gebhart/patrepeval huggingface dataset:
Structural Mechanism for Heparin-Binding of the Third Kunitz Domain of Human Tissue Factor Pathway Inhibitor, (2001)

Tissue factor pathway inhibitor (TFPI) inhibits the activity of coagulation factor VIIa and Xa through its K1 and K2 domain, respectively, and the inhibitory activity is enhanced by heparin. The function of the K3 domain of TFPI has not been established, but the domain probably harbors a heparin binding site (HBS-2). We determined the three-dimensional solution structure of the TFPI K3 domain (Glu182-Gly242) by heteronuclear multidimensional NMR. The results showed that the molecule is composed of one antiparallel beta-sheet and one alpha-helix, and in overall structure is very similar to the K2 domain, with the rms deviation of 1.55 A for the 58 defined C(alpha) positions. However, the surface electrostatic properties of both domains are different each other. The lack of inhibitory activity of the K3 domain is explained by the absence of electrostatic interaction with factor Xa over a large surface area. A titration experiment with size-fractionated heparin showed that a heparin binding site was located in the vicinity of the alpha-helix. In this region, a positively charged cluster is formed by Lys213, Lys232, and Lys240, and the negatively charged sulfate groups of heparin bind there. The enhancement of inhibitory activity by heparin probably was not due to a conformational change to TFPI itself. It is likely that heparin simply increases the local concentration of TFPI on the cell surface and stabilizes the initial complex that forms.
Planetary Spacecraft Debris: The Case for Protecting the Space Environment (1999)

Abstract In the early years of the Space Age spacecraft debris and spent rocket stages were deposited on the surface of the Moon, ostensibly in the name of space science. Although this was not considered ‘pollution’ then, as we look forward to further manned lunar missions and subsequent development, the status of the lunar surface and orbital environment should be of greater concern, not least with regard to the safety of future travellers. By extension, the effect of spacecraft impacts on the surfaces of other planetary bodies and the formation of planetary orbital debris should be of similar concern to the wider space community. In addition to a commentary on the origins and objectives of the Scientific-Legal Round Table of which this paper is a part, the paper presents an initial catalogue of spacecraft impacts on planetary bodies and the resulting debris that may still be found on their surfaces. It also considers the future of scientific exploration and commercial exploitation of the planetary bodies and presents the case for protecting the space environment. In conclusion, the paper calls for the formation of an international consultative study group, or similar body, to consider the issues relevant to ‘Protection of the Space Environment’ and to raise awareness of the subject among the growing body of space professionals and practitioners.
Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis: A general mechanism to accumulate effector cells in inflammation (1999)

Neutrophils are important effector cells in immunity to microorganisms, particularly bacteria. Here, we show that the process of neutrophil apoptosis is delayed in several inflammatory diseases, suggesting that this phenomenon may represent a general feature contributing to the development of neutrophilia, and, therefore, in many cases to host defense against infection. The delay of neutrophil apoptosis was associated with markedly reduced levels of Bax, a pro-apoptotic member of the Bcl-2 family. Such Bax-deficient cells were also observed upon stimulation of normal neutrophils with cytokines present at sites of neutrophilic inflammation, such as granulocyte and granulocyte-macrophage colony-stimulating factors, in vitro. Moreover, Bax-deficient neutrophils generated by using Bax antisense oligodeoxynucleotides demonstrated delayed apoptosis, providing direct evidence for a role of Bax as a pro-apoptotic molecule in these cells. Interestingly, the Bax gene was reexpressed in Bax-deficient neutrophils under conditions of cytokine withdrawal. Thus, both granulocyte expansion and the resolution of inflammation appear to be regulated by the expression of the Bax gene in neutrophils.
Normal Human Fibroblasts Express Pattern Recognition Receptors for Fungal (1→3)-β-d-Glucans (2001)

Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF). Membranes from NHDF exhibited saturable binding with an apparent dissociation constant (K(D)) of 8.9 +/- 1.9 microg of protein per ml and a maximum binding of 100 +/- 8 resonance units. Competition studies demonstrated the presence of at least two glucan binding sites on NHDF. Glucan phosphate competed for all binding sites, with a K(D) of 5.6 microM (95% confidence interval [CI], 3.0 to 11 microM), while laminarin competed for 69% +/- 6% of binding sites, with a K(D) of 3.7 microM (95% CI, 1.9 to 7.3 microM). Glucan (1 microg/ml) stimulated fibroblast NF-kappaB nuclear binding activity and interleukin 6 (IL-6) gene expression in a time-dependent manner. NF-kappaB was activated at 4, 8, and 12 h, while IL-6 mRNA levels were increased by 48% at 8 h. This is the first report of pattern recognition receptors for glucan on human fibroblasts and the first demonstration of glucan binding sites on cells other than leukocytes. It also provides the first evidence that glucans can directly modulate the functional activity of NHDF. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal (1-->3)-beta-D-glucans and suggests that the response to glucans may not be confined to cells of the immune system.
Therapeutic Immunization with Dendritic Cells Loaded with Heat‐Inactivated Autologous HIV‐1 in Patients with Chronic HIV‐1 Infection (2005)

Therapeutic immunization with autologous monocyte-derived dendritic cells (DCs) loaded with heat-inactivated autologous human immunodeficiency virus type 1 (HIV-1) in 12 patients with chronic HIV-1 infection who were receiving highly active antiretroviral therapy (HAART) was feasible, safe, and well tolerated. Virus was obtained during an initial interruption of HAART (hereafter, "stop 1") so that DCs could be pulsed. After immunization and a second interruption of HAART (hereafter, "stop 2"), set-point plasma viral load (PVL; 24 weeks after stop 2) decreased > or =0.5 log(10) copies/mL relative to baseline PVL in 4 of 12 patients. We observed a significant lengthening in mean doubling time of PVL rebound and significant decreases in the area under the curve and the mean peak of PVL rebound after stop 2, compared with those after stop 1. This response was associated with changes in HIV-1-specific CD4(+) lymphoproliferative and CD8(+) T cell responses. These changes were not observed in a group of nonimmunized control patients.
Induction of biologically active antibodies by a polyvalent synthetic vaccine constructed without carrier (1987)

Four synthetic peptides that copy fragments of two bacterial antigens (Streptococcus pyogenes M protein and diphtheria toxin), one viral antigen (hepatitis B surface antigen), and one parasitic antigen (circumsporozoite protein of Plasmodium knowlesi) were covalently bound within the same construct. This totally synthetic polyvalent administered to mice with Freund complete adjuvant or in saline with murabutide (an adjuvant-active muramyl peptide) elicited high levels of antibodies which, in certain cases, were shown to be biologically active. The results indicated that these antibodies recognized specifically the four peptides. None of the epitopes were immunodominant. It was also demonstrated that the association of several peptides enhanced their respective immunogenicities as compared with those of their homopolymers. Finally, this study shows that a totally synthetic vaccine administered in saline with a synthetic adjuvant can be immunogenic in the absence of a protein carrier.
The Provision of Pharmaceutical Care to Hospice Patients: Results of the National Hospice Pharmacist Survey (1993)

The purpose of this survey was to define pharmaceutical services in hospice programs in the united States. A survey was mailed to 577 pharmacists who had indicated involvement or interest in providing pharmaceutical services to hospice patients. The average respondent pharmacist had six years experience with hospice care. The survey identified the practice base of the pharmacists who practice in hospice care and an attempt was made to define the type of hospices served. The survey inquiries involved dispensing, home visits, participation in hospice team meetings, consultations, drug regimen monitoring, maintenance of medication profiles, provision information and provision of on-call pharmaceutical services. The most common services provided we& dispensing medications (73%) and attending weekly or regular team meetings (60%). These data show a growing-interest in including pharmacis6 as full members of hospice interdisciplinary teams.
Cell Broadband Engine Debugging for Unknown Events (2007)

The complexity of today's hundreds-of-million-transistor microprocessors all but guarantees imperfect first silicon, but leaves unanswered the question of what exactly will go wrong. This article describes features added to the cell broadband engine processor to enable debugging in the presence of such unknown events.
Interfacial interactions and the stability of oil-in-water emulsions (1992)

