gebhart/patrepeval huggingface dataset:
Selection of IgG Variants with Increased FcRn Binding Using Random and Directed Mutagenesis: Impact on Effector Functions (2015)

Despite the reasonably long half-life of immunoglogulin G (IgGs), market pressure for higher patient convenience while conserving efficacy continues to drive IgG half-life improvement. IgG half-life is dependent on the neonatal Fc receptor (FcRn), which among other functions, protects IgG from catabolism. FcRn binds the Fc domain of IgG at an acidic pH ensuring that endocytosed IgG will not be degraded in lysosomal compartments and will then be released into the bloodstream. Consistent with this mechanism of action, several Fc-engineered IgG with increased FcRn affinity and conserved pH dependency were designed and resulted in longer half-life in vivo in human FcRn-transgenic mice (hFcRn), cynomolgus monkeys, and recently in healthy humans. These IgG variants were usually obtained by in silico approaches or directed mutagenesis in the FcRn-binding site. Using random mutagenesis, combined with a pH-dependent phage display selection process, we isolated IgG variants with improved FcRn-binding, which exhibited longer in vivo half-life in hFcRn mice. Interestingly, many mutations enhancing Fc/FcRn interaction were located at a distance from the FcRn-binding site validating our random molecular approach. Directed mutagenesis was then applied to generate new variants to further characterize our IgG variants and the effect of the mutations selected. Since these mutations are distributed over the whole Fc sequence, binding to other Fc effectors, such as complement C1q and FcγRs, was dramatically modified, even by mutations distant from these effectors' binding sites. Hence, we obtained numerous IgG variants with increased FcRn-binding and different binding patterns to other Fc effectors, including variants without any effector function, providing distinct "fit-for-purpose" Fc molecules. We therefore provide evidence that half-life and effector functions should be optimized simultaneously as mutations can have unexpected effects on all Fc receptors that are critical for IgG therapeutic efficacy.
The origin of ambergris (2006)

Early and modern theories of the origin of ambergris are described. Ambergris occurs in both male and female sperm whales, and also in the pygmy sperm whale. It occurs in about one in 100 sperm whales. The largest find weighed 455kg and sold for £23,000 in 1914. Ambergris occurs in the rectum of the whale but neither causes nor betrays disease. The rectum is not damaged by squid beaks. Indigestible material, that is, squid beaks and pens and the cuticles of parasitic nematode worms, are regularly vomited by sperm whales and the intestine and rectum can only deal with liquid faeces. When, as sometimes happens, some indigestible material leaks into the intestine and, by at least partly blocking the flow of the faeces, the tangled mass is pushed into the rectum where there is reason to believe that the water absorbing capacity of the rectum is increased (p. 33). In this way the faecal matter is precipitated on the indigestible material to form a smooth concretion and the faeces can pass again. Then more foecal material arrives and the process is repeated. In this way the flow of liquid faeces is maintained, although at the expense of accretionary growth in size of the coprolith which becomes ambergris. Response processes in the whale are constructional. The biochemical processes which transform the coprolith into ambergris are consequential upon its incubation over a long period in the peculiar environment of the rectum teeming with bacteria. Eventually the rectum stretches until it breaks, causing the whale's death and the ambergris is released into the sea.
Modeling of losses in a sandwiched-winding matrix transformer (1995)

This paper assesses the suitability of the sandwiched-winding matrix HF power transformer for low-profile applications from the loss standpoint. Finite-element simulations and experiments suggest that the core loss can be adequately characterized by approximating the matrix transformer as a collection of identical uncoupled elements. Thus, a matrix transformer with a large number of elements may have higher core loss than a conventional (tall) transformer, and more core loss than winding loss. Eddy-current analysis reveals that the interconnects which parallel the elements incur a significant fraction of the winding loss. Thus, load distribution is recommended to eliminate the paralleling interconnects in matrix transformers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular cloning of human interleukin 2 cDNA and its expression inE. coli (1983)

