gebhart/patrepeval huggingface dataset:
Tissue fractionation by hydrostatic pressure cycling technology: the unified sample preparation technique for systems biology studies. (2008)

Major bottlenecks in systems biology studies arise from limitations of current sample preparation techniques. Multiple mutually exclusive sample preparation methods, which are often required to extract distinct classes of molecules from cells and tissues, are incompatible with studies of precious or very limited samples. Moreover, the strong detergents and chaotropic agents commonly required to solubilize sample constituents often interfere with subsequent separation and analysis. Here we describe a rapid, detergent-free sample preparation technique that allows efficient concurrent isolation and fractionation of protein, DNA, RNA, and lipids from biological samples, eliminating the need for multiple replicates. The method relies on a synergistic combination of physical disruption of the cellular material by hydrostatic pressure (pressure cycling technology) and novel extraction conditions to dissolve and partition distinct classes of molecules into separate fractions. We demonstrate parallel recovery of proteins, lipids, and intact DNA and RNA, from animal cells and tissues, for proteomic, lipidomic, and genomic analyses. The protein extracts require minimal cleanup and are compatible with 1D and 2D PAGE, liquid chromatography coupled with tandem mass spectrometry, and Western blotting. The lipid fractions have been profiled by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry without further processing. The isolated DNA and RNA were shown to be intact by agarose gel visualization, and the presence of intact mRNA was confirmed by real time reverse transcription polymerase chain reaction. Analysis and comparison of samples extracted using this method and a more traditional extraction technique revealed several protein species preferentially extracted by the new method.
Why is the intelligent peripheral so stupid? (2002)

This paper surveys the current state of standardisation for the intelligent peripheral, or IP. The IP provides the 'ears and mouth' of the intelligent network. It is responsible for playing announcements to, and collecting information from callers, as required by the service logic, and as directed by the service control point. IP functions are specified by IN standards, such as ITU-T CS1-R, ETSI Core INAP and Bellcore AIN 0.2. The level of the function required of an IP by these standards is very low; it is required simply to play individual announcements, or collect single items of user input. This level of function hardly deserves to be called 'intelligent'. In our view it is beneficial to assign a higher level of function to the IP for the following reasons: (1) to enable new services to be implemented which are impossible with current standards; (2) to exploit the capabilities which are typically available on modem implementations of the IP; and (3) to make efficient use of the available signalling network bandwidth.
A dose-escalation trial of GM-CSF-gene transduced allogeneic prostate cancer cellular immunotherapy in combination with a fully human anti-CTLA antibody (MDX-010, ipilimumab) in patients with metastatic hormone-refractory prostate cancer (mHRPC) (2006)

2500 Background: A Phase 1 trial is underway to study the combination of GM-CSF-gene-transduced allogeneic prostate cancer cellular immunotherapy (GVAX immunotherapy (IT) and ipilimumab in patients (pts) with mHRPC. Ipilimumab is a fully human IgG monoclonal antibody specific to the CTLA-4 receptor on T cells that augments immune responses by blocking the inhibitory CTLA-4/B7 interactions. Pre-clinical studies of antibodies to CTLA-4 in combination with GM-CSF secreting tumor cell vaccines demonstrate potent synergy. Methods: Eligible pts have documented mHRPC and are chemotherapy-naïve. All pts receive a 500 million cell priming dose of GVAX IT on day 1 followed by bi-weekly intradermal treatments (tx) of 300 million cells for a 24 week (wk) period. Ipilimumab is administered every 4 wks starting on day 1 for the same period. Pts are enrolled in cohorts of 3; each cohort is assigned an escalating dose of ipilimumab: 0.3, 1, 3 or 5 mg/kg. PSA is measured every 4 wks, and tumor assessments performed every 12 wks. 15 pts will be enrolled at the maximum tolerated dose. Pts are followed for disease progression and survival. Results: Ten pts have been enrolled. All 6 pts in Cohorts 1 and 2 have completed tx and are in follow-up; 5 of 6 completed all planned tx. Three pts in Cohort 3 have completed 75% of tx and are on-going. One pt in Cohort 4 has completed 25% of tx and is on-going. No dose-limiting or immune mediated toxicities have been observed. The most common adverse event is injection site reaction which occurs in 100% of pts. PSA responses by NCI working group criteria include 1 partial response (PR), 4 stable disease (SD), and 4 progressive disease (PD). Of note, 3 PD occurred in Cohort 1; 2 SD and 1 PD occurred in Cohort 2, and 1 PR and 2 SD occurred in Cohort 3. Any decline in PSA was evident within 2–4 wks of initiating tx. Conclusions: The combination of GVAX IT and ipilimumab appears well-tolerated in pts with mHPRC. These preliminary data suggest a relationship between PSA response and the dose level of ipilimumab in combination with GVAX IT. [Table: see text]
Cutting Edge: In Vitro-Generated Tolerogenic APC Induce CD8+ T Regulatory Cells That Can Suppress Ongoing Experimental Autoimmune Encephalomyelitis (2004)

