gebhart/patrepeval huggingface dataset:
Degradable-Brushed pHEMA–pDMAEMA Synthesized via ATRP and Click Chemistry for Gene Delivery (2007)

Brushed polymers composed of a backbone of poly(hydroxyethyl methacrylate) (pHEMA) onto which poly(2-(dimethylamino)ethyl methacrylate)s (pDMAEMAs) was grafted via a hydrolyzable linker were synthesized and evaluated as nonviral gene delivery vectors. Both pDMAEMA and pHEMA polymers with controlled molecular weights and narrow distributions were synthesized by controlled atom transfer radical polymerization (ATRP). The azide initiator was used to ensure complete and monoazide functionalization of the pDMAEMA polymer chains. Click reaction between pHEMA with alkyne side groups and the azide end group in the pDMAEMA resulted in a high-molecular-weight polymer composed of low-molecular-weight constituents via an easily degradable carbonate ester linker. The length of the pDMAEMA grafts as well as the number of grafts of the brushed pHEMA-pDMAEMA can be easily varied. At physiological conditions (pH 7.4 and 37 degrees C), the brushed polymer degraded by hydrolysis of the carbonate ester with a half-life of 96 h. The molecular weights of the formed degradation products was very close to that of the starting pDMAEMA, which is likely below the renal excretion limit (<30 kDa). It was shown that the degradable brushed pHEMA-pDMAEMAs were able to condense plasmid DNA into positively charged nanosized particles. The resulting polyplexes were able to transfect cells efficiently in the presence of the endosomal membrane disrupting INF-7 peptide, and all these degradable polymers showed lower cellular toxicity compared to a high-molecular-weight pDMAEMA reference. On the other hand, the low-molecular-weight pDMAEMA used for the grafting to pHEMA was neither able to condense the structure of DNA nor able to transfect cells. This study demonstrates that grafting a low-molecular-weight cationic polymer via a hydrolyzable linker to a neutral hydrophilic polymer is an effective approach to modulate the transfection activity and toxicity profile of gene delivery polymers.
A dually active anthrax vaccine that confers protection against both bacilli and toxins (2003)

Systemic anthrax is caused by unimpeded bacillar replication and toxin secretion. We developed a dually active anthrax vaccine (DAAV) that confers simultaneous protection against both bacilli and toxins. DAAV was constructed by conjugating capsular poly-gamma-d-glutamic acid (PGA) to protective antigen (PA), converting the weakly immunogenic PGA to a potent immunogen, and synergistically enhancing the humoral response to PA. PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax. DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense.
Viscous mechanism for Leidenfrost propulsion on a ratchet (2011)

\n An evaporating drop placed on a ratchet self-propels, as discovered by Linke et al. in 2006. Sublimating platelets do the same, and we discuss here a possible viscous mechanism for these motions. We report that the flow of vapor below the levitating material is rectified by the asymmetric teeth of the ratchet, in the direction of descending slopes along each tooth. As a consequence, the resulting viscous stress can entrain the material in the same direction, and we discuss the resulting self-propelling force.\n
Bacterial contamination in milk kitchens in pediatric hospitals in Salvador, Brazil (2008)

Milk may represent an important source of infectious agents to hospitalized pediatric patients. To describe the bacterial microflora isolated from the hands, stools, pharynx of all workers at milk kitchens in pediatric hospitals in the city of Salvador, Brazil, as well as in the formulas prepared by them, we carried out this cross-sectional study with all 91 workers from the 20 milk kitchens of all the public and private hospitals in Salvador, Brazil. Hand and pharynx swabs and stool samples were collected from all workers, as well as samples of the milk and formulas delivered by the kitchens. All samples were cultured for the detection of pathogenic and non-pathogenic bacteria. Pathogenic bacteria were isolated from 20 (22.0%) and 8 (8.8%) cultures of the hands and pharynx of the workers, respectively. No pathogenic bacteria were isolated from stool samples. Pathogenic bacteria were isolated from 17 (18.7%) milk samples. The prevalence of pathogenic bacteria in hand swabs was significantly higher in workers from public (37.8%) than from private (6.5%) hospitals (prevalence ratio [PR]=5.8; p<0.01). Pathogenic bacteria were isolated from two (4.4%) workers from public hospitals and six (13.0%) workers from private hospitals (PR=0.38; p=0.27). Pathogenic bacteria were isolated from 11 (24.4%) milk samples from public hospitals and 6 (13.0%) from private hospitals (PR=1.9; p=0.16). A high prevalence of contamination was found, mainly on the hands of workers on units for manipulation of milk. Preventive efforts should be intensified and focus primarily on effective hand washing and continuous work supervision.
MOF-based electronic and opto-electronic devices (2014)

