gebhart/patrepeval huggingface dataset:
Quantitation of Bacteria in Bone Marrow from Patients with Typhoid Fever: Relationship between Counts and Clinical Features (2001)

Enteric fever is the only bacterial infection of humans for which bone marrow examination is routinely recommended. A prospective study of the concentrations of bacteria in the bone marrow and their relationship to clinical features was conducted with 120 Vietnamese patients with suspected enteric fever, of whom 89 had confirmed typhoid fever. Ninety-three percent of the Salmonella enterica serovar Typhi samples isolated were resistant to ampicillin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicated typhoid and satisfactory bone marrow aspirates, the number of serovar Typhi CFU in bone marrow aspirates was a median value of 9 (interquartile range [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; range, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of individual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5). The number of bacteria in blood but not bone marrow was correlated inversely with the duration of preceding fever. Thus, with increasing duration of illness the ratio of bone marrow-to-blood bacterial concentrations increased; the median ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, 60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, reflecting the higher concentration of intracellular serovar Typhi in the bone marrow. Effective antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatment than bacteria in the blood. The numbers of bacteria in bone marrow correlated negatively with the white blood cell (R = -0.3, P = 0.006) and platelet counts (R = -0.32, P = 0.01) and positively with fever clearance time after treatment (R = 0.4, P < 0.001). The bacterial load in bone marrow therefore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.
Evolutionary link between prokaryotic and eukaryotic K+ channels. (1998)

Considering the importance of K+ channels in controlling the crucial K+ gradient across the plasma membranes of all living cells, it comes as no surprise that, besides being present in every eukaryotic cell, these integral membrane proteins have recently also been identified in prokaryotes. Today, approximately a dozen successfully completed and many more ongoing sequencing projects permit a search for genes related to K+ channels in the genomes of both eubacteria and archaea. The coding regions of homologues show a remarkable variety in primary structure. They predict membrane proteins with one, two, three and six hydrophobic segments surrounding a putative K(+)-selective pore (H5) and the presence or absence of a cytosolic putative NAD(+)-binding domain (PNBD) that probably senses the reducing power of the cell. The analysis of kinships on the basis of phylogenetic algorithms identifies sequences closely related to eukaryotic voltage-dependent Kv channels, but also defines members of a primordial class of prokaryotic K+ channel (containing the 2TMS/PNBD motif). Considering the unique mechanisms that may account for the assembly of modern proteins from different ancestral genes, and with more primary sequence data soon to appear, a scheme for the evolutionary origin of K+ channels comes within reach.
Polyamidoamine Dendrimers with a Modified Pentaerythritol Core Having High Efficiency and Low Cytotoxicity as Gene Carriers (2009)

Polyamidoamine (PAMAM) dendrimers represent one of the most efficient polymeric gene carriers. This study describes a new family of PAMAM dendrimers that can be synthesized using a Pentaerythritol derivative (PD) as a core that possesses 12 branches. This new approach in the synthesis of divergent dendrimers provided a rapid increase in the number of branches, which made it easier to obtain dendrimers with high generation and large enough molecular size. The PD dendrimers of generations 3-5 synthesized in this study could efficiently condense DNA into nanoscale complexes with slightly positive charges. Their transfection efficiency was evaluated in different cell lines. These PD dendrimers were found to show higher transfection efficiency, but much lower cytotoxicity, than the commercial nonviral gene carriers polyethyleneimine (PEI), polylysine (PLL), and PAMAM dendrimers with an ethylenediamine core (generations 5 and 7). The results indicate that, with high transfection efficiency and low cytotoxicity, the PD dendrimers hold promise as novel nonviral gene carriers.
Comparative Photodynamic Therapy of B16 Pigmented Melanoma with Different Generations of Sensitizers (1999)

