gebhart/patrepeval huggingface dataset:
Notch1 is essential for postimplantation development in mice. (1994)

The Notch gene of Drosophila encodes a large transmembrane protein involved in cell fate determination during embryonic and larval development. This gene is evolutionarily conserved, and Notch homologs have been cloned from several vertebrate species. To examine the in vivo role of the Notch1 gene, a mouse homolog of Notch, a mutation was introduced by targeted disruption in embryonic stem cells, and these cells were used to generate mutant mice. Intercrosses of animals heterozygous for the Notch1 mutation yielded no live-born homozygous mutant offspring. Homozygous mutant embryos died before 11.5 days of gestation. Morphological and histological analysis of the homozygous mutant embryos indicated that pattern formation through the first nine days of gestation appeared largely normal. However, histological analysis of mutant embryos subsequent to this stage revealed widespread cell death. Death of mutant embryos did not appear to be attributable to defects in placentation or vascularization. Examination of the RNA expression pattern of the Notch2 gene, another Notch gene family member, indicated that it partially overlapped the Notch1 expression pattern. Genetic analysis of the Notch1 mutation also demonstrated that it was not allelic to a mouse mutation described previously, Danforth's short tail (Sd). These results demonstrate that the Notch1 gene plays a vital role during early postimplantation development in mice.
Generation of a Spacing Pattern: The Role of TRIPTYCHON in Trichome Patterning in Arabidopsis (1999)

Trichomes in Arabidopsis are single-celled hairs that exhibit a regular spacing pattern. Here, the role of TRIPTYCHON (TRY) in the generation of this spacing pattern is studied. By using genetic mosaics, we demonstrate that the formation of trichome clusters in try mutants is not correlated with cell lineage, indicating that TRY is required to single out trichome cells in a process involving cellular interactions. The genetic interactions of TRY, GLABRA1 (GL1), and TRANSPARENT TESTA GLABRA (T TG) in trichome patterning are assessed by determining the cluster frequency in various genetic combinations. It is shown that TRY acts as a negative regulator of GL1- and TTG-dependent pathways. Furthermore, it is demonstrated that trichome initiation in ttg-1, a strong ttg allele, is rescued almost to wild-type levels in a try background in which GL1 is expressed under the control of the cauliflower mosaic virus 35S promoter, indicating that T TG acts upstream of GL1 and TRY. These findings are incorporated into a model to explain the generation of a trichome spacing pattern from a homogeneous population of epidermal cells.
Design and Semisynthesis of Photoactive Myoglobin Bearing Ruthenium Tris(2,2‘-bipyridine) Using Cofactor-Reconstitution (1998)

A new strategy for semisynthesis of a photoactivatable redox protein is described. Three protohemin molecules with ruthenium tris(2,2'-bipyridine) attached by different spacers were synthesized. The Ru(bpy)(3)-protohemins were incorporated into the heme crevice of apomyoglobin (apo-Mb) to yield semisynthetic Mbs carrying Ru(bpy)(3) as a photosensitizer (Ru(bpy)(3)-Mb). The photoactivation properties and the reaction mechanisms of Ru(bpy)(3)-Mbs were investigated by steady-state photoirradiation and laser flash photolysis. The photoactivation of Ru(bpy)(3)-Mbs was spectrophotometrically demonstrated by comparison with an intermolecular control, namely an equimolar mixture of Ru(bpy)(3) and native Mb. The spacer structure considerably influenced net activation efficiency over a wide pH range as measured by steady-state visible light irradiation and quantum yield. Laser flash photolysis yielded the rate of the photoinduced electron transfer (ET) from the lifetime of the excited Ru(bpy)(3) (k(et) = 4.4 x 10(7) s(-)(1) for Mb(1b) and k(et) = 3.7 x 10(7) s(-)(1) for Mb(1c)) and the back ET rate (k(back) = (2.0-3.7) x 10(7) s(-)(1) for Mb(1b) and k(back) = (1.4-2.4) x 10(7) s(-)(1) for Mb(1c)) from the decay of the transient absorption. These data consistently explained the results of the net photoreaction as follows. (i) The intermolecular control system was less photoactivated because little ET occurred from the excited state of Ru(bpy)(3) to Mb. (ii) The short lifetime of the charge-separated state after photoinduced ET greatly decreased the photoactivation efficiency of Ru(bpy)(3)-Mb with the shortest spacer. (iii) The photochemical and photophysical data of the other two Ru(bpy)(3)-Mb derivatives (the net photoreaction, quantum yield, and ET/back ET rates) were essentially identical, indicating that flexible spacers consisting of oxyethylene units do not rigidly fix the distance between Ru(bpy)(3) and the heme center of Mb. In addition, Ru(bpy)(3)-Mbs were highly photoactivated under aerobic conditions in a manner similar to that under anaerobic conditions, although O(2) usually quenches the photoexcited state of Ru(bpy)(3). This was probably due to the accelerated intramolecular ET from Ru(bpy)(3) to heme, not to O(2) in Ru(bpy)(3)-Mbs. We therefore showed that visible light affects the content of O(2)-bound Mb even in air.
Novel Anticancer Polymeric Conjugates of Activated Nucleoside Analogues (2011)

