gebhart/patrepeval huggingface dataset:
A study to establish reasonable action limits for patient‐specific quality assurance in intensity‐modulated radiation therapy (2007)

An effective patient quality assurance (QA) program for intensity-modulated radiation therapy (IMRT) requires accurate and realistic plan acceptance criteria--that is, action limits. Based on dose measurements performed with a commercially available two-dimensional (2D) diode array, we analyzed 747 fluence maps resulting from a routine patient QA program for IMRT plans. The fluence maps were calculated by three different commercially available (ADAC, CMS, Eclipse) treatment planning systems (TPSs) and were delivered using 6-MV X-ray beams produced by linear accelerators. To establish reasonably achievable and clinically acceptable limits for the dose deviations, the agreement between the measured and calculated fluence maps was evaluated in terms of percent dose error (PDE) for a few points and percent of passing points (PPP) for the isodose distribution. The analysis was conducted for each TPS used in the study (365 ADAC, 162 CMS,220 Eclipse), for multiple treatment sites (prostate, pelvis, head and neck, spine, rectum, anus, lung, brain), at the normalization point for 3% percentage difference (%Diff) and 3-mm distance to agreement (DTA) criteria. We investigated the treatment-site dependency of PPP and PDE. The results show that, at 3% and 3-mm criteria, a 95% PPP and 3% PDE can be achieved for prostate treatments and a 90% PPP and 5% PDE are attainable for any treatment site.
The Synthesis of the Isoquinoline Alkaloid Calycotomine via Functionalization of Enamide Double Bonds (1987)

Rbstract -The novel alkaloid calycotanine, a 1-hydroxymethyle~tetrahydroisoquimline, has been synthesized from 1-methyl-3.4-dihydroisoquinoli~ v i a the 2-benzyloxycarbonyl enamide derivative.Oxidation of t h e enamide with osmim t e t r o x i d e r e s u l t s i n bis-hydroxylatim and ring opening t o form hydroxyacetcphenone carbamates.Hydrogenation r e s u l t s i n reclosure of t h e isoquinoline rim and f u r t h e r reduction yielding l-hydroxymethylenetetrahydroisoquinolines.While t h e r e a r e a s u b s t a n t i a l number of simple tetrahydroisoquinoline a l k a l o i d s known, t h e presence of a 1-hydroxymethylene g r o q i n these alkaloids is a r a r e occurrence.Calycotomine (1) has been i s o l a t e d f m n Calycotome, Cytisus and Acacia species i n both 1 i t s o p t i c a l l y a c t i v e a s well as racemic Ponns .The only other member of t h i s family i s 2 a more highly functionalized d e r i v a t i v e (2) fould i n a Mexican cactus .This type of <OH 1 Calywtomine 2 \OH ' ~d d r e s s f a r correspondence alkaloid is of i n t e r e s t m a u s e it represents an alternative arrangement of the aromatic amino-alcohol system found i n the sympathmimetic hormone epinephrine.3 Several syntheses, including a recent enantio-selwtive one , of calycotmine have been reported4.These synthetic approaches have involved c l a s s i c a l isoquimline chemistry, Bischler-Napieralski reactions or Reissert chemistry, and have, i n many cases, teen plagued by troublesane steps and low yields.The ready a v a i l a b i l i t y of 5 6
Caspase-9, Bcl-XL, and Apaf-1 Form a Ternary Complex (1998)

Genetic analysis of apoptosis in the nematode Caenorhabditis elegans has revealed the cell death machine to be composed of three core interacting components. CED-4 (equivalent to mammalian Apaf-1) is a nucleotide binding molecule that complexes with the zymogen form of the death protease CED-3, leading to its autoactivation and cell death. CED-9 blocks death by complexing with CED-4 and attenuating its ability to promote CED-3 activation. An equivalent ternary complex was found to be present in mammalian cells involving Apaf-1, the mammalian death protease caspase-9, and Bcl-XL, an anti-apoptotic member of the Bcl-2 family. Consistent with a central role for caspase-9, a dominant negative form effectively inhibited cell death initiated by a wide variety of inducers.
A reproducible and stable model of acute ischaemic left ventricular failure in dogs (1982)

