gebhart/patrepeval huggingface dataset:
Control of the Regioselectivity in Catalytic Transformations Involving Amphiphilic Bis-allylpalladium Intermediates:  Mechanism and Synthetic Applications (2001)

Various dialkyl-substituted allyl chloride derivatives (2d-i) undergo regioselective palladium-catalyzed coupling reactions with allylstannanes (1a,b) and benzylidenemalonitrile (4), providing functionalized 1,7-octadienes in good yield. The catalytic reaction proceeds through an unsymmetrical amphiphilic bis-allylpalladium intermediate. An introductory electrophilic attack on the terminal position of the unsubstituted allyl moiety is followed by a nucleophilic attack on the alkyl-substituted allyl ligand. A theoretical analysis was performed by applying density functional theory at the B3PW91/DZ+P level to study the substituent effects on the electrophilic attack. According to the theoretical results, the high regioselectivity can be ascribed to the electronic effects of the alkyl substituents: The terminal alkyl groups destabilize the eta(1),eta(3)-bis-allylpalladium intermediate of the reaction; in addition, the alkyl substitution increases the activation barrier for the electrophilic attack.
Isolated Low HDL Cholesterol As a Risk Factor for Coronary Heart Disease Mortality (1997)

For the purpose of screening individuals at high risk for coronary heart disease (CHD), serum total cholesterol (TC) of 5.2 mmol/L, has been set as a value dividing "desirable" from intermediate high or elevated levels, and HDL cholesterol (HDL-C) < 0.9 mmol/L has been labeled as abnormally low, implying high CHD risk. It has been conjectured that low HDL-C poses no risk in the absence of elevated LDL cholesterol or TC. To assess the risk of CHD-free men with "isolated low HDL-C," ie, abnormally low HDL-C with desirable TC, we examined the CHD and all-cause mortality of some 8000 Israeli men aged 42 years and older during 1965 through 1986. Men with isolated low HDL-C represented one sixth of the cohort. CHD mortality among these men was 36% higher (age adjusted) than in counterparts with desirable TC, of which > 0.9 mmol/L was contained in the high-density fraction. In men with TC > 5.2 mmol/L, abnormally low HDL-C was associated with a virtually identical CHD mortality risk ratio, 38%. These findings persisted after adjustment for multiple CHD risk factors. The excess CHD risk associated with isolated low HDL-C appeared particularly increased in men with diabetes mellitus, whose death rate was 65% higher than in diabetics with HDL-C > 0.9 mmol/L. A second subgroup result was consistent with equal CHD mortality risk among men in the "desirable" TC range, with or without low HDL-C, if systolic blood pressure was > 160 mm Hg. These are post hoc findings, and hypotheses arising from these observations would require independent examination. Total mortality was not increased in men with isolated low HDL-C compared with men who had HDL-C < 0.9 mmol/L and TC > 5.2 mmol/L at baseline. These results indicate that an increased risk of CHD death is associated with abnormally low HDL-C for cholesterol ranges both below and above 5.2 mmol/L. For the individual, therefore, the risk is multiplied by the same amount regardless of TC. Quitting smoking, increasing physical activity, and decreasing body weight would all contribute to raise HDL-C in individuals of most or all age groups. When examined from a community perspective, the results are consistent with a relatively low population-attributable fraction among CHD-free men. This would tend to support the recommended practice of considering a TC level of 5.2 mmol/L (200 mg/dL) as a threshold for further evaluation in screened individuals without manifest CHD.
[Correlation of limb and myocardial ischemia postconditioning with acute myocardial reperfusion injury]. (2006)

Remote limb postconditioing applied just before the onset of coronary artery reperfusion provides potent myocardial infarct size reduction, which is similar to the cardioprotective effect of myocardial postconditioning exerted during the first minutes of coronary reperfusion. The potential mechanism of this inter-organ remote postconditioning phenomenon might be associated with decreasing the injury caused by oxygen free radicals and strengthening the action of antioxidation.
Improving the balance between treatment and diagnosis: a role for radioimmunodetection. (1995)