In order to apply photodynamic therapy to pigmented neoplasms, comparative photosensitizing studies of B 16 pigmented melanoma in C 57 B 1/6 mice were carried out with haematoporphyrin derivative (HpD), zinc(II) phthalocyanine ( ZnPc ), zinc(II) naphthalocyanine ( ZnNc ) and tetrabenzamido-substituted zinc(II) naphthalocyanine ( ZnNcA ). By injection of the optimal drug concentration and application of the optimal dose of light irradiation (the emission of the laser dye corresponding to the λ max value of the respective sensitizer) a phototherapeutic effect was observed only after photosensitization with the longest-wavelength-absorbing sensitizer, namely ZnNcA . It is supposed that the detected, through different assessment criteria, promising phototherapeutic effect after ZnNcA photosensitization of B 16 pigmented melanoma in mice is due to suitable structural, photophysical and photochemical properties of this sensitizer, but not due to a hyperthermic effect. This assumption is supported by the results obtained after irradiation of B 16 pigmented melanoma-bearing mice with the same fluence rate and fluence but without the sensitizer. In this case the tumour temperature did not increase by more than 35 °C and no changes in the mean tumour diameter or in the malignant subcellular components were detected.
Inhibition of the helper function of murine T cells with Fab'-anti-L3T4 ricin A chain immunotoxin. (1987)

The ability of Fab'-anti-L3T4 A chain-containing immunotoxins to inhibit the helper function of keyhole limpet hemocyanin-specific T helper lymphocytes was evaluated. Keyhole limpet hemocyanin-specific T helper cells were prepared from the lymph nodes of primed mice and were enriched for T cells. Enriched populations of trinitrophenyl-specific B cells were prepared from spleens of normal mice. In the presence of antigen, the keyhole limpet hemocyanin-specific T helper cells were able to induce proliferation and differentiation of the trinitrophenyl-specific B cells. However, when the T helper cells were first treated with an immunotoxin composed of Fab' fragments of anti-L3T4 antibody coupled to ricin A chain (Fab'-anti-L3T4-A), they failed to induce proliferation and differentiation of the antigen-specific B cells. The concentrations of Fab'-anti-L3T4-A required to inhibit T cell help for the proliferation and differentiation of trinitrophenyl-specific B cells by 50% were 1 X 10(-9)M and 4 X 10(-10) M, respectively. Fab'-anti-L3T4 antibody alone did not inhibit T cell-induced B cell proliferation and differentiation by 50% at greater than 100-fold higher concentrations.
Harvest of near infrared light in PbSe nanocrystal-polymer hybrid photovoltaic cells (2006)

We report a hybrid photovoltaic cell where PbSe nanocrystals were used to sensitize the conjugated polymer into the infrared. The device exhibited an incident monochromatic photon to current conversion efficiency of 1.3% at λ=805nm. Under 1 sun AM 1.5 illumination, the infrared response (780nm&amp;lt;λ&amp;lt;1600nm) of the embedded nanocrystals contributes to 33% of the overall photocurrent of the photovoltaic cell. The observed intensity dependences of the photocurrents have revealed the pseudomonomolecular recombination kinetics in the nanocrystal quantum dot polymer composite, indicating that the efficiency of the hybrid photovoltaic cells can be enhanced by reducing the potential barriers due to the ligand molecules at the surfaces of nanocrystals.
Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop. (1996)

In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28. Daily dose: 5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo.
Interactions of normal and mutant vesicular stomatitis virus matrix proteins with the plasma membrane and nucleocapsids (1994)

We demonstrated recently that a fraction of the matrix (M) protein of vesicular stomatitis virus (VSV) binds tightly to cellular membranes in vivo when expressed in the absence of other VSV proteins. This membrane-associated M protein was functional in binding purified VSV nucleocapsids in vitro. Here we show that the membrane-associated M protein is largely associated with a membrane fraction having the density of plasma membranes, indicating membrane specificity in the binding. In addition, we analyzed truncated forms of M protein to identify regions responsible for membrane association and nucleocapsid binding. Truncated M protein lacking the amino-terminal basic domain still associated with cellular membranes, although not as tightly as wild-type M protein, and could not bind nucleocapsids. In contrast, deletion of the carboxy-terminal 14 amino acids did not disrupt stable membrane association or nucleocapsid interaction. These results suggest that the amino terminus of M protein either interacts directly with membranes and nucleocapsids or stabilizes a conformation that is required for M protein to mediate both of these interactions.
(R)- and (S)-5,6,7,8-Tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-ylamine. Stereoselective interactions with 5-HT1A-receptors in the brain (1989)

