gebhart/patrepeval huggingface dataset:
The paradox of matrix metalloproteinases in infectious disease (2005)

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that perform multiple roles in the normal immune response to infection. MMPs facilitate leucocyte recruitment, cytokine and chemokine processing, defensin activation and matrix remodelling. However, excess MMP activity following infection may lead to immunopathology that causes host morbidity or mortality and favours pathogen dissemination or persistence. Here, we review the normal functions of MMPs in immunity and then discuss viral and bacterial infections where excess MMP activity has been implicated in pathology, specifically examining HIV, HTLV-1, hepatitis B, endotoxin shock, Helicobacter pylori and Mycobacterium tuberculosis. Tissue destruction may be exacerbated further by bacterial-derived enzymes which activate the host pro-MMPs. Finally, the potential for therapeutic targeting of excess MMP activity in infection is considered.
Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells (1990)

The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I- CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.
Dual-modulation laser line-locking scheme (1991)

Dual modulation laser line locking, useful for long-term trace species monitoring, achieves wavelength stability <0.1 ppm and rejects baseline drift in the measured absorbance3000-fold.
Trends in FDA drug approvals over last 2 decades: An observational study (2020)

There has been a steady rate of introduction of new drugs by CDER over the last two decades. Expedited approval of anticancer and biologics is seen as recent trend in drug development. Relatively, slow progress in approval of drugs for neurological disorders (depression, psychosis, multiple sclerosis, etc.) and lifestyle diseases like obesity, atherosclerosis, diabetes, etc., were seen. These findings reflect more emphasis being laid down in research for anticancer drugs and biologics.
A new mechanism for membrane iron transport in Pseudomonas aeruginosa (2002)

Various biochemical and biophysical studies have demonstrated the existence of a novel iron-uptake mechanism in Pseudomonas aeruginosa, different from that generally described for ferrichrome and ferric-enterobactin in Escherichia coli. This new iron-uptake mechanism involves all the proteins generally reported to be involved in the uptake of ferric-siderophore complexes in Gram-negative bacteria (i.e. the outer membrane receptor, periplasmic binding protein and ATP-binding-cassette transporter), but differs in the behaviour of the siderophore. One of the key features of this process is the binding of iron-free pyoverdin to the outer membrane receptor FpvA in conditions of iron deficiency.
Salicylate Is a Transcriptional Inhibitor of the Inducible Nitric Oxide Synthase in Cultured Cardiac Fibroblasts (1996)

We have previously reported that salicylate inhibits the inducible NO synthase (NOS 2) in cytokine-induced cardiac fibroblasts (Farivar, R. S., Chobanian, A. V., and Brecher, P. (1996) Circ. Res. 78, 759-768). To define further the mechanism of inhibition of NOS 2 by salicylate, we investigated NOS 2 mRNA induction by cytokines and determined the kinetics of inhibition by salicylate as compared to dexamethasone. Interferon-gamma plus tumor necrosis factor-alpha induced NOS 2 mRNA synergistically in a time- and dose-dependent manner. Both dexamethasone and salicylate equally inhibited the induction of NOS 2 mRNA in a time- and dose-dependent fashion, both before and after cytokine induction. Salicylate also inhibited interferon-gamma plus interleukin-1beta-induced NOS 2 mRNA. After 24 h of cytokine stimulation, salicylate stopped the induction of NOS 2 mRNA, whereas dexamethasone delayed the accumulation of transcript. In half-life experiments of NOS 2 mRNA, we found that dexamethasone reduced the half-life of NOS 2 mRNA from 7 to 4 h, whereas salicylate had no effect on mRNA stability. Tumor necrosis factor-alpha and interferon-gamma induced NF-kappaB (p50/p65) and STAT-1, respectively, as assessed by gel shift assays. Salicylate did not inhibit the cytokine induction of NF-kappaB or STAT-1. This study suggests that the anti-inflammatory mechanism of salicylate involves inhibition of NOS 2 transcription and shows that the effect is independent of NF-kappaB activation.
Monosaccharides: their chemistry and their roles in natural products (1996)

Preliminary Matters--Structures, Shapes and Sources. Reactions and Products of Reactions at the Anomeric Centre. Reactions and Products of Reactions at Non-Anomeric Carbon Atoms. Reactions and Products of Reactions of the Hydroxyl Groups. The Chemical Synthesis of Oligosaccharides. Synthesis of Enantiomerically Pure Non-Carbohydrate Compounds by Use of Monosaccharides. Natural Products Related to and Containing Monosaccharides. Appendices. Indexes.
High-Sensitivity Stark Spectroscopy Obtained by Surface Plasmon Resonance Measurement (2000)

The effect (Stark effect) of an applied electric field on the electronic states of molecular adsorbates was studied by measuring surface plasmon resonance (SPR) as a function of the wavelength of the incident light that excites the SPR. Using the Kramers-Kronig relation, Stark spectra comparable to those obtained with conventional methods were extracted from the electric field-induced SPR angular shift for several organic adsorbates. Because this method relies on detecting the SPR angular shift that can be measured precisely, high-sensitivity Stark spectroscopy can be achieved. In addition, the adsorbate coverage information can be determined from the SPR angular shift upon molecular adsorption.
Antibody-mediated alternative complement pathway activation resists inhibition by sialoglycolipids. (1985)

