gebhart/patrepeval huggingface dataset:
Neocortical Very Fast Oscillations (Ripples, 80–200 Hz) During Seizures: Intracellular Correlates (2003)

Multi-site field potential and intracellular recordings from various neocortical areas were used to study very fast oscillations or ripples (80-200 Hz) during electrographic seizures in cats under ketamine-xylazine anesthesia. The animals displayed spontaneously occurring and electrically induced seizures comprising spike-wave complexes (2-3 Hz) and fast runs (10-20 Hz). Neocortical ripples had much higher amplitudes during seizures than during the slow oscillation preceding the onset of seizures. A series of experimental data from the present study supports the hypothesis that ripples are implicated in seizure initiation. Ripples were particularly strong at the onset of seizures and halothane, which antagonizes the occurrence of ripples, also blocked seizures. The firing of electrophysiologically defined cellular types was phase-locked with ripples in simultaneously recorded field potentials. This indicates that ripples during paroxysmal events are associated with a coordination of firing in a majority of neocortical neurons. This was confirmed with dual intracellular recordings. Based on the amplitude that neocortical ripples reach during paroxysmal events, we propose a mechanism by which neocortical ripples during normal network activity could actively participate in the initiation of seizures on reaching a certain threshold amplitude. This mechanism involves a vicious feedback loop in which very fast oscillations in field potentials are a reflection of synchronous action potentials, and in turn these oscillations help generate and synchronize action potentials in adjacent neurons through electrical interactions.
Synthetic Peptides Derived from the Variable Regions of an Anti-CD4 Monoclonal Antibody Bind to CD4 and Inhibit HIV-1 Promoter Activation in Virus-infected Cells (1999)

The monoclonal antibody (mAb) ST40, specific for the immunoglobulin complementarity-determining region (CDR) 3-like loop in domain 1 of the CD4 molecule, inhibits human immunodeficiency virus type 1 (HIV-1) promoter activity and viral transcription in HIV-infected cells. To design synthetic peptides from the ST40 paratope that could mimic these biological properties, a set of 220 overlapping 12-mer peptides frameshifted by one residue, corresponding to the deduced ST40 amino acid sequence, was synthesized by the Spot method and tested for binding to recombinant soluble CD4 antigen. Several peptides that included in their sequences amino acids from the CDRs of the antibody and framework residues flanking the CDRs were found to bind soluble CD4. Eleven paratope-derived peptides (termed CM1-CM11) were synthesized in a cyclic and soluble form. All the synthetic peptides showed CD4 binding capacity with affinities ranging from 1.6 to 86.4 nM. Moreover, peptides CM2, CM6, CM7, CM9, and CM11 were able to bind a cyclic peptide corresponding to the CDR3-like loop in domain 1 of CD4 (amino acids 81-92 of CD4). Peptide CM9 from the light chain variable region of mAb ST40 and, to a lesser extent, peptides CM2 and CM11 were able to inhibit HIV-1 promoter long terminal repeat-driven beta-galactosidase gene expression in the HeLa P4 HIV-1 long terminal repeat beta-galactosidase indicator cell line infected with HIV-1. The binding of mAb ST40 to CD4 was also efficiently displaced by peptides CM2, CM9, and CM11. Our results indicate that the information gained from a systematic exploration of the antigen binding capacity of synthetic peptides from immunoglobulin variable sequences can lead to the identification of bioactive paratope-derived peptides of potential pharmacological interest.
Retargeting of Human Regulatory T Cells by Single-Chain Bispecific Antibodies (2011)

Bispecific Abs hold great potential for immunotherapy of malignant diseases. Because the first components of this new drug class are now entering clinical trials, all aspects of their mode of action should be well understood. Several studies proved that CD8(+) and CD4(+) effector T cells can be successfully redirected and activated against tumor cells by bispecific Abs both in vitro and in vivo. To our knowledge, this study provides the first evidence that bispecific Abs can also redirect and activate regulatory T cells against a surface Ag, independently of their TCR specificity. After cross-linking, via a bispecific Ab, redirected regulatory T cells upregulate the activation markers CD69 and CD25, as well as regulatory T cell-associated markers, like CTLA-4 and FOXP3. The activated regulatory T cells secrete the immunosuppressive cytokine IL-10, but, in contrast to CD8(+) and CD4(+) effector T cells, almost no inflammatory cytokines. In addition, the redirected regulatory T cells are able to suppress effector functions of activated autologous CD4(+) T cells both in vitro and in vivo. Therefore, the potential risk for activation of regulatory T cells should be taken into consideration when bispecific Abs are applied for the treatment of malignant diseases. In contrast, an Ag/tissue-specific redirection of regulatory T cells with bispecific Abs holds great potential for the treatment of autoimmune diseases and graft rejection.
Antibacterial Studies of 7-(α -Substituted sulphonamido) Methyl- and 7-(α- Substituted sulphonamido )Phenyl-8-Hydroxyquinolines (1984)

