gebhart/patrepeval huggingface dataset:
RTD-1Mimic Containing γPNA Scaffold Exhibits Broad-Spectrum Antibacterial Activities (2012)

Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities and high chemical, thermal, and enzymatic stability. However, for some, because of their intricate spatial arrangement and elaborate interstrand cross-linkages, they are difficult to prepare de novo in large quantities and high purity, due to the nonselective nature of disulfide-bond formation. We show that the disulfide bridges of RTD-1, a member of the θ-defensin subfamily, could be replaced with noncovalent Watson-Crick hydrogen bonds without significantly affecting its biological activities. The work provides a general strategy for engineering conformationally rigid, cyclic peptides without the need for disulfide-bond reinforcement.
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer (2006)

Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.
Frequency domain coding of speech (1979)

Frequency domain techniques for speech coding have recently received considerable attention. The basic concept of these methods is to divide the speech into frequency components by a filter bank (sub-band coding), or by a suitable transform (transform coding), and then encode them using adaptive PCM. Three basic factors are involved in the design of these coders: 1) the type of the filter bank or transform, 2) the choice of bit allocation and noise shaping properties involved in bit allocation, and 3) the control of the step-size of the encoders. This paper reviews the basic aspects of the design of these three factors for sub-band and transform coders. Concepts of short-time analysis/synthesis are first discussed and used to establish a basic theoretical framework. It is then shown how practical realizations of subband and transform coding are interpreted within this framework. Principles of spectral estimation and models of speech production and perception are then discussed and used to illustrate how the "side information" can be most efficiently represented and utilized in the design of the coder (particularly the adaptive transform coder) to control the dynamic bit allocation and quantizer step-sizes. Recent developments and examples of the "vocoder-driven" adaptive transform coder for low bit-rate applications are then presented.
Effects of liraglutide (NN2211), a long‐acting GLP‐1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes (2005)

Once-daily liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of liraglutide merit study in future clinical trials.
The Two Murein Lipoproteins ofSalmonella entericaSerovar Typhimurium Contribute to the Virulence of the Organism (2004)

Septic shock due to Salmonella and other gram-negative enteric pathogens is a leading cause of death worldwide. The role of lipopolysaccharide in sepsis is well studied; however, the contribution of other bacterial outer membrane components, such as Braun (murein) lipoprotein (Lpp), is not well defined. The genome of Salmonella enterica serovar Typhimurium harbors two copies of the lipoprotein (lpp) gene. We constructed a serovar Typhimurium strain with deletions in both copies of the lpp gene (lpp1 and lpp2) by marker exchange mutagenesis. The integrity of the cell membrane and the secretion of the effector proteins through the type III secretion system were not affected in the lpp double-knockout mutant. Subsequently, the virulence potential of this mutant was examined in a cell culture system using T84 intestinal epithelial and RAW264.7 macrophage cell lines and a mouse model of salmonellosis. The lpp double-knockout mutant was defective in invading and inducing cytotoxic effects in T84 and RAW264.7 cells, although binding of the mutant to the host cell was not affected when compared to the wild-type (WT) serovar Typhimurium. The motility of the mutant was impaired, despite the finding that the number of flagella was similar in the lpp double knockout mutant and the WT serovar Typhimurium. Deletion in the lpp genes did not affect the intracellular survival and replication of Salmonella in macrophages and T84 cells. Induction of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-8 (IL-8) was significantly reduced in macrophages and T84 cells infected with the lpp double-knockout mutant. The levels of IL-8 remained unaffected in T84 cells when infected with either live or heat-killed WT and lpp mutant, indicating that invasion was not required for IL-8 production and that Toll-like receptor 2 signaling might be affected in the Lpp double-knockout mutant. These effects of the Lpp protein could be restored by complementation of the isogenic mutant. The lpp double-knockout mutant was avirulent in mice, and animals infected with this mutant were protected from a lethal challenge dose of WT serovar Typhimurium. The severe combined immunodeficient mice, on the other hand, were susceptible to infection by the lpp double-knockout mutant. The serovar Typhimurium mutants from which only one of the lpp (lpp1 or lpp2) genes was deleted were also avirulent in mice. Taken together, our data indicated that Lpp specifically contributed to the virulence of the organism.
An evaluation of a novel safety catch linker for development of cyclic peptide libraries (2006)