A recombinant plasmid containing human interleukin 2 (IL2) cDNA was identified in a cDNA library constructed from mRNA derived from PHA-TPA induced splenocytes. Using this cDNA as a hybridization probe, a DNA fragment containing the IL2 gene was isolated from a collection of hybrid phages derived from human genomic DNA. A unique reading frame was identified from the nucleotide sequence derived from these plasmids coding for a polypeptide of 153 amino acids and containing a putative signal sequence of 20 amino acids. A mature polypeptide starting with either Met-Ala-Pro or Met-Pro was expressed in E. coli under control of the E. coli trp promoter or using a combination of the phage lambda PL promoter and a ribosome binding site derived from phage Mu. The bacterial IL2 polypeptide had a molecular weight of 15,000 daltons and accounted for more than 10% of the total E. coli proteins in fully induced cells; it was biologically active in the T-cell specific DNA synthesis assay, even after recovery from a SDS-containing polyacrylamide gel.
Restriction Fragment Length Polymorphism of Porcine Reproductive and Respiratory Syndrome Viruses Recovered from Ontario Farms, 1998–2000 (2002)

From January 1998 to July 2000, 2,456 clinical samples, including lung, tonsil, lymph node, and serum, from 760 cases submitted to the Animal Health Laboratory, Ontario, Canada, were tested for porcine reproductive and respiratory syndrome viruses (PRRSV) using reverse transcriptase polymerase chain reaction (RT-PCR) and RT-PCR product restriction fragment length polymorphism (RFLP) analysis. A total of 516 samples from 284 cases were RT-PCR positive for the PRRSV open reading frame (ORF) 7 sequence. The RT-PCR RFLP typing assay was performed using 2 different sets of primers, amplifying 716 or 933 base pairs of ORF 4, 5, and 6 of PRRSV. Samples from 254 cases were typeable, yielding 34 different RFLP types. Of these, 164 cases had 32 different RFLP types of field or intermediate strains, 86 had a pattern similar to a commercial PRRSV vaccine or VR 2332 strain of the virus, 4 had a RFLP type shared by another commercial vaccine and a field strain. In 4 cases, 2 different RFLP types were identified from tissues from different pigs that were submitted at the same time from the same farm. Of the 195 farms that submitted PRRSV PCR-positive samples, 48 submitted samples on more than 1 occasion during the specified time frame. In 23 of those 48 farms, RFLP patterns of PRRSV differed between submissions, whereas in the other 25 farms, the RFLP pattern remained unchanged. There were 34 different PRRSV patterns identified from 236 cases using the primer set amplifying 716 base pairs of PRRSV. There were 18 cases, consisting of 9 different patterns, typeable only by using the primers amplifying a 933-base pair fragment of the virus.
Evolution of Block Copolymer Lithography to Highly Ordered Square Arrays (2008)

The manufacture of smaller, faster, more efficient microelectronic components is a major scientific and technological challenge, driven in part by a constant need for smaller lithographically defined features and patterns. Traditional self-assembling approaches based on block copolymer lithography spontaneously yield nanometer-sized hexagonal structures, but these features are not consistent with the industry-standard rectilinear coordinate system. We present a modular and hierarchical self-assembly strategy, combining supramolecular assembly of hydrogen-bonding units with controlled phase separation of diblock copolymers, for the generation of nanoscale square patterns. These square arrays will enable simplified addressability and circuit interconnection in integrated circuit manufacturing and nanotechnology.
A dynamic importance sampling methodology for the efficient estimation of rare event probabilities in regenerative simulations of queueing systems (2003)

Importance sampling (IS) is recognized as a potentially powerful method for reducing simulation runtimes when estimating the probabilities of rare events in communication systems using Monte Carlo simulation. When simulating networks of queues, regenerative techniques must be used to make the application of IS feasible and efficient. The application of regenerative techniques is also crucial in obtaining correct confidence intervals for the estimates involved. The authors present a methodology that uses IS dynamically, within each regeneration cycle, to drive the system back to the regeneration state, after an accurate estimate has been obtained. They also extend a technique developed earlier for finding near-optimal biasing parameters for link simulations to discrete-event simulations of queuing systems. The combination of these techniques was demonstrated by estimating blocking probabilities for the M/M/1/K, M/D/1/K, and GI/D/1/K queues. Improvement factors of thirteen to fourteen orders of magnitude were obtained for these examples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
How Much Training is Required for Multiuser Mimo? (2006)

