gebhart/patrepeval huggingface dataset:
Immuno-oncology Trial Endpoints: Capturing Clinically Meaningful Activity (2017)

Immuno-oncology (I-O) has required a shift in the established paradigm of toxicity and response assessment in clinical research. The design and interpretation of cancer clinical trials has been primarily driven by conventional toxicity and efficacy patterns observed with chemotherapy and targeted agents, which are insufficient to fully inform clinical trial design and guide therapeutic decisions in I-O. Responses to immune-targeted agents follow nonlinear dose-response and dose-toxicity kinetics mandating the development of novel response evaluation criteria. Biomarker-driven surrogate endpoints may better capture the mechanism of action and biological response to I-O agents and could be incorporated prospectively in early-phase I-O clinical trials. While overall survival remains the gold standard for evaluation of clinical efficacy of I-O agents in late-phase clinical trials, exploration of potential novel surrogate endpoints such as objective response rate and milestone survival is to be encouraged. Patient-reported outcomes should also be assessed to help redefine endpoints for I-O clinical trials and drive more efficient drug development. This paper discusses endpoints used in I-O trials to date and potential optimal endpoints for future early- and late-phase clinical development of I-O therapies.
Biomolecular functionalization for enhanced cell–material interactions of poly(methyl methacrylate) surfaces (2015)

The integration of implants or medical devices into the body tissues requires of good cell-material interactions. However, most polymeric materials used for these applications lack on biological cues, which enhanced mid- and long-term implant failure due to weak integration with the surrounding tissue. Commonly used strategies for tissue-material integration focus on functionalization of the material surface by means of natural proteins or short peptides. However, the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs. Here, designed elastin-like recombinamers (ELRs) are used to enhance poly(methyl methacrylate) surface properties and compared against the use of short peptides. In this study, cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein, which interferes on surface-cell interaction by unspecific adsorption on the interface. The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides, being a better choice for surface functionalization.
Quality Initiatives: Strategies for Anticipating and Reducing Complications and Treatment Failures in Hepatic Radiofrequency Ablation (2010)

Radiofrequency (RF) ablation is one of several local treatment strategies that can be used for the destruction of a variety of primary and secondary liver tumors. As experience with RF ablation grows, it becomes increasingly evident that successful ablation requires meticulous technique. In addition, knowledge of potential complications is critical for both the interventionalist and the radiologist, whose postablation interpretation can facilitate identification of complications and treatment failures. Hepatic RF ablation offers significant advantages in that it is less invasive than surgery and carries a low risk of major complications. Successful prevention of complications and treatment failures begins at initial consultation and continues with preablation evaluation of specific patient factors such as coagulation profiles, use of medications, and risk factors for infection. Other predisposing factors include background liver cirrhosis, prior hepatectomy, and portal hypertension. During ablation, careful attention must be given to tumor size, number, and location. For large or multiple ablations, separate ablation sessions can help reduce the prevalence of postablation syndrome, and clustered electrodes and multiple overlapping treatment zones may be used to reduce the risk of treatment failure. It is critical to reevaluate tumors during ablation to determine the best approach and to compensate for changes in size and relative location due to patient positioning. With use of these strategies, hepatic RF ablation can be performed with greater safety, better patient tolerance, and a reduced risk of complications and treatment failures.
<title>Search for gravitational effects in diffusion</title> (1996)

We have measured the rate of diffusion of aqueous CuSO<SUB>4</SUB> into pure water across a free liquid interface both on the ground and in 'microgravity' aboard the STS-43 mission of the Space Shuttle. Because both experiments were carried out under isothermal conditions with the CuSO<SUB>4</SUB> solution on the bottom and the pure water on the top, there was no obvious source of buoyancy. Moreover, the expected decrease in the diffusion coefficient due to hydrostatic pressure diffusion of CuSO<SUB>4</SUB> was two orders of magnitude less than the experimental error, which was 3-4 percent. Thus, within this error, our experiments show that there is not effect of gravity on diffusion in the case of a gravitationally stabilized, isothermal liquid. This is in contrast to the results obtained by others using melts under non-isothermal conditions where effects as large as 10 percent have been reported.
Pulmonary densities during anaesthesia. An experimental study on lung morphology and gas exchange (1989)

