gebhart/patrepeval huggingface dataset:
Strain-Specific Pulmonary Defense Achieved after Repeated Airway Immunizations with Non-Typeable Haemophilus Influenzae in a Mouse Model (2006)

Strain-specific immune responses may play a critical role in the acute exacerbation of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of surface antigens of NTHi, which may contribute to the strain-specific protective immunity. We examined whether repeated airway immunizations with killed-NTHi strains bearing different P2 molecules were capable of inducing protective immunity against homologous or heterologous strains in the lungs of a mouse model. Three different strains of NTHi were used in this study. Three serial intratracheal (IT) immunizations of a single strain or three different strains of NTHi led to the production of cross-reactive immunoglobulins G and A in bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain enhanced the bacterial clearance of the homologous strain in the lungs, but no enhancement of bacterial clearance was found with three serial IT immunizations of heterologous strains. The enhancement in bacterial clearance, therefore, appears to be primarily strain-specific. Enhanced bacterial clearance of a heterologous strain was also found after three serial IT immunizations of a single strain among two of the three strains employed for bacterial challenge. These findings suggest that P2 molecules and surface antigens other than P2 are involved in the development of pulmonary defense against NTHi in mice. Our data may explain, in part, why patients with COPD experience recurrent NTHi infections.
Ester hydrolysis and conjugation reactions in intact skin and skin homogenate, and by liver esterase of rabbits (1992)

1. Procaine, 2-chloroprocaine, ethyl aminobenzoate and methyl salicylate were added at various concentrations to liver esterase, supernatant of skin homogenate, or single-pass perfused ears of rabbits. 2. Vmax of product formation by purified liver esterase correlated with the rank order of the distribution coefficients (n-octanol/buffer) of the substrates and ranged between 11 and 1100 pmol/min per micrograms protein. Km values were between 20 and 50 microM. 3. No correlation was observed when the apparent enzyme kinetics, calculated by non-linear adaptation, were compared with each other after substrate administration to skin, arterial influx, or incubation with skin homogenate. 4. An acid labile conjugate of ethyl 4-aminobenzoate was found, mainly during arterial perfusion and in supernatant of skin homogenate, after administration of ethyl 4-aminobenzoate. 5. Acetamidobenzoic acid was observed in quantities of about 10% of the free 4-aminobenzoic acid during dermal or arterial application of procaine. This metabolite was not found with ethyl 4-aminobenzoate. 6. The results from isolated rabbit ear perfusion differ quantitatively and qualitatively with those obtained from supernatant of skin homogenate or purified liver esterase.
Kramers–Kronig holographic imaging for high-space-bandwidth product (2019)

Modern optical imaging possesses a huge information capacity whose corresponding space-bandwidth product (SBP) reaches tens of megapixels. However, despite the advances in optical and electronic devices, the SBP of an optical microscope is greatly limited, resulting in a reduced field of view or resolution of an image. In this paper, we exploit the Kramers–Kronig relations in digital holography to achieve high SBP imaging, demonstrating a complex amplitude image that can surpass the SBP of a bright-field image. The capability of the proposed method is demonstrated by imaging static samples and biological tissues. We successfully measure a 4.2-megapixel complex amplitude image whose bright-field counterpart exhibits 16.7 megapixels.
Grace A. Goldsmith Award lecture. Trace element regulation of immunity and infection. (1985)

Protein-calorie malnutrition is associated with impaired immunocompetence and increased susceptibility to infection. Clinically evident nutritional deficiency syndromes, however, are composite of deficits of many essential nutrients, each of which may exert an important regulating effect on immunity. Among other nutrients, several trace elements have been shown to regulate immune responses, particularly cell-mediated immunity. Zinc undernutrition results in lymphoid atrophy and reduced capacity to respond to many T-cell-dependent antigens. Plaque forming cell response to heterologous erythrocytes is decreased, as is the function of B cells. In zinc deficient rodents, the generation of cytotoxic lymphocytes in the spleen is reduced. Antibody-dependent cell-mediated cytotoxicity is largely unchanged. In acrodermatitis enteropathica, lymphocyte proliferation response to mitogens is decreased and there are significant changes in delayed hypersensitivity responses and in the proportion of various T cell subsets. Neutrophil function is not changed by zinc deficiency. Iron deficiency results in a slight decrease in the number of rosette-forming T cells and a significant impairment of lymphocyte response to mitogens and antigens. Polymorphonuclear leukocytes are unable to kill ingested bacteria and fungi in an efficient manner. Copper deficiency impairs cell-mediated immunity, as does selenium deficiency when it is associated with vitamin E lack. Several pathogenetic mechanisms may underlie such alterations in immunity. Many heavy metals impair immune responses. These effects of trace elements on immunity may have important fundamental and practical implications.
Layered Lithium Insertion Material of LiNi1/2Mn1/2O2 : A Possible Alternative to LiCoO2 for Advanced Lithium-Ion Batteries (2001)

