gebhart/patrepeval huggingface dataset:
Monitoring M-Proteins in Patients with Multiple Myeloma Using Heavy-Chain Variable Region Clonotypic Peptides and LC–MS/MS (2014)

Multiple myeloma is a disease characterized by a clonal expansion of plasma cells that secrete a monoclonal immunoglobulin also referred to as an M-protein. In the clinical laboratory, protein electrophoresis (PEL), immunofixation electrophoresis (IFE), and free light chain nephelometry (FLC) are used to detect, monitor, and quantify an M-protein. Here, we present an alternative method based on monitoring a clonotypic (i.e., clone-specific) peptide from the M-protein heavy chain variable region using LC-MS/MS. Tryptic digests were performed on IgG purified serum from 10 patients with a known IgG M-protein. Digests were analyzed by shotgun LC-MS/MS, and the results were searched against a protein database with the patient specific, heavy chain variable region gene sequence added to the database. In all 10 cases, the protein database search matched multiple clonotypic peptides from each patient's heavy chain variable region. The clonotypic peptides were then used to quantitate the amount of M-protein in patient serum samples using selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The response for the clonotypic peptide observed by SRM correlated with the M-protein observed by PEL. In addition, the clonotypic peptide was clearly observed by SRM in samples that were negative by IFE and FLC. Monitoring clonotypic peptides using SRM has the capacity to redefine clinical residual disease because of its superior sensitivity and specificity compared with current analytical methods.
Signal Transduction Pathway through Activin Receptors as a Therapeutic Target of Musculoskeletal Diseases and Cancer (2008)

Activin, myostatin and other members of the TGF-beta superfamily signal through a combination of type II and type I receptors, both of which are transmembrane serine/threonine kinases. Activin type II receptors, ActRIIA and ActRIIB, are primary ligand binding receptors for activins, nodal, myostatin and GDF11. ActRIIs also bind a subset of bone morphogenetic proteins (BMPs). Type I receptors that form complexes with ActRIIs are dependent on ligands. In the case of activins and nodal, activin receptor-like kinases 4 and 7 (ALK4 and ALK7) are the authentic type I receptors. Myostatin and GDF11 utilize ALK5, although ALK4 could also be activated by these growth factors. ALK4, 5 and 7 are structurally and functionally similar and activate receptor-regulated Smads for TGF-beta, Smad2 and 3. BMPs signal through a combination of three type II receptors, BMPRII, ActRIIA, and ActRIIB and four type I receptors, ALK1, 2, 3, and 6. BMPs activate BMP-specific Smads, Smad1, 5 and 8. Smad proteins undergo multimerization with co-mediator Smad, Smad4, and translocated into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. The signal transduction pathway through activin type II receptors, ActRIIA and ActRIIB, with type I receptors is involved in various human diseases. In this review, we discuss the role of signaling through activin receptors as therapeutic targets of intractable neuromuscular diseases, endocrine disorders and cancers.
Thickness of graphene and single-wall carbon nanotubes (2006)

Young's modulus and the thickness of single wall carbon nanotubes (CNTs) obtained from prior atomistic studies are largely scattered. In this paper we establish an analytic approach to bypass atomistic simulations and determine the tension and bending rigidities of graphene and CNTs directly from the interatomic potential. The thickness and elastic properties of graphene and CNTs can also be obtained from the interatomic potential. But the thickness, and therefore elastic moduli, also depend on type of loading (e.g., uniaxial tension, uniaxial stretching, equibiaxial stretching), as well as the nanotube radius $R$ and chirality when $R&lt;1\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$. This explains why the thickness obtained from prior atomistic simulations is scattered. This analytic approach is particularly useful in the study of multiwall CNTs since their stress state may be complex even under simple loading (e.g., uniaxial tension) due to the van der Waals interactions between nanotube walls. The present analysis also provides an explanation of Yakobson's paradox that the very high Young's modulus reported from the atomistic simulations together with the shell model may be due to the not-well-defined CNT thickness.
A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. (1991)