Metal-organic frameworks (MOFs) are a class of hybrid materials with unique optical and electronic properties arising from rational self-assembly of the organic linkers and metal ions/clusters, yielding myriads of possible structural motifs. The combination of order and chemical tunability, coupled with good environmental stability of MOFs, are prompting many research groups to explore the possibility of incorporating these materials as active components in devices such as solar cells, photodetectors, radiation detectors, and chemical sensors. Although this field is only in its incipiency, many new fundamental insights relevant to integrating MOFs with such devices have already been gained. In this review, we focus our attention on the basic requirements and structural elements needed to fabricate MOF-based devices and summarize the current state of MOF research in the area of electronic, opto-electronic and sensor devices. We summarize various approaches to designing active MOFs, creation of hybrid material systems combining MOFs with other materials, and assembly and integration of MOFs with device hardware. Critical directions of future research are identified, with emphasis on achieving the desired MOF functionality in a device and establishing the structure-property relationships to identify and rationalize the factors that impact device performance.
CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane (2008)

Taxa-4(5),11(12)-diene is the first committed precursor of functionalized taxanes such as paclitaxel, a successful anticancer drug. Biosynthesis of taxanes in yew involves several oxidations, a number of which have been shown to be catalyzed by cytochrome P-450 oxygenases. Hydroxylation of the C-5alpha of taxa-4(5),11(12)-diene is believed to be the first of these oxidations, and a gene encoding a taxa-4(5),11(12)-diene 5alpha-hydroxylase (CYP725A4) was recently described (Jennewein, S., Long, R. M., Williams, R. M., and Croteau, R. (2004) Chem. Biol. 11, 379-387). In an attempt to produce the early components of the paclitaxel pathway by a metabolic engineering approach, cDNAs encoding taxa-4(5),11(12)-diene synthase and CYP725A4 were introduced in Nicotiana sylvestris for specific expression in trichome cells. Their co-expression did not lead to the production of the expected 5alpha-hydroxytaxa-4(20),11(12)-diene. Instead, taxa-4(5),11(12)-diene was quantitatively converted to a novel taxane that was purified and characterized. Its structure was determined by NMR analysis and found to be that of 5(12)-oxa-3(11)-cyclotaxane (OCT) in which the eight-carbon B-ring from taxa-4(5),11(12)-diene is divided into two fused five-carbon rings. In addition, OCT contains an ether bridge linking C-5 and C-12 from opposite sides of the molecule. OCT was also the sole major product obtained after incubation of taxa-4(5),11(12)-diene with NADPH and microsomes prepared from recombinant yeast expressing CYP725A4. The rearrangement of the taxa-4(5),11(12)-diene ring system is thus mediated by CYP725A4 only and does not rely on additional enzymes or factors present in the plant. The complex structure of OCT led us to propose a reaction mechanism involving a sequence of events so far unknown in P-450 catalysis.
DNA PROCESSING REACTIONS IN BACTERIAL CONJUGATION (1995)

Bacterial conjugation is an important source of genetic plasticity. The initiation complex for conjugative transfer of transmissible plasmids--the relaxosome--is a specific DNA-protein structure that has been isolated from cells and reconstituted from purified components in vitro. Complexes containing uncleaved DNA and DNA cleaved at the nicsite in the origin of transfer (oriT) coexist in equilibrium. Relaxase is usually loaded onto oriT by accessory DNA-binding proteins. Relaxase catalyzes cleavage of a specific phosphodiester bond at nic and becomes covalently linked through a tyrosyl residue to the 5' terminus of the cleaved strand. Cleaved DNA may be unwound for transfer by a plasmid-encoded helicase. Single-strand transfer is thought to occur by a replicative rolling circle mechanism. Termination of a round of transfer is achieved by the cleaving-joining activity of the relaxase linked to the 5' end of the transferring strand. Relationships between DNA processing reactions and conjugative interactions of cell envelopes are particularly obscure aspects of the conjugation cycle.
Nanoscale solid-state cooling: a review (2016)