APC exposed to TGFbeta2 and Ag (tolerogenic APC) promote peripheral Ag-specific tolerance via the induction of CD8(+) T regulatory cells capable of suppressing Th1 and Th2 immunity. We postulated that tolerogenic APC might reinstate tolerance toward self-neuronal Ags and ameliorate ongoing experimental autoimmune encephalomyelitis (EAE). Seven days after immunization with myelin basic protein (MBP), mice received MBP-specific tolerogenic APC, and EAE was evaluated clinically. To test for the presence and the phenotype of T regulatory cells, CD4 and/or CD8 T cells from tolerogenic APC-treated mice were transferred to naive mice before their immunization with MBP. The MBP-specific tolerogenic APC decreased both the severity and incidence of ongoing EAE. Tolerance to self-neuronal Ags was induced in naive recipient mice via adoptive transfer of CD8(+), but not CD4(+) T cells. Rational use of in vitro-generated tolerogenic APC may lead to novel therapy for autoimmune disease.
Insights into the cellular mechanisms of erythropoietin-thrombopoietin synergy. (1996)

Using suspension cultures of purified bone marrow CD34+ cells, we have analyzed the effects of the combination of erythropoietin (Epo) and thrombopoietin (Tpo) on the in vitro differentiation toward erythropoiesis and thrombopoiesis. The number of CD41+ cells that accumulated over 2 weeks of culture, as well as the number of globin+ cells in the same cultures, was found to be significantly higher with the Epo+Tpo combination compared to either cytokine alone. No evidence was found that Tpo affected the differentiative action of Epo. Instead, there was a significant expansion of erythroid progenitors, both erythroid colony-forming and burst-forming units (CRU-E and BFU-E), by 7 days in culture, suggesting a proliferative effect of Tpo on erythroid cells in vitro. To determine the phenotypic features of erythroid progenitor cells which were targets of Tpo's action, and specifically to inquire whether the effect was directed mainly toward bipotent erythroid/megakaryocytic (E+Mk) progenitors, we isolated subsets enriched for both erythroid and megakaryocytic progenitors from CD34+ cells. We found that 1) BFU-E and CFU-Mk co-segregate in the subset of CF34+ cells that is negative for the phosphatase isoform CD45RA; 2) the presence of CD41 on this subset appears to segregate late erythroid and late CFU-Mk from early erythroid and early CFU-Mk, which are CD41-negative; 3) bipotent erythroid/Mk progenitors, studied by single-cell culture assays, were found mainly in the CD41+ and rarely in the CD41- subsets which included more multipotent progenitors; 4) by comparing the frequencies of pure erythroid or pure megakaryocytic progenitors to that of bipotent E+Mk progenitors, we conclude that the erythroid-enhancing effect of Tpo is directed mainly toward pure erythroid progenitors expressing CD41 and Mpl, as suggested by independent experiments employing anti-Mpl antibody, rather than only on bipotent E+Mk progenitors.
Expression of a chimeric, cGMP‐sensitive regulatory subunit of the cAMP‐depedent protein kinase type Iα (1995)

