gebhart/patrepeval huggingface dataset:
A Novel Family in Medicago truncatula Consisting of More Than 300 Nodule-Specific Genes Coding for Small, Secreted Polypeptides with Conserved Cysteine Motifs, (2003)

Transcriptome analysis of Medicago truncatula nodules has led to the discovery of a gene family named NCR (nodule-specific cysteine rich) with more than 300 members. The encoded polypeptides were short (60-90 amino acids), carried a conserved signal peptide, and, except for a conserved cysteine motif, displayed otherwise extensive sequence divergence. Family members were found in pea (Pisum sativum), broad bean (Vicia faba), white clover (Trifolium repens), and Galega orientalis but not in other plants, including other legumes, suggesting that the family might be specific for galegoid legumes forming indeterminate nodules. Gene expression of all family members was restricted to nodules except for two, also expressed in mycorrhizal roots. NCR genes exhibited distinct temporal and spatial expression patterns in nodules and, thus, were coupled to different stages of development. The signal peptide targeted the polypeptides in the secretory pathway, as shown by green fluorescent protein fusions expressed in onion (Allium cepa) epidermal cells. Coregulation of certain NCR genes with genes coding for a potentially secreted calmodulin-like protein and for a signal peptide peptidase suggests a concerted action in nodule development. Potential functions of the NCR polypeptides in cell-to-cell signaling and creation of a defense system are discussed.
Targeting PD-1/PD-L1 interactions for cancer immunotherapy (2012)

Tumors have developed multiple immunosuppressive mechanisms to turn down the innate and the effector arms of the immune system, thus compromising most of the immunotherapeutic strategies that have been proposed during the last decade. Right after the pioneering success of Ipilimumab (anti-CTLA4) in metastatic melanoma, several groups have conducted trials aiming at subverting other immune checkpoints. Two articles that recently appeared in the New England Journal of Medicine.(1) (,) (2) highlight the therapeutic potential of agents that target PD-1 or its ligand PD-L1 in patients with advanced cancer, even individuals with lung or brain metastases. If confirmed, this clinical breakthrough will open novel avenues for cancer immunotherapy.
Blood and serum substances for markers of prostate cancer (2000)

Serummarkers for prostate carcinoma are widely applied for the purpose of early detection of cancer and the differentiation between benign and malignant disease, for the pre-treatment staging of detected prostatic cancers, and for the monitoring of prostate cancer after curative or palliative therapies. This review illustrates the limitations of current markers for prostatic disease in blood en serum. It gives an overview of what is known about PSA and its isoforms, hK2, PSMA, and PSCA, and discusses, based on this information, in what direction current research is developing in order to improve these markers.
Heparan Sulfate Phage Display Antibodies Identify Distinct Epitopes with Complex Binding Characteristics (2009)

Heparan sulfate (HS) binds and modulates the transport and activity of a large repertoire of regulatory proteins. The HS phage display antibodies are powerful tools for the analysis of native HS structure in situ; however, their epitopes are not well defined. Analysis of the binding specificities of a set of HS antibodies by competitive binding assays with well defined chemically modified heparins demonstrates that O-sulfates are essential for binding; however, increasing sulfation does not necessarily correlate with increased antibody reactivity. IC50 values for competition with double modified heparins were not predictable from IC50 values with corresponding singly modified heparins. Binding assays and immunohistochemistry revealed that individual antibodies recognize distinct epitopes and that these are not single linear sequences but families of structurally similar motifs in which subtle variations in sulfation and conformation modify the affinity of interaction. Modeling of the antibodies demonstrates that they possess highly basic CDR3 and surrounding surfaces, presenting a number of possible orientations for HS binding. Unexpectedly, there are significant differences between the existence of epitopes in tissue sections and observed in vitro in dot blotted tissue extracts, demonstrating that in vitro specificity does not necessarily correlate with specificity in situ/vivo. The epitopes are therefore more complex than previously considered. Overall, these data have significance for structure-activity relationships of HS, because the model of one antibody recognizing multiple HS structures and the influence of other in situ HS-binding proteins on epitope availability are likely to reflect the selectivity of many HS-protein interactions in vivo.
Inhibition of Calpain Cleavage of Huntingtin Reduces Toxicity (2004)

Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) tract expansion near the N terminus of huntingtin (Htt). Proteolytic processing of mutant Htt and abnormal calcium signaling may play a critical role in disease progression and pathogenesis. Recent work indicates that calpains may participate in the increased and/or altered patterns of Htt proteolysis leading to the selective toxicity observed in HD striatum. Here, we identify two calpain cleavage sites in Htt and show that mutation of these sites renders the polyQ expanded Htt less susceptible to proteolysis and aggregation, resulting in decreased toxicity in an in vitro cell culture model. In addition, we found that calpain- and caspase-derived Htt fragments preferentially accumulate in the nucleus without the requirement of further cleavage into smaller fragments. Calpain family members, calpain-1, -5, -7, and -10, have increased levels or are activated in HD tissue culture and transgenic mouse models, suggesting they may play a key role in Htt proteolysis and disease pathology. Interestingly, calpain-1, -5, -7, and -10 localize to the cytoplasm and the nucleus, whereas the activated forms of calpain-7 and -10 are found only in the nucleus. These results support the role of calpain-derived Htt fragmentation in HD and suggest that aberrant activation of calpains may play a role in HD pathogenesis.
Inhibition of purified collagenase from alkali-burned rabbit corneas. (1989)

The inhibitory potency of four classes of compounds that inhibit corneal ulceration (thiols, tetracyclines, sodium citrate and sodium ascorbate) was assessed with collagenase purified from culture medium of alkali-burned rabbit corneas. The most potent inhibitor, a beta-mercaptomethyl tripeptide HSCH2(DL)CH[CH2CH(CH3)2]CO-Phe-Ala-NH2, exhibited 50% inhibition (IC50) at approximately 10 nM using the synthetic metalloproteinase substrate Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2. The inhibitor was somewhat less potent with type 1 collagen as substrate (IC50 between 1 and 3 microM), possibly because autooxidation of the essential - SH moiety of the inhibitor occurred during the longer time required for assay with the natural substrate. An N-carboxyalkyl tripeptide, CH3(CH2)2(DL)CH-(COOH)-Leu-Phe-Ala-NH2, was less potent (IC50 = 25 microM) than the thiol peptide. N-acetylcysteine, which is used to treat corneal ulceration, gave IC50 values of 2.7 mM and less than 10 mM with the synthetic and natural substrates, respectively. The IC50 values for the tetracyclines using the synthetic substrate were 15, 190 and 350 microM for doxycycline, minocycline and tetracycline, respectively. Inhibition by sodium citrate, but not the tetracyclines, could be reversed by excess Ca2+. Sodium ascorbate did not inhibit collagenase-mediated hydrolysis of either collagen or the synthetic substrate, thus indicating that the mechanism by which this agent inhibits corneal ulceration is not related to inhibition of collagen degradation by collagenase.
Extraction of actinides using N, N, N′, N′-tetraoctyl diglycolamide (TODGA): a thermodynamic study (2006)

Summary The effect of temperature on the extraction behaviour of Am(III), Pu(IV) and U(VI) from nitric acid medium was studied employing N , N , N ′, N ′-tetraoctyl diglycolamide (TODGA) in n -dodecane. The two-phase equilibrium constants (log K ′ ex ) were calculated and compared with those of other extractants proposed for actinide partitioning, viz. octyl-(phenyl)- N , N -diisobutylcarbamoylmethyl phosphine oxide (CMPO) and N , N , N ′, N ′-dimethyl dibutyl tetradecyl malonamide (DMDBTDMA). Thermodynamic parameters, viz. Δ G , Δ H and Δ S for the extraction of actinides by TODGA were also compared with those of CMPO and DMDBTDMA. These studies indicate that the extraction processes of Am(III) and U(VI) are enthalpy driven whereas entropy factor counteracts the extraction. However, in the case of Pu(IV), the extraction process is enthalpy as well as entropy favoured. Role of diluent on the loading of Nd(III) in 0.1 M TODGA has also been investigated.
Clioquinol independently targets NF-kappaB and lysosome pathways in human cancer cells. (2010)

