gebhart/patrepeval huggingface dataset:
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis (1996)

As a paradigm for chronic infectious diseases, tuberculosis exhibits a variety of clinical presentations, ranging from primary pulmonary tuberculosis to reactivation tuberculosis and cavitary disease. To date, the animal models used in evaluating chemotherapy of tuberculosis have been high-dose intravenous models that mimic the disseminated forms of the disease. In the present study, we have used a low-dose aerosol exposure model which we feel better reflects newly diagnosed tuberculosis in patients converting to tuberculin positivity. As appropriate examples of chemotherapy, four rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) were tested, first in an in vitro murine macrophage model and then in the low-dose aerosol infection model, for their activity against Mycobacterium tuberculosis. In both models, KRM-1648 had the highest level of activity of the four compounds. In the infected-lung model, rifabutin, rifapentine, and KRM-1648 all had sterilizing activity when given orally at 5 mg/kg of body weight per day. When given at 2.5 mg/kg/day, KRM-1648 had the highest level of activity of the four drugs, reducing the bacterial load by 2.7 logs over 35 days of therapy.
Multi component EUV multilayer mirrors (2003)

It is well known that molybdenum and silicon is the combination with the highest EUV reflectivity of two-component multilayers in the wavelength range lambda=12.5-20nm. Using the magnetron sputter deposition method multilayers with reflectivities of typically 69% can be prepared. A further increase to R=70% was demonstrated by the introduction of tiny barrier layers (C and/or B4C) between the Mo and Si layers, which reduce the interdiffusion of both chemical elements. However, still higher reflectivities are desirable for the use of the multilayers as reflectors for EUV lithography. From model considerations we have concluded that the replacement of the Mo absorber layer by a multi-component layer consisting of two or three layers could result in an EUV reflectivity increase of up to 0.5% compared to the pure Mo/Si system assuming sharp interfaces without any roughness. Particularly Ag and Ru are promising candidates as additional elements within the absorber. Therefore we have systematically changed the thicknesses of the individual layers under the boundary condition of a fixed period thickness of dp=(6.90±0.05)nm. Microstructure and optical parameters of the multilayers have been investigated by HRTEM, X-ray diffractometry and Cu-Ka reflectometry. The most promising multilayers have also been characterized by EUV reflectometry.
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. (2020)

10006 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) leverages and enhances the body’s natural defense against cancer and has shown durable responses in heavily pretreated melanoma patients. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of efficacy &amp; safety of lifileucel in patients with unresectable metastatic melanoma who have progressed on checkpoint inhibitors and BRAF/MEK inhibitors, if BRAF v600 mutant. We report on Cohort 2 (N = 66) patients who have received TIL. Tumors were resected at local institutions, processed in central GMP facilities for TIL production, manufactured, cryopreserved &amp; shipped back to sites in a 22-day process. Therapy consisted of one week of lymphodepletion, a single lifileucel infusion, and up to 6 IL-2 doses. ORR was based on RECIST v1.1 by investigator assessment. Data cutoff was Feb 2, 2020. Results: Baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), high baseline tumor burden (106 mm mean target lesion sum of diameters), 44% liver/brain lesions, 40.9% LDH &gt; ULN. ORR by investigator was 36.4% (2 CR, 22 PR) and DCR was 80.3%. Mean time to response was 1.9 months (range: 1.3-5.6). After a median study follow-up of 17.0 months, median DOR (mDOR) was still not reached. Six responders have progressed, 2 have died and 2 started other anti-cancer therapy without progression. The adverse event profile was consistent with the underlying advanced disease and the lymphodepletion and IL-2 regimens. Additional follow-up data will be available for presentation. Conclusions: Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAF v600 mutant. Clinical trial information: NCT02360579.
Chemistry of Streptimidone, A New Antibiotic (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of Streptimidone, A New AntibioticRoger P. Frohardt, Henry W. Dion, Zbigniew L. Jakubowski, Albert Ryder, James C. French, and Quentin R. BartzCite this: J. Am. Chem. Soc. 1959, 81, 20, 5500–5506Publication Date (Print):October 1, 1959Publication History Published online1 May 2002Published inissue 1 October 1959https://pubs.acs.org/doi/10.1021/ja01529a059https://doi.org/10.1021/ja01529a059research-articleACS PublicationsRequest reuse permissionsArticle Views156Altmetric-Citations30LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Conjugates of Minor Groove DNA Binders with Oligodeoxynucleotides: Synthesis and Properties (1996)

