gebhart/patrepeval huggingface dataset:
Characterization and Modeling of Hot Carrier-Induced Variability in Subthreshold Region (2012)

We developed an analytical model that is able to predict the evolution of the subthreshold slope variability associated with hot carrier (HC) stress. The model assumes that HC stress generates interface states with a Poisson distribution and that the number of HC-induced interface states increases linearly with the HC-induced subthreshold slope variation. We validate the model by means of extensive variability data sets collected on n-channel MOSFETs in 45- and 65-nm CMOS technologies. Furthermore, we investigate the correlation between the threshold voltage and the subthreshold slope fluctuations in order to fully characterize their impact on the subthreshold current variability.
Regulatory Roles of Invariant Natural Killer T Cells in Adipose Tissue Inflammation: Defenders Against Obesity-Induced Metabolic Complications (2018)

Adipose tissue is a metabolic organ that plays a central role in controlling systemic energy homeostasis. Compelling evidence indicates that immune system is closely linked to healthy physiologic functions and pathologic dysfunction of adipose tissue. In obesity, the accumulation of pro-inflammatory responses in adipose tissue subsequently leads to dysfunction of adipose tissue as well as whole body energy homeostasis. Simultaneously, adipose tissue also activates anti-inflammatory responses in an effort to reduce the unfavorable effects of pro-inflammation. Notably, the interplay between adipocytes and resident invariant natural killer T (iNKT) cells is a major component of defensive mechanisms of adipose tissue. iNKT cells are leukocytes that recognize lipids loaded on CD1d as antigens, whereas most other immune cells are activated by peptide antigens. In adipose tissue, adipocytes directly interact with iNKT cells through presenting lipid antigens and stimulate iNKT cell activation to alleviate pro-inflammation. In this review, we provide an overview of the molecular and cellular determinants of obesity-induced adipose tissue inflammation. Specifically, we focus on the roles of iNKT cell-adipocyte interaction in maintaining adipose tissue homeostasis as well as the consequent modulation in systemic energy metabolism. We also briefly discuss future research directions regarding the interplay between adipocytes and adipose iNKT cells in adipose tissue inflammation.
Supplementary Figure 2 Legend from Circulating B-Cell Chronic Lymphocytic Leukemia Cells Display Impaired Migration to Lymph Nodes and Bone Marrow (2023)

Supplementary Figure 2 Legend from Circulating B-Cell Chronic Lymphocytic Leukemia Cells Display Impaired Migration to Lymph Nodes and Bone Marrow
A phase 1/3 multicenter trial of talimogene laherparepvec in combination with pembrolizumab for unresected, stage IIIB-IV melanoma (MASTERKEY-265). (2016)

TPS9598 Background: Talimogene laherparepvec, an oncolytic viral immunotherapy, was designed to selectively replicate in tumors resulting in lytic cell death, antigen release, and production of GM-CSF to enhance systemic antitumor immune responses. Talimogene laherparepvec improved durable response rate vs GM-CSF in unresectable stage IIIB-IV melanoma (Andtbacka et al, JCO 2015). Pembrolizumab, a human programmed death receptor-blocking antibody approved for the treatment of advanced melanoma, improved PFS and OS vs ipilimumab in patients (pts) with stage III-IV melanoma (Robert et al, NEJM 2015). Combining talimogene laherparepvec + pembrolizumab may further enhance antitumor immune responses. Here we describe the phase 3 design of a phase 1b/3 double-blind, placebo-controlled study assessing the safety and efficacy of talimogene laherparepvec + pembrolizumab in unresected stage IIIB-IV melanoma (NCT02263508). Phase 1b enrolled 21 pts treated with talimogene laherparepvec + pembrolizumab. No dose limiting toxicities were observed (primary endpoint), and preliminary responses were observed in 9 of 16 evaluable pts with median tumor follow-up of 17 weeks (Long et al, SMR 2016). Methods: Approximately 660 pts will receive pembrolizumab + placebo or pembrolizumab + talimogene laherparepvec (1:1 randomization). Co-primary endpoints: PFS and OS. Key secondary endpoints: adverse events and response-based endpoints. Key eligibility criteria: unresectable stage IIIB-IV melanoma naïve to systemic treatment except up to one prior line of BRAF inhibitor-based treatment, measurable and injectable lesions, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression, no active herpetic infection. Talimogene laherparepvec (106 PFU/mL first dose, 108 PFU/mL subsequent doses) or placebo is injected into cutaneous or nodal lesions on day 1, weeks 0, 3, 5, 7 then q3w starting day 1 week 9. Pembrolizumab 200 mg IV is given q3w starting day 1 week 0. Treatment continues until confirmed complete response or progressive disease, intolerance, up to 2 years, or for talimogene laherparepvec or placebo, when there are no longer injectable lesions. Clinical trial information: NCT02263508.
Device-based Therapy for Mitral Regurgitation and Ventricular Reshaping (2017)

