julilili42/papers huggingface dataset:
Proteomic analysis to improve adequacy of hemo‐ and peritoneal dialysis: Removal of small and high molecular weight proteins with high‐ and low‐flux filters or a peritoneal membrane
2008-07-01

Abstract The reduction of morbidity and mortality in patients undergoing hemo‐ or peritoneal dialysis is strongly related to an efficient and selective clearance of uremic toxins. We used proteomics methods to analyze and further characterize the dialytic removal of still undefined middle and high molecular weigh proteins as a basis for further improvement of dialysis assessment. Dialysates from 26 hemodialysis patients treated with different types of low‐ (F6HPS®) and high‐flux (FX80®, APS650®, FX60®) filters as well as peritoneal fluids from 10 continuous ambulatory peritoneal dialysis (CAPD) patients were analyzed by SELDI‐TOF and 2‐DE. The protein patterns showed selective differences in the proteins cleared depending on the dialysis method used and the filter membrane. While SELDI analyses of dialysates from the F6HPS revealed almost no protein clearance, high‐flux filters and CAPD dialysates showed protein release of different molecular weight ranges. Furthermore, 2‐DE and MS analysis identified 48 different proteins from the dialysate of high‐flux filters and 21 from peritoneal dialysis fluids. In F6HPS dialysates, however, only few proteins could be identified.
The scratch assay: A suitable in vitro tool for studying wound healing effects
2008-07-01

Wounds are physical injuries that result in an opening or break of the skin. Wound healing is a complex process requiring the collaborative efforts of many different tissues and cell lineages and involves proliferation, migration, matrix synthesis, and contraction. We here report the establishment of a scratch assay allowing first insights into the wound healing properties of possible therapeutic remedies including natural compounds and plant extracts. Using Swiss 3T3 albino mouse fibroblasts in monolayers the scratch assay can be used as a model imitating the migration to and proliferation within the wound site. Wound closure is simulated by mechanically creating defects in cell monolayers stratching a line through the layer. The cell-free area is then re-populated by fibroblasts through the combined action of migration and proliferation. Quantifying is done by inspecting the open gap microscopically and analysing the cells which move in and fill the damaged area after staining with 4',6-diamino-2-phenylindole (DAPI) using CellC software.
A Novel Polyarginine Containing Smac Peptide Conjugate that Mediates Cell Death in Tumor and Healthy Cells
2008-07-01

The seven N-terminal amino acids AVPIAQK (SmacN7) of the mitochondrial protein Smac (second mitochondria-derived activator of caspase) promote caspase activation by binding specifically to inhibitor of apoptosis proteins (IAPs) and blocking their inhibitory activity. SmacN7 cannot pass through the cell membrane, but to be of therapeutic use it would be essential for it to enter the cell. To achieve transmembrane transport of SmacN7 we coupled it to a novel fluorescein isothiocyanate (FITC)-labelled transmembrane transport peptide RRRRK(FITC)RRRR via ss-alanine to produce the conjugate AVPIAQKssA RRRRK(FITC)RRRR. Because IAPs are much more strongly expressed in the cytoplasm of tumor cells, we expected this conjugate to produce staining of the cytoplasm, and for this to be stronger in tumor cells than in healthy cells. Surprisingly, we found strong nuclear uptake of the Smac conjugate and of the transport peptide alone without subsequent release in both tumor cells and healthy cells from the bladder, prostate, and brain. This was accompanied by cell death. In contrast to expectations, it appears that the apoptotic effects observed do not result from the SmacN7 cargo alone.
Local Anesthetics Time-Dependently Inhibit Staphylococcus aureus Phagocytosis, Oxidative Burst and CD11b Expression by Human Neutrophils
2008-07-01

Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted.
Human CD4+ T Lymphocytes Recognize a Vascular Endothelial Growth Factor Receptor-2–Derived Epitope in Association with HLA-DR
2008-07-01