Abstract We have successfully prepared a layered nickel manganese oxide of LiNi1/2Mn1/2O2 (a = 2.89 Å and c = 14.30 Å in hexagonal setting) and shown that this material may be a possible alternative to LiCoO2 for advanced lithium batteries in terms of the operating voltage, rechargeable capacity, cycleability, safety, and materials economy.
Alphavirus Replicon Particles as Candidate HIV Vaccines (2002)

Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIVsm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIVsm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIVsm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.
Silicon α-Effect: A Systematic Experimental and Computational Study of the Hydrolysis of Cα- and Cγ-Functionalized Alkoxytriorganylsilanes of the Formula Type ROSiMe2(CH2)nX (R = Me, Et;n= 1, 3; X = Functional Group) (2014)

To understand the silicon α-effect in terms of an enhanced reactivity of the Si–OC bond of α-silanes of the formula type ROSiMe2CH2X compared to analogous γ-silanes ROSiMe2(CH2)3X (R = Me, Et; X = functional group), a systematic experimental and computational study of the kinetics and mechanisms of hydrolysis of such compounds was performed. For this purpose, a series of suitable model compounds was synthesized and studied for their hydrolysis kinetics in CD3CN/D2O under basic and acidic conditions, using 1H NMR spectroscopy as the analytical tool. To get more information about the reaction mechanisms, the experimental investigations were complemented by computational studies. These investigations demonstrated that the silicon α-effect cannot be rationalized in terms of a special single effect. The reactivities observed rather result from a summation of different components, such as electronic and steric effects, pD dependence, and hydrogen bonds between the functional group (or even protonated functional group) and the alkoxy leaving group. Therefore, the term “silicon α-effect” should not be used furthermore to explain the hydrolysis reactivity at the silicon atom of alkoxyorganylsilanes with functional groups in α- or γ-position of the organyl groups (so-called α- or γ-silanes).
Recognition of Native Hepatitis C Virus E1E2 Heterodimers by a Human Monoclonal Antibody (2002)

The majority of hepatitis C virus (HCV)-infected individuals progress from acute to chronic disease, despite the presence of a strong humoral immune response to the envelope glycoproteins E1 and E2. When expressed in mammalian cells, E1 and E2 form both noncovalently linked E1E2 heterodimers, believed to be properly folded, and disulfide-linked, high-molecular-weight aggregates that are misfolded. Previously, we identified 10 human monoclonal antibodies (HMAbs) that bind E2 glycoproteins from different genotypes. Here we demonstrate that one of these HMAbs, CBH-2, is unique in its ability to distinguish between properly folded and misfolded envelope proteins. This HMAb recognizes HCV-E2 only when complexed with E1. The E1E2 complexes recognized by CBH-2 are noncovalently linked heterodimers and not misfolded disulfide-linked, high-molecular-weight aggregates. The E1E2 heterodimers seen by CBH-2 no longer associate with the endoplasmic reticulum chaperone calnexin and are likely to represent the prebudding form of the HCV virion.
Exploiting drug-disease relationships for computational drug repositioning (2011)

Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients. As the ability to measure molecules in high-throughput ways has improved over the past decade, it is logical that such data might be useful for enabling drug repositioning through computational methods. Many computational predictions for new indications have been borne out in cellular model systems, though extensive animal model and clinical trial-based validation are still pending. In this review, we show that computational methods for drug repositioning can be classified in two axes: drug based, where discovery initiates from the chemical perspective, or disease based, where discovery initiates from the clinical perspective of disease or its pathology. Newer algorithms for computational drug repositioning will likely span these two axes, will take advantage of newer types of molecular measurements, and will certainly play a role in reducing the global burden of disease.
Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states (2014)

