gebhart/patrepeval huggingface dataset:
Selection of Variable-Joining Region Combinations in the α Chain of the T Cell Receptor (1988)

Most T lymphocytes express an antigen-specific receptor composed of two subunits, alpha and beta, each of which can exhibit structural variability. A complex selection process operates on T cells during development in the thymus such that cells expressing only particular alpha beta-receptors migrate to the periphery. The alpha-chain repertoire was dissected at different stages of the selection process by using the polymerase chain reaction (PCR) technique to amplify only those transcripts of a particular variable region gene (V58). Sequences from these V58 cDNAs reveal the predominant expression of four joining (J) segments by T cells in the adult thymus, suggesting that molecular or cellular processes select particular V alpha J alpha combinations during development. T cells expressing one of these V58J alpha chains appear to have been negatively selected at a later stage, since these transcripts were present in the spleen at approximately one-tenth the level in the thymus. Results also indicate that residues present at the V alpha J alpha junction may be important in an early selection process.
In vivo antitumor activity of neocarzinostatin (NCS)-tumor antibody conjugate against a transplantable human leukemia cell line (BALL-1). (1983)

The in vivo antitumor activity of NCS-immune immunoglobulin G (IgG) [Neocarzinostatin (NCS) conjugated with rabbit IgG antibody against a human leukemia cell line (NALL-1)] was evaluated in immunosuppressed newborn Syrian hamsters into which a transplantable human leukemia cell line, BALL-1 was implanted. After intraperitoneal (i.p.) injection of the conjugate, hamsters preinoculated i.p. with BALL-1 cells survived longer than hamsters treated with control solutions (p less than 0.01). The control solutions were NCS, immune IgG, a mixture of NCS and immune IgG, NCS-normal IgG conjugate and physiological saline. There was no change in body weight in the NCS-immune IgG-treated hamsters. The growth of subcutaneously (s.c.) implanted BALL-1 tumors was also inhibited by i.p. administration of NCS-immune IgG; however, the degree of inhibition was not significantly different from that obtained by administration of NCS alone, a mixture of NCS and immune IgG or NCS-normal IgG conjugate. These results indicate that NCS-immune IgG was effective against i.p. BALL-1 tumors, but was less effective against s.c. implanted tumors.
A simple method for semi-synthesis of peptidyl argininals as potent inhibitors of trypsin-like proteases. (1986)

A simple method was developed for the conversion of leupeptin (acetyl-Leu-Leu-argininal) to other peptidyl argininals. Argininal dibutylacetal, a key intermediate, was produced by enzymatic digestion of leupeptin dibutylacetal with Pronase E and was isolated by column chromatography on CM-52 cellulose. Nα-Blocked peptides (or amino acids) were connected to the α-amino group of this intermediate by conventional methods, and finally the acetal protecting group was removed by mild acid treatment to recover the essential aldehyde function. This novel method is applicable to large-scale preparation of many kinds of peptidyl argininals, which are promising candidates as specific inhibitors of trypsin-family proteases.
Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus (2021)

We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.
Wavefront sensing with random amplitude mask and phase retrieval (2007)

A light beam with an ideal wavefront that is transmitted or reflected from an object is modified by different characteristics of the object such as shape, refractive index, density, or temperature. Wavefront sensing therefore yields valuable information about the system or the changes happening to the system. A new method for wavefront sensing using a random amplitude mask and a phase retrieval method based on the Rayleigh-Sommerfeld wave propagation equation is described. The proposed method has many potential applications ranging from phase contrast imaging and measurement of lens aberration to shape measurement of three-dimensional objects.
ActA from Listeria monocytogenes Can Interact with Up to Four Ena/VASP Homology 1 Domains Simultaneously (2001)

The facultative intracellular human pathogenic bacterium Listeria monocytogenes actively recruits host actin to its surface to achieve motility within infected cells. The bacterial surface protein ActA is solely responsible for this process by mimicking fundamental steps of host cell actin dynamics. ActA, a modular protein, contains an N-terminal actin nucleation site and a central proline-rich motif of the 4-fold repeated consensus sequence FPPPP (FP(4)). This motif is specifically recognized by members of the Ena/VASP protein family. These proteins additionally recruit the profilin-G-actin complex increasing the local concentration of G-actin close to the bacterial surface. By using analytical ultracentrifugation, we show that a single ActA molecule can simultaneously interact with four Ena/VASP homology 1 (EVH1) domains. The four FP(4) sites have roughly equivalent affinities with dissociation constants of about 4 microm. Mutational analysis of the FP(4) motifs indicate that the phenylalanine is mandatory for ActA-EVH1 interaction, whereas in each case exchange of the third proline was tolerated. Finally, by using sedimentation equilibrium centrifugation techniques, we demonstrate that ActA is a monomeric protein. By combining these results, we formulate a stoichiometric model to describe how ActA enables Listeria to utilize efficiently resources of the host cell microfilament for its own intracellular motility.
Isolation, Characterization, and Expression in Escherichia coli of the DNA Polymerase Gene from Thermus aquaticus (1989)

