gebhart/patrepeval huggingface dataset:
Feral future: the untold story of Australia's exotic invaders (2003)

A decade ago, Tim Low journeyed to the remote northern-most tip of Australia. Instead of the pristine rainforests he expected, he found jungles infested with Latin American carpet grass and feral cattle. That incident helped inspire Feral Future, a passionate account of the history and implications of invasive species in that island nation, with consequences for ecological communities around the globe. Australia is far from alone in facing horrific ecological and economic damage from invading plants and animals, and in Low's capabale hands, Australia's experiences serve as a wake-up call for all of us. He covers how invasive species like cane toads and pond apple got to Australia (often through misguided but intentional introductions) and what we can do to stop them. He also covers the many pests that Australia has exported to the world, including the paperbark tree (Melaleuca) that infests hundreds of thousands of acres in south Florida.
Intermediates in V(D)J recombination: A stable RAG1/2 complex sequesters cleaved RSS ends (2001)

Rearrangement of gene segments to generate antigen receptor coding regions depends on the RAG1/2 recombinase, which assembles a synaptic complex between two DNA signal sequences and then cleaves the DNA directly adjacent to the paired signals. After coupled cleavage of complementary signal sequences, virtually all of the cleaved signal ends remained associated with RAG1/2 in stable complexes. These signal end complexes were distinct from various precleavage RAG1/2 signal complexes in that they were resistant to treatment with heparin. A mammalian joining apparatus consisting of purified Ku70/86, XRCC4, and DNA ligase IV proteins was sufficient to join deproteinized cleaved ends, but retention of signal sequences within the signal end complex blocked access to the DNA ends and prevented their joining by these proteins. Sequestration of cleaved ends within the signal end complex would account for the persistence of these ends in the cell after cleavage and may explain why they do not normally activate the DNA-damage-dependent cell cycle checkpoint.
Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage (2008)

The Rho/ROCK pathway plays a critical role in diabetic retinal microvasculopathy. Fasudil protects the vascular endothelium by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury. ROCK inhibition may become a new strategy in the management of diabetic retinopathy, especially in its early stages.
Effect of Increasing Glutathione With Cysteine and Glycine Supplementation on Mitochondrial Fuel Oxidation, Insulin Sensitivity, and Body Composition in Older HIV-Infected Patients (2013)

Abstract Background HIV-infected patients are reported to have impaired oxidation of fatty acids despite increased availability, suggesting a mitochondrial defect. We investigated whether diminished levels of a key mitochondrial antioxidant, glutathione (GSH), was contributing to defective fatty acid oxidation in older HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH deficiency in these patients. Methods In an open-label design, 8 older GSH-deficient HIV-infected males were studied before and after 14 days of oral supplementation with the GSH precursors cysteine and glycine. A combination of stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition, anthropometry, forearm-muscle strength, and lipid profiles. Results Impaired synthesis contributed to GSH deficiency in the patients and was restored with cysteine plus glycine supplementation. GSH improvement was accompanied by marked improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits included improvements in insulin sensitivity, body composition, anthropometry, muscle strength, and dyslipidemia. Conclusions This work identifies 2 novel findings in older HIV-infected patients: 1) diminished synthesis due to decreased availability of cysteine and glycine contributes to GSH deficiency and can be rapidly corrected by dietary supplementation of these precursors and 2) correction of GSH deficiency is associated with improvement of mitochondrial fat and carbohydrate oxidation in both fasted and fed states and with improvements in insulin sensitivity, body composition, and muscle strength. The role of GSH on ameliorating metabolic complications in older HIV-infected patients warrants further investigation. (J Clin Endocrinol Metab 99: 169–177, 2014)
Probability-Based Validation of Protein Identifications Using a Modified SEQUEST Algorithm (2002)