The nature of dense areas in dependent lung regions regularly seen in anaesthetized humans was examined in a sheep model. During anaesthesia with muscle paralysis and mechanical ventilation dense areas in dependent lung regions could be seen by means of computerized tomography (CT). They had the same location and the same attenuation as in anaesthetized humans. Gas exchange impairment tended to increase in proportion to the size of the dense area on the CT scan. Microscopy showed that the densities in the sheep were atelectatic lung regions, with no or little interstitial oedema and only minor vascular congestion. The atelectatic lung tissue was sharply demarcated and the lung tissue in the immediate vicinity was well aerated, or even hyperinflated. Gravimetry showed the same amount of extravascular fluid and blood per unit lung weight in the atelectatic lung and in the aerated lung region. It is concluded that the densities appearing in dependent lung regions during anaesthesia are caused by atelectasis.
A Novel Subunit of Vacuolar H+-ATPase Related to The b Subunit of F-ATPases (1996)

The subunit structure of the vacuolar H(+)-ATPase (V-ATPase) membrane sector is not entirely known. The proteolipid is the only subunit that has been implicated in the mechanism of energy transfer in the enzyme. We have identified a protein (M16) that co-purifies with the V-ATPase complex from bovine chromaffin granules. Information obtained from the amino acid sequence of a proteolytic fragment of M16 was used to clone a bovine adrenal cDNA encoding this protein. The cDNA encodes a hydrophilic protein of 118 amino acid residues with a calculated molecular mass of 13682Da. Amino acid sequence analysis revealed that M16 exhibits a significant homology to subunit b of F-ATPases. M16 is smaller than subunit b and contains no apparent transmembrane segment in its N terminus. The remainder of subunit b is related to M16 not only by its amino acid sequence but also in its predicted structure of helix-turn-helix. The structural and evolutionary implications of these findings are discussed.
Customization of an example-based dialog system with user data and distributed word representations (2018)

There is a need to develop spoken dialog systems which are capable of engaging in natural conversations with people, for example, the socially-isolated elderly. We propose an example-based dialog system featuring an adaptation method which customizes the dialog for each user. After retrieving user profile-related information from the Web, named entity extraction is applied to the retrieval results. Words with a high term frequency-inverse document frequency (TF-IDF) score are adopted as user related words. We then calculate the similarity between the selected user-related words and words in the existing example phrases of the dialog system. Cosine similarity between the distributed representations of the nouns is calculated using word2vec embedding. We then generate phrases adapted to the user by substituting user-related words for highly similar words in the original example phrases. Word2vec also has a special property which allows arithmetic operations such as plus and minus to be applied to distributed word representations. By applying operations to the words used in the original phrases, we were able to derive replacement words related to the user and insert them in the example phrases. We evaluated the naturalness of the generated phrases and found that the system could generate natural phrases.
Multi-bit Error Tolerant Caches Using Two-Dimensional Error Coding (2007)

In deep sub-micron ICs, growing amounts of on-die memory and scaling effects make embedded memories increasingly vulnerable to reliability and yield problems. As scaling progresses, soft and hard errors in the memory system will increase and single error events are more likely to cause large-scale multi- bit errors. However, conventional memory protection techniques can neither detect nor correct large-scale multi-bit errors without incurring large performance, area, and power overheads. We propose two-dimensional (2D) error coding in embedded memories, a scalable multi-bit error protection technique to improve memory reliability and yield. The key innovation is the use of vertical error coding across words that is used only for error correction in combination with conventional per-word horizontal error coding. We evaluate this scheme in the cache hierarchies of two representative chip multiprocessor designs and show that 2D error coding can correct clustered errors up to 32times32 bits with significantly smaller performance, area, and power overheads than conventional techniques.
Porphyrins. 34. Phosphorus complexes of octaethylporphyrin (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPorphyrins. 34. Phosphorus complexes of octaethylporphyrinPhillip Sayer, Martin Gouterman, and Charles R. ConnellCite this: J. Am. Chem. Soc. 1977, 99, 4, 1082–1087Publication Date (Print):February 1, 1977Publication History Published online1 May 2002Published inissue 1 February 1977https://pubs.acs.org/doi/10.1021/ja00446a018https://doi.org/10.1021/ja00446a018research-articleACS PublicationsRequest reuse permissionsArticle Views418Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Genetic Polymorphism and Natural Selection in the Malaria Parasite Plasmodium falciparum (1998)

Abstract We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the G↔C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.
An outer membrane-disorganizing peptide PMBN sensitizes E. coli strains to serum bactericidal action. (1984)

