gebhart/patrepeval huggingface dataset:
Active mapping: resisting NIDS evasion without altering traffic (2004)

A critical problem faced by a network intrusion detection system (NIDS) is that of ambiguity. The NIDS cannot always determine what traffic reaches a given host nor how that host will interpret the traffic, and attackers may exploit this ambiguity to avoid detection or cause misleading alarms. We present a lightweight solution, active mapping, which eliminates TCP/IP-based ambiguity in a NIDS analysis with minimal runtime cost. Active mapping efficiently builds profiles of the network topology and the TCP/IP policies of hosts on the network; a NIDS may then use the host profiles to disambiguate the interpretation of the network traffic on a per-host basis. Active mapping avoids the semantic and performance problems of traffic normalization, in which traffic streams are modified to remove ambiguities. We have developed a prototype implementation of active mapping and modified a NIDS to use the active mapping-generated profile database in our tests. We found wide variation across operating systems' TCP/IP stack policies in real-world tests (about 6700 hosts), underscoring the need for this sort of disambiguation.
Transcranial Color‐Coded Real‐Time Sonography of Intracranial Veins (1995)

Sonographic findings in patients with superior sagittal sinus thrombosis were compared to those in healthy adults. Two patients with angiographically venf1ed superior sagittal sinus thrombosis were exam1ned by transcranial color‐coded real‐time sonography (TCCS) after mtravenous application of a pulmonary stable ultrasound contrast agent For comparison, 10 patients without venous pathology had contrast‐enhanced TCCS; in addition, 30 healthy adults had plain TCCS to determme the identification rate for deep and superficial venous segments and to define normal values of venous blood flow velocities. The straight sinus was identified in 22 of 30 healthy subjects by plain TCCS, and in 9 of 10 pat1ents by contrast‐enhanced TCCS. The mean peak and angle‐corrected blood flow velocity was 19.1 ± 7.1 em/sec. The super1or and inferior sagittal sinuses were identified by contrast‐enhanced TCCS in 2 and 1 subjects, respectively; they were never seen on pla1n TCCS. In the 2 patients with sagittal smus thrombosis a distinct increase of blood flow velocity was recorded from the stra1ght sinus (83 and 92 em/sec), most likely reflecting collateral circulation. These preliminary data mdicate that TCCS and particularly contrast‐enhanced TCCS permit identification and blood flow measurements within the deep and occasionally, the superficial venous system. TCCS may contribute to an assessment of hemodynamic repercussions of venous thrombosis and may indicate the risk of venous infarction and hemorrhage.
Low-power CMOS design through VTH control and low-swing circuits (1997)

This paper describes some of the circuit level techniques for low-power CMOS designs.
The Genetics of Bipolar Disorder (1993)

Growing interest in the application of molecular biological techniques to psychiatric disorders has reinvigorated interest in the genetics of the psychoses. It is therefore timely to review the current state of knowledge of the genetics of bipolar disorder. Family, twin and adoption studies are all consistent in confirming the strongly heritable nature of this condition. As segregation analyses have been unable to determine the mode of transmission of bipolar disorder, ongoing linkage analyses using DNA markers will be crucial in determining whether this condition is due to a single major gene, a small number of genes, or multifactorial polygenic inheritance.
Fibrosis in Autoimmune and Cholestatic Liver Disease (2011)

Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease.
PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer (2016)

Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Here, we demonstrate that ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC.
Phosphorylation and Aggregation of Protein Tau in Humanized Yeast Cells and in Transgenic Mouse Brain (2005)

Summary Tau-4R and tau-P301L was expressed in neurons in the brain of transgenic mice and in the yeast Saccharomyces cerevisiae. Tau-4R was more phosphorylated than tau-P301L at three months of age in transgenic mice, but a fraction of tau became hyperphosphorylated only with age and onset of tauopathy. By contrast, a fraction of tau-4R became hyperphosphorylated in yeast as well, especially in a strain deficient in the yeast orthologue Pho85, while this fraction was not formed in a strain deficient in Mds1, the GSK-3â orthologue. This hyperphosphorylated form of tau (designated hP-tau) was mainly cytosolic in yeast but Sarkosylinsoluble in transgenic mice, while Sarkosyl-insoluble tau in yeast was phosphorylated at fewer sites than in brain of mice. Both hP-tau in yeast and in mice was conformationally altered, indicated by MC-1 reactivity. A comprehensive scheme for tau filament formation based on combined data of both models is presented. Phosphorylation by GSK-3β is a first step for tau filament formation, causing and/or stabilising conformational change of tau, and promoting filament formation and additonal
Micromachining Sensors for Electrochemical Measurement in Subnanoliter Volumes (1997)