Despite major advances in diagnostic testing, including the introduction and widespread availability of high-resolution computed tomography (CT) and magnetic resonance imaging, inadequate diagnostic information still interferes with proper management of many patients with cancers. This is particularly true for recurrent colorectal cancer, for example. In the course of this symposium, significant advances have been reported which are likely to improve management of this clinical situation. 111In, oncoscint for colorectal and ovarian cancer imaging, has been approved for single use only, and is a product licensed by the Food and Drug Administration. It has been shown to be significantly more effective than CT for detecting the presence of disease that is confined to the abdomen outside the liver. This agent is very useful in a limited role. A larger opportunity awaits other preparations reported at this conference, especially 99mTc-labeled Immu-4 carcinoembryonic antigen, which is significantly better than CT for determining resectability of recurrent cancer (T. Behr et al., Cancer Res. 55 (Suppl.): 5777S-5785S, 1995). The 99mTc-labeled compound preparations offer the advantages of low immunogenicity, excellent imaging energies of 99mTc, and "same-day" imaging. Even the most effective cancer treatment such as surgical resection, if applied to a patient who basically does not need it, can be a needless expense and a trauma to the patient. To date, our emphasis in oncology research has been heavily weighted toward developing new therapies. The success of radioimmunodetection is one indication of why it is time for a paradigm shift, during which we can move toward a more balanced program that emphasizes both diagnosis and therapy. To achieve this we must urge research institutions such as the National Cancer Institute and American Cancer Society to make major investments in the diagnostic aspects of cancer care. With the knowledge base that we have now, we can make improvements in patient care by emphasizing development of improved diagnostic methods and support for cost-effectiveness studies for developed methods, in order that currently available treatments can be more intelligently applied.
Molecular cloning of pneumonia virus of mice (1990)

cDNA clones representing nine genes of pneumonia virus of mice (PVM) have been generated. The sizes of the corresponding mRNAs and a provisional transcriptional map of the virus genome have been determined. The apparent gene order is very similar to that of respiratory syncytial virus. The sequences adjacent to the 3' termini of the PVM genes were determined and are very similar to those of respiratory syncytial virus. Several PVM gene polypeptide products have been assigned.
Recognition of two Dermatophagoides pteronyssinus-specific epitopes on antigen P1 by using monoclonal antibodies: binding to each epitope can be inhibited by serum from dust mite-allergic patients. (1984)

Monoclonal antibodies were raised against Antigen P1, the major allergen of the house dust mite (Dermatophagoides pteronyssinus). The majority were Antigen P1 specific, isotype IgG1, and did not react with a comparable D. farinae allergen. These antibodies bound 38 to 50% of 125I Antigen P1 in antigen-binding assays (titer greater than or equal to 1/1,000,000), and the quantities of IgG antibody in ascites were 2 to 4 logs greater than those in polyclonal mouse antiserum or in serum from a mite-allergic patient. Two IgM antibodies showed weak binding to Antigen P1 but reacted strongly with D. pteronyssinus in enzyme immunoassay (titer greater than or equal to 1/100,000). Assessments of the specificity of the IgG antibodies by using two inhibition radioimmunoassays suggested that they were directed against two different epitopes. Antibodies 10B9 F6 and 5H8 C12 were purified by preparative isoelectric focusing (isoelectric points of pI 6.25 and 7.4, respectively) and radiolabeled with 125I. Cross-inhibition experiments, using ascites dilutions to inhibit binding of each radiolabeled antibody to Antigen P1, confirmed that these antibodies recognized two distinct epitopes. Analysis of antibodies from 39 clones/hybrids showed that the majority were directed against the same epitopes as either 10B9 F6 or 5H8 C12 (3 out of 39 [8%] and 29 out of 39 [74%], respectively). None of the monoclonal antibodies significantly inhibited (greater than 10%) human IgE binding to Antigen P1 in the radioallergosorbent test. However, 12 of 14 sera from mite allergic patients inhibited binding by the monoclonal antibodies. One serum from a mite-allergic patient inhibited binding of both 10B9 F6 and 5H8 C12 by greater than 85% and showed parallel inhibition curves. The results suggest that these monoclonal antibodies could be used to assay Antigen P1 in both D. pteronyssinus and house dust extracts. It should also be possible to use monoclonal antibodies in inhibition assays to define the antigenic/allergenic determinants recognized by human IgG and IgE antibodies on this mite allergen.
Fusions of anthrax toxin lethal factor with shiga toxin and diphtheria toxin enzymatic domains are toxic to mammalian cells (1994)