We have reported that clioquinol alters lysosome integrity, inhibits nuclear factor kappa B (NF-kappaB) activity, and induces apoptosis in human cancer cells. The present study investigated whether clioquinol targets both pathways dependently or independently in human prostate cancer DU 145 cells. Clioquinol inhibited NF-kappaB activity, an effect being more pronounced in the presence of zinc. This inhibition was mediated through a reduced nuclear level of p65, the most frequently detected NF-kappaB subunit. Clioquinol also induced alterations of lysosome permeability in a zinc concentration-dependent manner. Pretreatment of the cells with ammonium, a lysosome protection agent, attenuated clioquinol-induced disruption of the lysosomes, yet ammonium had no effect on clioquinol-induced inhibition of NF-kappaB signaling. MG132, an established NF-kappaB inhibitor, suppressed NF-kappaB activity without causing alterations of lysosome permeability. These findings indicate that clioquinol targets NF-kappaB and lysosome pathways independently, favoring further development of clioquinol as a novel anticancer agent.
Efficient randomized pattern-matching algorithms (1987)

We present randomized algorithms to solve the following string-matching problem and some of its generalizations: Given a string X of length n (the pattern) and a string Y (the text), find the first occurrence of X as a consecutive block within Y. The algorithms represent strings of length n by much shorter strings called fingerprints, and achieve their efficiency by manipulating fingerprints instead of longer strings. The algorithms require a constant number of storage locations, and essentially run in real time. They are conceptually simple and easy to implement. The method readily generalizes to higher-dimensional pattern-matching problems.
NeuRobot: Telecontrolled Micromanipulator System for Minimally Invasive Microneurosurgery—Preliminary Results (2002)

The use of telecontrolled manipulator systems in neurosurgery is very promising, and we are convinced that this system will facilitate more accurate, less invasive microneurosurgery. The details of the NeuRobot system and preliminary results are presented.
Product Structure Based Reason Maintenance for Product Configuration (1996)

The aim of the process of product configuration in engineering design is to determine a set of elements and their relationships; i.e. to create an arrangement that satisfies design requirements and constraints. It becomes a difficult process when there are a large number of elements with various relationships and many design constraints. Current AI-based systems for product configuration have not been as successful as expected in their take-up by industry. This paper suggests that one reason for this is that the reasoning mechanisms in these systems are being developed without reference to product structures. Product structures on the other hand is a topic of increasing interest in both research in design and industrial practice in order to cope with a modern engineering design environment. This paper presents a linkage between configuration process and product structures. The approach, i.e., a Virtual Configuration Workbench, is product structure based in contrast with existing approaches which are mainly rule driven or decision tree/network driven, integrated with an effective reasoning engine with a reason maintenance mechanism. A demonstration system called CONFIGMAN has been developed and illustrated briefly in the paper.
Remediation and Recovery of Uranium from Contaminated Subsurface Environments with Electrodes (2005)

Previous studies have demonstrated that Geobacter species can effectively remove uranium from contaminated groundwater by reducing soluble U(VI) to the relatively insoluble U(IV) with organic compounds serving as the electron donor. Studies were conducted to determine whether electrodes might serve as an alternative electron donor for U(VI) reduction by a pure culture of Geobacter sulfurreducens and microorganisms in uranium-contaminated sediments. Electrodes poised at -500 mV (vs a Ag/AgCl reference) rapidly removed U(VI) from solution in the absence of cells. However, when the poise at the electrode was removed, all of the U(VI) returned to solution, demonstrating that the electrode did not reduce U(VI). If G. sulfurreducens was present on the electrode, U(VI) did not return to solution until the electrode was exposed to dissolved oxygen. This suggeststhat G. sulfurreducens on the electrode reduced U(VI) to U(IV) which was stably precipitated until reoxidized in the presence of oxygen. When an electrode was placed in uranium-contaminated subsurface sediments, U(VI) was removed and recovered from groundwater using poised electrodes. Electrodes emplaced in flow-through columns of uranium-contaminated sediments readily removed U(VI) from the groundwater, and 87% of the uranium that had been removed was recovered from the electrode surface after the electrode was pulled from the sediments. These results suggest that microorganisms can use electrons derived from electrodes to reduce U(VI) and that it may be possible to remove and recover uranium from contaminated groundwater with poised electrodes.
CD5 acts as a tyrosine kinase substrate within a receptor complex comprising T-cell receptor zeta chain/CD3 and protein-tyrosine kinases p56lck and p59fyn. (1992)

