gebhart/patrepeval huggingface dataset:
A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection (1989)

To investigate the pathogenesis of Legionnaires disease at a molecular level, we mutated by directed allelic exchange a gene encoding a Legionella pneumophila-specific 24,000-dalton (Da) surface protein. Southern hybridization and immunoblot analyses demonstrated that the predicted DNA rearrangement occurred in L. pneumophila with a specific loss of 24-kDa antigen expression. Compared with its isogenic parent, the mutant was significantly impaired in its ability to infect transformed U937 cells, a human macrophagelike cell line; i.e., the bacterial inoculum of the mutant strain that was required to initiate infection of the macrophage monolayer was ca. 80-fold greater than that of the isogenic parent strain. The mutant strain regained full infectivity on reintroduction of a cloned 24-kDa protein gene, indicating that the reduced infectivity was due specifically to the mutation in that gene. Compared with the parent strain, the mutant strain was recovered at titers that were ca. 10-fold lower shortly after infection, but it exhibited a similar intracellular growth rate over the next 40 h, indicating that the mutant was defective in its ability to initiate macrophage infection rather than in its ability to replicate intracellularly. When opsonized, the mutant strain was still significantly less infectious than the parent strain, despite equivalent macrophage association, suggesting that the mutant was not merely missing a ligand for macrophage attachment. The mutant also exhibited reduced infectivity in explanted human alveolar macrophages, demonstrating the relevance of the U937 cell model for analyzing this mutant phenotype. These results represent the first identification of a cloned L. pneumophila gene that is necessary for optimal intracellular infection; we designate this gene mip, for macrophage infectivity potentiator.
Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model (2020)

The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.
Modeling and simulation of hybrid control systems by Global Petri Nets (2002)

Petri nets have proven themselves to be an excellent modeling and analysis tool for discrete event or asynchronous systems. On the other hand, linear system analysis uses differential and difference equations to represent time dependent or synchronous systems. A new extension of Petri nets, called Global Petri Net (GPN) provides a means for combining these two powerful tools. Here, we define this tool and show how it can be used to model and simulate hybrid systems consisting of both time and event driven parts. An example of a distributed control system is used to illustrate the GPN modeling and simulation capabilities.
Lipid disorders in NIDDM: implications for treatment (1998)

Diabetes conveys high risk lipid status for cardiovascular disease (CVD). To target the management of diabetic dyslipidaemia requests the understanding of metabolic basis of diabetic dyslipidaemia and its components. Recent progress has opened new information to direct future lipid lowering intervention trials in type 2 diabetic patients. To reduce substantially the risk for CVD aggressive modification of all known risk factors is warranted on the basis of existing data.
Molecular and Biotechnological Aspects of Microbial Proteases (1998)

Proteases represent the class of enzymes which occupy a pivotal position with respect to their physiological roles as well as their commercial applications. They perform both degradative and synthetic functions. Since they are physiologically necessary for living organisms, proteases occur ubiquitously in a wide diversity of sources such as plants, animals, and microorganisms. Microbes are an attractive source of proteases owing to the limited space required for their cultivation and their ready susceptibility to genetic manipulation. Proteases are divided into exo- and endopeptidases based on their action at or away from the termini, respectively. They are also classified as serine proteases, aspartic proteases, cysteine proteases, and metalloproteases depending on the nature of the functional group at the active site. Proteases play a critical role in many physiological and pathophysiological processes. Based on their classification, four different types of catalytic mechanisms are operative. Proteases find extensive applications in the food and dairy industries. Alkaline proteases hold a great potential for application in the detergent and leather industries due to the increasing trend to develop environmentally friendly technologies. There is a renaissance of interest in using proteolytic enzymes as targets for developing therapeutic agents. Protease genes from several bacteria, fungi, and viruses have been cloned and sequenced with the prime aims of (i) overproduction of the enzyme by gene amplification, (ii) delineation of the role of the enzyme in pathogenecity, and (iii) alteration in enzyme properties to suit its commercial application. Protein engineering techniques have been exploited to obtain proteases which show unique specificity and/or enhanced stability at high temperature or pH or in the presence of detergents and to understand the structure-function relationships of the enzyme. Protein sequences of acidic, alkaline, and neutral proteases from diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology.
Tunneling states and localized mode in binary bulk metallic glass (2005)