Chronic pain is a global burden that promotes disability and unnecessary suffering. To date, efficacious treatment of chronic pain has not been achieved. Thus, new therapeutic targets are needed. Here, we demonstrate that increasing endogenous adenosine levels through selective adenosine kinase inhibition produces powerful analgesic effects in rodent models of experimental neuropathic pain through the A3 adenosine receptor (A3AR, now known as ADORA3) signalling pathway. Similar results were obtained by the administration of a novel and highly selective A3AR agonist. These effects were prevented by blockade of spinal and supraspinal A3AR, lost in A3AR knock-out mice, and independent of opioid and endocannabinoid mechanisms. A3AR activation also relieved non-evoked spontaneous pain behaviours without promoting analgesic tolerance or inherent reward. Further examination revealed that A3AR activation reduced spinal cord pain processing by decreasing the excitability of spinal wide dynamic range neurons and producing supraspinal inhibition of spinal nociception through activation of serotonergic and noradrenergic bulbospinal circuits. Critically, engaging the A3AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states. These studies reveal A3AR activation by adenosine as an endogenous anti-nociceptive pathway and support the development of A3AR agonists as novel therapeutics to treat chronic pain.
Immunization of mice with lipopeptides bypasses the prerequisite for adjuvant. Immune response of BALB/c mice to human immunodeficiency virus envelope glycoprotein (1992)

In vivo priming of CTL requires the association with MHC class I molecules of peptides derived from the processing of endogenously produced proteins. Immunization with exogenous proteins or peptides rarely induces MHC class I-restricted CTL unless they are associated with lipidic compounds. The capacity to induce CTL was compared in synthetic peptides and simple lipopeptides containing the Immunodominant MHC class I H-2Dd-restricted T-cell epitope of HIV-1 gp160. In contrast with free peptides in saline, lipopeptides induced strong primary CTL responses in vivo. These CTL were able to lyse cells infected with a recombinant vaccinia virus expressing the HIV-1 env gene. Priming of CTL was also successful when using 16-amino acid lipopeptides as 34-amino acid lipopeptides, suggesting that several epitopes might be included in a single construct. In vivo priming of CTL also requires CD4+ T cell help. We therefore searched for Th cell activation after priming with lipopeptides. Our results show that, as with CTL induction, Th cell activation with lipopeptides did not require mixing with adjuvant. In addition, lipopeptides were also efficient at stimulating antibody-mediated responses. Our results show that a single lipopeptidic construct can induce a total immune response, which is of importance in vaccine development.
Static Scheduling of Synchronous Data Flow Programs for Digital Signal Processing (1987)

Large grain data flow (LGDF) programming is natural and convenient for describing digital signal processing (DSP) systems, but its runtime overhead is costly in real time or cost-sensitive applications. In some situations, designers are not willing to squander computing resources for the sake of programmer convenience. This is particularly true when the target machine is a programmable DSP chip. However, the runtime overhead inherent in most LGDF implementations is not required for most signal processing systems because such systems are mostly synchronous (in the DSP sense). Synchronous data flow (SDF) differs from traditional data flow in that the amount of data produced and consumed by a data flow node is specified a priori for each input and output. This is equivalent to specifying the relative sample rates in signal processing system. This means that the scheduling of SDF nodes need not be done at runtime, but can be done at compile time (statically), so the runtime overhead evaporates. The sample rates can all be different, which is not true of most current data-driven digital signal processing programming methodologies. Synchronous data flow is closely related to computation graphs, a special case of Petri nets. This self-contained paper develops the theory necessary to statically schedule SDF programs on single or multiple processors. A class of static (compile time) scheduling algorithms is proven valid, and specific algorithms are given for scheduling SDF systems onto single or multiple processors.
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR (2008)

Regulatory T (Treg) cells safeguard against autoimmunity and immune pathology. Because determinants of the Treg cell fate are not completely understood, we have delineated signaling events that control the de novo expression of Foxp3 in naive peripheral CD4 T cells and in thymocytes. We report that premature termination of TCR signaling and inibition of phosphatidyl inositol 3-kinase (PI3K) p110alpha, p110delta, protein kinase B (Akt), or mammalian target of rapamycin (mTOR) conferred Foxp3 expression and Treg-like gene expression profiles. Conversely, continued TCR signaling and constitutive PI3K/Akt/mTOR activity antagonised Foxp3 induction. At the chromatin level, di- and trimethylation of lysine 4 of histone H3 (H3K4me2 and -3) near the Foxp3 transcription start site (TSS) and within the 5' untranslated region (UTR) preceded active Foxp3 expression and, like Foxp3 inducibility, was lost upon continued TCR stimulation. These data demonstrate that the PI3K/Akt/mTOR signaling network regulates Foxp3 expression.
Site-directed mutagenesis of the Cys residues in ClpA, the ATPase component of protease Ti (ClpAP) in Escherichia coli. (1997)