The thermostable properties of the DNA polymerase activity from Thermus aquaticus (Taq) have contributed greatly to the yield, specificity, automation, and utility of the polymerase chain reaction method for amplifying DNA. We report the cloning and expression of Taq DNA polymerase in Escherichia coli. From a lambda gt11:Taq library we identified a Taq DNA fragment encoding an epitope of Taq DNA polymerase via antibody probing. The fusion protein from the lambda gt11:Taq candidate selected an antibody from an anti-Taq polymerase polyclonal antiserum which reacted with Taq polymerase on Western blots. We used the lambda gt11 clone to identify Taq polymerase clones from a lambda Ch35:Taq library. The complete Taq DNA polymerase gene has 2499 base pairs. From the predicted 832-amino acid sequence of the Taq DNA polymerase gene, Taq DNA polymerase has significant similarity to E. coli DNA polymerase I. We subcloned and expressed appropriate portions of the insert from a lambda Ch35 library candidate to yield thermostable, active, truncated, or full-length forms of the protein in E. coli under control of the lac promoter.
IL-22 is related to development of human colon cancer by activation of STAT3 (2013)

In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation.
DESIGNING MICROORGANISMS FOR THE TREATMENT OF TOXIC WASTES (1994)

The genetic design of novel metabolic routes offers exciting possibilities for biological research and biotechnology, both in the exploration of the metabolic/evolutionary potential of cells and in the development of innovative applications. In this chapter, we review recent advances in the development of genetic tools and strategies for the design of new microorganisms for elimination of environmental pollutants. These include the design of regulated gene expression circuits that provide high levels of catalytic activity, even under environmental conditions that ordinarily repress expression of catabolic genes; the rational alteration of relevant properties of proteins that qualitatively or quantitatively restrict catabolic activities; the judicious assembly of gene blocks encoding selected metabolic modules to create novel metabolic routes and combinations of routes; and the design of microorganisms exhibiting properties that contribute to better process development.
Black multi‐crystalline silicon solar cells (2006)

Abstract A simple method for nano‐scale texturing of silicon surfaces based on local metal‐catalyzed wet chemical etching, which results in an almost complete suppression of reflectivity in a broad spectral range, has been successfully applied to produce black multi‐crystalline silicon solar cells. The performance of the cells is compared to that of reference cells without surface nano‐texturing. A considerable increase of the short circuit current (by 36–42% with respect to the reference cells) without deterioration of other performance parameters is observed under natural sun illumination. Means of further optimization of such black solar cells are discussed. (© 2007 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Lung Cancer Screening With Low-Dose Computed Tomography: Costs, National Expenditures, and Cost-Effectiveness (2012)

A recent randomized trial showed that low-dose CT (LDCT) screening reduces lung cancer mortality. Health care providers need an assessment of the national budget impact and cost-effectiveness of LDCT screening before this intervention is adopted in practice. Using data from the 2009 National Health Interview Survey, CMS, and the National Lung Screening Trial (NLST), the authors performed an economic analysis of LDCT screening that includes a budget impact model, an estimate of additional costs per lung cancer death avoided attributed to screening, and a literature search of cost-effectiveness analyses of LDCT screening. They conducted a one-way sensitivity analysis, reporting expenditures in 2011 U.S. dollars, and took the health care payer and patient perspectives. LDCT screening will add $1.3 to $2.0 billion in annual national health care expenditures for screening uptake rates of 50% to 75%, respectively. However, LDCT screening will avoid up to 8100 premature lung cancer deaths at a 75% screening rate. The prevalence of smokers who qualify for screening, screening uptake rates, and cost of LDCT scan were the most influential parameters on health care expenditures. The additional cost of screening to avoid one lung cancer death is $240,000. Previous cost-effectiveness analyses have not conclusively shown that LDCT is cost-effective. LDCT screening may add substantially to the national health care expenditures. Although LDCT screening can avoid more than 8000 lung cancer deaths per year, a cost-effectiveness analysis of the NLST will be critical to determine the value of this intervention and to guide decisions about its adoption.
Cytokines and Major Psychiatric Disorders (2010)