Abstract
Mechanism of action of a 16-membered macrolide. Characteristics of Dihydrorosaramicin binding to Escherichia coli ribosome and the effects of some competitors. (1982)

The macrolide [3H]dihydrorosaramicin binds specifically to 50S and 70S bacterial ribosomal particles. We have studied the influence of salts, pH and additives on the interaction and found that the optimum requirement for salts was 10 mM trs-HCl (pH 7.6), 6 mM MgCl2, 60 mM NH4Cl, and that beta-mercaptoethanol which reacts on rosaramicin and its dihydro derivative cannot be used. The parameters of the binding were not dependent on the technique used, i.e. equilibrium dialysis, ethanol precipitation or two-phase partitioning. In our search for effectors of this binding, we have found that it is inhibited by other macrolides, little effected by tobramycin and chloramphenicol and enhanced by puromycin.
Ligand-induced Conformational Alterations of the Androgen Receptor Analyzed by Limited Trypsinization (1995)

Limited proteolysis of in vitro produced human androgen receptor was used to probe the different conformations of the receptor after binding of androgens and several antiandrogens. The results provide evidence for five different conformations of the receptor, as detected by the formation of proteolysis resisting fragments: 1) an initial conformation of the unoccupied receptor not resisting proteolytic attack; and receptor conformations characterized by 2) a 35-kDa proteolysis resisting fragment spanning the ligand binding domain and part of the hinge region, obtained with most antagonists, and in an initial step after agonist binding; 3) a 29-kDa proteolysis resisting fragment spanning the ligand binding domain, obtained in the presence of agonists after an activation process; 4 and 5) 30- and 25-kDa fragments, derived from 2 and 3, but missing part of the C terminus, obtained with RU486 (RU486 has antiandrogenic properties, besides its effects as an antiprogestagen/antiglucocorticoid). Concomitantly with the change from 2 to 3 (and of 4 to 5 for RU486), dissociation of the 8 S complex of receptor with associated proteins occurred. With a mutant receptor (LNCaP cell mutation in C-terminal region), some antagonists activated transcription analogous to agonists, and induced the activated receptor conformation 3. A mutant lacking the C-terminal 12 amino acids bound RU486 but not androgens, and formed with RU486 conformation 5. These data imply that, after the initial rapid binding of ligand, androgens induce a conformational change of the receptor, a process that also involves release of associated proteins. RU486 induces an inappropriate conformation of the C-terminal end, similar as found for its effect on the progesterone receptor. In contrast, the other antiandrogens act at a different step in the mechanism of action: they do not induce an abnormal conformation, but act earlier and prevent a conformation change by stabilizing a complex with associated proteins.
RNA targeting gets competitive (2011)

![Figure][1] 

Compared to control neurons (left), BC1 RNA (white) isn’t delivered to dendrites in cells lacking hnRNP A2 (right).



Muslimov et al. reveal how noncanonical structural motifs target RNAs to neuronal dendrites and describe how this might go awry in a neurodegenerative disease
CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis (2010)

ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.
Capture of Peptides with N-Terminal Serine and Threonine:  A Sequence-Specific Chemical Method for Peptide Mixture Simplification (2002)

The objective of this study was to evaluate a sequence-specific chemistry for the ability to specifically capture peptides that contain N-terminal serine or threonine residues from mixtures. The first step is the oxidation of the 1,2-amino alcohol structure −CH(NH2)CH(OH)− of peptides containing N-terminal serine or threonine with periodate. The newly formed aldehyde reacts with a labeling reagent containing a hydrazide, RCONHNH2, to form a hydrazone-peptide conjugate, RCONHNCH−peptide. Biotin-labeled conjugates can then be isolated by affinity purification with streptavidin. The method described in this report can be useful in simplifying the complex mixtures of peptides that are generated in typical proteomic analysis, where proteins are digested with trypsin and analyzed using liquid chromatography mass spectrometry data. The sequence-specific peptide selection not only reduces the complexity of digest mixtures, but also provides additional information for peptide identification. The targeted peptides are those that have either serine or threonine adjacent to a protease cleavage site. The sequence information should greatly aid in both database matching for protein identification and for de novo sequence determination.
Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice. (1986)