Oligodeoxynucleotide conjugates of netropsin (Nt) and distamycin A (Dst) were synthesized, and the thermal stability of several model DNA duplexes containing conjugates was studied. Two Dst residues conjugated at both ends of the oligonucleotide were needed for substantial increase in the melting temperature of the corresponding duplex (delta Tm > 30 degrees C). Two attached Dst residues had a greater effect on the Tm value than did two free molecules of Dst per duplex. In contrast to Dst, one Nt molecule linked to the oligonucleotide was enough to influence the thermal stability of the duplexes. Like Dst, the attached Nt appeared to stabilize duplexes much more than free Nt molecules. Attachment of Nt to either the 5'- or 3'-end of the different nonadeoxynucleotides containing 5' ...TTAAA... or 5' ...TATA... sites increased Tm of their duplexes by 21 degrees C-25 degrees C, whereas delta Tm for free Nt was 8 degrees C-15 degrees C (delta delta Tm = 10 degrees C-14 degrees C). The same phenomenon was shown for oligonucleotide phosphorothioates (delta Tm were 18 degrees C-22 degrees C and 9 degrees C-13 degrees C for attached and free Nt, respectively; delta delta Tm = 9 degrees C). This effect was even more pronounced for a hairpin oligonucleotide (delta delta Tm = 18 degrees C).
The generic amyloid formation inhibition effect of a designed small aromatic β-breaking peptide (2011)

The development of generic inhibitors in order to control the formation of amyloid fibrils and early oligomers is still an unmet medical need. As it is hypothesized that amyloid assemblies represent a generic protein supramolecular structure of low free energy, targeting the key molecular recognition and self-assembly events may provide the route for the development of such potential therapeutic agents. We have previously demonstrated the ability of hybrid molecules composed of an aromatic moiety and the α-aminoisobutyric acid β-sheet breaker elements to act as excellent inhibitors of amyloid fibril formation. Specifically, the D-Trp-Aib was shown to be a superb inhibitor of the formation of Alzheimer's disease β-amyloid fibrils and oligomers both in vitro and in vivo. Here, we demonstrate that the rationally designed molecule has the generic ability to inhibit amyloid fibril formation by calcitonin, α-synuclein, and the islet amyloid polypeptide. Moreover, we demonstrate the inability of two modified peptides, D-Ala-Aib and D-Trp-Ala, to inhibit and disassemble amyloid fibril formation, a fact that provides an additional evidence for the suggested structural basis of the inhibitor activity. Taken together, we believe that the use of β-breaker elements combined with aromatic moiety may present a promising approach for the development of fibrillization inhibition drug candidate.
Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis (2004)

