gebhart/patrepeval huggingface dataset:
Design and characterization of wirebonds for use in high shock environments (2009)

MEMS inertial sensors, packaged in hermetic chip carriers, utilize free standing wirebonds to connect to the package I/O pads. Considerable care is taken in design of these wirebonds to balance impedances and minimize cross talk between excitation and readout channels. Many applications of MEMS inertial sensors require that they survive or operate in high acceleration or vibration environments. Any displacement of the wirebonds in these environments could adversely affect sensor bias and scale factor, or in extreme cases, cause sensor failure. Newer generations of high performance, navigation grade, inertial sensors are considerably larger than their predecessors and nearly fill the internal cavity of the chip carrier. Consequently, wirebond geometries can be highly constrained within these packages. Validating the wirebond design in an inertial sensor package, which is subject to a high-G environment, requires extensive testing on appropriate rail gun and shock table equipment. These tests are costly and equipment availability may be limited. It is also difficult to assess the sensitivity to variations in bond geometry or various bond defects using only physical testing. We are developing parameterized finite element models of wire bonds for use as tools to aid in design of sensor packages, and to guide the implementation of quality monitoring test and inspection requirements. Validation of the models is being done by subjecting well characterized wirebond configurations to air gun and drop table shock loads as well as conventional wire pull tests. We are also using a sensitive force gauge to measure the load required to displace a wire normal to the plane of its loop. Analytical expressions have also been developed for simple configurations, which serve as a check on both the finite element model and the experimental measurements.
Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration (2009)

The accumulation of preclinical and clinical evidence implicating VEGF-A in the pathogenesis of neovascular AMD has provided a strong rationale for the development of anti-VEGF agents for this disease. Anti-VEGF therapies have been used successfully in the clinic, encouraging their use in the treatment of other neovascular eye diseases.
New therapies for rheumatoid arthritis. (1995)

There are two major thrusts in the development of effective treatments in RA: the use and development of entirely new drugs; and the more effective usage of the currently available drugs. This represents a comprehensive review of the pharmacological agents that have been recently developed or will be available in the near future.
Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer (2016)

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.
Fe(salan)-Catalyzed Asymmetric Oxidation of Sulfides with Hydrogen Peroxide in Water (2007)

A new chiral Fe(salan) complex was synthesized, and it was found to serve as an efficient catalyst for asymmetric oxidation of sulfides using hydrogen peroxide in water without surfactant. Not only alkyl aryl sulfides but also various methyl alkyl sulfides were oxidized to the corresponding sulfoxides with high enantioselectivities up to 96% ee. It should be noted that the turnover number of complex 4 amounts to 8000.
Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. (1993)

Cancer chemotherapy is limited by adverse side effects resulting from toxicities to normal tissues. Targeted delivery of drugs to diseased tissues in vivo would help to reduce these side effects. Liposomes containing lipid derivatives of polyethylene glycol have circulation times sufficiently long to allow for effective in vivo drug delivery. Polyethylene glycol liposomes, containing entrapped doxorubicin, targeted to KLN-205 squamous cell carcinoma of the lung by means of specific antibodies attached at the liposome surface were capable of reducing tumor burden to a high degree and eradicating tumor in a significant percentage of mice.
Piperazinyl Glutamate Pyridines as Potent Orally Bioavailable P2Y12 Antagonists for Inhibition of Platelet Aggregation (2010)

Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position of the pyridine ring and the terminal nitrogen of the piperazine ring, leading to compound (4S)-4-[({4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 47s with good human PRP potency, selectivity, in vivo efficacy, and oral bioavailability. Compound 47s was selected for further preclinical evaluations.
THE PROTEASES AND PATHOGENICITY OF PARASITIC PROTOZOA (1993)

Protozoan parasites are among the most prevalent pathogens worldwide. Diseases like malaria, leishmaniasis, amebiasis, and trypanosomiasis affect hundreds of millions of people. Recent advances in our understanding of the biochemistry and molecular biology of these organisms has focused attention on specific parasite molecules that are key to the parasite life cycle or the pathogenesis of the diseases they produce. One group of enzymes that plays myriad roles in these processes are the parasite-derived proteases. Different types of proteases are frequently expressed at different stages of the parasite life cycle to support parasite replication and metamorphosis. Intracellular parasites such as those that produce malaria and Chagas' disease express high levels of protease activity to efficiently degrade host proteins like hemoglobin. In other instances, such as infection with Entamoeba histolytica, the causative agent of amebiasis, proteases released by the parasite can damage host cells and tissues, contributing to host tissue damage and parasite invasion. Detailed studies of these enzymes have led to model systems for the study of parasite gene regulation, parasite metabolism, and the host-parasite interplay. In some instances, proteases appear to be promising targets for the development of new antiparasitic chemotherapy.
Monocyte Chemotactic Protein-1 Increases Collateral and Peripheral Conductance After Femoral Artery Occlusion (1997)

