gebhart/patrepeval huggingface dataset:
Pilot-Plant Preparation of an αvβ3 Integrin Antagonist. Part 3. Process Research and Development of a Diisopropylcarbodiimide and Catalytic 1-Hydroxybenzotriazole Peptide Coupling (2009)

Studies directed toward the process research, development, and scale-up preparation of the potential αvβ3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H3PO4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4.
29 Bone Formation in Implants of Partially and Wholly Demineralized Bone Matrix (1970)

From the Bone Research Laboratory, Division of Orthopedic Surgery, Department of Surgery, U.C.L.A. School of Medicine, Los Angeles, Calif. 90024.
Generation of Recombinant Influenza Virus from Plasmid DNA (2010)

Efforts by a number of influenza research groups have been pivotal in the development and improvement of influenza A virus reverse genetics. Originally established in 1999 plasmid-based reverse genetic techniques to generate recombinant viruses have revolutionized the influenza research field because specific questions have been answered by genetically engineered, infectious, recombinant influenza viruses. Such studies include virus replication, function of viral proteins, the contribution of specific mutations in viral proteins in viral replication and/or pathogenesis and, also, viral vectors using recombinant influenza viruses expressing foreign proteins.
Restoration of a Functional Open Reading Frame by Homologous Recombination between Two Adenoviral Vectors (2002)

In this study, we examined the ability of adenoviral (Ad) vectors to undergo homologous recombination. The lacZ gene was divided between two parental, first-generation vectors such that neither encoded a functional product but both shared 494 bp in common. The open reading frame could only be restored by homologous recombination. We observed beta-galactosidase activity only upon co-infection of both parental vectors and after the onset of viral DNA replication, creating a delay in expression of 24-36 hours in HeLa cells. At peak efficiency, this recombination vector system resulted in beta-galactosidase activity levels 100x above background and just 18x less than a conventional, first-generation vector in HeLa cells. After recombination, the resultant progeny vector genomes containing reconstituted expression cassettes were devoid of all viral genes and contained two packaging signals. These progeny genomes were efficiently packaged, could be separated from their parental vectors based on their lighter buoyant densities in CsCl gradients, and were subsequently used as functional gene transfer vectors. This novel recombination vector system should be useful for transferring large transgenes (because the carrying capacity of two Ad vectors can be exploited) or expressing any cytotoxic or Ad replication inhibitory protein (because the parental vectors exhibit no background expression).
A randomized, double-blind, placebo-controlled trial of the safety of vaginal recombinant human relaxin for cervical ripening. (1993)

The use of recombinant human relaxin at a dose of 1.5 mg was not associated with any significant maternal or fetal-neonatal complications. The relatively small number of subjects in this study was chosen deliberately because this was the first use of the drug in pregnant subjects. Assessment of efficacy will require studies that include more patients and a range of relaxin doses.
Quantitative Real-Time PCR Assay for Determining Transgene Copy Number in Transformed Plants (2001)

The development of transgenic events can be limited by many factors. These include expression levels, insert stability and inheritance, and the identification of simple insertion events. All of the factors can be related to the copy number of the transgene. Traditionally, copy number has been determined by laborious blotting techniques. We have developed an alternative approach that utilizes the fluorogenic 5′ nuclease (TaqMan®) assay to quantitatively determine transgene copy level in plants. Using this assay, hundreds of samples can be analyzed per day in contrast to the low throughput encountered with traditional methods. To develop the TaqMan copy number assay, we chose to utilize our highly efficient Agrobacterium-mediated transformation system of maize. This transformation procedure generates predominantly low copy number insertion events, which simplified assay development. We have also successful applied this assay to other crops and transformation systems.
Characterization of the vaginal microflora in health and disease. (2014)

BV can be diagnosed by molecular methods performed either on swabs or urine but it is important to apply thresholds in order to improve the accuracy of the diagnosis. Furthers it was possible to identify clusters of BV dominated by single or paired bacteria, and these clusters could classify BV into subgroups, providing a more detailed understanding of the condition. Seven vaginal bacteria were highly accurate for BV diagnosis both in swabs and FVU. Finally a good agreement between Nugent and Claeys was found.
Generation of minor histocompatibility antigen HA-1–specific cytotoxic T cells restricted by nonself HLA molecules: a potential strategy to treat relapsed leukemia after HLA-mismatched stem cell transplantation (2002)