In order to define antigens that might be suitable as vaccines for pancreatic carcinoma, we investigated the composite expression of 10 cancer testis (CT) antigens (SCP-1, NY-ESO-1, SSX-1, SSX-2, SSX-4, GAGE, MAGE-3, MAGE-4, CT-7 and CT-8) by Reverse Transcriptase-PCR (RT-PCR) in fresh biopsies of human pancreatic adenocarcinoma, chronic pancreatitis and pancreatic carcinoma cell lines. While all CT genes were frequently expressed in cell lines derived from pancreatic cancer, no expression of MAGE-3, SSX-1, SSX-2, NY-ESO-1 and CT-7 was detected in fresh tumor biopsies, and MAGE-4 (1/52), SSX-4 (1/39) and CT-8 (2/41) were only rarely expressed. In contrast, HOM-TES-14/SCP-1 was expressed in 48% (29/61) and GAGE in 21% (13/61) of cases, respectively. One CT gene was expressed by 59% (75% in male, 46% in female patients; p = 0.05) and 2 or more CT genes by 15% of the samples. SCP-1 protein expression correlated well with mRNA expression. While SCP-1 and GAGE were absent in normal pancreas, they were found in 2/8 (SCP-1) and 1/8 (GAGE) samples of chronic pancreatitis, respectively, supporting the concept of chronic pancreatitis as a premalignant condition. SCP-1 and GAGE represent promising candidates for vaccine development in pancreatic carcinoma. Whether SCP-1 and GAGE expression identify cases of chronic pancreatitis with a high risk of malignant transformation remains to be shown.
Quantitative and Reversible Lectin-Induced Association of Gold Nanoparticles Modified with α-Lactosyl-ω-mercapto-poly(ethylene glycol) (2001)

Gold nanoparticles (1-10 nm size range) were prepared with an appreciably narrow size distribution by in situ reduction of HAuCl(4) in the presence of heterobifunctional poly(ethylene glycol) (PEG) derivatives containing both mercapto and acetal groups (alpha-acetal-omega-mercapto-PEG). The alpha-acetal-PEG layers formed on gold nanoparticles impart appreciable stability to the nanoparticles in aqueous solutions with elevated ionic strength and also in serum-containing medium. The PEG acetal terminal group was converted to aldehyde by gentle acid treatment, followed by the reaction with p-aminophenyl-beta-D- lactopyranoside (Lac) in the presence of (CH(3))(2)NHBH(3). Lac-conjugated gold nanoparticles exhibited selective aggregation when exposed to Recinus communis agglutinin (RCA(120)), a bivalent lectin specifically recognizing the beta-D-galactose residue, inducing significant changes in the absorption spectrum with concomitant visible color change from pinkish-red to purple. Aggregation of the Lac-functionalized gold nanoparticles by the RCA(120) lectin was reversible, recovering the original dispersed phase and color by addition of excess galactose. Further, the degree of aggregation was proportional to lectin concentration, allowing the system to be utilized to quantitate lectin concentration with nearly the same sensitivity as ELISA. This simple, yet highly effective, derivatization of gold nanoparticles with heterobifunctional PEG provides a convenient method to construct various colloidal sensor systems currently applied in bioassays and biorecognition.
Striatal Potassium Channel Dysfunction in Huntington's Disease Transgenic Mice (2005)

Huntington's disease (HD) is a neurodegenerative disorder that mainly affects the projection neurons of the striatum and cerebral cortex. Genetic mouse models of HD have shown that neurons susceptible to the mutation exhibit morphological and electrophysiological dysfunctions before and during development of the behavioral phenotype. We used HD transgenic mouse models to examine inwardly and outwardly rectifying K+ conductances, as well as expression of some related K+ channel subunits. Experiments were conducted in slices and dissociated cells from two mouse models, the R6/2 and TgCAG100, at the beginning and after full development of overt behavioral phenotypes. Striatal medium-sized spiny neurons (MSNs) from symptomatic transgenic mice had increased input resistances, depolarized resting membrane potentials, and reductions in both inwardly and outwardly rectifying K+ currents. These changes were more dramatic in the R6/2 model than in the TgCAG100. Parallel immunofluorescence studies detected decreases in the expression of K+ channel subunit proteins, Kir2.1, Kir2.3, and Kv2.1 in MSNs, which contribute to the formation of the channel ionophores for these currents. Attenuation in K+ conductances and channel subunit expression contribute to altered electrophysiological properties of MSNs and may partially account for selective cellular vulnerability in the striatum.
Geranylgeranylglyceryl Phosphate Synthase. Characterization of the Recombinant Enzyme from Methanobacterium thermoautotrophicum (2001)