A model of acute ischaemic left ventricular (LV) failure is presented. In closed-chest anaesthetized dogs 50 micrometer plastic microspheres were injected repeatedly into the left main coronary artery over a period of about 40 min. The injections effected stepwise elevations of LV end-diastolic pressure (LVEDP). Thus, LVEDP could be increased to a desired level, about 20 mmHg, in a very controlled manner. All dogs developed signs of markedly depressed LV performance. Haemodynamic conditions stabilized about 60 min after embolization. The maximum LVDP/dt decreased from 2696 +/- 169 to 1823 +/- 98 mmHg . x-1, cardiac output decreased from 2.81 +/- 0.20 to 1.98 +/- 0.14 l . min-1 and mean aortic blood pressure decreased from 144 +/- 4 to 127 +/- 3 mmHg, while total peripheral resistance increased from 56 +/- 3 to 69 +/- 3 mmHg . l-1 . min. Myocardial blood flow decreased from 103 +/- 7 to 79 +/- 6 ml . min-1 . 100 g-1 and myocardial oxygen consumption decreased from 12.5 +/- 0.9 to 8.3 +/- 0.8 ml . min-1. 100 g-5. Myocardial uptake of lactate and free fatty acids decreased markedly. Electrocardiography showed signs of acute ischaemia. There were no deaths due to ventricular fibrillation. Morphological studies showed multiple small infarcts throughout the entire LV. In conclusion, repeated coronary embolization with 50 micrometers plastic microspheres, guided by the rise of LVEDP represents a simple and reproducible method for induction of uniform and stable acute LV failure.
Nonlinear Thermal Stress/Strain Analyses of Copper Filled TSV (Through Silicon Via) and Their Flip-Chip Microbumps (2009)

Most TSVs are filled with copper; siliconpoly and tungsten are the alternatives. The coefficient of thermal expansion (CTE) of copper (~17.5 times 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> /degC) is a few times higher than that of silicon (~2.5 times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> /degC). Thus, when the copper filled through silicon via (TSV) is subjected to temperature loadings, there is a very large local thermal expansion mismatch between the copper and the silicon/dielectric (e.g., SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ), which will create very large stresses and strains at the interfaces between the copper and the silicon and between the copper and the dielectric. These stresses/strains can be high enough to introduce delamination between the interfaces. In this paper, the nonlinear thermal stresses and strains at the interfaces between the copper, silicon, and dielectric have been determined for a wide-range of aspect ratios (of the silicon thickness and the TSV diameter). One of the major applications of TSV is as an interposer. Because of Moore's (scaling/integration) law, the silicon chip is getting bigger, the pin-out is getting higher, and the pitch is getting finer. Thus, the conventional substrates, e.g., BT (bismaleimide triazine) cannot support these kinds of silicon chips anymore and a silicon interposer (substrate) is needed to redistribute the very fine-pitch and high pin-count pads on the chip to much larger pitch and less pin-count through the silicon vias on the silicon substrate. Depending on the via-size and pitch of the copper filled TSV, the effective CTE of the copper filled TSV interposer could be as high as 10 times 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> /degC. Consequently, the global thermal expansion mismatch between the silicon chip and the copper filled TSV substrate can be very large and the bumps (usually very small, e.g., microbumps) between them may not be able to survive under thermal conditions. In this study, the nonlinear stresses and strains in the microbumps between the silicon chip and copper filled TSV interposer (with and without underfills) have been determined for a wide-range of via sizes and pitches, and various temperature conditions. These results should be useful for 1) making a decision if underfill is necessary for the reliability of microbumps and 2) selecting underfill materials to minimize the stresses and strains in the microbumps.
Lymphangiogenic Gene Therapy With Minimal Blood Vascular Side Effects (2002)

