gebhart/patrepeval huggingface dataset:
Adenovirus enhancement of transferrin-polylysine-mediated gene delivery. (1991)

Gene transfer may be accomplished by the receptor-mediated endocytosis pathway using transferrin-polylysine conjugates. For some target cells, however, gene transfer by this vector is extremely limited, despite the presence of the appropriate surface receptors, a phenomenon attributed to lysosomal degradation of endosome-internalized conjugate-DNA complexes. To enhance DNA escape from the cell vesicle system and thus augment gene transfer by this route, we have used the capacity of adenoviruses to disrupt endosomes as part of their entry mechanism. Adenoviral infection augmented levels of gene transfer by transferrin-polylysine conjugates in a dose-dependent manner: levels of gene transfer of greater than 2000-fold above baseline were achieved. Use of the adenovirus in this context allowed enhanced levels of gene transfer in a variety of target cells, including cell lines otherwise refractory to gene transfer by transferrin-polylysine conjugates. This augmentation was based on adenoviral-mediated vesicle disruption, a process independent of viral gene expression. Thus, the development of specific mechanisms to effect release from the endosome in combination with gene transfer by the receptor-mediated endocytosis pathway will increase the utility of this delivery system by allowing high levels of gene expression in target cells.
Robust and efficient motion planning for a planar robot using hybrid control (2002)

An existing hybrid control strategy is extended and applied to the control of a novel courier robot based on planar (Sawyer) motor technology augmented with integral sensing. The controller is designed to accommodate actuator limits and the desired motion characteristics, eliminating the need for careful matching of trajectory parameters with controller gains. Controller extensions allow for the unusual actuator constraints of the planar motors and independent adjustment of the parameters for each axis. Simulation results are presented for several cases to demonstrate the diversity of situations within the capability of the controller.
The Evolutionary Basis of Some Clinical Disorders of the Human Foot: A Comparative Survey of the Living Primates (1983)

The living primates are a highly diverse group of essentially arboreal animals whose feet are variously adapted for grasping, climbing, and leaping in trees. One of the most remarkable aspects of the anatomical variation in the feet of the extant primates is that this diversity can be arranged in a graduated sequence ranging from the primitive transtarsal-opposition type of grasping foot found in the lemurs, through the specialized transmetarsal-adduction type that characterizes the higher primates, to the unique nongrasping foot of humans. The comparative study of this graded series makes it possible, without recourse to the fossil record, to appreciate the adaptive and functional stages through which the human foot passed in its evolution. It is hypothesized that the initial stage of human erect posture was characterized by a foot which was adapted to both hallucial grasping and short distance bipedal walking. In many respects, the structure of the foot of this primitive human was probably similar to that of the living highland gorilla. When compared with the feet of our closest living relatives, the African apes, the human foot is characterized by two major evolutionary specializations: the longitudinal and transverse arches, and the parallel first and second metatarsals. These two morphological adaptations, together with several associated specializations, are the structural basis of the bipedal human foot. Reconstructing the evolutionary and adaptive history of these specializations creates a better understanding of some of the more common clinical podiatric disorders. The modern human foot is structurally so well adapted to prolonged bipedal walking and standing that even slight deviations from its evolutionarily established pattern will produce debilitating clinical manifestations. In most cases, successful treatment of such disorders involves restoration of the foot's basic adaptive configuration.
Kernicterus at Low Levels of Serum Bilirubin: The Impact of Bilirubin Albumin-Binding Capacity (1982)

A retrospective survey of neonatal post-mortems over a 10-year period was made to establish the incidence of kernicterus and the associated laboratory abnormalities. Cases with evidence of kernicterus without hyperbilirubinaemia were found to have significantly lower reserve albumin-binding capacity (RABC) than the control group. The results suggest that RABC estimation is a necessary adjunct in the assessment of the jaundiced, low birthweight neonate.
Method for Measuring the Self-Assembly of Alkanethiols on Gold at Femtomolar Concentrations (2007)

