The present invention is directed to a compound of Formula (I) and to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, Y and Z have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

An objective of the present invention is to provide a process for producing 4-carbonyl oxyquinoline derivatives useful as agricultural and horticultural pesticides and fungicides. The objective can be attained by a process for producing 4-carbonyl oxyquinoline derivatives represented by general formula (1), the process including reacting a quinolone derivative with a halogenated compound or an acid anhydride in the presence of a phase transfer catalyst and a base.

Esters of 4,5-disubstituted-oxy-2-methyl-3,6-dioxo-cyclohexa-1,4-dienyl alkyl acids were prepared chemically and/or enzymatically. Depending upon the ester, improved melanocyte cytotoxicity was achieved. Improved cytotoxicity characteristics are consistent with ester analogs being more physiologically compatible and less irritating to skin than their corresponding acids.

Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

The present disclosure describes antibodies that target HM1.24. In various aspects, the antibodies have specific CDR, variable, or full length sequences, have modifications with the parent antibody, or include at least one modification relative to a parent antibody that alters affinity to an FcγR or alters effector function as compared to the parent antibody. Nucleic acids encoding the antibodies and methods of using the antibodies are also disclosed.

The invention relates to antibody molecules having specificity for antigenic determinants of human OX40, therapeutic uses of the antibody molecules and methods for producing said antibody molecules.

IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpaha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

A method of preparing 2-methyl-4-phenylbutan-2-ol from a Grignard-type reaction of a benzylmagnesium halide with isobutylene oxide, and the use of the 2-methyl-4-phenylbutan-2-ol as a fragrance or flavoring, cosmetic agent, or detergent component.

A novel maize variety designated X80B470 and seed, plants and plant parts thereof, produced by crossing Pioneer Hi-Bred International, Inc. proprietary inbred maize varieties. Methods for producing a maize plant that comprises crossing hybrid maize variety X80B470 with another maize plant. Methods for producing a maize plant containing in its genetic material one or more traits introgressed into X80B470 through backcross conversion and/or transformation, and to the maize seed, plant and plant part produced thereby. This invention relates to the maize variety X80B470, the seed, the plant produced from the seed, and variants, mutants, and minor modifications of maize variety X80B470. This invention further relates to methods for producing maize varieties derived from maize variety X80B470.

Disclosed are new members of a class of non-lipid small molecule inhibitors which interfere with the interaction between phosphoinositol-3,4,5-triphosphate (PIP3) and pleckstrin homology (PH) domains. These molecules target a broad range of PIP3-dependent signaling events in vitro and exert significant anti-tumor activity in vivo, with improved activity and selectivity toward particular PH domains. The small molecule inhibitors of the invention can be used alone or together with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or other cancer medicament to treat cancer. Small molecule inhibitors of the invention act synergistically in combination with TRAIL and with other Akt inhibitors in treating cancer. Pharmaceutical compositions and methods for treating cancer are provided.

A novel soybean variety, designated XB47X13 is provided. Also provided are the seeds of soybean variety XB47X13, cells from soybean variety XB47X13, plants of soybean XB47X13, and plant parts of soybean variety XB47X13. Methods provided include producing a soybean plant by crossing soybean variety XB47X13 with another soybean plant, methods for introgressing a transgenic trait, a mutant trait, and/or a native trait into soybean variety XB47X13, methods for producing other soybean varieties or plant parts derived from soybean variety XB47X13, and methods of characterizing soybean variety XB47X13. Soybean seed, cells, plants, germplasm, breeding lines, varieties, and plant parts produced by these methods and/or derived from soybean variety XB47X13 are further provided.

The present invention provides an inbred corn line designated FF7354, methods for producing a corn plant by crossing plants of the inbred line FF7354 with plants of another corn plant. The invention further encompasses all parts of inbred corn line FF7354, including culturable cells. Additionally provided herein are methods for introducing transgenes into inbred corn line FF7354, and plants produced according to these methods.

Polypeptides capable of binding human IL-13 and/or of binding human IL-4 in the presence of IL-4 Rα can be used in medicine, in diagnosis and in screening for agonists/antagonists of IL-13/IL-4. One such polypeptide is shown in FIG. 1.

The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

A recombinant vector comprises simian adenovirus 36, simian adenovirus 42.1, simian adenovirus 42.2 and/or simian adenovirus 44 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-36, -42.1, -42.2 or -44 gene(s) is also described. Methods of using the vectors and cell lines are provided.

A method for removing 4-methylimidazole (4-MEI) from solution may include contacting an alkaline earth metal silicate with a solution containing 4-MEI and adsorbing at least some of the 4-MEI using the alkaline earth metal silicate. The method may further include removing at least some of the alkaline earth metal silicate having the adsorbed 4-MEI from the solution. The alkaline earth metal silicate may include magnesium silicate or calcium silicate. A method for removing 4-MEI from solution may include contacting an adsorbent clay material with a solution containing 4-MEI and adsorbing at least some of the 4-MEI using the adsorbent clay material. The method may further include removing at least some of the adsorbent clay material having the adsorbed 4-MEI from the solution. The adsorbent clay material may include smectite, bentonite, or an activated or un-activated AOCS day material.

