gebhart/patrepeval huggingface dataset:
Superantigen-targeted therapy: phase I escalating repeat dose trial of the fusion protein PNU-214565 in patients with advanced gastrointestinal malignancies. (1998)

Antibody-directed, superantigen-induced cytotoxicity has been shown to have potent in vitro and in vivo antitumor effects in preclinical models. In the present study, PNU-214565, a recombinant fusion protein consisting of the Fab of the monoclonal antibody C242 and staphylococcal enterotoxin A (SEA), was used in an escalating repeat dose Phase I clinical trial in patients with advanced gastrointestinal malignancies. A prior single-dose Phase I clinical trial had demonstrated safety at doses of 1.5 ng/kg with toxicities of fever and hypotension that were not dose related. Twenty-seven patients (age range, 36-75 years; median, 62; 14 males and 13 females; 23 colorectal and 4 pancreatic) were treated in the present study with one cycle of four consecutive daily 3-h infusions of PNU-214565 at doses of 0.15 ng/kg (n = 3); 0.5 ng/kg (n = 3), 1.5 ng/kg (n = 4), 2.75 ng/kg (n = 12), and 3.5 ng/kg (n = 5). All patients had a good performance status [Eastern Cooperative Oncology Group: PS = 0 (n = 15), PS = 1 (n = 12)]. As in the single-dose trial, fever and hypotension were the most common toxicities. Dose-limiting toxicity (DLT), consisting of transient hypotension responsive to dopamine, was experienced by one patient treated at the 2.75 ng/kg dose level. One patient with pancreatic cancer metastatic to the liver experienced a partial response of hepatic metastases with stable pancreatic head abnormalities by computed tomography scan. Further dose escalation was suspended when two patients treated in a companion repeat dose Phase I study experienced DLT at the 4 ng/kg dose level. Multiparameter analyses on all patients treated in the two companion single-dose and two-repeated-dose Phase I trials revealed that the levels of patients' pretreatment anti-SEA antibodies protected against toxicity at a given drug dose. By jointly considering weight and the baseline anti-SEA concentration in a patient, it is possible to assign a PNU-214565 dose that will induce systemic cytokine release (a surrogate test to assess for the presence of uncomplexed drug and its ability to induce systemic cellular activation) without DLT. This pharmacodynamically based dosing scheme will be tested in future repeated-dose clinical trials and will define maximally tolerated doses of this powerful new immunotherapy approach.
Attention: the mechanisms of consciousness. (1994)

A number of recent papers and books discuss theoretical efforts toward a scientific understanding of consciousness. Progress in imaging networks of brain areas active when people perform simple tasks may provide a useful empirical background for distinguishing conscious and unconscious information processing. Attentional networks include those involved in orienting to sensory stimuli, activating ideas from memory, and maintaining the alert state. This paper reviews recent findings in relation to classical issues in the study of attention and anatomical and physical theories of the nature of consciousness.
Neurohistopathologic findings after a neurolytic celiac plexus block with alcohol in patients with pancreatic cancer pain (2002)

Pancreatic cancer has a very poor prognosis resulting in the death of 98% of patients. Pain may be severe and difficult to treat. Management of pain includes chemotherapy, radiotherapy, pharmacologic treatment, and neurolytic celiac plexus block. Recent reviews of the efficacy of neurolytic celiac plexus block however, have reached conflicting conclusions. In this paper, we present two patients with severe pancreatic cancer pain resistant to pharmacologic treatment. Analgesic effect following repeated neurolytic celiac plexus blocks with alcohol was limited in time. Post-mortem neurohistopathologic examination of the celiac plexus revealed an abnormal celiac architecture with a combination of abnormal neurons with vacuolization and normal looking neuronal structures (ganglionic structures and nerve fibers) embedded in fibrotic hyalinized tissue. Our results show that a neurolytic celiac plexus block with alcohol is capable of partially destroying the celiac plexus. These findings may explain the significant but short-lasting analgesic effect following neurolytic celiac plexus block with alcohol.
Vitamin D3 Confers Protection from Autoimmune Encephalomyelitis Only in Female Mice (2005)