Geranylgeranylglyceryl diphosphate synthase (GGGP synthase) catalyzes alkylation of (S)-glyceryl phosphate [(S)-GP] by geranylgeranyl diphosphate (GGPP) to produce (S)-geranylgeranylglyceryl phosphate [(S)-GGGP]. This reaction is the first committed step in the biosynthesis of ether-linked membrane lipids in Archaea. The gene encoding GGGP synthase from Methanobacterium thermoautotrophicum was cloned using probes designed from the N-terminal sequence determined from the purified enzyme. The open reading frame, which encoded a protein of 245 amino acids, was inserted into a pET expression vector and expressed in Escherichia coli. The recombinant GGGP synthase was purified to homogeneity. The enzyme is active as a homopentamer, as determined by size exclusion chromatography and equilibrium sedimentation experiments. GGGP synthase has optimal activity at 55 degrees C in pH 8.0 buffer containing 1 mM MgCl(2). V(max) = 4.0 +/- 0.1 micromol min(-1) mg(-1) (k(cat) = 0.34 +/- 0.03 s(-1) for pentameric GGGP synthase assuming all subunits are fully active), K(m)((S)-GP) = 13.5 +/- 1.0 microM, and K(m)(GGPP) = 506 +/- 47 nM. These steady-state catalytic constants were identical to those for enzyme isolated from cell extracts of M. thermoautotrophicum [Chen, A., Zhang, D., and Poulter, C. D. (1993) J. Biol. Chem. 268, 21701-21705]. Alignment of seven putative archaeal GGGP synthase sequences revealed a number of highly conserved residues consisting of five aspartate/glutamates, three serine/threonines, two prolines, and five glycines, including a conserved GGG motif.
Increased Bioelectric Potential Difference across Respiratory Epithelia in Cystic Fibrosis (1981)

To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis.
Functional characterization of organic cation drug transport in the pigmented rabbit conjunctiva. (2000)

A carrier-mediated organic cation transport process appears to exist in the conjunctiva, mediating the absorption of organic amines, including certain amine-type ophthalmic drugs. This process may be driven by an inside-negative apical membrane potential difference.
Binding of nucleic acids to E.coli RNase HI observed by NMR and CD spectroscopy (1993)

To clarify the mechanism by which the RNA portion of a DNA/RNA hybrid is specifically hydrolyzed by ribonuclease H (RNase H), the binding of a DNA/RNA hybrid, a DNA/DNA duplex, or an RNA/RNA duplex to RNase HI from Escherichia coli was investigated by 1H-15N heteronuclear NMR. Chemical shift changes of backbone amide resonances were monitored while the substrate, a hybrid 9-mer duplex, a DNA/DNA 12-mer duplex, or an RNA/RNA 12-mer duplex was titrated. The amino acid residues affected by the addition of each 12-mer duplex were almost identical to those affected by the substrate hybrid binding, and resided close to the active site of the enzyme. The results reveal that all the duplexes, hybrid-, DNA-, and RNA-duplex, bind to the enzyme. From the linewidth analysis of the resonance peaks, it was found that the exchange rates for the binding were different between the hybrid and the other duplexes. The NMR and CD data suggest that conformational changes occur in the enzyme and the hybrid duplex upon binding.
Acute stroke: evaluation with serial proton MR spectroscopic imaging. (1994)

Spectroscopic imaging enables mapping of ischemic and infarcted brain regions with greater sensitivity than does conventional MR imaging.
Diazo-ketones with potential tumour-inhibitory properties derived from L-aspartic and L-glutamic acids (1971)

Y. Liwschitz, E. Nemes and Z. Neiman, J. Chem. Soc. C, 1971, 223 DOI: 10.1039/J39710000223
Parallax: High Accuracy Three-Dimensional Single Molecule Tracking Using Split Images (2009)