The low-temperature specific heat of ${\mathrm{Cu}}_{50}{\mathrm{Zr}}_{50}$ binary bulk metallic glass is systemically measured from $1.8\phantom{\rule{0.3em}{0ex}}\mathrm{K}\phantom{\rule{0.3em}{0ex}}\text{to}\phantom{\rule{0.3em}{0ex}}50.5\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. The obvious effect of the tunneling states is determined at several Kelvin by both specific heat and electrical resistivity. The density of the electron-assisted tunneling states in the bulk metallic glass at several Kelvin exceed the typical value in insulating glasses below $1\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ by 2--3 orders of magnitude, and the entropy of the tunneling states is about $7.85\phantom{\rule{0.3em}{0ex}}\mathrm{mJ}∕\mathrm{mol}\phantom{\rule{0.2em}{0ex}}\mathrm{K}$. The specific heat in the wide temperature range was analyzed by the conventional Debye and Einstein models, and the results demonstrate the existence of the localized mode which is correlated to the boson peak in the metallic glass.
Incorporation of In Vitro Synthesized GPCR into a Tethered Artificial Lipid Membrane System (2006)

Controlling the context: A novel strategy for the in vitro expression and immediate post-translational membrane insertion of complex membrane proteins into an artificial membrane system is described. In this way problems are circumvented that arise when complex membrane proteins are overexpressed, detergent-solubilized, and subsequently reconstituted into suitable artificial membrane systems for biophysical characterization. GPCR= G-protein coupled receptor. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z602231_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Prediction of the Coding Sequences of Unidentified Human Genes. I. The Coding Sequences of 40 New Genes (KIAA0001-KIAA0040) Deduced by Analysis of Randomly Sampled cDNA Clones from Human Immature Myeloid Cell Line KG-1 (1994)

We established a protocol for the prediction of the coding sequences of unidentified human genes based on the double selection and sequence analysis of cDNA clones with inserts carrying unreported 5'-terminal sequences and with insert sizes corresponding to nearly full-length transcripts. By applying the protocol, cDNA clones with inserts longer than 2 kb were isolated from a cDNA library of human immature myeloid cell line KG-1, and the coding sequences of 40 new genes were predicted. A computer search of the sequences indicated that 20 genes contained sequences similar to known genes in the GenBank/EMBL databases. The sequences of the remaining 20 genes were entirely new, and characteristic protein motifs or domains were identified in 32 genes. Other sequence features noted were that the coding sequences of 23 genes were followed by relatively long stretches of 3'-untranslated sequences and that 5 genes contained repetitive sequences in their 3'-untranslated regions. The chromosomal location of these genes has been determined. By increasing the scale of the above analysis, the coding sequences of many unidentified genes can be predicted.
Filone di Alessandria, La filosofia mosaica: La creazione del mondo, secondo Mosè, trad, de C. Kraus Reggiani, Le allegorie delle Leggi, trad. di R.Radice; Prefazioni, apparati e commentari di R. Radice; Monografia introduttiva di G. Reale e R. Radice, Milano, 1987 (Rusconi, 580 páginas). (1990)

"Filone di Alessandria, La filosofia mosaica: La creazione del mondo, secondo Mosè, trad, de C. Kraus Reggiani, Le allegorie delle Leggi, trad. di R.Radice; Prefazioni, apparati e commentari di R. Radice; Monografia introduttiva di G. Reale e R. Radice, Milano, 1987 (Rusconi, 580 páginas)." published on 30 Mar 1990 by Brill.
Comparison of 2 Commercially Available Next-Generation Sequencing Platforms in Oncology (2016)

The growing use of next generation-sequencing to identify cancer-associated alterations as well as the increasing number of targeted drugs holds promise for better matching patients with cancer with effective therapies. The FoundationOne (F1; Foundation Medicine) test sequences clinical tumor samples to characterize the exons of 315 cancer-associated genes and introns from 28 genes involved in rearrangements. The Guardant360 (G360; Guardant Health) test uses cell-free circulating DNA from blood to sequence 70 genes. Both the F1 and G360 tests have high specificities (>99%) and somewhat lower sensitivities. 1,2 However, little is known about how different next-generation sequencing tests compare when used in the same patients with cancer. We compared reports from F1 and G360 testing in 9 patients from a community oncology practice to determine the level of concordance between the platforms.
Cancer vaccines, a critical review--Part I. (2002)

