gebhart/patrepeval huggingface dataset:
Sialyl-Tn in Cancer: (How) Did We Miss the Target? (2012)

Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue a2,6-linked to GalNAca-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine, named Theratope, has been designed towards the STn epitope. In spite of the great enthusiasm around this immunotherapy, Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel immunotherapies targeting other carbohydrate antigens and STn carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn immunotherapy strategies.
Delivery to mitochondria: a narrower approach for broader therapeutics (2012)

Numerous investigators have attempted to establish a mitochondrial drug delivery system; still, many hurdles yet remain to be overcome before mitochondrial medicine reaches clinical applications. We need to develop a delivery system to encapsulate drugs, proteins and genes that would be practically viable for scale-up and strategies to target and regulate drug release to the cytosol after endosomal escape, and thereafter to deliver the released drug to the mitochondria. Current innovations in the nanotechnology could be effectively utilized with mitochondrial medicine for designing optimal nanoparticle drug delivery system for mitochondrial diseases on clinical setting.
Potential for improvement of docetaxel-based chemotherapy: a pharmacological review (2005)

Since the introduction of docetaxel, research has focused on various approaches to overcome treatment limitations and improve outcome. This review discusses the pharmacological attempts at treatment optimisation, which include reducing interindividual pharmacokinetic and pharmacodynamic variability, optimising schedule, route of administration, reversing drug resistance and the development of structurally related second-generation taxanes.
Adding Debug Enhancements to Assertion Checkers for Hardware Emulation and Silicon Debug (2006)

This paper presents techniques that enhance automatically generated hardware assertion checkers to facilitate debugging within the assertion-based verification paradigm. Starting with techniques based on dependency graphs, we construct the algorithms for counting and monitoring the activity of checkers, monitoring assertion completion, as well as introduce the concept of assertion threading. These debugging enhancements offer increased traceability and observability within assertion checkers, as well as the improved metrics relating to the coverage of assertion checkers. The proposed techniques have been successfully incorporated into the MBAC checker generator.
Laparoscopic Ultrasound with Radiofrequency Ablation in Cirrhotic Patients with Hepatocellular Carcinoma: Technique and Technical Considerations (2001)

The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure.
Phase-sensitive optical coherence tomography at up to 370,000 lines per second using buffered Fourier domain mode-locked lasers (2007)

Buffered Fourier domain mode-locked (FDML) lasers are demonstrated for dynamic phase-sensitive optical coherence tomography (OCT) and 3D OCT phase microscopy. Systems are operated at sweep speeds of 42, 117, and 370 kHz, and displacement sensitivities of 39, 52, and 102 pm are achieved, respectively. Sensitivities are comparable to spectrometer-based OCT phase microscopy systems, but much faster acquisition speeds are possible. An additional factor of sqrt 2 improvement in noise performance is observed for differential phase measurements, which is important for Doppler OCT. Dynamic measurements of piezoelectric transducer motion and static 3D OCT phase microscopy are demonstrated. Buffered FDML lasers provide excellent displacement sensitivities at extremely high sweep speeds.
Quantitative Analysis of α-L-Iduronidase Expression in Immunocompetent Mice Treated with the Sleeping Beauty Transposon System (2013)

The Sleeping Beauty transposon system, a non-viral, integrating vector that can deliver the alpha-L-iduronidase-encoding gene, is efficient in correcting mucopolysaccharidosis type I in NOD/SCID mice. However, in previous studies we failed to attain reliable long-term alpha-L-iduronidase expression in immunocompetent mice. Here, we focused on achieving sustained high-level expression in immunocompetent C57BL/6 mice. In our standard liver-directed treatment we hydrodynamically infuse mice with plasmids containing a SB transposon-encoding human alpha-L-iduronidase, along with a source of SB transposase. We sought to 1) minimize expression of the therapeutic enzyme in antigen-presenting cells, while avoiding promoter shutdown and gender bias, 2) increase transposition efficiency and 3) improve immunosuppression. By using a liver-specific promoter to drive IDUA expression, the SB100X hyperactive transposase and transient cyclophosphamide immunosuppression we achieved therapeutic-level (>100 wild-type) stabilized expression for 1 year in 50% of C57BL/6 mice. To gain insights into the causes of variability in transgene expression, we quantified the rates of alpha-L-iduronidase activity decay vis-a-vis transposition and transgene maintenance using the data obtained in this and previous studies. Our analyses showed that immune responses are the most important variable to control in order to prevent loss of transgene expression. Cumulatively, our results allow transition to pre-clinical studies of SB-mediated alpha-L-iduronidase expression and correction of mucopolysaccharidosis type I in animal models.
Therapy of Cancer Using the Adoptive Transfer of Activated Killer Cells and Interleukin-2 (1987)