Abstract Successful stem cell transplantation (SCT) across HLA barriers can be performed with cord blood, megadoses of stem cells, or with nonmyeloablative conditioning strategies. Because the HLA-mismatched transplants are often T-cell depleted, leukemia relapse rates are high. Treatment of relapsed leukemia after HLA-mismatched SCT is difficult. A novel potential strategy to treat relapsed leukemia after HLA-mismatched SCT is the use of patients' mismatched HLA molecules as antigen-presenting molecules to generate hematopoietic system–specific cytotoxic T cells (CTLs) from the stem cell donor. Adoptive transfer of these hematopoietic system–specific CTLs that are restricted by nonself HLA molecules may eliminate leukemia without affecting the patient's nonhematopoietic cells or donor hematopoietic cells. We investigated the feasibility of this strategy using the hematopoietic system–specific minor histocompatibility antigen HA-1, which is known to induce HLA-A2–restricted CTLs. HLA-A2−peripheral blood mononuclear cells were stimulated with HLA-A2+ T2 cells pulsed with synthetic HA-1 peptide or with dendritic cells transduced with the HA-1 cDNA. Tetrameric HLA-A2/HA-1 peptide complexes were used to monitor and enrich HA-1–specific CTLs. In the alloreactive cultures, HA-1–specific CTLs were enriched up to 7% by 3 rounds of antigen-specific stimulations and up to 87% by fluorescence-activated cell sorting of tetramer-positive T cells. The HA-1–specific CTLs showed specific lysis of the relevant target cells, including leukemic cells. Because the polyclonal CTL cultures also contained natural killer cells and allo–HLA-A2–specific CTLs, CTL clones were generated that showed the expected HA-1 specificity only. Thus, HA-1–specific CTLs restricted by nonself HLA-A2 molecules can be generated in an HLA-A2–mismatched setting.
Thioguanine versus mercaptopurine for therapy of childhood lymphoblastic leukaemia: a comparison of haematological toxicity and drug metabolite concentrations (1998)

As a prelude to a nationwide randomized trial of thioguanine (TG) versus mercaptopurine (MP) for childhood lymphoblastic leukaemia we compared a pilot group of 23 children taking TG with a matched group taking MP. We assessed drug tolerance based on haematological toxicity and measured erythrocyte (RBC) concentrations of thioguanine nucleotides (TGN). The median tolerated dose of TG was 30 mg/m2 compared to 55 mg/m2 for MP. There was no difference in the pattern of anaemia or neutropenia between the two groups, but dose-limiting thrombocytopenia was more evident in the TG children (P< 0.001), four of whom had a decrease in platelet count to <20 x 10(9)/l compared to only one on MP. The median RBC TGN concentration for those on 40 mg/m2 TG was 1726 pmol/8 x 10(8) RBCs compared with 308 pmol/8 x 10(8) RBCs for those on 75 mg/m2 MP (P< 0.0001). There was an inverse correlation between RBC TGNs and neutrophil count in the MP group but not in those on TG. No correlation between metabolite concentration and thrombocytopenia was found in either group. These results provide further evidence that TG has a selective effect on platelets. They also showed that RBC TGN were, on average, 5-fold higher in those taking TG but did not obviously relate to myelotoxicity as found in children on MP. The higher concentrations seen may partly reflect the erythrocyte's ability to metabolize TG directly to TGN by pathways not open to MP.
Tyrosine kinase inhibitors suppress endotoxin- and IL-1 beta-induced NO synthesis in aortic smooth muscle cells (1993)

