gebhart/patrepeval huggingface dataset:
Functional Redundancy of Sos1 and Sos2 for Lymphopoiesis and Organismal Homeostasis and Survival (2013)

Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of Sos1 null mutants has hampered ascertaining the specific in vivo contributions of Sos1 and Sos2 to processes controlling adult organism survival or development of hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we generated a tamoxifen-inducible Sos1-null mouse strain allowing analysis of the combined disruption of Sos1 and Sos2 (Sos1/2) during adulthood. Sos1/2 double-knockout (DKO) animals died precipitously, whereas individual Sos1 and Sos2 knockout (KO) mice were perfectly viable. A reduced percentage of total bone marrow precursors occurred in single-KO animals, but a dramatic depletion of B-cell progenitors was specifically detected in Sos1/2 DKO mice. We also confirmed a dominant role of Sos1 over Sos2 in early thymocyte maturation, with almost complete thymus disappearance and dramatically higher reduction of absolute thymocyte counts in Sos1/2 DKO animals. Absolute counts of mature B and T cells in spleen and peripheral blood were unchanged in single-KO mutants, while significantly reduced in Sos1/2 DKO mice. Our data demonstrate functional redundancy between Sos1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes.
Damage-free Pattern Transfer by Low Energy Electron Enhanced Etching (LE4): Mechanisms and Applications (2008)

The conventional ion-enhanced dry etch methods inflict 2 nm or more of "etch process damage" through surface ion bombardment, and this inherent surface damage creates a potentially limiting condition for IC manufacturing at feature sizes below 45 nm. As an alternative we describe the LE4 dry etch method, in which electrons with energies below about 200 eV stimulate anisotropic etching for high-resolution feature definition. Features as small as 20 nm have been etched with no damage. Line edge roughness (LER) in poly-silicon etching with LE4 is substantially less than with ion-enhanced etching. LE4 avoids trenching, bowing, and notching effects in etched profiles. In addition to control of critical dimensions, LE4 gives atomically smooth etched surfaces and maintains stoichiometry of compound materials. The absence of ion bombardment damage and the ability to tune the process to specific material energy thresholds, enable very high selectivity in LE4.
Formation of the Semliki Forest Virus Membrane Glycoprotein Complexes in the Infected Cell (1980)

In Semliki Forest virus (SFV)-infected cells, all structural proteins are translated from a 26S mRNA using a single initiation site. The capsid protein which is made first is released into the cytoplasm whereas the two membrane proteins, p62 (the precursor for E2 and E3) and E1, are inserted into the rough endoplasmic reticulum membrane. Based on gradient centrifugation and cross-linking studies, it can be seen that the p62 and E1 polypeptides form a complex immediately after synthesis and migrate to the plasma membrane in the form of a p62-E1 complex. The processing of p62 to E2 and E3 is first seen 25 to 30 min after a 10 min pulse of radioactive amino acids. This cleavage can be inhibited by addition of antisera specific for E1 and E3, thus supporting the view that, as in the case of the related Sindbis virus, this cleavage occurs on the external face of the plasma membrane. Proteolytic digestion of crude vesicle preparations derived from plasma membranes, combined with peptide mapping, indicate that the carboxy-terminal end of E2 spans the cell plasma membrane, there being a portion of mol. wt about 3000 located towards the cytosol.
Osteoarthritis. (2001)

Arthritis is a common, disabling condition that affects an increasing percentage of the population. This article includes discussion of new theories of risk factors and treatment paradigms.
Hydrodynamics of particle formation following femtosecond laser ablation (2003)

Ablation driven by intense, femtosecond laser pulses offers a novel route to fabrication of nanometer-sized particles. I model particle formation by considering the hydrodynamics of material expansion into vacuum. Modeling reveals rapid material dilution and cooling. Vacuum expansion is found to quench the ejected material 1–3 orders of magnitude more efficiently than thermal conduction quenches the residual bulk surface. Efficient quenching implies that solid-phase particles are produced rapidly (in ≪1 ns) following laser excitation; this may allow unique material states to be frozen within the ejected particles. Finally, the mean particle size is estimated to range from ∼1 to ∼10 nm for initial lattice temperatures ranging from 0.3 to 10 eV.
Bromination of Aromatic Compounds Using Ammonium Bromide and Oxone® (2010)

A simple, efficient and mild method for the selective bromination of activated aromatic compounds using ammonium bromide as the source of bromine and Oxone® as the oxidant in methanol or water as solvent is reported. The reaction proceeds at ambient temperature in yields ranging from moderate to excellent without a catalyst.
Incorporation of n‐3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid‐rich oil among healthy young men (1997)

