gebhart/patrepeval huggingface dataset:
Clonal variability within dihydrofolate reductase-mediated gene amplified Chinese hamster ovary cells: Stability in the absence of selective pressure (1998)

Recombinant Chinese hamster ovary (rCHO) cells expressing a high level of chimeric antibody were obtained by cotransfection of heavy- and light-chain cDNA expression vectors into dihydrofolate reductase-deficient CHO cells and subsequent gene amplification in medium containing stepwise increments in methotrexate (MTX) level up to 1.0 microM. To determine the clonal variability within the amplified cell population in regard to antibody production stability, 20 subclones were randomly isolated from the amplified cell population at 1.0 microM MTX (CS13-1.0 cells). Clonal analysis showed that CS13-1.0 cells were heterogeneous with regard to specific growth rate (mu) and specific antibody productivity (qAb), although they were derived from a single clone. The mu and qAb of 20 subclones were in the range of 0.51 to 0.72 day-1 and 10.9 to 19.1 microgram/10(6) cells/day, respectively. During 8 weeks of cultivation in the absence of selective pressure, the mu of most subclones did not change significantly. On the other hand, their qAb decreased significantly. Furthermore, the relative decrease in qAb varied among subclones, ranging from 30% to 80%. Southern and Northern blot analyses showed that this decreased qAb resulted mainly from the loss of amplified immunoglobulin (Ig) gene copies and their respective cytoplasmic mRNAs. For the sake of screening convenience, an attempted was made to correlate the initial properties of subclones (such as mu, qAb, and Ig gene copies) with their antibody production stability during long-term culture. Among these initial properties examined, only qAb of subclones could help to predict their stability to some extent. The subclones with high qAb were relatively stable with regard to antibody production during long-term culture in the absence of selective pressure (P < 0. 005, ANOVA). Taken together, the clonal heterogeneity in an amplified CHO cell population necessitates clonal analysis for screening stable clones with high qAb.
A Comparison of Budesonide and Mesalamine for Active Crohn's Disease (1998)

In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.
5.4 Watt GaAs MESFET MMIC for phased array radar systems (2002)

This paper describes a MMIC that has been designed using the GMMT Medium Power Foundry process which produces 5.4 Watts of power at 9.2 GHz with a PAE of 22%. Integral heatsink technology and power circuit design techniques have facilitated the design of a compact, densely packed circuit occupying 20 mm/sup 2/ of GaAs. The small signal gain of the MMIC is 16 dB, with a 10 dB input match from 9 to 11 GHz. This MMIC is suitable for many X-band applications such as communications networks and safety radiolocation systems, but its high pulsed power output and low phase-gain distortion make it particularly ideal for use in phased array radar systems.
An adaptive resolution rate control method for intra coding in HEVC (2016)

Previous work has shown that spatial resampling can improve rate-distortion performance by providing a higher and more consistent level of video quality at low bitrates. Rate control aims to regulate the video bitrate in accordance to the bit budget. While this is a well studied problem in the single resolution case, very little progress has been made on the adaptive resolution case. In this paper we present an enhanced method of rate control for intra coding that allows the algorithm to learn from previously coded frames and make more accurate predictions, resulting in a lower average mismatch ratio. Our main contribution, however, lies in our adaptive resolution approach where the best scale factor is selected after prediction of the best Quantisation Parameter (QP). We show that our method closely conforms to the bit budget and provides a more stable bitrate. The likelihood of frame skipping is therefore reduced and a more consistent level of video quality is provided compared to standard single resolution methods.
Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway (2015)

Extracellular matrix (ECM) remodeling regulates angiogenesis. However, the precise mechanisms by which structural changes in ECM proteins contribute to angiogenesis are not fully understood. Integrins are molecules with the ability to detect compositional and structural changes within the ECM and integrate this information into a network of signaling circuits that coordinate context-dependent cell behavior. The role of integrin αvβ3 in angiogenesis is complex, as evidence exists for both positive and negative functions. The precise downstream signaling events initiated by αvβ3 may depend on the molecular characteristics of its ligands. Here, we identified an RGD-containing cryptic collagen epitope that is generated in vivo. Surprisingly, rather than inhibiting αvβ3 signaling, this collagen epitope promoted αvβ3 activation and stimulated angiogenesis and inflammation. An antibody directed to this RGDKGE epitope but not other RGD collagen epitopes inhibited angiogenesis and inflammation in vivo. The selective ability of this RGD epitope to promote angiogenesis and inflammation depends in part on its flanking KGE motif. Interestingly, a subset of macrophages may represent a physiologically relevant source of this collagen epitope. Here, we define an endothelial cell mechano-signaling pathway in which a cryptic collagen epitope activates αvβ3 leading to an Src and p38 MAPK-dependent cascade that leads to nuclear accumulation of Yes-associated protein (YAP) and stimulation of endothelial cell growth. Collectively, our findings not only provide evidence for a novel mechano-signaling pathway, but also define a possible therapeutic strategy to control αvβ3 signaling by targeting a pro-angiogenic and inflammatory ligand of αvβ3 rather than the receptor itself.
HIV Envelope Induces Virus Expression from Resting CD4+ T Cells Isolated from HIV-Infected Individuals in the Absence of Markers of Cellular Activation or Apoptosis (2003)

Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir.
The development of anthelmintic resistance in sheep nematodes (2000)

Anthelmintic resistance now poses problems to sheep farmers throughout the world. In some Southern hemisphere countries multiple resistance has reached levels which make sheep farming non-sustainable. Evidence from studies in the UK and Europe suggests (a) that the selection process occurs over a longer time frame than in Southern tropical/temperate regions and (b) that for some of the key ovine species little or no reversion to susceptibility may occur for many years after the withdrawal of the selecting agent. The dynamics of the selection process are influenced by a number of host, parasite, drug, management and environment-dependent factors. Recent mechanistic studies on resistance against avermectins and milbemycins (AM) suggest that there may be a number of mechanisms associated with resistance at the different target sites for these drugs. Within Europe endectocides within the AM drug group have now become the crucial element in strategies aimed at controlling important diseases such as sheep scab and nematodoses. Given that there is little likelihood of a series of novel action compounds emerging in the immediate future to replace this family the conservation of efficacy of the AM group should be accorded the highest priority for research in this area.
Molecular mechanisms of cell and tissue interactions during early tooth development (1996)

Background Morphogenesis and cell differentiation during the development of all organs, including the tooth, are regulated by interactions between cells and tissues. The developing tooth is one of the organs in which the molecular mechanisms of such interactions are starting to be elucidated. Results Homotypic cell interactions take place between cells of the same developmental history, and they are a central mechanism in the formation of mesenchymal cell condensates during the bud stage of tooth development. Syndecan-1, a cell surface heparan sulfate proteoglycan, is transiently expressed in the dental mesenchyme and may regulate dental mesenchymal cell condensation. It binds tenascin, a matrix glycoprotein abundant in dental mesenchyme, suggesting involvement of cell-matrix interactions. Syndecan also binds growth factors, and its association with cell proliferation in the dental mesenchyme suggests roles in the regulation of cell number in the condensing cells. Inductive interactions between the epithelial and mesenchymal tissues regulate tooth development at all stages. In the early dental mesenchyme, the expression of several molecules, including syndecan and tenascin, are regulated by the epithelium. There is evidence that growth factors act as diffusible signals mediating these interactions. BMP-2 and BMP-4 (bone morphogenetic proteins), which belong to the TGFβ superfamily, are expressed in the early dental epithelium, and their effects on the dental mesenchyme mimic those of the epithelium. In particular, BMPs induce the expression of the homeobox-containing transcription factors Msx-1 and Msx-2 in the dental mesenchyme. Conclusions Based on current knowledge about the molecular changes accompanying tooth development and the results of experimental studies, we present a model for molecular regulation of early tooth development. © 1996 Wiley-Liss, Inc.
Inactive pharmaceutical ingredients : implications for pregnancy. (2007)

dministration of pharmaceutical agents to pregnant women is a concern, because of safety issues to both mother and fetus. However, all medication formulations contain many other inactive ingredients in addition to the active drug. In contrast to the extensive research on the safety of active pharmaceutical ingredients in pregnant patients, the fetal safety of the inactive ingredients has been largely ignored. This is likely due to the fact that the inactive ingredients are considered to be in “small amounts” and are believed to be “inert”. However, this is often not the case. Most pharmaceutical preparations will typically contain 5 to 10 times more inactive ingredients in terms of weight versus the actual active ingredients. Therefore, most tablets, for example, are mainly made up of inactive ingredients. It is common for a medicine to have a dozen or so inactive ingredients within its formulation acting as lubricants, fillers, binders, disintegrating agents, stabilizers or silica flow conditioners. Also, there are numerous oral liquid or syrup drugs that contain 15-20% of ethanol, the most widespread human teratogen. For instance, a patient taking 2 teaspoons of Choledyl elixir 4 times daily will absorb 8g of alcohol. This is equal to the amount of ethanol in one bottle of beer. The Kaletra (oral solution of lopinavir /ritonavir) contains a surprising 42.4% of ethanol (Table 1). As this review highlights, many chemicals that are commonly used as inactive ingredients in drugs have adverse effects on reproductions. These inactive ingredients have been described in variety of models, and most often the NoObserved-Adverse-Effect-Level (NOAEL) in humans has not yet been established. Given these examples, a manufacturer should employ a great deal of prudence while formulating drugs that contain ethanol or other unstudied alcohols destined to be consumed by pregnant women. Hence, it seems logical that rather than risking fetal safety, the use of such compounds as inactive ingredients should be restricted or banned. We propose that to study the safety of medications in pregnancy, one should apply the principles of teratology not only to the active ingredients, but also to the ingredients termed in-active. The basic principles of evaluating teratogenic potential have been articulated by scores of different authors and include the following: 1. Biological plausibility for teratogenic potential, including mechanism of action, periods of greatest sensitivity, and genetic susceptibility. 2. Analysis of dose-response relationships and pharmacokinetics in an animal model and in humans. 3. Analysis and interpretation of human epidemiologic studies. 4. The examination of the relationship between the secular trend of birth defects and the population exposure to drugs.
High dielectric constant gate oxides for metal oxide Si transistors (2005)

