gebhart/patrepeval huggingface dataset:
Predicting and Testing Physical Locations of Genetically Mapped Loci on Tomato Pachytene Chromosome1 (2007)

Predicting the chromosomal location of mapped markers has been difficult because linkage maps do not reveal differences in crossover frequencies along the physical structure of chromosomes. Here we combine a physical crossover map based on the distribution of recombination nodules (RNs) on Solanum lycopersicum (tomato) synaptonemal complex 1 with a molecular genetic linkage map from the interspecific hybrid S. lycopersicum x S. pennellii to predict the physical locations of 17 mapped loci on tomato pachytene chromosome 1. Except for one marker located in heterochromatin, the predicted locations agree well with the observed locations determined by fluorescence in situ hybridization. One advantage of this approach is that once the RN distribution has been determined, the chromosomal location of any mapped locus (current or future) can be predicted with a high level of confidence.
Mechanism of Transdominant Inhibition of CCR5-mediated HIV-1 Infection by ccr5Δ32 (1997)

Human chemokine receptor 5 (CCR5) functions as a co-receptor for Human immunodeficiency virus (HIV-1) infection. CCR5 is a seven-transmembrane cell surface receptor. Recently, a naturally occurring mutation of CCR5, ccr5Delta32, has been described. A small number of Caucasians are homozygously ccr5Delta32/ccr5Delta32, while a larger number of individuals are heterozygously CCR5/ccr5Delta32. The ccr5Delta32/ccr5Delta32 genotype has been linked to a phenotype that is "highly" protected from HIV-1 infection. On the other hand, several studies have shown that the CCR5/ccr5Delta32 genotype confers "relative" protection from AIDS with onset of disease being delayed by 2-4 years. Although it is known that peripheral blood lymphocytes from heterozygous individuals (CCR5/ccr5Delta32) support ex vivo HIV-1 replication at a reduced level compared with CCR5/CCR5 cells, the molecular basis for this observation is unknown. Here we report on events that post-translationally modify CCR5. We show that CCR5 progresses through the endoplasmic reticulum prior to appearing on the cell surface. Mature CCR5 can be post-translationally modified by phosphorylation and/or co-translationally by multimerization. By contrast, mutant ccr5Delta32, although retaining the capacity for multimerization, was incapable of being phosphorylated. ccr5Delta32 heterocomplexes with CCR5, and this interaction retains CCR5 in the endoplasmic reticulum resulting in reduced cell surface expression. Thus, co-expression in cells of ccr5Delta32 with CCR5 produces a trans-inhibition by the former of ability by the latter to support HIV-1 infection. Taken together, our findings suggest CCR5/ccr5Delta32 heterodimerization as a molecular explanation for the delayed onset of AIDS in CCR5/ccr5Delta32 individuals.
Sequence analysis of the 2nd intron revealed common sequence motifs providing the means for a unique sequencing based typing protocol of the HLA‐A locus (1996)

We here present a sequencing strategy for the HLA-A locus which is generally applicable for all HLA class I genes. The typing strategy is based on a group-specific amplification according to the serologically defined antigens. The PCR products carry the typing-relevant polymorphic regions of the 2nd and 3rd exon including the 2nd intron. The sequencing primers were designed to match conserved sequence motifs in the 2nd intron allowing a nested sequencing approach in 3' and 5' direction. These conserved regions were identified after sequence compilation of the 2nd intron of 143 clinical samples and 48 cell lines mostly from the 9th and 10th IHWC representing all serologically defined groups of alleles. This strategy allowed the use of only one 5' and one 3' sequencing primer regardless of the amplified allele. Therefore, it was possible to use dye terminator as well as dye primer sequencing chemistry. The amplification strategy allowed the separation of the haplotypes in almost all cases. Thus, an assignment of heterozygous positions requiring high sequencing quality was not necessary, allowing the application of Sequenase as well as TaqPolymerase as sequencing enzyme. Concerning the resolution of heterozygosity it is obvious that this approach is superior to a typing system using a single pair of generic primers followed by direct sequencing, since the latter technique is not capable of defining the cis/trans linkage of polymorphic sequences and, hence, cannot exclude the presence of unknown alleles.
Interface roughness and asymmetry in InAs/GaSb superlattices studied by scanning tunneling microscopy (1994)

