gebhart/patrepeval huggingface dataset:
Crystal structure of wild-type human thrombin in the Na+-free state (2005)

Regulation of thrombin activity is critical for haemostasis and the prevention of thrombosis. Thrombin has several procoagulant substrates, including fibrinogen and platelet receptors, and essential cofactors for stimulating its own formation. However, thrombin is also capable of serving an anticoagulant function by activating protein C. The specificity of thrombin is primarily regulated by binding to the cofactor TM (thrombomodulin), but co-ordination of Na+ can also affect thrombin activity. The Na+-free form is often referred to as 'slow' because of reduced rates of cleavage of procoagulant substrates, but the slow form is still capable of rapid activation of protein C in the presence of TM. The molecular basis of the slow proteolytic activity of thrombin has remained elusive, in spite of two decades of solution studies and many published crystallographic structures. In the present paper, we report the first structure of wild-type unliganded human thrombin grown in the absence of co-ordinating Na+. The Na+-binding site is observed in a highly ordered position 6 A (1 A=0.1 nm) removed from that seen in the Na+-bound state. The movement of the Na+ loop results in non-catalytic hydrogen-bonding in the active site and blocking of the S1 and S2 substrate-binding pockets. Similar, if more dramatic, changes were observed in a previous structure of the constitutively slow thrombin variant E217K. The slow behaviour of thrombin in solutions devoid of Na+ can now be understood in terms of an equilibrium between an inert species, represented by the crystal structure described in the present paper, and an active form, where the addition of Na+ populates the active state.
A high cholesterol diet blocks the effect of calcium channel blockers on the uptake of sugars in rabbit intestine. (1997)

Two classes of calcium channel blockers, nisoldipine (NIS) and verapamil (VER), alter the intestinal uptake of sugars, and varying the lipid composition of the diet also modifies intestinal transport function. This study was undertaken in adult male New Zealand rabbits to assess the effect of 3 weeks of dosing with NIS (1 mg.kg-1.day-1) or VER (4 mg.kg-1.day-1) on the in vitro jejunal uptake of D-galactose and L- or D-glucose. The value of the maximal transport rate of D-galactose (Vmax) increased with NIS and VER, compared with control vehicle. The value of the apparent Michaelis constant (K(m)) rose with NIS and fell with VER, and the value of the passive permeability coefficient (Pd) estimated from the uptake of L-glucose fell with NIS and rose with VER. These effects of NIS and VER on Vmax, K(m), and Pd were prevented by feeding a high cholesterol (2.8%) supplemented chow diet (HCD), as compared with chow alone. These effects were not due to any change in the animal's weight gain or intestinal mucosal surface area. The acute exposure of the jejunal tissue in vitro to varying concentrations of NIS but not VER reduced the uptake of D-glucose but had no effect on basal short circuit current (Isc) in either chow or HCD. Isc stimulated with glucose or theophylline was less in chow-fed rabbits compared with HCD-fed rabbits given NIS or VER. Thus, the active transport of sugars by the sodium-dependent transporter in the brush-border membrane, SGLT1, and the passive uptake by the paracellular route are variably influenced by these two classes of calcium channel blockers, and this effect is modified by the cholesterol content of the diet.
Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen. (1991)

We have analyzed cytokine gene expression by a murine CD4+ T-cell clone that expresses three forms of T-cell recognition. The clone employs a V beta 6-containing T-cell receptor to recognize (i) a self class II major histocompatibility complex and an ovalbumin-derived peptide (OVA), (ii) an I-Ab alloantigen, and (iii) Mls-1a. All three responses are accompanied by similar levels of cell proliferation. However, although interferon gamma gene expression is strongly induced during both physiological recognition of the OVA peptide and allogeneic major histocompatibility complex recognition, expression of this gene was not detected during the Mls response. These studies indicate that Mls recognition is functionally distinct from T-cell recognition of peptides and alloantigens and leads to an alternative pattern of cytokine gene expression. They also suggest the possibility that encounter with these two classes of T-cell antigen in vivo may generate subsets of T helper cells that display different patterns of cytokine gene expression.
Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window (2009)

