gebhart/patrepeval huggingface dataset:
Palladium-Catalyzed Chemoselective Cross-Coupling of Acyl Chlorides and Organostannanes (2005)

Chemoselective cross-coupling of aliphatic and aromatic acyl chlorides with aryl-, heteroaryl-, and alkynylstannanes proceeds in up to 98% yield using 2.5 mol % of bis(di-tert-butylchlorophosphine)palladium(II) dichloride as the precatalyst. Various functional groups including aryl chlorides and bromides that usually undergo oxidative addition to palladium complexes bearing phosphinous acid or dialkylchlorophosphine ligands are tolerated. This procedure allows convenient ketone formation and eliminates inherent limitations of Friedel-Crafts acylations such as substituent-directing effects and typical reactivity requirements of Lewis acid-catalyzed electrophilic aromatic substitutions.
Pepper Spray and Politics (2012)

While protecting a tent encampment of student protesters on 18 November 2011, UC Davis freshman Ian Lee was pepper-sprayed by campus police. Boom assistant editor Ami Sommariva and Boom editor-in-chief Louis Warren sat down with Lee to talk about his experience with the Occupy movement, his radicalization, and the relationship between activism and education.
Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors (2000)

Further research is needed on the naturalistic long-term use of the TCAs and SSRIs in the treatment of anxiety disorders.
vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys (1995)

In previous experiments, animals infected with SIVmac239 containing a point mutation in the vpr and nef genes developed AIDS-like symptoms after early reversion of the vpr and nef genes. Here we show that two animals in which the nef gene but not the vpr gene had reverted in the first few months did not develop disease during a 3-year observation period even after reversion to a functional vpr gene 70 weeks postinfection. To study the influence of a stable vpr mutation on virus load and pathogenesis, a 43-bp deletion was introduced into the vpr gene of SIVmac239on, a nef-open mutant of SIVmac239. Four rhesus monkeys were inoculated with the vpr deletion mutant (SIV delta vpr), and two control animals were infected with SIVmac239on. Both control animals had persistent antigenemia, high cell-associated virus loads, and elevated neopterin levels. They had to be euthanized 20 and 30 weeks postinfection because of AIDS-related symptoms. However, all four rhesus monkeys inoculated with SIV delta vpr showed only transiently detectable antigenemia. The cell-associated virus loads were high in three of the four animals. Two animals with AIDS-like symptoms had to be euthanized 71 and 73 weeks postinfection. The two remaining monkeys infected with SIV delta vpr were still alive 105 weeks postinfection. In contrast to the SIVmac239on-infected animals, SIV delta vpr-infected animals had strong humoral immune responses and intermittent cellular immune responses to SIV antigens. Our data show that a functional vpr gene is not necessary for pathogenesis. However, vpr-deficient SIVmac239 variants might be slightly attenuated, allowing some animals to resist progression to disease for an extended period of time.
Vaccination with Live Plasmodium yoelii Blood Stage Parasites under Chloroquine Cover Induces Cross-Stage Immunity against Malaria Liver Stage (2008)

Immunity to malaria has long been thought to be stage-specific. In this study we show that immunization of BALB/c mice with live erythrocytes infected with nonlethal strains of Plasmodium yoelii under curative chloroquine cover conferred protection not only against challenge by blood stage parasites but also against sporozoite challenge. This cross-stage protection was dose-dependent and long lasting. CD4(+) and CD8(+) T cells inhibited malaria liver but not blood stage. Their effect was mediated partially by IFN-gamma, and was completely dependent of NO. Abs against both pre-erythrocytic and blood parasites were elicited and were essential for protection against blood stage and liver stage parasites. Our results suggest that Ags shared by liver and blood stage parasites can be the foundation for a malaria vaccine that would provide effective protection against both pre-erythrocytic and erythrocytic asexual parasites found in the mammalian host.
Decreased glutamate + glutamine in Alzheimer’s disease detected in vivo with 1 H-MRS at 0.5 T (2001)

Glutamate + glutamine reduction may be a biologic marker for AD and may be a potential aid in the early clinical diagnosis of AD.
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (2016)

Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
Fresh Osteochondral Allografting in the Treatment of Osteochondritis Dissecans of the Femoral Condyle (2007)

With greater than 70% good or excellent results, fresh osteochondral allograft transplantation is a successful surgical treatment for osteochondritis dissecans of the femoral condyle.
Protein Kinase Cε-dependent Regulation of Cystic Fibrosis Transmembrane Regulator Involves Binding to a Receptor for Activated C Kinase (RACK1) and RACK1 Binding to Na+/H+ Exchange Regulatory Factor (2002)