Nitric oxide (NO) formation via the expression of an endotoxin- and cytokine-inducible NO synthase (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse that occurs during septic shock and antitumor therapy with cytokines. Because the molecular mechanisms that underlie induction of iNOS are still unclear and because tyrosine kinases are implicated in interleukin-1 beta (IL-1 beta)-induced prostaglandin synthesis in mesangial cells and in NO generation by an insulinoma cell line, we investigated the influence of tyrosine kinase inhibitors on iNOS induction in cultured rat aortic smooth muscle cells (RASMC). The production of biologically active NO was demonstrated by L-arginine-dependent guanosine 3',5'-cyclic monophosphate (cGMP) accumulation after a 3-h exposure to either IL-1 beta or lipopolysaccharide (LPS). Pretreatment of RASMC for 30 min with the tyrosine kinase inhibitor genistein prevented both IL-1 beta- and LPS-elicited cGMP accumulation in a concentration-dependent manner. Geldanamycin, a chemically different tyrosine kinase inhibitor, also blocked cGMP formation in response to both LPS and IL-1 beta at nanomolar concentrations. Genistein and geldanamycin inhibited cGMP accumulation even when added 90 min after LPS exposure, but no inhibition was observed when they were included at later time points (120-180 min), suggesting that the inhibitors had no direct effect on iNOS activity after its induction. Formation of cGMP in response to sodium nitroprusside and to NO released from bovine aortic endothelial cells remained virtually unaffected by genistein and geldanamycin.(ABSTRACT TRUNCATED AT 250 WORDS)
An Improved Unified Scalable Radix-2 Montgomery Multiplier (2005)

This paper describes an improved version of the Tenca-Koc unified scalable radix-2 Montgomery multiplier with half the latency for small and moderate precision operands and half the queue memory requirement. Like the Tenca-Koc multiplier, this design is reconfigurable to accept any input precision in either GF(p) or GF(2/sup n/) up to the size of the on-chip memory. An FPGA implementation can perform 1024-bit modular exponentiation in 16 ms using 5598 4-input lookup tables, making it the fastest unified scalable design yet reported.
Picosecond Ellipsometry of Transient Electron-Hole Plasmas in Germanium (1974)

An ellipsometer has been used with picosecond pulses to measure the time evolution of optically generated plasmas in intrinsic Ge. By measuring the change in optical ellipticity of a weak probe beam following the absorption of an intense excitation pulse, the time evolution of the plasma density can be determined with a precision of a few picoseconds. At a density of 1.7 \ifmmode\times\else\texttimes\fi{} ${10}^{20}$ ${\mathrm{cm}}^{\ensuremath{-}3}$, the ambipolar diffusivity of the plasma was observed to be a factor of 3 greater than the low-density value, consistent with a simple theoretical model of diffusion in the degenerate regime.
Direct Transfer of α-Synuclein from Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies (2010)

Abnormal neuronal aggregation of alpha-synuclein is implicated in the development of many neurological disorders, including Parkinson disease and dementia with Lewy bodies. Glial cells also show extensive alpha-synuclein pathology and may contribute to disease progression. However, the mechanism that produces the glial alpha-synuclein pathology and the interaction between neurons and glia in the disease-inflicted microenvironment remain unknown. Here, we show that alpha-synuclein proteins released from neuronal cells are taken up by astrocytes through endocytosis and form inclusion bodies. The glial accumulation of alpha-synuclein through the transmission of the neuronal protein was also demonstrated in a transgenic mouse model expressing human alpha-synuclein. Furthermore, astrocytes that were exposed to neuronal alpha-synuclein underwent changes in the gene expression profile reflecting an inflammatory response. Induction of pro-inflammatory cytokines and chemokines correlated with the extent of glial accumulation of alpha-synuclein. Together, these results suggest that astroglial alpha-synuclein pathology is produced by direct transmission of neuronal alpha-synuclein aggregates, causing inflammatory responses. This transmission step is thus an important mediator of pathogenic glial responses and could qualify as a new therapeutic target.
Neurovirulence of Type 1 Polioviruses Isolated from Sewage in Japan (2002)