Cyclic peptides are excellent tools to examine the conformational requirements of proteinprotein recognition. However, as yet there is no generic method to access discrete libraries of cyclic peptides in high purity and yield. In addressing this problem we developed a backbone linker 1 suitable for Boc-based SPPS [1] based on the backbone amide linker approach [2]. However this approach requires strong acid treatment for simultaneous cleavage and deprotection, thereby causing removal difficulties of scavenger when large numbers of discrete cyclic peptides are synthesised. As a result we investigated a more suitable linker 2 [3] which is inert to strong acid treatment but photolytically cleavable. Although promising, several transformations on resin are still required. We therefore foccussed our attention on the 'safety catch' approach, linker 3 [4].
Structure of the gene encoding human casein kinase II subunit beta (1991)

Casein kinase II (CKII) is a ubiquitous serine/threonine protein kinase with numerous key functions in cell metabolism and growth. The human CKII has a tetrameric structure; two catalytic subunits (alpha and alpha') form the holoenzyme together with two presumably regulatory subunits (beta). The gene encoding CKII subunit beta was isolated from human genomic DNA and analyzed for its primary structure using exclusively nonradioactive procedures. The gene was found to span 4.2 kilobase pairs and to be composed of seven exons. Exon sizes range from 76 (exon 5) to 329 base pairs (bp) (exon 1), intron sizes from 145 (intron V) to 965 bp (intron II). All exon-intron junctional sequences conform to the canonical GT-AG rule. Primer extension analysis determined three transcription initiation sites, at 951, 919, and (minor) 840 bp upstream of the translation start site. The translation start is located early in the second exon; exon 1 is untranslated. The 3'-cleavage/polyadenylation signal sequence (AA-TAAA) is in the last exon at position 4173 bp relative to the first transcription initiation site. The coding sequence for CKII beta comprises 648 nucleotides identical to the published CKII beta-cDNA sequence (Jakobi, R., Voss, H., and Pyerin, W. (1989) Eur. J. Biochem. 183, 227-233). The upstream promoter region of the CKII beta gene contains multiple potential gene regulatory sequence elements, noticeable DNA structures, and the characteristics of a housekeeping gene (more than one transcription initiation site, lack of a TATA-box, presence of a CpG island, occurrence of multiple GC boxes and of nonstandard positioned CCAAT boxes). The CKII beta gene promoter shares common features with that of mammalian protein kinases and is closely related to the regulatory subunit gene promoter of cAMP-dependent protein kinase.
α4-Integrin+ endothelium derived from primate embryonic stem cells generates primitive and definitive hematopoietic cells (2006)

The mechanism of commencement of hematopoiesis in blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region during primate embryogenesis remains elusive. In this study, we demonstrated that VE-cadherin(+)CD45(-) endothelial cells derived from nonhuman primate embryonic stem cells are able to generate primitive and definitive hematopoietic cells sequentially, as revealed by immunostaining of floating erythrocytes and colony-forming assay in cultures. Single bipotential progenitors for hematopoietic and endothelial lineages are included in this endothelial cell population. Furthermore, hemogenic activity of these endothelial cells is observed exclusively in the alpha4-integrin(+) subpopulation; bipotential progenitors are 4-fold enriched in this subpopulation. The kinetics of this hemogenic subpopulation is similar to that of hemogenic endothelial cells previously reported in the yolk sac and the AGM region in vivo in that they emerge for only a limited time. We suggest that VE-cadherin(+)CD45(-)alpha4-integrin(+) endothelial cells are involved in primitive and definitive hematopoiesis during primate embryogenesis, though VE-cadherin(-)CD45(-)alpha4-integrin(+) cells are the primary sources for primitive hematopoiesis.
A generalized theory and new calibration procedures for network analyzer self-calibration (1991)