An M-element antenna array (the base station) transmits, on the downlink, K les M sequences of QAM symbols selectively and simultaneously to K autonomous single-antenna terminals through a linear pre-coder that is the pseudo-inverse of an estimate of the forward channel matrix. We assume time-division duplex (TDD) operation, so the base station derives its channel estimate from tau <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rp</sub> pilot symbols which the terminals transmit on the reverse link. A coherence interval of T symbols is expended as follows: tau <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rp</sub> reverse pilot symbols, one symbol for computations, and (T-l-tau <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rp</sub> ) forward QAM symbols for each terminal For a given coherence interval, number of base station antennas, and forward- and reverse-SINR's we determine the optimum number of terminals to serve simultaneously and the optimum number of reverse pilot symbols to employ by choosing these parameters to maximize a lower bound on the net sum-throughput. The lower bound rigorously accounts for channel estimation error, and is valid for all SINR's. Surprisingly it is always advantageous to increase the number of base station antennas, even when the reverse SINR is low and the channel estimate poor: greater numbers of antennas enable us to climb out of the noise and to serve more terminals. Even within short coherence intervals (T= 10 symbols) and with low SINR's (-10.0 dB reverse, 0.0 dB forward) given large numbers of base station antennas (M ges 16 ) it is both feasible and advantageous to learn the channel and to serve a multiplicity of terminals simultaneously as well.
Low Diagnostic Yield of Elective Coronary Angiography (2010)

In this study, slightly more than one third of patients without known disease who underwent elective cardiac catheterization had obstructive coronary artery disease. Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice.
Down-regulation of MicroRNAs 222/221 in Acute Myelogenous Leukemia with Deranged Core-Binding Factor Subunits (2010)

Core-binding factor leukemia (CBFL) is a subgroup of acute myeloid leukemia (AML) characterized by genetic mutations involving the subunits of the core-binding factor (CBF). The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for leukemia development. One of the most common mutations associated with CBF mutations involves the KIT receptor. A high expression of KIT is a hallmark of a high proportion of CBFL. Previous studies indicate that microRNA (MIR) 222/221 targets the 3' untranslated region of the KIT messenger RNA and our observation that AML1 can bind the MIR-222/221 promoter, we hypothesized that MIR-222/221 represents the link between CBF and KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid differentiation of normal bone marrow AC133(+) stem progenitor cells. CBFL blasts with either t(8;21) or inv(16) CBF rearrangements with high expression levels of KIT (CD117) display a significantly lower level of MIR-222/221 expression than non-CBFL blasts. Consistently, we found that the t(8;21) AML1-MTG8 fusion protein binds the MIR-222/221 promoter and induces transcriptional repression of a MIR-222/221-LUC reporter. Because of the highly conserved sequence homology, we demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the 32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study provides the first hint that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining the concomitant occurrence of CBF genetic rearrangements and overexpression of wild type or mutant KIT in AML.
Synthesis and Structure–Activity Relationships of 1‐Benzyl‐4,5,6‐trimethoxyindoles as a Novel Class of Potent Antimitotic Agents (2009)

A series of 1-benzyl-4,5,6-trimethoxyindoles was designed and prepared as a novel class of potent antimitotic agents acting through the colchicine binding site of tubulin. Compounds 10 and 11 showed excellent antiproliferative activity with mean IC(50) values of 26 and 27 nM, respectively, in a diverse set of human cancer lines from different organs, including a MDR+ line. They also displayed substantial antitubulin efficacy with IC(50) values of 3.5 and 2.6 muM, respectively, representing an improvement over colchicine (IC(50)=4.3 muM).
Relation between blood flow velocities in the ophthalmic artery and in nailfold capillaries (1999)

Gaze evoked amaurosis in dysthyroid orbitopathyEDITOR,-Gaze evoked amaurosis is an uncommon symptom usually associated with intraconal masses such as cavernous haemangioma 1 or optic nerve sheath meningioma. 2 3 Patients describe transient loss of vision in eccentric positions of gaze with full recovery of vision on returning to the primary position.The cases previously published have all been unilateral.We describe a case of bilateral gaze evoked amaurosis in a patient with dysthyroid orbitopathy.
Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. (2011)

