gebhart/patrepeval huggingface dataset:
Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate (2017)

Advancement of RNAi-based therapeutics depends on effective delivery to the site of protein synthesis. Although intravenously administered, multi-component delivery vehicles have enabled small interfering RNA (siRNA) delivery and progression into clinical development, advances of single-component, systemic siRNA delivery have been challenging. In pre-clinical models, attachment of a triantennary N-acetylgalactosamine (GalNAc) ligand to an siRNA mediates hepatocyte uptake via the asialoglycoprotein receptor enabling RNAi-mediated gene silencing. In this phase 1 study, we assessed translation of this delivery approach by evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a GalNAc-siRNA conjugate, revusiran, targeting transthyretin (TTR). Subjects received a placebo or ascending doses of revusiran subcutaneously ranging from 1.25-10 mg/kg in the single and 2.5-10 mg/kg in the multiple ascending dose phases. Revusiran was generally well tolerated, with transient, mild to moderate injection site reactions the most common treatment-emergent adverse events. Doses of 2.5-10 mg/kg revusiran elicited a significant reduction of serum TTR versus the placebo (p < 0.01), with mean TTR reductions of approximately 90% observed with multiple dosing. These results demonstrate translation of this novel delivery platform, enabling clinical development of subcutaneously administered GalNAc-siRNAs for liver-based diseases.
Protective Role of Nerve Growth Factor Against Postischemic Dysfunction of Sympathetic Coronary Innervation (1997)

We conclude that exogenously infused and endogenously released NGF protects against postischemic neural stunning of sympathetic cardiac innervation.
Validation of the general purpose tripos 5.2 force field (1989)

Abstract A molecular mechanics force field implemented in the Sybyl program is described along with a statistical evaluation of its efficiency on a variety of compounds by analysis of internal coordinates and thermodynamic barriers. The goal of the force field is to provide good quality geometries and relative energies for a large variety of organic molecules by energy minimization. Performance in protein modeling was tested by minimizations starting from crystallographic coordinates for three cyclic hexapeptides in the crystal lattice with rms movements of 0.019 angstroms, 2.06 degrees, and 6.82 degrees for bond lengths, angles, and torsions, respectively, and an rms movement of 0.16 angstroms for heavy atoms. Isolated crambin was also analyzed with rms movements of 0.025 angstroms, 2.97 degrees, and 13.0 degrees for bond lengths, angles, and torsions respectively, and an rms movement of 0.42 angstroms for heavy atoms. Accuracy in calculating thermodynamic barriers was tested for 17 energy differences between conformers, 12 stereoisomers, and 15 torsional barriers. The rms errors were 0.8, 1.7, and 1.13 kcal/mol, respectively, for the three tests. Performance in general purpose applications was assessed by minimizing 76 diverse complex organic crystal structures, with and without randomization by coordinate truncation, with rms movements of 0.025 angstroms, 2.50 degrees, and 9.54 degrees for bond lengths, angles and torsions respectively, and an average rms movement of 0.192 angstroms for heavy atoms.
Development of a potential bioartificial liver : selective adhesion of hepatocytes (1993)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1993.
Delayed Leaf Senescence in Tobacco Plants Transformed with tmr, a Gene for Cytokinin Production in Agrobacterium (1991)

Catherine M. Smart, Steven R. Scofield, Michael W. Bevan, Tristan A. Dyer, Delayed Leaf Senescence in Tobacco Plants Transformed with tmr, a Gene for Cytokinin Production in Agrobacterium, The Plant Cell, Vol. 3, No. 7 (Jul., 1991), pp. 647-656
Polymorphism of N-acetyltransferase 2 (NAT2) gene polymorphism in shanghai population: occupational and non-occupational bladder cancer patient groups. (2004)

The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.
Oncolytic Vaccinia Virus Expressing the Human Somatostatin Receptor SSTR2: Molecular Imaging after Systemic Delivery Using 111In-Pentetreotide (2004)

