gebhart/patrepeval huggingface dataset:
Dual asymmetric PCR: one-step construction of synthetic genes. (1992)

We have developed a one-step process for constructing synthetic genes. Four adjacent oligonucleotides 17-100 bases in length having short overlaps of 15-17 bases are used as primers in a PCR mixture. The quantity of the two internal primers is highly limited, and the resultant reaction causes an asymmetric single-stranded amplification of the two halves of the total sequence due to an excess of the two flanking primers. In subsequent PCR cycles, these dual asymmetrically amplified fragments, which overlap each other, yield a double-stranded, full-length product.
Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines. (1993)

The cyclin D1 gene can be transcriptionally activated in lymphoid tumours as a result of chromosomal rearrangements but is normally silent in B and T lymphocytes. By isolating cyclin D1-related cDNAs from a B-lymphoid cell line, we identified clones that contain the coding sequences of human cyclin D2. The predicted 289 amino acid protein shares 63% identity with human cyclin D1. Although cyclin D2 transcripts were detected in many lymphoid cell lines, it was not ubiquitously expressed and there was no apparent correlation with cyclin D1 levels. For example, two B-cell leukaemia lines, JVM-2 and Karpas 620, both of which have 11q13 translocations and express cyclin D1, contained markedly different amounts of cyclin D2. An obvious distinction between these cells is that the JVM-2 line, which expresses high levels of cyclin D2, was immortalized by Epstein-Barr virus (EBV). We subsequently found that cyclin D2 is consistently expressed in group III Burkitt's lymphoma (BL) and in lymphoblastoid cell lines immortalized by EBV, but not in group I BLs, in which expression of the EBV genome is more restricted. The data imply that the D-type cyclins may have non-overlapping functions at specific stages of lymphocyte differentiation and that the expression of cyclin D2 may be influenced, directly or indirectly, by EBV.
Band alignments of coherently strained GexSi1−x/Si heterostructures on 〈001〉 GeySi1−y substrates (1986)

The self-consistent ab initio pseudopotential results of C. G. Van de Walle and R. M. Martin [J. Vac. Sci. Technol. B 3, 1256 (1985)] have been combined with a phenomenological deformation potential theory to estimate the band gap and band offsets for coherently strained multilayers of GexSi1−x/Si for growth on 〈001〉 GeySi1−y substrates. It is found that ΔEc is negligible and the narrower GexSi1−x gap falls within the wider Si gap (type I band alignment) if the Si in the multilayers is cubic, whereas ΔEc can be appreciable and the GexSi1−x conduction-band edge tends to be higher in energy than the Si conduction-band edge(type II band alignment) if both the Si and the GexSi1−x are strained. In particular, the present results resolve the seeming paradox which arose from interpretations of modulation doping experiments using heterojunctions grown either on Si〈001〉 substrates or on an unstrained alloy buffer layer.
The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. (1990)

We have determined the domains of the mammalian high mobility group (HMG)I chromosomal proteins necessary and sufficient for binding to the narrow minor groove of stretches of A.T-rich DNA. Three highly conserved regions within each of the known HMG-I proteins is closely related to the consensus sequence T-P-K-R-P-R-G-R-P-K-K. A synthetic oligopeptide corresponding to this consensus "binding domain" (BD) sequence specifically binds to substrate DNA in a manner similar to the intact HMG-I proteins. Molecular Corey-Pauling-Koltun model building and computer simulations employing energy minimization programs to predict structure suggest that the consensus BD peptide has a secondary structure similar to the antitumor and antiviral drugs netropsin and distamycin and to the dye Hoechst 33258. In vitro these ligands, which also preferentially bind to A.T-rich DNA, have been demonstrated to effectively compete with both the BD peptide and the HMG-I proteins for DNA binding. The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins. The predicted BD peptide structure, which we refer to as the "A.T-hook," represents a previously undescribed DNA-binding motif capable of binding to the minor groove of stretches of A.T base pairs.
MatInspector and beyond: promoter analysis based on transcription factor binding sites (2005)

Motivation: Promoter analysis is an essential step on the way to identify regulatory networks. A prerequisite for successful promoter analysis is the prediction of potential transcription factor binding sites (TFBS) with reasonable accuracy. The next steps in promoter analysis can be tackled only with reliable predictions, e.g. finding phylogenetically conserved patterns or identifying higher order combinations of sites in promoters of co-regulated genes. Results: We present a new version of the program MatInspector that identifies TFBS in nucleotide sequences using a large library of weight matrices. By introducing a matrix family concept, optimized thresholds, and comparative analysis, the enhanced program produces concise results avoiding redundant and false-positive matches. We describe a number of programs based on MatInspector allowing in-depth promoter analysis (DiAlignTF, FrameWorker) and targeted design of regulatory sequences (SequenceShaper). Availability: MatInspector and the other programs described here can be used online at http://www.genomatix.de/matinspector.html. Access is free after registration within certain limitations (e.g. the number of analysis per month is currently limited to 20 analyses of arbitrary sequences). Contact: cartharius@genomatix.de Supplementary information: http://www.genomatix.de/matinspector.html
Use of Laparoscopy for Impalpable Testis (1996)

Laparoscopic intervention was successfully performed in twelve patients between 1.5 and 11.5 years of age, who had fourteen impalpable testes. Six of the 14 testes (43%) were found to be intraabdominally located. Simple orchiopexy was performed in four of them, and laparoscopic orchiectomy was do,ie smoothly in the other two due to severely hypo plastic changes of the testes and the ages of the patients. Two cases (14%) were found to have intra-abdominal vanishing testis with blind ends of vas deferens and obliterated spermatic vessels observed separately proximal to the internal inguinal ring. Vas deferens and spermatic vessels were noted to converge at the internal ring with patent processus vaginalis in five cases (six testes); inguinal exploration showed 5 testes of varying degrees of hypoplastic changes and one inguinal vanishing testis. Laparoscopic intervention is an important tool in the cryptorchid patients with impalpable testes because it can not only provide accurate diagnosis, well planning of the incisional site and minimal invasiveness, but also avoid unnecessary surgical exploration in the cases of intra-abdominal vanish testis.
Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS (2016)

Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy.
Trehalose transport and metabolism in Escherichia coli (1990)

Trehalose metabolism in Escherichia coli is complicated by the fact that cells grown at high osmolarity synthesize internal trehalose as an osmoprotectant, independent of the carbon source, although trehalose can serve as a carbon source at both high and low osmolarity. The elucidation of the pathway of trehalose metabolism was facilitated by the isolation of mutants defective in the genes encoding transport proteins and degradative enzymes. The analysis of the phenotypes of these mutants and of the reactions catalyzed by the enzymes in vitro allowed the formulation of the degradative pathway at low osmolarity. Thus, trehalose utilization begins with phosphotransferase (IITre/IIIGlc)-mediated uptake delivering trehalose-6-phosphate to the cytoplasm. It continues with hydrolysis to trehalose and proceeds by splitting trehalose, releasing one glucose residue with the simultaneous transfer of the other to a polysaccharide acceptor. The enzyme catalyzing this reaction was named amylotrehalase. Amylotrehalase and EIITre were induced by trehalose in the medium but not at high osmolarity. treC and treB encoding these two enzymes mapped at 96.5 min on the E. coli linkage map but were not located in the same operon. Use of a mutation in trehalose-6-phosphate phosphatase allowed demonstration of the phosphoenolpyruvate- and IITre-dependent in vitro phosphorylation of trehalose. The phenotype of this mutant indicated that trehalose-6-phosphate is the effective in vivo inducer of the system.
The RNA element encoded by the trans-activation-responsive region of human immunodeficiency virus type 1 is functional when displaced downstream of the start of transcription. (1995)

The human immunodeficiency virus type 1 (HIV-1) trans-activator protein, Tat, specifically stimulates transcription from the viral long terminal repeat. Tat binds to an RNA stem-loop structure encoded by the trans-activation response region (TAR). To test whether TAR is functional when displaced downstream of the start of transcription, we assayed a series of templates carrying duplicated TAR elements in cell-free transcription systems. When the normally positioned TAR element (TAR-1) is inactivated by mutations in either the Tat binding site or the apical loop sequence, which acts as the binding site for a cellular factor, transactivation can be rescued by a wild-type TAR element placed downstream (TAR-2). The TAR-2 element is functional even when placed > 200 nt downstream of TAR-1. TAR complementation experiments have also shown that a functional TAR element requires both an intact Tat binding site and an intact apical loop sequence. For example, if TAR-1 carries a mutation in the loop element it cannot be rescued by a TAR-2 element carrying a mutation in the Tat binding site. Substitution mutations in TAR-1 show that the 5' half of TAR also encodes an essential DNA element which is required for efficient transcription initiation. These results strongly suggest that Tat and cellular cofactors which bind TAR RNA associate with the transcription complex during its transit through TAR.
Characterization of a Novel Human-Specific STING Agonist that Elicits Antiviral Activity Against Emerging Alphaviruses (2015)

Pharmacologic stimulation of innate immune processes represents an attractive strategy to achieve multiple therapeutic outcomes including inhibition of virus replication, boosting antitumor immunity, and enhancing vaccine immunogenicity. In light of this we sought to identify small molecules capable of activating the type I interferon (IFN) response by way of the transcription factor IFN regulatory factor 3 (IRF3). A high throughput in vitro screen yielded 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (referred to herein as G10), which was found to trigger IRF3/IFN-associated transcription in human fibroblasts. Further examination of the cellular response to this molecule revealed expression of multiple IRF3-dependent antiviral effector genes as well as type I and III IFN subtypes. This led to the establishment of a cellular state that prevented replication of emerging Alphavirus species including Chikungunya virus, Venezuelan Equine Encephalitis virus, and Sindbis virus. To define cellular proteins essential to elicitation of the antiviral activity by the compound we employed a reverse genetics approach that utilized genome editing via CRISPR/Cas9 technology. This allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. Biochemical analysis indicates that G10 does not bind to STING directly, however. Thus the compound may represent the first synthetic small molecule characterized as an indirect activator of human STING-dependent phenotypes. In vivo stimulation of STING-dependent activity by an unrelated small molecule in a mouse model of Chikungunya virus infection blocked viremia demonstrating that pharmacologic activation of this signaling pathway may represent a feasible strategy for combating emerging Alphaviruses.
Putrescine N-Methyltransferase in Cultured Roots of Hyoscyamus albus (1992)

Biosynthesis of tropane alkaloids is thought to proceed by way of the diamine putrescine, followed by its methylation by putrescine N-methyltransferase (PMT; EC 2.1.1.53). High PMT activities were found in branch roots and/or cultured roots of several solanaceous plants. PMT was partially purified and characterized from cultured roots of Hyoscyamus albus that contain hyoscyamine as the main alkaloid. Initial velocity studies and product inhibition patterns of PMT are consistent with an ordered bi-bi mechanism, in which the K(m) values for putrescine and S-adenosyl-l-methionine are 277 and 203 mum, respectively, and the K(i) value for S-adenosyl-l-homocysteine is 110 mum. PMT efficiently N-methylated amines that have at least two amino groups separated by three or four methylene groups. Monoamines were good competitive inhibitors of PMT, among which n-butylamine, cyclohexylamine, and exo-2-aminonorbornane were most inhibitory, with respective K(i) values of 11.0, 9.1, and 10.0 mum. When n-butylamine was fed to root cultures of H. albus, the alkamine intermediates (tropinone, tropine, and pseudotropine) drastically decreased at 1 mm of the exogenous monoamine, and the hyoscyamine content decreased by 52% at 6 mm, whereas the contents of 6beta-hydroxyhyoscyamine and scopolamine did not change. Free and conjugated forms of polyamines were also measured. The n-butylamine treatment caused a large increase in the putrescine content (especially in the conjugated pool), and the spermine content also increased slightly, whereas the spermidine content decreased slightly. The increase in the putrescine pool size (approximately 40 nmol/mg dry weight) was large enough to account for the decrease in the total alkaloid pool size. Similar results were also obtained in root cultures of Datura stramonium. These studies further support the role of PMT as the first committed enzyme specific to alkaloid biosynthesis.
HRTF phase synthesis via sparse representation of anthropometric features (2014)

We propose a method for the synthesis of the phases of Head-Related Transfer Functions (HRTFs) using a sparse representation of anthropometric features. Our approach treats the HRTF synthesis problem as finding a sparse representation of the subjects anthropometric features w.r.t. the anthropometric features in the training set. The fundamental assumption is that the group delay of a given HRTF set can be described by thWe propose a method for the synthesis of the phases of Head-Related Transfer Functions (HRTFs) using a sparse representation of anthropometric features. Our approach treats the HRTF synthesis problem as finding a sparse representation of the subjects anthropometric features w.r.t. the anthropometric features in the training set. The fundamental assumption is that the group delay of a given HRTF set can be described by the same sparse combination as the anthropometric data. Thus, we learn a sparse vector that represents the subjects anthropometric features as a linear superposition of the anthropometric features of a small subset of subjects from the training data. Then, we apply the same sparse vector directly on the HRTF group delay data. For evaluation purpose we use a new dataset, containing both anthropometric features and HRTFs. We compare the proposed sparse representation based approach with ridge regression and with the data of a manikin (which was designed based on average anthropometric data), and we simulate the best and the worst possible classifiers to select one of the HRTFs from the dataset. For objective evaluation we use the mean square error of the group delay scaling factor. Experiments show that our sparse representation outperforms all other evaluated techniques, and that the synthesized HRTFs are almost as good as the best possible HRTF classifier.e same sparse combination as the anthropometric data. Thus, we learn a sparse vector that represents the subjects anthropometric features as a linear superposition of the anthropometric features of a small subset of subjects from the training data. Then, we apply the same sparse vector directly on the HRTF group delay data. For evaluation purpose we use a new dataset, containing both anthropometric features and HRTFs. We compare the proposed sparse representation based approach with ridge regression and with the data of a manikin (which was designed based on average anthropometric data), and we simulate the best and the worst possible classifiers to select one of the HRTFs from the dataset. For objective evaluation we use the mean square error of the group delay scaling factor. Experiments show that our sparse representation outperforms all other evaluated techniques, and that the synthesized HRTFs are almost as good as the best possible HRTF classifier.
Novel indole-2-carboxylates as ligands for the strychnine-insensitive N-methyl-D-aspartate-linked glycine receptor (1991)

A series of indole-2-carboxylates were prepared and evaluated for their ability to inhibit the binding at the strychnine-insensitive glycine receptor that is associated with the NMDA-PCP-glycine receptor complex. All of the compounds were selective for the glycine site relative to other sites on the receptor macrocomplex and several of the compounds in this series were found to have submicromolar affinity for this receptor. The lead compound, 2-carboxy-6-chloro-3-indoleacetic acid (Ki = 1.6 microM vs [3H]glycine), was also found to noncompetitively inhibit the binding of MK-801, a ligand for the phencyclidine site on the receptor macrocomplex. These latter data suggest that the compound functions as an antagonist at the strychnine-insensitive glycine receptor. The structural activity relationships within this series of indole-2-carboxylates is discussed and several key pharmacophores are identified for this series of glycine ligands. In general, the most potent compounds were the C-3 acetamides, with N-propyl-2-carboxy-6-chloro-3-indoleacetamide having the highest receptor affinity.
Efficient synthesis of glycosylated phenazine natural products and analogs with DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors (2003)

Inspired by the occurrence and function of phenazines in natural products, new glycosylated analogs were designed and synthesized. DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors were used in an efficient and easily-handled glycosylation protocol compatible with combinatorial chemistry. Benzoylated D-glucose, D-galactose and L-quinovose DISAL glycosyl donors were synthesized in high yields and used under mild conditions to glycosylate methyl saphenate and 2-hydroxyphenazine. The glycosides were screened for biological activity and one compound showed inhibitory activity towards topoisomerase II.
Simulated annealing for phasing using spatial constraints (1995)

Phase refinement using partial structural information is an important step in the treatment of crystallographic data. An optimization procedure is presented that, in contrast to conventional Fourier methods, takes into account the spatial dependence of the accuracy of the partial information for electron density. Annealing studies for a test case show that this optimization procedure is tractable for system sizes relevant to the treatment of protein diffraction data and requires substantially less structural information for accurate phase refinement than Fourier methods.
Effects of low-dose, noncytotoxic, intraarticular liposomal clodronate on development of erosions and proteoglycan loss in established antigen-induced arthritis in rabbits (2001)

Liposomal clodronate had temporary antiinflammatory and antierosive effects on established AIA in rabbits. Over the long-term, the loss of cartilage proteoglycans was halted. This observed treatment effect may be related to the inhibition of TNFalpha production and processing in the synovium.
mRNA-based gene transfer as a tool for gene and cell therapy. (2007)

In the field of nonviral gene therapy, mRNA-based gene transfer has generated much interest over the last decade. The combination of RNA as a versatile protein delivery molecule and the dendritic cell as the most potent antigen-presenting cell is an attractive approach to induce cellular and potentially therapeutic immune responses in patients with cancer. The success of mRNA transfection stems from its superior cytoplasmic expression efficiency, simplicity over viral transduction protocols, and clinical safety profile (due to a strictly transient expression and inability to integrate into the host genome). Most researchers have exploited low-voltage electrical pulses (electroporation) as a means to introduce RNA into cells, but other methods with an even higher degree of in vivo applicability are under development. Recently, more insights into the immunological properties of RNA and optimized strategies to produce highly translatable mRNA have increased its efficacy in cellular vaccination. In addition, application of RNA gene transfer into areas other than immunotherapy are slowly emerging and underscore the potential of RNA transfection as a versatile gene therapy tool.
High quality embedded wideband speech coding using an inherently layered coding paradigm (2002)

Presented is an embedded coding strategy for wideband signals using the multimode transform predictive coding (MTPC) framework. The design uses many of the inherently layered features of the original non-embedded MTPC including iterative bit assignments and frequency domain coding. The design also uses the mode decision of the MTPC to adapt the layering strategy to the type input signal. The result is a high quality embedded wideband coder with multiple enhancement layers and little compromise in performance when compared to non-embedded MTPC designs.