investigated in cell suspensions. The use of the new porphyrinato-palladium(II) in PDT applications is discussed.
Brain network connectivity-behavioral relationships exhibit trait-like properties: Evidence from hippocampal connectivity and memory (2015)

Despite a growing number of studies showing relationships between behavior and resting-state functional MRI measures of large-scale brain network connectivity, no study to our knowledge has sought to investigate whether intrinsic connectivity-behavioral relationships are stable over time. In this study, we investigated the stability of such brain-behavior relationships at two timepoints, approximately 1 week apart. We focused on the relationship between the strength of hippocampal connectivity to posterior cingulate cortex and episodic memory performance. Our results showed that this relationship is stable across samples of a different age and reliable over two points in time. These findings provide the first evidence that the relationship between large-scale intrinsic network connectivity and episodic memory performance is a stable characteristic that varies between individuals.
Dynamics of magnetic chains in a shear flow under the influence of a uniform magnetic field (2012)

We numerically investigate dynamics of magnetic chains and flow characteristics in a two-dimensional shear flow under the influence of a magnetic field applied externally. A direct simulation method is employed to solve the particulate flow in the creeping flow regime, taking into account both magnetic and hydrodynamic interactions in a coupled manner. In a periodic channel, the dynamics of chains is found to be significantly influenced by the Mason number (the ratio of viscous force to magnetic force), the magnetic susceptibility, and the particle fraction. Below a critical Mason number, a chain rotates and reaches an equilibrium. Above the critical value, however, the chain continuously rotates as a rigid body. Thinning behavior in the wall shear stress is found above a threshold value of the Mason number. As for chain rupture in the shear flow, three regimes of the Mason number are found, showing three typical conformations of the chains: (i) complex chains with branches rather than linear chains, (ii) tilted linear chains broken in the middle, generating a slip zone between the upper and lower chains, and (iii) shortened chains rotating in the channel.
Nitrolinoleate Inhibits Superoxide Generation, Degranulation, and Integrin Expression by Human Neutrophils (2002)

Nitration of unsaturated fatty acids such as linoleate by NO-derived reactive species forms novel derivatives (including nitrolinoleate [LNO2]) that can stimulate smooth muscle relaxation and block platelet activation by either NO/cGMP or cAMP-dependent mechanisms. Here, LNO2 was observed to inhibit human neutrophil function. LNO2, but not linoleic acid or the nitrated amino acid 3-nitrotyrosine, dose-dependently (0.2 to 1 micromol/L) inhibited superoxide (O2*-) generation, Ca2+ influx, elastase release, and CD11b expression in response to either phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. LNO2 did not elevate cGMP, and inhibition of guanylate cyclase by 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one did not restore neutrophil responses, ruling out a role for NO. In contrast, LNO2 caused elevations in intracellular cAMP in the presence and absence of phosphodiesterase inhibition, suggesting activation of adenylate cyclase. Compared with phorbol 12-myristate 13-acetate-activated neutrophils, N-formyl-Met-Leu-Phe-activated neutrophils were more susceptible to the inhibitory effects of LNO2, indicating that LNO2 may inhibit signaling both upstream and downstream of protein kinase C. These data suggest novel signaling actions for LNO2 in mediating its potent inhibitory actions. Thus, nitration of lipids by NO-derived reactive species yields products with antiinflammatory properties, revealing a novel mechanism by which NO-derived nitrated biomolecules can influence the progression of vascular disease.
Two related regulatory sequences are required for maximal induction of Saccharomyces cerevisiae his3 transcription. (1987)

In Saccharomyces cerevisiae, the coordinate induction of his3 and other amino acid biosynthesis genes is mediated by the binding of GCN4 activator protein to specific promoter sequences. The his3 regulatory region contains the sequence TGACTC, which with some variation is repeated six times upstream of the mRNA initiation site. The requirements for maximal his3 induction were examined with a series of sequential 5' deletion mutations as well as a set of small internal deletions. Deletions encroaching as far downstream as position -142 behave indistinguishably from the wild-type gene, thus indicating that the two proximal copies of the regulatory sequence are sufficient for maximal induction. Deletions with breakpoints between -137 and -99 confer inducibility, but not to the normal wild-type level. A deletion ending immediately upstream of the proximal TGACTC sequence (position -99) shows some constitutive expression that is independent of the gcn4 gene product. Deletions extending to -94 or beyond do not produce detectable levels of his3 mRNA. Small internal deletions that only remove the proximal regulatory sequence and a 1-base-pair deletion of the thymine residue at -99 abolish induction, but do not affect the basal level of transcription. These results indicate that the proximal copy between -99 and -94 is absolutely required for his3 induction, whereas the copy between -142 and -137 is required only for the maximal level of induction and is inactive by itself. From these and other observations, we suggest the possibility that these related regulatory sequences may be targets for two distinct proteins.
Generalized Chemical Reactivity of Curved Surfaces:  Carbon Nanotubes (2003)

We have developed a model to predict the chemical reactivity of carbon nanotubes (CNTs) quantitatively from their initial structures. The parameters, universal for each reaction, of the model can be obtained from a graphene sheet analysis. The chemical reactivity of hydrogenation, hydroxylation, and fluorination were predicted within 0.1−0.3 eV errors, compared with first principle simulation results. The model also predicted the enhanced chemical reactivity of mechanically bent CNTs. The predictions can be applied to the controlled functionalization of CNTs.