gebhart/patrepeval huggingface dataset:
Attacking cancer's Achilles heel: antagonism of anti‐apoptotic BCL‐2 family members (2015)

Malignant cells routinely violate cellular checkpoints that should initiate cell death in normal cells by triggering pro-apoptotic members of the BCL-2 family of proteins. To escape such death inducing signals, cancer cells often select for upregulation of anti-apoptotic BCL-2 family members including BCL-2, BCL-XL , BFL-1, BCL-W and MCL-1. These family members prevent death by sequestering pro-apoptotic molecules. To counter this resistance mechanism, small molecule inhibitors of anti-apoptotic BCL-2 family members have been under development. These molecules have shown promise in pre-clinical and clinical testing to overcome apoptotic resistance, prompting cancer cells to undergo apoptosis. Alternatively, other strategies have taken advantage of the normal regulatory machinery controlling anti-apoptotic molecules and have used inhibitors of signaling pathways to down-modulate the expression of anti-apoptotic molecules, thus tilting the balance in cancer cells to cell death. This review explores recent developments and strategies aimed at antagonizing anti-apoptotic BCL-2 family member action to promote the induction of cell death in cancer therapy.
Ethylene Tetramerization:  A New Route to Produce 1-Octene in Exceptionally High Selectivities (2004)

Linear alpha-olefins, such as 1-hexene and 1-octene, are important comonomers in the production of linear low-density polyethylene (LLDPE). The conventional method of producing 1-hexene and 1-octene is by oligomerization of ethylene, which yields a wide spectrum of linear alpha-olefins (LAOs). While there exists several processes for producing 1-hexene via ethylene trimerization, a similar route for the selective production of 1-octene has so far been elusive. We now, for the first time, report an unprecedented ethylene tetramerization reaction that produces 1-octene in selectivities exceeding 70%, using an aluminoxane-activated chromium/((R2)2P)2NR1 catalyst system.
Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma (1999)

mAb OV569 was made by immunizing mice with ovarian carcinoma cells. It binds to cells from ovarian carcinomas and, to a lesser extent, to cells from certain other carcinomas whereas the binding to normal tissues is low to nondetectable. It also binds to soluble molecule(s) in culture supernatants from antigen-positive carcinomas. OV569 recognizes a protein(s) of 42-45 kDa with the same N-terminal amino acid sequence as the membrane-bound portion of mesothelin and megakaryocyte potentiating factor (MPF). Binding assays with fusion proteins comprising either the N-terminal part of mesothelin/MPF (D1Ig), reported to be easily cleaved off, or a noncleavable, membrane-associated part (D2Ig) showed that OV569 only binds to D2hIg. A new member of the mesothelin/MPF family was discovered, which has an 82-bp insert in the membrane-associated part, leading to a frameshift of 212 bp, and whose predicted molecular structure indicates that it is soluble. To test patient sera for soluble tumor antigen, antigen was isolated from cell-free tumor culture supernatants via immunoadsorption with OV569 and used to generate murine mAbs to an epitope different from the one to which OV569 binds, after which mAbs to two different epitopes were used to develop a "sandwich ELISA." Using this assay, the level of circulating antigen was elevated significantly in 23 of 30 sera from patients with ovarian carcinoma, as compared with 0 of 68 sera from healthy controls, 0 of 3 sera from patients with nonneoplastic diseases, and 25 of 75 sera from patients with other tumors. Soluble molecules of the mesothelin/MPF family may provide useful new marker(s) for diagnosis of ovarian carcinoma and/or monitoring its response to therapy.
Intergeneric protplast fusion between xylanase producingBacillus subtilisLYT andCorynebacterium acetoacidphilumATCC 21476 (1990)