Protein kinase C (PKC) regulation of cystic fibrosis transmembrane regulator (CFTR) chloride function has been demonstrated in several cell lines, including Calu-3 cells that express native, wild-type CFTR. We demonstrated previously that PKC epsilon was required for cAMP-dependent CFTR function. The goal of this study was to determine whether PKC epsilon interacts directly with CFTR. Using overlay assay, immunoprecipitation, pulldown and binding assays, we show that PKC epsilon does not bind to CFTR, but does bind to a receptor for activated C kinase (RACK1), a 37-kDa scaffold protein, and that RACK1 binds to Na(+)/H(+) exchange regulatory factor (NHERF1), a binding partner of CFTR. In vitro binding assays demonstrate dose-dependent binding of PKC epsilon to RACK1 which is inhibited by an 8-amino acid peptide based on the sequence of the sixth Trp-Asp repeat in RACK1 or by an 8-amino acid sequence in the V1 region of PKC epsilon, epsilon V1-2. A 4-amino acid sequence INAL (70-73) expressed in CFTR shares 50% homology to the RACK1 inhibitory peptide, but it does not bind PKC epsilon. NHERF1 and RACK1 bind in a dose-dependent manner. Immunofluorescence and confocal microscopy of RACK1 and CFTR revealed colocalization of the proteins to the apical and lateral regions of Calu-3 cells. The results indicate the RACK1 binds PKC epsilon and NHERF1, thus serving as a scaffold protein to anchor the enzyme in proximity to CFTR.
Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery (2010)

In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).
Physical Stability of Liposomes Prepared from Milk Fat Globule Membrane and Soya Phospholipids (2006)

Previous research has shown that liposomes prepared from a milk fat globule membrane (MFGM) phospholipid fraction had a significantly higher phase transition temperature, thicker membrane, and lower membrane permeability than liposomes prepared from soya phospholipid material. Subsequent investigations into the relative stability of the two liposome dispersions have found that the MFGM phospholipid liposomes are more stable than their soya counterparts in a range of pH conditions, at a variety of storage and processing temperatures, and in the presence of mono- and divalent cations. These results illustrate some potential advantages in the use of MFGM phospholipids for the manufacture of liposomes for use in food systems.
An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin (1990)

Tetanus toxin is composed of a heavy chain (100 kDa) and a light chain (50 kDa) held together by a single interchain disulfide bridge. An additional intrachain disulfide is present in the carboxy-terminal part of the heavy chain. Reduction of the two disulfide bonds in tetanus toxin with both chemical and proteinaceous reducing agents was studied. Dithiothreitol and 2-mercaptoethanol cleaved both the inter- and intrachain disulfide bridges of the toxin, while glutathione and cysteine were ineffective. Specific reduction of the single interchain disulfide link was achieved with the thioredoxin-thioredoxin reductase system, thus indicating that this bond is exposed at the protein surface. Also, dead or permeabilized cells were able to reduce the toxin. Such reduced toxin bound to neuronal membranes as well as the native toxin but was not neurotoxic. These findings open the possibility that reduction by cytoplasmic agents released by dead cells contributes to detoxification of tetanus toxin. Moreover, together with the notion that the light chain is the active form of the toxin in the cytoplasm, these results suggest that the interchain disulfide bond of tetanus toxin plays a role in nerve cell penetration.
A non-absorbable rifamycin for treatment of hepatic encephalopathy. (1985)

Ammonia (NH3) plays a role in hepatic encephalopathy (HE). Agents affecting colonic ammonia production, such as non-absorbable antibiotics, decrease plasma levels of NH3 and findings of HE. The short-term efficacy of a non-absorbable rifamycin, rifaximin, was studied in comparison with paramomycin in 20 cirrhotic patients with high levels of NH3 and impaired number connection test (NCT). Both antibiotics significantly decreased ammonia-producing colonic bacteria. Rifaximin proved to be active on both aerobic and anaerobic bacteria and is thus effective, even at the dosage used, in the treatment of HE.
Transformation of mouse fibroblasts to methotrexate resistance by a recombinant plasmid expressing a prokaryotic dihydrofolate reductase. (1981)

A recombinant plasmid has been constructed for the expression of inserted DNA sequences coding for polypeptide chains using the simian virus 40 early promoter and splicing and polyadenylylation signals from the rabbit beta-globin gene. The coding regions for two prokaryotic methotrexate-resistant dihydrofolate reductases were introduced into the expression vector. When mouse fibroblasts were exposed to these recombinant plasmids, it was possible to select methotrexate-resistant clones that had integrated the plasmids and produced a chimeric RNA coding for the prokaryotic enzyme.
Fas and activation-induced Fas ligand mediate apoptosis of T cell hybridomas: inhibition of Fas ligand expression by retinoic acid and glucocorticoids. (1995)