Department of Chemistry, Holkar Science College, Indore-452 002 <em>Manuscript received 6 March 1982, revised 11 October 1982, accepted 26 November 1983</em> Antibacterial Studies of 7-(\(\propto\)-Substituted sulphonamido) Methyl- and 7- (\(\propto\)-Substituted sulphonamido)Phenyl-8-Hydroxyquinolines
Two-Point Calibration of Circular Dichrometer with d-10-Camphorsulfonic Acid (1977)

Abstract The circular dichroism (CD) of d-10-camphorsulfonic acid (CSA) in terms of ∊L - ∊R is 2.36 and -4.72 cm2 mmol−1 at 290.5 and 192.5 nm, respectively. The corresponding molar ellipticities, [⊝], are 7,800 and -15,600 deg cm2 dmol−1. A ratio of -2.00 for the negative and positive bands provides a simple two-point calibration. If a standardized spectropolarimeter is available, the ratio of [⊝]290.5/[M]306 = 1.75 to 1.76 or [⊝]290.5/([M]306−[M]270) = 0.77 at the extrema is recommended for CD calibration at the 290 nm region, which is unaffected by the presence of optically inactive impurities such as water. Alternately, CSA has a molar absorption coefficient of 34.5 cm2 mmol−1 at 285 nm, which can be used for concentration determination. This leads to (∊L−∊R)290.5/∊285 = 0.068 or [⊝]290.5/∊285 = 226. However, CSA must be purified to remove any impurities that are optically active or absorb light or both in the UV region.
III-V material and device aspects for the monolithic integration of GaAs devices on Si using GaAs/Si low temperature wafer bonding (2002)

A new process for wafer scale integration of GaAs optoelectronic devices with Si integrated circuits has been investigated, based on low temperature bonding of epitaxial GaAs wafers onto planarized fully processed CMOS/BiCMOS wafers. The basic process flow and the most important aspects of the work concerning the III-V material and devices are presented.
Fractional box-counting approach to fractal dimension estimation (1996)

The estimation of the fractal dimension is essential in fractal-based image segmentation, classification and shape analysis. The most popular estimation approach is based on box-counting. However, the partition and counting methods used in the regular box-counting scheme produces inaccurate results. In this paper, a more accurate fractional box-counting approach is proposed to estimate the fractal dimension in an image. By separating the concepts of base scale and counting scale, the new approach is able to use a deformable box to capture fractal property at some predetermined resolution. Preliminary results using the fractional box-counting approach have demonstrated that it is an accurate and efficient method.
IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice (2012)

MRL/MpJ-Fas(lpr/lpr)/J (MRL(lpr)) mice develop lupus-like disease manifestations in an IL-21-dependent manner. IL-21 is a pleiotropic cytokine that can influence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, autoreactive CD4(+) T and B cells spontaneously accumulate in MRL(lpr) mice and mediate disease pathogenesis. We sought to identify the particular lymphocyte effector subsets regulated by IL-21 in the context of systemic autoimmunity and, thus, generated MRL(lpr) mice deficient in IL-21R (MRL(lpr).IL-21R(-/-)). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRL(lpr) model were significantly reduced in the absence of IL-21R, suggesting that immune activation was likewise decreased. Indeed, spontaneous germinal center formation and plasma cell accumulation were absent in IL-21R-deficient MRL(lpr) mice. Correspondingly, we observed a significant reduction in autoantibody titers. Activated CD4(+) CD44(+) CD62L(lo) T cells also failed to accumulate, and CD4(+) Th cell differentiation was impaired, as evidenced by a significant reduction in CD4(+) T cells that produced the pronephritogenic cytokine IFN-γ. T extrafollicular helper cells are a recently described subset of activated CD4(+) T cells that function as the primary inducers of autoantibody production in MRL(lpr) mice. Importantly, we demonstrated that T extrafollicular helper cells are dependent on IL-21R for their generation. Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL(lpr) mice.
EMERALD: An object-based language for distributed programming (1987)