Although sialoglycolipids on liposome membranes were able to inhibit the activation of the alternative complement pathway (ACP) of guinea pigs mediated by trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine, they scarcely inhibited the ACP activation mediated by natural antibody to paragloboside (PG) inserted into the liposome membranes. Therefore, ACP activation was able to proceed regardless of the presence of sialoglycolipids on heterologous cell membranes when antibodies to constituents of the membranes were available. On the other hand, sialoglycolipids effectively inhibit undesirable ACP activation on self cell membranes, because little if any antibody is reacting on the self cell surface. Thus, the natural antibody reaction may effectively discriminate between self and non-self cell surface by cooperation with complement inhibitors on cell membranes such as sialoglycolipids.
Efficient Identification of Overlapping Communities (2005)

In this paper, we present an e#cient algorithm for finding overlapping communities in social networks. Our algorithm does not rely on the contents of the messages and uses the communication graph only.
What makes insulin injections painful? (1991)

Keeping in mind the limitations of the methods, we believe that long term effects in humans are very likely to occur at levels of maternal alcohol consumption during pregnancy of 300 g or more of absolute alcohol a week. Below this level the evidence is conflicting and open to methodological objections. We continue to support the recommendation from our results of immediate outcome of pregnancy that, allowing for a margin of safety, women should not have more than one standard drink a day (70-85 g absolute alcohol a week), and only as much as this if abstinence is not feasible.
Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer (2009)

BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.
Artificial neural networks for feature extraction and multivariate data projection (1995)

Classical feature extraction and data projection methods have been well studied in the pattern recognition and exploratory data analysis literature. We propose a number of networks and learning algorithms which provide new or alternative tools for feature extraction and data projection. These networks include a network (SAMANN) for J.W. Sammon's (1969) nonlinear projection, a linear discriminant analysis (LDA) network, a nonlinear discriminant analysis (NDA) network, and a network for nonlinear projection (NP-SOM) based on Kohonen's self-organizing map. A common attribute of these networks is that they all employ adaptive learning algorithms which makes them suitable in some environments where the distribution of patterns in feature space changes with respect to time. The availability of these networks also facilitates hardware implementation of well-known classical feature extraction and projection approaches. Moreover, the SAMANN network offers the generalization ability of projecting new data, which is not present in the original Sammon's projection algorithm; the NDA method and NP-SOM network provide new powerful approaches for visualizing high dimensional data. We evaluate five representative neural networks for feature extraction and data projection based on a visual judgement of the two-dimensional projection maps and three quantitative criteria on eight data sets with various properties.
A cryptography core tolerant to DFA fault attacks (2006)

This work describes a hardware approach for the concurrent fault detection and error correction in a cryptography core. It has been shown in the literature that transient faults injected in a cryptography core can lead to reveal the encryption code using quite inexpensive equipments. This kind of attack is a real threat to tamper resistant devices such as Smart Cards. To tackle such attacks, the cryptography core must be immune to transient faults. In this work the DES algorithm is taken as a vulnerable cryptosystem case study. We show how an attack against DES is performed through a fault injection campaign. Then, a countermeasure based on partial hardware replication is proposed and applied to DES. Experimental results show the efficiency of the proposed scheme to protect DES against DFA fault attacks. Furthermore, the proposed solution is independent of implementation and can be applied to other cryptography algorithms, such as AES.
Chemically assisted ion beam etching of GaAs, Ti, and Mo (1983)

Investigations with argon and chlorinated ion beams have shown that the etch rates of GaAs and Ti are strongly dependent on the flux of molecular and atomic chlorine. Etch rate increases were observed with an increase in the chlorine flux from the background gas composition or from the impinging ion beam. At increased chlorine concentrations in the presence of ion bombardment, wall profiles were altered from an overcut slope to nearly vertical. In the etching of Mo, etch rates were limited by the removal of low volatility chlorides by ion-assisted mechanisms.
An influenza A (H1N1) virus, closely related to swine influenza virus, responsible for a fatal case of human influenza (1994)

In July 1991, an influenza A virus, designated A/Maryland/12/91 (A/MD), was isolated from the bronchial secretions of a 27-year-old animal caretaker. He had been admitted to the hospital with bilateral pneumonia and died of acute respiratory distress syndrome 13 days later. Antigenic analyses with postinfection ferret antisera and monoclonal antibodies to recent H1 swine hemagglutinins indicated that the hemagglutinin of this virus was antigenically related to, but distinguishable from, those of other influenza A (H1N1) viruses currently circulating in swine. Oligonucleotide mapping of total viral RNAs revealed differences between A/MD and other contemporary swine viruses. However, partial sequencing of each RNA segment of A/MD demonstrated that all segments were related to those of currently circulating swine viruses. Sequence analysis of the entire hemagglutinin, nucleoprotein, and matrix genes of A/MD revealed a high level of identity with other contemporary swine viruses. Our studies on A/MD emphasize that H1N1 viruses in pigs obviously continue to cross species barriers and infect humans.
Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine (2010)