A method for processing explosives containing a high loading of CL-20 may advantageously include a binder system having naphthenic oil and/or paraffinic oil. Solid energetic ingredients are added into the binder system and mixed to form a free-flowing suspension in which the solid energetic ingredients are homogeneously mixed and coated with the binder system. The binder system is then cured and cast to form a cross-linked explosive.

The invention concerns soluble and antigenic HTLV p24 variants that can be fused to chaperones and their use in diagnostic applications such as immunoassays for detecting antibodies against HTLV-I or HTLV-II in an isolated biological sample. In particular, the invention relates to a soluble HTLV-I or HTLV-II p24 antigen comprising either the N- or the C-terminal domain of p24 and lacking the other domain. Moreover, the invention covers recombinant DNA molecules encoding these HTLV-I and -II fusion antigens as well as their recombinant production using expression vectors and host cells transformed with such expression vectors. In addition, the invention focuses on compositions of these HTLV p24 antigens with HTLV gp21 antigen and on an immunoassay method for detection of HTLV antibodies using the antigens of the invention. Also the use of HTLV p24 antigens in an in vitro diagnostic assay as well as a reagent kit for detection of anti-HTLV-antibodies comprising said HTLV antigens is encompassed.

Just in time to celebrate its ten-year anniversary, popular Filipino-fusion food truck Señor Sisig has established a long-term location in Oakland.

The brand-new spot is at 3331 Fruitvale Ave. in the Dimond District.…

The UK-based mixer-maker and audiophile favorite MasterSounds has a small piece of joy to brighten up DJs’ days. They’ve released the third generation of their Radius 2 and Radius 4 mixers, and have adjusted their price points to cater to artists with a lower spending budget (especially now). These mixers are homegrown, too—MasterSounds mixers are […]

The post A third generation of Radius 2 + 4 rotary mixers: New tech upgrades, lower price appeared first on DJ TechTools.

If you haven’t looked at Traktor DJ, Native Instruments’ iOS app (it runs on Mac and PC too) recently, a new update and the concurrent global stay-home happening seems like the perfect time to do it. The update to Traktor DJ 2.4 has a bunch of features that look like they’re straight out of a […]

The post Traktor DJ 2.4: Transport Control UI Improvements, Genre Sorting appeared first on DJ TechTools.

News you don't want to miss for April 7:

1. A nursing home in Orinda is being hit hard by a covid-19 outbreak that has infected 49 people, including 27 residents and 22 staff members, the East Bay Times reports.…

News you don't want to miss for Easter Weekend:

Oakland will temporarily close 74 miles of city streets to automobile traffic in an effort to give ample space for pedestrians, bike riders, and runners during the covid-19 shelter in place, The Guardian reports.…

News you don't want to miss for April 27:

1. Alameda County, along with five other Bay Area counties, announced the shelter in place order will be extended through the end of May, the San Francisco Chronicle reports.…

News you don't want to miss for May 7:

Just a few months ago, California was sitting on an overflowing reserve fund. After covid-19, the state is now reconciling with a massive $54.3 billion deficit over the next fiscal year, Calmatters reports.…

POLICE are appealing for information after a 'suspicious' 4X4 was seen pulling onto someone's drive with the number plates covered up.

It's 40 years today since Southampton FC began their memorable journey to glory in the 1976 FA Cup - and we've got some never before seen photos.

EASTLEIGH are through to the FA Cup first round after two penalties for Scott Rendell.

Scott Rendall admitted his confidence is sky high after his fine goalscoring continued with a match winning hat-trick.

NO further deaths from coronavirus have been reported in Hampshire hospitals in the past 24 hours.

Playing Agony feels like penance for all your past gaming sins.

St Mary's Stadium, Championship, Saturday September 17, 2011.

St Mary's Stadium, Championship, Saturday October 1, 2011.

St. Mary's Stadium, Championship, Saturday April 28, 2012.

THE GOOD times are back at St Mary's.

St Mary's Stadium, League One, Tuesday November 2, 2010

List of runners numbered 4,000 to 5,999

NO further deaths from coronavirus have been reported in Hampshire hospitals in the past 24 hours.

HAMPSHIRE is set to receive a massive £360m boost in a deal that aims to create thousands of jobs and new homes and revitalise the economy.

Vistas from Sydney to South Africa and Copenhagen to Canada could inspire Southampton’s own £450million Royal Pier development.

It's an à la carte menu of chilling narrative and crunch decisions, with each course graciously complementing each other.

Minecraft's blocky appearance may at first appear primitive and like a game of yesteryear, but they're in fact the building blocks of which a player is bestowed god-like creative powers, shackled only by the limitations of their own mind.

EVER fancied being a shepherd in a steampunk environment, filled with perilous danger which wouldn’t be out of place in a Saw movie?

IT’S been three months since we were treated to the rip-roaring hilarity-fest which was the opening episode of Tales from the Borderlands. It’s been a long wait.

Like Frankenstein, the guys at Activision have breathed new life in to something that was otherwise dead.

A VICTORY in the America’s Cup by Sir Ben Ainslie could generate as much as £140 million for the Hampshire economy.

SOUTHAMPTON’S iconic Go! Rhinos sculptures bowed out in style tonight.