Three-dimensional (3D) tracking can provide valuable biological insights that are missing in conventional microscopy. Here we developed a single molecule 3D tracking microscopy technique, named Parallax, with high localization precision and temporal resolution. We demonstrated its capabilities by studying the 3D trafficking of glucose-transporter-4 containing vesicles in living adipocytes as well as the walking path of single myosin VI molecules along actin filaments.
Transient Neonatal Diabetes Mellitus or an Exaggerated Steroid Response? A Case Study (1998)

Hyperglycemia is a common finding in the extremely premature neonate, especially during the first several days of life. Premature neonates have difficulty maintaining normal blood glucose levels in spite of normal or below-normal glucose infusion rates. Some infants experience intermittent episodes of hyperglycemia throughout the course of hospitalization that typically can be related to infection, medications, overinfusion of glucose, or episodes of stress. Transient neonatal diabetes mellitus (TNDM) is an uncommon diagnosis that is utilized when other reasons for the hyperglycemia cannot be determined. The article presents a case study describing an episode of hyperglycemia that could have been TNDM or an exaggerated response to the use of dexamethasone.
Transplantation of Neural Stem Cells: Cellular & Gene Therapy for Hypoxic-Ischemic Brain Injury (2000)

We have tracked the response of host and transplanted neural progenitors or stem cells to hypoxic-ischemic (HI) brain injury, and explored the therapeutic potential of neural stem cells (NSCs) injected into mice brains subjected to focal HI injury. Such cells may integrace appropriately into the degenerating central nervous system (CNS), and showed robust engraftment and foreign gene expression within the region of HI inury. They appeared to have migrated preferentially to the site of ischemia, experienced limited proliferation, and differentiated into neural cells lost to injury, trying to repopulate the damaged brain area. The transplantation of exogenous NSCs may, in fact, augment a natural self-repair process in which the damaged CNS "attempts" to mobilize its own pool of stem cells. Providing additional NSCs and trophic factors may optimize this response. Therefore, NSCs may provide a novel approach to reconstituting brains damaged by HI brain injury. Preliminary data in animal models of stroke lends support to these hypotheses.
Hydrophilic Aliphatic Polyesters:  Design, Synthesis, and Ring-Opening Polymerization of Functional Cyclic Esters (2000)

The synthesis and homo- and copolymerization of new cyclic esters containing protected functional groups (hydroxyl, bishydroxyl, amino, and carboxyl) are described. Each of the ε-caprolactone derivatives was generated by the Baeyer−Villiger oxidation of the corresponding cyclohexanone derivative. Monoprotection of 1,4-cyclohexanediol by benzylation or esterification was accomplished in moderate yields by reaction of benzyl bromide or 2,2‘-bis(phenyldioxymethyl)propionyl chloride. Each could be oxidized with pyridinium chlorochromate to yield the respective protected hydroxyl and bis(hydroxyl) functional cyclohexanones. The benzyl ether and benzyl ester protecting groups are readily removed by catalytic hydrogenolysis using Pd/C. Alternatively, ethyl-4-ketocyclohexylcarboxylate was hydrolyzed, and the free carboxylic acid was reesterified to the benzyl or tert-butyl 4-ketocyclohexylcarboxylate by esterification with either benzyl bromide or tert-butyl alcohol. These protecting groups were chosen because they are readily cleaved to the respective carboxylic acids under mild conditions. The aza-cyclohexanone derivative was produced from the commercially available ethylene ketal of 4-piperidone by acetylation with trifluoroacetic anhydride followed by transketalization using p-toluenesulfonic acid in excess acetone. The trifluoroacetyl protecting group is easily removed by NaBH4 reduction. Polymerization of the new monomers was accomplished either in bulk (110 °C) initiated from benzyl 2,2‘-bis(hydroxymethyl)propionate in the presence of stanneous 2-ethyl hexanoate (Sn(Oct)2) or from Al(OiPr)3 in toluene (0 °C), yielding polymers close to their targeted molecular weights (5000−15 000) with modestly narrow polydispersities (1.20−1.35). Removal of the protecting groups on the aliphatic polyesters yielded the functionalized polymers.