gebhart/patrepeval huggingface dataset:
Martindale: the complete drug reference (2005)

This book provides reliable, unbiased and evaluated information on drugs and medicines used throughout the world. Each new drug licensed for use has its own potential benefits and adverse effects, and its own profile for dosage, administration and indications. Furthermore, manufacturers make regular changes to existing drug names and formulations, which can affect their interactions and safe usage. Health professionals require the correct answers and need to have confidence in the drugs information they use - but with medicines evolving at this rate, how can they be sure their knowledge is up to date? Martindale contains up to date information about more than 5,800 substances. Each and every entry is reviewed by our pharmaceutical editors to ensure health professionals have the most current data. Formulations change. Definitions change. Names change. But you can always trust Martindale.
Increased Autoantibody Titers Against Epitopes of Oxidized LDL in LDL Receptor–Deficient Mice With Increased Atherosclerosis (1995)

Increasing evidence indicates that immune processes modulate atherogenesis. Oxidized LDL (Ox-LDL) is immunogenic, and autoantibodies recognizing epitopes of Ox-LDL have been described in plasma and in atherosclerotic lesions of several species. To determine whether the titer of such autoantibodies correlates with the extent of atherosclerosis, we followed the development of antibodies against malondialdehyde-lysine, an epitope of Ox-LDL, in two groups of LDL receptor-deficient mice for 6 months. One group was fed an atherogenic diet (21% fat and 0.15% cholesterol) that resulted in marked hypercholesterolemia and extensive aortic atherosclerosis; the other group was fed regular rodent chow (4% fat) that did not alter plasma cholesterol levels and induced minimal atherosclerosis. Autoantibody titers significantly increased over time in the group on the atherogenic diet, whereas they remained constant in the chow-fed group. When data from both groups were pooled, a significant correlation was found between the autoantibody titers and the extent of atherosclerosis (r = .61, P < .01). Autoantibody titers also correlated with plasma cholesterol levels (r = .48, P < .05). These results suggest that the rise in autoantibody titers to an epitope of Ox-LDL in this murine model is partially determined by the extent of atherosclerosis but could also be influenced by the degree of hypercholesterolemia or other factors that may influence lipid peroxidation.
Vimentin methylation as a marker for advanced colorectal carcinoma. (2009)

Vimentin was frequently methylated in advanced colorectal carcinoma.
Design Studies for a 200 MeV Proton Clinic for Radiotherapy (1972)

Protons of 200 MeV energy compete favourably with conventional radiations for radiotherapy and are useful for radiosurgery and radionuclide production. They provide flexibility of beam shaping and, since the radiation is dominantly low LET, dose modification by temporal or chemical means is possible. Radiotherapy can be based on conventional experience plus 15 years' minor experience with protons.In Sweden (8 million inhabitants), there is demand for about 1000 radiotherapy treatments per day. About one‐quarter of these would benefit from the outstanding dose distributions attainable with protons. Five treatment rooms are required for 220 treatments per day — providing vertical, horizontal and angled beams. Separate facilities are provided for radiosurgery and radionuclide production. The beam cross‐section should be up to 30 × 30 cm, intensity uniform within ±2% over the treatment volume, length of the plateau region variable from 2 to 27 cm and dose rate at least 200 rad/min. The operating reliability of the system must be extremely high.The medical requirements can be met with a fixed‐energy isochronous cyclotron with a beam transport system incorporating an eight‐channel beam distributor, bending and focusing magnets and beam sweeping magnets. The cost of the whole system, including building, all accessories and a radionuclide production facility but excluding wards and normal clinical laboratories, was estimated at US$7 million.
Molecular mechanisms of nucleic acid integration (1990)

There are three known mechanisms by which foreign DNA can be made a permanent part of the genome of an animal cell, and their properties are summarized in this report. Naked DNA introduced into cells is usually rapidly lost, but a small fraction can be integrated by illegitimate recombination, usually accompanied by major and unpredictable rearrangements in both inserted DNA and target. This mechanism, although inefficient and disruptive, accounts for virtually all integrated DNA seen in virus infections, and is often used for making cell lines carrying specific genes as well as transgenic mice. Homologous recombination between inserted and resident DNA is much rarer but can be detected and put to use. The best understood mechanism is that employed by retroviruses and related elements. In contrast to the other mechanisms, retroviral integration results in a predictable, stable association between virus and cell DNA with only minor sequence changes. However, it occurs only when the DNA is derived by reverse transcription of the RNA in an incoming viral particle and contains the correct sequences at its ends. Thus, from a standpoint of vaccine safety, only the first of the three mechanisms is at all relevant. Based on some prior experimentation in animals, the risk of introduction of activated oncogenes or other dangerous sequences by this means is extremely small.
Lnc-PCDH9-13:1 Is a Hypersensitive and Specific Biomarker for Early Hepatocellular Carcinoma (2018)

