gebhart/patrepeval huggingface dataset:
Intracellular pH homeostasis in the filamentous fungus Aspergillus niger (2002)

Intracellular pH homeostasis in the filamentous fungus Aspergillus niger was measured in real time by 31P NMR during perfusion in the NMR tube of fungal biomass immobilized in Ca2+-alginate beads. The fungus maintained constant cytoplasmic pH (pH(cyt)) and vacuolar pH (pH(vac)) values of 7.6 and 6.2, respectively, when the extracellular pH (pH(ex)) was varied between 1.5 and 7.0 in the presence of citrate. Intracellular metabolism did not collapse until a Delta pH over the cytoplasmic membrane of 6.6-6.7 was reached (pH(ex) 0.7-0.8). Maintenance of these large pH differences was possible without increased respiration compared to pH(ex) 5.8. Perfusion in the presence of various hexoses and pentoses (pH(ex) 5.8) revealed that the magnitude of Delta pH values over the cytoplasmic and vacuolar membrane could be linked to the carbon catabolite repressing properties of the carbon source. Also, larger Delta pH values coincided with a higher degree of respiration and increased accumulation of polyphosphate. Addition of protonophore (carbonyl cyanide m-chlorophenylhydrazone, CCCP) to the perfusion buffer led to decreased ATP levels, increased respiration and a partial (1 microm CCCP), transient (2 microm CCCP) or permanent (10 microm CCCP) collapse of the vacuolar membrane Delta pH. Nonlethal levels of the metabolic inhibitor azide (N3-, 0.1 mm) caused a transient decrease in pH(cyt) that was closely paralleled by a transient vacuolar acidification. Vacuolar H+ influx in response to cytoplasmic acidification, also observed during extreme medium acidification, indicates a role in pH homeostasis for this organelle. Finally, 31P NMR spectra of citric acid producing A. niger mycelium showed that despite a combination of low pH(ex) (1.8) and a high acid-secreting capacity, pH(cyt) and pH(vac) values were still well maintained (pH 7.5 and 6.4, respectively).
Function of the Vascular Endothelial Growth Factor Receptors Flt-1 and Flk-1/KDR in the Alloimmune Response In Vivo (2005)

Our data suggest that VEGF-VEGFR interactions function in the alloimmune response in vivo. Targeting VEGFRs may represent a novel therapy to protect allografts following clinical transplantation.
Bioreactor-based bone tissue engineering: The influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization (2004)

An important issue in tissue engineering concerns the possibility of limited tissue ingrowth in tissue-engineered constructs because of insufficient nutrient transport. We report a dynamic flow culture system using high-aspect-ratio vessel rotating bioreactors and 3D scaffolds for culturing rat calvarial osteoblast cells. 3D scaffolds were designed by mixing lighter-than-water (density, <1g/ml) and heavier-than-water (density, >1g/ml) microspheres of 85:15 poly(lactide-co-glycolide). We quantified the rate of 3D flow through the scaffolds by using a particle-tracking system, and the results suggest that motion trajectories and, therefore, the flow velocity around and through scaffolds in rotating bioreactors can be manipulated by varying the ratio of heavier-than-water to lighter-than-water microspheres. When rat primary calvarial cells were cultured on the scaffolds in bioreactors for 7 days, the 3D dynamic flow environment affected bone cell distribution and enhanced cell phenotypic expression and mineralized matrix synthesis within tissue-engineered constructs compared with static conditions. These studies provide a foundation for exploring the effects of dynamic flow on osteoblast function and provide important insight into the design and optimization of 3D scaffolds suitable in bioreactors for in vitro tissue engineering of bone.
Enhancing traceability using ontologies (2007)

Traceability refers to the ability to link information in a process chain. This paper proposes the integration of ontologies into the Unified Process (UP) [1] to provide concept-based traceability throughout the software lifecycle. This approach allows the integration of the different models of a software system including business, requirements, analysis and design models in a lower granularity degree than conventional requirements traceability approaches. To assist the designers in creating the ontology and linking concepts to artifacts we provide a tool integrated with an UML modeler.
Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists (2013)

We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)phenol derivatives that bind to the androgen receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound 22 is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC50 0.75 μM), LNCaP cell line bearing T877A-mutated AR (IC50 0.043 μM), and 22Rv1 cell line bearing H874Y-mutated AR (IC50 0.22 μM). Structure-activity relationship studies confirmed that the pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano-substituted anilide substructure of other nonsteroidal AR antagonists. This novel pharmacophore is expected to provide a basis for designing new antiprostate cancer agents.
Protein gene product (PGP) 9.5 in diagnostic (neuro-) oncology. An immunomorphological study. (1995)