Recent work from many laboratories has demonstrated that the vascular endothelial growth factor-C/VEGF-D/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and that mutations of the Vegfr3 gene are associated with hereditary lymphedema. Furthermore, VEGF-C gene transfer to the skin of mice with lymphedema induced a regeneration of the cutaneous lymphatic vessel network. However, as is the case with VEGF, high levels of VEGF-C cause blood vessel growth and leakiness, resulting in tissue edema. To avoid these blood vascular side effects of VEGF-C, we constructed a viral vector for a VEGFR-3-specific mutant form of VEGF-C (VEGF-C156S) for lymphedema gene therapy. We demonstrate that VEGF-C156S potently induces lymphangiogenesis in transgenic mouse embryos, and when applied via viral gene transfer, in normal and lymphedema mice. Importantly, adenoviral VEGF-C156S lacked the blood vascular side effects of VEGF and VEGF-C adenoviruses. In particular, in the lymphedema mice functional cutaneous lymphatic vessels of normal caliber and morphology were detected after long-term expression of VEGF-C156S via an adeno associated virus. These results have important implications for the development of gene therapy for human lymphedema.
Maintenance of Normoglycemia in Diabetic Mice by Subcutaneous Xenografts of Encapsulated Islets (1991)

The goal of islet transplantation in human diabetes is to maintain the islet grafts in the recipients without the use of immunosuppression. One approach is to encapsulate the donor islets in permselective membranes. Hollow fibers fabricated from an acrylic copolymer were used to encapsulate small numbers of rat islets that were immobilized in an alginate hydrogel for transplantation in diabetic mice. The fibers were biocompatible, prevented rejection, and maintained normoglycemia when transplanted intraperitoneally; hyperglycemia returned when the fibers were removed at 60 days. Normoglycemia was also maintained by subcutaneous implants that had an appropriately constructed outer surface on the fibers.
Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism. State of the art in the pig, and perspectives towards humans. (2006)

The correct functional development of the gastrointestinal tract is of special importance during the neonatal and weaning phases of reared piglets. Nutrition is obviously a critical determinant in the growth of the gut in the young swine. The mucosal epithelium of the small intestine is reputed anatomically and functionally immature in neonatal pigs, a feature that appears to be exacerbated at weaning, when a colonization of the gut occurs by "new" microorganisms entering the alimentary canal with the solid feed. This frequently exposes piglets to diarrhoeic syndromes and other intestinal disturbances. Functional feed additives, also called nutraceuticals, appear as promising alternative substances to the use of chemotherapeutics as growth promoters in the rearing farm, above all considering the near banning of them by the European Parliament in the view of reducing antibiotic resistance phenomena in human therapies. Several feed additives are available that may play a role in the pig nutritional plan because of their trophic and cyto-protective effects on the gastrointestinal apparatus. Paying special attention to the quantitative consequences (histometry) upon the gut of the examined dietary supplements, this review, even if not fully exhaustive, will focus on the function (and possibly the mechanism/s of action) of certain gut-trophic nutrient substrates. This in turn will sustain the potential use of these substances in human therapy, especially the one directed at resolving intestinal diseases, both in adult and infant ages. In nutritional studies as well as in other biomedical research fields, the swine is an excellent animal model.
N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine (2009)

Arylamine N-acetyltransferase 1 and 2 exhibit single nucleotide polymorphisms in human populations that modify drug and carcinogen metabolism. This paper updates the identity, location and functional effects of these single nucleotide polymorphisms and then follows with emerging concepts for understanding why pharmacogenetic findings may not be replicated consistently. Using this paradigm as an example, laboratory-based mechanistic analyses can reveal complexities such that genetic polymorphisms become biologically and medically relevant when confounding factors are more fully understood and considered. As medical care moves to a more personalized approach, the implications of these confounding factors will be important in understanding the complexities of personalized medicine.
New concepts in herpes simplex virus vaccine development: notes from the battlefield (2009)

The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide 'heterologous protection' from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an 'asymptomatic epitope'-based lipopeptide vaccine.
Androgenic Responses to Resistance Exercise (2006)