Monocytes are activated during collateral artery growth in vivo, and monocyte chemotactic protein-1 (MCP-1) has been shown to be upregulated by shear stress in vitro. In order to investigate whether MCP-1 enhances collateral growth after femoral artery occlusion, 12 rabbits were randomly assigned to receive either MCP-1, PBS, or no local infusion via osmotic minipump. Seven days after occlusion, isolated hindlimbs were perfused with autologous blood at different pressures, measuring flows at maximal vasodilation via flow probe and radioactive microspheres, as well as peripheral pressures. This allowed the calculation of collateral (thigh) and peripheral (lower limb) conductances from pressure-flow tracings (slope of the curve). Collateral growth on postmortem angiograms was restricted to the thigh and was markedly enhanced with MCP-1 treatment. Both collateral and peripheral conductances were significantly elevated in animals with MCP-1 treatment compared with the control group, reaching values of nonoccluded hindlimbs after only 1 week of occlusion (collateral conductance, 70.6 +/- 19.23 versus 25.1 +/- 2.59 mL/min per 100 mm Hg; P < .01; peripheral conductance, 119.3 +/- 22.37 versus 45.4 +/- 6.80 mL/min per 100 mm Hg; P < .05). These results suggest that activation of monocytes plays an important role in collateral growth as well as in capillary sprouting.
Protected thiol-polyethylene glycol: A new activated polymer for reversible protein modification (1993)

Monomethoxypolyethylene glycol (mPEG) of average molecular weight 5000 was transformed in a series of synthetic steps to a new activated form of PEG, a stable thiol-protected intermediary, for reaction with cysteine residues in proteins under mild conditions to produce PEG--protein conjugates as possible candidates for therapeutics. The modified protein has PEG polymer molecules attached to the backbone by the newly formed disulfide bonds, which are readily cleaved to regenerate the native protein under mild reducing conditions. The model protein papain, which has seven cysteine residues including a lone cysteine in its active site, was modified through the free available thiol. The resulting PEG--papain was characterized by matrix-assisted laser desorption mass spectrometry, SDS-PAGE, and high performance gel filtration chromatography. The major modified PEG--papain variant was demonstrated to be 5000 Da larger than the unreacted papain.
Oxazolone-Induced Colitis in BALB/C Mice: a New Method to Evaluate the Efficacy of Therapeutic Agents for Ulcerative Colitis (2004)

A number of experimental models of colitis have been proposed. However, few studies have presented T helper-2 (Th-2) type colitis models that substitute for human ulcerative colitis (UC). In recent years, the murine oxazolone (OXA)-induced colitis model came to be accepted as a Th-2 type model, but it has yet to be used in any pharmacological study. In the present study, we modified the OXA-induced colitis model in BALB/C mice to evaluate the efficacy of treatments for UC. Colitis was induced by intrarectal administration of OXA solution (7.5 mg/mL in 40% ethanol) in a BALB/C strain that is known to favor Th-2 immune responses. A lower mortality rate was obtained in the BALB/C strain than was found in the original method. Histological examination showed that there were morphological similarities to human UC. Increased mRNA expression of interleukin-13, a Th-2 cytokine, was observed in mesenteric lymph nodes. Intrarectal administration of 5-aminosalicylic acid or sodium prednisolone phosphate resulted in a significant improvement in the colitis. These results suggest that the OXA-induced colitis model in the BALB/C strain provides a new way to evaluate the efficacy of therapeutic agents for UC.
Concise Large-Scale Synthesis of Psilocin and Psilocybin, Principal Hallucinogenic Constituents of “Magic Mushroom” (2003)

The concise large-scale syntheses of psilocin (1) and psilocybin (2), the principal hallucinogenic constituents of "magic mushroom", were achieved without chromatographic purification. The key step in the synthesis of 2 was the isolation of the dibenzyl-protected intermediate (7) as a zwitterionic derivative (8), which was completely identified by means of 2D NMR analyses.
Protective effects of interleukin-11 in a murine model of ischemic bowel necrosis (1997)