Most likely identical to ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), protein gene product (PGP) 9.5 is one of the major constituents of cytoplasmic polypeptides in neurons. The antigen seems to be expressed almost exclusively in neuronal and neuroendocrine tissues and their neoplasms. PGP 9.5 is also present in undifferentiated embryonic neoplasms like primitive neuroectodermal tumors (PNETs). However, the significance of PGP 9.5 as a marker in diagnostic (neuro-) oncology has not been systematically evaluated yet. In the present study the sensitivity and specificity of the widely used antiserum against PGP 9.5 has been retrospectively examined on 290 formalin-fixed, paraffin-embedded tumors of the nervous system and small round blue cell tumors. The presence of the antigen in tumors of neuronal (24/24) and neuroendocrine (63/73) differentiation confirm PGP 9.5 as a sensitive marker of these tumor groups, particularly in the diagnosis of pituitary adenomas where the expression was neither related to the staining behavior of the tumors in the PAS-orange G-reaction nor to their degree of polypeptide- and glycoprotein hormone activity. The nearly constant immunostaining of medulloblastomas (18/19) and other PNETs (5/6) demonstrate the role of PGP 9.5 as an additional marker in the detection of these embryonic tumors as this peptide was not or only weakly found in glial (11/58), meningeal (5/29), and nerve sheath neoplasms (1/28). On the other hand, the significance in the differential diagnosis of small round blue cell tumors seems to be limited because of positive immunoreactions in neuroblastomas (7/7) and oat cell carcinomas of the lung (7/7) although rhabdomyosarcomas (1/6) and malignant Non-Hodgkin-lymphomas (0/13) react completely negative in our series.
Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates. (2000)

It has been known that melanoma cells can suppress the immune system by the Fas ligand. The present study investigated whether interleukin (IL)-18, which can enhance Fas ligand expression, is produced by B16F10 melanoma cells and is involved in immune escape of tumor cells. Immunohistology, reverse transcription-PCR, intracellular fluorescence-activated cell-sorting analysis, and immunoblotting demonstrated that melanoma cells express IL-18. C57BL/6 splenocytes cultured with culture supernatants of B16F10 melanoma cells enhanced IFN-gamma production, which was blocked by anti-IL-18 antibody, indicating that IL-18 in the culture supernatants is functional. In addition to IL-18, the IL-18 receptor was also detected in B16F10 melanoma cells, suggesting a role of this cytokine in regulating the functions of B16F10 melanoma cells. The functional effect of IL-18 on B16F10 melanoma cells was shown by reduction of Fas ligand expression in cells treated with anti-IL-18 antibody or transfected with IL-18 antisense cDNA. In addition, the same treatments decreased intracellular reactive oxygen intermediate levels in B16F10 melanoma cells, indicating that IL-18 regulates reactive oxygen intermediate production, which is involved in Fas ligand expression. Furthermore, transfection of IL-18 antisense cDNA into melanoma cells increased the susceptibility of tumor cells to natural killer cells in vitro. When IL-18 antisense transfectants were implanted into syngeneic mice, severe reduction of tumor cell growth was observed with concomitant infiltrated natural killer cells in the tumor area. Taken together, these results demonstrate that IL-18 has a critical role as a survival factor for B16F10 melanoma cells.
OSLO: improving the security of trusted computing (2007)

In this paper we describe bugs and ways to attack trusted computing systems based on a static root of trust such as Microsoft’s Bitlocker. We propose to use the dy-namic root of trust feature of newer x86 processors as this shortens the trust chain, can minimize the Trusted Computing Base of applications and is less vulnerable to TPM and BIOS attacks. To support our claim we implemented the Open Secure LOader (OSLO), the first publicly available bootloader based on AMDs skinit instruction. 1
Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function. (1991)

To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction we constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. With respect to hormone binding, substitution of the entire extracellular domain of the LH/CG receptor for the corresponding region of the TSH receptor resulted in high-affinity human CG binding with complete loss of TSH binding. Surprisingly, however, there was at least one chimera with a substitution at each of the five domains that still retained high-affinity TSH binding. Substitution of residues 1-170 of the TSH receptor with the corresponding region of the LH/CG receptor was associated with the retention of high-affinity TSH binding but ligand specificity was lost in that TSH and human CG could interact functionally with the receptor. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites.
Plasma morphine concentrations during chronic oral administration in patients with cancer pain (1982)

Plasma concentrations of morphine were studied in 16 patients with chronic pain due to advanced cancer, treated with regular doses of morphine chloride by the oral route. Doses ranged from 20 to 125 mg every 4 h and a significant, positive, linear correlation was found between dose (range 0.22-3.01 mg/kg) and mean plasma concentration (range 22-364 ng/ml). The profile of the 4 h concentration curve is described and found to be subject to considerable, individual variation. The present investigation supports the experience that good pain relief can be obtained, if individual requirements as to dose and dose interval are taken into consideration.
The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery (2000)

