gebhart/patrepeval huggingface dataset:
Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization (1985)

We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the memory for short-term sensitization grades smoothly into long-term memory with increased amounts of sensitization training. One cellular locus for the storage of the memory underlying short-term sensitization is the set of monosynaptic connections between the siphon sensory cells and the gill and siphon motor neurons. We have now also found that these same monosynaptic connections participate in the storage of the memory underlying long-term Sensitization. We examined the amplitudes of the direct synaptic connections produced by siphon sensory neurons on the gill motor neuron L7 in nervous systems removed from control and from long-term sensitized animals 1 day after the end of long-term sensitization training. The connections were significantly larger in long-term sensitized animals than in control animals. The finding that long-term memory occurs at the same synaptic locus as the short-term memory should facilitate study of the cellular and molecular mechanisms involved in the conversion of short-term to long-term memory.
AGILE: A phase 3, multicenter, randomized, placebo-controlled study of ivosidenib in combination with azacitidine in adult patients with previously untreated acute myeloid leukemia with an IDH1 mutation. (2018)

TPS7074 Background: Acute myeloid leukemia (AML) is a hematologic malignancy with limited treatment options for patients who are ineligible for intensive chemotherapy, corresponding to a median overall survival ≤1 year (Dombret et al. 2016). Mutations in isocitrate dehydrogenase 1 (IDH1) occur in 6–10% of AML cases (Xu et al. 2017). Ivosidenib (IVO; AG-120) is a first-in-class, oral, targeted inhibitor of the mutant IDH1 (mIDH1) enzyme that has demonstrated robust clinical activity and a manageable safety profile as a single agent in patients with AML. A phase 1 study of IVO in combination with azacitidine (AZA) is ongoing (NCT02677922). As of September 11, 2017, 11 treatment-naïve patients with mIDH1 AML have been treated with IVO 500 mg QD + AZA 75 mg/m2 subcutaneously (SC) for 7 days in a 28-day schedule (DiNardo et al. ASH 2017). Patients have been treated for a median of 3 cycles (range 1–13) and adverse events are consistent with the AML monotherapy experiences of IVO and AZA. One case of IDH differentiation syndrome has been reported. The objective response rate (ORR) was 8 of 11 patients, including 4 patients who achieved a complete remission (CR). Methods: AGILE is a global, randomized, double-blind, placebo-controlled trial in patients with previously untreated mIDH1 AML who are candidates for nonintensive treatment (NCT03173248). 392 patients are being randomized 1:1 to receive either IVO 500 mg QD + AZA 75 mg/m2 SC or intravenously for 7 days in 28-day cycles, or matched placebo + AZA. Randomization is stratified by region and by de novo versus secondary AML. Key eligibility criteria include patients with previously untreated mIDH1 AML (according to WHO criteria) who are not candidates for or not willing to receive intensive chemotherapy, ECOG performance status 0–2, and no prior treatment with a hypomethylating agent or mIDH1 inhibitor. The primary outcome measure is overall survival, and key secondary outcome measures include event-free survival, CR rate, CR + CR with partial hematologic recovery (CRh) rate, and ORR. AGILE is currently open for enrollment globally. Clinical trial information: NCT03173248.
15-Year Follow-up of a Multicenter, Randomized, Calcineurin Inhibitor Withdrawal Study in Kidney Transplantation (2014)

Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.
Runtime execution monitoring (REM) to detect and prevent malicious code execution (2004)

Many computer security threats involve execution of unauthorized foreign code on the victim computer. Viruses, network and email worms, Trojan horses, backdoor programs used in denial of service attacks are a few examples. In this paper, we present an architectural technique, which we call runtime execution monitoring (REM), to detect program flow anomalies associated with such malicious code. The key idea in REM is the verification of program code at the hash block (similar to a basic block) level. This is achieved by pre-computing keyed hashes (HMACs) for each hash block during program installation, and then verifying these values during program execution. By verifying program code integrity at the hash block level, REM can monitor instructions whose behavior is typically exploited by malicious code, such as branch, call, return instructions. Performance degradation with REM averages 6.4% on our benchmark programs, which can be reduced to under 5% by increasing the size of the L1 instruction cache.
Notice of Removal Coarse-to-fine human parsing with Fast R-CNN and over-segment retrieval (2016)

Removed.
Faecal interleukin-8 and tumour necrosis factor-alpha concentrations in cystic fibrosis. (1995)

Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured in faecal samples from nine patients with cystic fibrosis and nine healthy age matched controls. The patients were assessed with Shwachman score, apparent energy absorption, pancreatic enzyme dosage, simple spirometry, and presence of pseudomonal colonisation. Median (range) wet stool IL-8 and TNF-alpha concentrations in patients were 32,113 pg/g (21,656-178,128) and 3187 pg/g (368-17,611) respectively, compared with < 43.5 pg (IL-8)/g (< 22-4079) and 99 pg (TNF-alpha)/g (< 0.26-231) in controls. IL-8 concentration was negatively correlated with Shwachman score (r = -0.79) and pancreatic enzyme dosage (r = -0.77), but not with energy absorption. Seven patients were mature enough to cooperate with spirometry. Their IL-8 concentrations correlated with percentage predicted forced expiratory volume in one second (r = -0.78). IL-8 concentration was greater in four patients with, than five without, established pseudomonal colonisation: median difference 134,583 pg/g. TNF-alpha concentration was not correlated with measures of disease severity. Faecal IL-8 concentration might reflect the severity of pulmonary inflammation in cystic fibrosis and could provide an easily obtainable marker of disease activity.
Lead and Calcium Produce Rod Photoreceptor Cell Apoptosis by Opening the Mitochondrial Permeability Transition Pore (2000)

Calcium overload is suggested to play a fundamental role in the process of rod apoptosis in chemical-induced and inherited retinal degenerations. However, this hypothesis has not been tested directly. We developed an in vitro model utilizing isolated rat retinas to determine the mechanisms underlying Ca(2+)- and/or Pb(2+)-induced retinal degeneration. Confocal microscopy, histological, and biochemical studies established that the elevated [Ca(2+)] and/or [Pb(2+)] were localized to photoreceptors and produced rod-selective apoptosis. Ca(2+) and/or Pb(2+) induced mitochondrial depolarization, swelling, and cytochrome c release. Subsequently caspase-9 and caspase-3 were sequentially activated. Caspase-7 and caspase-8 were not activated. The effects of Ca(2+) and Pb(2+) were additive and blocked completely by the mitochondrial permeability transition pore (PTP) inhibitor cyclosporin A, whereas the calcineurin inhibitor FK506 had no effect. The caspase inhibitors carbobenzoxy-Leu-Glu-His-Asp-CH(2)F and carbobenzoxy-Asp-Glu-Val-Asp-CH(2)F, but not carbobenzoxy-Ile-Glu-Thr-Asp-CH(2)F, differentially blocked post-mitochondrial events. The levels of reduced and oxidized glutathione and pyridine nucleotides in rods were unchanged. Our results demonstrate that rod mitochondria are the target site for Ca(2+) and Pb(2+). Moreover, they suggest that Ca(2+) and Pb(2+) bind to the internal metal (Me(2+)) binding site of the PTP and subsequently open the PTP, which initiates the cytochrome c-caspase cascade of apoptosis in rods.
Shape separation of gold nanorods using centrifugation (2009)

We demonstrate the use of centrifugation for efficient separation of colloidal gold nanorods from a mixture of nanorods and nanospheres. We elucidate the hydrodynamic behavior of nanoparticles of various shapes and illustrate that the shape-dependent drag causes particles to have shape-dependent sedimentation behavior. During centrifugation, nanoparticles undergo Brownian motion under an external field and move with different sedimentation velocities dictated by their Svedberg coefficients. This effects a separation of particles of different shape and size. Our theoretical analysis and experiments demonstrate the viability of using centrifugation to shape-separate a mixture of colloidal particles.
C1C-3 expression in the cell cycle of nasopharyngeal carcinoma cells (2004)

The immunofluorescence approach, the confocal microscopy and the patch-clamp technique were used to investigate the expression of C1C-3 (one of the candidates of volume-activated chloride channels) and its relationships with the volume-activated chloride current and the capacity of regulatory volume decrease (RVD) in the cell cycle of nasopharyngeal carcinoma cells (CNE-2Z cells). The results indicated that CNE-2Z cells expressed C1C-3. C1C-3 was located predominantly inside the cells but not in the membrane. Both the expression level and the distribution of C1C-3 were cell cycle dependent. C1C-3 expression was low in Gl but high in S phase. The cells in G2/M phase possessed an intermediate level of the expression. C1C-3 expression level was negatively correlated to the RVD capacity and amplitude of the volume-activated chloride current in the cell cycle. The results suggest that C1C-3 may be an important factor in the regulation of cell cycle progression, but that it is probably not the chloride channel associated with RVD in these cancer cells.
Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages (2010)