The pharmacokinetics of an immunoglobulin G1 (IgG1) and its F(ab')2 and Fab' fragments following i.v. administration in mice has been studied by constructing a physiologically based, organ-specific model to describe antibody biodistribution, catabolism, and excretion. The antibody selected for study (MOPC-21) has no known binding sites in the body and therefore is useful for defining antibody metabolism by nontumor tissues. Whole IgG remains in the body for 8.3 days, the majority of time in the carcass (53.0% of the total residence time); has a distribution volume exceeding that of plasma plus interstitial fluid; distributes into these volumes rapidly for most enteral organs (equilibration time less than 2.6 min for liver, spleen, kidney, and lung), slower for the gut (less than 20 min), and slowest for the carcass (less than 260 min); produces interstitial:plasma concentration ratios of greater than 0.5 for enteral organs and 0.18 for carcass; has the greatest percentage of its catabolism due to the gut (72.8%), followed by the liver (20.5%), then the spleen (3.6%); has the highest extraction on a single pass by the gut (0.14%) and cycles through the interstitial spaces of the body at least 2.8 times/g of organ weight before being metabolized or excreted. When compared with whole IgG, the Fab' fragment is cleared from the body 35 times faster; has a larger total distribution volume; distributes more rapidly into this volume; produces higher interstitial:plasma concentration ratios; is catabolized principally by the kidney (73.4% of total catabolism), followed by the gut (22.9%), then the spleen (3.1%); is extracted from the circulation to the extent of 3.4% on each pass through the kidney, and less by gut (1.0%) and spleen (0.14%) and cycles through non-kidney interstitial spaces at least 0.4 cycles/g of tissue weight before metabolism or excretion. The F(ab')2 fragment has pharmacokinetic characteristics that fall between those of whole IgG and Fab'. These results provide pharmacokinetic criteria for selecting whole IgG, F(ab')2, or Fab' for various in vivo applications; provide a framework for predicting cumulative tissue exposure to antibody labeled with different isotopes; and provide a reference metabolic state for the analysis of more complex systems that do include antibody binding.
Serum Macrophage Inhibitory Cytokine 1 as a Marker of Pancreatic and Other Periampullary Cancers (2004)

Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma.
Providing Internet services to mobile phones: a case study with email (2002)

Mobile phones are quickly becoming one of the most ubiquitous wireless consumer devices. Separately, Internet services are growing by leaps and bounds. Thus, an interesting area of research is to see if and how the two can be married together to provide wireless ubiquitous access to the ever-growing Internet services. We highlight the challenges and issues in providing Internet services to mobile phones. As an example, we describe and examine a research prototype called Wireless Data Server, which provides, among other services, wireless email service to mobile phone users.
Caspase-mediated Cleavage of Hematopoietic Progenitor Kinase 1 (HPK1) Converts an Activator of NFκB into an Inhibitor of NFκB (2001)

Hematopoietic progenitor kinase 1 (HPK1), a mammalian Ste20-related protein kinase, is a potent stimulator of the stress-activated protein kinases (SAPKs/JNKs). Here we report activation of NFkappaB transcription factors by HPK1 that was independent of SAPK/JNK activation. Overexpression of a dominant-negative SEK1 significantly inhibited SAPK/JNK activation, whereas NFkappaB stimulation by HPK1 remained unaffected. Furthermore, activation of NFkappaB required the presence of full-length, kinase-active HPK1, whereas the isolated kinase domain of HPK1 was sufficient for activation of SAPK/JNK. We also demonstrate that overexpression of a dominant-negative IKKbeta blocks HPK1-mediated NFkappaB activation suggesting that HPK1 acts upstream of the IkappaB kinase complex. In apoptotic myeloid progenitor cells HPK1 was cleaved at a DDVD motif resulting in the release of the kinase domain and a C-terminal part. Although expression of the isolated HPK1 kinase domain led to SAPK/JNK activation, the C-terminal part inhibited NFkappaB activation. This dominant-negative effect was not only restricted to HPK1-mediated but also to NIK- and tumor necrosis factor alpha-mediated NFkappaB activation, suggesting an impairment of the IkappaB kinase complex. Thus HPK1 activates both the SAPK/JNK and NFkappaB pathway in hematopoietic cells but is converted into an inhibitor of NFkappaB activation in apoptotic cells.
Differential precoder IC modules for 20-and 40-Gbit/s optical duobinary transmission systems (1999)

