gebhart/patrepeval huggingface dataset:
Synthese von Haschisch‐Inhaltsstoffen. 4. Mitteilung (1969)

Abstract (−)‐Cannabidiol has been synthesized from (+)‐ cis ‐ and (+)‐ trans ‐ p ‐menthadien‐(2, 8)‐ol‐(1) and olivetol, using N, N‐dimethylformamide dineopentyl acetal or weak acids, such as oxalic, picric, or maleic acid, as catalysts. Since the chirality of (+)‐ trans ‐ p ‐menthadien‐(2, 8)‐ol‐(1) is known, the above synthesis constitutes an unambiguous prove for the absolute configuration of (−)‐cannabidiol and the two isomeric (−)‐6a, 10a‐ trans ‐tetrahydrocannabinols. If stronger acids, such as p ‐toluenesulfonic, trifluoroacetic, or hydrochloric acid, are used as mediators for the reaction, (−)‐Δ 8 ‐6a, 10a‐ trans ‐tetrahydrocannabinol is obtained as the main product. Transformation of the thermodynamically more stable Δ 8 ‐tetrahydrocannabinol into the less stable Δ 9 ‐isomer was achieved in a practically quantitative yield by addition of hydrochloric acid and elimination of the elements of hydrochloric acid by means of potassium t ‐amylate. If resorcinols I were used instead of olivetol in the condensation reaction with strong acids, the corresponding homologues of Δ 8 ‐tetrahydrocannabinol were obtained in varying yields.
The first international conference on vascular targeting: meeting overview. (2003)

The First International Conference on Vascular Targeting focused on vascular targeting agents (VTAs) that occlude or destroy the pre-existing blood vessels of solid tumors. The VTAs cause a rapid shutdown in the blood supply to the tumor that kills tumor cells by depriving them of oxygen and nutrients. The VTAs are distinct from antiangiogenic agents, which prevent new blood vessel formation. Two major types of VTAs are being developed for cancer: the ligand-directed VTAs that use antibodies, peptides, and growth factors to deliver toxins, procoagulants, and proapoptotic effectors to tumor endothelium, and the small molecule VTAs that do not specifically localize to tumor endothelium but exploit pathophysiological differences between tumor and normal tissue endothelia to induce acute vascular shutdown in tumors. Both approaches were described at the meeting and highlighted the variety of VTAs in preclinical development, their selectivity for tumor endothelium, their rapid antitumor effects, and the improved activity seen when combined with other anticancer approaches (antiproliferative chemotherapeutic drugs, radiation, radiolabeled antibodies, nitric oxide synthetase inhibitors, and antiangiogenic agents). Early clinical studies were summarized for the small molecule VTAs: the antitubulin drugs, combretastatin A4 phosphate (CA4P) and ZD6126, and the flavonoid, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). The agents lacked the bone marrow and gastrointestinal toxicities associated with antiproliferative chemotherapy. As a marker of biological effect, blood flow reductions in tumors were measured using magnetic resonance imaging or positron emission tomography for all of the agents tested, and single-agent clinical activity was seen. These agents are now being evaluated in combined modality studies to see whether the impressive results obtained in experimental models can be translated into humans.
Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression. (1988)

The human placental alkaline phosphatase gene has been cloned and reintroduced into mammalian cells. When a plasmid carrying the gene under control of the simian virus 40 early promoter (pSV2Apap) is transfected into a variety of different cell types, placental alkaline phosphatase activity can readily be detected by using whole cell suspensions or cell lysates. Alkaline phosphatase activity can also be visualized directly in individual transfected cells by histochemical staining. The gene is appropriate for use as a reporter in studies of gene regulation since its expression is dependent on the presence of exogenous transcription control elements. The overall assay to detect the expression of the gene is quantitative, very rapid, and inexpensive. Cotransfections of cells with pSV2Apap and a related plasmid carrying the bacterial chloramphenicol acetyltransferase gene (pSV2Acat) indicate that transcription of these two genes is detected with roughly the same sensitivity.
Functional switching of GABAergic synapses by ryanodine receptor activation (2000)

The role of the ryanodine receptor (RyR) in modifiability of synapses made by the basket interneurons onto the hippocampal CA1 pyramidal cells was examined in rats. Associating single-cell RyR activation with postsynaptic depolarization increased intracellular free Ca(2+) concentrations and reversed the basket interneuron-CA1 inhibitory postsynaptic potential into an excitatory postsynaptic potential. This synaptic transformation was accompanied by a shift of the reversal potential from that of chloride toward that of bicarbonate. This inhibitory postsynaptic potential-excitatory postsynaptic potential transformation was prevented by blocking RyR or carbonic anhydrase. Associated postsynaptic depolarization and RyR activation, therefore, changes GABAergic synapses from excitation filters to amplifier and, thereby, shapes information flow through the hippocampal network.
LP-DOS magnifies the PC screen (2003)

