gebhart/patrepeval huggingface dataset:
Micrognathia and Glossoptosis in the Newborn (1974)

This report discusses airway obstruction in newborn infants with micrognathia and glossop tosis, and describes three patients who required surgical relief of obstruction from glossoptosis. In two, glossoptosis was controlled by construction of lingual-labial flaps under local anesthesia. The third required tracheostomy because of absence of the mandibular symphysis; to be effective, a lingual-labial flap requires a complete mandibular arch for support. The lingual-labial flap is the best surgical procedure for glossoptosis of the newborn. It can be constructed under local anesthesia in the nursery or in the operating room. It holds the tongue forward, yet it allows adequate tongue mobility for feeding. Composed of the patient's own tissues, it can remain for an indefinite time.
Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL) (2005)

Tumor necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) play an important role in the biology of chronic lymphocytic leukemia (CLL) cells. Thalidomide is a first-generation immuno-modulating agent that down-regulates TNF-alpha and VEGF. We initiated a phase 1/2 clinical trial to determine the safety and efficacy of combining thalidomide with fludarabine in patients with treatment-naïve CLL. Patients received 6 months of continuous daily thalidomide with standard monthly doses of fludarabine. Three dose levels of thalidomide (100, 200, and 300 mg) were studied. Results from the phase 1 part of this study are reported here. Thirteen patients were enrolled in the phase 1 component of the study. Dose-limiting toxicity was not reached. The most common toxicities noted were fatigue, constipation, and peripheral sensory neuropathy. Overall response rate was 100% with 55% of patients achieving complete remissions. At a median follow-up of 15+ months none of the patients have had a relapse and the median time to disease progression has not yet been reached. Responses were noted at all dose levels. Thalidomide given up to 300 mg/day concurrently with fludarabine in patients with previously untreated CLL shows encouraging clinical efficacy and acceptable toxicity. An ongoing phase 2 part of this study will help validate the clinical efficacy of this regimen.
Heterocyclen durch Reaktion von Mercapto‐ und Hydroxycarbonsäureestern mit aktivierten Nitrilen (1978)

Abstract Aktivierte Nitrile Y‐CHR‐CN reagieren mit den α‐ und β‐Mercapto‐ oder α‐Hydroxy‐carbonsäureestern 2a ‐ k unter Basenkatalyse zu den cyclischen N ‐Acylketen‐S,N‐ und N ‐Acylketen‐O,N‐acetalen 3 [2‐Methylenthiazolidin‐4‐onen 3a ‐ w , ‐4 H ‐1,3‐benzothiazin‐4‐onen 3 gg ‐ ii , ‐oxazolidin‐4‐onen 3 x ‐ dd und‐tetrahydrothiazin‐4‐on ( 3ff )]. α‐und β‐Amino‐carbonsäureester zeigen mit Ausnahme des Glycin‐ethylesters 21 (zum Imidazolin‐4‐on 3ee ) diese Reaktion nicht; von Nitrilen der Struktur Y‐CN reagiert nur der Cyanameisensäureester mit 2b in ähnlicher Weise zum 4‐Hydroxythiazol 5 . Die 2‐Methylenheterocyclen 3 liegen in einem stereochemischen Gleichgewicht der E/Z ‐Isomeren und zugleich in einem tautomeren Gleichgewicht mit der Imidesterform 3 ′ vor; die Gleichgewichtslagen sind von der Acylgruppe Y, vom Ringheteroatom X und vom Lösungsmittel abhängig. Alle Verbindungen 3/3 ′ werden in der Ketenacetalform 3 am N‐3 alkyliert, einige unter verschärften Bedingungen zusätzlich am C‐5. Die Alkylierung fixiert im allgemeinen die Z ‐Form, bei bestimmten Kombinationen von X/Y führt sie zu E/Z ‐Gemischen oder, selten, zur ausschließlichen Bildung des E ‐Isomeren. Die auffallende Ringstabilität der Verbindungen 3 und ihrer Derivate, die für X = S am ausgeprägtesten ist, geht parallel mit der Reaktionsarmut von Y: sie reagieren unter Erhaltung des Heterocyclus mit elektrophilen Reagenzien in der 5‐ oder α‐Stellung; die zur Durchführung erforderlichen konzentrierten Säuren hydrolysieren selbst die 5‐Amino‐2‐ethoxycarbonylmethylenthiazolidinone 13a ‐ g , und die 2‐Cyanmethylenbenzothiazinone 3gg und 12a, e, h zu den entsprechenden Aminosäuren 25a ‐ e bzw. Amiden 26a ‐ d ohne Ringspaltung. Die 3‐Alkyl‐acylmethylenthiazolidin‐4‐one 9a, d, f, m erfahren bei längerer Einwirkung von Triethylamin Ringerweiterung zu den 6‐Aryl‐1,4‐thiazin‐3‐onen 28a ‐ d . Struktur und reaktives Verhalten von 3/3 ′ und Derivaten werden anhand von Eigenschaften bekannter, offenkettiger S(O),N‐Ketenacetale, von 1 H‐, 13 C‐NMR‐, IR‐ und UV‐spektroskopischen Daten von 3 und Derivaten und der quantitativen Analyse der lanthanidinduzierten chemischen Verschiebung von 9o und 9p diskutiert. Es wird über die biologischen Eigenschaften einiger Verbindungen berichtet.
Synaptotagmin IV is an immediate early gene induced by depolarization in PC12 cells and in brain. (1995)

