gebhart/patrepeval huggingface dataset:
Subject Index Vol. 5, 1998 (1998)

Agnus castus 6 272 Acid phosphatase 4 172 Action scheme for primary care S1 90 Acupuncture 2 81, 3 132, S1 8 Analgesia S1 12 Anthroposophical medicine 1 27 Apoptosis 3 164 Application of medical principles S1 90 Arsenicum album (As 2 O 3 ) 3 122 Autogenic training 4 211 Autohaemotherapy 2 54 Balneogynaecology 3 115 Basic research 4 172 Benefit analysis S1 90 Best-case analyses S1 68 Best-case series S1 68 Bias 4 184 Biochemical and physical modelling 5 236 Biochemistry 5 236 Bioelectrical oscillations 5 230 Bioresonance 5 230 Biosemiotics S1 18 Bone fracture 5 244 cAMP 3 122 cAMP 4 172 Carnivora S1 68 Case report 6 266 Case series S1 128 Case-control studies 6 266 Case-taking S1 15 Cell-free systems 3 122, 4 172 Cephalgia 6 279 Cerebral blood flow velocity 6 279 Chelation therapy 6 266 Chinese herbal therapy 2 81, 3 132 Chromosomal instability 3 164 Chronic inflammatory bowel diseases 4 178 Clinical trial methodology S1 47 Clinical trials S1 121, S1 125, S1 31, S1 8 Cohort study 1 18 Colitis ulcerosa 4 178 Comparison of therapeutic systems without placebo groups S1 131 Complementary medicine 4 184, S1 128 Combined modality treatment S1 136 Controlled clinical studies 4 211 Controlled studies 6
Exploring the DNA-recognition potential of homeodomains (2012)

The recognition potential of most families of DNA-binding domains (DBDs) remains relatively unexplored. Homeodomains (HDs), like many other families of DBDs, display limited diversity in their preferred recognition sequences. To explore the recognition potential of HDs, we utilized a bacterial selection system to isolate HD variants, from a randomized library, that are compatible with each of the 64 possible 3' triplet sites (i.e., TAANNN). The majority of these selections yielded sets of HDs with overrepresented residues at specific recognition positions, implying the selection of specific binders. The DNA-binding specificity of 151 representative HD variants was subsequently characterized, identifying HDs that preferentially recognize 44 of these target sites. Many of these variants contain novel combinations of specificity determinants that are uncommon or absent in extant HDs. These novel determinants, when grafted into different HD backbones, produce a corresponding alteration in specificity. This information was used to create more explicit HD recognition models, which can inform the prediction of transcriptional regulatory networks for extant HDs or the engineering of HDs with novel DNA-recognition potential. The diversity of recovered HD recognition sequences raises important questions about the fitness barrier that restricts the evolution of alternate recognition modalities in natural systems.
Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential (2001)

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited e x t r e m e l y h i g h m e t a s t a t i c a b i l i t y i n c l u d i n g spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis, antisense approach, metallopro teinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
Characterization of the Adeno-Associated Virus 1 and 6 Sialic Acid Binding Site (2016)

ABSTRACT The adeno-associated viruses (AAVs), which are being developed as gene delivery vectors, display differential cell surface glycan binding and subsequent tissue tropisms. For AAV serotype 1 (AAV1), the first viral vector approved as a gene therapy treatment, and its closely related AAV6, sialic acid (SIA) serves as their primary cellular surface receptor. Toward characterizing the SIA binding site(s), the structure of the AAV1-SIA complex was determined by X-ray crystallography to 3.0 Å. Density consistent with SIA was observed in a pocket located at the base of capsid protrusions surrounding icosahedral 3-fold axes. Site-directed mutagenesis substitution of the amino acids forming this pocket with structurally equivalent residues from AAV2, a heparan sulfate binding serotype, followed by cell binding and transduction assays, further mapped the critical residues conferring SIA binding to AAV1 and AAV6. For both viruses five of the six binding pocket residues mutated (N447S, V473D, N500E, T502S, and W503A) abolished SIA binding, whereas S472R increased binding. All six mutations abolished or decreased transduction by at least 50% in AAV1. Surprisingly, the T502S substitution did not affect transduction efficiency of wild-type AAV6. Furthermore, three of the AAV1 SIA binding site mutants—S472R, V473D, and N500E—escaped recognition by the anti-AAV1 capsid antibody ADK1a. These observations demonstrate that common key capsid surface residues dictate both virus binding and entry processes, as well as antigenic reactivity. This study identifies an important functional capsid surface “hot spot” dictating receptor attachment, transduction efficiency, and antigenicity which could prove useful for vector engineering. IMPORTANCE The adeno-associated virus (AAV) vector gene delivery system has shown promise in several clinical trials and an AAV1-based vector has been approved as the first gene therapy treatment. However, limitations still exist with respect to transduction efficiency and the detrimental effects of preexisting host antibodies. This study aimed to identify key capsid regions which can be engineered to overcome these limitations. A sialic glycan receptor recognition pocket was identified in AAV1 and its closely related AAV6, using X-ray crystallography. The site was confirmed by mutagenesis followed by cell binding and transduction assays. Significantly, residues controlling gene expression efficiency, as well as antibody escape variants, were also identified. This study thus provides, at the amino acid level, information for rational structural engineering of AAV vectors with improved therapeutic efficacy.
Characterization of the protein encoded by the flt3 (flk2) receptor-like tyrosine kinase gene. (1993)