A new approach to cancer treatment has been developed based on the adoptive transfer of activated lymphocytes into cancer patients. Lymphocytes harvested from patients by leukapheresis are converted into lymphokine-activated killer (LAK) cells by incubation with recombinant interleukin-2 (rIL-2). These LAK cells are then infused back into the patients in combination with intravenous IL-2. Among 25 patients treated with this form of adoptive immunotherapy there were 11 patients with measurable tumor reductions, including 1 complete responder. The majority of responses occurred in patients with metastatic renal cell carcinoma, melanoma and colorectal carcinoma. The toxicities of IL-2, including fluid retention and pulmonary edema, limit therapy, and laboratory investigation is now aimed toward understanding the mechanism of IL-2 toxicity. The use of LAK cells and IL-2 in cancer therapy is still in a developmental stage and needs to be refined before its role can be definitely established.
Diabetes Mellitus as a Risk Factor for Death From Stroke (1996)

Diabetic subjects have a very high risk of death from stroke, particularly women. Our data also suggest that the duration of diabetes is an important factor contributing to the risk of stroke.
Dielectric studies of native, unfolded and intermediate forms of beta -lactamase (1994)

Time-domain dielectric spectroscopy has been applied to native, intermediate and unfolded beta -lactamase structures both in the hydrated solid state and in solution. Gravimetric and dielectric measurements indicate that nearly three times as many water molecules are multiply hydrogen bonded to the unfolded compared with the native protein. By contrast, the primary hydration population of the state A intermediate is only 20% larger than that of the folded enzyme. Analysis of the beta -dispersions in terms of rotational relaxation of the protein's permanent dipole has indicated that there is no significant difference in the dimensions of the three structures. This is not consistent with the findings of previous studies employing different experimental techniques.
Effects of Montelukast and Budesonide on Airway Responses and Airway Inflammation in Asthma (2002)

Inhaled corticosteroids are effective antiinflammatory therapy for asthma; however, they do not completely abolish allergen-induced airway inflammation. Leukotriene modifiers attenuate both early and late allergen responses and have antiinflammatory properties. We reasoned that treatment with budesonide and montelukast in combination might provide greater antiinflammatory effects than either drug alone, and the purpose of this study was to compare the effects of treatment with budesonide and montelukast, alone or in combination, on outcome variables after allergen inhalation. Ten subjects with asthma with dual responses after allergen inhalation were included in this randomized, double-blind, crossover study. Outcomes included early and late asthmatic responses, and changes in airway responsiveness and sputum eosinophilia, measured before and after challenge. Treatment with montelukast attenuated the maximal early asthmatic response compared with placebo (p < 0.001) and budesonide (p = 0.002). Both budesonide and montelukast, alone and in combination, attenuated the maximal late asthmatic response compared with placebo (p < 0.01). Budesonide and montelukast, alone and in combination, afforded protection against allergen-induced airway hyperresponsiveness (p < 0.05), although the treatment effect of budesonide was greater than that of montelukast (p < 0.05). Treatment with budesonide and montelukast, alone and in combination, also attenuated allergen-induced sputum eosinophilia. Thus, montelukast and budesonide attenuated allergen-induced asthmatic responses, airway hyperresponsiveness, and sputum eosinophilia, although combination treatment did not provide greater antiinflammatory effects than either drug alone.
Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function (2011)

The role of the serine protease HtrA2 in neuroprotection was initially identified by the demonstration of neurodegeneration in mice lacking HtrA2 expression or function, and the interesting finding that mutations adjacent to two putative phosphorylation sites (S142 and S400) have been found in Parkinson's disease patients. However, the mechanism of this neuroprotection and the signalling pathways associated with it remain mostly unknown. Here we report that cyclin-dependent kinase-5 (Cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating HtrA2 at S400. HtrA2 and Cdk5 interact in human and mouse cell lines and brain, and Cdk5 phosphorylates S400 on HtrA2 in a p38-dependent manner. Phosphorylation of HtrA2 at S400 is involved in maintaining mitochondrial membrane potential under stress conditions and is important for mitochondrial function, conferring cells protection against cellular stress.
Containers and Cloud: From LXC to Docker to Kubernetes (2014)

This issue's "Cloud Tidbit" focuses on container technology and how it's emerging as an important part of the cloud computing infrastructure. It looks at Docker, an open source project that automates the faster deployment of Linux applications, and Kubernetes, an open source cluster manager for Docker containers.
Ataxia Telangiectasia Mutated (ATM) Signaling Network Is Modulated by a Novel Poly(ADP-ribose)-dependent Pathway in the Early Response to DNA-damaging Agents (2007)

