gebhart/patrepeval huggingface dataset:
A comparative study of the anticancer efficacy of doxorubicin carrying microspheres and liposomes using a rat liver tumour model. (1993)

Due to low efficacy of chemotherapy in the treatment of liver cancer, several methods of drug targeting have been investigated. Liposomes designed to carry cytotoxic drugs to the liver are currently under clinical evaluation. While experimental evidence shows promise, this method of drug delivery has several disadvantages that include short shelf life and poor drug delivery into tumour tissue. An alternative strategy for targeted drug delivery involving use of ion exchange microspheres may overcome these limitations while still reducing systemic toxicity and maintaining therapeutic efficacy. The purpose of this study was to determine the relative antitumour efficacy of these two drugs carrying systems in the treatment of liver cancer. Compared to controls, DOX treatment with free drug, liposomes or microspheres significantly reduced tumour growth by 56% (P < 0.001), 51% (P < 0.01) and 79% (P < 0.001) respectively. Furthermore, the DOX-microsphere treatment was significantly better than either of the other DOX treatments (53%, P < 0.05) or the sham-microsphere treated group (64%, P < 0.05). Thus, drug microspheres can increase the anti-tumour efficacy compared to either free or liposomal drug while simultaneously reducing systemic toxicity.
The Peace Support Operations Model: Strategic Interaction Process (2011)

Modeling complex social interaction creates a number of challenges for the strategic analyst. Firstly, the fundamental basis of an operational model has to be based on rational and verifiable metrics, but recognize that human interaction in the real world is often irrational and is rarely verifiable. Secondly, the evolving discourse between factions almost always influences the ongoing process of interaction — often creating entirely new modes of interaction as the scenario unfolds. Our solution was to continue to base the Peace Support Operations Model (PSOM) Operational Game on verifiable metrics and create an interaction process designed to include those modes of interaction that are ill-suited to structured analysis and better addressed by processes that can adapt to shifts in strategic emphasis. The PSOM Strategic Interaction Process thus follows the same turn-based design as the Operational Game, but creates a framework for political interaction and the recording of faction intent as the game proceeds.
Adenoviral Bak overexpression mediates caspase-dependent tumor killing. (2000)

One of the most promising strategies in cancer gene therapy is adenoviral transfer of proapoptotic genes. We therefore evaluated the novel strategy of adenovirally overexpressing the proapoptotic Bak gene. Our results showed marked apoptosis in cancer cells in vivo and in vitro after Bak gene transfer via a binary adenoviral vector system. This effect was not seen in a caspase 3-defective cell line (MCF-7) and was abrogated in Bak-sensitive tumors after administration of the caspase inhibitor z-DEVD-fmk. Our results suggest that adenoviral-mediated overexpression of Bak provides a novel therapeutic strategy for cancer therapy, but this process appears to be caspase dependent.
Moderate Calcium Channel Dysfunction in Adult Mice with Inducible Cardiomyocyte-specific Excision of the cacnb2 Gene (2011)

The major L-type voltage-gated calcium channels in heart consist of an α1C (Ca(V)1.2) subunit usually associated with an auxiliary β subunit (Ca(V)β2). In embryonic cardiomyocytes, both the complete and the cardiac myocyte-specific null mutant of Ca(V)β2 resulted in reduction of L-type calcium currents by up to 75%, compromising heart function and causing defective remodeling of intra- and extra-embryonic blood vessels followed by embryonic death. Here we conditionally excised the Ca(V)β2 gene (cacnb2) specifically in cardiac myocytes of adult mice (KO). Upon gene deletion, Ca(V)β2 protein expression declined by >96% in isolated cardiac myocytes and by >74% in protein fractions from heart. These latter protein fractions include Ca(V)β2 proteins expressed in cardiac fibroblasts. Surprisingly, mice did not show any obvious impairment, although cacnb2 excision was not compensated by expression of other Ca(V)β proteins or changes of Ca(V)1.2 protein levels. Calcium currents were still dihydropyridine-sensitive, but current density at 0 mV was reduced by <29%. The voltage for half-maximal activation was slightly shifted to more depolarized potentials in KO cardiomyocytes when compared with control cells, but the difference was not significant. In summary, Ca(V)β2 appears to be a much stronger modulator of L-type calcium currents in embryonic than in adult cardiomyocytes. Although essential for embryonic survival, Ca(V)β2 down-regulation in cardiomyocytes is well tolerated by the adult mice.
The Convergent Approach to the Synthesis of Lipid A and Its Analogs (1983)