The scaling of complementary metal oxide semiconductor transistors has led to the silicon dioxide layer, used as a gate dielectric, being so thin (1.4 nm) that its leakage current is too large. It is necessary to replace the SiO2 with a physically thicker layer of oxides of higher dielectric constant (κ) or 'high K' gate oxides such as hafnium oxide and hafnium silicate. These oxides had not been extensively studied like SiO2, and they were found to have inferior properties compared with SiO2, such as a tendency to crystallize and a high density of electronic defects. Intensive research was needed to develop these oxides as high quality electronic materials. This review covers both scientific and technological issues—the choice of oxides, their deposition, their structural and metallurgical behaviour, atomic diffusion, interface structure and reactions, their electronic structure, bonding, band offsets, electronic defects, charge trapping and conduction mechanisms, mobility degradation and flat band voltage shifts. The oxygen vacancy is the dominant electron trap. It is turning out that the oxides must be implemented in conjunction with metal gate electrodes, the development of which is further behind. Issues about work function control in metal gate electrodes are discussed.
Eddy-Current Losses in Laminated and Solid Steel Stator Back Iron in a Small Rotary Brushless Permanent-Magnet Actuator (2008)

The ever-increasing necessity to miniaturize smooth torque rotary actuators has placed severe constraints on the current slotless permanent-magnet technology. These constraints are mainly the consequence of the relatively large effective magnetic airgap which limits the achievable magnetic loading and, therefore, the torque density of slotless permanent-magnet rotary actuators. Further, the miniaturization has to be achieved at ever-decreasing costs and, therefore, it would be advantageous to implement solid back irons. However this, even at reduced magnetic loading, still results in considerable eddy-current losses. Therefore, a careful selection of the various actuator dimensions and most appropriate soft magnetic laminated or solid material is a prerequisite for applications that require smooth speed and torque characteristic. This paper will identify the influence of various parameters of the slotless permanent-magnet actuator on the eddy-current loss in the back iron using both 2-D and 3-D finite-element analysis.
The optimal transform of motion-compensated frame difference images in a hybrid coder (1993)

Using the statistical model proposed by the authors (1992), various statistical characteristics of motion-compensated frame difference (MCFD) images are derived. It is shown that the optimum Karhunen-Loeve (KLT) or the MCFD images is in fact identical to that of the original image sequence in intraframe mode, and that the discrete cosine transform (DCT) remains near optimal. The study this provides insights into the working of the MPEG and H.261 coders, including the justification for using the same DCT for both intra and interframe modes. Experiments on standard image sequences confirm the accuracy of the statistical model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Recent Advances in Singlet Fission (2013)

A survey is provided of recent progress in the understanding of singlet fission, a spin-allowed process in which a singlet excited molecule shares its energy with a ground-state neighbor to produce two triplet excited molecules. It has been observed to occur in single-crystal, polycrystalline, and amorphous solids, on timescales from 80 fs to 25 ps, producing triplet yields as high as 200%. Photovoltaic devices using the effect have shown external quantum efficiencies in excess of 100%. Almost all the efficient materials are alternant hydrocarbons of the acene series or their simple derivatives, and it is argued that a wider structural variety would be desirable. The current state of the development of molecular structure design rules, based on first-principles theoretical considerations, is described along with initial examples of implementation.
Dynamic Measurements of the Position, Orientation, and DNA Content of Individual Unlabeled Bacteriophages (2016)