Salivary lnc-PCDH9-13:1 is a desirable biomarker for early HCC. It may help warrant prospective validation with larger sample sizes in multi-centers.
Immunoglobulin treatment in sepsis—Is the answer “no”?* (2006)

Department of Medicine III, Martin-Luther-University Halle-Wittenberg, Klinikum Kröllwitz, Halle (Saale), Germany The author is engaged in clinical and experimental work on immunoglobulins in inflammation and sepsis. With this respect, the following categories of financial interest existed/do exist with Bayer, Germany (Polyglobin) and Biotest, Germany (Pentaglobin): consultancies, honoraria/speaking fees, and grants.
Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine (2000)

These comprehensive data demonstrate modest (< twofold) mean reductions in didanosine and stavudine susceptibilities at follow-up. The emergence of zidovudine associated mutations in this retroviral-naive population treated with combination didanosine and stavudine therapy is notable. Furthermore, the emergence of these mutations and of the Q151 M multinucleoside resistance complex raise concerns for potential nucleoside analog cross-resistance. The potential mechanisms driving the selection of the zidovudine associated mutations in the setting of didanosine and stavudine therapy and the relevance of these findings to current three and four drug regimens merit further evaluation.
Transgenic Mice Expressing Human β‐APP751, But Not Mice Expressing β‐APP695, Display Early Alzheimer's Disease‐like Histopathologya (1993)

Mice transgenic for the 751 amino acid isoform of the human beta-amyloid precursor protein (beta-APP) driven by the rat neuron specific enolase (NSE) promoter (NSE:beta-APP751) show features of early Alzheimer's disease (AD) pathology. These features, which were evident in multiple pedigrees, include: 1) preamyloid deposits which stain with antibodies that are specific for the beta-amyloid peptide and stain AD amyloid deposits and plaques, and 2) neuronal soma and processes which stain with an antibody (Alz50) that detects abnormal isoforms of tau which are characteristic of AD. The quality and distribution of both types of immunoreactivity revealed in the NSE:beta-APP751 mouse brains most closely resemble those seen in brains of young adults with Down's syndrome. Both structures are rarely, if ever, observed in brains from mice transgenic for the 695 amino acid isoform of beta-APP (NSE:beta-APP695) or in wild type mice.
Fcγ Receptor IIB on Follicular Dendritic Cells Regulates the B Cell Recall Response (2000)

Generation of the B cell recall response appears to involve interaction of Ag, in the form of an immune complex (IC) trapped on follicular dendritic cells (FDCs), with germinal center (GC) B cells. Thus, the expression of receptors on FDC and B cells that interact with ICs could be critical to the induction of an optimal recall response. FDCs in GCs, but not in primary follicles, express high levels of the IgG Fc receptor Fc gamma RIIB. This regulated expression of Fc gamma RIIB on FDC and its relation to recall Ab responses were examined both in vitro and in vivo. Trapping of IC in spleen and lymph nodes of Fc gamma RII-/- mice was significantly reduced compared with that in wild-type controls. Addition of ICs to cultures of Ag-specific T and B cells elicited pronounced Ab responses only in the presence of FDCs. However, FDCs derived from Fc gamma RIIB-/- mice supported only low level Ab production in this situation. Similarly, when Fc gamma RIIB-/- mice were transplanted with wild-type Ag-specific T and B cells and challenged with specific Ag, the recall responses were significantly depressed compared with those of controls with wild-type FDC. These results substantiate the hypothesis that FcgammaRIIB expression on FDCs in GCs is important for FDCs to retain ICs and to mediate the conversion of ICs to a highly immunogenic form and for the generation of strong recall responses.
Acute Interleukin-6 Administration Impairs Athletic Performance in Healthy, Trained Male Runners (2004)

Fatigue is an inevitable consequence of physical activity; yet its biological cause remains uncertain. During exercise, a polypeptide messenger molecule interleukin-6 (IL-6) is actively produced. Previously, the administration of recombinant IL-6 (rhIL-6) induced a heightened sensation of fatigue in healthy humans at rest. In contrast, anti-IL-6 receptor antibodies reduced the symptoms of chronic fatigue. In the present study, athletic performance during an exercise challenge consisting of a 10-km running time trial was significantly impaired in trained male runners following the administration of a low dose of rhIL-6 compared to the placebo trial.
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2 (2006)

Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of innate and adaptive responses stimulated by PSA. Optimization of the Th1 cytokine interferon-gamma in PSA-stimulated dendritic cell-CD4+ T cell co-cultures depends on both Toll-like receptor (TLR) 2 and antigen presentation. Synergy between the innate and adaptive responses was also shown when TLR2-/- mice exhibited impaired intraabdominal abscess formation in response to B. fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the Th1/Th2 cell balance and the response to infection by coordinating both the innate and adaptive pathways.
Jiangsu Rudong 25MW straw power project : supplemental to feasibility study, report dated Oct.2004 (2006)

This environmental assessment for the China Renewable Energy Scale-Up Program (CRESP), which expands the use of renewable energy resources, discusses likely negative environmental impacts and proposals to mitigate them. The issues include the following: Reduce water and land pollution caused by setting a sediment basin and oil trap for factory sewage, using septic tanks to control domestic sewage, treating domestic sewage, and isolating and fencing disposal sites, using temporary dump sites in the construction area, sending waste to a government-approved landfill weekly, and strictly executing a wastewater discharge standard, and recovering land after site removal and replanting. To control noise nuisance, select low-noise equipment, use shock absorbers and noise insulation, schedule reasonable operation times, ban night construction but if needed give local people advance notice, prohibit night driving, and warn local residents if blasting is needed. To control dust, use dustproof covers for machinery and cement areas, and spray area and access roads. To promote worker health and safety, set up medical facilities and encourage hygiene control, and train workers. To reduce soil erosion and surface water runoff, plan construction for the dry season, use designated sites for deposits, avoid disposal in water bodies, use silt traps, and restore farmland. Get official approval before proceeding with construction when finding cultural artifacts. Ban the purchase of any electrical or hydro mechanical equipment that contains polychlorinated biphenyls (PCBs).
Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production (2014)

Identifying signaling pathways that regulate hematopoietic stem and progenitor cell (HSPC) formation in the embryo will guide efforts to produce and expand HSPCs ex vivo. Here we show that sterile tonic inflammatory signaling regulates embryonic HSPC formation. Expression profiling of progenitors with lymphoid potential and hematopoietic stem cells (HSCs) from aorta/gonad/mesonephros (AGM) regions of midgestation mouse embryos revealed a robust innate immune/inflammatory signature. Mouse embryos lacking interferon γ (IFN-γ) or IFN-α signaling and zebrafish morphants lacking IFN-γ and IFN-ϕ activity had significantly fewer AGM HSPCs. Conversely, knockdown of IFN regulatory factor 2 (IRF2), a negative regulator of IFN signaling, increased expression of IFN target genes and HSPC production in zebrafish. Chromatin immunoprecipitation (ChIP) combined with sequencing (ChIP-seq) and expression analyses demonstrated that IRF2-occupied genes identified in human fetal liver CD34(+) HSPCs are actively transcribed in human and mouse HSPCs. Furthermore, we demonstrate that the primitive myeloid population contributes to the local inflammatory response to impact the scale of HSPC production in the AGM region. Thus, sterile inflammatory signaling is an evolutionarily conserved pathway regulating the production of HSPCs during embryonic development.
CYP153A6, a Soluble P450 Oxygenase Catalyzing Terminal-Alkane Hydroxylation (2006)

The first and key step in alkane metabolism is the terminal hydroxylation of alkanes to 1-alkanols, a reaction catalyzed by a family of integral-membrane diiron enzymes related to Pseudomonas putida GPo1 AlkB, by a diverse group of methane, propane, and butane monooxygenases and by some membrane-bound cytochrome P450s. Recently, a family of cytoplasmic P450 enzymes was identified in prokaryotes that allow their host to grow on aliphatic alkanes. One member of this family, CYP153A6 from Mycobacterium sp. HXN-1500, hydroxylates medium-chain-length alkanes (C6 to C11) to 1-alkanols with a maximal turnover number of 70 min(-1) and has a regiospecificity of > or =95% for the terminal carbon atom position. Spectroscopic binding studies showed that C6-to-C11 aliphatic alkanes bind in the active site with Kd values varying from approximately 20 nM to 3.7 microM. Longer alkanes bind more strongly than shorter alkanes, while the introduction of sterically hindering groups reduces the affinity. This suggests that the substrate-binding pocket is shaped such that linear alkanes are preferred. Electron paramagnetic resonance spectroscopy in the presence of the substrate showed the formation of an enzyme-substrate complex, which confirmed the binding of substrates observed in optical titrations. To rationalize the experimental observations on a molecular scale, homology modeling of CYP153A6 and docking of substrates were used to provide the first insight into structural features required for terminal alkane hydroxylation.
Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer (2000)