A miniaturized electrochemical cell was produced using lithographic patterning of metals and photopolymerizable polyimide to give a high aspect ratio circular well with clearly defined, clean gold microelectrodes at its bottom. The device, which consisted of a gold working and counter electrode and a Ag|AgI pseudoreference, located in a microchamber of diameter 200 μm and depth 20 μm (0.6 nL), was fabricated in order to analyze very small volumes of solution. An experimental procedure for routinely conducting assays in subnanoliter volumes, involving micropipetting of small quantities of reactants and solvents, was developed in order that the electrochemical characteristics of the device could be defined using the model redox compound ferrocene monocarboxylic acid. The motivation for developing this technology has been to establish a protocol that can be used to make measurements of the responses of single living cells to hormones or metabolic insult, although it is predicted that these general methods may also be of value to those interested in a variety of other fields, including technologies associated with fast-throughput diagnostics. As a consequence, issues concerning solvent evaporation and biocompatibility have also been addressed.
Distinct Regulatory Functions of Calpain 1 and 2 during Neural Stem Cell Self-Renewal and Differentiation (2012)

Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC) self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP). Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.
General weak random sources (2002)

The following model for a weak random source is considered. The source is asked only once for R bits, and the source outputs an R-bit string such that no string has probability more than 2/sup - delta R/ of being output. for some fixed delta >0. A pseudorandom generator that runs in time n/sup O(log n)/ and simulates RP using as a seed a string from such a source is exhibited. Under the generalized Paley graph conjecture, a generator that runs in polynomial time and simulates RP is given, as well as a different generator that produces almost perfectly random bits at a rate arbitrarily close to optimal using as seeds strings from a constant number of independent weak random sources.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Recombinant Apolipoprotein A-I Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks (2002)

Apolipoprotein A-I(Milano) (AIM), a natural variant of human apolipoprotein A-I, confers to carriers a significant protection against vascular disease. In previous studies, administration of recombinant AIM-phospholipid (AIM-PL) complexes to hypercholesterolemic rabbits markedly inhibited neointimal formation after arterial injury; moreover, repeated injections of AIM-PL in apoE-deficient mice significantly reduced atherosclerosis progression. The objective of the present study was to determine if a single localized infusion of AIM-PL complexes administered directly to atheromatous lesions could promote plaque regression. Lipid-rich, atheromatous plaques were generated at both common carotid arteries of 25 rabbits by applying a perivascular electric injury, followed by 1.5% cholesterol diet for 90 days. Rabbits were infused with either saline, phospholipid vesicles, or 3 different AIM-PL doses (250, 500, or 1000 mg of protein) delivered through an intravascular ultrasound (IVUS) catheter positioned at the origin of the right carotid. The lesions at the left carotid artery were therefore exposed to the agents systemically. Infusion of AIM-PL at the 2 highest doses caused reduction of right carotid artery plaque area by the end a 90-minute infusion as assessed by IVUS analysis. Plaque area regression was confirmed by histology in carotid arteries receiving direct (500 and 1000 mg doses) and systemic (500 mg dose) delivery, 72 hours after the start of the treatment. Plaque lipid content was associated with significant and similar decreases in Oil Red O staining in both arteries. These results suggest AIM-PL complexes enhanced lipid removal from arteries is the mechanism responsible for the observed plaque changes.
Recombination between genes encoding major outer surface proteins A and B of Borrelia burgdorferi (1992)

Borrelia burgdorferi causes Lyme disease, a multisystem illness that can persist in humans for many years. We describe recombination between homologous genes encoding the major outer surface proteins (Osps) A and B of B. burgdorferi which both deletes osp gene sequences and creates chimaeric gene fusions. Recombinant osp genes occur in multiple strains and encode unique proteins that lack some characteristic Osp epitopes. Antigenic variation in Osp through recombination may be relevant to the persistence of B. burgdorferi in an infected host, and has important implications for the utility of OspA and OspB as diagnostic or vaccine candidates for Lyme disease. We also describe Osp variation arising from nonsense mutations and sequence divergence, which may also represent significant sources of Osp polymorphism.
Applications of molecular ecology in the characterization of uncultured microorganisms associated with human disease (1997)

