gebhart/patrepeval huggingface dataset:
Multiband excitation vocoder (1988)

A speech model, referred to as the multiband excitation model, is presented. In this model the band around each harmonic of the fundamental frequency is declared voiced or unvoiced. Estimation methods for the parameters of the model are developed and methods to synthesize speech from the model parameters are described. To illustrate a potential application of the speech model, an 8 kb/s vocoder is developed and its performance is evaluated. Both informal listening and intelligibility tests show that the vocoder has very good performance both in speech quality and intelligibility, particularly for noisy speech.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A brilliant disguise for self RNA: 5’-end and internal modifications of primary transcripts suppress elements of innate immunity (2008)

Interferon inducible protein kinase PKR is a component of innate immunity and mediates antiviral actions by recognizing pathogen associated molecular patterns (PAMPs). A well-known activator of PKR is long dsRNA, which can be produced during viral replication. Our recent results indicate that PKR can also be activated by short stem-loop RNA in a 5'-triphosphate-dependent fashion. A 5'-triphosphate is present primarily in foreign RNAs such as viral and bacterial transcripts, while a non-activating 5'-cap or 5'-monophosphate is present in most cellular RNAs. Additional studies indicate that internal RNA modifications and non-Watson-Crick motifs also repress PKR activation, and do so in an RNA structure-specific fashion. Interestingly, self-RNAs have more nucleoside modifications than non-self RNAs. Internal and 5'-end RNA modifications have repressive effects on other innate immune sensors as well, including TLR3, TLR7, TLR8, and RIG-I, suggesting that nucleoside modifications suppress innate immunity on a wide scale.
“Seeing and Counting” Individual Antigens Captured on a Microarrayed Spot with Force-Based Atomic Force Microscopy (2010)

The mapping capability of atomic force microscopy (AFM) enabled us to see captured prostate-specific antigens (PSAs) on a spot microarrayed with the corresponding antibody and count the number of the antigens in a submicrometer area. To enhance the reliability and the reproducibility of the approach, a third-generation dendron was employed for the surface treatment. The specific force between the captured PSA and the detection antibody (5A6) was measured after cross-linking, and the mean unbinding force was 56 +/- 2 pN. At 100 fM, there were 12 captured antigens in 4.32 x 10(4) nm(2), and the number was dependent upon the concentration. A larger hydrodynamic distance (8 +/- 2 nm) of the immunocomplex resulted in a cluster of pixels corresponding to the single complex in a map recorded over a selected area with a positional interval of 3 nm, and this feature helped to discriminate between pixels of the specific interaction and the nonspecific ones. The results indicate that the approach can be applicable to the quantitative analysis of the antigen in a sample and imply that it can be extended to a sample of very low copy numbers as long as the size of the microarrayed spot is reduced.
Cell Cycle Protein Expression in Vascular Smooth Muscle Cells In Vitro and In Vivo Is Regulated Through Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin (2001)

Cell cycle progression represents a key event in vascular proliferative diseases, one that depends on an increased rate of protein synthesis. An increase in phosphatidylinositol 3-kinase (PI 3-kinase) activity is associated with vascular smooth muscle cell proliferation, and rapamycin, which blocks the activity of the mammalian target of rapamycin, inhibits this proliferation in vitro and in vivo. We hypothesized that these 2 molecules converge on a critical pathway of translational regulation that is essential for successful upregulation of cell cycle-regulatory proteins in activated smooth muscle cells. p70(S6) kinase, a target of PI 3-kinase and the mammalian target of rapamycin, was rapidly activated on growth factor stimulation of quiescent coronary artery smooth muscle cells and after balloon injury of rat carotid arteries. The translational repressor protein 4E-binding protein 1 was similarly hyperphosphorylated under these conditions. These events were associated with increases in the protein levels of cyclin B1, cyclin D1, cyclin E, cyclin-dependent kinase 1, cyclin-dependent kinase 2, proliferating cell nuclear antigen, and p21(Cip1) in vivo and in vitro, whereas inhibition of the PI 3-kinase signaling pathway with either rapamycin or wortmannin blocked the upregulation of these cell cycle proteins, but not mRNA, and arrested the cells in vitro before S phase. In contrast to findings in other cell types, growth factor- or balloon injury-induced downregulation of the cell cycle inhibitor p27(Kip1) was not affected by rapamycin treatment. These data suggest that cell cycle progression in vascular cells in vitro and in vivo depends on the integrity of the PI 3-kinase signaling pathway in allowing posttranscriptional accumulation of cell cycle proteins.
50 Jahre „Deutsche Gesellschaft für Erziehungswissenschaft“ (DGfE). Gedanken zu Jubiläum und Forschungslücken (2014)