The prevalence of multiple sclerosis (MS) increases significantly with decreasing UV B light exposure, possibly reflecting a protective effect of vitamin D(3). Consistent with this theory, previous research has shown a strong protective effect 1,25-dihydroxyvitamin D(3) in experimental autoimmune encephalomyelitis (EAE), an MS model. However, it is not known whether the hormone precursor, vitamin D(3), has protective effects in EAE. To address this question, B10.PL mice were fed a diet with or without vitamin D(3), immunized with myelin basic protein, and studied for signs of EAE and for metabolites and transcripts of the vitamin D(3) endocrine system. The intact, vitamin D(3)-fed female mice had significantly less clinical, histopathological, and immunological signs of EAE than ovariectomized females or intact or castrated males. Correlating with reduced EAE, the intact, vitamin D(3)-fed female mice had significantly more 1,25-dihydroxyvitamin D(3) and fewer CYP24A1 transcripts, encoding the 1,25-dihydroxyvitamin D(3)-inactivating enzyme, in the spinal cord than the other groups of mice. Thus, there was an unexpected synergy between vitamin D(3) and ovarian tissue with regard to EAE inhibition. We hypothesize that an ovarian hormone inhibited CYP24A1 gene expression in the spinal cord, so the locally-produced 1,25-dihydroxyvitamin D(3) accumulated and resolved the inflammation before severe EAE developed. If humans have a similar gender difference in vitamin D(3) metabolism in the CNS, then sunlight deprivation would increase the MS risk more significantly in women than in men, which may contribute to the unexplained higher MS incidence in women than in men.
Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. (1992)

An Mr = 524,000 oligomeric protein was isolated from bovine cartilage and designated COMP (Cartilage Oligomeric Matrix Protein). The protein is composed of disulfide-bonded subunits with an apparent Mr of 100,000 each. It is markedly anionic, probably due to its high contents of aspartic acid and glutamic acid, as well as to its substitution with negatively charged carbohydrates. COMP was found in all cartilages analyzed, but could not be detected in other tissues by enzyme-linked immunosorbent assay of guanidine HCl extracts. Within a given cartilage, COMP shows a preferential localization to the territorial matrix surrounding the chondrocytes.
Extreme Genetic Fragility of the HIV-1 Capsid (2013)

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies.
Anti-fibroblast growth factor 23 antibody therapy (2014)

These recent findings confirm that FGF23 has a pivotal role in phosphate metabolism. The inhibition of FGF23 production or activity is promising as a new therapy for FGF23-related hypophosphatemic diseases. Further studies are clearly necessary to establish the clinical utility and long-term safety of these measures.
Inducing cold resistance of alfalfa callus with diethylsulfate (2004)

Alfalfa calluses were induced with diethylsulfate (DES). The DES concentration leading to 50% death was confirmed, and cold-resistant mutants were screened out at -7 ℃. Physiological indices of cold resistance for mutants were determined including relative conductivity, dissociated proline content and peroxidase (POD) activity. The DES concentration resulting in 50% death was 0. 3%, and the cold resistance of alfalfa callus was increased.
A brief review of atomic layer deposition: from fundamentals to applications (2014)

Atomic layer deposition (ALD) is a vapor phase technique capable of producing thin films of a variety of materials. Based on sequential, self-limiting reactions, ALD offers exceptional conformality on high-aspect ratio structures, thickness control at the Angstrom level, and tunable film composition. With these advantages, ALD has emerged as a powerful tool for many industrial and research applications. In this review, we provide a brief introduction to ALD and highlight select applications, including Cu(In,Ga)Se2 solar cell devices, high-k transistors, and solid oxide fuel cells. These examples are chosen to illustrate the variety of technologies that are impacted by ALD, the range of materials that ALD can deposit – from metal oxides such as Zn1−xSnxOy, ZrO2, Y2O3, to noble metals such as Pt – and the way in which the unique features of ALD can enable new levels of performance and deeper fundamental understanding to be achieved.
Identification and functional characterization of a new member of the human Mcm protein family: hMcm8 (2003)

The six minichromosome maintenance proteins (Mcm2-7) are required for both the initiation and elongation of chromosomal DNA, ensuring that DNA replication takes place once, and only once, during the S phase. Here we report on the cloning of a new human Mcm gene (hMcm8) and on characterisation of its protein product. The hMcm8 gene contains the central Mcm domain conserved in the Mcm2-7 gene family, and is expressed in a range of cell lines and human tissues. hMcm8 mRNA accumulates during G(1)/S phase, while hMcm8 protein is detectable throughout the cell cycle. Immunoprecipitation-based studies did not reveal any participation of hMcm8 in the Mcm3/5 and Mcm2/4/6/7 subcomplexes. hMcm8 localises to the nucleus, although it is devoid of a nuclear localisation signal, suggesting that it binds to a nuclear protein. In the nucleus, the hMcm8 structure-bound fraction is detectable in S, but not in G(2)/M, phase, as for hMcm3. However, unlike hMcm3, the hMcm8 structure-bound fraction is not detectable in G(1) phase. Overall, our data identify a new Mcm protein, which does not form part of the Mcm2-7 complex and which is only structure-bound during S phase, thus suggesting its specific role in DNA replication.
In vivo characterization of fusion protein comprising of A1 subunit of Shiga toxin and human GM-CSF: Assessment of its immunogenicity and toxicity. (2010)