Medical microbiologists have relied heavily on the use of Koch's approach to cultivate, propagate and establish the involvement of organisms in disease. However, clinical observation is proving that some pathological conditions are associated with microbes that have not been detected by traditional cultural methods. Two recent advances have enabled the characterization of uncultured microorganisms: the introduction of the polymerase chain reaction for gene amplification and the establishment of a phylogenetically correct classification scheme for bacteria. This review seeks to summarize the advances that have been made in the characterization of uncultured microorganisms, including examples of new bacteria and disease associations which have been established. The review also describes how methods originally employed in microbial ecology have been applied to the analysis of complex bacterial communities, such as the oral microflora, and to the microbiology of purulent polymicrobial infections, without the biases of culture. The scope and limitations of these methods in future applications are discussed. We hope to illustrate how molecular biology and microbial ecology are being combined and applied to improve our understanding of human microbial disease, and how this may ultimately require a revision of Koch's postulates.
A formal description for two-dimensional patterns (1969)

A &amp;amp;quot;structural description &amp;amp;quot; for two-dimensional black and white patterns is defined as the set of contour lines for an appropriate function which fits the binary pattern. These contour lines are mutually nonintersecting closed polygonal curves with edges in only eight different directions and they represent the boundaries between connected black and white areas of the pattern. Rigorous procedures are described to transform a &amp;amp;quot;matrix pattern &amp;amp;quot; into a &amp;amp;quot;structural description&amp;amp;quot; and vice versa. Advantages of this method for describing patterns previous to pattern recognition are discussed at some length.
Mammalian artificial chromosome pilot production facility: Large‐scale isolation of functional satellite DNA‐based artificial chromosomes (1999)

Background: A pilot production facility has been established to isolate mammalian artificial chromosomes at high purity by using flow cytometric techniques. Dicentric chromosomes have been generated by the targeted amplification of pericentric heterochromatic and centromeric DNA by activating the “megareplicator.” Breakage of these dicentric chromosomes generates satellite DNA-based artificial chromosomes (SATAC) from 60 to 400 megabases. Methods: For large-scale production, we have developed cell lines capable of carrying one or two SATACs. A SATAC, because of a high adenine-thymine (AT) composition, is easily identified and sorted by using chromomycin A3 and Hoechst 33258 stains and a dual laser high-speed flow cytometer. A prototype SATAC (60 megabases) has been characterized. The prototype SATAC has been isolated from an original rodent/human hybrid cell line and transferred by using modified microcell fusion into a CHO production cell line. Results: Metaphase chromosomes from this production cell line were isolated in a modified polyamine buffer, stained, and sorted by using a modified sheath buffer that maintains condensed chromosomes. SATACs are routinely sorted at rates greater than 1 million per hour. Sorted SATACs have been transferred to a variety of cells by using microcell fusion technology and were found to be functional. Conclusions: By developing new SATAC containing cell lines with fewer numbers of chromosomes in conjunction with operating a high speed flow sorter we have effectively generated an efficient production facility geared purely for the isolation of SATACs. Cytometry 35:129–133, 1999. © 1999 Wiley-Liss, Inc.
Conversion of secopenicillanic acid derivatives into β-lactam sulphimides and oxazolines (1975)

4-(Methylthio)azetidin-2-ones when treated with chloramine T gave in each case a single sulphimide enantiomer, together with both possible sulphoxides. The sulphimides were readily converted by heating, or by attempted oxidation or reduction, into β-lactam fused oxazolines. The 4-methylthio-3-(triphenylmethylamino)azetidin-2-one derivative did not undergo comparable reaction with chloramine T.
Potential of the Cross-Flow Fan for Powered-Lift Regional Aircraft Applications (2009)

Previous investigations have indicated that the integration of cross-flow fans at the trailing edge of lifting surfaces has a high potential to increase the maximum lift coefficient, concurrently reducing drag through thrust generation and wake filling. Several studies have investigated these effects for thick airfoils. Ho wever, these airfoils are not applicable to commercial aircraft cruising at high subsonic Mach numbers. The application of cross-flow fans within propulsive wing configurations for commercial aircraft concepts is constrain ed by airfoil geometry. Besides that, two different operational modes including high -lift at low speed and high efficiency at cruise condition s have to be considered for the development of conceptual design solutions. Now, the major challenges associated with the described crossflow fan application are the understanding of the aerodynamic behavior and the constructive integration into the wing’s trailing edge. Presented in this paper is an analysis of the potentials of cross-flow fan based propulsive-wing configurations for the applicat ion to commercial aircraft featuring extreme short take off and landing (ESTOL) capabilities. The presented results involve kinematic considerations as well as aerodynamic simulations. Based hereon, a potential propulsive-wing concept using cross-flow fans is introduced.
A 3–350 K fast automatic small sample calorimeter (1997)