Subtractive library construction and differential screening were used to identify a cDNA for a cell type-specific immediate early gene induced in rat PC12 pheochromocytoma cells. Sequencing identified the protein product of this gene as rat synaptotagmin IV (SytIV). Synaptotagmins are synaptic vesicle proteins thought to play a role in depolarization-induced, calcium-mediated exocytosis and neurotransmitter release. SytIV mRNA accumulation is transiently induced in PC12 cells by potassium depolarization, calcium ionophore, ATP, and forskolin. In contrast, growth factors and phorbol 12-myristate 13-acetate induce little or no SytIV mRNA accumulation. Kainic acid-induced seizures in rats are followed by accumulation of SytIV message in the hippocampus and piriform cortex. The SytIV gene may provide a direct link between depolarization-induced neuronal gene expression and subsequent modulation of synaptic structure and function.
A single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with the ability to cause growth hormone deficiency syndrome (1996)

Persistent infection of C3H/St mice with certain strains of lymphocytic choriomeningitis virus (LCMV) causes a growth hormone (GH) deficiency syndrome (GHDS) manifested as growth retardation and hypoglycemia. Infected mice show high levels of viral replication in the GH-producing cells in the anterior pituitary leading to decreased synthesis of GH mRNA and protein despite the absence of detectable virus-induced cell structural damage. Virus clones isolated from the GHDS-negative LCMV WE strain can cause the disease, while others cannot. The genetic basis of this phenotypic difference is a nucleotide substitution resulting in a single amino acid difference in the viral glycoprotein. Reassortant studies indicate that the single amino acid substitution (Ser-153 to Phe) is sufficient to allow infection of the GH-producing cells and cause GHDS. These results show that a single change in the genome can affect viral pathogenicity by altering the tropism of the virus.
Mouse ribonucleotide reductase R2 protein: A new target for anaphase-promoting complex-Cdh1-mediated proteolysis (2003)

Ribonucleotide reductase consists of two nonidentical proteins, R1 and R2, and catalyzes the rate-limiting step in DNA precursor synthesis: the reduction of ribonucleotides to deoxyribonucleotides. A strictly balanced supply of deoxyribonucleotides is essential for both accurate DNA replication and repair. Therefore, ribonucleotide reductase activity is under exquisite control both transcriptionally and posttranscriptionally. In proliferating mammalian cells, enzyme activity is regulated by control of R2 protein stability. This control, which responds to DNA damage, is effective until cells pass into mitosis. We demonstrate that the mitotic degradation and hence the overall periodicity of R2 protein levels depends on a KEN box sequence, recognized by the Cdh1-anaphase-promoting complex. The mouse R2 protein specifically binds Cdh1 and is polyubiquitinated in an in vitro ubiquitin assay system. Mutating the KEN signal stabilizes the R2 protein during mitosisG(1) in R2 protein-overexpressing cells. The degradation process, which blocks deoxyribonucleotide production during G(1), may be an important mechanism protecting the cell against unscheduled DNA synthesis. The newly discovered p53-induced p53R2 protein that lacks a KEN box may supply deoxyribonucleotides for DNA repair during G(0)G(1).
Ex situ evaluation of the composition of protein corona of intravenously injected superparamagnetic nanoparticles in rats (2014)

It is now well recognized that the surfaces of nanoparticles (NPs) are coated with biomolecules (e.g., proteins) in a biological medium. Although extensive reports have been published on the protein corona at the surface of NPs in vitro, there are very few on the in vivo protein corona. The main reason for having very poor information regarding the protein corona in vivo is that separation of NPs from the in vivo environment has not been possible by using available techniques. Knowledge of the in vivo protein corona could lead to better understanding and prediction of the fate of NPs in vivo. Here, by using the unique magnetic properties of superparamagnetic iron oxide NPs (SPIONs), NPs were extracted from rat sera after in vivo interaction with the rat's physiological system. More specifically, the in vivo protein coronas of polyvinyl-alcohol-coated SPIONs with various surface charges are defined. The compositions of the corona at the surface of various SPIONs and their effects on the biodistribution of SPIONs were examined and compared with the corona composition of particles incubated for the same time in rat serum.
Passive immunization with antiserum to a nontoxic alpha-toxin mutant from Staphylococcus aureus is protective in a murine model (1996)