Cancer vaccines have been explored clinically against melanomas, adenocarcinomas and lymphomas. Breast cancer vaccines include Theratope, MUC1 mucin peptides and HER-2/neu peptide vaccines. Phase II trials suggest prolongation of survival of advanced breast cancer patients who generate high titers of antibody to Theratope. In contrast, melanoma ganglioside vaccines, which also elicit only antibodies, have not been effective in improving survival in controlled trials. Anti-idiotype vaccines for solid tumors, which depend upon mimicry of the tumor-associated antigens, have also had limited success. In lymphomas, where the idiotypes are the tumor-associated antigens, greater success has been achieved. A number of tumor-associated antigens have been identified in melanoma, such as the lineage related cancer-testis group (MAGE) and tyrosinase-related antigens. Non-lineage related antigens shared among a variety of very different tumors have recently been demonstrated too, which may permit immunization against more than one tumor group. Telomerase and MG50, one of several interleukin-1 receptor antagonist molecules, are both immunogenic and widespread in their representation. Carcinoembryonic antigen is the basis for vaccines against many adenocarcinomas. Both viral and non-viral vectors are being used to improve the reactivity to peptides in adenocarcinomas. Dendritic cell-carried vaccines, which package the antigens ex vivo rather than depending upon in vivo uptake, are being extensively explored in clinical models to improve the effectiveness of defined vaccines, such as peptides and RNA. 'Naked' DNA vaccines injected intramuscularly also have their advocates. Among the most recent attempts to improve the immunogenicity of vaccines is the use of antigens newly identified by genomic techniques and 'superagonist' peptide mimics, selected from combinatorial peptide libraries. These modern biochemical and molecular biological methods may greatly expand our ability to immunize against tumor antigens, which are essentially 'self' molecules. Finally, a greater understanding of ways in which tumors escape immunological detection or thwart immunological responses should lead to improved strategies against the tumor to augment the effect of vaccination.
Total Synthesis of (R)-Telomestatin (2006)

We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-(t)Bu) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.
Circuit optimization of the taper isolated dynamic gain RAM cell for VLSI memories (1979)

A one transistor only, ROM like dynamic RAM cell, whose operation depends on the modulation of the threshold of a buried channel device by a hole packet, derived from the channel stop region will be covered. Tapered oxide between the field and gate oxide is used to form a potential barrier for holes.
Surface expression, single-channel analysis and membrane topology of recombinant Chlamydia trachomatis Major Outer Membrane Protein (2005)

C. trachomatis MOMP was functionally expressed on the surface of E. coli cells under newly optimized conditions. Tests of its predicted membrane topology were consistent with beta-barrel oligomers in which major immunogenic regions are displayed on surface-exposed loops. Functional surface expression, coupled with improved understanding of MOMP's topology, could provide modified antigens for immunological studies and vaccination, including live subunit vaccines, and might be useful to co-express MOMP with other chlamydial membrane proteins.
Learning Deep Parsimonious Representations (2016)

In this paper we aim at facilitating generalization for deep networks while supporting interpretability of the learned representations. Towards this goal, we propose a clustering based regularization that encourages parsimonious representations. Our k-means style objective is easy to optimize and flexible supporting various forms of clustering, including sample and spatial clustering as well as co-clustering. We demonstrate the effectiveness of our approach on the tasks of unsupervised learning, classification, fine grained categorization and zero-shot learning.
Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma (2001)

The antiangiogenic activity of thalidomide (Thal), coupled with an increase in bone marrow angiogenesis in multiple myeloma (MM), provided the rationale for the use of Thal in MM. Previously, the direct anti-MM activity of Thal and its analogues (immunomodulatory drugs, IMiDs) on MM cells was demonstrated, suggesting multiple mechanisms of action. In this study, the potential immunomodulatory effects of Thal/IMiDs in MM were examined. It was demonstrated that Thal/IMiDs do not induce T-cell proliferation alone but act as costimulators to trigger proliferation of anti-CD3-stimulated T cells from patients with MM, accompanied by an increase in interferon-gamma and IL-2 secretion. However, an increase in autologous T-cell killing of patient MM cells could not be demonstrated. A role for natural killer (NK)- and LAK-cell-mediated killing is suggested because IL-2-primed peripheral blood mononuclear cells (PBMCs) treated with Thal/IMiDs demonstrated significantly increased lysis of MM cell lines. Cold target inhibition assays suggested NK- rather than LAK-cell-mediated killing. Furthermore, this killing was not major histocompatibility complex-class restricted, and the depletion of CD56(+) cells blocked the drug-induced MM cell lysis. It was significant that increased killing of patient MM cells by autologous PBMCs treated with Thal/IMiDs was also observed. Although the in vivo relevance of NK-cell-mediated MM cell killing is unknown, phenotypic analysis performed in MM patients receiving Thal therapy demonstrated an increase in CD3(-)CD56(+) cells in patients responding to therapy. Thus in vitro and in vivo data support the hypothesis that Thal may mediate its anti-MM effect, at least in part, by modulating NK cell number and function.
Optically monitoring and controlling nanoscale topography during semiconductor etching (2012)