This paper reports on 20- and 40-Gbit/s differential precoder modules for optical duobinary transmission systems. These precoder modules overcome the speed limit of a conventional precoder by parallel processing. The proposed precoders handle two or four parallel signals before multiplexing with data rates of one-half or one-quarter the transmission bit rate, and the final preceded signal is obtained by multiplexing the precoder output bit by bit, production-level 0.2-/spl mu/m gate-length GaAs MESFET's were used to fabricate the precoders. The precoders are mounted in an RF package. They successfully performed 20- and 40-Gbit/s precoding for the first time, and the 20-Gbit/s precoder achieved a maximum precoding rate of 22 Gbit/s, which is 76% faster than that of the conventional circuit using the same MESFETs. The 40-Gbit/s precoder performs 40-Gbit/s precoding when combined with a 40-Gbit/s multiplexer unit. Twenty-Gbit/s optical duobinary transmitter and receiver circuits using the 20-Gbit/s precoder module successfully generate fully encoded optical duobinary signal at this rate for the first time. These circuits show a receiver sensitivity of -28.6 dBm for a bit error rate of 1/spl times/10/sup -9/.
Biochemical Analysis of the Regulatory T Cell Protein Lymphocyte Activation Gene-3 (LAG-3; CD223) (2004)

Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4-related transmembrane protein that binds to MHC class II molecules. We have recently shown that LAG-3 is required for maximal regulatory T cell function, and that ectopic expression of LAG-3 is sufficient to confer regulatory activity. In this study we show that LAG-3 is cleaved within the D4 transmembrane domain connecting peptide into two fragments that remain membrane associated: a 54-kDa fragment that contains all the extracellular domains and oligomerizes with full-length LAG-3 (70 kDa) on the cell surface via the D1 domain, and a 16-kDa peptide that contains the transmembrane and cytoplasmic domains. This NH(2)-terminal fragment is subsequently released as soluble LAG-3 (sLAG-3), a process that is increased after T cell activation in vitro and in vivo, and is found in the sera of C57BL/6 and RAG-1(-/-) mice. Modulation of LAG-3 cleavage may contribute to the function of this key regulatory T cell protein.
Engraftment potential of human placenta-derived mesenchymal stem cells after in utero transplantation in rats (2008)

We conclude that hPMCs are mutipotent cells that can be engrafted long-term in immunocompetent rats after in utero transplantation.
Gene aberrations for precision medicine against lung adenocarcinoma (2016)

Lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, is often triggered by an aberration in a driver oncogene in tumor cells. Examples of such aberrations are EGFR mutation and ALK fusion. Lung adenocarcinoma harboring such mutations can be treated with anticancer drugs that target the aberrant gene products. Additional oncogene aberrations, including RET, ROS1, and NRG1 fusions, skipping of exon 14 of MET, and mutations in BRAF, HER2, NF1, and MEK1, were recently added to the list of such "druggable" driver oncogene aberrations, and their responses to targeted therapies are currently being evaluated in clinical trials. However, approximately 30% and 50% of LADCs in patients in Japan and Europe/USA, respectively, lack the driver oncogene aberrations listed above. Therefore, novel therapeutic strategies, such as those that exploit the vulnerabilities of cancer cells with non-oncogene aberrations, are urgently required. This review summarizes the current status of research on precision medicine against LADC and enumerates the research priorities for the near future.
Strategies for combining acoustic echo cancellation and adaptive beamforming microphone arrays (2002)

New concepts for efficient combination of acoustic echo cancellation (AEC) and adaptive beamforming microphone arrays (ABMA) are presented. By decomposing common beamforming methods into a time-invariant part, which the AEC can integrate, and a separate time-variant part, the number of echo cancellers is minimized without rendering the system identification problem more difficult. Methods for controlling the interaction of ABMA and AEC are outlined and implementations for typical microphone array applications are discussed.