Hybrids between a strain of Bacillus subtilis isolated in our laboratory and having the ability to degrade xylan and other complex polysaccharides and Corynebacterium acetoacidophilum, a lysine producer, were prepared by protoplast fusion. Based on distinctive parental biochemical characteristics the fusants were grouped into 9 categories, viz. BC1 through BC9. Three of the hybrids, BC5, BC7a and BC7b, were tested for their ability to produce xylanase and lysine. Both BC7a and BC7b produced xylanase but BC5 did not, however all of them produced lysine albeit to different degrees. These results demonstrate that intergeneric gene transfer takes place through protoplast fusion between these 2 important genera of bacteria and some of the fusants inherit the useful traits of both the parents.
-Enolase in blood plasma during open heart surgery (1989)

The enolase isoenzyme composed of the beta subunit (alpha beta or beta beta enolase) is distributed predominantly in the heart and skeletal muscles. To see whether it may be a useful indicator of myocardial damage, concentrations of beta-enolase (the beta subunit of enolase) were determined in serial blood samples taken from 18 patients who underwent mitral valve replacement, using a highly sensitive enzyme immunoassay method. They were compared with those of creatine kinase MB isoenzyme (CK-MB) in the same samples. The mean arterial beta-enolase concentration was 6.60 (SD 3.84) ng.ml-1 at the beginning of anaesthesia. It increased rapidly after reperfusion and rose to greater than 100 ng.ml-1 at 2 h post-reperfusion. It remained high until 12 h post-reperfusion, and then decreased slowly. The plasma beta-enolase concentrations were significantly higher in coronary sinus samples than in arterial samples in the early phase after reperfusion. Since plasma carbonic anhydrase III, which is known to be localised only in the skeletal muscle, did not increase during the surgery, we suggest that the major portion of the elevated plasma beta-enolase was derived from heart muscle. Plasma concentrations of beta-enolase increased as quickly as those of CK-MB after reperfusion. The CK-MB concentrations had returned to normal at 2 d but the beta-enolase concentrations remained elevated up to 7 d. These results show that the determination of beta-enolase in plasma may be useful for estimating myocardial damage during open heart surgery.
The human cornea proteome: bioinformatic analyses indicate import of plasma proteins into the cornea. (2006)

Increased biochemical knowledge of normal and diseased corneas is essential for the understanding of corneal homeostasis and pathophysiology. In a recent study, we characterized the proteome of the normal human cornea and identified 141 distinct proteins. This dataset represents the most comprehensive protein study of the cornea to date and provides a useful reference for further studies of normal and diseased human corneas. The list of identified proteins is available at the Cornea Protein Database. In the present paper, we review the utilized procedures for extraction and fractionation of corneal proteins and discuss the potential roles of the identified proteins in relation to homeostasis, diseases, and wound-healing of the cornea. In addition, we compare the list of identified proteins with high quality gene expression libraries (cDNA libraries) and Serial Analysis of Gene Expression (SAGE) data. Of the 141 proteins, 86 (61%) were recognized in cDNA libraries from the corneas of dogs and rabbits, or humans with keratoconus, and 98 (69.5%) were recognized in SAGE data of mouse and human corneas. However, the percentages of identified genes in each of the protein functional groups differed markedly. Thus, exceptionally few of the traditional blood/plasma proteins and immune defense proteins that were identified in the human cornea were recognized in the gene expression libraries of the cornea. This observation strongly indicates that these abundant corneal proteins are not expressed in the cornea but originate from the surrounding pericorneal tissue.
Retroviral integration and human gene therapy (2007)

Long-term correction of genetic diseases requires permanent integration of therapeutic genes into chromosomes of affected cells. Retroviral vectors are the most widely used delivery vehicles because of their efficiency and precision of integration. However, retroviral integration can take place at a variety of chromosomal sites, and examples have been reported of integration of therapeutic vectors activating oncogenes and causing cancer in patients. This issue of the JCI presents three articles that update successful human gene therapy trials and furthermore evaluate the sites of integration in cells from treated patients, including samples from individuals experiencing serious adverse events following therapy (see the related articles beginning on pages 2225, 2233, and 2241).
Antiphase domain boundaries in the superconducting phase of the Y-Ba-Cu-O system (1987)