A nonhemolytic, nonlethal variant of Staphylococcus aureus alpha-toxin constructed via oligonucleotide-directed mutagenesis and containing a single amino acid substitution (H-35 to L) was used to immunize a rabbit. The resulting antiserum was cross-reactive with wild-type alpha-toxin and neutralized its hemolytic activity in vitro. Passive immunization of mice with rabbit antiserum conferred protection against lethal challenge with wild-type alpha-toxin and against acute lethal challenge with a high-alpha-toxin -producing S. aureus strain. H35L alpha-toxin may be useful as a protective immunogen in S. aureus vaccine studies.
Group‐specific primer and probe sets to detect methanogenic communities using quantitative real‐time polymerase chain reaction (2005)

Real-time polymerase chain reaction (PCR) is a highly sensitive method that can be used for the detection and quantification of microbial populations without cultivating them in anaerobic processes and environmental samples. This work was conducted to design primer and probe sets for the detection of methanogens using a real-time PCR with the TaqMan system. Six group-specific methanogenic primer and probe sets were designed. These sets separately detect four orders (Methanococcales, Methanobacteriales, Methanomicrobiales, and Methanosarcinales) along with two families (Methanosarcinaceae and Methanosaetaceae) of the order Methanosarcinales. We also designed the universal primer and probe sets that specifically detect the 16S rDNA of prokaryotes and of the domain Bacteria and Archaea, and which are fully compatible with the TaqMan real-time PCR system. Target-group specificity of each primer and probe set was empirically verified by testing DNA isolated from 28 archaeal cultures and by analyzing potential false results. In general, each primer and probe set was very specific to the target group. The primer and probe sets designed in this study can be used to detect and quantify the order-level (family-level in the case of Methanosarcinales) methanogenic groups in anaerobic biological processes and various environments.
High speed and compact CMOS circuits with multi-pillar surrounding gate transistors (1989)

In order to overcome the scaling limitations on planar transistors for future LSIs, the authors propose a novel surrounding gate transistor (SGT), whose gate electrode surrounds multipillar silicon islands. The new SGT offers large drain currents even in a very small occupied area. The large channel width is achieved by using all the sidewalls of the crowded multipillar silicon islands as the channel regions. Owing to this multichannel structure, a transistor with extremely small occupied area and sufficient drivability can be obtained. The small occupied area and the mesh-structured gate electrode lead to small gate electrode RC delay and small junction capacitance, resulting in very high-speed operation, contrary to the cases of the planar transistor and the conventional SGT. A new SGT CMOS inverter chain was fabricated. The propagation delay is reduced to 20% of that for the case of the planar transistors. This new SGT is extremely attractive for future high-speed ULSI devices.
Intratumoral regulatory T cells with higher prevalence and more suppressive activity in hepatocellular carcinoma patients (2013)

Regulatory T cells (Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma (HCC). METHODS : The frequencies and phenotypes of CD4(+) CD25(+) CD127(low/-) CD49d(-) Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybridized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. RESULTS : Intratumoral Tregs exhibited higher frequencies and more suppressive phenotypic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. CONCLUSIONS : Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression.
A comparison of the effects of hydrallazine, diazoxide, sodium nitrite and sodium nitroprusside on human isolated arteries and veins. (1981)

1 Human common palmar digital arteries and dorsal metacarpal veins have been studied in vitro to investigate the responses of arterial and venous muscle to hydrallazine, diazoxide, nitroprusside and sodium nitrite. 2 Tissues were removed at autopsy, cut into helical strips and suspended in organ baths under identical conditions. The contractile response to noradrenaline was tested in the presence of the same concentrations of the vasodilator drugs in arteries and veins. 3 Hydrallazine antagonised contraction of arteries, but not veins to noradrenaline. Diazoxide, nitroprusside or sodium nitrite antagonised responses in both arteries and veins. Diazoxide and nitrite were more effective on arteries and nitroprusside was more effective on veins. 4 These results are in accord with clinical observations and confirm that there are differences in the susceptibility of human arterial and venous smooth muscle to vasorelaxant drugs.
Annexin II Enhances Cytomegalovirus Binding and Fusion to Phospholipid Membranes (1999)

