gebhart/patrepeval huggingface dataset:
Long-term survival of high-risk melanoma patients immunized with a Hyper-IL-6-modified allogeneic whole-cell vaccine after complete resection (2012)

Objective: Two single arm, Phase II trials (3 and 5) were undertaken to determine the efficacy and toxicity of an adjuvant treatment using Hyper-IL-6 gene-modified whole-cell allogeneic melanoma vaccine in patients with stage IIIB–IV resected disease. Research design and methods: Ninety-seven and 99 patients were enrolled into Trials 3 and 5, respectively. The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). Vaccine was administered eight times every 2 weeks (induction), every month (maintenance) until patient's death. At progression, maintenance was continued or induction was repeated followed by maintenance. Results: Median follow-up was 10.5 and 6.2 years for Trials 3 and 5, respectively. No grade 3 or 4 toxicities were observed. An extension of DFS and OS was observed, when compared with historical non-treated controls. DFS probability at 5 years for Trials 3 and 5 was, respectively, 54.8% and 40.6% for stage IIIB, 25.0% and 24.0% for IIIC, and 8.5% and 17.7% for IV. OS probability at 5 years was, respectively, 66.7% and 56.3% for IIIB, 43.8% and 39.8% for IIIC, and 26.1% and 41.2% for IV. Conclusions: Continuous vaccination, regardless of the disease progression, re-induction, and immunization of patients until death resulted in patients a long-term survival.
Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. (1994)

The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss.
A CMOS monolithic ΔΣ-controlled fractional-N frequency synthesizer for DCS-1800 (2002)

A monolithic 1.8-GHz /spl Delta//spl Sigma/-controlled fractional-N phase-locked loop (PLL) frequency synthesizer is implemented in a standard 0.25-/spl mu/m CMOS technology. The monolithic fourth-order type-II PLL integrates the digital synthesizer part together with a fully integrated LC VCO, a high-speed prescaler, and a 35-kHz dual-path loop filter on a die of only 2/spl times/2 mm/sup 2/. To investigate the influence of the /spl Delta//spl Sigma/ modulator on the synthesizer's spectral purity, a fast nonlinear analysis method is developed and experimentally verified. Nonlinear mixing in the phase-frequency detector (PFD) is identified as the main source of spectral pollution in /spl Delta//spl Sigma/ fractional-N synthesizers. The design of the zero-dead zone PFD and the dual charge pump is optimized toward linearity and spurious suppression. The frequency synthesizer consumes 35 mA from a single 2-V power supply. The measured phase noise is as low as -120 dBc/Hz at 600 kHz and -139 dBc/Hz at 3 MHz. The measured fractional spur level is less than -100 dBc, even for fractional frequencies close to integer multiples of the reference frequency, thereby satisfying the DCS-1800 spectral purity constraints.
Pegylated interferons: chemical and clinical differences (2004)

Pegylated interferon therapy for the treatment of chronic hepatitis C virus provides significant increases in sustained virological response rates compared with standard interferons. Two pegylated interferons are now available and are used in conjunction with ribavirin to maximize response rates in infected patients. The two pegylated interferons, peginterferonalpha-2a and peginterferonalpha-2b, differ substantially in terms of their chemical and structural characteristics, pharmacokinetic and pharmacodynamic properties, and dosing and administration. A full understanding of the differences between the two drugs is important to maximize the clinical benefits. Controlled studies designed to characterize the effects of the two drugs on viral kinetics and sustained virological response rates are emerging and may help to shed additional light on the use of these compounds in patients with chronic hepatitis C.
Jarid2 and PRC2, partners in regulating gene expression (2010)

The Polycomb group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the Polycomb-Repressive Complex 2 (PRC2) including the histone H3 Lys 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We found that Jarid2 associates with PRC2 and stimulates its enzymatic activity in vitro. Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial recruitment to a promoter in vivo resulted in corecruitment of PRC2 with resultant increased levels of di- and trimethylation of H3K27 (H3K27me2/3). Jarid2 colocalizes with Ezh2 and MTF2, a homolog of Drosophila Pcl, at endogenous genes in embryonic stem (ES) cells. Jarid2 can bind DNA and its recruitment in ES cells is interdependent with that of PRC2, as Jarid2 knockdown reduced PRC2 at its target promoters, and ES cells devoid of the PRC2 component EED are deficient in Jarid2 promoter access. In addition to the well-documented defects in embryonic viability upon down-regulation of Jarid2, ES cell differentiation is impaired, as is Oct4 silencing.
Palmitoylation is the Switch that Assigns Calnexin to Quality Control or ER Calcium Signaling (2013)