We describe a cantilever-based method for measuring the self-assembly of alkanethiols on a gold surface in a flow system that permits easy step changes in concentration and acquire a continuous in situ measure of the resulting chemisorption through the change in resonance frequency. A gold-coated (2.2 mm2), piezoelectric-excited, millimeter-sized cantilever (PEMC) sensor was exposed to 1-hexadecanethiol (HDT) in ethanol at concentrations ranging from 1 fM to 1 mM, sequentially and separately. A high-order flexural mode at approximately 850 kHz was monitored during the self-assembly. The resonance frequency decreases as a result of increased mass as chemisorption occurs on the surface. We show for the first time that the chemisorption of HDT at 1 fM is readily measurable and gave a response of 220 +/- 13 Hz (n = 4). At higher concentrations (10 and 100 fM; 1, 10, and 100 pM; 1, 10, and 100 nM; 1 microM; and 1 mM), the responses were proportionately, but nonlinearly, higher. At high concentrations (1 mM), the responses to C4, C8, C11, C16, and C18 alkanethiols were linearly proportional and were complete in approximately 25 min. We report for the first time that, once the Au surface is equilibrated at 1 pM, further chemisorption at a lower HDT concentration does not take place, even though over 99% of surface adsorption sites are available. At 1 fM, the overall chemisorption rate did not increase with a 2-fold increase in the HDT flow rate, suggesting that chemisorption at 1 fM is not transport-limited. The measured overall chemisorption rate constant at 1 fM was more rapid than 0.1 min-1.
A new and efficient method for inhibition of RNA viruses by DNA interference (2009)

We report here a new method for inhibition of RNA viruses induced by dsDNA. We demonstrated that both long dsDNA molecules and short interfering DNA with a sequence complementary to that of viral RNA inhibited tobacco mosaic virus expression and prevented virus spread. Also, the expression of the HIV‐1 gp41 gene in HeLa cells was inhibited by complementary short interfering DNA. We showed that Dicer processed dsDNA, which suggests activation of the cellular machinery involved in silencing of RNA. For the silencing of viral RNA effected with dsDNA, we coined the term DNA interference technology.
Characterization of antigen processing and presentation by resting B lymphocytes. (1988)

The production of antibody to a thymus-dependent Ag requires cooperation between the B cell and an Ag-specific Th cell. MHC restriction of this interaction implies that the Th cell recognizes Ag on the B cell surface in the context of MHC molecules and that the Ag-specific B cell gets help by acting as an APC for the Th cell. However, a number of studies have suggested that normal resting B cells are ineffective as APC, implying that the B cell must leave the resting state before it can interact specifically with a Th cell. Other studies, including our own with rabbit globulin-specific mouse T cell lines and hybridomas, show that certain T cell lines can be efficiently stimulated by normal resting B cells. One possible explanation for the above contradiction is that our B cells have become activated before presentation. Here we show that presentation by size-selected small B cells is not the result of nonspecific activation signals generated by the T cells or components of the medium. Also, although LPS activation does increase the efficiency of presentation by small B cells, use of large cells in place of small cells or preincubation of resting B cells with mitogenic doses of anti-Ig does not. Another possibility that we considered was that small B cells are unable to process Ag and that we had selected T cell lines that were capable of recognizing native Ag on the B cell surface. In the majority of cases, experiments with B cell lines and macrophages have shown that Ag presentation requires Ag processing, a sequence of events that includes internalization of Ag into an acid compartment, denaturation or digestion of Ag into fragments, and its return to the cell surface in the context of class II MHC molecules. The experiments reported here show that our T cell lines require an Ag processing step and that small resting B cells, like other APC, process Ag before presenting it to T cells. Specifically, we show that an incubation of 2 to 4 h is required after the Ag pulse before Ag presentation becomes resistant to irradiation. Shortly after the pulse, the Ag enters a pronase-resistant compartment. Although efficient Ag presentation requires initial binding to membrane Ig, Ag is no longer associated with membrane Ig at the time of presentation and is not presented in its intact form, because removal of membrane Ig by goat anti-Ig blocks presentation before but not after the Ag pulse.
A Novel Small-Molecule Inhibitor of Transforming Growth Factor β Type I Receptor Kinase (SM16) Inhibits Murine Mesothelioma Tumor Growth In vivo and Prevents Tumor Recurrence after Surgical Resection (2007)