A number of studies have suggested that the anionic phospholipid (anPL)-binding protein annexin II may play a role in cytomegalovirus (CMV) infection. Since annexin II has been shown to mediate aggregation and fusion of certain membranes, we investigated whether these properties could be exploited by CMV directly. The experiments showed that purified annexin II, but not the homologous protein annexin V (AnV), can mediate the binding of 35S-CMV (strain AD169) to anPL-coated microtiter wells. This association required Ca2+, could be titrated by varying either annexin II (apparent Kd = 4 x 10(-)8 M) or 35S-CMV, was inhibited by unlabeled CMV, and was observed for the heterotetrameric or monomeric form of annexin II. In experiments utilizing the fluorescence dequenching of octadecyl rhodamine incorporated into the CMV envelope, annexin II was furthermore found to enhance the rate of virus-anPL vesicle fusion. The observed fusion was dependent on the concentration of annexin II, Ca2+, and anPL and was mediated principally by the heterotetramer. Interestingly, AnV was observed to inhibit the effects of annexin II on CMV fusion but not binding to anPL, which indicates that annexin II enhances these processes by distinct mechanisms. The results presented here provide the first direct evidence that annexin II has the capacity to bridge CMV to a phospholipid membrane and to enhance virus-membrane fusion. These observations furthermore suggest that AnV may regulate the fusogenic function of annexin II.
Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride. (1993)

This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development.
Randomized Algorithms (1995)

Presents basic tools from probability theory used in algorithmic applications, with concrete examples.
Retrovirus-Mediated Transfer of Anti-MDR1 Ribozymes Fully Restores Chemosensitivity of P-Glycoprotein-Expressing Human Lymphoma Cells (1999)

Development of multidrug resistance (MDR) is the major obstacle to successful cancer chemotherapy. We have developed Daudi human lymphoma cells that are 20-fold more resistant than the parent cell line to vincristine (VCR) by infecting cells with pHaMDR1/A retroviral vector (Daudi/MDR20). Three DNA sequences of anti-MDR1 hammerhead ribozymes (Rzs), one cleaving codon 196 of MDR1 mRNA (196MDR1-Rz), the second a stem II base-modified (U9-->Gg, U13-->A13, G14-->A14, A18-->C18) Rz against codon 196 (196MDR1-sRz), and the third a stem II base-modified Rz directed against the -6 approximately -4 GUC sequence of the translation initiation site of the MDR1 mRNA (iMDR1-sRz), were synthesized and cloned into the retroviral vector N2A+tRNAiMet downstream of the RNA polymerase III promoter and adjacent to a tRNA gene sequence, forming the constructs N2A+tRNAiMet-196MDR1-Rz, N2A+tRNAiMet-196MDR1-sRz, and N2A+tRNAiMet-iMDR1-sRz. The three constructs were transfected into GP+envAM 12 cells for packaging the retroviral vectors. The supernatants containing the packaged retrovirus in high titers (1.1-2.5 X 10(5) CFU/ml as determined by infection of NIH 3T3 cells) were used to infect Daudi/MDR20 cells. The iMDR1-sRz- and 196MDR1-sRz-transduced Daudi/MDR20 cells completely restored chemosensitivity to VCR and doxorubicin, and were accompanied by blocked expression of MDR1 mRNA and P-glycoprotein as well as overexpression of anti-MDR1 Rz. In a cell-free system, the chimeric tRNA-sRz molecules were more stable and had more efficient catalytic activities than the corresponding naked Rz molecules. The stem II base-modified Rz were also more stable and efficient in catalytic activities than the unmodified Rz molecules. The base modification in the Rz stem II structure and the development of chimeric tRNA-Rz molecules were identified to enhance the cleavage efficacy. The combination of these two factors, together with the use of a retroviral vector, appear to have contributed to the complete reversal of MDR.
The Structure of Protonated Water Clusters (2004)

Acid-base reactions are among the most important chemical processes in aqueous solution, but it is very difficult to characterize the solvated ions that are involved, especially the solvated proton. In his Perspective,
 Zwier
 discusses reports by
 Shin
 et al.
 and
 Miyazaki
 et al.
 in the same issue that reveal details of the structure of protonated water by means of infrared spectroscopy. The infrared spectra of a series of protonated water clusters H(HO)with
 n
 = 6 to 27 shed new light and raise new questions about the nature of the proton in water, its position in the finite-sized cluster (surface or interior), and the structure of the cluster in the size region of the proposed dodecahedral cage (n
 = 21).
Nerve Microvessel Changes in Diabetes are Prevented by Aldose Reductase Inhibition (1995)

This study demonstrates that endoneurial microvessel abnormalities can be detected in experimental diabetic neuropathy. Microvessel basement membrane thickening will be prevented by an aldose reductase inhibitor. One mechanism by which abnormal polyol pathway activity may contribute to diabetic neuropathy could be through damage to microvessels.