The recent developments in nanoscale solid-state cooling are reviewed. This includes both theoretical and experimental studies of different physical concepts, as well as nanostructured material design and device configurations. We primarily focus on thermoelectric, thermionic and thermo-magnetic coolers. Particular emphasis is given to the concepts based on metal-semiconductor superlattices, graded materials, non-equilibrium thermoelectric devices, Thomson coolers, and photon assisted Peltier coolers as promising methods for efficient solid-state cooling. Thermomagnetic effects such as magneto-Peltier and Nernst-Ettingshausen cooling are briefly described and recent advances and future trends in these areas are reviewed. The ongoing progress in solid-state cooling concepts such as spin-calorimetrics, electrocalorics, non-equilibrium/nonlinear Peltier devices, superconducting junctions and two-dimensional materials are also elucidated and practical achievements are reviewed. We explain the thermoreflectance thermal imaging microscopy and the transient Harman method as two unique techniques developed for characterization of thermoelectric microrefrigerators. The future prospects for solid-state cooling are briefly summarized.
Forced evolution of glutathione S-transferase to create a more efficient drug detoxication enzyme. (1995)

Glutathione S-transferases (EC 2.5.1.18) in mammalian cells catalyze the conjugation, and thus, the detoxication of a structurally diverse group of electrophilic environmental carcinogens and alkylating drugs, including the antineoplastic nitrogen mustards. We proposed that structural alteration of the nonspecific electrophile-binding site would produce mutant enzymes with increased efficiency for detoxication of a single drug and that these mutants could serve as useful somatic transgenes to protect healthy human cells against single alkylating agents used in cancer chemotherapy protocols. Random mutagenesis of three regions (residues 9-14, 102-112, and 210-220), which together compose the glutathione S-transferase electrophile-binding site, followed by selection of Escherichia coli expressing the enzyme library with the nitrogen mustard mechlorethamine (20-500 microM), yielded mutant enzymes that showed significant improvement in catalytic efficiency for mechlorethamine conjugation (up to 15-fold increase in kcat and up to 6-fold increase in kcat/Km) and that confer up to 31-fold resistance, which is 9-fold greater drug resistance than that conferred by the wild-type enzyme. The results suggest a general strategy for modification of drug- and carcinogen-metabolizing enzymes to achieve desired resistance in both prokaryotic and eukaryotic plant and animal cells.
Gene therapy for head and neck cancer (1995)

These studies will provide insight into further applications of gene therapy and novel molecular interventions that may alter our management of solid malignancies; they may also reveal mechanisms for preventing or reversing the carcinogenic process.
Haem recognition by a Staphylococcus aureus NEAT domain (2006)

Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.
Quality Monitoring And Dynamic Pricing In Cold Chain Management (2012)

This paper presents a cold chain monitoring system which focuses on assessment of quality and dynamic pricing information about food in cold chain. Cold chain is composed of many actors and stages; however it can be seen as a single entity since a breakdown in temperature control at any stage can impact the final quality of the product. In a cold chain, the shelf life, quality, and safety of perishable food throughout the supply chain is greatly impacted by environmental factors especially temperature. In this paper, a prototype application is implemented to retrieve timetemperature history, the current quality and the dynamic price setting according to changing quality impacted by temperature fluctuations in real-time.
[Killing activity in DC and CIK co-culture against hepatocarcinoma cells]. (2006)

This study was aimed to investigate the proliferation activities and phenotype changes of DC, CIK and DC-CIK, and their cytotoxicity against hepatocarcinoma cells in co-culture of DC with CIK. Peripheral blood mononuclear cells (PBMNC) were isolated from healthy adult donors. After incubation of PBMNC for 2 hours, DCs were induced from adherent cells by some cytokines and CIKs were generated from non-adherent cells. Mature DCs were harvested after incubation for 9 days, and then were co-cultured with CIK at ratio of 1:5 for 3 days. The cytotoxicity activity against SMMC-7721 hepatocellular carcinoma cell line was detected by MTT assay. The results showed that CIK cells were able to lyse SMMC-7721 hepatocellular carcinoma cells at low ratios of effector to target. This effect was significantly enhanced by co-culture with DCs. It is concluded that CIK cells have high lytic activity against 7721 hepatocellular carcinoma cell line, which can be enhanced by co-culture with DC. DC-CIK cells are highly effective immune cells.
The Association Between Idiopathic Hemolytic Uremic Syndrome and Infection by Verotoxin-Producing Escherichia coli (1985)