A complete understanding of the cellular pathways involved in viral infections will ultimately require a diverse arsenal of experimental techniques, including methods for tracking individual viruses and their interactions with the host. Here we demonstrate the use of holographic microscopy to track the position, orientation, and DNA content of unlabeled bacteriophages (phages) in solution near a planar, functionalized glass surface. We simultaneously track over 100 individual λ phages at a rate of 100 Hz across a 33 μm × 33 μm portion of the surface. The technique determines the in-plane motion of the phage to nanometer precision, and the height of the phage above the surface to 100 nm precision. Additionally, we track the DNA content of individual phages as they eject their genome following the addition of detergent-solubilized LamB receptor. The technique determines the fraction of DNA remaining in the phage to within 10% of the total 48.5 kilobase pairs. Analysis of the data reveals that under certain conditions, λ phages move along the surface with their heads down and intermittently stick to the surface by their tails, causing them to stand up. Furthermore, we find that in buffer containing high concentrations of both monovalent and divalent salts, λ phages eject their entire DNA in about 7 s. Taken together, these measurements highlight the potential of holographic microscopy to resolve the fast kinetics of the early stages of phage infection.
Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome (2001)

The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
Method for perfusion decellularization of porcine whole liver and kidney for use as a scaffold for clinical‐scale bioengineering engrafts (2014)

Our SDS-perfusion protocol can be used for porcine liver and kidney decellularization to obtain organ scaffolds cleared of cellular material, xenoimmunogens, and preserved vital ECM components.
Serial killing of tumor cells by cytotoxic T cells redirected with a CD19‐/CD3‐bispecific single‐chain antibody construct (2005)

Certain bispecific antibodies exhibit an extraordinary potency and efficacy for target cell lysis by eliciting a polyclonal T-cell response. One example is a CD19-/CD3-bispecific single-chain antibody construct (bscCD19xCD3), which at femtomolar concentrations can redirect cytotoxic T cells to eliminate human B lymphocytes, B lymphoma cell lines and patient-derived malignant B cells. Here we have further explored the basis for this high potency. Using video-assisted microscopy, bscCD19xCD3 was found to alter the motility and activity of T cells from a scanning to a killing mode. Individual T cells could eliminate multiple target cells within a 9 hr time period, resulting in nuclear fragmentation and membrane blebbing of target cells. Complete target cell elimination was observed within 24 hr at effector-to-target cell ratios as low as 1:5. Under optimal conditions, cell killing started within minutes after addition of bscCD19xCD3, suggesting that the rate of serial killing was mostly determined by T-cell movement and target cell scanning and lysis. At all times, T cells remained highly motile, and no clusters of T and target cells were induced by the bispecific antibody. Bystanding target-negative cells were not detectably affected. Repeated target cell lysis by bscCD19xCD3-activated T cells increased the proportion of CD19/CD3 double-positive T cells, which was most likely a consequence of transfer of CD19 from B to T cells during cytolytic synapse formation. To our knowledge, this is the first study showing that a bispecific antibody can sustain multiple rounds of target cell lysis by T cells.
Identification of Distinct Specificity Determinants in Resistance Protein Cf-4 Allows Construction of a Cf-9 Mutant That Confers Recognition of Avirulence Protein AVR4 (2001)

The tomato resistance genes Cf-4 and Cf-9 confer specific, hypersensitive response-associated recognition of Cladosporium carrying the avirulence genes Avr4 and Avr9, respectively. Cf-4 and Cf-9 encode type I transmembrane proteins with extracellular leucine-rich repeats (LRRs). Compared with Cf-9, Cf-4 lacks two LRRs and differs in 78 amino acid residues. To investigate the relevance of these differences for specificity, we exchanged domains between Cf-4 and Cf-9, and mutant constructs were tested for mediating the hypersensitive response by transient coexpression with either Avr4 or Avr9. We show that the number of LRRs is essential for both Cf-4 and Cf-9 function. In addition, Cf-9 specificity resides entirely in the LRR domain and appears to be distributed over several distant LRRs. In contrast, Cf-4 specificity determinants reside in the N-terminal LRR-flanking domain and three amino acid residues in LRRs 13, 14, and 16. These residues are present at putative solvent-exposed positions, and all are required for full Cf-4 function. Finally, we show that Cf-9 carrying the specificity determinants of Cf-4 has recognitional specificity for AVR4. The data indicate that diversifying selection of solvent-exposed residues has been a more important factor in the generation of Cf-4 specificity than has sequence exchange between Cf-4 progenitor genes. The fact that most variant residues in Cf-4 are not essential for Cf-4 specificity indicates that the diverse decoration of R proteins is not fully adapted to confer recognition of a certain avirulence determinant but likely provides a basis for a versatile, adaptive recognition system.