Background: Severe mental disorders are chronic, recurrent and usually combined chronic physical illness. The pathophysiology of mental disorder still remains a mystery. Convincing evidence supports that cytokines play an integral role in the pathophysiology of certain psychiatric disorders including schizophrenia, major depressive disorder, and bipolar disorder. Method: In this comprehensive overview, we reviewed all available published articles on the topic of cytokines and major psychiatric disorders. Results: Cytokine are generally known as chemical messengers between immune cells. As such, they play a crucial role in mediating inflammatory and immune responses. Cytokines can signal the brain and serve as a mediators between immune and nerve cells. The brain is now seen as capable of influencing immune processes. Conversely, changes in brain activity can occur in association with an immunologic response. Cytokines can act as neuromodulators within the brain. Therefore, cytokines can affect important brain activities such as sleep, appetite, and neuroedocrine regulation. Conclusion: Discoveries about these processes have led to speculations about a possible link between cytokines and psychopathology. If we could identify the immunologic defects in psychiatric disorders, novel treatment strategies involving cytokines and/or cytokine inhibitors would be designed and tried clinically in the future.
Stability, Specific Binding Activity, and Plasma Concentration in Mice of an Oligodeoxynucleotide Modified at 5'-Terminal with Poly (ethylene glycol). (1995)

Oligodeoxynucleotide (ODN) composed of 15 nucleotides was modified at 5'-terminal phosphate with hexylamine linker and chemically activated poly(ethylene glycol). This derivative showed improved characteristics in terms of enzymatic stability, binding activity, and in vivo retention in mouse. The data are discussed in comparison with those of corresponding unmodified and phosphorothioate ODNs.
Photosensitized cleavage of a thymine dimer by an antibody (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotosensitized cleavage of a thymine dimer by an antibodyAndrea G. Cochran, Renee. Sugasawara, and Peter G. SchultzCite this: J. Am. Chem. Soc. 1988, 110, 23, 7888–7890Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://pubs.acs.org/doi/10.1021/ja00231a056https://doi.org/10.1021/ja00231a056research-articleACS PublicationsRequest reuse permissionsArticle Views200Altmetric-Citations81LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Docetaxel Administered on a Weekly Basis for Metastatic Breast Cancer (2000)

Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy.
Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1. (1993)

Bispecific monoclonal antibodies (BsmAb) with specificity for tumor Ag and effector cell trigger molecules have been shown to redirect the cytotoxicity of several peripheral blood mononuclear cell populations against relevant tumor. The BsmAb, 2B1, binds to the extracellular domain of the c-erbB-2 gene product of the HER2/neu proto-oncogene and to CD16. In this report, the binding and cytotoxic characteristics of 2B1 are presented. Maximal saturation binding of 2B1 to PBL and c-erbB-2 expressing SK-OV-3 cells occurred in the 1 microgram/ml concentration range. However, substantial lysis potentiation was observed at 1000-fold lower BsmAb concentrations. Optimal tumor lysis was obtained when the BsmAb, PBL, and target cells were continuously coincubated. When PBL were franked with 2B1, washed, and added to labeled targets, substantially less lysis was observed. These results suggest that the best way to therapeutically exploit the cytotoxic attributes of 2B1 may be to obtain continuous BsmAb exposure to tumor. Approaches based on franking of this BsmAb to PBL may not be warranted.
Rational Design of a Combination Medication for the Treatment of Obesity (2008)

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo-controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of beta-endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.\
Interleukin‐1: A master regulator of neuroinflammation (2004)

Interleukins 1alpha and 1beta (IL-1) are very potent signaling molecules that are expressed normally at low levels, but are induced rapidly in response to local or peripheral insults. IL-1 coordinates systemic host defense responses to pathogens and to injury and not surprisingly it has similar effects within the central nervous system (CNS). Numerous reports have correlated the presence of IL-1 in the injured or diseased brain, and its effects on neurons and nonneuronal cells in the CNS, but it is only recently that the importance of IL-1 signaling has been recognized. This article reviews studies that demonstrate that IL-1 is at or near the top of the hierarchical cytokine signaling cascade in the CNS that results in the activation of endogenous microglia and vascular endothelial cells to recruit peripheral leukocytes (i.e., neuroinflammation). The IL-1 system thus provides an attractive target for therapeutic intervention to ameliorate the destructive consequences of neuroinflammation.
A Combinatorial Polymer Library Approach Yields Insight into Nonviral Gene Delivery (2008)

