Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10% of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.
Which human disease is associated with mutated UBQLN2

The State of Rhode Island has become a popular family seaside destination. In addition to beach activities and water sports, kids can participate in supervised activities at cultural centres and tourist attractions around the state. The Kayak Centre of Rhode Island The Kayak Centre of Rhode Island offers Oceanplay to kids, a program for children between 9 and 14 years old. The course teaches basic kayak skills and safety protocol on the waters around historic Wickford Village. The all-day program includes games and skill-building activities at all skill levels. The package includes equipment, instructions and lunch. The Courthouse Centre for the Arts The Courthouse Centre for the Arts offers summer camp educational workshops and fine arts programs to kids who want to learn about theatre, dance, classical music and different art mediums. Kids and families can also enjoy concerts, film screenings and theatre performances. The Providence Children's Museum The Providence Children's Museum hosts daily drop-in programs for kids between 5 and 11 years of age and museum adventure classes. Kids can learn how water moves in the Water Ways exhibit, listen to music and learn about plants in the Children's Garden exhibit. The RISD Museum The RISD Museum hosts family workshops and activities for kids between 5 and 12 years of age on alternating Sunday afternoons. Kids can learn different types of art techniques and work with different mediums in a supervised setting. Families taking a self-guided tour of the museum can see exhibits.
What will a child interested in plants probably visit?

Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor B ligand and is a very potent antiresorptive drug. Its efficacy in reducing the risk of vertebral, hip and nonskeletal fracture has been proven in a large prospective, randomized multicenter study of 7808 postmenopausal women with osteoporosis [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial]. Denosumab causes somewhat greater increases in bone mineral density (BMD) than the class of bisphosphonate antiresorptives. Denosumab also causes an increase in bone mass and bone strength in the spine, ultradistal and diaphysis of the radius, proximal tibia and the hip. Recently long-term treatment with denosumab has been shown to cause a continued almost linear increase in total hip and femoral neck BMD beyond 3 years up to 8 years. In this respect, denosumab seems to differ from the bisphosphonate group in which the rate of improvement of BMD diminishes and for some drugs becomes negative after 3-4 years when the process of secondary mineralization flattens out. This unique property of an antiresorptive drug points towards mechanisms of action which differ from the bisphosphonate group. Both types of antiresorptives decrease cortical porosity but contrary to bisphosphonates the reduction in cortical porosity continues with denosumab which, in addition, also seems to cause a slight continuous modeling-based formation of new bone despite suppression of bone remodeling. The net effect is an increase in cortical thickening and bone mass, and increased strength of cortical bone. This may contribute substantially to the significant further reduction of the nonvertebral fracture risk which was found in the long-term denosumab arm of the FREEDOM extension trial during years 4-7.

Which is the target of the drug Denosumab?