To study the fluctuations of cGMP in living cells through changes of energy transfer of dissociable fluorescence labeled subunits, we constructed a cGMP-sensitive probe by combining the N-terminus of the type I regulatory subunit of cAMP-dependent protein kinase (PKA) with the cGMP binding sites of cGMP-dependent protein kinase I alpha (PKG). This chimeric regulatory subunit retained PKA-like dimerization and PKG-compatible cGMP binding constants (Kd = 53 nM) for both binding sites. High affinity interaction with the PKA catalytic subunit was verified by Surface Plasmon Resonance (Kd = 3.15 nM). Additionally, the chimera inhibits the formation of wild-type holoenzyme with an apparent Ki of 1.05 nM. Furthermore, cGMP dissociated the mutant holoenzyme with an apparent activation constant of 146 nM. Thus, our construct provides all the requirements needed to investigate changes in intracellular cGMP concentrations.
Scanning electron microscopy of corrosion casting in medicine. (1991)

The aims of this review are: 1. to provide a bibliography of the publications that have used the corrosion casting technique; 2. to describe the advantages and limitations of the methodology; 3. to illustrate possible applications in the field of medicine, and 4. to highlight the significance of this method in the teaching of medical students. Thus, this paper is primarily focused on the scanning electron microscopical examination of vascular corrosion casts. The unsurpassed three-dimensionality of the corrosion casting technique compared to any other means stands out in particular. This can be especially useful when complex vascular-anatomical relationships are present. This applies not only to the portrayal of the modes of branching and varying vascular densities but also to regulatory arrangements, such as sphincters and arteriovenous anastomoses. Between 1966 and 1990, a total of 549 publications were found in the Medline literature data bank, containing the key words "corrosion casting", "microvascular cast", or "vascular cast" (as of August, 1990). Of those publications, most dealt with applications to experimental animals. By contrast, only 142 reports were mainly or partially concerned with human investigational material. The normal vascular system of nearly all organs, insofar as this is of direct medical relevance, has been largely resolved. In our opinion, one of the most important potential applications of the corrosion casting technique lies in the investigation of gastrointestinal, renal or hepatic ailments, which coincide with the reconstruction or rarefication of the vascular bed, e.g., in ulcers, ileitis terminalis, colitis ulcerosa, cirrhosis or glomerulonephritis.
Randaugment: Practical automated data augmentation with a reduced search space (2020)

Recent work on automated augmentation strategies has led to state-of-the-art results in image classification and object detection. An obstacle to a large-scale adoption of these methods is that they require a separate and expensive search phase. A common way to overcome the expense of the search phase was to use a smaller proxy task. However, it was not clear if the optimized hyperparameters found on the proxy task are also optimal for the actual task. In this work, we rethink the process of designing automated augmentation strategies. We find that while previous work required a search for both magnitude and probability of each operation independently, it is sufficient to only search for a single distortion magnitude that jointly controls all operations. We hence propose a simplified search space that vastly reduces the computational expense of automated augmentation, and permits the removal of a separate proxy task. Despite the simplifications, our method achieves equal or better performance over previous automated augmentation strategies on on CIFAR-10/100, SVHN, ImageNet and COCO datasets. EfficientNet-B7, we achieve 85.0% accuracy, a 1.0% increase over baseline augmentation, a 0.6% improvement over AutoAugment on the ImageNet dataset. With EfficientNet-B8, we achieve 85.4% accuracy on ImageNet, which matches a previous result that used 3.5B extra images. On object detection, the same method as classification leads to 1.0-1.3% improvement over baseline augmentation. Code will be made available online.
How to roll a join (2000)

Incremental refresh of a materialized join view is often less expensive than a full, non-incremental refresh. However, it is still a potentially costly atomic operation. This paper presents an algorithm that performs incremental view maintenance as a series of small, asynchronous steps. The size of each step can be controlled to limit contention between the refresh process and concurrent operations that access the materialized view or the underlying relations. The algorithm supports point-in-time refresh, which allows a materialized view to be refreshed to any time between the last refresh and the present.
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction. Substituent Driven Enhancements of Annulation Efficiency and Stereoselectivity (2000)