The effects of n-3 fatty acid supplementation in the form of fresh fish, fish oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma lipid fractions, and platelets and erythrocyte membranes of young healthy male students were examined. Altogether 59 subjects (aged 19-32 yr, body mass index 16.8-31.3 kg/m2) were randomized into the following diet groups: (i) control group; (ii) fish diet group eating fish meals five times per week [0.38 +/- 0.04 g elcosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA per day]; (iii) DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form); and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14 wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte membranes was analyzed by gas chromatography. The subjects kept 4-d food records four times during the study to estimate the intake of nutrients. In the fish diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids increased and those of n-6 fatty acids decreased significantly in plasma lipid fractions and in platelets and erythrocyte membranes. A positive relationship was shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions analyzed. DHA was preferentially incorporated into phospholipid (PL) and triglyceride (TG) and there was very little uptake in cholesterol ester (CE), while EPA was preferentially incorporated into PL. and CE. The proportion of EPA in plasma lipids and platelets and erythrocyte membranes increased also by DHA supplementation, and the proportion of linoleic acid increased in platelets and erythrocyte membranes in the DHA oil group as well. These results suggest retroconversion of DHA to EPA and that DHA also interferes with linoleic acid metabolism.
Study on anisotropic diffraction properties of holographic dispersed liquid crystal transmission grating (2012)

In this paper, we study the anisotropic diffraction properties of transmission grating based on scaffolding morphology holographic dispersed liquid crystal. Due to the absence of liquid crystal droplet formation within the grating, a simple model is proposed and combined with the anisotropic coupled-wave theory to investigate the diffractive properties. The detailed comparison between experiment and theory indicates that the alignment of liquid crystal molecules in the LC-rich region is along the grating vector.
Heat transfer by high-frequency oscillations: A new hydrodynamic technique for achieving large effective thermal conductivities (1984)

Heat transfer between two fluid reservoirs maintained at different temperatures and connected to each other via a capillary bundle is examined when the fluid within the capillaries is oscillated axially. Very large effective axial heat conduction rates, exceeding those possible with heat pipes by several orders of magnitude, are found to be achievable. A laminar hydrodynamic theory is developed to describe the phenomenon and to show that the enhanced heat conduction is one involving radial heat transfer across very thin Stokes’s boundary layers existing in these flows. Experimental measurements using water as the working fluid show effective thermal diffusivities up to 17 900 times those existing in the absence of oscillations. Since the process involves no net convective mass transport, it offers considerable promise as a means for the rapid removal of heat from radioactive fluids.
Tunnel triode—a tunneling base transistor (1977)

Proposed is a triode structure made of semiconductor heterojunctions where carriers of one type tunnel through the base region to which carriers of the other type are confined. In1−xGaxAs and GaSb1−yAsy alloys are candidates for this heterostructure. As a three-terminal amplifier, the device is expected to exhibit high impedances for both input and output, a large current gain, and a marked improvement in high-frequency peformance.
Secure cross-domain data sharing architecture for crisis management (2010)

Crisis management requires rapid sharing of data among organizations responders. Existing crisis management practices rely on ad hoc or centralized data sharing based on agreements written in natural language. The ambiguity of natural language specifications often leads to errors and can hinder data availability. Therefore, it is desirable to develop automatic data sharing systems. This also presents additional challenges, such as evaluation of security constraints in different administrative domains and in situations with intermittent network connectivity. We compare two different architectural approaches to develop secure data sharing solutions. The first approach assumes reliable network connectivity, while the second approach works in ad hoc networks. We then suggest a unified architecture that caters for both scenarios.
Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010)

Reversible ubiquitination of activated receptor complexes signals their sorting between recycling and degradation and thereby dictates receptor fate. The deubiquitinating enzyme ubiquitin-specific protease 8 (USP8/UBPy) has been previously implicated in the regulation of the epidermal growth factor receptor (EGFR); however, the molecular mechanisms governing its recruitment and activity in this context remain unclear. Herein, we investigate the role of USP8 in countering ligand-induced ubiquitination and down-regulation of EGFR and characterize a subset of protein-protein interaction determinants critical for this function. USP8 depletion accelerates receptor turnover, whereas loss of hepatocyte growth factor-regulated substrate (Hrs) rescues this phenotype, indicating that USP8 protects EGFR from degradation via an Hrs-dependent pathway. Catalytic inactivation of USP8 incurs EGFR hyperubiquitination and promotes receptor localization to endosomes marked by high ubiquitin content. These phenotypes require the central region of USP8, containing three extended Arg-X-X-Lys (RXXK) motifs that specify direct low affinity interactions with the SH3 domain(s) of ESCRT-0 proteins, STAM1/2. The USP8·STAM complex critically impinges on receptor ubiquitination status and modulates ubiquitin dynamics on EGFR-positive endosomes. Consequently, USP8-mediated deubiquitination slows progression of EGFR past the early-to-recycling endosome circuit in a manner dependent upon the RXXK motifs. Collectively, these findings demonstrate a role for the USP8·STAM complex as a protective mechanism regulating early endosomal sorting of EGFR between pathways destined for lysosomal degradation and recycling.
Systemic and Specific Delivery of Small Interfering RNAs to the Liver Mediated by Apolipoprotein A-I (2007)

Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (i.v.) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I-mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (< or = 2 mg/kg) in only a single treatment, and its persistent antiviral effect up to 8 days. The liver-targeted gene silencing was also shown by in vivo images, in which bioluminescent signals emitted from the liver were efficiently reduced after i.v. administration of luciferase-specific siRNA and DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a foundation for the development of a new class of promising therapeutics against hepatitis viruses or hepatocyte genes related to tumor growth.
215GHz CMOS signal source based on a Maximum Gain Ring Oscillator topology (2012)

This paper introduces a Maximum Gain Ring Oscillator (MGRO) topology that maximizes the power gain achieved by the active devices using appropriately designed passive matching networks to maximize the frequency of oscillation. A design methodology is provided along with guidelines for the design of the passive matching network. In the absence of passive losses, the topology can oscillate at the f <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</inf> of the active devices. In the presence of passive loss, the losses can be taken into account in a closed-form fashion to maximize oscillation frequency. Based on this topology, an oscillator operating at approximately 107.5GHz is implemented using the 56-nm body-contacted devices of IBM's 45nm SOI CMOS technology (f <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</inf> is about 200GHz). The second harmonic of this oscillation is extracted using a load-pull-optimized, extraction network. This topology can be generalized for the extraction of any harmonic from MGROs with different number of stages. The oscillator generates −14.4dBm of power at 216.2GHz while drawing 57.5mW of DC power. The modeling of 45nm SOI devices for millimeter-wave design is also described.
Pose-Independent Automatic Target Detection and Recognition Using 3D Laser Radar Imagery (2005)

■ Although a number of object-recognition techniques have been developed to process terrain scenes scanned by laser radar (ladar), these techniques have had limited success in target discrimination, in part due to low-resolution data and limits in available computation power. We present a pose-independent automatic target detection and recognition system that uses data from an airborne threedimensional imaging ladar sensor. The automatic target recognition system uses geometric shape and size signatures from target models to detect and recognize targets under heavy canopy and camouflage cover in extended terrain scenes. The system performance was demonstrated on five measured scenes with targets both out in the open and under heavy canopy cover, where the target occupied between 1% to 10% of the scene by volume. The automatic target recognition section of the system was successfully demonstrated for twelve measured data scenes with targets both out in the open and under heavy canopy and camouflage cover. Correct target identification was also demonstrated for targets with multiple movable parts in arbitrary orientations. The system achieved a high recognition rate along with a low false-alarm rate. Immediate benefits of the presented work are in the area of automatic target recognition of military ground vehicles, in which the vehicles of interest may include articulated components with variable position relative to the body, and may come in many possible configurations. Other application areas include human detection and recognition for homeland security, and registration of large or extended terrain scenes.
Interpolating splines with local tension, continuity, and bias control (1984)

This paper presents a new method for using cubic interpolating splines in a key frame animation system. Three control parameters allow the animator to change the tension, continuity, and bias of the splines. Each of these three parameters can be used for either local or global control. Our technique produces a very general class of interpolating cubic splines which includes the cardinal splines as a proper subset.
Fuzzy-PI-Based Direct-Output-Voltage Control Strategy for the STATCOM Used in Utility Distribution Systems (2009)

In this paper, the control strategy for the static synchronous compensator (STATCOM) used in utility distribution systems is investigated, and a novel fuzzy-PI-based direct-output-voltage (DOV) control strategy is presented. Based on power balancing principle and feedforward decoupling control, this novel DOV control strategy cannot only reduce the active and reactive current control loops of a conventional double-loop control strategy but also achieve the decoupling control to regulate dc-link voltage and maintain the voltages at the point of common coupling (PCC). In order to effectively improve the immunity capability of this novel DOV control strategy to the uncertainties in system parameters, two fuzzy PI controllers are separately employed to maintain the voltages at the PCC and to simultaneously regulate dc-link voltage. The validity and effectiveness of this novel control strategy for the STATCOM used in utility distribution systems have been verified by simulation results, and a scaled physical prototype rated at plusmn300 kVAr is also developed to test the STATCOM system.
Improved Inhibition of Tumor Growth by Diabody-Drug Conjugates via Half-Life Extension (2019)