BackgroundA clinically effective treatment for functional mitral regurgitation (fMR) due to left ventricular (LV) remodeling may need to address both annular and LV dilation to improve symptoms of heart failure (HF). Here we describe the effects of a device intended to reduce mitral annular dimensions and also reduce the radius of curvature of the LV to improve function.MethodsPatient 202–051 is a 79-year-old man with ischemic cardiomyopathy and 3-to-4+ fMR treated with guideline recommended HF therapies. Echocardiography showed an effective regurgitant orifice (ERO) of 0.36 cm2, a regurgitant stroke volume of 69 ml, an LVEF of 14% and an LV diastolic diameter of 6.2 cm. The patient underwent percutaneous implantation of the Ancora Heart device which consists of a series of intramyocardial anchors connected via a cinching cable implanted into the LV free wall below the mitral annulus and behind the papillary muscles. Tension applied to the cable resulted in an acute ~15% decrease of the circumferential distance between the first and last anchors. Cinching was maintained with a locking mechanism placed at the end of the cable.ResultsEchocardiographic follow up performed over the course of 1 year showed that ERO decreased to 0.12 cm2, regurgitant stroke volume to 23 ml, LV dimension to 5.6 cm and EF improved to 34%. ntPro-BNP decreased from 3440 to 1450 pg/ml.ConclusionThese findings provide proof-of-concept that a percutaneously deployable, sub-valvular intramyocardial implant that cinches the myocardial wall below the mitral annulus has the potential to reduce the severity of fMR and improve LV function.
Performance Evaluation of Vertical Wells for Landfill Leachate Recirculation (2005)

A vertical leachate recirculation system was evaluated for its potential to recirculate leachate into landfilled waste. Leachate was recirculated through eleven vertical wells installed at three different depths. The results of recirculation tests performed over a 6-month duration are presented in this paper. The results indicated that specific capacity of vertical wells decreased with well depth. The specific capacity per unit screen length of the vertical wells ranged from 1.2 x 10–6 to 1.2 x 10–5 m3/s-m2. The mean specific capacity of lines installed at three different depths were significantly (p<0.025) different from each other and were in the following order: shallow well (depth ~6 to 8 m) > middle well (depth~12 to 16 m) > deep well (depth~18 m). A potential reason for lower specific capacity for deep wells is the lower hydraulic conductivity of the waste in deeper sections due to higher overburden pressure. While the data presented in this paper are based on preliminary injection tests and may not represent steady-state condition, the results provide important insight into the hydrodynamic behavior of bioreactors.
Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network (2012)

Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care.
Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels (1994)