T-cell antigens including CD2, CD4, CD6, CD8, and CD28 serve as coreceptors with the T-cell receptor (TCR)/CD3 complex in control of T-cell growth. The molecular basis by which these antigens fulfill this role has remained a major issue. An initial clue to this question came with our finding that the sensitivity of in vitro kinase labeling (specifically using protein-tyrosine kinase p56lck) allowed detection of a physical association between CD4-p56lck and the TCR/CD3 complexes. Another T-cell antigen, CD5, is structurally related to the macrophage scavenger receptor family and, as such, can directly stimulate and/or potentiate T-cell proliferation. In this study, we reveal that in Brij 96-based cell lysates, anti-CD5 antibodies coprecipitated TCR zeta chain (TCR zeta)/CD3 subunits as well as the protein-tyrosine kinases p56lck and p59fyn. Conversely, anti-CD3 antibody coprecipitated CD5, p56lck, and p59fyn. Indeed, anti-CD5 and anti-CD3 gel patterns were virtually identical, except for a difference in relative intensity of polypeptides. Anti-CD4 coprecipitated p56lck, p32, and CD3/TCR zeta subunits but precipitated less CD5, suggesting the existence of CD4-TCR zeta/CD3 complexes distinct from the CD5-TCR zeta/CD3 complexes. Consistent with the formation of a multimeric CD5-TCR zeta/CD3 complex, anti-CD5 crosslinking induced tyrosine phosphorylation of numerous T-cell substrates, similar to those phosphorylated by TCR zeta/CD3 ligation. Significantly, as for TCR zeta, CD5 was found to act as a tyrosine kinase substrate induced by TCR/CD3 ligation. The kinetics of phosphorylation of CD5 (t1/2 = 20 sec) was among the earliest of activation events, more rapid than seen for TCR zeta (t1/2 = 1 min). CD5 represents a likely TCR/CD3-associated substrate for protein-tyrosine kinases (p56lck or p59fyn) and an alternative signaling pathway within a multimeric TCR complex.
Synthesis of GDP-L-fucose by the Human FX Protein (1996)

FX is a homodimeric NADP(H)-binding protein of 68 kDa, first identified in human erythrocytes, from which it was purified to homogeneity. Its function has been unrecognized despite partial structural and genetic characterization. Recently, on the basis of partial amino acid sequence, it proved to be the human homolog of the murine protein P35B, a tumor rejection antigen. In order to address the biochemical role of FX, its primary structure was completed by cDNA sequencing. This sequence revealed a significant homology with many proteins from different organisms. Specifically, FX showed a remarkable similarity with a putative Escherichia coli protein, named Yefb, whose gene maps in a region of E. coli chromosome coding for enzymes involved in synthesis and utilization of GDP-D-mannose. Accordingly, a possible role of FX in this metabolism was investigated. The data obtained indicate FX as the enzyme responsible for the last step of the major metabolic pathway resulting in GDP-L-fucose synthesis from GDP-D-mannose in procaryotic and eucaryotic cells. Specifically, purified FX apparently catalyzes a combined epimerase and NADPH-dependent reductase reaction, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. This is the substrate of several fucosyltranferases involved in the correct expression of many glyconjugates, including blood groups and developmental antigens.
A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments (2015)

The DNA damage response kinase ATR may be a useful cancer therapeutic target. ATR inhibition synergizes with loss of ERCC1, ATM, XRCC1 and DNA damaging chemotherapy agents. Clinical trials have begun using ATR inhibitors in combination with cisplatin. Here we report the first synthetic lethality screen with a combination treatment of an ATR inhibitor (ATRi) and cisplatin. Combination treatment with ATRi/cisplatin is synthetically lethal with loss of the TLS polymerase ζ and 53BP1. Other DNA repair pathways including homologous recombination and mismatch repair do not exhibit synthetic lethal interactions with ATRi/cisplatin, even though loss of some of these repair pathways sensitizes cells to cisplatin as a single-agent. We also report that ATRi strongly synergizes with PARP inhibition, even in homologous recombination-proficient backgrounds. Lastly, ATR inhibitors were able to resensitize cisplatin-resistant cell lines to cisplatin. These data provide a comprehensive analysis of DNA repair pathways that exhibit synthetic lethality with ATR inhibitors when combined with cisplatin chemotherapy, and will help guide patient selection strategies as ATR inhibitors progress into the cancer clinic.
New members of the tomato ERF family show specific expression pattern and diverse DNA‐binding capacity to the GCC box element (2003)