InAs/GaSb superlattices are studied in cross section by scanning tunneling microscopy and spectroscopy. Electron subbands in 42 \AA{} thick InAs layers are clearly resolved in the spectra. Roughness of the superlattice interfaces is quantitatively measured. Interfaces of InAs grown on GaSb are found to be rougher, with different electronic properties, than those of GaSb on InAs, indicating some intermixing in the former case.
The Critical Role of Complement Alternative Pathway Regulator Factor H in Allergen-Induced Airway Hyperresponsiveness and Inflammation (2011)

Activation of the alternative pathway of complement plays a critical role in the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation in mice. Endogenous factor H, a potent inhibitor of the alternative pathway, is increased in the airways of sensitized and challenged mice, but its role in regulating inflammation or AHR has been unknown. We found that blocking the tissue-binding function of factor H with a competitive antagonist increased complement activation and tissue inflammation after allergen challenge of sensitized mice. Conversely, administration of a fusion protein that contains the iC3b/C3d binding region of complement receptor 2 linked to the inhibitory region of factor H, a molecule directly targeting complement-activating surfaces, protected mice in both primary and secondary challenge models of AHR and lung inflammation. Thus, although endogenous factor H does play a role in limiting the development of AHR, strategies to deliver the complement-regulatory region of factor H specifically to the site of inflammation provide greater protection than that afforded by endogenous regulators. Such an agent may be an effective therapy for the treatment of asthma.
Role of cell cycle regulatory molecules in retinoic acid‐ and vitamin D3‐induced differentiation of acute myeloid leukaemia cells (2014)

The important role of cell cycle regulatory molecules in all trans-retinoic acid (ATRA)- and vitamin D3-induced growth inhibition and differentiation induction has been intensively studied in both acute myeloid leukaemia primary cells and a variety of leukaemia cell lines. Cyclin-dependent kinases (CDK)-activating kinase has been demonstrated to interact with retinoic acid receptor (RAR)α in acute promyelocytic leukaemia cells, and inhibition of CDK-activating kinase by ATRA causes hypophosphorylation of PML-RARα, leading to myeloid differentiation. In many cases, downregulation of CDK activity by ATRA and vitamin D3 is a result of elevated p21- and p27-bound CDKs. Activation of p21 is regulated at the transcriptional level, whereas elevated p27 results from both (indirectly) transcriptional activation and post-translational modifications. CDK inhibitors (CKIs) of the INK family, such as p15, p16 and p18, are mainly involved in inhibition of cell proliferation, whereas CIP/KIP members, such as p21, regulate both growth arrest and induction of differentiation. ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Inhibition of cyclin E expression has only been observed in ATRA- but not in vitamin D3-treated leukaemic cells. In vitro, not only dephosphorylation of pRb but also elevation of total pRb is required for ATRA and vitamin D3 to suppress growth and trigger their differentiation. Finally, sharp reduction in c-Myc has been observed in several leukaemia cell lines treated with ATRA, which may regulate expression of CDKs and CKIs.
Effects of partial deletion of the wzm and wzt genes on lipopolysaccharide synthesis and virulence of Brucella abortus S19 (2014)

Brucellosis is a worldwide human and animal infectious disease, and the effective methods of its control are immunisation of animals by vaccination and elimination. Brucella abortus S19 is one of the popular vaccines with virulence in the control of cattle Brucellosis. In the present study, allelic exchange plasmids of wzm and wzt genes and partial knockout mutants of wzm and wzt were constructed to evaluate the resulting difference in virulence of B. abortus S19. PCR analysis revealed that the target genes were knocked out. The mutants were rough mutants and they could be differentiated from natural infection by the Rose Bengal plate and standard agglutination tests. The molecular weights of lipopolysaccharides of the Δwzm and Δwzt mutants were clustered between 25 and 40 kDa, and 30 and 35 kDa separately, and were markedly different from those in B. abortus S19. The virulence of B. abortus Δwzm and Δwzt was decreased compared with that of B. abortus S19 in mice. All these results identified that there were several differences between the wzm and wzt genes on lipopolysaccharide synthesis and on the virulence of B. abortus.
Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria (2015)

The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.
E Protein Domain III Determinants of Yellow Fever Virus 17D Vaccine Strain Enhance Binding to Glycosaminoglycans, Impede Virus Spread, and Attenuate Virulence (2008)

