gebhart/patrepeval huggingface dataset:
Water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes as potential antitumor agents. (1986)

A series of water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes (IDP) were synthesized and tested for chemical stability, antitumor activity, and toxicity. The results obtained suggest that these complexes are relatively stable for more than 48 h when dissolved in water or phosphate buffer. All complexes had good in vitro cytotoxicity and were not cross-resistant with cis-dichloro-diammineplatinum(II) (DDP) in a DDP-resistant cell line in vitro. When the complexes were administered as a single i.p. injection to C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice inoculated with L1210 leukemia cells, a significant increase in mean survival time was observed, but there were few long-term survivors. When the complexes were administered on Days 1, 5, and 9 after tumor inoculation, however, cure rates of 50 to 85% were obtained. The oncolytic activity of the IDP complexes against L1210 ascites appeared much greater than that of DDP. The IDP complexes also had good antitumor activity when administered i.p. on Days 1, 5, and 9 following i.p. inoculation of B16 melanoma to B6D2F1 mice. Five of the six IDP complexes had no significant nephrotoxicity (as evidenced by lack of elevated blood urea nitrogen levels). N-Benzyl-iminodiacetato(1,2-diaminocyclohexane)-platinum(II) resolved into three distinct peaks of UV-absorbing material that corresponded with three distinct peaks of platinum-containing material. The exact chemical identity of the active component of this mixture is currently under investigation. The results obtained to date, however, suggest that the N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes are good candidates for further developmental studies.
Inhibition of eye blinking reveals subjective perceptions of stimulus salience (2011)

Spontaneous eye blinking serves a critical physiological function, but it also interrupts incoming visual information. This tradeoff suggests that the inhibition of eye blinks might constitute an adaptive reaction to minimize the loss of visual information, particularly information that a viewer perceives to be important. To test this hypothesis, we examined whether the timing of blink inhibition, during natural viewing, is modulated between as well as within tasks, and also whether the timing of blink inhibition varies as a function of viewer engagement and stimulus event type. While viewing video scenes, we measured the timing of blinks and blink inhibition, as well as visual scanning, in a group of typical two-year-olds, and in a group of two-year-olds known for attenuated reactivity to affective stimuli: toddlers with Autism Spectrum Disorders (ASD). Although both groups dynamically adjusted the timing of their blink inhibition at levels greater than expected by chance, they inhibited their blinking and shifted visual fixation differentially with respect to salient onscreen events. Moreover, typical toddlers inhibited their blinking earlier than toddlers with ASD, indicating active anticipation of the unfolding of those events. These findings indicate that measures of blink inhibition can serve as temporally precise markers of perceived stimulus salience and are useful quantifiers of atypical processing of social affective signals in toddlers with ASD.
Comparison of three radiographic methods for diagnosis of hip dysplasia in eight-month-old dogs (2001)

Results suggested that specificities of the 3 methods for diagnosing hip dysplasia in dogs at 8 months of age were similar. However, the DLS score had higher sensitivity, indicating that there were fewer false-negative results.
Ultra-Fast Vitrification of Murine Embryonic Stem Cells Using a Low Concentration of Cryoprotectants (2008)

Effective cryopreservation of important mammalian cells and their derivatives is critical to the success of cell based medicine in 21st century [1]. There are currently two approaches to achieve cryopreservation of mammalian cells: conventional slow freezing and vitrification without ice formation. Although conventional slow freezing only requires a low relatively nontoxic concentration of cryoprotectants (1–2 M), it is always associated with cell injury due to ice formation and freeze concentration (i.e., solute effect) [2]. Cryopreservation by vitrification avoids ice formation all together. Existing protocols for vitrification, however, require a very high concentration of cryoprotectants (CPAs, generally more than 4M) that is usually toxic to most mammalian cells [3]. Therefore, it is of great interest to achieve vitrification using a low nontoxic concentration of cryoprotectants, which combines the advantages of the existing slow freezing and vitrification approaches while avoiding their shortcomings. In this study, we report the successful vitrification of murine embryonic stem (ES) cells at a low nontoxic level of cryoprotectants utilizing a thin walled (10μm) quartz microcapillary (outer diameter, 200μm). The ES cells post-vitrification retained high immediate viability, attachment efficiency and similar proliferation characteristic to fresh ES cells. Expression of markers characteristic to the ES cells suggests the ES cells retained the undifferentiated properties of pluripotent cells post-vitrification.
Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC‐Specific for Rapid <i>Mycobacterium tuberculosis</i> Detection (2014)

