gebhart/patrepeval huggingface dataset:
ASAP: a machine learning framework for local protein properties (2016)

Determining residue-level protein properties, such as sites of post-translational modifications (PTMs), is vital to understanding protein function. Experimental methods are costly and time-consuming, while traditional rule-based computational methods fail to annotate sites lacking substantial similarity. Machine Learning (ML) methods are becoming fundamental in annotating unknown proteins and their heterogeneous properties. We present ASAP (Amino-acid Sequence Annotation Prediction), a universal ML framework for predicting residue-level properties. ASAP extracts numerous features from raw sequences, and supports easy integration of external features such as secondary structure, solvent accessibility, intrinsically disorder or PSSM profiles. Features are then used to train ML classifiers. ASAP can create new classifiers within minutes for a variety of tasks, including PTM prediction (e.g. cleavage sites by convertase, phosphoserine modification). We present a detailed case study for ASAP: CleavePred, an ASAP-based model to predict protein precursor cleavage sites, with state-of-the-art results. Protein cleavage is a PTM shared by a wide variety of proteins sharing minimal sequence similarity. Current rule-based methods suffer from high false positive rates, making them suboptimal. The high performance of CleavePred makes it suitable for analyzing new proteomes at a genomic scale. The tool is attractive to protein design, mass spectrometry search engines and the discovery of new bioactive peptides from precursors. ASAP functions as a baseline approach for residue-level protein sequence prediction. CleavePred is freely accessible as a web-based application. Both ASAP and CleavePred are open-source with a flexible Python API.Database URL: ASAP's and CleavePred source code, webtool and tutorials are available at: https://github.com/ddofer/asap; http://protonet.cs.huji.ac.il/cleavepred.
Specific immunotherapy (2000)

The prevalence of atopic allergic disease increased substantially towards the end of the 20th century and is set to rise further. This group of diseases now constitutes the most common cause of chronic ill health in industrialised countries. Despite considerable attention from the pharmaceutical industry, little progress has been made in the development of disease-modifying therapies. In contrast, recent activity has focused almost exclusively on treatment of symptoms (palliation) rather than cause. The failure of palliative approaches to address the issue of increasing incidence of disease is in evidence in the case of allergic diseases and is a continuing focus of concern. At present, the most frequently employed non-palliative form of disease-modifying therapy is specific allergen immunotherapy (SIT) in which increasing doses of whole allergen extract are administered in increasing dose in order to desensitise the allergic subject.
Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenes infection: characteristics of monocyte subpopulations (1991)

Mice could well tolerate infection with a lethal dose of Listeria monocytogenes after intraperitoneal preinjections with 250 micrograms of macrophage colony-stimulating factor (M-CSF) per kg of body weight for 5 days. The characteristic changes in the surface markers (Mac-1, LFA-1, and F4/80) of peripheral monocytes were also investigated in order to analyze the mechanism of protection by M-CSF. This investigation shows the excellent effect of intraperitoneal preinjections of M-CSF on the reduction of viable Listeria organisms and the improvement of survival after an intravenous Listeria infection.
P95 Cost effectiveness of overnight face-to-face nurse led COPD service (2011)