Mouse and rat genomic DNA libraries were screened by reduced stringency hybridization with the DNA-binding domain of the c/ebp gene as a probe. Three genes were isolated that encode bZIP DNA-binding proteins (designated CRP1, CRP2, and CRP3) with strong amino acid sequence similarities to the C/EBP-binding domain. CRP2 is identical to the protein described recently by other groups as NF-IL6, LAP, IL-6DBP, and AGP/EBP, whereas CRP1 and CRP3 represent novel proteins. Several lines of evidence indicate that these three proteins, along with C/EBP, comprise a functional family. Each bacterially expressed polypeptide binds to DNA as a dimer with recognition properties that are virtually identical to those of C/EBP. Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices. We developed a gel assay for covalent dimers to assess leucine zipper specificities among the family members. The results demonstrate that all pairwise combinations of dimer interactions are possible. To the extent that we have examined them, the same heterodimeric complexes can be detected intracellularly following cotransfection of the appropriate pair of genes into recipient cells. All members are also capable of activating in vivo transcription from promoters that contain a C/EBP-binding site. Our findings indicate that a set of potentially interacting C/EBP-like proteins exists, whose complexity is comparable to that of other bZIP protein subfamilies such as Jun, Fos, and ATF/CREB.
γδ T Cells from Tolerized αβ T Cell Receptor (TCR)–deficient Mice Inhibit Contact Sensitivity-Effector T Cells In Vivo, and Their Interferon-γ Production In Vitro (1996)

Contact sensitivity (CS) responses to reactive hapten Ag, such as picryl chloride (PCl) or oxazolone (OX), are classical examples of T cell-mediated immune responses in vivo that are clearly subject to multifaceted regulation. There is abundant evidence that downregulation of CS may be mediated by T cells exposed to high doses of Ag. This is termed high dose Ag tolerance. To clarify the T cell types that effect CS responses and mediate their downregulation, we have undertaken studies of CS in mice congenitally deficient in specific subsets of lymphocytes. The first such studies, using alpha beta T cell-deficient (TCR alpha -/-) mice, are presented here. The results clearly show that TCR alpha -/- mice cannot mount CS, implicating alpha beta T cells as the critical CS-effector cells. However, TCR alpha -/- mice can, after high dose tolerance, downregulate alpha +/+ CS-effector T cells adoptively transferred into them. By mixing ex vivo and then adoptive cell transfers in vivo, the active downregulatory cells in tolerized alpha -/- mice are shown to include gamma delta TCR+ cells that also can downregulate interferon-gamma production by the targeted CS-effector cells in vitro. Downregulation by gamma delta cells showed specificity for hapten, but was not restricted by the MHC. Together, these findings establish that gamma delta T cells cannot fulfill CS-effector functions performed by alpha beta T cells, but may fulfill an Ag-specific downregulatory role that may be directly comparable to reports of Ag-specific downregulation of IgE antibody responses by gamma delta T cells. Comparisons are likewise considered with downregulation by gamma delta T cells occurring in immune responses to pathogens, tumors, and allografts, and in systemic autoimmunity.
Loudon Surfactant Flood Pilot—Overview and Update (1983)

ABSTRACT A successful surfactant (microemulsion) flood pilot test in a watered-out portion of the Weiler sand, Loudon Field, Illinois (USA) was completed in October, 1981. The microemulsion system tested was designed to be effective in the presence of high-salinity formation water containing 104,000 ppm (mg/l) total dissolved solids (TDS) without use of a preflush. The test was conducted in a single, 0.68-acre (2752 m2) 5-spot operated in a manner that approximated a confined pattern. The test was highly successful, recovering 60% of the oil remaining after waterflood. Cores from a post-flood well drilled within the pattern have confirmed the low final oil saturations and low surfactant retention achieved in the flood. Although oil recovery was excellent, loss of mobility control in the polymer drive bank and premature breakthrough of lower-salinity drive water were observed part-way through the test. Laboratory and field studies conducted since flood termination have confirmed that loss was caused by bacterial degradation of the xanthan biopolymer used. Several biocides were tested in the laboratory and in a field injection experiment to determine their effectiveness against the bacteria contaminating the pilot. Formaldehyde was shown to kill bacteria within the formation, have negligible adsorption on reservoir rock, and permit propagation of undegraded polymer. Based on these test results, formaldehyde should protect xanthan biopolymer from bacterial degradation in future microemulsion floods at Loudon.
Percutaneous progesterone delivery via cream or gel application in postmenopausal women (2013)