Abstract Purpose: Given the multiple escape mechanisms of tumor cells, immunotherapy targeting tumor-dependent stroma may be an effective cancer treatment strategy. Animal models indicate that inducing immunity to tumor endothelia engenders potent antitumor effects without significant pathology. Recently, the first human tumor endothelial antigen vascular endothelial growth factor receptor-2 (VEGFR-2) recognized by HLA class I–restricted CD8+ T cells has been characterized. In this study, we sought to investigate specific recognition of this molecule by human CD4+ T cells. Experimental Design: To identify HLA-DR–restricted antigenic peptides on VEGFR-2 recognized by CD4+ T cells of healthy donors and cancer patients. Results: Nine candidate VEGFR-2 peptides with high binding probability to six common HLA-DRB1 alleles were synthesized using the SYFPEITHI algorithm. One 15-mer peptide (EKRFVPDGNRISWDS), mapping to the 167-181 region of VEGFR-2, stimulated CD4+ T cells in association with several HLA-DR alleles, including DR4 and DR7. Importantly, the epitope could be naturally processed and presented both by HLA-DR–matched antigen-expressing proliferating endothelial cells and by dendritic cells loaded with the native antigen. Furthermore, circulating VEGFR-2–specific CD4+ T cells were detected in 4 of 10 healthy donors and 12 of 40 cancer patients even after single-round peptide stimulation in short-term culture. Patient's T cells could recognize antigen-expressing proliferating endothelial cells in a HLA-DR–restricted fashion. Conclusion: These findings indicate an important role for the 167-181 region of VEGFR-2 in the stimulation of CD4+ T cell responses to VEGFR-2 protein, and may be instrumental both for the development and monitoring of upcoming antitumor vessel vaccines against different cancers based on VEGFR-2 immunogens.
One-step Complete Melting of Paraffin Tissue Microarrays Using Stabilization Bodies
2008-07-01

Paraffin tissue microarrays (PTMAs) are constructed by putting paraffin tissue core biopsies (PTCBs) from donor blocks into the preformed holes of a recipient block. One problem that can occur during sectioning of a PTMA is that PTCBs can fold up. This may be caused by insufficient adhesion of the paraffins of the PTCBs and the recipient block. Mengel et al solved this problem by melting the PTMA block in a 2-step melting procedure. To simplify this melting procedure by reducing it to 1 step, we propose the use of paraffinized stabilization bodies, that is tissue or other biologic or synthetic material, for the construction of PTMAs. Because they keep their structure while the PTMA melts, they stabilize the PTCBs. Thus, a PTMA with a stabilization body can be fully melted in 1 step with a routine device like a hot plate without danger of the PTCBs toppling over.
Imaging of Extralobar Pulmonary Sequestration in a Patient with Tetralogy of Fallot with Pulmonary Atresia, Ventricular Septal Defect and Multiple Aorto-pulmonary Collateral Arteries with Multidetector Computed Tomography
2008-07-01

Complex pulmonary vascular blood supply is common in patients with tetralogy of Fallot with pulmonary atresia, major systemic to pulmonary collateral arteries and hypoplastic or deficient central pulmonary arteries. An extralobar lung sequestration, which has not been described previously in these patients, was imaged in a 6-week-old infant with multidetector computed tomography with sub-millimeter resolution. Arterial and venous vessels were analyzed using three-dimensional vascular exploration tools and results were confirmed with cardiac catheterization.
Does Business Corruption have to be Considered in all Cases as Moral Misconduct? Two Statements
2008-07-01

In the fight against corruption, stringent punishments are imposed on corrupt companies. This paper questions whether these punishments are always wise or justified. Therefore, we distinguish between two kinds of corruption. The first one refers to corruption leading to personal enrichment, while the second type of corruption aims to increase the competitive ability of the company. In many countries – even if officially illegal – corruption and bribery are common while conducting business. Further, in many cases it is only the tip of the iceberg. The majority stay exempt from punishment. Thereby the second variant of corruption turns to be a vital competitive factor. In other words, companies which want to survive in the market are forced to conform to existing conventions. In markets where paying bribes is omnipresent, corruption is not a moral mistake but a free-market need. Therefore, the following questions arise: Where does the companies’ responsibility for corruption start and end? And, in which situation is it appropriate to punish companies for corrupt actions? In this paper, we discuss different corruption scandals involving Siemens, ABB and other competitors. Further we analyse country case studies from India and Russia. The result shows that corruption is in special cases a competitive requirement and not a lack of morality or honesty. It is argued that avoiding corruption in these circumstances cannot be considered the responsibility of companies. In addition, we show that to avoid corruption we need to take a closer look at the particular conditions in which companies “misbehave”. This paper adds a further perspective in the discussion on corruption.
Prospects for further studies of effects of T-odd asymmetry in the emission of light particles in the polarized-neutron-induced ternary fission of heavy nuclei
2008-07-01