Compared to terminal alkynes, (methylthio)alkynes are generally superior substrates for the thermally promoted, Co2(CO)8 catalyzed Pauson-Khand reaction of enynes and allenynes, providing enones in higher yields and with enhanced diastereoselectivity. Improvements in yield dependent upon the use of 2,2,2-trifluoroethanol as co-solvent and an apparent preference for endo selectivity with (ethoxy)alkynes are also disclosed.
Crossing boundaries: The value of a comparative reading of oral histories (1997)

For many of us working in the field of oral history, our aim is a process of social reconciliation which values human diversity. In recent years, though, our appreciation of diversity has tended to focus on difference, and to enshrine that difference in an identity politics that risks constructing boundaries around and between groups.
Static magnetic field attenuates mortality rate of mice by increasing the production of IL-1 receptor antagonist (2009)

Exposure to an SMF increases the plasma levels of IL-1ra. This effect may inhibit the reduction in PLT in plasma, resulting in prevention in LPS induced DIC.
The Role of Complex Formation between the Escherichia coli Hydrogenase Accessory Factors HypB and SlyD (2007)

The Escherichia coli protein SlyD is a member of the FK-506-binding protein family of peptidylprolyl isomerases. In addition to its peptidylprolyl isomerase domain, SlyD is composed of a molecular chaperone domain and a C-terminal tail rich in potential metal-binding residues. SlyD interacts with the [NiFe]-hydrogenase accessory protein HypB and contributes to nickel insertion during biosynthesis of the hydrogenase metallocenter. This study examines the HypB-SlyD complex and its significance in hydrogenase activation. Protein variants were prepared to delineate the interface between HypB and SlyD. Complex formation requires the HypB linker region located between the high affinity N-terminal Ni(II) site and the GTPase domain of the protein. In the case of SlyD, the deletion of a short loop in the chaperone domain abrogates the interaction with HypB. Mutations in either protein that disrupt complex formation in vitro also result in deficient hydrogenase production in vivo, indicating that the contact between HypB and SlyD is important for hydrogenase maturation. Surprisingly, SlyD stimulates release of nickel from the high affinity Ni(II)-binding site of HypB, an activity that is also disrupted by mutations that affect complex formation. Furthermore, a SlyD truncation lacking the C-terminal metal-binding tail still interacts with HypB but is deficient in stimulating metal release and is not functional in vivo. These results suggest that SlyD could activate metal release from HypB during metallation of the [NiFe] hydrogenase.
Molecular Characterization of Golgin-245, a Novel Golgi Complex Protein Containing a Granin Signature (1995)

The serum from a Sjögren's syndrome patient with anti-Golgi antibodies was used as a probe to isolate a 4.6-kilobase pair cDNA insert from a HeLa cDNA library. Expression of the cDNA in Escherichia coli and the in vitro translation products of the cDNA yielded a recombinant protein that migrated in SDS-polyacrylamide gel electrophoresis at 180 kDa. This protein was immuno-precipitated by the human anti-Golgi serum and by immune rabbit serum but not by normal human serum or preimmune rabbit serum. Western blot analysis showed that the prototype human and immune rabbit sera recognized a 245-kDa protein, suggesting that the isolated clone contained a partial cDNA. The 5'-upstream sequence obtained by the rapid amplification of cDNA ends methodology using human placental cDNA and the combined HeLa cDNA contained 6965 base pairs and combined HeLa cDNA contained 6965 base pairs and encoded a protein of 245 kDa and, like other Golgi autoantigens described earlier, is highly rich in coiled-coils. The deduced amino acid sequence included the decapeptide ESLALEELEL, which was identified as one of two signature sequences previously reported in a family of peptide hormones and neuropeptides known as "granins". This is the first report of a Golgi complex autoantigen that bears structural similarities to the granin family of proteins.
Impaired Glucose Tolerance is Normalized by Treatment With the Thiazolidinedione Troglitazone (1997)

The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.
Freestanding Nanostructures via Layer‐by‐Layer Assembly (2006)