The present study examined the effect of interleukin-11 (IL-11) in a murine model of bowel ischemia (BI). Prophylactic IL-11 administration in BI mice (induced by occluding the superior mesenteric artery for 90 min) was associated with significantly decreased morbidity and mortality. IL-11-treated mice demonstrated rapid recovery of intestinal mucosa as evidenced by an increase in mitotic activity and suppression of apoptosis in intestinal crypt cells as well as increased peripheral platelet and leukocyte counts primarily due to an increase in peripheral lymphocyte number in BI mice. In contrast to vehicle-treated mice, which uniformly developed thrombocytopenia after ischemic injury, no IL-11-treated BI mice developed thrombocytopenia during the experimental period. These data suggest a role for IL-11 in the treatment of gastrointestinal mucosal diseases due to a wide variety of causative injuries.
Choline: Critical Role During Fetal Development and Dietary Requirements in Adults (2006)

Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.
Molecular Genetics of Human Color Vision: The Genes Encoding Blue, Green, and Red Pigments (1986)

Human color vision is based on three light-sensitive pigments. The isolation and sequencing of genomic and complementary DNA clones that encode the apoproteins of these three pigments are described. The deduced amino acid sequences show 41 +/- 1 percent identity with rhodopsin. The red and green pigments show 96 percent mutual identity but only 43 percent identity with the blue pigment. Green pigment genes vary in number among color-normal individuals and, together with a single red pigment gene, are proposed to reside in a head-to-tail tandem array within the X chromosome.
Audiometric Comparison of Lassa Fever Hearing Loss and Idiopathic Sudden Hearing Loss: Evidence for Viral Cause (1992)

A recently published prospective study on acute sensorineural deafness in Lassa fever among a West African population showed the audiometric pattern of a known virally induced hearing loss. Using the audiometric data from the patients with Lassa fever in that study, we analyzed and classified the initial hearing loss and final recovery into three groups by pure-tone average values and then did the same for 222 patients with idiopathic sudden hearing loss (SHL) in our study. Statistical analyses of the severity of initial hearing loss and the hearing recovery pattern indicate that the clinical course of our 222 patients with idiopathic SHL showed no statistically significant differences from the clinical course of the patients with Lassa fever. We found a marked difference in age, however, and a clinically significant difference in the incidence of bilateral hearing loss. In reviewing the literature on sudden sensorineural hearing loss, we found no apparent relation between severity of viral illness and initial hearing loss or subsequent recovery. Cummins et al. suggest that virally induced hearing loss in Lassa fever is linked to the host's immune response and not to the viremia. We thus propose a virally induced immune response mechanism for idiopathic sensorineural SHL. Further prospective studies are needed for verification.
Multimodal estimation of user interruptibility for smart mobile telephones (2006)

Context-aware computer systems are characterized by the ability to consider user state information in their decision logic. One example application of context-aware computing is the smart mobile telephone. Ideally, a smart mobile telephone should be able to consider both social factors (i.e., known relationships between contactor and contactee) and environmental factors (i.e., the contactee's current locale and activity) when deciding how to handle an incoming request for communication.Toward providing this kind of user state information and improving the ability of the mobile phone to handle calls intelligently, we present work on inferring environmental factors from sensory data and using this information to predict user interruptibility. Specifically, we learn the structure and parameters of a user state model from continuous ambient audio and visual information from periodic still images, and attempt to associate the learned states with user-reported interruptibility levels. We report experimental results using this technique on real data, and show how such an approach can allow for adaptation to specific user preferences.
Autocrine and paracrine growth stimulation of cells derived from human skin (1983)

A sensitive serum-free culture system was used to demonstrate that cells derived from normal human skin release soluble mediators which can modulate keratinocyte, melanocyte, and fibroblast growth in vitro. In M199 supplemented with epidermal growth factor, hydrocortisone, insulin, transferrin, triidothyronine, bovine serum albumin, and an extract of bovine hypothalamus, keratinocytes underwent approximately three to five cumulative population doublings (CPD) over a 7-day period. Addition of 20% keratinocyte-conditioned medium more than doubled keratinocyte growth and increased fibroblast growth 25-40% above controls. Dermal fibroblasts maintained in the same serum-free hormone-supplemented medium (SFHSM) alone underwent approximately 4.5-5.5 CPD over a 7-day period; 20% fibroblast-conditioned medium increased fibroblast growth 50-80% and increased keratinocyte growth 30-50%. Melanocytes maintained in the same SFHSM underwent approximately 1 CPD over a 14-day period and 2 CPD if the medium was supplemented with 2% fetal bovine serum (FBS). Addition of 20% melanocyte-conditioned medium more than doubled melanocyte growth in either SFHSM or in medium containing 2% FBS, but decreased both keratinocyte and fibroblast growth up to 30-60%. None of the conditioned media altered cellular morphology. These data provide the first demonstration of mutual growth modulation by cell types normally contiguous in vivo and expand existing evidence for autocrine and paracrine growth regulation by normal human cells.
X-ray and EUV laser-plasma sources based on cryogenic liquid-jet target (1999)

