gebhart/patrepeval huggingface dataset:
Dispersion, coherence and noise of Fourier domain mode locked lasers (2009)

We report on the effect of chromatic dispersion on coherence length and noise of Fourier Domain Mode Locked (FDML) lasers. An FDML laser with a sweep range of 100 nm around 1550 nm has been investigated. Cavity configurations with and without dispersion compensation have been analyzed using different widths of the intra-cavity optical band-pass filter. The measurements are compared to non-FDML wavelength swept laser sources. Based on these observations, a simple model is developed providing a connection between timing, photon cavity lifetime and characteristic time constant of the filter. In an optimized configuration, an instantaneous laser linewidth of 20 pm is observed, corresponding to a 10x narrowing compared to the intra-cavity optical bandpass filter. A relative intensity noise of -133 dBc/Hz or 0.2% at 100 MHz detection bandwidth during sweep operation is observed. For optimum operation, the filter drive frequency has to be set within 2 ppm or 120 mHz at 51 kHz.
Lectin Ingestion: Changes in Mucin Secretion and Bacterial Adhesion to Intestinal Tissue (2003)

Phytohemagglutinin (PHA), the lectin derived from red kidney been (Phaseolus vulgarus) causes reduced growth rates in several animal species, when incorporated at 0.5-5% of dietary protein. Lectin feeding results in diarrhea, impaired nutrient absorption, growth rate inhibition, and can even lead to the eventual death of PHA-fed animals. These effects are believed to result from changes in the autochthonous microflora induced by the presence of PHA in the diet, as germ-free animals do not display the same changes seen in conventional animals (1-11) Jayne-Williams' (1,2) now classical studies in the quail clearly demonstrate this point. It is established that these adverse effects are the result of PHA-induced changes in the normal endogenous flora and are not due to lectin selection of specific pathogenic bacteria (9, 10) The major change appears in the levels of facultative aerobes, which increase in PHA-fed animals without an increase in obligate anaerobes (2,6). These observations separate the effects of PHA feeding from blind loop syndrome or other stressrelated changes in bacterial flora, in which anaerobic bacterial overgrowth is observed (12,13). Phytohemagglutinin feeding has also been observed to affect small intestinal growth (14).
The Polymerase Chain Reaction: Getting Started (2003)

The polymerase chain reaction (PCR) uses two oligonucleotide primers to direct the synthesis of specific sequences of DNA. One primer anneals to the coding strand of DNA and the other to the anticoding strand; the primer binding sites are typically separated by a few hundred base pairs (100–1000 bp). Repeated cycles of polymerization and denaturation lead to the exponential increase of the sequence defined by the primers. The extraordinary sensitivity and specificity of PCR have established it as a standard technique in molecular biology in the short time since it was first described ().
Adaptive Step Size Window Matching for Detection (2006)

An often overlooked problem in matching lies in selecting an appropriate step size. The selection of the step size for real-time applications is critical both from the point of view of computational efficiency and detection performance. Current systems set the step size in an ad hoc manner. This paper describes an algorithm for selecting the step size based on a theoretical worst case analysis. We have implemented this adaptive step size method in an object detection algorithm. Experimental evaluation demonstrates the effectiveness of our proposed algorithm
Design considerations for an incoherent fiber optic gyroscope (1981)

Abstract : The components required for the construction of an incoherent fiber optic gyroscope are tested. The instrument uses an incoherent light source such as an LED or diode laser operating below threshold. Five LED's and one laser diode were tested. An acousto-optic modulator is investigated as a signal processing element. Equations are developed showing the effects of incoherence on the minimum expected rotation rate that can be observed. A review of optical rotation sensing in general, and the related technology is presented. The polarization properties of the source and fiber are discussed as they relate to gyro stability and minimum rotation rate. Two possible signal processing techniques are presented which promise to further reduce minimum rotation rate and improve system stability. The requirements on components for the fabrication of an inertial grade gyro are summarized along with a discussion of component contributions to gyro error. (Author)
Synthesis and Pharmacological Study of Rho-Kinase Inhibitors: Pharmacomodulations on the Lead Compound Fasudil (2003)