Activation of T cell hybridomas induces a G1/S cell cycle block and apoptosis. We isolated a variant of the 2B4.11 T cell hybridoma that, when activated via the TCR, produced IL-2 and underwent growth inhibition but did not die. Analysis of a variety of cell surface molecules revealed that the variant cell line, termed VD1, expressed very low levels of Fas compared to the wild type cells. Unlike 2B4.11 cells, VD1 cells were not killed by Fas ligand (FasL)-bearing effector cells. To determine if Fas is involved in activation-induced apoptosis, two different reagents that specifically bind Fas without killing the T cell hybridomas, a monoclonal antibody and a soluble Fas:Fc chimeric molecule, were added to activated T cell hybridomas. Both treatments prevented activation-induced apoptosis in a dose-dependent manner, but had no effect on IL-2 production or growth inhibition. Northern blot analysis revealed that unactivated 2B4.11 cells expressed negligible levels of FasL mRNA, but transcripts were detectable as early as 2 h after activation and continued to increase up to 4-6 h after activation. Anti-TCR induced activation of 2B4.11 cells in the presence of a TCR- 2B4.11 variant resulted in death of the unactivated "bystander" cells, which was inhibited by anti-Fas antibodies. Finally, treatment of T hybridoma cells with 9-cis retinoic acid or glucocorticoids, which are known to prevent activation-induced T cell apoptosis, inhibited the up-regulation of FasL. We conclude that up-regulated expression of FasL and its subsequent interaction with Fas accounts for the apoptotic response of T cell hybridomas to activation, and that retinoic acid and corticosteroids inhibit activation-induced apoptosis by preventing up-regulation of FasL.
Mitochondrial mutational spectra in human cells and tissues (1997)

We have found that human organs such as colon, lung, and muscle, as well as their derived tumors, share nearly all mitochondrial hotspot point mutations. Seventeen hotspots, primarily G → A and A → G transitions, have been identified in the mitochondrial sequence of base pairs 10,030–10,130. Mutant fractions increase with the number of cell generations in a human B cell line, TK6, indicating that they are heritable changes. The mitochondrial point mutation rate appears to be more than two orders of magnitude higher than the nuclear point mutation rate in TK6 cells and in human tissues. The similarity of the hotspot sets in vivo and in vitro leads us to conclude that human mitochondrial point mutations in the sequence studied are primarily spontaneous in origin and arise either from DNA replication error or reactions of DNA with endogenous metabolites. The predominance of transition mutations and the high number of hotspots in this short sequence resembles spectra produced by DNA polymerases in vitro .
Statistical Timing Analysis for Intra-Die Process Variations with Spatial Correlations (2003)

Process variations have become a critical issue in performance verification of high-performance designs. We present a new, statistical timing analysis method that accounts for inter- and intra-die process variations and their spatial correlations. Since statistical timing analysis has an exponential run time complexity, we propose a method whereby a statistical bound on the probability distribution function of the exact circuit delay is computed with linear run time. First, we develop a model for representing inter- and intra-die variations and their spatial correlations. Using this model, we then show how gate delays and arrival times can be represented as a sum of components, such that the correlation information between arrival times and gate delays is preserved. We then show how arrival times are propagated and merged in the circuit to obtain an arrival time distribution that is an upper bound on the distribution of the exact circuit delay. We prove the correctness of the bound and also show how the bound can be improved by propagating multiple arrival times. The proposed algorithms were implemented and tested on a set of benchmark circuits under several process variation scenarios. The results were compared with Monte Carlo simulation and show an accuracy of 3.32% on average over all test cases.
Milatuzumab – a promising new immunotherapeutic agent (2009)

Milatuzumab is a new immunotherapeutic agent targeting CD74, a membrane protein preferentially expressed in hematopoietic cancers and some solid tumors. Broad expression and fast internalization makes CD74 an ideal target for cancer therapy. We reviewed published articles about CD74 and milatuzumab. We present a comprehensive review of CD74 functions and provide explanation of milatuzumab antitumor effects. This review describes CD74 protein biology with the emphasis on the role of CD74 in tumor survival and its new role in regulation of the Fas death receptor. The development of CD74 targeting therapies to induce tumor regression and cancer cell apoptosis is described and results of clinical trials are discussed. Milatuzumab shows selective binding and rapid internalization into CD74-positive cancer cells. Milatuzumab with and without conjugated toxins synergizes with other chemotherapeutic agents and elicits significant antitumor effects in mice. In a Phase I trial, milatuzumab showed no severe adverse effects in patients with relapsed/refractory multiple myeloma and it stabilized the disease in some patients for up to 12 weeks. Ongoing trials testing different treatment schedules of milatuzumab in chronic lymphocytic leukemia, non-Hodgkin's lymphoma and multiple myeloma indicate that milatuzumab shows no severe adverse effects in humans.
Adjuvanted subunit vaccines for the control of Salmonella enteritidis infection in turkeys (1994)