Malignant mesothelioma is an aggressive and lethal pleural cancer that overexpresses transforming growth factor beta (TGFbeta). We investigated the efficacy of a novel small-molecule TGFbeta type I receptor (ALK5) kinase inhibitor, SM16, in the AB12 syngeneic model of malignant mesothelioma. SM16 inhibited TGFbeta signaling seen as decreased phosphorylated Smad2/3 levels in cultured AB12 cells (IC(50), approximately 200 nmol/L). SM16 penetrated tumor cells in vivo, suppressing tumor phosphorylated Smad2/3 levels for at least 3 h following treatment of tumor-bearing mice with a single i.p. bolus of 20 mg/kg SM16. The growth of established AB12 tumors was significantly inhibited by 5 mg/kg/d SM16 (P < 0.001) delivered via s.c. miniosmotic pumps over 28 days. The efficacy of SM16 was a result of a CD8+ antitumor response because (a) the antitumor effects were markedly diminished in severe combined immunodeficient mice and (b) CD8+ T cells isolated from spleens of mice treated with SM16 showed strong antitumor cytolytic effects whereas CD8+ T cells isolated from spleens of tumor-bearing mice treated with control vehicle showed minimal activity. Treatment of mice bearing large tumors with 5 mg/kg/d SM16 after debulking surgery reduced the extent of tumor recurrence from 80% to <20% (P < 0.05). SM16 was also highly effective in blocking and regressing tumors when given p.o. at doses of 0.45 or 0.65 g/kg in mouse chow. Thus, SM16 shows potent activity against established AB12 malignant mesothelioma tumors using an immune-mediated mechanism and can significantly prevent tumor recurrence after resection of bulky AB12 malignant mesothelioma tumors. These data suggest that ALK5 inhibitors, such as SM16, offer significant potential for the treatment of malignant mesothelioma and possibly other cancers.
Compact Virtual-Source Current–Voltage Model for Top- and Back-Gated Graphene Field-Effect Transistors (2011)

This paper presents a compact model for the current-voltage characteristics of graphene field-effect transistors (GFETs), which is based on an extension of the “virtual-source” model previously proposed for Si MOSFETs and is valid for both saturation and nonsaturation regions of device operation. This GFET virtual-source model provides a simple and intuitive understanding of carrier transport in GFETs, allowing extraction of the virtual-source injection velocity <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">v</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">VS</sub> , which is a physical parameter with great technological significance for short-channel graphene transistors. The derived <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> - <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> characteristics account for the combined effects of the drain-source voltage <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">VDS</i> , the top-gate voltage <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">VTGS</i> , and the back-gate voltage <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">VBGS</i> . With only a small set of fitting parameters, the model shows excellent agreement with experimental data. It is also shown that the extracted virtual-source carrier injection velocity for graphene devices is much higher than in Si MOSFETs and state-of-the-art III-V heterostructure FETs with similar gate length, demonstrating the great potential of GFETs for high-frequency applications. Comparison with experimental data for chemical-vapor-deposited GFETs from our group and epitaxial GFETs in the literature confirms the validity and flexibility of the model for a wide range of existing GFET devices.
Increased Susceptibility of the Left Compared to the Right Ventricle to Remote Ischemia/Reperfusion Injury in Human C1-Inhibitor-Overexpressing Transgene Mice (2002)

Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice ( n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with 125 I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 &#45 0.04, compared to 0.17 &#45 0.07 in controls (NS), and in the LV 0.36 &#45 0.08, compared to 0.21 &#45 0.05 in controls ( p < .01). The LV showed a significantly higher value compared to the right (0.22 &#45 0.04 vs. 0.36 &#45 0.08, p < .01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals ( p < .015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.
Scoring Models for Insurance Risk Sharing Pool Opimization (2008)

