gebhart/patrepeval huggingface dataset:
Reconstructing the Dynamics of HIV Evolution within Hosts from Serial Deep Sequence Data (2012)

At the early stage of infection, human immunodeficiency virus (HIV)-1 predominantly uses the CCR5 coreceptor for host cell entry. The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of progression to AIDS. The presence of a 'fitness valley' separating CCR5- and CXCR4-using genotypes is postulated to be a biological determinant of whether the HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the evolutionary dynamics of HIV within hosts enables us to discriminate between competing models of this process. We have developed a phylogenetic pipeline for the molecular clock analysis, ancestral reconstruction, and visualization of deep sequence data. These data were generated by next-generation sequencing of HIV RNA extracted from longitudinal serum samples (median 7 time points) from 8 untreated subjects with chronic HIV infections (Amsterdam Cohort Studies on HIV-1 infection and AIDS). We used the known dates of sampling to directly estimate rates of evolution and to map ancestral mutations to a reconstructed timeline in units of days. HIV coreceptor usage was predicted from reconstructed ancestral sequences using the geno2pheno algorithm. We determined that the first mutations contributing to CXCR4 use emerged about 16 (per subject range 4 to 30) months before the earliest predicted CXCR4-using ancestor, which preceded the first positive cell-based assay of CXCR4 usage by 10 (range 5 to 25) months. CXCR4 usage arose in multiple lineages within 5 of 8 subjects, and ancestral lineages following alternate mutational pathways before going extinct were common. We observed highly patient-specific distributions and time-scales of mutation accumulation, implying that the role of a fitness valley is contingent on the genotype of the transmitted variant.
Molecular cloning and expression in Escherichia coli of a Trichoderma viride endo-beta-(1 6)-galactanase gene (2004)

The nucleotide sequence depicted in Figure 1 has been submitted to the DDBJ nucleotide sequence database under the accession no. AB104898. A gene encoding endo-beta-(1-->6)-galactanase from Trichoderma viride was cloned by reverse transcriptase-PCR and expressed in Escherichia coli. The gene contained an open reading frame consisting of 1437 bp (479 amino acids). The deduced amino acid sequence of the protein showed little similarity with other known glycoside hydrolases. A signal sequence (20 amino acids) was found at the N-terminal region of the protein and the molecular mass of the mature form was calculated to be 50.488 kDa. The gene product expressed in E. coli as a recombinant protein fused with thioredoxin and His(6) tags had almost the same substrate specificity and mode of action as native enzyme purified from a commercial cellulase preparation of T. viride, i.e. recombinant enzyme endo-hydrolysed beta-(1-->6)-galacto-oligomers with a DP (degree of polymerization) higher than 3, and it could also hydrolyse alpha-L-arabinofuranosidase-treated arabinogalactan protein from radish. It produced beta-(1-->6)-galacto-oligomers ranging from DP 2 to at least 8 at the initial hydrolysis stage and galactose and beta-(1-->6)-galactobiose as the major products at the final reaction stage. These results indicate that the cloned gene encodes an endo-beta-(1-->6)-galactanase. As far as we know, this is the first time an endo-beta-(1-->6)-galactanase has been cloned.
Interval Estimation for a Binomial Proportion (2001)

We revisit the problem of interval estimation of a binomial proportion. The erratic behavior of the coverage probability of the standard Wald confidence interval has previously been remarked on in the literature (Blyth and Still, Agresti and Coull, Santner and others). We begin by showing that the chaotic coverage properties of the Wald interval are far more persistent than is appreciated. Furthermore, common textbook prescriptions regarding its safety are misleading and defective in several respects and cannot be trusted. This leads us to consideration of alternative intervals. A number of natural alternatives are presented, each with its motivation and context. Each interval is examined for its coverage probability and its length. Based on this analysis, we recommend the Wilson interval or the equal-tailed Jeffreys prior interval for small n and the interval suggested in Agresti and Coull for larger n. We also provide an additional frequentist justification for use of the Jeffreys interval.
계내김(鷄內金)에서 추출한 protease를 이용한 녹용(鹿茸) 추출 특성 연구 (2011)