Liposomes and immunostimulating complexes (ISCOM) are adjuvants that have been known to potentiate the immune response to membrane proteins. Adjuvanted outer membrane proteins (OMP) from Salmonella enteritidis were evaluated for their protective efficacy against S enteritidis infection in turkeys. The adjuvanted vaccines prepared for evaluation were: positive or negatively charged liposomes, lipid-conjugated ISCOM, and mineral oil vaccines. These preparations were compared with that of a whole cell bacterin and protein alone. After vaccination, turkeys were challenge-exposed with a nalidixic acid-resistant strain of S enteritidis. They were monitored for clinical signs of disease, antibody response, bacterial shedding pattern, and clearance of the challenge S enteritidis from internal organs. Results indicated a significantly (P < 0.05) higher antibody response to the positively charged liposomal OMP vaccine, compared with the whole cell bacterin. The antibody response to positively charged liposomal OMP vaccine was greater when a booster dose of this preparation was given. Shedding of S enteritidis was decreased in all vaccinated and challenge-exposed turkeys (P < 0.001). The tissues from a high percentage (90 to 100%) of birds that received a booster vaccination of the liposomal (+ or -) and ISCOM vaccine were culture-negative for S enteritidis.
Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance (2005)

The emergence of drug-resistant bacteria poses a serious threat to human health. In the case of several antibiotics, including those of the quinolone and rifamycin classes, bacteria rapidly acquire resistance through mutation of chromosomal genes during therapy. In this work, we show that preventing induction of the SOS response by interfering with the activity of the protease LexA renders pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results in the derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce resistance-conferring mutations. Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance.
Reverse Genetics for the Control of Avian Influenza (2003)

Avian influenza viruses are major contributors to viral disease in poultry as well as humans. Outbreaks of high-pathogenicity avian influenza viruses cause high mortality in poultry, resulting in significant economic losses. The potential of avian influenza viruses to reassort with human stains resulted in global pandemics in 1957 and 1968, while the introduction of an entirely avian virus into humans claimed several lives in Hong Kong in 1997. Despite considerable research, the mechanisms that determine the pathogenic potential of a virus or its ability to cross the species barrier are poorly understood. Reverse genetics methods, i.e., methods that allow the generation of an influenza virus entirely from cloned cDNAs, have provided us with one means to address these issues. In addition, reverse genetics is an excellent tool for vaccine production and development. This technology should increase our preparedness for future influenza virus outbreaks.
Gene Therapy for Bone Regeneration (2005)

Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone has the unique ability to regenerate and continuously remodel itself throughout life. However, clinical situations arise when bone is unable to heal itself, as with segmental bone loss, fracture non-union, and failed spinal fusion. This leads to significant morbidity and mortality. Current attempts at improved bone healing have been met with limited success, fueling the development of improved techniques. Gene therapy in many ways represents an ideal approach for augmenting bone regeneration. Gene therapy allows specific gene products to be delivered to a precise anatomic location. In addition, the level of transgene expression as well as the duration of expression can be regulated with current techniques. For bone regeneration, the gene of interest should be delivered to the fracture site, expressed at appropriate levels, and then deactivated once the fracture has healed. Delivery of biological factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results both in animal and clinical studies. There has also been tremendous work on discovering new growth factors and exploring previously defined ones. Finally, significant advances are being made in the delivery systems of the genes, ranging from viral and non-viral vectors to tissue engineering scaffolds. Despite some public hesitation to gene therapy, its use has great potential to expand our ability to treat a variety of human bone and musculoskeletal disorders. It is conceivable that in the near future gene therapy can be utilized to induce bone formation in virtually any region of the body in a minimally invasive manner. As bone biology and gene therapy research progresses, the goal of successful human gene transfer for augmentation of bone regeneration draws nearer.
Ribonuclease-Activated Cancer Prodrug (2012)

Cancer chemotherapeutic agents often have a narrow therapeutic index that challenges the maintenance of a safe and effective dose. Consistent plasma concentrations of a drug can be obtained by using a timed-release prodrug strategy. We reasoned that a ribonucleoside 3'-phosphate could serve as a pro-moiety that also increases the hydrophilicity of a cancer chemotherapeutic agent. Herein, we report an efficient route for the synthesis of the prodrug uridine 3'-(4-hydroxytamoxifen phosphate) (UpHT). UpHT demonstrates timed-released activation kinetics with a half-life of approximately 4 h at the approximate plasma concentration of human pancreatic ribonuclease (RNase 1). MCF-7 breast cancer cells treated with UpHT showed decreased proliferation upon co-incubation with RNase 1, consistent with the release of the active drug-4-hydroxytamoxifen. These data demonstrate the utility of a human plasma enzyme as a useful activator of a prodrug.