Abstract Freestanding flexible nanocomposite structures fabricated by layer‐by‐layer (LbL) assembly are promising candidates for many potential applications, such as in the fields of thermomechanical sensing, controlled release, optical detection, and drug delivery. In this article, we review recent advances in the fabrication and characterization of different types of freestanding LbL structures in air and at air/liquid and liquid/liquid interfaces, including micro‐ and nanocapsules, microcantilevers, freely suspended membranes, encapsulated nanoparticle arrays, and sealed‐cavity arrays. Several recently developed fabrication techniques, such as spin‐assisted coating, dipping, and micropatterning, make the assembly process more efficient and impart novel physical properties to the freestanding films.
Site-directed Mutagenesis of Arginine 72 of HIV-1 Reverse Transcriptase (1995)

In order to determine the catalytic role of Arg72 of HIV-1 reverse transcriptase (RT), we carried out site-directed mutagenesis at codon 72. Two mutant proteins (R72A and R72K) were purified and characterized. With Arg to Ala substitution the kcat of the polymerase reaction was reduced by nearly 100-fold with poly(rA) template, but only about 5-15-fold with poly(rC) and poly(dC) templates. The Arg to Lys substitution exhibited a qualitatively similar pattern, although the overall reduction in kcat was less severe. Most interestingly, we noted a large difference in the rate constant of the first and second nucleotide incorporation by R72A, suggesting that Arg72 participates in the reaction after the formation of the first phosphodiester bond. We propose this step to be the pyrophosphate binding and removal step following the nucleotidyltransferase reaction. Support for this proposal is obtained from the observation that the R72A mutant (i) exhibited a pronounced translocation defect in the processivity analysis, (ii) lacked the ability to catalyze pyrophosphorolysis, and (iii) showed complete resistance to phosphonoformate, an analog of PPi.Arg72 is the first residue of HIV-1 RT proposed to be involved in the pyrophosphate binding/removal function of RT.
Direct Visualization of Long-Range Heterogeneous Structure in Dense Colloidal Gels (2002)

By means of confocal laser scanning microscopy, we directly visualize and quantify the local spatial structure of dense colloidal gels of varying volume fraction formed by short-range attractive interparticle interactions. We find that the short-range structure of the gels is similar to that of dense amorphous hard-sphere systems. However, the long-range structure is characterized by voids and density correlations that differ remarkably from amorphous hard spheres and glasses formed through repulsive interactions. Quantification of the volume fraction dependence of the gel isothermal compressibility and Voronoi volume distribution establishes that long-range structural heterogeneity is a distinguishing feature of the static structure of dense colloidal gels formed by short-range attractions.
Analysis of bovine herpesvirus 1 glycoprotein gIV truncations and deletions expressed by recombinant vaccinia viruses (1993)

Glycoprotein gIV is an envelope component of bovine herpesvirus type 1 and appears to be involved in attachment, penetration, and cell fusion. Four antigenic domains which include both continuous and discontinuous epitopes have been previously defined by competition binding assays using gIV-specific monoclonal antibodies (MAbs). Here we describe the construction of C-terminal truncations and internal deletions in the gIV-encoding gene and analyses of the effects of these mutations on the synthesis, processing, transport, and antigenicity of glycoprotein gIV as expressed by recombinant vaccinia viruses. Wild-type gIV expressed by recombinant vaccinia virus STgIV was indistinguishable from authentic gIV produced in bovine herpesvirus 1-infected cells with respect to molecular weight, processing, transport, and antigenicity. Analysis of the mutant proteins showed that the binding sites for MAbs 9D6 and 3D9S, which recognize linear epitopes, lie between amino acids 164 and 216 and amino acids 320 and 355, respectively. Discontinuous epitopes recognized by MAbs 3E7, 4C1, 2C8, and 3C1 were located between amino acids 19 and 320, whereas amino acids 320 to 355 were critical for binding of MAb 136. All mutant proteins containing amino acids 245 to 320 were processed, possess endo-beta-N-acetylglucosaminidase H-resistant oligosaccharides, and were transported to the cell surface or secreted into the medium. In contrast, mutant proteins missing amino acids 245 to 320 were retained in the rough endoplasmic reticulum. These findings suggest that residues 245 to 320 are important for proper processing and transport of gIV to the cell surface.