Objective: Kyenegum has been frequently used for characterizing digestive symptoms in the traditional and oriental medicines. This study was conducted to investigate the characteristics of extracts from velvet antlers using the 4 different kinds of extracting methods. Methods: The extracts of velvet antlers were extracted using a 65℃ DW (9hrs), a Kyenegum crude enzyme, a 121℃ DW (2hrs), and a Kyenegum protease. To evaluate the characteristic of velvet antler extracts, we examined the brix, soluble solid, amino acid, mineral composition, and collagen protein. Results: As a result of the comparisons of velvet antlers extracted by the traditional extraction and the crude enzyme of kyenegum, the brix and soluble solid showed the higher contents for kyenegum enzymes. Also, mineral contents of the extracted velvet antlers were higher, particularly in Ca and P for those. The contents of collagen protein, hydroxyproline and hydroxylysine, were found to be more than twice in kyenegum protease compared with other extracting methods. Conclusion: These results indicated that the Kyenegum crude enzyme and protease are very effective to extract of velvet antlers.
Inhibition of Transcription Elongation by the VHL Tumor Suppressor Protein (1995)

Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here, a cellular transcription factor, Elongin (SIII), is identified as a functional target of the VHL protein. Elongin (SIII) is a heterotrimer consisting of a transcriptionally active subunit (A) and two regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro. These findings reveal a potentially important transcriptional regulatory network in which the VHL protein may play a key role.
Terahertz integrated device: high-Q silicon dielectric resonators (2017)

We design, fabricate, and characterize the terahertz integrated resonators on the silicon platform. Based on mode analysis and selection, the high-Q feature of resonators made of low-loss high-resistivity Si material is achieved due to the excitation of the whispering gallery mode on waveguide-coupled single-mode racetrack rings and disk cavities. The experimental results demonstrate that the Q-factor can reach up to 2839 at 218.345 GHz, which is significantly improved compared with conventional THz cavities. These high Q-factor integrated resonators can be used as on-chip terahertz ultrasensitive sensors and as terahertz functional integrated circuits.
Suppression of cancer relapse and metastasis by inhibiting cancer stemness (2015)

Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemness-high cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.
Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le(x) and other lacto-series type 2 chain antigens:absence of reactivity with normal hematopoietic progenitor cells (1992)

We investigated the expression profiles of lacto-series type 2 antigens in hematopoietic cells and their progenitors, in comparison with leukemic leukocytes. Reactivity profiles of various anti-type 2 chain monoclonal antibodies (MoAbs) with leukemic blasts from 12 patients with acute myeloblastic leukemia (AML) and those from two patients with acute unclassified leukemia (AUL) show that anti-sialosyl-Le(x) MoAb SNH3 reacted strongly with greater than 95% of leukemic blast leukocyte populations from all patients (14 of 14). Another anti-sialosyl-Le(x) MoAb, FH6, showed less reactivity than SNH3 (12 of 14 patients), while anti-Le(y) MoAb AH6 showed reactivity with only 8 of 14 patients. On the other hand, none of the anti-type 2 chain MoAbs reacted with CD34+ normal adult bone marrow (BM) mononuclear cells obtained independently from three healthy volunteers. MoAb SNH3, but not FH6 or AH6, showed complement-mediated cytotoxicity to leukemic blasts from these patients, as well as to myelogenous leukemia cell line HL60. Colony-forming unit granulocyte-macrophage (CFU-GM), but not burst-forming unit-erythroid (BFU-E), was incompletely inhibited by treatment of normal BM mononuclear cells with SNH3 and complement. The absence of type 2 chain antigen expression in hematopoietic progenitor cells and in in vitro hematopoietic colonies (CFU-GM and BFU-E) strongly suggests that application of anti-carbohydrate MoAbs, particularly anti-sialosyl-Le(x) could be useful for elimination of leukemic myeloblasts infiltrating in BM, for purging of leukemic blasts in BM, and for facilitation of autologous BM transplantation.
Light Propagation Prediction through Multimode Optical Fibers with a Deep Neural Network (2018)

This work demonstrates a computational method for predicting the light propagation through a single multimode fiber using a deep neural network. The experiment for gathering training and testing data is performed with a digital micro-mirror device that enables the spatial light modulation. The modulated patterns on the device and the captured intensity-only images by the camera form the aligned data pairs. This sufficiently-trained deep neural network frame has very excellent performance for directly inferring the intensity-only output delivered though a multimode fiber. The model is validated by three standards: the mean squared error (MSE), the correlation coefficient (corr) and the structural similarity index (SSIM).
Rapid DNA content analysis by the propidium iodide-hypotonic citrate method. (1990)