The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.
A Review of the Compatibility of Liposome Bupivacaine with Other Drug Products and Commonly Used Implant Materials (2014)

The compatibility of a medication with other drugs and implanted materials is an important factor impacting drug safety and efficacy. The liposomal formulation of the local anesthetic bupivacaine is designed to provide prolonged postsurgical analgesia. Its compatibility with other drugs and materials depends on the compatibility of the drug itself, along with the integrity of liposome and liposomal components. A series of studies was conducted to evaluate the compatibility of liposome bupivacaine with diluents, implanted materials, and other drugs likely to be encountered in the surgical settings in which it is used. Liposome bupivacaine demonstrated compatibility with diluents (normal saline, lactated Ringer's solution) and with implanted materials (silicone, stainless steel, titanium, polypropylene, expanded polytetrafluoro-ethylene), with little or no change in percent of free bupivacaine, packed particle volume, or particle size distribution; liposome bupivacaine exhibited little or no change in the properties of the test materials. Liposome bupivacaine had clinically meaningful interactions with other local anesthetics, including lidocaine, ropivacaine, mepivacaine, or bupivacaine HCl (at liposome bupivacaine to bupivacaine HCl ratios < 2:1), which resulted in substantial displacement and release of free bupivacaine from liposomes. Liposome bupivacaine may be locally administered after ≥ 20 minutes following local administration of lidocaine, ropivacaine, or mepivacaine. Co-administration of liposome bupivacaine and bupivacaine HCl into the same site should be at ratios ≥ 2:1. Interactions between liposome bupivacaine and epinephrine, corticosteroids, antibiotics, non-steroidal anti-inflammatory drugs, tranexamic acid, and opioid analgesics were not clinically meaningful; liposome bupivacaine may be safely co-administered with these agents. No adverse synergistic effects on liposome bupivacaine were observed in evaluations involving multiple medications compared with each drug's individual effects.
Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. (1995)

Exposure of osteosarcoma cell lines to chronic intermittent strain increases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been well studied. We analyzed the expression and production of bone matrix proteins in human osteoblast-like osteosarcoma cells, OHS-4, in response to chronic intermittent mechanical strain. The OHS-4 cells exhibit type I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalcin, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells exposed to 1-4 days of chronic intermittent strain. Northern analysis for type I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin message levels were increased several-fold by the application of mechanical load in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyclic strain. Osteocalcin levels were not detectable in vitamin D-untreated control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D present, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical strain of osteoblast-like cells is sufficient to increase the transcription and secretion of matrix proteins via mechano-transduction without hormonal induction.
A Model-Based Methodology for Spray-Drying Process Development (2009)

Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales.
Evaluation of technetium-99m-ethylenedicysteine in renal disorders and determination of extraction ratio. (1995)

Technetium-99m-EC is a suitable radiopharmaceutical for routine renal dynamic studies. Although the biological behavior of 99mTc-EC seems to be different from that of OIH, their clearances demonstrate high correlation. Technetium-99m-EC provides excellent quality images and has high potential in the evaluation of quantitative renal functions.
Detection of breast cancer by liquid crystal thermography.A preliminary report (1972)

Liquid crystal (L.C.) thermographic study of 105 women with abnormal breast characteristics was undertaken to evaluate the efficiency of L.C. thermography in breast cancer detection. Six general thermographic signs were noted to occur in breasts affected by breast cancer. These signs were derived from L.C. thermograms of 17 patients with histologically proven carcinoma. Detection of palpable malignancies with L.C. thermography had a true-positive rate of 82.3%. The false-positive rate was 13.6%, and only one of 17 histologically proven malignancies gave no thermographic signs of malignancy. Liquid crystal thermograms of 197 apparently healthy women with no breast abnormalities were classified according to pattern type. Six distinct thermal pattern types were characterized with 3 subgroups distinguishable in each of 3 vascular pattern groups. The L.C. pattern type was studied as a function of age, past pregnancies, previous lactation, use or non-use of oral contraceptives, and breast size. In general, women under 30 years of age, women with several past pregnancies, women who had lactated more than 10 months' total lifetime, women using oral contraceptives, and women with large breasts had a greater occurence of the vascular patterns. Women with abnormal breast characteristics (n = 100) and known lesions (fibrocystic disease, fibroadenoma, or carcinoma) were classified according to L.C. thermal pattern type. As expected, women with malignant lesions had a higher percentage of the vascular thermal pattern types.
External-cavity diode laser using a grazing-incidence diffraction grating (1991)

An external cavity has been developed for use with commercial diode lasers. It uses a diffraction grating at grazing incidence for wavelength selection and output coupling. This configuration allows a GaAlAs diode laser to be tuned conveniently anywhere in a range greater than 20 nm. Also, the linewidth is reduced by a factor of more than 1000 from 40 MHz to less than 10 kHz. The new laser system should be useful for high-resolution spectroscopy, laser cooling of atoms, time standards, and coherent optical communications.