gebhart/patrepeval huggingface dataset:
Modulating splicing with small molecular inhibitors of the spliceosome (2016)

Small molecule inhibitors that target components of the spliceosome have great potential as tools to probe splicing mechanism and dissect splicing regulatory networks in cells. These compounds also hold promise as drug leads for diseases in which splicing regulation plays a critical role, including many cancers. Because the spliceosome is a complicated and dynamic macromolecular machine comprised of many RNA and protein components, a variety of compounds that interfere with different aspects of spliceosome assembly is needed to probe its function. By screening chemical libraries with high-throughput splicing assays, several labs have added to the collection of splicing inhibitors, although the mechanistic insight into splicing yielded from the initial compound hits is somewhat limited so far. In contrast, SF3B1 inhibitors stand out as a great example of what can be accomplished with small molecule tools. This group of compounds were first discovered as natural products that are cytotoxic to cancer cells, and then later shown to target the core spliceosome protein SF3B1. The inhibitors have since been used to uncover details of SF3B1 mechanism in the spliceosome and its impact on gene expression in cells. Continuing structure activity relationship analysis of the compounds is also making progress in identifying chemical features key to their function, which is critical in understanding the mechanism of SF3B1 inhibition. The knowledge is also important for the design of analogs with new and useful features for both splicing researchers and clinicians hoping to exploit splicing as pressure point to target in cancer therapy. WIREs RNA 2017, 8:e1381. doi: 10.1002/wrna.1381 For further resources related to this article, please visit the WIREs website.
The expansion of the carbon-carbon bond length in potassium graphites (1969)

Studies of the x-ray diffraction pattern from different potassium graphites have shown that intercalation of graphite by potassium is accompanied by an expansion of the carbon layers. This expansion is uniform within a single layer and is constant for all n carbon layers separating successive intercalate layers in the stagen compound of composition C12nK (n > 1). Preferred values of the C-C bond length for stages 1 to 6, derived from the value of the a-axis parameter extrapolated to θ = 90° are:
High-frequency GaAs transversal filter (1984)

A transversal filter integrated circuit, fabricated using 1 μm GaAs MESFET technology, is described. The filter uses 280 MESFETs, has a clocked delay line and on-chip tap weighting to give three different filter responses. Operation has been demonstrated up to a clock frequency of 400 MHz, which is believed to be the fastest reported operation of a clocked transversal filter.
Pozabljeni nokturno Ferda Livadića (1968)

Pozabljeni nokturno Ferda Livadića
LES TRIBROMURES DE PHOSPHONIUMS. AGENTS DE BROMATION DE SUBSTRATS ORGANIQUES (1985)

Abstract The reactivities and selectivities of phosphonium tribromides 1–4 towards ketones and their ketals, in the presence of other functional group reactive towards bromide (free enolic position, activated aromatic ring or double bond), are studied and compared with the trimethyl phenyl ammonium tribromide 5. The abilities of the two kinds of tribromides are similar, with a better selectivity of phosphoniums salts toward unsaturated ketones, which is probably induced by the greater stability of the ion-pair in phosphonium salts. They act essentially by the tribromide without specific bond interactions between phosphorus and heteroatom of the substrate.
Effects of hydrostatic pressure on leporine meniscus cell‐seeded PLLA scaffolds (2009)

Hydrostatic pressure (HP) is an important component of the loading environment of the knee joint. Studies with articular chondrocytes and TMJ disc fibrochondrocytes have identified certain benefits of HP for tissue engineering purposes. However, similar studies with meniscus cells are lacking. Thus, in this experiment, the effects of applying 10 MPa of HP at three different frequencies (0, 0.1, and 1 Hz) to leporine meniscus cell-seeded PLLA scaffolds were examined. HP was applied once every 3 days for 1 h for a period of 28 days. Constructs were analyzed for cellular, biochemical, and biomechanical properties. At t = 4 weeks, total collagen/scaffold was found to be significantly higher in the 10 MPa, 0 Hz group when compared with other groups. This despite the fact that the cell numbers/scaffold were found to be lower in all HP groups when compared with the culture control. Additionally, the total GAG/scaffold, instantaneous modulus, and relaxation modulus were significantly increased in the 10 MPa, 0 Hz group when compared with the culture control. In summary, this experiment provides evidence for the benefit of a 10 MPa, 0 Hz stimulus, on both biochemical and biomechanical aspects, for the purposes of meniscus tissue engineering using PLLA scaffolds.
Performance analysis in loosely-coupled distributed systems (2002)