Drug delivery to brain tumors has been a controversial subject.Some believe the blood-brain barrier is not important, while others believe it is the major obstacle in treatment and have devised innovative approaches to circumvent it.These approaches can be divided into two categories: those that attempt to increase drug delivery of intravascularly administered drugs by manipulating either the drugs or capillary permeability, and those that attempt to increase drug delivery by local administration.Several strategies have been developed to increase the fraction of intravascular drug reaching the tumor, including intraarterial administration, barrier disruption, new ways of packaging drugs, and, most recently, inhibiting drug ef ux from tumor.When given intravascularly, all drugs have a common drawback: the body acts as a sink, and, even in the best situations, only a small fraction of administered drug actually reaches the tumor.A consequence is that systemic toxicity is usually the dose-limiting factor.When given locally, such as into the cerebrospinal uid or directly into the tumor, 100% of an administered dose is delivered to the target site.However, local delivery is associated with variable and unpredictable spatial distribution and variation in drug concentration.The major dose-lim-iting factor of most local delivery methods will be neurotoxicity.The relative advantages and disadvantages of the different methods of circumventing the blood-brain barrier are presented in this review, and special attention is given to convection-enhanced delivery, which has particular promise for the local delivery of large therapeutic agents such as monoclonal antibodies, antisense oligonucleotides, or viral vectors.
Summarizing Scientific Articles: Experiments with Relevance and Rhetorical Status (2002)

In this article we propose a strategy for the summarization of scientific articles that concentrates on the rhetorical status of statements in an article: Material for summaries is selected in such a way that summaries can highlight the new contribution of the source article and situate it with respect to earlier work. We provide a gold standard for summaries of this kind consisting of a substantial corpus of conference articles in computational linguistics annotated with human judgments of the rhetorical status and relevance of each sentence in the articles. We present several experiments measuring our judges' agreement on these annotations. We also present an algorithm that, on the basis of the annotated training material, selects content from unseen articles and classifies it into a fixed set of seven rhetorical categories. The output of this extraction and classification system can be viewed as a single-document summary in its own right; alternatively, it provides starting material for the generation of task-oriented and user-tailored summaries designed to give users an overview of a scientific field.
Solution conformation of conotoxin GI determined by proton nuclear magnetic resonance spectroscopy and distance geometry calculations (1989)

Conformational analysis of conotoxin GI, one of the neurotoxic peptides produced by a marine snail, genus Conus, was performed by a combination of nuclear magnetic resonance spectroscopy (NMR) and distance geometry calculations. The resulting conformers on minimization of the target function were classified into two groups. The difference in the structures of the conformers is mainly due to the difference in the orientation of the side chain of the tyrosyl residue. The results show that the solution structure of conotoxin GI satisfies the conformational requirements for the biological activity of an antagonist toward nicotinic cholinergic receptors elucidated in a series of studies on alkaloids. The structure is discussed on the basis of the results of comparison of the atomic arrangements of the active sites of snake venom peptides and molecular models based on the results of secondary structure prediction.
Effectiveness and duration of two-arch fixed appliance treatment (2000)

Abstract The aims of this study were to determine the effectiveness and duration of single-phase two-arch fixed appliance treatment and to evaluate factors that may influence these two variables. Data were collected from 177 consecutively completed cases at the Orthodontic Department, Government Dental Clinic, Singapore, during a three-month period. Pre-treatment and post-treatment models were assessed using the Peer Assessment Rating (PAR) index. The result showed that two-arch fixed appliance treatment reduced the malocclusions on average by 77.80 per cent over a period of 25 months. Multiple regression techniques revealed that 22 per cent of the variability in treatment effectiveness could be explained by the pre-treatment PAR score, the age at the start of treatment, the frequency of office visits and whether or not the treatment involved extractions. The variation in treatment duration was due to the frequency of office visits, the pre-treatment PAR score and whether or not the treatment involved extractions or headgear.
Semi-structured messages are surprisingly useful for computer-supported coordination (1986)

This paper argues that using a set of semi-structured message templates is surprisingly helpful in designing a variety of computer-based communication and coordination systems. Semi-structured messages can help provide automatic aids for: (1) composing messages to be sent, (2) selecting, sorting, and prioritizing messages that are received, (3) responding automatically to some messages, and (4) suggesting likely responses to other messages. The use of these capabilities is illustrated in a range of applications including electronic mail, computer conferencing, calendar management, and task tracking. The applications show how ideas from artificial intelligence (such as inheritance and production rules) and ideas from user interface design (such as interactive graphical editors) can be combined in novel ways for dealing with semi-structured messages. The final part of the paper discusses how communities can evolve a useful set of message type definitions.
Genotyping of Single-Nucleotide Polymorphisms by High-Resolution Melting of Small Amplicons (2004)

