gebhart/patrepeval huggingface dataset:
Vectored antibody gene delivery protects againstPlasmodium falciparumsporozoite challenge in mice (2014)

Malaria caused by Plasmodium falciparum kills nearly one million children each year and imposes crippling economic burdens on families and nations worldwide. No licensed vaccine exists, but infection can be prevented by antibodies against the circumsporozoite protein (CSP), the major surface protein of sporozoites, the form of the parasite injected by mosquitoes. We have used vectored immunoprophylaxis (VIP), an adeno-associated virus-based technology, to introduce preformed antibody genes encoding anti-P. falciparum CSP mAb into mice. VIP vector-transduced mice exhibited long-lived mAb expression at up to 1,200 µg/mL in serum, and up to 70% were protected from both i.v. and mosquito bite challenge with transgenic Plasmodium berghei rodent sporozoites that incorporate the P. falciparum target of the mAb in their CSP. Serum antibody levels and protection from mosquito bite challenge were dependent on the dose of the VIP vector. All individual mice expressing CSP-specific mAb 2A10 at 1 mg/mL or more were completely protected, suggesting that in this model system, exceeding that threshold results in consistent sterile protection. Our results demonstrate the potential of VIP as a path toward the elusive goal of immunization against malaria.
Isolation, Identification, and Characterization of Small Bioactive Peptides From Lactobacillus GG Conditional Media That Exert Both Anti‐Gram‐negative and Gram‐positive Bactericidal Activity (2009)

Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity. NPSRQERR showed the most potent antibacterial effect that was detected both in Gram-negative and Gram-positive microorganisms. These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.
Compensation schemes and performance analysis of IQ imbalances in OFDM receivers (2005)

The implementation of orthogonal frequency division multiplexing (OFDM)-based physical layers suffers from the effect of In-phase and Quadrature-phase (IQ) imbalances in the front-end analog processing. The IQ imbalances can severely limit the achievable operating signal-to-noise ratio (SNR) at the receiver and, consequently, the supported constellation sizes and data rates. In this paper, the effect of IQ imbalances on OFDM receivers is studied, and system-level algorithms to compensate for the distortions are proposed. The algorithms include post-fast Fourier transform (FFT) least-squares and least mean squares (LMS) equalization, as well as pre-FFT correction using adaptive channel/distortion estimation and special pilot tones to enable accurate and fast training. Bounds on the achievable performance of the compensation algorithms are derived and evaluated as a function of the physical distortion parameters. A motivation is included for the physical causes of IQ imbalances and for the implications of the approach presented in this paper on designing and implementing wireless transceivers.
Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes. (1992)

It is possible to estimate shock gradient fields in three dimensions. Of the four configurations tested, V----A+P produced the highest gradients and V+A----P produced the lowest high gradient. The gradient fields were uneven throughout the ventricles.
Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer (2019)

In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.<i>See related commentary by Meador and Oxnard, p. 4583</i>.
Chemical Modification of Thiangazole A in the Oxazole and Styryl Region (1999)

The partial synthesis of 54 derivatives of thiangazole A (1a), a new polythiazoline antibiotic from Polyangium spec. (myxobacteria), is described. Derivatives with chemical modification of the carboxamide group in the oxazole region were prepared either by N-alkylation to amides 5–14 or by methanolysis to ester 15, and its transformation products 16, 19, 20. Oxidation of the C-5 methyl group of 1a with molecular oxygen led to the hydroxymethyl derivative 21, and two by-products lacking the C-5 methyl group (22), or the entire oxazole ring (23). Key intermediate for analogues with modifications in the styryl region is the aldehyde 27, obtained by direct cleavage of the C-21/C-22 double bond. 27 was transformed into the oximes 37–42 and by Wittig reaction to (21Z)-thiangazole (43) and analogues 44–46 with proton and alkyl residues replacing phenyl. 21,22-Didehydrothiangazole (50) was synthesized in a multi-step reaction from 27 via the 20-alkinyl intermediate 49. The insecticidal activities and inhibition of the respiratory chain (complex I) by the thiangazole analogues were determined and compared with the natural product.
Diastereoselective Syntheses of N-Protected Derivatives of 1α,5α,6β-6-Amino-3-azabicyclo[3.1.0]hexane; A Route to Trovafloxacin 6β-Diastereomer (1998)

trovafloxacin 6β-diastereomer - synthesis - chloroenamines - N-protected 1α,5α,6β-6-amino-3-azabicyclo[3.1.0]hexanes
Hydrodynamic characteristics of jet‐spouted beds (1983)