Four new members of the ERF (ethylene-response factor) family of plant-specific DNA-binding (GCC box) factors were isolated from tomato fruit (LeERF1-4). Phylogenetic analysis indicated that LeERF2 belongs to a new ERF class, characterized by a conserved N-terminal signature sequence. Expression patterns and cis/trans binding affinities differed between the LeERFs. Combining experimental data and modeled three-dimensional analysis, it was shown that binding affinity of the LeERFs was affected by both the variation of nucleotides surrounding the DNA cis-element sequence and the nature of critical amino acid residues within the ERF domain.
Vein Cuff Interposition Prevents Juxta-Anastomotic Neointimal Hyperplasia (1988)

This study sought to minimize juxta-anastomotic neointimal hyperplasia (JNIH) following the use of polytetrafluorethylene (PTFE) conduits. PTFE anastomoses to canine carotid arteries (noncuff grafts) were compared with grafts with vein cuffs interposed proximally and distally between the graft and native artery. This technique has been suggested clinically for below-knee PTFE femoropopliteal reconstruction. Twelve dogs received aspirin for 1 week before operation, which was continued after each animal received bilateral cuff and noncuff 4-mm PTFE grafts. At sacrifice, after 3-12 weeks, graft patency was assessed and luminal diameters measured with ophthalmic calipers at three sites along the anastomoses and 1 mm proximal or distal to graft toe (A' diameter). Specimens were perfusion fixed at arterial pressure for gross and histologic study; selected arteries were additionally fixed with 4% buffered glutaraldehyde, stored at 4 C, and examined immunochemically using antimyosin antibody immunopurified for smooth muscle. Overall patency of noncuff grafts in 11 long-term surviving dogs was 4 of 11; patency of the cuff grafts was 7 of 11. Regardless of graft thrombosis, antibody positive cellular proliferation occurred mainly at noncuffed PTFE anastomoses. Luminal encroachment was predominantly due to subintimal proliferation of cells highly reactive to smooth muscle derived antibody. JNIH was most prominent 1 mm distal to the graft toe (A' distal diameter). Average A' for noncuff grafts was 1.82 mm +/- 0.97 SEM; average A' diameter for cuff grafts was 3.41 mm +/- 0.74 SEM (p less than 0.001). Vein cuff inhibition of proliferation of smooth muscle or cells derived from smooth muscle possibly relates to wider distribution of kinetic energy (less compliance mismatch) or to interposition of venous endothelium.
Facile crystallization ofEscherichia coliketol-acid reductoisomerase (2004)

Ketol-acid reductoisomerase (EC 1.1.1.86) catalyses the second reaction in the biosynthesis of branched-chain amino acids. The reaction involves an Mg2+ -dependent alkyl migration followed by an NADPH-dependent reduction of the 2-keto group. Here, the crystallization of the Escherichia coli enzyme is reported. A form with a C-terminal hexahistidine tag could be crystallized under 18 different conditions in the absence of NADPH or Mg2+ and a further six crystallization conditions were identified with one or both ligands. With the hexahistidine tag on the N-terminus, 20 crystallization conditions were found, some of which required the presence of NADPH, NADP+, Mg2+ or a combination of ligands. Finally, the selenomethionine-substituted enzyme with the N-terminal tag crystallized under 15 conditions. Thus, the enzyme is remarkably easy to crystallize. Most of the crystals diffract poorly but several data sets were collected at better than 3.2 A resolution; attempts to phase them are currently in progress.
ALCAM/CD166 is up‐regulated in low‐grade prostate cancer and progressively lost in high‐grade lesions (2002)

ALCAM expression is commonly disturbed in prostate cancer, which might indicate a role of ALCAM in the progression of this disease.
HLA class II antigen associated invariant chain gene expression in malignant lymphoma (1987)

Expression of the gene encoding HLA class II antigen-associated invariant chain was studied in several types of fresh human malignant lymphoma by Northern blot analysis or slot-blot analysis. The invariant chain mRNA levels decreased with the stage of B-lymphocyte differentiation to plasma cells such as in immunoblastic lymphoma (IBL) or multiple myeloma (MM). The invariant chain gene (In-gene) was expressed in diffuse large cell lymphoma (DLCL), while its expression was hardly detected in IBL. It is suggested that the difference in In-gene expression between DLCL and IBL could be useful in distinguishing these two morphologically similar diseases.