Distributed systems have become more common, however constructing distributed applications remains a very difficult task. Numerous operating systems and programming languages have been proposed that attempt to simplify the programming of distributed applications. We present a programming language called Emerald that simplifies distributed programming by extending the concepts of object-based languages to the distributed environment.
Emerald supports a single model of computation: the object. Emerald objects include private entities such as integers and Booleans, as well as shared, distributed entities such as compilers, directories, and entire file systems. Emerald objects may move between machines in the system, but object invocation is location independent. The uniform semantic model used for describing all Emerald objects makes the construction of distributed applications in Emerald much simpler than in systems where the differences in implementation between local and remote entities are visible in the language semantics.
Emerald incorporates a type system that deals only with the specification of objects--ignoring differences in implementation. Thus two different implementations of the same abstraction may be freely mixed in an Emerald program.
Emerald has been implemented. The compiler accepts the responsibility of providing an efficient implementation from object definitions, generating multiple implementations tuned to different usage patterns from the same source code. We discuss these implementation considerations and provide performance data to justify our claim that Emerald can be efficiently implemented.
Microarray Methods and Protocols (2009)

A Step-by-Step Guide to Present and Future Uses of Microarray TechnologyMicroarray technology continues to evolve, taking on a variety of forms. From the spotting of cDNA and the in situ synthesis of oligonucleotide arrays now come microarrays comprising proteins, carbohydrates, drugs, tissues, and cells. With contributions from microarray experts
Novel tobramycin inhalation powder in cystic fibrosis subjects: Pharmacokinetics and safety (2007)

Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy. We evaluated the pharmacokinetics (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder formulation designed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections. This was a multi-center, open-label, sequential-cohort, single-dose, dose-escalation study using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of five cohorts. Measurements included serum and sputum tobramycin concentrations, administration time, serum chemistries, acute change in lung function, and adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third the administration time. The most common AEs associated with TIP were cough (20%) and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation. The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation. The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections.
Potent Inhibitors of LpxC for the Treatment of Gram-Negative Infections (2011)

In this paper, we present the synthesis and SAR as well as selectivity, pharmacokinetic, and infection model data for representative analogues of a novel series of potent antibacterial LpxC inhibitors represented by hydroxamic acid.
Bringing sketching tools to keychain computers with an acceleration-based interface (1999)

We report the use of an embedded accelerometer as a gestural interface for an extremely small ("keychain") computer. This tilt- and shake-sensitive interface captures the expressive nuances of continuously varying spatio-temporal input, making possible a set of applications heretofore difficult or impossible to implement in such a small device. We provide examples of such applications, including a paint program and some simple animation authoring systems.
A design of analog predistortion linearizer for RF power amplifier to reduce IMD (2008)

This paper proposes a predistortion linearizer to reducing the third and fifth order intermodulation products in RF power amplifier. Power amplifier linearity has been improved by independently controlling the amplitudes and phases of the third order (IMD3) and fifth order (IMD5) intermodulation distorted products, which are generated by using low frequency second order intermodulation components. Simulation results show that the method is effective and convenient.
Targeting cytokines to tumors to induce active antitumor immune responses by recombinant fusion proteins (1999)

Cytokines such as interleukin-2(IL-2), gamma interferon (IFN-gamma) and alpha tumor necrosis factor (TNF-alpha) are important mediators in immune responses against tumors. However, their therapeutic efficacy and clinical utilities in treatment of human malignancies are in large part limited due to the low concentrations of cytokine in tumors and the severe toxic side-effects derived from high-dose administration of cytokines. One critical issue to improve therapeutic efficacy is how to increase the local concentration of cytokine in tumors without causing severe side-effects. A series of recent reports demonstrated that the introduction of cytokine genes into tumor cells and subsequent local secretion can circumvent the limitations associated with the systemic cytokine administration. An alternative means of cytokine delivery is to target cytokines to tumor cells with tumor specific antibodies. Thereby, effective local cytokine concentrations can be achieved at the tumor sites without resorting to patient-specific therapy. With the advance in biotechnology, two structurally disparate domains of immunoglobulin and cytokine can be brought together into one fusion protein molecule by protein engineering These engineered antibody-cytokine fusion proteins combine the unique targeting ability of tumor-specific antibodies with the multifunctional activity of cytokines. In general, there are two commonly engineered fusion proteins, the F(ab')2/cytokine expressed in mammalian cells and the single-chain FV/cytokine expressed in Escherichia coli. Both the tumor-binding reactivity and the functional cytokine activity are maintained in most of fusion proteins. Therefore, these fusion proteins may be useful in targeting cytokine to tumors to stimulate immune destruction of tumors, while limiting severe toxic side-effects by the high dose of cytokine administration. Recent preclinical studies have shown that these fusion proteins are able to target cytokines to tumors expressing the tumor-associated antigen in vivo, and to inhibit both the primary and metastatic tumors in an immune competent animal model. Therefore, these recombinant fusion proteins may represent a new generation of novel immunotherapeutic reagents for the treatment of human malignant diseases.
Virus-like particles: a new family of delivery systems (2002)