After application of topical progesterone, saliva and capillary blood levels are approximately 10-fold and 100-fold greater, respectively, than those seen in serum or whole blood. High capillary blood and saliva levels indicate high absorption and transport of progesterone to tissues. Reliance on serum levels of progesterone for monitoring topical dose could lead to underestimation of tissue levels and consequent overdose.
Cloning of granulocyte colony-stimulating factor cDNA from human macrophages and its expression in Escherichia coli. (1987)

Human granulocyte colony-stimulating factor (hG-CSF) cDNA was cloned, by using a synthetic oligonucleotide probe, from an Okayama-Berg cDNA library of lipopolysaccharide-stimulated human peripheral blood macrophages. The cDNA encodes a polypeptide with an amino acid sequence which completely matches that of the known polypeptide with hG-CSF activity derived from human tumor cell lines. Expression in E. coli of high levels of the protein (about 10% of total cellular proteins) was accomplished under control of the trp promoter, and the purified protein was proved to have hG-CSF activity. Our data provide evidence that human peripheral blood macrophages do produce hG-CSF mRNA when stimulated exogenously, suggesting they are the producer of naturally occurring hG-CSF.
The murine transforming growth factor-beta precursor. (1986)

Transforming growth factor-beta (TGF-beta) is a homodimeric polypeptide which can act, often in cooperation with other growth factors, as a mitogenic factor for a variety of cells. TGF-beta can also exert growth inhibitory activity on many other cell lines. We have isolated cDNAs coding for the murine TGF-beta cDNA precursor. The deduced amino acid sequence localizes the 112-amino acid long TGF-beta monomer to the C terminus of the precursor. Two areas of the precursor exhibit a marked degree of homology to the human counterpart. One of these regions comprises the mature TGF-beta monomer, while the other corresponds to the NH2 terminus of the precursor and suggests an important biological function for this area. Northern hybridization results identify a major 2.5-kilobase TGF-beta mRNA and several minor TGF-beta mRNA species.
Hydrodynamics of Fishlike Swimming (2000)

▪ Abstract Interest in novel forms of marine propulsion and maneuvering has sparked a number of studies on unsteadily operating propulsors. We review recent experimental and theoretical work identifying the principal mechanism for producing propulsive and transient forces in oscillating flexible bodies and fins in water, the formation and control of large-scale vortices. Connection with studies on live fish is made, explaining the observed outstanding fish agility.
Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup. (1984)

In a 25-year prospective followup of 209 patients with rheumatoid arthritis, median life expectancy was shortened by 7 years in males and by 3 years in females when compared with the general population. The surplus mortality was associated in decreasing order with the disease itself, associated respiratory, urogenital and general infections, and with upper gastrointestinal tract disease, mainly bleeding.
Chapter 12 Semaphorin III: Role in neuronal development and structural plasticity (1998)

Semaphorins comprise a large family of secreted and transmembrane anchored glycoproteins, several members of which have been implicated in repulsive axon guidance. Members of the semaphorin family display specific patterns of expression and are predominantly found within the developing embryo. This chapter discusses the data indicating that in the developing nervous system Sema III plays a critical role in repulsive axon guidance, nerve fasciculation, and the timing of target innervation of a number of neuropilin-1 positive fibers tracts. In addition, the distribution of Sema III binding sites, as assessed by direct binding of a chimeric Sema III-AP probe to sections, neuropilin-1 protein distribution, and sema III RNA expression are compared to elucidate where in the embryo Sema III is likely to function as a guidance cue. Finally, continued adult expression of sema III and neuropilin-1 in distinct structures of the mammalian nervous system is discussed in the context of the role Sema III might play in structural plasticity.
Exploring Network Structure, Dynamics, and Function using NetworkX (2008)

NetworkX is a Python language package for exploration and analysis of networks and network algorithms. The core package provides data structures for representing many types of networks, or graphs, including simple graphs, directed graphs, and graphs with parallel edges and self-loops. The nodes in NetworkX graphs can be any (hashable) Python object and edges can contain arbitrary data; this flexibility makes NetworkX ideal for representing networks found in many different scientific fields. In addition to the basic data structures many graph algorithms are implemented for calculating network properties and structure measures: shortest paths, betweenness centrality, clustering, and degree distribution and many more. NetworkX can read and write various graph formats for easy exchange with existing data, and provides generators for many classic graphs and popular graph models, such as the Erdos-Renyi, Small World, and Barabasi-Albert models. The ease-of-use and flexibility of the Python programming language together with connection to the SciPy tools make NetworkX a powerful tool for scientific computations. We discuss some of our recent work studying synchronization of coupled oscillators to demonstrate how NetworkX enables research in the field of computational networks.
Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion (2020)