The palmitoylation of calnexin serves to enrich calnexin on the mitochondria-associated membrane (MAM). Given a lack of information on the significance of this finding, we have investigated how this endoplasmic reticulum (ER)-internal sorting signal affects the functions of calnexin. Our results demonstrate that palmitoylated calnexin interacts with sarcoendoplasmic reticulum (SR) Ca(2+) transport ATPase (SERCA) 2b and that this interaction determines ER Ca(2+) content and the regulation of ER-mitochondria Ca(2+) crosstalk. In contrast, non-palmitoylated calnexin interacts with the oxidoreductase ERp57 and performs its well-known function in quality control. Interestingly, our results also show that calnexin palmitoylation is an ER-stress-dependent mechanism. Following a short-term ER stress, calnexin quickly becomes less palmitoylated, which shifts its function from the regulation of Ca(2+) signaling towards chaperoning and quality control of known substrates. These changes also correlate with a preferential distribution of calnexin to the MAM under resting conditions, or the rough ER and ER quality control compartment (ERQC) following ER stress. Our results have therefore identified the switch that assigns calnexin either to Ca(2+) signaling or to protein chaperoning.
Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. (1995)

One of the hallmarks of Alzheimer disease is the pathological aggregation of tau protein into paired helical filaments (PHFs) and neurofibrillary tangles. Here we describe the in vitro assembly of recombinant tau protein and constructs derived from it into PHFs. Though whole tau assembled poorly, constructs containing three internal repeats (corresponding to the fetal tau isoform) formed PHFs reproducibly. This ability depended on intermolecular disulfide bridges formed by the single Cys-322. Blocking the SH group, mutating Cys for Ala, or keeping tau in a reducing environment all inhibited assembly. With constructs derived from four-repeat tau (having the additional repeat no. 2 and a second Cys-291), PHF assembly was blocked because Cys-291 and Cys-322 interact within the molecule. PHF assembly was enabled again by mutating Cys-291 for Ala. The synthetic PHFs bound the dye thioflavin S used in Alzheimer disease diagnostics. The data imply that the redox potential in the neuron is crucial for PHF assembly, independently or in addition to pathological phosphorylation reactions.
Interaction of chronic sleep restriction and circadian system in humans (2008)

Nocturnal sleep restriction and compensation with daytime naps is common in today's society. In a between-participants design, we examined the effects of chronic (10 nights) sleep restriction on 24 h plasma melatonin profiles in humans. Following a baseline period with 8.2 h time in bed (TIB) for sleep, participants were randomized to a control (8.2 h TIB) or sleep-restriction condition (4.2 h TIB), with and without diurnal naps. Sleep restriction was achieved via delaying bedtime and advancing wake time by 2 h each relative to the baseline sleep period. Participants were maintained in a controlled, time isolated laboratory environment throughout the protocol, with light levels below 40 lx at all times. Twenty-four hour plasma melatonin profiles were assessed at baseline and at the end of the sleep-restriction period, with subjects maintained in a constant posture protocol. Compared with the baseline assessment and the 8.2 h TIB control group, a significant phase delay in melatonin onset (1.2 +/- 0.9 h) occurred in all sleep-restriction (4.2 h TIB) groups (P < 0.05). There was no evidence of a phase advance or shortening of the period of melatonin secretion associated with the advanced waking time. These results suggest that nocturnal light and dark exposure may be more potent in effecting circadian phase shifts than exposure to morning light, at least in conditions of controlled, dim lighting in the laboratory.
Rad52 forms ring structures and co‐operates with RPA in single‐strand DNA annealing (1998)

Rad52 forms a ring-like structure and binds to ssDNA. Its structure and DNA binding properties are different from those of Rad51. The interaction of Rad52 with RPA plays an important role in the enhancement of annealing of complementary ssDNAs. We therefore propose that Rad52 mediates the RAD51-independent recombination through an ssDNA annealing, assisted by RPA.
Pairs of Latin Squares to Counterbalance Sequential Effects and Pairing of Conditions and Stimuli (1989)