The development of antiviral vaccines has almost exclusively been based on live attenuated vaccines up until now. However, the efficacy of HBsAg particles as an antiHBV vaccine has clearly demonstrated that protective antiviral immunity can be achieved by other strategies. Virus-like particles formed by structural proteins were proven to be highly immunogenic and capable of inducing protective immunity against various viral infections in preclinical studies. Clinical trials using virus-like particles confirmed their safety and immunogenicity. Moreover, chimeric virus-like particles carrying foreign peptidic sequences were shown to elicit potent B- and T-cell responses. Virus-like particles formed by a fusion protein between the HBsAg and the circumsporozoïte surface protein are safe and immunogenic in volunteers and induce a partial protection against natural Plasmodium falciparum infection.
Progress in the treatment of Friedreich ataxia (2018)

Friedreich ataxia (FRDA) is a progressive neurological disorder affecting approximately 1 in 29,000 individuals of European descent. At present, there is no approved pharmacological treatment for this condition however research into treatment of FRDA has advanced considerably over the last two decades since the genetic cause was identified. Current proposed treatment strategies include decreasing oxidative stress, increasing cellular frataxin, improving mitochondrial function as well as modulating frataxin controlled metabolic pathways. Genetic and cell based therapies also hold great promise. Finally, physical therapies are being explored as a means of maximising function in those affected by FRDA.
Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes (2004)

In addition to obesity, many factors, including the distribution of body fat, contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Lipid contained within skeletal muscle as triglyceride is a parameter of regional fat accumulation thought to be an important link among obesity, insulin resistance, and type 2 diabetes, even in the pediatric population. Intramuscular triglycerides can also be a fuel source for healthy muscle during periods of physical activity. Thus, the balance between storage and efficient utilization of muscle triglycerides is likely a key to a better understanding of the interaction between dysregulated fat and glucose metabolism by muscle in both adults and children. This review examines the evidence that muscle lipid accumulation is linked with insulin resistance and type 2 diabetes of both adults and children. In addition, we explore the potential mechanisms for muscle lipid accumulation as well as the effects of weight loss and physical activity on muscle lipid. Further defining the links between muscle lipid accumulation and insulin action should help develop more effective strategies to prevent or treat type 2 diabetes and other obesity-associated disorders.
Genome-Wide Views of Chromatin Structure (2009)

Eukaryotic genomes are packaged into a nucleoprotein complex known as chromatin, which affects most processes that occur on DNA. Along with genetic and biochemical studies of resident chromatin proteins and their modifying enzymes, mapping of chromatin structure in vivo is one of the main pillars in our understanding of how chromatin relates to cellular processes. In this review, we discuss the use of genomic technologies to characterize chromatin structure in vivo, with a focus on data from budding yeast and humans. The picture emerging from these studies is the detailed chromatin structure of a typical gene, where the typical behavior gives insight into the mechanisms and deep rules that establish chromatin structure. Important deviation from the archetype is also observed, usually as a consequence of unique regulatory mechanisms at special genomic loci. Chromatin structure shows substantial conservation from yeast to humans, but mammalian chromatin has additional layers of complexity that likely relate to the requirements of multicellularity such as the need to establish faithful gene regulatory mechanisms for cell differentiation.
A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity (2007)

IRAK4 is a member of IL-1 receptor (IL-1R)-associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)-mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase-inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R-mediated nuclear factor kappaB activation, a reduction of LPS-, R848-, and IL-1-mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow-derived macrophages from IRAK4 kinase-inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus-induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.
Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? (1980)

Both microvascular damage and myocardial cell injury occur after coronary occlusion, but the relationship of these two events is unclear; specifically, it is unknown whether microvascular damage causes myocardial cell injury. Dogs were subjected to coronary occlusion for 20, 40, 60, 90 or 180 minutes, after which subendocardial and subepicardial biopsies were obtained for electron and light microscopy of 1-mu sections. Of 312 biopsies of ischemic myocadium, 181 showed myocardial cell injury with no microvascular damage; 131 showed myocardial cell injury and microvascular damage; but none showed microvascular damage without myocardial cell injury. Although ultrastructural evidence of myocardial cell damage was present in the subendocardium after 20-40 minutes of ischemia, ultrastructural evidence of microvascular damage was not prominent until 60-90 minutes after coronary artery occlusion. Morphologic ultrastructural evidence of microvascular damage lagged behind myocardial cell injury, suggesting that ultrastructural microvascular damage is not a primary cause of ultrastructural myocardial cell injury.