Database-searching algorithms compatible with shotgun proteomics match a peptide tandem mass spectrum to a predicted mass spectrum for an amino acid sequence within a database. SEQUEST is one of the most common software algorithms used for the analysis of peptide tandem mass spectra by using a cross-correlation (XCorr) scoring routine to match tandem mass spectra to model spectra derived from peptide sequences. To assess a match, SEQUEST uses the difference between the first- and second-ranked sequences (ACn). This value is dependent on the database size, search parameters, and sequence homologies. In this report, we demonstrate the use of a scoring routine (SEQUEST-NORM) that normalizes XCorr values to be independent of peptide size and the database used to perform the search. This new scoring routine is used to objectively calculate the percent confidence of protein identifications and posttranslational modifications based solely on the XCorr value.
The Adjuvant Effect of Interleukin-12 in a Vaccine Against Leishmania major (1994)

Protection induced by vaccination depends on the capacity of the vaccine to elicit an appropriate immune response. In leishmaniasis, protection requires leishmanial-specific CD4+ T helper (TH) cells. Vaccination of BALB/c mice with leishmanial antigens and interleukin-12 (IL-12) promoted the development of leishmanial-specific CD4+ TH1 cells. These mice were resistant to subsequent infection with Leishmania major. Thus, IL-12 is an effective adjuvant for the initiation of protective cell-mediated immunity against leishmaniasis and may be an important component in other vaccines that need to induce cell-mediated immunity.
Implementation of a System for Reagent Selection and Library Enumeration, Profiling, and Design (1999)

We describe an integrated suite of computational tools which are used to assist in the selection of compounds for biological assays and the design of combinatorial libraries. These functions are delivered in a platform-independent manner via a corporate intranet and are used by computational experts and nonexperts alike. While the system was primarily designed to be used prior to synthesis, it can also be used to provide structural information for library registration and for decoding beads in tagged libraries. We describe a simple statistical method for monomer selection and compare it to computationally more demanding approaches.
Drug targeting systems for cancer chemotherapy (1998)

Tumour specific drug targeting has been a very actively investigated area for over 2 decades. Various approaches have involved the use of drug delivery systems that can localise the anticancer agent at the tumour site without damaging the normal cells. For this purpose, various delivery systems that have been utilised are liposomes, microspheres and recently, nanoparticles. Two liposome formulations containing anticancer drugs for example, adriamycin and daunomycin are already on the market in the USA and Europe. Microspheres are also being investigated for delivering various anticancer drugs and protein/peptides for anticancer treatment, and several formulations are in Phase I/II clinical trials. Antitumour drugs have also been linked to tumour specific monoclonal antibodies via various chemical linkages. Doxorubicin was linked to a chimeric monoclonal antibody that was targeted to the Lewis Y antigen. Though this conjugate initially showed potential, it was recently dropped from Phase II clinical trials. Another approach with monoclonal antibodies has been the use of immunotoxins. Immunotoxins initially showed promise as potential anticancer agents at picomolar concentrations but several clinical and preclinical studies have not shown much promise in this regard. Drug containing liposomes and microspheres have been further linked to tumour specific monoclonal antibodies to enhance their tumour specificity. Most of the studies with immunoliposomes or targeted microspheres have not gone beyond the preclinical studies. New therapeutic approaches are presently emerging based on natural products like cytokines, peptide growth factor antagonists, antisense oligonucleotides and specific genes. These approaches need the help of delivery systems to deliver these complex molecules to tumour cells. One of the current pursued approaches is the use of cationic liposomes. Several clinical studies are undergoing with various cationic liposomes and the next few years will demonstrate the usefulness of this approach. In recent years, the problems in cancer treatment have been complicated with the emergence of resistance strains leading to resistant and cross-resistant tumour cells. Several agents have been used to overcome or reverse drug-resistance in solid tumours and it remains a highly pursued area in cancer treatment.
Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder (1998)

Nerve growth factor (NGF) is a mediator of hyperalgesia and has been previously associated with sensory and reflex changes after inflammation of the urinary bladder. A sensitive assay was developed to examine neurotrophin gene expression after bladder inflammation by turpentine, which causes a short-lived inflammatory response. Two hours, but not 6 or 24 h after induction of inflammation, there were significant increases in levels of NGF, brain-derived neurotrophic factor and neurotrophin-3 mRNAs. NGF immunoreactivity was elevated with a similar time course to its mRNA. Our results suggest that during bladder inflammation, endogenous NGF is rapidly up-regulated and released to mediating sensory and reflex changes. Brain-derived neurotrophic factor and neurotrophin-3 may also have a role in the inflammatory response.
Evaluation of Tumor Response, Disease Control, Progression-Free Survival, and Time to Progression As Potential Surrogate End Points in Metastatic Breast Cancer (2008)