The chemistry and biological activities of lipid A are reviewed in earlier chapters of this volume. As noted there, the components of the lipid A complexes from Salmonella species and E. coli are derivatives of a disaccharide comprised of two D-glucosamine units linked β,1→6. The disaccharide is substituted at positions 1 and 4′ by phosphate functions and on the amino nitrogens by β-hydroxymyristoyl groups. A variable number (up to 5) of ester-linked fatty acyl residues is also present. In the simplest components the phosphates are present as monoester groups. Once these structural features were established, the synthesis of compounds of the lipid A group appeared feasible, and was undertaken in a number of laboratories. Successful efforts, based on distinctive strategies, are described by Kusumoto et al., Kiso and Hasegawa, and Szabó et al. elsewhere in this volume, and in the present chapter. In common with the Osaka and Gifu groups,
Acousto-optic multifrequency modulators: reduction of the phase-grating intermodulation products (1993)

The multifrequency acousto-optic modulator efficiency is limited mainly by the two-tone, third-order intermodulation products. We show here that a suitable anisotropic interaction can greatly reduce this undesirable effect. Numerical computations have been drawn for a paratellurite acousto-optic cell, and it is shown that a reduction of ~ 16 dB can be reached, limited by the acoustic nonlinearity intermodulation products. A specific method for experimental validation, based on optical heterodyning on a photodetector, is presented. The experimental results agree well with the theoretical ones.
The novel subset of CD14<sup>+</sup>/CD16<sup>+</sup> blood monocytes exhibits features of tissue macrophages (1993)

The CD14+/CD16+ cells account for about 10% of all blood monocytes. They are characterized by a low level expression of the CD14 molecule and a high level expression of the CD16 (Fc gamma R III) molecule. Polymerase chain reaction analysis of mRNA prevalence in CD14+/CD16+ cells (compared to the regular CD14++ blood monocytes) demonstrates low levels of CD14 transcripts and high levels of CD16 transcripts, suggestive of a transcriptional control for both of these proteins. Analysis of additional cell surface molecules in three-color immunofluorescence reveals that CD14+/CD16+ cells express the Fc gamma R II in all, and Fc gamma R I and ICAM-1 in some donors. Furthermore, class II antigens are expressed at fourfold higher levels, while both, CD11b and CD33 cell surface proteins, are decreased by a factor of two. Transcript levels were reduced in CD14+/CD16+ cells for all three cell surface molecules. Since these phenotypic markers of the CD14+/CD16+ blood monocytes are reminiscent of tissue macrophages, we performed a comparative analysis with alveolar macrophages (AM). These cells are similar to the CD14+/CD16+ monocytes in that they show low levels of CD14 and strong expression of CD16. Furthermore, similar to the CD14+/CD16+ cells, the AM also exhibit higher levels of class II and lower levels of CD11b and CD33 when compared to the regular CD14++ blood monocytes. In vitro induction of maturation of blood monocytes by 5 day culture of peripheral blood mononuclear cells in 10% human serum will result in decreased CD14 and increased CD16 cell surface expression on the monocyte derived macrophages. At the same time, these cells acquire increased levels of class II and decreased levels of CD11b and CD33. Taken together, these data show that CD14+/CD16+ monocytes, while still in circulation, have acquired features in common with mature tissue macrophages.
Improving Immunotherapy by Conditionally Enhancing MHC Class I Presentation of Tumor Antigen-Derived Peptide Epitopes (2007)

Tumors represent an altered self cell type that can be recognized by both the host humoral (B cells, antibodies) and cellular (T cells) adaptive immune systems. Because most known tumor-associated antigens (TAA) recognized by T cells represent overexpressed or aberrantly expressed proteins, which are not mutated and to which tolerance has been developed, the anti-TAA T-cell repertoire available to the cancer patient is of moderate-to-low avidity. Specific vaccinations typically amplify the absolute number of such T cells, but may have little consequence on improving their functional avidity, which may fall below a critical threshold required for effective recognition of tumor cells in situ. This review will discuss methods to improve low-avidity T-cell recognition of cancer cells by manipulating the tumor cells themselves to conditionally express higher levels of TAA-derived peptide epitopes presented in major histocompatibility (MHC) complexes. This may facilitate the design and performance of novel combinational therapies for the effective treatment of a broad range of cancer types.
Ultrasonically enhanced sedimentation—Results of an empirical scale-up approach (1999)