Canonical Notch signaling is thought to control the endocrine/exocrine decision in early pancreatic progenitors. Later, RBP-Jkappa interacts with Ptf1a and E12 to promote acinar differentiation. To examine the involvement of Notch signaling in selecting specific endocrine lineages, we deregulated this pathway by targeted deletion of presenilin1 and presenilin2, the catalytic core of gamma-secretase, in Ngn3- or Pax6-expressing endocrine progenitors. Surprisingly, whereas Pax6(+) progenitors were irreversibly committed to the endocrine fate, we discovered that Ngn3(+) progenitors were bipotential in vivo and in vitro. When presenilin amounts are limiting, Ngn3(+) progenitors default to an acinar fate; subsequently, they expand rapidly to form the bulk of the exocrine pancreas. gamma-Secretase inhibitors confirmed that enzymatic activity was required to block acinar fate selection by Ngn3 progenitors. Genetic interactions identified Notch2 as the substrate, and suggest that gamma-secretase and Notch2 act in a noncanonical titration mechanism to sequester RBP-Jkappa away from Ptf1a, thus securing selection of the endocrine fate by Ngn3 progenitors. These results revise the current view of pancreatic cell fate hierarchy, establish that Ngn3 is not in itself sufficient to commit cells to the endocrine fate in the presence of Ptf1a, reveal a noncanonical action for Notch2 protein in endocrine cell fate selection, and demonstrate that acquisition of an endocrine fate by Ngn3(+) progenitors is gamma-secretase-dependent until Pax6 expression begins.
Caracterización de algunas celestinas españolas por espectroscopía Raman e Infrarroja (1988)

espanolSe pretende en este trabajo un estudio espectroscopico de celestinas espanolas mediante IR y Raman con el animo por un lado, de contribuir a la caracterizacion estructural de estos minerales desde el punto de vista dinamico y por otro, con el animo de establecer una metodologia de analisis mineral complementaria a la difraccion de RX y las propiedades fisicas. EnglishIn this paper we attempt a spectroscopic study of Spanish celestites by means of ER and Raman techniques. The mains purposes of such analysis are, a) contribute to a better structural characterisation of these minerals from a vibrational point of view and b) stablish the methodological basis of spectroscopic study of minerals as complementary against XRD and physical properties.
Molecular Cloning, Characterization, and Expression of a Novel Human Neutral Sphingomyelinase (1999)

Neutral sphingomyelinase (N-SMase) has emerged as an important cell membrane-associated enzyme that participates in several signal transduction and cell regulatory phenomena. Using expression cloning, we have identified a 3.7-kilobase pair cDNA transcript for N-SMase whose open reading frame predicts a 397-amino acid polypeptide. Transfection of COS-7 cells with cDNA for N-SMase resulted in a marked increase in N-SMase activity. Recombinant N-SMase (r-N-SMase) had the following physical-chemical properties. Mg(2+) activated and Cu(2+) and glutathione inhibited the activity of r-N-SMase. In contrast, dithiothreitol did not alter the activity of the enzyme. Of several phospholipids examined, sphingomyelin was the preferred substrate for r-N-SMase. The apparent molecular mass of r-N-SMase derived from COS-7 cells was approximately 90 kDa, similar to the native neutral sphingomyelinase prepared from human urine. However, upon expression in Escherichia coli, the apparent molecular mass of the recombinant enzyme was approximately 45 kDa. We speculate that this apparent difference in recombinant enzymes derived from COS-7 and E. coli cells may be due to extensive post-transcriptional changes. r-N-SMase has numerous post-transcriptional modification sites such as phosphorylation sites via protein kinase C, casein kinase II, tyrosine kinase, and cAMP- and cGMP-dependent protein kinases as well as sites for glycosylation and myristoylation. Amino acid sequence alignment studies revealed that r-N-SMase has some similarity to acid sphingomyelinase and significant homology to the death domains of tumor necrosis factor-alpha receptor-1 and Fas/Apo-I. We believe that the molecular cloning and characterization of N-SMase cDNA will accelerate the process to define its role as a key regulator in apoptosis, lipid and lipoprotein metabolism, and other cell regulatory pathways.
Phase 1 trial of linifanib (ABT-869) in patients with refractory or relapsed acute myeloid leukemia (2012)