SNP genotyping by high-resolution melting analysis is simple, rapid, and inexpensive, requiring only PCR, a DNA dye, and melting instrumentation. The method is closed-tube, performed without probes or real-time PCR, and can be completed in less than 2 min after completion of PCR.
A flexible, thermostable nanostructured lipid carrier platform for RNA vaccine delivery (2022)

Current RNA vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited by instability of both the RNA and the lipid nanoparticle delivery system, requiring storage at -20°C or -70°C and compromising universally accessible vaccine distribution. This study demonstrates the thermostability and adaptability of a nanostructured lipid carrier (NLC) delivery system for RNA vaccines that has the potential to address these concerns. Liquid NLC alone is stable at refrigerated temperatures for ≥1 year, enabling stockpiling and rapid deployment by point-of-care mixing with any vaccine RNA. Alternatively, NLC complexed with RNA may be readily lyophilized and stored at room temperature for ≥8 months or refrigerated temperature for ≥21 months while still retaining the ability to express protein <i>in vivo</i>. The thermostability of this NLC/RNA vaccine delivery platform could significantly improve distribution of current and future pandemic response vaccines, particularly in low-resource settings.
Lysosomal and Proteasomal Degradation Play Distinct Roles in the Life Cycle of Cx43 in Gap Junctional Intercellular Communication-deficient and -competent Breast Tumor Cells (2003)

The present study was designed to determine the specific roles played by lysosomes and proteasomes in the degradation of Cx43 in both gap junctional intercellular communication-deficient MDA-MB-231 and -competent BICR-M1Rk cells. In MDA-MB-231 cells, immunolocalization and brefeldin A protein transport blocking studies revealed that there was a propensity for newly synthesized Cx43 to be transported to lysosomes. On the other hand, light and electron microscopic analysis of BICR-M1Rk cells showed that Cx43 gap junctions were prevalent with a subpopulation of intracellular Cx43 localized to lysosomes. In both cell types, Western blots revealed a notable increase in total cellular Cx43 in response to lysosome inhibitors. Interestingly, lactacystin inhibition of proteosomal degradation in MDA-MB-231 cells resulted in a marked increase in phosphorylated Cx43 at the expense of non-phosphorylated Cx43, and this change corresponded with an increase in "oversized" gap junction plaques. In BICR-M1Rk cells, lactacystin treatment partially prevented the BFA-induced loss of gap junctions. Together, our data suggests that lysosomes play a key role in not only degrading internalized gap junction in BICR-M1Rk cells but also in degrading Cx43 delivered from early secretory compartments to lysosomes in MDA-MB-231 cells. Overall proteasomal degradation regulates the stability of phosphorylated Cx43 and appears to promote the internalization of Cx43 from the cell surface.
Extending Carbon Chain Length of 1-Butanol Pathway for 1-Hexanol Synthesis from Glucose by Engineered Escherichia coli (2011)

An Escherichia coli strain was engineered to synthesize 1-hexanol from glucose by extending the coenzyme A (CoA)-dependent 1-butanol synthesis reaction sequence catalyzed by exogenous enzymes. The C4-acyl-CoA intermediates were first synthesized via acetyl-CoA acetyltransferase (AtoB), 3-hydroxybutyryl-CoA dehydrogenase (Hbd), crotonase (Crt), and trans-enoyl-CoA reductase (Ter) from various organisms. The butyryl-CoA synthesized was further extended to hexanoyl-CoA via β-ketothiolase (BktB), Hbd, Crt, and Ter. Finally, hexanoyl-CoA was reduced to yield 1-hexanol by aldehyde/alcohol dehydrogenase (AdhE2). Enzyme activities for the C6 intermediates were confirmed by assays using HPLC and GC. 1-Hexanol was secreted to the fermentation medium under anaerobic conditions. Furthermore, co-expressing formate dehydrogenase (Fdh) from Candida boidinii increased the 1-hexanol titer. This demonstration of 1-hexanol production by extending the 1-butanol pathway provides the possibility to produce other medium chain length alcohols using the same strategy.
DNA-mediated transfer of a human gene required for low-density lipoprotein receptor expression and for multiple Golgi processing pathways. (1986)

Transfection of a hamster cell mutant with human DNA corrected both the low-density lipoprotein receptor-deficient phenotype and the multiple glycosylation defects of the cells. Independently transfected colonies contained a small set of common human DNA fragments. These fragments may correspond to the human analog of a single gene required for several different Golgi processing pathways.