This paper considers some of the performance-related issues which must be tackled in order that the potential for Web Services to provide a truly global distributed system be achieved
Caffeine Enhancement of the Effect of Anticancer Agents on Human Sarcoma Cells (1989)

It is necessary to find modifiers which enhance the effects of known anticancer agents in order to improve both survival rate and local curability of patients with high-grade sarcomas. In this study, the effect of anticancer agents combined with caffeine was examined on cultured sarcoma cells and fresh human sarcoma specimens, utilizing the human tumor clonogenic assay technique. The combination of cisplatin and caffeine showed a synergistic inhibition of the growth of two strains of cultured sarcoma cells tested, and 14 of 18 fresh human sarcoma specimens (77.8%). This synergistic effect of caffeine was also observed with cyclophosphamide (44.8%), mitomycin C (44.8%) and adriamycin (27.8%). The combination of vincristine or methotrexate with caffeine, however, did not exhibit a synergistic effect. Caffeine, therefore, enhanced the effect of four cytotoxic DNA damaging agents. No antagonistic effects were seen in our series. This study suggests that caffeine may be useful in enhancing the tumoricidal effect of anticancer drugs, especially DNA-damaging agents, and possibly may aid in overcoming natural drug resistance.
Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration (1995)

Partial hepatectomy (PH) in rats induces a synchronized burst of DNA replication in the remnant liver that peaks at 24 h post-PH. We report here that removal of the major salivary glands before one-third and two-thirds PH prevents the proliferative response in the remaining liver. Twelve days after one-third PH, the remnant liver is 89% of the normal liver weight in nonsalivectomized rats but only 55% in salivectomized animals. This indicates that salivectomy does not merely delay the first round of cell division but that it prevents actual regeneration. Salivectomy alters the early protooncogene response to partial hepatectomy. In salivectomized rats, the characteristic peak of c-myc mRNA synthesis at 2-4 h after PH is significantly decreased compared with nonsalivectomized rats. The peak of DNA synthesis at 24 h after PH in salivectomized rats is also dramatically decreased. DNA synthesis as measured by [3H]thymidine incorporation into DNA of hepatic cells is decreased approximately 90% in salivectomized rats vs. nonsalivectomized rats 22-26 h after PH. Ligation of the venous drainage of the salivary gland results in the same inhibitory effect on DNA synthesis, indicating 1) that the salivary gland must release circulating factor(s), and 2) that the early increase in c-myc expression and the subsequent DNA synthesis, both of which reflect the stimulation of cellular proliferation in the regenerating liver, are induced by humoral factor(s) released from the salivary glands. Injection of exogenous epidermal growth factor (EGF) in salivectomized rats results in restoration of both the DNA synthetic and c-myc responses at levels characteristic of those of liver regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
Biosynthesis of chrysomycins A and B origin of the chromophore. (1985)

The biosynthetic origin of the carbon atoms in the chromophores of chrysomycins A and B was investigated in feeding experiments using 13C labeled acetates and propionate. A biosynthetic scheme is proposed involving the condensation and rearrangement of a decaketide intermediate which contains either propionate (chrysomycin A) or acetate (chrysomycin B) as the chain initiator.
A 40 nm CMOS 0.4–6 GHz Receiver Resilient to Out-of-Band Blockers (2011)