Linifanib, a potent oral inhibitor of fms-like tyrosine kinase 3 (FLT3) and vascular endothelial growth factor receptor tyrosine kinases, has demonstrated promising preclinical single-agent and synergistic anti-leukemic activity in combination with cytarabine. In this phase 1, multicenter, open-label, dose-escalation study, 45 adults with relapsed/refractory acute myeloid leukemia (AML) received linifanib alone in arm A (n = 29) and linifanib plus intermediate-dose cytarabine in arm B (n = 16). Median treatment duration was 21 days (range 5-110). Linifanib was well tolerated overall. The most common grade 3/4 events were fatigue (arm A) and febrile neutropenia (arm B). The recommended phase 2 dose was 15 mg (alone), and 10 mg (with cytarabine). Evidence of on-target kinase inhibition in patients with FLT3-mutant and wild-type AML was seen. Decreased phosphorylated FLT3 was seen in 3/3 patients with FLT3-internal tandem duplication (ITD) with peripheral blast reductions and in 8/24 (33%) patients with wild-type, D835 or unknown FLT3 mutation. Eight/29 (28%) patients had decreased phosphorylated extracellular signal-regulated kinase (ERK).
A hierarchical approach to facial aging (2010)

Active Appearance Models (AAMs) have been used as a promising tool in the field of synthetic age progression. However, they are yet to be demonstrated on a large human population with wide variation. This paper presents a novel AAM-based hierarchical approach to facial aging. This work is motivated from studies in medical and anthropological literature on classification of human faces based on gender, ethnic and age groups. The proposed hierarchical model approach is a ethnicity and gender specific aging paradigm. Specifically, the Caucasian (European descent) and African American ethnic groups are considered. This work will further show that using individual hierarchical models generate better age-progressed synthetic images when compared to a general model approach. The results are evaluated by visual perception of the intended age group and preservation of identity. Also, a quantitative evaluation was performed using FaceVACS, a commercial face recognition system, as a surrogate measure. Higher match scores for synthetic images generated by hierarchical models when compared to those generated by a general model suggests the efficiency of the proposed hierarchical model approach.
Inhibition of Furin by Polyarginine-containing Peptides (2004)

Polyarginine-containing peptides represent potent inhibitors of furin, a mammalian endoprotease that plays an important role in metabolism, activation of pathogenic toxins, and viral proliferation. The therapeutic use of D-polyarginines is especially interesting because they are not cleaved by furin and possess inhibitory potency almost equal to L-polyarginines. In this study we attempted to determine the important elements within polyarginines that contribute to effective inhibition. Structure-function analyses of polyarginine peptides showed that inhibition by polyarginine-containing peptides appeared to depend on the total number of basic charges of the positively charged inhibitors bound to the negatively charged substrate binding pocket; peptide positioning did not appear to be rigorously determined. Screening of L- and D-decapeptide positional scanning combinatorial peptide libraries indicated a preference for basic residues in nearly all positions, similar to previous results with hexapeptide libraries. Length and terminal modification studies showed that the most potent D-polyarginine tested was nona-D-arginine (D9R) amide with a K(i) of 1.3 nm. D9R amide was shown to protect RAW264.7 cells against anthrax toxemia with an IC(50) of 3.7 microm. Because of its high stability, specificity, low toxicity, small molecular weight, and extremely low K(i) against furin, D9R amide or its derivatives may represent promising compounds for therapeutic use.
Use of Highly Encapsulated Streptococcus pneumoniae Strains in a Flow-Cytometric Assay for Assessment of the Phagocytic Capacity of Serotype-Specific Antibodies (1998)

A phagocytosis assay for Streptococcus pneumoniae based on flow cytometry (FACS) with human polymorphonuclear cells and human complement was developed for the study of human vaccination antisera. Human prevaccination sera already contain high levels of C-polysaccharide (C-PS) antibodies, which are not protective in humans but which might give false positive results in a flow-cytometry-based assay. Cultures of S. pneumoniae grown to log phase on three consecutive days, followed by heat inactivation, yielded stable and highly encapsulated strains for serotypes 6A, 6B, 14, 19F, and 23F. As a result, only serotype-specific antibodies were able to facilitate phagocytosis of these strains, whereas no phagocytosis was observed with antibodies against C-PS or pneumococcal surface proteins. No, or weak, phagocytosis was observed with human prevaccination sera, whereas in general, postvaccination antisera facilitated phagocytosis. A highly significant correlation was observed between enzyme-linked immunosorbent assay titers and FACS phagocytosis titers (r = 0.98, P < 0.001) for serotype 23F pneumococci with human vaccination antisera. For all serotypes, interassay variation was below 10%. Major advantages of this assay over the classical killing assay are that (i) limited amounts of sera are required (10 microliter per titration curve), (ii) 600 samples can be processed in one day by one person, and (iii) cells can be fixed and measurement of the samples can be performed up to 1 week later.
Inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis B vaccine (1987)