Sixteen type 1 poliovirus strains were isolated from a sewage disposal plant located downstream of the Oyabe River in Japan between October 1993 and September 1995. The isolates were intratypically differentiated as vaccine-derived strains. Neutralizing antigenicity analysis with monoclonal antibodies and estimation of neurovirulence by mutant analysis by PCR and restriction enzyme cleavage (MAPREC) were performed for 13 type 1 strains of these isolates. The isolates were classified into three groups. Group I (five strains) had a variant type of antigenicity and neurovirulent phenotype. Group II (four strains) had the vaccine type of antigenicity and neurovirulent phenotype. Group III (four strains) had the vaccine type of antigenicity and an attenuated phenotype. Furthermore, it was demonstrated that the virulent isolates were neutralized by human sera obtained after oral poliomyelitis vaccine (OPV) administration, and the sera of rats immunized with inactivated poliovirus vaccine. Although vaccination was effective against virulent polioviruses, virulent viruses will continue to exist in the environment as long as OPV is in use.
The effects of crystallographic orientation and strain of thin Hf0.5Zr0.5O2 film on its ferroelectricity (2014)

To elucidate the origin of the formation of the ferroelectric phase in Hf0.5Zr0.5O2 films, the effects of film strain and crystallographic orientation on the properties were examined. Using a (111)-textured Pt bottom electrode, Hf0.5Zr0.5O2 films with a (111)-preferred texture inappropriate for transforming their phase from non-ferroelectric tetragonal to ferroelectric orthorhombic phase were deposited. In contrast, randomly oriented Hf0.5Zr0.5O2 films, grown on the TiN electrode, showed feasible ferroelectric properties due to their transformation to the ferroelectric orthorhombic phase. The origin of such transformation is the large in-plane tensile strain for the elongation of the c-axis of the tetragonal phase.
Solid state oxygen anion and electron mediating membrane and catalytic membrane reactors containing them (2023)

A process for production of synthesis gas employing a catalytic membrane reactor wherein the membrane comprises a mixed metal oxide material.
Recurrent Infections, Hypotonia, and Mental Retardation Caused by Duplication of MECP2 and Adjacent Region in Xq28 (2006)

Although many of the phenotypic features of our patients are rather nonspecific in cohorts of individuals with syndromic and nonsyndromic mental retardation, the proneness to infection is quite striking because the patients had normal growth and were not physically debilitated. Although the etiology of the infections is not understood, we recommend considering MECP2 dosage studies and a genetics referral in individuals with severe developmental delay and neurologic findings, especially when a history of recurrent respiratory ailments has been documented.
Sulphiting agents in foods: Some risk/benefit considerations (1985)

The current toxicological status of sulphiting agents is reviewed, including evidence of adverse reactions to sulphited foods by a sub-population of asthmatics. Against this background are assessed the applications and benefits of sulphiting agents in foods. It is concluded that further information is required to determine the magnitude of risk and that, in the interim, the controlled use of sulphiting agents is justifiable.
Double-blind, placebo-controlled, proof-of-concept trial of bexarotene in moderate Alzheimer’s disease (2016)

ClinicalTrials.gov identifier NCT01782742 . Registered 29 January 2013.
Der Sport und seine Rolle in der nationalsozialistischen Elitetruppe SS (2007)

Reichsführer-SS Heinrich Himmler maß körperlicher Ertüchtigung und sportlichem Wettbewerb einen hohen Stellenwert zu. Die Angehörigen der SS waren verpflichtet, das SA-Sportabzeichen zu erwerben, um - gemäß der nationalsozialistischen Weltanschauung - eine natürliche Auslese zu erzielen und die Formierung einer elitären Truppe sicherzustellen. Während des 'SS-Sportjahres' fanden paramilitärische Übungen statt, in denen sich die Schutzstaffeln auf deutschlandweite Wettbewerbe gegen andere NS-Organisationen vorbereiteten. Doch klafften Anspruch und Realität häufig weit auseinander. Die 'Schwarzen Reiter' erwiesen sich hingegen als sportlich äußerst erfolgreich - die Hauptreitschule München versuchte am Vorabend des Zweiten Weltkrieges der Einberufung zu entgehen mit dem Hinweis, dass man sich auf die Olympischen Spiele von 1940 vorbereiten müsse.
Development of a stable Leishmania expression vector and application to the study of parasite surface antigen genes. (1990)