7505 Background: Met is associated with a poor outcome in many cancers, including NSCLC. Met activation is a mechanism of resistance to EGFR inhibition, supporting dual inhibition of Met/EGFR. MetMAb is a monovalent monoclonal antibody that specifically binds the Met receptor. Methods: OAM4558g is a global randomized, double-blind phase II study comparing MetMAb plus erlotinib (ME) to placebo plus erlotinib (PE) in 2nd/3rd line NSCLC. Tissue collection was mandatory to assess c-Met IHC expression levels (Met Dx). Co-primary endpoints were PFS in the Met Dx+ and ITT populations. Safety and OS were additional endpoints. Following the initial unblinding, Met Dx- patients (pts) were removed from ME. Results: 128 NSCLC pts were equally randomized to receive ME or PE. 95% of tissue was evaluable for c-Met IHC, 88% for EGFR and KRAS mutations (mut), and 75% for MET FISH. Baseline characteristics were well balanced. 54% of pts had Met Dx+ NSCLC, which was associated with a worse outcome (OS HR 2.52, PE cohort). A total of 99 PFS and 70 OS events have occurred, median follow up is 9.9mos. In the Met Dx+ group, ME resulted in a statistically and clinically significant improvement in both PFS and OS. An OS benefit from ME was observed in MET FISH+ NSCLC as well as in FISH-/IHC+; removing pts with EGFR mut did not alter results. Selective benefit of ME was not observed in other subgroups. E-related toxicities were comparable between treatment arms. Conclusions: Met Dx+ NSCLC represented more than half the population and was associated with a worse outcome. The addition of M to E in these pts significantly improved PFS and OS, resulting in a near 3-fold reduction in the risk of death. This benefit was not exclusive to EGFR mut or MET FISH+ and was observed in FISH-/IHC+ pts suggesting IHC is a more sensitive predictor of benefit from MetMAb. Median (mo) Population N PFS HR OS HR PE ME 95% CI P c-Met IHC+ 65 0.47 1.5 3.0 0.26–0.85 0.01 0.37 4.6 12.6 0.20–0.71 0.002 MET FISH+ (≥5 copies) 19 0.47 2.4 12.6 0.15–1.49 0.19 FISH-/IHC+ 37 0.44 3.6 7.1 0.17–1.15 0.09 FISH-/IHC+/EGFR wt 32 0.59 3.6 7.1 0.22–1.59 0.29 c-Met IHC-* 56 3.02 9.2 5.5 1.13–8.11 0.021 ITT* 128 1.09 8.2 7.1 0.62–1.91 0.76 * Initial data cut.
Chromosome instability with bleomycin and x-ray hypersensitivity in a boy with Nijmegen breakage syndrome (1997)

We report on a Mexican boy with microcephaly, short stature, and a high frequency of chromosome aberrations with rearrangements involving chromosomes 7 and 14, typical of ataxia telangiectasia (AT) patients. He had neither ataxia nor telangiectasia, and his immunological status and serum alpha feto protein (AFP) level were normal. Bleomycin hypersensitivity, which has been demon-strated in AT patients, was tested in the patient using AT and normal subjects for comparison. The frequency of spontaneously occurring chromosome aberrations in lymphocyte cultures was significantly higher in the patient and the AT patient than in the normal subject. Four cells from the patient showed structural rearrangements involving chromosomes 7 or 14, with breakpoints typical for AT. When exposed to 5.0 micrograms bleomycin, the lymphocytes from the AT patient showed the highest sensitivity to this agent; our patient had an intermediate sensitivity. In both patients several rearrangements involving chromosomes 7 and 14 were scored, while none were observed in the normal subject. A colony survival assay (CSA) [Huo et al., 1994: Cancer Res 54:2544-2547], using a lymphoblastoid cell line (LCL) derived from our patient, showed a survival fraction (SF) of 7%, which is in the same range as in AT patients. The clinical picture, together with the cytogenetic and radiosensitivity results, suggests that our patient fits the variable spectrum of Nijmegen breakage syndrome.
Suppression of EGFRvIII‐mediated proliferation and tumorigenesis of breast cancer cells by ribozyme (2003)