Congenital deficiency in coagulation factor XIII is a rare autosomal recessive bleeding disorder. Although the defect was characterized over 30 years ago, little is known about the molecular basis of the disorder. Here, we show two novel point mutations in the gene of the A-subunit of factor XIII in the genetically isolated population of Finland. All eight factor XIII-deficient families identified in Finland were studied. The exons of the gene of A-subunit were amplified individually by polymerase chain reaction and subsequently screened by single-strand conformation polymorphism. Sequence analysis of the abnormally migrating fragments showed two point mutations resulting in an amino acid alteration. A C-to-T transition at Arg-661 in exon XIV created a premature stop codon. This mutation was detected in six of the eight families, thus being the major alteration causing FXIII deficiency in Finland. In two of the six families, the patients were compound heterozygotes with the Arg-661-Stop mutation in one allele and either a T-to-C point mutation in exon VI or a thus far uncharacterized mutation in the other allele. The T-to-C transition in exon VI resulted in a substitution of threonine for methionine 242. The transition was found in one family only, where it was in the heterozygote form combined with the Arg-661-Stop mutation. To evaluate the consequences of these mutations, steady-state FXIII mRNA levels were quantitated by solid-phase minisequencing. In addition to the termination of translation 70 amino acids before the initial stop codon, the Arg-661-Stop mutation causes a 10- to 30-fold reduction in FXIII mRNA levels. This is also likely to result in a low translation level in the truncated polypeptide. In contrast, Met-242-Thr mutation does not seem to affect the level of mRNA. Here, the absence of a functional and immunodetectable protein is probably caused by an altered conformation of the mutant polypeptide, resulting in early degradation of the defective protein.
Regeneration of the Ferrous Heme of Soluble Guanylate Cyclase from the Nitric Oxide Complex:  Acceleration by Thiols and Oxyhemoglobin (1998)

Soluble guanylate cyclase (sGC) catalyzes the conversion of GTP to cGMP and is activated several hundred-fold by binding of nitric oxide (*NO) to the heme prosthetic group. We have examined the stability of the nitrosyl-heme complex of sGC (*NO-sGC) at 37 degreesC in order to determine whether simple dissociation of *NO from sGC could account for the observed in vivo deactivation time. Recombinant sGC was purified from Sf9 cells coinfected with baculoviruses containing the cDNAs for the alpha1 and beta1 subunits of rat lung sGC. The purified protein contained a stoichiometric equivalent of ferrous high-spin heme. Characterization of the purified protein found it to be essentially identical to that purified from bovine lung. Ferrous-nitrosyl sGC prepared anaerobically and exchanged into aerobic buffer containing no reducing agents was essentially stable on ice and had a half-life of approximately 90 min at 37 degreesC. In the presence of thiols [DTT, glutathione (GSH), or L-cysteine], *NO was rapidly lost from sGC regenerating the ferrous high-spin form of the heme. The half-life of *NO-sGC in the presence of 1 mM GSH at 37 degreesC was 6.3 min. In the presence of oxyhemoglobin, the half-life was further reduced to 2.9 min. Although these rates are not fast enough to account for that observed in vivo, and thus probably involve additional agent(s), these data do imply a role for low molecular weight thiols, such as GSH, and oxyferrohemoproteins, such as oxymyoglobin, in the deactivation of sGC.
Antibodies to protozoan variable surface antigens induce antigenic variation (2022)

Abstract The genomes of most protozoa encode families of variant surface antigens, whose mutually exclusive changes in expression allow parasitic microorganisms to evade the host immune response 1,2 . It is widely assumed that antigenic variation in protozoan parasites is accomplished by the spontaneous appearance within the population of cells expressing antigenic variants that escape antibody-mediated cytotoxicity 1,2 . Here we show, both in vitro and in animal infections, that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering into liquid-ordered phase membrane microdomains that trigger a massive release of microvesicles carrying the original VSP and switch in expression to different VSPs by a calcium-dependent mechanism. Surface microvesiculization and antigenic switching are also stimulated when Trypanosoma brucei and Tetrahymena thermophila are confronted to antibodies directed to their GPI-anchored variable surface glycoproteins. This novel mechanism of surface antigen clearance throughout its release into microvesicles coupled to the stochastic induction of new phenotypic variants not only changes the current paradigm of spontaneous antigenic switching but also provides a new framework for understanding the course of protozoan infections as a host/parasite adaptive process.
A best known methodology for transfer machine metrics from technology development facility to high volume manufacturing facility (2005)

In advanced semi-conductor manufacturing capital equipment depreciation drives the largest cost in producing products. Therefore, it is critical to have the exact amount of machines (or tools). Several parameters dictate machine quantities for a given technology launch to high volume manufacturing, such as: availability, utilization, run rate, synergies with other technologies and time factors. These machine parameters, also known as "machine metrics", must be optimized. This paper presents a best known methodology to transfer the machine metrics from technology development (TD) site to high volume manufacturing (HVM) site in order to minimize the changes in tools' quantities forecast
ChemInform Abstract: Metal‐Metal Bonds Involving Actinoids. Functionalization of Activated C‐H Bonds and Unusual Oligomerization Chemistry Mediated by a Thorium‐Ruthenium Complex. (1988)