To investigate the ability of anthrax toxin lethal factor (LF) to translocate foreign proteins into the cytosol of eukaryotic cells and to characterize the structural requirements of this process, fusion proteins containing a portion of LF and the catalytic domains of either diphtheria toxin or Shiga toxin were constructed. Previous work showed that residues 1 to 254 of anthrax toxin lethal factor (LF1-254) are sufficient for binding to the protective antigen component of the toxin and that portions of Pseudomonas exotoxin A fused to LF1-254 are efficiently translocated to the cytosol of eukaryotic cells (N. Arora and S. H. Leppla, J. Biol. Chem. 268:3334-3341, 1993). In this study, it was found that fusion proteins containing the ADP-ribosylation domain of diphtheria toxin fused at either the amino end or the carboxyl end of LF1-254 are highly toxic to Chinese hamster ovary (CHO) cells, indicating that translocation does not strictly require that the amino terminus of LF be free. A fusion protein containing the ribosome-inactivating A1 subunit of Shiga toxin fused to the carboxyl terminus of LF1-254 was also highly toxic for CHO cells. All fusion proteins were toxic only when administered with the anthrax toxin protective antigen component. The data show that the combination of protective antigen and LF fusion proteins can efficiently import polypeptides from diverse bacterial sources to the cytosol of eukaryotic cells and that LF fusion proteins may have the passenger polypeptides fused at either the amino terminus or the carboxyl terminus of LF1-254. These LF fusion proteins could potentially be used as components of a therapeutic agent when the destruction of certain types of cells is desired (e.g., in treating cancer).
<title>Adaptive Karhunen-Loeve transform for enhanced multichannel audio coding</title> (2001)

A modified MPEG Advanced Audio Coding (AAC) scheme based on the Karhunen-Loeve transform (KLT) to remove inter-channel redundancy, which is called the MAACKL method, has been proposed in our previous work. However, a straightforward coding of elements of the KLT matrix generates about 240 bits per matrix for typical 5 channel audio contents. Such an overhead is too expensive so that it prevents MAACKL from updating KLT dynamically in a short period of time. In this research, we study the de-correlation efficiency of adaptive KLT as well as an efficient way to encode elements of the KLT matrix via vector quantization. The effect due to different quantization accuracy and adaptation period is examined carefully. It is demonstrated that with the smallest possible number of bits per matrix and a moderately long KLT adaptation time, the MAACKL algorithm can still generate a very good coding performance.
Cyclopentadithiophene based electroactive materials (2005)

A wide variety of electroactive materials are accessible based on a cyclopentadithiophene skeleton. This Feature Article describes the synthesis of these materials, examines their intriguing properties (i.e. high electrical conductivity, low band-gap and extended π-conjugation) and discusses the complex relationship between structure and function in this system.
In vitro toxicity of A 3'-azido-3'-deoxythymidine and hydroxyurea combination on normal myeloid progenitors. (1998)