Oncolytic vaccinia viruses (VV) have demonstrated tumor specificity, high levels of transgene expression, and anti-tumor effects. The ability to visualize vector biodistribution noninvasively will be necessary as gene therapy vectors come to clinical trials, and the creation of a VV that can both treat tumors and permit noninvasive imaging after systemic delivery is therefore an exciting concept. To facilitate imaging, a VV expressing the human somatostatin receptor type 2 (SSTR2) was created. Cells infected with the SSTR2-expressing VV or controls were incubated with the somatostatin analog 111In-pentetreotide with or without an excess of nonradiolabeled pentetreotide. The SSTR2-infected cells bound 111In-pentetreotide sixfold more efficiently than control virus-infected cells and this binding was specifically blocked by nonradiolabeled pentetreotide. Nude mice bearing subcutaneous murine colon CA xenografts were injected intraperitoneally with the SSTR2-expressing VV or control VV. After 6 days, mice were injected with 111In-pentetreotide and imaged. Mice were sacrificed and organs collected and counted in a gamma counter. The uptake of radioactivity in tumors and normal tissues (percentage injected dose per gram) and tumor-to-normal tissue ratios were determined. Tumors infected with the SSTR2-expressing VV accumulated significantly higher concentrations of radioactivity compared to tumors in animals receiving the control virus. SSTR2-infected tumors were visible on imaging 6 days after VV injection and could be visualized for up to 3 weeks post-viral injection using repeat injections of 111In-pentetreotide. This reporter gene imaging strategy could be a very effective method to visualize vector distribution, expression, and persistence over time and enhances the potential of VV as a novel anti-cancer therapeutic.
GB VIRUS C INFECTION IN PATIENTS WITH CHRONIC HEPATITIS B AND C BEFORE AND AFTER LIVER TRANSPLANTATION (1996)

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).
Epithelial Defensins Impair Adenoviral Infection: Implication for Adenovirus-Mediated Gene Therapy (1999)

Epithelial cells have been to participate actively in host defense by producing small cationic peptides called defensins. To investigate the biological activity of epithelial defensins in more detail, we expressed two defensins, hBD-1 and HD-5, in eukaryotic cell lines. Defensins were localized in the cytoplasm and in cell culture medium and exhibited strong microbicidal activity toward Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Moreover, our data indicate that the presence of defensins protected the cells from adenoviral infection. The presence of HD-5 or hBD-1 reduced the infectivity of Av1CF2 three- to fivefold. These results imply that defensins must be considered a serious obstacle whenever adenovirus is used to deliver genes to epithelial cells.
Optimized Synthesis and Enhanced Efficacy of Novel Triplex-Forming Camptothecin Derivatives Based on Gimatecan (2009)

Sequence-specific camptothecins are useful tools to inhibit specifically gene expression. The camptothecins are attached to the 3' end of triplex-forming oligonucleotides (TFO), sequence-specific DNA ligands that position the camptothecin moiety exclusively in proximity to their binding site. We studied here different gimatecan derivatives or analogues, a potent lipophilic camptothecin compound in clinical trials. We optimized the synthesis procedure in order to increase the yields and the purity and obtain the conjugates on a large scale. The greatly improved synthesis is now based on the conjugation of a bromoalkyl analogue of gimatecan to the 3' phosphorothioate of the TFO. We showed that the most efficient conjugate, both in vitro and in HeLa cells, bears the TFO on position 7 of the gimatecan analogue, and it is more efficient than the previous camptothecin conjugates. In addition, the gimatecan-like moiety at the 3' end of the TFO protects from nuclease degradation.
10 Gbit/s repeaterless transmission experimentof optical duobinary modulated signal (1995)

The repeaterless transmission of an optical duobinary modulated signal at 10 Gbit/s is reported. The power penalty due to the fibre chromatic dispersion is effectively reduced in comparison with conventional binary intensity modulated (IM) signals. In the case of a 164 km standard singlemode fibre, the power penalty is &lt;1.8 dB.
On the Delay Distribution of Random Linear Network Coding (2011)

A fundamental understanding of the delay behavior of network coding is key towards its successful application in real-time applications with strict message deadlines. Previous contributions focused mostly on the average decoding delay, which although useful in various scenarios of interest is not sufficient for providing worst-case delay guarantees. To overcome this challenge, we investigate the entire delay distribution of random linear network coding for any field size and arbitrary number of encoded symbols (or generation size). By introducing a Markov chain model we are able to obtain a complete solution for the erasure broadcast channel with two receivers. A comparison with Automatic Repeat reQuest (ARQ) with perfect feedback, round robin scheduling and a class of fountain codes reveals that network coding on GF(2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> ) offers the best delay performance for two receivers. We also conclude that GF(2) induces a heavy tail in the delay distribution, which implies that network coding based on XOR operations although simple to implement bears a relevant cost in terms of worst-case delay. For the case of three receivers, which is mathematically challenging, we propose a brute-force methodology that gives the delay distribution of network coding for small generations and field size up to GF(2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> ).
PURIFICATION AND SOME PROPERTIES OF TWO ACID RIBONUCLEASES FROM THE MYCELIA OF ASPERGILL US NIGER (1980)