We have developed rabbit polyclonal antibodies to the C-terminus of the flt3-encoded protein, which is a member of the receptor tyrosine kinase family. Immunoprecipitation using this antiserum brings down two protein bands, a major band of 143 kDa and a less abundant, more diffuse, band of 158 kDa. Pulse-chase analysis of flt3 protein from transfected COS-7 cells shows that the larger band is derived from the smaller one and presumably represents maturation of the protein from a glycosylated high-mannose form to a complex carbohydrate form. N-glycosidase F digestion confirmed the presence of N-linked carbohydrates, and cell-surface labeling of flt3-transfected cells indicated that the 158-kDa glycoprotein is the species found on the cell surface. A mutated form of the flt3 protein that was defective in its glycosylational processing was identified. Western blotting of the immunoprecipitated flt3 protein showed that it is heavily phosphorylated on tyrosine, and that this phosphorylation probably occurs in the absence of ligand. In this regard, the flt3 protein resembles the c-erbB2 protein, which is also highly phosphorylated in the absence of ligand. These data suggest that the flt3 receptor regulates the growth and differentiation of cells via an as yet unknown ligand.
[The evaluation of insulin resistance]. (2005)

胰岛素抵抗(IR)是近年研究的热点,为此往往要求定量地检测IR或胰岛素敏感指数(ISI,即IR的倒数).检测IR的方法很多,现作一简单复习[1]. IR是指一定量胰岛素的生物学效应减少.胰岛素的生物学效应有许多方面,如外周对葡萄糖(G)的廓清,抑制肝糖输出或对激素敏感的脂酶作用等.不同组织对胰岛素作用的敏感性也不同.现主要讨论对G的代谢.
Stability of Plasminogen Activator Inhibitor 1 (PAI-1) (1989)

The stability of PAI-activity has been studied at different conditions. The inactivation followed first order kinetics. Lowering the temperature and decreasing the pH both, increased the stability of PAI-1 dramatically. Addition of the PAI-1 binding protein, vitronectin, to reactivated PAI-1, about doubled the half-life of PAI-1 at all conditions studied. In the presence of chloramine T, the inactivation of reactivated PAI-1 was very rapid. In this case the protective effect of purified vitronectin, human plasma or fetal calf serum, but not of bovine serum albumin, was pronounced. The stability of the spontaneously active high Mr form of PAI-1 (partially purified or in plasma), constituting a complex between PAI-1 and vitronectin, was quite similar to reactivated PAI-1 in the presence of vitronectin. Addition of pure vitronectin, human plasma or fetal calf serum to such material had no further stabilizing effect. Reactivated PAI-1, which was inactivated by incubation at physiological conditions could again be fully reactivated, in contrast to chloramine T-oxidized PAI-1, which was irreversibly inactivated.
Apoptotic Caspase Activation and Activity (2008)

Caspases are central to the execution of apoptosis. Their proteolytic activity is responsible for the demise of cells in many physiological and pathological states. Great advances in understanding caspases have been made using recombinant caspase expression and enzymatic characterization. Assays to measure caspase activity in apoptotic cell extracts and the development of a reconstituted cell-free assay were also critical in establishing the hierarchy in the caspase activation cascade and comprehend how caspase-9 is activated by the apoptosome. More recently, new tools such as activity-based probes allowed us to detect caspase activation in their working environment providing readout of the system with minimal interference. This chapter describes some of the methods used by our group to study the activation mechanisms of caspases and their activity.
[Thalidomide treatment of prurigo nodularis]. (1993)