We studied the effectiveness of monoclonal anti-CD40 + cytosine-phosphate-guanosine-containing oligodeoxynucleotide 1826 (CpG-ODN) immunotherapy (IT) in mice treated with multidrug chemotherapy (CT) consisting of vincristine, cyclophosphamide and doxorubicin. Combining CT with IT led to synergistic anti-tumour effects in C57BL/6 mice with established B16 melanoma or 9464D neuroblastoma. CT suppressed the functions of T cells and natural killer (NK) cells, but primed naïve peritoneal macrophages (Mφ) to in vitro stimulation with lipopolysaccharide (LPS), resulting in augmented nitric oxide (NO) production. IT, given after CT, did not restore the responsiveness of T cells and NK cells, but further activated Mφ to secrete NO, interferon-γ (IFN-γ) and interleukin (IL)-12p40 and to suppress the proliferation of tumour cells in vitro. These functional changes were accompanied by immunophenotype alterations on Mφ, including the up-regulation of Gr-1. CD11b(+) F4/80(+) Mφ comprised the major population of B16 tumour-infiltrating leucocytes. CT + IT treatment up-regulated molecules associated with the M1 effector Mφ phenotype [CD40, CD80, CD86, major histocompatibility complex (MHC) class II, IFN-γ, tumour necrosis factor-α (TNF-α) and IL-12] and down-regulated molecules associated with the M2 inhibitory Mφ phenotype (IL-4Rα, B7-H1, IL-4 and IL-10) on the tumour-associated Mφ compared with untreated controls. Together, the results show that CT and anti-CD40 + CpG-ODN IT synergize in the induction of anti-tumour effects which are associated with the phenotypic repolarization of tumour-associated Mφ.
Grounded Language Learning from Video Described with Sentences (2013)

We present a method that learns representations for word meanings from short video clips paired with sentences. Unlike prior work on learning language from symbolic input, our input consists of video of people interacting with multiple complex objects in outdoor environments. Unlike prior computer-vision approaches that learn from videos with verb labels or images with noun labels, our labels are sentences containing nouns, verbs, prepositions, adjectives, and adverbs. The correspondence between words and concepts in the video is learned in an unsupervised fashion, even when the video depicts simultaneous events described by multiple sentences or when different aspects of a single event are described with multiple sentences. The learned word meanings can be subsequently used to automatically generate description of new video. 1
Patent Review of Manufacturing Routes to Recently Approved PARP Inhibitors: Olaparib, Rucaparib, and Niraparib (2017)

Olaparib, rucaparib, and niraparib are three inhibitors of poly(ADP-ribose) polymerase (PARP) enzymes that have been recently approved for the treatment of ovarian cancer. The current article reviews the patent and journal literature regarding synthetic routes and final forms of these PARP inhibitors.
Effects of incubation temperatures and bovine viral diarrhea virus immune serum on bovine turbinate cells persistently infected with a noncytopathogenic isolate of bovine viral diarrhea virus. (1981)

Noncytopathogenic bovine viral diarrhea virus (BVDV) on initial inoculation in receptive cells induced a persistence in vitro at incubation temperatures of 33, 37, and 39 C. The mechanisms of this persistence were not the result of the induction of defective interfering particles or the selection of temperature-sensitive mutants, but were the result of a naturally occurring noncytopathogenic isolate of BVDV. Persistently infected cells were not freed of the infection by continuous passage in media containing homologous antibody. Persistently infected cells appeared to undergo an earlier senescence than did noninoculated cells of the same passage level and age. This phenomenon was reversed by renewal of the culture media.
Attenuation of influenza A virus by insertion of a foreign epitope into the neuraminidase (1992)

As the initial step in generating a live attenuated influenza A vaccine, we attempted to substitute an unrelated amino acid sequence (FLAG) for a portion of the neuraminidase (NA) molecule in influenza virus A/WSN/33 (H1N1), using a recently developed technique (reverse genetics [W. Luytjes, M. Krystal, M. Enami, J. D. Parvin, and P. Palese, Cell 59:1107-1113, 1989]). This technique allowed us to rescue the NA molecules containing the FLAG sequence (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys) at the bottom portion of the boxlike head of the molecule immediately above the stalk region (amino acid residues 63 to 70 [WSN NA numbering]). An anti-FLAG monoclonal antibody immunoprecipitated the NA molecules with the FLAG sequence, demonstrating that the foreign epitope was exposed on the virion surface. The dose of FLAG-containing transfectant virus required to kill 50% of mice was 100-fold higher than the required dose of parent virus. The FLAG sequence was stably maintained in the NA molecule during passage of the virus in tissue culture and in mice. These findings demonstrate that live influenza A vaccine strains with stable attenuating mutations in the coding region of the viral genes can be generated by reverse genetics.
Evidence-based feeding strategies before and after the development of necrotizing enterocolitis (2014)