The efficacy of two heating cycles (90 sec at 103 degrees C and 10 hr at 65 degrees C) used during manufacture of a plasma-derived hepatitis-B vaccine was validated for the inactivation of 12 virus families. A period of 15 min warming up to 65 degrees C had already completely inactivated representatives of nine virus families, ie, poxvirus (vaccinia), picornavirus (encephalomyocarditis virus), togavirus (sindbis virus), coronavirus (mouse hepatitis virus), orthomyxovirus (influenza virus), rhabdovirus (vesicular stomatitis virus), herpes virus (cytomegalovirus), lentivirus (human immunodeficiency virus), and retrovirus (murine leukemia virus). After prolonged heating at 65 degrees C or heating for 90 sec at 103 degrees C, parvovirus (canine parvovirus) and the phage phiX174 were also completely inactivated. Papovavirus represented by simian virus 40 (SV-40) was the most heat-resistant virus evaluated. The infectivity of SV-40 was reduced by 10(4) Tissue Culture Infectious Doses (TCID50) per ml after 90 sec at 103 degrees C, but a marginal residual activity (less than 1.5 TCID50 per ml) was observed. Subsequent pasteurization for 10 h at 65 degrees C did not further reduce the infectivity of SV-40. This study shows that the two heat-inactivation steps used during the production of this vaccine kill a wide variety of viruses that might be present in human blood.
Complex carbohydrate synthesis tools for glycobiologists: enzyme-based approach and programmable one-pot strategies (2000)

The ultimate goal in complex carbohydrate synthesis is to develop synthetic tools which are simple and easily accessible to glycobiologists. This review will describe methods which have the potential to reach this goal, with particular focus on enzymatic and computer-based one-pot approaches for the preparation of complex carbohydrates and glycoconjugates.
Mucus Secretory Vesicles in Conjunctival Epithelial Cells of Wearers of Contact Lenses (1980)

Biopsy specimens from the upper tarsal conjunctivae of ten patients with clinically evident contact-lens-associated giant papillary conjunctivitis (GPC) and eight asymptomatic contact lens wearers without clinically evident conjunctival changes were compared by light and transmission electron microscopy to determine the contribution of nongoblet epithelial cells to increased mucus. A control group consisted of five subjects who had never worn contact lenses. The apical cytoplasm of superficial nongoblet epithelial cells in specimens from all groups showed single-membrane-limited vesicular inclusions that stained metachromatically with toluidine blue and were positive with PAS staining, which indicated muco-protein content. Some vesicles appeared to discharge their contents into the conjunctival sac. More vesicles were found in the GPC subjects and the asymptomatic contact lens wearers than in the normal subjects. These observations, coupled with the sign of increased or excessive mucus discharge in GPC subjects and in asymptomatic lens wearers, support the premise that the superficial layers of non-goblet conjunctival epithelial cells can contribute to an increase in mucus production.
"Wir schneiden uns unsere Religion nicht dort ab, wo es den anderen vielleicht jucken könnte": Christlich-muslimische Erziehung 2004 (2005)

Kinder aus christlich-muslimischen Familien dürfen heute als besonders wichtiges Beispiel einer interreligiösen Verständigung gelten. In den Erfahrungen eines hier vorgestellten christlichen Vaters wird die Bedeutung von gemeinsam praktizierter Familienreligiosität, die christlichem und muslimischen Glauben gerecht wird, deutlich. (DIPF/Orig.)
Coagulum Pelviolithotomy; An Improved Technique (1952)