Twenty-two patients suffering from prurigo nodularis were treated with thalidomide 50-300 mg daily for an average of 12 months (two weeks to five years), following a special arrangement between the Danish Government and the producer Grünenthal GMBH, by which the Government took full economical responsibility for any claims related to the treatment. All patients received prior to treatment a detailed written information about all potential side-effects from the treatment, and had by their signature acknowledged, that they wished to be treated. All but two of the patients had an immediate pronounced effect on their main symptom, the tormenting itching. The same patients had a significant decrease in size and numbers of skin lesions after one to two months of treatment. However, the therapy had to be discontinued in thirteen patients (59%) due to side-effects. The most important side-effect, neuropathy, was the reason for discontinuation of thalidomide in five patients (22%). In spite of the high frequency of side-effects, we consider that this treatment modality should still be offered to the patients with the most severe symptoms due to the pronounced effect on this otherwise therapy resistant disease.
KRASMutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer (2007)

KRAS mutation should be included as indicator of resistance in the panel of markers used to predict response to EGFR-TKIs in NSCLC.
Effects of polydextrose on serum lipids, lipoproteins, and apolipoproteins in healthy subjects. (1991)

The subjects were 61 healthy volunteers who received 15 gm of polydextrose daily for two months. A significant increase in the incidence of soft feces and diarrhea and in the volume of feces was reported during polydextrose treatment. These had returned to normal one month after treatment. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change during treatment. Levels of apolipoprotein (apo) A-I and A-II were significantly lowered at one month and high-density lipoprotein cholesterol (HDL-C) and apo A-I were significantly decreased at two months; these returned to normal after treatment. Levels of HDL2-C decreased and HDL3-C levels increased significantly during treatment. The results indicate that polydextrose selectively affected the metabolism of HDL and its major proteins, apo A-I and A-II.
A new paradigm for use of ultrafast lasers in ophthalmology for enhancement of corneal mechanical properties and permanent correction of refractive errors (2017)

A new paradigm for strengthening of corneal tissue as well as permanent correction of refractive errors has been proposed. Ultrafast laser irradiation is confined to the levels below optical breakdown such that tissue damage is avoided while creating an ionization field responsible for subsequent photochemical modification of the stroma. The concept was assed using newly developed platform for precise application of a near-IR femtosecond laser irradiation to the cornea in in-vitro experiments. Targeted irradiation with tightly focused ultrafast laser pulses allows spatially resolved crosslinking in the interior of the porcine cornea in the absence of photosensitizers. The formation of intra- or interstromal covalent bonds in collagen matrix locally increases lamellar density. Due to high resolution, treatment is spatially resolved and therefore can be tailored to either enhance structure of corneal stroma or adjust corneal curvature towards correcting refractive errors. As the induced modification is primarily driven by nonlinear absorption, the treatment is essentially wavelength independent, and as such potentially less harmful than current method of choice, joint application of UVA light irradiation in conjunction with riboflavin. Potential applicability of a near-IR femtosecond laser for biomechanical stabilization of cornea and non-invasive refractive eye corrections is discussed.
INDUCTION OF CHRONIC AUTOIMMUNE ARTHRITIS IN DBA/1 MICE BY ORAL ADMINISTRATION OF TYPE II COLLAGEN AND ESCHERICHIA COLl LIPOPOLYSACCHARIDE (1996)

We have developed a new model of autoimmune arthritis in DBA/1 mice by feeding chick type II collagen (CII) for 2-3 week intervals over a 15 week period. Clinically evident arthritis occurred in 8/10 mice receiving native CII (nCII; 100 micrograms/mouse) alone at 9-13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 micrograms/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10 micrograms/mouse) with CII enhanced the antibody production and T-cell responses to CII, and induced a more chronic arthritis that progressed spontaneously without further administration of CII or LPS. Long-term oral administration of LPS alone also induced a mild arthritis characterized by destruction of bone rather than cartilage. These observations suggest that abnormal gastrointestinal absorption of dietary mimic antigens and intestinal bacterial toxins can potentially disrupt self-tolerance mechanisms, thereby precipitating or exacerbating autoimmune disease in genetically susceptible individuals.
Learning to Reweight Examples for Robust Deep Learning (2018)

Deep neural networks have been shown to be very powerful modeling tools for many supervised learning tasks involving complex input patterns. However, they can also easily overfit to training set biases and label noises. In addition to various regularizers, example reweighting algorithms are popular solutions to these problems, but they require careful tuning of additional hyperparameters, such as example mining schedules and regularization hyperparameters. In contrast to past reweighting methods, which typically consist of functions of the cost value of each example, in this work we propose a novel meta-learning algorithm that learns to assign weights to training examples based on their gradient directions. To determine the example weights, our method performs a meta gradient descent step on the current mini-batch example weights (which are initialized from zero) to minimize the loss on a clean unbiased validation set. Our proposed method can be easily implemented on any type of deep network, does not require any additional hyperparameter tuning, and achieves impressive performance on class imbalance and corrupted label problems where only a small amount of clean validation data is available.
Prostaglandin D2 synthase: Apoptotic factor in alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines and dialysis dementia. (2013)