Prospects for further studies of TRI and ROT effects of T-odd asymmetry in the emission of light particles in the ternary and binary fission of heavy nuclei that is induced by slow polarized neutrons are considered with a view to studying the mechanism for the formation of these effects and using them to get new information about fission dynamics. It is planned to investigate the dependence of the corresponding T-odd-asymmetry coefficients on the main characteristics of the fission reaction.
How to Add Threads to a Sequential LanguageWithout Getting Tangled Up
2008-07-01

Abstract It is possible to integrate Scheme-style first-class continuations andthreads in a systematic way. We expose the design choices, discuss their consequences, and present semantical frameworks that spec-ify the behavior of Scheme programs in the presence of threads. While the issues concerning the addition of threads to Scheme-like languages are not new, many questions have remained open. Among the pertinent issues are the exact relationship between con-tinuations and the call-with-current-continuation primi-tive, the interaction between threads, first-class continuations, and dynamic-wind, the semantics of dynamic binding in the presenceof threads, and the semantics of thread-local store. Clarifying these issues is important because the design decisions related to themhave profound effects on the programmer&amp;apos;s ability to write modular abstractions. 1 What&amp;apos;s in a Continuation? Scheme [21] was one the first languages to endorse call-with-current-continuation as a primitive. Callwith-current-continuation (or call/cc, for short) is anessential ingredient in the implementation of a wide range of useful abstractions, among them non-local control flow, exceptionsystems, coroutines, non-deterministic computation, and Web programming session management. So much is often repeated,non-controversial and clear. Nowadays, even the name call-with-current-continuationis confusing. It suggests erroneously that call/cc applies its ar-gument to a reified version of the current continuation--the metalevel object the underlying machine uses to remember what shouldhappen with the value of the expression currently being evaluated.
O2‐03–04: Aph1B gamma‐secretase generates long Abeta peptides and genetic ablation improves Alzheimer's disease phenotypes without affecting notch signaling in the mouse
2008-07-01

Gamma-secretase cleavage releases the Abeta peptides of Alzheimer's disease (AD), but is also involved in regulated intramembrane proteolysis of Notch and other important signaling pathways. Epsilon-cleavage releases intracellular domains and is physiologically essential, while gamma-cleavages process the remnant peptide until it is soluble and is released. Abeta is heterogeneous as a consequence of gamma-activity and the ratio of long versus short Abeta is central to AD pathogenesis. Gamma-secretase activity is mediated by a multiprotein complex, minimally consisting of Presenilin 1 or 2 (Psen), Aph1A or B/C, Pen2 and Nicastrin. Differential association of Psen or Aph1 isoforms results in structural heterogeneity in the gamma-secretase complex in vivo. This structural diversity raises questions with regard to specificity and biological activity of the different complexes. In the current work, we analyze the activity in reconstituted knock-out cell lines, in purified complexes from mouse and human brain and test the in vivo consequences of this functional heterogeneity in a murine AD model. In contrast with recent in vitro overexpression studies, we find significant differences in the profiles of the Abeta peptides generated by complexes with different Aph1 components. Furthermore, when we specifically inactivate the Aph1B/C gamma-secretase complex in a mouse AD model, we find remarkable improvements of disease-relevant phenotypes without serious Notch side effects. We show that gamma-secretase exists as structurally heterogeneous complexes and that the Aph1 subunit affects gamma-cleavage through a shift in the longer versus shorter Abeta species, but does not affect the release of intracellular domains. This allows dissociation of toxicity and therapeutic effects because specific inactivation of Aph1B(C) in an AD model results in decreased amyloid plaque, Abeta and Abeta oligomer accumulation, and rescue of AD-related phenotypes without significantly altering Notch signalling. Our work suggests that the different Aph1 gamma-secretases contribute differentially to biological and pathological functions and opens a new avenue for more specific and less toxic AD therapy.
P1‐110: Microglia ablation does not alter plaque formation and maintenance in a mouse model of cerebral amyloidosis
2008-07-01