Abstract Jet‐spouted beds characterised by high velocity gas jets (above 1.7 U msl ), and shallow bed depths H 0 of around 2 D 1 were investigated on laboratory scale beds and industrial scale beds and the results obtained thereof are correlated and presented in this work. Compared with the classical spouted beds, important differences in bed structure, solid movements and basic hydrodynamic characteristics were observed. The minimum spouting velocity, bed voidage and pressure drop during stabilized spouting are described in terms of dimensionless equations. Bed expansion was used as the basis for the classification of different jet‐spouting regimes (incoherent spouting, fast spouting, pneumatic conveying) and changes in the slope of the bed expansion curve are correlated with regime changes. This classification could be useful in the optimization of industrial scale jet‐spouted beds. A typically applicable regime of fast spouting was identified.
Inflammation and Adaptive Immunity in Parkinson's Disease (2011)

The immune system is designed to protect the host from infection and injury. However, when an adaptive immune response continues unchecked in the brain, the proinflammatory innate microglial response leads to the accumulation of neurotoxins and eventual neurodegeneration. What drives such responses are misfolded and nitrated proteins. Indeed, the antigen in Parkinson's disease (PD) is an aberrant self-protein, although the adaptive immune responses are remarkably similar in a range of diseases. Ingress of lymphocytes and chronic activation of glial cells directly affect neurodegeneration. With this understanding, new therapies aimed at modulating the immune system's response during PD could lead to decreased neuronal loss and improved clinical outcomes for disease.
Chromosome t(11;14)(q13;q32) breakpoints in centrocytic lymphoma are highly localized at the bcl-1 major translocation cluster. (1993)

Chromosome 11q13 translocation breakpoints have been found dispersed over more than 100 kb of genomic DNA in centrocytic lymphoma and lymphocytic lymphoma of intermediate differentiation (mantle cell lymphoma). Approximately one-half of these translocations occur at the bcl-1 major translocation cluster (MTC) and appear tightly clustered by Southern blot restriction mapping. In order to specifically characterize these t(11;14)(q13;q32) translocations, six cases of centrocytic lymphoma with MTC rearrangements on Southern blot were studied. Genomic DNA was amplified by PCR (polymerase chain reaction) using a consensus immunoglobulin heavy-chain joining gene (JH) primer and two separate MTC primers. Sequencing of the PCR products revealed the MTC breakpoints in all six cases to be clustered within a 61 basepair span, very similar to those previously reported in t(11;14)-containing human B-cell lines. No two breakpoints were identical. JH breakpoints involved JH4 in five cases and JH6 in the other. Tight clustering of the MTC breakpoints thus permits PCR detection of the t(11;14) in many cases of centrocytic lymphoma, which may be of value in classifying this subtype of non-Hodgkin's lymphoma.
Stabilization of the speckle pattern of a multimode fiber undergoing bending (1996)

The propagation of light in a multimode optical fiber waveguide results in speckle, a complicated mapping of the input field onto the output field. The speckle pattern changes as the fiber undergoes twists and bends. We show theoretically and demonstrate experimentally that changes in the mapping caused by bends in one region of the fiber can be compensated with bends applied along a fixed region of the fiber. In this way the output speckle pattern of the fiber can be stabilized. In this method it is supposed that the modes evolve adiabatically without intermixing and that the analytical dependence of perturbed propagation eigenvalues of the modes follows R(-2) behavior, where R is the local value of bend radius.
A randomised, blinded, controlled field study to assess the efficacy and safety of lotilaner tablets (Credelio™) in controlling fleas in client-owned dogs in European countries (2017)

Under field conditions in Europe, lotilaner flavoured chewable tablets were greater than 99% effective in eliminating fleas from dogs at the first post-treatment assessment (Day 14). Efficacy was maintained through Day 84, with corresponding improvements in FAD. Lotilaner tablets were palatable and safe and provided superior flea control to fipronil.
α3 Domain Mutants of Peptide/MHC Class I Multimers Allow the Selective Isolation of High Avidity Tumor-Reactive CD8 T Cells (2003)