<h3>Background</h3> Prevalence of Chronic Obstructive Pulmonary Disease (COPD) is twice the UK average with emergency admission rate 175% higher in Knowsley Primary Care Trust (PCT). A primary care nurse led COPD service was initially operational from 08:00 to 10:00, thereafter telephone advice was available overnight for management of patients with exacerbation of COPD. This was later commissioned by the PCT to provide a 24 h, 365 days face-to-face rapid response contact assessment at home or in the Accident and Emergency department. The Nurses were contracted to assess the patients within 2 h of the contact. Following this, staffing levels needed to be considerably increased. This development led to an increased burden on the COPD service. <h3>Aim</h3> To assess the cost-effectiveness of the this new service provision as contracted to direct further commissioning and planning within the restricted budget. <h3>Methods</h3> A database of patients with confirmed diagnosis of COPD was setup. The database included 3500 patients. They were provided with contact numbers in an event of exacerbation. Activity was monitored over 24 h from September 2009 to July 2010 (10 month9s duration). Data were analysed using Excel. <h3>Results</h3> 399 contacts made over the study period. The majority of the first contacts (18%) were on Mondays during the day hours. Another 17% first contacts were made over the weekends. 62 patients (15%) made contact overnight from 23:00 to 08:00 over the 10 months duration. Only 17 home visits were required and 45 patients reviewed in A&amp;E. Of the patients reviewed in A&amp;E only five were suitable for supported discharge. <h3>Conclusion</h3> Overnight face-to-face COPD nurse led service was not found to be cost-effective. This provides valuable information to inform the COPD national strategy consultation in development for further services.
Extremely Alkaline (pH > 12) Ground Water Hosts Diverse Microbial Community (2006)

Chemically unusual ground water can provide an environment for novel communities of bacteria to develop. Here, we describe a diverse microbial community that inhabits extremely alkaline (pH > 12) ground water from the Lake Calumet area of Chicago, Illinois, where historic dumping of steel slag has filled in a wetland. Using microbial 16S ribosomal ribonucleic acid gene sequencing and microcosm experiments, we confirmed the presence and growth of a variety of alkaliphilic beta-Proteobacteria, Bacillus, and Clostridium species at pH up to 13.2. Many of the bacterial sequences most closely matched those of other alkaliphiles found in more moderately alkaline water around the world. Oxidation of dihydrogen produced by reaction of water with steel slag is likely a primary energy source to the community. The widespread occurrence of iron-oxidizing bacteria suggests that reduced iron serves as an additional energy source. These results extend upward the known range of pH tolerance for a microbial community by as much as 2 pH units. The community may provide a source of novel microbes and enzymes that can be exploited under alkaline conditions.
Microbial Biogeography: From Taxonomy to Traits (2008)

The biogeographic variation of life has predominantly been studied using taxonomy, but this focus is changing. There is a resurging interest in understanding patterns in the distribution not only of taxa but also of the traits those taxa possess. Patterns of trait variation shed light on fundamental questions in biology, including why organisms live where they do and how they will respond to environmental change. Technological advances such as environmental genomics place microbial ecology in a unique position to move trait-based biogeography forward. We anticipate that as trait-based biogeography continues to evolve, micro- and macroorganisms will be studied in concert, establishing a science that is informed by and relevant to all domains of life.
Priming of a Novel Subset of CD28+ Rapidly Expanding High-Avidity Effector Memory CTL by Post Maturation Electroporation-CD40L Dendritic Cells Is IL-12 Dependent (2008)

Dendritic cell (DC)-based immunotherapeutics must induce robust CTL capable of killing tumor or virally infected cells in vivo. In this study, we show that RNA electroporated post maturation and coelectroporated with CD40L mRNA (post maturation electroporation (PME)-CD40L DC) generate high-avidity CTL in vitro that lyse naturally processed and presented tumor Ag. Unlike cytokine mixture-matured DC which induce predominantly nonproliferative effector memory CD45RA(+) CTL, PME-CD40L DC prime a novel subset of Ag-specific CTL that can be expanded to large numbers upon sequential DC stimulation in vitro. We have defined these cells as rapidly expanding high-avidity (REHA) CTL based on: 1) the maintenance of CD28 expression, 2) production of high levels of IFN-gamma and IL-2 in response to Ag, and 3) the demonstration of high-avidity TCR that exhibit strong cytolytic activity toward limiting amounts of native Ag. We demonstrate that induction of REHA CTL is dependent at least in part on the production of IL-12. Interestingly, neutralization of IL-12 did not effect cytolytic activity of REHA CTL when Ag is not limiting, but did result in lower TCR avidity of Ag-reactive CTL. These results suggest that PME-CD40L DC are uniquely capable of delivering the complex array of signals needed to generate stable CD28(+) REHA CTL, which if generated in vivo may have significant clinical benefit for the treatment of infectious disease and cancer.
From Coahoma County to Cook County: The Music of Muddy Waters (2004)