The enantiomers of 5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-++ +ylamine (3) have been synthesized and evaluated for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor activity by use of behavioral and biochemical tests in rats. In addition, the ability of the compounds to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The absolute configuration of the enantiomers of 3 was determined indirectly by X-ray diffraction of (+)-(8R,alpha R)-5,6,7,8-tetrahydro-1-methoxy-N-(alpha-phenethyl)-9H- benzocyclohepten-8-ylamine hydrochloride (9.HCl), a resolved synthetic precursor. The stereoselectivity of the interaction of 3 with 5-HT1A receptors was more pronounced than that of 8-hydroxy-2-(dipropylamino)tetralin (1; 8-OH-DPAT); only (R)-3 displayed 5-HT activity. However, (R)-3 was of lower potency than any of the enantiomers of 1. The enantiomer (S)-3, which was found to be inactive as a 5-HT-receptor agonist, appeared to be a weakly potent DA-receptor agonist whereas (R)-3 seemed to be devoid of dopaminergic activity. The conformational preferences of 3 were studied by use of NMR spectroscopy and molecular mechanics calculations. Preferred conformations of (R)-3 are similar in shape to those of the stereoselective 5-HT1A-receptor agonist (2R,3S)-8-hydroxy-3-methyl-2-(dipropylamino)tetralin.
Radioimmunotherapy and colorectal cancer (2005)

RIT might be an effective adjuvant treatment modality in colorectal cancer. Future studies should focus on its application in patients with small-volume or minimal residual disease.
Crystal Structure of Chiral γPNA with Complementary DNA Strand: Insights into the Stability and Specificity of Recognition and Conformational Preorganization (2010)

We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple-wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete gamma-backbone modification ("gammaPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular gammaPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred P-helical conformation upon hybridization with DNA. The unusual structural adaptability found in the gammaPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral gammaPNA is preorganized and stabilized, before and after hybridization with a cDNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology, and medicine.
Autoimmune Pancreatitis: Disease Evolution, Staging, Response Assessment, and CT Features That Predict Response to Corticosteroid Therapy (2008)

CT features like diffuse swelling and halo respond favorably to CST and likely reflect an early inflammatory phase, whereas features like ductal strictures and focal masslike swelling are predictive of a suboptimal response and symbolize a late stage with predominance of fibrosis.
Stem Cells, Regenerative Medicine, and Animal Models of Disease (2007)

The field of stem cell biology and regenerative medicine is rapidly moving toward translation to clinical practice, and in doing so has become even more dependent on animal donors and hosts for generating cellular reagents and assaying their potential therapeutic efficacy in models of human disease. Advances in cell culture technologies have revealed a remarkable plasticity of stem cells from embryonic and adult tissues, and transplantation models are now needed to test the ability of these cells to protect at-risk cells and replace cells lost to injury or disease. With such a mandate, issues related to acceptable sources and controversial (e.g., chimeric) models have challenged the field to provide justification of their potential efficacy before the passage of new restrictions that may curb anticipated breakthroughs. Progress from the use of both in vitro and in vivo regenerative medicine models already offers hope both for the facilitation of stem cell phenotyping in recursive gene expression profile models and for the use of stem cells as powerful new therapeutic reagents for cancer, stroke, Parkinson's, and other challenging human diseases that result in movement disorders. This article describes research in support of the following three objectives: (1) To discover the best stem or progenitor cell in vitro protocols for isolating, expanding, and priming these cells to facilitate their massive propagation into just the right type of neuronal precursor cell for protection or replacement protocols for brain injury or disease, including those that affect movement such as Parkinson's disease and stroke; (2) To discover biogenic factors--compounds that affect stem/progenitor cells (e.g., from high-throughput screening and other bioassay approaches)--that will encourage reactive cell genesis, survival, selected differentiation, and restoration of connectivity in central nervous system movement and other disorders; and (3) To establish the best animal models of human disease and injury, using both small and large animals, for testing new regenerative medicine therapeutics.
Josephson Effects in the Ba-Y-Cu-O Compounds (1987)

