gebhart/patrepeval huggingface dataset:
Enantioselective Total Synthesis of (+)-Gliocladine C: Convergent Construction of Cyclotryptamine-Fused Polyoxopiperazines and a General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors (2011)

A concise second-generation total synthesis of the fungal-derived alkaloid (+)-gliocladin C (11) in 10 steps and 11% overall yield from isatin is reported. In addition, the epipolythiodioxopiperazine (ETP) natural product (+)-gliocladine C (6) has been prepared in six steps and 29% yield from the di-(tert-butoxycarbonyl) precursor of 11. The total synthesis of 6 constitutes the first total synthesis of an ETP natural product containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter in the pyrrolidine ring.
Flood-Filling Networks (2016)

State-of-the-art image segmentation algorithms generally consist of at least two successive and distinct computations: a boundary detection process that uses local image information to classify image locations as boundaries between objects, followed by a pixel grouping step such as watershed or connected components that clusters pixels into segments. Prior work has varied the complexity and approach employed in these two steps, including the incorporation of multi-layer neural networks to perform boundary prediction, and the use of global optimizations during pixel clustering. We propose a unified and end-to-end trainable machine learning approach, flood-filling networks, in which a recurrent 3d convolutional network directly produces individual segments from a raw image. The proposed approach robustly segments images with an unknown and variable number of objects as well as highly variable object sizes. We demonstrate the approach on a challenging 3d image segmentation task, connectomic reconstruction from volume electron microscopy data, on which flood-filling neural networks substantially improve accuracy over other state-of-the-art methods. The proposed approach can replace complex multi-step segmentation pipelines with a single neural network that is learned end-to-end.
Nerve Injury-Induced Mechanical but Not Thermal Hyperalgesia Is Attenuated in Neurokinin-1 Receptor Knockout Mice (2000)

Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve. Mechanical hyperalgesia was evaluated by determining the frequency of withdrawal to von Frey monofilaments applied to the hind paws. Nerve injury-induced hyperalgesia to thermal stimuli was examined by determining responses to radiant heat and cooling stimuli. The contribution of the sympathetic nervous system to mechanical hyperalgesia was evaluated by administering 3 mg/kg phentolamine, an alpha-adrenergic antagonist, subcutaneously. Following spinal nerve injury, withdrawal frequencies to mechanical stimulation increased in wild-type mice within 1 day and persisted during the 9-week observation period, whereas in the knockout mice, withdrawal frequencies did not increase significantly. In contrast, withdrawal latencies to radiant heat decreased up to 2 weeks after nerve injury in both the NK-1 and the wild-type mice. Similarly, the increase in withdrawal frequency to the cooling stimuli following the nerve injury was not different in the NK-1 knockout and wild-type mice. Mechanical hyperalgesia in the wild-type mice was not reversed by systemic administration of phentolamine, suggesting that the pain is not sympathetically maintained. The results indicate that NK-1 receptors contribute to the development of mechanical, but not thermal, hyperalgesia in neuropathic pain.
The Size Distribution of Business Firms (1958)

Examines the skewed distribution of firms by size. Discusses the adequacy of previous economic explanations regarding firm size that are based on the static cost curve. It is shown that the static cost curve for the firm may predict the minimum size of a firm in an industry with a known size value, but it will not predict the size distribution of firms. Therefore, an alternative theory of firm size based on a stochastic model of the growth process is proposed. It is postulated that size has no effect on the expected percentage of firm growth--i.e., that each firm in every size class has the same average chance of increasing or decreasing in size regardless of its current size. The empirical data from a transition matrix for the 500 largest U.S. industrial corporations from 1954 to 1956 show that the frequency distributions of percentage changes in size of small, medium, and large firms were similar. However, this data encompasses an entire economy rather than a single industry. In order to find the size distribution of firms by industry, Bain's estimates of minimum efficient plant size and the U.S. Census of Manufacturers data on the size distribution of plants are used to compare the minimum efficient scales suggested for several industries. The findings suggest that the stochastic model provides new ways of interpreting the data on firm size distribution, and any deviation from the results predicted by the model reflect some departure from the law of proportionate effect or from one of the other assumptions in the model. Concludes with implications for economic policy and further research. (SFL)
BONE MARROW TRANSPLANTATION ACROSS MAJOR HISTOCOMPATIBILITY BARRIERS IN MICE (1982)

Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed.
Policy-based shared path protection for dual link failures (2003)

In this paper, we study novel shared path protection schemes that use different policies to deal with different dual-link failure scenarios in order to minimize total bandwidth consumption (or spare capacity allocation). Our work addresses two open problems. The first is minimum total bandwidth allocation under deterministic routing (i.e., when three link-disjoint paths, one active path and two backup paths are pre-selected for each connection). For the dual-link failure case, this problem is much more complex than a similar problem for the single-link failure case because one needs to decide which one of the two backup paths for a connection is preferred to reroute the traffic along its active path affected by a single-link (or a simultaneously dual-link) failure. We propose a new concept of <b>policy</b>, which specifies the <i>preferred</i> backup path to use, and study different policies (including no policy) which will result in different performances in terms of amount of bandwidth needed and different implementation complexity. The second open problem we address in this paper is to minimize additional bandwidth to be allocated for each connection under several different policies and adaptive routing in on-line setting. In this case, the solution entails how to find optimal paths for each connection. From our simulation results, we find that shared path protection with a policy can considerably reduce bandwidth consumption compared with shared path protection without a policy.
T-Cell Recognition of<i>Mycobacterium tuberculosis</i>Culture Filtrate Fractions in Tuberculosis Patients and Their Household Contacts (1999)

We examined the immune responses of patients with active pulmonary tuberculosis (TB) and their healthy household contacts to short-term culture filtrate (ST-CF) of Mycobacterium tuberculosis or molecular mass fractions derived from it. Our goal was to identify fractions strongly recognized by donors and differences among the donor groups of possible relevance for vaccine development. The study population consisted of 65 human immunodeficiency virus-negative donors from the Hossana Regional Hospital, Hossana, Ethiopia. Peripheral blood leukocytes from the donors were stimulated with different antigens and immune responses were determined. Household contacts produced significantly higher levels of gamma interferon (IFN-gamma) than the TB patients in response to antigens present in ST-CF and the 10 narrow-molecular-mass fractions. A similar difference in leukocyte proliferative responses to the antigens between the two groups was also found. In general, while all fractions stimulated immune responses, the highest activity was seen with the low-molecular-mass fractions, which include well-defined TB antigens such as ESAT-6. Leukocytes from contacts of TB patients with severe disease produced higher levels of antigen-specific IFN-gamma than those from contacts of patients with minimal disease. Both groups of contacts exhibited higher cell-mediated responses than the patients themselves. The enhanced immune response of healthy contacts, especially those of patients with severe disease, to secreted mycobacterial antigens is suggestive of an early stage of infection by M. tuberculosis, which could in time result in overt disease or containment of the infection. This possibility is currently being investigated by follow-up studies of the household contacts.
Characterization of an<i>in vivo</i>model for the study of eyelash biology and trichomegaly: mouse eyelash morphology, development, growth cycle, and anagen prolongation by bimatoprost (2010)

This study shows that mouse eyelashes offer an excellent in vivo model for the quantitative and qualitative analysis of eyelash morphology, development, growth cycle, exogen and pharmacological modulation. This model will help to elucidate the unknown molecular controls of eyelash growth, and to develop novel drugs to treat eyelash disorders.
Efficient and stable polymer solar cells with annealing-free solution-processible NiO nanoparticles as anode buffer layers (2014)

Annealing-free solution-processible nickel oxide (NiO) nanoparticles are prepared via sonochemical synthesis. In contrast to the common sol–gel route to prepare a NiOx film that had to undergo high-temperature post-annealing to be converted into NiO nanoparticles, herein, colloidal crystalline NiO nanoparticles with diameters of 4–8 nm are prepared with the metal salt at low temperature via ultrasonic irradiation. The colloidal crystalline NiO nanoparticles were directly used as the anode buffer layer in polymer solar cells (PSCs) without post-thermal annealing, which was compatible with flexible substrates and low-cost high-throughput fabrication. After O2-plasma treatment to the as-deposited buffer layer of NiO nanoparticles, the ITO/NiO contact work function was increased from −4.8 to −5.3 eV, providing superior contact with the highest occupied molecular orbital energy levels of polymer donors. Compared to PCDTBT:PC70BM PSCs with a PEDOT:PSS buffer layer, the power conversion efficiency of PSCs with an O2-plasma treated anode buffer layer of NiO nanoparticles was increased from 5.84% to 6.30% and the device stability was also enhanced.
ChemInform Abstract: A CONVENIENT METHOD FOR THE SYNTHESIS OF 1,3‐BENZOXATHIOLES (1977)