No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.
Processing of the Semliki Forest virus structural polyprotein: role of the capsid protease (1987)

The protease activities responsible for the cotranslational processing of the Semliki Forest virus structural polyprotein were investigated by using an in vitro transcription-translation system. Three cleavages released the individual chains from the nascent polyprotein in the order capsid, p62, 6K (a nonstructural peptide), and E1. We showed directly that the protease activity responsible for the release of the capsid protein resides in the capsid itself: by progressive truncation of the cDNA used for the SP6 transcription, we showed that a precursor containing as few as 38 residues of the p62 protein left at the C terminus of the capsid was still very efficiently cleaved in vitro. We further tested the possibility that serine-219 of the capsid is involved in autoproteolysis by site-directed in vitro mutagenesis. A change in the sequence Gly-Asp-Ser(219)-Gly, a tetrapeptide conserved among several animal serine proteases, to Gly-Asp-Arg-Ser-Thr was shown to completely abolish in vitro cleavage. This supports the notion that the capsid is a serine protease. The role of the capsid protease in the processing of the 6K junctions was then investigated by translations of a hybrid polyprotein in which the capsid and most of the p62 sequences are replaced by those of the secretory protein lysozyme. The cleavages and concomitant appearance of the 6K peptide occurred efficiently and were shown to require the presence of membranes. This demonstrates that the capsid protease is not required for those cleavages and suggests that a membrane-associated host protease is responsible for the cleavage.
Inhibition of endothelial cell proliferation by SPARC is mediated through a Ca2+‐binding EF‐hand sequence (1995)

SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin and BM-40) is a metal-binding glycoprotein secreted by a variety of cultured cells and characteristic of tissues undergoing morphogenesis, remodeling, and repair. Recently it has been shown that SPARC inhibits the progression of the endothelial cell cycle in mid-G1, and that a synthetic peptide (amino acids 54-73 of secreted murine SPARC, peptide 2.1) from a cationic, disulfide-bonded region was in part responsible for the growth-suppressing activity [Funk and Sage (1991): Proc Natl Acad Sci USA 88:2648-2652]. Moreover, SPARC was shown to interact directly with bovine aortic endothelial (BAE) cells through a C-terminal EF-hand sequence comprising a high-affinity Ca(2+)-binding site of SPARC and represented by a synthetic peptide (amino acids 254-273) termed 4.2 [Yost and Sage (1993): J Biol Chem 268:25790-25796]. In this study we show that peptide 4.2 is a more potent inhibitor of DNA synthesis that acts cooperatively with peptide 2.1 to diminish the incorporation of [3H]-thymidine by both BAE and bovine capillary endothelial (BCE) cells. At concentrations of 0.019-0.26 mM peptide 4.2, thymidine incorporation by BAE cells was decreased incrementally, relative to control values, from approximately 100 to 10%. Although somewhat less responsive, BCE cells exhibited a dose-responsive decrement in thymidine incorporation, with a maximal inhibition of 55% at 0.39 mM. The inhibitory effect of peptide 4.2 was essentially independent of heparin and basic fibroblast growth factor and was blocked by anti-SPARC peptide 4.2 IgG, but not by antibodies specific for other domains of SPARC. To identify residues that were necessary for inhibition of DNA synthesis, we introduced single amino acid substitutions into synthetic peptide 4.2 and tested their activities and cell-surface binding characteristics on endothelial cells. Two peptides displayed null to diminished effects in the bioassays that were concentration-dependent: peptide 4.2 K, containing an Asp258 --> Lys substitution, and peptide 4.2 AA, in which the two disulfide-bonded Cys (positions 255 and 271) were changed to Ala residues. Peptide 4.2 K, which failed to fulfill the EF-hand consensus formula, exhibited an anomalous fluorescence emission spectrum, in comparison with the wild-type 4.2 sequence, that was indicative of a compromised affinity for Ca2(+).(ABSTRACT TRUNCATED AT 400 WORDS)
Vitamin E Treatment for Tardive Dyskinesia (1999)