Hydroxyurea (HU) appears to increase 3'-azido-3'-deoxythymidine (AZT) antiretroviral activity and cytotoxicity by inhibiting thymidilate synthesis. The combination of AZT and HU may therefore be of clinical usefulness. We evaluated the in vitro hemotoxicities of different combinations of AZT and HU in comparison with the hemotoxicities exerted by either of the two drugs alone. Peripheral blood granulocyte macrophage committed progenitors (CFU-GM) of healthy donors were selected as targets of hemotoxicity. Both AZT and HU separately had a dose-dependent inhibitory effect on the in vitro growth of normal circulating CFU-GM. The combination of the two drugs induced a statistically significant synergistic cytotoxicity. In fact, addition of HU induced a remarkable reduction of AZT ID50. Thus, future clinical application of AZT, HU combination should take into account the greater hemosuppressive action of the combination in respect to that observed following administration of either drug alone.
Derivation of Type II Alveolar Epithelial Cells from Murine Embryonic Stem Cells (2002)

Embryonic stem (ES) cell pluripotency is being investigated increasingly to obtain specific cell lineages for tissue engineering. However, the possibility that ES cells can give rise to lung tissue has not been tested. We hypothesized that lung epithelial cells (type II pneumocytes) can be derived in vitro from murine ES cells. After withdrawal of leukemia inhibitory factor (LIF) and formation of embryoid bodies in maintenance medium for 10, 20, and 30 days, differentiating ES cells were kept in the same medium or transferred to serum-free small airway growth medium (SAGM) for a further 3 or 14 days of culture. The presence of type II pneumocytes in the resulting mixed cultures was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) of surfactant protein C (SPC) mRNA, immunostaining of SPC, and electron microscopy of osmiophilic lamellar bodies only at 30 days sampling time. SAGM appeared to be more favorable for type II cell formation than ES medium. No SPC transcripts were found in differentiating cells grown under the same conditions without formation of embryoid bodies. These findings could form the basis for the enrichment of ES cell-derived cultures with type II pneumocytes, and provide an in vitro system for investigating mechanisms of lung repair and regeneration.
Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection (2014)

RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated cytotoxicity, seem to play a predominant role in protection against HIV-1 acquisition and that plasma envelope (Env)-specific IgA antibodies were directly correlated with risk. RV144 and recent nonhuman primate challenge studies suggest that Env is essential, and perhaps sufficient, to induce protective antibody responses against mucosal HIV-1 acquisition. Follow-up clinical trials are ongoing to further dissect the immune responses elicited by the RV144 ALVAC-HIV and AIDSVAX® B/E regimen. The study of gp120 Env immunogens and immune correlates of risk has resulted in the development of improved antigens. Whether the RV144 immune correlates of risk will generalize to other populations vaccinated with similar immunogens with different modes and intensity of transmission remains to be demonstrated. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand.
The DNABII family of proteins: Diagnostic markers and therapeutic targets of bacterial biofilms (2014)

B are organized bacterial communities adhered to a surface. These communities are embedded in extracellular matrix also known as extracellular polymeric substances (EPS), the bulk of which is often comprised of abundant extracellular DNA (eDNA). Although biofilms are pervasive in the environment, they present specialized problems when they reside within the human body, contributing significantly to the pathogenesis, chronicity and recurrence of many infectious diseases. The EPS is so recalcitrant to the actions of the host’s immune system that biofilms act as impenetrable reservoirs of bacteria that occasionally slough off, thereby eliciting further acute infections and inducing additional remote sequelae. Even more problematic, as the host immune system mounts an attack on the biofilm, are the bystander effects to surrounding healthy tissue. We have identified that the DNABII family of proteins commonly expressed by virtually all Eubacteria is essential for EPS integrity. These proteins appear to function through the stabilization of eDNA at unusual structural motifs which have properties shared with DNA repair intermediates. Furthermore, treatment with antisera directed against members of the DNABII family is highly effective in debulking all biofilms tested in vitro to date. Data will be provided to show the mechanism of action of this protein and the failure of the immune system to mount a sufficient neutralizing response under normal disease conditions. Finally, various insights will be described to show the utility of using this family of proteins as a diagnostic marker for biofilm infections. Steven D. Goodman, J Bacteriol Parasitol 2013, 4:4 http://dx.doi.org/10.4172/2155-9597.S1.002
High‐throughput screening of chromatographic separations: II. Hydrophobic interaction (2008)