Phenylamidine cationic groups linked by a furan ring (furamidine) and related compounds bind as monomers to AT sequences of DNA. An unsymmetric derivative (DB293) with one of the phenyl rings of furamidine replaced with a benzimidazole has been found by quantitative footprinting analyses to bind to GC-containing sites on DNA more strongly than to pure AT sequences. NMR structural analysis and surface plasmon resonance binding results clearly demonstrate that DB293 binds in the minor groove at specific GC-containing sequences of DNA in a highly cooperative manner as a stacked dimer. Neither the symmetric bisphenyl nor bisbenzimidazole analogs of DB293 bind significantly to the GC containing sequences. DB293 provides a paradigm for design of compounds for specific recognition of mixed DNA sequences and extends the boundaries for small molecule-DNA recognition.
Toward One Symbol Network Coding Vectors (2012)

In this paper, we propose a novel design for network coding vectors that limits the overhead information. Network coding vectors contain information regarding the operations the packets have undergone in the network nodes. They are used at the decoder side to invert coding operations and recover the data. We propose to reduce the size of this side information with the use of Vandermonde-like generator matrices at the sources. These matrices permit to describe the coding operations performed on packets with only one symbol. We analytically investigate the limitations arising from such design constraints. Interestingly, we find that the feasible generation size is upper bounded by log <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> q in Galois field F <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">q</sub> of size q as this is the maximum packet diversity allowed by the employed generator matrices. In addition, we show that network coding nodes should only perform addition operations in order to maintain the properties of the coding vectors. We finally discuss the benefits and limitations of the proposed coding vectors in practical systems.
Expression of Jak2V617F causes a polycythemia vera–like disease with associated myelofibrosis in a murine bone marrow transplant model (2006)

An acquired somatic mutation, Jak2V617F, was recently discovered in most patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), and essential thrombocythemia (ET). To investigate the role of this mutation in vivo, we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wild-type (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt, resulted in clinicopathologic features that closely resembled PV in humans. These included striking elevation in hemoglobin level/hematocrit, leukocytosis, megakaryocyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathologic and flow cytometric analyses showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polyploidization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine-independent growth of erythroid colony-forming unit (CFU-E) and erythropoietin hypersensitivity, and Southern blot analysis for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype, with Balb/c mice demonstrating markedly elevated leukocyte counts, splenomegaly, and reticulin fibrosis compared with C57Bl/6 mice. We conclude that Jak2V617F expression in bone marrow progenitors results in a PV-like syndrome with myelofibrosis and that there are strain-specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans.
Surface-enhanced resonance Raman scattering nanostars for high-precision cancer imaging (2015)

The inability to visualize the true extent of cancers represents a significant challenge in many areas of oncology. The margins of most cancer types are not well demarcated because the cancer diffusely infiltrates the surrounding tissues. Furthermore, cancers may be multifocal and characterized by the presence of microscopic satellite lesions. Such microscopic foci represent a major reason for persistence of cancer, local recurrences, and metastatic spread, and are usually impossible to visualize with currently available imaging technologies. An imaging method to reveal the true extent of tumors is desired clinically and surgically. We show the precise visualization of tumor margins, microscopic tumor invasion, and multifocal locoregional tumor spread using a new generation of surface-enhanced resonance Raman scattering (SERRS) nanoparticles, which are termed SERRS nanostars. The SERRS nanostars feature a star-shaped gold core, a Raman reporter resonant in the near-infrared spectrum, and a primer-free silication method. In genetically engineered mouse models of pancreatic cancer, breast cancer, prostate cancer, and sarcoma, and in one human sarcoma xenograft model, SERRS nanostars enabled accurate detection of macroscopic malignant lesions, as well as microscopic disease, without the need for a targeting moiety. Moreover, the sensitivity (1.5 fM limit of detection) of SERRS nanostars allowed imaging of premalignant lesions of pancreatic and prostatic neoplasias. High sensitivity and broad applicability, in conjunction with their inert gold-silica composition, render SERRS nanostars a promising imaging agent for more precise cancer imaging and resection.
Characterization of the Cellular and Antitumor Effects of MPI-0479605, a Small-Molecule Inhibitor of the Mitotic Kinase Mps1 (2011)

Mps1 is a dual specificity protein kinase that is essential for the bipolar attachment of chromosomes to the mitotic spindle and for maintaining the spindle assembly checkpoint until all chromosomes are properly attached. Mps1 is expressed at high levels during mitosis and is abundantly expressed in cancer cells. Disruption of Mps1 function induces aneuploidy and cell death. We report the identification of MPI-0479605, a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.