We introduce a flexible scoring model that can be used by property and casualty insurers that have access to a risk-sharing pool to better select the insureds to transfer to the pool. The model discriminates between insureds whose transfer is likely to be profitable under the pool regulations against those paying a fair premium. This model makes use of feature selection methods to automatically discover the most relevant model inputs, yet is robust to overfitting due to the use of a rank averaging technique. By analogy to the knapsack problem, we show what should be the most suitable sorting criterion depending on the pool regulations. We illustrate the performance of the approach by testing against the historical data of a mid-sized Canadian insurer.
The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11) (2011)

We report a patient with T-lymphoblastic leukemia/lymphoma and a t(7;8)(q22;p11). CUX1 was identified as the fusion partner of FGFR1 by fluorescence in situ hybridization and 5' RACE-PCR. We further investigated this novel FGFR1 fusion using the interleukin-3 (IL-3) dependent Ba/F3 cell line and demonstrated IL-3 independent cell growth of CUX1-FGFR1 expressing cells. TKI258 and PKC412 potently inhibited proliferation of CUX1-FGFR1 transformed Ba/F3 cells. This growth inhibition was shown to be mediated by inhibition of CUX1-FGFR1 kinase activity for TKI258 but not PKC412. In summary, we identified a novel CUX1-FGFR1 fusion oncogene in a patient with the 8p11 myeloproliferative syndrome and demonstrated its transforming potential in the Ba/F3 cell line. Our in vitro data support the further investigation of TKI258 for the treatment of constitutively active FGFR1 fusion proteins.
Randomized Phase III Trial of Fluorouracil Alone Versus Fluorouracil Plus Cisplatin Versus Uracil and Tegafur Plus Mitomycin in Patients With Unresectable, Advanced Gastric Cancer: The Japan Clinical Oncology Group Study (JCOG9205) (2002)

Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.
Diagnostic Biosensor Polymers (1994)

Advances in materials science and technology, notably polymers, have resulted in many successful implants, therapeutic devices and diagnostic assays in the medical field. Diagnostic polymers and coatings play a very important functional role in dry chemistries, immunodiagnostics, and biosensors. Enzymes, also polymeric in nature are extensively used to measure or amplify signals of many, but specific, metabolites. Furthermore, polymers, plastics and other polymeric materials are invariably utilized in such devices for functions other than chemical, biochemical, and electrochemical reactions. We will describe chemistry, technology, design, applications and future prospects of diagnostic polymers and coatings in this report.
Electro-membrane microcurrent therapy reduces signs and symptoms of muscle damage (2002)

LAMBERT, M. I., P. MARCUS, T. BURGESS, and T. D. NOAKES. Electro-membrane microcurrent therapy reduces signs and symptoms of muscle damage. Med. Sci. Sports Exerc., Vol. 34, No. 4, pp. 602–607, 2002. Purpose Delayed onset muscle soreness (DOMS) occurs after unaccustomed physical activity or competitive sport, resulting in stiff, painful muscles with impaired function. Acustat® electro-membrane microcurrent therapy has been used to treat postoperative pain and soft tissue injury; however, its efficacy in reducing symptoms of muscle damage is not known. Methods Thirty healthy men were recruited for a double-blind, placebo-controlled trial. The muscles of their nondominant arms were damaged using an eccentric-exercise protocol. Subjects were then randomly assigned to treatment with either Acustat or a matching placebo membrane for 96 h and monitored for a total of 168 h. Results Subjects in both groups experienced severe pain and swelling of the elbow flexors after the eccentric exercise. After 24 h, the elbow joint angle of the placebo group had increased significantly more than those in the Acustat group (13.7 ± 8.9° vs 7.5 ± 5.5°; placebo vs Acustat, P < 0.05), possibly as a consequence of the elbow flexor muscles shortening. For the first 48 h after exercise, maximum voluntary contraction of the elbow flexor muscles was significantly impaired in the placebo group by up to 25% (P < 0.05), whereas muscle function was unchanged in the Acustat group. Peak plasma creatine kinase activity was also lower in the Acustat group (peak = 777 ± 1438 U·L−1) versus the placebo group (peak = 1918 ± 2067 U·L−1; (P < 0.05). The membranes were well tolerated by the subjects in both groups without any adverse effects. Conclusion These data show that treatment of muscle damage with Acustat electro-membrane microcurrent therapy reduces the severity of the symptoms. The mechanisms of action are unknown but are likely related to maintenance of intracellular Ca2+ homeostasis after muscle damaging exercise.
The Weil Osteotomy (2014)