Transmission-electron-microscopy examination of the superconducting phase of the Y-Ba-Cu-O system reveals the presence of dense antiphase boundaries. The structure of the superconducting phase was determined to be orthorhombic with space group Pm2m. The orthorhombic a and b axes are found to alternate across the antiphase boundary which runs parallel to the [110] direction.
Salary study 2009 (2009)

Subtitle: After unprecedented growth the market has fallen drastically, dealing a major blow to corporate pilot employment. No forecasts show a return to earlier levels for at least 3 years. Many companies have closed their flight depts entirely or sold off some of their aircraft. Hours flown have dropped but thoughtful operators still employing professional pilots are keeping salaries fairly level. As we go to press, activity on the ramps is coming back.
Blockade of PD-1 immunosuppression boosts CAR T-cell therapy (2013)

The presence of an immunosuppressive microenvironment can limit the full potential of adoptive T cell immunotherapy. However, specific blockade of the PD-1 immunosuppressive pathway can significantly enhance the function of gene-modified T cells expressing a chimeric antigen receptor (CAR) leading to enhanced tumor eradication.
Characterization of the Integrase Gene and Attachment Site for the Myxococcus xanthus Bacteriophage Mx9 (2003)

Bacteriophage Mx9 is a temperate phage that infects Myxococcus xanthus. It lysogenizes the bacteria by integrating into the bacterial chromosome by site-specific recombination at one of two sites, attB1 or attB2. Integration at attB1 results in deletion of DNA between the two attB sites. The attB2 site lies within the 5' region of the M. xanthus tRNA(Gly) gene. Mx9 integration requires a single protein, Int. Analysis of integration revealed that the phage attachment site (attP) is contained in the int gene and that upon integration, the 3' end of the int gene is altered. Plasmids containing fusions of the pilA or mgl promoter to lacZ integrated at either Mx9 attB site have higher levels of transcription than the same fusions integrated at the Mx8 attB site.
Clinical Recognition and Diagnosis ofClostridium difficileInfection (2008)

Prompt and precise diagnosis is an important aspect of effective management of Clostridium difficile infection (CDI). CDI causes 15%-25% of all cases of antibiotic-associated diarrhea, the severity of which ranges from mild diarrhea to fulminant pseudomembranous colitis. Several factors, especially advanced age and hospitalization, should be considered in the diagnosis of CDI. In particular, nosocomial diarrhea arising >72 hours after admission among patients receiving antibiotics is highly likely to have resulted from CDI. Testing of stool for the presence of C. difficile toxin confirms the diagnosis of CDI. However, performance of an enzyme immunoassay is the usual method by which CDI is confirmed, but this test appears to be relatively insensitive, compared with the cell cytotoxicity assay and stool culture for toxigenic C. difficile on selective medium. Endoscopy and computed tomography are less sensitive than stool toxin assays but may be useful when immediate results are important or other confounding conditions rank high in the differential diagnosis. Often overlooked aspects of this diagnosis are high white blood cell counts (which are sometimes in the leukemoid range) and hypoalbuminemia.
Immunocytochemical localization of the α7 subunit of the nicotinic acetylcholine receptor in the rat central nervous system (1994)

Previous molecular cloning studies have revealed that alpha-bungarotoxin binding proteins present in the brain are members of the neuronal nicotinic acetylcholine receptor gene family. The alpha 7 subunit is structurally related to the agonist binding subunits present in the central and peripheral nervous systems and, when expressed in Xenopus oocytes, forms functional channels blockable by alpha-bungarotoxin. In the present study, three different monoclonal antibodies raised against the alpha 7 subunit were used to map its distribution throughout the central nervous system of the rat. Immunohistochemical localization revealed that the alpha 7 subunit is expressed in most regions of the brain, being, overall, well correlated with previous "in situ" localization of alpha 7 transcripts and alpha-bungarotoxin autoradiographic binding studies. Particularly strong immunoreactivity was observed in several sensory and motor nuclei of the brainstem as well as the red nucleus. At the cellular level, alpha 7 immunostaining was usually found both in somata and dendrites, whereas axonal and terminal labeling was not observed. The widespread distribution of the alpha 7 subunit polypeptide is consistent with immunoprecipitation data demonstrating that it is a component of the predominant subtype of brain alpha-bungarotoxin-sensitive nicotinic receptors.
Theory of tunneling magnetoresistance of an epitaxial Fe/MgO/Fe(001) junction (2001)