Ultrasonic standing waves are suitable for both coagulation of dilute suspensions and thickening of already settled sludge. For each purpose the right choice of process parameters and reactor design is important. The used ultrasonic effects are acoustic radiation and acoustic as well as hydrodynamic particle interaction forces. Acoustic and convective streaming cause shear stress on particle clusters and can therefore disperse aggregates. To achieve good efficiency at high flow rates, these undesirable streaming effects must be controlled, especially for the realization of larger reactors. One suitable measure is to divide the sonicated volume into several smaller parts separated by thin polyethylene films. Basic investigations in various batch and continuous flow lab systems led to an empirically derived scale-up concept. A prototype 3-MHz transducer array consisting of 16 single piezos used for coagulation has been developed and manufactured in cooperation with ELAC Nautik (Kiel). Preliminary results of two new pilot plants (sonicated volume 10 L for coagulation, respectively, 70 L for thickening) show good performance of the reactors. Comparison with previous lab scale data prove the applicability of the scale-up method as it will be presented at the meeting.
Vitamin A Levels and Immunity in Humans (2002)

ABSTRACT In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 μg/dl), 34% had moderate deficiency (10 to <20 μg/dl), and 36% had normal levels (≥20 μg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 μg/dl, respectively). Vitamin A-deficient children (<20 μg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis , or other type 1 pathogens.
A use of sigma-delta modulation in power digital-to-analogue conversion (1997)

Power digital-to-analogue (D–A) converters have applications in digital audio, portable equipment and industrial control systems. This paper discusses the use of sigma–delta modulation as the primary processing block in power D–A systems. The focus is on the pulse repetition frequency (PRF) of the one-bit output and its suitability for power switching. It is shown that in order to preserve high power efficiency and tolerance to a non-ideal output stage, the PRF of the output may be reduced and made constant by the use of a technique termed bit flipping. The performance of different bit flipping algorithms is discussed which aim to regulate the PRF whilst maintaining the stability of the modulation process. Results are presented which compare the performance of the different systems under the conditions of an ideal and a non-ideal output stage. © 1997 by John Wiley & Sons, Ltd.
Metadata harvesting framework in P2P-based digital libraries (2004)

This paper reviews the main efforts in the research of harvesting metadata records in distributed digital libraries environment. The advantages and remained issues are briefly presented in order to have a comparison in our new approaches.\n\nA general scenario of integrating metadata in Peer-to-Peer based environment is introduced with respect to three situations, such as sharing a common schema; different schema but in thesame community; different schema and community. There are many issues in the framework, whilst in this paper we present ourapproaches in extending OAI metadata harvesting protocol to fulfill the requirements in P2P network and adopting popular inference engine for heterogeneous schema mappings. Additionally, a rough idea is also presented for locating peer in such a framework.
Which Variables Should I Log? (2019)

Developers usually depend on inserting logging statements into the source code to collect system runtime information. Such logged information is valuable for software maintenance. A logging statement usually prints one or more variables to record vital system status. However, due to the lack of rigorous logging guidance and the requirement of domain-specific knowledge, it is not easy for developers to make proper decisions about which variables to log. To address this need, in this work, we propose an approach to recommend logging variables for developers during development by learning from existing logging statements. Different from other prediction tasks in software engineering, this task has two challenges: 1) Dynamic labels - different logging statements have different sets of accessible variables, which means in this task, the set of possible labels of each sample is not the same. 2) Out-of-vocabulary words - identifiers' names are not limited to natural language words and the test set usually contains a number of program tokens which are out of the vocabulary built from the training set and cannot be appropriately mapped to word embeddings. To deal with the first challenge, we convert this task into a representation learning problem instead of a multi-label classification problem. Given a code snippet which lacks a logging statement, our approach first leverages a neural network with an RNN (recurrent neural network) layer and a self-attention layer to learn the proper representation of each program token, and then predicts whether each token should be logged through a unified binary classifier based on the learned representation. To handle the second challenge, we propose a novel method to map program tokens into word embeddings by making use of the pre-trained word embeddings of natural language tokens. We evaluate our approach on 9 large and high-quality Java projects. Our evaluation results show that the average MAP of our approach is over 0.84, outperforming random guess and an information-retrieval-based method by large margins.
Head Orientation Estimation using Characteristic Points of Face (2006)

Head pose determination represents an important area of research in human computer interaction (HCI). There are many researches in the area of estimation with monocular vision [1]. Methods for head pose estimation
A Mouse Model of the Cornea Pocket Assay for Angiogenesis Study (2011)