----- Bibliographie : Behm, Britta: 50 Jahre „Deutsche Gesellschaft für Erziehungswissenschaft“ (DGfE). Gedanken zu Jubiläum und Forschungslücken, Erziehungswissenschaft, 1-2014, S. 11-24. https://doi.org/10.3224/ezw.v25i1.19133
Remineralization of enamel subsurface lesions in situ by sugar‐free lozenges containing casein phosphopeptideamorphous calcium phosphate (2003)

This study demonstrates that lozenges are a suitable vehicle for the delivery of CPP-ACP to promote enamel remineralization.
Polyhedral face reconstruction and modeling from a single image with structured light (1993)

The determination of the 3-D geometric model of visible polyhedral faces from a single view is addressed. It applies a grid coding technique to derive the normal vector of each visible polyhedral face and the depth parameter of the face equation based on the given dimensions of the grid on the code plate. It is shown that the method is correspondenceless. Furthermore, it also determines the 3-D face model for all visible polyhedral faces including the occlusion relations between faces. Two edge reconstruction methods are given and their goodness are compared. For the determination of the final object model, three different integration methods are given. Some experiments are reported to illustrate the method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hyporesponsiveness to erythropoietic therapy due to chronic inflammation (2005)

The anaemia associated with chronic renal failure is multi-factorial. Although a relative erythropoietin deficiency is a major factor, it has also been recognized in recent times that uraemia is a chronic inflammatory state, and thus patients with renal failure also develop anaemia due to mechanisms associated with chronic inflammation. Thus, patients with chronic renal failure have activation of various immune cells, both monocytes and T-cells. These mononuclear cells have also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF-alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon gamma, are known to cause significant suppression of erythropoiesis. The exact molecular mechanism for this effect is not yet clear, but interferon gamma is an important stimulator of apoptosis in various cell types, including erythroid progenitor cells. This effect may be potentiated by other cytokines such as TNF-alfa, and this might then antagonise the anti-apoptotic action of erythropoietin on erythroid progenitors cells, thus reducing responsiveness to exogenous erythropoietic therapy. Chronic renal failure is also associated with increased hepcidin production which may also exacerbate the anaemia by inducing a functional iron deficiency in such patients.
Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes (2003)

Adiponectin is an adipocyte-derived hormone, which has been shown to play important roles in the regulation of glucose and lipid metabolism. Eight mutations in human adiponectin have been reported, some of which were significantly related to diabetes and hypoadiponectinemia, but the molecular mechanisms of decreased plasma levels and impaired action of adiponectin mutants were not clarified. Adiponectin structurally belongs to the complement 1q family and is known to form a characteristic homomultimer. Herein, we demonstrated that simple SDS-PAGE under non-reducing and non-heat-denaturing conditions clearly separates multimer species of adiponectin. Adiponectin in human or mouse serum and adiponectin expressed in NIH-3T3 or Escherichia coli formed a wide range of multimers from trimers to high molecular weight (HMW) multimers. A disulfide bond through an amino-terminal cysteine was required for the formation of multimers larger than a trimer. An amino-terminal Cys-Ser mutation, which could not form multimers larger than a trimer, abrogated the effect of adiponectin on the AMP-activated protein kinase pathway in hepatocytes. Among human adiponectin mutations, G84R and G90S mutants, which are associated with diabetes and hypoadiponectinemia, did not form HMW multimers. R112C and I164T mutants, which are associated with hypoadiponectinemia, did not assemble into trimers, resulting in impaired secretion from the cell. These data suggested impaired multimerization and/or the consequent impaired secretion to be among the causes of a diabetic phenotype or hypoadiponectinemia in subjects having these mutations. In conclusion, not only total concentrations, but also multimer distribution should always be considered in the interpretation of plasma adiponectin levels in health as well as various disease states.
Phase II study of FK228 in patients with hormone refractory prostate cancer (HRPC) (2006)

14554 Background: FK228 is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. FK228 can also inhibit HSP90, ablating androgen receptor expression. Methods: FK228 was administered intravenously at 13mg/m 2 on days 1, 8 and 15 of a 28-day schedule for up to 6 cycles. Sixteen patients were treated in stage 1. If ≥ 1 response was seen, an additional 9 patients were to be recruited. Eligibility criteria included: no prior chemotherapy, metastatic disease, ≤3 lines of hormonal therapy, QTcB &lt;500 msec, Karnofsky PS ≥80. The primary endpoint was to measure rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate, time to PSA and objective disease progression, safety profile, effect on disease related symptoms and pharmacokinetics (PK) of FK228. Results: Interim results are available after 16 patients were enrolled in stage 1 and 5 patients in stage 2. Median age (n = 21): 65 years (range 43–77). 3 patients have completed 6 cycles of treatment, 4 are ongoing and 14 have discontinued. 16 patients are evaluable for radiological response and 18 for PSA response: 1 has achieved a confirmed radiological PR (6 months [m]), and 6 have confirmed SD (2 for 6m, 1 for 5 m, 1 for 4 m+, 1 for 3 m+). 2 of 18 have had a 50% fall in PSA (6 m, 4 m+) and another a 40% fall (5m). Most common drug related adverse events are (grade [gr],%): fatigue (gr 1–2, 88%), nausea (gr 1–2, 77%; gr 3, 10%), anorexia (gr 1–2, 72%), vomiting (gr 1–2, 55%; gr 3, 10%), non-specific asymptomatic ECG changes (gr 1–3, 44%), diarrhoea (gr 1–2, 38%), thrombocytopaenia (gr 1–2, 33%) and weight loss (gr 1, 20%). Conclusions: Interim results of treatment with FK228 suggest clinically relevant antitumor activity with an 18% disease control rate and a 11% PSA response rate. Toxicity is manageable. Accrual into the study continues. [Table: see text]
Synthesis and antimicrobial activity of oxazolidin-2-ones and related heterocycles (1994)