A general theory for performing network analyzer calibration is presented. Novel calibration procedures are derived which allow for partly unknown standards. The most general procedure derived is called TAN and allows for five unknown parameters in the three calibration standards. The values of the unknown parameters are determined during the calibration procedure via eigenvalue conditions. The good performance of all the procedures has been shown experimentally. This wide spectrum of procedures using different calibration standards makes it possible to choose an optimal algorithm for any environment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Summary of the N1-P2 Cortical Auditory Evoked Potential to Estimate the Auditory Threshold in Adults (2016)

This article introduces the cortical auditory evoked potential (CAEP) and describes the use of the N1-P2 response complex as an objective predictor of hearing threshold in adults and older children. The generators of the CAEP are discussed together with issues of maturation, subject factors, and stimuli and recording parameters for use in the clinic. The basic methods for response identification are outlined and suggestions are made for determining the CAEP threshold. Clinical applications are introduced and the accuracy of the CAEP as an estimator of hearing threshold is given. Finally, a case study provides an example of the technique in the context of medicolegal assessment.
Properties of the NAD(P)H-dependent xylose reductase from the xylose-fermenting yeast Pichia stipitis (1985)

Xylose reductase from the xylose-fermenting yeast Pichia stipitis was purified to electrophoretic and spectral homogeneity via ion-exchange, affinity and high-performance gel chromatography. The enzyme was active with various aldose substrates, such as DL-glyceraldehyde, L-arabinose, D-xylose, D-ribose, D-galactose and D-glucose. Hence the xylose reductase of Pichia stipitis is an aldose reductase (EC 1.1.1.21). Unlike all aldose reductases characterized so far, the enzyme from this yeast was active with both NADPH and NADH as coenzyme. The activity with NADH was approx. 70% of that with NADPH for the various aldose substrates. NADP+ was a potent inhibitor of both the NADPH- and NADH-linked xylose reduction, whereas NAD+ showed strong inhibition only with the NADH-linked reaction. These results are discussed in the context of the possible use of Pichia stipitis and similar yeasts for the anaerobic conversion of xylose into ethanol.
Selective drug delivery to the colon using pectin-coated pellets. (2009)

A combination of ethylcellulose and pectin, when applied as a film coat, has a potential value as a colon-specific delivery system. Dispersions of pectin in ethylcellulose were used as the film former for coating of 5-aminosalicylic acid (5-ASA) pellet cores. Drug release behavior was assessed, in vitro, under simulating conditions in term of pH and time in vivo during transit to the colon. Negligible drug release occurred during first 5 h, when the coated pellets were in the simulated gastric and small intestinal conditions. After that, rat cecal contents were added into the pH 6.8 medium to simulate the in vivo condition where there is the digestion of bacteria in the colon. Drug release depended on the composition of the mixed film, as well as the ratio of ethylcellulose to pectin. Drug release profiles seemed to conform to the mechanism involving the osmotically driven release and formation of channels in the film caused by dissolution of pectin. Channel formation was, in most cases, activated by the presence of rat cecal contents, showing that the pectin in the mixed film was subjected to enzymic breakdown. In conclusion, pectin could be used as an additive in ethylcellulose films to control the release of colonic delivery system. In addition, the mechanism of the hydrophilic drug release from pellets coated with ethylcellulose aqueous dispersions containing an aqueous gel-forming polymer (pectin) is also discussed.
Taurine and Vitamin C Modify Monocyte and Endothelial Dysfunction in Young Smokers (2003)

These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.
Dose-response resistance to HIV-1/MuLV pseudotype virus ex vivo in a hairpin ribozyme transgenic mouse model (1999)

We have investigated the efficacy of a hairpin ribozyme targeting the 5' leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribozyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response between ribozyme expression and viral resistance, with an estimated cut off value below 0.2 copies of hairpin ribozyme per cell. These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.
Early evening light mitigates sleep compromising physiological and alerting responses to subsequent late evening light (2019)