Poly(ADP-ribosyl)ation is a post-translational modification that is instantly stimulated by DNA strand breaks creating a unique signal for the modulation of protein functions in DNA repair and cell cycle checkpoint pathways. Here we report that lack of poly(ADP-ribose) synthesis leads to a compromised response to DNA damage. Deficiency in poly(ADP-ribosyl)ation metabolism induces profound cellular sensitivity to DNA-damaging agents, particularly in cells deficient for the protein kinase ataxia telangiectasia mutated (ATM). At the biochemical level, we examined the significance of poly(ADP-ribose) synthesis on the regulation of early DNA damage-induced signaling cascade initiated by ATM. Using potent PARP inhibitors and PARP-1 knock-out cells, we demonstrate a functional interplay between ATM and poly(ADP-ribose) that is important for the phosphorylation of p53, SMC1, and H2AX. For the first time, we demonstrate a functional and physical interaction between the major DSB signaling kinase, ATM and poly(ADP-ribosyl)ation by PARP-1, a key enzyme of chromatin remodeling. This study suggests that poly(ADP-ribose) might serve as a DNA damage sensory molecule that is critical for early DNA damage signaling.
Assay of carboxypeptidase N activity in serum by liquid-chromatographic determination of hippuric acid. (1985)

We describe conditions for determining carboxypeptidase N (EC 3.4.17.3) activity by liquid chromatography. Serum (10 microL) is mixed with the artificial substrates hippuryl-L-arginine (30 mmol/L) and hippuryl-L-lysine (100 mmol/L) in 50 mmol/L 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution at pH 8.2 and 7.8, respectively. The hippuric acid product is separated from the substrate in less than 2 min by reversed-phase "high-performance" liquid chromatography and measured spectrophotometrically. o-Methyl hippuric acid is used as internal standard. By this method, optimized for activity and sensitivity of detection, carboxypeptidase N activities are 60-fold greater than those by another procedure (J Chromatogr 266:173-177, 1983). The mean value for 80 normal control subjects was 74.8 (SD 10.3) nmol of hippuric acid released per milliliter of serum per minute for hippuryl-L-arginine substrate, 378 (SD 55) for hippuryl-L-lysine substrate. The sensitivity and precision of the method make it suitable both for routine clinical determinations and as a reference procedure.
Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse (2005)

These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
Interferon-α8b the Only Variant of Interferon-α8 Identified in a Large Human Population (1996)

Three variants of human interferon (IFN)-alpha 8a gene, that is, IFN-alpha 8b, and IFN-alpha 8c, have been reported previously. They differ from each other by changes in their coding region at nucleotide positions 359-360, 372, and 550. Human genomic DNA obtained from over 28,000 healthy blood donors and from 4 human cell lines was used in the polymerase chain reaction (PCR) designed for specific amplification of the IFN-alpha 8 gene fragments. The resulting PCR product was analyzed by (1) restriction endonuclease digestion, (2) DNA sequencing, and (3) allele-specific secondary PCR amplification. Only one sequence for IFN-alpha 8 was identified, and that was for IFN-alpha 8b. The sequences for IFN-alpha 8a and IFN-alpha 8c were not detected after PCR amplification either in the pooled leukocytes obtained from > 28,000 individuals or in cell lines tested. These data suggest that the naturally occurring variant or allele for IFN-alpha 8 in the population is IFN-alpha 8b. IFN-alpha 8a and IFN-alpha 8c variants were consistently below the level of detection of the assays and, if present at all in the population, are very rare.
Combination Treatment of Clozapine and Topiramate in Resistant Rapid-Cycling Bipolar Disorder (2005)

Several open-label studies or case reports have suggested the effectiveness of clozapine or topiramate in the treatment of resistant rapid-cycling bipolar patients, but none of these publications report the long-term effectiveness of these two agents in combination. The authors present a 38-year-old woman with a 22-year history of rapid-cycling bipolar I disorder who failed to respond satisfactorily to various somatic therapies, including combination therapy for complex regimens and a course of bilateral electroconvulsive therapy, but finally responded well to a combination treatment of clozapine and topiramate. Such a combination therapy led the patient to a complete remission for more than 3 years without inducing side effects such as weight gain, hyperglycemia, type II diabetes mellitus, or hyperlipidemia. In addition, she had a weight loss of 12 kg over the past 3 years. This case suggests that the combination treatment of clozapine and topiramate can be safe and effective in some resistant rapid-cycling bipolar patients.
First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer (2015)

clinicaltrials.gov Identifier: NCT01310036.
Rapid Diagnosis of a Coronavirus Associated with Severe Acute Respiratory Syndrome (SARS) (2003)