The yellow fever virus (YFV) 17D strain is one of the most effective live vaccines for human use, but the in vivo mechanisms for virulence attenuation of the vaccine and the corresponding molecular determinants remain elusive. The vaccine differs phenotypically from wild-type YFV by the loss of viscerotropism, despite replicative fitness in cell culture, and genetically by 20 amino acid changes predominantly located in the envelope (E) protein. We show that three residues in E protein domain III inhibit spread of 17D in extraneural tissues and attenuate virulence in type I/II interferon-deficient mice. One of these residues (Arg380) is a dominant glycosaminoglycan-binding determinant, which mainly accounts for more rapid in vivo clearance of 17D from the bloodstream in comparison to 17D-derived variants with wild-type-like E protein. While other mutations will account for loss of neurotropism and phenotypic stability, the described impact of E protein domain III changes on virus dissemination and virulence is the first rational explanation for the safety of the 17D vaccine in humans.
Resource-conscious customization of CORBA for CAN-based distributed embedded systems (2002)

While recently emerging middleware technologies such as CORBA and DCOM address the complexity of distributed programming, they cannot be directly applied to distributed control system design due to their excessive resource demand and inadequate communication models. We propose a new CORBA design for CAN-based distributed embedded control systems. Our design goal is to minimize its resource need and make it support group communication without losing the IDL (interface definition language) level compliance to the OMG standards. To achieve this, we develop a transport protocol on the CAN and a group communication scheme based on the well-known publisher/subscriber model. The protocol effectively realizes subject-based addressing and supports anonymous publisher/subscriber communication. We also customize the method invocation and message passing protocol, referred to as the general inter-ORB protocol (GIOP), of CORBA so that CORBA method invocations are efficiently serviced on a low-bandwidth network such as the CAN. This customization includes packed data encoding and variable-length integer encoding for compact representation of IDL data types. The new CORBA design clearly demonstrates that it is feasible to use CORBA in developing distributed embedded systems on real-time networks possessing severe resource limitations.
Light harvesting schemes for high-performance polymer solar cells (2010)

In this paper, we will present approaches for light harvesting for enhancing the performance of polymer solar cells. We have employed indium tin oxide (ITO) as an optical spacer in inverted structures. We have found that the optical interference effect led to spatial redistribution of the optical field in the devices, resulting in favorable distribution of photogenerated excitons. Therefore, the introduction of the ITO optical spacer at an appropriate thickness increased the short-circuit current density and the overall power conversion efficiency.
Expression of bone-specific genes by hypertrophic chondrocytes: Implications of the complex functions of the hypertrophic chondrocyte during endochondral bone development (1996)

Endochondral bone formation is one of the most extensively examined developmental sequences within vertebrates. This process involves the coordinated temporal/spatial differentiation of three separate tissues (cartilage, bone, and the vasculature) into a variety of complex structures. The differentiation of chondrocytes during this process is characterized by a progressive morphological change associated with the eventual hypertrophy of these cells. These cellular morphological changes are coordinated with proliferation, a columnar orientation of the cells, and the expression of unique phenotypic properties including type X collagen, high levels of bone, liver, and kidney alkaline phosphatase, and mineralization of the cartilage matrix. Several studies indicate that hypertrophic chondrocytes also express osteocalcin, osteopontin, and bone sialoprotein, three proteins which until very recently were widely believed to be restricted in their expression to osteoblasts. Recent studies suggest that the hypertrophic chondrocytes are regulated by the calcitropic hormones, morphogenic steroids, and local tissue factors. These considerations are based on the regulation by 1,25 (OH)2D3 and retinoids of the cartilage specific genes as well as osteopontin and osteocalcin expression in hypertrophic chondrocytes. They are also based on the effects on growth plate development caused by 1) transgenic ablation of autocrine/paracrine regulators such as PTHrP and of the transcriptional regulator c-fos and 2) naturally occurring genetic mutations of the FGF receptor. These studies further suggest that specific transcriptional factors mediate exogenous regulatory signals in a coordinated manner with the development of bone. While it has been widely demonstrated that the majority of hypertrophic chondrocytes undergo apoptosis during terminal stages of the developmental sequence, their response to specific exogenous regulatory signals and their expression of bone-specific proteins give rise to questions about whether all growth chondrocytes have the same developmental fates and have identical functions. Furthermore, specific questions arise as to whether there are similar mechanisms of regulation for commonly expressed genes found in both cartilage and bone or whether these genes have unique regulatory mechanisms in these different tissues. These recent findings suggest that hypertrophic chondrocytes are functionally coupled during endochondral bone formation to the recruitment of osteoblasts, vascular cells, and osteoclasts.
Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies (2016)

With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent or acquired resistance and to be more efficient angiogenesis inhibitors. Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies also have broad application prospects in bone disorders and infections and diseases of the central nervous system. The latest developments of the formats and application of bispecific antibodies will be reviewed. Furthermore, the challenges and perspectives are summarized in this review.
Milk flavor quality on the farm (1986)

Milk consumption is influenced by the quality and flavor of the milk a person drinks. Today the consumer evaluates milk solely on its taste and keeping quality. Since the flavor of milk cannot be improved after it leaves the dairy farm, it is of the utmost importance to produce milk with the best flavor quality possible. Milk is a highly perishable food and must be produced under conditions that will ensure keeping quality. Generally speaking, dairymen are doing a good job of producing high quality milk but we need to be aware that problems may occur with feeding, cow health, cleaning, sanitizing and general handling of the milk. It is important to know what is good tasting milk and then use this standard to produce top quality milk free of off flavors. Following are brief discussions regarding some of the milk flavor problems that still exist today, with suggestions on how to reduce these problems.; Dairy Day, 1986, Kansas State University, Manhattan, KS, 1986;
Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes (1993)

The cytochrome P-450 3A gene family comprises the dominant forms of cytochrome P-450 found in human liver. We examined as a possible useful system for studying the regulation of cytochrome P-450 3A under controlled conditions in vitro, primary monolayer cultures of human hepatocytes and compared the results with those obtained from the study of cytochrome P-450 3A in the human hepatoblastoma cell line HepG2 or in the human hepatocellular carcinoma cell line TONG/HCC. Using 3A antibodies, 3A cDNAs and 3A3, 3A4, 3A5 and 3A7 isozyme-specific oligonucleotides as probes, we determined that primary human hepatocyte cultures routinely expressed a 3A3/4* immunoreactive protein and 3A mRNA. These gene products were well maintained for many days and were induced by treatment of the cultures with dexamethasone, phenobarbital, macrolide antibiotics, the HMG CoA reductase inhibitor lovastatin or an antifungal agent, clotrimazole. Of six donor livers examined, only two contained mRNA or protein for 3A5, a form found in only a few adult human subjects. In cultures prepared from one of these two livers, 3A5 mRNA was detectable for several days. In cultures of hepatocytes from the remaining four human livers that did not contain 3A5 mRNA or protein, we detected neither spontaneous nor inducible 3A5 proteins or mRNAs. HepG2 cells contained only 3A7 protein, a form found in human fetal liver, even after treatment with inducers. treatment of HepG2 cells with dexamethasone, macrolide antibiotics, phenobarbital and phenobarbital-like inducers or lovastatin produced dose-dependent induction of 3A7 mRNA and 3A7 immunoreactive protein. TONG/HCC cells contained 3A3, 3A4 and 3A5 mRNAs, but only 3A5 immunoreactive protein could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Sulfhydryl-modifying reagents reversibly inhibit binding of glucocorticoid-receptor complexes to DNA-cellulose (1984)

Glucocorticoid -receptor complexes from intact rat thymus cells incubated with [3H]dexamethasone at 0 degree C are in the nonactivated form and do not bind to DNA-cellulose. Upon being warmed, they are transformed to activated complexes that bind to DNA-cellulose at 0 degree C. We have found that treatment of dexamethasone-receptor complexes with the sulfhydryl-modifying reagents methyl methanethiosulfonate ( MMTS ) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), either before or after the warming, inhibits subsequent binding to DNA-cellulose. The effects of these reagents can be reversed at 0 degree C by dithioerythritol and other sulfhydryl-containing compounds. These results provide the first clear evidence that sulfhydryl-modifying reagents inhibit the binding of activated dexamethasone-receptor complexes to DNA-cellulose and suggest that sulfhydryl groups may be located in or near the DNA binding domain of the rat thymus glucocorticoid-receptor complex. Furthermore, addition of dithioerythritol at 0 degree C to nonactivated receptor complexes that have been treated with MMTS or DTNB produces a substantial increase in the capacity of these complexes to bind to DNA-cellulose, raising the possibility that sulfhydryl groups may be associated with a region on the receptor that plays a critical role in the activation process.