African Americans developed the blues as a reaction to the harsh conditions in the Mississippi Delta. The music found a new home during the first half of the twentieth century when thousands of African Americans migrated to northern cities. Inevitably, the sounds and styles of the bluesmen that journeyed North changed in response to their new environment. My research focuses on the music of Muddy Waters because of his unique experiences in both the Delta and Chicago. This portion of research analyzes Waters’ Stovall Plantation recordings, as they are a reflection of his life in the Delta. Later study will explore his early work in Chicago.
Management of Fibromyalgia Syndrome (2004)

Despite the chronicity and complexity of FMS, there are pharmacological and nonpharmacological interventions available that have clinical benefit. Based on current evidence, a stepwise program emphasizing education, certain medications, exercise, cognitive therapy, or all 4 should be recommended.
Abstract 1644: Combination of MT-3724 with sirolimus reduces anti-drug antibody response and prolongs drug exposure (2017)

Abstract Molecular Templates is developing engineered toxin bodies (ETBs), potent recombinant immunotoxins that combine the specificity of an antibody fragment with the powerful direct cytotoxicity of the Shiga-like toxin A subunit. ETBs can induce their own internalization, route through the cell in a predictable manner, enzymatically and irreversibly destroy ribosomes to shutdown protein synthesis and induce apoptosis of tumor cells. This mechanism of action is distinct from that of other therapeutics, making ETBs an attractive treatment for patients who have become resistant to chemotherapy and other treatment modalities. MT-3724 is Molecular Templates’ first-generation ETB targeting CD20, a surface receptor that is highly expressed on malignant B cells in hematological malignancies. Pre-clinical and clinical studies have shown promising results for non-Hodgkin’s lymphoma cell lines and patients; however anti-drug antibodies are formed in experimental animals and patients after repeat dosing. Sirolimus (rapamycin) is a macrolide compound approved to prevent organ rejection and in LAM, and has been used in tolerization protocols with replacement enzymes. In pre-clinical studies, we have co-administered sirolimus in combination with MT-3724 in rodents as well as in a non-human primate model in order to reduce the anti-drug antibody response to MT-3724. These studies demonstrated that the combination of sirolimus with MT-3724 decreased anti-drug antibody response, prolonged serum exposure of MT-3724, and improved B-cell depletion as compared to MT-3724 alone. Molecular Template’s ETB technology has resulted in potent and targeted therapeutic agents that have a unique mechanism of action in the field of oncology. Our first-generation, CD20-targeted therapeutic, MT-3724, has promising clinical results in the refractory setting for non-Hodgkin’s lymphoma. The combination of sirolimus with MT-3724 is an attractive and feasible regimen which will be further explored in clinical studies. Citation Format: Jack P. Higgins, Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jensing Liu, Erin K. Willert. Combination of MT-3724 with sirolimus reduces anti-drug antibody response and prolongs drug exposure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1644. doi:10.1158/1538-7445.AM2017-1644
Activation of Stat-3 Is Involved in the Induction of Apoptosis After Ligation of Major Histocompatibility Complex Class I Molecules on Human Jurkat T Cells (1998)

Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasma and subsequently translocated to the cell nucleus. Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-γ activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I–induced signal transduction in T cells.
Sialyl Oligosaccharides of Human Colostrum: Changes in Concentration during the First Three Days of Lactation (2007)