Inherent or therapy-induced drug resistance is a major clinical setback in cancer treatment. The extensive usage of cytotoxic nucleobases and nucleoside analogues in chemotherapy also results in the development of specific mechanisms of drug resistance, such as nucleoside transport or activation deficiencies. These drugs are prodrugs; and being converted into the active mono-, di-, and triphosphates inside cancer cells following administration, they affect nucleic acid synthesis, nucleotide metabolism, or sensitivity to apoptosis. Previously, we actively promoted the idea that the nanodelivery of active nucleotide species, e.g., 5'-triphosphates of nucleoside analogues, can enhance drug efficacy and reduce nonspecific toxicity. In this study, we report the development of a novel type of drug nanoformulations, polymeric conjugates of nucleoside analogues, which are capable of the efficient transport and sustained release of phosphorylated drugs. These drug conjugates have been synthesized, starting from cholesterol-modified mucoadhesive polyvinyl alcohol or biodegradable dextrin, by covalent attachment of nucleoside analogues through a tetraphosphate linker. Association of cholesterol moieties in aqueous media resulted in intramolecular polymer folding and the formation of small nanogel particles containing 0.5 mmol/g of a 5'-phosphorylated nucleoside analogue, e.g., 5-fluoro-2'-deoxyuridine (floxuridine, FdU), an active metabolite of anticancer drug 5-fluorouracyl (5-FU). The polymeric conjugates demonstrated rapid enzymatic release of floxuridine 5'-phosphate and much slower drug release under hydrolytic conditions (pH 1.0-7.4). Among the panel of cancer cell lines, all studied polymeric FdU-conjugates demonstrated an up to 50× increased cytotoxicity in human prostate cancer PC-3, breast cancer MCF-7, and MDA-MB-231 cells, and more than 100× higher efficacy against cytarabine-resistant human T-lymphoma (CEM/araC/8) and gemcitabine-resistant follicular lymphoma (RL7/G) cells as compared to free drugs. In the initial in vivo screening, both PC-3 and RL7/G subcutaneous tumor xenograft models showed enhanced sensitivity to sustained drug release from polymeric FdU-conjugate after peritumoral injections and significant tumor growth inhibition. All these data demonstrate a remarkable clinical potential of novel polymeric conjugates of phosphorylated nucleoside analogues, especially as new therapeutic agents against drug-resistant tumors.
Linear mRNA Amplification from as Little as 5 ng Total RNA for Global gene Expression Analysis (2004)