A highly-linear software-defined radio operating from 400 MHz to 6 GHz is presented, with the purpose of removing any dedicated filtering at the antenna. Very high resilience to out-of-band interference is achieved thanks to a 2.5 V linear LNA and mixer-based RF blocker filter. The 2 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 40 nm digital CMOS receiver achieves +10 dBm out-of-band IIP <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> and >; +70 dBm calibrated IIP <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> at 3 dB NF. It tolerates 0 dBm blockers at 20 MHz offset with acceptable blocker NF.
Chromosomal fragile site FRA16D and DNA instability in cancer. (2000)

It has been proposed that common aphidicolin-inducible fragile sites, in general, predispose to specific chromosomal breakage associated with deletion, amplification, and/or translocation in certain forms of cancer. Although this appears to be the case for the fragile site FRA3B and may be the case for FRA7G, it is not yet clear whether this association is a general property of this class of fragile site. The major aim of the present study was to determine whether the FRA16D chromosomal fragile site locus has a role to play in predisposing DNA sequences within and adjacent to the fragile site to DNA instability (such as deletion or translocation), which could lead to or be associated with neoplasia. We report the localization of FRA16D within a contig of cloned DNA and demonstrate that this fragile site coincides with a region of homozygous deletion in a gastric adenocarcinoma cell line and is bracketed by translocation breakpoints in multiple myeloma, as reported previously (Chesi, M., et al., Blood, 91: 4457-4463, 1998). Therefore, given similar findings at the FRA3B and FRA7G fragile sites, it is likely that common aphidicolin-inducible fragile sites exhibit the general property of localized DNA instability in cancer cells.
Middle Ear Implants: Historical and futuristic perspective (2011)

Technological advancements are continuously changing the paradigm of human existence. Human beings are constantly engaging in various measures to reduce the extent of sensory and motor impairment. This has been in the form of various devices, e.g. orthopedic prosthesis, visual aids (spectacles) and hearing aids. Countless attempts throughout the centuries have been made in an effort to improve sound amplification in patients. This article seeks to highlights the technological journey of one such implant, the middle ear implant, from its inception to the more technological advanced futuristic proposals. While there are many amplification devices available presently, there still remains a group of patients who have not experienced adequate amplification for their hearing loss and this subset may gain the greatest benefit from middle ear implants.
Immune response to parental and rough mutant strains of Salmonella minnesota (1981)

Specificity of immune response to smooth and rough mutant strains of Salmonella minnesota was investigated. Immunization of mice with Rd and Re rough mutants resulted in formation of bactericidal plaque-forming cells directed against the lipopolysaccharide structure of both the mutants and the parental smooth strain. These antibody plaques, however, were not bactericidal for smooth strains of other gram-negative species, i.e., Escherichia coli, Salmonella typhosa, Klebsiella pneumoniae, Shigella dysenteriae, and Pseudomonas aeruginosa. Plaques produced against the smooth strain of S. minnesota or other species were not bactericidal for rough strains. It was concluded that immunization with rough mutants produces bactericidal antibodies directed against the closely related parental strain but not against smooth strains of unrelated bacterial species. The relevance of these observations to the nonspecific protection by rough mutants is discussed.
The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis (2011)

Excisional treatment was associated with a significantly increased risk of preterm birth. It provides new evidence that some types of ablative treatment may also be associated with a small increased risk. The type of comparison group used is an important consideration when comparing the outcomes of studies.
Determinants of cardiac augmentation by elevations in intrathoracic pressure (1985)