Abstract Complex (I) undergoes a rapid reaction with MeCN (no detectable intermediates) to yield (III) (besides the Ru compound (IV)), which crystallizes in the space group P2 1 2 1 2 1 with Z=4.
Advanced whole genome sequencing and analysis of fetal genomes from amniotic fluid (2017)

Amniocentesis is typically performed to identify large chromosomal abnormalities within the fetus. Here we demonstrate that it is feasible to generate an accurate whole genome sequence (WGS) of a fetus from an amniotic sample. DNA from cells and the amniotic fluid were isolated and sequenced from 31 amniocenteses. Concordance of variant calls between the two DNA sources and with parental libraries was high. Two fetal genomes were found to harbor potentially detrimental variants in CHD8 and LRP1 , variations in these genes have been associated with Autism Spectrum Disorder (ASD) and Keratosis pilaris atrophicans, respectively. We also discovered drug sensitivities and carrier information of fetuses for a variety of diseases. In this study, we demonstrate for the first time the sequencing of the whole genome of fetuses from amniotic fluid and show that much more information than large chromosomal abnormalities can be gained from an amniocentesis.
Calcium and vitamin D supplementation is associated with decreased intra‐abdominal fat mass (2011)

Calcium and vitamin D may play an important role in the regulation of abdominal fat mass. The effect of calcium (Ca) and vitamin D (D) supplemented regular (Reg) and reduced-calorie (Lite) orange juice (OJ), in combination with a hypocaloric diet, was studied on weight loss and visceral fat mass in overweight and obese adults. Two, parallel, double-blind, placebo-controlled trials were conducted, one with Reg OJ and one with Lite OJ. In each 16-wk trial, participants were randomized into 1 of 2 groups. Each day the first group consumed three 240 mL glasses of OJ (Lite or Reg) fortified with 350 mg Ca and 100 IU D per serving (Reg-CaD and Lite-CaD, respectively), and the second group consumed unfortified OJ (Reg-C or Lite-C, respectively). Visceral and total abdominal fat measurements were performed by computed tomography by a single cut at L4. After 16 wk, weight change was not different in the Lite and Reg trials. While a trend in absolute reduction of intra-abdominal fat mass was found in the Lite-CaD group, an actual significant reduction of intra-abdominal fat mass occurred in the Reg-CaD group. This effect remained highly significant when results of both trials were combined (p=0.007). Analysis of the combined data demonstrated a significant percentage decrease in intra-abdominal fat mass in the CaD groups. Thus, Ca and D supplementation reduced intra-abdominal fat mass suggesting Ca and/or vitamin D may contribute to a preferential reduction of visceral fat. Sources of Support: NIDDK (DK046200), The Coca-Cola Company, MGH Weight Center
Design and fabrication of chemically robust three-dimensional microfluidic valves (2007)

A current problem in microfluidics is that poly(dimethylsiloxane) (PDMS), used to fabricate many microfluidic devices, is not compatible with most organic solvents. Fluorinated compounds are more chemically robust than PDMS but, historically, it has been nearly impossible to construct valves out of them by multilayer soft lithography (MSL) due to the difficulty of bonding layers made of "non-stick" fluoropolymers necessary to create traditional microfluidic valves. With our new three-dimensional (3D) valve design we can fabricate microfluidic devices from fluorinated compounds in a single monolithic layer that is resistant to most organic solvents with minimal swelling. This paper describes the design and development of 3D microfluidic valves by molding of a perfluoropolyether, termed Sifel, onto printed wax molds. The fabrication of Sifel-based microfluidic devices using this technique has great potential in chemical synthesis and analysis.
A Fast, Flexible and Low Cost Process for Neo-Epitope Based Immune Monitoring (2017)