We describe new high-brightness laser-plasma sources for x- ray and extreme UV (EUV) radiation. By utilizing a microscopic liquid-jet or liquid-droplet target the harmful emission of debris is significantly reduced or completely eliminated. The spectrum can be spectrally tailored by choosing a suitable liquid. In this paper we summarize our work on this type of source and include some recent developments on cryogenic liquified gases such as nitrogen and xenon. We believe that this new source is a suitable choice for EUV lithography as well as for proximity x-ray lithography.
Wideband, gain-flattened, erbium-doped fibre amplifierswith 3 dBbandwidths of >50 nm (1997)

3 dB bandwidths of 52 nm (1556 – 1608 nm) for a silicate erbium-doped fibre amplifier (EDFA) and 50 nm (1554 – 1604 nm) for a fluoride EDFA have been obtained by a novel scheme with two-stage erbium-doped fibres and an intermediate equaliser. Low noise figures and high pump efficiencies of the EDFAs have been confirmed.
Effects of Porosity on the Creep Behavior of Hydrate-Bearing Sediments (2012)

In this paper, a triaxial apparatus system was set up. The creep behavior of hydrate-bearing sediments was measured by loading different shear stress on various porosity sediments. The creep curves were attempted to simulate. The experimental results indicated that, the internal cementation of the sediments was changed with the change of porosity. The viscoplastic structural was also changed with the change of porosity. High porosity sediments have a high viscosity and hardness. Moreover, the high porosity sediments have larger initial strain than the low porosity sediments.
Novel Role for Na,K-ATPase in Phosphatidylinositol 3-Kinase Signaling and Suppression of Cell Motility (2004)

The Na,K-ATPase, consisting of alpha- and beta-subunits, regulates intracellular ion homeostasis. Recent studies have demonstrated that Na,K-ATPase also regulates epithelial cell tight junction structure and functions. Consistent with an important role in the regulation of epithelial cell structure, both Na,K-ATPase enzyme activity and subunit levels are altered in carcinoma. Previously, we have shown that repletion of Na,K-ATPase beta1-subunit (Na,K-beta) in highly motile Moloney sarcoma virus-transformed Madin-Darby canine kidney (MSV-MDCK) cells suppressed their motility. However, until now, the mechanism by which Na,K-beta reduces cell motility remained elusive. Here, we demonstrate that Na,K-beta localizes to lamellipodia and suppresses cell motility by a novel signaling mechanism involving a cross-talk between Na,K-ATPase alpha1-subunit (Na,K-alpha) and Na,K-beta with proteins involved in phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. We show that Na,K-alpha associates with the regulatory subunit of PI3-kinase and Na,K-beta binds to annexin II. These molecular interactions locally activate PI3-kinase at the lamellipodia and suppress cell motility in MSV-MDCK cells, independent of Na,K-ATPase ion transport activity. Thus, these results demonstrate a new role for Na,K-ATPase in regulating carcinoma cell motility.
Polyphonic audio matching and alignment for music retrieval (2004)

We describe a method that aligns polyphonic audio recordings of music to symbolic score information in standard MIDI files without the difficult process of polyphonic transcription. By using this method, we can search through a MIDI database to find the MIDI file corresponding to a polyphonic audio recording.
Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus. (1987)

Nuclease-resistant phosphorothioate analogs of certain oligodeoxynucleotides have been tested in vitro as antiviral agents against human immunodeficiency virus (HIV) in human T cells. Phosphorothioate analogs complementary to HIV sequences, as well as noncomplementary analogs including homooligomers, exhibited potent antiviral activity. The antiviral activity was related to the base composition of the analogs, and longer phosphorothioates were more effective than shorter ones. A 28-mer phosphorothioate oligodeoxycytidine (S-dC28) at a concentration of 1 microM exhibited potent antiviral activity and inhibited de novo viral DNA synthesis as shown by Southern blot analysis. However, S-dC28 failed to inhibit gag expression in chronically infected T cells assessed by immunofluorescent assay at concentrations up to 25 microM. An N3-methylthymidine-containing phosphorothioate analog, which does not hybridize efficiently in vitro to complementary normal DNA, showed no antiviral activity. A 14-mer phosphorothioate oligodeoxycytidine (S-dC14) synergistically enhanced the antiviral activity of 2',3'-dideoxyadenosine, an anti-HIV nucleoside. Therefore, phosphorothioate analogs of oligodeoxynucleotides could represent a unique class of experimental therapeutic agents against the acquired immunodeficiency syndrome and related diseases. However, their mechanism of action is likely to be complex.