The small cationic outer membrane-disorganizing peptide PMBN sensitized four smooth, encapsulated strains of Escherichia coli (serotypes 02:K1, 04:K12, 018:K1, and 018:K5) to the lethal action of serum. The concentrations of PMBN required were low (0.3 to 1.0 microgram/ml). One E. coli strain (IH 11030; 075:K5) remained virtually resistant to serum and also to anti-075 hyperimmune serum plus complement (C) even in the presence of PMBN. This strain was nevertheless sensitive to the outer membrane permeability-increasing action of PMBN. In the bactericidal system, PMBN could be replaced by high concentrations of lysine20 or protamine but not lysine4. The PMBN-dependent bactericidal activity of GPS was abolished by heating or zymosan treatment that inactivate its C but not by lack of the action of the classical pathway of the C in C4-deficient GPS. PMBN formed a bactericidal system also with normal rabbit, rat, and human serum but not with mouse serum. The bactericidal system against E. coli 018:K1 and its derivative EH 817 (018:K1-) was found to require a factor that can be removed from normal sera by absorption with a rough E. coli strain. This factor could be replaced by specific anti-018 antibodies. The bactericidal activity of fetal calf serum plus PMBN against E. coli 018:K1 was enhanced by normal rabbit or anti-E. coli 018 hyperimmune serum. We suggest that PMBN unshields the deep structures and the hydrophobic membrane milieu of the outer membrane and facilitates the insertion of the membrane attack complex of the C into this milieu.
Efficient coding of DCT coefficients by joint position-dependent encoding (2002)

In a typical MC-DCT encoding scheme, a large portion of the bit rate is used to encode the location and amplitude information of the nonzero quantized DCT coefficients. Therefore efficient encoding of the DCT coefficients is extremely important. We describe the joint position-dependent encoding (PDE) approach to encode the DCT coefficients. Joint PDE exploits the variations in statistical properties of the runlengths and amplitudes as a function of position by introducing a set of 2-D codebooks in which each quantized DCT coefficient is assigned to one codebook in the set based on its location. Utilizing an MPEG-2 codec, we compare the bit rates using the joint PDE variable length codes (VLCs) with the bit rates produced by the MPEG-2 VLCs. We also examine how performance is affected by the number of codebooks.
The two-microphone transfer function method for measuring absorption coefficients and impedance: Some limitations and precautions (1984)

The transfer function (TF) method described by Chung and Blaser [J. Acoust. Soc. Am. 68, 907–921 (1980)] is an attractive alternative to the conventional, and tedious, standing wave ratio technique. Many laboratories have already implemented the new method and are obtaining useful results. However, several problems are being encountered that have not been satisfactorily addressed in the literature. This paper discusses some of these problems, points out the limitations of the TF method as it is currently implemented, and suggests some necessary precautions. In addition, the importance of calibration is stressed and demonstrated through some examples (here, unlike two-microphone intensity measurements, the relative phase match between the microphone channels is just as critical at the higher frequencies as at lower frequencies). The results of measurements with the TF method, using two impedance tubes (100- and 30-mm diameters) to cover a frequency range of 90–6300 Hz, will be discussed.
Recovery of Molybdenum from Copper Slags (2012)

Slags as the by-product of copper making have been produced in large amounts in Chile, and about 5 million tons of slags are estimated to be disposed every year and about 50 million tons have been already accumulated near the mine site. Typical Chilean copper slag contains about 0.3 mass% Mo which is the same to the grade of primary mine production of molybdenite and the copper slags also contain about 40 mass% of Fe and 1 mass% Cu. Recovery of Mo from Chilean copper slags is quite attractive to secure a stable Mo supply. The feasibility of the recovery of Mo from copper slags as Fe–Mo alloys by carbothermic reduction is investigated in the present study. Mo in the copper slag is found to be fully recovered as Fe rich Fe–Mo alloy. The recovered alloy contains about 0.60 mass% Mo and 2.4 mass% Cu. To use the recovered Fe–Mo alloy effectively in the special steel industry, which is the most important market for molybdenum, Cu in the produced Fe–Mo alloy is successfully decreased from 2.4 mass% to 0.1 mass% by using FeS–Na2S flux. Thus, Mo recovery from Chilean copper slag can be promising.
Integrin α2 I-domain is a binding site for collagens (1995)