EGFRvIII is a tumor specific, ligand-independent, constitutively active variant of the epidermal growth factor receptor. Its expression has been detected in many human malignancies including breast cancer. No detectable level of EGFRvIII has, however, been observed in adult tissues, including normal breast tissues. These unique features of the EGFRvIII make it an excellent target for biologically based therapies. We have designed and generated a tumor specific ribozyme targeted to EGFRvIII. This specific EGFRvIII ribozyme is able to effectively cleave EGFRvIII mRNA under physiological conditions in a cell-free system, but does not cleave wild-type EGFR and other EGF-family receptors. While expressing this EGFRvIII-ribozyme in breast cancer cells, EGFRvIII-ribozyme is capable of downregulating endogenous EGFRvIII expression at the mRNA and protein levels. Inhibition of proliferation was observed in EGFRvIII-ribozyme transfectants. In addition, downregulation of EGFRvIII in breast cancer cells significantly inhibited tumor growth in athymic nude mice. Furthermore, this ribozyme has no effect on EGF-family receptor expression or the proliferation of breast cancer cells, which do not express EGFRvIII but express wild-type EGFR and other EGF-family receptors. These results suggest that we have generated a tumor-specific, biologically functional ribozyme and further demonstrate that EGFRvIII plays a significant role in breast cancer cell proliferation. The ultimate goal of this approach is to provide a potential treatment for breast cancer by specifically targeting this receptor.
Pulse Oximetry Plethysmographic Waveform During Changes in Blood Volume (1999)

Department of Anaesthesiology and CCM and Department of Orthopaedic Surgery, Hadassah Medical Center, Hebrew University Medical School, Jerusalem, Israel Br. J. Anesth., 82: 178-181, 1999
Interaction of omeprazole with enteric-coated salicylate tablets. (1998)

Findings of the present study demonstrate that omeprazole treatment significantly increases the rate of absorption of single-unit enteric-coated medication. Enhanced rate of absorption is most probably due to an early disruption of enteric coating and the intragastric release of the drug secondary to an omeprazole-mediated increase in gastric pH. The results of the present study also corroborate previous findings which have demonstrated highly variable absorption of enteric-coated single units.
THE ACTIVE TRANSPORT OF Mg++ AND Mn++ INTO THE YEAST CELL (1958)

Certain bivalent cations, particularly Mg(++) and Mn(++), can be absorbed by yeast cells, provided that glucose is available, and that phosphate is also absorbed. The cation absorption is stimulated by potassium in low concentrations, but inhibited by higher concentrations. From the time course studies, it is apparent that the absorption rather than the presence of phosphate and the potassium is the important factor. Competition studies with pairs of cations indicate that binding on the surface of the cell is not a prerequisite to absorption. The absorption mechanism if highly selective for Mg(++) and Mn(++), as compared to Ca(++), Sr(++), and UO(2) (++), whereas the binding affinity is greatest for UO(2) (++), with little discrimination between Mg(++), Ca(++), Mn(++), and Sr(++). In contrast to the surface-bound cations which are completely exchangeable, the absorbed cations are not exchangeable. It is concluded that Mg(++) and Mn(++) are actively transported into the cell by a mechanism involving a phosphate and a protein constituent.
MOS devices with high quality ultra thin CVD ZrO/sub 2/ gate dielectrics and self-aligned TaN and TaN/poly-Si gate electrodes (2002)

In this paper, we have successfully fabricated and characterized self-aligned TaN and TaN/poly-Si gated n-MOSFETs with ultra thin (EOT=11 /spl Aring/) CVD ZrO/sub 2/ gate dielectrics. It is show that while both gate stacks show excellent leakage current and good thermal stability after a 900/spl deg/C, 30 s, N/sub 2/ anneal, the TaN/poly-Si ZrO/sub 2/ devices exhibit superior thermal stability even after 1000/spl deg/C, 30 s, N/sub 2/ anneal. In addition, the TaN/poly-Si devices show negligible frequency dependence of CV, charge trapping, and superior TDDB characteristics, compared to TaN devices. Well-behaved N-MOSFETs with both TaN and TaN/poly-Si gate electrodes are demonstrated.