We studied the cardiovascular effects of phasic increases in intrathoracic pressure (ITP) by high-frequency jet ventilation in an acute pentobarbital-anesthetized intact canine model both before and after the induction of acute ventricular failure by large doses of propranolol. Chest and abdominal pneumatic binders were used to further increase ITP. Respiratory frequency, percent inspiratory time, mean ITP, and swings in ITP throughout the respiratory cycle were independently varied at a constant-circulating blood volume. We found that pertubations in mean ITP induced by ventilator adjustments accounted for all observable steady-state hemodynamic changes independent of respiratory frequency, inspiratory time, or phasic respiratory swings in ITP. Changes in ITP were associated with reciprocal changes in both intrathoracic vascular pressures (P less than 0.01) and blood volume (P less than 0.01). When cardiac function was normal, left ventricular (LV) stroke volume decreased, whereas in acute ventricular failure, LV stroke volume increased in response to increasing ITP when apneic LV filling pressure was high (greater than or equal to 17 Torr) and did not change if apneic LV filling pressure was low (less than or equal to 12 Torr). However, in all animals in acute ventricular failure, LV stroke work increased with increasing ITP. Our study demonstrates that the improved cardiac function seen with increasing ITP in acute ventricular failure is dependent upon adequate LV filling and decreased LV afterload in a manner analogous to that seen with arterial vasodilator therapy in heart failure.
A Novel Cyanobacterial SmtB/ArsR Family Repressor Regulates the Expression of a CPx-ATPase and a Metallothionein in Response to Both Cu(I)/Ag(I) and Zn(II)/Cd(II) (2004)

A novel SmtB/ArsR family metalloregulator, denoted BxmR, has been identified and characterized from the cyanobacterium Oscillatoria brevis. Genetic and biochemical evidence reveals that BxmR represses the expression of both bxa1, encoding a CPx-ATPase metal transporter, as well as a divergently transcribed operon encoding bxmR and bmtA, a heavy metal sequestering metallothionein. Derepression of the expression of all three genes is mediated by both monovalent (Ag(I) and Cu(I)) and divalent (Zn(II) and Cd(II)) heavy metal ions, a novel property among SmtB/ArsR metal sensors. Electrophoretic gel mobility shift experiments reveal that apoBxmR forms multiple resolvable complexes with oligonucleotides containing a single 12-2-12 inverted repeat derived from one of the two operator/promoter regions with similar apparent affinities. Preincubation with either monovalent or divalent metal ions induces disassembly of both the BxmR-bxa1 and BxmR-bxmR/bmtA operator/promoter complexes. Interestingly, the temporal regulation of expression of bxa1 and bmtA mRNAs is different in O. brevis with bxa1 induced first upon heavy metal treatment, followed by bmtA/bxmR. A dynamic interplay among Bxa1, BmtA, and BxmR is proposed that maintains metal homeostasis in O. brevis by balancing the relative rates of metal storage and efflux of multiple heavy metal ions.
Evaluation of a Recombinant 27‐kDa Outer Membrane Protein of <i>Coxiella burnetii</i> as an Immunodiagnostic Reagent (1998)

The 27-kDa outer membrane protein from eight strains of Coxiella burnetii was expressed in the pET-21c protein expression system. Two fusion proteins with molecular masses of 30 and 32 kDa were evident in all eight of the recombinants by SDS-PAGE and immunoblotting. A protein having an approximate size of 30 kDa was purified from the Escherichia coli lysates by one-step affinity purification. The utility of the purified recombinant protein in ELISA was also evaluated by testing its reactivity with human sera and comparing this reactivity with that of Nine Mile phase II antigen. All of the 40 IF-positive serum samples were ELISA-positive for both the Nine Mile phase II and recombinant antigens, and negative serum controls were negative for both antigens. These results suggest that ELISA with the 27-kDa recombinant antigen is a sensitive and specific method for detecting anti-C. burnetii antibodies in human sera.
Concomitant TAR-DNA-Binding Protein 43 Pathology Is Present in Alzheimer Disease and Corticobasal Degeneration but Not in Other Tauopathies (2008)