The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.
Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma. (2019)

2538 Background: There is a high unmet medical need for effective treatments for patients with recurrent, metastatic, or persistent cervical cancer. Most patients are young and survival rates are poor. ORR for second line therapies is between 4 and 14% for chemotherapy and recently approved immunotherapy. Adoptive cell transfer using tumor infiltrating lymphocytes (TIL) have demonstrated durable responses in some patients with recurrent cervical cancer thus offering the potential for long-term disease control. Methods: Study C-145-04 is an ongoing, open-label, multicenter Phase 2 clinical trial evaluating the safety and efficacy of LN-145 TIL therapy in patients with advanced cervical cancer who have undergone at least one prior line of chemotherapy. Prior checkpoint inhibitor therapy is an exclusion criterion. The primary endpoint is ORR per RECIST 1.1; secondary endpoints include duration of response (DOR), disease control rate (DCR), and LN-145 safety. Tumors surgically harvested at local institutions are shipped to central GMP facilities for TIL generation in a 22-day manufacturing process. Final LN-145 TIL product is cryopreserved and shipped to sites. Patients receive one week of preconditioning lymphodepletion (cyclophosphamide, fludarabine), a single LN-145 infusion, followed by up to 6 doses of IL-2 (600,000 IU/kg). Results: As of 4 Feb 2019, 27 efficacy-c patients have received Gen 2 of LN-145, with a mean age of 47 years and 2.6 mean prior lines of therapy. Preliminary efficacy results: ORR was 44% (1 CR, 9 PR, 2 uPR), DCR was 89% at 3.5-month median study follow-up with 11/12 patients maintaining their response. Improved responses were observed in 4 patients with longer follow-up. Mean TIL cells infused was 28x10 9 . Median IL-2 doses administered was 6.0. The adverse event profile was generally consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens. Conclusions: LN-145 results in 44% ORR in previously treated cervical cancer patients with acceptable safety and efficacy profile. LN-145 offers patients a viable therapeutic option warranting further investigation. Clinical trial information: NCT03108495.
A NEW METHOD FOR THE SYNTHESIS OF 3-ALKYLFURAN AND 2,4-DIALKYLFURAN (1975)

Abstract A convenient method for the preparations of 3-alkylfuran and 2,4-dialkylfuran has been established via three step-procedures starting from α-(alkylthio)carbonyl compounds.
Enhanced Immunogenicity of gp120 Protein When Combined with Recombinant DNA Priming To Generate Antibodies That Neutralize the JR-FL Primary Isolate of Human Immunodeficiency Virus Type 1 (2005)

Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmid-based and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized.
Group B streptococcal conjugate vaccine: A timely concept for which the time has come (2008)

Invasive disease due to group B Streptococcus (GBS) has been recognized as a threat to the health of pregnant women and their infants for almost half a century. Development of GBS vaccine candidates has progressed at an exemplary pace given lack of sponsorship by manufacturers. A trivalent or pentavalent vaccine will be required, and decisions must be made as to the criteria by which efficacy will be determined and the population in whom efficacy will be assessed. Concerns regarding durability of conjugate vaccine-derived immunity, pregnant women as a possible target group and regulatory issues required for licensing must be resolved if the prospect of impacting GBS disease burden through immunization is to become a reality.
Tiger team: a panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes (2020)

Abstract The novel highly transmissible human coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Thus far, there is no approved therapeutic drug, specifically targeting this emerging virus. Here we report the isolation and characterization of a panel of human neutralizing monoclonal antibodies targeting the SARS-CoV-2 receptor binding domain (RBD). These antibodies were selected from a phage display library constructed using peripheral circulatory lymphocytes collected from patients at the acute phase of the disease. These neutralizing antibodies are shown to recognize distinct epitopes on the viral spike RBD, therefore they represent a promising basis for the design of efficient combined post-exposure therapy for SARS-CoV-2 infection.