Sialyl oligosaccharides of human milk/colostrum are generally believed to be of biological significance, for example with respect to anti-adhesion of pathogenic organism, providing precursors for biosynthesis of brain, and so on. However, the levels of each of the sialyl oligosaccharides in human colostrum have not so far been determined. The present study was designed to determine the concentrations of nine major sialyl oligosaccharides in human colostrum, collected during the first 3 d (days 1-3) from the start of lactation. We found that the concentration of 3'-sialyllactose was significantly higher on day 1 than on day 2 and 3, but the levels of 6'-sialyllactose and sialyllacto-N-tetraose a were higher on day 3 than on day 1. These results are consistent with the view that during the first 3 d of lactation, the concentration of sialyl oligosaccharides in human colostrum change in accordance with the physiological demands of newborn infants.
UK-1, a novel cytotoxic metabolite from Streptomyces sp. 517-02. II. Structural elucidation. (1993)

The structure of UK-1 isolated from the mycelium of Streptomyces sp. 517-02 was elucidated to be a novel benzoxazole dimmer derivative (1) on the basis of spectroscopic methods.
Placental evidence of cytomegalovirus infection of the fetus and neonate. (1984)

Nine cases of congenital cytomegalovirus infection were diagnosed at Brigham and Women's Hospital in Boston from September 1977 through July 1982. The majority of infected fetuses and newborn infants had intrauterine growth retardation, congenital malformations, microcephaly, or hydrops fetalis. In four cases, cytomegalovirus was recovered from placentas. Eight placentas were examined morphologically. Varying degrees of chronic villitis were noted in all. The most frequent lesion, found in six cases, was focal villous inflammation with mononuclear cell infiltrates. Lymphocytes predominated in this reaction. In three cases, however, the villi were also intensely infiltrated by plasma cells. Typical cytomegalic inclusion bodies were noted in these three placentas. The fetus and infants in whose placentas the plasmacytic villitis and inclusion bodies were discovered displayed the most severe manifestations of cytomegalovirus infection.
Germ cell‐specific heat shock protein 70‐2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells (2010)

The current findings suggested that HSP70-2 may play an important role in disease progression in cervical carcinogenesis. Patients who had early stage disease and low-grade tumors had HSP70-2 expression, supporting its potential role in early detection and aggressive treatment modalities for cervical cancer management.
Measurements of spontaneous rates of mutations in the recent past and the near future (2010)

The rate of spontaneous mutation in natural populations is a fundamental parameter for many evolutionary phenomena. Because the rate of mutation is generally low, most of what is currently known about mutation has been obtained through indirect, complex and imprecise methodological approaches. However, in the past few years genome-wide sequencing of closely related individuals has made it possible to estimate the rates of mutation directly at the level of the DNA, avoiding most of the problems associated with using indirect methods. Here, we review the methods used in the past with an emphasis on next generation sequencing, which may soon make the accurate measurement of spontaneous mutation rates a matter of routine.
Gi Protein-mediated Functional Compartmentalization of Cardiac β2-Adrenergic Signaling (1999)

In contrast to beta(1)-adrenoreceptor (beta(1)-AR) signaling, beta(2)-AR stimulation in cardiomyocytes augments L-type Ca(2+) current in a cAMP-dependent protein kinase (PKA)-dependent manner but fails to phosphorylate phospholamban, indicating that the beta(2)-AR-induced cAMP/PKA signaling is highly localized. Here we show that inhibition of G(i) proteins with pertussis toxin (PTX) permits a full phospholamban phosphorylation and a de novo relaxant effect following beta(2)-AR stimulation, converting the localized beta(2)-AR signaling to a global signaling mode similar to that of beta(1)-AR. Thus, beta(2)-AR-mediated G(i) activation constricts the cAMP signaling to the sarcolemma. PTX treatment did not significantly affect the beta(2)-AR-stimulated PKA activation. Similar to G(i) inhibition, a protein phosphatase inhibitor, calyculin A (3 x 10(-8) M), selectively enhanced the beta(2)-AR but not beta(1)-AR-mediated contractile response. Furthermore, PTX and calyculin A treatment had a non-additive potentiating effect on the beta(2)-AR-mediated positive inotropic response. These results suggest that the interaction of the beta(2)-AR-coupled G(i) and G(s) signaling affects the local balance of protein kinase and phosphatase activities. Thus, the additional coupling of beta(2)-AR to G(i) proteins is a key factor causing the compartmentalization of beta(2)-AR-induced cAMP signaling.
Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis (2013)