Abstract Advances in genomic technologies have paved the way to developing personalized cancer vaccines targeting neo-antigens. Patient-specific vaccines, targeting several neo-antigens in one go have already entered the clinic. Such personalized, multi-target approach poses a challenge for immune monitoring of vaccine-specific T-cell responses in a fast, flexible and cost-effective fashion. Most immune monitoring protocols use 9–15-mer synthetic peptides originating from the vaccine target antigen. In contrast to detection of shared antigen-specific T-cells, for which the same peptide batch can be used for several patients, immune monitoring of individual neo-antigen-specific T-cell responses requires small amounts of large numbers of peptides (e.g. 40 × 15-mer peptides for 10 neo-epitopes of 27 amino-acids), which can only be used for one single patient. Therefore, standard peptide synthesis approaches applying commercial peptide synthesizers not only lack required throughput and speed but also generate peptides at prohibitive costs. Here, we present data demonstrating the flexible application of our high-throughput, low cost FastTrack peptide synthesis approach in comparison with different specifications of standard peptides in ex-vivo ELISPOT to monitor neo-antigen specific immune responses in patients participating in the IVAC MUTANOME Phase I clinical trial (NCT02035956). Application of the new peptide synthesis method enables the assembly of up to 1200 peptides in less than 3 weeks at appr. 20% of standard synthesis costs.
Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive and thymidine-kinase-negative herpesviruses (2008)

The effect of anise oil, dwarf-pine oil and chamomile oil against different thymidine-kinase-positive (aciclovir-sensitive) and thymidine-kinase-negative (aciclovir-resistant) herpes simplex virus type 1 (HSV-1) strains was examined. Clinical HSV-1 isolates containing frameshift mutations in the thymidine kinase (TK) gene, an insertion or a deletion, yield a non-functional thymidine kinase enzyme resulting in phenotypical resistance against aciclovir. The inhibitory activity of three different essential oils against herpes simplex virus isolates was tested in-vitro using a plaque reduction assay. All essential oils exhibited high levels of antiviral activity against aciclovir-sensitive HSV strain KOS and aciclovir-resistant clinical HSV isolates as well as aciclovir-resistant strain Angelotti. At maximum noncytotoxic concentrations of the plant oils, plaque formation was significantly reduced by 96.6-99.9%, when herpesviruses were preincubated with drugs before attachment to host cells. No significant effect on viral infectivity could be achieved by adding these compounds during the replication phase. These results indicate that anise oil, dwarf-pine oil and chamomile oil affected the virus by interrupting adsorption of herpesviruses and in a different manner than aciclovir, which is effective after attachment inside the infected cells. Thus the investigated essential oils are capable of exerting a direct effect on HSV and might be useful in the treatment of drug-resistant viruses. Chamomile oil did not reveal any irritating potential on hen's egg chorioallantoic membrane, demonstrated the highest selectivity index among the oils tested and was highly active against clinically relevant aciclovir-resistant HSV-1 strains.
Global trade requirements and compliance with World Trade Organization agreements: the role of tracing animals and animal products (2001)

The use of a measure incorporating traceability that directly or indirectly affects international trade is permitted under the World Trade Organization Agreement on the Application of Sanitary and Phytosanitary Measures, provided that the measure is applied in accordance with the provisions of the Agreement. These provisions state that the measure must be necessary, scientifically justified, no more trade restrictive than required and consistent with the appropriate level of protection of the importing country. If requested, importing countries are required to assess claims by exporting countries regarding an alternative measure(s) providing an equivalent level of protection or with regard to regionalisation.
Production of 1,3-Butadiene from Renewable Oxygenated Feedstocks (Abstract) (2023)

Reproduce and ascertain additional experimental catalyst performance data for 1-step conversion of oxygenated feedstocks to butadiene. Experimental data will also be obtained for a 2-step processing configuration where we will tailor the PNNL catalyst originally developed for 1-step processing by tailoring the Lewis acidity and metal properties, with a limited number of experiments. We will measure preliminary catalyst performance results for producing Butadiene from the two oxygenated feedstocks. Additionally, we will produce 30 g of butadiene that will be sent to the client for use in producing polybutadiene. Finally, experimental results will inform techno-economic analysis (TEA) modeling. TEA will focus on identifying the most economically favorable processing route to BD from either oxygenated feedstock. We will also project GHG emissions associated with each of the process models being considered for BD production, and compare such results to GHG emissions when produced from conventional methods (e.g., cracking of naphtha) using values from the literature.