These data collectively suggest that L-PGDS might play an important role in the development of dementia in patients on dialysis and of AD.
Lipid-like materials for low-dose, in vivo gene silencing (2010)

Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.
Visualizing nanoparticle mobility in liquid at atomic resolution (2013)

Gold nanorods are widely known for their photothermal properties to treat solid tumors. Our work demonstrates the unrealized capacity to image these reagents in liquid at high resolution using Transmission Electron Microscopy (TEM). Here we perform the first atomic measurements of functionalized nanorods in solution while visualizing their dynamic behaviour with TEM.
Thrombolysis in Brain Ischemia (TIBI) Transcranial Doppler Flow Grades Predict Clinical Severity, Early Recovery, and Mortality in Patients Treated With Intravenous Tissue Plasminogen Activator (2001)

Emergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPA-treated stroke patients. A flow-grade improvement correlated with clinical improvement.
An unusual novel anti-oxidant dibenzoyl glycoside from Salvinia natans (2009)

An unusual novel and significant anti-oxidant 1,2-dibenzoyl glycoside, natansnin (1), has been isolated from Salvinia natans. The structure of 1 was established by the study of NMR and CD spectral data.
Plasma vascular endothelial growth factor and interleukin-8 as biomarkers of antitumor efficacy of a prototypical erbB family tyrosine kinase inhibitor (2005)

CI-1033 (N-[4-[N-(3-chloro-4-fluorophenyl)amino-7-[3-(4-morpholynyl)propoxy]quinazolin-6-yl]acrylamide, PD 0183805-mesylate salt) was identified as a potent, selective inhibitor of erbB family tyrosine kinases, which are overexpressed in a number of solid tumors and have been shown to be involved in tumor progression. Because objective response of clinical patients to erbB-targeted therapies like CI-1033 has been observed only in a subset of cancer patients that exhibit the intended molecular targets, much emphasis has been placed on the identification of biomarkers of antitumor efficacy. Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) were considered as potential biomarkers for CI-1033 due to ease of detection in patient plasma and showed roles in angiogenesis and cancer progression and positive regulation by the erbB receptor family. In the present studies, mice bearing established xenografts (A431 epidermoid carcinoma, H125 non-small cell lung carcinoma, SF767 glioblastoma, and MDA-MB-468 mammary carcinoma) were treated with efficacious and subefficacious doses of CI-1033, and plasma levels and xenograft gene expression of VEGF and IL-8 were evaluated. Oral administration of CI-1033 to tumor-bearing mice at efficacious doses resulted in markedly decreased levels of VEGF and/or IL-8 plasma levels and tumor mRNA levels relative to vehicle-treated control mice in xenograft models that exhibited evaluable levels of these markers. In contrast, subefficacious doses of CI-1033 did not significantly affect VEGF or IL-8 levels in any of the xenograft models. These studies indicate that plasma VEGF and IL-8 may have use as biomarkers of antitumor efficacy for epidermal growth factor receptor/erbB-targeted therapies such as CI-1033 and suggest that further clinical study of these markers in cancer patients are warranted.
Comparison of polarized-light propagation in biological tissue and phantoms (1999)

We demonstrate significant differences in the propagation of polarized light through biological tissue compared with two common tissue phantoms. Depolarization of linearly and circularly polarized light was measured versus propagation distance by use of two independent measurement techniques. The measurements were performed on adipose and myocardial tissues and on tissue phantoms that consisted of polystyrene microsphere suspensions and Intralipid. The results indicate that, in contrast with results obtained in tissue phantoms, linearly polarized light survives through longer propagation distances than circularly polarized light in biological tissue.
The many faces of radiation-induced changes (2006)

During diffraction experiments even cryo-cooled protein crystals can be significantly damaged due to chemical and physical changes induced by absorbed X-ray photons. The character and scale of the observed effects depend strongly on the temperature and the composition of crystals. The absorption of radiation energy results in incremental regular changes to the crystal structure, making its impact on the process of solving the structure strongly correlated with other experimental variables. An understanding of all the dependencies is still limited and does not allow for a precise prediction of the outcome of a particular diffraction experiment. Results are presented of diffraction experiments performed under different experimental conditions. The influence of temperature and crystal composition on different characteristics of radiation damage is analyzed. The observed effects are discussed in terms of their impact on data processing and phasing procedures.