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants and is associated with significant morbidity and mortality. While the pathogenesis of NEC remains incompletely understood, it is well established that the risk of disease is increased by the administration of infant formula and decreased by the administration of breast milk. This review will focus on the mechanisms by which breast milk may serve to protect against NEC, and will review the evidence regarding various feeding strategies that may be utilized before and after an episode of NEC.
Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential (2011)

The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). hmAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naïve and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain, and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs that can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections.
Push-Pull Optical Pumping of Pure Superposition States (2004)

A new optical pumping method, "push-pull pumping," can produce very nearly pure, coherent superposition states between the initial and the final sublevels of the important field-independent 0-0 clock resonance of alkali-metal atoms. The key requirement for push-pull pumping is the use of D1 resonant light which alternates between left and right circular polarization at the Bohr frequency of the state. The new pumping method works for a wide range of conditions, including atomic beams with almost no collisions, and atoms in buffer gases with pressures of many atmospheres.
Differential inhibition of transforming growth factor beta 1 and beta 2 activity by alpha 2-macroglobulin. (1990)

Affinity labeling and immunoprecipitation studies demonstrate that alpha 2-macroglobulin (alpha 2M) is the major serum-binding protein for transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2). Purified alpha 2M inhibits the binding of both 125I-TGF-beta 1 and 125I-TGF-beta 2 to cell surface receptors at I50 values of 200 and 10 micrograms/ml, respectively. alpha 2M (200 micrograms/ml) does not block TGF-beta 1 inhibition of CCL-64 mink lung cell growth but reduces this activity of TGF-beta 2 10-fold. The electrophoretic migration of 125I-TGF-beta.alpha 2M complexes on polyacrylamide gels under nondenaturing conditions demonstrates that alpha 2M has 10-fold greater affinity for TGF-beta 2 than for TGF-beta 1. Each of these complexes comigrates as a single band with the fast form of alpha 2M. We suggest that alpha 2M is an important differential regulator of the biological activities of TGF-beta 1 and TGF-beta 2 in vivo.
Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing (2011)

Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160x average target coverage, 93% of nucleotides had at least 20x coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders.
A Dielectric Omnidirectional Reflector (1998)

A design criterion that permits truly omnidirectional reflectivity for all polarizations of incident light over a wide selectable range of frequencies was used in fabricating an all-dielectric omnidirectional reflector consisting of multilayer films. The reflector was simply constructed as a stack of nine alternating micrometer-thick layers of polystyrene and tellurium and demonstrates omnidirectional reflection over the wavelength range from 10 to 15 micrometers. Because the omnidirectionality criterion is general, it can be used to design omnidirectional reflectors in many frequency ranges of interest. Potential uses depend on the geometry of the system. For example, coating of an enclosure will result in an optical cavity. A hollow tube will produce a low-loss, broadband waveguide, whereas a planar film could be used as an efficient radiative heat barrier or collector in thermoelectric devices.
ISOLATION OF CIRCADIAN CLOCK MUTANTS OF NEUROSPORA CRASSA (1973)

Three mutants of Neurospora crassa have been isolated which have altered period lengths of their circadian rhythm of conidiation. The strains, designated "frequency" (frq), were obtained after mutagenesis of the band (bd) strain with N-methyl-N'-nitro-N-nitrosoguanidine. In continuous darkness at 25 degrees bd has a period length of 21.6 +/- 0.5 hours; under the same conditions the period length of frq-1 is 16.5 +/- 0.5 hours; frq-2, 19.3 +/- 0.4 hours; and frq-3, 24.0 +/- 0.4 hours. Each of the mutants segregates as a single nuclear gene. All three mutants appear very tightly linked to each other, but it has not yet been determined whether the mutants are allelic. No major changes in the responses to light and temperature have been observed in any of the mutants. It is suggested that these mutants represent alterations in the basic timing mechanism of the circadian clock of Neurospora.