We present epi-diffraction phase microscopy (epi-DPM) as a non-destructive optical method for monitoring semiconductor fabrication processes in real time and with nanometer level sensitivity. The method uses a compact Mach–Zehnder interferometer to recover quantitative amplitude and phase maps of the field reflected by the sample. The low temporal noise of 0.6 nm per pixel at 8.93 frames per second enabled us to collect a three-dimensional movie showing the dynamics of wet etching and thereby accurately quantify non-uniformities in the etch rate both across the sample and over time. By displaying a gray-scale digital image on the sample with a computer projector, we performed photochemical etching to define arrays of microlenses while simultaneously monitoring their etch profiles with epi-DPM. Semiconductor etching can now be monitored in real time at nanoscale resolution using a non-destructive optical imaging technique that combines a conventional microscope with a compact Mach–Zehnder interferometer. Developed by Chris Edwards, Amir Arbabi, Gabriel Popescu, and Lynford Goddard at the University of Illinois at Urbana-Champaign in the United States, epi-diffraction phase microscopy makes it possible to collect three-dimensional videos of semiconductor fabrication processes using a CCD camera. The approach is able to measure etch rates at each location across the sample with a resolution of 0.085 nm s−1 per pixel. Such an in situ monitoring capability could be useful for improving the manufacturing quality of a wide variety of semiconductor devices.
PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer (2020)

The identification of colorectal cancer (CRC) molecular targets is needed for the development of drugs that improve patient survival. We investigated the functional role of phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a de novo purine biosynthetic enzyme involved in DNA synthesis, in CRC progression and metastasis by using cell and animal models. Its clinical utility was assessed in human CRC samples. The expression of PAICS was regulated by miR-128 and transcriptionally activated by Myc in CRC cells. Increased expression of PAICS was involved in proliferation, migration, growth, and invasion of CRC cells irrespective of the p53 and microsatellite status. In mice, the depletion of PAICS in CRC cells led to reduced tumor growth and metastatic cell dissemination to the liver, lungs, and bone. Positron emission tomography imaging showed significantly reduced metastatic lesions in stable PAICS knockdown CRC cells. In cells with PAICS knockdown, there was upregulation of the epithelial mesenchymal transition marker, E-cadherin, and bromodomain inhibitor, JQ1, can target its increased expression by blocking Myc. PAICS was overexpressed in 70% of CRCs, and was associated with poor 5-year survival independent of the pathologic stage, patient's race, gender, and age. Overall, the findings point to the usefulness of PAICS targeting in the treatment of aggressive colorectal cancer.
Structural instability of human tandemly repeated DNA sequences cloned in yeast artificial chromosome vectors (1990)

The suitability of yeast artificial chromosome vectors (YACs) for cloning human Y chromosome tandemly repeated DNA sequences has been investigated. Clones containing DYZ3 or DYZ5 sequences were found in libraries at about the frequency anticipated on the basis of their abundance in the genome, but clones containing DYZ1 sequences were under-represented and the three clones examined contained junctions between DYZ1 and DYZ2. One DYZ3 clone was quite stable and had a long-range structure corresponding to genomic DNA. All other clones had long-range structures which either did not correspond to genomic DNA, or were too unstable to allow a simple comparison. The effects of the transformation process and host genotype on YAC structural stability were investigated. Gross structural rearrangements were often associated with re-transformation of yeast by a YAC. rad1-deficient yeast strains showed levels of instability similar to wild-type for all YAC clones tested. In rad52-deficient strains, DYZ5 containing YACs were as unstable as in the wild-type host, but DYZ1/DYZ2 or DYZ3 containing YACs were more stable. Thus the use of rad52 hosts for future library construction is recommended, but some sequences will still be unstable.