Forefoot pain is a common presenting symptom to foot and ankle specialists. Common diagnosis for forefoot pain includes metatarsal stress fracture, neuroma, capsulitis, and or synovitis of metatarsophalangeal joints, or plantar plate tear. An abnormal parabola is commonly encountered causing changes in the biomechanics of the foot leading to metatarsalgia. When conservative treatment fails, surgery is often indicated. The Weil osteotomy is a common, reproducible osteotomy that can rebalance the parabola, decompress the metatarsophalangeal joint, and alleviate forefoot pain. Level of Evidence: Diagnostic Level 5. See Instructions for Authors for a complete description of levels of evidence.
17-Imidazolyl, Pyrazolyl, and Isoxazolyl Androstene Derivatives. Novel Steroidal Inhibitors of Human Cytochrome Cl7,20-Lyase (P45017α) (1997)

We recently described a number of inhibitors of P450(17 alpha), the key enzyme of androgen biosynthesis. Here, we report the synthesis and activity of novel 17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives as potential agents for the treatment of prostatic cancer. A number of 17-(4'-Imidazolyl) derivatives were prepared by condensing the corresponding 17-ketol acetate side chain with aldehyde and ammonium hydroxide. The 17 beta-(4'imidazolyl) derivatives (2a, 2e, 4a, 4c) were found to be potent inhibitors of human testicular P450(17 alpha), with greater activity than ketoconazole. The juxtaposition between the imidazole ring and the steroid D ring appears to be important in contributing inhibitory properties, Compounds having a 17 beta-(2'-imidazolyl) ring (9a, 10) or a 20 beta-(2'-imidazolyl) ring (12), instead of the 17 beta-(4'-imidazolyl) ring (2a, 4a), are weak inhibitors. Among the 17-(4'-imidazolyl) derivatives, introduction of the 17 alpha-hydroxy group (4b) and 16 alpha,17 alpha-epoxide group (2d) diminished potency (2a-->2d; lC50 66-->430 nM; 4a-->4b; lC50 58-->1200 nM), while the 16,17 double bond increased the inhibitory activity by almost three times in the 5-en-3 beta-ol inhibitors (2a-->2e; lC50 60-->24 nM). There was virtually no difference in the inhibitory activity in the 4-en-3-one inhibitors (4a-->4c; IC50 58-->50 nM). The introduction of a methyl (2b) or phenyl group (2c) on the 2'-position of 4'-imidazolyl ring caused a dramatic decrease in the potency. As to modification of the A,B rings, the 3-acetate (2f, 2g) decreased the potency almost 3-fold compared with the 3-alcohol (2e-->2f, IC50 24-->75 nM; 2a-->2g, 66-->199 nM) and the conversion from the 5-en-3 beta-ol into the 4-en-3-one hardly affected the potency. As expected, 4c was more potent than 2e for the rat p450(17 alpha). 17-(3'Pyrazolyl)-(14b) and 17-(5'-isoxazolyl)-androsta-5,16-dien-3 beta-ol (15b) were also potent inhibitors of P450(17 alpha), whereas the 17-(2'-imidazolyl) compound (9b) was one of the most potent inhibitor in this series. However, their 16-saturated counterparts (9a, 14a, 15a) were weak inhibitors. The 17 beta-(3'-isoxazolyl)- (16) and 17 beta-(5'-methyl-3'-oxazolyl)androst-5-en-3 beta-ol (18) were also inactive. The introduction of a methyl of phenyl group on the nitrogen of the pyrazolyl ring of 14b [see 14c, 14d, and 14e] also caused some loss of inhibition for P450(17 alpha). Compounds 2e, 4a, 4c, 9b, 14d, 17a, and 17b are among the most potent inhibitors of human P450(17 alpha) so far reported.