The lymphocyte proliferation assay, induction of specific IgG response and a mixed (Th1/Th2) response were observed only in BALB/c mice. The mixed response in BALB/c mice (Th1/Th2) could be explained on the basis of the two components of the fusion protein i.e. A1 and GM-CSF.
2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) (2006)

For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH) with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ ESC specific guidelines based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment. In 2007 the ESC/ESH decide to release new guidelines in consideration of considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available.
Cloning, characterization and functionality of the orotidine‐5′‐phosphate decarboxylase gene (URA3) of the glycolipid‐producing yeast Candida bombicola (2007)

Candida bombicola is a yeast species known to synthesize glycolipids. Although these glycolipids find several industrial, cosmetic and pharmaceutical applications, very little is known about the genetics of C. bombicola. A basic tool for genetic study and modification is the availability of an efficient transformation and selection system. In order to develop such a system, the URA3 gene of Candida bombicola was isolated using degenerate PCR and genomic walking. The gene encodes for an enzyme of 262 amino acids and shows high homology with the known orotidine-5'-phosphate decarboxylases of several other yeast species. The functionality of the gene was proved by complementation of a URA3-negative Saccharomyces cerevisiae strain.
MULTIDIMENSIONAL NMR TO STUDY THE STRUCTURE AND DYNAMICS OF PROTEINS (1998)

During the past thirty years, deuterium labeling has been used to improve the resolution and sensitivity of protein NMR spectra used in a wide variety of applications. Most recently, the combination of triple resonance experiments and 2 H, 13 C, 15 N labeled samples has been critical to the solution structure determination of several proteins with molecular weights on the order of 30 kDa. Here we review the developments in isotopic labeling strategies, NMR pulse sequences, and structure-determination protocols that have facilitated this advance and hold promise for future NMR-based structural studies of even larger systems. As well, we detail recent progress in the use of solution 2 H NMR methods to probe the dynamics of protein sidechains.
The Brian simulator (2009)

"Brian" is a simulator for spiking neural networks (http://www.briansimulator.org). The focus is on making the writing of simulation code as quick and easy as possible for the user, and on flexibility: new and non-standard models are no more difficult to define than standard ones. This allows scientists to spend more time on the details of their models, and less on their implementation. Neuron models are defined by writing differential equations in standard mathematical notation, facilitating scientific communication. Brian is written in the Python programming language, and uses vector-based computation to allow for efficient simulations. It is particularly useful for neuroscientific modelling at the systems level, and for teaching computational neuroscience.
Expression of MHC Class II-Associated Invariant Chain (Ii;CD74) in Thymic Epithelial Neoplasms (2000)

Thymic epithelial cells express major histocompatibility complex (MHC) class II and are involved in T-cell ontogeny. In these cells, MHC class II-associated invariant chain (CD74) is involved in antigen presentation during T-cell selection. We studied a range of thymic epithelial neoplasms for CD74 expression by neoplastic epithelial cells to determine whether such expression correlates with MHC class II expression and tumor type. Sixty-four thymic epithelial neoplasms (27 cases of benign thymoma, 20 cases of invasive thymoma, and 17 cases of true thymic carcinoma) were studied for neoplastic epithelial cell expression of CD74 and MHC class II molecules by immunohistochemical staining of paraffin-embedded tissue. Neoplastic epithelial cells in 88% of thymic carcinomas (15/17), 70% of invasive thymomas (14/20), but only 33% of benign thymomas (9/27) were immunoreactive for CD74. A subset of CD74-positive neoplasms was positive for MHC class II as well, with higher relative rates of dual positivity in more aggressive neoplasms. In addition, specific histologic subtypes of thymic epithelial neoplasms displayed differing patterns of CD74 positivity. Based on these findings, CD74 and MHC class II are useful markers for the classification of thymic epithelial neoplasms.
Determination of liquid crystal orientation in holographic polymer dispersed liquid crystals by linear and nonlinear optics (2008)