As a visually impaired computer user the author needed a simple solution that would allow him and others to see and use the vast range of PC text and graphics programs. He created LP-DOS (Large Print DOS). LP-DOS is a software package that can run on any PC or laptop. It can be used anywhere: business, home, or school. Once loaded, LP-DOS magnifies wordprocessors, spreadsheets, educational software, and video games. Now, LP-DOS is also the first product to also completely support the Microsoft Windows environment opening the world of Windows to people with low vision.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fin-Width Dependence of BJT-Based 1T-DRAM Implemented on FinFET (2010)

This letter investigates fin-width dependence on single-transistor latch (STL) for bipolar-junction-transistor (BJT)-based 1T-DRAM through experiments. The minimum drain voltage <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$(V_{\rm latch})$</tex></formula> for the activation of a parasitic lateral BJT in SOI FinFET was measured at various gate lengths ( <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$L_{G}$</tex></formula> 's) and fin widths ( <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">$W_{\rm fin}$</tex></formula> 's). The multiplication factor and current gain of the parasitic BJT in SOI MOSFET are introduced as determinant factors. The experimental results clearly show that the value of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$V_{\rm latch}$</tex></formula> is reduced in a shorter <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$L_{G}$</tex></formula> and wider <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$W_{\rm fin}$</tex></formula> device. It was found that the nonlocal effect retards the reduction of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$V_{\rm latch}$</tex></formula> as FinFET scales down.
Glaucoma, apoptosis, and neuroprotection (1997)

The demise of the retinal ganglion cell represents the final common pathway of glaucomatous vision loss. Various studies demonstrate that ganglion cells die by the mechanism of apoptosis in conditions such as experimental animal models of glaucoma and optic nerve transection, and in human glaucoma. Apoptosis is a basic cell death mechanism noted in a number of neurodegenerative conditions. It constitutes a genetically coded "suicide" program activated when cells are no longer needed or have been seriously damaged, and is typified by rapid phagocytosis without inflammation. These cells demonstrate characteristic morphological changes on electron microscopy: nuclear chromatin condensation, compaction of cytoplasmic organelles, and membrane blebbing. Neurotrophin withdrawal and excitotoxic neurotransmitters have been implicated in apoptosis in ganglion cells damaged by glaucoma. Understanding the cellular and molecular biological events involved in ganglion cell death may lead to novel approaches to the treatment of glaucoma.
Oxygen Therapy Reduces Secondary Hemorrhage after Thrombolysis in Thromboembolic Cerebral Ischemia (2010)

Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n=96) breathed either air, 100% O(2) (NBO), or 100% O(2) at 3 bar (HBO) for 1 hour. Immediately thereafter, recombinant tissue plasminogen activator (rt-PA, 9 mg/kg) was injected. Although significant reperfusion was observed after thrombolysis in TT-tMCAO, vascular occlusion persisted in CT-tMCAO. In TT-tMCAO, NBO and HBO significantly reduced diffusion-weighted imaging-magnetic resonance imaging (MRI) lesion volume and postischemic blood-brain barrier (BBB) permeability on postcontrast T1-weighted images. NBO and, significantly more potently, HBO reduced macroscopic hemorrhage on T2* MRI and on corresponding postmortem cryosections. Oxygen therapy lowered hemoglobin content and attenuated activation of matrix metalloproteinases in the ischemic hemisphere. In contrast, NBO and HBO failed to reduce infarct size in CT but both decreased BBB damage and microscopic hemorrhagic transformation. Only HBO reduced hemoglobin extravasation in the ischemic hemisphere. In conclusion, NBO and HBO decrease infarct size after thromboembolic ischemia only if recanalization is successful. As NBO and HBO also reduce postthrombolytic intracerebral hemorrhage, combining the two with thrombolysis seems promising.
The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma (2013)

Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts--including physicians, nurses, and patient advocates--to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-α2b, pegylated-interferon-α2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted.
Inhibition of TGFβ signaling and its implications in anticancer treatments. (2012)

The transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis. In cancer, two distinctive behaviors of TGFβ have been reported as a tumor suppressor at early stage of the disease, and as a tumor promoter at later stages. The past decades, the dualistic role of TGFβ has garnered a lot of attention. As a result, cancer researchers' has been tasked to elucidate how TGFβ signaling may lead to metastatic dissemination, how to tackle carcinogenesis and which therapeutic strategies should be adopted. Consequently, TGFβ signaling pathways have been considered as appropriate targets for cancer therapy. The TGFβ therapeutic strategies have emerged at three levels: ligand, ligand-receptor interaction and intracellular signaling level. Promising inhibitors of TGFβ signaling have entered clinical trials and shown encouraging results. Here we review the three strategies of TGFβ signa-ling inhibition and theirs applications in treatment of cancer.
<title>Image acquisition system for traffic monitoring applications</title> (1995)