Gene expression analysis has become an invaluable tool for understanding gene function and regulation. However, global expression analysis requires large RNA quantities or RNA preamplification. We describe an isothermal messenger RNA (mRNA) amplification method, Ribo-SPIA, which generates micrograms of labeled cDNA from 5 ng of total RNA in 1 day for analysis on arrays or by PCR quantification. Highly reproducible GeneChip array performance (R2 > 0.95) was achieved with independent reactions starting with 5-100 ng Universal Human Reference total RNA. Targets prepared by the Ribo-SPIA procedure (20 ng total RNA input) or the Affymetrix Standard Protocol (10 microg total RNA) perform similarly, as indicated by gene call concordance (86%) and good correlation of differential gene expression determination (R2 = 0.82). Accuracy of transcript representation in cDNA generated by the Ribo-SPIA procedure was also demonstrated by PCR quantification of 33 transcripts, comparing differential expression in amplified and nonamplified cDNA (R2 = 0.97 over a range of nearly 10(6) infold change). Thus Ribo-SPIA amplification of mRNA is rapid, robust, highly accurate and reproducible, and sensitive enough to allow quantification of very low abundance transcripts.
Acid Rain Reduced in Eastern United States (2000)

Concentrations of sulfate (SO42-) and free hydrogen ions (H+) in precipitation decreased from 10% to 25% over a large area of the Eastern United States from 1995 through 1997 as compared to the previous 12-year (1983−1994) reference period. These decreases were unprecedented in magnitude and spatial extent. In contrast, nitrate (NO3-) concentrations generally did not change over this period. The largest decreases in both H+ and SO42- concentrations, which nearly mimicked one another, occurred in and downwind of the Ohio River Valley, the same area where Title IV of the 1990 Clean Air Act Amendments (CAAA) set limitations on sulfur dioxide (SO2) emissions from a large number of utility-owned coal-fired sources. Phase I of the CAAA required that these limitations be met by January 1, 1995. On the basis of our analysis of precipitation chemistry and emissions data, we conclude that significant declines in acid rain occurred in many parts of the Eastern United States from 1995 through 1997 because of large reductions in SO2 emissions in this region and a corresponding reduction in SO42- concentrations in precipitation.
An architectural framework for supporting heterogeneous instruction-set architectures (1993)

An architectural framework that allows software applications and operating system code written for a given instruction set to migrate to different, higher performance architectures is described. The framework provides a hardware mechanism that enhances application performance while keeping the same program behavior from a user perspective. The framework is designed to accommodate program exceptions, self-modifying code, tracing, and debugging. Examples are given for IBM System/390 operating-system code and AIX utilities, showing the performance potential of the scheme using a very long instruction word (VLIW) machine as the high-performance target architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Functional reconstitution of β2-adrenergic receptors utilizing self-assembling Nanodisc technology (2006)

Integral membrane G protein-coupled receptors (GPCRs) compose the single most prolific class of drug targets, yet significant functional and structural questions remain unanswered for this superfamily. A primary reason for this gap in understanding arises from the difficulty of forming soluble, monodisperse receptor membrane preparations that maintain the transmembrane signaling activity of the receptor and provide robust biophysical and biochemical assay systems. Here we report a technique for self-assembling functional beta2-adrenergic receptor (beta2AR) into a nanoscale phospholipid bilayer system (Nanodisc) that is highly soluble in aqueous solution. The approximately 10-nm nanobilayer particles contain beta2AR in a native-like phospholipid bilayer domain of approximately 100 phospholipid molecules circumferentially bound by a membrane scaffold protein (MSP). The resulting construct allows for access to the physiologically intracellular and extracellular faces of the receptor and thus allows unrestricted access of antagonists, agonists, and G proteins. These Nanodisc-solubilized GPCRs can be directly purified by normal chromatographic procedures. We define the resultant Nanodisc-embedded monomeric beta2AR by antagonist and agonist binding isotherms and demonstrate faithful G protein coupling.
Facilitating oligonucleotide delivery: helping antisense deliver on its promise. (1996)

*Departments of Pathology, Internal Medicine, and the Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104; tDivision of Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168 Street, New York, NY 10032; and tDepartment of Therapeutic Radiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, P.O. Box 9812, New Haven, CT 06536
Collection, Tumor Contamination, and Engraftment Kinetics of Highly Purified Hematopoietic Progenitor Cells to Support High Dose Therapy in Multiple Myeloma (1998)