With a view to specifying structure-activity relationships we have synthesised a new series of analogues of the Rho-kinase inhibitor 1-(5-isoquinolinesulfonyl)-homopiperazine (Fasudil). The structural modifications concerned the isoquinolinyl heterocycle and the sulfonyl group which are the two main features of this lead compound. These analogues were evaluated on the actin cytoskeleton and on the enzymatic activity of Rho-kinase. Most of the chemical modifications result in a loss of activity showing that interactions of Fasudil with the catalytic domain of Rho-kinase seem to be particularly definite and sensitive to structural variations. The presence of an isoquinolinyl nitrogen and a basic amino group separated by a spacer bearing a sulfonamide function are of utmost importance. Only the tetra-hydroisoquinoline analogue 3 shows the same activity as Fasudil. Moreover, this compound is unable to inhibit PKC biological activity contrary to Fasudil. The loss of the aromatic property could increase the selectivity level in favour of compound 3.
Investigation and management of Clostridium difficile colonisation in a paediatric oncology unit. (1995)

Little is known about Clostridium difficile infection in children with cancer but a presumed outbreak has previously been described. The carriage rate before admission to hospital and morbidity is reported to be high, especially in younger children. The prevalence of C difficile infection on a paediatric oncology ward was monitored from June 1991 to May 1992. Twenty eight (13%) of 214 children were found to be infected. Though the temporal distribution suggested an outbreak, polyacrylamide gel electrophoresis identified several different types. Unlike previous reports, infection appeared to be possibly endogenous or possibly environmental in origin rather than due to cross infection; the morbidity was low and age was not a determinant for infection. The duration of hospital stay and the primary diagnosis were found to be determinants for infections, those with lymphoid malignancies being at the highest risk. The diagnostic category at greatest risk were those most intensively treated, with protracted neutropenia and prolonged antibiotic exposure. Early identification of cases and prompt institution of simple control measures will prevent cross infection. It is therefore important that diarrhoea is not accepted as a normal symptom of cancer chemotherapy and stool specimens are sent for full bacteriological and viral investigation.
Zika Virus Infection in Patient with No Known Risk Factors, Utah, USA, 2016 (2017)

In 2016, Zika virus disease developed in a man (patient A) who had no known risk factors beyond caring for a relative who died of this disease (index patient). We investigated the source of infection for patient A by surveying other family contacts, healthcare personnel, and community members, and testing samples for Zika virus. We identified 19 family contacts who had similar exposures to the index patient; 86 healthcare personnel had contact with the index patient, including 57 (66%) who had contact with body fluids. Of 218 community members interviewed, 28 (13%) reported signs/symptoms and 132 (61%) provided a sample. Except for patient A, no other persons tested had laboratory evidence of recent Zika virus infection. Of 5,875 mosquitoes collected, none were known vectors of Zika virus and all were negative for Zika virus. The mechanism of transmission to patient A remains unknown but was likely person-to-person contact with the index patient.
Emergence of a replicating species from an in vitro RNA evolution reaction. (1994)

The technique of self-sustained sequence replication allows isothermal amplification of DNA and RNA molecules in vitro. This method relies on the activities of a reverse transcriptase and a DNA-dependent RNA polymerase to amplify specific nucleic acid sequences. We have modified this protocol to allow selective amplification of RNAs that catalyze a particular chemical reaction. During an in vitro RNA evolution experiment employing this modified system, a unique class of "selfish" RNAs emerged and replicated to the exclusion of the intended RNAs. Members of this class of selfish molecules, termed RNA Z, amplify efficiently despite their inability to catalyze the target chemical reaction. Their amplification requires the action of both reverse transcriptase and RNA polymerase and involves the synthesis of both DNA and RNA replication intermediates. The proposed amplification mechanism for RNA Z involves the formation of a DNA hairpin that functions as a template for transcription by RNA polymerase. This arrangement links the two strands of the DNA, resulting in the production of RNA transcripts that contain an embedded RNA polymerase promoter sequence.
The “promiscuous drug concept” with applications to Alzheimer's disease (2005)

Arguably, Alzheimer's disease (AD) is a multifactorial syndrome, rather than single disease, arising from a complex array of neurochemical factors. Numerous studies on the molecular pathogenesis of AD implicate a diversity of factors ranging from neurotoxic peptides (beta-amyloid) to inflammatory processes (interleukins), but all culminating in a common neuropathology. This diversity of molecular causation is an impediment to the design of effective therapies for AD. To address this design problem, we sought to identify a single, common motif (a "common receptor") shared by multiple structurally and functionally diverse proteins implicated in AD. This search revealed the presence of a common BBXB peptide motif and upon refinement, an AXBBXB motif; these regions can be exploited for the design of a "promiscuous drug" that exploits a "one-drug-multiple-receptors" therapeutic strategy for AD.
Notecards in a nutshell (1986)

