Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

Abstract: Disclosed herein is an implantable accommodative IOL system for insertion into an eye of a patient, the system comprising: an optical element and a housing including an opaque frame. The optical element comprises an optical lens having variable optical power, and the opaque frame is circumferentially disposed around a periphery of the optical element.

Abstract: An apparatus for cleaning an instrument with a cleaning fluid includes a vessel defining a chamber and a port for at least partially filling the chamber with the fluid. The apparatus further includes an ultrasonic transducer for delivering ultrasonic energy to the fluid, and a vacuum pump for depressurizing the chamber. The apparatus further includes a rotatable device removably disposable in the chamber and having a rack defining a cavity for supporting the instrument. The rotatable device also has a fluid delivery member extending toward the cavity and having a fluid channel between an inlet and an outlet. The apparatus further includes a fluid transmission system in fluid communication with the chamber and the fluid channel of the fluid delivery member for circulating the fluid from the chamber through the fluid channel of the fluid delivery member. A method of cleaning an instrument is also provided.

Abstract: A diagnostic test for ovarian cysts is based on the detection of mutations characteristic of the most common neoplasms giving rise to these lesions. With this test, tumor-specific mutations were detected in the cyst fluids of 19 of 24 (79%) borderline tumors and 28 of 31 (90%) malignant ovarian cancers. In contrast, we detected no mutations in the cyst fluids from 10 non-neoplastic cysts and 12 benign tumors. When categorized by the need for exploratory surgery (i.e., presence of a borderline tumor or malignant cancer), the sensitivity of this test was 85% and the specificity was 100%. These tests could inform the diagnosis of ovarian cysts and improve the clinical management of the large number of women with these lesions.

Abstract: A system for administering biologically active substances produced by foaming techniques using compressed gases or supercritical fluids relates to a porous system containing biologically active substances. The system includes a polymer matrix of poly(D,L-lactic-co-glycolic acid) or a polymer mixture containing poly(D,L-lactic-co-glycolic acid) of an intrinsic viscosity of less than 0.5 dL/g with other biodegradable synthetic or semisynthetic polyesters, a release-regulating component (starch and derivatives), and at least one biologically active substance. The matrix is biodegradable with a solid or semisolid consistency and a homogeneous appearance. A method for producing these systems using foaming with compressed fluids, and the use for the production of implants and scaffolds having this system are also disclosed. Optionally, a porogenic agent can be used for the formation of macropores by thermal decomposition.

Abstract: Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.

Abstract: An apparatus for cleaning an instrument with a cleaning fluid includes a vessel defining a chamber and a port for at least partially filling the chamber with the fluid. The apparatus further includes an ultrasonic transducer for delivering ultrasonic energy to the fluid, and a vacuum pump for depressurizing the chamber. The apparatus further includes a rotatable device removably disposable in the chamber and having a rack defining a cavity for supporting the instrument. The rotatable device also has a fluid delivery member extending toward the cavity and having a fluid channel between an inlet and an outlet. The apparatus further includes a fluid transmission system in fluid communication with the chamber and the fluid channel of the fluid delivery member for circulating the fluid from the chamber through the fluid channel of the fluid delivery member. A method of cleaning an instrument is also provided.

Abstract: We queried DNA from saliva or plasma of 93 HNSCC patients, searching for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% (95% CI, 84% to 99%) of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n=10) and 95% (n=37), respectively. Saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in the saliva and plasma is a valuable biomarker for detection of HNSCC.

Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

Abstract: An optical projection system provides part of a display system that presents a displayed virtual image at a predetermined distance in front of a viewing position. Said display system comprises a projection system and a primary reflecting optic that deflects an off-axis incoming optical signal from the projection system toward the viewing position. Said projection system is arranged to provide an adapted output image signal that compensates for optical aberration effects introduced by the reflecting optic to ensure provision of a reduced aberration display image to the viewing position, and where the reflecting optic comprises a grating structure.

Abstract: To help reveal the pathogenesis of these lesions, we purified the DNA from Intraductal Papillary Mucinous Neoplasm (IPMN) cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. We identified recurrent mutations at codon 201 of GNAS. We found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. These data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.

Abstract: The present disclosure involves ctDNA assays that interrogate many regions from a single sample with high precision and accuracy, while evaluating multiple forms of cancer-related genomic alterations including sequence mutations and structural alterations. The disclosure provides simplified yet robust methods that achieve high sensitivity and specificity by analyzing cancer genes using a limited pool of non-unique barcodes in combination with endogenous barcodes. Samples are captured and sequenced using high coverage next-generation sequencing to allow tumor-specific somatic mutations, amplifications, and translocations to be identified.

Abstract: The invention refers to compounds of general formula (I) wherein the variables take the various meanings, pharmaceutical compositions containing them and their use in medicine, particularly in pain therapy.

Abstract: Increased sensitivity and specificity of characterizing patient-specific variations as mutations that are indicative of a cancer or other disease by identifying patient-specific tumor mutations by comparing tumor and normal sequence reads from the patient and filtering for mutations that are unique to the tumor. By comparing tumor sequence to a normal sequence from the same patient, false-positive mutation calls are minimized in the analysis.

Abstract: Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.

Abstract: Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We generated single chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by human leukocyte antigen (HLA) molecules. These scFvs can be converted to full-length antibodies, termed MANAbodies, targeting “Mutation Associated Neo-Antigens” bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for peptides bound to pre-defined HLA types. In this way, we obtained scFvs, including one specific for a peptide encoded by a common KRAS mutant and another by a common EGFR mutant. Molecules targeting MANA can be developed that specifically react with mutant peptide-HLA complexes even when these peptides differ by only one amino acid from the normal, wild-type form.

Abstract: The invention refers to compounds of general formula (I) wherein the variables take the various meanings, pharmaceutical compositions containing them and their use in medicine, particularly in pain therapy.

Abstract: The present inventions provide, among other things, tapered burner tubes having raised gas ports and a smooth interior surface free from obstructions. Venturi members creating a smooth flow of the gas/air mixture along the top of the burner tube are also provided.

Abstract: A method of recovering metals from electronic waste comprises providing a powder comprising electronic waste in at least a first reactor and a second reactor and providing an electrolyte comprising at least ferric ions in an electrochemical cell in fluid communication with the first reactor and the second reactor. The method further includes contacting the powders within the first reactor and the second reactor with the electrolyte to dissolve at least one base metal from each reactor into the electrolyte and reduce at least some of the ferric ions to ferrous ions. The ferrous ions are oxidized at an anode of the electrochemical cell to regenerate the ferric ions. The powder within the second reactor comprises a higher weight percent of the at least one base metal than the powder in the first reactor. Additional methods of recovering metals from electronic waste are also described, as well as an apparatus of recovering metals from electronic waste.

Abstract: Disclosed herein are positive allosteric modulators of melanocortin receptor and methods of using such modulators.