No AccessJournal of Urology1 May 1952Coagulum Pelviolithotomy; An Improved Technique Thomas D. Moore, and Theodore H. Sweetser Thomas D. MooreThomas D. Moore More articles by this author , and Theodore H. SweetserTheodore H. Sweetser More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)68390-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1952 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited BySherer J (2018) Cryoprecipitate Coagulum PyelolithotomyJournal of Urology, VOL. 123, NO. 5, (621-624), Online publication date: 1-May-1980.Marshall S (2018) Commercial Fibrinogen, Autogenous Plasma, Whole Blood and Cryoprecipitate for Coagulum Pyelolithotomy: A Comparative StudyJournal of Urology, VOL. 119, NO. 3, (310-311), Online publication date: 1-Mar-1978.Marshall S, Lyon R and Scott M (2018) Further Simplifications for Coagulum PyelolithotomyJournal of Urology, VOL. 119, NO. 5, (588-588), Online publication date: 1-May-1978.Rathore A and Harrison J (2018) Coagulum Pyelolithotomy using Autogenous Plasma and Bovine ThrombinJournal of Urology, VOL. 116, NO. 1, (8-10), Online publication date: 1-Jul-1976.Dees J (2018) Coagulum PyelolithotomyJournal of Urology, VOL. 73, NO. 3, (445-450), Online publication date: 1-Mar-1955. Volume 67Issue 5May 1952Page: 579-584 Advertisement Copyright & Permissions© 1952 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas D. Moore More articles by this author Theodore H. Sweetser More articles by this author Expand All Advertisement PDF DownloadLoading ...
The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. (2002)

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of malignant plasma cells with slow proliferative rate but enhanced survival. MM cells express multiple Bcl-2 family members, including Bcl-2, Bcl-XL, and Mcl-1, which are thought to play a key role in the survival and drug resistance of myeloma. The cyclin-dependent kinase inhibitor flavopiridol has antitumor activity against hematopoietic malignancies, including CLL, in which induction of apoptosis was associated with reduced expression of antiapoptotic proteins. Therefore, we sought to characterize the effect of flavopiridol on the proliferation and survival of myeloma cells and to define its mechanisms of action. Treatment of MM cell lines (8226, ANBL-6, ARP1, and OPM-2) with clinically achievable concentrations of flavopiridol resulted in rapid induction of apoptotic cell death that correlated temporally with the decline in Mcl-1 protein and mRNA levels. Levels of other antiapoptotic proteins did not change. Overexpression of Mcl-1 protected MM cells from flavopiridol-induced apoptosis. Additional analysis demonstrated that flavopiridol treatment resulted in a dose-dependent inhibition of phosphorylation of the RNA polymerase II COOH-terminal domain, thus blocking transcription elongation. These data indicate that Mcl-1 is an important target for flavopiridol-induced apoptosis of MM that occurs through inhibition of Mcl-1 mRNA transcription coupled with rapid protein degradation via the ubiquitin-proteasome pathway.
The Cytoplasmic Domain of the Drosophila Cell Adhesion Molecule Neuroglian Is Not Essential for Its Homophilic Adhesive Properties in S2 Cells (1995)

Drosophila neuroglian is a transmembrane glycoprotein that has strong structural and sequence homology to the vertebrate L1 gene family of cell adhesion molecules (Bieber, A.J., Snow, P.M., Hortsch, M., Patel, N.H., Jacobs, J.R., Traquina, Z.R., Schilling, J., and Goodman, C.S. (1989) Cell 59, 447-460. Two different neuroglian protein forms that are generated by a differential splicing process are expressed in a tissue-specific fashion by embryonic and larval cells (Hortsch, M., Bieber, A.J., Patel, N.H., and Goodman, C.S. (1990) Neuron 4, 697-709). The two neuroglial polypeptides differ only in their cytoplasmic domains. Both of these neuroglian species, when transfected into the expressed in Drosophila S2 cells, induce the calcium-independent, homophilic aggregation of transformed cells. A third artificial neuroglian protein form was constructed by substituting the neuroglian transmembrane segment and cytoplasmic domains with the glycosyl phosphatidylinositol attachment signal of the Drosophila fasciclin I protein. This cDNA construct generates a glycosyl phosphatidylinositol-anchored form of neuroglian, which retains the ability to induce homophilic cell aggregation when expressed in S2 cells, and was able to interact with both of the two naturally occurring neuroglian polypeptides. These results demonstrate that neuroglian mediates a calcium-independent, homophilic cell adhesion activity and that neither cytoplasmic neuroglian domains nor a direct interaction with cytoskeletal elements is essential for this property.
Clinical pseudophakic cystoid macular edema (2007)

A history of RVO, ERM, and preoperative prostaglandin use were associated with an increased risk for pseudophakic CME. Treatment with NSAIDs plus steroids was associated with faster resolution of CME than no treatment. Treating high-risk patients with NSAIDs after cataract surgery decreases the incidence of postoperative CME to that of patients who are not at high risk.