Calculation of the tunneling magnetoresistance (TMR) of an epitaxial Fe/MgO/Fe(001) junction is reported. The conductances of the junction in its ferromagnetic and antiferromagnetic configurations are determined without any approximations from the real-space Kubo formula using tight-binding bands fitted to an ab initio band structure of iron and MgO. The calculated optimistic TMR ratio is in excess of 1000% for an MgO barrier of $\ensuremath{\approx}20$ atomic planes and the spin polarization of the tunneling current is positive for all MgO thicknesses. It is also found that spin-dependent tunneling in an Fe/MgO/Fe(001) junction is not entirely determined by states at the $\ensuremath{\Gamma}$ point $({\mathbf{k}}_{\ensuremath{\Vert}}=0)$ even for MgO thicknesses as large as $\ensuremath{\approx}20$ atomic planes. All these results are explained qualitatively in terms of the Fe majority- and minority-spin surface spectral densities and the complex MgO Fermi surface.
Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism (2009)

For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
The role of neutrophils in the formation of peritoneal adhesions (1999)

The most common cause of intraperitoneal adhesions which may result in infertility and intestinal obstruction is previous abdominal surgery. Surgical trauma of the peritoneum in the absence of infection elicits a rapid and transient influx of polymorphonuclear leukocytes (PMN) into the peritoneal cavity. The role of neutrophils in intraperitoneal adhesion formation has not been studied. We aimed to study the effects of PMN counts and PMN functions on peritoneal adhesion formation. Forty peritoneal adhesion-induced rats were randomly divided into three groups; group I, receiving saline; group II, receiving cyclophosphamide; and group III, receiving granulocyte-macrophage colony-stimulating factor (GM-CSF). In all groups, peritoneal lavage was performed to determine PMN counts the day after adhesion induction. Blood neutrophil counts and neutrophil functions were also determined. Adhesions were evaluated blindly 14 days after the operation. Adhesion tissue samples were microscopically evaluated. Tissue hydroxyproline and collagen concentrations were measured. The neutrophil counts and phagocytosis significantly increased in group III and neutrophil counts decreased in group II (P < 0.05). The score of adhesion formation in group II was significantly less than that in groups I and III (P < 0.05). Hydroxyproline concentrations of adhesion tissue were significantly decreased in group II when compared with group III (P < 0.05). The present study shows that neutropenia lowers the degree of postoperative adhesion formation. It is concluded that PMN may have a role to play in modulating post-operative adhesion formation.
Has Trench Fever Returned? (1995)

To those unfamiliar with the disease the man who has never been in the trenches cannot be suffering from trench fever, and for this reason the spread of the disease to new districts, and among those unfamiliar with its symptoms, will go unrecognised. . . . That trench fever might come amongst us is no idle supposition.— William Byam1 Although trench fever has probably been a part of human life for more than a thousand years, it was not until World War I that the disease came under intense scrutiny. In that war it afflicted approximately 1 million soldiers, . . .
Efficacy of Chemotherapy in BRCA1/2 Mutation Carrier Ovarian Cancer in the Setting of PARP Inhibitor Resistance: A Multi-Institutional Study (2013)

Heavily pretreated PBMCOC who are PARPi-resistant retain the potential to respond to subsequent chemotherapy, including platinum-based agents. These data support the further development of PARPi in PBMCOC.
Anti-MAP Therapy for Pediatric Crohnʼs Disease (2013)