A point-contact Josephson junction between a bulk Ba-Y-Cu-O compound (${T}_{c}\ensuremath{\sim}90$ K) and a Nb needle has been made. The $I\ensuremath{-}V$ characteristics under microwave radiation show Shapiro steps, confirming the Josephson nature of the formed contact. Spin-singlet superconductivity in the Ba-Y-Cu-O system is implied from the voltage of the steps. The temperature dependence of the critical currents suggests that the Josephson junction if formed between Nb and another material with much higher ${T}_{c}$. Internal Josephson structure within the bulk ceramics is not found in the Ba-Y-Cu-O system.
Oligonucleotides—Assembled Au Nanorod-Assisted Cancer Photothermal Ablation and Combination Chemotherapy with Targeted Dual-Drug Delivery of Doxorubicin and Cisplatin Prodrug (2014)

External stimuli responsive dual drugs carrier was synthesized with Au nanorods (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5' thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into the duplexes. The cDNA designed with the 5' amine functional group assisted to tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated with the folic acid (FA) to target folate receptors overexpressed in the cancer cells. This targeting vehicle provided remote-controlled delivery of this high toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm diode laser irradiation. The dehybridization set the Dox free to bind the cell nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an active drug. The in vitro and in vivo studies revealed that this external stimulus responsive combination drug delivery was significantly effective.
Inhibitors of Apoptosis in Lymphocytes:  Synthesis and Biological Evaluation of Compounds Related to Pifithrin-α (2005)

The chemoprotection of cells from apoptosis induced by toxins or ionizing radiation could be important for biodefense and in the treatment of acute injuries. We describe a series of small heterocycles, including fused benzothiazoles, benzimidazoles, and related compounds, that abrogate thymocyte apoptosis induced by dexamethasone and gamma-irradiation. To optimize the protective activity of the previously reported pifithrin-alpha (PFT-alpha, 1), various derivatives and analogues of this and the corresponding ring-closed imidazobenzothiazole (IBT, 39) were synthesized. The aromatic analogues of 39 were more protective than 39, while the aromatic analogues of 1 were not active. Compound 19 containing a pyrrolidinyl substituent on the phenyl ring provided potent antiapoptotic activity (EC50 of 1.31 microM compared to 4.16 microM for 1). Modification of aromatic 39 with a pyrrolidinyl para substituent (compound 60) enhanced the activity, lowering the EC50 to 0.35 microM. Also, 60 provided significant protection against gamma-irradiation-induced apoptosis, as expected. Compounds 19 and 60 may be promising for potential clinical development.
Machine learning classifiers for glaucoma diagnosis based on classification of retinal nerve fibre layer thickness parameters measured by Stratus OCT (2010)

No differences between ANN and SVM were observed in this study. Both MLCs performed very well, with similar diagnostic performance. Input parameters have a larger impact on diagnostic performance than the type of machine classifier. Our results suggest that parameters based on transformed A-scan thickness measurements of the RNFL processed by machine classifiers can improve OCT-based glaucoma diagnosis.
Structural analysis of human 2′-O-ribose methyltransferases involved in mRNA cap structure formation (2014)

The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.
Intelligent Polymerized Crystalline Colloidal Arrays:  Novel Chemical Sensor Materials (1998)

We report the development of a novel sensing material that reports on analyte concentrations via diffraction of visible light from a polymerized crystalline colloidal array (PCCA). The PCCA is a mesoscopically periodic crystalline colloidal array (CCA) of spherical polystyrene colloids polymerized within a thin, intelligent polymer hydrogel film. CCAs are brightly colored, and they efficiently diffract visible light meeting the Bragg condition. The intelligent hydrogel incorporates chemical molecular recognition agents that cause the gel to swell in response to the concentration of particular analytes; the gel volume is a function of the analyte concentration. The color diffracted from the hydrogel film is, thus, a function of analyte concentration: the swelling of the gel changes the periodicity of the CCA, which results in a shift in the diffracted wavelength. We have fabricated a sensor, utilizing a crown ether as the recognition agent, that detects Pb2+ in the 0.1 μM−20mM (∼20 ppb−∼4000 ppm) concenration range. We have also fabricated glucose and galactose sensors, utilizing glucose oxidase or β-d-galactosidase as the recognition elements. The glucose oxidase sensor detects glucose in the 0.1−0.5 mM (18−90 ppm) concentration range in the presence of oxygen and detects as little as 10-12 M glucose (0.18 ppt) in the absence of oxygen. In addition, this sensor reports on dissolved oxygen concentration from ∼1 to 6 ppm in the presence of constant glucose concentrations.