Severe acute respiratory syndrome (SARS) is a recently emerged disease associated with pneumonia in infected patients (1 ). The disease is unusual in its severity, and patients suffering from this disease do not respond to empirical antimicrobial treatment for acute communityacquired typical or atypical pneumonia (2 ). By the end of March 2003, a cumulative total of 1622 cases and 58 deaths had been reported from 13 countries (3 ). The disease is highly infectious, and attach rates 56% have been reported in healthcare workers caring for SARS patients (2 ).
Hotspot Patterns: The Formal Definition and Automatic Detection of Architecture Smells (2015)

In this paper, we propose and empirically validate a suite of hotspot patterns: recurring architecture problems that occur in most complex systems and incur high maintenance costs. In particular, we introduce two novel hotspot patterns, Unstable Interface and Implicit Cross-module Dependency. These patterns are defined based on Baldwin and Clark's design rule theory, and detected by the combination of history and architecture information. Through our tool-supported evaluations, we show that these patterns not only identify the most error-prone and change-prone files, they also pinpoint specific architecture problems that may be the root causes of bug-proneness and change-proneness. Significantly, we show that 1) these structure-history integrated patterns contribute more to error- and change-proneness than other hotspot patterns, and 2) the more hotspot patterns a file is involved in, the more error- and change-prone it is. Finally, we report on an industrial case study to demonstrate the practicality of these hotspot patterns. The architect and developers confirmed that our hotspot detector discovered the majority of the architecture problems causing maintenance pain, and they have started to improve the system's maintainability by refactoring and fixing the identified architecture issues.
A monoclonal antibody, specific for human fibrinogen, fibrinopeptide A- containing fragments and not reacting with free fibrinopeptide A (1985)

Spleen cells of BALB/c mice, immunized with fragments Y of normal human fibrinogen, were fused with P3 X 63 Ag 8653 myeloma cells. A clone was found which produces monoclonal antibodies (Mab-Y18) of the IgM kappa type. Mab-Y18 is immunoreactive with normal human fibrinogen, and its fragments X, Y, N-terminal disulphide knot, A alpha-chain, and A alpha stretch 1–51. The immunoreactivity with these same fragments disappears upon treatment with thrombin or arvin. This strongly suggests that fibrinopeptide A is an essential component of the Mab-Y18 epitope. This is supported by the finding that Mab-Y18 prolongs the thrombin and arvin clotting times of human fibrinogen by inhibition of the fibrinopeptide A release. More detailed information about the nature of the Mab-Y18 epitope was obtained from studies with genetic variants of human fibrinogen (especially fibrinogen Metz) and with fibrinogens from other mammalian species. These studies show that amino acid residue A alpha 16 (arginine) of fibrinopeptide A is essential for the Mab-Y18 epitope. Mab-Y18 does not react with free fibrinopeptide A.
Resistivity to denaturation of the apoprotein of aequorin and reconstitution of the luminescent photoprotein from the partially denatured apoprotein (1981)

Although native aequorin is highly susceptible to inactivation, apoaequorin is highly resistant to various processes of denaturation. Apoaequorin was inactivated only partially at a temperature of 95 degrees C or by treatments with 6 M-urea, 4 M-guanidine hydrochloride, 1 M-HCl and 1 M-NaOH. It was nearly completely inactivated in 85% ethanol or by heating at 95 degrees C in 2 M-(NH4)2SO4, but over 50% of apoaequorin activity was restored in both cases merely by dissolving the coagulated protein in 4 M-guanidine hydrochloride. In the reconstitution of aequorin, partially inactivated apoaequorin yielded more aequorin than expected from the activity of the partially inactivated apoaequorin used, suggesting that the process of reconstitution promotes the renaturation of denatured apoaequorin.
Ionic liquids for addressing unmet needs in healthcare (2017)

Advances in the field of ionic liquids have opened new applications beyond their traditional use as solvents into other fields especially healthcare. The broad chemical space, rich with structurally diverse ions, and coupled with the flexibility to form complementary ion pairs enables task-specific optimization at the molecular level to design ionic liquids for envisioned functions. Consequently, ionic liquids now are tailored as innovative solutions to address many problems in medicine. To date, ionic liquids have been designed to promote dissolution of poorly soluble drugs and disrupt physiological barriers to transport drugs to targeted sites. Also, their antimicrobial activity has been demonstrated and could be exploited to prevent and treat infectious diseases. Metal-containing ionic liquids have also been designed and offer unique features due to incorporation of metals. Here, we review application-driven investigations of ionic liquids in medicine with respect to current status and future potential.