For the rapid quantitation of DNA and protein content of fixed cells by flow cytometry (FCM), direct staining of isolated nuclei is experimented with various DNA-binding fluorochromes. The propidium iodide (PI)-citrate method has been developed for the rapid determination of cell cycle distribution in leukemic peripheral blood and bone marrow samples of patients on high-dose methotrexate rescue protocols. The method is employed and found suitable for rapid cell cycle analysis. It has also been used by several workers to study the cell cycle phase distribution of mammalian tissue culture cells and a variety of tumor cells. Modifications have involved inclusion of RNase and a detergent in the staining solution. This rapid method is, especially suitable for small samples, such as a drop of blood from a fingerprick, tissue culture cells from multiwell plates, and small bone marrow aspirates. For solid-tumor material, mincing of tissue with scissors or crossed scalpels and filtering through nylon cloth are essential.
Regulation of Blood Flow in the Microcirculation (2005)

The regulation of blood flow has rich history of investigation and is exemplified in exercising skeletal muscle by a concerted interaction between striated muscle fibers and their microvascular supply. This review considers blood flow control in light of the regulation of capillary perfusion by and among terminal arterioles, the distribution of blood flow in arteriolar networks according to metabolic and hemodynamic feedback from active muscle fibers, and the balance between peak muscle blood flow and arterial blood pressure governed by sympathetic nerve activity. As metabolic demand increases,the locus of regulating oxygen delivery to muscle fibers "ascends" from terminal arterioles, through intermediate distributing arterioles, and into the proximal arterioles and feed arteries, which govern total flow into a muscle. At multiple levels, venules are positioned to provide feedback to nearby arterioles regarding the metabolic state of the tissue through the convection, production and diffusion of vasodilator stimuli. Electrical signals initiated on microvascular smooth muscle and endothelial cells can travel rapidly for millimeters through cell-to-cell conduction via gap junction channels, rapidly coordinating vasodilator responses that govern the distribution and magnitude of blood flow to active muscle fibers. Sympathetic constriction of proximal arterioles and feed arteries can restrict functional hyperemia while dilation prevails in distal arterioles to promote oxygen extraction. With vasomotor tone reflecting myogenic contraction of smooth muscle cells modulated by shear stress on the endothelium, the initiation of functional vasodilation and its modulation by sympathetic innervation dictate how and where blood flow is distributed in response to metabolic demand. A remarkable ensemble of signaling pathways underlies the integration of smooth muscle and endothelial cell function in microvascular networks. These pathways are being defined with refreshing new insight as novel approaches are applied to understanding the cellular and molecular mechanisms of blood flow control.
New Global Hydrography Derived From Spaceborne Elevation Data (2008)

To study the Earth system and to better understand the implications of global environmental change, there is a growing need for large‐scale hydrographic data sets that serve as prerequisites in a variety of analyses and applications, ranging from regional watershed and freshwater conservation planning to global hydrological, climate, biogeochemical, and land surface modeling. Yet while countless hydrographic maps exist for well‐known river basins and individual nations, there is a lack of seamless high‐quality data on large scales such as continents or the entire globe. Data for many large international basins are patchy, and remote areas are often poorly mapped. In response to these limitations, a team of scientists has developed data and created maps of the world's rivers that provide the research community with more reliable information about where streams and watersheds occur on the Earth's surface and how water drains the landscape. The new product, known as HydroSHEDS (Hydrological Data and Maps Based on Shuttle Elevation Derivatives at Multiple Scales), provides this information at a resolution and quality unachieved by previous global data sets, such as HYDRO1k [ U.S. Geological Survey (USGS) , 2000].
Can the mild clinical course of crimean–congo hemorrhagic fever in children be explained by cytokine responses? (2013)