A description of a fully automated calorimeter for rapid measuring the heat capacity of solids in the temperature region from ∼3 to ∼350 K and in magnetic fields from 0 to 10 T is given. A comprehensive mathematical analysis of the semiadiabatic heat pulse technique for heat capacity measurements on solid materials resulted in the development of the necessary formal algorithms for the complete automatization of the data collection process. Simultaneously a procedure for the on-line evaluation of uncertainties in the measured heat capacity data is developed. An approach which eliminates the need for a separate temperature sensor(s) attached to an adiabatic heat shield(s) used to maintain semiadiabatic conditions during heat pulse heat capacity measurements has been proposed and tested. The sensorless technique provides reliable control of the heat transfer inside a vacuum chamber and results in accurate heat capacity data. The calibration results show that the heat capacity can be measured with an average accuracy better than 1% on small samples (∼1 g) over the whole temperature region.
Valine 904, Tyrosine 898, and Cysteine 908 in Na,K-ATPase α Subunits Are Important for Assembly with β Subunits (1998)

A 26-amino acid sequence in an extracellular loop of the Na,K-ATPase alpha subunit between membrane-spanning segments 7 and 8 has been shown to bind to the beta subunit of Na,K-ATPase and to promote alphabeta assembly (Lemas, M. V., Hamrick, M., Takeyasu, K., and Fambrough, D. M. (1994) J. Biol. Chem. 269, 8255-8259) When this 26-amino acid sequence of the rat Na,K-ATPase alpha3 subunit was replaced by the corresponding sequence of the rat gastric H,K-ATPase alpha subunit, the chimeric alpha subunit assembled preferentially with the rat gastric H,K-ATPase beta subunit (Wang, S.-G., Eakle, K. A., Levenson, R., and Farley, R. A. (1997) Am. J. Physiol. 272, C923-C930). In the present study, these 26 amino acids (Asn886-Ala911) of rat Na,K-ATPase alpha3 were replaced by the corresponding amino acids Asn908-Ala933 of rat distal colon H, K-ATPase. Site-directed mutagenesis of the chimeric alpha subunits and Na,K-ATPase alpha3 showed that Val904, Tyr898, and Cys908 in the Na,K-ATPase alpha3 subunit are key residues in alphabeta subunit interactions. The V904Q mutation in Na,K-ATPase alpha3 reduced the Bmax for ouabain binding and the ATPase activity of alpha3beta1 complexes by approximately 95%, and Y898R reduced the Bmax and ATPase activity by approximately 60%. The complementary mutations Q904V and R898Y increased the amount of ouabain bound by yeast membranes expressing the chimera with the colon H,K-ATPase sequence. The amount of ouabain bound by complexes assembled between Na, K-ATPase alpha3 containing the Y898R,C908G mutations and gastric H, K-ATPase beta was less than 10% of wild type Na,K-ATPase alpha3 expressed with the same beta subunit. The R898Y,G908C mutations in the chimeric alpha subunits also increased ouabain binding.
Microfabrication through Electrostatic Self-Assembly (1997)

We use electrostatic interactions to direct the patterning of gold disks having ∼10-μm diameters on functionalized surfaces. Planar and curved substrates with patterned surface charge were generated either by microcontact printing or by photolithography. Small charged gold disks were generated by electroplating gold into photoresist molds and derivatizing these disks with charged self-assembled monolayers. When agitated as a suspension in contact with the patterned surfaces, the charged gold disks deposited specifically but as disordered aggregates on regions presenting the opposite charge. Positively-charged disks deposited on phosphonate-, carboxylate-, and SiOH-terminated surfaces but not on trimethylammonium- and dimethylammonium-terminated surfaces, and vice versa for negatively-charged disks. Methyl- and CF3-terminated surfaces resisted deposition of disks of either charge. Selective and dense assembly was achieved in methanol, ethanol, 2-propanol, and dioxane; in water, deposition was nonspecific. The overlap of disks was eliminated by using disks with ∼1:1 aspect ratios.