NoteCards is an extensible environment designed to help people formulate, structure, compare, and manage ideas. NoteCards provides the user with a “semantic network” of electronic notecards interconnected by typed links. The system provides tools to organize, manage, and display the structure of the network, as well as a set of methods and protocols for creating programs to manipulate the information in the network. NoteCards is currently being used by more than 50 people engaged in idea processing tasks ranging from writing research papers through designing parts for photocopiers. In this paper we briefly describe NoteCards and the conceptualization of idea processing tasks that underlies its design. We then describe the NoteCards user community and several prototypical NoteCards applications. Finally, we discuss what we have learned about the system's strengths and weaknesses from our observations of the NoteCards user community.
Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy (2012)

Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.
Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991. (2002)

Epidemiological studies suggest potent anticancer effects of tea catechins. Previously, we have reported (I. Naasani et aL, Biochem. Biophys. Res. Commun., 249: 391-396, 1998) that epigallocatechin gallate (EGCG), a major tea catechin, strongly and directly inhibits telomerase, a ribonucleoprotein that maintains telomeres and has been implicated in tumorigenesis. Here, we describe newly synthesized compounds MST-312, MST-295, and MST-199, as more effective telomerase inhibitors than EGCG. Continuous treatment of human monoblastoid leukemia U937 cells with a nontoxic dose of each drug caused progressive telomere shortening and eventual reduction of growth rate accompanied by induction of the senescence-associated beta-galactosidase activity. Particularly, in the case of MST-312, the effective dose required for the telomere shortening was 1-2 microM, which was 15- to 20-fold lower than that of EGCG. These compounds may provide a novel chemotherapeutic strategy for the treatment of cancers.
Identification of DNA methylation markers for human breast carcinomas using the methylation-sensitive restriction fingerprinting technique. (1997)

We have developed a PCR-based method, called methylation-sensitive restriction fingerprinting (MSRF), to screen changes in DNA methylation in breast carcinomas. Two hypermethylation-containing fragments, HBC-1 (for "hypermethylation in breast cancer") and HBC-2, were identified in the amplified breast tumor DNA relative to the amplified normal breast DNA of a patient. Nucleotide sequence analysis revealed no significant matches between the sequence of HBC-1 and the known sequences in the GenBank database, whereas the sequence of HBC-2 matched the upstream region of an antisense WT1 (Wilms' tumor suppressor gene) promoter. The methylation status in the breast tumor DNA from this patient was confirmed by Southern hybridization using HBC-1 and HBC-2 as probes, respectively. Further analysis showed that HBC-1 was methylated aberrantly in 90% (17 of 19 patients) of the primary breast carcinomas examined. This study demonstrates that MSRF provides a useful means for screening aberrant changes in DNA methylation during tumorigenesis. The commonly methylated fragments identified by MSRF could potentially supplement pathological markers currently used for cancers and additionally lead to the discovery of novel methylated tumor suppressor genes.
The quinone reductase gene: A unique estrogen receptor-regulated gene that is activated by antiestrogens (1997)

Antiestrogens are thought to exert most of their beneficial effects in breast cancer by antagonizing the actions of estrogen. We report here that antiestrogens also stimulate the expression of quinone reductase (QR) [NAD(P)H:quinone oxidoreductase, EC 1.6.99.2], which may provide protective effects against the toxicity and mutagenicity caused by quinones. QR is up-regulated by low concentrations of antiestrogens (trans-hydroxytamoxifen, tamoxifen, and ICI182,780) in estrogen receptor (ER)-containing breast cancer cells, and this increase is suppressed by estrogen via an ER-dependent mechanism. Since regulation of the QR gene, as well as other genes involved in detoxification such as the glutathione S-transferase Ya subunit (GST Ya) gene, is known to be mediated by an electrophile/antioxidant response element (EpRE/ARE), we examined the effects of antiestrogens on a 41-bp electrophile responsive region derived from the GST Ya gene. Transfection of this EpRE-containing region into ER-negative breast cancer cells in the presence or absence of an expression vector for the human ER, as well as mutagenesis studies, revealed that the EpRE-containing construct was activated by antiestrogen to the same extent as by tert-butylhydroquinone (TBHQ), a known activator of EpREs; however, only the stimulation by antiestrogen, and not TBHQ, required ER and was repressed by estradiol, although activation by both inducers mapped to the same 10-bp EpRE consensus sequence. Thus, there appear to be two pathways for QR induction, one that is activated by electrophile inducers such as TBHQ and is ER independent, and a second that is antiestrogen regulated and ER dependent; both pathways act through the EpRE. The anticancer action of antiestrogens may thus derive not only from the already well-known repression of estrogen-stimulated activities but also from the activation of detoxifying enzymes, such as QR, that may contribute to the beneficial antioxidant activity of antiestrogens.
Characterization of the hca Cluster Encoding the Dioxygenolytic Pathway for Initial Catabolism of 3-Phenylpropionic Acid in Escherichia coli K-12 (1998)