Integrins alpha 1 beta 1 and alpha 2 beta 1 are major cellular receptors for collagens. The alpha 1 and alpha 2 subunits contain a approximately 200 amino acid inserted domain (I-domain) in their N-terminal region and, because of the homology between the I-domains and the collagen-binding A-domains of von Willebrand factor, it has been suggested that the I-domains might mediate the collagen-binding functions of alpha 1 beta 1 and alpha 2 beta 1. In order to fully investigate this hypothesis, we have generated recombinant human alpha 2 I-domain (r alpha 2I) by reverse transcriptase-polymerase chain reaction/bacterial expression and tested its ability to mediate the collagen-binding functions of alpha 2 beta 1. R alpha 2 I binds specifically to type I collagen in a concentration-dependent manner: binding is cation dependent and, like the complete receptor, is supported by magnesium and manganese ions but not by calcium ions. R alpha 2I is recognised by anti-functional anti-alpha 2 monoclonal antibodies 6F1, 5E8 and P1E6 in capture ELISAs, and anti-functional antibodies inhibited r alpha 2I-collagen binding. In addition, r alpha 2I inhibits cell spreading on collagen. R alpha 2I is therefore a collagen-binding domain and can account for many of the collagen-binding functions of integrin alpha 2 beta 1. We have also determined the collagen specificity of r alpha 2I and found that it binds types I, II and XI collagen.
Naturally processed and HLA‐B8‐presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer (2004)

Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA-B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA-B8-binding peptide TLHEYMLDL (HPV16 E7(7-15)), which is able to drive HPV16 E7-specific and MHC class I-restricted T-cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDL-specific T cells recognize the naturally processed and presented peptide on HPV16+ cervical cancer cells transfected with the HLA-B8 gene defined by IFN-gamma production. This peptide epitope is also recognized by freshly harvested tumor-infiltrating T cells or T cells from tumor-draining lymph nodes from patients with cervical cancer determined by flow cytometry as well as by tetramer in situ staining. HLA-B8-restricted HPV E7(7-15)-specific T cells reside predominantly in the CD8+ CD45RA+ CCR7+ precursor or in the differentiated CD8+ CD45RA+ CCR7- T-cell population.
Practical Aspects of Freeze-Drying of Pharmaceutical and Biological Products Using Nonaqueous Cosolvent Systems (2016)

INTRODUCTION Freeze-drying of pharmaceutical and biological solutions to produce an elegant stable powder has been a standard practice employed to manufacture many marketed pharmaceutical and biological products for over 50 years. The vast majority of these products are lyophilized from simple aqueous solutions. Water is typically the only solvent of significant quantity that is present, which must be removed from the solution via the freeze-drying process. However, frozen water (ice) is not the only frozen liquid that can sublime under reduced pressures. Numerous organic and mineral solvents have been shown to possess this property (1). It is also noteworthy that during the freeze-drying of pharmaceutical or biological products it is not unusual for small quantities of organic solvents to be present in either the active pharmaceutical ingredient or one of the excipients. These low levels of organic solvent are commonly found because they may be carried through as part of the manufacture of these individual components since the ingredient may be precipitated, crystallized, or spray dried from organic solvents. Therefore, many freeze-dried products may be dried from solutions, which contain low levels of a variety of organic solvents. Additionally, there may be instances where freeze-drying from substantial quantities of organic solvents or mixtures of water and organic solvent may offer the formulation scientist advantages over simply drying from an aqueous solution. An example of at least one pharmaceutical product on the market that has utilized an organic cosolvent system during freeze-drying is CAVERJECT1Sterile Powder (2,3). This particular product has been successfully manufactured by freeze-drying from a 20% vol/vol tert-butanol/water cosolvent system. Another example is the anticancer drug Imexon. This drug, which is undergoing clinical testing, utilized dimethyl sulfoxide (DMSO) as a formulation vehicle prior to lyophilization (4).
Time-resolved polarimetry for photoexcited QP dynamics in Bi2212 (2015)

The dynamics of quasi-particle (QP) excitations with different symmetry is investigated in the superconducting (SC) and pseudogap (PG) states of the high-temperature superconductor [Formula: see text] (Bi2212) using a polarization-sensitive optical pump-probe measurement. The observation of distinct anisotropies for SC excitations and for PG excitations by the probe beam polarization and absence of any dependence on the pump beam polarization evidence the existence of a spontaneous spatial symmetry breaking in the PG state.
Ruthenium-Catalyzed Formation of Aryl(diphenyl)phosphine Oxides by Reactions of Propargylic Alcohols with Diphenylphosphine Oxide (2005)

1,1-Diaryl-1-penten-4-yn-3-ols react with diphenylphosphine oxide in the presence of a thiolate-bridged diruthenium complex as a catalyst and give high yields of aryl(diphenyl)phosphine oxide products via an initial substitution followed by a cyclization at the produced allene intermediate. [reaction: see text]