The liquid crystal alignment imposed during the fabrication process of one-dimensional transmission gratings, holographically formed in a polymer dispersed liquid crystal, is determined by linear optical birefringence as well as rotational second harmonic generation. For a mixture consisting of nematic liquid crystal E7, a pentafunctional acrylate monomer, and a photoinitiator, the director orientation inside the liquid-crystal-rich layer is found to be approximately along the grating direction. We suggest that this molecular orientation is the consequence of the strong flow during the grating formation.
Managing trust in an information‐labeling system (1997)

Abstract Many network services need to make “trust management” decisions; in particular, processing users' requests for action often requires using labels and credentials that may not be authentic or trustworthy. In this paper, we address the problem of trust management in information labeling. The Platform for Internet Content Selection (PICS), proposed by Resnick and Miller [13], establishes a flexible way to label documents according to various aspects of their contents, thus permitting a large and diverse group of potential viewers to make (automated) informed judgments about whether or not to view them. For some viewers, the relevant aspects may be quantity or quality of material in certain topical areas, and, for others, they may be the presence or absence of potentially offensive language or images. Thus PICS users need a language in which to specify their PICS profiles, i.e. , the aspects according to which they want documents to be labeled, the acceptable values of those labels, and the parties whom they trust to do the labeling. Furthermore, PICS‐compliant client software ( e.g. , a web browser) needs a mechanism for checking whether a document meets the requirements set forth in a viewer's profile. A trust management solution for the PICS information‐labeling system must provide both a language for specifying profiles and a mechanism for checking whether a document meets the requirements given in a profile. This paper describes our design and implementation of a PICS profile language and our experience integrating the Policy Maker trust management engine with a PICS‐compliant browser to provide a checking mechanism. Policy Maker was originally designed to address trust management problems in network services that process signed requests for action and use public‐key cryptography [2]. Because information labeling is not inherently a cryptographically based service and thus is outside the original scope of the Policy Maker framework, our work on information labeling is evidence of Policy Maker's power and adaptability.
Multimedia Security Handbook (2004)

GENERAL ISSUES Protection of Multimedia Content in Distribution Networks A. M. Eskicioglu and E.J. Delp Vulnerability of Multimedia Protection Schemes M. F. Mansour and A.H. Tewfik MULTIMEDIA ENCRYPTION Fundamentals of Multimedia Encryption Techniques B. Furht, D. Socek, and A. M. Eskicioglu Chaos-Based Encryption for Digital Image and Video S. Li, G. Chen, and X. Zheng Key Management and Protection for IP Multimedia R. Blom, E. Carrara, F. Lindholm, K. Norrman, and M. Naslund Streaming Media Encryption H. Yu MULTIMEDIA WATERMARKING Survey of Multimedia Watermarking Techniques E. Muharemagic and B. Furht Robust Identification of Audio Using Watermarking and Fingerprinting J. Haitsma and T. Kalker High Capacity Real-Time Audio Watermarking with Perfect Correlation Sequence and Repeated Insertion S-C Pei, Y-F Hsu, and Y-W Lu Multidimensional Watermark for Still Image: Parallel Embedding and Detection Bo Hu Image Watermarking Method Resistant to Geometric Distortions H. Kim Fragile Watermarking for Image Authentication E. Izquierdo New Trends and Challenges in Digital Watermark Technologies: Applications for Printed Materials Z. Liu Robust Watermark Detection from Quantized MPEG Video Data D. Simitopoulos, A. Briassouli, and M. G. Strintzis Image Watermarking Robust to Both Geometric Distortion and JPEG Compression X. Kang, J. Huang, and Y. Q. Shi Reversible Watermarks Using a Difference Expansion A.M. Alattar MULTIMEDIA DATA HIDING, FINGERPRINTING, AND AUTHENTICATION Lossless Data Hiding: Fundamentals, Algorithms and Applications Y. Q. Shi, G. Xuan, and W. Su Attacking Multimedia Protection Systems via Blind Pattern Matching D. Kirovski and J-L Dugelay Digital Media Fingerprinting: Techniques and Trends W. Luh and D. Kundur Scalable Image and Video Authentication D. Skraparlis Signature-Based Media Authentication Q. Sun and S-F Chang APPLICATIONS Digital Watermarking Framework: Applications, Parameters and Requirements K. Levy and T. Rodriguez Digital Rights Management for Consumer Devices J. Lotspiech Adult Image Filtering for Internet Safety H. Zheng, M. Daudi, C. Tombelle, and C. Djeraba Combined Indexing and Watermarking of 3D Models Using the Generalized 3D Radon Transforms P. Daras, D. Zarpalas, D. Tzovaras, D. Simitopoulos, and M. G.Strintzis Digital Rights Management Issues for Video S. Emmanuel and M. S. Kankanhalli