β-Amyloid plaques are a major hallmark of Alzheimer's disease (AD). These plaque deposits are invariably accompanied by an inflammatory reaction involving microglia, which are the primary immune effector cells of the brain. It is known that microglia cells are attracted to and surround amyloid deposits in transgenic mice and in AD brains. Microglia cells have been suggested to be involved in amyloid plaque formation, maintenance and phagocytosis. To study the effect of microglia in cerebral amyloidosis, we crossed CD11b-HSVTK transgenic mice (TK mice) with APPPS1 transgenic mice. TK mice allow depletion of microglia cells upon treatment with Ganciclovir (GCV) (Heppner et al., Nat Med 11:146–52, 2005) while APPPS1 transgenic mice develop rapid and early onset of amyloid pathology (Radde et al., EMBO Rep 7:940–6, 2006). APPPS1/TK mice received intracerebral administration of GCV via an osmotic minipump. Furthermore, microglia ablation was monitored in vivo using 2-photon microscopy by crossing APPPS1/TK mice with Iba1-GFP mice. Mice were immunohistochemically analyzed after 1–4 weeks. We first tested the impact of microglia on the formation of amyloid plaques by applying GCV to predepositing APPPS1+/TK+ and APPPS1+/TK- mice. Surprisingly, APPPS1+/TK+ mice developed amyloid plaques even in the absence of microglia at levels similar to littermateAPPPS1+/TK- control mice. Ultrastructural analyses confirmed the absence of microglia in GCV-treated APPPS1+/TK+ mice. To study the impact of microglia on amyloid maintenance, we applied GCV to amyloid-bearing APPPS1+/TK+ and APPPS1+/TK- mice. Again, microglia ablated APPPS1+/TK+ mice displayed no statistically significant change in amyloid plaque load compared to APPPS1+/TK- mice. In vivo 2-photon microscopy analysis confirmed that during the process of GCV-mediated microglial ablation, amyloid deposits in APPPS1+/TK+ mice remained unaltered. We conclude that amyloid plaque formation and maintenance—at least at the investigated time points in the mouse model studied here—can occur in the absence of microglia without any significant change in amyloid load, amyloid plaque morphology or composition.
Spasmolytic effects of STW 5 and its components on ileal contractions induced by acetylcholine, prostaglandin F2α and substance P
2008-07-01

Irritable bowel syndrome (IBS) is one of the most frequent diseases in the gastroenterological practice, and phytotherapy is an option of increasing importance in actual therapy. A phytomedicine with clinically proven efficacy in this indication [1] is STW 5 (Iberogast®), which is used in an increasing number of countries including the USA, Australia and Canada.
P1‐076: Modeling Familial Danish dementia
2008-07-01