Acid ribonuclease (RNase) was extracted from mycelia of Aspergillus niger 1617 and separated into two fractions designated acid RNases I (EC 3.1.27.1) and II (EC 3.1.27.3). Each fraction was partially purified and its enzymatic properties were examined. The molecular weight of acid RNase I was approximately 45, 000, and that of II was 13, 000. The optimal pH of acid RNase I was 3.5 and that of II, 4.5. Acid RNase I was inhibited markedly by Fe3+, Cu2+, Hg2+ and 5′-ATP, whereas II was inhibited markedly by Fe3+. Acid RNase I had no base specificity producing 3′-monophosphates of the four nucleosides and guanosine-2′, 3′-cyclic monophosphate. Acid RNase II was a guanine-specific RNase.Changes in the activity of acid RNases I and II were studied during culture on agar medium. The activity of acid RNases I and II increased and reached their maxima during the late phase of active growth. After their maxima, the activity of acid RNase I remained unchanged, while that of II decreased and finally disappeared.
The Protein Network Surrounding the Human Telomere Repeat Binding Factors TRF1, TRF2, and POT1 (2010)

Telomere integrity (including telomere length and capping) is critical in overall genomic stability. Telomere repeat binding factors and their associated proteins play vital roles in telomere length regulation and end protection. In this study, we explore the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification in combination with multidimensional protein identification technology liquid chromatography--tandem mass spectrometry (MudPIT LC-MS/MS). After control subtraction and data filtering, we found that TRF2 and POT1 co-purified all six members of the telomere protein complex, while TRF1 identified five of six components at frequencies that lend evidence towards the currently accepted telomere architecture. Many of the known TRF1 or TRF2 interacting proteins were also identified. Moreover, putative associating partners identified for each of the three core components fell into functional categories such as DNA damage repair, ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA replication, cell cycle and transcription regulation, nucleotide metabolism, RNA processing, and nuclear transport. These putative protein-protein associations may participate in different biological processes at telomeres or, intriguingly, outside telomeres.
Monoclonal Antibody Conjugates of Doxorubicin Prepared with Branched Linkers:  A Novel Method for Increasing the Potency of Doxorubicin Immunoconjugates (1999)

Immunoconjugates of monoclonal antibody BR96 and Doxorubicin have been prepared using a novel series of branched hydrazone linkers. Since each linker bound to the mAb carries two DOX molecules, the DOX/mAb molar ratios of these conjugates were approximately 16, twice that of those previously prepared with single-chain hydrazone linkers. The conjugates were stable at a physiological pH of 7, but released DOX rapidly at lysosomal pH 5. The branched series of BR96 conjugates demonstrated antigen-specific cytotoxicity, and were more potent in vitro than the single-chain conjugate on both a DOX (4-14-fold) and mAb (7-23-fold) basis. The results suggest that, by using the branched linker methodology, it is possible to significantly reduce the amount of mAb required to achieve antigen-specific cytotoxic activity. In this paper, the synthesis and in vitro biology of branched chain immunoconjugates are described.
HLA class I-specific inhibitory receptors in human T lymphocytes: Interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells (1998)

A fraction of human T lymphocytes, predominantly CD8+, express receptors for HLA class I molecules typical of natural killer cells (natural killer receptors or NKRs) that inhibit T cell receptor-mediated functions. Herein, we analyzed possible mechanism(s) leading to the expression of NKRs by T cells responding to superantigens or allogeneic cells in vitro. We show that, in the presence of interleukin 15 (IL-15), T cells (depleted of NKR+ cells) responding to toxic shock syndrome toxin 1 de novo express CD94, a molecule that is part of a heterodimeric NKR with a broad specificity for different HLA class I alleles. Maximal CD94 expression occurred when IL-15 was added shortly after the cells were placed into culture, and CD94 expression started 4-6 days after addition of IL-15. Although both CD4+ and CD8+ cells expressed CD94, the simultaneous expression of NKG2A (i.e., the other component of the CD94/NKG2A inhibitory NKR) was confined to CD8+ cells. Similar data were obtained in T cell populations activated in mixed lymphocyte cultures in the presence of IL-15. The expression of CD94/NKG2A led to an impairment of allo-specific cytolytic activity by mixed lymphocyte culture-derived T cell populations or clones. Remarkably, cytolysis could be restored by the addition of anti-CD94 mAb, i.e., by masking the inhibitory NKRs.
Comparison of the specificities of laminin, thrombospondin, and von Willebrand factor for binding to sulfated glycolipids. (1986)