We have identified, cloned, and sequenced the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid (PP) in Escherichia coli K-12. This cluster maps at min 57.5 of the chromosome and is composed of five catabolic genes arranged as a putative operon (hcaA1A2CBD) and two additional genes transcribed in the opposite direction that encode a potential permease (hcaT) and a regulator (hcaR). Sequence comparisons revealed that while hcaA1A2CD genes encode the four subunits of the 3-phenylpropionate dioxygenase, the hcaB gene codes for the corresponding cis-dihydrodiol dehydrogenase. This type of catabolic module is homologous to those encoding class IIB dioxygenases and becomes the first example of such a catabolic cluster in E. coli. The inducible expression of the hca genes requires the presence of the hcaR gene product, which acts as a transcriptional activator and shows significant sequence similarity to members of the LysR family of regulators. Interestingly, the HcaA1A2CD and HcaB enzymes are able to oxidize not only PP to 3-(2,3-dihydroxyphenyl)propionate (DHPP) but also cinnamic acid (CI) to its corresponding 2, 3-dihydroxy derivative. Further catabolism of DHPP requires the mhp-encoded meta fission pathway for the mineralization of 3-hydroxyphenylpropionate (3HPP) (A. Ferrández, J. L. García, and E. Díaz, J. Bacteriol. 179:2573-2581, 1997). Expression in Salmonella typhimurium of the mhp genes alone or in combination with the hca cluster allowed the growth of the recombinant bacteria in 3-hydroxycinnamic acid (3HCI) and CI, respectively. Thus, the convergent mhp- and hca-encoded pathways are also functional in S. typhimurium, and they are responsible for the catabolism of different phenylpropanoid compounds (3HPP, 3HCI, PP, and CI) widely available in nature.
Thermally insulated structures for IR bolometers, made of polycrystalline silicon germanium alloys (2002)

This paper reports the first realization of surface micromachined, suspended structures, made of poly crystalline silicon germanium alloys (poly Si/sub 0.7/Ge/sub 0.3/). The electrical and mechanical properties of this material are presented. The effect of the deposition conditions on the above properties is also investigated. The complete process for realizing the suspended structure is described and the possibility of reducing the process temperature down to 650/spl deg/C is demonstrated.
Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain (2013)

Recombinant Adeno-associated virus vectors (rAAV) are widely used for gene delivery and multiple naturally occurring serotypes have been harnessed to target cells in different tissues and organs including the brain. Here, we provide a detailed and quantitative analysis of the transduction profiles of rAAV vectors based on six of the most commonly used serotypes (AAV1, AAV2, AAV5, AAV6, AAV8, AAV9) that allows systematic comparison and selection of the optimal vector for a specific application. In our studies we observed marked differences among serotypes in the efficiency to transduce three different brain regions namely the striatum, hippocampus and neocortex of the mouse. Despite the fact that the analyzed serotypes have the general ability to transduce all major cell types in the brain (neurons, microglia, astrocytes and oligodendrocytes), the expression level of a reporter gene driven from a ubiquitous promoter varies significantly for specific cell type / serotype combinations. For example, rAAV8 is particularly efficient to drive transgene expression in astrocytes while rAAV9 appears well suited for the transduction of cortical neurons. Interestingly, we demonstrate selective retrograde transport of rAAV5 along axons projecting from the ventral part of the entorhinal cortex to the dentate gyrus. Furthermore, we show that self-complementing rAAV can be used to significantly decrease the time required for the onset of transgene expression in the mouse brain.
The human sympathetic nervous system: its relevance in hypertension and heart failure (2012)

Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in hypertension pathogenesis, and perhaps suggests a wider role for anti-adrenergic antihypertensives, such as the imidazoline drug class (moxonidine, rilmenidine) which act within the CNS to inhibit central sympathetic outflow, although the lack of large-scale outcome trials with this drug class remains a very material deficiency.