This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.
Additive Manufacturing of Al Alloys and Aluminium Matrix Composites (AMCs) (2014)

In this chapter a large description of additive manufacturing techniques for obtaining Al alloys and Al matrix composites is given. Results on mechanical properties, roughness and microstructure achievable with such fabrication route on Al alloys are reported
Targeted Integration of a Recombinant Globin Gene Adeno‐Associated Viral Vector into Human Chromosome 19a (1998)

Transfer of a globin gene into stem cells along with the regulatory elements required to achieve high level expression in maturing erythroid cells would provide effective gene therapy for Cooley's Anemia. We have explored the use of recombinant adeno-associated viral (rAAV) vectors for this purpose. A vector designated rHS32A gamma*3'RE that contains regulatory elements from the locus control and flanking regions, integrates as a stable head-to-tail concatamer in erythroleukemia cells at a high multiplicity of infection and exhibits high level, regulated gamma globin gene expression. Inducible expression of the non-structural Rep proteins of wild-type AAV in HeLa cells transduced with rAAV vectors does not increase overall integration frequency, but targeted integration of rHS32A gamma*'3'RE into human chromosome 19 was documented.
Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: role of the number of rings and positive charges in the specific binding leading to miscoding (2005)

The crystal structures of six complexes between aminoglycoside antibiotics (neamine, gentamicin C1A, kanamycin A, ribostamycin, lividomycin A and neomycin B) and oligonucleotides containing the decoding A site of bacterial ribosomes are reported at resolutions between 2.2 and 3.0 A. Although the number of contacts between the RNA and the aminoglycosides varies between 20 and 31, up to eight direct hydrogen bonds between rings I and II of the neamine moiety are conserved in the observed complexes. The puckered sugar ring I is inserted into the A site helix by stacking against G1491 and forms a pseudo base pair with two H-bonds to the Watson-Crick sites of the universally conserved A1408. This central interaction helps to maintain A1492 and A1493 in a bulged-out conformation. All these structures of the minimal A site RNA complexed to various aminoglycosides display crystal packings with intermolecular contacts between the bulging A1492 and A1493 and the shallow/minor groove of Watson-Crick pairs in a neighbouring helix. In one crystal, one empty A site is observed. In two crystals, two aminoglycosides are bound to the same A site with one bound specifically and the other bound in various ways in the deep/major groove at the edge of the A sites.
Clinicopathologic Study of PRAD1/Cyclin D1 Overexpressing Lymphoma with Special Reference to Mantle Cell Lymphoma (1996)

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.
Radical Nephrectomy for pT1a Renal Masses May be Associated With Decreased Overall Survival Compared With Partial Nephrectomy (2008)

Our results suggest that, compared with partial nephrectomy, radical nephrectomy is associated with decreased overall survival in younger patients with small renal masses.
The enigma of sepsis (2003)

Sepsis remains a serious cause of morbidity and mortality, and the pathophysiology of the disease is not clear. The definition of the clinical manifestations of sepsis is ever evolving. This review discusses the search for effective therapeutic interventions, hurdles in translational sepsis research, and new therapies in development in current clinical trials.
Interstitial implantation techniques in prostate cancer (1997)

Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance. J. Surg. Oncol. 1997;66:65–75. © 1997 Wiley-Liss, Inc.
Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice (2017)

Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or induce resilience is a gap in our knowledge of its therapeutic potential. Here, we show that an α-klotho protein fragment (αKL-F), administered peripherally, surprisingly induced cognitive enhancement and neural resilience despite impermeability to the blood-brain barrier in young, aging, and transgenic α-synuclein mice. αKL-F treatment induced cleavage of the NMDAR subunit GluN2B and also enhanced NMDAR-dependent synaptic plasticity. GluN2B blockade abolished αKL-F-mediated effects. Peripheral αKL-F treatment is sufficient to induce neural enhancement and resilience in mice and may prove therapeutic in humans.