The goal of adoptive T cell therapy in cancer is to provide effective antitumor immunity by transfer of selected populations of tumor Ag-specific T cells. Transfer of T cells with high TCR avidity is critical for in vivo efficacy. In this study, we demonstrate that fluorescent peptide/MHC class I multimeric complexes incorporating mutations in the alpha3 domain (D227K/T228A) that abrogate binding to the CD8 coreceptor can be used to selectively isolate tumor Ag-specific T cells of high functional avidity from both in vitro expanded and ex vivo T cell populations. Sorting, cloning, and expansion of alpha3 domain mutant multimer-positive CD8 T cells enabled rapid selection of high avidity tumor-reactive T cell clones. Our results are relevant for ex vivo identification and isolation of T cells with potent antitumor activity for adoptive T cell therapy.
Intestinal Rehabilitation and the Short Bowel Syndrome: Part 2 (2004)

The management of patients with intestinal failure due to short bowel syndrome is complex, requiring a comprehensive approach that frequently necessitates long-term, if not life-long, use of parenteral nutrition. Despite tremendous advances in the provision of parenteral nutrition over the past three decades, which have allowed significant improvements in the survival and quality of life of these patients, this mode of nutritional support carries with it significant risks to the patient, is very costly, and ultimately, does not attempt to improve the function of the remaining bowel. Intestinal rehabilitation refers to the process of restoring enteral autonomy, and thus, allowing freedom from parenteral nutrition, usually by means of dietary, medical, and occasionally, surgical strategies. While recent investigations have focused on the use of trophic substances to increase the absorptive function of the remaining gut, whether intestinal rehabilitation occurs as a consequence of enhanced bowel adaptation or is simply a result of an optimized, comprehensive approach to the care of these patients remains unclear. In Part 1 of this review, we provided an overview of short bowel syndrome and pathophysiological considerations related to the remaining bowel anatomy in these patients. We also reviewed intestinal adaptation and factors that may enhance the adaptive process, focusing on evidence derived from animal studies. In Part 2, relevant data on the development of intestinal adaptation in humans are reviewed as is the general management of short bowel syndrome. Lastly, the potential benefits of a multidisciplinary intestinal rehabilitation program in the care of these patients are also discussed.
C3 nephritic factor (C3NeF): stabilization of fluid phase and cell-bound alternative pathway convertase. (1976)

C3 nephritic factor (C3NeF) defined by the capacity of nephritic serum and its fractions to initiate loss of the B antigen of C3 in normal serum was purified from the serum of three different donors and shown to function by stabilization of membrane-bound and fluid phase alternative pathway C3 convertase. C3NeF converts cell-bound C3B sites in a dose-related manner to CEB(NeF) sites, which exhibit an approximate 10-fold increase in half-life. The linear relationship between the C3NeF input and the residual hemolytic sites on EAC43B present after incubation for 20 min at 30 degrees C, during which labile C3B sites have decayed, indicates that the number of residual C3B sites is directly related to the dose of C3NeF. The capacity of C3NeF to stabilize the C3B convertase in a temperature- and dose-dependent manner, which is independent of binding or consumption of C3NeF, in a fluid phase reaction mixture of 125I-B, 131I-C3 and D permits isolation of a 10S complex containing radiolabeled C3 and B and exhibiting C3, convertase activity on an exogenous C3 source. Thus, the stabilizing effect of C3NeF is not limited to membrane-bound C3B but is also sufficient to permit recovery of a fluid phase C3 convertase formed during the interaction of C3, B, and D.
Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination (2010)

Ig and T-cell receptor (TCR) variable-region gene exons are assembled from component variable (V), diversity (D) and joining (J) gene segments during early B and T cell development. The RAG1/2 endonuclease initiates V(D)J recombination by introducing DNA double-strand breaks at borders of the germ-line segments. In mice, the Ig heavy-chain (IgH) locus contains, from 5' to 3', several hundred V(H) gene segments, 13 D segments, and 4 J(H) segments within a several megabase region. In developing B cells, IgH variable-region exon assembly is ordered with D to J(H) rearrangement occurring on both alleles before appendage of a V(H) segment. Also, IgH V(H) to DJ(H) rearrangement does not occur in T cells, even though DJ(H) rearrangements occur at low levels. In these contexts, V(D)J recombination is controlled by modulating substrate gene segment accessibility to RAG1/2 activity. To elucidate control elements, we deleted the 100-kb intergenic region that separates the V(H) and D clusters (generating ΔV(H)-D alleles). In both B and T cells, ΔV(H)-D alleles initiated high-level antisense and, at lower levels, sense transcription from within the downstream D cluster, with antisense transcripts extending into proximal V(H) segments. In developing T lymphocytes, activated germ-line antisense transcription was accompanied by markedly increased IgH D-to-J(H) rearrangement and substantial V(H) to DJ(H) rearrangement of proximal IgH V(H) segments. Thus, the V(H)-D intergenic region, and likely elements within it, can influence silencing of sense and antisense germ-line transcription from the IgH D cluster and thereby influence targeting of V(D)J recombination.
Specific Protein-Membrane Contacts Are Required for Prepore and Pore Assembly by a Cholesterol-dependent Cytolysin (2007)