Familial British Dementia (FBD) and Familial Danish Dementia (FDD) are neurodegenerative diseases involving aberrant protein accumulation. The features of these diseases, such as the accumulation of the ABri and ADan peptides in the form of amyloid plaques and vascular amyloid, as well as the associated neurofibrillary tau pathology and neuroinflammation, are remarkably similar to those seen in Alzheimer's Disease (AD). Objective: To advance our understanding of disease pathogenesis and that of amyloid hypotheses in general, we have created several transgenic mouse models. Transgenic mice harboring the human FBD and FDD mutations were produced on a C57BL/6J background expressing the respective transgenes under the control of the SHaPrP promoter. Analyses have been performed using ultrastructural, histological, and biochemical methods. Initial characterization has revealed that the Danish transgenic mice in particular deposit significant ADan-amyloid with age with a concomitant microglial and astrocytic response. Amyloid predominantly accumulates in the vasculature, as cerebral amyloid angiopathy (CAA), as well as in the form of parenchymal plaques. At 2 months of age, endogenous levels of mouse ABeta 40 and 42 are significantly decreased. This has lead us to investigate these effects further with human ABeta in vivo through crosses with APP transgenic mice. Furthermore, investigations regarding a similar synergy between ADanish expression and Tau pathology are currently underway through crosses with human Tau transgenic mice. Our results suggest that amyloid proteins, irrespective of their lack of sequence homology or potential function, participate in similar pathways leading to neuroinflammation and dementia.
Gamow-Teller strength distributions for ββ-decaying nuclei within continuum QRPA
2008-07-01

A version of the pn continuum QRPA is outlined and applied to describe the Gamow-Teller strength distributions for beta beta-decaying open-shell nuclei. The calculation results obtained for the pairs of nuclei (116)Cd-Sn and (130)Te-Xe are compared with available experimental data.
S5‐03–03: Induction of cerebral beta‐amyloidosis in transgenic mice
2008-07-01

We have previously shown (Meyer-Lühmann et al., Science 313: 1781–84, 2006) that intracerebral injections of dilute, amyloid-beta (Abeta)-containing human or APP transgenic mouse brain extract can induce cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. After injecting extracts from APP/PS1 transgenic mice into APP hosts and vice versa, our results suggest the occurrence of polymorphic Abeta species, reminiscent of prion strains. We use dilute brain extracts as described in Meyer-Lühmann et al., Science 313: 1781–84, 2006. Results from ongoing experiments will be presented. The nature of the seeding agent and of the induced amyloid will be further characterized and peripheral routes of extract applications studied.
Voting and Economic Asymmetry
2008-07-01

The vast majority of presidential voters decide their votes on the basis of policies other than those that shape high-tech markets, but election results have enormous consequence for high tech. That asymmetry has been with us for many years, and it explains a lot of what we see in federal government policy. It shapes the tenor of elections, the prevalence of backroom decision making, and the type of policies for high-tech markets the US government makes.
Boswellic acids from the anti-inflammatory remedy frankincense: Identification and functional analysis of novel molecular targets within the arachidonic acid cascacde
2008-07-01

Boswellic acids (BAs) are pharmacologically active principles from frankincense that is traditionally applied in the treatment of inflammatory disorders. Initially, BAs were found to block the formation of leukotrienes by inhibiting 5-lipoxygenase (5-LO), whereas interference with platelet-type 12-lipoxygenase (p12-LO) and cyclooxygenases (COX) has been excluded [1]. Here, we provide evidence for a molecular interference of select BAs with COX-1 or 12p-LO. We show that 11-keto-β-BAs concentration-dependently inhibit COX-1 and p12-LO product formation in stimulated human platelets (IC50=6–17μM) and in cell-free assays [2, 3]. The inhibitory effect of BAs on COX-1 is reversible, and increasing the arachidonic acid concentration impairs the efficacy. In a protein fishing assay, both COX-1 and p12-LO from platelet lysates selectively bound to a BA-affinity matrix. Also isolated COX-1 enzyme bound to the immobilized BAs and this binding was reversed by ibuprofen or arachidonic acid. Automated molecular docking of BAs into X-ray structures of COX-1 indicate favorable binding to the active site of the enzyme. In contrast, COX-2 was hardly inhibited by BAs. To improve the potency of BAs, structural derivatives were designed and synthesized. Structure-activity-relationship studies revealed potent BA-derivatives with submicromolar IC50 values for both COX-1 and p12-LO. In conclusion, BAs directly interfere with COX-1 and p12-LO and may mediate their anti-inflammatory actions not only by suppression of 5-LO, but also by inhibiting COX-1 and p12-LO. These findings underline the anti-inflammatory effectiveness of frankincense extracts on one hand, but also may unravel novel therapeutic indications for pharmacological intervention using frankincense.