In summary, these data demonstrated that: 1) feeding after RE increased AR content, which may result in increased testosterone uptake, and thus enhanced luteinizing hormone secretion via feedback mechanisms; and 2) LCLT supplementation upregulated AR content, which may promote recovery from RE.
A Digital Microfluidic Approach to Proteomic Sample Processing (2009)

A common characteristic for proteomic analyses is the need for extensive biochemical processing. Digital microfluidics (DMF), a technique characterized by the manipulation of discrete microdroplets (100 nL-10 microL) on an open array of electrodes, is a good match for carrying out rapid, automated solution-phase reactions. Here, we report a DMF-based method integrating several common processing steps in proteomics, including reduction, alkylation, and enzymatic digestion. Fluorogenic assays were used to quantitatively evaluate the kinetics and reproducibility of each reaction step, and MALDI-MS was used for qualitative confirmation. The method is fast, facile, and reproducible, and thus has the potential to be a useful new tool in proteomics.
Large Intervening Non-Coding RNA HOTAIR Is an Indicator of Poor Prognosis and a Therapeutic Target in Human Cancers (2014)

In the human genome, the fraction of protein-coding genes that are stably transcribed is only up to 2%, with the remaining numerous RNAs having no protein-coding function. These non-coding RNAs (ncRNAs) have received considerable attention in cancer research in recent years. Breakthroughs have been made in understanding microRNAs and small interfering RNAs, but larger RNAs such as long ncRNAs (lncRNAs) remain an enigma. One lncRNA, HOX antisense intergenic RNA (HOTAIR), has been shown to be dysregulated in many types of cancer, including breast cancer, colorectal cancer, and hepatoma. HOTAIR functions as a regulatory molecule in a wide variety of biological processes. However, its mechanism of action has not been clearly elucidated. It is widely believed that HOTAIR mediates chromosomal remodeling and coordinates with polycomb repressive complex 2 (PRC2) to regulate gene expression. Further study of HOTAIR-related pathways and the role of HOTAIR in tumorigenesis and tumor progression may identify new treatment targets. In this review, we will focus on the characteristics of HOTAIR, as well as data pertaining to its mechanism and its association with cancers.
Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection (2013)

Nod-like receptor family, pyrin domain-containing 3 (NLRP3), is involved in the early stages of the inflammatory response by sensing cellular damage or distress due to viral or bacterial infection. Activation of NLRP3 triggers its assembly into a multimolecular protein complex, termed "NLRP3 inflammasome." This event leads to the activation of the downstream molecule caspase-1 that cleaves the precursor forms of proinflammatory cytokines, such as interleukin 1 beta (IL-1β) and IL-18, and initiates the immune response. Recent studies indicate that the reactive oxygen species produced by mitochondrial respiration is critical for the activation of the NLRP3 inflammasome by monosodium urate, alum, and ATP. However, the precise mechanism by which RNA viruses activate the NLRP3 inflammasome is not well understood. Here, we show that loss of mitochondrial membrane potential [ΔΨ(m)] dramatically reduced IL-1β secretion after infection with influenza, measles, or encephalomyocarditis virus (EMCV). Reduced IL-1β secretion was also observed following overexpression of the mitochondrial inner membrane protein, uncoupling protein-2, which induces mitochondrial proton leakage and dissipates ΔΨ(m). ΔΨ(m) was required for association between the NLRP3 and mitofusin 2, a mediator of mitochondrial fusion, after infection with influenza virus or EMCV. Importantly, the knockdown of mitofusin 2 significantly reduced the secretion of IL-1β after infection with influenza virus or EMCV. Our results provide insight into the roles of mitochondria in NLRP3 inflammasome activation.
Response Rates Using International Working Group (IWG) Criteria in Patients with Myelodysplastic Syndromes (MDS) Treated with Azacitidine. (2005)