Pathologic TAR-DNA-binding protein 43 (TDP-43) is a disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. We studied the presence, frequency, and distribution of TDP-43 pathology by immunohistochemistry and biochemistry in a series of clinically well-characterized tauopathy patient brains, including 182 Alzheimer disease (AD), 39 corticobasal degeneration, 77 progressive supranuclear palsy, and 12 Pick disease cases and investigated the clinical impact of concomitant TDP-43 pathology in these cases. TAR-DNA-binding protein 43 pathology was found in 25.8% of AD cases. It was restricted to the dentate gyrus and entorhinal cortex in approximately 75% of cases; approximately 25% showed more widespread TDP-43 pathology in frontal and temporal cortices, resembling the FTLD-U subtype associated with progranulin mutations. TAR-DNA-binding protein 43 pathology in AD was associated with significantly longer disease duration, but there was no association with the clinical presentation (148 cases diagnosed as AD and 34 cases diagnosed as frontotemporal lobar degeneration). Progressive supranuclear palsy and Pick disease cases showed no TDP-43 inclusions and no biochemical alterations of TDP-43. There was, however, a unique, predominantly glial TDP-43 pathology with staining of astrocytic plaque-like structures and coiled bodies in 15.4% of corticobasal degeneration cases; this was associated with biochemical TDP-43 changes similar to those in FTLD-U. These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis.
The activity of hydroxynaphthoquinones against Leishmania donovani (1992)

The hydroxynaphthoquinones, buparvaquone, 250C80 and 56W82, showed high activity in vitro against Leishmania donovani amastigotes in mouse peritoneal macrophages, with ED50 values of 0.05, 2.95 and 13.82 microM, respectively. Fourteen other hydroxynaphthoquinones were tested, of which only 566C80 and 608C86 showed significant activity against amastigotes. Buparvaquone, 250C80 and 56W82 were also highly-active against cultured promastigotes. In a BALB/c mouse model, treatment with 100 mg/kg/day for five days with buparvaquone, 250C80 and 566C80 (atovaquone) reduced liver amastigote numbers by 60%, 22% and 30.5%, respectively.
Use of CdZnTe detectors in hand-held and portable isotope identifiers to detect illicit trafficking of nuclear material and radioactive sources (2002)

The use of large volume CdZnTe detectors for hand-held isotope identification devices for field use is described. It is shown, that if used with well-designed identification software, the many advantages of these detectors prevail over their main disadvantage-their low detection efficiency.
Development and Testing of Instrumentation for UAV-Based Flux Measurements within Terrestrial and Marine Atmospheric Boundary Layers (2013)

Abstract Instrumentation packages have been developed for small (18–28 kg) unmanned aerial vehicles (UAVs) to measure momentum fluxes as well as latent, sensible, and radiative heat fluxes in the atmospheric boundary layer (ABL) and the topography below. Fast-response turbulence, hygrometer, and temperature probes permit turbulent momentum and heat flux measurements, and shortwave and longwave radiometers allow the determination of net radiation, surface temperature, and albedo. UAVs flying in vertical formation allow the direct measurement of fluxes within the ABL and, with onboard high-resolution visible and infrared video and laser altimetry, simultaneous observation of surface topography or ocean surface waves. The low altitude required for accurate flux measurements (typically assumed to be 30 m) is below the typical safety limit of manned research aircraft; however, with advances in laser altimeters, small-aircraft flight control, and real-time kinematic differential GPS, low-altitude flight is now within the capability of small UAV platforms. Flight tests of instrumented BAE Systems Manta C1 UAVs over land were conducted in January 2011 at McMillan Airfield (Camp Roberts, California). Flight tests of similarly instrumented Boeing Insitu ScanEagle UAVs were conducted in April 2012 at the Naval Surface Warfare Center, Dahlgren Division (Dahlgren, Virginia), where the first known measurements of water vapor, heat, and momentum fluxes were made from low-altitude (down to 30 m) UAV flights over water (Potomac River). This study presents a description of the instrumentation, summarizes results from flight tests, and discusses potential applications of these UAVs for (marine) atmospheric boundary layer studies.
Brain-wide pathway for waste clearance captured by contrast-enhanced MRI (2013)

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.