Trypanosomatid protozoan parasites cause several important tropical diseases and have been a fertile ground for the discovery of molecular paradigms such as trans-splicing and RNA editing. Transfection-based methods for the study of these organisms have recently been developed, and we have now designed an expression vector, pX, which contains only 2.3 kilobases of Leishmania DNA and can be stably transfected with high efficiency. Genes encoding Escherichia coli beta-galactosidase or a Leishmania amazonensis protective membrane glycoprotein (GP46A/M-2) were inserted into the pX expression site and transfected into Leishmania major, where they directed the synthesis of high levels of mRNAs formed by 5' and 3' processing events occurring predominantly at the sites used by the normal transcripts. Colony assays and immunoblot analysis showed that both proteins were produced; enzymatically active beta-galactosidase comprised approximately 1% of total protein. Sizes of the GP46A protein synthesized in transfected L. major or L. amazonensis were similar and differed from the predominant L. amazonensis GP46, suggesting that the GP46A gene may encode a variant GP46 family member. Because these vectors function efficiently in pathogenic species of Leishmania, pX will facilitate the genetic analyses of parasite proteins crucial for infectivity as well as the identification of cis-acting elements mediating transcription and replication.
‘Two is better than one’—probes for dual-modality molecular imaging (2009)

Molecular or personalised medicine is the future of patient management and healthcare, and molecular imaging plays a key role towards this goal. However, amongst molecular imaging techniques, no single modality is perfect and sufficient to gain all the necessary information. For instance, optical fluorescence imaging is difficult to quantify--especially in tissue more than a few millimetres in depth within a subject; magnetic resonance imaging (MRI) has superb resolution but low sensitivity and positron emission tomography (PET) has very high sensitivity but poor resolution. The combination of multiple molecular imaging techniques can therefore offer synergistic advantages over any modality alone. However, the problem cannot be solved by simply adding two different classes of imaging probes together, unless they happen to have identical pharmacodynamic properties. Therefore, multi-modal contrast agents or imaging probes have been developed to solve this problem. Despite the great wealth of information that such probes can provide, their development is far from trivial and represents an important challenge to synthetic chemists. In this feature article, we provide an overview of recent findings in the synthesis, evaluation and application of dual-modality molecular imaging probes.
The DCC gene product in cellular differentiation and colorectal tumorigenesis. (1994)

The analysis of human colorectal tumors has revealed frequent loss of heterozygosity (LOH) of the long arm of chromosome 18. A novel gene, DCC (deleted in colorectal cancer), located within the region of LOH on chromosome 18q was identified and has been implicated as a tumor suppressor gene. We have now shown that DCC encodes a membrane-bound protein of the immunoglobulin-CAM family, as demonstrated by cell-surface labeling, immunohistochemical analysis, and sequencing of cDNA clones. The DCC protein was found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lacked DCC expression and loss of a chromosome 18q allele was often accompanied by loss of DCC expression in colon tumors. These results provide evidence that DCC encodes a cell surface-localized protein and emphasize the inverse relationship between differentiation and tumorigenesis.
Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia (2010)

Tumor-induced immune defects can weaken host immune response and permit tumor cell growth. In a systemic model of murine acute myeloid leukemia (AML), tumor progression resulted in increased regulatory T cells (Treg) and elevation of program death-1 (PD-1) expression on CD8(+) cytotoxic T cells (CTLs) at the tumor site. PD-1 knockout mice were more resistant to AML despite the presence of similar percentage of Tregs compared with wild type. In vitro, intact Treg suppression of CD8(+) T-cell responses was dependent on PD-1 expression by T cells and Tregs and PD-L1 expression by antigen-presenting cells. In vivo, the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs. Anti-PD-L1 monoclonal antibody treatment increased the proliferation and function of CTLs at tumor sites, reduced AML tumor burden, and resulted in long-term survivors. Treg depletion followed by PD-1/PD-L1 blockade showed superior efficacy for eradication of established AML. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response. PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease.