gebhart/patrepeval huggingface dataset:
Optimized procedure for renaturation of recombinant human bone morphogenetic protein‐2 at high protein concentration (2004)

The human gene encoding the mature form of bone morphogenetic protein-2 (hBMP-2), a dimeric disulfide-bonded protein of the cystine knot growth factor family, was expressed in recombinant Escherichia coli using a temperature-inducible expression system. The recombinant protein was produced in the form of cytoplasmic inclusion bodies and the effect of different variables on the renaturation of rhBMP-2 was investigated. In particular, variables such as pH, redox conditions, protein concentration, temperature, the presence of different types of aggregation suppressors, and host cell contaminants were studied with respect to their effect on aggregation during refolding and on the final renaturation yield of rhBMP-2. It is shown that the renaturation yield is particularly sensitive to pH, temperature, protein concentration, and the presence of aggregation suppressors. In contrast, little effect of the redox conditions and the ionic strength on the renaturation yield was observed, as equal yields were obtained in a broad range of reduced to oxidized glutathione ratios and concentrations of NaCl, respectively. The aggregation suppressor 2-(cyclohexylamino)ethanesulfonic acid (CHES) proved to be superior with respect to the final renaturation yield, although, in comparison to the more common arginine, it was less efficient in preventing aggregation of rhBMP-2 during refolding. Detergent washing of inclusion bodies was sufficient, as further purification of rhBMP-2 prior to refolding was without effect on the final renaturation yield. An increase in the concentration of renatured rhBMP-2 was achieved by a pulsed refolding procedure by which up to a total amount of 2.1 mg mL(-1) rhBMP-2 could be transferred in seven pulses into the renaturation buffer with an overall refolding yield of 38%, corresponding to 0.8 mg mL(-1) renatured dimeric rhBMP-2. Furthermore, a simplified purification procedure is presented that also includes freeze-drying for long-term storage of biologically active rhBMP-2. Finally, it is shown that the appearance of rhBMP-2 variants could be avoided by using a host strain overexpressing rare codon tRNAs.
Coordinated beamforming with limited feedback in the MIMO broadcast channel (2008)

In this paper, we propose a new joint optimization of linear transmit beamforming and receive combining vectors for the multiple-input multiple-output (MIMO) broadcast channel. We consider the transmission of a single information stream to two users with two or more receive antennas. Unlike past work in which iterative computation is required to design the beamformers, we derive specific formulations for the transmit beamformers for two active users via a power iteration and a generalized eigen analysis. To enable practical implementation, a new limited feedback algorithm is proposed that exploits the structure of the algorithm to avoid full channel quantization. The feedback overhead of the proposed algorithm is independent of the number of receive antennas. Monte Carlo simulations are used to evaluate the bit error rate and the sum rate performances of the proposed algorithm. Simulation results show that the proposed method performs close to the sum capacity of the MIMO broadcast channel even with limited feedback.
Di- and Oligonucleotide Synthesis Using <I>H</I>-Phosphonate Chemistry (2004)

In this chapter, a concise account of the synthesis of oligonucleotides using the H-phosphonate methodology is given. It includes various methods for the preparation of the starting material, nucleoside 3'-H-phosphonate monoesters, their conversion into dinucleoside H-phosphonate diesters, oxidative transformations of dinucleoside H-phosphonates into the corresponding phosphate and phosphorothioate derivatives, and protocols for the synthesis of oligonucleotides and their phosphorothio analogs.
Silicon-Organic Hybrid (SOH) Mach-Zehnder Modulators for 100 Gbit/s on-off Keying (2018)

Electro-optic modulators for high-speed on-off keying (OOK) are key components of short- and medium-reach interconnects in data-center networks. Small footprint, cost-efficient large-scale production, small drive voltages and ultra-low power consumption are of paramount importance for such devices. Here we demonstrate that the concept of silicon-organic hybrid (SOH) integration perfectly meets these challenges. The approach combines the unique processing advantages of large-scale silicon photonics with unrivalled electro-optic (EO) coefficients obtained by molecular engineering of organic materials. Our proof-of-concept experiments demonstrate generation and transmission of OOK signals at line rates of up to 100 Gbit/s using a 1.1 mm-long SOH Mach-Zehnder modulator (MZM) featuring a π-voltage of only 0.9 V. The experiment represents the first demonstration of 100 Gbit/s OOK on the silicon photonic platform, featuring the lowest drive voltage and energy consumption ever demonstrated for a semiconductor-based device at this data rate. We support our results by a theoretical analysis showing that the nonlinear transfer characteristic of the MZM can help to overcome bandwidth limitations of the modulator and the electric driver circuitry. We expect that high-speed, power-efficient SOH modulators may have transformative impact on short-reach networks, enabling compact transceivers with unprecedented efficiency, thus building the base of future interfaces with Tbit/s data rates.
An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo (1989)

Embryonic stem cells (ES) cells were injected into host blastocysts either in groups of 10-15 cells or as single cells in order to test their developmental potential in the developing embryo. The analysis of midgestation chimaeras, by electrophoretic separation of glucose phosphate isomerase (GPI) isozymes, showed that ES cells were capable of colonizing trophectoderm and primitive endoderm derivatives at a low frequency, as well as producing a high rate of chimaerism in tissues of the fetus and extraembryonic mesoderm.
Efficient adaptive media scaling and streaming of layered multimedia in heterogeneous environment (2003)

The fast increasing network connectivities to a wider range of end-users and cheaper and diverse end-user devices further exacerbate the need for adaptive and scalable streaming solutions. Motivated by these streaming requirements, we introduce the notion of a layered multimedia presentation and outline a framework for the media scaling and streaming of such presentations across heterogeneous networks to different end-user devices. Layered multimedia is designed to handle heterogeneous and fluctuating resource conditions by trading-off the presentation quality. Based on the results of streaming buffer effects, an efficient on-demand media scaling technique is devised to deliver the highest quality presentation to the end-users, according to their specific network bandwidth and device constraints. Once a presentation is selected, an associated on-the-fly transmission scheduling and streaming technique is used for the streaming of multimedia with high efficiency. Efficient media scaling and streaming reduce startup and quality switch delays and facilitates scalable media server design under heavy loads.
Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization (2012)

Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
Reduced uterine perfusion pressure induces hypertension in the pregnant mouse (2014)

Despite preeclampsia being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for its pathogenesis have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting placental ischemia triggers the cascade of events leading to this maternal disorder. While the well-established rat model of reduced uterine perfusion pressure (RUPP) is providing invaluable insight into the etiology of preeclampsia, the aim of this study was to develop a mouse model of reduced uterine perfusion to expand mechanistic investigation by incorporation with novel gene-targeted mice. To accomplish this aim, a sham surgical procedure or a restriction of blood flow at the abdominal aorta and the ovarian arteries was initiated at day 13 of gestation in C57BL/6J mice. Mean arterial pressure measured in conscious, chronically instrumented mice was significantly elevated in the RUPP (120 ± 4 mmHg) compared with the sham (104 ± 4 mmHg) mice at day 18 of gestation (P < 0.01). Placental ischemia reduced fetal weights (0.95 ± 0.04 and 0.80 ± 0.02 g; RUPP vs. Sham, respectively; P < 0.02) and increased circulating levels of antiangiogenic soluble fms-related tyrosine kinases (sFlt)-1 (P < 0.05) in the RUPP at day 18 of gestation. Plasma concentrations of sFlt-1 are increased in preeclamptic patients and in response to reduced uterine perfusion in the rat. Thus, these results suggest that the mouse model of reduced uterine perfusion is applicable to facilitate novel mechanistic investigation into the etiology of hypertension that results from placental ischemia during pregnancy.
The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae (2000)

Saccharomyces cerevisiae is able to use a wide variety of nitrogen sources for growth. Not all nitrogen sources support growth equally well. In order to select the best out of a large diversity of available nitrogen sources, the yeast has developed molecular mechanisms. These mechanisms consist of a sensing mechanism and a regulatory mechanism which includes induction of needed systems, and repression of systems that are not beneficial. The first step in use of most nitrogen sources is its uptake via more or less specific permeases. Hence the first level of regulation is encountered at this level. The next step is the degradation of the nitrogen source to useful building blocks via the nitrogen metabolic pathways. These pathways can be divided into routes that lead to the degradation of the nitrogen source to ammonia and glutamate, and routes that lead to the synthesis of nitrogen containing compounds in which glutamate and glutamine are used as nitrogen donor. Glutamine is synthesized out of ammonia and glutamate. The expression of the specific degradation routes is also regulated depending on the availability of a particular nitrogen source. Ammonia plays a central role as intermediate between degradative and biosynthetic pathways. It not only functions as a metabolite in metabolic reactions but is also involved in regulation of metabolic pathways at several levels. This review describes the central role of ammonia in nitrogen metabolism. This role is illustrated at the level of enzyme activity, translation and transcription
Kramers-Kronig Receiver Without Digital Upsampling (2018)

We propose a new Kramers-Kronig receiver which does not require digital upsampling. The experimental demonstration performed in 80-km transmission of 112-Gb/s SSB-OFDM signal shows that our proposed receiver exhibits similar performance to the conventional one.
Adenoviral Vectors Expressing siRNAs for Discovery and Validation of Gene Function (2003)

RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts.
Effect of T4 Count and Cofactors on the Incidence of AIDS in Homosexual Men Infected With Human Immunodeficiency Virus (1987)

We prospectively evaluated potential markers and cofactors for the acquired immunodeficiency syndrome (AIDS) in 86 homosexual men who were seropositive for human immunodeficiency virus antibodies. During three years of follow-up, 19 men developed AIDS. Risk of AIDS was clearly predicted by the total number of circulating OKT4-positive lymphocytes (T4 count) at enrollment, while the corresponding T8 count was unrelated to subsequent AIDS development. Subjects in Manhattan had a higher risk of Kaposi's sarcoma than did subjects in Washington, DC, and the risk of AIDS tended to increase with numerous homosexual partners. Several of 40 potential cofactors defined ex post facto, including receptive fellatio, enemas, methaqualone use, and high levels of antibody to hepatitis B surface antigen, appeared to be associated with Kaposi's sarcoma but not with Pneumocystis pneumonia. Our data suggest that potent cofactors for Pneumocystis pneumonia were not prominent, pointing to the need for effective drug therapies, particularly to reduce the high AIDS risk of persons with human immunodeficiency virus infection and low T4 counts.
Self-similar vortex clusters in the turbulent logarithmic region (2006)

The organization of vortex clusters above the buffer layer of turbulent channels is analysed using direct numerical simulations at friction Reynolds numbers up to $\hbox{\it Re}_{\tau}\,{=}\,1900$ . Especial attention is paid to a family of clusters that reach from the logarithmic layer to the near-wall region below $y^+\,{=}\,20$ . These tall attached clusters are markers of structures of the turbulent fluctuating velocity that are more intense than their background. Their lengths and widths are proportional to their heights $\Delta_y$ and grow self-similarly with time after originating at different wall-normal positions in the logarithmic layer. Their influence on the outer region is measured by the variation of their volume density with $\Delta_y$ . That influence depends on the vortex identification threshold, and becomes independent of the Reynolds number if the threshold is low enough. The clusters are parts of larger structures of the streamwise velocity fluctuations whose average geometry is consistent with a cone tangent to the wall along the streamwise axis. They form groups of a few members within each cone, with the larger individuals in front of the smaller ones. This behaviour is explained considering that the streamwise velocity cones are ‘wakes’ left behind by the clusters, while the clusters themselves are triggered by the wakes left by yet larger clusters in front of them. The whole process repeats self-similarly in a disorganized version of the vortex-streak regeneration cycle of the buffer layer, in which the clusters and the wakes spread linearly under the effect of the background turbulence. These results characterize for the first time the structural organization of the self-similar range of the turbulent logarithmic region.
Guidelines for Management of Small Pulmonary Nodules Detected on CT Scans: A Statement from the Fleischner Society (2005)

Lung nodules are detected very commonly on computed tomographic (CT) scans of the chest, and the ability to detect very small nodules improves with each new generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years or older have pulmonary nodules on CT scans. However, the existing guidelines for follow-up and management of noncalcified nodules detected on nonscreening CT scans were developed before widespread use of multi-detector row CT and still indicate that every indeterminate nodule should be followed with serial CT for a minimum of 2 years. This policy, which requires large numbers of studies to be performed at considerable expense and with substantial radiation exposure for the affected population, has not proved to be beneficial or cost-effective. During the past 5 years, new information regarding prevalence, biologic characteristics, and growth rates of small lung cancers has become available; thus, the authors believe that the time-honored requirement to follow every small indeterminate nodule with serial CT should be revised. In this statement, which has been approved by the Fleischner Society, the pertinent data are reviewed, the authors' conclusions are summarized, and new guidelines are proposed for follow-up and management of small pulmonary nodules detected on CT scans.
Functional Beta Cell Mass from Device-Encapsulated hESC-Derived Pancreatic Endoderm Achieving Metabolic Control (2018)

Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice. This study with device-encapsulated hES-PE (4 × 10<sup>6</sup> cells/mouse) determines the biologic characteristics at which implants establish metabolic control during a 50-week follow-up. A metabolically adequate FBM was achieved by (1) formation of a sufficient beta cell number (>0.3 × 10<sup>6</sup>/mouse) at >50% endocrine purity and (2) their maturation to a functional state comparable with human pancreatic beta cells, as judged by their secretory responses during perifusion, their content in typical secretory vesicles, and their nuclear NKX6.1-PDX1-MAFA co-expression. Assessment of FBM in implants and its correlation with in vivo metabolic markers will guide clinical translation of stem cell-derived grafts in diabetes.
Sequential action of six virus-encoded DNA-packaging RNAs during phage phi29 genomic DNA translocation (1997)

A 120-base pRNA encoded by bacteriophage b29 has a novel and essential role in genomic DNA packaging. Six DNA-packaging RNAs (pRNAs) were bound to the sixfold symmetrical portal vertex of procapsids during the DNA translocation process and left the procapsid after the DNA-packaging reaction was completed, suggesting that the pRNA participated in the translocation of genomic DNA into procapsids. To further investigate the mechanism of DNA packaging, it is crucial to determine whether these six pRNA molecules work as an integrated entity or each pRNA acts as a functional individual. If pRNAs work individually, then do they work in sequence with communication or in random order without interaction? Results from compensation and complementation analysis did not support the integrated model. Computation of the probability of combination between wild-type and mutant pRNAs and experimental data of competitive inhibition excluded the random model while favoring the proposal that the six pRNAs functioned sequentially. Sequential action of the pRNA also explains why the pRNA is so sensitive to mutation, since the effect of a pRNA mutation will be amplified by 6 orders of magnitude after six consecutive steps, resulting in the observed complete loss of DNA-packaging activity caused by small alterations. When any one of the six pRNAs was replaced with an inactive one, complete blockage of DNA packaging resulted, strongly supporting the speculation that individual pRNAs, presumably together with other components such as the packaging ATPase gp16, take turns mediating successive steps of packaging. Although the data provided here could not exclude the integrated model completely, there is no evidence so far to argue against the model of sequential action.
G-protein-coupled receptors, phosphoinositide hydrolysis, and cell proliferation. (1991)

Great interest is currently being focused on understanding signal transduction by growth factor receptors. Depending on their molecular structure and mechanism of transmembrane signaling, cell surface receptors fall into separate categories, the best known examples of which are the family of growth factor tyrosine kinase receptors and the G-protemn3-coupled receptors possessing seven membrane-spanning domains. Many “early” biochemical events in response to growth factor receptor activation have been identified to date, but to link these early changes (detectable within minutes) with the ultimate stimulation of DNA synthesis, occurring at least 10-20 h later, remains a central problem in the growth factor field. Yet, there are compelling reasons to believe that the initial biochemical events are of critical importance,
Glutamatergic Approaches to the Treatment of Cognitive and Behavioural Symptoms of Alzheimer’s Disease (2008)

The glutamatergic system has long been recognised for its role in learning and memory and recent studies indicate an early loss of glutamatergic synapses in Alzheimer's disease (AD). Efforts to produce drugs which address changes in the glutamatergic system in AD are well advanced (e.g. memantine and drugs in development such as ampakines). Much less is known about the possible role of glutamate in non-cognitive behavioural changes; however, recent data from clinical trials suggest that memantine reduces agitation and aggressive behaviour in AD patients. In this context, it is important to help identify new treatment approaches to replace the use of antipsychotics in this vulnerable population.
Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97 (2001)

Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.
A Fault-Tolerant Communication Library for Grid Environments (2003)

With increasing numbers of processors and applications running in virtual Grid environments, application level fault-tolerance is getting more of an important issue. This paper presents the semantics of a fault tolerant version of the Message Passing Interface, the de-facto standard for communication in scientific applications, which gives applications the possibility to recover from a node or link error and continue execution in a well defined way. The architecture of FT-MPI, an implementation of MPI using the semantics presented above as well as some tools supporting end-users during the application development step with FT-MPI are presented. Furthermore, a performance comparison of FT-MPI to the most relevant MPI-libraries for point-to-point benchmarks and the High Performance Linpack Benchmark, is shown.