Abstract 2‐Hydroxyphenylmercaptane (I) werden mit Methylenbromid (II) in Gegenwart von Natronlauge′ und Methyltrialkylammoniumchlorid in guten Ausbeuten zu 1,3‐Benzoxathiolen (III) umgesetzt.
Fast Routing in Road Networks with Transit Nodes (2007)

When you drive to somewhere far away, you will leave your current location via one of only a few important traffic junctions. Starting from this informal observation, we developed an algorithmic approach, transit node routing, that allows us to reduce quickest path queries in road networks to a small number of table lookups. For road maps of Western Europe and the United States, our best query times improved over the best previously published figures by two orders of magnitude. This is also more than one million times faster than the best known algorithm for general networks.
Identification of a prevalent functional missense polymorphism in the UGT2B10 gene and its association with UGT2B10 inactivation against tobacco-specific nitrosamines (2008)

The UGT2B10(67Tyr) variant corresponding to the UGT2B10 haplotype C is a functional single nucleotide polymorphism that may be responsible for inter individual variation in NNAL-N-glucuronidation activity and may increase susceptibility to smoking-related cancers.
Silicon single hole quantum dot transistors for complementary digital circuits (2002)

Novel p-channel quantum-dot transistors were fabricated in silicon-on-insulator (SOI). Strong oscillations in the drain current as a function of the gate voltage have been observed at temperatures over 81 K and drain biases over 66 mV. Measurements show that the average energy level spacing is approximately 33 meV and it is due to both single hole charging effect and quantum confinement effect. A digital inverter using a complementary pair of n and p-channel quantum dot transistors is also proposed.
Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. (1990)

Proteolytic cleavage of the von Willebrand factor subunit may be important for processing and/or function of the molecule and is altered in certain subtypes of von Willebrand disease. It results in the generation of two main fragments with apparent molecular masses of 140 kDa and 176 kDa from the 225-kDa subunit. We have now obtained chemical evidence to locate the protease-sensitive bond between residues Tyr-842 and Met-843, a site that appears to reflect the specificity of calcium-dependent neutral proteases (calpains). Antibodies were raised against four synthetic peptides that represented sequences immediately preceding or following or including the cleavage site. One antibody (against the fragment from Ala-837 through Asp-851) reacted only with the intact subunit, and its epitope included the cleavage site. All others reacted specifically with either the 140-kDa or the 176-kDa fragment, demonstrating their origin from a single cleavage. In samples of purified von Willebrand factor from four of five patients with type IIA von Willebrand disease, the anti-peptide antibodies showed markedly decreased reactivity with either the 140-kDa or the 176-kDa fragment, suggesting the existence of distinct molecular abnormalities clustered around the cleavage site. Thus, in the majority of type IIA patients, a common pathogenetic mechanism may lead to the disappearance of the larger multimers as a consequence of structural changes that may expose a sensitive bond to the action of specific proteases. These studies demonstrate the use of anti-peptide antibodies directed at a relevant structural domain for the immunochemical differentiation of normal and mutant molecules.
Blue or Red? Exploring the Effect of Color on Cognitive Task Performances (2009)

Existing research reports inconsistent findings with regard to the effect of color on cognitive task performances. Some research suggests that blue or green leads to better performances than red; other studies record the opposite. Current work reconciles this discrepancy. We demonstrate that red (versus blue) color induces primarily an avoidance (versus approach) motivation (study 1, n = 69) and that red enhances performance on a detail-oriented task, whereas blue enhances performance on a creative task (studies 2 and 3, n = 208 and 118). Further, we replicate these results in the domains of product design (study 4, n = 42) and persuasive message evaluation (study 5, n = 161) and show that these effects occur outside of individuals' consciousness (study 6, n = 68). We also provide process evidence suggesting that the activation of alternative motivations mediates the effect of color on cognitive task performances.
Organic Syntheses without Solvent: Preparation of Sulfones and Dithioacetals (1987)