A series of 5-membered heterocycles, structurally related to the known antibacterial oxazolidin-2-ones 1, have been prepared by modifying the model compound 1a at the 1-, 2-, 2′- and 3-positions. The antibacterial activity of compound 1a was strongly affected by these modifications to the heterocycle, although none of these resulted in an improvement in the microbiological activity. The physicochemical and antibacterial properties of the synthesized compounds are reported.
Optimizing TCP receive performance (2008)

The performance of receive side TCP processing has traditionally been dominated by the cost of the ‘per-byte’ operations, such as data copying and checksumming. We show that architectural trends in modern processors, in particular aggressive prefetching, have resulted in a fundamental shift in the relative overheads of per-byte and per-packet operations in TCP receive processing, making per-packet operations the dominant source of overhead. Motivated by this architectural trend, we present two optimizations, receive aggregation and acknowledgment offload, that improve the receive side TCP performance by reducing the number of packets that need to be processed by the TCP/IP stack. Our optimizations are similar in spirit to the use of TCP Segment Offload (TSO) for improving transmit side performance, but without need for hardware support. With these optimizations, we demonstrate performance improvements of 45-67 % for receive processing in native Linux, and of 86 % for receive processing in a Linux guest operating system running on Xen. 1
Conditioned Pharmacotherapeutic Effects: A Preliminary Study (2009)

A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under standard treatment conditions. Conceivably, corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis. We posit, however, that these preliminary observations implicate conditioning processes in-and for the design of-regimens of pharmacotherapy.
Assembly and dynamics of the bacteriophage T4 homologous recombination machinery (2010)

Homologous recombination (HR), a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR) processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR). T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms.
New multidimensional reconstructions for the 12-detector, scanned focal point, single-photon tomograph (1992)

The heuristic reconstruction process used for the highly focused, scanned focal point tomographs from 1978 and described by the authors in 1979 was changed to a much more accurate two-dimensional iterative reconstruction in 1988. The new algorithm is specific to the unique geometry of the multidetector tomograph and produces dramatically improved images that approximate least mean-square estimates of the objects. This paper describes the algorithm and its generalization to three dimensions. The handling of attenuation, scattering and object power density spectra are discussed. Results are shown as a sampling of 3D brain phantom and clinical images.
Incidence of Dementia is Increased in Type 2 Diabetes and Reduced by the Use of Sulfonylureas and Metformin (2011)

To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan’s National Health Insurance database. Those who, as of on January 1, 2000, were 50 years or older and dementia free (n = 127,209) were followed until December 31, 2007, in relation to absence (n = 101,816) or presence (n = 25,393) of T2DM, and whether any OA was used. Dementia was ascertained by ICD9-CM or A-code. Dementia incidence densities (DID) and fully adjusted Cox proportional hazard models were used to estimate association between dementia, DM, and OA. Notably, DID (per 10,000 person-years)was markedly increased with DM (without medication), compared to DM free subjects (119 versus 46). Using non-DM as reference, the adjusted hazard ratios (HRs) (95% confidence interval) for DM without and with OA were 2.41 (2.17–2.66) and 1.62 (1.49–1.77), respectively. For T2DM, compared with no medication, sulfonylureas alone reduced the HR from 1 to 0.85 (0.71–1.01), metformin alone to 0.76 (0.58–0.98), while with combined oral therapy the HR was 0.65 (0.56–0.74). Adjustments included cerebrovascular diseases so that non-stroke related dementias were found to be decreased in DM with sulfonylurea and metformin therapy. T2DM increases the risk of dementia more than 2-fold. On the other hand, sulfonylureas may decrease the risk of dementia, as does metformin; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years.
CXCR4/CXCL12 expression and signalling in kidney cancer (2002)

CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have recently been shown to be involved in tumourgenesis, proliferation and angiogenesis. Therefore, we analysed CXCL12alpha/CXCR4 expression and function in four human kidney cancer cell lines (A-498, CAKI-1, CAKI-2, HA-7), 10 freshly harvested human tumour samples and corresponding normal kidney tissue. While none of the analysed tumour cell lines expressed CXCL12alpha, A-498 cells were found to express CXCR4. More importantly, real-time RT-PCR analysis of 10 tumour samples and respective adjacent normal kidney tissue disclosed a distinct and divergent downregulation of CXCL12alpha and upregulation of CXCR4 in primary tumour tissue. To prove that the CXCR4 protein is functionally active, rhCXCL12alpha was investigated for its ability to induce changes of intracellular calcium levels in A-498 cells. Moreover, we used cDNA expression arrays to evaluate the biological influence of CXCL12alpha. Comparing gene expression profiles in rhCXCL12alpha stimulated vs unstimulated A-498 kidney cancer cells revealed specific regulation of 31 out of 1176 genes tested on a selected human cancer array, with a prominent stimulation of genes involved in cell-cycle regulation and apoptosis. The genetic changes reported here should provide new insights into the developmental paths leading to tumour progression and may also aid the design of new approaches to therapeutic intervention.
Role of Histidine 46 in the Hydrolysis and the Reverse Transphosphorylation Reaction of RNase Rh from Rhizopus niveus (1997)

In order to study the reaction mechanism of RNase Rh from Rhizopus niveus, the rates of cleavage of four 2',3'-cyclic nucleotides by mutant enzymes of RNase Rh, H46F, H109F, E105Q, and K108L were measured. H46F is virtually inactive towards cyclic nucleotides, but H109F hydrolyzed these substrates at 0.7-4.5% of the rates of the native RNase Rh. The other mutants hydrolyzed 2',3'-cyclic nucleotides at 15-20% of the rates of the native enzyme. Relative enzymatic activities towards four cyclic nucleotides of H109F in the hydrolysis reaction (2nd step) were much higher than in the transphosphorylation reaction (the 1st step). In the presence of a 13-fold excess of uridine, H109F catalyzed the transphosphorylation reaction of 2',3'-cyclic AMP (A>p) to ApU. However, this reaction was not catalyzed by H46F mutant or native RNase Rh. These results showed that His46 is crucial to the hydrolysis reaction, and to the reversed reaction of the transphosphorylation reaction. We suggest that His46 in RNase Rh plays a major role in these reactions by acting as a base catalyst to activate water and the 5'-hydroxyl group of nucleosides, respectively.
Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. (2006)

MT1-MMP (membrane type-1 matrix metalloproteinase), otherwise known as MMP14 is a proteolytic enzyme known to be involved in degradating extracellular matrix and assist progression of cancer invasion and progression. We investigated the impact of targeting the expression of MT1-MMP in breast cancer and its clinical relevance. Human breast cancer cell line MDA-MB-231 was used. Expression of MT1-MMP in the breast cancer cell line was manipulated by way of retroviral ribozyme transgene. The in vitro invasion, growth and cell migration were determined on cell lines transfected with either the transgene or control plasmid. Protein and message levels of MMP14 was also assessed using immunohistochemistry and real-time quantitative analysis, and correlated with clinical and pathological information of the patients. Retroviral ribozyme transgene to human MT1-MMP successfully knocked down the levels of MT1-MMP mRNA from MDA-MB-231 cells. Reduction of MT1-MMP from the breast cancer cells resulted in significant reduction of in vitro invasiveness and loss of response to an invasion stimulus, HGF, compared with control and wild-type cells. The invasion index for MT1-MMP knockdown cells were 13+/-3.1 (without HGF) and 16.4+/-2.3 (with HGF, p=0.14), and the index for transfection control cells 25.3+/-4.3 (without HGF) and 40.4+/-4.1 (with HGF, p=0.0049). Transfection with the transgenes did not change the rate of cell growth. In clinical breast cancer, MT1-MMP staining was both membranous and cytoplasmic. Tumour cells displayed stronger staining compared with normal mammary epithelial cells. Tumour tissues had a marginally higher levels of the MMP14 transcript (8.6+/-1.9), compared with normal tissues (4.7+/-1.4), p=0.13. No significant difference was observed between node positive and node negative tumours (9.0+/-2.2 vs 8.7+/-3.1, p=0.24). Marginally higher levels of the MMP14 transcript were seen in tumours which developed metastasis and local recurrence. However, tumours from patients who died of breast cancer related causes had significantly higher levels of the transcript, compared with tumours from patients who remained disease-free 10 years after initial surgery (12.2+/-2.5 vs 6.3+/-1.2, p=0.0091). MT1-MMP is a proteolytic enzyme that is pivotal in controlling the invasiveness of breast cancer cells. It is highly expressed in aggressive breast tumours and is associated with clinical outcome. The enzyme is a potential therapeutic target in breast cancer.