The adhesive glycoproteins laminin, thrombospondin, and von Willebrand factor bind specifically and with high affinity to sulfated glycolipids. These three glycoproteins differ, however, in their sensitivity to inhibition of binding by sulfated monosaccharides and polysaccharides. Heparin strongly inhibits binding of thrombospondin but only weakly inhibits binding of laminin and von Willebrand factor. Fucoidan strongly inhibits binding of both laminin and thrombospondin but not of von Willebrand factor. Laminin shows significant specificity for inhibition by monosaccharides, whereas thrombospondin does not. Thus, specific spacial orientations of sulfate esters may be primary determinants of binding for the three proteins. Laminin, thrombospondin, and von Willebrand factor also differ in their relative binding affinities for purified sulfated glycosphingolipids. The three proteins strongly prefer terminal-sulfated lipids and bind only weakly to sulfated gangliotriaosyl ceramide with a sulfate ester on the penultimate galactose. Thrombospondin binds with highest affinity to galactosyl sulfatide but only weakly to more complex sulfatides, whereas von Willebrand factor prefers galactosyl sulfatide but binds with moderate affinity to various sulfated glycolipids. Laminin also is less selective than thrombospondin but is less sensitive for detection of low sulfatide concentrations. Galactosyl sulfatide at 1-5 pmol can be detected by staining of lipids separated on high performance TLC with 125I-thrombospondin or 125I-von Willebrand factor. 125I-von Willebrand factor was examined as a reagent for detecting sulfated glycolipids in tissue extracts. Rat kidney lipids contain 5 characterized sulfated glycolipids: galactosyl ceramide I3-sulfate, lactosyl ceramide II3-sulfate, gangliotriaosyl ceramide II3-sulfate, and bis-sulfated gangliotriaosyl and gangliotetraosyl ceramides. von Willebrand factor detects all of these lipids as well as several additional minor sulfated lipids. Complex monosulfated lipids are detected in several human tissues including kidney, erythrocytes, and platelets by this technique.
GPS-less low-cost outdoor localization for very small devices (2000)

Instrumenting the physical world through large networks of wireless sensor nodes, particularly for applications like environmental monitoring of water and soil, requires that these nodes be very small, lightweight, untethered, and unobtrusive. The problem of localization, that is, determining where a given node is physically located in a network, is a challenging one, and yet extremely crucial for many of these applications. Practical considerations such as the small size, form factor, cost and power constraints of nodes preclude the reliance on GPS of all nodes in these networks. We review localization techniques and evaluate the effectiveness of a very simple connectivity metric method for localization in outdoor environments that makes use of the inherent RF communications capabilities of these devices. A fixed number of reference points in the network with overlapping regions of coverage transmit periodic beacon signals. Nodes use a simple connectivity metric, which is more robust to environmental vagaries, to infer proximity to a given subset of these reference points. Nodes localize themselves to the centroid of their proximate reference points. The accuracy of localization is then dependent on the separation distance between two-adjacent reference points and the transmission range of these reference points. Initial experimental results show that the accuracy for 90 percent of our data points is within one-third of the separation distance. However, future work is needed to extend the technique to more cluttered environments.
Electrostriction in liquidHe4 (1982)

The two-fluid model of liquid $^{4}\mathrm{He}$ is extended to include effects of applied electric fields. New terms that account for electrostriction in equations of motion for superfluid and normal fluid are derived with the aid of a variational principle subject to the assumption that the Clausius-Mossotti relation for the dielectric constant is applicable. Corresponding additions to conservation laws for momentum and energy are presented.
Stem Cells Are Coaxed to Produce Insulin (2001)

In a boost for scientists who hope to turn the potential of undifferentiated stem cells into medical miracles, researchers have found a way to produce insulin-producing cells from mouse embryonic stem (ES) cells.
Exit routes for secretory proteins from the dog pancreas. (1980)

during pancreatic stimulation biologically important amounts of secretory proteins enter the blood circulation. The lymphatic transport is negligible, since pancreatic lymph flow is several hundred times less than blood flow.
Purification and properties of arylsulfatase. A from human urine. (1975)

Arylsulfatase A (cerebroside sulfate sulfohydrolase) was purified 3500-fold at a 7% yield from human urine. A crude urinary protein concentrate was prepared by treating pooled urine with ammonium sulfate and subsequently drying the precipitate with acetone. The powder thus obtained was extracted with buffer and was subjected to chromatographic and electrophoretic procedures as follows: (a) ammonium sulfate reverse gradient solubilization chromatography; (b) DEAE-cellulose chromatography; (c) Sephadex G-200 gel filtration; (d) preparative polyacrylamide gel electrophoresis; (e) SP-Sephadex chromatography; and (f) antialbumin-Sepharose chromatography. The enzyme was judged to be essentially homogeneous by: (a) a single band on polyacrylamide gel electrophoresis at two pH values; (b) formation of a single precipitin line on immunodiffusion against its antiserum: (c) complete freedom from albumin, the major contaminating protein; and (d) a single band on sodium dodecyl sulfate gel electrophoresis.