Forty pediatric patients with idiopathic hemolytic uremic syndrome (HUS) were investigated for evidence of infection by Verotoxin-producing Escherichia coli (VTEC). Fecal VTEC (belonging to at least six different O serogroups including O26, O111, O113, O121, O145, and O157) or specifically neutralizable free-fecal Verotoxin (VT) or both were detected in 24 (60%) patients but were not detected in 40 matched controls. Ten of 15 of the former developed fourfold or greater rises in VT-neutralizing antibody titers, as did six other patients who were negative for both fecal VTEC and VT. A total of 30 (75%) patients had evidence of VTEC infection by one or more criteria. We concluded that a significant association exists between idiopathic HUS and infection by VTEC. The detection of free-fecal VT was the most important procedure for the early diagnosis of this infection because, in our study, VTEC were never isolated in the absence of fecal VT, whereas fecal VT was often present even when VTEC were undetectable.
Silver-coated prosthetic heart valve: a double-bladed weapon (2001)

A St. Jude Medical Silzone was implanted in a 72-year-old female, suffering from mitral valve disease. Four months later, the patient had acute cardiac failure due to partial detachment of the prosthetic valve. The mitral annulus was ulcerated and there were multiple erosions in the myocardial tissue in contact with the prosthetic valve. Histological examination revealed chronic inflammation with hemosiderine deposits and giant cells. No allergy to silver ions was found. The silver-coated sewing cuff had caused a chronic inflammatory reaction due to a toxic reaction to silver. The Silzone valve was withdrawn from the market on January 2000.
A chimeric IL-2/Ig molecule possesses the functional activity of both proteins (1991)

An expression vector (pIL-2/IgG1) was constructed with the coding sequence of human IL-2 inserted upstream of the four exons (CH1, hinge, CH2, and CH3) that encode the human IgG1 H chain constant region. Introduction of this vector into a nonsecreting murine myeloma cell line resulted in the production of a chimeric molecule (IL-2/IgG1) consisting of IL-2 attached to the three Ig constant region domains. This molecule was secreted by the transfectant as a homodimer. Functional characterization revealed that the IL-2/IgG1 chimeric molecule exhibited the binding and proliferation-mediating activities of IL-2. On a per molecule basis, IL-2/IgG1 was indistinguishable from human rIL-2 in the ability to induce the proliferation of an IL-2-dependent T cell line. This chimeric molecule also possesses Ig effector function, in that it can mediate the specific lysis of IL-2R-positive cells in the presence of complement. These results demonstrate that it is possible to maintain Ig effector function in molecules ("immunoligands") in which the binding specificity is conferred not by Ig variable regions, but rather, by a ligand of choice.
A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1) (2005)

LBA3 Background: PTK787/ZK 222584 (PTK/ZK) is a novel, oral, small molecule, anti-angiogenesis compound that blocks tyrosine kinase signaling from all known vascular endothelial growth factor (VEGF) receptors. Phase I/II studies of PTK/ZK as a single agent showed that it is safe and well tolerated. Dose response was observed by DCE-MRI. An expanded phase I/II study evaluating escalating doses of PTK/ZK in combination with oxaliplatin/5-FU/LV as first-line therapy of metastatic colorectal cancer (CRC) demonstrated that chemotherapy and PTK/ZK could be safely administered as combination therapy. An overall response rate of 49% was observed; an additional 44% of Pts achieved stable disease. Methods: A multinational, randomized double-blind, placebo controlled phase III study has recently been completed to evaluate PTK/ZK in combination with the FOLFOX-4 regimen (oxaliplatin/5-FU/LV) in Pts with metastatic adenocarcinoma of the colon or rectum. Pts were included if they had histologically documented metastatic CRC, the presence of measurable disease, WHO Performance Status of 0–2 and adequate organ and bone marrow function. Pts were stratified in a 1:1 randomization scheme to receive oxaliplatin/5-FU/LV every 2 weeks according to the FOLFOX-4 regimen (de Gramont 2000) with either placebo or PTK/ZK given at a dose of 1250 mg, administered on a once-daily continuous schedule. Adjuvant therapy for primary CRC was acceptable providing that at least 6 months had elapsed from the conclusion of therapy to the time disease recurrence was documented. The primary endpoint was progression free survival (PFS). The study was designed to have at least 90% power to detect an increase in median PFS from approximately 9 months to 12 months at 5% significance level (two-sided). PFS data for the two treatment arms will be compared using a stratified log-rank test. Results: A total of 1168 Pts were randomized. Data for the primary endpoint (PFS) and secondary endpoints (overall response rate, time to progression, safety) will be presented for both treatment groups. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering AG Novartis