Unfractionated peripheral blood stem cell (PBSC) grafts contain measurable quantities of myeloma cells and are therefore a potential source of relapse posttransplantation. In contrast, fluorescence-activated cell sorting (FACS)-sorted CD34+Thy1+ Lin− peripheral blood cells are substantially enriched for stem cell activity, yet contain virtually no clonal myeloma cells. A study was performed in patients with symptomatic myeloma, who had received 12 months or less of preceding standard chemotherapy, to evaluate the feasibility of large scale purification of primitive hematopoietic stem cells in order to study engraftment kinetics posttransplantation and the degree of tumor cell contamination of this cell population, based on polymerase chain reaction (PCR) analysis for the patient-specific complementarity-determining region III (CDR III). PBSC were mobilized with high dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF). A combination of elutriation and chemical lysis was used to deplete PBSC collections of monocytes, granulocytes, erythrocytes, and platelets. Subsequently, CD34+ Thy1+ Lin−progenitor cells were purified with high speed cell sorting. Of the 10 evaluable patients, nine met the required minimum criteria of ≥7.2 × 105 cells/kg to support tandem transplants. After high dose melphalan (200 mg/m2) eight engrafted successfully, although granulocyte (absolute neutrophil count [ANC] &gt;0.5 × 109/L, 16 days) and platelet recovery (platelets &gt; 50 × 109/L, 39 days) was substantially delayed when compared with unmanipulated PBSC grafts; one patient required infusion of a reserve graft because of lack of evidence of engraftment by day +28. Three patients proceeded to a second graft with high dose melphalan and total body irradiation; two required infusion of a reserve graft and both died of infectious complications; one showed delayed, but complete, engraftment after this myeloablative regimen. Two of the nine evaluable patients attained a clinical complete remission (CR). The grafts from three patients were tested for tumor contamination and contained no detectable clonal myeloma cells. Larger quantities of purified cells may be required to resolve the problem of delayed engraftment.
Elevation of Nerve Growth Factor and Antisense Knockdown of TrkA Receptor during Contextual Memory Consolidation (2001)

We report here a series of experiments establishing a role for nerve growth factor and its high-affinity receptor TrkA in contextual memory consolidation. In all experiments, we trained rats in a novel chamber using tone and shock. Our first experiment revealed that endogenous nerve growth factor (NGF) increases in the hippocampus at a critical time during consolidation that occurs 1 week after training. NGF levels at other intervals (24 hr and 2 and 4 weeks after training) did not differ from those of naive control animals. In our second experiment, we blocked effects that NGF has at 1 week after training by infusing antisense TrkA phosphorothioate DNA oligonucleotide. Reduction of septohippocampal TrkA receptor expression selectively impaired memory consolidation for context but not for tone. Animals with antisense TrkA oligonucleotide infused into the medial septal area or CA1 of the hippocampus froze less when placed in the training chamber than did animals infused with inactive randomized oligonucleotide. At 4 weeks after training, antisense TrkA oligonucleotide had no effect on freezing. Third, we correlated levels of freezing with choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunohistochemistry. Antisense TrkA infused into CA1 of the hippocampus reduced cell body cross-sectional area for cholinergic cells in the medial septal area and decreased the density of hippocampal terminals labeled for ChAT and VAChT proteins. Cholinergic cell body measurements were significantly correlated with freezing. Taken together, these results indicate a role for nerve growth factor acting via the TrkA receptor on ChAT and VAChT proteins in contextual memory consolidation.
RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells (2002)

Duplexes of 21-nt RNAs, known as short-interfering RNAs (siRNAs), efficiently inhibit gene expression by RNA interference (RNAi) when introduced into mammalian cells. We show that siRNAs can be synthesized by in vitro transcription with T7 RNA polymerase, providing an economical alternative to chemical synthesis of siRNAs. By using this method, we show that short hairpin siRNAs can function like siRNA duplexes to inhibit gene expression in a sequence-specific manner. Further, we find that hairpin siRNAs or siRNAs expressed from an RNA polymerase III vector based on the mouse U6 RNA promoter can effectively inhibit gene expression in mammalian cells. U6-driven hairpin siRNAs dramatically reduced the expression of a neuron-specific beta-tubulin protein during the neuronal differentiation of mouse P19 cells, demonstrating that this approach should be useful for studies of differentiation and neurogenesis. We also observe that mismatches within hairpin siRNAs can increase the strand selectivity of a hairpin siRNA, which may reduce self-targeting of vectors expressing siRNAs. Use of hairpin siRNA expression vectors for RNAi should provide a rapid and versatile method for assessing gene function in mammalian cells, and may have applications in gene therapy.
A Virus-Encoded "Superantigen" in a Retrovirus-Induced Immunodeficiency Syndrome of Mice (1991)