This paper discusses methods with which one can simultaneously counterbalance immediate sequential effects and pairing of conditions and stimuli in a within-subjects design using pairs of Latin squares. Within-subjects (repeated measures) experiments are common in human factors research. The designer of such an experiment must develop a scheme to ensure that the conditions and stimuli are not confounded, or randomly order stimuli and conditions. While randomization ensures balance in the long run, it is possible that a specific random sequence may not be acceptable. An alternative to randomization is to use Latin squares. The usual Latin square design ensures that each condition appears an equal number of times in each column of the square. Latin squares have been described which have the effect of counterbalancing immediate sequential effects. The objective of this work was to extend these earlier efforts by developing procedures for designing pairs of Latin squares which ensure complete counterbalancing of immediate sequential effects for both conditions and stimuli, and also ensure that conditions and stimuli are paired in the squares an equal number of times.
ACMS: the Akamai configuration management system (2005)

An important trend in information technology is the use of increasingly large distributed systems to deploy increasingly complex and mission-critical applications. In order for these systems to achieve the ultimate goal of having similar ease-of-use properties as centralized systems they must allow fast, reliable, and lightweight management and synchronization of their configuration state. This goal poses numerous technical challenges in a truly Internet-scale system, including varying degrees of network connectivity, inevitable machine failures, and the need to distribute information globally in a fast and reliable fashion.In this paper we discuss the design and implementation of a configuration management system for the Akamai Network. It allows reliable yet highly asynchronous delivery of configuration information, is significantly fault-tolerant, and can scale if necessary to hundreds of thousands of servers.The system is fully functional today providing configuration management to over 15,000 servers deployed in 1200+ different networks in 60+ countries.
Magnetic sensing technology for molecular analyses (2014)

Magnetic biosensors, based on nanomaterials and miniature electronics, have emerged as a powerful diagnostic platform. Benefiting from the inherently negligible magnetic background of biological objects, magnetic detection is highly selective even in complex biological media. The sensing thus requires minimal sample purification and yet achieves a high signal-to-background contrast. Moreover, magnetic sensors are also well-suited for miniaturization to match the size of biological targets, which enables sensitive detection of rare cells and small amounts of molecular markers. We herein summarize recent advances in magnetic sensing technologies, with an emphasis on clinical applications in point-of-care settings. Key components of sensors, including magnetic nanomaterials, labeling strategies and magnetometry, are reviewed.
Volumetric imaging using 2D capacitive micromachined ultrasonic transducer arrays (CMUTs): initial results (2003)

This paper presents the first volumetric images obtained using a 2D CMUT array with through-wafer via interconnects. An 8/spl times/6-element portion of a 32/spl times/64-element array flip-chip bonded onto a glass fanout chip was used in the experiments. This study experimentally demonstrates that 2D CMUT arrays can be fabricated with high yield using silicon micromachining processes, individual electrical connections can be provided using through-wafer interconnects, and the flip-chip bonding technique can be used to integrate the dense 2D arrays with electronic circuits for practical imaging applications.
OpenSlice: an OpenFlow-based Control Plane for Spectrum Sliced Elastic Optical Path Networks (2012)

We present an OpenFlow-based control plane for spectrum sliced elastic optical path networks, called OpenSlice, for dynamic end-to-end path provisioning and IP traffic offloading. Experimental demonstration and numerical evaluation show its overall feasibility and efficiency.
Predecibilidad de la forma de los tejidos blandos alrededor de restauraciones de implantes individuales (2003)

Con este estudio se pretendia resolver algunas dudas importantes sobre la respuesta gingival a los implantes dentales individuales: 1) ?son previsibles la regeneracion papilar y la recesion sulcular?, 2) ?el perfil de los tejidos blandos mantiene su forma sulcular durante mucho tiempo?, y 3) ?requieren los restauraciones de implantes individuales alguna manipulacion especial para poder conseguir una forma predecible en los tejidos blandos? Se llevo o cabo un analisis fotografico retrospectivo para seguir la evolucion de 55 restauraciones con implantes individuales en 51 pacientes durante un periodo de 1 a 9 anos (media 3, 5 anos). Las popilas se regeneraron sobre el 83, 9% de los implantes, con un crecimiento medio mesial de 0, 65 y distal de 0, 62 mm. El fondo sulcular retrocedio en el 59% de los pacientes una distancia media de 0, 06 mm. Se observo un relleno papilar completo en el 75% de los pacientes examinados. Las mediciones a corto y largo plazo revelaron que la regeneracion papilar continuo ligeramente y que la recesion sulcular disminuyo. La regeneracion papilar alrededor de los implantes individuales era un resultado predecible en esta poblacion; la recesion sulcular no fue un hallazgo previsto. La altura papilar tendio a aumentar, mientras que los niveles sulculares se mantuvieron bastante constantes a largo plazo. Con un protocolo protesico- implantologico simplificado se obtuvieron unos perfiles mucosos predecibles, y en la mayoria de los casos se pudo pasar directamente de los pilares de cicatrizacion a los coronas definitivas.
Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered (2006)