An imaging system for monitoring traffic on multilane highways is discussed. The system, named Safe-T-Cam, is capable of operating 24 hours per day in all but extreme weather conditions and can capture still images of vehicles traveling up to 160 km/hr. Systems operating at different remote locations are networked to allow transmission of images and data to a control center. A remote site facility comprises a vehicle detection and classification module (VCDM), an image acquisition module (IAM) and a license plate recognition module (LPRM). The remote site is connected to the central site by an ISDN communications network. The remote site system is discussed in this paper. The VCDM consists of a video camera, a specialized exposure control unit to maintain consistent image characteristics, and a 'real-time' image processing system that processes 50 images per second. The VCDM can detect and classify vehicles (e.g. cars from trucks). The vehicle class is used to determine what data should be recorded. The VCDM uses a vehicle tracking technique to allow optimum triggering of the high resolution camera of the IAM. The IAM camera combines the features necessary to operate consistently in the harsh environment encountered when imaging a vehicle 'head-on' in both day and night conditions. The image clarity obtained is ideally suited for automatic location and recognition of the vehicle license plate. This paper discusses the camera geometry, sensor characteristics and the image processing methods which permit consistent vehicle segmentation from a cluttered background allowing object oriented pattern recognition to be used for vehicle classification. The image capture of high resolution images and the image characteristics required for the LPRMs automatic reading of vehicle license plates, is also discussed. The results of field tests presented demonstrate that the vision based Safe-T-Cam system, currently installed on open highways, is capable of producing automatic classification of vehicle class and recording of vehicle numberplates with a success rate around 90 percent in a period of 24 hours.
Protein Sculptors That Help Turn on Genes (1995)

Over the past decade or so, molecular biologists have learned that cells use various combinations of the proteins called transcription factors to turn genes on and off. But recent research has shown that the precise three-dimensional shapes of those transcription factor complexes are just as critical for correct gene control as the identities of the proteins that make them up. What's more, these shapes are often sculpted with the aid of “architectural proteins,” which are themselves part of the complexes and which help assemble them by forcing large bends into the DNA to which the complexes bind.
Demyelinating Myelin Oligodendrocyte Glycoprotein-Specific Autoantibody Response Is Focused on One Dominant Conformational Epitope Region in Rodents, (2008)

Conformational epitopes of myelin oligodendrocyte glycoprotein (MOG) provide a major target for demyelinating autoantibodies in experimental autoimmune encephalomyelitis and recent studies indicate that a similar situation may exist in multiple sclerosis. We recently solved the crystal structure of the extracellular domain of MOG (MOG(ex)) in complex with a Fab derived from the demyelinating mAb 8-18C5 and identified the conformational 8-18C5 epitope on MOG that is dominated by the surface exposed FG loop of MOG. To determine the importance of this epitope with regard to the polyclonal Ab response to MOG(ex) we investigated the effects of mutating His(103) and Ser(104), the two central amino acids of the FG loop, on Ab binding. Mutation of these two residues reduced binding of a panel of eight demyelinating conformation-dependent mAbs to <20% compared with binding to wild-type MOG(ex), whereas substitution of amino acids that do not contribute to the 8-18C5 epitope had only a minor effect on Ab binding. The same restriction was observed for the polyclonal MOG-specific Ab response of MOG DNA-vaccinated BALB/c and SJL/J mice. Our data demonstrate that the pathogenic anti-MOG Ab response primarily targets one immunodominant region centered at the FG loop of MOG. Comparison of the structure of MOG(ex) with the structures of related IgV-like domains yields a possible explanation for the focused Ab response.
Genetically Encoded Cholesterol-Modified Polypeptides (2019)

Biological systems use post-translational modifications (PTMs) to control the structure, location, and function of proteins after expression. Despite the ubiquity of PTMs in biology, their use to create genetically encoded recombinant biomaterials is limited. We have utilized a natural lipidation PTM (hedgehog-mediated cholesterol modification of proteins) to create a class of hybrid biomaterials called cholesterol-modified polypeptides (CHaMPs) that exhibit programmable self-assembly at the nanoscale. To demonstrate the biomedical utility of CHaMPs, we used this approach to append cholesterol to biologically active peptide exendin-4 that is an approved drug for the treatment of type II diabetes. The exendin-cholesterol conjugate self-assembled into micelles, and these micelles activate the glucagon-like peptide-1 receptor with a potency comparable to that of current gold standard treatments.
Optimizing Adoptive Polyclonal T Cell Immunotherapy of Lymphomas, Using a Chimeric T Cell Receptor Possessing CD28 and CD137 Costimulatory Domains (2007)