The widespread use of electric light and electronic devices has resulted in an excessive exposure to light during the late-evening and at night. This late light exposure acutely suppresses melatonin and sleepiness and delays the circadian clock. Here we investigate whether the acute effects of late-evening light exposure on our physiology and sleepiness are reduced when this light exposure is preceded by early evening bright light. Twelve healthy young females were included in a randomised crossover study. All participants underwent three evening (18:30-00:30) sessions during which melatonin, subjective sleepiness, body temperature and skin blood flow were measured under different light conditions: (A) dim light, (B) dim light with a late-evening (22:30-23:30) light exposure of 750 lx, 4000 K, and (C) the same late-evening light exposure, but now preceded by early-evening bright light exposure (18.30-21.00; 1200 lx, 4000 K). Late-evening light exposure reduced melatonin levels and subjective sleepiness and resulted in larger skin temperature gradients as compared to dim. Interestingly, these effects were reduced when the late-evening light was preceded by an early evening 2.5-hour bright light exposure. Thus daytime and early-evening exposure to bright light can mitigate some of the sleep-disruptive consequences of light exposure in the later evening.
Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells: involvement of CD4+ and CD8+ T cells in protection. (2002)

An important goal of immunotherapy against human papillomavirus (HPV) infection and the cervical cancer is to control viral infection and the cancer cell growth. Here we investigate the utility of HPV 16 E7 along with CpG-oligodeoxynucleotide (ODN) for protection against HPV-immortalized tumor cells using an animal model. E7+ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels. However, no such effect was observed without addition of both E7 and ODN. We additionally evaluated levels of immune responses by E7+ODN coinjection. E7+ODN resulted in E7-specific antibody (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell proliferative responses significantly higher than E7 alone. However, CTL responses were induced only by E7+ODN. Moreover, IFN-gamma production was detected only in E7+ODN immunized groups in which IFN-gamma releasing CD4+ (T-helper 1 type) and CD8+ T cells (CTL) were induced only by E7+ODN. Moreover, tumor protection appears to be mediated by CD4+ and in most CD8+ T cells, as determined by in vivo T-cell subset depletion. Taken together, these data suggest that E7+ODN codelivery could be an effective approach to induce E7-specific protective immune responses as a possible immunotherapeutic strategy for cervical cancer.
The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2 (2006)

To determine whether CCL2 mRNA expression is beneficial or detrimental for cervical cancer patients, the association between the expression of this molecule by cervical tumour cells, the number of tumour-associated macrophages, and clinicopathological parameters such as recurrence, relapse-free survival, and overall patient survival was investigated. In cervical cancer samples from 93 untreated cervical cancer patients, the CCL2 mRNA expression level was quantified using RNA in situ hybridization and verified using real-time quantitative RT-PCR. The number of tumour-associated macrophages was determined using immunohistochemistry. Furthermore, the study investigated whether lack of CCL2 expression was due to genetic alterations near the 17q11.2 (CCL2 genomic) region. CCL2 mRNA expression by cervical tumour cells was associated with the number of tumour-associated macrophages (p < 0.001). Lack of CCL2 mRNA expression (15 samples; 16%) was associated with increased cumulative relapse-free survival (log rank test, p = 0.030), increased cumulative overall survival (log rank test, p = 0.024), less post-operative surgery, reduced local and distant recurrence, reduced vascular invasion, and smaller tumour size (<40 mm). The absence of CCL2 mRNA expression corresponded with loss of heterozygosity (LOH) at 17q11.2 in five of six samples. The increased cumulative relapse-free survival and cumulative overall survival of cervical cancer patients lacking tumour cell-associated CCL2 mRNA suggest that the tumour-associated macrophages support tumour progression, presumably by promoting angiogenesis and production of growth factors.
Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation (2012)

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab')(2) and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.
Cancer Statistics, 2007 (2007)

Each year, the American Cancer Society (ACS) estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. This report considers incidence data through 2003 and mortality data through 2004. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,444,920 new cancer cases and 559,650 deaths for cancers are projected to occur in the United States in 2007. Notable trends in cancer incidence and mortality rates include stabilization of the age-standardized, delay-adjusted incidence rates for all cancers combined in men from 1995 through 2003; a continuing increase in the incidence rate by 0.3% per year in women; and a 13.6% total decrease in age-standardized cancer death rates among men and women combined between 1991 and 2004. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. While the absolute number of cancer deaths decreased for the second consecutive year in the United States (by more than 3,000 from 2003 to 2004) and much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.