Sulfones are prepared by alkylation of sulfinate salts under solid-liquid phase-transfer catalysis without solvent; dithioacetals are obtained by heterogeneous uncatalyzed reactions of potassium arenethiolates and gem-dihaloalkanes. In both cases, the yields are high and the reaction conditions are mild. Some limitations are given.
<i>Staphylococcus aureus</i> infection induces protein A–mediated immune evasion in humans (2014)

Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation.
Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis (2004)

Burkholderia pseudomallei is the causative agent of melioidosis, which is a major cause of morbidity and mortality in endemic regions. Currently there is no human vaccine against melioidosis. In this study, LPS or capsular polysaccharide was used to immunize BALB/c mice. The different polysaccharide antigens induced antibody responses. Mice vaccinated with LPS developed predominantly IgM and IgG3 responses. Contrastingly, mice vaccinated with capsular polysaccharide developed a predominantly IgG2b response. After immunization, mice were challenged by the intra-peritoneal route and an increased mean time to death was observed compared with unvaccinated controls. Immunization with LPS provided an optimal protective response. Mice challenged by the aerosol route showed a small increase in the mean time to death compared with the unvaccinated controls. The passive transfer of antigen from immunized into naïve mice provided protection against a subsequent challenge. This study is the first time antigens protective by active immunization have been identified and suggests that polysaccharides have potential as vaccine candidates against melioidosis.
Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices (2009)

Microfluidic paper-based analytical devices (microPADs) are a new class of point-of-care diagnostic devices that are inexpensive, easy to use, and designed specifically for use in developing countries. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.).
<i>Escherichia coli</i> Translocation at the Blood-Brain Barrier (2001)

The mortality and morbidity associated with bacterial meningitis have remained significant despite advances in antimicrobial chemotherapy and supportive care. A major contributing factor is the incomplete understanding of the pathogenesis of this disease. For example, most cases of bacterial meningitis develop as a result of hematogenous spread, but it is unclear how circulating bacteria cross the blood-brain barrier (12, 25, 33, 46). Recent studies have shown that Escherichia coli K1, group B Streptococcus, Streptococcus pneumoniae, and Citrobacter spp., the important pathogens that cause meningitis, translocate from blood to the central nervous system (CNS) without altering the integrity of the blood-brain barrier (2, 23, 27, 36, 42). These studies of bacterial translocation from blood to the CNS have become possible because of the availability of both in vitro and in vivo models of the blood-brain barrier (1, 3, 4, 7, 11, 13, 17–20, 22, 26, 28, 32, 41, 43, 47). The in vitro model of the blood-brain barrier is composed of brain microvascular endothelial cells (BMEC), which exhibit transendothelial resistance of 200 to 600 Ω/cm2, a unique property of the brain microvascular endothelium monolayer compared to systemic vascular endothelium. The in vivo model of the blood-brain barrier utilizes experimental hematogenous meningitis in animals. In these experimental meningitis models, bacteria are injected via intravenous, intraperitoneal, subcutaneous, or intracardiac administration, resulting in bacteremia and subsequent entry into the CNS. At present, E. coli-BMEC interactions represent the most characterized system concerning how circulating bacteria cross the blood-brain barrier. This review summarizes our current understanding of the pathogenetic mechanisms involved in bacterial translocation of the blood-brain barrier, using E. coli as a paradigm.
Intracerebral penetration of infrared light (1992)

Near infrared transmission spectroscopy of the human cerebrum may allow noninvasive evaluation of cerebral hemoglobin saturation in humans. The emerging spectroscopy configuration for this application is a side-by-side source-receiver construct. The ability of this spectroscopy paradigm to detect changes in intracerebral attenuation by selective injection of the infrared tracer indocyanine green into the internal and external carotid arteries during endarterectomy is evaluated in five adult patients. In all five, simultaneous two-channel infrared transmission spectroscopy over the ipsilateral hemisphere documented tracer bolus transit with a signal-to-noise ratio greater than 100:1. In addition, the two channels could be configured to achieve depth resolution of the collected spectra.