The development of an immunodeficiency syndrome of mice caused by a replication-defective murine leukemia virus (MuLV) is paradoxically associated with a rapid activation and proliferation of CD4+ T cells that are dependent on the presence of B cells. The responses of normal spleen cells to B cell lines that express the defective virus indicated that these lines express a cell surface determinant that shares "superantigenic" properties with some microbial antigens and Mls-like self antigens. This antigen elicited a potent proliferative response that was dependent on the presence of CD4+ T cells and was associated with selective expansion of cells bearing V beta 5. This response was markedly inhibited by a monoclonal antibody specific for the MuLV gag-encoded p30 antigen.
Argon entrapment in metal films by dc triode sputtering (1975)

Sputtered films of 12 elementary metals were analyzed for argon content by an rf spark−source mass−spectrographic method. All films were deposited using dc triode sputtering under similar conditions. Corrections in the data have been made to account for variations in target size and deposition rate. The experimental results are compared with sticking probabilities calculated using the Born−Mayer interatomic potentials; the agreement is fair except for elements having low atomic numbers, e.g., Cu and lower. The data confirm the role of reflected argon atoms in the entrapment mechanism at the substrate—as the atomic mass of the target material increases, the average energy of the reflected energetic argon atoms also increases, leading to the increased argon content in the film. The data also suggest that the entrapped argon content is dependent upon the atomic spacing of the film material.
Quasi-perfect state transfer in a bosonic dissipative network (2010)

In this paper we propose a scheme for quasi-perfect state transfer in a network of dissipative harmonic oscillators. We consider ideal sender and receiver oscillators connected by a chain of nonideal transmitter oscillators coupled by nearest-neighbour resonances. From the algebraic properties of the dynamical quantities describing the evolution of the network state, we derive a criterion, fixing the coupling strengths between all the oscillators, apart from their natural frequencies, enabling perfect state transfer in the particular case of ideal transmitter oscillators. Our criterion provides an easily manipulated formula enabling perfect state transfer in the special case where the network nonidealities are disregarded. We also extend such a criterion to dissipative networks where the fidelity of the transferred state decreases due to the loss mechanisms. To circumvent almost completely the adverse effect of decoherence, we propose a protocol to achieve quasi-perfect state transfer in nonideal networks. By adjusting the common frequency of the sender and the receiver oscillators to be out of resonance with that of the transmitters, we demonstrate that the sender`s state tunnels to the receiver oscillator by virtually exciting the nonideal transmitter chain. This virtual process makes negligible the decay rate associated with the transmitter line at the expense of delaying the time interval for the state transfer process. Apart from our analytical results, numerical computations are presented to illustrate our protocol.
State-of-the-Art in Visual Attention Modeling (2012)

Modeling visual attention--particularly stimulus-driven, saliency-based attention--has been a very active research area over the past 25 years. Many different models of attention are now available which, aside from lending theoretical contributions to other fields, have demonstrated successful applications in computer vision, mobile robotics, and cognitive systems. Here we review, from a computational perspective, the basic concepts of attention implemented in these models. We present a taxonomy of nearly 65 models, which provides a critical comparison of approaches, their capabilities, and shortcomings. In particular, 13 criteria derived from behavioral and computational studies are formulated for qualitative comparison of attention models. Furthermore, we address several challenging issues with models, including biological plausibility of the computations, correlation with eye movement datasets, bottom-up and top-down dissociation, and constructing meaningful performance measures. Finally, we highlight current research trends in attention modeling and provide insights for future.