Despite some clinical success with antibody-drug conjugates (ADCs) in patients with solid tumors and hematological malignancies, improvements in ADC design are still desirable due to the narrow therapeutic window of these compounds. Tumor-targeting antibody fragments have distinct advantages over monoclonal antibodies, including more rapid tumor accumulation and enhanced penetration, but are subject to rapid clearance. Half-life extension technologies such as PEGylation and albumin-binding domains (ABDs) have been widely used to improve the pharmacokinetics of many different types of biologics. PEGylation improves pharmacokinetics by increasing hydrodynamic size to reduce renal clearance, whereas ABDs extend half-life via FcRn-mediated recycling. In this study, we used an anti-oncofetal antigen 5T4 diabody conjugated with a highly potent cytotoxic pyrrolobenzodiazepine (PBD) warhead to assess and compare the effects of PEGylation and albumin binding on the in vivo efficacy of antibody fragment drug conjugates. Conjugation of 2× PEG20K to a diabody improved half-life from 40 min to 33 h, and an ABD-diabody fusion protein exhibited a half-life of 45 h in mice. In a xenograft model of breast cancer MDA-MB-436, the ABD-diabody-PBD showed greater tumor growth suppression and better tolerability than either PEG-diabody-PBD or diabody-PBD. These results suggest that the mechanism of half-life extension is an important consideration for designing cytotoxic antitumor agents.
Cytoskeletal responsiveness to progestins is dependent on progesterone receptor A levels (2003)

Changes in the cell cytoskeleton occur in cell transformation and recent data suggest the involvement of ovarian hormones, which are implicated in cancer development and progression. In human breast and endometrial tumors, there is disrupted expression of progesterone receptor (PR) isoforms and predominance of one isoform, usually PRA. PRA predominance is an early event in carcinogenesis, and in cancers is associated with poor clinical features. Overexpression of PRA in vitro causes altered progestin regulation of cell morphology, suggesting that PRA overexpression may provoke deleterious changes in cell functioning. This study aimed to identify pathways of cytoskeleton regulation responsive to progestins and to determine whether these are perturbed when PRA is overexpressed to the levels seen in cancers. Progestin treatment of PR-positive breast cancer cells caused increased cell surface area whereas after induction of a stably integrated PRA construct, cells became rounded and the cell surface was decreased. The effect of PRA induction on cell rounding was reversed by the anti-progestin RU38486. Altered tropomyosin (Tm) isoforms were implicated in these morphological differences, as there was a PRA-mediated alteration in Tm5 isoform levels, and transfection of Tm5a mimicked progestin-mediated cell rounding in PRA-overexpressing cells. Ezrin was redistributed from the membrane to cytoplasmic locations in the presence of progestin, and discrete focal localization was evident in cells with PRA predominance. Progestin effects on the cytoskeleton in PRA-overexpressing cells provide evidence for novel endocrine regulation of aspects of actin microfilament composition, suggesting that changes in the cytoskeleton known to be associated with cancer development and progression may be regulated in part by altered PRA expression which develops early in carcinogenesis.
Regulation of Oleoresinosis in Grand Fir (Abies grandis) (Coordinate Induction of Monoterpene and Diterpene Cyclases and Two Cytochrome P450-Dependent Diterpenoid Hydroxylases by Stem Wounding) (1994)

Oleoresin (pitch) is a defensive secretion composed of monoterpene olefins (turpentine) and diterpene resin acids (rosin) that is produced in grand fir (Abies grandis Lindl.) stems in response to wounding. Monoterpene and diterpene biosynthesis are coordinately induced in wounded stems as determined by monitoring the activity of monoterpene and diterpene cyclases, as well as two cytochrome P450-dependent diterpenoid hydroxylases involved in the formation of ([mdash])-abietic acid, the principal resin acid of this species. The activity of these enzymes reaches maximum levels that are 5- to 100-fold higher than those of nowwounded control stems 10 d after wounding and this is followed by a synchronous decline. The increase in biosynthetic activity is consequently followed by the accumulation of a viscous mass of resin acids, with the loss of the volatile monoterpenes, at the site of injury. The observed coordinate induction of monoterpene olefin and abietic acid bio-synthesis and the results of oleoresin analysis are consistent with the role of the volatile monoterpenes as a solvent for the mobilization and deposition of resin acids at the wound site to seal the injury with a rosin barrier after the evaporation of the turpentine. The last step of resin acid biosynthesis is catalyzed by an operationally soluble aldehyde dehydrogenase that is not inducible by wounding but seemingly is expressed constitutively at a high level. In vivo [14C]acetate feeding and resin analysis indicate that this enzyme is not efficiently coupled to the earlier steps of the pathway.