We previously demonstrated the feasibility of generating therapeutic numbers of cytotoxic T lymphocyte (CTL) clones expressing a CD20-specific scFvFc:CD3zeta chimeric T cell receptor (cTCR), making them specifically cytotoxic for CD20+ B lymphoma cells. However, the process of generating and expanding he CTL clones was laborious, the CTL clones expressed the cTCR at low surface density, and they exhibited suboptimal proliferation and cytotoxicity. To improve the performance of the CTLs in vitro and in vivo, we engineered "second-generation'' plasmid constructs containing a translational enhancer (SP163) and CD28 and CD137 costimulatory domains in cis with the CD3zeta intracellular signaling domain of the cTCR gene. Furthermore, we verified the superiority of generating genetically modified polyclonal T cells expressing the second-generation cTCR rather than T cell clones. Our results demonstrate that SP163 enhances the surface expression of the cTCR; that the second-generation cTCR improves CTL activation, proliferation, and cytotoxicity; and that polyclonal T cells proliferate rapidly in vitro and mediate potent CD20-specific cytotoxicity. This study provides the preclinical basis for a clinical trial of adoptive T cell immunotherapy for patients with relapsed CD20+ mantle cell lymphoma and indolent lymphomas.
Microbial community and metabolomic comparison of irritable bowel syndrome faeces (2011)

Human health relies on the composition of microbiota in an individual's gut and the synthesized metabolites that may alter the gut environment. Gut microbiota and faecal metabolites are involved in several gastrointestinal diseases. In this study, 16S rRNA-specific denaturing gradient gel electrophoresis and quantitative PCR analysis showed that the mean similarity of total bacteria was significantly different (P<0.001) in faecal samples from patients with irritable bowel syndrome (IBS; n = 11) and from non-IBS (nIBS) patients (n = 8). IBS subjects had a significantly higher diversity of total bacteria, as measured by the Shannon index (H') (3.36<H'<4.37, P = 0.004), Bacteroidetes and lactobacilli; however, less diversity was observed for Bifidobacter (1.7< H'<3.08, P<0.05) and Clostridium coccoides (0.9< H'<2.98, P = 0.007). In this study, no significant difference was found in total bacterial quantity (P>0.05). GC/MS-based multivariate analysis delineated the faecal metabolites of IBS from nIBS samples. Elevated levels of amino acids (alanine and pyroglutamic acid) and phenolic compounds (hydroxyphenyl acetate and hydroxyphenyl propionate) were found in IBS. These results were highly correlated with the abundance of lactobacilli and Clostridium, which indicates an altered metabolism rate associated with these gut micro-organisms. A higher diversity of Bacteroidetes and Lactobacillus groups in IBS faecal samples also correlated with the respective total quantity. In addition, these changes altered protein and carbohydrate energy metabolism in the gut.
Functional Analysis and Regulation of the Divergent spuABCDEFGH-spuI Operons for Polyamine Uptake and Utilization in Pseudomonas aeruginosa PAO1 (2002)

A multiple-gene locus for polyamine uptake and utilization was discovered in Pseudomonas aeruginosa PAO1. This locus contained nine genes designated spuABCDEFGHI (spu for spermidine and putrescine utilization). The physiological functions of the spu genes in utilization of two polyamines (putrescine and spermidine) were analyzed by using Tn5 transposon-mediated spu knockout mutants. Growth and uptake experiments support that the spuDEFGH genes specify components of a major ABC-type transport system for spermidine uptake, and enzymatic measurements indicated that spuC encodes putrescine aminotransferase with pyruvate as the amino group receptor. Although spuA and spuB mutants showed an apparent defect in spermidine utilization, the biochemical functions of the gene products have yet to be elucidated. Assays of lacZ fusions demonstrated the presence of agmatine-, putrescine-, and spermidine-inducible promoters for the spuABCDEFGH operon and the divergently transcribed spuI gene of unknown function. Since the observed induction effect of agmatine was abolished in an aguA mutant where conversion of agmatine into putrescine was blocked, putrescine or spermidine, but not agmatine, serves as the inducer molecule of the spuA-spuI divergent promoters. S1 nuclease mappings confirmed further the induction effects of the polyamines on transcription of the divergent promoters and localized the transcription initiation sites. Gel retardation assays with extracts from the cells grown on putrescine or spermidine demonstrated the presence of a polyamine-responsive regulatory protein interacting with the divergent promoter region. Finally, the absence of the putrescine-inducible spuA expression and putrescine aminotransferase (spuC) formation in the cbrB mutant indicated that the spu operons are regulated by the global CbrAB two-component system perhaps via the putative polyamine-responsive transcriptional activator.