Purpose:Mycobacterium avium subspecies paratuberculosis (MAP) is associated with Crohn's disease (CD)1, although its etiological capacity remains highly controversial. Previous studies in adults suggest anti-MAP, a combination antibiotic therapy, is a safe and effective treatment for CD, with remission rates ranging from 50-88.5%2. No work exists, however, regarding the use of anti-MAP in a pediatric population. Purpose: to evaluate the safety and efficacy of anti-MAP therapy for CD in pediatric patients. Methods: A retrospective review was performed on 10 pediatric CD patients (five male, five female; 8-17 years old, male: 14.4±2.7years) treated with anti-MAP therapy. Patients underwent a ramp-up dosing regimen to final daily doses of 8.78±2.93 mg/kg rifabutin (max 600mg/d); 15.87±3.41mg/kg clarithromycin (max 1000mg/d), and 2.10±0.59 mg/kg clofazimine (100mg/d). Treatment duration ranged from 4.5-114 months (9.5 years). LFTs and FBC were measured regularly throughout treatment, with clinical state recorded at scheduled visits. Remission was defined as ≥ 3 month improvement in disease state with CDAI<150, and stable or reducing CD medication (with the exception of anti-MAP dose escalation). Results: Eight patients (80%) achieved clinical remission, ranging from 3-60 months (5 years). Four patients have maintained remission to date (mdn: 22.5 mo), with an average time-to-relapse of 14 months. Of the two apparent treatment failures, one improved for 2 months before contracting a secondary infection, while the other was non-compliant. Additionally, the only time-to-relapse <12 months coincided with a reduction in anti-MAP dose and concurrent C. difficile infection. Red/brown skin discoloration occurred in all patients, and was the most common adverse effect. Raised LFTs were observed in three patients; however, one pre-dated the commencement of therapy. An isolated raised ALT was observed in a second patient, which resolved without dose adjustment. ALP was raised in a third patient at 4 months, and persisted for 5 months after the unrelated cessation of treatment. Isolated observations of mild neutropenia (ANC<1.5 x 109/L) were seen in two patients; however, both resolved without dose adjustment. No adverse ocular effects were observed. Conclusion: Anti-MAP is an effective therapy for pediatric CD, with 8/10 patients achieving clinical remission of ≥3 months. Treatment failures were associated with insufficient dosing and/or secondary infection. Furthermore, in contrast to the safety profiles of other CD therapeutics, adverse effects were mild and transient in nature, with none necessitating dose adjustment. As such, this review supports the use of anti-MAP therapy for CD in a pediatric population.
Experimental demonstration of 16 Gbit/s millimeter-wave communications using MIMO processing of 2 OAM modes on each of two transmitter/receiver antenna apertures (2014)

This paper reports an experimental demonstration of a 16 Gbit/s millimeter-wave communication link using MIMO processing of 2 OAM modes on each of two transmitter/receiver antenna apertures. Two groups of multiplexed OAM beams, each containing OAM beams of ℓ =1 and +3 are generated and transmitted through two transmitter apertures respectively. The two transmitter apertures are separated with a certain distance such that the two groups of OAM beams are spatially overlapping at the receiver aperture plane. Each channel carries 1-GBaud 16-QAM signals at the same carrier frequency of 28 GHz. Our experimental results show that MIMO equalization processing can help mitigate the interferences from the other OAM channels and the BER performance of each channel improves significantly after MIMO processing. Our results indicate that OAM multiplexing and traditional spatial multiplexing combined with MIMO processing can be compatible and complementary with each other.
Molecular Characterization of Gene-For-Gene Systems in Plant-Fungus Interactions and the Application of Avirulence Genes in Control of Plant Pathogens (1992)

Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for ...Read More
A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma (2010)

This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid pre-medication). An initial dose of 4 mg/kg dacetuzumab exceeded the maximum-tolerated dose for uniform weekly dosing. Intrapatient dose escalation with steroid pre-medication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. Adverse events potentially related to dacetuzumab included cytokine release syndrome symptoms, non-infectious ocular inflammation, and elevated hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing. Clinical trials gov identifier: NCT00079716.