We show that cyclic AMP (cAMP) elevating agents protect blasts from patients with acute promyelocytic leukemia (APL) against death induced by first-line anti-leukemic anthracyclines like daunorubicin (DNR). The cAMP effect was reproduced in NB4 APL cells, and shown to depend on activation of the generally cytoplasmic cAMP-kinase type I (PKA-I) rather than the perinuclear PKA-II. The protection of both NB4 cells and APL blasts was associated with (inactivating) phosphorylation of PKA site Ser118 of pro-apoptotic Bad and (activating) phosphorylation of PKA site Ser133 of the AML oncogene CREB. Either event would be expected to protect broadly against cell death, and we found cAMP elevation to protect also against 2-deoxyglucose, rotenone, proteasome inhibitor and a BH3-only mimetic. The in vitro findings were mirrored by the findings in NSG mice with orthotopic NB4 cell leukemia. The mice showed more rapid disease progression when given cAMP-increasing agents (prostaglandin E2 analog and theophylline), both with and without DNR chemotherapy. The all-trans retinoic acid (ATRA)-induced terminal APL cell differentiation is a cornerstone in current APL treatment and is enhanced by cAMP. We show also that ATRA-resistant APL cells, believed to be responsible for treatment failure with current ATRA-based treatment protocols, were protected by cAMP against death. This suggests that the beneficial pro-differentiating and non-beneficial pro-survival APL cell effects of cAMP should be weighed against each other. The results suggest also general awareness toward drugs that can affect bone marrow cAMP levels in leukemia patients.
Cracking the Phosphatase Code: Docking Interactions Determine Substrate Specificity (2009)

Phosphoserine- and phosphothreonine-directed phosphatases display remarkable substrate specificity, yet the sites that they dephosphorylate show little similarity in amino acid sequence. Studies reveal that docking interactions are key for the recognition of substrates and regulators by two conserved phosphatases, protein phosphatase 1 (PP1) and the Ca2+-calmodulin-dependent phosphatase calcineurin. In each case, a small degenerate sequence motif in the interacting protein directs low-affinity binding to a docking surface on the phosphatase that is distinct from the active site; several such interactions combine to confer overall binding specificity. Some docking surfaces are conserved, such as a hydrophobic groove on a face opposite the active site that serves as a major recognition surface for the "RVxF" motif of proteins that interact with PP1 and the "PxIxIT" motif of substrates of calcineurin. Secondary motifs combine with this primary targeting sequence to specify phosphatase binding. A comprehensive interactome for mammalian PP1 was described, analysis of which defines several PP1-binding motifs. Studies of "LxVP," a secondary calcineurin-binding sequence, establish that this motif is a conserved feature of calcineurin substrates and that the immunosuppressants FK506 and cyclosporin A inhibit the phosphatase by interfering with LxVP-mediated docking.
Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells. (1986)

The stability locus parB+ of plasmid R1 has been found to specify a unique type of plasmid maintenance function. Two genes, hok (host killing) and sok (suppressor of killing), are required for the stabilizing activity. The hok gene encodes a highly toxic gene product, whose overexpression causes a rapid killing and a concomitant dramatic change in morphology of the host cell. The other gene, sok, was found to encode a product that counteracts the hok gene-mediated killing. The parB+ region was inserted in a plasmid with a temperature-sensitive replication system. At nonpermissive temperature, the parB+ plasmid was maintained in the population for a significantly longer period than the corresponding parB- plasmid. Coupled to this extended maintenance, a large fraction of the population was shown to be nonviable plasmid-free cells with the characteristic hok-induced change in morphology. Based on these findings, we propose that the parB+ locus mediates plasmid stability by killing cells that have lost the parB+ plasmid during the preceding cell division, thereby ensuring that a growing bacterial culture predominantly consists of plasmid-containing cells.