Cytokines are possibly one of the factors responsible for death due to Crimean-Congo hemorrhagic fever (CCHF). This study aimed to determine the differences between the cytokine levels in children and adult patients with CCHF; the influence of cytokines; and the severity of the course of the disease, which seems to be milder in children. Thirty-four children and 36 adult patients diagnosed with CCHF between 2010 and 2011 were included in this study. Diagnosis was performed by serology or by the polymerase chain reaction for CCHF virus. Levels of IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p70, IL-13, IL-17A, and IL-22 were measured in all serum samples. Although the disease had a fatal course in three adult patients, there were no deaths in children. Statistically significant differences were not observed between the cytokine concentrations in the adults and children. No differences were detected between the serum cytokine levels in the children with moderate and those with a severe clinical course of the disease. In the adult patients with fatal outcome, significantly higher serum levels of IL-2, IL-5, IL-9, IL-12 p70, and IL-13 were detected as compared to the cytokine levels in patients who survived the infection. No differences were detected between the serum levels of IFN-γ, IL-1β, IL-17A, IL-22, IL-10, IL-6, IL-4, and TNF-α in the patients who died and those who survived. Thus, the milder clinical course in children with CCHF cannot be explained by the cytokine network alone. The incomplete maturation of the immune system and timing and scale of immune responses could change the outcome dramatically.
The optical design of intraocular lens implants. (1975)

Intraocular lens implants have been around for more than 25 years. On the verge of a major breakthrough to ever widening popularity, there is, however, a general lack of understanding of the pertinent optical principles. A critical comparison is made between this new method and conventional methods of correcting aphakia. From this it appears that the visual needs of the patient are a decisive factor in the selection of the method of correction. Moreover, the full potential of intraocular lens implants can only be realized by appropriate selection of the power of the implant in each situation. To this end, ultrasonic measurement of the ocular axial length is indispensable. The use of standard power lens implants is inadequate. Formulas are presented to make an eye emmetropic or to give it any refractive error. Guidelines are given for the use of these formulas. Two methods for obtaining equal image size in unilateral antiphakia are described.
Novel Covalently Linked Insulin Dimer Engineered to Investigate the Function of Insulin Dimerization (2012)

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.
Identifying the major proteome components of Haemophilus influenzae type‐strain NCTC 8143 (1997)

With the completion of the Haemophilus influenzae Rd genomic sequence, we know the identity of most of the theoretical proteins in the proteome of this bacterium. However, the most abundant components of the actual proteome are unknown. Using mass spectrometry and two-dimensional gel electrophoresis (2-DE), we sequenced and analyzed the most abundant proteins observed in the ATCC reference strain of H. influenzae, NCTC 8143 (303 of approximately 400 Coomassie-stained 2-DE spots). To automate the identification of 2-DE spots, we coupled a liquid autosampler to a microcolumn liquid chromatography electrospray ionization tandem mass spectrometer capable of identifying 22 spots per day. From the 303 sequenced spots, we identified 263 unique proteins. Most of the abundant proteins lie in an isoelectric point range of pH 4-7 and a molecular mass range of 10-100 kDa. Of the observed proteins, the most abundant is the outer membrane protein P2. Based on variety and abundance, proteins involved in energy metabolism and macromolecular synthesis are the dominant classes of proteins. Unexpectedly, tryptophanase was identified as a highly abundant protein in the strain NCTC 8143 whose sequence is not present in the genome of the Rd strain. By searching the tandem mass spectra against the translated genomic sequence, we identified several proteins which were not annotated in the genomic sequence. Surprisingly, 22% of the identified 2-DE spots represent isoforms in which gene products with the same primary sequence have different observed pI and M(r), indicating that these proteins are post-translationally processed. Although most proteins' predicted and observed isoelectric points and molecular masses show reasonable concordance, the observed values for several proteins deviate significantly from the predicted values. These anomalies may represent either highly processed proteins or misinterpretations of the genomic sequence. Using the technology developed in this project, the protein expression of other strains of H. influenzae grown under different environmental conditions can be compared to identify differences in their proteomes.
3D CELL BIOPRINTING FOR REGENERATIVE MEDICINE RESEARCH AND THERAPIES (2011)

Tissue engineering tools and technologies are critical for regenerative medicine and the translational research supporting development of cell-based therapies. 3D cell bioprinting is a relatively new engineering tool being used to design 3D cell constructs (rather than cell suspensions) for transplantation therapies. In this review, we describe a broad range of printing technologies now being used to deliver cells and biomaterials in preclinical studies. We focus on 3D cell bioprinting, in which the building blocks (or 'bioink') used in printing process are three-dimensional cell structures, that are placed by the bioprinter into precise architectures to generate small tissues or organs. 3D cell bioprinting is a flexible research tool for basic and translational stem cell biology.