A high-throughput screen (HTS) was developed to evaluate the selectivity of various hydrophobic interaction chromatography (HIC) resins for separating a mAb from aggregate species. Prior to the resin screen, the solubility of the protein was assessed to determine the allowable HIC operating region by examining 384 combinations of pH, salt, and protein concentration. The resin screen then incorporated 480 batch-binding and elution conditions with eight HIC resins in combination with six salts. The results from the screen were reproducible, and demonstrated quantitative recovery of the mAb and aggregate. The translation of the HTS batch-binding data to lab-scale chromatography columns was tested for four conditions spanning the range of product binding and selectivity. After accounting for the higher number of theoretical plates in the columns, the purity and recovery of the lab-scale column runs agreed with the HTS results demonstrating the predictive power of the filterplate system. The HTS data were further analyzed by the calculation of pertinent thermodynamic parameters such as the partition coefficient, K(P), and the separation factor, alpha. The separation factor was used to rank the purification capabilities of the resin and salt conditions explored.
Evidence for the loop model of signal-sequence insertion into the endoplasmic reticulum. (1988)

The insertion of proteins into the endoplasmic reticulum is mediated by short hydrophobic domains called signal sequences, which are usually cleaved during insertion. We previously constructed DNAs encoding vesicular stomatitis virus glycoproteins with N-terminal extensions preceding the signal sequence and showed that these extensions allowed normal signal-sequence function and cleavage in vivo. To analyze signal sequence topology during membrane insertion, we generated a point mutation that blocks cleavage of these signal sequences. After expressing these proteins in HeLa cells, we used proteolysis of microsomal membranes to determine that the N terminus of the signal sequence and the C terminus of each protein remain on the cytoplasmic side of the endoplasmic reticulum after insertion. This result indicates that the proteins were inserted in a looped configuration. Extending this finding, we were able to reverse the orientation of such a mutant protein by deleting its normal C-terminal transmembrane and cytoplasmic domains. In addition to demonstrating that a signal sequence can function as a membrane anchor, these findings show that except for the presence of a cleavage site, the cleaved signal sequence of a type I transmembrane protein is structurally and functionally equivalent to the noncleaved signal sequences of type II transmembrane proteins.
Magnetocardiography with sensors based on giant magnetoresistance (2011)

Biomagnetic signals, mostly due to the electrical activity in the body, are very weak and they can only be detected by the most sensitive magnetometers, such as Superconducting Quantum Interference Devices (SQUIDs). We report here biomagnetic recordings with hybrid sensors based on Giant MagnetoResistance (GMR). We recorded magnetic signatures of the electric activity of the human heart (magnetocardiography) in healthy volunteers. The P-wave and QRS complex, known from the corresponding electric recordings, are clearly visible in the recordings after an averaging time of about 1 min. Multiple recordings at different locations over the chest yielded a dipolar magnetic field map and allowed localizing the underlying current sources. The sensitivity of the GMR-based sensors is now approaching that of SQUIDs and paves way for spin electronics devices for functional imaging of the body.
Highly efficient all‐nitride phosphor‐converted white light emitting diode (2005)

Abstract The development and demonstration of a highly efficient warm‐white all‐nitride phosphor‐converted light emitting diode (pc‐LED) is presented utilizing a GaN based quantum well blue LED and two novel nitrogen containing luminescent materials, both of which are doped with Eu 2+ . For color conversion of the primary blue the nitridosilicates M 2 Si 5 N 8 (orange‐red) and MSi 2 O 2 N 2 (yellow‐green), with M = alkaline earth, were employed, thus achieving a high luminous efficiency (25 lumen/W at 1 W input), excellent color quality (correlated color temperature CCT = 3200 K, general color rendering index Ra &gt; 90) and the highest proven color stability of any pc‐LED obtained so far. Thus, these novel all‐nitride LEDs are superior to both incandescent and fluorescent lamps and may therefore become the next generation of general lighting sources. (© 2005 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)