A normal cornea is clear of vascular tissues. However, blood vessels can be induced to grow and survive in the cornea when potent angiogenic factors are administered (1). This uniqueness has made the cornea pocket assay one of the most used models for angiogenesis studies. The cornea composes multiple layers of cells. It is therefore possible to embed a pellet containing the angiogenic factor of interest in the cornea to investigate its angiogenic effect (2,3). Here, we provide a step by step demonstration of how to (I) produce the angiogenic factor-containing pellet (II) embed the pellet into the cornea (III) analyze the angiogenesis induced by the angiogenic factor of interest. Since the basic fibroblast growth factor (bFGF) is known as one of the most potent angiogenic factors (4), it is used here to induce angiogenesis in the cornea.
Selective glucocorticoid receptor modulation prevents and reverses non-alcoholic fatty liver disease in male mice (2018)

Medication for nonalcoholic fatty liver disease (NAFLD) is an unmet need. Glucocorticoid (GC) stress hormones drive fat metabolism in the liver, but both full blockade and full stimulation of GC signaling aggravate NAFLD pathology. We investigated the efficacy of selective glucocorticoid receptor (GR) modulator CORT118335, which recapitulates only a subset of GC actions, in reducing liver lipid accumulation in mice. Male C57BL/6J mice received a low-fat diet or high-fat diet mixed with vehicle or CORT118335. Livers were analyzed histologically and for genome-wide mRNA expression. Functionally, hepatic long-chain fatty acid (LCFA) composition was determined by gas chromatography. We determined very-low-density lipoprotein (VLDL) production by treatment with a lipoprotein lipase inhibitor after which blood was collected to isolate radiolabeled VLDL particles and apoB proteins. CORT118335 strongly prevented and reversed hepatic lipid accumulation. Liver transcriptome analysis showed increased expression of GR target genes involved in VLDL production. Accordingly, CORT118335 led to increased lipidation of VLDL particles, mimicking physiological GC action. Independent pathway analysis revealed that CORT118335 lacked induction of GC-responsive genes involved in cholesterol synthesis and LCFA uptake, which was indeed reflected in unaltered hepatic LCFA uptake in vivo. Our data thus reveal that the robust hepatic lipid-lowering effect of CORT118335 is due to a unique combination of GR-dependent stimulation of lipid (VLDL) efflux from the liver, with a lack of stimulation of GR-dependent hepatic fatty acid uptake. Our findings firmly demonstrate the potential use of CORT118335 in the treatment of NAFLD and underscore the potential of selective GR modulation in metabolic disease.
ChemInform Abstract: Chiral Primary Amine Catalyzed Asymmetric Direct Cross‐Aldol Reaction of Acetaldehyde. (2011)

Abstract Aqueous acetaldehyde solution and paraldehyde can be conveniently applied in this reaction.
Preferred Embodiments in Patents, 9 J. Marshall Rev. Intell. Prop. L. 398 (2009) (2009)

It is a tradition in patent drafting to refer to one or more examples as “preferred” or as a “preferred embodiment.” While these “preferred embodiments” reside in the specification, they can influence the interpretation of the claims. The role of preferred embodiments in claim construction was the issue in two cases, Laitram Corp. v. Cambridge Wire Cloth Co. and Vitronics Corp. v. Conceptronic, Inc. These cases represent two different lineages of the case law that refer to preferred embodiments, where application of these cases broadens (or prevents narrowing of) claim scope. Laitram warns against confining the claim to a specific example disclosed in the specification, where the example is a preferred embodiment. Vitronics warns that the claims should not be interpreted in a way that excludes the preferred embodiment. Where an example is labeled as “preferred,” this labeling almost always works to the advantage of the patentee during litigation. But, this labeling can also backfire against the patentee, resulting in claim invalidation. Two arguments can turn the preferred embodiment against the patentee. The first causes the claim to fall under the scope of the prior art, resulting in invalidation under 35 U.S.C. § 102. The second invokes the best mode requirement, thereby demanding a high degree of enablement under 35 U.S.C. § 112. Where a high degree of enablement is required, it can raise the question of validity for lack of enablement.
Viral vectors as tools to model and treat neurodegenerative disorders (2005)

The identification of disease-causing genes in familial forms of neurodegenerative disorders and the development of genetic models closely replicating human central nervous system (CNS) pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions, including gene-based therapies, the presence of the blood-brain barrier and the post-mitotic and poor regenerative nature of the target cells constitute important challenges. Efficient delivery systems taking into account the specificity of the CNS are required to administer potential therapeutic candidates. In addition, genetic models in large animals that replicate the late stages of the diseases are in most cases not available for pre-clinical studies. The present review summarizes the potential of viral vectors as tools to create new genetic models of CNS disorders in various species including primates and the recent progress toward viral gene therapy clinical trials for the administration of therapeutic candidates into the brain.