Abstract The CALGB conducted a series of clinical trials with azacitidine (Vidaza®) administered subcutaneously or intravenously in patients with MDS using the FAB classification (JCO2002;20:2429). Since the publication of these CALGB studies (8421, 8921, 9221), new response criteria for evaluating new treatments for MDS have been published by the IWG (Blood2000;96:3671). Two general differences between the CALGB and IWG response criteria are the required duration of improvement (CALGB: ≥4 weeks; IWG: ≥8 weeks) and peripheral blood values (CALGB: different criteria for hemoglobin targets for males and females; IWG: same criteria for males and females). The results reported here are based on re-collected data from patients described in the published report. After applying the IWG response criteria, the overall response rate (CR+PR+HI) in the azacitidine groups were similar across studies 8421, 8921, and 9221: 44% (21/48), 40% (28/70), and 48% (47/99), respectively. Best Response using IWG Response Criteria for MDS in Studies 8421, 8921, and 9221 Median duration of any response (CR, PR or HI) in the 114 azacitidine-treated responders was 366 days (range: 56 to 4641+ days). The median duration of CR in the 32 azacitidine-treated responders was 379 days (range: 92 to 4412+ days). The median number of cycles from first treatment with azacitidine to any response (CR, PR or HI) was 3 cycles (range: 1 to 17 cycles). Although 75% of the responders achieved a response by cycle 4, the other 25% achieved a response as late as cycle 17. The majority (90%) of responders achieved a response by cycle 6. Best response was observed, on average, 2 cycles after the initial response. In summary, reanalysis of the response rates using IWG criteria demonstrate consistent results across three sequential studies and further validate the superiority of azacitidine over supportive care alone.
Small cache, big effect (2011)

Load balancing requests across a cluster of back-end servers is critical for avoiding performance bottlenecks and meeting service-level objectives (SLOs) in large-scale cloud computing services. This paper shows how a small, fast popularity-based front-end cache can ensure load balancing for an important class of such services; furthermore, we prove an O(n log n) lower-bound on the necessary cache size and show that this size depends only on the total number of back-end nodes n, not the number of items stored in the system. We validate our analysis through simulation and empirical results running a key-value storage system on an 85-node cluster.
Practical Considerations for the Use of Spatial Carrier-Frequency Filters (1966)

The article discusses several practical problems in the use of spatial carrier-frequency filters in coherent optical systems, and describes an interferometric system that offers many practical advantages in constructing such filters. Also described is an optical configuration that can easily search for the scale of a signal, as well as its location and orientation. The use of a prism in the optical configuration simplifies the search for the orientation and scale of the signal. The spatial carrier-frequency filter introduces some aberrations, but only astigmatism and distortion remain uncorrected. The necessary magnitude of the spatial carrier frequency depends upon the size of the signal and of the input data. A natural extension of this consideration leads directly to a corresponding requirement on the spatial carrier frequencies for multiplexed filters.
Molecular cloning and site-specific mutagenesis of a gene involved in arylsulfatase production in Campylobacter jejuni (1996)

The arylsulfatase gene from Campylobacter jejuni 81-176 encodes a predicted protein of 69,293 Da which shows no sequence similarity with other known arylsulfatases. The gene hybridizes to other Ast+ strains of C. jejuni and Campylobacter sputorum subsp. bubulus, as well as to many Ast- strains of C. jejuni.
P‐126: Ultra‐Compact LED based Image Projector for Portable Applications (2003)

Abstract By using a single high power Light Emitting Diode (LED) and a small size transmissive LCD very compact projectors, which can be run from batteries, can be built. Such a projector can be used in combination with or integrated into a PDA or digital camera to project images or presentations in a small size format, and would be used whenever a laptop would be unavailable or clumsy. For these types of applications the required flux can be low. We have build a very small (prototype) projector using a single, high power LED, a small LCD, and a small projection lens. The light output of such a configuration is in the range of 5 to 10 lm, which is sufficient for the projected image sizes as indicated above. In this paper we well describe the system and its performance and size, and elaborate on alternative configurations and performance.