Abstract: Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that composite clinical measures of “phenotypic age”, may facilitate the development of a more powerful epigenetic biomarker of aging. Here we show that our newly developed epigenetic biomarker of aging “DNAm PhenoAge” strongly outperforms previous measure in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, physical functioning, and, age-related dementia. It is also associated with Down syndrome, HIV infection, socioeconomic status, and various life style factors such as diet, exercise, and smoking. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and in moving forward, will facilitate the development of anti-aging interventions.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer, in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of an alkylating agent; and (b) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody contains: (i) a heavy chain variable region (VH), which includes an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:7; and (ii) a light chain variable region (VL), which includes an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

Abstract: Disclosed are devices and methods for delivering a sheet of tissue into the eye in such a way that damage to the tissue is minimized, damage to the eye during insertion and manipulation of the tissue is minimized, and the tissue is released and delivered in a precise and controlled fashion.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a molecularly targeted agent; and (b) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody contains: (i) a heavy chain variable region (VH), which includes an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:7; and (ii) a light chain variable region (VL), which includes an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer, in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a topoisomerase inhibitor; and (b) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody contains: (i) a heavy chain variable region (VH), which includes an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:7; and (ii) a light chain variable region (VL), which includes an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

Abstract: Described are devices and methods for delivering a sheet of tissue into the eye in such a way that damage to the tissue is minimized, damage to the eye during insertion and manipulation of the tissue is minimized, and the tissue is released and delivered in a precise and controlled fashion.

Abstract: A fermentation state monitoring apparatus includes: a terahertz wave generation element that outputs inspection light using a terahertz wave to a fermented food under fermentation in a sealed product container; a terahertz wave detection element that detects return light of the inspection light reflected by the fermented food in the product container; and a determination unit that determines a fermentation progress of the fermented food based on an index value including a reflectance of the return light with respect to the inspection light or an absorption coefficient of the return light with respect to the inspection light.

Abstract: Disclosed are specific biomarkers that allow for early testing of preeclampsia/HELLP syndrome. Thus, a method is provided predicting preeclampsia in a pregnant woman. Also disclosed is a kit comprising means for assaying a sample from a pregnant woman for the concentrations of the specific biomarkers.

Abstract: An HDAC6-specific inhibitor (i.e., a compound of Formula I or II) is shown to reduce the pathogenesis associated with polycystic disease. Administration of an HDAC6-specific inhibitor attenuated many of the symptoms characteristic of polycystic liver disease including cyst formation, cyst growth and cholangiocyte proliferation. Treatment with a HDAC6-specific inhibitor also increased the amount of bile duct acetylated tubulin and ?-catenin phosphorylation and/or acetylation while reducing bile duct ?-catenin synthesis. These results demonstrate that HDAC6 is overexpressed in cystic cholangiocytes and that its pharmacological inhibition reduces cholangiocyte proliferation and cyst growth.

Abstract: The present invention is directed to methods of inhibiting p97 and compounds and compositions useful in such methods. Diseases and conditions the can be treated with the compounds and compositions of the invention include, but are not limited to, cancer and neurodegenerative disorders susceptible to treatment by inhibition of p97.

Abstract: Novel human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2R? receptor and a decreased binding capacity for IL-2R?c receptor, as compared to wild-type IL-2. Such IL-2 muteins are useful, for example, as IL-2 partial agonist and antagonists in applications where reduction or inhibition of one or more IL-2 and/or IL-15 functions is useful (e.g., in the treatment of graft versus host disease (GVHD) and adult T cell leukemia). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

Abstract: The present invention is directed to methods of inhibiting p97 and compounds and compositions useful in such methods. Diseases and conditions the can be treated with the compounds and compositions of the invention include, but are not limited to, cancer and neurodegenerative disorders susceptible to treatment by inhibition of p97.

Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Abstract: Methods are disclosed for treating a subject with a vascular or cardiac disorder associated with oxidative stress. Methods are disclosed for treating a subject with GNE myopathy that has impaired cardiac function. These methods include administering to the subject a therapeutically effective amount of a acid, or one or more sialylated compounds, mannosamine, N-acetyl mannosamine or a derivative thereof. In other embodiments, methods are disclosed for detecting a disorder associated with oxidative stress.

Abstract: A fusion molecule is provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety. The targeting polypeptide and the nucleic acid binding moiety include specific the amino acid sequences. A fusion molecule is also provided that includes one or more inhibitory nucleic acids, a targeting polypeptide, and a nucleic acid binding moiety adapted to bind a double-stranded RNA or to a small hairpin RNA. The targeting polypeptide being CCL27 or CCL11 or a fragment thereof.

Abstract: This invention relates, e.g., to a molecular delivery system comprising A. a substrate having a nanostructured surface region which comprises a plurality of nanostructures and, covalently attached to the substrate, multiple copies of a first member of a binding pair; and B. at least one vector nanoparticle which comprises, encapsulated therein, a molecule of interest, and on its surface, multiple copies of second member of the binding pair. Methods of using the molecular delivery system to deliver a molecule of interest to a cell are also described.

Abstract: This invention concerns imageable, radiopaque embolic beads, which are particularly useful for monitoring embolization procedures. The beads comprise iodine containing compounds which are covalently incorporated into the polymer network of a preformed hydrogel bead. The beads are prepared by activating pre-formed hydrogel beads towards nucleophilic attack and then covalently attaching iodinated compounds into the polymer network. The radiopaque beads may be loaded with chemotherapeutic agents and used in methods of embolizing hyperplastic tissue or solid tumors.

Abstract: Antibody VRC01 represents a human immunoglobulin that neutralizes—˜90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains.

Abstract: Disclosed herein are capillary fabrication devices comprising living cells within a support medium. Culture of the cells produces viable lumenized capillary networks with natural or pre-determined geometries and ECM and basement membrane associated with the capillary networks. The capillary networks and the ECM and basement membrane detachable from the capillary networks are useful for tissue engineering applications.

Abstract: The invention relates to a method for synthesizing a selectively labeled RNA, and an apparatus for performing the method. Specific segments or discrete residues within the RNA may be selectively labeled, and different segments may include different labels.