Abstract Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point‐of‐care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG‐3 is based on cephalosporin with substitutions at the 2 and 7 positions and it demonstrates over 120 000‐fold selectivity for BlaC over TEM‐1 Bla, the most common β‐lactamase. CDG‐3 can detect 10 colony‐forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating β‐lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG‐3 detected tuberculosis with 90 % sensitivity and 73 % specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low‐cost point‐of‐care test for use in resource‐limited areas.
Retrovirus-mediated transfer of the human glucocerebrosidase gene to Gaucher fibroblasts. (1986)

A recombinant retrovirus carrying complementary DNA containing the complete coding sequence for human glucocerebrosidase was constructed and used to infect mouse cells and human fibroblasts from a type 2 Gaucher patient. The cDNA stably integrated in the genome of the recipient cell. Infected cells made glucocerebrosidase-cross-reacting material, and the protein was glycosylated and contained the epitope(s) missing in the type 2 mutant glucocerebrosidase. This study demonstrates the feasibility of efficiently transferring the gene encoding glucocerebrosidase to Gaucher cells using retrovirus as vector.
Panoramic lens (1994)

An infrared panoramic lens system that utilizes two lens groups to project a full 3600 cylindrical field of view onto a two-dimensional annular format is described. Each lens group has its well-defined role. The first group is a lens block that converts a cylindrical field of view into a two-dimensional annular format located within the lens itself, and the second group relays this image to some accessible location downstream from the optical system.
Screening metal–organic frameworks for selective noble gas adsorption in air: effect of pore size and framework topology (2013)

The adsorption of noble gases and nitrogen by sixteen metal-organic frameworks (MOFs) was investigated using grand canonical Monte Carlo simulation. The MOFs were chosen to represent a variety of net topologies, pore dimensions, and metal centers. Three commercially available MOFs (HKUST-1, AlMIL-53, and ZIF-8) and PCN-14 were also included for comparison. Experimental adsorption isotherms, obtained from volumetric and gravimetric methods, were used to compare krypton, argon, and nitrogen uptake with the simulation results. Simulated trends in gas adsorption and predicted selectivities among the commercially available MOFs are in good agreement with experiment. In the low pressure regime, the expected trend of increasing adsorption with increasing noble gas polarizabilty is seen. For each noble gas, low pressure adsorption correlates with several MOF properties, including free volume, topology, and metal center. Additionally, a strong correlation exists between the Henry's constant and the isosteric heat of adsorption for all gases and MOFs considered. Finally, we note that the simulated and experimental gas selectivities demonstrated by this small set of MOFs show improved performance compared to similar values reported for zeolites.
A frame center matching technique for precise registration of multitemporal airborne frame imagery (2003)

Accurate spatial registration between multitemporal imagery is necessary if pixel-level changes are to be detected. Registration of multitemporal airborne frame imagery is complicated by image distortions resulting from wide view angles and variable terrain. A novel technique for acquiring and precisely registering multitemporal airborne frame imagery is presented. This technique, referred to as frame center (FC) matching, may enable precise registration between a long series of multitemporal airborne imagery. Polynomial warping and orthorectification algorithms were tested for registering multitemporal imagery acquired with matched FCs. Registration results were compared to those derived using imagery not acquired with matched FC locations. The FC matching approach to image acquisition yielded substantially lower misregistration errors between all multitemporal image sets for each method evaluated. Special tools and protocols required for operationally replicating FCs in time sequential image acquisitions were evaluated. The effectiveness of these tools and protocols for frame-center matched acquisition and registration of multidate imagery is demonstrated.
Development and analytical performance evaluation of an automated chemiluminescent immunoassay for pro-gastrin releasing peptide (ProGRP) (2009)

These results demonstrate that the ARCHITECT ProGRP assay has excellent sensitivity, precision, and correlation to a reference method. This assay provides a convenient automated method for ProGRP measurement in serum and plasma in hospitals and clinical laboratories.
Arabidopsis nonhost resistance gene PSS1confers immunity against an oomycete and a fungal pathogen but not a bacterial pathogen that cause diseases in soybean (2012)

The study revealed that Arabidopsis PSS1 is a novel nonhost resistance gene that confers a new form of nonhost resistance against both a hemibiotrophic oomycete pathogen, P. sojae and a necrotrophic fungal pathogen, F. virguliforme that cause diseases in soybean. However, this gene does not play any role in the immunity of Arabidopsis to the bacterial pathogen, P. syringae pv. glycinea, which causes bacterial blight in soybean. Identification and further characterization of the PSS1 gene would provide further insights into a new form of nonhost resistance in Arabidopsis, which could be utilized in improving resistance of soybean to two serious pathogens.
Glutamate mediates platelet activation through the AMPA receptor (2008)

Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N-methyl-D-aspartate (NMDA) receptor, and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each receptor was first characterized and cloned in the central nervous system (CNS). Glutamate is also present in the periphery, and glutamate receptors have been identified in nonneuronal tissues, including bone, heart, kidney, pancreas, and platelets. Platelets play a central role in normal thrombosis and hemostasis, as well as contributing greatly to diseases such as stroke and myocardial infarction. Despite the presence of glutamate in platelet granules, the role of glutamate during hemostasis is unknown. We now show that activated platelets release glutamate, that platelets express AMPAR subunits, and that glutamate increases agonist-induced platelet activation. Furthermore, we demonstrate that glutamate binding to the AMPAR increases intracellular sodium concentration and depolarizes platelets, which are important steps in platelet activation. In contrast, platelets treated with the AMPAR antagonist CNQX or platelets derived from GluR1 knockout mice are resistant to AMPA effects. Importantly, mice lacking GluR1 have a prolonged time to thrombosis in vivo. Our data identify glutamate as a regulator of platelet activation, and suggest that the AMPA receptor is a novel antithrombotic target.
Novel amphiphilic block copolymers derived from the selective fluorination and sulfonation of poly(styrene‐<i>block</i>‐1,3‐cyclohexadiene) (2011)

Abstract Diblock copolymers of polystyrene‐ block ‐(1,3‐cyclohexadiene) (PS‐ b ‐PCHD), with varied molecular weights and compositions, were synthesized by sequential polymerization of styrene and 1,3‐cyclohexadiene (CHD) initiated by sec ‐butyllithium in cyclohexane in the presence of appropriate additives during formation of the PCHD block. The residual double bonds in the PCHD block were saturated by addition of in situ generated difluorocarbene and/or hydrogen to enhance thermal and chemical stability. The fluorinated and/or hydrogenated polydiene blocks were chemically stable, allowing for controlled sulfonation of the PS blocks using acetyl sulfate. 1 H NMR and FT‐IR characterization confirmed successful fluorination/hydrogenation and sulfonation of the respective blocks. The resulting amphiphilic block copolymers consist of a semiflexible fluorine‐containing hydrophobic block having a bridged double ring structure and a hydrophilic sulfonated PS block. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Imidazo[1,2-<i>a</i>]pyridines: Orally Active Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor (2012)

Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With good potency and selectivity for the mGlu2 receptor, 27o affected sleep-wake architecture in rats after oral treatment, which we have previously shown to be indicative of mGlu2 receptor-mediated central activity.
Don't shoot down TLB shootdowns! (2020)

Translation Lookaside Buffers (TLBs) are critical for building performant virtual memory systems. Because most processors do not provide coherence for TLB mappings, TLB shootdowns provide a software mechanism that invokes inter-processor interrupts (IPLs) to synchronize TLBs. TLB shootdowns are expensive, so recent work has aimed to avoid the frequency of shootdowns through techniques such as batching. We show that aggressive batching can cause correctness issues and addressing them can obviate the benefits of batching. Instead, our work takes a different approach which focuses on both improving the performance of TLB shootdowns and carefully selecting where to avoid shootdowns. We introduce four general techniques to improve shootdown performance: (1) concurrently flush initiator and remote TLBs, (2) early acknowledgement from remote cores, (3) cacheline consolidation of kernel data structures to reduce cacheline contention, and (4) in-context flushing of userspace entries to address the overheads introduced by Spectre and Meltdown mitigations. We also identify that TLB flushing can be avoiding when handling copy-on-write (CoW) faults and some TLB shootdowns can be batched in certain system calls. Overall, we show that our approach results in significant speedups without sacrificing safety and correctness in both microbenchmarks and real-world applications.
Cross-linked poly(N-acetylethylenimine) as an isoelectric focusing matrix (1999)

Agarose and polyacrylamide are the gels used for most analytical and micropreparative electrophoresis of biopolymers. In an alternative approach that offers different physico-chemical properties from these standard gels, nonionic hydrogels and amphigels composed of poly(N-acetylethylenimine) (PAEI) and a variety of cross-linkers were prepared and used as anticonvective matrices for isoelectric focusing. PAEI was prepared from the ring opening, ionic polymerization of 2-methyl-2-oxazoline. The N-acetyl side chains were hydrolyzed with aqueous sodium hydroxide to produce secondary amine sites which were used for the attachment of cross-linkers. Several cross-linkers were tested for their suitability for electrophoresis, and the cross-linker system based on the Diels-Alder reaction between a furan and maleimide tethered to PAEI gave a moldable gel that can be reversibly converted to a sol at 80 degrees C. This gel was used for isoelectric focusing under both denaturing and nondenaturing conditions. Several protein standards were resolved as well as was achieved with polyacrylamide.
Development and Validation of a Mass Spectrometry–Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease (2016)

Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date. The inherently difficult nature of this mutation required an alternative method for routine detection and clinical diagnosis of the disease. We therefore developed and validated a mass spectrometry-based probe extension assay with a series of internal controls to detect the insertion event using 24 previously characterized positive samples from patients with mucin-1 kidney disease and 24 control samples known to be wild type for the variant. Validation results indicate an accurate and reliable test for clinically establishing the molecular diagnosis of mucin-1 kidney disease with 100% sensitivity and specificity across 275 tests called.
Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer (2007)

The S100A4 protein, which is involved in the metastasis process, is a member of the S100 superfamily of Ca-binding proteins. Members of this family are multifunctional signaling proteins with dual extra and intracellular functions involved in the regulation of diverse cellular processes. Several studies have established a correlation between S100A4 protein expression and worse prognosis for patients with various malignancies including breast cancer. In this article, we have used specific antibodies in combination with immunohistochemistry (IHC) to identify the cell types that express S100A4 in human breast cancer biopsies obtained from high-risk patients. IHC analysis of 68 tumor biopsies showed that the protein is expressed preferentially by various cell types present in the tumor microenvironment (macrophages, fibroblasts, activated lymphocytes), rather than by the tumor cells themselves. Moreover, we show that the protein is externalized by the stroma cells to the fluid that bathes the tumor microenvironment, where it is found in several forms that most likely correspond to charge variants. Using a specific ELISA test, we detected a significant higher concentration of S100A4 in the tumor interstitial fluid (TIF) as compared to their corresponding normal counterparts (NIF).
Humoral response to oligomeric human immunodeficiency virus type 1 envelope protein (1996)

The humoral immune response to human immunodeficiency virus type 1 (HIV-1) is often studied by using monomeric or denatured envelope proteins (Env). However, native HIV-1 Env complexes that maintain quaternary structure elicit immune responses that are qualitatively distinct from those seen with monomeric or denatured Env. To more accurately assess the levels and types of antibodies elicited by HIV-1 infection, we developed an antigen capture enzyme-linked immunosorbent assay using a soluble, oligomeric form of HIV-1IIIB Env (gp140) that contains gp120 and the gp41 ectodomain. The gp140, captured by various monoclonal antibodies (MAbs), retained its native oligomeric structure: it bound CD4 and was recognized by MAbs to conformational epitopes in gp120 and gp41, including oligomer-specific epitopes in gp41. We compared the reactivities of clade B and clade E serum samples to captured Env preparations and found that while both reacted equally well with oligomeric gp140, clade B seras reacted more strongly with monomeric gp120 than did clade E samples. However, these differences were minimized when gp120 was captured by a V3 loop MAb, which may lead to increased exposure of the CD4 binding site. We also measured the ability of serum samples to block binding of MAbs to epitopes in gp120 and gp41. Clade B serum samples consistently blocked binding of oligomer-dependent MAbs to gp41 and, to a slightly lesser extent, MAbs to the CD4 binding site in gp120. Clade E serum samples showed equivalent or greater blocking of oligomer-dependent gp41 antibodies and considerably less blocking of CD4-binding-site MAbs. Finally, we found that < 5% of the antibodies in clade B sera bound to epitopes present only in monomeric gp120, 30% bound to epitopes present in both monomeric gp120 and oligomeric gp140, and 70% bound to epitopes present in oligomeric gp140, which includes gp41. Thus, captured oligomeric Env closely reflects the antigenic characteristics of Env protein on the surface of virions and infected cells, retains highly conserved epitopes that are recognized by antibodies raised against different clades, and makes it possible to detect a much greater fraction of total anti-HIV-1 Env activity in sera than does native monomeric gp120.
The integrin α <sub>4</sub> β <sub>7</sub> forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1 (2009)

Both activated and resting CD4(+) T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) CD4(+) T cells are more susceptible to productive infection than are alpha(4)beta(7)(low-neg) CD4(+) T cells in part because this cellular subset is enriched with metabolically active CD4(+) T cells. alpha(4)beta(7)(high) CD4(+) T cells are CCR5(high) and CXCR4(low); on these cells, alpha(4)beta(7) appears in a complex with CD4. The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.