Three short hydrophobic loops and a conserved undecapeptide at the tip of domain 4 (D4) of the cholesterol-dependent cytolysins (CDCs) mediate the binding of the CDC monomers to cholesterol-rich cell membranes. But intermedilysin (ILY), from Streptococcus intermedius, does not bind to cholesterol-rich membranes unless they contain the human protein CD59. This observation suggested that the D4 loops, which include loops L1-L3 and the undecapeptide, of ILY were no longer required for its cell binding. However, we show here that membrane insertion of the D4 loops is required for the cytolysis by ILY. Receptor binding triggers changes in the structure of ILY that are necessary for oligomerization, but membrane insertion of the D4 loops is critical for oligomer assembly and pore formation. Defects that prevent membrane insertion of the undecapeptide also block assembly of the prepore oligomer, while defects in the membrane insertion of the L1-L3 loops prevent the conversion of the prepore oligomer to the pore complex. These studies reveal that pore formation by ILY, and probably other CDCs, is affected by an intricate and coupled sequence of interactions between domain 4 and the membrane.
Conserved amino acids in metal-binding motifs of PDE3A are involved in substrate and inhibitor binding (2000)

The activity of phosphodiesterase (PDE)3A requires divalent cations. Putative metal-binding sites are expected at 2 highly conserved metal-binding motifs, HXXXH(X)25E. A functional truncated recombinant PDE3A containing the catalytic domain (PDE3A▵1) and mutant proteins were expressed in a baculovirus/Sf9 cell system. All the mutant proteins had decreased catalytic efficiency (kcat/Km). Mutants H752A, H756A, and E825A had kcat of less than 0.0008 s−1 to 0.0475 s−1 compared to PDE3A▵1, with 1.86 second−1, with unchanged Km. Although E866A had a kcat of 0.235 s−1, the Kmfor cyclic adenosine monophosphate (cAMP) was increased 11-fold and the Ki for cyclic guanosine monophosphate (cGMP) was 27-fold higher than PDE3A▵1. The Ki of H836A for cGMP was 177-fold higher than that of PDE3A▵1. The Km for E971A was 5-fold higher than PDE3A▵1. These results suggest that the cAMP and cGMP binding sites are overlapping, but not identical, involving both common and different amino acids. Mutants E825A, H836A, and E866A showed low activity in a metal ion-free assay; however, their enzymatic activities were increased 4- to 10-fold in buffers containing Mn2+, Mg2+, or Co2+. This observation indicates that conserved amino acids in the second metal-binding motif might not be involved in binding divalent cations but may serve other functions such as substrate or inhibitor binding in PDE3A.
The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. (1979)

In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells.
In vitro and in vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression (1997)

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4(+)CD8- thymocytes in DR alpha 30A0/0 beta 20/0 and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.
A Graphite-Assisted Laser Desorption/Ionization Study of Light-Induced Aging in Triterpene Dammar and Mastic Varnishes (1998)

The light-induced aging of natural triterpenes used in varnishes was studied using graphite-assisted laser desorption/ionization mass spectrometry. This method was found to be superior to conventional matrix-assisted laser desorption/ionization for these materials because of higher signal levels and less chemical noise from the matrix. The dammar and mastic raw materials were found to be partially oxidized compared to their nominal composition, with up to six oxygens incorporated. The light-induced aging process leads initially to polymerization, up to trimers. Further aging leads to a decrease in average molecular weight. These observations are supplemented by FTIR and 13C NMR spectra which show complete reaction of keto groups to acids and peroxy species. A general mechanism for the process is proposed, and the consequences for properties of varnish films are investigated.