The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 to 4, the substantia nigra and other nuclei of the basal mid- and forebrain become the focus of initially subtle and, then, severe changes. During this phase, the illness probably becomes clinically manifest. In the final stages 5 to 6, the lesions appear in the neocortex. This cross-sectional study originally was performed on 168 autopsy cases using material from 69 incidental cases and 41 clinically diagnosed PD patients as well as 58 age- and gender-matched controls. Here, the staging hypothesis is critically reconsidered and discussed.
DNA Display I. Sequence-Encoded Routing of DNA Populations (2004)

Recently reported technologies for DNA-directed organic synthesis and for DNA computing rely on routing DNA populations through complex networks. The reduction of these ideas to practice has been limited by a lack of practical experimental tools. Here we describe a modular design for DNA routing genes, and routing machinery made from oligonucleotides and commercially available chromatography resins. The routing machinery partitions nanomole quantities of DNA into physically distinct subpools based on sequence. Partitioning steps can be iterated indefinitely, with worst-case yields of 85% per step. These techniques facilitate DNA-programmed chemical synthesis, and thus enable a materials biology that could revolutionize drug discovery.
Cloning and characterization of the guinea pig neutrophil cationic peptide-1 and-2 genes (1993)

Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules. Using cDNA probes, four different GNCP gene clones were isolated from a guinea pig genomic library. Two clones encoded GNCP-1 and other two clones encoded GNCP-2. The nucleotide sequence of GNCP-1 and GNCP-2 gene clones were highly homologous (> 97%) in the region sequenced. The GNCP-1 and GNCP-2 genes spanned 3 kb, and consisted of three exons and two introns. Exon 1 encoded the 5' untranslated region, exon 2 encoded the prepro-peptide region, and exon 3 encoded the mature peptide region and the 3' untranslated region. The transcription start site was located to a thymidine residue 93 bp upstream of the start codon (ATG) of GNCP-1 or GNCP-2 mRNA, and TATA-like sequence was located 24 to 30 bp upstream of the transcription start site. Glucocorticoid regulating element-like sequence was found in the 5' flanking region of the GNCP-1 or GNCP-2 gene, and the GNCP gene transcription rate of bone marrow cells was upregulated by dexamethasone treatment. Together these observations indicate that GNCP-1 and GNCP-2 are encoded by the very homologous but different genes, and that GNCP gene expression is regulated by glucocorticoid.
A Review on Conduction Mechanisms in Dielectric Films (2014)

The conduction mechanisms in dielectric films are crucial to the successful applications of dielectric materials. There are two types of conduction mechanisms in dielectric films, that is, electrode-limited conduction mechanism and bulk-limited conduction mechanism. The electrode-limited conduction mechanism depends on the electrical properties at the electrode-dielectric interface. Based on this type of conduction mechanism, the physical properties of the barrier height at the electrode-dielectric interface and the effective mass of the conduction carriers in dielectric films can be extracted. The bulk-limited conduction mechanism depends on the electrical properties of the dielectric itself. According to the analyses of bulk-limited conduction mechanisms, several important physical parameters in the dielectric films can be obtained, including the trap level, the trap spacing, the trap density, the carrier drift mobility, the dielectric relaxation time, and the density of states in the conduction band. In this paper, the analytical methods of conduction mechanisms in dielectric films are discussed in detail.
Alkaloid Biogenesis: Molecular Aspects (1994)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Power and Temperature Control on a 90-nm Itanium Family Processor (2005)

This paper describes the embedded feedback and control system on a 90-nm Itanium family processor, code-named Montecito, that maximizes performance while staying within a target power and temperature (PT) envelope. This system, referred to as Foxton Technology (FT), utilizes on-chip sensors and an embedded microcontroller to measure PT and modulate both voltage and frequency (VF) to optimize performance while meeting PT constraints. Changing both VF takes advantage of the cubic relationship of P/spl prop/CV/sup 2/F. We present measured results that show a 31% reduction in power for only a 10% drop in frequency. Montecito is able to implement FT using only 0.5% of the die area and 0.5% of the die power.