The ATP-dependent casein hydrolysis by protease Ti (ClpAP) has been shown to be inhibited by sulfhydryl blocking agents, such as N-ethylmaleimide (NEM), when preincubated with ClpA but not with ClpP. To define the role of three Cys residues in ClpA, site-directed mutagenesis was performed to substitute each of them with Ser or Ala. None of the mutations showed any effect on the ATPase activity of ClpA or its ability to support the casein degradation by ClpP. However, NEM could no longer block the ability of ClpA/C47S or ClpA/C47A in supporting the ClpP-mediated proteolysis, unlike that of ClpA, ClpA/C203S, or ClpA/C243S. Furthermore, in the presence of NEM, casein could stimulate the ATPase activities of ClpA/C47S and ClpA/C47A and protect from their degradation by ClpP, but not of the other ClpA proteins. These results suggest that the inhibitory effect of NEM is due to prevention of the interaction of ClpA with casein by introduction of a bulky alkyl group to Cys47, but not linked to the catalytic function of the ATPase.
Quantification of Therapeutic miRNA Mimics in Whole Blood from Nonhuman Primates (2014)

MRX34, a microRNA (miRNA)-based therapy for cancer, has recently entered clinical trials as the first clinical candidate in its class. It is a liposomal nanoparticle loaded with a synthetic mimic of the tumor suppressor miRNA miR-34a as the active pharmaceutical ingredient. To understand the pharmacokinetic properties of the drug and to rationalize an optimal dosing regimen in the clinic, a method is needed to quantitatively detect the miRNA mimic. Here, we report the development and qualification of a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay in support of pharmacokinetic and toxicokinetic assessments in the nonhuman primate. Detection and quantification were performed on total ribonucleic acid (RNA) isolated from whole blood. The qualified range of the standard curve spans 6 orders of magnitude from 2.5 × 10(-7) to 2.5 × 10(-1) ng per reverse transcription (RT) reaction, corresponding to an estimated blood concentration from 6.2 × 10(-5) to 6.2 × 10(1) ng/mL. Our results demonstrate that endogenous as well as the exogenous miR-34a can be accurately and precisely quantified. The assay was used to establish the pharmacokinetic profile of MRX34, showing a favorable residence time and exposure of the miRNA mimic in whole blood from nonhuman primates.
RNA structural motifs: building blocks of a modular biomolecule (2005)

RNAs are modular biomolecules, composed largely of conserved structural subunits, or motifs. These structural motifs comprise the secondary structure of RNA and are knit together via tertiary interactions into a compact, functional, three-dimensional structure and are to be distinguished from motifs defined by sequence or function. A relatively small number of structural motifs are found repeatedly in RNA hairpin and internal loops, and are observed to be composed of a limited number of common 'structural elements'. In addition to secondary and tertiary structure motifs, there are functional motifs specific for certain biological roles and binding motifs that serve to complex metals or other ligands. Research is continuing into the identification and classification of RNA structural motifs and is being initiated to predict motifs from sequence, to trace their phylogenetic relationships and to use them as building blocks in RNA engineering.
ChemInform Abstract: TRIAZOLO(4,5‐D)PYRIMIDINES. VII. THE PHOTOCHEMICAL TRANSFORMATION OF 3‐PHENYL‐3H‐1,2,3‐TRIAZOLO(4,5‐D)PYRIMIDINES INTO 9H‐PYRIMIDO(4,5‐B)INDOLES (1981)

Abstract Die Triazolopyrimidine (I) liefern bei der Bestrahlung Gemische der Pyrimidinderivate (II)‐(IV).
TMPRSS2/ERG fusion gene expression alters chemo‐ and radio‐responsiveness in cell culture models of androgen independent prostate cancer (2011)

The effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity and chemosensitivity depending on cell line and fusion type. Further work is needed with clinical samples to establish whether TMPRSS2/ERG gene fusions affect radio- and chemosensitivity in vivo.
Linux Device Drivers, 1st Ed (1998)

Objective - study of the features of Trichomonas vaginalis invasion in pregnant women and newborns. The cultures of Trichomonas isolated from a pregnant woman, her newborn girl, as well as amniotic fluid were examined. The ultrastructure of the cells was studied using a TEM-125K microscope equipped with a SAI-01A system (SELMI), using a DX 2 CCD camera and the KAPPA software package. The verification of STI pathogens was carried out by PCR, in particular, Trichomonas tenax and Pentatrichomonas hominis were identified by experimental original primers that were developed using real-time PCR (PCR-RT). The invasion of Trichomonas vaginalis of the genital tract of a newborn girl, amniotic fluid and amniotic membrane is characterized clinically and instrumentally. We proved the possibility of Trichomonas vaginalis invasion of newborn children not only during the passage of the child through the infected birth canal, but also due to a defect in the fetal membranes with the development of chorioamnionitis, followed by infection of the amniotic fluid and possible infection of the fetus.