The potential of gene therapy to benefit human health is tremendous because almost all human diseases have a genetic component, from untreatable monogenic disorders to cancer and heart disease. Unfortunately, a method for gene therapy that is both effective and safe has remained elusive. It has been said that "there are only three problems in gene therapy - delivery, delivery, and delivery." (quote from I. M. Verma in Jaroff, L. TIME, 1999; Jan 11). This Account describes an alternative strategy to viral gene delivery: the design of biodegradable polymers that are able to deliver DNA like a synthetic virus. Using high-throughput synthesis and screening techniques, we have created libraries of over 2000 structurally unique poly(β-amino esters) (PBAEs). PBAEs are formed by the conjugate addition of amines to diacrylates. These biomaterials are promising for nonviral gene delivery due to their ability to condense plasmid DNA into small and stable nanoparticles and their ability to promote cellular uptake and endosomal escape. Our laboratory has iteratively improved PBAE nanoparticles through polymer end modifications and nanoparticle coatings. Lead PBAEs have high gene delivery efficacy and low cytotoxicity both in vitro and in vivo. Certain polymer structural characteristics are important for effective gene delivery. The best PBAEs are linear polymers of ~10 kDa that contain hydroxyl side chains and primary amine end groups. These polymers bind DNA to form nanoparticles that are small (<200 nm) and stable and have near-neutral ζ potential in the presence of serum-containing media. Lead PBAEs also contain tertiary amines that can buffer the low pH environment of endosomes and facilitate escape of polymer/DNA particles into the cytoplasm. Diamine end-modified 1,4-butanediol diacrylate-co-5-amino-1-pentanol polymers (C32) bind DNA more tightly and form smaller nanoparticles than other PBAEs. These nanoparticles also have higher cellular uptake and the best gene expression of all gene delivery polymers in the library. These polymers are more effective for gene delivery than top commercially available nonviral vectors including jet-PEI and Lipofectamine 2000 and are comparable to adenovirus for in vitro gene delivery to human primary cells. In vivo, these PBAE/DNA particles are promising as cancer therapeutics. This Account summarizes the results of our laboratory in using a combinatorial polymer library approach to elucidate polymer structure/function relationships and enable the development of polymeric gene delivery nanoparticles with viral-like efficacy.
Synthesis and DNA-binding properties of polyamine analogs (1991)

The synthesis of a series of novel polyamine analogues is reported. The DNA binding of these compounds and a variety of other polyamines were compared with their IC50 values against HeLa cell. There seemed to be no apparent correlation between the DNA binding and toxicity against HeLa cells.
Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes (2011)

Cell division, membrane rigidity, and strong adhesion to a rigid matrix are all promoted by myosin-II, and so multinucleated cells with distended membranes--typical of megakaryocytes (MKs)--seem predictable for low myosin activity in cells on soft matrices. Paradoxically, myosin mutations lead to defects in MKs and platelets. Here, reversible inhibition of myosin-II is sustained over several cell cycles to produce 3- to 10-fold increases in polyploid MK and a number of other cell types. Even brief inhibition generates highly distensible, proplatelet-like projections that fragment readily under shear, as seen in platelet generation from MKs in vivo. The effects are maximized with collagenous matrices that are soft and 2D, like the perivascular niches in marrow rather than 3D or rigid, like bone. Although multinucleation of other primary hematopoietic lineages helps to generalize a failure-to-fission mechanism, lineage-specific signaling with increased polyploidy proves possible and novel with phospho-regulation of myosin-II heavy chain. Label-free mass spectrometry quantitation of the MK proteome uses a unique proportional peak fingerprint (ProPF) analysis to also show upregulation of the cytoskeletal and adhesion machinery critical to platelet function. Myosin-inhibited MKs generate more platelets in vitro and also in vivo from the marrows of xenografted mice, while agonist stimulation activates platelet spreading and integrin αIIbβ3. Myosin-II thus seems a central, matrix-regulated node for MK-poiesis and platelet generation.
A Practical Buchwald−Hartwig Amination of 2-Bromopyridines with Volatile Amines (2007)

A practical Buchwald-Hartwig amination of 2-bromopyridines with volatile amines is developed in sealed tubes. The method provides an expedient entry to a variety of secondary and tertiary aminopyridines that are otherwise not readily synthesized.